Solid forms of naphthyridine compounds

Abstract

Disclosed herein are various solid forms of Compound A, including crystalline and amorphous forms of Compound A free base, as well as salt forms, co-crystals, and solvates thereof. Also disclosed are methods of making these salts, co-crystals and solvate forms, and methods of treating diseases and disorders using these salts, co-crystals and solvate forms (Compound A). # imgabs0 #

Description

Background Art

[0001] Naphthyridine compounds have shown importance in a variety of biological applications. To study their efficacy, large amounts of material are required. Therefore, there is a need for solid forms of naphthyridine compounds, including their crystalline forms, amorphous forms, salts, cocrystals, and solvates, as well as methods for isolating them. Summary of the Invention

[0002] The present disclosure provides solid forms of Compound A, including crystalline forms, amorphous forms, and salts, solvates, and co-crystals thereof, wherein Compound A has the structure

[0003] In some embodiments, the present disclosure provides an amorphous form of Compound A free base.

[0004] In some embodiments, the present disclosure provides a crystalline form of Compound A.

[0005] In some embodiments, the present disclosure provides crystalline Compound A in free base form.

[0006] In some embodiments, the present disclosure provides a crystalline form of Compound A free base ("Form 1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.5, 9.0, 13.3, 16.2, and 18.8 ± 0.2 degrees 2θ using CuKa radiation.

[0007] In some embodiments, the present disclosure provides a crystalline form of Compound A free base ("Form 3") characterized by an XRPD pattern comprising peaks at 4.3, 12.6, 14.4, 16.2, and 25.6 ± 0.2 degrees 2Θ using CuKa radiation.

[0008] In some embodiments, the present disclosure provides a crystalline form of Compound A free base ("Form 6") characterized by an XRPD pattern comprising peaks at 4.5, 8.6, 9.0, 12.9, and 14.9 ± 0.2° 2Θ using CuKa radiation.

[0009] In some embodiments, the present disclosure provides a crystalline form of Compound A free base ("Form 7") characterized by an XRPD pattern comprising peaks at 4.3, 8.5, 12.3, 13.1, and 14.8 ± 0.2° 2Θ using CuKa radiation.

[0010] In some embodiments, the present disclosure provides a crystalline form of Compound A free base hydrate ("Form 8") characterized by an XRPD pattern comprising peaks at 4.0, 7.7, 8.0, 12.3, and 15.1 ± 0.2 °2Θ using CuKa radiation.

[0011] In some embodiments, the present disclosure also provides a crystalline form of Compound A ethanol solvate ("Form 2A") characterized by an XRPD pattern comprising peaks at 5.8, 11.6, 12.7, 18.0, and 25.7 ± 0.2 degrees 2θ using CuKα radiation.

[0012] In some embodiments, the present disclosure also provides a crystalline form of Compound A isopropanol solvate ("Form 3A") characterized by an XRPD pattern comprising peaks at 5.6, 12.8, 16.4, 17.5, and 25.1 ± 0.2 degrees 2θ using CuKα radiation.

[0013] In some embodiments, the present disclosure also provides a crystalline form of Compound A acetone solvate ("Form 4A") characterized by an XRPD pattern comprising peaks at 5.7, 7.7, 11.5, 14.8, and 15.3 ± 0.2° 2θ using CuKα radiation.

[0014] In some embodiments, the present disclosure also provides a crystalline form of Compound A methanol solvate ("Form 5A") characterized by an XRPD pattern comprising peaks at 4.8, 7.7, 12.3, 15.3, and 16.1 ± 0.2° 2θ using CuKα radiation.

[0015] In some embodiments, the present disclosure also provides a crystalline form of Compound A methyltetrahydrofuran solvate ("Form 6A") characterized by an XRPD pattern comprising peaks at 7.6, 11.3, 15.1, 18.3, and 28.0 ± 0.2 degrees 2θ using CuKα radiation.

[0016] In some embodiments, the present disclosure also provides an amorphous form of Compound A free base, characterized in that it is substantially as follows Figure 105 Differential scanning calorimetry scans are shown.

[0017] In some embodiments, the present disclosure also provides a crystalline form of Compound A tosylate salt ("Form A1") characterized by an XRPD pattern comprising peaks at 6.0, 19.1, 20.3, 24.1, 24.9, and 28.9 ± 0.2 degrees 2θ using Cu Ka radiation.

[0018] In some embodiments, the present disclosure also provides a crystalline form of Compound A tosylate salt ("Form A2") characterized by an XRPD pattern comprising peaks at 12.7, 15.5, 16.2, 18.7, 19.7, and 21.8 ± 0.2 degrees 2θ using Cu Ka radiation.

[0019] In some embodiments, the present disclosure also provides a crystalline form of Compound A tosylate salt ("Form A3") characterized by an XRPD pattern comprising peaks at 4.9, 15.2, 18.8, 19.5, and 24.5 ± 0.2 degrees 2Θ using Cu Ka radiation.

[0020] In some embodiments, the present disclosure also provides a crystalline form of Compound A besylate salt ("Form Bl") characterized by an XRPD pattern comprising peaks at 5.1, 16.1, 17.9, 19.0, and 25.2 ± 0.2 degrees 2Θ using Cu Ka radiation.

[0021] In some embodiments, the present disclosure also provides a crystalline form of the chloride salt of Compound A ("Form C1") characterized by an XRPD pattern comprising peaks at 6.8, 11.9, 16.6, 20.7, 23.8, 25.3, and 27.6 ± 0.2 degrees 2θ using Cu Ka radiation.

[0022] In some embodiments, the present disclosure also provides a crystalline form of the chloride salt of Compound A ("Form C2") characterized by an XRPD pattern comprising peaks at 4.2, 5.6, 12.2, 12.9, and 18.1 ± 0.2 degrees 2Θ using Cu Ka radiation.

[0023] In some embodiments, the present disclosure also provides a crystalline form of Compound A sulfate ("Form D1") characterized by an XRPD pattern comprising peaks at 16.0, 16.5, 16.7, 20.0, and 20.4 ± 0.2 degrees 2Θ using CuKa radiation.

[0024] In some embodiments, the present disclosure also provides a crystalline form of Compound A malonate salt ("Form E1") characterized by an XRPD pattern comprising peaks at 6.8, 12.6, 16.6, 20.4, and 22.0 ± 0.2° 2θ using CuKa radiation.

[0025] In some embodiments, the present disclosure also provides a crystalline form of Compound A naphthalene-2-sulfonate salt ("Form F1") characterized by an XRPD pattern comprising peaks at 4.7, 14.7, 14.9, 17.0, 19.6, and 22.1 ± 0.2 degrees 2θ using CuKa radiation.

[0026] In some embodiments, the present disclosure also provides a crystalline form of Compound A naphthalene-2-sulfonate salt ("Form F2") characterized by an XRPD pattern comprising peaks at 5.8, 11.6, 14.0, 17.5, and 19.7 ± 0.2 degrees 2θ using CuKa radiation.

[0027] In some embodiments, the present disclosure also provides a crystalline form of Compound A naphthalene-2-sulfonate salt ("Form F3") characterized by an XRPD pattern comprising peaks at 3.8, 7.6, 9.7, 11.5, and 15.3 ± 0.2 degrees 2θ using CuKa radiation.

[0028] In some embodiments, the present disclosure also provides a crystalline form of Compound A mesylate ("Form G1") characterized by an XRPD pattern comprising peaks at 5.1, 6.5, 13.6, 13.8, and 19.5 ± 0.2° 2θ using CuKa radiation.

[0029] In some embodiments, the present disclosure also provides a crystalline form of Compound A mesylate ("Form G2") characterized by an XRPD pattern comprising peaks at 5.6, 13.1, 13.3, 16.3, and 18.3 ± 0.2° 2θ using CuKα radiation.

[0030] In some embodiments, the present disclosure also provides a crystalline form of Compound A oxalate salt ("Form H2") characterized by an XRPD pattern comprising peaks at 6.9, 8.7, 13.6, 17.4, and 24.6 ± 0.2° 2θ using CuKa radiation.

[0031] In some embodiments, the present disclosure also provides a crystalline form of Compound A tartrate salt ("Form I1") characterized by an XRPD pattern comprising peaks at 3.4, 14.7, 15.6, 18.02, and 24.3 ± 0.2° 2θ using CuKα radiation.

[0032] In some embodiments, the present disclosure also provides a crystalline form of Compound A esylate salt ("Form J1") characterized by an XRPD pattern comprising peaks at 5.6, 7.9, 13.6, 15.7, and 17.9 ± 0.2° 2θ using CuKa radiation.

[0033] In some embodiments, the present disclosure also provides a crystalline form of Compound A esylate salt ("Form J2") characterized by an XRPD pattern comprising peaks at 4.0, 6.3, 7.7, 15.8, and 20.9 ± 0.2 degrees 2Θ using CuKa radiation.

[0034] In some embodiments, the present disclosure also provides a crystalline form of Compound A N-cyclohexylsulfamate ("Form K1") characterized by an XRPD pattern comprising peaks at 5.8, 14.0, 15.6, 16.7, and 28.1 ± 0.2 degrees 2θ using CuKa radiation.

[0035] In some embodiments, the present disclosure also provides a crystalline form of Compound A maleate salt ("Form L1") characterized by an XRPD pattern comprising peaks at 5.7, 17.0, 17.5, 25.6, and 26.1 ± 0.2° 2θ using CuKa radiation.

[0036] In some embodiments, the present disclosure also provides a crystalline form of Compound A phosphate salt ("Form M1") characterized by an XRPD pattern comprising peaks at 5.4, 16.2, 20.3, and 22.5 ± 0.2 degrees 2Θ using CuKa radiation.

[0037] In some embodiments, the present disclosure also provides a crystalline form of Compound A phosphate ("Form M2") characterized by an XRPD pattern comprising peaks at 7.1, 14.2, 14.9, 17.9, and 19.6 ± 0.2° 2θ using CuKa radiation.

[0038] In some embodiments, the present disclosure also provides a crystalline form of Compound A phosphate salt ("Form M3") characterized by an XRPD pattern comprising peaks at 7.5, 7.8, 14.8, 15.0, and 15.4 ± 0.2° 2Θ using CuKa radiation.

[0039] In some embodiments, the present disclosure also provides a crystalline form of Compound A salicylic acid cocrystal ("Form CC-1A") characterized by an XRPD pattern comprising peaks at 9.3, 5.9, 9.7, 6.0, and 13.9 24±0.2° 2θ using CuKα radiation.

[0040] In some embodiments, the present disclosure also provides a crystalline form of Compound A salicylic acid cocrystal ("Form CC-2A") characterized by an XRPD pattern comprising peaks at 8.2, 9.2, 16.5, 18.5, and 16.0 ± 0.2 degrees 2θ using CuKa radiation.

[0041] In some embodiments, the present disclosure also provides a crystalline form of Compound A salicylic acid cocrystal ("Form CC-3A") characterized by an XRPD pattern comprising peaks at 3.6, 12.6, 8.0, 14.4, and 7.2 ± 0.2 degrees 2θ using CuKα radiation.

[0042] In some embodiments, the present disclosure also provides a crystalline form of Compound A salicylic acid cocrystal ("Form CC-4A") characterized by an XRPD pattern comprising peaks at 10.3, 16.2, 9.9, 16.3, 19.9 ± 0.2° 2θ using CuKα radiation.

[0043] In some embodiments, the present disclosure also provides a crystalline form of Compound A salicylic acid cocrystal ("Form CC-5A") characterized by an XRPD pattern comprising peaks at 5.3, 17.8, 10.6, 18.3, and 15.9 ± 0.2 degrees 2θ using CuKa radiation.

[0044] In some embodiments, the present disclosure also provides a crystalline form of Compound A formic acid co-crystal ("Form CC-1B") characterized by an XRPD pattern comprising peaks at 8.6, 4.6, 17.8, 17.4, and 23.0 ± 0.2° 2θ using CuKα radiation.

[0045] In some embodiments, the present disclosure also provides a crystalline form of Compound A benzoic acid cocrystal ("Form CC-1C") characterized by an XRPD pattern comprising peaks at 11.6, 16.1, 14.2, 3.9, and 19.8 ± 0.2 degrees 2θ using CuKα radiation.

[0046] In some embodiments, the present disclosure also provides a crystalline form of Compound A isobutyric acid cocrystal ("Form CC-1D") characterized by an XRPD pattern comprising peaks at 5.6, 6.1, 13.1, 16.0, and 17.1 ± 0.2° 2θ using CuKα radiation.

[0047] In some embodiments, the present disclosure also provides a crystalline form of Compound A isobutyric acid cocrystal ("Form CC-2D") characterized by an XRPD pattern comprising peaks at 5.2, 5.5, 6.3, 10.3, and 12.6 ± 0.2 degrees 2θ using CuKa radiation.

[0048] In some embodiments, the present disclosure also provides a crystalline form of Compound A benzoic acid cocrystal ("Form CC-1C") characterized by an XRPD pattern comprising peaks at 11.6, 16.1, 14.2, 3.9, and 19.8 ± 0.2 degrees 2θ using CuKα radiation.

[0049] In some embodiments, the present disclosure also provides a crystalline form of Compound A octanoic acid co-crystal ("Form CC-1E") characterized by an XRPD pattern comprising peaks at 4.8, 6.2, 6.5, 18.1, and 21.1 ± 0.2 degrees 2θ using CuKa radiation.

[0050] In some embodiments, the present disclosure also provides a crystalline form of Compound A sorbic acid cocrystal ("Form CC-1F") characterized by an XRPD pattern comprising peaks at 8.18, 10.8, 11.4, 18.2, and 21.2 ± 0.2 degrees 2θ using CuKa radiation.

[0051] In some embodiments, the present disclosure also provides a crystalline form of Compound A saccharin co-crystal ("Form CC-1G") characterized by an XRPD pattern comprising peaks at 5.1, 9.8, 10.1, 16.5, and 20.4 ± 0.2 degrees 2θ using CuKa radiation.

[0052] In some embodiments, the present disclosure also provides a crystalline form of Compound A succinic acid cocrystal ("Form CC-1H") characterized by an XRPD pattern comprising peaks at 11.3, 11.5, 18.3, 19.0, and 20.6 ± 0.2 degrees 2θ using CuKa radiation.

[0053] In some embodiments, the present disclosure also provides a crystalline form of Compound A succinic acid co-crystal ("Form CC-2H") characterized by an XRPD pattern comprising peaks at 4.2, 5.3, 8.3, 9.0, and 9.2 ± 0.2 °2θ using CuKa radiation.

[0054] In some embodiments, the present disclosure also provides a crystalline form of Compound A adipic acid co-crystal ("Form CC-II") characterized by an XRPD pattern comprising peaks at 7.7, 10.5, 18.5, 18.9, and 21.7 ± 0.2 degrees 2θ using CuKa radiation.

[0055] In some embodiments, the present disclosure also provides pharmaceutical compositions comprising a crystalline form, an amorphous form, a salt, a co-crystal, and a solvate of Compound A disclosed herein and at least one pharmaceutically acceptable excipient.

[0056] In some embodiments, the present disclosure also provides methods of treating cancer in a subject, comprising administering to the subject a therapeutically effective amount of a crystalline form, amorphous form, salt, co-crystal, and solvate of Compound A disclosed herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0057] Figure 1 Depicted is the XRPD pattern of the crystalline form of Compound A free base Form 1.

[0058] Figure 2 Depicted are a Differential Scanning Calorimetry (DSC) thermogram and Thermogravimetric Analysis ("TGA") trace of a crystalline form of Compound A free base Form 1 indicating an extrapolated onset at 225°C and a weight loss of 0.03% from 35-150°C.

[0059] Figure 3 Depicted is the moisture sorption curve (DVS) of the crystalline form of Compound A free base Form 1, showing non-hygroscopicity at 25°C between 0% and 95% relative humidity.

[0060] Figure 4 Depicted is the XRPD pattern of the crystalline form of Compound A free base Form 3.

[0061] Figure 5 Depicted are a DSC thermogram and thermogravimetric analysis ("TGA") trace of a crystalline form of Compound A free base Form 3, indicating exothermic events with onset temperatures of 105° C. and 173° C. and peak temperatures of 111° C. and 173° C.; an endothermic event was observed with onset and peak temperatures of 226° C. and 229° C. Negligible weight loss was shown up to 200° C.

[0062] Figure 6 Depicted is the DVS of the crystalline form of Compound A free base Form 3.

[0063] Figure 7 Depicted is the XRPD pattern of the crystalline form of Compound A free base Form 6.

[0064] Figure 8 Depicted are the DSC thermogram and thermogravimetric analysis ("TGA") trace of a crystalline form of Compound A free base Form 6.

[0065] Figure 9 Depicted is the XRPD pattern of the crystalline form of Compound A free base Form 7.

[0066] Figure 10 Depicted are a DSC thermogram and thermogravimetric analysis ("TGA") trace of a crystalline form of Compound A free base Form 7, indicating an endothermic event with an onset temperature of 61° C. and other endothermic events at higher temperatures, with peak temperatures at 87° C., 221° C., and 223° C. Exothermic events were observed with onset and peak temperatures of 129° C. and 141° C. A weight loss of 1.2% was observed at 94° C., with an additional weight loss of 0.3% at temperatures as high as 176° C.

[0067] Figure 11 Depicted is the XRPD pattern of the crystalline form of Compound A free base form 8-hydrate.

[0068] Figure 12 Depicted are a DSC thermogram and thermogravimetric analysis ("TGA") trace of a crystalline form of Compound A free base form 8-hydrate, indicating endothermic events with onset temperatures of 57° C. and 219° C. and peak temperatures of 79° C. and 225° C., respectively. A 3.3% weight loss was observed by TGA at temperatures as high as 128° C.

[0069] Figure 13 Depicted is an XRPD pattern of the crystalline form of Compound A ethanol solvate Form 2A.

[0070] Figure 14Depicted are the DSC thermogram and thermogravimetric analysis ("TGA") of the crystalline form of Compound A ethanol solvate Form 2A. The DSC shows a first endotherm with an extrapolated onset at 132°C due to desolvation of ethanol, and a second endotherm overlapping with an exotherm of subsequent recrystallization and followed by an extrapolated melting onset at 224°C, and a weight loss of 2.9% from 26°C to 160°C.

[0071] Figure 15 Depicted is an XRPD pattern of the crystalline form of Compound A isopropanol solvate Form 3A.

[0072] Figure 16 Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of the crystalline form of Compound A isopropanol solvate Form 3A. The DSC shows a first endotherm with an extrapolated onset at 123°C due to desolvation of isopropanol (IPA), and a second endotherm overlapping with an exotherm of subsequent recrystallization and followed by an extrapolated melting onset at 223°C, and a weight loss of 6.6% from 28°C to 150°C.

[0073] Figure 17 Depicted is the XRPD pattern of the crystalline form of Compound A Acetone Solvate Form 4A.

[0074] Figure 18 Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of the crystalline form of Compound A Acetone Solvate Form 4A. The DSC showed endothermic events with onset temperatures of 111° C., 143° C., and 226° C., and peak temperatures of 124° C., 151° C., and 227° C. An exothermic event was observed with onset and peak temperatures of 158° C. and 162° C. A weight loss of 4.2% was observed by TGA at temperatures as high as 152° C.

[0075] Figure 19 Depicted is an XRPD pattern of the crystalline form of Compound A methanol solvate Form 5A.

[0076] Figure 20 Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of the crystalline form of Compound A methanol solvate Form 5A. The DSC showed endothermic events with onset temperatures of 50°C and 226°C and peak temperatures of 70°C and 227°C. An exothermic event was observed with onset and peak temperatures of 117°C and 137°C. A weight loss of 1.7% was observed by TGA at temperatures up to 200°C.

[0077] Figure 21 Depicted is the XRPD pattern of the crystalline form of Compound A tosylate salt Form A1.

[0078] Figure 22Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of the crystalline form of Compound A tosylate salt Form Al, indicating an extrapolated onset of 293°C and a weight loss of 0.15% from 32°C to 200°C.

[0079] Figure 23 Depicted is a DVS of the crystalline form of Compound A tosylate salt Form Al showing a 0.5% weight gain at 25°C due to 90% relative humidity.

[0080] Figure 24 Depicted is the XRPD pattern of the crystalline form of Compound A tosylate Salt Form A2.

[0081] Figure 25 Depicted is a DSC thermogram and thermogravimetric analysis ("TGA") of the crystalline form of Compound A tosylate Salt Form A2. The DSC shows an exotherm due to recrystallization with an extrapolated onset at 242°C followed by an extrapolated melt / decomposition at 287°C and a weight loss of 0.04% from 32°C to 150°C.

[0082] Figure 26 Depicted is the XRPD pattern of the crystalline form of Compound A tosylate salt Form A3.

[0083] Figure 27 Depicted are a DSC thermogram and thermogravimetric analysis ("TGA") of a crystalline form of Compound A tosylate salt Form A3. The DSC shows an endothermic event with an onset and peak temperatures of 281° C. and 289° C., respectively. Form A3 exhibits negligible weight loss by TGA up to 256.4° C.

[0084] Figure 28 Depicted is the DVS of the crystalline form of Compound A tosylate salt Form A3.

[0085] Figure 29 Depicted is an XRPD pattern of a crystalline form of Compound A besylate salt Form Bl.

[0086] Figure 30 Depicted is a DSC thermogram of a crystalline form of Compound A besylate salt Form Bl. The DSC showed an endotherm with an extrapolated onset at 97 °C, followed by an extrapolated endothermic melt / decomposition at 254 °C.

[0087] Figure 31 Depicted is the XRPD pattern of the crystalline form of Compound A hydrochloride Form C1.

[0088] Figure 32Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of the crystalline form of Compound A chloride salt Form C1. The DSC showed a broad endotherm with an extrapolated onset at 34°C and an extrapolated endotherm melting / decomposition / salt disproportionation at 166°C, and a weight loss of 12.6% from 30°C to 200°C.

[0089] Figure 33 Depicted is an XRPD pattern of a crystalline form of Compound A chloride salt Form C2.

[0090] Figure 34 Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of crystalline Compound A chloride salt Form C2. The DSC showed endothermic melting with onset temperatures of 54°C and 121°C and peak temperatures of 75°C and 133°C, respectively. Form C2 exhibited an 8.6% weight loss observed by TGA at up to 212°C.

[0091] Figure 35 Depicted is an XRPD pattern of a crystalline form of Compound A sulfate salt Form D1.

