WO2025217209A2 - Formes cristallines d'inhibiteur de hdac et leurs utilisations - Google Patents

Formes cristallines d'inhibiteur de hdac et leurs utilisations

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Publication number
WO2025217209A2
WO2025217209A2 PCT/US2025/023734 US2025023734W WO2025217209A2 WO 2025217209 A2 WO2025217209 A2 WO 2025217209A2 US 2025023734 W US2025023734 W US 2025023734W WO 2025217209 A2 WO2025217209 A2 WO 2025217209A2
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Prior art keywords
crystalline form
compound
formula
ray powder
diffraction pattern
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PCT/US2025/023734
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English (en)
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WO2025217209A3 (fr
Inventor
Hongming Li
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Tango Therapeutics Inc
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Tango Therapeutics Inc
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Publication of WO2025217209A2 publication Critical patent/WO2025217209A2/fr
Publication of WO2025217209A3 publication Critical patent/WO2025217209A3/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
    • C07C381/10—Compounds containing sulfur atoms doubly-bound to nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Definitions

  • compositions comprising one or more novel active ingredients requires a variety of considerations, such as route of administration (e.g., enteral, parenteral, topical, etc.), dosage form (e.g., solid - tablet, capsule, etc.; liquid - solution, suspension, syrup, etc.), strength of active ingredient(s) (e.g., 1 mg - 1,000 mg), non-therapeutic component(s) (e.g., excipients) and their respective amounts, and each of these considerations may involve additional considerations such as stability, degradation, sensitivity to light, solubility, taste if administered enterally, palatability, pH, skin irritability, microbial growth, etc.
  • route of administration e.g., enteral, parenteral, topical, etc.
  • dosage form e.g., solid - tablet, capsule, etc.; liquid - solution, suspension, syrup, etc.
  • strength of active ingredient(s) e.g., 1 mg - 1,000 mg
  • non-therapeutic component(s)
  • compositions comprising compounds (e.g., HDAC inhibitors) that exhibit desirable properties treat diseases or disorders (e.g., cancers) in human patients.
  • compounds e.g., HDAC inhibitors
  • anhydrous crystalline form, Form A of (R)-N-(4- amino-4'-fluoro-[1,1'-biphenyl]-3-yl)-4-(S-methylsulfonimidoyl)benzamide, having Formula (I): Attorney Docket No.
  • TGO-025WO wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • anhydrous crystalline form, Form D of (R)-N-(4- amino-4'-fluoro-[1,1'-biphenyl]-3-yl)-4-(S-methylsulfonimidoyl)benzamide, having Formula (I): Formula (I), wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • anhydrous crystalline form, Form G of (R)-N-(4- amino-4'-fluoro-[1,1'-biphenyl]-3-yl)-4-(S-methylsulfonimidoyl)benzamide, having Formula (I): Attorney Docket No.
  • TGO-025WO Formula (I) wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • TGO-025WO Formula (I) wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • a pharmaceutical composition comprising a crystalline form as described in any of the embodiments herein.
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of a compound of formula (I), crystalline form or pharmaceutical composition thereof as described in any of the embodiments herein, wherein the cancer is identified as having modified STK11 activity or expression.
  • a method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and an effective amount of a compound of formula (I), crystalline form or pharmaceutical composition thereof as described in any of the embodiments herein, wherein the treatment modulates and/or improves the Teff cell to Treg cell ratio in the tumor or tumor microenvironment, wherein the cancer is identified as having modified STK11 activity or expression.
  • a method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and an effective amount of a compound of formula (I), crystalline form or pharmaceutical composition thereof as described in any of the embodiments herein, wherein the treatment reduces or depletes Treg cells in the tumor or tumor microenvironment, wherein the cancer is identified as having modified STK11 activity or expression.
  • a method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and an effective amount of a Attorney Docket No.
  • the treatment induces or increases the expression of cytokines that promote anti-tumor activity, wherein the cancer is identified as having modified STK11 activity or expression.
  • a method of treating a cancer in a subject comprising administering to the subject an effective amount of a compound of formula (I), crystalline form or pharmaceutical composition thereof as described in any of the embodiments herein, wherein the administering of the crystalline form or the composition does not reduce erythroid or myeloid cell viability, wherein the cancer is identified as having modified STK11 activity or expression.
  • a method of treating cancer in a subject, wherein the cancer presents an immune evasion phenotype characterized by STK11 mutant expression comprising: administering an effective amount of a compound of formula (I), crystalline form or pharmaceutical composition thereof as described in any of the embodiments herein, wherein the crystalline form, or the composition is capable of attenuating or reversing the immune evasion phenotype.
  • a method of treating a cancer in a subject comprising administering to the subject an effective amount of a compound of formula (I), crystalline form or pharmaceutical composition thereof as described in any of the embodiments herein, wherein an immune checkpoint modulator has been, is, or will be administered to the subject, wherein the cancer is identified as having modified STK11 activity or expression.
  • a method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator, wherein an effective amount of a compound of formula (I), crystalline form or pharmaceutical composition thereof as described in any of the embodiments herein, is, or will be administered to the subject, wherein the cancer is identified as having modified STK11 activity or expression.
  • a method for ascertaining susceptibility of a subject having or having been diagnosed with cancer to treatment with a compound of formula (I), crystalline form or pharmaceutical composition thereof as described in any of the embodiments herein comprising: determining: i) the presence or absence of a STK11 mutation; and/or ii) the level of STK11 activity or expression in the subject or a sample derived from the subject; wherein the presence of a STK11 mutation and/or a modified level of STK11 activity or expression is indicative of susceptibility to treatment with the crystalline form or composition.
  • a method for ascertaining susceptibility of a subject having or having been diagnosed with cancer to treatment with a combination of a compound of formula (I), crystalline form or pharmaceutical composition thereof as described in any of the embodiments herein and an immune checkpoint modulator comprising: determining: i) the presence or absence of a STK11 mutation; and/or ii) the level of STK11 activity or expression in the subject or a sample derived from the subject; wherein the presence of a STK11 mutation and/or a modified level of STK11 activity or expression is indicative of susceptibility to treatment with a combination of an HDAC inhibitor and an immune checkpoint modulator.
  • FIG.1A is an exemplary X-ray powder diffraction pattern of crystalline Form A of the compound of Formula (I).
  • FIG.1B shows an exemplary thermogravimetric analysis (TGA) thermogram of crystalline Form A of the compound of Formula (I) showing about 0.3% weight loss at about 150°C.
  • FIG.1C shows a differential scanning calorimetry (DSC) thermogram for crystalline Form A the compound of Formula (I), under a heat-cool-heat protocol, showing a melt peak at T onset of about 170.7 °C with an enthalpy of 95J/g.
  • TGA thermogravimetric analysis
  • DSC differential scanning calorimetry
  • FIG.1D shows the change of water content as a function of relative humidity in an exemplary DVS experiment for crystalline Form A of the compound of Formula (I).
  • FIG.1E shows a 1 H NMR spectrum for crystalline Form A of the compound of Formula (I).
  • FIG.2A is an exemplary X-ray powder diffraction pattern of crystalline Form B1 of the compound of Formula (I).
  • FIG.2B shows an exemplary thermogravimetric analysis (TGA) thermogram of crystalline Form B1 of the compound of Formula (I) showing about 0.6% weight loss at about 100°C and about 5.5% weight loss from about 100°C to 150°C.
  • TGA thermogravimetric analysis
  • FIG.2C shows a differential scanning calorimetry (DSC) thermogram for crystalline Form B1 the compound of Formula (I), under a heat-cool-heat protocol, showing a desolvation peak from 110.7°C, an exothermic peak at T onset of 142.0°C and a melting peak at T onset of 203.4°C and an enthalpy of about 75 J/g.
  • FIG.2D shows a 1 H NMR spectrum for crystalline Form B1 of the compound of Formula (I).
  • FIG.3A is an exemplary X-ray powder diffraction pattern of crystalline Form B2 of the compound of Formula (I) showing .
  • FIG.3B shows an exemplary thermogravimetric analysis (TGA) thermogram of crystalline Form B2 of the compound of Formula (I) showing about 1.1% weight loss at about 100°C and about 3.4% weight loss from about 100°C to 150°.
  • FIG.3C shows a differential scanning calorimetry (DSC) thermogram for crystalline Form B2 the compound of Formula (I), under a heat-cool-heat protocol, showing a desolvation peak from 111.1°C, an exothermic peak at T onset of 138.1°C and a melting peak at T onset of 201.0°C with an enthalpy of about 79J/g.
  • FIG.3D shows a 1 H NMR spectrum for crystalline Form B2 of the compound of Formula (I).
  • FIG.5A is an exemplary X-ray powder diffraction pattern of crystalline Form C of the compound of Formula (I).
  • FIG.5A is an exemplary X-ray powder diffraction pattern of crystalline Form D of the compound of Formula (I).
  • FIG.5B shows an exemplary thermogravimetric analysis (TGA) thermogram of crystalline Form D of the compound of Formula (I) showing about 0.8% weight loss at about 150°.
  • FIG.5C shows a differential scanning calorimetry (DSC) thermogram for crystalline Form D the compound of Formula (I), under a heat-cool-heat protocol, showing shows a melting peak at T onset of 160.2°C, an exothermic peak at T onset of 165.5°C and a melting peak at T onset of 181.7°C.
  • FIG.5D shows a 1 H NMR spectrum for crystalline Form D of the compound of Formula (I).
  • FIG.6A is an exemplary X-ray powder diffraction pattern of crystalline Form E of the compound of Formula (I).
  • FIG.6B shows an exemplary thermogravimetric analysis (TGA) thermogram of crystalline Form E of the compound of Formula (I) showing about 1.5% weight loss at about 100°C and about 6.6% weight loss from about 100°C to 150°C.
  • TGA thermogravimetric analysis
  • FIG.6C shows a differential scanning calorimetry (DSC) thermogram for crystalline Form E the compound of Formula (I), under a heat-cool-heat protocol, showing a desolvation peak from 89.7°C and 2 combined endothermic peaks at T onset of 155.0°C and 167.5°C, respectively.
  • FIG.6D shows a 1 H NMR spectrum for crystalline Form E of the compound of Formula (I).
  • FIG.7A is an exemplary X-ray powder diffraction pattern of crystalline Form F of the compound of Formula (I).
  • FIG.7B shows an exemplary thermogravimetric analysis (TGA) thermogram of crystalline Form F of the compound of Formula (I) showing about 0.8% weight loss at about 150°C.
  • DSC differential scanning calorimetry
  • FIG.7C shows a differential scanning calorimetry (DSC) thermogram for crystalline Form F the compound of Formula (I), under a heat-cool-heat protocol, showing a melting peak at Tonset of 203.9°C with an enthalpy of about 87J/g.
  • FIG.7D shows a 1H NMR spectrum for crystalline Form F of the compound of Formula (I).
  • FIG.8A is an exemplary X-ray powder diffraction pattern of crystalline Form G of the compound of Formula (I).
  • FIG.8B shows an exemplary thermogravimetric analysis (TGA) thermogram of crystalline Form G of the compound of Formula (I) showing about 0.4% weight loss at about 150°C.
  • TGA thermogravimetric analysis
  • FIG.8C shows a differential scanning calorimetry (DSC) thermogram for crystalline Form G the compound of Formula (I), under a heat-cool-heat protocol, showing a small melting peak at Tonset of 165.3°C and a melting peak at Tonset of 180.1°C with an enthalpy of about 78J/g.
  • FIG.8D shows a 1H NMR spectrum for crystalline Form G of the compound of Formula (I).
  • FIG.9A is an exemplary X-ray powder diffraction pattern of crystalline Form H of the compound of Formula (I).
  • FIG.9B shows an exemplary thermogravimetric analysis (TGA) thermogram of crystalline Form H of the compound of Formula (I) about 1.8% weight loss at about 100°C.
  • TGA thermogravimetric analysis
  • FIG.9C shows a differential scanning calorimetry (DSC) thermogram for crystalline Form H the compound of Formula (I), under a heat-cool-heat protocol, showing a dehydration form Attorney Docket No. TGO-025WO 20.5°C, an exothermic peak at 88.2°C, an endothermic peak at 133.4°C and a melting peak at Tonset of 197.2°C with an enthalpy of about 9J/g.
  • FIG.9D shows a 1H NMR spectrum for crystalline Form H of the compound of Formula (I).
  • FIG.9E shows an overlay of the results of the VT-XRPD experiments conducted with Form H.
  • FIG.10A is an exemplary X-ray powder diffraction pattern of crystalline Form I of the compound of Formula (I).
  • FIG.10B shows a differential scanning calorimetry (DSC) thermogram for crystalline Form I the compound of Formula (I), under a heat-cool-heat protocol, showing a dehydration endothermic peak from about 52°C and a melting peak at Tonset of 192.4°C with an enthalpy of about 55J/.
  • FIG.10C shows a 1H NMR spectrum for crystalline Form H of the compound of Formula (I).
  • FIG.11A is an exemplary X-ray powder diffraction pattern of tosylate salt crystalline Form A of the compound of Formula (I).
  • FIG.11B shows an exemplary thermogravimetric analysis (TGA) thermogram of tosylate salt crystalline Form A of the compound of Formula (I) showing about 0.3% weight loss at about 150°C.
  • FIG.11C shows a differential scanning calorimetry (DSC) thermogram for tosylate salt crystalline Form A the compound of Formula (I), under a heat-cool-heat protocol, showing a melt peak at T onset of about 170.7 °C with an enthalpy of 95J/g.
  • FIG.11D shows the change of water content as a function of relative humidity in an exemplary DVS experiment for tosylate salt crystalline Form A of the compound of Formula (I).
  • FIG.11E shows a 1 H NMR spectrum for tosylate salt crystalline Form A of the compound of Formula (I).
  • FIG.12A is an exemplary X-ray powder diffraction pattern of mono-fumaric acid cocrystal Form A of the compound of Formula (I).
  • FIG.12B shows an exemplary thermogravimetric analysis (TGA) thermogram of mono-fumaric acid cocrystal Form A of the compound of Formula (I) showing about 0.3% weight loss at about 150°C.
  • TGA thermogravimetric analysis
  • FIG.12C shows a differential scanning calorimetry (DSC) thermogram for mono-fumaric acid cocrystal Form A the compound of Formula (I), under a heat-cool-heat protocol, showing a melt peak at T onset of about 170.7 °C with an enthalpy of 95J/g.
  • FIG.12D shows the change of water content as a function of relative humidity in an exemplary DVS experiment for mono-fumaric acid cocrystal Form A of the compound of Formula (I).
  • FIG.12E shows a 1 H NMR spectrum for mono-fumaric acid cocrystal Form A of the compound of Formula (I).
  • FIG.13 is an exemplary X-ray powder diffraction pattern of hydrochloric acid salt Form A of the compound of Formula (I)
  • FIG.14A depicts the tumor growth curve for mice bearing MC38_sgSTK11 tumors treated with a control antibody anti-IgG2a (10 mg/kg i.p. BIW), a combination of Compound I (3, 10, 30, 75 and 150/100 mg/kg p. o., QD) + the control antibody anti-IgG2a (10 mg/kg i.p.
  • FIG.14B depicts the tumor growth curve in the MC38 STK11 knockout mouse model treated with either anti-IgG2a (10 mg/kg i.p., BIW), Anti-PD1 (10 mg/kg i.p., BIW), Compound I (30 mg/kg p.o., QD), or Anti-PD1 (10 mg/kg i.p., BIW) + Compound I (30 mg/kg p.o., QD) was monitored over the course of treatment and plotted by individual animal.
  • FIG.15A depicts the survival curve for mice bearing MC38_sgSTK11 tumors treated with a control antibody anti-IgG2a (10 mg/kg i.p., BIW), a combination of Compound I (3, 10, 30, 75 and 150/100 mg/kg p.o., QD) + the control antibody anti-IgG2a (10 mg/kg i.p. BIW), or an anti- PD1 inhibitor (10 mg/kg i.p., BIW).
  • the data is plotted according to the groups described in Example 1.
  • FIG.15B depicts the survival curve for mice bearing MC38_sgSTK11 tumors treated with a control antibody anti-IgG2a (10 mg/kg i.p., BIW), a combination of Compound I (3, 10, 30, 75 and 150/100 mg/kg p.o. QD) + anti-PD1 inhibitor (10 mg/kg i.p., BIW), or an anti-PD1 inhibitor (10 mg/kg i.p., BIW)
  • the data is plotted according to the groups described in Example 1.
  • FIG.15C shows a survival plot of mice with STK11-deleted MC38 tumors treated with Anti- IgG2a 10 mg/kg, i.p., BIW, Anti-IgG2a 10 mg/kg, i.p., BIW + Compound I, 30 mg/kg, p.o., QD, Attorney Docket No. TGO-025WO Anti-PD110 mg/kg, i.p., BIW, or Anti-PD110 mg/kg, i.p., BIW + Compound I, 30 mg/kg, p.o., QD as indicated.
  • FIG.16A depicts the tumor growth curve for untreated control mice and mice that had survived treatment with either a combination of Compound I (75 mg/kg, p.o., QD) + a control antibody anti-IgG2a (10 mg/kg i.p. BIW) or a combination of Compound I (3, 10, 30, 75 and 150/100 mg/kg) + anti-PD1 inhibitor (10 mg/kg, i.p., BIW) and were rechallenged with MC38_sgSTK11 implants as described in Example 2.
  • FIG.16B shows a plot of the tumor volume in mice that were re-challenged with STK11-deleted MC38 tumors as described in Example 2 (combined in a single group) in parallel with a control group of previously untreated mice. All animals remained off-treatment, and tumor size was plotted over time after re-challenge.
  • FIG.17 depicts the tumor growth curve for mice bearing MC38_sgSTK11 tumors treated with a control antibody anti-IgG2a (10 mg/kg i.p. BIW), Compound I (30 mg/kg, p.o.
  • FIG.18A shows a volcano plot of an unbiased in vivo CRISPR screen identifying HDAC1 knockout as a sensitizer to anti-PD1 in STK11-deleted MC38 tumors.
  • FIG.18B shows waterfall plots of the Project Achilles CRISPR scores for HDAC1, HDAC2, and HDAC3 in a panel of cell lines.
  • FIG.19A shows a graph of a dose-dependent binding of Compound I to HDAC1, by cellular NanoBRET target engagement assay.
  • FIG.19B show graphs of a dose-dependent binding of Compound I to HDAC2, by cellular NanoBRET target engagement assay.
  • FIG.19C show graphs of a dose-dependent binding of Compound I inhibitor to HDAC3 by cellular NanoBRET target engagement assay.
  • FIG.20A depicts the tumor growth curve in the CT26 STK11 knockout mouse model treated with either control antibody Anti-IgG2a (10 mg/kg, i.p., BIW), Anti-IgG2a (10 mg/kg, i.p., BIW) + Compound I (75 mg/kg, p.o., QD), Anti-PD1 (10 mg/kg, i.p., BIW), or (Anti-PD110 mg/kg, i.p., BIW) + Compound I (75 mg/kg, p.o., QD).
  • the tumor volume was monitored over Attorney Docket No. TGO-025WO the course of treatment and plotted by individual animal.
  • FIG.20B shows a survival plot of mice with STK11-deleted CT26 tumors treated with control antibody Anti-IgG2a (10 mg/kg, i.p., BIW), Anti-IgG2a (10 mg/kg, i.p., BIW) + Compound I (75 mg/kg, p.o., QD), Anti-PD1 (10 mg/kg, i.p., BIW), or Anti-PD1 (10 mg/kg, i.p., BIW) + Compound I (75 mg/kg, p.o., QD) as indicated.
  • Anti-IgG2a 10 mg/kg, i.p., BIW
  • Anti-IgG2a 10 mg/kg, i.p., BIW
  • Compound I 75 mg/kg, p.o., QD
  • FIG.21A depicts the tumor growth curve of STK11-deficient MC38 tumor cells in C57BL/6 animals and athymic BALB/c Nude mice treated with Anti-IgG2a (10 mg/kg, i.p., BIW), Anti- IgG2a (10 mg/kg, i.p., BIW) + Compound I (30 mg/kg, p.o., QD), Anti-PD110 mg/kg, i.p., BIW, or Anti-PD110 mg/kg, i.p., BIW + Compound I, 30 mg/kg, p.o., QD as indicated.
  • Anti-IgG2a 10 mg/kg, i.p., BIW
  • Anti- IgG2a 10 mg/kg, i.p., BIW
  • Compound I 30 mg/kg, p.o., QD as indicated.
  • FIG.21B depicts the tumor growth curve of STK11-deficient MC38 tumor cells in C57BL/6 animals and athymic BALB/c Nude mice treated with Anti-IgG2a (10 mg/kg, i.p., BIW), Anti- IgG2a (10 mg/kg, i.p., BIW) + Compound I (75 mg/kg, p.o., QD), Anti-PD1 (10 mg/kg, i.p., BIW), or Anti-PD1 (10 mg/kg, i.p., BIW) + Compound I (75 mg/kg, p.o., QD) as indicated.
  • Anti-IgG2a 10 mg/kg, i.p., BIW
  • Anti- IgG2a 10 mg/kg, i.p., BIW
  • Compound I 75 mg/kg, p.o., QD
  • FIG.22A shows a graph depicting the change in gene expression for CXCL9, 10, and 11 as measured by Nanostring PanCancer IO 360 in STK11-/- MC38 tumors treated for 7 days with 30 mg/kg of Compound I or anti-PD1 alone or in combination.
  • FIG.22B shows a graph depicting the change in gene expression for CCL1 and CCL22 as measured by Nanostring PanCancer IO 360 in STK11-/- MC38 tumors treated for 7 days with 30 mg/kg of Compound I or anti-PD1 alone or in combination.
  • FIG.22C shows a graph depicting the change in gene expression for HLA genes as measured by Nanostring PanCancer IO 360 in STK11-/- MC38 tumors treated for 4 days with 0.2 uM of Compound I or solvent control.
  • FIG.23A shows graphs of T cells, C4+ T cells, CD8+ Tcells and CD8+ TEM cells profiling by flow cytometry of STK11-deleted MC38 tumors treated for 7 days with 10 mg/kg of Compound I alone or in combination with anti-PD1.
  • FIG.23B shows graphs of Treg cells and ratio of CD8+/Treg cells by flow cytometry of STK11- deleted MC38 tumors treated for 7 days with 10 mg/kg of Compound I alone or in combination with anti-PD1.
  • FIG.23C show graphs of IFNgamma expression by a tumor treated with Compound I alone or in combination with anti-PD1 for 72 hrs.
  • FIG.23D shows graphs of IFNgamma expression in co-culture of human NSCLC cells with PBMCS and fibroblasts treated with Compound I alone or in combination with anti-PD1 for 72 hrs.
  • FIG.23E shows graphs profiling the relative abundance of All T cells and T regulatory cells of STK11-deleted MC38 tumors from mice treated for 7 days with vehicle, 10 mg/kg of Compound I alone or in combination with anti-PD1.
  • FIG.24A shows plots of gene expression changes in A549 cells treated with vorinostat using the PanCancer IO360 panel and the top three ranked gene ontology groups for each compound as determined from the Nanostring data in using the nSolver software.
  • FIG.24B shows plots of gene expression changes in A549 cells treated with domatinostat using the PanCancer IO360 panel and the top three ranked gene ontology groups for each compound as determined from the Nanostring data in using the nSolver software.
  • FIG.24C shows plots of gene expression changes in A549 cells treated with Compound I using the PanCancer IO360 panel and the top three ranked gene ontology groups for each compound as determined from the Nanostring data in using the nSolver software.
  • FIG.25A shows plots for the erythroid and myeloid cell viability after treatment Compound I at different concentrations as indicated. The efficacious dose range of Compound I is also plotted (shaded area, 3 mg/kg to 75 mg/kg).
  • FIG.25B depicts the tumor growth curves STK11-deleted MC38 tumors in a mouse model treated with a clinically relevant dose of vorinostat alone or in combination with anti-PD1 antibody.
  • FIG.25C depicts the tumor growth curves STK11-deleted MC38 tumors in a mouse model treated with a clinically relevant dose of Compound I alone or in combination with anti-PD1 antibody.
  • FIG.25D shows a plot comparing Compound I concentrations to HDAC1 or HDAC3 inhibition in vivo. Shaded boxes indicate tolerated and efficacious dose ranges of Compound I.
  • FIG.26 shows a plot of the predicted plasma concentration (ng/mL) over time upon administration to humans and the predicted window between the efficacious and non-selective dose.
  • FIG.27A shows a Western blot of acetylated histone 3 lysine 9 (H3K9Ac) from mouse MC38 tumor tissue after treatment with Compound I for 7 days at the indicated dose. Attorney Docket No. TGO-025WO
  • FIG.27B shows a Quantification of the H3K9Ac western blot in (E) and normalized to total histone H3.
  • FIG.27C shows the plasma concentration of Compound I administered at 30 mg/kg, 100 mg/kg and 300 mg/kg QD for two days, starting 1 hour after the last dose.
  • FIG.27D shows a quantification of the levels of acetyl-histone H2B by flow cytometry in PBMC samples at the prescribed time points following administration of Compound I at 30 mg/kg, 100 mg/kg and 300 mg/kg QD for two days to MC38 tumor-bearing mice.
  • FIG.27E shows a quantification of the levels of acetyl-histone H3B by Western Blot in tumor samples collected at the prescribed time points following administration of Compound I at 30 mg/kg, 100 mg/kg and 300 mg/kg QD for two days to MC38 tumor-bearing mice.
  • FIG.28A depicts the tumor growth curve in a STK11-null CT26 (KRAS G12D mutant colon cancer) syngeneic mouse model.
  • the mice were treated with either anti-IgG2, Anti-PD1 (10 mg/kg), Compound I (75 mg/kg), or Anti-PD1 (10 mg/kg ) + Compound I (75 mg/kg). Tumor volume was monitored over the course of treatment and plotted by individual animal.
  • FIG.28B depicts the tumor growth curve in a STK11-null CT26 (KRAS G12D mutant colon cancer) model.
  • FIG.28C depicts the survival curve for the KRAS G12D mutant CT26-STK11 knockout syngeneic mouse model treated with either anti-IgG2 , Anti-PD1 (10 mg/ kg), Compound I (75 mg/kg), or Anti-PD1 (10 mg/kg ) + Compound I (75 mg/kg).
  • FIG.28D depicts the tumor growth curve in a wild-type/parental CT26 (KRAS G12D mutant colon cancer) model.
  • FIG.28E depicts the tumor growth curve in a wild-type/parental CT26 (KRAS G12D mutant colon cancer) model. Animals were treated with either anti-IgG2, Compound I (75 mg/kg), Anti- PD1 (10 mg/ kg), or Anti-PD1 (10 mg/kg ) + Compound I (75 mg/kg). Tumor volume was monitored over the course of treatment and plotted by individual animal for group 1 and group 4.
  • FIG.29A depicts the tumor growth curve in a wild-type/parental CT26 (KRAS G12D mutant colon cancer) model. Animals were treated with either anti-IgG2, Compound I (75 mg/kg), Anti- Attorney Docket No. TGO-025WO CTL4A (10 mg/ kg), or Anti-CTL4A (10 mg/kg ) + Compound I (75 mg/kg). Tumor volume was monitored over the course of treatment and plotted by treatment group.
  • FIG.29B depicts the tumor growth curve in a wild-type/parental CT26 (KRAS G12D mutant colon cancer) model.
  • FIG.29C depicts the tumor growth curve in a STK11-null CT26 (KRAS G12D mutant colon cancer) model treated with either anti-IgG2, Compound I (75 mg/kg), Anti-CTL4A (10 mg/ kg), or Anti-CTL4A (10 mg/kg ) + Compound I (75 mg/kg). Tumor volume was monitored over the course of treatment and plotted by treatment group.
  • FIG.29D depicts the tumor growth curve in a STK11-null CT26 (KRAS G12D mutant colon cancer) model treated with either anti-IgG2, Compound I (75 mg/kg), Anti-CTL4A (10 mg/ kg), or Anti-CTL4A (10 mg/kg ) + Compound I (75 mg/kg). Tumor volume was monitored over the course of treatment and plotted by individual animal for group 1 and group 4.
  • FIG.30A depicts the tumor growth curve in the STK11-null 3LL model treated with either anti- IgG2, Anti-PD1 (10 mg/ kg), Compound I (75 mg/kg), or Anti-PD1 (10 mg/kg ) + Compound I (75 mg/kg) Tumor volume was monitored for the depicted duration and was plotted by treatment group.
  • FIG.30B depicts the survival curve for the STK11-null 3LL model treated with either anti- IgG2, Anti-PD1 (10 mg/ kg), Compound I (75 mg/kg), or Anti-PD1 (10 mg/kg ) + Compound I (75 mg/kg) Survival is plotted by treatment group.
  • FIG.31A depicts the overall design of the first-in-human, non-randomized, open-labeled, phase 1 (dose escalation) and phase 2 (dose expansion) sequential assignment study for TNG260.
  • FIG.31B depicts the overall results of phase 1 (dose escalation) in the study, with 80 mg QD as the dose for the highest exposure with maximal preclinical activity and 40 mg QD as the dose for the lowest exposure with maximal preclinical activity.
  • FIG.31C depicts the patient flow in phase 1 of the study, which separates into three periods: screening (up to 28 days), treatment (cycle 1, cycle 2, cycle 3+) and follow up (EOT + 120 days). Attorney Docket No.
  • FIG.31D depicts the pharmacokinetics of TNG260 on day 15 in cycle 1 of the treatment period. Exposure increases with dose and 80 mg exposure approximates preclinical maximum efficacy exposure. Represented as arithmetic mean plasma concentration-time profiles
  • FIG.31E depicts the correlation between the exposures of TNG260 in preclinical and human studies. Doses of TNG260 at 40 mg and 80 mg QD in the clinical study described in Example 27 achieved exposures that correspond to the exposures required for full efficacy in preclinical models, while higher doses resulted in exposures that in preclinical models were associated with diminished efficacy.
  • FIG.32A depicts the tumor growth curve in the STK11-deficient, syngeneic MC38 mouse tumor model treated with anti-IgG2, Anti-PD1 (10 mg/ kg, BIW), Compound I (30 mg/kg), dosed QD, QD (1 week on/2 week off), QD (2 week on/1 week off), QD (2 day on/ 5 day off), QW (once a week) or BIW (twice a week). Tumor volume was monitored for the depicted duration and was plotted by treatment group.
  • FIG.32B depicts the tumor growth curve in the STK11-deficient, syngeneic MC38 mouse tumor model treated with anti-IgG2, Anti-PD1 (10 mg/ kg, BIW), Compound I (30 mg/kg), dosed QD vs QD (2 week on/1 week off). Tumor volume was monitored for the depicted duration and was plotted for each individual animal.
  • FIG.32C depicts the tumor growth curve in the STK11-deficient, syngeneic MC38 mouse tumor model treated with anti-IgG2, Anti-PD1 (10 mg/ kg, BIW), Compound I (30 mg/kg), dosed QD vs QD (1 week on/2 week off). Tumor volume was monitored for the depicted duration and was plotted for each individual animal.
  • FIG.32D depicts the tumor growth curve in the STK11-deficient, syngeneic MC38 mouse tumor model treated with anti-IgG2, Anti-PD1 (10 mg/ kg, BIW), Compound I (30 mg/kg), dosed QD vs QD (2 days on/5 days off). Tumor volume was monitored for the depicted duration and was plotted for each individual animal.
  • FIG.32E depicts the tumor growth curve in the STK11-deficient, syngeneic MC38 mouse tumor model treated with anti-IgG2, Anti-PD1 (10 mg/ kg, BIW), Compound I (30 mg/kg), dosed QD vs QW (once a week). Tumor volume was monitored for the depicted duration and was plotted for each individual animal.
  • FIG.32F depicts the tumor growth curve in the STK11-deficient, syngeneic MC38 mouse tumor model treated with anti-IgG2, Anti-PD1 (10 mg/ kg, BIW), Compound I (30 mg/kg), dosed QD Attorney Docket No. TGO-025WO vs BIW (biweekly). Tumor volume was monitored for the depicted duration and was plotted for each individual animal.
  • DETAILED DESCRIPTION [0026] As generally described herein, provided are methods of treating a subject having, or at risk of developing, a cancer, the method comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein), wherein the cancer is identified as having modified STK11 activity or expression.
  • Compound I e.g., a crystalline form described herein
  • STK11 Serine/threonine kinase 11 protein, abbreviated as STK11 and also referred to as PJS, liver kinase B1(LKB1), renal carcinoma antigen NY-REN-19 and hLKB1 protein, is a protein kinase that in humans is encoded by the STK11 gene (HGNC symbol STK11, Ensembl ID ENSG00000118046.16). As described in Koenig, M.
  • LKB1 belongs to the calcium calmodulin family, which is ubiquitously expressed in several tissues and highly conserved among eukaryotes. Over the past 15 years, LKB1 has been implicated in a number of essential biological processes such as: cell cycle control, cellular energy metabolism, angiogenesis, cell polarity, and DNA damage response. The sub-cellular localization and activity of LKB1 is controlled through its interaction with STRAD and the armadillo repeat-containing mouse protein 25 (Mo25).
  • LKB1 regulates the activity of at least 14 downstream kinases related to the AMPK family and phosphorylates other substrates including STRAD, PTEN, and p21CDKN1A.
  • LKB1 is phosphorylated on at least eight residues, and evidence suggests that LKB1 auto-phosphorylates itself on at least four of these, whereas the other four are phosphorylated by upstream kinases. While these post- Attorney Docket No. TGO-025WO translational modifications seem not to modify its kinase activity, they are involved in the different biological responses associated with LKB1, and likely in its interactions with other partners.”
  • the STK11 gene is located on human chromosome 19p 13.
  • the gene includes nine coding exons and one noncoding exon and codes for the 433 amino acid serine/threonine-protein kinase STK11 protein, which is widely expressed in all tissues (Hemminki A, et al. Nature, 1998, 18,184-187; Alessi, D.R., et al. Annu. Rev. Biochem.2006, 75, 137-163; Sanchez- Cespedes M. Oncogene 2007, 26, 7825-7832).
  • Somatic mutations or deletions of the STK11 gene are present in many cancers, including, but not limited to, lung adenocarcinomas ( ⁇ 15%), non-melanoma skin cancer ( ⁇ 5%), cholangiocarcinomas ( ⁇ 3%), ovarian carcinomas (approximately 3%) and pancreatic adenocarcinomas ( ⁇ 2%)
  • lung adenocarcinomas ⁇ 15%), non-melanoma skin cancer ( ⁇ 5%), cholangiocarcinomas ( ⁇ 3%), ovarian carcinomas (approximately 3%)
  • pancreatic adenocarcinomas ⁇ 2%
  • STK11 mutations found in cancer include point mutations (e.g., nonsense or frame shift mutations) predicted to be deleterious and oncogenic (Chakravarty D, et al. JCO Precis Oncol.2017, 2017) or small indels.
  • Non-mutational mechanisms for modified expression (e.g., loss of expression) or modified activity (e.g., loss of wildtype activity) include genomic loss or promoter methylation.
  • LKB1 The role of LKB1 in controlling cell metabolism through AMPK signaling has been widely documented. We know that the LKB1- AMPK axis controls lipid and glucose metabolism, and acts as a negative regulator of the Attorney Docket No. TGO-025WO Warburg effect suppressing tumor growth. LKB1 is also important in the regulation of catabolic pathways leading to the increase of glucose uptake and modulation of glycolysis or the mobilization of lipid stores by stimulating lipases, such as adipose triglyceride lipase, to release fatty acids from triglyceride stores.
  • lipases such as adipose triglyceride lipase
  • LKB1-AMPK-stimulated pathways also include increased turnover of macromolecules by autophagy, allowing the turnover of old and damaged molecules, or the replenishment of nutrient stores under starvation. Additionally, several investigations have suggested the role of LKB1 in regulation of physiological and pathological angiogenesis through the regulation of VEGF, MMP-2, MMP-9, bFGF, and NOX1 expression, and its participation in neurophilin-1 degradation. Studies of LKB1 loss of function have also revealed its role in cell polarity and motility through the regulation of PAK115 and the modulation of the phosphorylation status of FAK and CDC42 activation. Together, these functions contribute to the induction of epithelial mesenchymal transition (EMT) and metastasis.
  • EMT epithelial mesenchymal transition
  • STK11 A pooled CRISPR-Cas9 based in vivo screen was performed and identified STK11 as an immune evasion context, where depletion of STK11 drives resistance to immune pressure in immune competent mice.
  • STK11 mutations have been associated with low levels of T-cell inflammation and tumor PD-L1 expression. Biton J, et al. Clin Cancer Res 2018; 24:5710–23, which is hereby incorporated by reference in its entirety.
  • modified expression refers to a change in the expression levels (i.e., a decrease or increase in expression levels) of a protein in a Attorney Docket No. TGO-025WO cell (e.g., a cancer cell) in comparison to a reference cell (e.g., a healthy cell).
  • increased or decreased expression levels of a protein can be assessed by determining the copy number of the gene encoding the protein (e.g., the copy number of the STK11 gene) in a patient sample (e.g., a tumor sample) and comparing the levels with those present in a control sample (e.g., a healthy tissue sample).
  • increased or decreased expression levels of a protein can be assessed by determining the level of the protein (e.g., STK11 protein) or mRNA in a patient sample (e.g., a tumor sample) and comparing the levels with those present in a control sample (e.g., a healthy tissue sample).
  • modified activity refers to a change in the biological activity (e.g., enzyme activity) levels (i.e., a decrease or increase in the serine/threonine kinase activity levels of STK11) of a protein in a cell (e.g., a cancer cell) in comparison to a reference cell (e.g., a healthy cell).
  • Mutations in the gene encoding the protein e.g., STK11 mutations
  • an “STK11 mutation” is a mutation selected from: (i) a mutation in the nucleotide sequence encoding STK11; (ii) a mutation in a regulatory sequence controlling expression of the nucleotide sequence encoding STK11; (iii) a mutation in a nucleotide encoding a protein which interacts with the transcription product of the STK11 gene; (iv) a mutation in the translation product of the STK11 gene; and (v) a mutation in the transcription product of the STK11 gene.
  • the STK11 mutation is a mutation selected from: (i) a mutation in the nucleotide sequence encoding STK11; (ii) a mutation in a regulatory sequence controlling expression of the nucleotide sequence encoding STK11; and (iii) a mutation in a nucleotide encoding a protein which interacts with the transcription product of the STK11 gene.
  • Attorney Docket No. TGO-025WO [0040]
  • the STK11 mutation is a mutation in the nucleotide sequence encoding STK11.
  • the STK11 mutation is a mutation in a regulatory sequence controlling expression of the nucleotide sequence encoding STK11.
  • the STK11 mutation is a mutation in a nucleotide encoding a protein which interacts with the transcription product of the STK11 gene. In some embodiments, the STK11 mutation is a mutation in the translation product of the STK11 gene. In some embodiments, the STK11 mutation is a mutation in the transcription product of the STK11 gene. [0041] In some embodiments, the STK11 mutation is an inactivating or loss-of function mutation. [0042] As used herein, a “loss-of-function mutation,” also referred to as “an inactivating mutation” refers to a mutation that results in expression of a mutant protein that exhibits reduced or absent biological activity or enzymatic activity compared to wild-type protein.
  • a loss-of- function mutation in a gene can also result in no expression of the wild- type protein, or the expression of only a fragment of the protein that exhibits reduced or absent biological or enzymatic activity compared to a wild-type protein.
  • the mutation can be in a DNA nucleotide sequence, mRNA sequence, or protein sequence.
  • the mutation is a DNA mutation (e.g., a substitution, deletion, insertion, truncation, splice site, translation start site, fusion, or frameshift mutation).
  • a loss-of-function mutation is one of the following: 1) a nonsense mutation (a genetic alteration that causes the premature termination of a protein). The altered protein may be partially or completely inactivated, resulting in a change or loss of protein function; 2) a frameshift mutation (an insertion or deletion involving a number of base pairs that is not a multiple of three, which consequently disrupts the triplet reading frame of a DNA sequence).
  • Frameshift mutations generally cause the creation of a premature termination (stop) codon, and result in a truncated protein product; 3) a splice-site mutation (a genetic alteration in the DNA sequence that occurs at the boundary of an exon and an intron (splice site)). This change can disrupt RNA splicing resulting in the loss of exons or the inclusion of introns and an altered protein-coding sequence; Attorney Docket No. TGO-025WO 4) a translation start site mutation (a mutation that disrupts the translation initiation sequence, abolishing the initiation of translation at the normal start site, resulting in loss of mRNA translation or translation of an abnormal messenger RNA (mRNA)).
