Crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile

Abstract

This specification relates to crystalline forms of salt polymorphs of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile, pharmaceutically acceptable compositions containing these crystalline forms, and methods of using these crystalline forms.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority from U.S. Provisional Application No. 63 / 484,604, filed February 13, 2023, the disclosures of each of which are incorporated herein by reference in their entireties. [Technical Field]

[0002] FIELD OF THE INVENTION The present invention relates to salts of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile and specific crystalline forms thereof, methods for preparing the crystalline forms, and pharmaceutical compositions containing the crystalline forms. The crystalline forms are useful for treating and / or preventing diseases and / or conditions associated with cell proliferation, such as cancer. In particular, the crystalline forms exert therapeutic effects as MTA-cooperative inhibitors of protein arginine N-methyltransferase 5 (PRMT5). [Background technology]

[0003] BACKGROUND OF THE INVENTION Protein arginine N-methyltransferase (PRMT5) is a type II arginine methyltransferase that catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to the omega-nitrogen of the guanidino group of L-arginine residues in proteins (omega-monomethylation) and a second methyl group transfer to the other omega-nitrogen to generate symmetric dimethylarginine (sDMA). PRMT5 forms a complex with MEP50 (methylosomal protein 50), which is required for substrate recognition and orientation and for PRMT5-dependent SDMA modification of histone 2A and histone 4 methyltransferase activity (see, e.g., Ho et al. (2013) PLOS ONE 8(8):10.1371 / annotation / e6b5348e-9052-44ab-8f06-90d01dc88fc2).

[0004] Homozygous deletions of p16 / CDKN2a are common in cancer, and these mutations are commonly associated with co-deletions of neighboring genes, including the gene encoding methylthioadenosine phosphorylase (MTAP). It is estimated that approximately 15% of all human cancers harbor homozygous deletions of the MTAP gene (see, e.g., Firestone & Schramm (2017) J. Am. Chem Soc. 139(39):13754-13760. doi:10.1021 / jacs.7b05803. Epub 2017 Sep 20).

[0005] Cells lacking MTAP activity have elevated concentrations of the MTAP substrate methylthioadenosine (MTA), a potent inhibitor of PRMT5. Inhibiting PRMT5 activity reduces its methylation activity and sensitizes cell proliferation to PRMT5 depletion or loss of activity. Thus, loss of MTAP activity reduces the methylation activity of PRMT5 and renders cells selectively dependent on PRMT5 activity.

[0006] Therefore, MTA-cooperative inhibition of PRMT5 activity in MTAP-deficient cancers may have therapeutic benefits for a wide range of cancers. The compounds of the present invention provide therapeutic benefit as MTA-cooperative inhibitors of PRMT5 that negatively regulate the activity of MTA-bound PRMT5 in cells (particularly MTAP-deficient cells), or for treating various forms of MTAP-associated cancers.

[0007] In particular, 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile has been shown to be a potent and selective inhibitor of PRMT5 and to be pharmacologically active. In the present application, crystalline salts of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile, such as sulfate, tosylate, glutamate, fumarate, glycolate, hippurate, and phosphate, have been found to be suitable for use in pharmaceutical compositions.

[0008] (Summary of the Invention) In one aspect, the present disclosure provides a crystalline form of a salt of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile (hereinafter Compound 1), shown below. [ka]

[0009] The salt of Compound 1 may be selected from sulfate, tosylate, glutamate, fumarate, glycolate, hippurate, and phosphate.

[0010] In another aspect, the present disclosure also provides a particular crystalline form of Compound 1 (hereinafter, Form A of the Sulfate Salt). The present disclosure further provides a method for making Form A of the Sulfate Salt. The present disclosure also provides a pharmaceutical composition comprising Form A of the Sulfate Salt and a pharmaceutically acceptable carrier.

[0011] In another aspect, the present disclosure also provides a particular crystalline form of Compound 1 (hereinafter, Form A of the tosylate salt). The present disclosure further provides a method for making Form A of the tosylate salt. The present disclosure also provides a pharmaceutical composition comprising Form A of the tosylate salt and a pharmaceutically acceptable carrier.

[0012] In another aspect, the present disclosure also provides a particular crystalline form of Compound 1 (hereinafter, Form A of the Glutamate Salt). The present disclosure further provides a method for making Form A of the Glutamate Salt. The present disclosure also provides a pharmaceutical composition comprising Form A of the Glutamate Salt and a pharmaceutically acceptable carrier.

[0013] In another aspect, the present disclosure also provides a particular crystalline form of Compound 1 (hereinafter, Form A of the fumarate salt). The present disclosure further provides a method for making Form A of the fumarate salt. The present disclosure also provides a pharmaceutical composition comprising Form A of the fumarate salt and a pharmaceutically acceptable carrier.

[0014] In another aspect, the present disclosure also provides a particular crystalline form of Compound 1 (hereinafter Form B of the fumarate salt). The present disclosure further provides a method for making Form B of the fumarate salt. The present disclosure also provides a pharmaceutical composition comprising Form B of the fumarate salt and a pharmaceutically acceptable carrier.

[0015] In another embodiment, the present disclosure also provides a particular crystalline form of Compound 1 (hereinafter, Form A of the Glycolic Acid Salt). The present disclosure further provides a method for making Form A of the Glycolic Acid Salt. The present disclosure also provides a pharmaceutical composition comprising Form A of the Glycolic Acid Salt and a pharmaceutically acceptable carrier.

[0016] In another embodiment, the present disclosure also provides a particular crystalline form of Compound 1 (hereinafter, Form B of the Glycolic Acid Salt). The present disclosure further provides a method for making Form B of the Glycolic Acid Salt. The present disclosure also provides a pharmaceutical composition comprising Form B of the Glycolic Acid Salt and a pharmaceutically acceptable carrier.

[0017] In another aspect, the present disclosure also provides a particular crystalline form of Compound 1 (hereinafter, Form A of the hippurate salt). The present disclosure further provides a method for making Form A of the hippurate salt. The present disclosure also provides a pharmaceutical composition comprising Form A of the hippurate salt and a pharmaceutically acceptable carrier.

[0018] In another embodiment, the present disclosure also provides a particular crystalline form of Compound 1 (hereinafter, Form A of the Phosphate Salt). The present disclosure further provides a method for making Form A of the Phosphate Salt. The present disclosure also provides a pharmaceutical composition comprising Form A of the Phosphate Salt and a pharmaceutically acceptable carrier.