[0092] Figure 36 Depicted is the XRPD pattern of crystalline Compound A malonate salt Form El.

[0093] Figure 37 Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of crystalline Compound A malonate salt Form E1. The DSC showed an endothermic melt with an onset and peak temperatures of 182° C. and 183° C., respectively. Form E1 showed negligible weight loss by TGA up to 153° C.

[0094] Figure 38 Depicted is the XRPD pattern of crystalline Compound A naphthalene-2-sulfonate salt, Form F1.

[0095] Figure 39 Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of crystalline Compound A naphthalene-2-sulfonate salt Form F1. The DSC showed an endothermic melt with an onset and peak temperatures of 206° C. and 211° C., respectively. Form F1 showed negligible weight loss by TGA up to 212° C.

[0096] Figure 40 Depicted is the DVS of crystalline Compound A naphthalene-2-sulfonate salt Form F1.

[0097] Figure 41 Depicted is the XRPD pattern of crystalline Compound A naphthalene-2-sulfonate salt Form F2.

[0098] Figure 42Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of crystalline Compound A naphthalene-2-sulfonate salt Form F2. The DSC showed an endothermic melt with an onset and peak temperatures of 273° C. and 280° C. Form F2 showed negligible weight loss by TGA up to 223° C.

[0099] Figure 43 Depicted is the DVS of crystalline Compound A naphthalene-2-sulfonate salt Form F2.

[0100] Figure 44 Depicted is the XRPD pattern of crystalline Compound A naphthalene-2-sulfonate salt Form F3.

[0101] Figure 45 Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of crystalline Compound A naphthalene-2-sulfonate salt Form F3. The DSC showed endothermic events with onset temperatures of 50°C and 147°C and peak temperatures of 76°C and 212°C, respectively. Form F3 showed a 3.6% weight loss as measured by TGA at temperatures as high as 209°C.

[0102] Figure 46 Depicted is the XRPD pattern of crystalline Compound A mesylate salt Form G1.

[0103] Figure 47 Depicted is the XRPD pattern of crystalline Compound A mesylate salt Form G2.

[0104] Figure 48 Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of crystalline Compound A mesylate salt Form G2. The DSC showed an endothermic transition with an onset and peak temperature of 271° C. and 272° C., respectively. Form G3 showed negligible weight loss by TGA up to 206° C.

[0105] Figure 49 Depicted is the DVS of crystalline Compound A mesylate salt Form G2.

[0106] Figure 50 Depicted is the XRPD pattern of crystalline Compound A oxalate salt Form H2.

[0107] Figure 51 Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of crystalline Compound A oxalate salt Form H2. The DSC showed an endothermic event with an onset and peak temperature of 241° C. and 243° C., respectively. Form H2 showed negligible weight loss by TGA up to 196° C.

[0108] Figure 52 Depicted is the XRPD pattern of crystalline Compound A tartrate salt Form I1.

[0109] Figure 53 Depicted are the DSC thermogram and thermogravimetric analysis (TGA) of crystalline Compound A tartrate salt Form I1. The DSC showed endothermic events with onset temperatures of 79°C and 144°C and peak temperatures of 105°C and 152°C, respectively. Form I1 showed a 3.0% weight loss by TGA at temperatures as high as 151°C.

[0110] Figure 54 Depicted is the XRPD pattern of crystalline Compound A esylate salt Form J1.

[0111] Figure 55 Depicted are the DSC thermogram and TGA of crystalline Compound A esylate salt Form J1. The DSC showed endothermic events with onset temperatures of 30° C. and 244° C. and peak temperatures of 64° C. and 254° C. Form J1 showed a 6.2% weight loss by TGA up to 250° C.

[0112] Figure 56 Depicted is the XRPD pattern of crystalline Compound A esylate salt Form J2.

[0113] Figure 57 Depicted are the DSC thermogram and TGA of crystalline Compound A esylate salt Form J2. The DSC showed endothermic events with onset temperatures of 34.4°C and 238.0°C and peak temperatures of 63°C and 249°C, respectively. Form J2 showed a 2.5% weight loss by TGA at temperatures as high as 219°C.

[0114] Figure 58 Depicted is the XRPD pattern of crystalline Compound A N-cyclamate salt Form K1.

[0115] Figure 59 Depicted are the DSC thermogram and TGA of crystalline Compound A N-cyclamate salt Form K1. The DSC showed an endothermic event with onset and peak temperatures of 201° C. and 211° C., respectively. Form K1 showed a 2.5% weight loss by TGA at temperatures as high as 213° C.

[0116] Figure 60 Depicted is the XRPD pattern of crystalline Compound A maleate salt Form L1.

[0117] Figure 61 Depicted are the DSC thermogram and TGA of crystalline Compound A maleate salt Form L1. The DSC showed an endothermic event with onset and peak temperatures of 198° C. and 203° C. Form L1 showed a 2.0% weight loss by TGA at temperatures as high as 181° C.

[0118] Figure 62 Depicted is the XRPD pattern of crystalline Compound A phosphate salt Form M1.

[0119] Figure 63 Depicted are the DSC thermogram and TGA of crystalline Compound A phosphate salt Form M1. The DSC showed an endothermic event with an onset temperature of 214° C. and a peak temperature of 217° C. Form M1 showed negligible weight loss by TGA up to 188° C.

[0120] Figure 64 Depicted is the DVS of crystalline Compound A phosphate salt Form M1.

[0121] Figure 65 Depicted is the XRPD pattern of crystalline Compound A phosphate salt Form M2.

[0122] Figure 66 Depicted are the DSC thermogram and TGA of crystalline Compound A phosphate salt Form M2. The DSC showed endothermic events with onset temperatures of 57° C., 88° C., 141° C., and 198° C., and peak temperatures of 74° C., 109° C., 149° C., and 205° C. Form M2 showed a weight loss of 1.1% as measured by TGA at temperatures as high as 106° C.

[0123] Figure 67 Depicted is the XRPD pattern of crystalline Compound A phosphate salt Form M3.

[0124] Figure 68 Depicted are the DSC thermogram and TGA of crystalline Compound A phosphate salt Form M3. The DSC showed endothermic events with peak temperatures of 69°C, 88°C, and 102°C. In addition, there were endothermic events with onset temperatures of 157°C and 208°C and peak temperatures of 165°C and 214°C, respectively. There were exothermic events with onset and peak temperatures of 174°C and 181°C, respectively. Form M3 showed a weight loss of 8.1% by TGA.

[0125] Figure 69 Depicted is the XRPD pattern of crystalline Compound A salicylic acid cocrystal Form CC-1A.

[0126] Figure 70 Depicted are the DSC thermogram and TGA of crystalline Compound A salicylic acid cocrystal Form CC-1A. The DSC showed endothermic events with onset temperatures of 43°C and 103°C and peak temperatures of 75°C, 107°C, and 239°C, respectively. Form CC1-A showed an 11.7% weight loss as measured by TGA at temperatures as high as 126°C.

[0127] Figure 71 Depicted is the XRPD pattern of crystalline Compound A salicylic acid cocrystal Form CC-2A.

[0128] Figure 72Depicted are the DSC thermogram and TGA of crystalline Compound A salicylic acid cocrystal Form CC-2A. The DSC shows endothermic events with onset temperatures of 107°C and 195°C and peak temperatures of 119°C and 196°C, respectively. Form CC2-A shows a 13.6% weight loss as measured by TGA at temperatures as high as 133°C.

[0129] Figure 73 Depicted is the XRPD pattern of crystalline Compound A salicylic acid cocrystal Form CC-3A.

[0130] Figure 74 Depicted are the DSC thermogram and TGA of crystalline Compound A salicylic acid cocrystal Form CC-3A. The DSC shows an endothermic event with an onset and peak temperatures of 182° C. and 185° C., respectively. Form CC-3A shows negligible weight loss by TGA up to 127° C.

[0131] Figure 75 Depicted is the DVS of crystalline Compound A salicylic acid cocrystal Form CC-3A, which has a mass gain of 1.3% up to 80% relative humidity.

[0132] Figure 76 Depicted is the XRPD pattern of crystalline Compound A salicylic acid cocrystal Form CC-4A.

[0133] Figure 77 Depicted are the DSC thermogram and TGA of crystalline Compound A salicylic acid cocrystal Form CC-4A. The DSC shows an endothermic event with onset and peak temperatures of 143°C and 198°C, respectively, and peak temperatures of 152°C and 200°C. Form CC-4A shows a 5.7% weight loss as measured by TGA at temperatures as high as 171°C.

[0134] Figure 78 Depicted is the XRPD pattern of crystalline Compound A salicylic acid cocrystal Form CC-5A.

[0135] Figure 79 Depicted are the DSC thermogram and TGA of crystalline Compound A salicylic acid cocrystal Form CC-5A. The DSC showed an endothermic event with a peak temperature of 1224° C. Form CC-5A showed an 8.3% weight loss by TGA at temperatures as high as 134° C.

[0136] Figure 80 Depicted is the XRPD pattern of crystalline Compound A formic acid cocrystal Form CC-1B.

[0137] Figure 81Depicted are the DSC thermogram and TGA of crystalline Compound A formic acid cocrystal Form CC-1B. The DSC showed endothermic events with peak temperatures at 62° C. and 105° C. Form CC-1B showed a 1.1% weight loss as high as 63° C. as observed by TGA.

[0138] Figure 82 Depicted is the XRPD pattern of crystalline Compound A benzoic acid cocrystal Form CC-1C.

[0139] Figure 83 Depicted are the DSC thermogram and TGA of crystalline Compound A benzoic acid cocrystal Form CC-1C. DSC shows an endothermic melt with an onset and peak temperatures of 186° C. and 187° C., respectively. Form CC-1C shows negligible weight loss by TGA up to 117° C.

[0140] Figure 84 Depicted is the DVS of crystalline Compound A benzoic acid cocrystal Form CC-1C, which has a mass gain of 0.3% up to 80% relative humidity.

[0141] Figure 85 Depicted is the XRPD pattern of crystalline Compound A isobutyric acid cocrystal Form CC-1D.

[0142] Figure 86 Depicted are the DSC thermogram and TGA of crystalline Compound A isobutyric acid cocrystal Form CC-1D. The DSC shows endothermic events with onset temperatures of 155° C. and 226° C. and peak temperatures of 176° C. and 227° C., respectively. Form CC-1D shows a 16.3% weight loss as measured by TGA at temperatures up to 180° C.

[0143] Figure 87 Depicted is the DVS of crystalline Compound A isobutyric acid cocrystal Form CC-ID, which has a mass gain of 0.2% up to 80% relative humidity.

[0144] Figure 88 Depicted is the XRPD pattern of crystalline Compound A isobutyric acid cocrystal Form CC-2D.

[0145] Figure 89 Depicted are the DSC thermogram and TGA of crystalline Compound A isobutyric acid cocrystal Form CC-2D. The DSC showed endothermic events with onset temperatures of 163° C. and 228° C. Form CC-2D showed an 18.1% weight loss by TGA at temperatures as high as 192° C.

[0146] Figure 90 Depicted is the DVS of crystalline Compound A isobutyric acid cocrystal Form CC-2D, which has a mass gain of 0.2% up to 80% relative humidity.

[0147] Figure 91 Depicted is the XRPD pattern of crystalline Compound A octanoic acid cocrystal Form CC-1E.

[0148] Figure 92 Depicted are the DSC thermogram and TGA of crystalline Compound A octanoic acid cocrystal Form CC-1E. The DSC showed an endothermic event with an onset and peak temperature of 131° C. and 136° C., respectively. Degradation was observed by TGA concurrently with the endothermic event in the DSC.

[0149] Figure 93 Depicted is the XRPD pattern of crystalline Compound A sorbic acid cocrystal Form CC-1F.

[0150] Figure 94 Depicted are the DSC thermogram and TGA of crystalline Compound A sorbic acid cocrystal Form CC-1F. DSC shows endothermic events with onset temperatures of 62°C and 160°C and peak temperatures of 90°C and 170°C, respectively. Form CC-1F shows a 20.8% weight loss as measured by TGA at temperatures as high as 218°C.

[0151] Figure 95 Depicted is the XRPD pattern of crystalline Compound A saccharin cocrystal Form CC-1G.

[0152] Figure 96 Depicted are the DSC thermogram and TGA of crystalline Compound A saccharin cocrystal Form CC-1G. The DSC shows an endothermic event with an onset and peak temperature of 243° C. and 244° C., respectively. Form CC-1G shows negligible weight loss by TGA up to 182° C.

[0153] Figure 97 Depicted is the DVS of crystalline Compound A saccharin cocrystal Form CC-1G, which has a mass gain of 0.2% up to 80% relative humidity.

[0154] Figure 98 Depicted is the XRPD pattern of crystalline Compound A succinic acid cocrystal Form CC-1H.

[0155] Figure 99 Depicted are the DSC thermogram and TGA of crystalline Compound A succinic acid cocrystal Form CC-1H. DSC showed endothermic melting with onset temperatures of 59°C and 186°C and peak temperatures of 82°C and 187°C, respectively. Form CC-1H showed a 2.9% weight loss as measured by TGA at temperatures as high as 102°C.

[0156] Figure 100 Depicted is the XRPD pattern of crystalline Compound A succinic acid cocrystal Form CC-2H.

[0157] Figure 101 Depicted are the DSC thermogram and TGA of crystalline Compound A succinic acid cocrystal Form CC-2H. DSC shows endothermic transitions with onset temperatures of 94°C and 166°C and peak temperatures of 99°C and 172°C, respectively. Form CC-2H shows a 24.4% weight loss as measured by TGA at temperatures as high as 235°C.

[0158] Figure 102 Depicted is the XRPD pattern of crystalline Compound A adipic acid cocrystal Form CC-II.

[0159] Figure 103 Depicted are the DSC thermogram and TGA of crystalline Compound A adipic acid cocrystal Form CC-II. The DSC showed endothermic melting with onset temperatures of 91°C and 137°C and peak temperatures of 91°C and 140°C, respectively. Form CC-II showed a 2.7% weight loss as measured by TGA at temperatures as high as 78°C.

[0160] Figure 104 Depicted is the XRPD pattern of the amorphous form of Compound A free base.

[0161] Figure 105 Depicted is a modulated differential scanning calorimetry (mDSC) thermogram of the amorphous form of Compound A free base, indicating a Tg of 119°C. DETAILED DESCRIPTION

[0162] Disclosed herein is a solid form of Compound A having the following structure:

[0163] Compound A is a small molecule MTA-cooperative PRMT5 inhibitor in development for the treatment of MTAP-deficient cancers with high unmet needs, such as squamous non-small cell lung cancer (NSCLC) and pancreatic cancer. The disclosed solid forms include crystalline and amorphous forms of Compound A free base, as well as crystalline salts, co-crystals, and solvates of Compound A. The disclosed solid forms can have unique physical properties, which are advantageous for new pharmaceutical compositions of Compound A.

[0164] Also disclosed herein are pharmaceutical compositions comprising the disclosed solid form of Compound A and methods of treating a subject having cancer comprising administering to the subject a therapeutically effective amount of the disclosed solid form of Compound A.

[0165] International Patent Application Nos. PCT / US22 / 75648 and PCT / US21 / 63540, each of which is incorporated herein by reference in its entirety, disclose synthetic procedures for synthesizing PRMT5 inhibitors such as Compound A.

[0166] Applicants have discovered various solid forms disclosed herein using high throughput (HT) screening (including HT salt screening and HT polymorph screening). For example, various crystalline salts and free base polymorphs have been identified, including, for example, benzenesulfonic acid (BSA) and methanesulfonic acid (MSA) salts, toluenesulfonic acid (TSA) salts, maleates, ethanesulfonic acid (ESA) salts, ethylenedisulfonic acid (EDSA) salts, hydrochlorides (HCl) salts, sulfates (H2SO4) salts, and bromides (HBr). In addition, new XRPD groups associated with the free base have been identified from the HT salt screening.

[0167] As used herein, the term "solid form" refers to a crystalline form, an amorphous form, a salt, a co-crystal, or a solvate, including but not limited to the specific solid forms disclosed herein. In some cases, the term "crystalline form" is used herein to refer to various crystalline forms disclosed herein (e.g., free base form, salt, solvate, and / or co-crystal).

[0168] As used herein, the term "salt" refers to a zwitterionic compound composed of a cation and an anion. As used herein, the term "pharmaceutically acceptable salt" refers to those salts that are suitable for use in contact with the tissues of humans and lower animals without excessive toxicity, irritation, allergic response, etc., and are commensurate with a reasonable benefit / risk ratio, within the scope of sound medical judgment. Pharmaceutically acceptable salts are well known in the art. For example, SM Berge et al., in J. Pharmaceutical Pharmaceutically acceptable salts are described in detail in Sciences, 1977, 66, 1-19 (incorporated herein by reference). Pharmaceutically acceptable salts of the compounds of the present disclosure include those derived from suitable inorganic and organic acids and inorganic and organic bases. Examples of pharmaceutically acceptable non-toxic acid addition salts are salts of amino groups formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, trifluoroacetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other illustrative pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, gluconate heptanoate, glycerophosphate, gluconate, glutamate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate , 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate etc.The salt of the compound containing carboxylic acid or other acidic functional group can be prepared by reaction with suitable base.Such salt includes but is not limited to alkali metal salt, alkaline earth metal salt, aluminum salt, ammonium salt, N+(C1-4 alkyl)4 salt, and organic base such as trimethylamine, triethylamine, morpholine, pyridine, Piperidine, picoline, dicyclohexylamine, N,N'-dibenzylethylenediamine, 2-hydroxyethylamine, bis-(2-hydroxyethyl)amine, tris-(2-hydroxyethyl)amine, procaine, dibenzylpiperidine, dehydroabietylamine, N,N'-didehydroabietylamine, glucosamine, N-methylglucosamine, collidine, quinine, quinoline, and salts of basic amino acids such as lysine and arginine. The present invention also contemplates the quaternization of any basic nitrogen-containing group of the compounds disclosed herein. Water- or oil-soluble or dispersible products can be obtained by such quaternization. Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like.Additional pharmaceutically acceptable salts include non-toxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates, where appropriate.

[0169] As used herein, the term "co-crystal" refers to a crystalline material comprising two or more compounds at ambient temperature (e.g., 20°C-25°C), wherein at least two of the compounds are held together by weak interactions, wherein at least one of the compounds is a co-crystal former and the other is Compound 1. Weak interactions are defined as interactions that are neither ionic nor covalent, and include, for example, hydrogen bonding, van der Waals forces, and π-π interactions. The term "co-crystal" includes solvate forms.

[0170] As used herein, the term "amorphous form" or "amorphous" refers to a material that lacks long-range order and, therefore, does not exhibit distinct X-ray diffraction peaks (i.e., Bragg diffraction peaks). The XRPD pattern of an amorphous material is characterized by one or more amorphous halos. As used herein, the term "amorphous halo" refers to an approximately bell-shaped maximum in the X-ray powder pattern of an amorphous substance.

[0171] As used herein with reference to DSC data, "substantially" refers to a variation of ± 3°C.

[0172] As used herein, the terms "pharmaceutical composition" and "pharmaceutical formulation" are used interchangeably.

[0173] The disclosed solid forms of Compound A were prepared and analyzed as described in the Examples using one or more of the following techniques: X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), nuclear magnetic resonance spectroscopy (NMR) (e.g., 13 C NMR).

[0174] Free base form

[0175] Crystalline Compound A free base ("Form 1")

[0176] In some embodiments, the present disclosure provides Compound A as a free base, wherein the free base is crystalline (e.g., crystalline Compound A free base). In some embodiments, the present disclosure provides a crystalline form of Compound A free base ("Form 1") characterized by an XRPD pattern comprising peaks at 4.5, 9.0, 13.3, 16.2, and 18.9 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, Form 1 is further characterized by XRPD pattern peaks at 14.7, 15.7, 16.7, 17.6, 22.5, 26.2, and 26.4 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, Form 1 has substantially Figure 1 The XRPD pattern shown.

[0177] In some embodiments, Form 1 is characterized by using CuKα radiation comprising at least three selected from 4.5, 6.7, 9.0, 12.2, 12.5, 12.8, 13.3, 13.7, 14.3, 14.7, 15.7, 16.2, 16.7, 17.4, 17.6, 18.0, 18.4, 18.8, 19.6, 20.0, 20.3, 20.8, 2 4, 35.1 , 35.6, 36.4, 37.8, and 39.4 ± 0.2° 2Θ.

[0178] In some embodiments, Form 1 is characterized by using CuKα radiation comprising at least five selected from 4.5, 6.7, 9.0, 12.2, 12.5, 12.8, 13.3, 13.7, 14.3, 14.7, 15.7, 16.2, 16.7, 17.4, 17.6, 18.0, 18.4, 18.8, 19.6, 20.0, 20.3, 20.8, 2 4, 35.1 , 35.6, 36.4, 37.8, and 39.4 ± 0.2° 2Θ.

[0179] In some embodiments, Form 1 is characterized by using CuKα radiation comprising at least seven selected from 4.5, 6.7, 9.0, 12.2, 12.5, 12.8, 13.3, 13.7, 14.3, 14.7, 15.7, 16.2, 16.7, 17.4, 17.6, 18.0, 18.4, 18.8, 19.6, 20.0, 20.3, 20.8, 2 4, 35.1 , 35.6, 36.4, 37.8, and 39.4 ± 0.2° 2Θ.

[0180] In some embodiments, Form 1 is characterized by the use of CuKα radiation comprising at least eight selected from 4.5, 6.7, 9.0, 12.2, 12.5, 12.8, 13.3, 13.7, 14.3, 14.7, 15.7, 16.2, 16.7, 17.4, 17.6, 18.0, 18.4, 18.8, 19.6, 20.0, 20.3, 20.8, 2 4, 35.1 , 35.6, 36.4, 37.8, and 39.4 ± 0.2° 2Θ.

[0181] In some embodiments, Form 1 is characterized by comprising at least three peaks selected from 39.2, 43.8, 51.6, 58.1, 65.9, 71.8, 73.6, 114.7, 120.8, 125.1, 126.1, 128.2, 130.8, 142.2, 143.3, 145.3, 148.5, 149.2, 156.9, and 169.6 ppm. 13 C solid-state NMR.

[0182] In some embodiments, Form 1 is characterized by comprising at least five peaks selected from 39.2, 43.8, 51.6, 58.1, 65.9, 71.8, 73.6, 114.7, 120.8, 125.1, 126.1, 128.2, 130.8, 142.2, 143.3, 145.3, 148.5, 149.2, 156.9, and 169.6 ppm. 13 C solid-state NMR.