  • mRNA messenger RNA
  • Translation start site mutations result in loss of protein expression or in synthesis of a protein with an abnormal amino acid sequence; 5) a recurrent somatic mutation (having at least 5 instances recorded in the Catalogue of Somatic Mutations in Cancer (COSMIC) database) (Tate JG, et al. Nucleic Acids Res (2019) 47(D1), D941-D947); 6) a DNA fusion (a gene created by joining parts of two different genes; may be made when part of DNA from a chromosome moves to another chromosome); 7) any other mutation predicted to reduce the function of the encoded protein by the OncoKB algorithm (Chakravarty D, et al.
  • the mutation is not a variant of unknown significance (a mutation for which the association with disease risk is unclear, also known as an unclassified variant, a variant of uncertain significance, or VUS (Richards S, et al. Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med.2015 May; 17(5): 405-424.).
  • the mutation is not a germline mutation (a gene change in a reproductive cell (egg or sperm) that becomes incorporated into the DNA of every cell in the body of the offspring), identified in the dbSNP (Sherry, S.T., et al.. Nucleic Acids Res, 2001, 29: 308-311).
  • Loss of function mutations of the STK11 gene e.g., in a cancer cell
  • Loss of function mutations of the STK11 gene can result in the loss of expression of STK11 protein, the expression of only a fragment of the STK11 protein or the expression of a STK11 protein with reduced or absent enzymatic activity. (e.g., no serine/threonine kinase enzymatic activity).
  • STK11 mutations that are loss-of-function mutations as defined herein are listed in Table 1 (adapted from WO2022087270).
  • the mutations included in Table 1 were predicted to have deleterious function by OncoKB or had at least 5 occurrences in Attorney Docket No. TGO-025WO COSMIC, and excluded mutations and copy number alterations of unknown significance (i.e., VUS) and germline mutations.
  • VUS unknown significance
  • STK11 mutations may co-occur with other mutations. Mutations in STK11 co-occur frequently with KRAS mutations. (Koivunen, J. et al. Br J Cancer 2008, 99, 245–252). STK11 somatic mutations also co-occur frequently with KEAP1 mutations (See Papillon-Cavanagh S. et al. ESMO Open, 2020, 5, E000706).
  • the cancer is identified as having modified STK11 activity or expression and as having modified KRAS activity or expression.
  • the modified KRAS activity or expression is the presence of a mutant KRAS.
  • the mutant KRAS is selected from KRAS G12C , KRAS G12D , KRAS G12V , KRAS G12A , KRAS G12S , KRAS G12R , KRAS G13C , KRAS G13D , KRAS G13S , KRAS Q61H and Attorney Docket No. TGO-025WO KRAS Q61K .
  • the mutant KRAS is selected from KRAS G12C , KRAS G12D and KRAS G12V .
  • the cancer is identified as having modified STK11 activity or expression and as having wildtype KRAS activity or expression.
  • the cancer is identified as having modified STK11 activity or expression and as having modified KRAS (e.g., KRAS G12C , KRAS G12D , KRAS G12V ) activity or expression or wildtype KRAS activity or expression.
  • the cancer is further identified as having modified KEAP1 activity or expression (e.g., KEAP1 mutations).
  • modified KRAS e.g., KRAS G12C , KRAS G12D , KRAS G12V
  • modified KEAP1 activity or expression e.g., KEAP1 mutations.
  • STK11 mutations may frequently occur in certain diseases (e.g., cancer).
  • HDAC histone deacetylase
  • HDAC1,2-selective inhibitor e.g., HDAC1,2-selective inhibitor, CoREST-selective deacetylase inhibitor
  • R histone deacetylase
  • R N-(4-amino-4'- fluoro-[1,1'-biphenyl]-3-yl)-4-(S-methylsulfonimidoyl)benzamide
  • Formula (I) Formula (I)
  • the compound of Formula (I) is also known as TNG260.
  • the compound of Formula (I) can be referred to as “Compound I” interchangeably.
  • the compound of Formula (I) is a free base.
  • the compound of Formula (I) is a crystalline form of the free base of compound of formula (I) (e.g., a crystalline form selected from Form A, Form B1, Form B2, Form C, Form D, Form E, Form F, Form G, Form H and Form I).
  • Crystalline Form A [0056] In certain embodiments, the crystalline form of the free base of the compound of formula (I) is crystalline Form A. Crystalline Form A is an anhydrous crystalline form of the Attorney Docket No. TGO-025WO compound of formula (I). References to “Form A” without additional modifiers refer to the free base crystalline Form A.
  • Form A Bulk stability of Form A was evaluated at 25°C/92.5%RH in an open container, at 40°C/75%RH in an open container and at 60°C in a tight container over 1 week, and it was determined that Form A is chemically stable under these conditions. Though Form A is only thermodynamically stable when RH is 40% at 25°C, it shows good kinetic stability in physical form under these conditions over 1 week, even in high RH (Example 8). [0061] Hygroscopicity of Form A was evaluated by dynamic vapor sorption (DVS) test at 25°C.
  • DVDS dynamic vapor sorption
  • Form A is slightly hygroscopic in ⁇ 70%RH, and it becomes hygroscopic and shows ⁇ 13% water uptake in 95%RH at 25°C (FIG.1D, Example 2). No change in crystalline form was observed after DVS experiment.
  • Solubility of the Form A was measured in 7 pH buffers and bio-relevant fluids including pH 1.2 HCl solution (0.2N), pH 4.5 acetate buffer (50mM), pH 6.8 phosphate buffer (50mM), pH 2.0 SGF, pH 6.5 FaSSIF-v1, pH 5.0 FeSSIF-v1 and pure water at 37°C for 1h and 24h, respectively, and was compared with the solubility of a crystalline tosylate salt (tosylate Form A) and a mono-fumaric acid cocrystal (fumaric cocrystal Form A). Residual solids after the solubility test were analyzed by XRPD.
  • Form A and the salt/cocrystal candidates showed comparable and pH dependent solubility in the aqueous media. Their solubility reached about 1.5- >2mg/mL in pH 1.2 HCl solution but decreased to about 30 ⁇ g/mL in pH 6.8 phosphate buffer. Solubility in SGF (pH 2.0) and in water was slightly higher for Tosylate Form A (1.4mg/mL) and the fumaric cocrystal Form A (1mg/mL) compared to free base Form A (0.8mg/mL). However, the tosylate Form A, resulted in an HPLC-detectable degradation product in supernatant after solubility test in SGF (pH 2.0).
  • Form A has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three or four) characteristic peaks at values of 2 in degrees selected from 13.1 ⁇ 0.2, 15 ⁇ 0.2, 22.3 ⁇ 0.2 and 24 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 13.1 ⁇ 0.2, 15 ⁇ 0.2, 22.3 ⁇ 0.2 and 24 ⁇ 0.2. In certain embodiments, Form A has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 13.1 ⁇ 0.2, 15 ⁇ 0.2, 22.3 ⁇ 0.2 and 24 ⁇ 0.2. In certain embodiments, Form A has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 13.1 ⁇ 0.2, 15 ⁇ 0.2, 22.3 ⁇ 0.2 and 24 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 13.1 ⁇ 0.2, 15 ⁇ 0.2, 22.3 ⁇ 0.2 and 24 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 13.1 ⁇ 0.2, 15 ⁇ 0.2, 22.3 ⁇ 0.2 and 24 ⁇ 0.2 and at least one (e.g., one, two, three, four, five or six) additional characteristic peak at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • at least one e.g., one, two, three, four, five, six, seven, eight, nine or ten
  • Form A has an X- ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, Attorney Docket No. TGO-025WO 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • Form A has an X- ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three or four) characteristic peaks between and including the following values of 2 in degrees: 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2) and 23.8 to 24.2 (e.g., 24 ⁇ 0.2).
  • 12.9 to 13.3 e.g., 13.1 ⁇ 0.2
  • 14.8 to 15.2 e.g., 15 ⁇ 0.2
  • 22.1 to 22.5 e.g., 22.3 ⁇ 0.2
  • 23.8 to 24.2 e.g., 24 ⁇ 0.2
  • Form A has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2) and 23.8 to 24.2 (e.g., 24 ⁇ 0.2).
  • Form A has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2) and 23.8 to 24.2 (e.g., 24 ⁇ 0.2).
  • Form A has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2) and 23.8 to 24.2 (e.g., 24 ⁇ 0.2).
  • Form A has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2) and 23.8 to 24.2 (e.g., 24 ⁇ 0.2) and at least one (e.g., one, two, three, four, five or six) additional characteristic peaks between and including values of 2 in degrees selected from: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (
  • Form A has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), Attorney Docket No.
  • TGO-025WO 19.4 to 19.8 e.g., 19.6 ⁇ 0.2
  • 20.7 to 21.1 e.g., 20.9 ⁇ 0.2
  • 20.9 to 21.3 e.g., 21.1 ⁇ 0.2
  • 22.1 to 22.5 e.g., 22.3 ⁇ 0.2
  • 22.5 to 22.9 e.g., 22.7 ⁇ 0.2
  • 22.6 to 23 e.g., 22.8 ⁇ 0.2
  • 23.8 to 24.2 e.g., 24 ⁇ 0.2
  • 25.6 to 26 e.g., 25.8 ⁇ 0.2
  • 26.1 to 26.5 e.g., 26.3 ⁇ 0.2
  • 26.3 to 26.7 e.g., 26.5 ⁇ 0.2
  • 28.1 to 28.5 e.g., 28.3 ⁇ 0.2
  • 28.3 to 28.7 e.g., 28.5 ⁇ 0.2
  • Form A has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8 ⁇
  • Form A has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • Form A has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • Form A has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • TGO-025WO 24 ⁇ 0.2 25.6 to 26 (e.g., 25.8 ⁇ 0.2), 26.1 to 26.5 (e.g., 26.3 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 28.1 to 28.5 (e.g., 28.3 ⁇ 0.2) and 28.3 to 28.7 (e.g., 28.5 ⁇ 0.2).
  • Form A has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • Form A has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • Form A has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • Form A has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 21.1 ⁇ 0.2), 22.1 to 2
  • Form A has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e
  • Form A has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • Form A has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 21.1 ⁇ 0.2),
  • Form A has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 13.1 ⁇ 0.2, 15 ⁇ 0.2, 22.3 ⁇ 0.2 and 24 ⁇ 0.2 and at least one (e.g., one, two, three, four, five or six) additional characteristic peak at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at Attorney Docket No.
  • Form A has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • Form A has an X- ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • Form A has an X- ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, Attorney Docket No. TGO-025WO 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • Form A has an X- ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2.
  • Form A has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2) and 23.8 to 24.2 (e.g., 24 ⁇ 0.2) and at least one (e.g., one, two, three, four, five or six) additional characteristic peaks between and including values of 2 in degrees selected from: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (
  • Form A has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 2
  • Form A has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8 ⁇
  • Form A has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • Form A has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), Attorney Docket No.
  • TGO-025WO 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8 ⁇ 0.2), 23.8 to 24.2 (e.g., 24 ⁇ 0.2), 24.2 to 24.6 (e.g., 24.4 ⁇ 0.2), 25.6 to 26 (e.g., 25.8 ⁇ 0.2), 26.1 to 26.5 (e.g., 26.3
  • Form A has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • Form A has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • Form A has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., Attorney Docket No.
  • TGO-025WO 22.7 ⁇ 0.2 22.6 to 23 (e.g., 22.8 ⁇ 0.2), 23.8 to 24.2 (e.g., 24 ⁇ 0.2), 24.2 to 24.6 (e.g., 24.4 ⁇ 0.2), 25.6 to 26 (e.g., 25.8 ⁇ 0.2), 26.1 to 26.5 (e.g., 26.3 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 28.1 to 28.5 (e.g., 28.3 ⁇ 0.2), 28.3 to 28.7 (e.g., 28.5 ⁇ 0.2), 29.1 to 29.5 (e.g., 29.3 ⁇ 0.2), 31.7 to 32.1 (e.g., 31.9 ⁇ 0.2), 37.1 to 37.5 (e.g., 37.3 ⁇ 0.2), 37.3 to 37.7 (e.g., 37.5 ⁇ 0.2), 37.1 to 37.5 (e.g., 37.3 ⁇ 0.2) and 37.3 to 37.7 (e.g., 37.5 ⁇ 0.2).
  • 37.1 to 37.5 e.g., 3
  • Form A has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • Form A has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • Form A has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 22.8
  • Form A has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9
  • Form A has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 5.1 to 5.5 (e.g., 5.3 ⁇ 0.2), 10.4 to 10.8 (e.g., 10.6 ⁇ 0.2), 12.9 to 13.3 (e.g., 13.1 ⁇ 0.2), 14.8 to 15.2 (e.g., 15 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.4 to 19.8 (e.g., 19.6 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22.1 to 22.5 (e.g., 22.3 ⁇ 0.2), 22.5 to 22.9 (e.g., 22.7 ⁇ 0.2), 22.6 to 23 (e.g., 21.1 ⁇ 0.2), 22.1 to 2
  • Form A has an XRPD pattern (obtained using CuKa radiation) substantially corresponding to the XRPD diffraction pattern shown in FIG. 1A.
  • Form A has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2 values in degrees shown in Table 2 ( ⁇ 0.2 degrees).
  • Form A has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2 values in degrees and with relative intensities shown in Table 2 allowing for variation due to experimental conditions.
  • Form A is substantially characterized by the thermal gravimetric analysis (TGA) as shown in FIG.1B.
  • TGA thermal gravimetric analysis
  • Form A is substantially characterized by the differential scanning calorimetry profile (DSC) shown in FIG.1C.
  • DSC differential scanning calorimetry profile
  • Form A can be characterized by the differential scanning calorimetry profile (DSC) shown in FIG.1C, showing DSC shows a melting peak at Tonset of 170.7°C with an enthalpy of 95J/g.
  • Form A is substantially characterized by the DVS profile as shown in FIG.1D.
  • Crystalline Form B1 [0086] In certain embodiments, the crystalline form of the free base of the compound of formula (I) is crystalline Form B1. Crystalline Form B1 is an ethyl acetate (EA) solvate crystalline form of the compound of formula (I). [0087] Form B1 can obtained from THF/EA solvent mixtures by anti-solvent addition. Form B1 is of high crystallinity.
  • DSC shows a desolvation peak from 110.7°C, an exothermic peak at Tonset of 142.0°C and a melting peak at Tonset of 203.4°C with an enthalpy of about 75J/g, which corresponds to melting of Form F.
  • TGA shows about 0.6% weight loss at about 100°C and about 5.5% weight loss from about 100°C to 150°C.
  • 1 H-NMR shows 4.4% EA residue by weight.
  • Form B1 has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2.
  • at least one e.g., one, two, three, four, five, six, seven, eight, nine or ten
  • Form B1 has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, Attorney Docket No. TGO-025WO 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2.
  • Form B1 has an X- ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 19.2 to 19.
  • 4.9 to 5.3 e.g.,
  • Form B1 has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 23.2 to 23.6 (e.g., 23.4 ⁇ 0.2), 23.3 to 23.7 (e.g.
  • Form B1 has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 23.2 to 23.6 (e.g., 23.4 ⁇ 0.2), 23.3 to 23.7 (e.g., 5.1
  • Form B1 has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 23.2 to 23.6 (e.g., 23.4 ⁇ 0.2), 23.3 to 23.7 (e.g.
  • Form B1 has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 23.2 to 23.6 (e.g., 23.4 ⁇ 0.2), 23.3 to 23.7 (e.g.
  • Form B1 has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 23.2 to 23.6 (e.g., 23.4 ⁇ 0.2
  • Form B1 has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 23.2 to 23.6 (e.g., 23.4 ⁇ 0.2), 23.3 to 23.7 (e.g.
  • Form B1 has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 23.2 to 23.6 (e.g., 23.4 ⁇ 0.2), 23.3 to 23.7 (e.g.
  • Form B1 has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 23.2 to 23.6 (e.g., 23.4 ⁇ 0.2), 23.3 to 23.7 (e.g.
  • Form B1 has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 23.2 to 23.6 (e.g., 23.4 ⁇ 0.2), 23.3 to 23.7 (e.g.
  • Form B1 has an X-ray powder Attorney Docket No. TGO-025WO diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 23.2 to 23.6 (e.g., 2
  • Form B1 has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 23.2 to 23.6 (e.g., 23.4 ⁇ 0.2), 23.3 to 23.7 (e.
  • 4.9 to 5.3
  • Form B1 has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 20.1 ⁇ 0.2, 21.4 ⁇ 0.2, 21.8 ⁇ 0.2, 22.5 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 25.5 ⁇ 0.2, 26 ⁇ 0.2, 26.6 ⁇ 0.2, 27.3 ⁇ 0.2, 28.3 ⁇ 0.2, 29.6 ⁇ 0.2, 31.6 ⁇ 0.2 and 32.1 ⁇ 0.2.
  • at least one e.g., one, two, three, four, five, six, seven, eight, nine or ten
  • Form B1 has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 20.1 ⁇ 0.2, 21.4 ⁇ 0.2, 21.8 ⁇ 0.2, 22.5 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 25.5 ⁇ 0.2, 26 ⁇ 0.2, 26.6 ⁇ 0.2, 27.3 ⁇ 0.2, 28.3 ⁇ 0.2, 29.6 ⁇ 0.2, 31.6 ⁇ 0.2 and 32.1 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 20.1 ⁇ 0.2, 21.4 ⁇ 0.2, 21.8 ⁇ 0.2, 22.5 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 25.5 ⁇ 0.2, 26 ⁇ 0.2, 26.6 ⁇ 0.2, 27.3 ⁇ 0.2, 28.3 ⁇ 0.2, 29.6 ⁇ 0.2, 31.6 ⁇ 0.2 and 32.1 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, Attorney Docket No.
  • Form B1 has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 20.1 ⁇ 0.2, 21.4 ⁇ 0.2, 21.8 ⁇ 0.2, 22.5 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 25.5 ⁇ 0.2, 26 ⁇ 0.2, 26.6 ⁇ 0.2, 27.3 ⁇ 0.2, 28.3 ⁇ 0.2, 29.6 ⁇ 0.2, 31.6 ⁇ 0.2 and 32.1 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 20.1 ⁇ 0.2, 21.4 ⁇ 0.2, 21.8 ⁇ 0.2, 22.5 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 25.5 ⁇ 0.2, 26 ⁇ 0.2, 26.6 ⁇ 0.2, 27.3 ⁇ 0.2, 28.3 ⁇ 0.2, 29.6 ⁇ 0.2, 31.6 ⁇ 0.2 and 32.1 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 20.1 ⁇ 0.2, 21.4 ⁇ 0.2, 21.8 ⁇ 0.2, 22.5 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 25.5 ⁇ 0.2, 26 ⁇ 0.2, 26.6 ⁇ 0.2, 27.3 ⁇ 0.2, 28.3 ⁇ 0.2, 29.6 ⁇ 0.2, 31.6 ⁇ 0.2 and 32.1 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 20.1 ⁇ 0.2, 21.4 ⁇ 0.2, 21.8 ⁇ 0.2, 22.5 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 25.5 ⁇ 0.2, 26 ⁇ 0.2, 26.6 ⁇ 0.2, 27.3 ⁇ 0.2, 28.3 ⁇ 0.2, 29.6 ⁇ 0.2, 31.6 ⁇ 0.2 and 32.1 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 20.1 ⁇ 0.2, 21.4 ⁇ 0.2, 21.8 ⁇ 0.2, 22.5 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 25.5 ⁇ 0.2, 26 ⁇ 0.2, 26.6 ⁇ 0.2, 27.3 ⁇ 0.2, 28.3 ⁇ 0.2, 29.6 ⁇ 0.2, 31.6 ⁇ 0.2 and 32.1 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 20.1 ⁇ 0.2, 21.4 ⁇ 0.2, 21.8 ⁇ 0.2, 22.5 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 25.5 ⁇ 0.2, 26 ⁇ 0.2, 26.6 ⁇ 0.2, 27.3 ⁇ 0.2, 28.3 ⁇ 0.2, 29.6 ⁇ 0.2, 31.6 ⁇ 0.2 and 32.1 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, Attorney Docket No.
  • Form B1 has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 20.1 ⁇ 0.2, 21.4 ⁇ 0.2, 21.8 ⁇ 0.2, 22.5 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 25.5 ⁇ 0.2, 26 ⁇ 0.2, 26.6 ⁇ 0.2, 27.3 ⁇ 0.2, 28.3 ⁇ 0.2, 29.6 ⁇ 0.2, 31.6 ⁇ 0.2 and 32.1 ⁇ 0.2.
  • Form B1 has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10 to 10.4 (e.g., 10.2 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 14.1 to 14.5 (e.g., 14.3 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g.,
  • Form B1 has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10 to 10.4 (e.g., 10.2 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 14.1 to 14.5 (e.g., 14.3 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g.,
  • Form B1 has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 4.9 Attorney Docket No. TGO-025WO to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10 to 10.4 (e.g., 10.2 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 14.1 to 14.5 (e.g., 14.3 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇
  • Form B1 has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10 to 10.4 (e.g., 10.2 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 14.1 to 14.5 (e.g., 14.3 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g.
  • Form B1 has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10 to 10.4 (e.g., 10.2 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 14.1 to 14.5 (e.g., 14.3 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g.
  • Form B1 has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10 to 10.4 (e.g., 10.2 ⁇ 0.2), 10.9 to 11.3 (e.g., Attorney Docket No.
  • Form B1 has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10 to 10.4 (e.g., 10.2 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 14.1 to 14.5 (e.g., 14.3 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g.
  • Form B1 has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10 to 10.4 (e.g., 10.2 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 14.1 to 14.5 (e.g., 14.3 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g.
  • Form B1 has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10 to 10.4 (e.g., 10.2 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 14.1 to 14.5 (e.g., 14.3 ⁇ 0.2), Attorney Docket No.
  • Form B1 has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10 to 10.4 (e.g., 10.2 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 14.1 to 14.5 (e.g., 14.3 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g.
  • Form B1 has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10 to 10.4 (e.g., 10.2 ⁇ 0.2), 10.9 to 11.3 (e.g., 11.1 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 14.1 to 14.5 (e.g., 14.3 ⁇ 0.2), 15.1 to 15.5 (e.g., 15.3 ⁇ 0.2), 15.5 to 15.9 (e.g., 15.7 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 18.9 to 19.3 (e.g.
  • Form B1 has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.7 to 6.1 (e.g., 5.9 ⁇ 0.2), 10 to 10.4 (e.g., 10.2 ⁇ 0.2), 10.9 to 11.3 (e.g., Attorney Docket No.
  • Form B1 has an XRPD pattern (obtained using CuKa radiation) substantially corresponding to the XRPD diffraction pattern shown in FIG.2A.
  • Form B1 has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2 values in degrees shown in Table 3 ( ⁇ 0.2 degrees).
  • Form B1 has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2 values in degrees and with relative intensities shown in Table 3 allowing for variation due to experimental conditions.
  • Form B1 is substantially characterized by the thermal gravimetric analysis (TGA) as shown in FIG.2B.
  • TGA thermal gravimetric analysis
  • Form B1 is substantially characterized by the differential scanning calorimetry profile (DSC) shown in FIG.2C.
  • DSC differential scanning calorimetry profile
  • Form B1 can be characterized by the differential scanning calorimetry profile (DSC) shown in FIG.2C, showing a desolvation peak from 110.7°C, an exothermic peak at Tonset of 142.0°C and a melting peak at Tonset of 203.4°C with an enthalpy of about 75J/g.
  • the crystalline form of the free base of the compound of formula (I) is crystalline Form B2.
  • Crystalline Form B2 is an acetonitrile (ACN) solvate crystalline form of the compound of formula (I).
  • ACN acetonitrile
  • Form B2 can be obtained from ACN by competitive equilibration experiments.
  • Form B2 is of high crystallinity.
  • DSC (FIG.3C) shows a desolvation peak from 111.1°C, an exothermic peak at Tonset of 138.1°C and a melting peak at Tonset of 201.0°C with an enthalpy of about 79J/g.
  • FIG.3B shows about 1.1% weight loss at about 100°C and about 3.4% weight loss from about 100°C to 150°C.1H-NMR (FIG.3D) shows 3.1% ACN residue by weight.
  • Form B2 shows similar XRPD pattern to that of Form B1, suggesting they are isostructural solvates.
  • Form B2 has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2.
  • at least one e.g., one, two, three, four, five, six, seven, eight, nine or ten
  • Form B2 has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2.
  • Form B2 has an X-ray Attorney Docket No.
  • TGO-025WO powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 2
  • Form B2 has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.3 to 26.7 (e.g., Attorney Docket No.
  • Form B2 has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 26.3
  • Form B2 has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2)
  • Form B2 has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2)
  • Form B2 has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2)
  • Form B2 has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2)
  • Form B2 has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 Attorney Docket No. TGO-025WO in degrees: 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.3 to 2
  • Form B2 has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2)
  • Form B2 has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2)
  • Form B2 has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.3 to
  • Form B2 has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.3 to 26.7 (e
  • Form B2 has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 24.2 ⁇ 0.2, 24.9 ⁇ 0.2, 25.7 ⁇ 0.2, 26.5 ⁇ 0.2, 26.8 ⁇ 0.2, 27.7 ⁇ 0.2, 31.5 ⁇ 0.2 and 32.6 ⁇ 0.2.
  • at least one e.g., one, two, three, four, five, six, seven, eight, nine or ten
  • Form B2 has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 24.2 ⁇ 0.2, 24.9 ⁇ 0.2, 25.7 ⁇ 0.2, 26.5 ⁇ 0.2, 26.8 ⁇ 0.2, 27.7 ⁇ 0.2, 31.5 ⁇ 0.2 and 32.6 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 24.2 ⁇ 0.2, 24.9 ⁇ 0.2, 25.7 ⁇ 0.2, 26.5 ⁇ 0.2, 26.8 ⁇ 0.2, 27.7 ⁇ 0.2, 31.5 ⁇ 0.2 and 32.6 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 24.2 ⁇ 0.2, 24.9 ⁇ 0.2, 25.7 ⁇ 0.2, 26.5 ⁇ 0.2, 26.8 ⁇ 0.2, 27.7 ⁇ 0.2, 31.5 ⁇ 0.2 and 32.6 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 24.2 ⁇ 0.2, 24.9 ⁇ 0.2, 25.7 ⁇ 0.2, 26.5 ⁇ 0.2, 26.8 ⁇ 0.2, 27.7 ⁇ 0.2, 31.5 ⁇ 0.2 and 32.6 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 24.2 ⁇ 0.2, 24.9 ⁇ 0.2, 25.7 ⁇ 0.2, 26.5 ⁇ 0.2, 26.8 ⁇ 0.2, 27.7 ⁇ 0.2, 31.5 ⁇ 0.2 and 32.6 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, Attorney Docket No.
  • Form B2 has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 24.2 ⁇ 0.2, 24.9 ⁇ 0.2, 25.7 ⁇ 0.2, 26.5 ⁇ 0.2, 26.8 ⁇ 0.2, 27.7 ⁇ 0.2, 31.5 ⁇ 0.2 and 32.6 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 24.2 ⁇ 0.2, 24.9 ⁇ 0.2, 25.7 ⁇ 0.2, 26.5 ⁇ 0.2, 26.8 ⁇ 0.2, 27.7 ⁇ 0.2, 31.5 ⁇ 0.2 and 32.6 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 24.2 ⁇ 0.2, 24.9 ⁇ 0.2, 25.7 ⁇ 0.2, 26.5 ⁇ 0.2, 26.8 ⁇ 0.2, 27.7 ⁇ 0.2, 31.5 ⁇ 0.2 and 32.6 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 24.2 ⁇ 0.2, 24.9 ⁇ 0.2, 25.7 ⁇ 0.2, 26.5 ⁇ 0.2, 26.8 ⁇ 0.2, 27.7 ⁇ 0.2, 31.5 ⁇ 0.2 and 32.6 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 24.2 ⁇ 0.2, 24.9 ⁇ 0.2, 25.7 ⁇ 0.2, 26.5 ⁇ 0.2, 26.8 ⁇ 0.2, 27.7 ⁇ 0.2, 31.5 ⁇ 0.2 and 32.6 ⁇ 0.2.
  • Form B2 has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 9 to 9.4 (e.g., 9.2 ⁇ 0.2), 9.9 to 10.3 (e.g., 10.1 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2),
  • at least one e.
  • TGO-025WO 18.5 to 18.9 e.g., 18.7 ⁇ 0.2
  • 18.8 to 19.2 e.g., 19 ⁇ 0.2
  • 19.1 to 19.5 e.g., 19.3 ⁇ 0.2
  • 19.3 to 19.7 e.g., 19.5 ⁇ 0.2
  • 20 to 20.4 e.g., 20.2 ⁇ 0.2
  • 20.3 to 20.7 e.g., 20.5 ⁇ 0.2
  • 21.3 to 21.7 e.g., 21.5 ⁇ 0.2
  • 21.6 to 22 e.g., 21.8 ⁇ 0.2
  • 22.6 to 23 e.g., 22.8 ⁇ 0.2
  • 23.3 to 23.7 e.g., 23.5 ⁇ 0.2
  • 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 24 to 24.4 e.g., 24.2 ⁇ 0.2
  • 24.7 to 25.1 e.g., 24.9 ⁇ 0.2
  • 25.5 to 25.9 e.g., 25.7 ⁇ 0.2
  • 26.3 to 26.7 e.g., 26.5 ⁇ 0.2
  • Form B2 has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 9 to 9.4 (e.g., 9.2 ⁇ 0.2), 9.9 to 10.3 (e.g., 10.1 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.
  • Form B2 has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 9 to 9.4 (e.g., 9.2 ⁇ 0.2), 9.9 to 10.3 (e.g., 10.1 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2),
  • Form B2 has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 9 to 9.4 (e.g., 9.2 ⁇ 0.2), 9.9 to 10.3 (e.g., 10.1 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2),
  • TGO-025WO 19.7 e.g., 19.5 ⁇ 0.2
  • 20 to 20.4 e.g., 20.2 ⁇ 0.2
  • 20.3 to 20.7 e.g., 20.5 ⁇ 0.2
  • 21.3 to 21.7 e.g., 21.5 ⁇ 0.2
  • 21.6 to 22 e.g., 21.8 ⁇ 0.2
  • 22.6 to 23 e.g., 22.8 ⁇ 0.2
  • 23.3 to 23.7 e.g., 23.5 ⁇ 0.2
  • 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 24 to 24.4 e.g., 24.2 ⁇ 0.2
  • 24.7 to 25.1 e.g., 24.9 ⁇ 0.2
  • 25.5 to 25.9 e.g., 25.7 ⁇ 0.2
  • 26.3 to 26.7 e.g., 26.5 ⁇ 0.2
  • 26.6 to 27 e.g., 26.8 ⁇ 0.2
  • 27.5 to 27.9 e.g., 27.7 ⁇ 0.2
  • 31.3 to 31.7 e.g., 31.5 ⁇ 0.2
  • Form B2 has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 9 to 9.4 (e.g., 9.2 ⁇ 0.2), 9.9 to 10.3 (e.g., 10.1 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2),
  • Form B2 has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 9 to 9.4 (e.g., 9.2 ⁇ 0.2), 9.9 to 10.3 (e.g., 10.1 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2),
  • Form B2 has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 9 to 9.4 (e.g., 9.2 ⁇ 0.2), 9.9 to 10.3 (e.g., 10.1 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2),
  • TGO-025WO 21.5 ⁇ 0.2 21.6 to 22 (e.g., 21.8 ⁇ 0.2), 22.6 to 23 (e.g., 22.8 ⁇ 0.2), 23.3 to 23.7 (e.g., 23.5 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 24 to 24.4 (e.g., 24.2 ⁇ 0.2), 24.7 to 25.1 (e.g., 24.9 ⁇ 0.2), 25.5 to 25.9 (e.g., 25.7 ⁇ 0.2), 26.3 to 26.7 (e.g., 26.5 ⁇ 0.2), 26.6 to 27 (e.g., 26.8 ⁇ 0.2), 27.5 to 27.9 (e.g., 27.7 ⁇ 0.2), 31.3 to 31.7 (e.g., 31.5 ⁇ 0.2) and 32.4 to 32.8 (e.g., 32.6 ⁇ 0.2).
  • 24.7 to 25.1 e.g., 24.9 ⁇ 0.2
  • 25.5 to 25.9 e.g., 25.7 ⁇ 0.2
  • 26.3 to 26.7 e.g., 26.5 ⁇ 0.2
  • Form B2 has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 9 to 9.4 (e.g., 9.2 ⁇ 0.2), 9.9 to 10.3 (e.g., 10.1 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2),
  • Form B2 has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 9 to 9.4 (e.g., 9.2 ⁇ 0.2), 9.9 to 10.3 (e.g., 10.1 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2),
  • Form B2 has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 9 to 9.4 (e.g., 9.2 ⁇ 0.2), 9.9 to 10.3 (e.g., 10.1 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2),
  • TGO-025WO 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 24 to 24.4 e.g., 24.2 ⁇ 0.2
  • 24.7 to 25.1 e.g., 24.9 ⁇ 0.2
  • 25.5 to 25.9 e.g., 25.7 ⁇ 0.2
  • 26.3 to 26.7 e.g., 26.5 ⁇ 0.2
  • 26.6 to 27 e.g., 26.8 ⁇ 0.2
  • 27.5 to 27.9 e.g., 27.7 ⁇ 0.2
  • 31.3 to 31.7 e.g., 31.5 ⁇ 0.2
  • 32.4 to 32.8 e.g., 32.6 ⁇ 0.2
  • Form B2 has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 9 to 9.4 (e.g., 9.2 ⁇ 0.2), 9.9 to 10.3 (e.g., 10.1 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2
  • Form B2 has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 4.9 to 5.3 (e.g., 5.1 ⁇ 0.2), 5.8 to 6.2 (e.g., 6 ⁇ 0.2), 9 to 9.4 (e.g., 9.2 ⁇ 0.2), 9.9 to 10.3 (e.g., 10.1 ⁇ 0.2), 11 to 11.4 (e.g., 11.2 ⁇ 0.2), 11.8 to 12.2 (e.g., 12 ⁇ 0.2), 12.4 to 12.8 (e.g., 12.6 ⁇ 0.2), 15 to 15.4 (e.g., 15.2 ⁇ 0.2), 15.4 to 15.8 (e.g., 15.6 ⁇ 0.2), 16.8 to 17.2 (e.g., 17 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2
  • Form B2 has an XRPD pattern (obtained using CuKa radiation) substantially corresponding to the XRPD diffraction pattern shown in FIG.3A.
  • Form B2 has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2 values in degrees shown in Table 4 ( ⁇ 0.2 degrees).
  • Form B2 has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2 values in degrees and with relative intensities shown in Table 4 allowing for variation due to experimental conditions. Table 4 – XRPD peaks for Form B2 of a compound of Formula (I) Attorney Docket No. TGO-025WO [0115]
  • Form B2 is substantially characterized by the thermal gravimetric analysis (TGA) as shown in FIG.3B.
  • TGA thermal gravimetric analysis
  • DSC differential scanning calorimetry profile
  • Form B2 can be characterized by the differential scanning calorimetry profile (DSC) shown in FIG.3C, showing a desolvation peak from 111.1°C, an exothermic peak at Tonset of 138.1°C and a melting peak at Tonset of 201.0°C with an enthalpy of about 79J/g. TGA.
  • Crystalline Form C [0117] In certain embodiments, the crystalline form of the free base of the compound of formula (I) is crystalline Form C. Crystalline Form C is an 1,4-dioxane solvate crystalline form of the compound of formula (I). [0118] Form C can be obtained from 1,4-dioxane by fast cooling. [0119] Crystalline Form C is of medium crystallinity.
  • Form C is unstable and converts to anhydrate Form D after exposure to about 25°C/40% RH for about 1 day.
  • Form C has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least one Attorney Docket No. TGO-025WO characteristic peak at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3), 10.3 to 10.7 (e
  • Form C has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25.6 to 26 (e.g., 25.8 ⁇ 0.2), 25.9 to 26.3 (e.g., 2
  • Form C has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25.6 to 26 (e.g., 25.8 ⁇ 0.2), 25.9 to 26.3 (e.g.,
  • Form C has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25.6 to 26 (e.g., 25.8 ⁇ 0.2), 25.9 to 26.3 (e.g.,
  • Form C has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 15.7 to 16.1 Attorney Docket No.
  • TGO-025WO e.g., 15.9 ⁇ 0.2
  • 15.8 to 16.2 e.g., 16 ⁇ 0.2
  • 16.3 to 16.7 e.g., 16.5 ⁇ 0.2
  • 16.9 to 17.3 e.g., 17.1 ⁇ 0.2
  • 18.2 to 18.6 e.g., 18.4 ⁇ 0.2
  • 18.5 to 18.9 e.g., 18.7 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 20.5 to 20.9 e.g., 20.7 ⁇ 0.2
  • 21 to 21.4 e.g., 21.2 ⁇ 0.2
  • 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 24.1 to 24.5 e.g., 24.3 ⁇ 0.2
  • 25.6 to 26 e.g., 25.8 ⁇ 0.2
  • 25.9 to 26.3 e.g., 26.1 ⁇ 0.2
  • 26.1 to 26.5 e.g., 26.3 ⁇ 0.2
  • Form C has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25.6 to 26 (e.g., 25.8 ⁇ 0.2), 25.9 to 26.3 (e.g.,
  • Form C has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25.6 to 26 (e.g., 25.8 ⁇ 0.2), 25.9 to 26.3 (e.g.,
  • Form C has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25.6 to 26 (e.g., 25.8 ⁇ 0.2), 25.9 to 26.3 (e.g.,
  • Form C has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25.6 to 26 (e.g., 25.8 ⁇ 0.2), 25.9 to 26.3 (e.g.,
  • Form C has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to Attorney Docket No.
  • 10.3 to 10.7 e.g., 10.5 ⁇ 0.2
  • 15.7 to 16.1 e.g., 15.9 ⁇ 0.2
  • 15.8 to 16.2 e.g., 16 ⁇ 0.2
  • 16.3 to 16.7 e.g., 16.5 ⁇ 0.2
  • 16.9 to 17.3 e.g., 17.1 ⁇ 0.2
  • 18.2 to 18.6 e.g., 18.4 ⁇ 0.2
  • TGO-025WO 18.9 e.g., 18.7 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 20.5 to 20.9 e.g., 20.7 ⁇ 0.2
  • 21 to 21.4 e.g., 21.2 ⁇ 0.2
  • 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 24.1 to 24.5 e.g., 24.3 ⁇ 0.2
  • 25.6 to 26 e.g., 25.8 ⁇ 0.2
  • 25.9 to 26.3 e.g., 26.1 ⁇ 0.2
  • 26.1 to 26.5 e.g., 26.3 ⁇ 0.2
  • Form C has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25.6 to 26 (e.g., 25.8 ⁇ 0.2), 25.9 to 26.3 (e.g.
  • Form C has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25.6 to 26 (e.g., 25.8 ⁇ 0.2), 25.9 to 26.3 (e.g.
  • Form C has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2.
  • at least one e.g., one, two, three, four, five, six, seven, eight, nine or ten
  • Form C has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, Attorney Docket No. TGO-025WO 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2.