[0019] The present disclosure further provides a method for treating cancer, comprising administering to a subject in need thereof a crystalline form of Compound 1 or a pharmaceutical composition comprising a crystalline form of Compound 1 disclosed herein. [Brief explanation of the drawings]

[0020] [Figure 1A] FIG. 1A is an X-ray powder diffraction (XRPD) pattern for a solid of sulfate salt Form A of Compound 1. [Figure 2A] FIG. 2A is a differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) overlay for solid Form A of the tosylate salt of Compound 1. [Figure 2B] FIG. 2B is an X-ray powder diffraction (XRPD) pattern for solid Form A of the tosylate salt of Compound 1. [Figure 3A] FIG. 3A is a differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) overlay for solid Form A of the glutamate salt of Compound 1. [Figure 3B] FIG. 3B is an X-ray powder diffraction (XRPD) pattern for solid Form A of the glutamate salt of Compound 1. [Figure 4A] FIG. 4A is a differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) overlay for solid Form A of the fumarate salt of Compound 1. [Figure 4B] FIG. 4B is an X-ray powder diffraction (XRPD) pattern for solid Form A of the fumarate salt of Compound 1. [Figure 4C] FIG. 4C is a differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) overlay for solid Form B of the fumarate salt of Compound 1. [Figure 4D] FIG. 4D is an X-ray powder diffraction (XRPD) pattern for solid Form B of the fumarate salt of Compound 1. [Figure 5A] FIG. 5A is a differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) overlay for solid Form A of the glycolic acid salt of Compound 1. [Figure 5B] FIG. 5B is an X-ray powder diffraction (XRPD) pattern for solid Form A of the glycolic acid salt of Compound 1. [Figure 5C] FIG. 5C is a differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) overlay for solid Form B of the glycolic acid salt of Compound 1. [Figure 5D] FIG. 5D is an X-ray powder diffraction (XRPD) pattern for solid Form B of the glycolic acid salt of Compound 1. [Figure 6A] FIG. 6A is a differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) overlay for solid Form A of the hippuric acid salt of Compound 1. [Figure 6B] FIG. 6B is an X-ray powder diffraction (XRPD) pattern for solid Form A of the hippuric acid salt of Compound 1. [Figure 6C] FIG. 6C is a polarized light microscope (PLM) image of solid Form A of the hippuric acid salt of Compound 1. [Figure 7A] FIG. 7A is a differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) overlay for solid Form A of the phosphate salt of Compound 1. [Figure 7B] FIG. 7B is an X-ray powder diffraction (XRPD) pattern for solid Form A of the phosphate salt of Compound 1. [Figure 8A] FIG. 8A is a powder X-ray diffraction (XRPD) pattern for a solid of the amorphous free base of Compound 1. [Figure 8B] FIG. 8B is a polarized light microscope (PLM) image of the amorphous free base solid of Compound 1. [Figure 8C]FIG. 8C is a differential scanning calorimetry (DSC) thermogram and thermogravimetric analysis (TGA) overlay for the amorphous free base solid of Compound 1. [Figure 8D] FIG. 8D is a proton nuclear magnetic resonance ( 1 H NMR) spectrum of the amorphous free base of Compound 1 in a solid state. Detailed Description of the Invention

[0021] As mentioned above, the present invention provides certain crystalline forms of salts of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile. In various embodiments, the salts can be selected from sulfate, tosylate, glutamate, fumarate, glycolate, hippurate, and phosphate.

[0022] In some embodiments, the present invention also provides Form A of the Sulfate Salt, a specific crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile sulfate.

[0023] In some embodiments, the present invention also provides Form A of the tosylate salt, a specific crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate.

[0024] In some embodiments, the present invention also provides Form A of the glutamate salt, i.e., a specific crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate.

[0025] In some embodiments, the present invention also provides Form A of the Fumarate Salt, a specific crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate.

[0026] In some embodiments, the present invention also provides Form B of the Fumarate Salt, a specific crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate.

[0027] In some embodiments, the present invention also provides Form A of the glycolate salt, a particular crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate.

[0028] In some embodiments, the present invention also provides Form B of the glycolate salt, a particular crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate.

[0029] In some embodiments, the present invention also provides Form A of the hippurate salt, a specific crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate.

[0030] In some embodiments, the present invention also provides Form A of the Phosphate Salt, i.e., a particular crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate.

[0031] Crystalline forms as described herein can be identified by numerous methods known to those skilled in the art, such as thermal analysis [e.g., differential scanning calorimetry (DSC), thermogravimetric analysis (TGA)], powder X-ray diffraction (XRPD), microscopy (e.g., scanning electron microscopy (SEM), polarized light microscopy (PLM)), and spectroscopy [e.g., infrared, Raman, solid-state nuclear magnetic resonance, and proton nuclear magnetic resonance ( 1 The purity of the crystalline forms provided herein can be determined by standard analytical methods, such as thin layer chromatography (TLC), gel electrophoresis, gas chromatography, high performance liquid chromatography (HPLC) and mass spectrometry (MS).

[0032] Sulfate Form A In one embodiment, the disclosure provides a crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile sulfate, i.e., Form A of the Sulfate Salt. In various embodiments, Form A of the Sulfate Salt has an X-ray powder diffraction (XRPD) pattern. In some embodiments, Form A of the Sulfate Salt has an XRPD pattern including a peak at a 2θ angle of 6.6°±0.2°. In some embodiments, Form A of the Sulfate Salt has an XRPD pattern including a peak at a 2θ angle of 10.9°±0.2°. In some embodiments, Form A of the Sulfate Salt has an XRPD pattern including a peak at a 2θ angle of 20.4°±0.2°. In some embodiments, Form A of the Sulfate Salt has an XRPD pattern including a peak at a 2θ angle of 22.9°±0.2°. In some embodiments, Form A of the Sulfate Salt has an XRPD pattern comprising peaks at 2θ angles of 6.6°±0.2°, 10.9°±0.2°, 20.4°±0.2°, and 22.9°±0.2°. For example, in some embodiments, Form A of the Sulfate Salt has an XRPD pattern substantially as shown in FIG. 1A.

[0033] In some embodiments described herein, Form A of the Sulfate Salt has a purity of at least 97% by weight 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile sulfate. In some embodiments, Form A of the Sulfate Salt has a purity of at least 98% by weight 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile sulfate.