[0183] In some embodiments, Form 1 is characterized by comprising at least seven peaks selected from 39.2, 43.8, 51.6, 58.1, 65.9, 71.8, 73.6, 114.7, 120.8, 125.1, 126.1, 128.2, 130.8, 142.2, 143.3, 145.3, 148.5, 149.2, 156.9, and 169.6 ppm. 13 C solid-state NMR.

[0184] In some embodiments, Form 1 is characterized by a chromatographic structure comprising peaks at -62.0 and -63.9 ppm. 19 F solid-state NMR.

[0185] A single crystal of compound A free base form 1 was grown by slow evaporation from ethyl acetate and used for single crystal X-ray structure determination. The results confirmed that it is an anhydrous form crystallized in a monoclinic chiral C2 space group with two compound A molecules (Z'=2) in the asymmetric unit. The absolute configuration was confirmed, and for all molecules in the unit cell, the chiral carbon was in the S-configuration (Z=8).

[0186] In some embodiments, Form 1 has the following unit cell dimensions: α=90°; β=106.722(3)°; and γ=90°.

[0187] Alternatively, or in addition, Form 1 can be characterized using differential scanning calorimetry (DSC). In some embodiments, Form 1 has substantially Figure 2 As described in the Examples, a differential scanning calorimetry (DSC) thermogram of Form 1 was obtained. The DSC curve indicated an endothermic transition at 218° C. to 235° C. In some embodiments, Form 1 has an extrapolated onset at 225° C. ± 3° C. Form 1 showed negligible weight loss by TGA up to 226° C.

[0188] Alternatively, or in addition, the crystalline Compound A free base Form 1 is characterized using thermogravimetric analysis (TGA). In some embodiments, the crystalline Compound A free base Form 1 has substantially Figure 3 Dynamic vapor sorption (DVS) is shown.

[0189] Furthermore, Form 1 is stable under compression forces representative of the tableting process. For example, Form 1 exhibited no form changes by DSC and XRPD after compression up to 200 MPa. Furthermore, Form 1 exhibited reasonable stability. For example, in studies of various excipient blends under various conditions, including, for example, 40°C / 75% RH, 25°C / 60% RH open, and 40°C / 75% RH closed conditions, Form 1 was physically and chemically stable as determined by ssNMR, with no signs of degradation associated with the Maillard reaction observed after 2 weeks. Furthermore, Form 1 has high solubility in many organic solvents, particularly with water as a co-solvent (e.g., acetonitrile (13.2 mg / mL), 1:1 acetonitrile / water (31.1 mg / mL), ethanol 4.8 mg / mL, 1:1 ethanol / water (15.9 mg / mL), acetone (33.0 mg / mL), 1:4 acetone / water (0.2 mg / mL), and isopropanol (9.1 mg / mL). Solubility studies demonstrated that Form 1 exhibited a desirable solubility of greater than 10 μg / mL in aqueous media at pH 1-8.

[0190] Crystalline Compound A free base ("Form 3")

[0191] In some embodiments, the present disclosure provides a crystalline form of Compound A free base ("Form 3") characterized by an XRPD pattern comprising peaks at 4.3, 12.6, 14.4, 16.2, and 25.6 ± 0.2 ° 2θ using CuKα radiation. In some embodiments, Form 3 is further characterized by XRPD pattern peaks at 8.6, 13.9, 15.6, 16.7, and 25.3 ± 0.2 ° 2θ using CuKα radiation. In yet other embodiments, Form 3 is further characterized by XRPD pattern peaks at 18.4, 19.7, 20.3, 26.7, 27.9, and 28.4 ± 0.2 ° 2θ using CuKα radiation. In some embodiments, Form 3 has substantially Figure 4 The XRPD pattern shown.

[0192] Alternatively, or in addition, Form 3 can be characterized using DSC. In some embodiments, Form 3 has substantially Figure 5 DSC shown. A DSC thermogram of Form 3 was obtained as described in the Examples. The DSC curve indicated an exothermic event with onset temperatures of 105°C and 173°C and peak temperatures of 111°C and 173°C. An endothermic event was observed with onset and peak temperatures of 226°C and 229°C.

[0193] Alternatively, or in addition, Form 3 is characterized using thermogravimetric analysis (TGA). In some embodiments, Compound A free base Form 3 has substantially Figure 5As shown in the TGA. Figure 5 As shown, Form 3 exhibits negligible weight loss up to 200°C.

[0194] Alternatively, or in addition, Form 3 uses DVS characterization. In some embodiments, Form 3 has Figure 6 DVS isotherm curve shown.

[0195] Crystalline Compound A free base ("Form 6")

[0196] In some embodiments, the present disclosure provides a crystalline form of Compound A free base ("Form 6") characterized by an XRPD pattern comprising peaks at 4.5, 8.6, 9.0, 12.9, and 14.9 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form 6 is further characterized by XRPD pattern peaks at 7.4, 12.3, 13.3, 16.2, 17.8, and 18.8 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form 6 has substantially Figure 7 The XRPD pattern shown.

[0197] Alternatively, or additionally, Form 6 can be characterized using DSC. In some embodiments, Form 6 has substantially Figure 8 As described in the Examples, a differential scanning calorimetry (DSC) thermogram of Form 6 was obtained. Figure 8 As shown, an endothermic event was observed with onset and peak temperatures of 225°C and 227°C.

[0198] Alternatively, or in addition, Form 6 is characterized using thermogravimetric analysis (TGA). In some embodiments, Compound A free base Form 6 has substantially Figure 8 As shown in the TGA. Figure 8 As shown, Form 6 exhibits negligible weight loss up to 216°C.

[0199] Crystalline Compound A free base ("Form 7")

[0200] In some embodiments, the present disclosure provides a crystalline form of Compound A free base ("Form 7") characterized by an XRPD pattern comprising peaks at 4.3, 8.5, 12.3, 13.1, and 14.8 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, Form 7 is further characterized by XRPD pattern peaks at 15.5, 19.1, and 20.9 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, Form 7 has substantially Figure 9 The XRPD pattern shown.

[0201] Alternatively, or additionally, Form 7 can be characterized using DSC. In some embodiments, Form 7 has substantially Figure 10 DSC shown. A differential scanning calorimetry (DSC) thermogram of Form 7 was obtained as described in the Examples.

[0202] Alternatively, or additionally, Form 7 is characterized using thermogravimetric analysis (TGA). In some embodiments, Compound A free base Form 7 has substantially Figure 10 TGA shown.

[0203] like Figure 10 As shown, Form 7 exhibited an endothermic event with an onset temperature of 61°C and other endothermic events at higher temperatures. The endothermic events had peak temperatures at 87°C, 221°C, and 223°C. Exothermic events were observed with onset and peak temperatures of 129°C and 141°C. In addition, Form 7 exhibited a 1.2% weight loss as measured by TGA at temperatures up to 94°C and an additional 0.3% weight loss at temperatures up to 176°C.

[0204] Amorphous Compound A free base

[0205] In some embodiments, the present disclosure provides amorphous form of Compound A free base. In some embodiments, the present disclosure provides an amorphous form of Compound A free base characterized by being as described in the Examples and substantially as described in the Examples. Figure 103 In some embodiments, the amorphous form of Compound A free base has a glass transition temperature (Tg) of 115°C to 125°C, for example, 118°C ± 3°C.

[0206] An amorphous form of Compound A free base can be formed upon cooling a melt of Compound A free base under suitable conditions. For example, in some embodiments, Compound A free base Form 1 can be heated to a temperature of 300° C. at a rate of 20° C. / min and melted in a hot stage microscope, after which the sample can be removed and rapidly cooled to room temperature.

[0207] Crystalline solvate

[0208] In certain embodiments, present disclosure provides solvates and hydrates of crystalline compound A. Typically, solvates and hydrates are formed (for example, by slurrying or evaporation) by a mixture comprising compound A and water and / or one or more organic solvents. Non-limiting examples of suitable organic solvents for forming the solvate of compound A include ethanol, isopropanol, methanol and acetonitrile. For example, ethanol and isopropanol solvates of compound A disclosed herein can be obtained by slowly evaporating or slurrying a mixture comprising compound A and ethanol and / or isopropanol.

[0209] Crystalline Compound A Free Base Hydrate ("Form 8")

[0210] In some embodiments, the present disclosure provides a crystalline form of Compound A free base hydrate ("Form 8") characterized by an XRPD pattern comprising peaks at 4.0, 7.7, 8.0, 12.3, and 15.1 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, Form 8 is further characterized by XRPD pattern peaks at 6.1, 10.0, 13.7, 17.0, 18.4, and 19.9 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, Form 8 has substantially Figure 11 The XRPD pattern shown.

[0211] Alternatively, or additionally, Form 8 can be characterized using DSC. In some embodiments, Form 8 has substantially Figure 12 DSC shown. A differential scanning calorimetry (DSC) thermogram of Form 8 was obtained as described in the Examples.

[0212] Alternatively, or in addition, Form 8 can be characterized using thermogravimetric analysis (TGA). In some embodiments, Compound A free base Form 8 has substantially Figure 12 TGA shown.

[0213] like Figure 12 As shown, Form 8 exhibited endothermic events with onset temperatures of 57° C. and 219° C. and peak temperatures of 79° C. and 225° C., respectively. In addition, Form 8 exhibited a weight loss of 3.3% as determined by TGA at temperatures as high as 128° C.

[0214] Crystalline Compound A ethanol solvate ("Form 2A")

[0215] In some embodiments, the present disclosure provides a crystalline Compound A ethanol solvate ("Form 2A") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.8, 11.6, 12.7, 18.0, and 25.7 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form 2A is further characterized by XRPD peaks at 16.5, 22.6, 23.3, and 25.8 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form 2A has substantially Figure 13 The XRPD pattern shown.

[0216] In some embodiments, the present disclosure provides Form 2A having the following unit cell dimensions: α=90°; β=95.5093(8)°; and γ=90°.

[0217] Alternatively, or additionally, Form 2A can be characterized using DSC. In some embodiments, Form 2A has substantially Figure 14 DSC shown. A differential scanning calorimetry (DSC) thermogram of Form 2A was obtained as described in the Examples.

[0218] Alternatively, or in addition, Form 2A can be characterized using thermogravimetric analysis (TGA). In some embodiments, Compound A free base Form 2A has substantially Figure 14 TGA shown.

[0219] like Figure 14 As shown, the DSC curve of Form 2A shows a first small endotherm with an extrapolated onset at 132° C. due to desolvation of ethanol, and a second endotherm overlapping with the exotherm of subsequent recrystallization and followed by an extrapolated melting onset at 224° C. and a melting endothermic transition at 218° C. to 236° C. In some embodiments, the extrapolated onset is at 224° C. ± 3° C. All melting onsets of the solvate / hydrate are close to that of the free base Form 1. The DSC heating process can cause the solvate / hydrate to recrystallize into the free base Form 1.

[0220] Crystalline Compound A Isopropanol Solvate ("Form 3A")

[0221] In some embodiments, the present disclosure provides crystalline Compound A isopropanol solvate ("Form 3A") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.6, 12.8, 16.4, 17.5, and 25.1 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the XRPD of Form 3A is further characterized by XRPD pattern peaks at 8.2, 11.2, 12.5, 18.6, and 21.8 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the XRPD of Form 3A is further characterized by XRPD pattern peaks at 6.4, 8.8, 9.2, 13.6, 21.0, 22.4, 22.9, 24.5, and 25.9 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form 3A has substantially Figure 15 The XRPD pattern shown.

[0222] Alternatively, or additionally, Form 3A can be characterized using DSC. In some embodiments, Form 3A has substantially Figure 16 DSC shown. A differential scanning calorimetry (DSC) thermogram of Form 3A was obtained as described in the Examples.

[0223] Alternatively, or in addition, Form 3A can be characterized using thermogravimetric analysis (TGA). In some embodiments, Compound A free base Form 3A has substantially Figure 16 TGA shown.

[0224] In some embodiments, Form 3A exhibits a first small endotherm with an extrapolated onset at 122.6° C. due to desolvation of isopropyl alcohol (IPA), and a second endotherm overlapping with an exotherm of subsequent recrystallization and followed by an extrapolated melting onset at 223° C. ± 3° C. In some embodiments, the DSC of Form 3A has an endothermic onset transition at 223° C. ± 3° C.

[0225] Crystalline Compound A Acetone Solvate ("Form 4A")

[0226] In some embodiments, the present disclosure provides crystalline Compound A acetone solvate ("Form 4A") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.7, 7.7, 11.5, 14.8, and 15.3 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form 4A is further characterized by XRPD peaks at 4.3, 7.3, 13.4, 16.2, and 24.0 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form 4A is further characterized by XRPD peaks at 11.2, 18.5, 19.6, and 20.4 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form 4A has substantially Figure 17 The XRPD pattern shown.

[0227] Alternatively, or additionally, Form 4A can be characterized using DSC. In some embodiments, Form 4A has substantially Figure 18 DSC shown. A differential scanning calorimetry (DSC) thermogram of Form 4A was obtained as described in the Examples.

[0228] Alternatively, or in addition, Form 4A can be characterized using thermogravimetric analysis (TGA). In some embodiments, Compound A free base Form 4A has substantially Figure 18 TGA shown.

[0229] Crystalline Compound A Free Base Methanol Solvate ("Form 5A")

[0230] In some embodiments, the present disclosure provides crystalline Compound A methanol solvate ("Form 5A") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.8, 7.7, 12.3, 15.3, and 16.1 ± 0.2° 2θ using CuKa radiation. In some embodiments, Form 5A is further characterized by XRPD peaks at 8.9, 10.5, 13.1, 13.4, 14.5, 17.6, 21.5, and 25.0 ± 0.2° 2θ using CuKa radiation. In some embodiments, Form 5A is further characterized by XRPD peaks at 9.7, 14.1, 18.7, 19.6, 22.7, 24.7, 26.0, and 26.6 ± 0.2° 2θ using CuKa radiation. In some embodiments, Form 5A has substantially Figure 19 The XRPD pattern shown.

[0231] Alternatively, or in addition, Form 5A can be characterized using DSC. In some embodiments, Form 5A has substantially Figure 20 DSC shown. A differential scanning calorimetry (DSC) thermogram of Form 5A was obtained as described in the Examples.

[0232] Alternatively, or in addition, Form 5A can be characterized using thermogravimetric analysis (TGA). In some embodiments, Compound A free base Form 5A has substantially Figure 20 TGA shown.

[0233] Crystalline Compound A Free Base Methyl-THF Solvate ("Form 6A") In some embodiments, the present disclosure provides crystalline Compound A methyl-THF Solvate ("Form 6A") characterized by an XRPD pattern comprising peaks at 7.6, 11.3, 15.1, 18.3, and 28.0 ± 0.2 ° 2θ using CuKa radiation. In some embodiments, Form 6A is further characterized by XRPD pattern peaks at 12.4, 15.7, 17.3, 17.7, 18.8, 19.7, 21.3, 22.7, 25.8, 26.1, and 26.5 ± 0.2 ° 2θ using CuKa radiation. In some embodiments, Form 6A is further characterized by XRPD pattern peaks at 13.6, 14.2, 16.5, 16.9, 20.5, 26.9, and 28.4 ± 0.2 ° 2θ using CuKa radiation.

[0234] In some embodiments, the present disclosure provides a crystalline salt form of Compound A. Compound A has an ionizable functional group with a weakly basic pKa value of 4.27 suitable for salt formation. Suitable non-limiting examples of counterions for forming salts with Compound A include benzenesulfonic acid (BSA), toluenesulfonic acid (TSA), sulfuric acid, hydrochloric acid, malonic acid, naphthalene-2-sulfonic acid, methanesulfonic acid, oxalic acid, tartaric acid, ethanesulfonic acid, cyclamic acid, maleic acid or phosphoric acid.

[0235] Crystalline Compound A Tosylate Salt ("Form A1")

[0236] In some embodiments, the crystalline form of the tosylate salt of Compound A ("Form A1") is characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 6.0, 19.1, 20.3, 24.1, 24.9, and 28.9 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the XRPD of Form A1 is further characterized by peaks at 9.5, 11.9, 14.3, 17.9, 26.2, 33.8, and 35.4 ± 0.2 degrees 2θ using CuKa radiation. Alternatively, or additionally, in some embodiments, Form A1 disclosed herein has substantially Figure 21 The XRPD pattern shown.

[0237] Alternatively, or in addition, Form A1 can be characterized using DSC and / or TGA. In some embodiments, Form A1 has substantially Figure 22 As shown in DSC. Figure 22 As shown, Form Al has an endothermic transition at 290° C. to 300° C. as measured by DSC. In some embodiments, the extrapolated onset is at 293° C.±3° C. due to endothermic melting and / or decomposition.

[0238] In some embodiments, Form A1 has substantially Figure 22 The TGA curve is shown.

[0239] In some embodiments, Form A1 has substantially Figure 23 DVS shown.

[0240] Crystalline Compound A Tosylate Salt ("Form A2")

[0241] In some embodiments, the present disclosure provides a crystalline Compound A tosylate salt ("Form A2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 12.7, 15.5, 16.2, 18.7, 19.7, and 21.8 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, Form A2 is characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 10.2, 23.2, 24.1, 24.6, 26.3, and 27.2 ± 0.2 degrees 2θ using CuKα radiation. Alternatively, or additionally, in some embodiments, the XRPD pattern of Form A2 is as follows: Figure 24 shown.

[0242] Alternatively, or additionally, Form A2 can be characterized using DSC and / or TGA. In some embodiments, Form A2 has substantially Figure 25 As shown in DSC. Figure 25 As shown, Form A2 shows an exotherm due to recrystallization with an extrapolated onset at 241.9° C. followed by an extrapolated melting / decomposition at 287° C. Form A2 has an endothermic transition at 270° C. to 300° C. as measured by DSC due to endothermic melting or decomposition. In some embodiments, the extrapolated onset is at 287° C. ± 3° C.

[0243] In some embodiments, Form A2 has substantially Figure 25 The TGA curve is shown.

[0244] Crystalline Compound A Tosylate Salt ("Form A3")

[0245] In some embodiments, the present disclosure provides a crystalline Compound A tosylate salt ("Form A3") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.9, 15.2, 18.8, 19.5, and 24.5 ± 0.2 degrees 2θ using CuKα radiation. Alternatively, or additionally, in some embodiments, the XRPD pattern of Form A3 is as follows: Figure 26 shown.

[0246] Alternatively, or in addition, Form A3 can be characterized using DSC, TGA, and / or DVS. In some embodiments, Form A3 has substantially Figure 27 In some embodiments, Form A3 has Figure 27 TGA shown.

[0247] In addition, Form A3 can be characterized using DVS. In some embodiments, the present disclosure provides Figure 28 The DVS form A3 is shown.

[0248] Crystalline Compound A benzenesulfonate salt ("Form B1")

[0249] In some embodiments, the present disclosure provides a crystalline form of Compound A besylate ("Form B1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.1, 16.1, 17.9, 19.0, and 25.2 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, Form B1 is further characterized by XRPD peaks at 20.2, 20.6, 23.2, 26.0, 27.0, and 30.4 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, Form B1 has substantially Figure 29 The XRPD pattern shown.

[0250] In some embodiments, Form B1 DSC shows an endotherm with an extrapolated onset at 97°C, followed by an extrapolated endotherm of melting / decomposition at 254°C. Form B1 has an endothermic transition at 240°C to 260°C as measured by DSC. In some embodiments, the extrapolated onset due to endothermic melting and / or decomposition is at 254°C ± 3°C. In some embodiments, Form B1 has substantially Figure 30 DSC shown.

[0251] Crystalline Compound A chloride ("Form C1")

[0252] In some embodiments, the crystalline form of the chloride salt of Compound A ("Form C1") is characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 6.8, 11.9, 16.6, 20.7, 23.8, 25.3, and 27.6 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the crystalline Form C1 of the chloride salt of Compound A has substantially Figure 31 The XRPD pattern shown.

[0253] In some embodiments, Form C1 has substantially Figure 32 As shown in DSC. Figure 32 As shown, DSC of Form C1 shows a first broad endotherm with an extrapolated onset at 34°C and a first endothermic transition at 30°C to 110°C. The extrapolated endotherm of melting / decomposition / salt disproportionation is at 166.4°C. In some embodiments, the extrapolated onset is at 34°C ± 3°C. In some embodiments, Form C1 is further characterized by a second endothermic transition at 160°C to 170°C, as measured by DSC. In some embodiments, the second extrapolated onset due to endothermic melting and / or decomposition is at 166°C ± 3°C.

[0254] Crystalline Compound A chloride salt Form C1 can be characterized by TGA. In some embodiments, the disclosed Form C1 has substantially Figure 32 TGA shown.

[0255] Crystalline Compound A chloride ("Form C2")

[0256] In some embodiments, the crystalline form of the chloride salt of Compound A ("Form C2") is characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.2, 5.6, 12.2, 12.9, and 18.1 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form C2 is further characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 6.8, 7.1, 9.4, 13.4, 14.0, 16.5, and 17.7 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form C2 is further characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 7.8, 8.7, 10.9, 11.8, 14.9, 15.4, and 19.1 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline form of the chloride salt of Compound A ("Form C2") having substantially Figure 33 The XRPD pattern of a crystalline form of the chloride salt of Compound A ("Form C2") is shown.

[0257] Alternatively, or additionally, Form C2 can be characterized using DSC, TGA, and or DVS.

[0258] In some embodiments, the present disclosure provides a method having substantially Figure 34 The DSC of form C2 is shown. Figure 34 As shown, DSC of Form C2 shows a first broad endotherm with an extrapolated onset at 34°C and a first endothermic transition at 30°C to 110°C. The extrapolated endotherm of melting / decomposition / salt disproportionation is at 166°C. In some embodiments, the extrapolated onset is at 34°C ± 3°C. In some embodiments, Form C2 is further characterized by a second endothermic transition at 160°C to 170°C, as measured by DSC. In some embodiments, the second extrapolated onset due to endothermic melting and / or decomposition is at 166°C ± 3°C.

[0259] In some embodiments, the disclosed Form C2 has substantially Figure 34 TGA shown.