  • Form C has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 5 to 5.4 (e.g., 5.2 ⁇ 0.2), 7.7 to 8.1 (e.g., 7.9 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.4 to 17.8 (e.g., 17.6 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4
  • Form C has an X- ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 5 to 5.4 (e.g., 5.2 ⁇ 0.2), 7.7 to 8.1 (e.g., 7.9 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.4 to 17.8 (e.g., 17.6 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2
  • Form C has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 5 to 5.4 (e.g., 5.2 ⁇ 0.2), 7.7 to 8.1 (e.g., 7.9 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.4 to 17.8 (e.g., 17.6 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2
  • Form C has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 5 Attorney Docket No. TGO-025WO to 5.4 (e.g., 5.2 ⁇ 0.2), 7.7 to 8.1 (e.g., 7.9 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.4 to 17.8 (e.g., 17.6 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2),
  • Form C has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 5 to 5.4 (e.g., 5.2 ⁇ 0.2), 7.7 to 8.1 (e.g., 7.9 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.4 to 17.8 (e.g., 17.6 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2
  • Form C has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 5 to 5.4 (e.g., 5.2 ⁇ 0.2), 7.7 to 8.1 (e.g., 7.9 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.4 to 17.8 (e.g., 17.6 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2
  • Form C has an X- ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 5 to 5.4 (e.g., 5.2 ⁇ 0.2), 7.7 to 8.1 (e.g., 7.9 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.4 to 17.8 (e.g., 17.6 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 2
  • Form C has an X-ray powder diffraction pattern Attorney Docket No. TGO-025WO comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 5 to 5.4 (e.g., 5.2 ⁇ 0.2), 7.7 to 8.1 (e.g., 7.9 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.4 to 17.8 (e.g., 17.6 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2),
  • Form C has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 5 to 5.4 (e.g., 5.2 ⁇ 0.2), 7.7 to 8.1 (e.g., 7.9 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.4 to 17.8 (e.g., 17.6 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2
  • Form C has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 5 to 5.4 (e.g., 5.2 ⁇ 0.2), 7.7 to 8.1 (e.g., 7.9 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.4 to 17.8 (e.g., 17.6 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 21.2
  • Form C has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 5 to 5.4 (e.g., 5.2 ⁇ 0.2), 7.7 to 8.1 (e.g., 7.9 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.4 to 17.8 (e.g., 17.6 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 2
  • TGO-025WO 25.9 to 26.3 e.g., 26.1 ⁇ 0.2
  • 26.1 to 26.5 e.g., 26.3 ⁇ 0.2
  • 28.2 to 28.6 e.g., 28.4 ⁇ 0.2
  • 29 to 29.4 e.g., 29.2 ⁇ 0.2
  • 35.3 to 35.7 e.g., 35.5 ⁇ 0.2
  • Form C has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 5 to 5.4 (e.g., 5.2 ⁇ 0.2), 7.7 to 8.1 (e.g., 7.9 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.7 to 16.1 (e.g., 15.9 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 16.9 to 17.3 (e.g., 17.1 ⁇ 0.2), 17.4 to 17.8 (e.g., 17.6 ⁇ 0.2), 18.2 to 18.6 (e.g., 18.4 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21 to 21.4 (e.g., 2 to 5.4 (e.g.
  • Form C has an XRPD pattern (obtained using CuKa radiation) substantially corresponding to the XRPD diffraction pattern shown in FIG.4.
  • Form C has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2 values in degrees shown in Table 5 ( ⁇ 0.2 degrees).
  • Form C has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2 values in degrees and with relative intensities shown in Table 5 allowing for variation due to experimental conditions.
  • Crystalline Form D is an anhydrous crystalline form of the compound of formula (I).
  • Form D can be obtained after exposing Form C to about 25°C/40%RH for 1 day.
  • Form D is of medium crystallinity.
  • DSC (FIG.5C) shows a melting peak at T onset of 160.2°C, an exothermic peak at T onset of 165.5°C and a melting peak at T onset of 181.7°C.
  • Form D converts to Form G after heating to 170°C. [0134]
  • Form D has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four or five) characteristic peaks at values of 2 in degrees selected from 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2 and 24.3 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2 and 24.3 ⁇ 0.2. In certain embodiments, Form D has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2 and 24.3 ⁇ 0.2. In certain embodiments, Form D has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 16.1 ⁇ 0.2, Attorney Docket No. TGO-025WO 16.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2 and 24.3 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2 and 24.3 ⁇ 0.2. [0135] In certain embodiments, Form D has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2 and 24.3 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four or five) characteristic peaks between and including the following values of 2 in degrees: 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2) and 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2).
  • 15.9 to 16.3 e.g., 16.1 ⁇ 0.2
  • 16.7 to 17.1 e.g., 16.9 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 20.5 to 20.9 e.g., 20.7 ⁇ 0.2
  • 24.1 to 24.5 e.g., 24.3 ⁇ 0.2
  • Form D has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2) and 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2).
  • 15.9 to 16.3 e.g., 16.1 ⁇ 0.2
  • 16.7 to 17.1 e.g., 16.9 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 20.5 to 20.9 e.g., 20.7 ⁇ 0.2
  • 24.1 to 24.5 e.g., 24.3 ⁇ 0.2
  • Form D has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2) and 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2).
  • 15.9 to 16.3 e.g., 16.1 ⁇ 0.2
  • 16.7 to 17.1 e.g., 16.9 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 20.5 to 20.9 e.g., 20.7 ⁇ 0.2
  • 24.1 to 24.5 e.g., 24.3 ⁇ 0.2
  • Form D has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2) and 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2).
  • 15.9 to 16.3 e.g., 16.1 ⁇ 0.2
  • 16.7 to 17.1 e.g., 16.9 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 20.5 to 20.9 e.g., 20.7 ⁇ 0.2
  • 24.1 to 24.5 e.g., 24.3 ⁇ 0.2
  • Form D has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2) and 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2).
  • 15.9 to 16.3 e.g., 16.1 ⁇ 0.2
  • 16.7 to 17.1 e.g., 16.9 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 20.5 to 20.9 e.g., 20.7 ⁇ 0.2
  • 24.1 to 24.5 e.g., 24.3 ⁇ 0.2
  • Form D has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2) and 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2).
  • Form D has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • at least one e.g., one, two, three, four, five, six, seven, eight, nine or ten
  • Form D has an X-ray powder diffraction pattern comprising at least one characteristic peak at Attorney Docket No. TGO-025WO values of 2 in degrees selected from 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, Attorney Docket No. TGO-025WO 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • Form D has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 10.6 to 11 (e.g., 10.8 ⁇ 0.2), 13.3 to 13.7 (e.g., 13.5 ⁇ 0.2), 13.8 to 14.2 (e.g., 14 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 17.1 to 17.5 (e.g., 17.3 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.4 to 21.8 (e.g., 21.6 ⁇ 0.2), 23.1 to 23.5 (e.g., 2a.
  • Form D has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 10.6 to 11 (e.g., 10.8 ⁇ 0.2), 13.3 to 13.7 (e.g., 13.5 ⁇ 0.2), 13.8 to 14.2 (e.g., 14 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 17.1 to 17.5 (e.g., 17.3 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.4 to 21.8 (e.g., 21.6 ⁇ 0.2), 23.1 to 23.5 (e.g., 23.3 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25 to 25.4 (e.g., 25.2).
  • Form D has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 10.6 to 11 (e.g., 10.8 ⁇ 0.2), 13.3 to 13.7 (e.g., 13.5 ⁇ 0.2), 13.8 to 14.2 (e.g., 14 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 17.1 to 17.5 (e.g., 17.3 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.4 to 21.8 (e.g., 21.6 ⁇ 0.2), 23.1 to 23.5 (e.g., 23.3 ⁇ 0.2), 24.1 to 24.5 (e.g., Attorney Docket No.
  • 10.6 to 11 e.g., 10.8
  • TGO-025WO 24.3 ⁇ 0.2 25 to 25.4 (e.g., 25.2 ⁇ 0.2), 25.8 to 26.2 (e.g., 26 ⁇ 0.2), 26.1 to 26.5 (e.g., 26.3 ⁇ 0.2), 26.8 to 27.2 (e.g., 27 ⁇ 0.2), 28.3 to 28.7 (e.g., 28.5 ⁇ 0.2), 33.1 to 33.5 (e.g., 33.3 ⁇ 0.2), 35.3 to 35.7 (e.g., 35.5 ⁇ 0.2), 35.6 to 36 (e.g., 35.8 ⁇ 0.2) and 37.7 to 38.1 (e.g., 37.9 ⁇ 0.2).
  • Form D has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 10.6 to 11 (e.g., 10.8 ⁇ 0.2), 13.3 to 13.7 (e.g., 13.5 ⁇ 0.2), 13.8 to 14.2 (e.g., 14 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 17.1 to 17.5 (e.g., 17.3 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.4 to 21.8 (e.g., 21.6 ⁇ 0.2), 23.1 to 23.5 (e.g., 23.3 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25 to 25.4 (e.g., 2
  • Form D has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 10.6 to 11 (e.g., 10.8 ⁇ 0.2), 13.3 to 13.7 (e.g., 13.5 ⁇ 0.2), 13.8 to 14.2 (e.g., 14 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 17.1 to 17.5 (e.g., 17.3 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.4 to 21.8 (e.g., 21.6 ⁇ 0.2), 23.1 to 23.5 (e.g., 23.3 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25 to 25.4 (e.g., 2
  • Form D has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 10.6 to 11 (e.g., 10.8 ⁇ 0.2), 13.3 to 13.7 (e.g., 13.5 ⁇ 0.2), 13.8 to 14.2 (e.g., 14 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 17.1 to 17.5 (e.g., 17.3 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.4 to 21.8 (e.g., 21.6 ⁇ 0.2), 23.1 to 23.5 (e.g., 23.3 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25 to 25.4 (e.g., 2
  • Form D has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 10.6 to 11 (e.g., 10.8 ⁇ 0.2), 13.3 to 13.7 (e.g., 13.5 ⁇ 0.2), 13.8 to 14.2 (e.g., 14 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 17.1 to 17.5 (e.g., 17.3 ⁇ 0.2), 17.9 to 18.3 (e.g., Attorney Docket No.
  • 10.6 to 11 e.g., 10.8 ⁇ 0.2
  • 13.3 to 13.7 e.g., 13.5 ⁇ 0.2
  • 13.8 to 14.2 e.g., 14 ⁇ 0.2
  • 15.9 to 16.3 e.g., 16.1 ⁇ 0.2
  • 16.7 to 17.1 e.g., 16.9 ⁇ 0.2
  • 17.1 to 17.5 e.g., 17.3 ⁇ 0.2
  • 17.9 to 18.3 e.
  • TGO-025WO 18.1 ⁇ 0.2 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.4 to 21.8 (e.g., 21.6 ⁇ 0.2), 23.1 to 23.5 (e.g., 23.3 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25 to 25.4 (e.g., 25.2 ⁇ 0.2), 25.8 to 26.2 (e.g., 26 ⁇ 0.2), 26.1 to 26.5 (e.g., 26.3 ⁇ 0.2), 26.8 to 27.2 (e.g., 27 ⁇ 0.2), 28.3 to 28.7 (e.g., 28.5 ⁇ 0.2), 33.1 to 33.5 (e.g., 33.3 ⁇ 0.2), 35.3 to 35.7 (e.g., 35.5 ⁇ 0.2), 35.6 to 36 (e.g., 35.8 ⁇ 0.2) and 37.7 to 38.1 (e.g., 37.9 ⁇ 0.2).
  • Form D has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 10.6 to 11 (e.g., 10.8 ⁇ 0.2), 13.3 to 13.7 (e.g., 13.5 ⁇ 0.2), 13.8 to 14.2 (e.g., 14 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 17.1 to 17.5 (e.g., 17.3 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.4 to 21.8 (e.g., 21.6 ⁇ 0.2), 23.1 to 23.5 (e.g., 23.3 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25 to 25.4 (e.g., 2
  • Form D has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 10.6 to 11 (e.g., 10.8 ⁇ 0.2), 13.3 to 13.7 (e.g., 13.5 ⁇ 0.2), 13.8 to 14.2 (e.g., 14 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 17.1 to 17.5 (e.g., 17.3 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.4 to 21.8 (e.g., 21.6 ⁇ 0.2), 23.1 to 23.5 (e.g., 23.3 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25 to 25.4 (e.g., 2
  • Form D has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 10.6 to 11 (e.g., 10.8 ⁇ 0.2), 13.3 to 13.7 (e.g., 13.5 ⁇ 0.2), 13.8 to 14.2 (e.g., 14 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 17.1 to 17.5 (e.g., 17.3 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.4 to 21.8 (e.g., 21.6 ⁇ 0.2), 23.1 to 23.5 (e.g., 23.3 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25 to 25.4 (e.g., 2
  • Form D has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 10.6 to 11 Attorney Docket No. TGO-025WO (e.g., 10.8 ⁇ 0.2), 13.3 to 13.7 (e.g., 13.5 ⁇ 0.2), 13.8 to 14.2 (e.g., 14 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 17.1 to 17.5 (e.g., 17.3 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.4 to 21.8 (e.g., 21.6 ⁇ 0.2), 23.1 to 23.5 (e.g., 23.3 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇
  • Form D has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 10.6 to 11 (e.g., 10.8 ⁇ 0.2), 13.3 to 13.7 (e.g., 13.5 ⁇ 0.2), 13.8 to 14.2 (e.g., 14 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.7 to 17.1 (e.g., 16.9 ⁇ 0.2), 17.1 to 17.5 (e.g., 17.3 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.4 to 21.8 (e.g., 21.6 ⁇ 0.2), 23.1 to 23.5 (e.g., 23.3 ⁇ 0.2), 24.1 to 24.5 (e.g., 24.3 ⁇ 0.2), 25 to 25.4 (e.g.,
  • Form D has an XRPD pattern (obtained using CuKa radiation) substantially corresponding to the XRPD diffraction pattern shown in FIG. 5A.
  • Form D has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2 values in degrees shown in Table 6 ( ⁇ 0.2 degrees).
  • Form D has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2 values in degrees and with relative intensities shown in Table 6 allowing for variation due to experimental conditions.
  • Form D is substantially characterized by the thermal gravimetric analysis (TGA) as shown in FIG.5B.
  • TGA thermal gravimetric analysis
  • Form D is substantially characterized by the differential scanning calorimetry profile (DSC) shown in FIG.5C.
  • DSC differential scanning calorimetry profile
  • Form D can be characterized by the differential scanning calorimetry profile (DSC) shown in FIG.5C, showing a melting peak at Tonset of 160.2°C, an exothermic peak at Tonset of 165.5°C and a melting peak at T onset of 181.7°C.
  • Crystalline Form E [0146] In certain embodiments, the crystalline form of the free base of the compound of formula (I) is crystalline Form E. Crystalline Form E is an 1,4-dioxane solvate crystalline form of the compound of formula (I). [0147] Form E can be obtained from 1,4-dioxane by slow evaporation. [0148] Form E is of high crystallinity. DSC (FIG.6C) shows a desolvation peak from 89.7°C and 2 combined endothermic peaks at T onset of 155.0°C and 167.5°C, respectively. TGA (FIG.6B) shows about 1.5% weight loss at about 100°C and about 6.6% weight loss from about Attorney Docket No.
  • Form E has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three or four) characteristic peaks at values of 2 in degrees selected from 11.8 ⁇ 0.2, 16.5 ⁇ 0.2, 21.3 ⁇ 0.2 and 26.1 ⁇ 0.2. In certain embodiments, Form E has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 11.8 ⁇ 0.2, 16.5 ⁇ 0.2, 21.3 ⁇ 0.2 and 26.1 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 11.8 ⁇ 0.2, 16.5 ⁇ 0.2, 21.3 ⁇ 0.2 and 26.1 ⁇ 0.2. In certain embodiments, Form E has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 11.8 ⁇ 0.2, 16.5 ⁇ 0.2, 21.3 ⁇ 0.2 and 26.1 ⁇ 0.2. [0150] In certain embodiments, Form E has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 11.8 ⁇ 0.2, 16.5 ⁇ 0.2, 21.3 ⁇ 0.2 and 26.1 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 11.8 ⁇ 0.2, 16.5 ⁇ 0.2, 21.3 ⁇ 0.2 and 26.1 ⁇ 0.2 and at least one (e.g., one, two, three, four, five or six) additional characteristic peaks at values of 2 in degrees selected from: 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 16.1 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three or four) characteristic peaks between and including the following values of 2 in degrees: 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2) and 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2).
  • 11.6 to 12 e.g., 11.8 ⁇ 0.2
  • 16.3 to 16.7 e.g., 16.5 ⁇ 0.2
  • 21.1 to 21.5 e.g., 21.3 ⁇ 0.2
  • 25.9 to 26.3 e.g., 26.1 ⁇ 0.2
  • Form E has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2) and 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2).
  • Form E has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2) and 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2).
  • Form E has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2) and 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2).
  • 11.6 to 12 e.g., 11.8 ⁇ 0.2
  • 16.3 to 16.7 e.g., 16.5 ⁇ 0.2
  • 21.1 to 21.5 e.g., 21.3 ⁇ 0.2
  • 25.9 to 26.3 e.g., 26.1 ⁇ 0.2
  • Form E has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2) and 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2).
  • Form E has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2) and 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2) and at least at least one (e.g., one, two, three, four, five or six) additional characteristic peaks between and including values of 2 in degrees selected from: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.3 to 21.7 (e.g., 21.5 ⁇ 0.2), 23.5 to 23.9 (e.g., 23.7 ⁇ 0.2),
  • Form E has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 11.8 ⁇ 0.2, 16.1 ⁇ 0.2, 16.5 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.3 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2, 26.1 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • at least one e.g., one, two, three, four, five, six, seven, eight, nine or ten
  • Form E has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 11.8 ⁇ 0.2, 16.1 ⁇ 0.2, 16.5 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.3 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2, 26.1 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 11.8 ⁇ 0.2, 16.1 ⁇ 0.2, 16.5 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.3 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2, 26.1 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 11.8 ⁇ 0.2, 16.1 ⁇ 0.2, 16.5 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.3 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2, 26.1 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 11.8 ⁇ 0.2, 16.1 ⁇ 0.2, 16.5 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.3 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2, 26.1 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Form E has an X- ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 11.8 ⁇ 0.2, 16.1 ⁇ 0.2, 16.5 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.3 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2, 26.1 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of Attorney Docket No.
  • Form E has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 11.8 ⁇ 0.2, 16.1 ⁇ 0.2, 16.5 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.3 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2, 26.1 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 11.8 ⁇ 0.2, 16.1 ⁇ 0.2, 16.5 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.3 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2, 26.1 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 11.8 ⁇ 0.2, 16.1 ⁇ 0.2, 16.5 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.3 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2, 26.1 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 11.8 ⁇ 0.2, 16.1 ⁇ 0.2, 16.5 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.3 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2, 26.1 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 11.8 ⁇ 0.2, 16.1 ⁇ 0.2, 16.5 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.3 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2, 26.1 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 11.8 ⁇ 0.2, 16.1 ⁇ 0.2, 16.5 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.3 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2, 26.1 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Form E has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2), 21.3 to 21.7 (e.g., 21.5 ⁇ 0.2), 23.5 to 23.9 (e.g., 23.7 ⁇ 0.2), 24 to 24.4 (e.g., 24.2 ⁇ 0.2), 25.9 to 26.3 (e.g.,
  • Form E has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2), 21.3 to 21.7 (e.g., 21.5 ⁇ 0.2), 23.5 to 23.9 (e.g., 23.7 ⁇ 0.2), 24 to 24.4 (e.g., 24.2 ⁇ 0.2), 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2) and 33.1 to 33.5 (e.g., 33.3 ⁇ 0.2).
  • 6.9 to 7.3 e.g.,
  • Form E has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), Attorney Docket No.
  • TGO-025WO 11.6 to 12 e.g., 11.8 ⁇ 0.2
  • 15.9 to 16.3 e.g., 16.1 ⁇ 0.2
  • 16.3 to 16.7 e.g., 16.5 ⁇ 0.2
  • 18.7 to 19.1 e.g., 18.9 ⁇ 0.2
  • 20.5 to 20.9 e.g., 20.7 ⁇ 0.2
  • 21.1 to 21.5 e.g., 21.3 ⁇ 0.2
  • 21.3 to 21.7 e.g., 21.5 ⁇ 0.2
  • 23.5 to 23.9 e.g., 23.7 ⁇ 0.2
  • 24 to 24.4 e.g., 24.2 ⁇ 0.2
  • 25.9 to 26.3 e.g., 26.1 ⁇ 0.2
  • 33.1 to 33.5 e.g., 33.3 ⁇ 0.2
  • Form E has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2), 21.3 to 21.7 (e.g., 21.5 ⁇ 0.2), 23.5 to 23.9 (e.g., 23.7 ⁇ 0.2), 24 to 24.4 (e.g., 24.2 ⁇ 0.2), 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2) and 33.1 to 33.5 (e.g., 33.3 ⁇ 0.2).
  • 6.9 to 7.3 e.g.,
  • Form E has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2), 21.3 to 21.7 (e.g., 21.5 ⁇ 0.2), 23.5 to 23.9 (e.g., 23.7 ⁇ 0.2), 24 to 24.4 (e.g., 24.2 ⁇ 0.2), 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2) and 33.1 to 33.5 (e.g., 33.3 ⁇ 0.2).
  • 6.9 to 7.3 e.g.,
  • Form E has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2), 21.3 to 21.7 (e.g., 21.5 ⁇ 0.2), 23.5 to 23.9 (e.g., 23.7 ⁇ 0.2), 24 to 24.4 (e.g., 24.2 ⁇ 0.2), 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2) and 33.1 to 33.5 (e.g., 33.3 ⁇ 0.2).
  • 6.9 to 7.3 e.g.,
  • Form E has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2), 21.3 to 21.7 (e.g., 21.5 ⁇ 0.2), 23.5 to 23.9 (e.g., 23.7 ⁇ 0.2), 24 to 24.4 (e.g., 24.2 ⁇ 0.2), 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2) and 33.1 to 33.5 (e.g., 33.3 ⁇ 0.2).
  • 6.9 to 7.3 e.g.,
  • Form E has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2), 21.3 to 21.7 (e.g., 21.5 ⁇ 0.2), 23.5 to 23.9 (e.g., 23.7 ⁇ 0.2), 24 to 24.4 (e.g., 24.2 ⁇ 0.2), 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2) and 33.1 to 33.5 (e.g., 33.3 ⁇ 0.2).
  • 6.9 to 7.3 e.g.,
  • Form E has an X-ray powder Attorney Docket No. TGO-025WO diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2), 21.3 to 21.7 (e.g., 21.5 ⁇ 0.2), 23.5 to 23.9 (e.g., 23.7 ⁇ 0.2), 24 to 24.4 (e.g., 24.2 ⁇ 0.2), 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2) and 33.1 to 33.5 (e.g., 33.3
  • Form E has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2), 21.3 to 21.7 (e.g., 21.5 ⁇ 0.2), 23.5 to 23.9 (e.g., 23.7 ⁇ 0.2), 24 to 24.4 (e.g., 24.2 ⁇ 0.2), 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2) and 33.1 to 33.5 (e.g., 33.3 ⁇ 0.2).
  • 6.9 to 7.3 e.g.,
  • Form E has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2), 21.3 to 21.7 (e.g., 21.5 ⁇ 0.2), 23.5 to 23.9 (e.g., 23.7 ⁇ 0.2), 24 to 24.4 (e.g., 24.2 ⁇ 0.2), 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2) and 33.1 to 33.5 (e.g., 33.3 ⁇ 0.2).
  • 6.9 to 7.3 e.g.
  • Form E has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 6.9 to 7.3 (e.g., 7.1 ⁇ 0.2), 10.5 to 10.9 (e.g., 10.7 ⁇ 0.2), 11.6 to 12 (e.g., 11.8 ⁇ 0.2), 15.9 to 16.3 (e.g., 16.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 20.5 to 20.9 (e.g., 20.7 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2), 21.3 to 21.7 (e.g., 21.5 ⁇ 0.2), 23.5 to 23.9 (e.g., 23.7 ⁇ 0.2), 24 to 24.4 (e.g., 24.2 ⁇ 0.2), 25.9 to 26.3 (e.g., 26.1 ⁇ 0.2) and 33.1 to 33.5 (e.g., 33.3 ⁇ 0.2).
  • 6.9 to 7.3 e.g., 7.1 ⁇
  • Form E has an XRPD pattern (obtained using CuKa radiation) substantially corresponding to the XRPD diffraction pattern shown in FIG. 6A.
  • Form E has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2 values in degrees shown in Table 7 ( ⁇ 0.2 degrees).
  • Form E has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2 values in degrees and with relative intensities shown in Table 7 allowing for variation due to experimental conditions.
  • Form E is substantially characterized by the thermal gravimetric analysis (TGA) as shown in FIG.6B.
  • TGA thermal gravimetric analysis
  • Form E is substantially characterized by the differential scanning calorimetry profile (DSC) shown in FIG.6C.
  • DSC differential scanning calorimetry profile
  • Form E can be characterized by the differential scanning calorimetry profile (DSC) shown in FIG.6C, showing a desolvation peak from 89.7°C and 2 combined endothermic peaks at Tonset of 155.0°C and 167.5°C, respectively.
  • Crystalline Form F [0164] In certain embodiments, the crystalline form of the free base of the compound of formula (I) is crystalline Form F. Crystalline Form F is an anhydrous crystalline form of the compound of formula (I). [0165] Form F can be obtained from desolvation of EA solvate Form B1. Form F is of high crystallinity. DSC (FIG. 7C) shows a melting peak at T onset of 203.9°C with an enthalpy of about 87J/g. TGA (FIG.7B) shows about 0.8% weight loss at about 150°C. 1 H-NMR (FIG.7D) shows no detectable residual solvent.
  • Form F has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six or seven) characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 18.1 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2 and 24.6 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 18.1 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2 and 24.6 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 18.1 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2 and 24.6 ⁇ 0.2. In certain embodiments, Form F has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 18.1 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2 and 24.6 ⁇ 0.2. In certain embodiments, Form F has an X-ray powder diffraction pattern comprising at least four Attorney Docket No.
  • Form F has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 18.1 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2 and 24.6 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 18.1 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2 and 24.6 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 18.1 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2 and 24.6 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six or seven) characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 23.8 to 24.2 (e.g., 24 ⁇ 0.2) and 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2).
  • 4.8 to 5.2 e.g., 5 ⁇ 0.2
  • 7.8 to 8.2 e.g., 8 ⁇ 0.2
  • 9.8 to 10.2 e.g., 10 ⁇ 0.2
  • 17.9 to 18.3 e.g., 18.1 ⁇ 0.2
  • 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 23.8 to 24.2 e.g.
  • Form F has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 23.8 to 24.2 (e.g., 24 ⁇ 0.2) and 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2).
  • 4.8 to 5.2 e.g., 5 ⁇ 0.2
  • 7.8 to 8.2 e.g., 8 ⁇ 0.2
  • 9.8 to 10.2 e.g., 10 ⁇ 0.2
  • 17.9 to 18.3 e.g., 18.1 ⁇ 0.2
  • 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 23.8 to 24.2 e.g., 24 ⁇ 0.2
  • 24.4 to 24.8 e.g., 24.6 ⁇ 0.2
  • Form F has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 23.8 to 24.2 (e.g., 24 ⁇ 0.2) and 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2).
  • 4.8 to 5.2 e.g., 5 ⁇ 0.2
  • 7.8 to 8.2 e.g., 8 ⁇ 0.2
  • 9.8 to 10.2 e.g., 10 ⁇ 0.2
  • 17.9 to 18.3 e.g., 18.1 ⁇ 0.2
  • 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 23.8 to 24.2 e.g., 24 ⁇ 0.2
  • 24.4 to 24.8 e.g., 24.6 ⁇
  • Form F has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 23.8 to 24.2 (e.g., 24 ⁇ 0.2) and 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2).
  • 4.8 to 5.2 e.g., 5 ⁇ 0.2
  • 7.8 to 8.2 e.g., 8 ⁇ 0.2
  • 9.8 to 10.2 e.g., 10 ⁇ 0.2
  • 17.9 to 18.3 e.g., 18.1 ⁇ 0.2
  • 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 23.8 to 24.2 e.g., 24 ⁇ 0.2
  • 24.4 to 24.8 e.g., 24.6 ⁇
  • Form F has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 23.8 to 24.2 (e.g., 24 ⁇ 0.2) and 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2).
  • 4.8 to 5.2 e.g., 5 ⁇ 0.2
  • 7.8 to 8.2 e.g., 8 ⁇ 0.2
  • 9.8 to 10.2 e.g., 10 ⁇ 0.2
  • 17.9 to 18.3 e.g., 18.1 ⁇ 0.2
  • 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 23.8 to 24.2 e.g., 24 ⁇ 0.2
  • 24.4 to 24.8 e.g., 24.6 ⁇
  • Form F has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 23.8 to 24.2 (e.g., Attorney Docket No. TGO-025WO 24 ⁇ 0.2) and 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2).
  • 4.8 to 5.2 e.g., 5 ⁇ 0.2
  • 7.8 to 8.2 e.g., 8 ⁇ 0.2
  • 9.8 to 10.2 e.g., 10 ⁇ 0.2
  • 17.9 to 18.3 e.g., 18.1 ⁇ 0.2
  • 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 23.8 to 24.2 e.g., Attorney Docket No. T
  • Form F has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 23.8 to 24.2 (e.g., 24 ⁇ 0.2) and 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2).
  • 4.8 to 5.2 e.g., 5 ⁇ 0.2
  • 7.8 to 8.2 e.g., 8 ⁇ 0.2
  • 9.8 to 10.2 e.g., 10 ⁇ 0.2
  • 17.9 to 18.3 e.g., 18.1 ⁇ 0.2
  • 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 23.8 to 24.2 e.g., 24 ⁇ 0.2
  • 24.4 to 24.8 e.g., 24.6 ⁇
  • Form F has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 23.8 to 24.2 (e.g., 24 ⁇ 0.2) and 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2).
  • 4.8 to 5.2 e.g., 5 ⁇ 0.2
  • 7.8 to 8.2 e.g., 8 ⁇ 0.2
  • 9.8 to 10.2 e.g., 10 ⁇ 0.2
  • 17.9 to 18.3 e.g., 18.1 ⁇ 0.2
  • 23.6 to 24 e.g., 23.8 ⁇ 0.2
  • 23.8 to 24.2 e.g., 24 ⁇ 0.2
  • 24.4 to 24.8 e.g., 24.6 ⁇ 0.2
  • Form F has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2.
  • at least one e.g., one, two, three, four, five, six, eight, nine or ten
  • Form F has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2.
  • Form F has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.3 to 7.7 (e.g., 7.5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 12.3 to 12.7 (e.g., 12.5 ⁇ 0.2), 14.9 to 15.3 (e.g., 15.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 17.6 to 18 (e.g., 17.8 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 20.4 to 20.8 (e.g., 20.6 ⁇
  • Form F has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.3 to 7.7 (e.g., 7.5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 12.3 to 12.7 (e.g., 12.5 ⁇ 0.2), 14.9 to 15.3 (e.g., 15.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 17.6 to 18 (e.g., 17.8 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 20.4 to 20.8 (e.g., 20.6 ⁇ 0.2), 20.8 to 21.2 (e.g., 21 ⁇ 0.2), 21.1 to
  • Form F has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.3 to 7.7 (e.g., 7.5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 12.3 to 12.7 (e.g., 12.5 ⁇ 0.2), 14.9 to 15.3 (e.g., 15.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 17.6 to 18 (e.g., 17.8 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 20.4 to 20.8 (e.g., 20.6 ⁇ 0.2), 20.8 to 21.2 (e.g., 21 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇
  • Form F has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.3 to 7.7 (e.g., 7.5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 12.3 to 12.7 (e.g., 12.5 ⁇ 0.2), 14.9 to 15.3 (e.g., 15.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 17.6 to 18 (e.g., 17.8 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 20.4 to 20.8 (e.g., 20.6 ⁇ 0.2), 20.8 to 21.2 (e.g., 21 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇
  • Form F has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.3 to 7.7 (e.g., 7.5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 12.3 to 12.7 (e.g., 12.5 ⁇ 0.2), 14.9 to 15.3 (e.g., 15.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 17.6 to 18 (e.g., 17.8 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 20.4 to 20.8 (e.g., 20.6 ⁇ 0.2), 20.8 to 21.2 (e.g., 21 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇
  • Form F has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the Attorney Docket No. TGO-025WO following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.3 to 7.7 (e.g., 7.5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 12.3 to 12.7 (e.g., 12.5 ⁇ 0.2), 14.9 to 15.3 (e.g., 15.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 17.6 to 18 (e.g., 17.8 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 20.4 to 20.8 (e.g., 20.6 ⁇ 0.2), 20.8 to 21.2 (e.g., 21 ⁇ 0.2), 21.1
  • Form F has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.3 to 7.7 (e.g., 7.5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 12.3 to 12.7 (e.g., 12.5 ⁇ 0.2), 14.9 to 15.3 (e.g., 15.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 17.6 to 18 (e.g., 17.8 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 20.4 to 20.8 (e.g., 20.6 ⁇ 0.2), 20.8 to 21.2 (e.g., 21 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇
  • Form F has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.3 to 7.7 (e.g., 7.5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 12.3 to 12.7 (e.g., 12.5 ⁇ 0.2), 14.9 to 15.3 (e.g., 15.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 17.6 to 18 (e.g., 17.8 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 20.4 to 20.8 (e.g., 20.6 ⁇ 0.2), 20.8 to 21.2 (e.g., 21 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇
  • Form F has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.3 to 7.7 (e.g., 7.5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 12.3 to 12.7 (e.g., 12.5 ⁇ 0.2), 14.9 to 15.3 (e.g., 15.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 17.6 to 18 (e.g., 17.8 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 20.4 to 20.8 (e.g., 20.6 ⁇ 0.2), 20.8 to 21.2 (e.g., 21 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇
  • Form F has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.3 to 7.7 (e.g., 7.5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., Attorney Docket No.
  • TGO-025WO 10 ⁇ 0.2 12.3 to 12.7 (e.g., 12.5 ⁇ 0.2), 14.9 to 15.3 (e.g., 15.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 17.6 to 18 (e.g., 17.8 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 20.4 to 20.8 (e.g., 20.6 ⁇ 0.2), 20.8 to 21.2 (e.g., 21 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3 ⁇ 0.2), 22.6 to 23 (e.g., 22.8 ⁇ 0.2), 23.6 to 24 (e.g., 23.8 ⁇ 0.2), 23.8 to 24.2 (e.g., 24 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 25.1 to 25.5 (e.g., 25.3 ⁇ 0.2), 25.9 to 26.3 (e.g
  • Form F has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.3 to 7.7 (e.g., 7.5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 12.3 to 12.7 (e.g., 12.5 ⁇ 0.2), 14.9 to 15.3 (e.g., 15.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 17.6 to 18 (e.g., 17.8 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 20.4 to 20.8 (e.g., 20.6 ⁇ 0.2), 20.8 to 21.2 (e.g., 21 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3
  • Form F has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 4.8 to 5.2 (e.g., 5 ⁇ 0.2), 7.3 to 7.7 (e.g., 7.5 ⁇ 0.2), 7.8 to 8.2 (e.g., 8 ⁇ 0.2), 9.8 to 10.2 (e.g., 10 ⁇ 0.2), 12.3 to 12.7 (e.g., 12.5 ⁇ 0.2), 14.9 to 15.3 (e.g., 15.1 ⁇ 0.2), 16.3 to 16.7 (e.g., 16.5 ⁇ 0.2), 17.6 to 18 (e.g., 17.8 ⁇ 0.2), 17.9 to 18.3 (e.g., 18.1 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.9 to 19.3 (e.g., 19.1 ⁇ 0.2), 20.4 to 20.8 (e.g., 20.6 ⁇ 0.2), 20.8 to 21.2 (e.g., 21 ⁇ 0.2), 21.1 to 21.5 (e.g., 21.3
  • Form F has an XRPD pattern (obtained using CuKa radiation) substantially corresponding to the XRPD diffraction pattern shown in FIG.7A.
  • Form F has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2 values in degrees shown in Table 8 ( ⁇ 0.2 degrees).
  • Form F has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2 values in degrees and with relative intensities shown in Table 8 allowing for variation due to experimental conditions.
  • Form F is substantially characterized by the thermal gravimetric analysis (TGA) as shown in FIG.7B.
  • TGA thermal gravimetric analysis
  • Form F is substantially characterized by the differential scanning calorimetry profile (DSC) shown in FIG.7C.
  • DSC differential scanning calorimetry profile
  • Form F can be characterized by the differential scanning calorimetry profile (DSC) shown in FIG.7C, showing a melting peak at Tonset of 203.9°C with an enthalpy of about 87J/g.
  • DSC differential scanning calorimetry profile
  • the crystalline form of the free base of the compound of formula (I) is crystalline Form G.
  • Crystalline Form G is an anhydrous crystalline form of the compound of formula (I).
  • Form G can be obtained by heating Form D to 170°C.
  • Form G is of high crystallinity.
  • DSC (FIG.8C) shows a small melting peak at Tonset of 165.3°C and a melting peak at Tonset of 180.1°C with an enthalpy of about 78J/g.
  • TGA (FIG. 8B) shows about 0.4% weight loss at about 150°C.
  • 1 H-NMR (FIG. 8D) shows no detectable residual solvent.
  • Form G has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four or five) characteristic peaks at values of 2 in degrees selected from 16.7 ⁇ 0.2, 19.3 ⁇ 0.2, 21.2 ⁇ 0.2, 24.4 ⁇ 0.2 and 26.7 ⁇ 0.2. In certain embodiments, Form G has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 16.7 ⁇ 0.2, 19.3 ⁇ 0.2, 21.2 ⁇ 0.2, 24.4 ⁇ 0.2 and 26.7 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 16.7 ⁇ 0.2, 19.3 ⁇ 0.2, 21.2 ⁇ 0.2, 24.4 ⁇ 0.2 and 26.7 ⁇ 0.2. In certain embodiments, Form G has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 16.7 ⁇ 0.2, 19.3 ⁇ 0.2, 21.2 ⁇ 0.2, 24.4 ⁇ 0.2 and 26.7 ⁇ 0.2. In certain embodiments, Form G has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 16.7 ⁇ 0.2, 19.3 ⁇ 0.2, 21.2 ⁇ 0.2, 24.4 ⁇ 0.2 and 26.7 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 16.7 ⁇ 0.2, 19.3 ⁇ 0.2, 21.2 ⁇ 0.2, 24.4 ⁇ 0.2 and 26.7 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four or five) characteristic peaks between and including the following values of 2 in degrees: 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 24.2 to 24.6 (e.g., 24.4 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • 16.5 to 16.9 e.g., 16.7 ⁇ 0.2
  • 19.1 to 19.5 e.g., 19.3 ⁇ 0.2
  • 21 to 21.4 e.g., 21.2 ⁇ 0.2
  • 24.2 to 24.6 e.g., 24.4 ⁇ 0.2
  • Form G has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 24.2 to 24.6 (e.g., 24.4 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • Form G has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including Attorney Docket No.
  • TGO-025WO the following values of 2 in degrees: 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 24.2 to 24.6 (e.g., 24.4 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • Form G has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 24.2 to 24.6 (e.g., 24.4 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • 16.5 to 16.9 e.g., 16.7 ⁇ 0.2
  • 19.1 to 19.5 e.g., 19.3 ⁇ 0.2
  • 21 to 21.4 e.g., 21.2 ⁇ 0.2
  • 24.2 to 24.6 e.g., 24.4 ⁇ 0.2
  • 26.5 to 26.9 e.g., 26.7 ⁇ 0.2
  • Form G has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 24.2 to 24.6 (e.g., 24.4 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • 16.5 to 16.9 e.g., 16.7 ⁇ 0.2
  • 19.1 to 19.5 e.g., 19.3 ⁇ 0.2
  • 21 to 21.4 e.g., 21.2 ⁇ 0.2
  • 24.2 to 24.6 e.g., 24.4 ⁇ 0.2
  • 26.5 to 26.9 e.g., 26.7 ⁇ 0.2
  • Form G has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 21 to 21.4 (e.g., 21.2 ⁇ 0.2), 24.2 to 24.6 (e.g., 24.4 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • Form G has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • at least one e.g., one, two, three, four, five, six, seven, eight, nine or ten
  • Form G has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern Attorney Docket No. TGO-025WO comprising at least four characteristic peaks at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 5.4 to 5.8 (e.g., 5.6 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 13.7 to 14.1 (e.g., 13.9 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.1 to 18.5 (e.g., 18.3 ⁇ 0.2), 18.3 to 18.7 (e.g., 18.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 19.7 to 20.1 (e.g.,
  • Form G has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 5.4 to 5.8 (e.g., 5.6 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 13.7 to 14.1 (e.g., 13.9 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.1 to 18.5 (e.g., 18.3 ⁇ 0.2), 18.3 to 18.7 (e.g., 18.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 19.7 to 20.1 (e.g., 19.9 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 21 to 21.4 (e.g., 2
  • Form G has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 5.4 to 5.8 (e.g., 5.6 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 13.7 to 14.1 (e.g., 13.9 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.1 to 18.5 (e.g., 18.3 ⁇ 0.2), 18.3 to 18.7 (e.g., 18.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 19.7 to 20.1 (e.g., 19.9 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 21 to 21.4 (e.g.,
  • TGO-025WO 24.2 to 24.6 (e.g., 24.4 ⁇ 0.2), 24.5 to 24.9 (e.g., 24.7 ⁇ 0.2), 25 to 25.4 (e.g., 25.2 ⁇ 0.2), 26.1 to 26.5 (e.g., 26.3 ⁇ 0.2), 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2), 27.4 to 27.8 (e.g., 27.6 ⁇ 0.2), 27.8 to 28.2 (e.g., 28 ⁇ 0.2), 28.7 to 29.1 (e.g., 28.9 ⁇ 0.2), 31.5 to 31.9 (e.g., 31.7 ⁇ 0.2), 34 to 34.4 (e.g., 34.2 ⁇ 0.2) and 35.8 to 36.2 (e.g., 36 ⁇ 0.2).