[0034] Tosylate Form A Another embodiment described herein, this disclosure provides a crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate, i.e., Form A of the tosylate salt. In various embodiments, Form A of the tosylate salt has a differential scanning calorimetry (DSC) thermogram. In various embodiments, the DSC thermogram includes both an exothermic peak and an endothermic peak. In some embodiments, Form A of the tosylate salt has an endothermic DSC peak temperature of about 55° C. (e.g., within about 55° C. ± 2%). In some embodiments, Form A of the tosylate salt has an endothermic DSC peak temperature within 55° C. ± 1% or within 55° C. ± 0.5%. In some embodiments, Form A of the tosylate salt has an endothermic DSC peak temperature of about 163°C (e.g., within about 2% of 163°C). In some embodiments, Form A of the tosylate salt has an endothermic DSC peak temperature of about 163°C ± 1% or within 0.5% of 163°C. In some embodiments, Form A of the tosylate salt has an endothermic DSC peak temperature of about 247°C (e.g., within about 247°C ± 2%). In some embodiments, Form A of the tosylate salt has an endothermic DSC peak temperature of about 247°C ± 1% or within 0.5% of 247°C. In various embodiments, Form A of the tosylate salt has a DSC thermogram with peak temperatures at about 55°C (e.g., within 55°C ± 2%, within 55°C ± 1%, or within 55°C ± 0.5%), about 163°C (e.g., within 163°C ± 2%, within 163°C ± 1%, or within 163°C ± 0.5%), and about 247°C (e.g., within 247°C ± 2%, within 247°C ± 1%, or within 247°C ± 0.5%). For example, in some embodiments, Form A of the tosylate salt has a DSC thermogram substantially as shown in Figure 2A.

[0035] In various embodiments, Form A of the tosylate salt has an X-ray powder diffraction (XRPD) pattern. In some embodiments, Form A of the tosylate salt has an XRPD pattern including a peak at 4.4°±0.2° 2θ. In some embodiments, Form A of the tosylate salt has an XRPD pattern including a peak at 5.2°±0.2° 2θ. In some embodiments, Form A of the tosylate salt has an XRPD pattern including a peak at 8.2°±0.2° 2θ. In some embodiments, Form A of the tosylate salt has an XRPD pattern including a peak at 13.1°±0.2° 2θ. In some embodiments, Form A of the tosylate salt has an XRPD pattern including a peak at 15.9°±0.2° 2θ. In some embodiments, Form A of the tosylate salt has an XRPD pattern including a peak at 16.5°±0.2° 2θ. In some embodiments, Form A of the tosylate salt has an XRPD pattern comprising peaks at 2θ angles of 4.4°±0.2°, 5.2°±0.2°, 8.2°±0.2°, 13.1°±0.2°, 15.9°±0.2°, and 16.5°±0.2°. For example, in some embodiments, Form A of the tosylate salt has an XRPD pattern substantially as shown in Figure 2B. In some embodiments described herein, Form A of the tosylate salt is a hydrate, solvate, or anhydrate.

[0036] In some embodiments described herein, Form A of the tosylate salt has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 2.7% when heated from about 25° C. to about 150° C. For example, in some embodiments, Form A of the tosylate salt has a TGA plot substantially as shown in FIG. 2A.

[0037] In some embodiments described herein, Form A of the tosylate salt has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate. In some embodiments, Form A of the tosylate salt has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate.

[0038] Glutamate Form A Another embodiment described herein, this disclosure provides a crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate, i.e., Form A of the glutamate salt. In various embodiments, Form A of the glutamate salt has a differential scanning calorimetry (DSC) thermogram. In various embodiments, the DSC thermogram includes an endothermic peak. In some embodiments, Form A of the glutamate salt has an endothermic DSC peak temperature of about 51°C (e.g., within about 51°C ± 2%). In some embodiments, Form A of the glutamate salt has an endothermic DSC peak temperature within 51°C ± 1% or within 51°C ± 0.5%. In some embodiments, Form A of the glutamate salt has an endothermic DSC peak temperature of about 94°C (e.g., within about 94°C ± 2%). In some embodiments, Form A of the glutamate salt has an endothermic DSC peak temperature within 94°C ± 1% or within 94°C ± 0.5%. In some embodiments, Form A of the glutamate salt has an endothermic DSC peak temperature of about 174°C (e.g., within 174°C ± 2%). In some embodiments, Form A of the glutamate salt has an endothermic DSC peak temperature within 174°C ± 1% or within 174°C ± 0.5%. In some embodiments, Form A of the glutamate salt has peak temperatures in a DSC thermogram at about 51°C (e.g., within about 51°C ± 2%, about 51°C ± 1%, or about 51°C ± 0.5%), about 94°C (e.g., within about 94°C ± 2%, about 94°C ± 1%, or about 94°C ± 0.5%), and about 174°C (e.g., within about 174°C ± 2%, about 174°C ± 1%, or about 174°C ± 0.5%). For example, in some embodiments, Form A of the glutamate salt has a DSC thermogram substantially as shown in Figure 3A.

[0039] In various embodiments, Form A of the Glutamate Salt has an X-ray powder diffraction (XRPD) pattern. In some embodiments, Form A of the Glutamate Salt has an XRPD pattern including a peak at a 2θ angle of 9.9°±0.2°. In some embodiments, Form A of the Glutamate Salt has an XRPD pattern including a peak at a 2θ angle of 14.3°±0.2°. In some embodiments, Form A of the Glutamate Salt has an XRPD pattern including a peak at a 2θ angle of 16.9°±0.2°. In some embodiments, Form A of the Glutamate Salt has an XRPD pattern including a peak at a 2θ angle of 22.4°±0.2°. In some embodiments, Form A of the Glutamate Salt has an XRPD pattern including a peak at a 2θ angle of 24.6°±0.2°. In some embodiments, Form A of the Glutamate Salt has an XRPD pattern including a peak at a 2θ angle of 25.2°±0.2°. In some embodiments, Form A of the glutamate salt has an XRPD pattern comprising peaks at 2θ angles of 9.9°±0.2°, 14.3°±0.2°, 16.9°±0.2°, 22.4°±0.2°, 24.6°±0.2°, and 25.2°±0.2°. For example, in some embodiments, Form A of the glutamate salt has an XRPD pattern substantially as shown in Figure 3B. In some embodiments described herein, Form A of the glutamate salt is a hydrate or solvate.