[0260] Crystalline Compound A Sulfate ("Form D1")

[0261] In some embodiments, the present disclosure provides a crystalline Compound A sulfonate salt ("Form D1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 16.0, 16.5, 16.7, 20.0, and 20.4 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form D1 is further characterized by XRPD peaks at 8.4, 12.1, 13.8, 14.2, 23.6, 24.6, and 25.2 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A sulfonate salt ("Form D1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 16.0, 16.5, 16.7, 20.0, and 20.4 ± 0.2 degrees 2θ using CuKa radiation. Figure 35 XRPD of the Form D1 salt is shown.

[0262] Crystalline Compound A malonate salt ("Form E1")

[0263] In some embodiments, the present disclosure provides a crystalline Compound A malonate salt ("Form E1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 6.8, 12.6, 16.6, 20.4, and 22.0 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form E1 is further characterized by XRPD peaks at 5.4, 8.3, 17.2, 19.4, 21.0, 22.9, and 26.2 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A malonate salt ("Form E1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 6.8, 12.6, 16.6, 20.4, and 22.0 ± 0.2 degrees 2θ using CuKa radiation. Figure 36 Shown is the XRPD of crystalline Compound A malonate salt Form E1.

[0264] In some embodiments, Form E1 is characterized by DSC, TGA, and / or DVS. In some embodiments, the disclosure provides a method having substantially Figure 37 DSC of Form E1 is shown.

[0265] In some embodiments, the present disclosure provides a method having substantially Figure 37 TGA of form E1 is shown.

[0266] Crystalline Compound A naphthalene-2-sulfonate salt ("Form F1")

[0267] In some embodiments, the present disclosure provides crystalline Compound A naphthalene-2-sulfonate salt ("Form F1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.7, 14.7, 14.9, 17.0, 19.6, and 22.1 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, the present disclosure provides a crystalline Compound A naphthalene-2-sulfonate salt ("Form F1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.7, 14.7, 14.9, 17.0, 19.6, and 22.1 ± 0.2 degrees 2θ using CuKα radiation. Figure 38 Shown is the XRPD of crystalline Compound A naphthalene-2-sulfonate salt, Form F1.

[0268] In some embodiments, Form F1 is characterized by DSC, TGA, and / or DVS. In some embodiments, the disclosure provides a method having substantially Figure 39 DSC form F1 is shown.

[0269] In some embodiments, the present disclosure provides a method having substantially Figure 39 TGA form F1 is shown.

[0270] In some embodiments, the present disclosure provides a method having substantially Figure 40 The DVS form F1 is shown.

[0271] Crystalline Compound A naphthalene-2-sulfonate salt ("Form F2")

[0272] In some embodiments, the present disclosure provides crystalline Compound A naphthalene-2-sulfonate salt ("Form F2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.8, 11.6, 14.0, 17.5, and 19.7 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, the present disclosure provides a crystalline Compound A naphthalene-2-sulfonate salt ("Form F2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.8, 11.6, 14.0, 17.5, and 19.7 ± 0.2 degrees 2θ using CuKα radiation. Figure 41 Shown is the XRPD of crystalline Compound A naphthalene-2-sulfonate salt Form F2.

[0273] In some embodiments, Form F2 is characterized by DSC, TGA, and / or DVS. In some embodiments, the disclosure provides a method having substantially Figure 42 DSC of Form F2 is shown.

[0274] In some embodiments, the present disclosure provides a method having substantially Figure 42 TGA form F2 is shown.

[0275] In some embodiments, the present disclosure provides a method having substantially Figure 43 The DVS form F2 is shown.

[0276] Crystalline Compound A naphthalene-2-sulfonate salt ("Form F3")

[0277] In some embodiments, the present disclosure provides crystalline Compound A naphthalene-2-sulfonate salt ("Form F3") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 3.8, 7.6, 9.7, 11.5, and 15.3 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, the present disclosure provides a crystalline Compound A naphthalene-2-sulfonate salt ("Form F3") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 3.8, 7.6, 9.7, 11.5, and 15.3 ± 0.2 degrees 2θ using CuKα radiation. Figure 44 Shown is the XRPD of crystalline Compound A naphthalene-2-sulfonate salt Form F3.

[0278] In some embodiments, Form F3 is characterized by DSC, TGA, and / or DVS. In some embodiments, the disclosure provides a method having substantially Figure 45 DSC form F3 shown.

[0279] In some embodiments, the present disclosure provides a method having substantially Figure 45 TGA form F3 is shown.

[0280] Crystalline Compound A mesylate salt ("Form G1")

[0281] In some embodiments, the present disclosure provides crystalline Compound A mesylate salt ("Form G1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.1, 6.5, 13.6, 13.8, and 19.5 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form G1 is further characterized by XRPD peaks at 6.9, 9.3, 18.5, 20.8, and 21.5 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A mesylate salt ("Form G1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.1, 6.5, 13.6, 13.8, and 19.5 ± 0.2 degrees 2θ using CuKa radiation. Figure 46 Shown is the XRPD of crystalline Compound A mesylate salt Form G1.

[0282] Crystalline Compound A mesylate salt ("Form G2")

[0283] In some embodiments, the present disclosure provides crystalline Compound A mesylate ("Form G2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.6, 13.1, 13.3, 16.3, and 18.3 ± 0.2° 2θ using CuKα radiation. In some embodiments, Form G2 is further characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 12.5, 19.8, 21.5, and 9.4 ± 0.2° 2θ using CuKα radiation. In some embodiments, the present disclosure provides a crystalline Compound A mesylate ("Form G2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.6, 13.1, 13.3, 16.3, and 18.3 ± 0.2° 2θ using CuKα radiation. Figure 47 Shown is the XRPD of crystalline Compound A mesylate salt Form G2.

[0284] Form G2 can be characterized by DSC, TGA and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 48 Shown is the DSC of crystalline Compound A mesylate salt Form G2.

[0285] In some embodiments, the present disclosure provides a method having substantially Figure 48 Shown is the TGA of crystalline Compound A mesylate salt Form G2.

[0286] In some embodiments, the present disclosure provides a method having substantially Figure 49Shown is the DVS curve of crystalline Compound A mesylate salt Form G2.

[0287] Crystalline Compound A oxalate ("Form H2")

[0288] In some embodiments, the present disclosure provides crystalline Compound A oxalate salt ("Form H2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 6.9, 8.7, 13.6, 17.4, and 24.6 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, Form H2 is further characterized by XRPD peaks at 11.0, 19.6, 20.8, 21.0, 22.0, 25.3, and 27.3 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, the present disclosure provides a crystalline Compound A oxalate salt ("Form H2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 6.9, 8.7, 13.6, 17.4, and 24.6 ± 0.2 degrees 2θ using CuKα radiation. Figure 50 Shown is the XRPD of the crystalline form of Compound A oxalate salt, Form H2.

[0289] Form H2 can be characterized by DSC, TGA and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 51 Shown is the DSC of crystalline Compound A oxalate salt Form H2.

[0290] In some embodiments, the present disclosure provides a method having substantially Figure 51 Shown is the TGA of crystalline Compound A oxalate salt Form H2.

[0291] Crystalline Compound A tartrate salt ("Form I1")

[0292] In some embodiments, the present disclosure provides crystalline Compound A tartrate salt ("Form I1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 3.4, 14.7, 15.6, 18.0, and 24.3 ± 0.2° 2θ using CuKα radiation. In some embodiments, Form I1 is further characterized by XRPD pattern peaks at 14.3, 15.1, 18.7, 19.4, and 19.7 ± 0.2° 2θ using CuKα radiation. In some embodiments, Form I1 is further characterized by XRPD pattern peaks at 13.3, 13.5, 20.6, 21.1, 23.1, 23.5, 24.9, 26.7, and 27.2 ± 0.2° 2θ using CuKα radiation. In some embodiments, the present disclosure provides a crystalline Compound A tartrate salt ("Form I1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 3.4, 14.7, 15.6, 18.0, and 24.3 ± 0.2° 2θ using CuKα radiation. Figure 52 Shown is the XRPD of crystalline Compound A tartrate salt Form I1.

[0293] Form II can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 53Shown is the DSC of crystalline Compound A tartrate salt Form I1.

[0294] In some embodiments, the present disclosure provides a method having substantially Figure 53 Shown is the TGA of crystalline Compound A tartrate salt Form I1.

[0295] Crystalline Compound A ethanesulfonate ("Form J1")

[0296] In some embodiments, the present disclosure provides crystalline Compound A ethanesulfonate salt ("Form J1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.6, 7.9, 13.6, 15.7, and 17.9 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, Form J1 is further characterized by XRPD peaks at 6.6, 11.1, 13.1, 16.8, 18.7, and 20.4 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, the present disclosure provides a crystalline Compound A ethanesulfonate salt ("Form J1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.6, 7.9, 13.6, 15.7, and 17.9 ± 0.2 degrees 2θ using CuKα radiation. Figure 54 The XRPD of the crystalline form Form J1 of the ethanesulfonate salt of Compound A is shown.

[0297] Form J1 can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 55 Shown is the DSC of crystalline Compound A esylate salt Form J1.

[0298] In some embodiments, the present disclosure provides a method having substantially Figure 55 Shown is the TGA of crystalline Compound A esylate salt Form J1.

[0299] Crystalline Compound A ethanesulfonate ("Form J2")

[0300] In some embodiments, the present disclosure provides crystalline Compound A ethanesulfonate salt ("Form J2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.0, 6.3, 7.7, 15.8, and 20.9 ± 0.2° 2θ using CuKa radiation. In some embodiments, Form J2 is further characterized by XRPD peaks at 7.9, 16.8, 18.4, 18.6, 19.5, and 20.0 ± 0.2° 2θ using CuKa radiation. In some embodiments, Form J2 is further characterized by XRPD peaks at 6.9, 17.6, 21.6, 23.3, 23.8, 24.1, 24.7, and 26.1 ± 0.2° 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A ethanesulfonate salt ("Form J2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.0, 6.3, 7.7, 15.8, and 20.9 ± 0.2° 2θ using CuKa radiation. Figure 56 The XRPD of the crystalline form Form J2 of the esylate salt of Compound A is shown.

[0301] Form J2 can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 57 Shown is the DSC of crystalline Compound A esylate salt Form J2.

[0302] In some embodiments, the present disclosure provides a method having substantially Figure 57 Shown is the TGA of crystalline Compound A esylate salt Form J2.

[0303] Crystalline Compound A N-cyclohexylsulfamate ("Form K1")

[0304] In some embodiments, the present disclosure provides crystalline Compound A N-cyclohexylaminosulfonate ("Form K1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.8, 14.0, 15.6, 16.7, and 28.1 ± 0.2 degrees 2θ using CuKα radiation. In some embodiments, the present disclosure provides a crystalline Compound A N-cyclohexylaminosulfonate ("Form K1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.8, 14.0, 15.6, 16.7, and 28.1 ± 0.2 degrees 2θ using CuKα radiation. Figure 58 Shown is the XRPD of crystalline Compound A N-cyclohexylsulfamate salt Form K1.

[0305] Form K1 can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 59 DSC form K1 is shown.

[0306] In some embodiments, the present disclosure provides a method having substantially Figure 59 TGA form K1 is shown.

[0307] Crystalline Compound A maleate salt ("Form L1")

[0308] In some embodiments, the present disclosure provides a crystalline Compound A maleate salt ("Form L1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.7, 17.0, 17.5, 25.6, and 26.1 ± 0.2 degrees 2θ using CuKα radiation. ... Figure 60 Shown is the XRPD of crystalline Compound A maleate salt Form L1.

[0309] Form L1 can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 61 Shown is the DSC of crystalline Compound A maleate salt Form L1.

[0310] In some embodiments, the present disclosure provides a method having substantially Figure 61 Shown is the TGA of crystalline Compound A maleate salt Form L1.

[0311] Crystalline Compound A Phosphate ("Form M1")

[0312] In some embodiments, the present disclosure provides crystalline Compound A phosphate ("Form M1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.4, 16.2, 20.3, and 22.5 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form M1 is further characterized by XRPD peaks at 10.8, 12.3, 21.8, and 32.9 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A phosphate salt ("Form M1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.4, 16.2, 20.3, and 22.5 ± 0.2 degrees 2θ using CuKa radiation. Figure 62 Shown is the XRPD of Compound A phosphate salt, crystalline Form M1.

[0313] Form M1 can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 63 DSC form M1 is shown.

[0314] In some embodiments, the present disclosure provides a method having substantially Figure 63 TGA form M1 is shown.

[0315] In some embodiments, the present disclosure provides a method having substantially Figure 64 The DVS shown is in the form of M1.

[0316] Crystalline Compound A Phosphate Salt ("Form M2")

[0317] In some embodiments, the present disclosure provides crystalline Compound A phosphate ("Form M2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 7.1, 14.2, 14.9, 17.8, and 19.6 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form M2 is further characterized by XRPD peaks at 8.9, 10.6, 10.9, 13.4, 16.4, 16.8, and 21.4 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form M2 is further characterized by XRPD peaks at 3.6, 7.4, 21.0, 21.8, 23.0, 25.0, 25.4, 26.3, and 26.9 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A phosphate salt ("Form M2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 7.1, 14.2, 14.9, 17.8, and 19.6 ± 0.2 degrees 2θ using CuKa radiation. Figure 65 Shown is the XRPD of Compound A phosphate salt, crystalline Form M2.

[0318] Form M2 can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 66 DSC form M2 is shown.

[0319] In some embodiments, the present disclosure provides a method having substantially Figure 66 TGA form M2 is shown.

[0320] Crystalline Compound A Phosphate Salt ("Form M3")

[0321] In some embodiments, the present disclosure provides crystalline Compound A phosphate ("Form M3") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 7.5, 7.8, 14,8, 15.0, and 15.4 ± 0.2° 2θ using CuKa radiation. In some embodiments, Form M3 is further characterized by XRPD peaks at 9.0, 9.8, 11.6, 11.7, 18.3, 22.2, and 25.2 ± 0.2° 2θ using CuKa radiation. In some embodiments, Form M3 is further characterized by XRPD peaks at 3.9, 16.2, 27.2, and 27.2 ± 0.2° 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A phosphate salt ("Form M3") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 7.5, 7.8, 14,8, 15.0, and 15.4 ± 0.2° 2θ using CuKa radiation. In some embodiments, Form M3 is further characterized by XRPD peaks at 3.9, 16.2, 27.2, and 27.2 ± 0.2° 2θ using CuKa radiation. Figure 67 Shown is the XRPD of Compound A phosphate salt, crystalline Form M3.

[0322] Form M3 can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 68 DSC form M3 shown.

[0323] In some embodiments, the present disclosure provides a method having substantially Figure 68 TGA form M3 is shown.

[0324] eutectic

[0325] In some embodiments, the present disclosure provides a crystalline co-crystal comprising Compound A and a coformer. Non-limiting examples of molecules suitable as coformers include, for example, salicylic acid, formic acid, benzoic acid, isobutyric acid, octanoic acid, sorbic acid, succinic acid, and adipic acid.

[0326] Crystalline Compound A salicylic acid cocrystal ("Form CC-1A")

[0327] In some embodiments, the present disclosure provides crystalline Compound A salicylic acid cocrystal ("Form CC-1A") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 9.3, 5.9, 9.7, 6.0, and 13.9 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-1A is further characterized by XRPD peaks at 13.1, 8.3, and 18.6 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a cocrystal having substantially Figure 69 Shown is the XRPD of Compound A salicylic acid cocrystal, Form CC-1A.

[0328] Form CC-1A can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 70 Shown is the DSC form CC-1A.

[0329] In some embodiments, the present disclosure provides a method having substantially Figure 70 TGA of form CC-1A is shown.

[0330] Crystalline Compound A salicylic acid cocrystal ("Form CC-2A")

[0331] In some embodiments, the present disclosure provides crystalline Compound A salicylic acid cocrystal ("Form CC-2A") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 8.2, 9.2, 16.5, 18.5, and 16.0 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-2A is further characterized by XRPD peaks at 17.2, 11.1, 3.2, 11.8, 24.6, and 25.9 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a cocrystal having substantially Figure 71 Shown is the XRPD of Compound A salicylic acid cocrystal, Form CC-2A.

[0332] Form CC-2A can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 72 Shown is the DSC form CC-2A.

[0333] In some embodiments, the present disclosure provides a method having substantially Figure 72 TGA of form CC-2A is shown.

[0334] Crystalline Compound A salicylic acid cocrystal ("Form CC-3A")

[0335] In some embodiments, the present disclosure provides crystalline Compound A salicylic acid cocrystal ("Form CC-3A") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 3.6, 12.6, 8.0, 14.4, and 7.2 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-3A is further characterized by XRPD peaks at 15.7, 11.2, 13.0, 21.5, 10.8, and 16.1 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a cocrystal having substantially Figure 73Shown is the XRPD of Compound A salicylic acid cocrystal, Form CC-3A.

[0336] Form CC-3A can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 74 Shown is the DSC form CC-3A.

[0337] In some embodiments, the present disclosure provides a method having substantially Figure 74 TGA of form CC-3A is shown.

[0338] In some embodiments, the present disclosure provides a method having substantially Figure 75 The DVS curve shown is of form CC-3A.

[0339] Crystalline Compound A salicylic acid cocrystal ("Form CC-4A")

[0340] In some embodiments, the present disclosure provides a crystalline Compound A salicylic acid cocrystal ("Form CC-4A") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 10.3, 16.2, 9.9, 16.3, 19.9 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-4A is further characterized by XRPD peaks at 26.3, 27.0, 25.3, 18.0, 12.8, and 9.7 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-4A is further characterized by XRPD peaks at 28.5, 28.1, 24.8, 24.4, 23.4, and 22.3 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-4A is further characterized by an XRPD pattern peak at 17.8, 16.2, 15.7, 15.67, 15.4, 13.6, and 13.4 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a compound having substantially Figure 76 Shown is the XRPD of Compound A salicylic acid cocrystal, Form CC-4A.

[0341] Form CC-4A can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 77 Shown is the DSC form CC-4A.

[0342] In some embodiments, the present disclosure provides a method having substantially Figure 77 TGA of form CC-4A is shown.

[0343] Crystalline Compound A salicylic acid cocrystal ("Form CC-5A")

[0344] In some embodiments, the present disclosure provides crystalline Compound A salicylic acid cocrystal ("Form CC-5A") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.3, 17.8, 10.6, 18.3, and 15.9 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-5A is further characterized by XRPD pattern peaks at 25.7, 15.5, 19.1, 28.7, 9.2, 12.2, 11.0, and 12.9 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-5A is further characterized by XRPD pattern peaks at 21.3, 19.8, 20.7, 24.3, 13.2, 26.6, 27.2, and 11.3 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a cocrystal having substantially Figure 78 Shown is the XRPD of Compound A salicylic acid cocrystal, Form CC-5A.

[0345] Form CC-5A can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 79 The DSC shown is form CC-5A.

[0346] In some embodiments, the present disclosure provides a method having substantially Figure 79 TGA of form CC-5A is shown.

[0347] Crystalline Compound A formic acid cocrystal ("Form CC-1B")

[0348] In some embodiments, the present disclosure provides crystalline Compound A formic acid cocrystal ("Form CC-1B") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 8.6, 4.6, 17.8, 17.4, and 23.0 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-1B is further characterized by XRPD peaks at 11.3, 14.8, 15.7, 16.5, 18.4, 19.3, 20.7, 24.9, and 26.8 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A formic acid cocrystal ("Form CC-1B") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 8.6, 4.6, 17.8, 17.4, and 23.0 ± 0.2 degrees 2θ using CuKa radiation. Figure 80 Shown is the XRPD of Compound A formic acid co-crystal Form CC-1B.

[0349] Form CC-1B can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 81 DSC form CC-1B is shown.

[0350] In some embodiments, the present disclosure provides a method having substantially Figure 81 TGA of form CC-1B is shown.

[0351] Crystalline Compound A benzoic acid cocrystal ("Form CC-1C")

[0352] In some embodiments, the present disclosure provides crystalline Compound A benzoic acid cocrystal ("Form CC-1C") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 11.6, 16.1, 14.2, 3.9, and 19.8 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-1C is further characterized by XRPD pattern peaks at 10.4, 10.6, 12.4, 14.5, 17.3, 18.3, and 19.4 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-1C is further characterized by XRPD pattern peaks at 7.7, 8.8, 17.7, 21.7, 23.2, 26.3, and 26.69 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A benzoic acid cocrystal ("Form CC-1C") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 11.6, 16.1, 14.2, 3.9, and 19.8 ± 0.2 degrees 2θ using CuKa radiation. Figure 82 Shown is the XRPD of crystalline Compound A benzoic acid cocrystal Form CC-1C.

[0353] Form CC-1C can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 83 Shown is the DSC form CC-1C.

[0354] In some embodiments, the present disclosure provides a method having substantially Figure 83 TGA of form CC-1C is shown.

[0355] In some embodiments, the present disclosure provides a method having substantially Figure 84 The DVS curve shown is of form CC-1C.

[0356] Crystalline Compound A isobutyric acid cocrystal ("Form CC-1D")

[0357] In some embodiments, the present disclosure provides crystalline Compound A isobutyric acid cocrystal ("Form CC-1D") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.6, 6.1, 13.1, 16.0, and 17.1 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-1D is further characterized by XRPD peaks at 6.5, 8.0, 8.6, 10.7, 11.1, 12.2, and 19.6 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A isobutyric acid cocrystal ("Form CC-1D") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.6, 6.1, 13.1, 16.0, and 17.1 ± 0.2 degrees 2θ using CuKa radiation. Figure 85Shown is the XRPD of crystalline Compound A isobutyric acid cocrystal Form CC-1D.

[0358] Form CC-ID can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 86 The DSC shown is of form CC-1D.

[0359] In some embodiments, the present disclosure provides a method having substantially Figure 86 TGA form CC-1D is shown.

[0360] In some embodiments, the present disclosure provides a method having substantially Figure 87 The DVS curve shown is of form CC-1D.

[0361] Crystalline Compound A isobutyric acid cocrystal ("Form CC-2D")

[0362] In some embodiments, the present disclosure provides crystalline Compound A isobutyric acid cocrystal ("Form CC-2D") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.2, 5.5, 6.3, 10.3, and 12.6 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-2D is further characterized by XRPD peaks at 6.8, 12.1, 13.0, and 14.3 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A isobutyric acid cocrystal ("Form CC-2D") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.2, 5.5, 6.3, 10.3, and 12.6 ± 0.2 degrees 2θ using CuKa radiation. Figure 88 Shown is the XRPD of crystalline Compound A isobutyric acid cocrystal Form CC-2D.

[0363] Form CC-2D can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 89 The DSC shown is in the form of CC-2D.