  • 34.4 e.g., 34.2 ⁇ 0.2
  • 35.8 to 36.2 e.g., 36 ⁇ 0.2.
  • Form G has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 5.4 to 5.8 (e.g., 5.6 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 13.7 to 14.1 (e.g., 13.9 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.1 to 18.5 (e.g., 18.3 ⁇ 0.2), 18.3 to 18.7 (e.g., 18.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 19.7 to 20.1 (e.g., 19.9 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 21 to 21.4 (e.g.,
  • Form G has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 5.4 to 5.8 (e.g., 5.6 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 13.7 to 14.1 (e.g., 13.9 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.1 to 18.5 (e.g., 18.3 ⁇ 0.2), 18.3 to 18.7 (e.g., 18.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 19.7 to 20.1 (e.g., 19.9 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 21 to 21.4 (e.g.,
  • Form G has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 5.4 to 5.8 (e.g., 5.6 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 13.7 to 14.1 (e.g., 13.9 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.1 to 18.5 (e.g., 18.3 ⁇ 0.2), 18.3 to 18.7 (e.g., 18.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 19.7 to 20.1 (e.g., 19.9 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 21 to 21.4 (e.g.,
  • Form G has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 5.4 to 5.8 (e.g., 5.6 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 13.7 to 14.1 (e.g., 13.9 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.1 to 18.5 (e.g., 18.3 ⁇ 0.2), 18.3 to 18.7 (e.g., 18.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 19.7 to 20.1 (e.g., 19.9 ⁇ 0.2), 20.7 to 21.1 (e.g.
  • Form G has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 5.4 to 5.8 (e.g., 5.6 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 13.7 to 14.1 (e.g., 13.9 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.1 to 18.5 (e.g., 18.3 ⁇ 0.2), 18.3 to 18.7 (e.g., 18.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 19.7 to 20.1 (e.g., 19.9 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 21 to 21.4 (e.g.,
  • Form G has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 5.4 to 5.8 (e.g., 5.6 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 13.7 to 14.1 (e.g., 13.9 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.1 to 18.5 (e.g., 18.3 ⁇ 0.2), 18.3 to 18.7 (e.g., 18.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 19.7 to 20.1 (e.g., 19.9 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 21 to 21.4 (e.g.,
  • Form G has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 5.4 to 5.8 (e.g., 5.6 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 13.7 to 14.1 (e.g., 13.9 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), Attorney Docket No.
  • TGO-025WO 16.5 to 16.9 e.g., 16.7 ⁇ 0.2
  • 17.7 to 18.1 e.g., 17.9 ⁇ 0.2
  • 18.1 to 18.5 e.g., 18.3 ⁇ 0.2
  • 18.3 to 18.7 e.g., 18.5 ⁇ 0.2
  • 18.7 to 19.1 e.g., 18.9 ⁇ 0.2
  • 19.1 to 19.5 e.g., 19.3 ⁇ 0.2
  • 19.3 to 19.7 e.g., 19.5 ⁇ 0.2
  • 19.7 to 20.1 e.g., 19.9 ⁇ 0.2
  • 20.7 to 21.1 e.g., 20.9 ⁇ 0.2
  • 21 to 21.4 e.g., 21.2 ⁇ 0.2
  • 22.4 to 22.8 e.g., 22.6 ⁇ 0.2
  • 23.7 to 24.1 e.g., 23.9 ⁇ 0.2
  • 24.2 to 24.6 e.g., 24.4 ⁇ 0.2
  • 24.5 to 24.9 e.g., 24.7 ⁇ 0.2
  • 25 to 25.4 e.g., 2
  • Form G has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 5.4 to 5.8 (e.g., 5.6 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 13.7 to 14.1 (e.g., 13.9 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.1 to 18.5 (e.g., 18.3 ⁇ 0.2), 18.3 to 18.7 (e.g., 18.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 19.7 to 20.1 (e.g., 19.9 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 21 to 21.4 (e.g.
  • Form G has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 5.4 to 5.8 (e.g., 5.6 ⁇ 0.2), 10.3 to 10.7 (e.g., 10.5 ⁇ 0.2), 13.7 to 14.1 (e.g., 13.9 ⁇ 0.2), 15.6 to 16 (e.g., 15.8 ⁇ 0.2), 16.5 to 16.9 (e.g., 16.7 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.1 to 18.5 (e.g., 18.3 ⁇ 0.2), 18.3 to 18.7 (e.g., 18.5 ⁇ 0.2), 18.7 to 19.1 (e.g., 18.9 ⁇ 0.2), 19.1 to 19.5 (e.g., 19.3 ⁇ 0.2), 19.3 to 19.7 (e.g., 19.5 ⁇ 0.2), 19.7 to 20.1 (e.g., 19.9 ⁇ 0.2), 20.7 to 21.1 (e.g., 20.9 ⁇ 0.2), 21 to 21.4 (e.g.
  • Form G has an XRPD pattern (obtained using CuKa radiation) substantially corresponding to the XRPD diffraction pattern shown in FIG. 8A.
  • Attorney Docket No. TGO-025WO [0190]
  • Form G has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2 values in degrees shown in Table 9 ( ⁇ 0.2 degrees).
  • Form G has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2 values in degrees and with relative intensities shown in Table 9 allowing for variation due to experimental conditions.
  • Table 9 – XRPD peaks for Form G of a compound of Formula (I) Attorney Docket No. TGO-025WO
  • Form G is substantially characterized by the thermal gravimetric analysis (TGA) as shown in FIG.8B.
  • TGA thermal gravimetric analysis
  • DSC differential scanning calorimetry profile
  • Form G can be characterized by the differential scanning calorimetry profile (DSC) shown in FIG.8C, showing a small melting peak at T onset of 165.3°C and a melting peak at T onset of 180.1°C with an enthalpy of about 78J/g.
  • Crystalline Form H [0194] In certain embodiments, the crystalline form of the free base of the compound of formula (I) is crystalline Form H. Crystalline Form H is a hydrate crystalline form of the compound of formula (I). [0195] Form H can be obtained from water by competitive equilibration. [0196] Form H is of high crystallinity.
  • FIG.9C shows a dehydration from 20.5°C, an exothermic peak at 88.2°C, an endothermic peak at 133.4°C and a melting peak at T onset of 197.2°C with an enthalpy of about 9J/g.
  • TGA shows about 1.8% weight loss at about 100°C.
  • 1 H-NMR shows no detectable residual solvent.
  • Form H has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three or four) characteristic peaks at values of 2 in degrees selected from 18.7 ⁇ 0.2, 19 ⁇ 0.2, 20.5 ⁇ 0.2 and 20.8 ⁇ 0.2. In certain embodiments, Form H has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 18.7 ⁇ 0.2, 19 ⁇ 0.2, 20.5 ⁇ 0.2 and 20.8 ⁇ 0.2. In certain embodiments, Form H has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in Attorney Docket No. TGO-025WO degrees selected from 18.7 ⁇ 0.2, 19 ⁇ 0.2, 20.5 ⁇ 0.2 and 20.8 ⁇ 0.2.
  • TGO-025WO degrees selected from 18.7 ⁇ 0.2, 19 ⁇ 0.2, 20.5 ⁇ 0.2 and 20.8 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 18.7 ⁇ 0.2, 19 ⁇ 0.2, 20.5 ⁇ 0.2 and 20.8 ⁇ 0.2. [0199] In certain embodiments, Form H has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 18.7 ⁇ 0.2, 19 ⁇ 0.2, 20.5 ⁇ 0.2 and 20.8 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 18.7 ⁇ 0.2, 19 ⁇ 0.2, 20.5 ⁇ 0.2 and 20.8 ⁇ 0.2 and at least one (e.g., one, two, three, four, five or six) additional characteristic peaks at values of 2 in degrees selected from: 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 19.7 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three or four) characteristic peaks between and including the following values of 2 in degrees: 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2) and 20.6 to 21 (e.g., 20.8 ⁇ 0.2).
  • 18.5 to 18.9 e.g., 18.7 ⁇ 0.2
  • 18.8 to 19.2 e.g., 19 ⁇ 0.2
  • 20.3 to 20.7 e.g., 20.5 ⁇ 0.2
  • 20.6 to 21 e.g., 20.8 ⁇ 0.2
  • Form H has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2) and 20.6 to 21 (e.g., 20.8 ⁇ 0.2).
  • Form H has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2) and 20.6 to 21 (e.g., 20.8 ⁇ 0.2).
  • Form H has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2) and 20.6 to 21 (e.g., 20.8 ⁇ 0.2).
  • Form H has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2) and 20.6 to 21 (e.g., 20.8 ⁇ 0.2).
  • Form H has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2) and 20.6 to 21 (e.g., 20.8 ⁇ 0.2) and at least one (e.g., one, two, three, four, five or six) additional characteristic peaks Attorney Docket No.
  • TGO-025WO between and including values of 2 in degrees selected from: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25 ⁇ 0.2) or 25.5 to 25.9 (e.g., 25.7 ⁇ 0.2).
  • 12.1 to 12.5 e.g., 12.3 ⁇ 0.2
  • 14.7 to 15.1 e.g., 14.9 ⁇ 0.2
  • 16.2 to 16.6 e.g., 16.4 ⁇ 0.2
  • 17.7 to 18.1 e.g., 17.9 ⁇ 0.2
  • 19.5 to 19.9 e.g., 19.7 ⁇ 0.2
  • 21.5 to 21.9
  • Form H has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • at least one e.g., one, two, three, four, five, six, seven, eight, nine or ten
  • Form H has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at Attorney Docket No.
  • Form H has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Form H has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2), 20.6 to 21 (e.g., 20.8 ⁇ 0.2), 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25), a X-ray powder
  • Form H has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2), 20.6 to 21 (e.g., 20.8 ⁇ 0.2), 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25 ⁇ 0.2) and 25.5 to 25.9 (e.g., 25.7 ⁇ 0.2).
  • 12.1 to 12.5 e.g., 12.3
  • Form H has an X- ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2), 20.6 to 21 (e.g., 20.8 ⁇ 0.2), 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25 ⁇ 0.2) and 25.5 to 25.9 (e.g., 25.7 ⁇ 0.2).
  • 12.1 to 12.5 e.g.,
  • Form H has an X- ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2), 20.6 to 21 (e.g., 20.8 ⁇ 0.2), 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25 ⁇ 0.2) and 25.5 to 25.9 (e.g., 25.7 ⁇ 0.2).
  • 12.1 to 12.5 e.g.,
  • Form H has an X- Attorney Docket No. TGO-025WO ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2), 20.6 to 21 (e.g., 20.8 ⁇ 0.2), 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25 ⁇ 0.2) and 25.5 to 25.9 (e.g., 25.7
  • Form H has an X- ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2), 20.6 to 21 (e.g., 20.8 ⁇ 0.2), 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25 ⁇ 0.2) and 25.5 to 25.9 (e.g., 25.7 ⁇ 0.2).
  • 12.1 to 12.5 e.g.,
  • Form H has an X- ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2), 20.6 to 21 (e.g., 20.8 ⁇ 0.2), 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25 ⁇ 0.2) and 25.5 to 25.9 (e.g., 25.7 ⁇ 0.2).
  • 12.1 to 12.5 e.g.,
  • Form H has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2), 20.6 to 21 (e.g., 20.8 ⁇ 0.2), 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25 ⁇ 0.2) and 25.5 to 25.9 (e.g., 25.7 ⁇ 0.2).
  • 12.1 to 12.5 e.g., 12.
  • Form H has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2), 20.6 to 21 (e.g., 20.8 ⁇ 0.2), 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25 ⁇ 0.2) and 25.5 to 25.9 (e.g., 25.7 ⁇ 0.2).
  • 12.1 to 12.5 e.g., 12.
  • Form H has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2), 20.6 to 21 (e.g., Attorney Docket No.
  • 12.1 to 12.5 e.g., 12.3 ⁇ 0.2
  • 14.7 to 15.1 e.g., 14.9 ⁇ 0.2
  • 16.2 to 16.6 e.g., 16.4 ⁇ 0.2
  • 17.7 to 18.1 e.g., 17.9 ⁇ 0.2
  • 18.5 to 18.9 e.
  • TGO-025WO 20.8 ⁇ 0.2 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25 ⁇ 0.2) and 25.5 to 25.9 (e.g., 25.7 ⁇ 0.2).
  • Form H has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2), 20.6 to 21 (e.g., 20.8 ⁇ 0.2), 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25 ⁇ 0.2) and 25.5 to 25.9 (e.g., 25.7 ⁇ 0.2).
  • 12.1 to 12.5 e.g.,
  • Form H has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.7 to 15.1 (e.g., 14.9 ⁇ 0.2), 16.2 to 16.6 (e.g., 16.4 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18.5 to 18.9 (e.g., 18.7 ⁇ 0.2), 18.8 to 19.2 (e.g., 19 ⁇ 0.2), 19.5 to 19.9 (e.g., 19.7 ⁇ 0.2), 20.3 to 20.7 (e.g., 20.5 ⁇ 0.2), 20.6 to 21 (e.g., 20.8 ⁇ 0.2), 21.5 to 21.9 (e.g., 21.7 ⁇ 0.2), 24.4 to 24.8 (e.g., 24.6 ⁇ 0.2), 24.8 to 25.2 (e.g., 25 ⁇ 0.2) and 25.5 to 25.9 (e.g., 25.7 ⁇ 0.2).
  • 12.1 to 12.5 e.g., 12.3 ⁇ 0.2
  • Form H has an XRPD pattern (obtained using CuKa radiation) substantially corresponding to the XRPD diffraction pattern shown in FIG. 9A.
  • Form H has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2 values in degrees shown in Table 10 ( ⁇ 0.2 degrees).
  • Form H has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2 values in degrees and with relative intensities shown in Table 10 allowing for variation due to experimental conditions.
  • Form H is substantially characterized by the thermal gravimetric analysis (TGA) as shown in FIG.9B.
  • TGA thermal gravimetric analysis
  • DSC differential scanning calorimetry profile
  • Form H can be characterized by the differential scanning calorimetry profile (DSC) shown in FIG.9C, showing a dehydration from 20.5°C, an exothermic peak at 88.2°C, an endothermic peak at 133.4°C and a melting peak at T onset of 197.2°C with an enthalpy of about 9J/g.
  • Crystalline Form I [0213] In certain embodiments, the crystalline form of the free base of the compound of formula (I) is crystalline Form I. Crystalline Form I is likely a hydrate crystalline form of the compound of formula (I). [0214] Form I can be obtained after heating Form A to 180°C. [0215] Form I is of high crystallinity. Attorney Docket No.
  • Form I DSC shows a dehydration endothermic peak from about 52°C and a melting peak at Tonset of 192.4°C with an enthalpy of about 55J/g.
  • 1 H-NMR shows no detectable residual solvent.
  • Form I has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven or eight) characteristic peaks at values of 2 in degrees selected from 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2 and 26.7 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2 and 26.7 ⁇ 0.2. In certain embodiments, Form I has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2 and 26.7 ⁇ 0.2.
  • Form I has an X- ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2 and 26.7 ⁇ 0.2. In certain embodiments, Form I has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2 and 26.7 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2 and 26.7 ⁇ 0.2. In certain embodiments, Form I has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2 and 26.7 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2 and 26.7 ⁇ 0.2. [0218] In certain embodiments, Form I has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2 and 26.7 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • 17.7 to 18.1 e.g., 17.9 ⁇ 0.2
  • 18 to 18.4 e.g., 18.2 ⁇ 0.2
  • 18.4 to 18.8 e.g., 18.6 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • Form I has an X-ray Attorney Docket No. TGO-025WO powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • 17.7 to 18.1 e.g., 17.9 ⁇ 0.2
  • 18 to 18.4 e.g., 18.2 ⁇ 0.2
  • 18.4 to 18.8 e.g., 18.6 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 19.6 to 20 e.g., 19.8 ⁇ 0.2
  • Form I has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • 17.7 to 18.1 e.g., 17.9 ⁇ 0.2
  • 18 to 18.4 e.g., 18.2 ⁇ 0.2
  • 18.4 to 18.8 e.g., 18.6 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 19.6 to 20 e.g., 19.8 ⁇ 0.2
  • 20.9 to 21.3 e.g
  • Form I has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • 17.7 to 18.1 e.g., 17.9 ⁇ 0.2
  • 18 to 18.4 e.g., 18.2 ⁇ 0.2
  • 18.4 to 18.8 e.g., 18.6 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 19.6 to 20 e.g., 19.8 ⁇ 0.2
  • 20.9 to 21.3 e.g
  • Form I has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • 17.7 to 18.1 e.g., 17.9 ⁇ 0.2
  • 18 to 18.4 e.g., 18.2 ⁇ 0.2
  • 18.4 to 18.8 e.g., 18.6 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 19.6 to 20 e.g., 19.8 ⁇ 0.2
  • 20.9 to 21.3 e.g
  • Form I has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • 17.7 to 18.1 e.g., 17.9 ⁇ 0.2
  • 18 to 18.4 e.g., 18.2 ⁇ 0.2
  • 18.4 to 18.8 e.g., 18.6 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 19.6 to 20 e.g., 19.8 ⁇ 0.2
  • 20.9 to 21.3 e.g
  • Form I has an X-ray powder diffraction pattern comprising at least six characteristic peaks between and including the following values of 2 in degrees: 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • 17.7 to 18.1 e.g., 17.9 ⁇ 0.2
  • 18 to 18.4 e.g., 18.2 ⁇ 0.2
  • 18.4 to 18.8 e.g., 18.6 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 19.6 to 20 e.g., 19.8 ⁇ 0.2
  • 20.9 to 21.3 e.g
  • Form I has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • 17.7 to 18.1 e.g., 17.9 ⁇ 0.2
  • 18 to 18.4 e.g., 18.2 ⁇ 0.2
  • 18.4 to 18.8 e.g., 18.6 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 19.6 to 20 e.g., 19.8 ⁇ 0.2
  • 20.9 to 21.3 e.g
  • Form I has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 17.7 to 18.1 Attorney Docket No. TGO-025WO (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2) and 26.5 to 26.9 (e.g., 26.7 ⁇ 0.2).
  • TGO-025WO e.g., 17.9 ⁇ 0.2
  • 18 to 18.4 e.g., 18.2 ⁇ 0.2
  • 18.4 to 18.8 e.g., 18.6 ⁇ 0.2
  • 19.2 to 19.6 e.g., 19.4 ⁇ 0.2
  • 19.6 to 20 e.g., 19.8 ⁇ 0.2
  • Form I has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks at values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • at least one e.g., one, two, three, four, five, six, seven, eight, nine or ten
  • Form I has an X- ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least two characteristic peaks at values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least three characteristic peaks at values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least four characteristic peaks at values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least six characteristic peaks at values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least seven characteristic peaks at values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, Attorney Docket No.
  • Form I has an X-ray powder diffraction pattern comprising at least eight characteristic peaks at values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least nine characteristic peaks at values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least ten characteristic peaks at values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • Form I has an X-ray powder diffraction pattern comprising at least one (e.g., one, two, three, four, five, six, seven, eight, nine or ten) characteristic peaks between and including the following values of 2 in degrees: 8.7 to 9.1 (e.g., 8.9 ⁇ 0.2), 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.4 to 14.8 (e.g., 14.6 ⁇ 0.2), 15.3 to 15.7 (e.g., 15.5 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 20.9 to 8.7 to 9.
  • Form I has an X-ray powder diffraction pattern comprising at least one characteristic peak between and including the following values of 2 in degrees: 8.7 to 9.1 (e.g., 8.9 ⁇ 0.2), 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.4 to 14.8 (e.g., 14.6 ⁇ 0.2), 15.3 to 15.7 (e.g., 15.5 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2),
  • Form I has an X-ray powder diffraction pattern comprising at least two characteristic peaks between and including the following values of 2 in degrees: 8.7 to 9.1 (e.g., 8.9 ⁇ 0.2), 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.4 to 14.8 (e.g., 14.6 ⁇ 0.2), 15.3 to 15.7 (e.g., 15.5 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4
  • Form I has an X-ray powder diffraction pattern comprising at least three characteristic peaks between and including the following values of 2 in degrees: 8.7 to 9.1 (e.g., 8.9 ⁇ 0.2), 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.4 to 14.8 (e.g., 14.6 ⁇ 0.2), 15.3 to 15.7 (e.g., 15.5 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2),
  • Form I has an X-ray powder diffraction pattern comprising at least four characteristic peaks between and including the following values of 2 in degrees: 8.7 to 9.1 (e.g., 8.9 ⁇ 0.2), 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.4 to 14.8 (e.g., 14.6 ⁇ 0.2), 15.3 to 15.7 (e.g., 15.5 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2),
  • Form I has an X-ray powder diffraction pattern comprising at least five characteristic peaks between and including the following values of 2 in degrees: 8.7 to 9.1 (e.g., 8.9 ⁇ 0.2), 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.4 to 14.8 (e.g., 14.6 ⁇ 0.2), 15.3 to 15.7 (e.g., 15.5 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2),
  • Form I has an X-ray powder diffraction pattern comprising at least six Attorney Docket No. TGO-025WO characteristic peaks between and including the following values of 2 in degrees: 8.7 to 9.1 (e.g., 8.9 ⁇ 0.2), 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.4 to 14.8 (e.g., 14.6 ⁇ 0.2), 15.3 to 15.7 (e.g., 15.5 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to
  • Form I has an X-ray powder diffraction pattern comprising at least seven characteristic peaks between and including the following values of 2 in degrees: 8.7 to 9.1 (e.g., 8.9 ⁇ 0.2), 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.4 to 14.8 (e.g., 14.6 ⁇ 0.2), 15.3 to 15.7 (e.g., 15.5 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2),
  • Form I has an X-ray powder diffraction pattern comprising at least eight characteristic peaks between and including the following values of 2 in degrees: 8.7 to 9.1 (e.g., 8.9 ⁇ 0.2), 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.4 to 14.8 (e.g., 14.6 ⁇ 0.2), 15.3 to 15.7 (e.g., 15.5 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2),
  • Form I has an X-ray powder diffraction pattern comprising at least nine characteristic peaks between and including the following values of 2 in degrees: 8.7 to 9.1 (e.g., 8.9 ⁇ 0.2), 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.4 to 14.8 (e.g., 14.6 ⁇ 0.2), 15.3 to 15.7 (e.g., 15.5 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇ 0.2),
  • Form I has an X-ray powder diffraction pattern comprising at least ten characteristic peaks between and including the following values of 2 in degrees: 8.7 to 9.1 (e.g., 8.9 ⁇ 0.2), 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.4 to 14.8 (e.g., 14.6 ⁇ 0.2), 15.3 to 15.7 (e.g., 15.5 ⁇ 0.2), Attorney Docket No.
  • Form I has an X-ray powder diffraction pattern comprising characteristic peaks between and including the following values of 2 in degrees: 8.7 to 9.1 (e.g., 8.9 ⁇ 0.2), 12.1 to 12.5 (e.g., 12.3 ⁇ 0.2), 14.4 to 14.8 (e.g., 14.6 ⁇ 0.2), 15.3 to 15.7 (e.g., 15.5 ⁇ 0.2), 15.8 to 16.2 (e.g., 16 ⁇ 0.2), 17 to 17.4 (e.g., 17.2 ⁇ 0.2), 17.7 to 18.1 (e.g., 17.9 ⁇ 0.2), 18 to 18.4 (e.g., 18.2 ⁇ 0.2), 18.4 to 18.8 (e.g., 18.6 ⁇ 0.2), 19.2 to 19.6 (e.g., 19.4 ⁇ 0.2), 19.6 to 20 (e.g., 19.8 ⁇ 0.2), 20 to 20.4 (e.g., 20.2 ⁇ 0.2), 20.9 to 21.3 (e.g., 21.1 ⁇ 0.2), 22 to 22.4 (e.g., 22.2 ⁇
  • Form I has an XRPD pattern (obtained using CuKa radiation) substantially corresponding to the XRPD diffraction pattern shown in FIG.10A.
  • Form I has an XRPD pattern (obtained using CuKa radiation) with characteristic peaks comprising one, two, three, four, five, six, seven, eight, nine, or ten characteristic peaks, in terms of 2 values in degrees shown in Table 11 ( ⁇ 0.2 degrees).
  • Form I has an XRPD pattern (obtained using CuKa radiation) comprising at least 50% of the peaks at 2 values in degrees and with relative intensities shown in Table 11 allowing for variation due to experimental conditions.
  • Form I is substantially characterized by the differential scanning calorimetry profile (DSC) shown in FIG.10B.
  • DSC differential scanning calorimetry profile
  • Form I can be characterized by the differential scanning calorimetry profile (DSC) shown in FIG.10B, showing a dehydration endothermic peak from about 52°C and a melting peak at T onset of 192.4°C with an enthalpy of about 55J/g.
  • Compound I e.g., a crystalline form described herein
  • an effective amount e.g., a therapeutically effective amount
  • the amount of Compound I (e.g., a crystalline form described herein) actually administered will typically be determined by a physician, in the light of the relevant circumstances, including the condition to be treated, the chosen route of administration, the age, weight, and response of the individual patient, the severity of the patient’s symptoms, and the like.
  • the effective amount of Compound I e.g., a crystalline form described herein
  • the effective amount of Compound I is 40 mg or 80 mg.
  • the effective amount of Compound I (e.g., a crystalline form described herein) is 40 mg or 80 mg administered once daily. In some embodiments, the effective amount of Compound I (e.g., a crystalline form described herein) is 80 mg. In some embodiments, the effective amount of Compound I (e.g., a crystalline form described herein) is 80 mg administered once daily. In some embodiments, the effective amount of Compound I (e.g., a crystalline form described herein) is 40 mg. In some embodiments, the effective amount of Compound I (e.g., a crystalline form described herein) is 40 mg administered once daily.
  • references to numeric amounts of Compound I in crystalline forms, pharmaceutical compositions and the like refer to the amount of a specific crystalline form or pharmaceutical composition that delivers the recited numeric amount of Compound I free base equivalent.
  • Compound I e.g., a crystalline form described herein
  • Such compositions can be prepared in a manner well known in the pharmaceutical art and comprise at least one active compound.
  • Compound I (e.g., a crystalline form described herein) is administered as a pharmaceutical composition comprising an effective amount of Compound I (e.g., a crystalline form described herein), and a pharmaceutically acceptable carrier.
  • the carrier is a parenteral carrier, oral or topical carrier.
  • pharmaceutically acceptable carrier refers to a carrier, adjuvant, or vehicle that may be administered to a patient, together with a compound provided herewith, and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic amount of the compound.
  • Pharmaceutically acceptable carriers that may be used in the pharmaceutical compositions provided herewith include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, self-emulsifying drug delivery systems (SEDDS) such as d– -tocopherol polyethyleneglycol 1000 succinate, surfactants used in pharmaceutical dosage forms such as Tweens or other similar polymeric delivery matrices, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene polyoxypropylene block polymers
  • Cyclodextrins such as –, –, and -cyclodextrin, or chemically modified derivatives such as hydroxyalkylcyclodextrins, including 2 and 3 hydroxypropyl- -cyclodextrins, or other solubilized derivatives may also be advantageously used to enhance delivery of Compound I (e.g., a crystalline form described herein) described herein.
  • the pharmaceutical compositions provided herewith may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally or via an implanted reservoir, preferably by oral administration or administration by injection.
  • the pharmaceutical compositions provided herewith may contain any conventional nontoxic pharmaceutically acceptable carriers, adjuvants or vehicles.
  • the pH of the formulation may be adjusted with pharmaceutically acceptable acids, bases or buffers to enhance the stability of the formulated compound or its delivery form.
  • parenteral as used herein includes subcutaneous, intracutaneous, intravenous, intramuscular, intraarticular, intraarterial, intrasynovial, intrasternal, intrathecal, intralesional and intracranial injection or infusion techniques.
  • Attorney Docket No. TGO-025WO [0230]
  • the compositions for oral administration can take the form of bulk liquid solutions or suspensions, or bulk powders. More commonly, however, the compositions are presented in unit dosage forms to facilitate accurate dosing.
  • unit dosage forms refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient.
  • Typical unit dosage forms include prefilled, premeasured ampules or syringes of the liquid compositions or pills, tablets, capsules or the like in the case of solid compositions.
  • the compound is usually a minor component (from about 0.1 to about 50% by weight or preferably from about 1 to about 40% by weight) with the remainder being various vehicles or carriers and processing aids helpful for forming the desired dosing form.
  • Liquid forms suitable for oral administration may include a suitable aqueous or nonaqueous vehicle with buffers, suspending and dispensing agents, colorants, flavors and the like.
  • Solid forms may include, for example, any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.
  • a binder such as microcrystalline cellulose, gum tragacanth or gelatin
  • an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch
  • Injectable compositions are typically based upon injectable sterile saline or phosphate-buffered saline or other injectable carriers known in the art.
  • the active compound in such compositions is typically a minor component, often being from about 0.05 to 10% by weight with the remainder being the injectable carrier and the like.
  • the pharmaceutical compositions may be in the form of a sterile injectable preparation, for example, as a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated according to techniques known in the art using suitable dispersing or wetting agents (such as, for example, Tween 80) and suspending agents.
  • the sterile injectable preparation may also be a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3–butanediol.
  • a non-toxic parenterally acceptable diluent or solvent for example, as a solution in 1,3–butanediol.
  • acceptable vehicles and solvents that may be employed are mannitol, water, Ringer’s solution and isotonic sodium chloride solution.
  • sterile, fixed oils are conventionally employed as a solvent or suspending medium.
  • any bland fixed oil may be employed including synthetic mono– or diglycerides. Fatty acids, such as oleic acid and its glyceride derivatives are useful in the preparation of Attorney Docket No.
  • TGO-025WO injectables as are natural pharmaceutically acceptable oils, such as olive oil or castor oil, especially in their polyoxyethylated versions.
  • oils such as olive oil or castor oil, especially in their polyoxyethylated versions.
  • These oil solutions or suspensions may also contain a long chain alcohol diluent or dispersant, or carboxymethyl cellulose or similar dispersing agents which are commonly used in the formulation of pharmaceutically acceptable dosage forms such as emulsions and or suspensions.
  • Other commonly used surfactants such as Tweens or Spans and/or other similar emulsifying agents or bioavailability enhancers which are commonly used in the manufacture of pharmaceutically acceptable solid, liquid, or other dosage forms may also be used for the purposes of formulation.
  • Transdermal compositions are typically formulated as a topical ointment or cream containing the active ingredient(s), generally in an amount ranging from about 0.01 to about 20% by weight, preferably from about 0.1 to about 20% by weight, preferably from about 0.1 to about 10% by weight, and more preferably from about 0.5 to about 15% by weight.
  • the active ingredients When formulated as an ointment, the active ingredients will typically be combined with either a paraffinic or a water-miscible ointment base. Alternatively, the active ingredients may be formulated in a cream with, for example an oil-in-water cream base.
  • Such transdermal formulations are well-known in the art and generally include additional ingredients to enhance the dermal penetration of stability of the active ingredients or the formulation.
  • transdermal formulations and ingredients are included within the scope provided herein.
  • Compound I e.g., a crystalline form described herein
  • transdermal administration can be accomplished using a patch either of the reservoir or porous membrane type, or of a solid matrix variety.
  • the pharmaceutical compositions provided herewith may also be administered in the form of suppositories for rectal administration. These compositions can be prepared by mixing a compound provided herewith with a suitable nonirritating excipient which is solid at room temperature but liquid at the rectal temperature and therefore will melt in the rectum to release the active components.
  • compositions provided herewith may be administered by nasal aerosol or inhalation.
  • Such compositions are prepared according to techniques well known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other solubilizing or dispersing agents known in the art.
  • Attorney Docket No. TGO-025WO [0237]
  • the above-described components for orally administrable, injectable or topically administrable, rectally administrable and nasally administrable compositions are merely representative.
  • Compound I e.g., a crystalline form described herein
  • Compound I can also be administered in sustained release forms or from sustained release drug delivery systems.
  • sustained release materials can be found in Remington’s Pharmaceutical Sciences.
  • compositions provided herewith comprise a combination of Compound I (e.g., a crystalline form described herein) and one or more additional therapeutic or prophylactic agents
  • both the compound and the additional agent should be present at dosage levels of between about 1 to 100%, and more preferably between about 5 to 95% of the dosage normally administered in a monotherapy regimen.
  • the additional agents may be administered separately, as part of a multiple dose regimen, from the compounds provided herewith. Alternatively, those agents may be part of a single dosage form, mixed together with the compounds provided herewith in a single composition.
  • Compound I (e.g., a crystalline form described herein) can, for example, be administered by injection, intravenously, intraarterially, subdermally, intraperitoneally, intramuscularly, or subcutaneously; or orally, buccally, nasally, transmucosally, topically, in an ophthalmic preparation, or by inhalation, with a dosage ranging from about 0.5 to about 100 mg/kg of body weight, alternatively dosages between 1 mg and 1000 mg/dose, every 4 to 120 hours, or according to the requirements of the particular drug.
  • the methods herein contemplate administration of an effective amount of compound or composition to achieve the desired or stated effect.
  • the pharmaceutical compositions provided herewith will be administered from about 1 to about 6 times per day or alternatively, as a continuous infusion. Such administration can be used as a chronic or acute therapy.
  • the amount of active ingredient that may be combined with the carrier materials to produce a single dosage form will vary depending upon the host treated and the particular mode of administration.
  • a typical preparation will contain from about 5% to about 95% active compound (w/w).
  • such preparations contain from about 20% to about 80% active compound.
  • Lower or higher doses than those recited above may be required.
  • Specific dosage and treatment regimens for any particular patient will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health status, sex, Attorney Docket No.
  • a maintenance dose of Compound I e.g., a crystalline form described herein
  • composition or combination provided herewith may be administered, if necessary.
  • the dosage or frequency of administration, or both may be reduced, as a function of the symptoms, to a level at which the improved condition is retained when the symptoms have been alleviated to the desired level.
  • Patients may, however, require intermittent treatment on a long term basis upon any recurrence of disease symptoms.
  • the “effective amount” of a compound refers to an amount sufficient to elicit the desired biological response e.g., to treat a disease or disorder described herein.
  • the effective amount of a compound of the disclosure may vary depending on such factors as the desired biological endpoint, the pharmacokinetics of the compound, the disease being treated, the mode of administration, and the age, health, and condition of the subject.
  • An effective amount encompasses therapeutic and prophylactic treatment (i.e., encompasses a “therapeutically effective amount” and a “prophylactically effective amount”).
  • a “therapeutically effective amount” of a compound is an amount sufficient to provide a therapeutic benefit in the therapeutic treatment of a disease, disorder or condition, or to delay or minimize one or more symptoms associated with the disease, disorder or condition.
  • a therapeutically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the therapeutic treatment of the disease, disorder or condition.
  • the term “therapeutically effective amount” can encompass an amount that improves overall therapy, reduces or avoids symptoms or causes of disease or condition, or enhances the therapeutic efficacy of another therapeutic agent.
  • a “prophylactically effective amount” of a compound is an amount sufficient to prevent a disease, disorder or condition, or one or more symptoms associated with the disease, disorder or condition, or prevent its recurrence.
  • a prophylactically effective amount of a compound means an amount of a therapeutic agent, alone Attorney Docket No. TGO-025WO or in combination with other agents, which provides a prophylactic benefit in the prevention of the disease, disorder or condition.
  • the term “prophylactically effective amount” can encompass an amount that improves overall prophylaxis or enhances the prophylactic efficacy of another prophylactic agent.
  • Methods of Treatment are methods of treating a subject having, or at risk of developing, a disease or disorder, the method comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein).
  • the effective amount of Compound I is 40 mg or 80 mg.
  • the effective amount of Compound I is 40 mg or 80 mg administered once daily.
  • the effective amount of Compound I is 80 mg.
  • the effective amount of Compound I is 80 mg administered once daily.
  • the effective amount of Compound I is 40 mg.
  • the effective amount of Compound I is 40 mg administered once daily.
  • Compound I is administered intermittently (e.g., QD 2 weeks on/one week off, QD 1 week on/2 weeks off, QD 2 days on/5 days off, once weekly (QW), biweekly (BIW).
  • Compound I is administered intermittently QD 2 weeks on/one week off.
  • Compound I is administered intermittently QD 1 week on/2 weeks off.
  • Compound I is administered intermittently QD 2 days on/5 days off.
  • Compound I is administered intermittently once weekly (QW).
  • Compound I is administered intermittently biweekly (BIW).
  • the effective amount of Compound I is 40 mg or 80 mg administered once daily (2 weeks on/1 week off). In some embodiments, the effective amount of Compound I is 80 mg administered once daily (2 weeks on/1 week off). In some embodiments, the effective amount of Compound I is 40 mg administered once daily (2 weeks on/1 week off). [0249] In some embodiments, the effective amount of Compound I is 40 mg or 80 mg administered once daily (1 week on/2 weeks off). In some embodiments, the effective amount of Compound I is 80 mg administered once daily (1 week on/2 weeks off). In some embodiments, the effective amount of Compound I is 40 mg administered once daily (1 week on/2 weeks off).
  • the effective amount of Compound I is 40 mg or 80 mg administered once daily (2 days on/5 days off). In some embodiments, the effective amount of Attorney Docket No. TGO-025WO Compound I is 80 mg administered once daily (2 days on/5 days off). In some embodiments, the effective amount of Compound I is 40 mg administered once daily (2 days on/5 days off). [0251] In some embodiments, the effective amount of Compound I is 40 mg or 80 mg administered once weekly. In some embodiments, the effective amount of Compound I is 80 mg administered once weekly. In some embodiments, the effective amount of Compound I is 40 mg administered once weekly. [0252] In some embodiments, the effective amount of Compound I is 40 mg or 80 mg administered twice weekly.
  • the effective amount of Compound I is 80 mg administered twice weekly. In some embodiments, the effective amount of Compound I is 40 mg administered twice weekly.
  • embodiments referencing a “method of treatment” “methods of treating” and the like using Compound I are meant to be applicable to Compound I for use in a method of treatment, Compound I (e.g., the crystalline forms described herein) for use in the manufacturing of a medicament, uses of Compound I (e.g., the crystalline forms described herein) in the manufacturing of a medicament, and uses of Compound I (e.g., the crystalline forms described herein) in a therapeutic method.
  • Compound I e.g., crystalline forms of Compound I
  • Methods of treating a subject having, or at risk of developing, a disease or disorder comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein).
  • Compound I e.g., crystalline forms of Compound I
  • uses of Compound I e.g., crystalline forms of Compound I in the manufacture of a medicament for treating a subject having, or at risk of developing, a disease or disorder.
  • Compound I e.g., crystalline forms of Compound I
  • a method of treating a subject having, or at risk of developing, a disease or disorder comprising administering to the subject an Attorney Docket No. TGO-025WO effective amount of Compound I (e.g., a crystalline form described herein), wherein the disease or disorder is identified as having modified STK11 activity or expression.
  • Compound I e.g., crystalline forms of Compound I
  • the method comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein), wherein the disease or disorder is identified as having modified STK11 activity or expression.
  • Compound I e.g., crystalline forms of Compound I
  • Compound I for use in the manufacture of a medicament for treating a subject having, or at risk of developing, a disease or disorder, wherein the disease or disorder is identified as having modified STK11 activity or expression.
  • Compound I e.g., crystalline forms of Compound I
  • uses of Compound I in the manufacture of a medicament for treating a subject having, or at risk of developing, a disease or disorder, wherein the disease or disorder is identified as having modified STK11 activity or expression.