[0040] In some embodiments described herein, Form A of the glutamate salt has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 6.5% when heated from about 25° C. to about 150° C. For example, in some embodiments, Form A of the glutamate salt has a TGA plot substantially as shown in FIG.

[0041] In some embodiments described herein, Form A of the glutamate salt has a purity of at least 97% by weight 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate. In some embodiments, Form A of the glutamate salt has a purity of at least 98% by weight 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate.

[0042] Fumarate Form A Another embodiment described herein, this disclosure provides a crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate, i.e., Form A of the fumarate salt. In various embodiments, Form A of the fumarate salt exhibits a differential scanning calorimetry (DSC) thermogram. In various embodiments, the DSC thermogram includes an endothermic peak. In some embodiments, Form A of the fumarate salt has an endothermic DSC peak temperature of about 36°C (e.g., within about 36°C ± 2%). In some embodiments, Form A of the fumarate salt has an endothermic DSC peak temperature within 36°C ± 1% or within 36°C ± 0.5%. In some embodiments, Form A of the fumarate salt has an endothermic DSC peak temperature of about 256°C (e.g., within about 256°C ± 2%). In some embodiments, Form A of the fumarate salt has an endothermic DSC peak temperature within 256°C ± 1% or within 256°C ± 0.5%. In various embodiments, Form A of the fumarate salt has a DSC thermogram with endothermic peak temperatures of about 36°C (e.g., within about 36°C ± 2%, about 36°C ± 1%, or about 36°C ± 0.5%) and about 256°C (e.g., within about 256°C ± 2%, about 256°C ± 1%, or about 256°C ± 0.5%). For example, in some embodiments, Form A of the fumarate salt has a DSC thermogram substantially as shown in Figure 4A.

[0043] In various embodiments, Form A of the fumarate salt has an X-ray powder diffraction (XRPD) pattern. In some embodiments, Form A of the fumarate salt has an XRPD pattern including a peak at 4.3°±0.2° 2θ. In some embodiments, Form A of the fumarate salt has an XRPD pattern including a peak at 6.0°±0.2° 2θ. In some embodiments, Form A of the fumarate salt has an XRPD pattern including a peak at 9.8°±0.2° 2θ. In some embodiments, Form A of the fumarate salt has an XRPD pattern including a peak at 19.6°±0.2° 2θ. In some embodiments, Form A of the fumarate salt has an XRPD pattern including a peak at 25.0°±0.2° 2θ. In some embodiments, Form A of the fumarate salt has an XRPD pattern comprising peaks at 2θ angles of 4.3°±0.2°, 6.0°±0.2°, 9.8°±0.2°, 19.6°±0.2°, and 25.0°±0.2°. For example, in some embodiments, Form A of the fumarate salt has an XRPD pattern substantially as shown in Figure 4B. In some embodiments described herein, Form A of the fumarate salt is a hydrate or solvate.

[0044] In some embodiments described herein, Form A of the fumarate salt has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 7.0% when heated from about 25° C. to about 150° C. For example, in some embodiments, Form A of the fumarate salt has a TGA plot substantially as shown in FIG.

[0045] In some embodiments described herein, Form A of the fumarate salt has a purity of at least 97% by weight 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate. In some embodiments, Form A of the fumarate salt has a purity of at least 98% by weight 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate.

[0046] Fumarate Form B

[0010] Another embodiment described herein, this disclosure provides a crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate, i.e., Form B of the fumarate salt. In various embodiments, Form B of the fumarate salt has a differential scanning calorimetry (DSC) thermogram. In various embodiments, the DSC thermogram includes an endothermic peak. In some embodiments, Form B of the fumarate salt has an endothermic DSC peak temperature of about 259°C (e.g., within about 259°C ± 2%). In some embodiments, Form B of the fumarate salt has an endothermic DSC peak temperature within 259°C ± 1% or within 259°C ± 0.5%. For example, in some embodiments, Form B of the fumarate salt has a DSC thermogram substantially as shown in Figure 4C.

[0047] In various embodiments, Form B of the fumarate salt has an X-ray powder diffraction (XRPD) pattern. In some embodiments, Form B of the fumarate salt has an XRPD pattern including a peak at a 2θ angle of 3.6°±0.2°. In some embodiments, Form B of the fumarate salt has an XRPD pattern including a peak at a 2θ angle of 14.3°±0.2°. In some embodiments, Form B of the fumarate salt has an XRPD pattern including a peak at a 2θ angle of 20.6°±0.2°. In some embodiments, Form B of the fumarate salt has an XRPD pattern including a peak at a 2θ angle of 23.7°±0.2°. In some embodiments, Form B of the fumarate salt has an XRPD pattern including a peak at a 2θ angle of 25.3°±0.2°. In some embodiments, Form B of the fumarate salt has an XRPD pattern including a peak at a 2θ angle of 26.9°±0.2°. In some embodiments, Form B of the fumarate salt has an XRPD pattern comprising peaks at 2θ angles of 3.6°±0.2°, 14.3°±0.2°, 20.6°±0.2°, 23.7°±0.2°, 25.3°±0.2°, and 26.9°±0.2°. For example, in some embodiments, Form B of the fumarate salt has an XRPD pattern substantially as shown in Figure 4D. In some embodiments described herein, Form B of the fumarate salt is a hydrate or solvate.

[0048] In some embodiments described herein, Form B of the fumarate salt has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 3.9% when heated from about 25° C. to about 150° C. For example, in some embodiments, Form B of the fumarate salt has a TGA plot substantially as shown in FIG.

[0049] In some embodiments described herein, Form B of the fumarate salt has a purity of at least 97% by weight 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate. In some embodiments, Form B of the fumarate salt has a purity of at least 98% by weight 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate.