[0364] In some embodiments, the present disclosure provides a method having substantially Figure 89 TGA form CC-2D is shown.

[0365] In some embodiments, the present disclosure provides a method having substantially Figure 90 The DVS curve shown is of the form CC-2D.

[0366] Crystalline Compound A octanoic acid cocrystal ("Form CC-1E")

[0367] In some embodiments, the present disclosure provides crystalline Compound A octanoic acid cocrystal ("Form CC-1E") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.8, 6.2, 6.5, 18.1, and 21.1 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-1E is further characterized by XRPD peaks at 15.6, 20.6, 21.4, 22.4, and 24.9 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A octanoic acid cocrystal ("Form CC-1E") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.8, 6.2, 6.5, 18.1, and 21.1 ± 0.2 degrees 2θ using CuKa radiation. Figure 91 Shown is the XRPD of crystalline Compound A octanoic acid cocrystal Form CC-1E.

[0368] Form CC-1E can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 92 The DSC shown is of form CC-1E.

[0369] In some embodiments, the present disclosure provides a method having substantially Figure 92 TGA form CC-1E is shown.

[0370] Crystalline Compound A sorbic acid cocrystal ("Form CC-1F")

[0371] In some embodiments, the present disclosure provides a crystalline Compound A sorbic acid cocrystal ("Form CC-1F") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 8.2, 10.8, 11.4, 18.2, and 21. ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-1F is further characterized by XRPD peaks at 5.4, 7.1, 8.9, 12.7, 13.4, 14.8, 17.7, 21.6, and 24.6 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A sorbic acid cocrystal ("Form CC-1F") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 8.2, 10.8, 11.4, 18.2, and 21. ± 0.2 degrees 2θ using CuKa radiation. Figure 93 Shown is the XRPD of crystalline Compound A sorbic acid cocrystal Form CC-1F.

[0372] Form CC-1F can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 94 Shown is the DSC form CC-1F.

[0373] In some embodiments, the present disclosure provides a method having substantially Figure 94 TGA of form CC-1F is shown.

[0374] Crystalline Compound A saccharin cocrystal ("Form CC-1G")

[0375] In some embodiments, the present disclosure provides crystalline Compound A saccharin co-crystals ("Form CC-1G") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.1, 9.8, 10.1, 16.5, and 20.4. ... Figure 95 Shown is the XRPD of crystalline Compound A saccharin cocrystal Form CC-1G.

[0376] Form CC-1G can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 96 The DSC shown is form CC-1G.

[0377] In some embodiments, the present disclosure provides a method having substantially Figure 96 TGA form CC-1G is shown.

[0378] In some embodiments, the present disclosure provides a method having substantially Figure 97 The DVS shown is in the form of CC-1G.

[0379] Crystalline Compound A succinic acid cocrystal ("Form CC-1H")

[0380] In some embodiments, the present disclosure provides crystalline Compound A succinic acid cocrystal ("Form CC-1H") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 11.3, 11.5, 18.3, 19.0, and 20.6 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-1H is further characterized by XRPD peaks at 13.7, 24.2, 25.2, and 28.3 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a crystalline Compound A succinic acid cocrystal ("Form CC-1H") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 11.3, 11.5, 18.3, 19.0, and 20.6 ± 0.2 degrees 2θ using CuKa radiation. Figure 98 Shown is the XRPD of crystalline Compound A succinic acid cocrystal Form CC-1H.

[0381] Form CC-1H can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 99 DSC shown is Form CC-1H.

[0382] In some embodiments, the present disclosure provides a method having substantially Figure 99 TGA shown in form CC-1H.

[0383] Crystalline Compound A succinic acid cocrystal ("Form CC-2H")

[0384] In some embodiments, the present disclosure provides a crystalline Compound A succinic acid cocrystal ("Form CC-2H") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.2, 5.3, 8.3, 9.0, and 9.2 ± 0.2 degrees 2θ using CuKα radiation. ... Figure 100 Shown is the XRPD of crystalline Compound A succinic acid cocrystal Form CC-2H.

[0385] Form CC-2H can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 101 DSC shown is Form CC-2H.

[0386] In some embodiments, the present disclosure provides a method having substantially Figure 101 TGA shown as Form CC-2H.

[0387] Crystalline Compound A adipic acid cocrystal ("Form CC-II")

[0388] In some embodiments, the present disclosure provides crystalline Compound A adipic acid cocrystal ("Form CC-II") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 7.7, 10.5, 18.5, 18.9, and 21.7 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, Form CC-II is further characterized by XRPD peaks at 5.3, 12.1, 20.7, 24.2, and 25.7 ± 0.2 degrees 2θ using CuKa radiation. In some embodiments, the present disclosure provides a cocrystal having substantially Figure 102 XRPD of crystalline Compound A adipic acid cocrystal Form CC-II is shown.

[0389] Form CC-II can be characterized using DSC, TGA, and / or DVS. In some embodiments, the present disclosure provides a method having substantially Figure 103 The DSC form CC-1I is shown.

[0390] In some embodiments, the present disclosure provides a method having substantially Figure 103 TGA form CC-II is shown.

[0391] Pharmaceutical composition

[0392] Further provided herein are pharmaceutical compositions of solid forms of Compound A and methods of treating a subject having cancer comprising administering to the subject a therapeutically effective amount of the disclosed solid forms of Compound A.

[0393] In some embodiments, the present disclosure provides a pharmaceutical composition comprising a crystalline form, an amorphous form, or a co-crystal disclosed herein, or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient. In some embodiments, the present disclosure provides a pharmaceutical composition comprising Form 1.

[0394] In some instances, the crystalline form or amorphous form disclosed herein or a pharmaceutically acceptable salt thereof is present in a pharmaceutical composition in an amount effective for treating PRMT5-dependent cancer. In some aspects, the pharmaceutical composition is formulated for oral delivery or administration, and in other embodiments, the pharmaceutical composition is formulated for intravenous delivery or administration. In some embodiments, the pharmaceutical composition is formulated for once a day or QD oral administration, and in some such formulations, is a tablet, wherein the effective amount of the active ingredient ranges from 1 mg to 2000 mg (e.g., 1, 25, 50, 100, 200, 400, 500, 750, 800, 1000, 1200, 1500 or 2000 mg).

[0395] Methods of treating subjects

[0396] Further provided herein are methods of treating a subject having cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a crystalline form or amorphous form of Compound A as disclosed herein, or a pharmaceutically acceptable salt thereof, optionally as a pharmaceutical composition as disclosed herein. In some embodiments, the present disclosure provides methods of treating a subject having cancer, comprising administering to a subject in need thereof a therapeutically effective amount of crystalline Form 1.

[0397] In some embodiments, the cancer is ovarian cancer, lung cancer, lymphoma, glioblastoma, colon cancer, melanoma, gastric cancer, pancreatic cancer, or bladder cancer. In some embodiments, the cancer is non-small cell lung cancer. In some embodiments, the cancer is pancreatic cancer.

[0398] MTAP-deficient cancers are cancers that lack expression of the enzyme methylthioadenosine phosphorylase (MTAP). The MTAP gene, located at chromosome locus 9p21, is frequently co-deleted along with the CDKN2A and CDKN2B genes. Selective MTAP deficiency refers to a defect caused by selective deletion of the MTAP locus or methylation of the MTAP promoter in the absence of co-deletion of the CDKN2 gene. MTAP-deficient cancers are characterized by MTAP deficiency in at least 1% of diseased cells. The terms "MTAP-deficient," "MTAP-deficient," and "MTAP-negative" are used interchangeably.

[0399] "MTAP deficiency-associated" or "MTAP deficiency" or "MTAP-deficient" disease (e.g., a proliferative disease, such as cancer) or a disease "associated with MTAP deficiency" (e.g., a proliferative disease, such as cancer) or a disease "characterized by MTAP deficiency" (e.g., a proliferative disease, such as cancer), etc., refers to a disease (e.g., a proliferative disease, such as cancer) in which a large number of cells are MTAP-deficient cells. For example, in an MTAP deficiency-associated disease, one or more disease cells may have significantly reduced post-translational modification, production, expression, level, stability and / or activity of MTAP. Examples of MTAP deficiency-associated diseases include, but are not limited to, cancers, including, but not limited to, glioblastoma, malignant peripheral nerve sheath tumor (MPNST), esophageal cancer (e.g., esophageal squamous cell carcinoma or esophageal adenocarcinoma), bladder cancer (e.g., bladder urothelial carcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), mesothelioma, melanoma, non-small cell lung cancer (NSCLC, e.g., lung squamous cell carcinoma or lung adenocarcinoma), astrocytoma, undifferentiated pleomorphic sarcoma, diffuse large B-cell lymphoma (DLBCL), leukemia, head and neck cancer, gastric adenocarcinoma, myxofibrosarcoma, bile duct cancer, brain cancer, gastric cancer, kidney cancer, breast cancer, endometrial cancer, urinary tract cancer, liver cancer, soft tissue cancer, pleural cancer, and colorectal cancer or sarcoma. In patients with MTAP deficiency-associated diseases, some disease cells (e.g., cancer cells) may be MTAP-deficient cells, while other disease cells are not. Similarly, some disease cells may be MTA-accumulating cells, while other disease cells are not. Thus, the present disclosure encompasses methods for treating diseases involving these tissues, or any other tissues, in which the proliferation of MTAP-deficient and / or MTA-accumulating cells can be inhibited by administering a PRMT5 inhibitor. Some MTAP-deficient cancer cells also lack CDKN2A; post-translational modification, production, expression, levels, stability, and / or activity of the CDKN2A gene or its product are attenuated in these cells. The genes for MTAP and CDKN2A are located in close proximity on chromosome 9p21; MTAP is located approximately 100 kb telomeric to CDKN2A. Many cancer cell types contain CDKN2A / MTAP loss (loss of both genes). Thus, in some embodiments, MTAP-deficient cells also lack CDKN2A.

[0400] In some embodiments, the cancer is acute myeloid leukemia, juvenile cancer, childhood adrenocortical carcinoma, AIDS-related cancers (e.g., lymphoma and Kaposi's sarcoma), anal cancer, appendix cancer, astrocytoma, atypical teratoid, basal cell carcinoma, bile duct cancer, bladder cancer, bone cancer, brain stem cell glioma, brain tumor, breast cancer, bronchial tumor, Burkitt lymphoma, carcinoid tumor, atypical teratoid, embryonal tumor, blastoma, primary lymphoma, cervical cancer, childhood cancer, chordoma, heart tumor, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), chronic myeloproliferative disorder, Colon cancer, colorectal cancer, craniopharyngioma, cutaneous T-cell lymphoma, extrahepatic ductal carcinoma in situ (DCIS), embryonal tumor, CNS cancer, endometrial cancer, ependymoma, esophageal cancer, nasal glioma, Ewing sarcoma, extracranial ectodermal tumor, gonadal ectodermal tumor, eye cancer, fibrous histiocytoma of bone, gallbladder cancer, stomach cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), blastoma, gestational trophoblastic tumor, hairy cell leukemia, head and neck cancer, heart cancer, liver cancer, Hodgkin lymphoma, hypopharyngeal cancer, intraocular melanoma, islet cell tumor, pancreatic neuroendocrine tumor, kidney cancer, laryngeal cancer, lip and oral cancer, liver Cancer, lobular carcinoma in situ (LCIS), lung cancer, lymphoma, metastatic squamous neck cancer with occult primary, midline cancer, oral cancer, multiple endocrine neoplasia syndrome, multiple myeloma / plasma cell neoplasms, mycosis fungoides, myelodysplastic syndrome, myelodysplasia / myeloproliferative neoplasms, multiple myeloma, Merkel cell carcinoma, malignant mesothelioma, malignant fibrous histiocytoma and osteosarcoma of bone, nasal cavity and paranasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non-Hodgkin lymphoma, non-small cell lung cancer (NSCLC), oral cancer, lip and oral cavity cancer, oropharyngeal cancer, ovarian cancer, pancreatic cancer, In some cases, the cancer is pancreatic cancer; esophageal cancer; melanoma; lung cancer; mixed Müllerian cancer; ovarian cancer; or gallbladder cancer.

[0401] In some embodiments, the cancer is glioblastoma, malignant peripheral nerve sheath tumor (MPNST), esophageal cancer (e.g., esophageal squamous cell carcinoma or esophageal adenocarcinoma), bladder cancer (e.g., cystourethral carcinoma), pancreatic cancer (e.g., pancreatic adenocarcinoma), mesothelioma, melanoma, non-small cell lung cancer (NSCLC, e.g., lung squamous cell carcinoma or lung adenocarcinoma), astrocytoma, undifferentiated pleomorphic sarcoma, diffuse large B-cell lymphoma (DLBCL), leukemia, head and neck cancer, gastric adenocarcinoma, myxofibrosarcoma, bile duct cancer, brain cancer, stomach cancer, kidney cancer, breast cancer, endometrial cancer, urinary tract cancer, liver cancer, soft tissue cancer, pleural cancer, and colorectal cancer or sarcoma.

[0402] In some embodiments, the MTAP-deficient cancer is lung cancer, biliary tract cancer, head and neck squamous cell carcinoma, pancreatic adenocarcinoma, gallbladder cancer, or mesothelioma.

[0403] In some embodiments, the MTAP-deficient cancer is lung cancer. In some embodiments, the lung cancer is non-squamous cell lung cancer (NSCLC).

[0404] In some embodiments, the MTAP-deficient cancer is a solid tumor. Exemplary MTAP-deficient solid tumors include, but are not limited to, MTAP-deficient brain cancer (including but not limited to MTAP-deficient gliomas, MTAP-deficient oligodendrogliomas, MTAP-deficient glioblastomas multiforme, MTAP-deficient astrocytomas, MTAP-deficient medulloblastomas, MTAP-deficient ependymomas, and MTAP-deficient meningiomas), MTAP-deficient head and neck cancers (including but not limited to MTAP-deficient salivary gland (parotid) tumors, MTAP-deficient head and neck squamous cell carcinomas, and MTAP-deficient thyroid cancers), MTAP-deficient breast cancers (including but not limited to infiltrating ductal breast cancer, mixed mucinous breast cancer, and lobular carcinoma), MTAP-deficient mesothelioma, MTAP-deficient gastrointestinal cancers (including but not limited to MTAP-deficient esophageal cancer (including but not limited to adenocarcinoma and squamous cell carcinoma), MTAP-deficient gastroesophageal junction cancer, MTAP-deficient gastric cancer (including but not limited to adenocarcinoma and signet ring cell carcinoma), MTAP-deficient small intestine cancer, MTAP-deficient colon cancer, MTAP-deficient rectal cancer, and MTAP-deficient gastrointestinal stromal tumors), MTAP-deficient neuroendocrine tumors, MTAP-deficient Hepatobiliary cancer (including but not limited to MTAP-null biliary cancer (including bile duct cancer, gallbladder cancer and ampullary cancer) and MTAP-null hepatocellular carcinoma), MTAP-null pancreatic cancer (including pancreatic adenocarcinoma), MTAP-null renal cancer (including but not limited to MTAP-null renal cell carcinoma), MTAP-null adrenocortical carcinoma, MTAP-null bladder cancer (including but not limited to MTAP-null urothelial carcinoma), MTAP-null adrenocortical carcinoma, MTAP-null endometrial cancer, MTAP-null uterine cancer, MTAP-null testicular cancer, MTAP-null germ cell tumor or MTAP-null prostate cancer, MTAP-null sarcoma or MTAP-null bone cancer (including but not limited to MTAP-null osteosarcoma, MTAP-null chondrosarcoma, MTAP-null soft tissue sarcoma, MTAP-null Ewing sarcoma, MTAP-null liposarcoma, MTAP-null leiomyosarcoma and MTAP-null myxofibrosarcoma), MTAP-null skin tumors (MTAP-null cutaneous squamous cell carcinoma and MTAP-null melanoma), MTAP-null schwannoma and MTAP-null cancer of unknown primary (CUP).

[0405] In some embodiments, the MTAP-deficient cancer is a hematological tumor. Exemplary hematological tumors include, but are not limited to, MTAP-deficient leukemias (including but not limited to MTAP-deficient acute lymphoblastic leukemia, MTAP-deficient acute myeloid leukemia), MTAP-deficient lymphomas (including but not limited to MTAP-deficient mantle cell lymphoma, MTAP-deficient follicular lymphoma, MTAP-deficient diffuse large B-cell lymphoma, and MTAP-deficient mycosis fungoides).

[0406] In some embodiments, the cancer is not a primary brain tumor or lymphoma.

[0407] In some embodiments, the subject does not have or has never had interstitial lung disease or pneumonia.

[0408] Example

[0409] 1. A crystalline form of Compound A:

[0410] 2. The crystalline form of embodiment 1, wherein Compound A is in the form of a free base.

[0411] 3. The crystalline form of Example 1 or 2, as Compound A free base ("Form 1"), characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.5, 9.0, 13.3, 16.2, and 18.8 ± 0.2° 2θ using CuKα radiation.

[0412] 4. The crystalline form of embodiment 1 or 2, wherein the CuKα radiation comprises at least three of the following: 4.5, 6.7, 9.0, 12.2, 12.5, 12.8, 13.3, 13.7, 14.3, 14.7, 15.7, 16.2, 16.7, 17.4, 17.6, 18.0, 18.4, 18.8, 19.6, 20.0, 20.3, 20.8, 21 The present invention also has an X-ray powder diffraction (XRPD) pattern of peaks at 20.4, 21.6, 22.2, 22.5, 23.0, 23.8, 24.1, 24.6, 25.1, 26.2, 26.4, 26.8, 27.8, 28.4, 28.8, 29.7, 30.5, 30.9, 32.7, 34.4, 35.1, 35.6, 36.4, 37.8 and 39.4 ± 0.2 ° 2θ.

[0413] 5. The crystalline form of embodiment 1 or 2, wherein the CuKα radiation comprises at least five of the following: 4.5, 6.7, 9.0, 12.2, 12.5, 12.8, 13.3, 13.7, 14.3, 14.7, 15.7, 16.2, 16.7, 17.4, 17.6, 18.0, 18.4, 18.8, 19.6, 20.0, 20.3, 20.8, 21 The present invention also has an X-ray powder diffraction (XRPD) pattern of peaks at 20.4, 21.6, 22.2, 22.5, 23.0, 23.8, 24.1, 24.6, 25.1, 26.2, 26.4, 26.8, 27.8, 28.4, 28.8, 29.7, 30.5, 30.9, 32.7, 34.4, 35.1, 35.6, 36.4, 37.8 and 39.4 ± 0.2 ° 2θ.

[0414] 6. The crystalline form of embodiment 1 or 2, wherein the CuKα radiation comprises at least seven of the following: 4.5, 6.7, 9.0, 12.2, 12.5, 12.8, 13.3, 13.7, 14.3, 14.7, 15.7, 16.2, 16.7, 17.4, 17.6, 18.0, 18.4, 18.8, 19.6, 20.0, 20.3, 20.8, 21 The present invention also has an X-ray powder diffraction (XRPD) pattern of peaks at 20.4, 21.6, 22.2, 22.5, 23.0, 23.8, 24.1, 24.6, 25.1, 26.2, 26.4, 26.8, 27.8, 28.4, 28.8, 29.7, 30.5, 30.9, 32.7, 34.4, 35.1, 35.6, 36.4, 37.8 and 39.4 ± 0.2 ° 2θ.

[0415] 7. The crystalline form of embodiment 1 or 2, wherein the CuKα radiation comprises at least eight of the following: 4.5, 6.7, 9.0, 12.2, 12.5, 12.8, 13.3, 13.7, 14.3, 14.7, 15.7, 16.2, 16.7, 17.4, 17.6, 18.0, 18.4, 18.8, 19.6, 20.0, 20.3, 20.8, 21. The present invention also has an X-ray powder diffraction (XRPD) pattern of peaks at 20.4, 21.6, 22.2, 22.5, 23.0, 23.8, 24.1, 24.6, 25.1, 26.2, 26.4, 26.8, 27.8, 28.4, 28.8, 29.7, 30.5, 30.9, 32.7, 34.4, 35.1, 35.6, 36.4, 37.8 and 39.4 ± 0.2 ° 2θ.

[0416] 8. The crystalline form of any one of embodiments 1-7, characterized by a differential scanning calorimetry (DSC) thermogram comprising an endotherm with an onset of 225°C ± 3°C.

[0417] 9. The crystalline form of any one of embodiments 1-8, comprising at least three peaks selected from 39.2, 43.8, 51.6, 58.1, 65.9, 71.8, 73.6, 114.7, 120.8, 125.1, 126.1, 128.2, 130.8, 142.2, 143.3, 145.3, 148.5, 149.2, 156.9, and 169.6 ppm. 13 C solid-state NMR.

[0418] 10. The crystalline form of any one of embodiments 1-8, comprising at least five peaks selected from 39.2, 43.8, 51.6, 58.1, 65.9, 71.8, 73.6, 114.7, 120.8, 125.1, 126.1, 128.2, 130.8, 142.2, 143.3, 145.3, 148.5, 149.2, 156.9, and 169.6 ppm. 13 C solid-state NMR.

[0419] 11. The crystalline form of any one of embodiments 1-8, comprising at least seven peaks selected from 39.2, 43.8, 51.6, 58.1, 65.9, 71.8, 73.6, 114.7, 120.8, 125.1, 126.1, 128.2, 130.8, 142.2, 143.3, 145.3, 148.5, 149.2, 156.9, and 169.6 ppm. 13 C solid-state NMR.

[0420] 12. The crystalline form of any one of embodiments 1-11, comprising peaks at -62.0 and -63.9 ppm. 19 F solid-state NMR.

[0421] 13. A crystalline form of Compound A free base ("Form 3") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 4.3, 12.6, 14.4, 16.2, and 25.6 ± 0.2 degrees 2Θ.

[0422] 14. The crystalline form of embodiment 13, further characterized by XRPD peaks at 8.6, 13.9, 15.6, 16.7, and 25.3 ± 0.2 degrees 2θ using CuKa radiation.

[0423] 15. The crystalline form of embodiment 13 or 14, further characterized by XRPD peaks at 18.4, 19.7, 20.3, 26.7, 27.9, and 28.4 ± 0.2 degrees 2Θ using CuKa radiation.

[0424] 16. A crystalline form of Compound A free base ("Form 6") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 4.5, 8.6, 9.0, 12.9, and 14.9 ± 0.2° 2Θ.