  • Compound I e.g., crystalline forms of Compound I
  • the disease or disorder is identified as having modified STK11 activity or expression.
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein), wherein the cancer is identified as having modified STK11 activity or expression.
  • Compound I e.g., crystalline forms of Compound I
  • the method comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein), wherein the cancer is identified as having modified STK11 activity or expression.
  • Compound I e.g., crystalline forms of Compound I
  • the cancer is identified as having modified STK11 activity or expression.
  • Attorney Docket No. TGO-025WO Also provided herein are uses of Compound I (e.g., crystalline forms of Compound I) in the manufacture of a medicament for treating a subject having, or at risk of developing, a cancer, wherein the cancer is identified as having modified STK11 activity or expression.
  • Compound I e.g., crystalline forms of Compound I
  • the method or use involves selecting a patient for treatment using one of the Patient Selection methods described herein, prior to administering to the patient the histone deacetylase inhibitor and optionally one or more additional therapeutic agents.
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with a second therapeutic agent, wherein the cancer is identified as having modified STK11 activity or expression.
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with a second therapeutic agent, wherein the cancer is identified as having modified STK11 activity or expression and the cancer is identified as having wildtype KRAS activity or expression.
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with a second therapeutic agent, wherein the cancer is identified as having modified STK11 activity or expression and the cancer is identified as having modified KRAS (e.g., KRAS G12C , KRAS G12D , KRAS G12V ) activity or expression.
  • Compound I e.g., a crystalline form described herein
  • KRAS e.g., KRAS G12C , KRAS G12D , KRAS G12V
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with a second therapeutic agent, wherein the cancer is identified as having modified STK11 activity or expression and the cancer is identified as having modified KRAS (e.g., KRAS G12C , KRAS G12D , KRAS G12V ) activity or expression or wildtype KRAS activity or expression.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with an immune checkpoint modulator, wherein the cancer is identified as having modified STK11 activity or Attorney Docket No. TGO-025WO expression.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with an anti-PD1 agent or an anti-PD-L1 agent, wherein the cancer is identified as having modified STK11 activity or expression.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with an anti-PD1 agent or an anti-PD-L1 agent, wherein the cancer is identified as having modified STK11 activity or expression, wherein the anti-PD1 agent or the anti-PD-L1 agent is selected from the group consisting of nivolumab; CT-011; AMP-224; pembrolizumab; pidilizumab; cemiplimab; dostarlimab; prolgolimab; spartalizumab; camrelizumab; sasanlimab, sintilimab; tislelizumab; toripalimab; retifanlimab; MEDI0680; budigalimab; geptanolimab, BMS936559; durvalum
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with an anti-PD1 therapy or an anti- PD-L1 therapy, wherein the cancer is identified as having modified STK11 activity or expression.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein), wherein the cancer is identified as having modified STK11 activity or expression and the cancer is identified as resistant to anti-PD1 therapy or anti-PD-L1 therapy.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein), wherein the cancer is identified as having modified STK11 activity or expression and the cancer is identified as having intrinsic resistance to anti-PD1 therapy or anti-PD-L1 therapy.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein), wherein the cancer is identified as having modified STK11 activity or expression and the cancer is identified as having acquired resistance to anti-PD1 therapy or anti- PD-L1 therapy.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with a second therapeutic agent, wherein the lung cancer is identified as having modified STK11 activity or expression.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with a second therapeutic agent, wherein the lung cancer is identified as having modified STK11 activity or expression and the lung cancer is identified as having wildtype KRAS activity or expression.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with a second therapeutic agent, wherein the lung cancer is identified as having modified STK11 activity or expression and the lung cancer is identified as having modified KRAS (e.g., KRAS G12C , KRAS G12D , KRAS G12V ) activity or expression.
  • Compound I e.g., a crystalline form described herein
  • KRAS e.g., KRAS G12C , KRAS G12D , KRAS G12V
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with a second therapeutic agent, wherein the lung cancer is identified as having modified STK11 activity or expression and the lung cancer is identified as having modified KRAS (e.g., KRAS G12C , KRAS G12D , KRAS G12V ) activity or expression or wildtype KRAS activity or expression.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with an immune checkpoint modulator, wherein the lung cancer is identified as having modified STK11 activity or expression.
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with an anti-PD1 agent or an anti-PD-L1 agent, wherein the lung cancer is identified as having modified STK11 activity or expression.
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with an anti-PD1 agent or an anti-PD-L1 agent, wherein the lung cancer is identified as having modified STK11 activity or expression, wherein the anti-PD1 agent or the anti-PD-L1 agent is selected from the group consisting of nivolumab; CT-011; AMP-224; Attorney Docket No.
  • Compound I e.g., a crystalline form described herein
  • TGO-025WO pembrolizumab TGO-025WO pembrolizumab; pidilizumab; cemiplimab; dostarlimab; prolgolimab; spartalizumab; camrelizumab; sasanlimab, sintilimab; tislelizumab; toripalimab; retifanlimab; MEDI0680; budigalimab; geptanolimab, BMS936559; durvalumab; avelumab; envafolimab; cosibelimab; sugemalimab, AUNP-12; atezolizumab and CA-170.
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with an anti-PD1 therapy or an anti-PD-L1 therapy, wherein the lung cancer is identified as having modified STK11 activity or expression.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein), wherein the lung cancer is identified as having modified STK11 activity or expression and the lung cancer is identified as resistant to anti-PD1 therapy or anti-PD-L1 therapy.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein), wherein the lung cancer is identified as having modified STK11 activity or expression and the lung cancer is identified as having intrinsic resistance to anti-PD1 therapy or anti-PD-L1 therapy.
  • Compound I e.g., a crystalline form described herein
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein), wherein the lung cancer is identified as having modified STK11 activity or expression and the lung cancer is identified as having acquired resistance to anti-PD1 therapy or anti-PD-L1 therapy.
  • Compound I e.g., a crystalline form described herein
  • the method comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with a second therapeutic agent, wherein the lung cancer is identified as having modified STK11 activity or expression.
  • provided is a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with an immune checkpoint modulator, wherein the lung cancer is identified as having modified STK11 activity or expression.
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with Attorney Docket No.
  • an anti-PD1 agent or an anti-PD-L1 agent wherein the lung cancer is identified as having modified STK11 activity or expression.
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with an anti-PD1 agent or an anti-PD-L1 agent, wherein the lung cancer is identified as having modified STK11 activity or expression, wherein the anti-PD1 agent or the anti-PD-L1 agent is selected from the group consisting of nivolumab; CT-011; AMP-224; pembrolizumab; pidilizumab; cemiplimab; dostarlimab; prolgolimab; spartalizumab; camrelizumab; sasanlimab, sintilimab; tislelizumab; toripalim
  • Compound I e.g., a
  • a method of treating a subject having, or at risk of developing, a lung cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with an anti-PD1 therapy or an anti-PD-L1 therapy, wherein the lung cancer is identified as having modified STK11 activity or expression.
  • Compound I e.g., a crystalline form described herein
  • the combination of Compound I (e.g., a crystalline form described herein) and an immune checkpoint modulator is synergistic.
  • the method comprises identifying the subject as having one or more cancer cells that have modified STK11 activity or expression.
  • the method comprises identifying the subject as having one or more cancer cells that have modified STK11 activity or expression and are resistant to anti-PD1 therapy or anti-PD-L1 therapy.
  • the method comprises administering to the subject an immune checkpoint modulator and Compound I (e.g., a crystalline form described herein), wherein the treatment modulates and/or improves the Teff cell to Treg cell ratio in the tumor or tumor microenvironment.
  • the method comprises administering to the subject an immune checkpoint modulator Compound I (e.g., a crystalline form described herein), wherein the treatment reduces or depletes Treg cells in the tumor or tumor microenvironment.
  • the method comprises administering to the subject an immune checkpoint modulator and Compound I (e.g., a crystalline form described herein), wherein the treatment induces or increases the expression of cytokines that promote Attorney Docket No. TGO-025WO anti-tumor activity.
  • the method further comprises the cytokines are selected from the group of CXCL9, CXCL10, and CXCL11.
  • the method comprises administering to the subject an immune checkpoint modulator and Compound I (e.g., a crystalline form described herein), wherein the treatment reduces the expression of cytokines that promote Treg cell recruitment.
  • the cytokines are CCL1 or CCL22.
  • the method comprises administering to the subject an immune checkpoint modulator and Compound I (e.g., a crystalline form described herein), wherein the administering of the Compound I (e.g., a crystalline form described herein) does not substantially reduce erythroid or myeloid cell viability (e.g., reduces the cell viability by less than 10%, by less than 20%, by less than 30%, by less than 40% or by less than 50%).
  • the cancer presents an immune evasion phenotype characterized by STK11 mutant expression comprising: administering Compound I (e.g., a crystalline form described herein), wherein Compound I (e.g., a crystalline form described herein) is capable of attenuating or reversing the immune evasion phenotype.
  • the method further comprises administering an immune checkpoint modulator.
  • the method comprises administering to the subject an immune checkpoint modulator and Compound I (e.g., a crystalline form described herein), wherein the treatment results in increased IFNgamma expression in the tumor or tumor microenvironment.
  • a method of treating a subject having, or at risk of developing, an immune evasive cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein), wherein the immune evasive cancer is identified as having modified STK11 activity or expression.
  • a method of treating a subject having, or at risk of developing, an immune evasive cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with a second therapeutic agent, wherein the immune evasive cancer is identified as having modified STK11 activity or expression.
  • the second therapeutic agent is an immune checkpoint modulator as described herein.
  • a method of reversing immune evasion in a subject having, or at risk of developing, a cancer comprising administering to the Attorney Docket No. TGO-025WO subject an effective amount of Compound I (e.g., a crystalline form described herein), wherein the cancer is identified as having modified STK11 activity or expression.
  • a method of reversing immune evasion in a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with a second therapeutic agent, wherein the cancer is identified as having modified STK11 activity or expression.
  • Compound I e.g., a crystalline form described herein
  • a method of reversing immune evasion in a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) in combination with a second therapeutic agent, wherein the cancer is identified as having modified STK11 activity or expression and the immune evasion is caused by anti-PD1 therapy or anti-PD-L1 therapy.
  • the second therapeutic agent is an immune checkpoint modulator as described herein.
  • the subject has a cancer.
  • the subject is at risk of developing a cancer.
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC), squamous cell lung carcinoma), colorectal cancer (e.g., colon adenocarcinoma, rectal adenocarcinoma), breast cancer (e.g., invasive ductal carcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), endometrial cancer (e.g., endometrioid carcinoma), neuroendocrine cancer (e.g., large cell neuroendocrine carcinoma), melanoma, non-melanoma skin cancer (e.g., skin squamous cell carcinoma), cholangiocarcinoma, gallbladder cancer, ovarian cancer (e.g., ovarian serous adenocarcinoma), bladder cancer (e.g., bladder urothelial carcinoma), prostate cancer (e.g., prostate a
  • lung cancer e.g., lung
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)), colorectal cancer (e.g., colon adenocarcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), endometrial cancer (e.g., endometrioid carcinoma), melanoma, non-melanoma skin cancer (e.g., skin squamous cell carcinoma), cholangiocarcinoma, ovarian cancer (e.g., ovarian serous adenocarcinoma), cervical cancer, endocervical cancer or cancer of unknown primary (e.g., adenocarcinoma of unknown primary).
  • lung cancer e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)
  • colorectal cancer e.g., colon adenocarcinoma
  • pancreatic cancer e.g.,
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)), colorectal cancer (e.g., colon adenocarcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), endometrial cancer (e.g., endometrioid carcinoma), melanoma, non-melanoma skin cancer (e.g., skin squamous cell carcinoma), cholangiocarcinoma, ovarian cancer (e.g., ovarian serous adenocarcinoma) or cancer of unknown primary (e.g., adenocarcinoma of unknown primary).
  • lung cancer e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)
  • colorectal cancer e.g., colon adenocarcinoma
  • pancreatic cancer e.g., pancreatic adenocarcino
  • the cancer is lung cancer. In some embodiments described herein, the cancer is lung adenocarcinoma. In some embodiments described herein, the cancer is non-small cell lung cancer (NSCLC). [0291] In some embodiments described herein, the cancer is colon cancer. In some embodiments described herein, the cancer is colon adenocarcinoma. In some embodiments described herein, the cancer is colorectal cancer. [0292] In some embodiments described herein, the cancer is breast cancer (e.g., invasive ductal carcinoma). In some embodiments described herein, the cancer is pancreatic cancer (e.g., pancreatic adenocarcinoma).
  • NSCLC non-small cell lung cancer
  • the cancer is colon cancer. In some embodiments described herein, the cancer is colon adenocarcinoma. In some embodiments described herein, the cancer is colorectal cancer.
  • the cancer is breast cancer (e.g., invasive ductal carcinoma). In some embodiments described herein, the
  • the cancer is endometrial cancer (e.g., endometrioid carcinoma).
  • the cancer is neuroendocrine cancer (e.g., large cell neuroendocrine carcinoma).
  • the cancer is melanoma.
  • the cancer is non-melanoma skin cancer (e.g., skin squamous cell carcinoma).
  • the cancer is cholangiocarcinoma.
  • the cancer is gallbladder cancer.
  • the cancer is ovarian cancer (e.g., ovarian serous adenocarcinoma).
  • the cancer is bladder cancer (e.g., bladder urothelial carcinoma).
  • the cancer is prostate cancer (e.g., prostate adenocarcinoma).
  • the cancer is cervical cancer.
  • the cancer is endocervical cancer.
  • the cancer is cancer of unknown primary (e.g., adenocarcinoma of unknown primary). [0293] In some of the embodiments described herein (e.g., in this section), the cancer has increased or decreased STK11 expression.
  • the increased or decreased STK expression is assessed by determining copy number of the gene encoding STK11 relative to a control sample, wherein an increase in the copy number indicates an increased level of expression and a decrease in the copy number indicates a decreased level of expression.
  • the increased or decreased STK expression is assessed by determining the level of Attorney Docket No. TGO-025WO STK11 protein or mRNA relative to a control sample.
  • the cancer has decreased STK11 expression. [0294] In some of the embodiments described herein (e.g., in this section), the cancer has a STK11 mutation.
  • the STK11 mutation is a mutation selected from: mutation selected from:(i) a mutation in the nucleotide sequence encoding STK11; (ii) a mutation in a regulatory sequence controlling expression of the nucleotide sequence encoding STK11; (iii) a mutation in a nucleotide encoding a protein which interacts with the transcription product of the STK11 gene; (iv) a mutation in the translation product of the STK11 gene; and (v) a mutation in the transcription product of the STK11 gene.
  • the STK11 mutation is a mutation selected from (i) a mutation in the nucleotide sequence encoding STK11; (ii) a mutation in a regulatory sequence controlling expression of the nucleotide sequence encoding STK11; and (iii) a mutation in a nucleotide encoding a protein which interacts with the transcription product of the STK11 gene.
  • the STK11 mutation a mutation in the nucleotide sequence encoding STK11
  • the STK11 mutation is a mutation in the translation product of the STK11 gene.
  • the STK11 mutation is a mutation in the transcription product of the STK11 gene.
  • the STK11 mutation is an inactivating (loss of function) mutation.
  • the cancer is resistant to anti-PD1 therapy or anti-PD-L1 therapy.
  • the cancer has intrinsic resistance to anti-PD1 therapy or anti-PD-L1 therapy.
  • the cancer has acquired resistance to anti-PD1 therapy or anti-PD-L1 therapy.
  • the cancer is resistant to chemotherapy (e.g., platinum-containing chemotherapy).
  • the cancer has intrinsic resistance to chemotherapy (, platinum-containing chemotherapy).
  • the cancer has acquired resistance to chemotherapy (e.g., platinum-containing chemotherapy).
  • the cancer does not respond to or benefit from treatment with an immune checkpoint modulator when administered alone or as part of a treatment regimen that does not include Compound I (e.g., a crystalline form described herein).
  • an immune checkpoint modulator when administered alone or as part of a treatment regimen that does not include Compound I (e.g., a crystalline form described herein).
  • a “subject” to which administration is contemplated includes, but is not limited to, humans (i.e., a male or female of any age group, e.g., a pediatric subject (e.g., infant, child, adolescent) or adult subject (e.g., young adult, middle–aged adult or senior adult)) and/or a non- human animal, e.g., a mammal such as primates (e.g., cynomologus monkeys, rhesus monkeys), cattle, pigs, horses, sheep, goats, rodents, cats, and/or dogs.
  • the subject is a human.
  • the subject is a non-human animal.
  • the terms “human,” “patient,” and “subject” may be used interchangeably herein, as context permits.
  • “Treating” [0301] As used herein, and unless otherwise specified, the terms “treat,” “treating” and “treatment” contemplate an action that occurs while a subject is suffering from the specified disease, disorder or condition (e.g., cancer), which reduces the severity of the disease, disorder or condition, or retards or slows the progression of the disease, disorder or condition (“therapeutic treatment”), and also contemplates an action that occurs before a subject begins to suffer from the specified disease, disorder or condition (“prophylactic treatment”).
  • provided herein are contemplated methods of therapeutic treatment wherein the action occurs while a subject is suffering from the specified disease, disorder or condition (e.g., cancer) and results in a reduction in the severity of the disease, disorder or condition, or retardation or slowing of the progression of the disease, disorder or condition.
  • methods of prophylactic treatment wherein the action occurs before a subject begins to suffer from the specified disease, disorder or condition (e.g., cancer) and results in preventing a disease, disorder or condition, or one or more symptoms associated with the disease, disorder or condition, or preventing the recurrence of the disease, disorder or condition.
  • Combination Therapy Provided herein are methods of treatment of diseases or disorders (e.g., cancers with modified STK11 activity or expression) with Compound I (e.g., a crystalline form described herein) in combination with one or more additional therapeutic agents.
  • Compound I e.g., a crystalline form described herein
  • additional therapeutic agent e.g., another drug as explained below, also referred to as “additional therapeutic agent” or “co-agent”
  • TGO-025WO separately within time intervals, especially where these time intervals allow that the combination partners show a cooperative, e.g., synergistic effect.
  • the single components may be packaged in a kit or separately.
  • One or both of the components e.g., powders or liquids
  • co-administration or “combined administration” or the like as utilized herein are meant to encompass administration of the selected combination partner to a single subject in need thereof (e.g., a patient), and are intended to include treatment regimens in which the agents are not necessarily administered by the same route of administration or at the same time.
  • pharmaceutical combination means a product that results from the mixing or combining of more than one therapeutic agent and includes both fixed and non–fixed combinations of the therapeutic agents.
  • fixed combination means that the therapeutic agents, e.g., Compound I (e.g., a crystalline form described herein) and a combination partner, are both administered to a patient simultaneously in the form of a single entity or dosage.
  • non- fixed combination means that the therapeutic agents, e.g., Compound I (e.g., a crystalline form described herein) and a combination partner, are both administered to a patient as separate entities either simultaneously, concurrently or sequentially with no specific time limits, wherein such administration provides therapeutically effective levels of the two compounds in the body of the patient.
  • cocktail therapy e.g., the administration of three or more therapeutic agent.
  • combination therapy refers to the administration of two or more therapeutic agents to treat a therapeutic condition or disorder described in the present disclosure. Such administration encompasses co-administration of these therapeutic agents in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of active ingredients.
  • such administration encompasses co-administration in multiple, or in separate containers (e.g., tablets, capsules, powders, and liquids) for each active ingredient. Powders and/or liquids may be reconstituted or diluted to a desired dose prior to administration.
  • administration also encompasses use of each type of therapeutic agent in a sequential manner, either at approximately the same time or at different times.
  • Compound I (e.g., a crystalline form described herein) is combined with one or more other therapeutic agents, including, but not limited to, immune checkpoint modulators and other immunotherapies, other anti-cancer agents (e.g., chemotherapeutic agents, targeted agents), anti-allergic agents, anti-nausea agents (or anti- emetics), pain relievers, cytoprotective agents, radiation therapy and combinations thereof.
  • other anti-cancer agents e.g., chemotherapeutic agents, targeted agents
  • anti-allergic agents e.g., anti-nausea agents (or anti- emetics)
  • pain relievers e.g., cytoprotective agents, radiation therapy and combinations thereof.
  • the combination therapy modulates the ratio of Tem to Treg cells.
  • the combination therapy increases the ratio of Tem to Treg cells in the tumor or the tumor microenvironment.
  • Effector memory T cells express CD45RO but lack expression of CCR7 and CD62L. They also have intermediate to high expression of CD44. CD62L acts as a “homing receptor” for lymphocytes to enter secondary lymphoid tissues. Thus, Tem cells are typically found in the peripheral circulation and tissues, rather than in the lymph nodes, and exhibit immediate effector function. In response to antigen stimulation, Tem cells proliferate and differentiate into CD62L effector T cells. Effector T cells (Teff) are fully differentiated T cells. Effector T cells are short-lived cells, as opposed to memory cells which have a potential of long-term survival but have strong cytotoxic activity.
  • Regulatory T cells are a specialized subpopulation of T cells that act to suppress immune response, thereby maintaining homeostasis and self-tolerance. Tregs are able to inhibit T cell proliferation and cytokine production and play a critical role in preventing autoimmunity.
  • the combination therapy modulates cytokine secretion in the tumor or tumor microenvironment.
  • the cytokine is selected from the group of CXCL9, CXCL10, and CXCL11.
  • the expression of CXCL9, CXCL10, and/or CXCL11 increases.
  • the cytokine is selected from the group of CCL1 and CCL22.
  • the expression of CCL1 and/ or CCL22 decreases.
  • the combination therapy modulates IFNgamma expression and/or secretion in the tumor or tumor microenvironment.
  • the IFNgamma expression and/or secretion is increased.
  • Immunotherapies [0310] In some embodiments, at least one of the other therapeutic agents is an immunotherapeutic agent.
  • a disease or disorder e.g., cancer having modified STK11 activity or expression
  • Compound I e.g., a crystalline form described herein
  • the immunotherapeutic agent is a cell-based therapy.
  • a method of treating a disease or disorder comprising administering or coadministering, in any Attorney Docket No. TGO-025WO order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and an adoptive cell-based therapy.
  • the adoptive cell-based therapy is a CAR-T therapy or a TIL therapy.
  • the adoptive cell-based therapy is a CAR-T therapy.
  • the adoptive cell-based therapy is a TIL therapy.
  • the immunotherapeutic agent is a cancer vaccine such as a neoantigen. These vaccines can be developed using peptides or RNA,
  • the immunotherapeutic agent is an oncolytic virus.
  • the immunotherapeutic agent is a STING pathway agonist. Exemplary STING agonists include MK-1454 and ADU- S100.
  • the immunotherapeutic agent is an immune checkpoint modulator as described herein. Immune Checkpoint Modulators [0313] As used herein, an “immune checkpoint modulator” is an agent that modulates the immune checkpoint pathway, either by blocking any inhibitory immune checkpoint protein or by activating any stimulatory immune checkpoint protein.
  • the immune checkpoint modulator is a T cell co-stimulatory receptor agonist or a dendritic cell co-stimulatory receptor agonist. In one embodiment, the immune checkpoint modulator is a T cell co-stimulatory receptor agonist. In one embodiment, the immune checkpoint modulator is a dendritic cell co-stimulatory receptor agonist. [0315] In some embodiments, the immune checkpoint modulator is an immune checkpoint inhibitor. In some embodiments, the immune checkpoint inhibitor is an antibody.
  • the immune checkpoint modulator is a co-stimulatory antibody (e.g., anti-4-1BB antibody, anti-OX40 antibody, anti-GITR antibody, anti-CD28 antibody, anti- CD27 antibody, anti-ICOS antibody, anti-CD40 antibody).
  • the immune checkpoint modulator is an anti-4-1BB antibody.
  • the immune checkpoint modulator is an anti-OX40 antibody.
  • the immune checkpoint modulator is an anti-GITR antibody.
  • the immune checkpoint modulator is an anti-CD28 antibody.
  • the immune checkpoint modulator is an anti-CD27 antibody.
  • the immune checkpoint modulator is an anti-ICOS antibody. In one embodiment, the immune checkpoint modulator is an anti-CD40 antibody. [0317] In one embodiment, the immune checkpoint modulator is an anti-CTLA agent. In one embodiment, the immune checkpoint modulator is an anti–CTLA-4 antibody (e.g., ipilimumab, tremelimumab). In one embodiment, the immune checkpoint modulator is ipilimumab. In one embodiment, the immune checkpoint modulator is tremelimumab.
  • Anti-PD-1/PD-L1 therapies aim to block the activity of PD-1 and PDL1 immune checkpoint proteins, preventing the transmission of an “off” signal to T cells, thus allowing the T cells to infiltrate and destroy tumors.
  • Anti-PD-1/PD-L1 agents prevent the association of the programmed death-ligand 1 (PD-L1) with its receptor, programmed cell death protein 1 (PD-1).
  • Anti-PD-1 agents bind to the PD-1 protein, whereas anti-PD-L1 agents bind to the PD-L1 ligand.
  • the immune checkpoint modulator is a PD-1 ligand (i.e., PD-LI, B7–HI or CD274) or PD-2 ligand (i.e., PD-L2, B7-DC or CD273)).
  • the immune checkpoint modulator is an anti-PD-1 agent (PD-1 inhibitor).
  • the immune checkpoint modulator is an anti-PD-1 antibody (e.g., nivolumab (i.e., MDX-1106, BMS–936558, ONO-4538); AMP-224; pembrolizumab (MK- 3475); pidilizumab (CT-011), cemiplimab; dostarlimab; prolgolimab; spartalizumab; camrelizumab; sasanlimab, sintilimab; tislelizumab; toripalimab; retifanlimab; MEDI0680; budigalimab; geptanolimab).
  • nivolumab i.e., MDX-1106, BMS–936558, ONO-4538
  • AMP-224 pembrolizumab (MK- 3475); pidilizumab (CT-011), cemiplimab; dostarlimab; pro
  • the immune checkpoint modulator is nivolumab. In one embodiment, the immune checkpoint modulator is pembrolizumab. In one embodiment, the immune checkpoint modulator is pidilizumab. In one embodiment, the immune checkpoint inhibitor is cemiplimab. In one embodiment, the immune checkpoint inhibitor is dostarlimab. In one embodiment, the immune checkpoint inhibitor is prolgolimab. In one embodiment, the immune checkpoint inhibitor is spartalizumab. In one embodiment, the immune checkpoint inhibitor is camrelizumab. In one embodiment, the immune checkpoint inhibitor is sasanlimab, sintilimab. In one embodiment, the immune checkpoint inhibitor is tislelizumab.
  • the immune checkpoint inhibitor is toripalimab. In one embodiment, the immune checkpoint inhibitor is retifanlimab. In one embodiment, the immune checkpoint inhibitor is MEDI0680. In one embodiment, the immune checkpoint inhibitor is budigalimab. In one embodiment, the immune checkpoint inhibitor is geptanolimab. [0321] In one embodiment, the immune checkpoint modulator is an anti-PD-L1 agent (PD- L1 inhibitor). In one embodiment, the immune checkpoint modulator is an anti-PD-L1 antibody Attorney Docket No.
  • TGO-025WO e.g., BMS936559 (i.e., MDX-1105); durvalumab (MEDI4736); avelumab (MSB0010718C) envafolimab; cosibelimab; sugemalimab, AUNP-12; or atezolizumab (MPDL-3280A).
  • the immune checkpoint modulator is durvalumab.
  • the immune checkpoint modulator is atezolizumab.
  • the immune checkpoint modulator is avelumab.
  • the immune checkpoint modulator is envafolimab.
  • the immune checkpoint modulator is cosibelimab.
  • the immune checkpoint modulator is sugemalimab. In one embodiment, the immune checkpoint modulator is AUNP-12. In one embodiment, the immune checkpoint inhibitor is anti-PD-L1 small molecule (e.g., CA-170). [0322] In one embodiment, the immune checkpoint modulator is a checkpoint co-inhibitory antibody (e.g., anti-TIM3, anti-LAG3, Eftilagimod alpha (IMP321), anti-TIGIT, anti B7-H3 (e.g., enoblituzumab (MGA271)).
  • IMP321 anti-TIM3, anti-LAG3, Eftilagimod alpha
  • anti-TIGIT anti-TIGIT
  • anti B7-H3 e.g., enoblituzumab (MGA271)
  • the immune checkpoint modulator is an anti-TWEAKR antibody, an anti-HVEM antibody, an anti-TIM-1 antibody, or an anti-VISTA antibody.
  • a method of treating a subject having, or at risk of developing, a cancer, wherein the cancer is identified as having modified STK11 activity or expression comprising administering to the subject an effective amount of Compound I (e.g., a crystalline form described herein) and one or more immune checkpoint modulators independently selected from an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-4-1 BB antibody, an anti-OX-40 antibody, an anti-GITR antibody, an anti-CD27 antibody, an anti-CD28 antibody, an anti-CD40 antibody, an anti-LAG3 antibody, an anti-ICOS antibody, an anti-TWEAKR antibody, an anti-HVEM antibody, an anti-TIM-1 antibody, an anti-TIM-3 antibody, an anti-VISTA
  • Compound I e.g., a crystalline form described here
  • Chemotherapy [0325] In one embodiment, at least one of the other therapeutic agents is a chemotherapeutic agent.
  • Chemotherapeutic agents considered for use in combination therapies include anastrozole (Arimidex®), bicalutamide (Casodex®), bleomycin sulfate (Blenoxane®), busulfan (Myleran®), busulfan injection (Busulfex®), capecitabine (Xeloda®), N4-pentoxycarbonyl-5- deoxy-5-fluorocytidine, carboplatin (Paraplatin®), carmustine (BiCNU®), chlorambucil (Leukeran®), cisplatin (Platinol®), cladribine (Leustatin®), cyclophosphamide (Cytoxan® or Neosar®), cytarabine, cytosine arabinoside (Cytosar-U®), cytarabine
  • each chemotherapeutic agent is independently selected from cisplatin (Platinol®), carboplatin (Paraplatin®), paclitaxel (Taxol®), nab–paclitaxel (Abraxane®), docetaxel (Taxotere®), Gemcitabine (difluorodeoxycitidine), vinorelbine (Navelbine®), etoposide (Vepesid®), epemetrexed (Alimta®).
  • at least one chemotherapeutic agent is a platinum containing therapeutic agent (e.g., cisplatin or carboplatin).
  • At least one chemotherapeutic agent is cisplatin. In one embodiment, one chemotherapeutic agent is a platinum-containing chemotherapeutic agent, and a second chemotherapeutic agent is pemetrexed.
  • Targeted Therapy [0329] In one embodiment, at least one of the other therapeutic agents is a targeted agent. [0330] In one embodiment, each targeted agent is independently selected from an anti- angiogenesis agent (e.g., an anti-VEGF agent), a KRAS inhibitor, an ALK inhibitor, a ROS1 inhibitor, a BRAF inhibitor, a RET inhibitor, a MEK inhibitor, a MET inhibitor and a TRK inhibitor.
  • an anti- angiogenesis agent e.g., an anti-VEGF agent
  • each targeted agent is independently selected from bevacizumab, ramucirumab, sotorasib, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, entrectinib, dabrafenib, trametinib, capmatinib, tepotinib and larotrectinib.
  • TGO-025WO TGO-025WO
  • a disease or disorder e.g., cancer having modified STK11 activity or expression
  • administering or co- administering in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a KRAS inhibitor.
  • the KRAS inhibitor is a KRAS G12C inhibitor (e.g., sotorasib, adagrasib, ARS-3248, LY3499446, LY3537982, GDC- 6036, D3s-001, D-1553, JDQ443, BI 1823911, RMC-6291, GFH925, JAB-21822, BPI-421286, HBI-2438).
  • the KRAS G12C inhibitor is sotorasib.
  • the KRAS inhibitor is a KRAS G12D inhibitor (e.g., MRTX1133, RMC-9805).
  • the KRAS inhibitor is a KRAS Q61H inhibitor (e.g., RMC-0708). In some embodiments, the KRAS inhibitor is a KRAS G13C inhibitor (e.g., RMC-8839). In some embodiments, the KRAS inhibitor is a pan-KRAS inhibitor (e.g., RMC-6236, BI 1701963).
  • a disease or disorder e.g., cancer having modified STK11 activity or expression
  • Compound I e.g., a crystalline form described herein
  • an HDM2 inhibitor e.g., 5-FU.
  • a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a CDK4 inhibitor, including, but not limited to, LEE011 or a CDK 4/6 inhibitor (e.g., palbociclib (Ibrance®), ribociclib (Kisqali®), and abemaciclib (Verzenio ®).
  • Compound I e.g., a crystalline form described herein
  • CDK4 inhibitor including, but not limited to, LEE011 or a CDK 4/6 inhibitor (e.g., palbociclib (Ibrance®), ribociclib (Kisqali®), and abemaciclib (Verzenio ®).
  • a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and targeted treatments contingent on the dependency of individual target tumors on relevant pathways as determined by suitable predictive markers, including but not limited to: inhibitors of HDM2i, PI3K/mTOR-I, MAPKi, RTKi (FGFRi, METi, IGFiRi, JAKi, and WNTi).
  • suitable predictive markers including but not limited to: inhibitors of HDM2i, PI3K/mTOR-I, MAPKi, RTKi (FGFRi, METi, IGFiRi, JAKi, and WNTi).
  • a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a disease-specific huMABs (e.g., an anti–HER3 huMAB).
  • Compound I e.g., a crystalline form described herein
  • a disease-specific huMABs e.g., an anti–HER3 huMAB.
  • a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and ADCs/ADCCs contingent on the expression of relevant surface targets on target tumors of interest.
  • a disease or disorder e.g., cancer having modified STK11 activity or expression
  • a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a CAAP1 inhibitor.
  • a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a BCL2L1 inhibitor.
  • the BCL2L1 inhibitor is AT- 101.
  • a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a TSC1/2 inhibitor.
  • a method of treating a disease or disorder comprising administering or co-administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a UBE2H inhibitor.
  • a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a NF2 inhibitor.
  • a method of treating a disease or disorder comprising administering or co- Attorney Docket No. TGO-025WO administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a ZC3HC1 inhibitor.
  • a disease or disorder e.g., cancer having modified STK11 activity or expression
  • a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a CNOT4 inhibitor.
  • a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a API5 inhibitor.
  • a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a HEXIM1 inhibitor.
  • provided is a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a PTEN inhibitor.
  • a method of treating a disease or disorder comprising administering or co- administering, in any order, to a patient in need thereof, Compound I (e.g., a crystalline form described herein) and a DNA damage pathway inhibitor.
  • the DNA damage pathway inhibitor is selected from the group consisting of bleomycin, an ATM inhibitor (e.g., AZD1390), a USP1 inhibitor, a WEE1 inhibitor (e.g., AZD1775), and a Chk1 inhibitor (e.g., AZD7762).
  • an ATM inhibitor e.g., AZD1390
  • USP1 inhibitor e.g., AZD1390
  • WEE1 inhibitor e.g., AZD1775
  • Chk1 inhibitor e.g., AZD7762
  • Suitable anti-allergic agents include corticosteroids, including, but not limited to, dexamethasone (e.g., Decadron®), beclomethasone (e.g., Beclovent®), hydrocortisone (also known as cortisone, hydrocortisone sodium succinate, hydrocortisone sodium phosphate, and sold under the tradenames Ala–Cort®, hydrocortisone phosphate, Solu–Cortef®, Hydrocort Acetate® and Lanacort®), prednisolone (sold under the tradenames Delta–Cortel®, Orapred®, Pediapred® and Prelone®), prednisone (sold under the tradenames Deltasone®, Liquid Red®, Meticorten® and Orasone®), methylprednisolone (also known as 6–methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, sold under the
  • anti–emetics are used in preventing nausea (upper stomach) and vomiting.
  • Suitable anti-emetics include aprepitant (Emend®), ondansetron (Zofran®), granisetron HCl (Kytril®), lorazepam (Ativan®. dexamethasone (Decadron®), prochlorperazine (Compazine®), casopitant (Rezonic® and Zunrisa®), and combinations thereof.
  • Medication to alleviate the pain experienced during the treatment period is often prescribed to make the patient more comfortable.
  • opioid analgesic drugs including, but not limited to, hydrocodone/paracetamol or hydrocodone/acetaminophen (e.g., Vicodin®), morphine (e.g., Astramorph® or Avinza®), oxycodone (e.g., OxyContin® or Percocet®), oxymorphone hydrochloride (Opana®), and fentanyl (e.g., Duragesic®) are also useful for moderate or severe pain.
  • hydrocodone/paracetamol or hydrocodone/acetaminophen e.g., Vicodin®
  • morphine e.g., Astramorph® or Avinza®
  • oxycodone e.g., OxyContin® or Percocet®
  • OxyContin® oxymorphone hydrochloride
  • fentanyl e.g., Duragesic®
  • cytoprotective agents such as neuroprotectants, free-radical scavengers, cardioprotectors, anthracycline extravasation neutralizers, nutrients and the like
  • Suitable cytoprotective agents include Amifostine (Ethyol®), glutamine, Attorney Docket No. TGO-025WO dimesna (Tavocept®), mesna (Mesnex®), dexrazoxane (Zinecard® or Totect®), xaliproden (Xaprila®), and leucovorin (also known as calcium leucovorin, citrovorum factor and folinic acid).
  • compositions comprising Compound I (e.g., a crystalline form described herein) together with a pharmaceutically acceptable carrier suitable for administration to a human or animal subject, either alone or together with other anti-cancer agents.
  • compositions will either be formulated together as a combination therapeutic or administered separately.
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject a combination of Compound I (e.g., a crystalline form described herein), an immune checkpoint modulator as described herein (e.g., an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody or a combination thereof) and an additional therapeutic agent as described herein (e.g., targeted agent, a chemotherapeutic agent, radiation or a combination thereof).
  • Compound I e.g., a crystalline form described herein
  • an immune checkpoint modulator as described herein
  • an additional therapeutic agent e.g., targeted agent, a chemotherapeutic agent, radiation or a combination thereof.
  • Compound I e.g., a crystalline form described herein
  • other anti-cancer agent(s) may be administered either simultaneously, concurrently or sequentially with no specific time limits, wherein such administration provides therapeutically effective levels of the two compounds in the body of the patient.
  • Compound I e.g., a crystalline form described herein
  • Compound I is administered simultaneously with the additional therapeutic agents.
  • Compound I e.g., a crystalline form described herein
  • Compound I e.g., a crystalline form described herein
  • Compound I is administered sequentially with the additional therapeutic agents.
  • Compound I e.g., a crystalline form described herein
  • Compound I (e.g., a crystalline form described herein) is administered subsequent to the additional therapeutic agents.
  • the method comprises administering to the subject an immune checkpoint modulator followed by administering to the subject Compound I (e.g., a crystalline form described herein).
  • the method comprises administering to the subject Compound I (e.g., a crystalline form described herein) followed by administering to the subject an immune checkpoint modulator.
  • the method comprises administering to the subject an immune checkpoint modulator, followed by administering to the subject a targeted agent, a chemotherapeutic agent, radiation or a combination thereof, followed by administering to the subject Compound I (e.g., a crystalline form described herein).
  • the method comprises administering to the subject an immune checkpoint modulator, followed by administering to the subject Compound I (e.g., a crystalline form described herein), followed by administering to the subject a targeted agent, a chemotherapeutic agent, radiation or a combination thereof.
  • the method comprises administering to the subject Compound I (e.g., a crystalline form described herein), followed by administering to the subject a targeted agent, a chemotherapeutic agent, radiation or a combination thereof, followed by administering to the subject an immune checkpoint modulator.
  • the method comprises administering to the subject Compound I (e.g., a crystalline form described herein), followed by administering to the subject an immune checkpoint modulator, followed by administering to the subject a targeted agent, a chemotherapeutic agent, radiation or a combination thereof.
  • the method comprises administering to the subject a targeted agent, a chemotherapeutic agent, radiation or a combination thereof, followed by administering to the subject an immune checkpoint modulator, followed by administering to the subject Compound I (e.g., a crystalline form described herein).
  • the method comprises administering to the subject a targeted agent, a chemotherapeutic agent, radiation or a combination thereof, followed by administering Attorney Docket No. TGO-025WO to the subject Compound I (e.g., a crystalline form described herein), followed by administering to the subject an immune checkpoint modulator.