[0050] Glycolate salt form A Another embodiment of the disclosure described herein provides a crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate, i.e., Form A of the Glycolate Salt. In various embodiments, Form A of the Glycolate Salt has a differential scanning calorimetry (DSC) thermogram. In various embodiments, the DSC thermogram includes both an endothermic peak and an exothermic peak. In some embodiments, Form A of the Glycolate Salt has an endothermic DSC peak temperature of about 36°C (e.g., within about 36°C ± 2%). In some embodiments, Form A of the Glycolate Salt has an endothermic DSC peak temperature within 36°C ± 1% or within 36°C ± 0.5%. In some embodiments, Form A of the Glycolate Salt has an exothermic DSC peak temperature of about 119°C (e.g., within about 119°C ± 2%). In some embodiments, Form A of the Glycolic Acid Salt has an exothermic DSC peak temperature within 119°C ± 1% or within 119°C ± 0.5%. In some embodiments, it has an exothermic DSC peak temperature of about 161°C (e.g., within about 161°C ± 2%). In some embodiments, Form A of the Glycolic Acid Salt has an exothermic DSC peak temperature within 161°C ± 1% or within 161°C ± 0.5%. In some embodiments, Form A of the Glycolic Acid Salt has an endothermic DSC peak temperature of about 253°C (e.g., within about 253°C ± 2%). In some embodiments, Form A of the Glycolic Acid Salt has an endothermic DSC peak temperature within 253°C ± 1% or within 253°C ± 0.5%. In various embodiments, Form A of the glycolate salt has peak temperatures in a DSC thermogram at about 36°C (e.g., within about 36°C ± 2%, about 36°C ± 1%, or about 36°C ± 0.5%), about 119°C (e.g., within 119°C ± 2%, 119°C ± 1%, or 119°C ± 0.5%), about 161°C (e.g., within 161°C ± 2%, 161°C ± 1%, or 161°C ± 0.5%), and about 253°C (e.g., within 253°C ± 2%, 253°C ± 1%, or 253°C ± 0.5%).For example, in some embodiments, Form A of the glycolate salt has a DSC thermogram substantially as shown in FIG. 5A.

[0051] In various embodiments, Form A of the Glycolic Acid Salt has an X-ray powder diffraction (XRPD) pattern. In some embodiments, Form A of the Glycolic Acid Salt has an XRPD pattern including a peak at a 2θ angle of 9.8°±0.2°. In some embodiments, Form A of the Glycolic Acid Salt has an XRPD pattern including a peak at a 2θ angle of 15.3°±0.2°. In some embodiments, Form A of the Glycolic Acid Salt has an XRPD pattern including a peak at a 2θ angle of 16.1°±0.2°. In some embodiments, Form A of the Glycolic Acid Salt has an XRPD pattern including a peak at a 2θ angle of 25.0°±0.2°. In some embodiments, Form A of the Glycolic Acid Salt has an XRPD pattern including peaks at 2θ angles of 9.8°±0.2°, 15.3°±0.2°, 16.1°±0.2°, and 25.0°±0.2°. For example, in some embodiments, Form A of the Glycolic Acid Salt has an XRPD pattern substantially as shown in FIG. 5B. In some embodiments described herein, Form A of the glycolate salt is a hydrate or solvate.

[0052] In some embodiments described herein, Form A of the Glycolic Acid Salt has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 2.1% when heated from about 25° C. to about 150° C. For example, in some embodiments, Form A of the Glycolic Acid Salt has a TGA plot substantially as shown in FIG. 5A.

[0053] In some embodiments described herein, Form A of the glycolate salt has a purity of at least 97% by weight 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate. In some embodiments, Form A of the glycolate salt has a purity of at least 98% by weight 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate.

[0054] Glycolate salt form B Another embodiment of the disclosure described herein provides a crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate, i.e., Form B of the Glycolate Salt. In various embodiments, Form B of the Glycolate Salt has a differential scanning calorimetry (DSC) thermogram. In various embodiments, the DSC thermogram includes both an endothermic peak and an exothermic peak. In some embodiments, Form B of the Glycolate Salt has an endothermic DSC peak temperature of about 56°C (e.g., within about 56°C ± 2%). In some embodiments, Form B of the Glycolate Salt has an endothermic DSC peak temperature of about 56°C ± 1% or within 56°C ± 0.5%. In some embodiments, Form B of the Glycolate Salt has an endothermic DSC peak temperature of about 138°C (e.g., within about 138°C ± 2%). In some embodiments, Form B of the Glycolic Acid Salt has an endothermic DSC peak temperature within 138°C ± 1% or within 138°C ± 0.5%. In some embodiments, Form B of the Glycolic Acid Salt has an exothermic DSC peak temperature of about 259°C (e.g., within about 259°C ± 2%). In some embodiments, Form B of the Glycolic Acid Salt has an exothermic DSC peak temperature within 259°C ± 1% or within 259°C ± 0.5%. In various embodiments, Form B of the Glycolic Acid Salt has peak temperatures in a DSC thermogram at about 56°C (e.g., within about 56°C ± 2%, about 56°C ± 1%, or about 56°C ± 0.5%), about 138°C (e.g., within 138°C ± 2%, 138°C ± 1%, or 138°C ± 0.5%), and about 259°C (e.g., within 259°C ± 2%, 259°C ± 1%, or 259°C ± 0.5%). For example, in some embodiments, Form B of the glycolate salt has a DSC thermogram substantially as shown in Figure 5C.

[0055] In various embodiments, Form B of the Glycolic Acid Salt has an X-ray powder diffraction (XRPD) pattern. In some embodiments, Form B of the Glycolic Acid Salt has an XRPD pattern including a peak at a 2θ angle of 2.9°±0.2°. In some embodiments, Form B of the Glycolic Acid Salt has an XRPD pattern including a peak at a 2θ angle of 5.8°±0.2°. In some embodiments, Form B of the Glycolic Acid Salt has an XRPD pattern including a peak at a 2θ angle of 8.4°±0.2°. In some embodiments, Form B of the Glycolic Acid Salt has an XRPD pattern including a peak at a 2θ angle of 10.2°±0.2°. In some embodiments, Form B of the Glycolic Acid Salt has an XRPD pattern including a peak at a 2θ angle of 27.0°±0.2°. In some embodiments, Form B of the Glycolic Acid Salt has an XRPD pattern comprising peaks at 2θ angles of 2.9°±0.2°, 5.8°±0.2°, 8.4°±0.2°, 10.2°±0.2°, and 27.0°±0.2°. For example, in some embodiments, Form B of the Glycolic Acid Salt has an XRPD pattern substantially as shown in Figure 5D. In some embodiments described herein, Form B of the Glycolic Acid Salt is a hydrate, solvate, or anhydrous.

[0056] In some embodiments described herein, Form B of the Glycolic Acid Salt has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 1.3% when heated from about 25° C. to about 150° C. For example, in some embodiments, Form B of the Glycolic Acid Salt has a TGA plot substantially as shown in FIG. 5C.