[0425] 17. The crystalline form of Example 16, further characterized by XRPD peaks at 7.4, 12.3, 13.3, 16.2, 17.8, and 18.8 ± 0.2 degrees 2Θ using CuKa radiation.

[0426] 18. A crystalline form of Compound A free base ("Form 7") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 4.3, 8.5, 12.3, 13.1, and 14.8 ± 0.2° 2Θ.

[0427] 19. The crystalline form of Example 18, further characterized by XRPD peaks at 15.5, 19.1, and 20.9 ± 0.2 degrees 2θ using CuKa radiation.

[0428] 20. A crystalline form of Compound A free base hydrate ("Form 8") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 4.0, 7.7, 8.0, 12.3, and 15.1 ± 0.2° 2Θ.

[0429] 21. The crystalline form of embodiment 20, further characterized by XRPD peaks at 6.1, 10.0, 13.7, 17.0, 18.4, and 19.9 ± 0.2 degrees 2Θ using CuKa radiation.

[0430] 22. A crystalline form of Compound A ethanol solvate ("Form 2A") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.8, 11.6, 12.7, 18.0, and 25.7 ± 0.2° 2θ.

[0431] 23. The crystalline form of embodiment 22, further characterized by XRPD peaks at 16.5, 22.6, 23.3, and 25.8 ± 0.2 degrees 2θ using CuKa radiation.

[0432] 24. A crystalline form of Compound A isopropanol solvate ("Form 3A") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.6, 12.8, 16.4, 17.5, and 25.1 ± 0.2° 2θ.

[0433] 25. The crystalline form of embodiment 24, further characterized by XRPD peaks at 8.2, 11.2, 12.5, 18.6, and 21.8 ± 0.2 degrees 2Θ using CuKa radiation.

[0434] 26. The crystalline form of embodiment 24 or 25, further characterized by XRPD peaks at 6.4, 8.8, 9.2, 13.6, 21.0, 22.4, 22.9, 24.5, and 25.9 ± 0.2 degrees 2Θ using CuKa radiation.

[0435] 27. A crystalline form of Compound A acetone solvate ("Form 4A") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.7, 7.7, 11.5, 14.8, and 15.3 ± 0.2° 2Θ.

[0436] 28. The crystalline form of embodiment 27, further characterized by XRPD peaks at 4.3, 7.3, 13.4, 16.2, and 24.0 ± 0.2 degrees 2Θ using CuKa radiation.

[0437] 29. The crystalline form of embodiment 27 or 28, further characterized by XRPD peaks at 11.2, 18.5, 19.6, and 20.4 ± 0.2 degrees 2θ using CuKa radiation.

[0438] 30. A crystalline form of Compound A methanol solvate ("Form 5A") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 4.8, 7.7, 12.3, 15.3, and 16.1 ± 0.2° 2Θ.

[0439] 31. The crystalline form of embodiment 30, further characterized by XRPD peaks at 8.9, 10.5, 13.1, 13.4, 14.5, 17.6, 21.5, and 25.0 ± 0.2 degrees 2Θ using CuKa radiation.

[0440] 32. The crystalline form of embodiment 30 or 31, further characterized by XRPD peaks at 9.7, 14.1, 18.7, 19.6, 22.7, 24.7, 26.0, and 26.6 ± 0.2 degrees 2Θ using CuKa radiation.

[0441] 33. A crystalline form of Compound A methyltetrahydrofuran solvate ("Form 6A") characterized by an XRPD pattern comprising peaks at 7.6, 11.3, 15.1, 18.3, and 28.0 ± 0.2 degrees 2Θ using CuKa radiation.

[0442] 34. The crystalline form of embodiment 33, further characterized by XRPD peaks at 12.4, 15.7, 17.3, 17.7, 18.8, 19.7, 21.3, 22.7, 25.8, 26.1, and 26.5 ± 0.2 degrees 2Θ using CuKa radiation.

[0443] 35. The crystalline form of embodiment 33 or 34, further characterized by XRPD peaks at 13.6, 14.2, 16.5, 16.9, 20.5, 26.9, and 28.4 ± 0.2 degrees 2Θ using CuKa radiation.

[0444] 36. A crystalline form of the tosylate salt of Compound A ("Form A1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 6.0, 19.0, 20.3, 24.1, 24.9, and 28.9 ± 0.2 degrees 2-theta using CuKa radiation.

[0445] 37. The crystalline form of embodiment 36, further characterized by XRPD peaks at 9.5, 11.9, 14.3, 17.9, 26.2, 33.8, and 35.4 ± 0.2 degrees 2Θ using CuKa radiation.

[0446] 38. A crystalline form of a tosylate salt of Compound A ("Form A2") characterized by an X-ray powder diffraction (XRPD) pattern using Cu Ka radiation comprising peaks at 12.7, 15.5, 16.2, 18.7, 19.7, and 21.8 ± 0.2 degrees 2Θ.

[0447] 39. The crystalline form of embodiment 38, further characterized by XRPD peaks at 10.2, 23.2, 24.1, 24.6, 26.3, and 27.2 ± 0.2 degrees 2θ using CuKa radiation.

[0448] 40. A crystalline form of a tosylate salt of Compound A ("Form A3") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.9, 15.2, 18.8, 19.5, and 24.5 ± 0.2 degrees 2-theta using Cu Ka radiation.

[0449] 41. A crystalline form of a besylate salt of Compound A ("Form B1") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.1, 16.1, 17.9, 19.0, and 25.2 ± 0.2° 2Θ.

[0450] 42. The crystalline form of embodiment 41, further characterized by XRPD peaks at 20.2, 20.6, 23.2, 26.0, 27.0, and 30.4 ± 0.2 degrees 2Θ using CuKa radiation.

[0451] 43. A crystalline form of the chloride salt of Compound A ("Form C1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 6.8, 11.9, 16.6, 20.7, 23.8, 25.3, and 27.6 ± 0.2 degrees 2-theta using Cu Ka radiation.

[0452] 44. A crystalline form of the chloride salt of Compound A ("Form C2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.2, 5.6, 12.2, 12.9, and 18.1 ± 0.2 degrees 2-theta using Cu Ka radiation.

[0453] 45. The crystalline form of embodiment 44, further characterized by XRPD peaks at 6.8, 7.1, 9.4, 13.4, 14.0, 16.5, and 17.7 ± 0.2 degrees 2Θ using CuKa radiation.

[0454] 46. ​​The crystalline form of embodiment 44 or 45, further characterized by XRPD peaks at 7.8, 8.7, 10.9, 11.8, 14.9, 15.4, and 19.1 ± 0.2 degrees 2Θ using CuKa radiation.

[0455] 47. A crystalline form of the sulfate salt of Compound A ("Form D1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 16.0, 16.5, 16.7, 20.0, and 20.4 ± 0.2 degrees 2Θ using CuKa radiation.

[0456] 48. The crystalline form of embodiment 47, further characterized by XRPD peaks at 8.4, 12.1, 13.8, 14.2, 23.6, 24.6, and 25.2 ± 0.2 degrees 2Θ using CuKa radiation.

[0457] 49. A crystalline form of a malonate salt of Compound A ("Form E1") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 6.8, 12.6, 16.6, 20.4, and 22.0 ± 0.2° 2Θ.

[0458] 50. The crystalline form of embodiment 49, further characterized by XRPD peaks at 5.4, 8.3, 17.2, 19.4, 21.0, 22.9, and 26.2 ± 0.2 degrees 2-theta using CuKa radiation.

[0459] 51. A crystalline form of Compound A naphthalene-2-sulfonate salt ("Form F1") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 4.7, 14.7, 14.9, 17.0, 19.6, and 22.1 ± 0.2 degrees 2-theta.

[0460] 52. A crystalline form of Compound A naphthalene-2-sulfonate salt ("Form F2") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.8, 11.6, 14.0, 17.5, and 19.7 ± 0.2° 2Θ.

[0461] 53. A crystalline form of Compound A naphthalene-2-sulfonate salt ("Form F3") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 3.8, 7.6, 9.7, 11.5, and 15.3 ± 0.2 degrees 2-theta using CuKa radiation.

[0462] 54. A crystalline form of the mesylate salt of Compound A ("Form G1") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.1, 6.5, 13.6, 13.8, and 19.5 ± 0.2° 2Θ.

[0463] 55. The crystalline form of embodiment 54, further characterized by XRPD peaks at 6.9, 9.3, 18.5, 20.8, and 21.5 ± 0.2 degrees 2Θ using CuKa radiation.

[0464] 56. A crystalline form of the mesylate salt of Compound A ("Form G2") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.6, 13.1, 13.3, 16.3, and 18.3 ± 0.2° 2Θ.

[0465] 57. The crystalline form of embodiment 56, further characterized by XRPD peaks at 12.5, 19.8, 21.5, and 9.4 ± 0.2 degrees 2Θ using CuKa radiation.

[0466] 58. A crystalline form of Compound A oxalate salt ("Form H2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 6.9, 8.7, 13.6, 17.4, and 24.6 ± 0.2 degrees 2Θ using CuKa radiation.

[0467] 59. The crystalline form of embodiment 58, further characterized by XRPD peaks at 11.0, 19.6, 20.8, 21.0, 22.0, 25.3, and 27.3 ± 0.2 degrees 2θ using CuKa radiation.

[0468] 60. A crystalline form of the tartrate salt of Compound A ("Form I1") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 3.4, 14.7, 15.6, 18.0, and 24.3 ± 0.2° 2Θ.

[0469] 61. The crystalline form of embodiment 60, further characterized by XRPD peaks at 14.3, 15.1, 18.7, 19.4, and 19.7 ± 0.2 degrees 2Θ using CuKa radiation.

[0470] 62. The crystalline form of embodiment 60 or 61, further characterized by XRPD peaks at 13.3, 13.5, 20.6, 21.1, 23.1, 23.5, 24.9, 26.7, and 27.2 ± 0.2 degrees 2θ using CuKa radiation.

[0471] 63. A crystalline form of the esylate salt of Compound A ("Form J1") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.6, 7.9, 13.6, 15.7, and 17.9 ± 0.2° 2Θ.

[0472] 64. The crystalline form of embodiment 63, further characterized by XRPD peaks at 6.6, 11.1, 13.1, 16.8, 18.7, and 20.4 ± 0.2 degrees 2Θ using CuKa radiation.

[0473] 65. A crystalline form of the esylate salt of Compound A ("Form J2") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.0, 6.3, 7.7, 15.8, and 20.9 ± 0.2 degrees 2-theta using CuKa radiation.

[0474] 66. The crystalline form of embodiment 65, further characterized by XRPD peaks at 7.9, 16.8, 18.4, 18.6, 19.5, and 20.0 ± 0.2 degrees 2Θ using CuKa radiation.

[0475] 67. The crystalline form of embodiment 65 or 66, further characterized by XRPD peaks at 6.9, 17.6, 21.6, 23.3, 23.8, 24.1, 24.7, and 26.1 ± 0.2 degrees 2θ using CuKa radiation.

[0476] 68. A crystalline form of Compound A cyclamate salt ("Form K1") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.8, 14.0, 15.6, 16.7, and 28.1 ± 0.2 degrees 2-theta.

[0477] 69. A crystalline form of the maleate salt of Compound A ("Form L1") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.7, 17.0, 17.5, 25.6, and 26.1 ± 0.2° 2Θ.

[0478] 70. A crystalline form of the phosphate salt of Compound A ("Form M1") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 5.4, 16.2, 20.3, and 22.5 ± 0.2 degrees 2-theta using CuKa radiation.

[0479] 71. The crystalline form of embodiment 70, further characterized by XRPD peaks at 10.8, 12.3, 21.8, and 32.9 ± 0.2 degrees 2θ using CuKa radiation.

[0480] 72. A crystalline form of the phosphate salt of Compound A ("Form M2") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 7.1, 14.2, 14.9, 17.8, and 19.6 ± 0.2 degrees 2Θ.

[0481] 73. The crystalline form of embodiment 72, further characterized by XRPD peaks at 8.9, 10.6, 10.9, 13.4, 16.4, 16.8, and 21.4 ± 0.2 degrees 2θ using CuKa radiation.

[0482] 74. The crystalline form of embodiment 72 or 73, further characterized by XRPD peaks at 3.6, 7.4, 21.0, 21.8, 23.0, 25.0, 25.4, 26.3, and 26.9 ± 0.2 degrees 2Θ using CuKa radiation.

[0483] 75. A crystalline form of the phosphate salt of Compound A ("Form M3") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 7.5, 7.8, 14.8, 15.0, and 15.4 ± 0.2 degrees 2Θ using CuKa radiation.

[0484] 76. The crystalline form of embodiment 75, further characterized by XRPD peaks at 9.0, 9.8, 11.6, 11.7, 18.3, 22.2, and 25.2 ± 0.2 degrees 2Θ using CuKa radiation.

[0485] 77. The crystalline form of embodiment 75 or 76, further characterized by XRPD peaks at 3.9, 16.2, 27.2, and 27.2 ± 0.2 degrees 2θ using CuKa radiation.

[0486] 78. A crystalline form of Compound A salicylic acid cocrystal ("Form CC-1A") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 9.3, 5.9, 9.7, 6.0, and 13.9, 24.0 ± 0.2° 2θ.

[0487] 79. The crystalline form of embodiment 78, further characterized by XRPD peaks at 13.1, 8.3, and 18.6 ± 0.2 degrees 2-theta using CuKa radiation.

[0488] 80. A crystalline form of Compound A salicylic acid cocrystal ("Form CC-2A") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 8.2, 9.2, 16.5, 18.5, and 16.0 ± 0.2° 2Θ.

[0489] 81. The crystalline form of embodiment 80, further characterized by XRPD peaks at 17.2, 11.1, 3.2, 11.8, 24.6, and 25.9 ± 0.2 degrees 2θ using CuKa radiation.

[0490] 82. A crystalline form of Compound A salicylic acid cocrystal ("Form CC-3A") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 3.6, 12.6, 8.0, 14.4, and 7.2 ± 0.2° 2Θ.

[0491] 83. The crystalline form of embodiment 82, further characterized by XRPD peaks at 15.7, 11.2, 13.0, 21.5, 10.8, and 16.1 ± 0.2 degrees 2Θ using CuKa radiation.

[0492] 84. A crystalline form of Compound A salicylic acid cocrystal ("Form CC-4A") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 10.3, 16.2, 9.9, 16.3, 19.9 ± 0.2° 2Θ.

[0493] 85. The crystalline form of embodiment 84, further characterized by XRPD peaks at 26.3, 27.0, 25.3, 18.0, 12.8, and 9.7 ± 0.2 degrees 2Θ using CuKa radiation.

[0494] 86. The crystalline form of embodiment 84 or 85, further characterized by XRPD peaks at 28.5, 28.0, 24.8, 24.4, 23.4, and 22.3 ± 0.2 degrees 2Θ using CuKa radiation.

[0495] 87. The crystalline form of any one of embodiments 84-86, further characterized by 17.8, 16.2, 15.7, 15.6, 15.4, 13.6, and 13.4 ± 0.2 °2Θ using CuKa radiation.

[0496] 88. A crystalline form of Compound A salicylic acid cocrystal ("Form CC-5A") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.3, 17.8, 10.6, 18.3, and 15.9 ± 0.2° 2Θ.

[0497] 89. The crystalline form of embodiment 88, further characterized by XRPD peaks at 25.7, 15.5, 19.1, 28.7, 9.2, 12.2, 11.0, and 12.9 ± 0.2 degrees 2Θ using CuKa radiation.

[0498] 90. The crystalline form of embodiment 88 or 89, further characterized by XRPD peaks at 21.3, 19.8, 20.7, 24.3, 13.2, 26.6, 27.2, and 11.3 ± 0.2 degrees 2Θ using CuKa radiation.

[0499] 91. A crystalline form of Compound A formic acid cocrystal ("Form CC-1B") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 8.6, 4.6, 17.8, 17.4, and 23.0 ± 0.2° 2Θ.

[0500] 92. The crystalline form of embodiment 91, further characterized by XRPD peaks at 11.3, 14.8, 15.7, 16.5, 18.4, 19.3, 20.7, 24.9, and 26.8 ± 0.2 degrees 2Θ using CuKa radiation.

[0501] 93. A crystalline form of Compound A benzoic acid cocrystal ("Form CC-1C") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 11.6, 16.1, 14.2, 3.9, and 19.8 ± 0.2° 2θ.

[0502] 94. The crystalline form of embodiment 93, further characterized by XRPD peaks at 10.4, 10.6, 12.4, 14.5, 17.3, 18.3, and 19.4 ± 0.2 degrees 2Θ using CuKa radiation.

[0503] 95. The crystalline form of embodiment 93 or 94, further characterized by XRPD peaks at 7.7, 8.8, 17.7, 21.7, 23.2, 26.3, and 26.7 ± 0.2 degrees 2Θ using CuKa radiation.

[0504] 96. A crystalline form of Compound A isobutyric acid cocrystal ("Form CC-1D") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.6, 6.1, 13.1, 16.0, and 17.1 ± 0.2° 2Θ.

[0505] 97. The crystalline form of embodiment 96, further characterized by XRPD peaks at 6.5, 8.0, 8.6, 10.7, 11.1, 12.2, and 19.6 ± 0.2 degrees 2Θ using CuKa radiation.

[0506] 98. A crystalline form of Compound A isobutyric acid cocrystal ("Form CC-2D") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.2, 5.5, 6.3, 10.3, and 12.6 ± 0.2° 2Θ.

[0507] 99. The crystalline form of embodiment 98, further characterized by XRPD peaks at 6.8, 12.1, 13.0, and 14.3 ± 0.2 degrees 2Θ using CuKa radiation.

[0508] 100. A crystalline form of Compound A octanoic acid cocrystal ("Form CC-1E") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.8, 6.2, 6.5, 18.1, and 21.1 ± 0.2 degrees 2-theta using CuKa radiation.

[0509] 101. The crystalline form of embodiment 100, further characterized by XRPD peaks at 15.6, 20.6, 21.4, 22.4, and 24.9 ± 0.2 degrees 2Θ using CuKa radiation.

[0510] 102. A crystalline form of Compound A sorbic acid cocrystal ("Form CC-1F") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 8.2, 10.8, 11.4, 18.2, and 21.2 ± 0.2° 2Θ.

[0511] 103. The crystalline form of embodiment 102, further characterized by XRPD peaks at 5.4, 7.1, 8.9, 12.7, 13.4, 14.8, 17.7, 21.6, and 24.6 ± 0.2 degrees 2θ using CuKa radiation.

[0512] 104. A crystalline form of Compound A saccharin cocrystal ("Form CC-1G") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 5.1, 9.8, 10.1, 16.5, and 20.4 ± 0.2 degrees 2Θ.

[0513] 105. A crystalline form of Compound A succinic acid cocrystal ("Form CC-1H") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 11.3, 11.5, 18.3, 19.0, and 20.6 ± 0.2° 2Θ.

[0514] 106. The crystalline form of embodiment 105, further characterized by XRPD peaks at 13.7, 24.2, 25.2, and 28.3 ± 0.2 degrees 2Θ using CuKa radiation.

[0515] 107. A crystalline form of Compound A succinic acid cocrystal ("Form CC-2H") characterized by an X-ray powder diffraction (XRPD) pattern comprising peaks at 4.2, 5.3, 8.3, 9.0, and 9.2 ± 0.2 °2Θ using CuKa radiation.

[0516] 108. A crystalline form of Compound A adipic acid cocrystal ("Form CC-II") characterized by an X-ray powder diffraction (XRPD) pattern using CuKa radiation comprising peaks at 7.7, 10.5, 18.5, 18.9, and 21.7 ± 0.2° 2Θ.

[0517] 109. The crystalline form of embodiment 108, further characterized by XRPD peaks at 5.3, 12.1, 20.7, 24.2, and 25.7 ± 0.2 degrees 2Θ using CuKa radiation.

[0518] 110. A free base of compound A amorphous form.

[0519] 111. The amorphous form of embodiment 110, having a glass transition temperature (Tg) of 119°C ± 3°C.

[0520] 112. A pharmaceutical composition comprising the crystalline form or amorphous form of any one of embodiments 1 to 111 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

[0521] 113. The pharmaceutical composition of embodiment 112, wherein the composition is formulated for oral delivery.

[0522] 114. The pharmaceutical composition of embodiment 112 or 113, wherein the composition is formulated for once-daily administration.

[0523] 115. The pharmaceutical composition of any one of embodiments 112-114, wherein the composition is an oral tablet.

[0524] 116. The pharmaceutical composition of any one of embodiments 112-115, comprising 1-4000 mg of the crystalline form or amorphous form.

[0525] 117. The pharmaceutical composition of embodiment 116, comprising 1-2000 mg of the compound or crystalline form.

[0526] 118. A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the crystalline form or amorphous form of any one of embodiments 1 to 108, or a pharmaceutically acceptable salt thereof.

[0527] 119. The method of embodiment 118, wherein the cancer is ovarian cancer, lung cancer, lymphoma, glioblastoma, colon cancer, melanoma, gastric cancer, pancreatic cancer, or bladder cancer.

[0528] 120. The method of embodiment 119, wherein the cancer is non-small cell lung cancer.

[0529] 121. The method of embodiment 119, wherein the cancer is pancreatic cancer.

[0530] 122. The method of any one of embodiments 118-121, wherein the cancer is an MTAP-deficient cancer.

[0531] 123. The method of embodiment 122, wherein the cancer is an MTAP-deficient cancer selected from lung cancer, biliary tract cancer, head and neck squamous cell carcinoma, pancreatic adenocarcinoma, gallbladder cancer, and mesothelioma.

[0532] 124. The method of embodiment 123, wherein the MTAP-deficient cancer is lung cancer.

[0533] 125. The method of embodiment 124, wherein the lung cancer is non-squamous cell lung cancer (NSCLC).

[0534] 126. The method of any one of embodiments 118-123, wherein the cancer is not a primary brain tumor or lymphoma.

[0535] 127. The method of any one of embodiments 118-126, wherein the subject does not have or has never had interstitial lung disease or pneumonia.

[0536] 128. The method of any one of embodiments 118-127, wherein the crystalline form is crystalline Form 1.

[0537] Other embodiments

[0538] It is to be understood that while this disclosure is to be read in conjunction with its detailed description, the foregoing description is intended to illustrate and not limit the scope of this disclosure, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

[0539] Examples

[0540] The following examples are provided for illustration and are not intended to limit the scope of the invention.