  • Compound I e.g., a crystalline form described herein
  • the other anti-cancer agent(s) is generally administered sequentially in any order by infusion or orally.
  • the dosing regimen may vary depending upon the stage of the disease, physical fitness of the patient, safety profiles of the individual drugs, and tolerance of the individual drugs, as well as other criteria well-known to the attending physician and medical practitioner(s) administering the combination.
  • Compound I e.g., a crystalline form described herein
  • other anti-cancer agent(s) may be administered within minutes of each other, hours, days, or even weeks apart depending upon the particular cycle being used for treatment.
  • kits that include Compound I (e.g., a crystalline form described herein) and a second therapeutic agent as disclosed herein.
  • Representative kits include (a) Compound I (e.g., a crystalline form described herein) and (b) at least one other therapeutic agent, e.g., as indicated above, whereby such kit may comprise a package insert or other labeling including directions for administration.
  • Compound I e.g., a crystalline form described herein
  • Compound I may also be used in combination with known therapeutic processes, for example, the administration of hormones or especially radiation.
  • a method of selecting a subject for treatment with Compound I comprising: identifying subjects having a cancer characterized by the presence of cells having modified STK11 activity or expression; and selecting thus identified subjects for treatment with one of the methods of treatment described herein.
  • a method of selecting a subject for treatment with Compound I e.g., a crystalline form described herein the method comprising: identifying subjects having a cancer characterized by the presence of cells having modified STK11 activity Attorney Docket No.
  • a method of selecting a subject for treatment with a combination of Compound I (e.g., a crystalline form described herein) and one or more additional therapeutic agents comprising: identifying subjects having a cancer characterized by the presence of cells having modified STK11 activity or expression; and selecting thus identified subjects for treatment with Compound I (e.g., a crystalline form described herein) and one or more additional therapeutic agents.
  • a method of selecting a subject for treatment with a combination of Compound I (e.g., a crystalline form described herein) and one or more additional therapeutic agents comprising: identifying subjects having a cancer characterized by the presence of cells having modified STK11 activity or expression; and selecting thus identified subjects for treatment with Compound I (e.g., a crystalline form described herein) and one or more immune checkpoint modulators.
  • a method of selecting a subject for treatment with a combination of Compound I (e.g., a crystalline form described herein) and two or more additional therapeutic agents comprising: identifying subjects having a cancer characterized by the presence of cells having modified STK11 activity or expression; and selecting thus identified subjects for treatment with Compound I (e.g., a crystalline form described herein) and two or more additional therapeutic agents, wherein at least two of the additional therapeutic agents are immune checkpoint modulators.
  • a method of selecting a subject for treatment with a combination of Compound I e.g., a crystalline form described herein
  • an immune checkpoint modulator and one or more additional therapeutic agents selected from a chemotherapeutic agent, a targeted agent and radiotherapy comprising: identifying subjects that have previously been treated with a combination of an immune checkpoint modulator and one or more additional therapeutic agents selected from a chemotherapeutic agent, a targeted agent and radiotherapy, wherein treatment with the combination of immune checkpoint modulator and additional therapeutic agent did not provide any additional benefit as compared to treatment with the additional therapeutic agent alone; and selecting thus identified subjects for treatment.
  • the method further comprises: identifying subjects having a cancer characterized by the presence of cells having decreased STK11 activity or expression; and, selecting thus identified subjects for treatment.
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC), squamous cell lung carcinoma), colorectal cancer (e.g., colon adenocarcinoma, rectal adenocarcinoma), breast cancer (e.g., invasive ductal carcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), endometrial cancer (e.g., endometrioid carcinoma), neuroendocrine cancer (e.g., large cell neuroendocrine carcinoma), melanoma, non-melanoma skin cancer (e.g., skin squamous cell carcinoma), cholangiocarcinoma, gallbladder cancer, ovarian cancer
  • lung cancer e.g., lung adenocarcinoma
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)), colorectal cancer (e.g., colon adenocarcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), endometrial cancer (e.g., endometrioid carcinoma), melanoma, non-melanoma skin cancer (e.g., skin squamous cell carcinoma), cholangiocarcinoma, ovarian cancer (e.g., ovarian serous adenocarcinoma), cervical cancer, endocervical cancer or cancer of unknown primary (e.g., adenocarcinoma of unknown primary).
  • lung cancer e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)
  • colorectal cancer e.g., colon adenocarcinoma
  • pancreatic cancer e.g.,
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)), colorectal cancer (e.g., colon adenocarcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), endometrial cancer (e.g., endometrioid carcinoma), melanoma, non-melanoma skin cancer (e.g., skin squamous cell carcinoma), cholangiocarcinoma, ovarian cancer (e.g., ovarian serous adenocarcinoma) or cancer of unknown primary (e.g., adenocarcinoma of unknown primary).
  • lung cancer e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)
  • colorectal cancer e.g., colon adenocarcinoma
  • pancreatic cancer e.g., pancreatic adenocarcino
  • the cancer is lung cancer. In some embodiments described herein, the cancer is lung adenocarcinoma. In some embodiments described herein, the cancer is non-small cell lung cancer (NSCLC). [0384] In some embodiments described herein, the cancer is colon cancer. In some embodiments described herein, the cancer is colon adenocarcinoma. In some embodiments described herein, the cancer is colorectal cancer. Attorney Docket No. TGO-025WO [0385] In some of the embodiments described herein (e.g., in this section), the cancer has increased or decreased STK11 expression.
  • NSCLC non-small cell lung cancer
  • the increased or decreased STK expression is assessed by determining copy number of the gene encoding STK11 relative to a control sample, wherein an increase in the copy number indicates an increased level of expression and a decrease in the copy number indicates a decreased level of expression. In one embodiment, the increased or decreased STK expression is assessed by determining the level of STK11 protein or mRNA relative to a control sample. In one embodiment, the cancer has decreased STK11 expression. [0386] In some of the embodiments described herein (e.g., in this section), the cancer has a STK11 mutation.
  • the STK11 mutation is a mutation selected from: mutation selected from:(i) a mutation in the nucleotide sequence encoding STK11; (ii) a mutation in a regulatory sequence controlling expression of the nucleotide sequence encoding STK11; (iii) a mutation in a nucleotide encoding a protein which interacts with the transcription product of the STK11 gene; (iv) a mutation in the translation product of the STK11 gene; and (v) a mutation in the transcription product of the STK11 gene.
  • the STK11 mutation is a mutation selected from (i) a mutation in the nucleotide sequence encoding STK11; (ii) a mutation in a regulatory sequence controlling expression of the nucleotide sequence encoding STK11; and (iii) a mutation in a nucleotide encoding a protein which interacts with the transcription product of the STK11 gene.
  • the STK11 mutation a mutation in the nucleotide sequence encoding STK11
  • the STK11 mutation is a mutation in the translation product of the STK11 gene.
  • the STK11 mutation is a mutation in the transcription product of the STK11 gene.
  • the STK11 mutation is an inactivating (loss of function) mutation.
  • the cancer is further characterized by one or more additional mutations.
  • the additional mutations are selected from KRAS mutations and KEAP1 mutations.
  • the additional mutations are KRAS mutations.
  • the KRAS mutations are selected from G12C, G12D, G12V, G12A, G12S, G12R, G13C, G13D, G13S, Q61H and Q61K mutations.
  • the KRAS mutations are a mutations at position G12, optionally wherein the KRAS mutations are selected from G12D mutations, G12C mutations, G12V mutations or combinations thereof.
  • the KRAS mutations are activating mutations.
  • the additional mutations are KEAP1 mutations.
  • the KEAP1 mutations are inactivating mutations.
  • the additional mutations are KRAS mutations and KEAP1 mutations.
  • the cancer is characterized by the lack of an EGFR mutation. [0390] In one embodiment, the cancer is resistant to anti-PD1 therapy or anti-PD-L1 therapy.
  • the cancer has intrinsic resistance to anti-PD1 therapy or anti-PD-L1 therapy. In one embodiment, the cancer has acquired resistance to anti-PD1 therapy or anti-PD- L1 therapy. [0391] In one embodiment, the cancer is resistant to chemotherapy (e.g., platinum- containing chemotherapy). In one embodiment, the cancer has intrinsic resistance to chemotherapy (e.g., platinum-containing chemotherapy). In one embodiment, the cancer has acquired resistance to chemotherapy (e.g., platinum-containing chemotherapy). [0392] In one embodiment, the cancer does not respond to or benefit from treatment with an immune checkpoint modulator when administered alone or as part of a treatment regimen that does not include Compound I (e.g., a crystalline form described herein).
  • Compound I e.g., a crystalline form described herein.
  • the patient is immunocompetent.
  • the patient has received an adoptive cell therapy.
  • the adoptive cell therapy is a TIL therapy or a CAR-T cell therapy. Determining Whether a Subject Will Respond to Treatment with Compound I [0394]
  • a method for ascertaining susceptibility of a subject having or having been diagnosed with cancer to treatment with Compound I e.g., a crystalline form described herein
  • the method comprising: determining: i) the presence or absence of a STK11 mutation; and/or ii) the level of STK11 activity or expression in the subject or a sample derived from the subject; wherein the presence of a STK11 mutation (e.g., an STK loss-of-function mutation) and/or a modified (e.g., decreased) level of STK11 activity or expression is indicative of susceptibility to treatment with Compound I (e.g., a crystalline form
  • a method for ascertaining susceptibility of a subject having or having been diagnosed with cancer to treatment with a combination of Compound I (e.g., a crystalline form described herein) as described herein and an immune checkpoint modulator as described herein comprising: determining: i) the presence or absence of a STK11 mutation; and/or ii) the level of STK11 activity or expression in the subject or a sample derived from the subject; wherein the presence of a STK11 mutation (e.g., an STK loss- of-function mutation) and/or a modified (e.g., decreased) level of STK11 activity or expression Attorney Docket No.
  • TGO-025WO is indicative of susceptibility to treatment with a combination of Compound I (e.g., a crystalline form described herein) and an immune checkpoint modulator.
  • the level of STK11 expression is assessed by determining the copy number of the gene encoding STK11 relative to a control sample, wherein an increase in the copy number indicates an increased level of expression and a decrease in the copy number indicates a decreased level of expression.
  • the level of STK11 expression is assessed by determining the level of STK11 protein or mRNA relative to a control sample.
  • a method for ascertaining whether a subject having or having been diagnosed with cancer will respond to treatment with Compound I comprising: determining the presence or absence of a STK11 mutation in the subject or a sample derived from the subject, wherein the presence of a STK11 mutation (e.g., an STK loss-of-function mutation) indicates that the subject will respond to treatment with Compound I (e.g., a crystalline form described herein).
  • a method for ascertaining whether a subject having or having been diagnosed with cancer will respond to treatment with Compound I (e.g., a crystalline form described herein) as described herein and an immune checkpoint modulator as described herein comprising: determining the presence or absence of a STK11 mutation in the subject or a sample derived from the subject, wherein the presence of a STK11 mutation (e.g., an STK loss-of-function mutation) indicates that the subject will respond to treatment with a combination of Compound I (e.g., a crystalline form described herein) and an immune checkpoint modulator.
  • a method for ascertaining whether a subject having or having been diagnosed with cancer will respond to treatment with Compound I e.g., a crystalline form described herein
  • the method comprising: a) detecting levels of STK11 (e.g., STK11 protein and/or STK11 mRNA) in a cancer test sample (e.g., in a cancer sample obtained from the subject); b) comparing the cancer test sample with a reference (e.g., a reference sample taken from a non-cancerous or normal control subject), wherein modified (e.g., decreased) levels of STK11 in said test sample indicates that the subject will respond to treatment with Compound I (e.g., a crystalline form described herein).
  • a reference e.g., a reference sample taken from a non-cancerous or normal control subject
  • a method for ascertaining whether a subject having or having been diagnosed with cancer will respond to treatment with Compound I (e.g., a crystalline form described herein) as described herein and an immune checkpoint modulator as described herein comprising: a) detecting levels of STK11 (e.g., STK11 protein and/or STK11 mRNA) in a cancer test sample (e.g., in a cancer sample obtained from the subject); b) comparing the cancer test sample with a reference (e.g., a reference sample taken from a non-cancerous or normal control subject), wherein modified (e.g., decreased) levels of STK11 in said test sample indicates that the subject will respond to treatment with a combination of Compound I (e.g., a crystalline form described herein) and an immune checkpoint modulator.
  • a reference e.g., a reference sample taken from a non-cancerous or normal control subject
  • a method for ascertaining whether a subject having or having been diagnosed with cancer will respond to treatment with Compound I e.g., a crystalline form described herein
  • the method comprising: a) determining the copy number of the gene encoding STK11 in a cancer test sample (e.g., in a cancer sample obtained from the subject); b) comparing the cancer test sample with a reference (e.g., a reference sample taken from a non-cancerous or normal control subject), wherein a decrease in the copy number indicates that the subject will respond to treatment with Compound I (e.g., a crystalline form described herein).
  • a reference e.g., a reference sample taken from a non-cancerous or normal control subject
  • a method for ascertaining whether a subject having or having been diagnosed with cancer will respond to treatment with Compound I (e.g., a crystalline form described herein) as described herein and an immune checkpoint modulator as described herein comprising: a) determining the copy number of the gene encoding STK11 in a cancer test sample (e.g., in a cancer sample obtained from the subject); b) comparing the cancer test sample with a reference (e.g., a reference sample taken from a non-cancerous or normal control subject), wherein a decrease in the copy number indicates that the subject will respond to treatment with a combination of Compound I (e.g., a crystalline form described herein) and an immune checkpoint modulator.
  • a reference e.g., a reference sample taken from a non-cancerous or normal control subject
  • the STK11 mutation is a loss of function mutation.
  • the modified level of STK11 activity or expression is determined by comparing the level of activity or expression in the subject or sample derived from the subject (e.g., a tumor sample) and comparing it with a control (e.g., a healthy subject or a sample derived from a healthy subject).
  • the modified level of STK11 activity is a reduced level of STK11 activity.
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC), squamous cell lung carcinoma), colorectal cancer (e.g., colon adenocarcinoma, rectal adenocarcinoma), breast cancer (e.g., invasive ductal carcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), endometrial cancer (e.g., endometrioid carcinoma), neuroendocrine cancer (e.g., large cell neuroendocrine carcinoma), melanoma, non- melanoma skin cancer (e.g., skin squamous cell carcinoma), cholangiocarcinoma, gallbladder cancer, ovarian cancer (e.g., ovarian serous adenocarcinoma), bladder cancer (e.g., bladder urothelial carcinoma), prostate cancer (e.g., prostate adenocarcinoma, non-small
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)), colorectal cancer (e.g., colon adenocarcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), endometrial cancer (e.g., endometrioid carcinoma), melanoma, non-melanoma skin cancer (e.g., skin squamous cell carcinoma), cholangiocarcinoma, ovarian cancer (e.g., ovarian serous adenocarcinoma), cervical cancer, endocervical cancer or cancer of unknown primary (e.g., adenocarcinoma of unknown primary).
  • lung cancer e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)
  • colorectal cancer e.g., colon adenocarcinoma
  • pancreatic cancer e.g.,
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)), colorectal cancer (e.g., colon adenocarcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), endometrial cancer (e.g., endometrioid carcinoma), melanoma, non-melanoma skin cancer (e.g., skin squamous cell carcinoma), cholangiocarcinoma, ovarian cancer (e.g., ovarian serous adenocarcinoma) or cancer of unknown primary (e.g., adenocarcinoma of unknown primary).
  • lung cancer e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)
  • colorectal cancer e.g., colon adenocarcinoma
  • pancreatic cancer e.g., pancreatic adenocarcino
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)). In one embodiment, the cancer is lung adenocarcinoma. In one embodiment, the cancer is non-small cell lung cancer (NSCLC). Attorney Docket No. TGO-025WO [0408] In some embodiments described herein, the cancer is colon cancer. In some embodiments described herein, the cancer is colon adenocarcinoma. In some embodiments described herein, the cancer is colorectal cancer.
  • NSCLC non-small cell lung cancer
  • a method for ascertaining susceptibility of a cancer to treatment with Compound I comprising: determining: i) the presence or absence of a STK11 mutation; and/or ii) the level of STK11 activity or expression in a cancer test sample (e.g., a sample derived from a subject); wherein the presence of a STK11 mutation (e.g., an STK loss-of-function mutation) and/or a modified (e.g., decreased) level of STK11 activity or expression is indicative of susceptibility to treatment with Compound I (e.g., a crystalline form described herein).
  • a cancer test sample e.g., a sample derived from a subject
  • a method for ascertaining susceptibility of a cancer to treatment with a combination of Compound I (e.g., a crystalline form described herein) as described herein and an immune checkpoint modulator as described herein comprising: determining: i) the presence or absence of a STK11 mutation; and/or ii) the level of STK11 activity or expression in a cancer test sample (e.g., a sample derived from a subject); wherein the presence of a STK11 mutation (e.g., an STK loss-of-function mutation) and/or a modified (e.g., decreased) level of STK11 activity or expression is indicative of susceptibility to treatment with a combination of Compound I (e.g., a crystalline form described herein) and an immune checkpoint modulator.
  • a cancer test sample e.g., a sample derived from a subject
  • the level of STK11 expression is assessed by determining the copy number of the gene encoding STK11 relative to a control sample, wherein an increase in the copy number indicates an increased level of expression and a decrease in the copy number indicates a decreased level of expression. In one embodiment, the level of STK11 expression is assessed by determining the level of STK11 protein or mRNA relative to a control sample.
  • a method for ascertaining whether a cancer will respond to treatment with Compound I comprising: determining the presence or absence of a STK11 mutation in a cancer test sample (e.g., a sample derived from a subject), wherein the presence of a STK11 mutation (e.g., an STK loss-of-function mutation) indicates that the cancer will respond to treatment with Compound I (e.g., a crystalline form described herein).
  • a cancer test sample e.g., a sample derived from a subject
  • the presence of a STK11 mutation e.g., an STK loss-of-function mutation
  • a method for ascertaining whether a cancer will respond to treatment with Compound I e.g., a crystalline form described herein
  • an immune checkpoint modulator as described herein, the method comprising: determining the presence or absence of a STK11 mutation in a cancer test sample (e.g., a sample derived from a subject), wherein the presence of a STK11 mutation (e.g., an STK loss-of- function mutation) indicates that the cancer will respond to treatment with a combination of Compound I (e.g., a crystalline form described herein) and an immune checkpoint modulator.
  • a cancer test sample e.g., a sample derived from a subject
  • a STK11 mutation e.g., an STK loss-of- function mutation
  • a method for ascertaining whether a cancer will respond to treatment with Compound I comprising: a) detecting levels of STK11 (e.g., STK11 protein and/or STK11 mRNA) in a cancer test sample (e.g., in a cancer sample obtained from a subject); b) comparing the cancer test sample with a reference (e.g., a reference sample taken from a non-cancerous or normal control subject), wherein modified (e.g., decreased) levels STK11 in said test sample indicates that the cancer will respond to treatment with Compound I (e.g., a crystalline form described herein).
  • a reference e.g., a reference sample taken from a non-cancerous or normal control subject
  • a method for ascertaining whether a cancer will respond to treatment with Compound I e.g., a crystalline form described herein
  • an immune checkpoint modulator as described herein, the method comprising: a) detecting levels of STK11 (e.g., STK11 protein and/or STK11 mRNA) in a cancer test sample (e.g., in a cancer sample obtained from a subject); b) comparing the cancer test sample with a reference (e.g., a reference sample taken from a non-cancerous or normal control subject), wherein modified (e.g., decreased) levels STK11 in said test sample indicates that the cancer will respond to treatment with a combination of Compound I (e.g., a crystalline form described herein) and an immune checkpoint modulator.
  • a reference e.g., a reference sample taken from a non-cancerous or normal control subject
  • a method for ascertaining whether a cancer will respond to treatment with Compound I (e.g., a crystalline form described herein) as described herein, the method comprising: a) determining the copy number of the gene encoding STK11 in a cancer test sample (e.g., in a cancer sample obtained from a subject); Attorney Docket No. TGO-025WO b) comparing the cancer test sample with a reference (e.g., a reference sample taken from a non-cancerous or normal control subject), wherein a decrease in the copy number indicates that the cancer will respond to treatment with Compound I (e.g., a crystalline form described herein).
  • a reference e.g., a reference sample taken from a non-cancerous or normal control subject
  • a method for ascertaining whether a cancer will respond to treatment with Compound I e.g., a crystalline form described herein
  • an immune checkpoint modulator as described herein, the method comprising: a) determining the copy number of the gene encoding STK11 in a cancer test sample (e.g., in a cancer sample obtained from a subject); b) comparing the cancer test sample with a reference (e.g., a reference sample taken from a non-cancerous or normal control subject), wherein a decrease in the copy number indicates that the cancer will respond to treatment with a combination of Compound I (e.g., a crystalline form described herein) and an immune checkpoint modulator.
  • a reference e.g., a reference sample taken from a non-cancerous or normal control subject
  • the STK11 mutation is a loss of function mutation.
  • the modified level of STK11 activity or expression is determined by comparing the level of activity or expression in a cancer test sample (e.g., a sample derived from a subject) and comparing it with a control (e.g., a sample derived from a healthy subject).
  • the modified level of STK11 activity is a reduced level of STK11 activity.
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC), squamous cell lung carcinoma), colorectal cancer (e.g., colon adenocarcinoma, rectal adenocarcinoma), breast cancer (e.g., invasive ductal carcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), endometrial cancer (e.g., endometrioid carcinoma), neuroendocrine cancer (e.g., large cell neuroendocrine carcinoma), melanoma, non- melanoma skin cancer (e.g., skin squamous cell carcinoma), cholangiocarcinoma, gallbladder cancer, ovarian cancer (e.g., ovarian serous adenocarcinoma), bladder cancer (e.g., bladder urothelial carcinoma), prostate cancer (e.g., prostate adenocarcinoma, non-small
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)), colorectal cancer (e.g., colon adenocarcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), endometrial cancer (e.g., endometrioid carcinoma), melanoma, non-melanoma skin cancer (e.g., skin squamous cell carcinoma), Attorney Docket No.
  • NSCLC non-small cell lung cancer
  • colorectal cancer e.g., colon adenocarcinoma
  • pancreatic cancer e.g., pancreatic adenocarcinoma
  • endometrial cancer e.g., endometrioid carcinoma
  • melanoma melanoma
  • non-melanoma skin cancer e.g., skin squamous cell carcinoma
  • TGO-025WO cholangiocarcinoma ovarian cancer (e.g., ovarian serous adenocarcinoma), cervical cancer, endocervical cancer or cancer of unknown primary (e.g., adenocarcinoma of unknown primary).
  • ovarian cancer e.g., ovarian serous adenocarcinoma
  • cervical cancer e.g., cervical cancer
  • endocervical cancer or cancer of unknown primary e.g., adenocarcinoma of unknown primary.
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)), colorectal cancer (e.g., colon adenocarcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), endometrial cancer (e.g., endometrioid carcinoma), melanoma, non-melanoma skin cancer (e.g., skin squamous cell carcinoma), cholangiocarcinoma, ovarian cancer (e.g., ovarian serous adenocarcinoma) or cancer of unknown primary (e.g., adenocarcinoma of unknown primary).
  • lung cancer e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)
  • colorectal cancer e.g., colon adenocarcinoma
  • pancreatic cancer e.g., pancreatic adenocarcino
  • the cancer is lung cancer (e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC)). In one embodiment, the cancer is lung adenocarcinoma. In one embodiment, the cancer is non-small cell lung cancer (NSCLC). [0422] In some embodiments described herein, the cancer is colon cancer. In some embodiments described herein, the cancer is colon adenocarcinoma. In some embodiments described herein, the cancer is colorectal cancer. Sample preparation [0423] The present methods can comprise detecting somatic mutations, loss of heterozygosity, whole gene deletions, decreased expression, or DNA methylation in the promoter region of STK11.
  • NSCLC non-small cell lung cancer
  • mutations in STK11 may arise in a variety of sites in a cancer.
  • the disclosure further provides assays for the detection of levels of STK11, (e.g., STK11 protein and/or STK11 mRNA).
  • the disclosure provides assays for the detection of loss of STK11 protein expression (e.g., as measured by immunohistochemistry).
  • the disclosure further provides assays for detecting STK11 mutations (e.g., STK11 loss of function mutations).
  • the gene mutation or expression may be analyzed from a patient sample.
  • the patient sample can be any bodily tissue or fluid that includes nucleic acids from the cancer (e.g., lung cancer) in the subject.
  • the sample is a bodily fluid such as blood (e.g., serum or plasma) bone marrow, cerebral spinal fluid, peritoneal/pleural fluid, lymph fluid, ascites, serous fluid, sputum, lacrimal fluid, stool, and urine.
  • the sample is a blood sample comprising circulating tumor cells or cell free DNA.
  • the sample is not a blood sample.
  • the sample can be a tissue, including normal or tumor tissue (e.g., a lung tissue). The tissue can be fresh frozen or formalin-fixed, Attorney Docket No. TGO-025WO paraffin- embedded (FFPE).
  • a tumor FFPE e.g., lung tumor FFPE
  • Methods and reagents are known in the art for obtaining, processing, and analyzing samples.
  • Cells can be harvested from a biological sample using standard techniques known in the art. Methods for extracting cellular DNA from fluid or tissue samples are known in the art. For example, cells can be harvested by centrifuging a cell sample and resuspending the pelleted cells. The cells can be resuspended in a buffered solution such as phosphate-buffered saline (PBS).
  • PBS phosphate-buffered saline
  • the cells can be lysed (e.g., with detergents) to extract DNA. After cell lysis, proteins are removed from DNA using various proteases. DNA is then extracted with phenol, precipitated in alcohol, and dissolved in an aqueous solution. Alternatively, genomic DNA can be extracted with kits such as the QIAamp® Tissue Kit (Qiagen, Chatsworth, Calif.) and the Wizard® Genomic DNA purification kit (Promega). Measurement of Gene Expression [0428] In some embodiments, modified (e.g., reduced) levels of STK11 are modified (e.g., reduced) STK11 gene expression levels.
  • modified (e.g., reduced) levels of STK11 are modified (e.g., reduced) STK11 mRNA levels.
  • Measurement of gene expression can be performed using any method or reagent known in the art.
  • Detection of gene expression can be by any appropriate method, including for example, detecting the quantity of mRNA transcribed from the gene or the quantity of cDNA produced from the reverse transcription of the mRNA transcribed from the gene or the quantity of the polypeptide or protein encoded by the gene. These methods can be performed on a sample-by-sample basis or modified for high throughput analysis. For example, using AffymetrixTM U133 microarray chips.
  • gene expression is detected and quantitated by hybridization to a probe that specifically hybridizes to the appropriate probe for that biomarker.
  • the probes also can be attached to a solid support for use in high throughput screening assays using methods known in the art.
  • Attorney Docket No. TGO-025WO [0431]
  • the expression level of a gene is determined through exposure of a nucleic acid sample to the probe-modified chip. Extracted nucleic acid is labeled, for example, with a fluorescent tag, preferably during an amplification step.
  • Hybridization of the labeled sample is performed at an appropriate stringency level. The degree of probe-nucleic acid hybridization is quantitatively measured using a detection device.
  • any one of gene copy number, transcription, or translation can be determined using known techniques.
  • an amplification method such as PCR may be useful.
  • General procedures for PCR are taught in MacPherson et al., PCR: A Practical Approach, (IRL Press at Oxford University Press (1991)).
  • PCR conditions used for each application reaction are empirically determined. A number of parameters influence the success of a reaction. Among them are annealing temperature and time, extension time, Mg 2+ and /or ATP concentration, pH, and the relative concentration of primers, templates, and deoxyribonucleotides.
  • the resulting DNA fragments can be detected by agarose gel electrophoresis followed by visualization with ethidium bromide staining and ultraviolet illumination.
  • the hybridized nucleic acids are detected by detecting one or more labels attached to the sample nucleic acids.
  • the labels can be incorporated by any of a number of means well known to those of skill in the art. However, in some embodiments, the label is simultaneously incorporated during the amplification step in the preparation of the sample nucleic acid.
  • PCR polymerase chain reaction
  • transcription amplification as described above, using a labeled nucleotide (e.g., fluorescein-labeled UTP and/or CTP) incorporates a label into the transcribed nucleic acids.
  • a label may be added directly to the original nucleic acid sample (e.g., mRNA, polyA, mRNA, cDNA, etc.) or to the amplification product after the amplification is completed.
  • Means of attaching labels to nucleic acids are well known to those of skill in the art and include, for example nick translation or end-labeling (e.g., with a labeled RNA) by kinasing of the nucleic acid and subsequent attachment (ligation) of a nucleic acid linker joining the sample nucleic acid to a label (e.g., a fluorophore).
  • a label e.g., a fluorophore
  • the gene expression can be measured through an in-situ hybridization protocol that can detect RNA molecules on a slide containing tissue sections or cells (e.g., through RNAscope®).
  • Detectable labels suitable for use in the methods disclosed herein include any composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means.
  • Useful labels include biotin for staining with labeled streptavidin conjugate, magnetic beads (e.g., DynabeadsTM), fluorescent dyes (e.g., fluorescein, texas red, rhodamine, green fluorescent protein, and the like), radiolabels (e.g., 3 H, 125 I, 35 S, 14 C, or 32 P) enzymes (e.g., horseradish peroxidase, alkaline phosphatase and others commonly used in an ELISA), and calorimetric labels such as colloidal gold or colored glass or plastic (e.g., polystyrene, polypropylene, latex, etc.) beads.
  • fluorescent dyes e.g., fluorescein, texas red, rhodamine, green fluorescent protein, and the like
  • Radiolabels may be detected using photographic film or scintillation counters
  • fluorescent markers may be detected using a photodetector to detect emitted light.
  • Enzymatic labels are typically detected by providing the enzyme with a substrate and detecting the reaction product produced by the action of the enzyme on the substrate, and calorimetric labels are detected by simply visualizing the colored label.
  • the detectable label may be added to the target (sample) nucleic acid(s) prior to, or after the hybridization, such as described in WO 97/10365. These detectable labels are directly attached to or incorporated into the target (sample) nucleic acid prior to hybridization.
  • indirect labels are joined to the hybrid duplex after hybridization.
  • the indirect label is attached to a binding moiety that has been attached to the target nucleic acid prior to the hybridization.
  • the target nucleic acid may be biotinylated before the hybridization.
  • an avidin-conjugated fluorophore will bind the biotin bearing hybrid duplexes providing a label that is easily detected.
  • the detection of modified (e.g., reduced) levels of STK11 is by quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR), RNA-Seq, or microarray. Detection of polypeptides [0439] Protein levels of STK11 can be determined by examining protein expression or the protein product. Determining the protein level involves measuring the amount of any immunospecific binding that occurs between an antibody that selectively recognizes and binds to Attorney Docket No. TGO-025WO the polypeptide of the biomarker in a sample obtained from a subject and comparing this to the amount of immunospecific binding of at least one biomarker in a control sample. [0440] A variety of techniques are available in the art for protein analysis.
  • radioimmunoassays include but are not limited to radioimmunoassays, ELISA (enzyme linked immunosorbent assays), “sandwich” immunoassays, immunoradiometric assays, in situ immunoassays (using e.g., colloidal gold, enzyme or radioisotope labels), Western blot analysis, immunoprecipitation assays, immunofluorescent assays, flow cytometry, immunohistochemistry, HPLC, mass spectrometry, confocal microscopy, enzymatic assays, surface plasmon resonance and PAGE- SDS.
  • the detection of modified (e.g., reduced) STK11 protein levels is by Western blot.
  • the detection of modified (e.g., reduced) STK11 protein levels is by fluorescence- activated cell sorting (FACS). In some embodiments, the detection of modified (e.g., reduced) STK11 protein levels is by immunohistochemistry.
  • FACS fluorescence- activated cell sorting
  • the detection of modified (e.g., reduced) STK11 protein levels is by immunohistochemistry.
  • Other detection methods Mutations in targets of interest (e.g., STK11 mutations) can be detected by methods known to those of skill in the art.
  • sequencing may be performed on DNA extracted from a tissue such as a tumor tissue.
  • the tumor tissue can be fresh tissue or preserved tissue (e.g., formalin fixed tissue, e.g., paraffin-embedded tissue). Sequencing may also be performed using cell-free DNA.
  • Embodiment 1 An anhydrous crystalline form, Form A, of (R)-N-(4-amino-4'- fluoro-[1,1'-biphenyl]-3-yl)-4-(S-methylsulfonimidoyl)benzamide, having Formula (I): Attorney Docket No.
  • Embodiment 3 The crystalline form of embodiment 1, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2. [0446] Embodiment 3.
  • Embodiment 4 The crystalline form of embodiment 1, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2. [0447] Embodiment 4.
  • Embodiment 5 The crystalline form of embodiment 1, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2. [0448] Embodiment 5.
  • Embodiment 6 The crystalline form of embodiment 1, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 13.1 ⁇ 0.2, 15 ⁇ 0.2, 22.3 ⁇ 0.2 and 24 ⁇ 0.2.
  • Embodiment 6 The crystalline form of embodiment 1, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at values of 2 in degrees selected from 13.1 ⁇ 0.2, 15 ⁇ 0.2, 22.3 ⁇ 0.2 and 24 ⁇ 0.2.
  • Embodiment 8 The crystalline form of embodiment 1, wherein the crystalline form wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 13.1 ⁇ 0.2, 15 ⁇ 0.2, 22.3 ⁇ 0.2 and 24 ⁇ 0.2 and at least one (e.g., one, two, three, four, five or six) additional characteristic peak at values of 2 in degrees selected from 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2. [0451] Embodiment 8.
  • Embodiment 9 The crystalline form of embodiment 1, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2 and 28.5 ⁇ 0.2. [0452] Embodiment 9.
  • Embodiment 10 The crystalline form of embodiment 1, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5.3 ⁇ 0.2, 10.6 ⁇ 0.2, 13.1 ⁇ 0.2, 15 ⁇ 0.2, 15.8 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 19.3 ⁇ 0.2, 19.6 ⁇ 0.2, 20.9 ⁇ 0.2, 21.1 ⁇ 0.2, 22.3 ⁇ 0.2, 22.7 ⁇ 0.2, 22.8 ⁇ 0.2, 24 ⁇ 0.2, 24.4 ⁇ 0.2, 25.8 ⁇ 0.2, 26.3 ⁇ 0.2, 26.5 ⁇ 0.2, 28.3 ⁇ 0.2, 28.5 ⁇ 0.2, 29.3 ⁇ 0.2, 31.9 ⁇ 0.2, 37.3 ⁇ 0.2, 37.5 ⁇ 0.2, 37.3 ⁇ 0.2 and 37.5 ⁇ 0.2. [0453] Embodiment 10.
  • Embodiment 11 The crystalline form of embodiment 1, wherein the crystalline form has an X-ray powder diffraction pattern substantially corresponding to FIG.1A.
  • Embodiment 11 The crystalline form of any one of embodiments 1-10, wherein the crystalline form has an differential scanning calorimetry (DSC) pattern substantially corresponding to FIG.1C.
  • Embodiment 12 The crystalline form of any one of embodiments 1-11, wherein the crystalline form has a thermogravimetric analysis (TGA) pattern substantially corresponding to FIG.1B.
  • Embodiment 13 Embodiment 13.
  • TGO-025WO Formula (I) wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 20.1 ⁇ 0.2, 21.4 ⁇ 0.2, 21.8 ⁇ 0.2, 22.5 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 25.5 ⁇ 0.2, 26 ⁇ 0.2, 26.6 ⁇ 0.2, 27.3 ⁇ 0.2, 28.3 ⁇ 0.2, 29.6 ⁇ 0.2, 31.6 ⁇ 0.2 and 32.1 ⁇ 0.2.
  • Embodiment 14 The crystalline form of embodiment 13, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 10.2 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 14.3 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 16.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 20.1 ⁇ 0.2, 21.4 ⁇ 0.2, 21.8 ⁇ 0.2, 22.5 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 25.5 ⁇ 0.2, 26 ⁇ 0.2, 26.6 ⁇ 0.2, 27.3 ⁇ 0.2, 28.3 ⁇ 0.2, 29.6 ⁇ 0.2, 31.6 ⁇ 0.2 and 32.1 ⁇ 0.2.
  • Embodiment 15 The crystalline form of embodiment 13, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2. [0459] Embodiment 16.
  • Embodiment 17 The crystalline form of embodiment 13, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2. [0460] Embodiment 17.
  • Embodiment 18 The crystalline form of embodiment 13, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5.1 ⁇ 0.2, 5.9 ⁇ 0.2, 11.1 ⁇ 0.2, 11.8 ⁇ 0.2, 12.6 ⁇ 0.2, 15.3 ⁇ 0.2, 15.7 ⁇ 0.2, 17.1 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.1 ⁇ 0.2, 19.4 ⁇ 0.2, 23.4 ⁇ 0.2, 23.5 ⁇ 0.2 and 26 ⁇ 0.2. [0461] Embodiment 18. The crystalline form of embodiment 13, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in Attorney Docket No.
  • Embodiment 13 The crystalline form of embodiment 13, wherein the crystalline form has an X-ray powder diffraction pattern substantially corresponding to FIG.2A.
  • Embodiment 20 The crystalline form of any one of embodiments 13-19, wherein the crystalline form has an differential scanning calorimetry (DSC) pattern substantially corresponding to FIG.2C.
  • Embodiment 21 The crystalline form of any one of embodiments 13-20, wherein the crystalline form has a thermogravimetric analysis (TGA) pattern substantially corresponding to FIG.2B.
  • TGA thermogravimetric analysis
  • Embodiment 23 The crystalline form of embodiment 22, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.1 ⁇ 0.2, 6 ⁇ 0.2, 9.2 ⁇ 0.2, 10.1 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 12.6 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 17.2 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 20.5 ⁇ 0.2, 21.5 ⁇ 0.2, 21.8 ⁇ 0.2, 22.8 ⁇ 0.2, 23.5 ⁇ 0.2, 23.8 ⁇ 0.2, 24.2 ⁇ 0.2, 24.9 ⁇ 0.2, 25.7 ⁇ 0.2, 26.5 ⁇ 0.2, 26.8 ⁇ 0.2, 27.7 ⁇ 0.2, 31.5 ⁇ 0.2 and 32.6 ⁇ 0.2.
  • Embodiment 24 The crystalline form of embodiment 22, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2. [0468] Embodiment 25.
  • Embodiment 26 The crystalline form of embodiment 22, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2. [0469] Embodiment 26.
  • Embodiment 27 The crystalline form of embodiment 22, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 6 ⁇ 0.2, 11.2 ⁇ 0.2, 12 ⁇ 0.2, 15.2 ⁇ 0.2, 15.6 ⁇ 0.2, 17 ⁇ 0.2, 18.4 ⁇ 0.2, 19 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 20.2 ⁇ 0.2, 23.8 ⁇ 0.2, 26.5 ⁇ 0.2, 26.5 ⁇ 0.2 and 27.7 ⁇ 0.2. [0470] Embodiment 27.
  • Embodiment 28 The crystalline form of embodiment 22, wherein the crystalline form has an X-ray powder diffraction pattern substantially corresponding to FIG.3A.
  • Embodiment 29 The crystalline form of any one of embodiments 22-28, wherein the crystalline form has an differential scanning calorimetry (DSC) pattern substantially corresponding to FIG.3C.
  • Embodiment 30 The crystalline form of any one of embodiments 22-29, wherein the crystalline form has a thermogravimetric analysis (TGA) pattern substantially corresponding to FIG.3B.
  • Embodiment 31 Embodiment 31.
  • TGO-025WO Formula (I) wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2. [0475] Embodiment 32.
  • Embodiment 33 The crystalline form of embodiment 31, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2. [0476] Embodiment 33.
  • Embodiment 34 The crystalline form of embodiment 31, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2. [0477] Embodiment 34.
  • Embodiment 35 The crystalline form of embodiment 31, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2. [0478] Embodiment 35.
  • Embodiment 36 The crystalline form of embodiment 31, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 10.5 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.3 ⁇ 0.2. [0479] Embodiment 36.