[0057] In some embodiments described herein, Form B of the glycolate salt has a purity of at least 97% by weight 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate. In some embodiments, Form B of the glycolate salt has a purity of at least 98% by weight 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate.

[0058] Hippurate Form A Another embodiment described herein, this disclosure provides a crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate, i.e., Form A of the hippurate salt. In various embodiments, Form A of the hippurate salt has a differential scanning calorimetry (DSC) thermogram. In various embodiments, the DSC thermogram has an endothermic peak. In some embodiments, Form A of the hippurate salt has an endothermic DSC peak temperature of about 36°C (e.g., within about 36°C ± 2%). In some embodiments, Form A of the hippurate salt has an endothermic DSC peak temperature of about 36°C ± 1% or within 36°C ± 0.5%. In some embodiments, Form A of the hippurate salt has an endothermic DSC peak temperature of about 177°C (e.g., within about 177°C ± 2%). In some embodiments, Form A of the hippurate salt has an endothermic DSC peak temperature within 177°C ± 1% or within 177°C ± 0.5%. In some embodiments, Form A of the hippurate salt has an endothermic DSC peak temperature of about 208°C (e.g., within 208°C ± 2%). In some embodiments, Form A of the hippurate salt has an endothermic DSC peak temperature within 208°C ± 1% or within 208°C ± 0.5%. In various embodiments, Form A of the hippurate salt has endothermic DSC peak temperatures of about 36°C (e.g., within about 36°C ± 2%, about 36°C ± 1%, or about 36°C ± 0.5%), about 177°C (e.g., within about 177°C ± 2%, about 177°C ± 1%, or about 177°C ± 0.5%), and about 208°C (e.g., within about 208°C ± 2%, about 208°C ± 1%, or about 208°C ± 0.5%). For example, in some embodiments, Form A of the hippurate salt has a DSC thermogram substantially as shown in Figure 6A.

[0059] In various embodiments, Form A of the hippuric acid salt has an X-ray powder diffraction (XRPD) pattern. In some embodiments, Form A of the hippuric acid salt has an XRPD pattern including a peak at a 2θ angle of 3.2°±0.2°. In some embodiments, Form A of the hippuric acid salt has an XRPD pattern including a peak at a 2θ angle of 19.1°±0.2°. In some embodiments, Form A of the hippuric acid salt has an XRPD pattern including a peak at a 2θ angle of 20.8°±0.2°. In some embodiments, Form A of the hippuric acid salt has an XRPD pattern including a peak at a 2θ angle of 27.4°±0.2°. In some embodiments, Form A of the hippuric acid salt has an XRPD pattern including peaks at 2θ angles of 3.2°±0.2°, 19.1°±0.2°, 20.8°±0.2°, and 27.4°±0.2°. For example, in some embodiments, Form A of the hippuric acid salt has an XRPD pattern substantially as shown in FIG. 6B. In some embodiments described herein, Form B of the hippurate salt is a hydrate, solvate, or anhydrous.

[0060] In some embodiments described herein, Form A of the hippurate salt has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 2.7% when heated from about 25° C. to about 150° C. For example, in some embodiments, Form A of the hippurate salt has a TGA plot substantially as shown in FIG.

[0061] In some embodiments described herein, Form A of the hippurate salt has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate. In some embodiments, Form A of the hippurate salt has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate.

[0062] Phosphate Form A Another embodiment of the disclosure described herein provides a crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate, i.e., Form A of the phosphate salt. In various embodiments, Form A of the phosphate salt has a differential scanning calorimetry (DSC) thermogram. In various embodiments, the DSC thermogram includes an endothermic peak. In some embodiments, Form A of the phosphate salt has an endothermic DSC peak temperature of about 36°C (e.g., within about 36°C ± 2%). In some embodiments, Form A of the phosphate salt has an endothermic DSC peak temperature within 36°C ± 1% or within 36°C ± 0.5%. In some embodiments, Form A of the phosphate salt has an endothermic DSC peak temperature of about 82°C (e.g., within about 82°C ± 2%). In some embodiments, Form A of the phosphate salt has an endothermic DSC peak temperature within 82°C ± 1% or within 82°C ± 0.5%. In some embodiments, Form A of the phosphate salt has an endothermic DSC peak temperature of about 162°C (e.g., within about 162°C ± 2%). In some embodiments, Form A of the phosphate salt has an endothermic DSC peak temperature within 162°C ± 1% or within 162°C ± 0.5%. In various embodiments, Form A of the phosphate salt has peak temperatures in a DSC thermogram at about 36°C (e.g., within about 36°C ± 2%, about 36°C ± 1%, or about 36°C ± 0.5%), about 82°C (e.g., within 82°C ± 2%, 82°C ± 1%, or 82°C ± 0.5%), and about 162°C (e.g., within 162°C ± 2%, 162°C ± 1%, or 162°C ± 0.5%). For example, in some embodiments, Form A of the Phosphate Salt has a DSC thermogram substantially as shown in Figure 7A.

[0063] In various embodiments, Form A of the phosphate salt has an X-ray powder diffraction (XRPD) pattern. In some embodiments, Form A of the phosphate salt has an XRPD pattern including a peak at a 2θ angle of 6.6°±0.2°. In some embodiments, Form A of the phosphate salt has an XRPD pattern including a peak at a 2θ angle of 17.0°±0.2°. In some embodiments, Form A of the phosphate salt has an XRPD pattern including a peak at a 2θ angle of 18.9°±0.2°. In some embodiments, Form A of the phosphate salt has an XRPD pattern including a peak at a 2θ angle of 20.4°±0.2°. In some embodiments, Form A of the phosphate salt has an XRPD pattern including a peak at a 2θ angle of 22.9°±0.2°. In some embodiments, Form A of the Phosphate Salt has an XRPD pattern comprising peaks at 2θ angles of 6.6°±0.2°, 17.0°±0.2°, 18.9°±0.2°, 20.4°±0.2°, and 22.9°±0.2°. For example, in some embodiments, Form A of the Phosphate Salt has an XRPD pattern substantially as shown in Figure 7B. In some embodiments described herein, Form A of the Phosphate Salt is a hydrate or solvate.

[0064] In some embodiments described herein, Form A of the Phosphate Salt has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 2.2% when heated from about 25° C. to about 150° C. For example, in some embodiments, Form A of the Phosphate Salt has a TGA plot substantially as shown in FIG.