[0541] Materials and Methods

[0542] Unless specified, commercially available reagents were used as received without further purification.

[0543] The crystalline forms disclosed herein can be characterized using conventional means, including physical constants, diffraction data, and spectroscopic data.

[0544] X-ray powder diffraction - Method 1: X-ray powder diffraction (XRPD) data were obtained on a PANalytical X'Pert PRO X-ray diffraction system with an RTMS detector. The X-ray powder diffraction was carried out at 45 kV and 40 mA with a step time of 50 s, in a continuous mode from 5 to 45° or 3 to 40° (2θ) with a step size of 0.0334° or 0.0167°, respectively, at ambient temperature. Scan samples. Some X-ray powder diffraction (XRPD) data were also obtained on a Burker D8 Advance with a Twin twin optical path and an Eiger detector. The samples were irradiated at 40 kV and 40 mA with a time of 0.2 s per step (7 min scan time) in a continuous mode from 3 to 40° (2θ) with a step size of 0.02° at ambient temperature using Cu irradiation. Scan the sample with line focus.

[0545] X-ray Powder Diffraction - Method 2: In some cases, XRPD was performed on a Si zero-background stand using a Panalytical Aeris powder XRPD. The 2θ position was calibrated relative to a Panalytical Si reference standard disk. The parameters used are listed in the table below.

[0546] XRPD parameters

[0547]

[0548]

[0549] X-ray powder diffraction - Method 3: Powder X-ray diffraction patterns were collected using a Bruker D8 Advance diffractometer equipped with a twin-twin optical path and an Eiger X-ray detector in reflection mode. The powder X-ray diffraction patterns were collected using CuKα radiation at 40 kV and 40 mA in a continuous mode from 3 to 45° 2θ with a step size of 0.02° 2θ at ambient temperature. Scan the sample. The incident beam path is equipped with a nickel filter 0.2 mm and an anti-air scattering slit. The sample is prepared on a low-background sample holder and placed on a rotating stage with a rotation time of 10 rpm. Data are collected using DIFFRAC.MEASUREMENT CENTER (version 7.5) and processed using DIFFRAC.EVA (version 5.2).

[0550] Single crystal structure: High-quality single crystals were mounted on MiteGEN rings using mineral oil. Cu K α radiation Data were collected at 100 K on a Bruker-AXS X8 Kappa diffractometer coupled to a Bruker Photon2 CPAD detector. All non-hydrogen atoms were anisotropically refined. All carbon-bound hydrogen atoms were placed in geometrically calculated positions and refined using the riding model while constraining their Uiso to 1.2 times the Ueq of the atom to which they are bound. Data reduction was performed using the SAINT program, and semi-empirical absorption correction based on equivalent terms was performed using the SADABS program.

[0551] Differential Scanning Calorimetry (DSC) - Method 1: The calorimeter was run on a TA Instruments Discovery series calorimeter at 10°C / min from 30°C to 300°C on a coiled aluminum T zero DSC analysis was performed in the pan under dry nitrogen at 50 mL / min using a nickel reference standard. The sample size was approximately 2-4 mg.

[0552] Thermogravimetric Analysis (TGA) - Method 1: TGA was performed on a TA Instruments Discovery Series analyzer at 10°C / min from ambient temperature to 300°C in a platinum pan under dry nitrogen at 25 mL / min using an indium reference standard. The sample size was approximately 5 mg. The detailed parameters used are listed in the table below.

[0553] TGA and DSC thermal analysis parameters

[0554] parameter TGA DSC method rise rise Sample tray Platinum, opening aluminum temperature RT - desired temperature 25℃-required temperature Heating rate 10℃ / min 10℃ / min Purge gas <![CDATA[N2]]> <![CDATA[N2]]>

[0555] Differential Scanning Calorimetry - Method 2: Use approximately 1-5 mg of sample weight on a TA Instruments Q2000, Q1000, and / or Discovery series calorimeter at 10°C / min from -5°C to 30°C to 250°C to 350°C at a curled T zero Differential scanning calorimetry (DSC) analysis was performed in an aluminum pan under a dry nitrogen flow at 50 mL / min.

[0556] Alternatively, DSC was performed using a TA Instruments Q2000 differential scanning calorimeter. Temperature calibration was performed using NIST-traceable indium metal. The sample was placed in an aluminum Tzero pan, covered, clamped, and the weight accurately recorded. A weighed aluminum pan configured as a sample pan was placed on the reference side of the cell. The data acquisition parameters and pan configuration for each thermogram are shown in the images in the data section of this report.

[0557] An illustrative procedure for mDSC of the amorphous form of Compound A free base Form 4 was performed using the following program / settings: 1) equilibrate at 0.00°C; 2) data storage on; 3) adjust + / - 0.50°C every 60 seconds; 4) ramp to 26.00°C at 2.00°C / min; 5) mark end of cycle 1; and 6) end of method.

[0558] Thermogravimetric Analysis - Method 2: Thermogravimetric analysis (TGA) was performed on a TA Instruments Q5000, Q500 and / or Discovery series analyzer using approximately 1-5 mg sample size at 10°C / min from ambient temperature to 250-400°C in a platinum pan under dry nitrogen at 25 mL / min.

[0559] DVS - Method 1: DVS is measured by SMS (Surface Measurement Systems) DVS Resolution. Relative humidity at 25°C is calibrated to the deliquescent point of LiCl, Mg(NO3)2, and KCl. The actual DVS parameters are listed in the table below.

[0560] DVS parameters

[0561] project value temperature 25℃ Sample size 10-20 mg Gas and flow <![CDATA[N2,200mL / min]]> dm / dt 0.002% / min Minimum dm / dt stability duration 10min Maximum balancing time 180 minutes RH range 30%RH - 95%RH - 0%RH - 95%RH RH step length 10％

[0562] DVS-Method 2: Water sorption data were collected using a DVS vapor sorption analyzer. Sample sizes of approximately 10-20 mg were used in glass or metal pans. Hygroscopicity was assessed in 5% RH increments from 40% to 90% to 0% to 90% to 40% RH, or in 10% RH increments from 40% to 0% to 95% to 0% to 95% RH. Data were collected for both adsorption and desorption cycles. The equilibrium criterion was set to a 0.002% weight change in 1 minute, with a maximum equilibration time of 180 minutes.

[0563] NMR: Acquired at 11.7 T at 298 K on a wide-aperture Bruker Avance III spectrometer equipped with a 4 mm H / F / X magic angle spinning probe 13 C solid-state NMR spectroscopy. 19 The F resonance is set to -123.2 ppm for Teflon (PTFE) and 13 The CCH2 resonance was set to 38.48 ppm for adamantane, and the chemical shift was externally referenced. Approximately 100 mg of sample was loaded into a 4 mm zirconia rotor and a magic angle spinning frequency of 14 kHz was used. NMR data were processed using Topspin 3.6.4 or 3.5 software.

[0564] For example, for form 1, use the following parameters: 1 H- 13C Cross Polarization (CP), using 64kHz 1 H excitation pulse followed by a 70%-100% amplitude ramp 1 H pulse and constant amplitude 13 C pulse with a contact time of 3ms; during the acquisition, SPINAL-64 was used to achieve 1 H heteronuclear decoupling. 2048 transients were collected using a 28s recycle delay; and for 19 F experiment, using 45kHz 19 F excitation pulse, during the acquisition process, was implemented using SPINAL-64 1 H heteronuclear decoupling was performed, and 256 transients were collected using a recycle delay of 4.03 s.

[0565] Example 1: Crystalline Compound A Form 1

[0566] The crystalline form of Compound A free base (Form 1) is first prepared by slurrying Compound A in water at 37° C. For example, Form 1 can be prepared by slurry conversion of Form 8. Alternatively, Form 1 can be prepared by slurry conversion of the free base amorphous form.

[0567] The following procedures illustrate various methods for preparing Form 1. Form 1 can be formed by: a) slurry conversion in heptane, cyclohexane, 2-methyltetrahydrofuran, 1,2-dichloroethane / heptane (1:1), acetonitrile / heptane (1:1), water, isopropanol / water (1:4), ethanol / water (1:1), ethanol / water (1:4), acetonitrile / water (1:4), dimethylformamide / water (1:1), dimethylformamide / water (1:4) at 55°C for 8 hours; b) slow evaporation from toluene, acetone, dioxane, dimethoxyethane, isopropyl acetate, or ethyl acetate at room temperature; c) slurry conversion in acetone. d) slurry conversion in acetone / water 40 / 60, acetone / water 20 / 80, acetonitrile / water 20 / 80, acetonitrile / water 10 / 90, ethanol / water 40 / 60, ethanol / water 50 / 50, ethanol / water 70 / 30, ethanol / water 80 / 20, ethanol / water 90 / 10, isopropanol / water 10 / 90, isopropanol / water 30 / 70, isopropanol / water 40 / 60, isopropanol / water 60 / 40, isopropanol / water 80 / 10, isopropanol / water 90 / 10 at room temperature for 5 days; and / or d) adding an antisolvent to acetone or DMSO.

[0568] The obtained solid was identified as crystalline Form 1 by XRPD, as shown in Tables 1 and Figure 1 In addition, DSC and DVS are respectively Figure 2 and 3 As shown in Figure 2As shown, DSC indicated an extrapolated onset of melting at 225°C and a weight loss of 0.03% from 35°C to 150°C and thermal decomposition above 250°C. Figure 3 As shown, DVS indicated that Form 1 was non-hygroscopic at 25°C between 0% and 95% relative humidity with no observable form change.

[0569] Table 1: Form 1 XRPD Data

[0570]

[0571]

[0572]

[0573] In addition, single crystals of the free base form 1 were grown in ethyl acetate by slow evaporation at room temperature and used for single crystal X-ray structure determination.

[0574] Table 2: X-ray single structure data

[0575]

[0576] 13 C ssNMR data. 13 C NMR isotropic peaks: 39.2, 43.8, 51.6, 58.1, 65.9, 71.8, 73.6, 114.7, 120.8, 125.1, 126.1, 128.2, 130.8, 142.2, 143.3, 145.3, 148.5, 149.2, 156.9, and 169.6 ppm. 19 Fss NMR data: -62.0 and -63.9 ppm at 25°C.

[0577] Crystalline Compound A Form 3 was prepared using any of the following conditions: a) adding a solution of Compound A in 2-methyltetrahydrofuran to heptane such that the volume ratio of 2-methyltetrahydrofuran to heptane was 1:2 at room temperature; b) adding a solution of Compound A in tetrahydrofuran to methyl tert-butyl ether such that the volume ratio of tetrahydrofuran to methyl tert-butyl ether was 1:2 at 5°C; c) slow evaporation from methanol / methyl tert-butyl ether (1:2); d) slow evaporation from dichloromethane at room temperature; e) slow evaporation from dichloromethane; Form 3 was also formed by slow evaporation from dichloromethane at room temperature.

[0578] Example 2: Crystalline Compound A Free Base Form 3

[0579] Crystalline Compound A free base Form 3 was prepared using any of the following conditions: a) adding heptane as an antisolvent to a solution of Compound A in 2-methyltetrahydrofuran / heptane (1:2) at room temperature; b) adding methyl tert-butyl ether as an antisolvent to a solution of Compound A in tetrahydrofuran / methyl tert-butyl ether (1:2) at 5° C.; c) evaporation from methanol / methyl tert-butyl ether (1:2); d) evaporation from dichloromethane at room temperature; e) adding pentane as an antisolvent to a solution of Compound A in dichloromethane / pentane (1:2) at room temperature; f) formation by slurry conversion in dichloromethane at 5° C.; and g) formation by liquid vapor diffusion from a dioxane solution and an antisolvent of methyl tert-butyl ether at 5° C. Form 3 was also formed by slow evaporation from dichloromethane at room temperature.

[0580] The obtained solid was identified as crystalline Form 3 by XRPD, as shown in Table 3 and Figure 4 shown.

[0581] Table 3: Form 3 XRPD Data

[0582]

[0583]

[0584] Example 3: Crystalline Compound A Free Base Form 6

[0585] Crystalline Compound A free base Form 6 was prepared by slurrying Compound A in ethanol at room temperature. The resulting solid was identified as crystalline Form 6 by XRPD, as shown in Tables 4 and Figure 7 shown.

[0586] Table 4: Form 6 XRPD Data

[0587]

[0588]

[0589]

[0590] Example 4: Crystalline Compound A Free Base Form 7

[0591] Crystalline Compound A free base Form 7 was prepared using the following conditions: a) slow evaporation from acetonitrile and pentane (1:2); b) slow evaporation from ethyl acetate and toluene (1:2); and c) slow evaporation from acetonitrile. The resulting solid was identified as crystalline Form 7 by XRPD, as shown in Tables 5 and Figure 9 shown.

[0592] Table 5: Form 7 XRPD Data

[0593]

[0594] Example 5 Crystallization of Compound A Free Base Form 8-hydrate

[0595] Crystalline Compound A free base form 8 hydrate was prepared by slow evaporation from acetonitrile and water. The resulting solid was identified as crystalline form 8 hydrate by XRPD, as shown in Tables 6 and Figure 11 shown.

[0596] Table 6: Form 8 Hydrate XRPD Data

[0597]

[0598]

[0599] Example 6: Crystalline Compound A Ethanol Solvate (Form 2A)

[0600] Crystalline Compound A monoethanol solvate (Form 2A) was first prepared by slurrying Compound A in ethanol at room temperature. The resulting solid was identified as crystalline by XRPD, as shown in Tables 7 and Figure 13 shown.

[0601] Table 7: Form 2A XRPD Data

[0602]

[0603]

[0604]

[0605] Single crystals of Form 2A were grown in ethanol at room temperature and used for single crystal X-ray structure determination.

[0606] Table 8: X-ray single structure data

[0607]

[0608]

[0609] Example 3: Crystalline Compound A Isopropanol Solvate (Form 3A)

[0610] Crystalline Compound A isopropanol solvate (Form 3A) was first prepared by slurrying Compound A in isopropanol at room temperature. The resulting solid was identified as crystalline Form 3A by XRPD, as shown in Tables 9 and Figure 15 shown.

[0611] Table 9: Form 3A XRPD Data

[0612]

[0613]

[0614]

[0615] Example 4: Crystalline Compound A Acetone Solvate (Form 4A)

[0616] Crystalline Compound A acetone solvate Form 4A was prepared by conversion of a slurry of Compound A in acetone at 5°C and at room temperature. The resulting solid was identified as crystalline Form 4A by XRPD, as shown in Tables 10 and Figure 17 shown.

[0617] Table 10: Form 4A XRPD Data

[0618]

[0619]

[0620] Example 5: Crystallized Compound A Methanol Solvate (Form 5A)

[0621] Crystalline Compound A methanol solvate Form 5A was prepared by conversion of a slurry of Compound A in methanol at 5°C and at room temperature. Form 5A was also prepared by slow evaporation of Compound A from methanol at room temperature. The resulting solid was identified as crystalline Form 5A by XRPD, as shown in Tables 11 and Figure 19 shown.

[0622] Table 11: Form 5A XRPD Data

[0623]

[0624]

[0625] Example 6: Amorphous Compound A Free Base (Form 4AA)

[0626] Amorphous Compound A free base (Form 4AA) was formed after cooling the melt at 300°C. XRPD ( Figure 104 ) and DSC( Figure 105 ) Evaluate the resulting solid.

[0627] An amorphous form of Compound A free base can be formed upon cooling a melt of Compound A free base under suitable conditions. For example, in some embodiments, Compound A free base Form 1 can be heated to a temperature of 300° C. at a rate of 20° C. / min and melted in a hot stage microscope, after which the sample can be removed and rapidly cooled to room temperature.

[0628] DSC was performed in a sealed crimp pan heated at 2°C / min (+ / - 0.5°C modulation every 60 seconds) and showed a glass transition (Tg) at approximately 1189°C.

[0629] Example 7: Crystalline Compound A Tosylate Salt (Form A1)

[0630] Crystalline Compound A tosylate salt (Form A1) was prepared by slurrying one equivalent of toluenesulfonic acid and Compound A in a 50 / 50 toluene / methanol solvent mixture under ambient conditions. The resulting solid was identified as crystalline by XRPD, as shown in Tables 12 and Figure 21 shown.

[0631] Table 12: Form A1 XRPD Data

[0632]

[0633]

[0634] Example 8: Crystalline Compound A Tosylate Salt (Form A2)

[0635] Crystalline Compound A tosylate salt (Form A2) was prepared by slurrying a 1:1 molar ratio of Compound A and the counterion toluenesulfonic acid in 2-methyltetrahydrofuran, acetone, or ethyl acetate under ambient conditions. The resulting solid was identified as crystalline by XRPD, as shown in Tables 13 and Figure 24 shown.

[0636] Table 13: Form A2 XRPD Data

[0637]

[0638]

[0639]

[0640] Example 9: Crystalline Compound A Tosylate Salt (Form A3)

[0641] Crystalline Compound A tosylate salt (Form A3) was prepared by crystallization from p-toluenesulfonic acid in acetone / heptane (1:1) at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. It was also formed by crystallization from p-toluenesulfonic acid in methyl isobutyl ketone and dioxane at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. The resulting solid was identified as crystalline Form A3 by XRPD, as shown in Tables 14 and 14. Figure 26 shown.

[0642] Table 14: Form A3 XRPD Data

[0643]

[0644]

[0645] Example 10: Crystalline Compound A Benzenesulfonate Salt (Form B1)

[0646] Crystalline Compound A benzenesulfonate salt (Form B1) was prepared by cooling a 1:1 molar ratio of Compound A and the counterion benzenesulfonic acid in a 50:50 toluene:methanol solvent mixture. It was also formed by crystallization in ethanol, methyl isobutyl ketone, dioxane, acetone / heptane (1:1) or dichloromethane at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. It was also formed by slow evaporation in acetonitrile / water (1:1) at room temperature. The resulting solid was identified as crystalline Form B1 by XRPD, as shown in Tables 15 and 16. Figure 29 shown.

[0647] Table 15: Form B1 XRPD Data

[0648]

[0649]

[0650] Example 11: Crystalline Compound A Chloride Salt (Form C1)

[0651] Crystalline Compound A chloride salt (Form C1) was prepared by slurrying a 1:1 molar ratio of Compound A and counterion HCl in isopropanol under ambient conditions. The resulting solid was identified as crystalline Form C1 by XRPD, as shown in Tables 16 and Figure 31 shown.

[0652] Chloride Table 16: Form C1 XRPD Data

[0653]

[0654]

[0655]

[0656] Example 12: Crystalline Compound A Chloride Salt (Form C2)

[0657] Crystalline Compound A chloride salt (Form C2) was prepared by crystallization with HCl in methyl isobutyl ketone at room temperature, wherein the molar ratio of Compound A to counterion was 1:1. The resulting solid was identified as crystalline Form C1 by XRPD, as shown in Tables 17 and Figure 33 shown.

[0658] Table 17: Form C2 XRPD Data

[0659]

[0660]

[0661] Example 13: Crystalline Compound A Sulfate (Form D1)

[0662] Crystalline Compound A sulfate (Form D1) was prepared by slurrying a 1:1 molar ratio of Compound A and counterion sulfuric acid in isopropanol under ambient conditions. The resulting solid was identified as crystalline Form D1 by XRPD, as shown in Tables 18 and Figure 35 shown.

[0663] Table 18: Form D1 XRPD Data

[0664]

[0665]

[0666] Example 14: Crystalline Compound A Malonate Salt (Form E1)

[0667] Crystalline Compound A malonate (Form E1) was prepared by crystallization from malonic acid in methyl isobutyl ketone at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. The resulting solid was identified as crystalline Form E1 by XRPD, as shown in Tables 19 and Figure 36 shown.

[0668] Table 19: Form E1 XRPD Data

[0669]

[0670]

[0671] Example 15: Crystalline Compound A Naphthalene-2-Sulfonate Salt (Form F1)

[0672] Crystalline Compound A naphthalene-2-sulfonate salt Form F1 was prepared by crystallization from naphthalene-2-sulfonic acid in acetone / heptane (1:1) at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. Form F1 was also prepared by crystallization from dioxane and methyl isobutyl ketone at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. The resulting solid was identified as crystalline Form F1 by XRPD, as shown in Tables 20 and 21. Figure 40 shown.

[0673] Table 20: Form F1 XRPD Data

[0674]

[0675]

[0676] Example 16: Crystalline Compound A Naphthalene-2-Sulfonate Salt (Form F2)

[0677] Crystalline Compound A naphthalene-2-sulfonate salt Form F2 was crystallized by reaction with naphthalene-2-sulfonic acid in ethanol at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. The resulting solid was identified as crystalline Form F2 using XRPD, as shown in Tables 21 and Figure 43 shown.

[0678] Table 21: Form F2 XRPD Data

[0679]

[0680]

[0681] Example 17: Crystalline Compound A Naphthalene-2-Sulfonate Salt (Form F3)

[0682] Crystalline Compound A naphthalene-2-sulfonate salt Form F3 was crystallized from naphthalene-2-sulfonic acid in dichloromethane at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. Form F3 was also crystallized from naphthalene-2-sulfonic acid in acetonitrile / water (1:1) at 5°C, wherein the molar ratio of Compound A to the counterion was 1:1. The resulting solid was identified as crystalline Form F3 using XRPD, as shown in Tables 22 and 3. Figure 44 shown.

[0683] Table 22: Form F3 XRPD Data

[0684]

[0685]

[0686] Example 18: Crystalline Compound A Methanesulfonate (Form G1)

[0687] Crystalline Compound A mesylate salt Form G1 was prepared by crystallization with methanesulfonic acid in methyl isobutyl ketone at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. The resulting solid was identified as crystalline Form G1 using XRPD, as shown in Tables 23 and Figure 46 shown.

[0688] Table 23: Form G1 XRPD Data

[0689]

[0690] Example 19: Crystalline Compound A Methanesulfonate (Form G2)

[0691] Crystalline Compound A mesylate salt Form G2 was prepared by crystallization from methanesulfonic acid in ethanol at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. Form G2 was also formed by crystallization from dichloromethane at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. The resulting solid was identified as crystalline Form G2 using XRPD, as shown in Tables 24 and 25. Figure 47 shown.

[0692] Table 24: Form G21 XRPD Data

[0693]

[0694]

[0695] Example 20: Crystalline Compound A Oxalate (Form H2)

[0696] Crystalline Compound A oxalate Form H2 was prepared by crystallization from oxalic acid in dichloromethane at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. Form H2 was also formed by crystallization from acetonitrile / water (1:1) at 5°C, wherein the molar ratio of Compound A to the counterion was 1:1. The resulting solid was identified as crystalline Form H2 using XRPD, as shown in Tables 25 and Figure 50 shown.