  • Embodiment 37 The crystalline form of embodiment 31, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5.2 ⁇ 0.2, 7.9 ⁇ 0.2, 10.5 ⁇ 0.2, 11.8 ⁇ 0.2, 15.9 ⁇ 0.2, 16 ⁇ 0.2, 16.5 ⁇ 0.2, 17.1 ⁇ 0.2, 17.6 ⁇ 0.2, Attorney Docket No. TGO-025WO 18.4 ⁇ 0.2, 18.7 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.2 ⁇ 0.2, 23.8 ⁇ 0.2, 24.3 ⁇ 0.2, 24.8 ⁇ 0.2, 25.8 ⁇ 0.2, 26.1 ⁇ 0.2, 26.3 ⁇ 0.2, 28.4 ⁇ 0.2, 29.2 ⁇ 0.2 and 35.5 ⁇ 0.2. [0480] Embodiment 37.
  • Embodiment 38 An anhydrous crystalline form, Form D, of (R)-N-(4-amino-4'- fluoro-[1,1'-biphenyl]-3-yl)-4-(S-methylsulfonimidoyl)benzamide, having Formula (I): Formula (I), wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.
  • Embodiment 39 The crystalline form of embodiment 38, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 10.8 ⁇ 0.2, 13.5 ⁇ 0.2, 14 ⁇ 0.2, 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 17.3 ⁇ 0.2, 18.1 ⁇ 0.2, 18.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2, 21.6 ⁇ 0.2, 23.3 ⁇ 0.2, 24.3 ⁇ 0.2, 25.2 ⁇ 0.2, 26 ⁇ 0.2, 26.3 ⁇ 0.2, 27 ⁇ 0.2, 28.5 ⁇ 0.2, 33.3 ⁇ 0.2, 35.5 ⁇ 0.2, 35.8 ⁇ 0.2 and 37.9 ⁇ 0.2.
  • Embodiment 40 Embodiment 40.
  • Embodiment 41 The crystalline form of embodiment 38, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 16.1 ⁇ 0.2, 16.9 ⁇ 0.2, 19.4 ⁇ 0.2, 20.7 ⁇ 0.2 and 24.3 ⁇ 0.2.
  • Embodiment 42 Embodiment 42.
  • Embodiment 44 The crystalline form of any one of embodiments 38-43, wherein the crystalline form has an differential scanning calorimetry (DSC) pattern substantially corresponding to FIG.5C.
  • Embodiment 45 The crystalline form of any one of embodiments 38-44, wherein the crystalline form has a thermogravimetric analysis (TGA) pattern substantially corresponding to FIG.5B.
  • Embodiment 46 Embodiment 46.
  • Embodiment 48 The crystalline form of embodiment 46, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 11.8 ⁇ 0.2, 16.5 ⁇ 0.2, 21.3 ⁇ 0.2 and 26.1 ⁇ 0.2.
  • Embodiment 49 The crystalline form of embodiment 46, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at values of 2 in degrees selected from 11.8 ⁇ 0.2, 16.5 ⁇ 0.2, 21.3 ⁇ 0.2 and 26.1 ⁇ 0.2. [0493] Embodiment 50.
  • the crystalline form of embodiment 46 wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 11.8 ⁇ 0.2, 16.5 ⁇ 0.2, 21.3 ⁇ 0.2 and 26.1 ⁇ 0.2 and at least one (e.g., one, two, three, four, five or six) additional characteristic peaks at values of 2 in degrees selected from: 7.1 ⁇ 0.2, 10.7 ⁇ 0.2, 16.1 ⁇ 0.2, 18.9 ⁇ 0.2, 20.7 ⁇ 0.2, 21.5 ⁇ 0.2, 23.7 ⁇ 0.2, 24.2 ⁇ 0.2 and 33.3 ⁇ 0.2.
  • Embodiment 51 Embodiment 51.
  • Embodiment 52 The crystalline form of embodiment 46, wherein the crystalline form has an X-ray powder diffraction pattern substantially corresponding to FIG.6A.
  • Embodiment 53 The crystalline form of embodiment 46, wherein the crystalline form has an X-ray powder diffraction pattern substantially corresponding to FIG.6A.
  • Embodiment 54 The crystalline form of any one of embodiments 46-52, wherein the crystalline form has an differential scanning calorimetry (DSC) pattern substantially corresponding to FIG.6C.
  • Embodiment 54 The crystalline form of any one of embodiments 46-53, wherein the crystalline form has a thermogravimetric analysis (TGA) pattern substantially corresponding to FIG.6B.
  • TGA thermogravimetric analysis
  • TGO-025WO 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2. [0499] Embodiment 56.
  • Embodiment 57 The crystalline form of embodiment 55, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 7.5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 12.5 ⁇ 0.2, 15.1 ⁇ 0.2, 16.5 ⁇ 0.2, 17.8 ⁇ 0.2, 18.1 ⁇ 0.2, 18.7 ⁇ 0.2, 19.1 ⁇ 0.2, 20.6 ⁇ 0.2, 21 ⁇ 0.2, 21.3 ⁇ 0.2, 22.8 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2, 24.6 ⁇ 0.2, 25.3 ⁇ 0.2, 26.1 ⁇ 0.2 and 26.4 ⁇ 0.2. [0500] Embodiment 57.
  • Embodiment 55 The crystalline form of embodiment 55, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 18.1 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2 and 24.6 ⁇ 0.2.
  • Embodiment 58 The crystalline form of embodiment 55, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 18.1 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2 and 24.6 ⁇ 0.2.
  • Embodiment 59 Embodiment 59.
  • Embodiment 60 The crystalline form of embodiment 55, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5 ⁇ 0.2, 8 ⁇ 0.2, 10 ⁇ 0.2, 18.1 ⁇ 0.2, 23.8 ⁇ 0.2, 24 ⁇ 0.2 and 24.6 ⁇ 0.2. [0503] Embodiment 60.
  • Embodiment 61 The crystalline form of embodiment 55, wherein the crystalline form has an X-ray powder diffraction pattern substantially corresponding to FIG.7A.
  • Embodiment 62 The crystalline form of any one of embodiments 55-61, wherein the crystalline form has an differential scanning calorimetry (DSC) pattern substantially corresponding to FIG.7C.
  • Embodiment 63 The crystalline form of any one of embodiments 55-62, wherein the crystalline form has a thermogravimetric analysis (TGA) pattern substantially corresponding to FIG.7B. Attorney Docket No. TGO-025WO [0507] Embodiment 64.
  • DSC differential scanning calorimetry
  • TGA thermogravimetric analysis
  • Embodiment 65 The crystalline form of embodiment 64, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Embodiment 66 The crystalline form of embodiment 64, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 16.7 ⁇ 0.2, 19.3 ⁇ 0.2, 21.2 ⁇ 0.2, 24.4 ⁇ 0.2 and 26.7 ⁇ 0.2.
  • Embodiment 67 The crystalline form of embodiment 64, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 16.7 ⁇ 0.2, 19.3 ⁇ 0.2, 21.2 ⁇ 0.2, 24.4 ⁇ 0.2 and 26.7 ⁇ 0.2.
  • Embodiment 68 Embodiment 68.
  • the crystalline form of embodiment 64 wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 5.6 ⁇ 0.2, 10.5 ⁇ 0.2, 13.9 ⁇ 0.2, 15.8 ⁇ 0.2, 16.7 ⁇ 0.2, 17.9 ⁇ 0.2, 18.3 ⁇ 0.2, 18.5 ⁇ 0.2, 18.9 ⁇ 0.2, 19.3 ⁇ 0.2, 19.5 ⁇ 0.2, 19.9 ⁇ 0.2, 20.9 ⁇ 0.2, 21.2 ⁇ 0.2, 22.6 ⁇ 0.2, 23.9 ⁇ 0.2, 24.4 ⁇ 0.2, 24.7 ⁇ 0.2, 25.2 ⁇ 0.2, 26.3 ⁇ 0.2, 26.7 ⁇ 0.2, 27.6 ⁇ 0.2, 28 ⁇ 0.2, 28.9 ⁇ 0.2, 31.7 ⁇ 0.2, 34.2 ⁇ 0.2 and 36 ⁇ 0.2.
  • Embodiment 69 The crystalline form of embodiment 64, wherein the crystalline form has an X-ray powder diffraction pattern substantially corresponding to FIG.8A.
  • Embodiment 70 The crystalline form of any one of embodiments 64-69, wherein the crystalline form has an differential scanning calorimetry (DSC) pattern substantially corresponding to FIG.8C.
  • Embodiment 71 The crystalline form of any one of embodiments 64-70, wherein the crystalline form has a thermogravimetric analysis (TGA) pattern substantially corresponding to FIG.8B.
  • TGA thermogravimetric analysis
  • Embodiment 72 The crystalline form of embodiment 72, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 18.7 ⁇ 0.2, 19 ⁇ 0.2, 19.7 ⁇ 0.2, 20.5 ⁇ 0.2, 20.8 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2.
  • Embodiment 74 The crystalline form of embodiment 72, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 18.7 ⁇ 0.2, 19 ⁇ 0.2, 20.5 ⁇ 0.2 and 20.8 ⁇ 0.2.
  • Embodiment 75 Embodiment 75.
  • Embodiment 76 The crystalline form of embodiment 72, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at values of 2 in degrees selected from 18.7 ⁇ 0.2, 19 ⁇ 0.2, 20.5 ⁇ 0.2 and 20.8 ⁇ 0.2.
  • Embodiment 77 The crystalline form of embodiment 72, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 18.7 ⁇ 0.2, 19 ⁇ 0.2, 20.5 ⁇ 0.2 and 20.8 ⁇ 0.2 and at least one (e.g., one, two, three, four, five or six) additional characteristic peaks at values of 2 in degrees selected from: 12.3 ⁇ 0.2, 14.9 ⁇ 0.2, 16.4 ⁇ 0.2, 17.9 ⁇ 0.2, 19.7 ⁇ 0.2, 21.7 ⁇ 0.2, 24.6 ⁇ 0.2, 25 ⁇ 0.2 and 25.7 ⁇ 0.2. [0520] Embodiment 77.
  • Embodiment 78 The crystalline form of embodiment 72, wherein the crystalline form has an X-ray powder diffraction pattern substantially corresponding to FIG.9A.
  • Embodiment 79 The crystalline form of embodiment 72, wherein the crystalline form has an X-ray powder diffraction pattern substantially corresponding to FIG.9A.
  • Embodiment 80 The crystalline form of any one of embodiments 72-78, wherein the crystalline form has an differential scanning calorimetry (DSC) pattern substantially corresponding to FIG.9C.
  • Embodiment 80 The crystalline form of any one of embodiments 72-79, wherein the crystalline form has a thermogravimetric analysis (TGA) pattern substantially corresponding to FIG.9B.
  • Embodiment 81 Embodiment 81.
  • Embodiment 82 The crystalline form of embodiment 81, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at Attorney Docket No. TGO-025WO values of 2 in degrees selected from 8.9 ⁇ 0.2, 12.3 ⁇ 0.2, 14.6 ⁇ 0.2, 15.5 ⁇ 0.2, 16 ⁇ 0.2, 17.2 ⁇ 0.2, 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 20.2 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2, 22.9 ⁇ 0.2, 24.5 ⁇ 0.2, 24.8 ⁇ 0.2, 26.7 ⁇ 0.2, 27.4 ⁇ 0.2 and 30 ⁇ 0.2.
  • Embodiment 83 Embodiment 83.
  • Embodiment 84 The crystalline form of embodiment 81, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least one characteristic peak at values of 2 in degrees selected from 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2 and 26.7 ⁇ 0.2.
  • Embodiment 84 The crystalline form of embodiment 81, wherein the crystalline form has an X-ray powder diffraction pattern comprising at least five characteristic peaks at values of 2 in degrees selected from 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2 and 26.7 ⁇ 0.2.
  • Embodiment 85 Embodiment 85.
  • Embodiment 86 The crystalline form of embodiment 81, wherein the crystalline form has an X-ray powder diffraction pattern comprising characteristic peaks at a value of 2 in degrees of 17.9 ⁇ 0.2, 18.2 ⁇ 0.2, 18.6 ⁇ 0.2, 19.4 ⁇ 0.2, 19.8 ⁇ 0.2, 21.1 ⁇ 0.2, 22.2 ⁇ 0.2 and 26.7 ⁇ 0.2. [0529] Embodiment 86.
  • Embodiment 87 The crystalline form of embodiment 81, wherein the crystalline form has an X-ray powder diffraction pattern substantially corresponding to FIG.10A.
  • Embodiment 88 The crystalline form of any one of embodiments 81-87, wherein the crystalline form has an differential scanning calorimetry (DSC) pattern substantially corresponding to FIG.10B.
  • Embodiment 89 The crystalline form of any one of embodiments 81-88, wherein the crystalline form is a hydrate.
  • Embodiment 90 A pharmaceutical composition comprising a crystalline form of any one of embodiments 1-89.
  • Embodiment 91 Embodiment 91.
  • a method of treating a subject having, or at risk of developing, a cancer comprising administering to the subject an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an Attorney Docket No. TGO-025WO effective amount of compound of Formula (I) wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 92 A method of treating a subject having, or at risk of developing, a cancer, the method comprising administering to the subject (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Formula (I) wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 93 The method of embodiment 91 or 92, wherein the compound, crystalline form or pharmaceutical composition is administered in combination with one or more additional therapeutic agents.
  • Embodiment 94 The method of embodiment 93, wherein at least one of the additional therapeutic agents is an immune checkpoint modulator.
  • Embodiment 95 Embodiment 95.
  • Embodiment 96 A method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I) wherein the treatment modulates and/or improves the Teff cell to Treg cell ratio in the tumor or tumor microenvironment, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 96 A method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Attorney Docket No.
  • Embodiment 97 A method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I) wherein the treatment reduces or depletes Treg cells in the tumor or tumor microenvironment, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 98 Embodiment 98.
  • a method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Formula (I) wherein the treatment reduces or depletes Treg cells in the tumor or tumor microenvironment, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 99 A method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 Attorney Docket No.
  • Embodiment 100 A method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Formula (I) wherein the treatment induces or increases the expression of cytokines that promote anti-tumor activity, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 101 Embodiment 101.
  • Embodiment 102 A method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I) wherein the treatment reduces the expression of cytokines that promote Treg cell recruitment, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 103 A method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I) wherein the treatment reduces the expression of cytokines that promote Treg cell recruitment, wherein the cancer is identified as having modified STK11 activity or expression.
  • a method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Attorney Docket No. TGO-025WO Formula (I) wherein the treatment reduces the expression of cytokines that promote Treg cell recruitment, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 104 The method of embodiment 102 or 103, wherein the cytokines are CCL1 or CCL22.
  • Embodiment 105 Embodiment 105.
  • a method of treating a cancer in a subject comprising administering to the subject an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I) wherein the administering of the crystalline form or the composition does not reduce erythroid or myeloid cell viability, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 106 Embodiment 106.
  • a method of treating a cancer in a subject comprising administering to the subject (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Formula (I) wherein the treatment does not reduce erythroid or myeloid cell viability, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 107 A method of treating a cancer in a subject, wherein the cancer presents an immune evasion phenotype characterized by STK11 mutant expression comprising: administering an effective amount of a crystalline form of any one of embodiments 1-89, or the Attorney Docket No.
  • Embodiment 108 A method of treating a cancer in a subject, wherein the cancer presents an immune evasion phenotype characterized by STK11 mutant expression comprising: administering (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Formula (I) wherein the treatment is capable of attenuating or reversing the immune evasion phenotype.
  • Embodiment 109 A method of treating a cancer in a subject, wherein the cancer presents an immune evasion phenotype characterized by STK11 mutant expression comprising: administering (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Formula (I) wherein the treatment is capable of attenuating or reversing the immune evasion phenotype.
  • Embodiment 110 A method of treating a cancer in a subject comprising administering to the subject an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I) wherein an immune checkpoint modulator has been, is, or will be administered to the subject, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 111 A method of treating a cancer in a subject comprising administering to the subject (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I),
  • Embodiment 112 A method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator, wherein an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I), is, or will be administered to the subject, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 113 Embodiment 113.
  • a method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator, wherein (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Formula (I) is, or will be administered to the subject, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 114 The method of any one of embodiments 91-113, wherein the crystalline form, compound or the composition is administered in combination with two or more additional therapeutic agents, wherein at least one of the additional therapeutic agents is an immune checkpoint modulator, optionally wherein at least two of the additional therapeutic agents are immune checkpoint modulators.
  • Embodiment 115 Embodiment 115.
  • each immune checkpoint modulator is independently a checkpoint inhibitor, a T cell co- stimulatory receptor agonist or a dendritic cell co-stimulatory receptor agonist.
  • Embodiment 116 The method of any one of embodiments 94-104 and 109-114, wherein at least one immune checkpoint modulator is independently a T cell co-stimulatory receptor agonist or a dendritic cell co-stimulatory receptor agonist.
  • Attorney Docket No. TGO-025WO [0560]
  • Embodiment 117 The method of any one of embodiments 94-104 and 109-114, wherein at least one immune checkpoint modulator is a checkpoint inhibitor.
  • Embodiment 118 The method of embodiment 117, wherein each checkpoint inhibitor is independently selected from an anti-CTLA-4 agent, an anti-PD-1 agent, an anti-PD- L1 agent, an anti-4-1 BB agent, an anti-OX-40 agent, an anti-GITR agent, an anti- CD27 agent, an anti-CD28 agent, an anti-CD40 agent, an anti-LAG3 agent, an anti-ICOS agent, an anti- TWEAKR agent, an anti-HVEM agent, an anti-TIM-1 agent, an anti-TIM-3 agent, an anti- VISTA agent, and an anti-TIGIT agent.
  • Embodiment 119 Embodiment 119.
  • each checkpoint inhibitor is independently selected from an anti-CTLA-4 agent, an anti-PD-1 agent and an anti- PD-L1 agent.
  • Embodiment 120 The method of embodiment 117, wherein the checkpoint inhibitor is an anti-CTLA-4 agent.
  • Embodiment 121 The method of embodiment 117, wherein the checkpoint inhibitor is an anti-PD1 agent.
  • Embodiment 122 The method of embodiment 117, wherein the checkpoint inhibitor is an anti-PD-L1 agent.
  • Embodiment 123 Embodiment 123.
  • Embodiment 124 The method of any one of embodiments 94-104 and 109-123, wherein each immune checkpoint inhibitor is independently an antibody.
  • Embodiment 125 Embodiment 125.
  • each checkpoint inhibitor is independently selected from an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-4-1 BB antibody, an anti-OX-40 antibody, an anti-GITR antibody, an anti-CD27 antibody, an anti-CD28 antibody, an anti-CD40 antibody, an anti-LAG3 antibody, an anti-ICOS antibody, an anti-TWEAKR antibody, an anti-HVEM antibody, an anti-TIM-1 antibody, an anti-TIM-3 antibody, an anti-VISTA antibody, and an anti-TIGIT antibody.
  • each checkpoint inhibitor is independently selected from an anti-CTLA-4 antibody, an anti-PD-1 antibody and an anti-PD-L1 antibody.
  • each checkpoint inhibitor is independently selected from an anti-CTLA-4 antibody, an anti-PD-1 antibody and an anti-PD-L1 antibody.
  • each immune checkpoint inhibitor is independently selected from nivolumab; CT-011; AMP-224; pembrolizumab; pidilizumab; cemiplimab; dostarlimab; prolgolimab; spartalizumab; camrelizumab; sasanlimab, sintilimab; tislelizumab; toripalimab; retifanlimab; MEDI0680; budigalimab and geptanolimab.
  • each checkpoint inhibitor is independently selected from an anti-PD1 antibody and an anti-PD-L1 antibody.
  • Embodiment 129 The method of embodiment 124, wherein the checkpoint inhibitor is an anti-CTLA-4 antibody.
  • Embodiment 130 The method of embodiment 124, wherein the checkpoint inhibitor is an anti-PD1 antibody.
  • Embodiment 131 The method of embodiment 124, wherein the checkpoint inhibitor is an anti-PD1-L1 antibody.
  • Embodiment 132 The method of embodiment 125, 126 and 129, wherein the anti- CTLA-4 antibody is ipilimumab.
  • Embodiment 133 Embodiment 133.
  • Embodiment 134 The method of any one of embodiments 125, 126, 128 and 130, wherein the anti-PD-1 antibody is pembrolizumab or nivolumab.
  • Embodiment 135. The method of any one of embodiments 125, 126, 128 and 130, wherein the anti-PD-1 antibody is nivolumab.
  • Embodiment 136 The method of any one of embodiments 125, 126, 128 and 130, wherein the anti-PD-1 antibody is nivolumab.
  • Embodiment 137 The method of any one of embodiments 94-104 and 109-116, wherein the immune checkpoint modulator is a T cell co-stimulatory receptor agonist or a dendritic cell co-stimulatory receptor agonist.
  • Embodiment 138 The method of any one of embodiments 125, 126, 128 and 131, wherein the anti-PD-L1 antibody is atezolizumab (CAS number 1380723-44-3), avelumab (CAS number 1537032-82-8), or durvalumab (CAS number 1428935-60-7).
  • Embodiment 137 The method of any one of embodiments 94-104 and 109-116, wherein the immune checkpoint modulator is a T cell co-stimulatory receptor agonist or a dendritic cell co-stimulatory receptor agonist.
  • Embodiment 140 The method of any one of embodiments 93-137, wherein the method further comprises administering at least one additional therapeutic agent wherein the additional therapeutic agent is a targeted agent.
  • an anti-angiogenesis agent e.g., an anti-VEGF agent
  • KRAS inhibitor an anti-angiogenesis agent
  • ALK inhibitor e.g., an anti-VEGF agent
  • ROS1 inhibitor e.g., an anti-VEGF agent
  • BRAF inhibitor e.g., a ROS1 inhibitor
  • MEK inhibitor e.g., MEK inhibitor
  • MET inhibitor e.g., a MET inhibitor
  • TRK inhibitor e.g., a TRK inhibitor.
  • each targeted agent is independently selected from bevacizumab, ramucirumab, sotorasib, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, entrectinib, dabrafenib, trametinib, capmatinib, tepotinib and larotrectinib.
  • Embodiment 141 The method of any one of embodiments 94-140, wherein the method further comprises administering at least one additional therapeutic agent wherein the additional therapeutic agent is a chemotherapeutic agent.
  • Embodiment 142 Embodiment 142.
  • each chemotherapeutic agent is independently selected from cisplatin, carboplatin, paclitaxel, Albumin-bound paclitaxel (nab-paclitaxel), docetaxel, gemcitabine, vinorelbine, etoposide and pemetrexed.
  • Embodiment 143 The method of embodiment 141, wherein at least one chemotherapeutic agent is a platinum-containing therapeutic agent.
  • Embodiment 144 The method of embodiment 141, wherein one chemotherapeutic agent is a platinum-containing chemotherapeutic agent (e.g., cisplatin) and a second chemotherapeutic agent is pemetrexed.
  • Embodiment 145 The method of any one of embodiments 94-144, wherein the method further comprises administering at least one additional therapeutic agent wherein the additional therapeutic agent is radiation.
  • Embodiment 146 The method of any one of embodiments 91-145, wherein the cancer is resistant to anti-PD1 therapy or anti-PD-L1 therapy.
  • Embodiment 147 The method of any one of embodiments 91-146, wherein the cancer is resistant to chemotherapy (e.g., platinum-containing chemotherapy).
  • Embodiment 148 Embodiment 148.
  • lung cancer e.g., lung adenocarcinoma, non- small cell lung cancer (NSCLC), squamous cell lung carcinoma
  • colorectal cancer e.g., colon adenocarcinoma, rectal adenocarcinoma
  • breast cancer e.g., invasive ductal carcinoma
  • pancreatic cancer e.g., pancreatic adenocarcinoma
  • endometrial cancer e.g., endometrioid carcinoma
  • neuroendocrine cancer e.g., large cell neuroendocrine carcinoma
  • melanoma non- melanoma skin cancer
  • cholangiocarcinoma gallbladder cancer
  • ovarian cancer e.g., ovarian serous adenocarcinoma
  • bladder cancer e.g., bladder urothelial carcinoma
  • Embodiment 150 The method of embodiment 149, wherein the cancer is lung cancer.
  • Embodiment 151 The method of embodiment 150, wherein the cancer is lung adenocarcinoma.
  • Embodiment 152 The method of embodiment 150, wherein the cancer is non-small cell lung cancer (NSCLC).
  • Embodiment 153 The method of embodiment 152, wherein the cancer is non- squamous non-small cell lung cancer (NSCLC).
  • Embodiment 154 The method of embodiment 149, wherein the cancer is colorectal cancer or colon adenocarcinoma.
  • Embodiment 155 Embodiment 155.
  • Embodiment 157 The method of any one of embodiments 91-154, wherein the cancer is identified as having a STK11 mutation and one or more additional mutations.
  • Embodiment 158 The method of embodiment 157, wherein the additional mutations are selected from KRAS mutations and KEAP1 mutations.
  • Embodiment 159 The method of embodiment 157, wherein the additional mutations are KRAS mutations. Attorney Docket No.
  • Embodiment 160 The method of embodiment 158 or 159, wherein the KRAS mutations are mutations at position G12, optionally wherein the KRAS mutations are selected from G12D mutations, G12C mutations, G12V mutations or combinations thereof.
  • Embodiment 161. The method of embodiment 158, wherein the additional mutations are KEAP1 mutations.
  • Embodiment 162. The method of embodiment 158, wherein the additional mutations are KRAS mutations and KEAP1 mutations.
  • Embodiment 163. The method of any one of embodiments 156-162, wherein the STK11 mutation is an inactivating (loss of function) mutation.
  • Embodiment 164 The method of any one of embodiments 91-163 wherein the effective amount of compound is 80 mg administered once daily (QD).
  • Embodiment 165 The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 80 mg of free base equivalent of compound of Formula (I) once daily (QD).
  • Embodiment 166 The method of any one of embodiments 91-163 wherein the effective amount of compound is 40 mg administered once daily (QD).
  • Embodiment 167 The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 40 mg of free base equivalent of compound of Formula (I) once daily (QD).
  • Embodiment 168 The method of any one of embodiments 91-163 wherein the effective amount of compound is 40 mg or 80 mg administered once daily (QD).
  • Embodiment 169 The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 40 mg or 80 mg of free base equivalent of compound of Formula (I) once daily (QD).
  • Embodiment 170 The method of any one of embodiments 91-163 wherein the effective amount of compound is 80 mg administered once daily (QD) 2 weeks on/1 week off.
  • Embodiment 172 The method of any one of embodiments 91-163 wherein the effective amount of composition is 40 mg administered once daily (QD) 2 weeks on/1 week off.
  • Embodiment 173 The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 40 mg of free base equivalent of compound of Formula (I) once daily (QD) 2 weeks on/1 week off.
  • Embodiment 175. The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 40 mg or 80 mg of free base equivalent of compound of Formula (I) once daily (QD) 2 weeks on/1 week off.
  • Embodiment 176. The method of any one of embodiments 91-163 wherein the effective amount of compound is 80 mg administered once daily (QD) 1 week on/2 weeks off.
  • Embodiment 180 The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 80 mg of free base equivalent of compound of Formula (I) once daily (QD) 1 week on/2 weeks off.
  • Embodiment 178 The method of any one of embodiments 91-163 wherein the effective amount of compound is 40 mg administered once daily (QD) 1 week on/2 weeks off.
  • Embodiment 179 The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 40 mg of free base equivalent of compound of Formula (I) once daily (QD) 1 week on/2 weeks off.
  • Embodiment 180 Embodiment 180.
  • Embodiment 181 The method of any one of embodiments 91-163 wherein the effective amount of compound is calculated to administer 40 mg or 80 mg of free base equivalent of compound of Formula (I) once daily (QD) 1 week on/2 weeks off.
  • Embodiment 182. The method of any one of embodiments 91-163 wherein the effective amount of compound is 80 mg administered once daily (QD) 2 days on/5 days off.
  • Attorney Docket No. TGO-025WO Embodiment 183.
  • Embodiment 184 The method of any one of embodiments 91-163 wherein the effective amount of compound is 40 mg administered once daily (QD) 2 days on/5 days off.
  • Embodiment 185 The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 40 mg of free base equivalent of compound of Formula (I) once daily (QD) 2 days on/5 days off.
  • Embodiment 186 The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 40 mg of free base equivalent of compound of Formula (I) once daily (QD) 2 days on/5 days off.
  • Embodiment 187 The method of any one of embodiments 91-163 wherein the effective amount of compound is calculated to administer 40 mg or 80 mg of free base equivalent of compound of Formula (I) once daily (QD) 2 days on/5 days off.
  • Embodiment 188 The method of any one of embodiments 91-163 wherein the effective amount of compound is 80 mg administered once weekly (QW).
  • Embodiment 189 The method of any one of embodiments 91-163 wherein the effective amount of compound is 40 mg or 80 mg administered once daily (QW).
  • Embodiment 193 The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 80 mg of free base equivalent of compound of Formula (I) once weekly (QW).
  • Embodiment 190 The method of any one of embodiments 91-163 wherein the effective amount of compound is 40 mg administered once weekly (QW).
  • Embodiment 191. The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 40 mg of free base equivalent of compound of Formula (I) once weekly (QW).
  • Embodiment 192 The method of any one of embodiments 91-163 wherein the effective amount of compound is 40 mg or 80 mg administered once weekly (QW).
  • Embodiment 194 The method of any one of embodiments 91-163 wherein the effective amount of compound is 80 mg administered twice weekly (QW).
  • Embodiment 195 The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 80 mg of free base equivalent of compound of Formula (I) twice weekly (QW).
  • Embodiment 196 The method of any one of embodiments 91-163 wherein the effective amount of compound is 40 mg administered twice weekly (QW).
  • Embodiment 197 The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 40 mg of free base equivalent of compound of Formula (I) twice weekly (QW).
  • Embodiment 198 The method of any one of embodiments 91-163 wherein the effective amount of compound is 40 mg or 80 mg administered twice weekly (QW).
  • Embodiment 199 The method of any one of embodiments 91-163 wherein the effective amount of composition is calculated to administer 40 mg or 80 mg of free base equivalent of compound of Formula (I) twice weekly (QW).
  • Embodiment 200 Embodiment 200.
  • a method for ascertaining susceptibility of a subject having or having been diagnosed with cancer to treatment with a crystalline form of any one of embodiments 1-89 or a composition of embodiment 90 comprising: determining: i) the presence or absence of a STK11 mutation; and/or ii) the level of STK11 activity or expression in the subject or a sample derived from the subject; wherein the presence of a STK11 mutation and/or a modified level of STK11 activity or expression is indicative of susceptibility to treatment with the crystalline form or composition.
  • a method for ascertaining susceptibility of a subject having or having been diagnosed with cancer to treatment with a combination of a crystalline form of any one of embodiments 1-89 or a composition of embodiment 90 and an immune checkpoint modulator comprising: determining: i) the presence or absence of a STK11 mutation; and/or ii) the level of STK11 activity or expression in the subject or a sample derived from the subject; wherein the presence of a STK11 mutation and/or a modified level of STK11 activity or expression is indicative of susceptibility to treatment with a combination of an HDAC inhibitor and an immune checkpoint modulator.
  • Embodiment 202 Embodiment 202.
  • Embodiment 203 Embodiment 203.
  • a compound of Formula (I) or a pharmaceutical composition comprising a compound of Formula (I) for use in a method of treating a subject having, or at risk of developing, a cancer Formula (I) the method comprising administering to the subject an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I), wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 204 The crystalline form, compound or pharmaceutical composition for use of embodiment 202 or 203, wherein the compound or composition is administered in combination with one or more additional therapeutic agents.
  • Embodiment 205 Embodiment 205.
  • Embodiment 206 A crystalline form of any one of embodiments 1-89, or a composition of embodiment 90 for use in a method of treating a cancer in a subject, the method comprising administering to the subject an immune checkpoint modulator and an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I) wherein the treatment modulates and/or improves the Teff cell to Treg cell ratio in the tumor or tumor microenvironment, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 207 A compound of Formula (I) or a pharmaceutical composition comprising a compound of Formula (I) for use in a method of treating a cancer in a subject, the method comprising administering to the subject an immune checkpoint modulator and (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Formula (I) wherein the treatment modulates and/or improves the Teff cell to Treg cell ratio in the tumor or tumor microenvironment, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 208 Embodiment 208.
  • a crystalline form of any one of embodiments 1-89, or a composition of embodiment 90 for use in a method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I) wherein the treatment reduces or depletes Treg cells in the tumor or tumor microenvironment, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 210 Embodiment 210.
  • a crystalline form of any one of embodiments 1-89, or a composition of embodiment 90 for use in a method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I) wherein the treatment induces or increases the expression of cytokines that promote anti-tumor activity, wherein the cancer is identified as having modified STK11 activity or expression.
  • a compound of Formula (I) or a pharmaceutical composition comprising a compound of Formula (I) for use in a method of treating a cancer in a subject comprising administering to the subject an immune checkpoint modulator and (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Formula (I) wherein the treatment induces or increases the expression of cytokines that promote anti-tumor activity, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 213 A crystalline form of any one of embodiments 1-89, or a composition of embodiment 90 for use in a method of treating a cancer in a subject, the method comprising administering to the subject an immune checkpoint modulator and an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I) wherein the treatment reduces the expression of cytokines that promote Treg cell recruitment, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 214 A compound of Formula (I) or a pharmaceutical composition comprising a compound of Formula (I) for use in a method of treating a cancer in a subject, the method comprising administering to the subject an immune checkpoint modulator and (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Formula (I) wherein the treatment reduces the expression of cytokines that promote Treg cell recruitment, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 215. The crystalline form, compound or pharmaceutical composition for use of embodiment 213 or 214, wherein the cytokines are CCL1 or CCL22.
  • Embodiment 216 A crystalline form of any one of embodiments 1-89, or a composition of embodiment 90 for use in a method of treating a cancer in a subject, the method comprising administering to the subject an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I) wherein the administering of the crystalline form or the composition Attorney Docket No. TGO-025WO does not reduce erythroid or myeloid cell viability, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 217 Embodiment 217.
  • a compound of Formula (I) or a pharmaceutical composition comprising a compound of Formula (I) for use in a method of treating a cancer in a subject comprising administering to the subject (a) an effective amount of a compound of Formula (I) or (b) a pharmaceutical composition comprising an effective amount of a compound of Formula (I), Formula (I) wherein the treatment does not reduce erythroid or myeloid cell viability, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 220 Embodiment 220.
  • Embodiment 22 A crystalline form of any one of embodiments 1-89, or a composition of embodiment 90 for use in a method of treating a cancer in a subject, the method comprising administering to the subject an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I) wherein an immune checkpoint modulator has been, is, or will be administered to the subject, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 222 Embodiment 222.
  • Embodiment 22 A crystalline form of any one of embodiments 1-89, or a composition of embodiment 90 for use in a method of treating a cancer in a subject, the method comprising administering to the subject an immune checkpoint modulator, wherein an effective amount of a crystalline form of any one of embodiments 1-89, or the composition of embodiment 90 comprising an effective amount of compound of Formula (I), is, or will be administered to the subject, wherein the cancer is identified as having modified STK11 activity or expression.
  • Embodiment 224 Embodiment 224.
  • Embodiment 226 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 205-215 and 220-225, wherein each immune checkpoint modulator is independently a checkpoint inhibitor, a T cell co-stimulatory receptor agonist or a dendritic cell co-stimulatory receptor agonist. Attorney Docket No. TGO-025WO [0670] Embodiment 227.
  • Embodiment 228 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 205-215 and 220-225, wherein at least one immune checkpoint modulator is independently a T cell co-stimulatory receptor agonist or a dendritic cell co-stimulatory receptor agonist.
  • Embodiment 228 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 205-215 and 220-225, wherein at least one immune checkpoint modulator is a checkpoint inhibitor.
  • each checkpoint inhibitor is independently selected from an anti-CTLA-4 agent, an anti-PD-1 agent, an anti-PD-L1 agent, an anti-4-1 BB agent, an anti-OX- 40 agent, an anti-GITR agent, an anti- CD27 agent, an anti-CD28 agent, an anti-CD40 agent, an anti-LAG3 agent, an anti-ICOS agent, an anti-TWEAKR agent, an anti-HVEM agent, an anti- TIM-1 agent, an anti-TIM-3 agent, an anti-VISTA agent, and an anti-TIGIT agent.
  • each checkpoint inhibitor is independently selected from an anti-CTLA-4 agent, an anti-PD-1 agent and an anti-PD-L1 agent.
  • Embodiment 231. The crystalline form, compound or pharmaceutical composition for use of embodiment 228, wherein the checkpoint inhibitor is an anti-CTLA-4 agent.
  • Embodiment 232. The crystalline form, compound or pharmaceutical composition for use of embodiment 228, wherein the checkpoint inhibitor is an anti-PD1 agent.
  • Embodiment 233 The crystalline form, compound or pharmaceutical composition for use of embodiment 228, wherein the checkpoint inhibitor is an anti-PD-L1 agent.
  • Embodiment 235 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 205-215 and 220-234, wherein each immune checkpoint inhibitor is independently an antibody.
  • Embodiment 236 The crystalline form, compound or pharmaceutical composition for use of embodiment 235, wherein the each checkpoint inhibitor is independently selected from an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-4-1 BB Attorney Docket No.
  • Embodiment 237 The crystalline form, compound or pharmaceutical composition for use of embodiment 235, wherein each checkpoint inhibitor is independently selected from an anti-CTLA-4 antibody, an anti-PD-1 antibody and an anti-PD-L1 antibody.
  • each checkpoint inhibitor is independently selected from an anti-CTLA-4 antibody, an anti-PD-1 antibody and an anti-PD-L1 antibody.
  • each immune checkpoint inhibitor is independently selected from nivolumab; CT-011; AMP-224; pembrolizumab; pidilizumab; cemiplimab; dostarlimab; prolgolimab; spartalizumab; camrelizumab; sasanlimab, sintilimab; tislelizumab; toripalimab; retifanlimab; MEDI0680; budigalimab and geptanolimab.
  • each checkpoint inhibitor is independently selected from an anti-PD1 antibody and an anti-PD-L1 antibody.
  • Embodiment 240 The crystalline form, compound or pharmaceutical composition for use of embodiment 235, wherein the checkpoint inhibitor is an anti-CTLA-4 antibody.
  • Embodiment 241 The crystalline form, compound or pharmaceutical composition for use of embodiment 235, wherein the checkpoint inhibitor is an anti-PD1 antibody.
  • Embodiment 242. The method of embodiment 235, wherein the checkpoint inhibitor is an anti-PD1-L1 antibody.
  • Embodiment 243 Embodiment 243.
  • Embodiment 244 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 236, 237, 239 and 241, wherein the anti-PD-1 antibody is pembrolizumab or nivolumab.
  • Embodiment 245. The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 236, 237, 239 and 241, wherein the anti-PD-1 antibody is pembrolizumab. Attorney Docket No. TGO-025WO [0689] Embodiment 246.
  • Embodiment 247 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 236, 237, 239 and 241, wherein the anti-PD-1 antibody is nivolumab.
  • Embodiment 247 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 236, 237, 239 and 241, wherein the anti-PD-L1 antibody is atezolizumab (CAS number 1380723-44-3), avelumab (CAS number 1537032-82-8), or durvalumab (CAS number 1428935-60-7).
  • Embodiment 248 Embodiment 248.
  • Embodiment 249. The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 204-248, wherein the method further comprises administering at least one additional therapeutic agent wherein the additional therapeutic agent is a targeted agent.
  • each targeted agent is independently selected from an anti- angiogenesis agent (e.g., an anti-VEGF agent), a KRAS inhibitor, an ALK inhibitor, a ROS1 inhibitor, a BRAF inhibitor, a RET inhibitor, a MEK inhibitor, a MET inhibitor and a TRK inhibitor.
  • an anti- angiogenesis agent e.g., an anti-VEGF agent
  • KRAS inhibitor e.g., an anti-VEGF agent
  • ALK inhibitor e.g., a ROS1 inhibitor
  • BRAF inhibitor e.g., a RET inhibitor
  • MEK inhibitor e.g., MEK inhibitor
  • MET inhibitor e.g., a MET inhibitor
  • TRK inhibitor e.g., a TRK inhibitor
  • each targeted agent is independently selected from bevacizumab, ramucirumab, sotorasib, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, entrectinib, dabrafenib, trametinib, capmatinib, tepotinib and larotrectinib.
  • each targeted agent is independently selected from bevacizumab, ramucirumab, sotorasib, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, entrectinib, dabrafenib, trametinib, capmatinib, tepotinib and larotrectinib.