[0065] In some embodiments described herein, Form A of the Phosphate Salt has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate. In some embodiments, Form A of the Phosphate Salt has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate.

[0066] Methods for preparing crystalline forms of Compound 1 In another aspect, the disclosure provides methods of preparing crystalline forms of Compound 1 (e.g., sulfate Form A, tosylate Form A, glutamate Form A, fumarate Form A, fumarate Form B, glycolate Form A, glycolate Form B, hippurate Form A, and phosphate Form A). The sulfate Form A, tosylate Form A, glutamate Form A, fumarate Form A, fumarate Form B, glycolate Form A, glycolate Form B, hippurate Form A, and phosphate Form A crystalline forms can be prepared by various methods known to those of skill in the art, as discussed in the Examples below. For example, the crystalline forms described herein may be prepared by a slurry process.

[0067] In various embodiments, the slurry process can be carried out at various temperatures and using various solvents. For example, in some embodiments, the slurry process is carried out at room temperature or at an elevated temperature (e.g., 50°C). To produce a crystalline form using the slurry process, the amorphous free base of Compound 1 is suspended in a solvent with a corresponding acid (e.g., sulfuric acid, toluenesulfonic acid, glutamic acid, fumaric acid, glycolic acid, hippuric acid, and phosphoric acid) at a certain temperature (e.g., room temperature or an elevated temperature) and stirred to obtain a solid. In various embodiments, to provide a crystalline form as disclosed herein, about 30 mg of the amorphous free base of Compound 1 and about 30 mg of the corresponding acid can be combined in about 0.1 to 5 mL of solvent (based on approximate solubility) to achieve a molar charge ratio of 1:1. The solvent can be selected from methanol (MeOH), tetrahydrofuran (THF), ethyl acetate (EtOAc), or acetone / water (1:1, v / v). The mixture may be stirred (e.g., magnetically) for at least 24 hours (e.g., at least 48 hours, at least 72 hours, or at least 96 hours). In some embodiments, the mixture is stirred at room temperature for at least 96 hours (i.e., 4 days). The precipitate that forms may be isolated by centrifugation or another solid-liquid separation technique known in the art. In some embodiments, if no precipitate is observed after 4 days at room temperature, the mixture may be stirred at 5°C for 24 hours. In some embodiments, if no solids are still observed, the mixture may be allowed to slowly evaporate at room temperature for 4 days. In various embodiments, the isolated solids may be allowed to air dry under ambient conditions.

[0068] In some embodiments, a slurry method can be used to obtain Form A of the Sulfate Salt. When using a slurry method, the solvent can be THF and the acid can be sulfuric acid.

[0069] In some embodiments, a slurry method can be used to obtain the tosylate salt Form A. When using the slurry method, the solvent can be THF or EtOAc and the acid can be toluenesulfonic acid.

[0070] In some embodiments, a slurry method can be used to obtain glutamic acid salt Form A. When using the slurry method, the solvent can be acetone / water (1:1, v / v) and the acid can be glutamic acid.

[0071] In some embodiments, a slurry method can be used to obtain Form A of the fumarate salt. When using the slurry method, the solvent can be THF and the acid can be fumaric acid.

[0072] In some embodiments, a slurry method can be used to obtain the fumarate salt Form B. When using the slurry method, the solvent can be acetone / water (1:1, v / v) and the acid can be fumaric acid.

[0073] In some embodiments, a slurry method can be used to obtain the glycolate salt Form A. When using a slurry method, the solvent can be THF and the acid can be glycolic acid.

[0074] In some embodiments, a slurry method can be used to obtain the glycolate salt Form B. When using a slurry method, the solvent can be MeOH and the acid can be glycolic acid.

[0075] In some embodiments, a slurry method can be used to obtain the hippuric acid salt Form A. When using the slurry method, the solvent can be THF and the acid can be hippuric acid.

[0076] In some embodiments, a slurry method can be used to obtain Form A of the Phosphate Salt. When using a slurry method, the solvent can be MeOH and the acid can be phosphoric acid.

[0077] Pharmaceutical Composition In another aspect, the present disclosure provides pharmaceutical compositions comprising a crystalline form of Compound 1 (e.g., sulfate Form A, tosylate Form A, glutamate Form A, fumarate Form A, fumarate Form B, glycolate Form A, glycolate Form B, hippurate Form A, and phosphate Form A) and a suitable carrier, excipient, or diluent. The exact nature of the carrier, excipient, or diluent will vary depending on the desired use of the composition and may be suitable or acceptable for a range of uses, from veterinary to human. The present compositions may optionally include one or more additional compounds. In certain embodiments, the compositions may include one or more antibiotics. In another aspect, the present disclosure provides pharmaceutical compositions comprising sulfate Form A and a pharmaceutically acceptable carrier. In another aspect, the present disclosure provides pharmaceutical compositions comprising tosylate Form A and a pharmaceutically acceptable carrier. In another aspect, the present disclosure provides pharmaceutical compositions comprising glutamate Form A and a pharmaceutically acceptable carrier. In another embodiment, the present disclosure provides a pharmaceutical composition comprising Form A of the fumarate salt and a pharmaceutically acceptable carrier. In another embodiment, the present disclosure provides a pharmaceutical composition comprising Form B of the fumarate salt and a pharmaceutically acceptable carrier. In another embodiment, the present disclosure provides a pharmaceutical composition comprising Form A of the glycolate salt and a pharmaceutically acceptable carrier. In another embodiment, the present disclosure provides a pharmaceutical composition comprising Form B of the glycolate salt and a pharmaceutically acceptable carrier. In another embodiment, the present disclosure provides a pharmaceutical composition comprising Form A of the hippurate salt and a pharmaceutically acceptable carrier. In another embodiment, the present disclosure provides a pharmaceutical composition comprising Form A of the phosphate salt and a pharmaceutically acceptable carrier.

[0078] When used to treat or prevent the above-described diseases, Compound 1 described herein can be administered alone, as a mixture of one or more compounds, or as a mixture or combination with other drugs useful for treating the above-described diseases and / or symptoms associated with the above-described diseases. The compound can also be administered in combination with or in admixture with drugs useful for treating other disorders or diseases, such as steroids, membrane stabilizers, 5LO inhibitors, leukotriene synthesis inhibitors and receptor inhibitors, inhibitors of IgE isotype switching or IgE synthesis, β-agonists, tryptase inhibitors, aspirin, COX inhibitors, methotrexate, anti-TNF drugs, retuxin, PD4 inhibitors, p38 inhibitors, PDE4 inhibitors, and antihistamines. Compound 1 can be administered in the crystalline form described herein or as a pharmaceutical composition comprising the crystalline form described herein.