[0697] Table 25: Form H2 XRPD Data

[0698]

[0699]

[0700] Example 21: Crystalline Compound A Tartrate (Form I1)

[0701] Crystalline Compound A tartrate salt Form I1 was prepared by crystallization with tartaric acid in dioxane at room temperature, wherein the molar ratio of Compound A to counterion was 1:1. The resulting solid was identified as crystalline Form I1 using XRPD, as shown in Tables 26 and Figure 52 shown.

[0702] Table 26: Form I1 XRPD Data

[0703]

[0704]

[0705] Example 22: Crystalline Compound A Ethylate Salt (Form J1)

[0706] Crystalline Compound A ethanesulfonate salt Form J1 was prepared by crystallization with ethanesulfonic acid in ethanol at room temperature, wherein the molar ratio of Compound A to the counterion was 1:1. The resulting solid was identified as crystalline Form J1 using XRPD, as shown in Tables 27 and Figure 54 shown.

[0707] Table 27: Form J1 XRPD Data

[0708]

[0709]

[0710] Example 23: Crystalline Compound A Ethylate Salt (Form J2)

[0711] Crystalline Compound A esylate salt Form J1 was prepared by crystallization from ethanesulfonic acid in 1:1 acetone / heptane at room temperature, wherein the molar ratio of Compound A to counterion was 1:1. Form J1 was also formed by crystallization from ethanesulfonic acid in methyl isobutyl ketone at room temperature, wherein the molar ratio of Compound A to counterion was 1:1. The resulting solid was identified as crystalline Form J1 using XRPD, as shown in Tables 28 and Figure 56 shown.

[0712] Table 28: Form J2 XRPD Data

[0713]

[0714]

[0715]

[0716] Example 24: Crystalline Compound A N-cyclohexylsulfamate (Form K1)

[0717] Crystalline Compound A N-cyclohexylaminosulfonate Form K1 was prepared by crystallization from cyclohexylaminosulfonic acid in dioxane at room temperature, with a molar ratio of Compound A to counterion of 1:1. Form K1 was also formed by crystallization from cyclohexylaminosulfonic acid in ethanol, dichloromethane, and acetone / heptane (1:1) at room temperature, with a molar ratio of Compound A to counterion of 1:1. Form K1 was also formed by crystallization from cyclohexylaminosulfonic acid in acetonitrile / water (1:1) at 5°C, with a molar ratio of Compound A to counterion of 1:1. The resulting solid was identified as crystalline Form K1 using XRPD, as shown in Tables 29 and Figure 58 shown.

[0718] Table 29: Form K1 XRPD Data

[0719]

[0720]

[0721] Example 25: Crystalline Compound A Maleate Salt (Form L1)

[0722] Crystalline Compound A maleate salt Form L1 was prepared by crystallization from maleic acid in ethanol at room temperature, wherein the molar ratio of Compound A to counterion was 1:1. Form L1 was also formed by crystallization from maleic acid in methyl isobutyl ketone, dichloromethane, dioxane, and acetone / heptane (1:1) at room temperature, wherein the molar ratio of API to counterion was 1:1. Form L1 was also observed by crystallization from maleic acid in acetonitrile / water (1:1) at 5°C, wherein the molar ratio of Compound A to counterion was 1:1. The resulting solid was identified as crystalline Form L1 using XRPD, as shown in Tables 30 and 31. Figure 60 shown.

[0723] Table 30: Form L1 XRPD Data

[0724]

[0725]

[0726] Example 26: Crystalline Compound A Phosphate (Form M1)

[0727] Crystalline Compound A phosphate Form M1 was prepared by crystallization with phosphoric acid in ethanol at room temperature, wherein the molar ratio of Compound A to counterion was 1:1. The resulting solid was identified as crystalline Form M1 using XRPD, as shown in Tables 30 and Figure 62 shown.

[0728] Table 31: Form M1 XRPD Data

[0729]

[0730]

[0731] Example 27: Crystalline Compound A Phosphate (Form M2)

[0732] Crystalline Compound A phosphate Form M2 was prepared by crystallization with phosphoric acid in dichloromethane at room temperature, wherein the molar ratio of Compound A to counterion was 1:1. The resulting solid was identified as crystalline Form M2 using XRPD, as shown in Tables 31 and Figure 65 shown.

[0733] Table 31: Form M2 XRPD Data

[0734]

[0735]

[0736] Example 28: Crystalline Compound A Phosphate (Form M3)

[0737] Crystalline Compound A phosphate Form M3 was prepared by crystallization from phosphoric acid in dioxane at 5°C, wherein the molar ratio of Compound A to the counterion was 1:1. The resulting solid was identified as crystalline Form M3 using XRPD, as shown in Tables 32 and Figure 67 shown.

[0738] Table 32: Form M3 XRPD Data

[0739]

[0740]

[0741] Example 29: Crystallization of Compound A Salicylic Acid Cocrystal (Form CC-1A)

[0742] Crystalline Compound A salicylic acid co-crystal Form CC-1A was prepared by crystallization with salicylic acid in ethanol at room temperature, wherein the molar ratio of Compound A to salicylic acid co-former was 1:1. The resulting solid was identified as crystalline Form CC-1A using XRPD, as shown in Tables 33 and Figure 69 shown.

[0743] Table 33: Form CC-1A XRPD Data

[0744]

[0745] Example 30: Crystallization of Compound A Salicylic Acid Cocrystal (Form CC-2A)

[0746] Crystalline Compound A salicylic acid cocrystal Form CC-2A was prepared by crystallization with salicylic acid in methyl isobutyl ketone at room temperature, wherein the molar ratio of Compound A to salicylic acid coformer was 1:1. The resulting solid was identified as crystalline Form CC-2A using XRPD, as shown in Tables 34 and Figure 71 shown.

[0747] Table 34: Form CC-2A XRPD Data

[0748]

[0749] Example 31: Crystallization of Compound A Salicylic Acid Cocrystal (Form CC-3A)

[0750] Crystalline Compound A salicylic acid co-crystal Form CC-3A was prepared by crystallization with salicylic acid in dichloromethane at room temperature, wherein the molar ratio of Compound A to salicylic acid co-former was 1:1. The resulting solid was identified as crystalline Form CC-3A using XRPD, as shown in Tables 35 and Figure 73 shown.

[0751] Table 35: Form CC-3A XRPD Data

[0752]

[0753] Example 32: Crystallized Compound A Salicylic Acid Cocrystal (Form CC-4A)

[0754] Crystalline Compound A salicylic acid cocrystal Form CC-4A was prepared by crystallization with salicylic acid in acetonitrile / water (1:1) or acetone / heptane (1:1) at room temperature, wherein the molar ratio of Compound A to salicylic acid coformer was 1:1. The resulting solid was identified as crystalline Form CC-4A using XRPD, as shown in Tables 36 and Figure 76 shown.

[0755] Table 36: Form CC-4A XRPD Data

[0756]

[0757]

[0758] Example 33: Crystallized Compound A Salicylic Acid Cocrystal (Form CC-5A)

[0759] Crystalline Compound A salicylic acid cocrystal Form CC-5A was prepared by slow evaporation of salicylic acid in dioxane at 25°C with a molar ratio of Compound A to coformer of 1:1. The resulting solid was identified as crystalline Form CC-5A using XRPD, as shown in Tables 37 and Figure 78 shown.

[0760] Table 37: Form CC-5A XRPD Data

[0761]

[0762]

[0763] Example 34: Crystallization of Compound A Formic Acid Cocrystal (Form CC-1B)

[0764] Crystalline Compound A formic acid co-crystal Form CC-1B was prepared by slow evaporation with formic acid in dichloromethane at 25°C, wherein the molar ratio of Compound A and formic acid co-former was 1:1. The resulting solid was identified as crystalline Form CC-1B using XRPD, as shown in Tables 38 and Figure 80 shown.

[0765] Table 38: Form CC-1B XRPD Data

[0766]

[0767]

[0768] Example 35: Crystallization of Compound A Benzoic Acid Cocrystal (Form CC-1C)

[0769] Crystalline Compound A benzoic acid cocrystal Form CC-1C was prepared by crystallization from benzoic acid in methyl isobutyl ketone at room temperature, wherein the molar ratio of Compound A to the benzoic acid coformer was 1:1. Form CC-1C was also crystallized from benzoic acid in dichloromethane or acetonitrile / water (1:1) at 5°C, wherein the molar ratio of Compound A to the coformer was 1:1. The resulting solid was identified as crystalline Form CC-1C using XRPD, as shown in Tables 39 and Figure 82 shown.

[0770] Table 39: Form CC-1C XRPD Data

[0771]

[0772]

[0773]

[0774] Example 36: Crystallization of Compound A Isobutyric Acid Cocrystal (Form CC-1D)

[0775] Crystalline Compound A isobutyric acid cocrystal Form CC-1D was prepared by crystallization from isobutyric acid in acetone / heptane (1:1) or methyl isobutyl ketone at room temperature, with a molar ratio of isobutyric acid coformer to Compound A of 1:1. Form CC-1D was also formed by slow evaporation from acetonitrile / water (1:1) at room temperature, with a molar ratio of coformer to Compound A of 1:1. The resulting solid was identified as crystalline Form CC-1D using XRPD, as shown in Tables 40 and 41. Figure 85 shown.

[0776] Table 40: Form CC-1D XRPD Data

[0777]

[0778]

[0779] Example 37: Crystallization of Compound A Isobutyric Acid Cocrystal (Form CC-2D)

[0780] Crystalline Compound A isobutyric acid cocrystal Form CC-2D was prepared by slow evaporation of isobutyric acid from dichloromethane at room temperature with a molar ratio of Compound A to isobutyric acid coformer of 1:1. The resulting solid was identified as crystalline Form CC-2D using XRPD, as shown in Tables 41 and Figure 88 shown.

[0781] Table 41: Form CC-2D XRPD Data

[0782]

[0783]

[0784] Example 38: Crystallization of Compound A Octanoic Acid Cocrystal (Form CC-1E)

[0785] Crystalline Compound A octanoic acid co-crystals were prepared by slow evaporation with octanoic acid in acetonitrile / water (1:1) at room temperature, with a 1:1 ratio of octanoic acid coformer to Compound A. The resulting solid was identified as crystalline Form CC-1E using XRPD, as shown in Tables 42 and Figure 91 shown.

[0786] Table 42: Form CC-1E XRPD Data

[0787]

[0788]

[0789] Example 39: Crystalline Compound A Sorbic Acid Cocrystal (Form CC-1F)

[0790] Crystalline Compound A sorbic acid co-crystal Form CC-1F was prepared by crystallization with sorbic acid in acetonitrile / water (1:1) at 5°C, wherein the ratio of Compound A to sorbic acid co-former was 1:1. The resulting solid was identified as crystalline Form CC-1F using XRPD, as shown in Tables 43 and Figure 93 shown.

[0791] Table 43: Form CC-1F XRPD Data

[0792]

[0793]

[0794] Example 40: Crystallized Compound A Saccharin Cocrystal (Form CC-1G)

[0795] Crystalline Compound A saccharin co-crystal Form CC-1G was prepared by crystallization from saccharin in acetone / heptane (1:1) at room temperature, wherein the ratio of Compound A to saccharin co-former was 1:1. Form CC-1G was also formed by crystallization from saccharin in ethanol, methyl isobutyl ketone, dichloromethane, or acetonitrile / water (1:1) at room temperature, wherein the molar ratio of Compound A to saccharin co-former was 1:1. Form CC-1G was also formed by slow evaporation from dioxane with saccharin at room temperature, wherein the molar ratio of Compound A to co-former was 1:1. The resulting solid was identified as crystalline Form CC-1G using XRPD, as shown in Tables 44 and 45. Figure 95 shown.

[0796] Table 44: Form CC-1G XRPD Data

[0797]

[0798] Example 41: Crystallization of Compound A Succinic Acid Cocrystal (Form CC-1H)

[0799] Crystalline Compound A succinate cocrystal Form CC-1H was prepared by crystallization with succinic acid in dichloromethane at room temperature in a 1:1 ratio. Form CC-1H was also crystallized with succinic acid in ethanol, acetonitrile / water (1:1), or acetone / heptane (1:1) at room temperature. The resulting solid was identified as crystalline Form CC-1H using XRPD, as shown in Tables 45 and 46. Figure 98 shown.

[0800] Table 45: Form CC-1H XRPD Data

[0801]

[0802]

[0803] Example 42: Crystallization of Compound A Succinic Acid Cocrystal (Form CC-2H)

[0804] Crystalline Compound A succinic acid cocrystal Form CC-2H was prepared by crystallization with succinic acid in methyl isobutyl ketone at room temperature, with a molar ratio of Compound A to succinic acid coformer of 1:1. The resulting solid was identified as crystalline Form CC-2H using XRPD, as shown in Tables 46 and Figure 100 shown.

[0805] Table 46: Form CC-2H XRPD Data

[0806]

[0807]

[0808] Example 43: Crystallization of Compound A Adipic Acid Cocrystal (Form CC-II)

[0809] Crystalline Compound A adipic acid co-crystal Form CC-II was prepared by crystallization from adipic acid in acetone / heptane (1:1) at room temperature, wherein the ratio of Compound A to adipic acid co-former was 1:1. Form CC-II was also formed by crystallization from methyl isobutyl ketone or dichloromethane at room temperature. Form CC-II was also formed by slow evaporation from acetonitrile / water (1:1) at room temperature, wherein the molar ratio of Compound A to adipic acid co-former was 1:1. The resulting solid was identified as crystalline Form CC-II using XRPD, as shown in Tables 47 and 48. Figure 102 shown.

[0810] Table 47: Form CC-II XRPD Data

[0811]

[0812]

[0813] Example 44: Crystalline Compound A Methyltetrahydrofuran Solvate (Form 6A)

[0814] Crystalline Compound A methyltetrahydrofuran solvate Form 6A was prepared using the following procedure. Compound A (3.2 g) was added to methyltetrahydrofuran (40 mL) at 20° C. and allowed to equilibrate for 24 hours. Heptane (40 mL) was then added over a 2-hour period and the slurry was allowed to equilibrate for 24 hours. The wet cake was analyzed by XRPD as shown in Table 48.

[0815] Table 48: Form 6A XRPD Data

[0816]

[0817]

[0818] The foregoing description has been given for clearness of understanding only, and no unnecessary limitations should be understood as modifications within the scope of the invention will be apparent to those skilled in the art.

[0819] Throughout this specification and the following claims, unless the context requires otherwise, the word "comprise" and variations such as "comprises" and "comprising" will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

[0820] Unless otherwise indicated, the use of the terms "a / an," "the," and similar references in the context of the disclosure herein (especially in the context of the claims) should be interpreted to encompass both the singular and the plural. Unless otherwise indicated herein, the recitation of ranges of values ​​herein is intended merely to serve as a shorthand method of referring individually to each individual value within the range, and each individual value is incorporated into the specification as if it were individually recited herein. Unless otherwise indicated, the use of any and all examples, or exemplary language (e.g., "such as") provided herein is intended to better illustrate the disclosure herein and is not a limitation on the scope of the disclosure herein. The language in the specification should not be interpreted as indicating that any unclaimed element is necessary to practice the disclosure herein.

Claims

1. A crystalline form of Compound A: (Compound A).

2. The crystalline form of claim 1, wherein Compound A is in the free base form.

3. The crystalline form of claim 1 or 2, as Compound A free base ("Form 1"), characterized in that An X-ray powder diffraction (XRPD) pattern comprising peaks at 4.5, 9.0, 13.3, 16.2, and 18.8 ± 0.2° 2Θ using CuKa radiation.

4. The crystalline form according to claim 1 or 2, wherein The use of CuKα radiation comprises at least three selected from 4.5, 6.7, 9.0, 12.2, 12.5, 12.8, 13.3, 13.7, 14.3, 14.7, 15.7, 16.2, 16.7, 17.4, 17.6, 18.0, 18.4, 18.8, 19.6, 20.0, 20.3, 20.8, 21.2, 21.6, 22. The X-ray powder diffraction (XRPD) pattern of the present invention comprises peaks at 2, 22.5, 23.0, 23.8, 24.1, 24.6, 25.1, 26.2, 26.4, 26.8, 27.8, 28.4, 28.8, 29.7, 30.5, 30.9, 32.7, 34.4, 35.1, 35.6, 36.4, 37.8 and 39.4 ± 0.2 ° 2θ.

5. The crystalline form according to claim 1 or 2, wherein The CuKα radiation comprises at least five selected from 4.5, 6.7, 9.0, 12.2, 12.5, 12.8, 13.3, 13.7, 14.3, 14.7, 15.7, 16.2, 16.7, 17.4, 17.6, 18.0, 18.4, 18.8, 19.6, 20.0, 20.3, 20.8, 21.2, 21.6, 22. The X-ray powder diffraction (XRPD) pattern of the present invention comprises peaks at 2, 22.5, 23.0, 23.8, 24.1, 24.6, 25.1, 26.2, 26.4, 26.8, 27.8, 28.4, 28.8, 29.7, 30.5, 30.9, 32.7, 34.4, 35.1, 35.6, 36.4, 37.8 and 39.4 ± 0.2 ° 2θ.

6. The crystalline form of claim 1 or 2, wherein The CuKα radiation comprises at least seven selected from 4.5, 6.7, 9.0, 12.2, 12.5, 12.8, 13.3, 13.7, 14.3, 14.7, 15.7, 16.2, 16.7, 17.4, 17.6, 18.0, 18.4, 18.8, 19.6, 20.0, 20.3, 20.8, 21.2, 21.6, 22. The X-ray powder diffraction (XRPD) pattern of the present invention comprises peaks at 2, 22.5, 23.0, 23.8, 24.1, 24.6, 25.1, 26.2, 26.4, 26.8, 27.8, 28.4, 28.8, 29.7, 30.5, 30.9, 32.7, 34.4, 35.1, 35.6, 36.4, 37.8 and 39.4 ± 0.2 ° 2θ.

7. The crystalline form of claim 1 or 2, wherein The CuKα radiation comprises at least eight selected from 4.5, 6.7, 9.0, 12.2, 12.5, 12.8, 13.3, 13.7, 14.3, 14.7, 15.7, 16.2, 16.7, 17.4, 17.6, 18.0, 18.4, 18.8, 19.6, 20.0, 20.3, 20.8, 21.2, 21.6, 22. The X-ray powder diffraction (XRPD) pattern of the present invention comprises peaks at 2, 22.5, 23.0, 23.8, 24.1, 24.6, 25.1, 26.2, 26.4, 26.8, 27.8, 28.4, 28.8, 29.7, 30.5, 30.9, 32.7, 34.4, 35.1, 35.6, 36.4, 37.8 and 39.4 ± 0.2 ° 2θ.

8. The crystalline form according to any one of claims 1 to 7, wherein A Differential Scanning Calorimetry (DSC) thermogram comprising an endotherm with an onset at 225°C ± 3°C.

9. The crystalline form according to any one of claims 1 to 8, wherein comprising at least three peaks selected from 39.2, 43.8, 51.6, 58.1, 65.9, 71.8, 73.6, 114.7, 120.8, 125.1, 126.1, 128.2, 130.8, 142.2, 143.3, 145.3, 148.5, 149.2, 156.9, and 169.6 ppm 13 C solid-state NMR.

10. The crystalline form according to any one of claims 1 to 8, wherein comprising at least five peaks selected from 39.2, 43.8, 51.6, 58.1, 65.9, 71.8, 73.6, 114.7, 120.8, 125.1, 126.1, 128.2, 130.8, 142.2, 143.3, 145.3, 148.5, 149.2, 156.9, and 169.6 ppm 13 C solid-state NMR.

11. The crystalline form according to any one of claims 1 to 8, wherein comprising at least seven peaks selected from 39.2, 43.8, 51.6, 58.1, 65.9, 71.8, 73.6, 114.7, 120.8, 125.1, 126.1, 128.2, 130.8, 142.2, 143.3, 145.3, 148.5, 149.2, 156.9, and 169.6 ppm 13 C solid-state NMR.

12. The crystalline form according to any one of claims 1 to 11, wherein Contains peaks at -62.0 and -63.9 ppm 19 F solid-state NMR.

13. A free base of compound A (Amorphous form of Compound A).

14. The amorphous form of claim 13, having a glass transition temperature (Tg) of 119°C ± 3°C.

15. A pharmaceutical composition comprising the crystalline form or amorphous form or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 14, and at least one pharmaceutically acceptable excipient.

16. The pharmaceutical composition according to claim 15, wherein The composition is formulated for oral delivery.

17. The pharmaceutical composition according to claim 15 or 16, wherein The composition is formulated for once-daily administration.

18. The pharmaceutical composition according to any one of claims 15 to 17, wherein The composition is a tablet for oral administration.

19. The pharmaceutical composition of any one of claims 15-18, comprising 1-4000 mg of the crystalline form or amorphous form.

20. The pharmaceutical composition of claim 19, comprising 1-2000 mg of the compound or crystalline form.

21. A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the crystalline form or amorphous form of any one of claims 1 to 14, or a pharmaceutically acceptable salt thereof.

22. The method of claim 21, wherein: The cancer is ovarian cancer, lung cancer, lymphoma, glioblastoma, colon cancer, melanoma, stomach cancer, pancreatic cancer, or bladder cancer.

23. The method of claim 22, wherein: The cancer is non-small cell lung cancer.

24. The method of claim 22, wherein: The cancer is pancreatic cancer.

25. The method of any one of claims 21 to 24, wherein This cancer is an MTAP-deficient cancer.

26. The method of claim 25, wherein: The MTAP-deficient cancer is selected from the group consisting of lung cancer, biliary tract cancer, head and neck squamous cell carcinoma, pancreatic adenocarcinoma, gallbladder cancer, and mesothelioma.

27. The method of claim 26, wherein: The MTAP-deficient cancer is lung cancer.

28. The method of claim 27, wherein: The lung cancer is non-squamous cell lung cancer (NSCLC).

29. The method of any one of claims 21 to 28, wherein The cancer is not a primary brain tumor or lymphoma.

30. The method of any one of claims 21 to 29, wherein The subject does not have or has never had interstitial lung disease or pneumonitis.

31. The method of any one of claims 21 to 30, wherein The crystalline form is crystalline Form 1.

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