  • Embodiment 252 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 205-251, wherein the method further comprises administering at least one additional therapeutic agent wherein the additional therapeutic agent is
  • each chemotherapeutic agent is independently selected from cisplatin, carboplatin, paclitaxel, Albumin-bound paclitaxel (nab-paclitaxel), docetaxel, gemcitabine, vinorelbine, etoposide and pemetrexed.
  • chemotherapeutic agent is independently selected from cisplatin, carboplatin, paclitaxel, Albumin-bound paclitaxel (nab-paclitaxel), docetaxel, gemcitabine, vinorelbine, etoposide and pemetrexed.
  • each chemotherapeutic agent is independently selected from cisplatin, carboplatin, paclitaxel, Albumin-bound paclitaxel (nab-paclitaxel), docetaxel, gemcitabine, vinorelbine, etoposide and pemetrexed.
  • chemotherapeutic agent is independently selected from cisplatin, carboplatin, paclitaxel,
  • Embodiment 252 The crystalline form, compound or pharmaceutical composition for use of embodiment 252, wherein one chemotherapeutic agent is a platinum-containing chemotherapeutic agent (e.g., cisplatin) and a second chemotherapeutic agent is pemetrexed.
  • Embodiment 256 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 205-255, wherein the method further comprises administering at least one additional therapeutic agent wherein the additional therapeutic agent is radiation.
  • Embodiment 257 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 202-256, wherein the cancer is resistant to anti-PD1 therapy or anti-PD-L1 therapy.
  • Embodiment 258 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 202-256, wherein the cancer is resistant to anti-PD1 therapy or anti-PD-L1 therapy.
  • lung cancer e.g., lung adenocarcinoma, non-small cell lung cancer (NSCLC), squamous cell lung carcinoma
  • colorectal cancer e.g., colon adenocarcinoma, rectal adenocarcinoma
  • breast cancer e.g., invasive ductal carcinoma
  • pancreatic cancer e.g., pancreatic adenocarcinoma
  • endometrial cancer e.g., endometrioid carcinoma
  • neuroendocrine cancer e.g., large cell neuroendocrine carcinoma
  • melanoma non-melanoma skin cancer
  • cholangiocarcinoma gallbladder cancer
  • ovarian cancer e.g., ovarian serous adenocarcinoma
  • bladder cancer e.g.,
  • Embodiment 26 The crystalline form, compound or pharmaceutical composition for use of embodiment 260, wherein the cancer is lung cancer.
  • Embodiment 262. The crystalline form, compound or pharmaceutical composition for use of embodiment 261, wherein the cancer is lung adenocarcinoma.
  • Embodiment 263. The crystalline form, compound or pharmaceutical composition for use of embodiment 261, wherein the cancer is non-small cell lung cancer (NSCLC).
  • Embodiment 264 The crystalline form, compound or pharmaceutical composition for use of embodiment 263, wherein the cancer is non-squamous non-small cell lung cancer (NSCLC).
  • Embodiment 266 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 202-265, wherein the cancer has decreased STK11 expression.
  • Embodiment 267 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 202-154, wherein the cancer has a STK11 mutation.
  • Embodiment 268 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 202-265, wherein the cancer is identified as having a STK11 mutation and one or more additional mutations.
  • Embodiment 272 The crystalline form, compound or pharmaceutical composition for use of embodiment 268, wherein the additional mutations are selected from KRAS mutations and KEAP1 mutations.
  • Embodiment 270 The crystalline form, compound or pharmaceutical composition for use of embodiment 268, wherein the additional mutations are KRAS mutations.
  • Embodiment 271. The crystalline form, compound or pharmaceutical composition for use of embodiment 269 or 270, wherein the KRAS mutations are mutations at position G12, optionally wherein the KRAS mutations are selected from G12D mutations, G12C mutations, G12V mutations or combinations thereof.
  • Embodiment 273 The crystalline form, compound or pharmaceutical composition for use of embodiment 269, wherein the additional mutations are KRAS mutations and KEAP1 mutations.
  • Embodiment 274 The crystalline form, compound or pharmaceutical composition for use of any one of embodiments 267-273, wherein the STK11 mutation is an inactivating (loss of function) mutation.
  • Embodiment 275 The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 80 mg administered once daily (QD).
  • Embodiment 276 The pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 80 mg of free base equivalent of compound of Formula (I) once daily (QD).
  • Embodiment 277 The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 40 mg administered once daily (QD).
  • Embodiment 278 The pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 40 mg of free base equivalent of compound of Formula (I) once daily (QD).
  • Embodiment 282 The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 40 mg or 80 mg administered once daily (QD).
  • Embodiment 280 The pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 40 mg or 80 mg of free base equivalent of compound of Formula (I) once daily (QD).
  • Embodiment 281. The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 80 mg administered once daily (QD) 2 weeks on/1 week off. [0725] Embodiment 282.
  • Embodiment 286 The pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 40 mg or 80 mg of free base equivalent of compound of Formula (I) once daily (QD) 2 weeks on/1 week off.
  • Embodiment 287 The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 80 mg administered once daily (QD) 1 week on/2 weeks off.
  • Embodiment 288 Embodiment 288.
  • Embodiment 292 The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 40 mg or 80 mg administered once daily (QD) 1 week on/2 weeks off.
  • Attorney Docket No. TGO-025WO [0735] Embodiment 292.
  • Embodiment 293. The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 80 mg administered once daily (QD) 2 days on/5 days off.
  • the pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 80 mg of free base equivalent of compound of Formula (I) once daily (QD) 2 days on/5 days off.
  • Embodiment 295. The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 40 mg administered once daily (QD) 2 days on/5 days off.
  • Embodiment 296. The pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 40 mg of free base equivalent of compound of Formula (I) once daily (QD) 2 days on/5 days off.
  • Embodiment 297 Embodiment 297.
  • Embodiment 298 The pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 40 mg or 80 mg of free base equivalent of compound of Formula (I) once daily (QD) 2 days on/5 days off.
  • Embodiment 299. The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 80 mg administered once weekly (QW).
  • Embodiment 300 Embodiment 300.
  • Embodiment 301 The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 40 mg administered once weekly (QW).
  • Embodiment 302. The pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 40 mg of free base equivalent of compound of Formula (I) once weekly (QW).
  • Embodiment 303 The pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 40 mg of free base equivalent of compound of Formula (I) once weekly (QW).
  • Embodiment 304 The pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 40 mg or 80 mg of free base equivalent of compound of Formula (I) once weekly (QW).
  • Embodiment 305 The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 80 mg administered twice weekly (QW).
  • Embodiment 307 The pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 80 mg of free base equivalent of compound of Formula (I) twice weekly (QW).
  • Embodiment 308 The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 40 mg administered twice weekly (QW).
  • Embodiment 308 The pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 40 mg of free base equivalent of compound of Formula (I) twice weekly (QW).
  • Embodiment 309 The crystalline form or compound for use of any one of embodiments 202-274 wherein the effective amount of compound is 40 mg or 80 mg administered twice weekly (QW).
  • Embodiment 310 The pharmaceutical composition for use of any one of embodiments 202-274 wherein the effective amount of composition is calculated to administer 40 mg or 80 mg of free base equivalent of compound of Formula (I) twice weekly (QW).
  • Attorney Docket No. TGO-025WO Examples [0754] The following examples are given for the purpose of illustrating various embodiments of the invention and are not meant to limit the present invention in any fashion. The present examples, along with the methods described herein are presently representative of preferred embodiments, are exemplary, and are not intended as limitations on the scope of the invention. Changes therein and other uses which are encompassed within the spirit of the invention as defined by the scope of the claims will occur to those skilled in the art.
  • API active pharmaceutical ingredient AUC area under the curve BA bioavailability Cmax maximum observed plasma concentration DMA N,N-dimethylacetamide DP drug product DS drug substance DSC differential scanning calorimetry dm/dt change in mass per unit of time DVS dynamic vapor sorption EA ethyl acetate FaSSIF fasted state simulated intestinal fluid FeSSIF fed state simulated intestinal fluid GMP Good Manufacturing Practice HPLC high performance liquid chromatography LOD limit of detection max maximum min minimum MCC microcrystalline cellulose NA not applicable RSD relative standard deviation RH relative humidity RT room temperature or real time sccm standard cubic centimeter per minute Attorney Docket No.
  • TGA Thermal Gravimetric Analysis
  • DSC Differential Scanning Calorimetry
  • XRPD X-ray Powder Diffraction
  • Example 1 Exemplary preparation and characterization of crystalline form A Small scale: Approximately 20 mg of Compound 1, free base was dissolved in acetone (0.8-2 mL). The resulting solution was filtered through a 0.45 ⁇ m nylon membrane filter, and the resulting clear solution was slowly evaporated in ambient condition (about 25°C, 40%RH). The residue was collected by filtration. Larger Scale: [0759] (N-[2-amino-5-(4-fluorophenyl)phenyl]-4-(methylsulfonimidoyl)benzamide (Compound 1) (5.0 g) was charged into a reactor.
  • Form A was characterized by XRPD (FIG.1A), DSC (FIG.1C), TGA (FIG.1B) and 1 H-NMR (FIG.1D).
  • Example 2 Exemplary Dynamic Vapor Sorption measurements
  • Dynamic vapor sorption DVS measurements were performed with an SMS Dynamic Vapor Sorption Intrinsic, Advantage or Adventure System with a total gas flow of 200 sccm, at an oven temperature of 25 °C. Humidity changes were performed in steps of 10%, in a sequence of 40-95-0-95-40% humidity, with dm/dt 0.002, min. equilibration time 60 min and max. equilibration time 360 min.
  • Tosylate salt Form A has high crystallinity as evidenced by its X-ray Powder Diffraction pattern (XRPD) (FIG.11A). No solvent residue is observed by NMR (FIG.11E).
  • DSC shows a melting peak at Tonset of 129.0 °C with an enthalpy of 29J/g.
  • TGA shows about 1.7% weight loss at about 130°C.
  • Attorney Docket No. TGO-025WO Example 7. Preparation of mono-fumaric acid cocrystal Form A [0774] Free base Form A (0.5g) and 153mg of fumaric acid (1.0 equivalent by molar ratio) were weighed into a 20mL glass vial. 14.5mL of acetonitrile and 20 L of water were added into the vial under stirring at 50°C for about 2 hours to obtain a suspension.
  • Mono-fumaric acid cocrystal Form A has high crystallinity as evidenced by its X-ray Powder Diffraction pattern (XRPD) (FIG.12A).
  • Free base Form A has good chemical and physical stability under the tested conditions (Table 20)
  • the mono-fumaric acid cocrystal Form A showed good physical and chemical stability at 25°C/92.5%RH over 1 week but had slight chemical purity decrease of about 1% after stress at 40°C/75%RH and 60°C for 1 week (Table 21).
  • the tosylate salt Form A is physically and chemically unstable. It showed obvious degradation by HPLC and discoloration after stress at 25°C/92.5%RH and 40°C/75%RH after 1 week. It also showed form change after stress at 60°C after 1 week (Table 21).
  • Humidity changes were performed in steps of 10%, in a sequence of 40-95-0-95-40% humidity, with dm/dt 0.002, min. equilibration time 60 min and max. equilibration time 360 min.
  • the results from the DVS test are presented in Table 22 for tosylate form A and for mono-fumaric cocrystal form A.
  • the tosylate salt Form A is highly hygroscopic and absorbs 18.6% water uptake from 40%RH to 95%RH (FIG.11D). Form change was observed after the DVS test.
  • the mono-fumaric acid cocrystal Form A is slightly hygroscopic in ⁇ 80%RH.
  • Solubility of free base Form A, tosylate Form A and mono-fumaric acid cocrystal Form A in aqueous media was measured in 7 pH buffers and bio-relevant fluids including pH 1.2 HCl solution (0.2N), pH 4.5 acetate buffer (50mM), pH 6.8 phosphate buffer (50mM), pH 2.0 SGF, pH 6.5 FaSSIF-v1, pH 5.0 FeSSIF-v1 and pure water at 37°C for 1h and 24h, respectively. Residual solids after the solubility test were analyzed by XRPD.
  • the results are summarized in Table 23.
  • the free base Form A, tosylate Form A and mono-fumaric acid cocrystal Form A showed comparable and pH dependent solubility in the aqueous media. Their solubility reached to about 1.5- >2 mg/mL in pH 1.2 HCl solution but decreased to about 30 ⁇ g/mL in pH 6.8 phosphate buffer.
  • the tosylate salt Form A (1.4 mg/mL) and the mono-fumaric acid cocrystal Form A (1 mg/mL) showed slightly higher solubility than that of the free base Form A (0.8 mg/mL) in SGF (pH 2.0) and in water.
  • the tosylate salt Form A a degradation product was detected by HPLC in supernatant after solubility test in SGF (pH 2.0). After the solubility test, the tosylate salt Form A and the mono-fumaric acid cocrystal Form A dissociated to crystalline free base Form A in pH 4.5 buffer, pH 6.8 buffer, water, FaSSIF-v1 and FeSSIF-v1. Both the Form A and the salt/cocrystal candidates converted to HCl salt Form A (XRPD shown in FIG. 13) after solubility test in pH 1.2 HCl solution Attorney Docket No.
  • mice TGO-025WO a Dosing volume for each dose was 10 L/g.
  • Materials Animals [0785] 96 mice plus 39 spare mice of the species: mus musculus; strain: C57BL/6; age 8-10 weeks; sex: female; and body weight: 16.9-20.0 g [0786] Animal supplier: Shanghai SLAC Laboratory Animal Co., Ltd [0787] The mice were kept in individual ventilation cages at constant temperature (about 20- 26 oC) and humidity (about 40-70%) with 4 animals in each cage. The size of each cage was about 300 mm x 200 mm x 180 mm. The bedding material in each cage was corn cob, which was changed twice per week.
  • the identification labels for each cage contained the following information: number of animals, sex, strain, date received, treatment, study number, group number and the starting date of the treatment.
  • Animals had free access to irradiation sterilized dry granule food during the entire study period. Animals had free access to sterile drinking water. Animals were identified by ear tags.
  • Compounds [0789] Anti-PD1 (solution) supplied by BioXcell and stored at about 4oC. Anti-IgG2a (solution) supplied by BioXcell and stored at about 4oC. Compound I (solid) supplied by Tango Therapeutics and stored at about room temperature. Compound I used in Example 1 exhibits a >10-fold selectivity for HDAC1 compared to HDAC3 in intact cells.
  • Compound I used in Example 1 exhibits a significant selectivity for CoREST deacetylase compared to NCoR, NuRD, and Sin3 as described herein.
  • Methods Cell Culture [0790] The MC38_ sgStk11 tumor cells were maintained in vitro as a monolayer culture in DMEM + 2 mM glutamine supplemented with about 10% heat inactivated fetal bovine serum, about 100 U/ml penicillin and 100 g/ml streptomycin at about 37oC in an atmosphere of about 5% CO 2 in air. The tumor cells were routinely sub-cultured twice weekly by trypsin-EDTA Attorney Docket No. TGO-025WO treatment.
  • mice The cells growing in an exponential growth phase were harvested and counted for tumor inoculation.
  • Tumor Inoculation and Animal Grouping [0791] Each mouse was inoculated subcutaneously at the right upper flank with MC38_ sgStk11 tumor cells (0.5 x 106) in 0.1 ml of PBS for tumor development. Treatments were started on day 4 after tumor inoculation when the average tumor size reached 52 mm 3 . The animals were assigned into groups according to a sorting standard operating procedures based upon their tumor volumes. Each group consisted of 8 tumor bearing mice. The testing article was administrated to the mice according to the predetermined regimen as shown in the experimental design table (Table 1-1).
  • the T/C value (in percent) is an indication of antitumor effectiveness; T and C are the mean volume of the treated and control groups, respectively, on a given day.
  • TGI (%) [1- (Ti-T0)/ (Vi-V0)] ⁇ 100
  • Ti is the average tumor volume of a treatment group on a given day
  • T0 is the average tumor volume of the treatment group on the day of treatment start
  • Vi is the average tumor volume of the vehicle control group on the same day with Ti
  • V0 is the average tumor volume of the vehicle group on the day of treatment start.
  • Attorney Docket No. TGO-025WO [0794] Statistical analysis of difference in the tumor volume among the groups were conducted on the data obtained at the best
  • TGO-025WO a Mean ⁇ SEM.
  • b Tumor Growth Inhibition is calculated by dividing the group average tumor volume for the treated group by the group average tumor volume for the control group (T/C).
  • TGI (%) [1-(T11-T0)/ (V11-V0)] ⁇ 100; T11 is the average tumor volume of a treatment group on day 11, T0 is the average tumor volume of the treatment group on day 0 after treatment, V11 is the average tumor volume of the vehicle control group on the same day with T11, and V0 is the average tumor volume of the vehicle group on day 0 after treatment.
  • d All data were analyzed using SPSS 17.0.
  • Example 12 Re-Challenge Study of Example 11 Summary: A re-challenge study of Example 11 was performed to evaluate whether the survived animals from Example 11 had acquired T memory against the same tumor. Experimental Design & Materials: The survived animals of the efficacy part were re-challenged with MC38_sgStk11 cells respectively in the opposite side of primary tumors. A table summarizing the survived animals from Example 11 is provided in Table 29.
  • the MC38_ sgStk11 tumor cells were maintained in vitro as a monolayer culture in DMEM + 2 mM glutamine supplemented with about 10% heat inactivated fetal bovine serum, 100 U/ml penicillin and 100 g/ml streptomycin at about 37oC in an atmosphere of about 5% CO 2 in air.
  • the tumor cells were routinely sub-cultured twice weekly by trypsin-EDTA treatment.
  • the cells growing in an exponential growth phase were harvested and counted for tumor inoculation.
  • mice were inoculated subcutaneously at the left lower flank with MC38_ sgStk11 tumor cells (0.5 x 106) in 0.1 ml of PBS for tumor development. The animal numbers and the cell numbers for each group are shown in the experimental design (Table 2-1). The survived animals from the Example 1 were under post-treatment monitoring for 21 days before re- challenge. Observations [0799] All the procedures related to animal handling, care and the treatment in the study were performed according to the guidelines approved by the Institutional Animal Care and Use Committee (IACUC) of vendor following the guidance of the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC).
  • IACUC Institutional Animal Care and Use Committee
  • TGO-025WO Results Mean tumor volume over time in C57BL/6 mice re-challenged with MC38_ sgStk11 is shown in Table 30.
  • Table 30 - Tumor Volume (mm3) Per MC38_sgStk11 Re-Challenge Group Over Time a Mean ⁇ SEM b Days after cell inoculation Attorney Docket No. TGO-025WO There was no tumor growth on the survived animals re-challenged with MC38_sgStk11 cells. The results may suggest that the survived animals had acquired T memory against MC38_sgStk11 tumor.
  • FIG.16A shows tumor size by groups; all previously treated groups overlap with no tumor growth;
  • FIG.16B shows tumor size for a pooled group of previously treated mice vs. untreated control group).
  • FIG.17 shows a complete timeline and tumor sizes at the time points indicated for Example 11 and Example 12.
  • Example 13 Identification of anti-PD1 Antibody Sensitizer Genes in STK-11 Deleted Tumors [0802] In this example, genes whose inhibition reverses anti-PD1 resistance driven by loss of STK11 were determined.
  • HDAC1, HDAC2, or HDAC3 were deleted or disabled with CRISPR in an in vivo knockout screen in STK-11 deleted MC38 tumor cells grown in C57Bl/6 mice that were treated with anti-PD1 antibody.
  • the results show that HDAC1 is a sensitizer to anti-PD1 in STK11-deleted cancer (FIG.18A).
  • toxicity of HDAC1, HDAC2, or HDAC3 by CRISPR mediated deletion/disruption in several cell lines was tested. The results show depletion of cells with HDAC1, HDAC2, or HDAC3 knockout, with HDAC3 knockout showing the highest toxicity in the panel of cell lines (FIG.18B).
  • a CoREST complex selective Compound I was identified using an NanoBRET (Bioluminescence resonance energy transfer) target engagement assay. Briefly, cells were treated with Compound 1 for 4 hours prior to measuring the BRET signal. The dose-dependent binding of Compound I to purified HDAC1, HDAC2, and HDAC3 was then measured at various concentrations of Compound I and the respective IC50 values determined. The results show that the IC50s of Compound I for HDAC1 is 0.01uM, HDAC20.17uM, and HDAC3 1.07uM (FIG.19A, FIG.19B, FIG.19C, and Table 31).
  • HDAC inhibition of the HDAC complexes CoREST, NCoR, NuRD and Sin3 by Compound I was determined by a fluorescence-based deacetylase assay.
  • HDAC complexes CoREST, NCoR, NuRD and Sin3 were co-immunoprecipitated with complex selective antibodies from A549 cells (a model for lung adenocarcinoma), the complexes were incubated with Compound I or the less selective HDAC inhibitors Vorinostat, Tucidinostat, and Domatinostat.
  • Compound I Compound I or the less selective HDAC inhibitors Vorinostat, Tucidinostat, and Domatinostat.
  • Suberoylanilide hydroxamic acid a pan HDAC inhibitor that targets all 4 complexes, was used as a positive control for complex activity to demonstrate that the isolated complexes retained functional deacetylase activity, and to establish background assay fluorescence.
  • the HDAC inhibition was profiled in a fluorescence-based deacetylase assay.
  • Exemplary IC 50 s are shown in Table 32. The results in Table 32 show that Compound I is selective for the CoREST complex. Table 32 - IC50’s for Compound I and other HDAC inhibitors (Vorinostat, Tucidinostat, Domatinostat) in an in vitro deacetylase assay of cell-derived, intact HDAC complexes, CoREST, NCoR, NuRD, and Sin3 Example 15.
  • mice were inoculated with STK11-deleted CT26 (murine colorectal carcinoma cell line) tumor model in a manner similar to that described in Example 1. The tumor model was resistant to murine anti-PD1 antibody by knockout of the STK11.
  • mice were treated with Compound I orally once daily and with anti-PD1, anti-IgG2a control, or anti-PD1 control twice per week as Attorney Docket No. TGO-025WO indicated.
  • Tumor volume and survival was monitored over the course of treatment and plotted by individual animal for tumor volume (FIG.20A) and by group for survival (FIG.20B).
  • the results of Example 11 and Example 15 show that Compound I reverses resistance to immune checkpoint blockade driven by loss of STK11 in tumor models for colon adenocarcinoma and colorectal carcinoma.
  • Example 16 Example 16
  • Cytokine profiling of tumors treated with Compound I The cytokine expression of tumors from mice treated with Compound I was determined by Nanostring PanCancer IO 360 analysis. [0809] Briefly, STK11-/- MC38 tumors from mice treated for 7 days with 30 mg/kg of Compound I or anti-PD1 antibody alone or in combination were collected 8 hours post last dose. The gene expression profiles of CXCL9, CXCL10, and CXCL11 of the tumors were determined by Nanostring PanCancer IO 360 (FIG.22A). Additionally, the gene expression profiles of Treg-recruiting chemokines CCL1 and CCL22 of the tumors were determined by Nanostring PanCancer IO 360 (FIG.22B).
  • mice with STK11-deleted MC38 tumors were treated for 7 days with 10 mg/kg of Compound I alone or in combination with anti-PD1 as described above.
  • Tumor tissue was collected 8 hours post last dose and tumor infiltrating lymphocytes (TILs) were profiled by flow cytometry.
  • T cell populations were analysed for total CD45+ cells, CD4+ cells, CD8+ cells, and CD8+ T effector memory (TEM) cells and Treg cells (FIG.23A and FIG.23B).
  • TEM tumor infiltrating lymphocytes
  • Treg cells Flow cytometry of Tregulatory (Treg) cells showed a significant decrease in frequency of Treg cells in the combination arm (FIG.23B).
  • the ratio of CD8+ T effector cells to T regulatory cells in each of the treatment groups showed a significantly increased ratio in the combination arm (FIG. 23B).
  • IFN levels were evaluated by Luminex analysis in tumors treated with 30 mg/kg of Compound I or in combination with anti-PD1 (FIG.23C).
  • a co-culture of human NSCLC cells with PBMCs and fibroblasts was treated with a dose response of Compound I alone or in combination with a fixed dose of anti-PD1 for 72 hours.
  • the IFN levels were quantified from tissue culture supernatant by ELISA (FIG. 23D).
  • the top three ranked gene ontology groups for each compound as determined from the Nanostring data in were determined using the nSolver software (FIG.24A, FIG. 24B, FIG.24C bottom panel).
  • the results show that Compound I regulates the expression of fewer genes than the less-selective HDAC inhibitors vorinostat and domatinostat.
  • Example 20. Therapeutic Index and cytotoxicity analysis of Compound I [0821] In this example, the toxicity and therapeutic index of Compound I was determined in vitro and in vivo.
  • a colony forming unit assay was performed in vitro to evaluate the impact of HDAC inhibitors on the viability of erythroid and myeloid cells.
  • Cells were treated with a dose response of each compound for 14 days. Cell colonies were quantified at the end of the experiment and compared to a solvent control.
  • the efficacious dose range of Compound I was also plotted (the range was between 3 mg/kg and 75 mg/kg) (FIG.25A).
  • the IC50s for each compound were calculated from the erythroid and myeloid colony formation unit assay. These IC50s were normalized to the compound’s potency against HDAC1 in the cellular NanoBRET assay to allow for head-to-head compound comparison (Table 33).
  • IC50s from the erythroid and myeloid colony formation unit assay normalized to the potency against HDAC1 (Table 33) .
  • Table 33 - IC50's for erythroid and myeloid colony formation Attorney Docket No. TGO-025WO
  • a clinically relevant dose of vorinostat for mouse was calculated using body surface area conversion. Mice with STK11-deleted MC38 tumors were treated in vivo with vorinostat or Compound I alone or vorinostat or Compound I in combination with anti-PD1. Tumor volumes were monitored over the course of treatment (FIG.25B for vorinostat, FIG.25C for Compound 1).
  • PK Pharmacological properties of Compound I
  • the pharmacokinetics (PK) of Compound I in rats was determined following single IV bolus of 1 mg/kg in 20% wt /vol HP CD, 1% vol /vol DMSO in saline or single PO dose of 3 mg/kg in 0.5 % methylcellulose (MC) in water to male Sprague Dawley rats (fed for IV, fasted for PO).
  • Plasma samples were collected from 3 animals/group at 0.05, 0.25, 0.5, 1, 2, 3, 48 , and Attorney Docket No. TGO-025WO 24 hours after dosing.
  • Selected PK parameters of Compound I are presented in Table 35.
  • the PO bioavailability was 95.4%.
  • the PK of Compound I in beagle dogs was determined in plasma following single IV bolus and PO administration to non-na ⁇ ve male and female beagle dogs.
  • the vehicle used for IV was 20% wt/vol 2-hydroxypropyl cyclodextrin (HP CD ), 1% vol/vol DMSO in saline, and PO was in 5% DMA, 30% PEG400 and 65% (30% HP CD in water) (solution) or 0.5% MC (suspension).
  • Plasma samples were collected from 3 animals/group at 0.083, 0.25, 0.5, 1, 3, 6, 9, 12, 24 and 48 hours after dosing. Selected PK parameters of Compound I are presented in Table 35.
  • the PO bioavailability was 67.4% when Compound I was given as a solution at 3 mg/kg under fasted condition.
  • the PK of Compound I in male cynomolgus monkeys was determined in plasma following single IV bolus and PO administration to non-na ⁇ ve male cynomolgus monkeys
  • the vehicle used for IV was 20% wt/vol HP CD, 1% vol/vol DMSO in saline and for PO was in 0.5% MC (suspension).
  • Plasma samples were collected from 3 animals/group at 0.083, 0.25, 0.5, 1, 3, 6, 9, 12, 24, and 48 hours after dosing. Selected PK parameters of Compound I are presented in Table 35.
  • the PO bioavailability was 83 % when Compound I was given as a suspension at 3 mg/kg under fed conditions.
  • the effects of Compound I on a cloned human ether-à-go-go-related gene (hERG) potassium channels stably expressed in human embryonic kidney (HEK) 293 cells were measured using manual patch-clamp technique. Briefly, Compound I was soluble at 100 uM in 0.3% DMSO, pH 6.9. A does range-finding (DRF) assay was performed with Compound I at 3. 30, and 100 uM concentrations. Compound I inhibited hERG currents by 15.67%, 45.85%, and 73.57% at 3, 30, and 100 M, respectively.
  • DPF range-finding
  • the definitive hERG assays was used to detect the IC50 of Compound I.
  • each concentration was measured in replicates of 3.
  • the IC50 value for the inhibitory effect of Compound I on the hERG potassium current was 71.07 M.
  • Drug metabolizing enzymes involved in the biotransformation of Compound I were investigated using human liver microsomes (HLM) and recombinant enzymes.
  • HLM human liver microsomes
  • CYP selective inhibitor experiments were not performed due to lack of appreciable Compound I turnover.
  • Compound I was minimally metabolized by recombinant human CYPs (rh CYPs ; terminal half life (T1 ⁇ 2) > 60 mins for CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4/5).
  • rh CYPs terminal half life
  • T1 ⁇ 2 terminal half life
  • PK pharmacokinetics
  • T 1/2 terminal half life
  • CL total body clearance
  • hERG human ether-à-go-go-related gene
  • Predicted Human PK of Compound I [0832] The human PK parameters for a dose of Compound I that is predicted to be efficacious were calculated based on the data from rodent and dog studies and are presented in Table 36. Table 36 - Predicted human PK parameters The predicted human pharmacokinetics and therapeutic window are modeled in FIG.26.
  • Example 23. Mouse PK/PD of Compound I [0833] Formation and accumulation of acetylated histone 3 lysine 9 (H3K9Ac) in MC38 tumor tissue from mouse after treatment with Compound I was determined by Western blot.
  • Plasma samples were collected at 1, 2, 8 and 24 hours after last dose and analyzed for Compound I concentrations.
  • Peripheral blood mononuclear cells (PBMC) and tumor samples were harvested at 2, 8, and 24 hours after last dose.
  • the PBMC samples were processed for determination of mean florescent level of acetyl- histone H2B by flow cytometry.
  • Plasma concentrations of Compound I were dose proportional with maximal concentrations observed at 1 hour after the last dose (FIG.27C).
  • the free unbound exposures in plasma based upon a 10.05% free fraction in C57BL/6 mouse plasma, were 5470, 17238, and 69665 h.ng/mL, respectively, for the 30, 100 and 300 mg/kg QD doses, indicating dose proportionality achieved within the dosing range.
  • CT26_STK11KO a colon carcinoma cell line with an endogenous KRAS G12D mutation.
  • the experiment was performed in the parental/wild type line and in a line engineered with an STK11 knock-out (CT26_STK11KO) resulting in an anti- PD1 resistant model with lower CD8+ T cell infiltration.
  • the animals (8/group) were divided into four groups.
  • Group I was treated with a control antibody Anti-IgG2
  • group 2 was treated with Compound I 75 Attorney Docket No. TGO-025WO mg/kg
  • group 3 was treated with anti-PD1 antibody
  • group 4 was treated with Compound I 75 mg/kg and anti-PD1 antibody.
  • Tumor volume and survival was monitored over the course of treatment.
  • the tumor volume was plotted by individual animal (FIG.28A) and by treatment group (FIG.28B). Survival was plotted by treatment group (FIG. 28C).
  • CT26 is a colon carcinoma cell line with an endogenous KRAS G12D mutation.
  • the experiment was performed in the parental/wild type line and in a line engineered with an STK11 knock-out (CT26_STK11KO) resulting in an anti- CTLA4-resistant model.
  • CT26_STK11KO STK11 knock-out
  • CT26 is a colon carcinoma cell line.
  • the experiment was also performed with an STK11-null CT26 model, this model is CTLA4 resistant.
  • Group I was treated with a control antibody Anti-IgG2
  • group 2 was treated with Compound I 75 mg/kg
  • group 3 was treated with anti-CTLA4 antibody
  • group 4 was treated with Compound I 75 mg/kg and anti- CTLA4 antibody.
  • Tumor volume was monitored over the course of treatment.
  • the tumor volume was plotted by treatment group (FIG.29A), and the individual animals were plotted for group 1 and group 4 (FIG.29B), for the parental model.
  • the tumor volume was plotted by treatment group (FIG.29C), and the individual animals were plotted for group 1 and group 4 (FIG.29D), for the STK11 knockout model.
  • Anti-Tumor Activity of Anti-PD-1 and Compound I Combination in a Lewis Lung Carcinoma model
  • An in vivo anti-tumor efficacy of double combination treatment of Anti-PD1 and Compound I in a PD-1 resistant STK11-null 3LL model was performed.
  • the parental (non STK11KO) 3LL line is relatively resistant to anti-PD1 treatment.
  • the animals (8/group) were divided into 4 groups: Group I was treated with a control antibody Anti-IgG2, group 2 was treated with anti-PD1 antibody, group 3 was treated with Compound I 75 mg/kg, and group 4 was treated with Compound I 75 mg/kg and anti-PD1 antibody. Tumor volume and survival was monitored over the course of treatment.
  • the tumor volume and survival was plotted by treatment group (FIG.30A and FIG.30B, respectively).
  • the combination treatment with Compound I decreased the PD-1 resistance of this model caused by the SKT11 knockout to the baseline characteristic of the parental line as shown by Group 4’s decreased tumor volume and increased survival over time compared to the other groups.
  • the median Time-To-Event (TTE and P values compared to control group 1 (Vehicle) are summarized in Table 38.
  • Attorney Docket No. TGO-025WO Table 38 - Median TTE of PD-1 resistant STK11-null 3LL model groups of the indicated treatment Example 27.
  • Tumor volumes were determined in individual mice over the duration of the study.
  • vehicle 1 5% DMSO with 30% PEG 400 and 65% of 30% HP- -CD in water
  • Compound I at 30 mg/kg was dosed as single agent or combined with 10mg/kg of rat IgG2a isotype control or anti-mouse PD-1 antibody.
  • Several dosing regimens of Compound I were evaluated and compared to once daily dosing that was previously demonstrated to be preclinically efficacious in mice bearing STK11-deficient MC38 tumors (Table 39 provides study design). The duration for the study was 28 days. All treatments were well-tolerated with no decreases in body weight.
  • Table 39 Attorney Docket No.
  • TGO-025WO Attorney Docket No. TGO-025WO Abbreviations: PO, oral; IP, intraperitoneal; QD, once daily; BIW, bi-weekly; QW, once weekly a b .
  • Compound 1 Vehicle 5% DMSO with 30% PEG 400 and 65% of 30% HP- -CD in water .
  • Antibodies diluted in PBS [0850] In the study, starting tumor volumes were ⁇ 52 mm 3 .
  • Anti-PD1 with Compound I vehicle (Group 2) and Compound I with anti-IgG2a Groups 3, 5, 7, 9, 11, 13).
  • TGI tumor growth inhibition
  • Bi- weekly dosing of Compound I with anti-PD1 (Group 14) also provided similar TGI (78.5%), but 2 animals had strong tumor regrowth at the end of the study that limited its overall efficacy (FIG.32A, FIG.32F).
  • Other Compound I dosing regimens included 1 week of daily dosing followed by two weeks off (Group 8) (FIG.32C), 2 days of dosing followed by 5 days off (Group 12)(FIG.32D), and once weekly dosing (Group 6)(FIG.32E). Each of these dosing schedules provided reductions in tumor growth but had inferior efficacy to either Compound I daily dosing or the 2 week on, 1 week off schedule.
  • Eligibility criteria Inclusion Criteria • Is 18 years of age at the time of signature of the main study ICF. • Has ECOG performance status of 0 or 1. • Has measurable disease based on RECIST v1.1. • All participants must have documented STK11 mutation in a solid tumor, which is identified through a validated analytical method. • Has confirmed histologic or cytologic diagnosis of a locally advanced or metastatic solid tumor. • Adequate organ function/reserve per local labs. • Adequate liver function per local labs. • Adequate renal function per local labs. • Negative serum pregnancy test result at screening. • Written informed consent must be obtained according to local guidelines.

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Abstract

La divulgation concerne des formes cristallines d'un inhibiteur de HDAC, des compositions pharmaceutiques de ceux-ci et des méthodes de traitement de cancers, y compris des cancers ayant une activité ou une expression STK11 modifiée, par administration d'une quantité efficace des formes ou compositions cristallines.
PCT/US2025/023734 2024-04-08 2025-04-08 Formes cristallines d'inhibiteur de hdac et leurs utilisations Pending WO2025217209A2 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997010365A1 (fr) 1995-09-15 1997-03-20 Affymax Technologies N.V. Mesure de l'expression par l'hybridation avec des systemes tres denses d'oligonucleotides
WO2022087270A1 (fr) 2020-10-23 2022-04-28 Mirati Therapeutics, Inc. Méthodes de traitement de cancers du poumon

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL313081A (en) * 2021-12-03 2024-07-01 Tango Therapeutics Inc New HDAC inhibitors and their medical use

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997010365A1 (fr) 1995-09-15 1997-03-20 Affymax Technologies N.V. Mesure de l'expression par l'hybridation avec des systemes tres denses d'oligonucleotides
WO2022087270A1 (fr) 2020-10-23 2022-04-28 Mirati Therapeutics, Inc. Méthodes de traitement de cancers du poumon

Non-Patent Citations (29)

* Cited by examiner, † Cited by third party
Title
"Hybridization with Nucleic Acid Probes", vol. 24, 1993, ELSEVIER, article "Laboratory Techniques in Biochemistry and Molecular Biology"
"Remington's Pharmaceutical Sciences", 1985, MACK PUBLISHING COMPANY
ALESSI, D.R. ET AL., ANNU. REV. BIOCHEM., vol. 75, 2006, pages 137 - 163
BITON J ET AL., CLIN CANCER RES, vol. 24, 2018, pages 5710 - 23
CERAMI E ET AL., CANCER DISCOV, vol. 2, 2012, pages 401 - 404
CHAKRAVARTY D ET AL., JCO PRECIS ONCOL. 2017, 2017
CHAKRAVARTY D ET AL., JCO PRECIS ONCOL., 2017
GAO J ET AL., SCI SIGNAL, vol. 6, no. 269, 2013
GILL RK ET AL., ONCOGENE, vol. 30, 2011, pages 3784 - 3791
GURUMURTHY S ET AL., NATURE, vol. 468, 2010, pages 659 - 63
HEMMINKI A ET AL., NATURE, vol. 18, 1998, pages 184 - 187
JI H ET AL., NATURE, vol. 448, 2007, pages 807 - 10
KOENIG, M. ET AL., CANCER RESEARCH, vol. 81, no. 16, 2021, pages 1905 - 4204
KOIVUNEN, J. ET AL., BR J CANCER, vol. 99, 2008, pages 245 - 252
MACPHERSON ET AL.: "PCR: A Practical Approach", 1991, IRL PRESS
no. 1428935-60-7
PAPILLON-CAVANAGH S. ET AL., ESMO OPEN, vol. 5, 2020, pages E000706
REVA BANTIPIN YSANDER C, NUCLEIC ACIDS RESEARCH, vol. 39, no. 17, 2011
RICCIUTI B. ET AL., JOURNAL OF THORACIC ONCOLOGY, vol. 17, 2021, pages 400 - 410
RICHARDS S ET AL.: "Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology", GENET MED., vol. 17, no. 5, May 2015 (2015-05-01), pages 405 - 424, XP093036319, DOI: 10.1038/gim.2015.30
ROBINSON DR ET AL., NATURE, vol. 548, 2017, pages 297 - 303
SANCHEZ-CESPEDES M ET AL., CANCER RES, vol. 62, 2002, pages 3659 - 62
SANCHEZ-CESPEDES M., ONCOGENE, vol. 26, 2007, pages 7825 - 7832
SANCHEZ-VEGA F ET AL., CELL, vol. 173, 2018, pages 321 - 337
SHERRY, S.T. ET AL., NUCLEIC ACIDS RES, vol. 29, 2001, pages 308 - 311
SKOULIDIS, F. ET AL., CANCER DISCOVERY, vol. 8, no. 7, 2018, pages 822 - 835
SKOULIDIS, F. ET AL., JOURNAL OF CLINICAL ONCOLOGY, vol. 37, no. 15, 2019
TATE JG ET AL., NUCLEIC ACIDS RES, vol. 47, no. 1, 2019, pages 941 - 947
ZEHIR A ET AL., NAT MED., vol. 23, no. 6, 2017, pages 703 - 713

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