[0079] Pharmaceutical compositions containing various crystalline forms of Compound 1 can be prepared by conventional mixing, dissolving, granulating, sugar-coating, pulverizing, emulsifying, encapsulating, entrapping, or lyophilizing processes. The compositions may be formulated by conventional methods using one or more physiologically acceptable carriers, diluents, excipients, or adjuvants to facilitate processing of the compound into pharmaceutically usable preparations.

[0080] Pharmaceutical compositions can be in a form suitable for virtually any mode of administration (e.g., topical, ophthalmic, oral, buccal, systemic, nasal, injectable, transdermal, rectal, vaginal, etc.) or by administration by inhalation or insufflation.

[0081] For topical administration, the compounds may be formulated as solutions, gels, ointments, creams, suspensions, etc., as are well known in the art. Systemic formulations include formulations designed for administration by injection, e.g., subcutaneous, intravenous, intramuscular, intrathecal, or intraperitoneal injection, as well as formulations designed for transdermal, transmucosal oral, or pulmonary administration.

[0082] Useful injection preparations include sterile suspensions, solutions, or emulsions of the active compound in aqueous or oily vehicles. The compositions may also contain compounding agents such as suspending agents, stabilizing agents, and / or dispersing agents. The injection preparations may be in unit dosage forms, such as ampoules or multi-dose containers, and may contain additional preservatives. Alternatively, the injection preparations may be provided in powder form, for dissolving in a suitable vehicle (including, but not limited to, sterile pyrogen-free water, buffer, glucose solution, etc.) before use. For this purpose, the active compound can be dried using techniques known in the art, such as lyophilization, and then dissolved before use.

[0083] For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are known in the art.

[0084] For oral administration, the pharmaceutical compositions may be in the form of lozenges, tablets, or capsules prepared by conventional techniques with pharmaceutically acceptable excipients such as binders (e.g., pregelatinized corn starch, polyvinylpyrrolidone, or hydroxypropylmethylcellulose); fillers (e.g., lactose, microcrystalline cellulose, calcium hydrogen phosphate); lubricants (e.g., magnesium stearate, talc, or silica); disintegrants (e.g., potato starch or sodium starch glycolate); or wetting agents (e.g., sodium lauryl sulfate). Tablets may be coated by methods well known in the art, such as with sugars, films, or enteric coatings.

[0085] Liquid preparations for oral administration may be in the form of, for example, elixirs, solutions, syrups, or suspensions, or may be presented as a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations can be prepared by conventional means using pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, cellulose derivatives, or hydrogenated edible fats and oils); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol, Cremophor®, or fractionated vegetable oils); and preservatives (e.g., methyl or propyl p-hydroxybenzoates or sorbic acid). The preparations may also contain buffer salts, preservatives, flavoring agents, coloring agents, and sweeteners, as desired.

[0086] As is well known, the preparation for oral administration can be appropriately formulated to control the release of compound.For oral administration, composition can be in the form of tablets or lozenges that are formulated by conventional methods.For rectal and vaginal administration, compound can be formulated as a solution (for enemas) suppository or ointment that contains conventional suppository bases such as cocoa butter or other glycerides.

[0087] For nasal administration or administration by inhalation or insufflation, the compounds can be conveniently delivered in the form of an aerosol spray from a pressurized pack or nebulizer using a suitable propellant (e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, fluorocarbons, carbon dioxide or other suitable gas). In the case of a pressurized aerosol, the dosage unit can be determined by providing a valve that delivers a metered amount. Capsules and cartridges (e.g., capsules and cartridges made of gelatin) for use in an inhaler or insufflator can be formulated containing a powder mix of the compound and a suitable powder base, such as lactose or starch.

[0088] When administered to the eye, the compounds may be formulated as solutions, emulsions, suspensions, etc. suitable for administration to the eye. A variety of vehicles suitable for administering compounds to the eye are known in the art.

[0089] For long-term delivery, the compound can be formulated as a depot preparation and administered by implantation or intramuscular injection.The compound(s) can be formulated with suitable polymer or hydrophobic material (for example, emulsion in acceptable oil) or ion exchange resin, or as a poorly soluble derivative (for example, as a poorly soluble salt).Alternatively, for transdermal absorption, a transdermal administration system can be used, which is manufactured as an adhesive disk or patch that releases the compound in a sustained release.For this reason, a penetration enhancer can be used to promote the percutaneous penetration of the compound.

[0090] Alternatively, other pharmaceutical delivery systems can be employed. Liposomes and emulsions are well-known examples of delivery vehicles that can be used to deliver compounds. Organic solvents such as dimethyl sulfoxide (DMSO) can also be used, but are usually more toxic.

[0091] The pharmaceutical compositions may optionally be placed in a pack or dispenser device that can contain one or more unit dosage forms containing the compound. The pack can be, for example, a metal or plastic foil, such as a blister pack. The pack or dispenser may be accompanied by instructions for administration.

[0092] How to use The crystalline forms or compositions thereof described herein are generally used in an amount effective to achieve the intended result (e.g., an amount effective to treat or prevent the particular disease being treated). Therapeutic benefit refers to eradication or alleviation of the underlying disease being treated and / or eradication or alleviation of one or more symptoms associated with the underlying disease, such that the patient reports an improvement in mood or condition. Therapeutic benefit also generally includes halting or slowing the progression of the disease, regardless of whether improvement is achieved.

[0093] In yet another aspect, the present invention provides a method for inhibiting PRMT5 activity in a cell, comprising contacting the cell in which inhibition of PRMT5 activity is desired in vitro with an effective amount of a crystalline form of Compound 1, as described herein, or a pharmaceutical composition comprising an effective amount of a crystalline form of Compound 1, as described herein. In one embodiment, the cell is an MTAP-deficient cell.

[0094] The compositions and methods provided herein are believed to be particularly useful for inhibiting PRMT5 activity in cells in vivo. In one embodiment, cells in which inhibition of PRMT5 activity is desired are contacted in vivo with a therapeutically effective amount of a crystalline form of Compound 1 described herein or a pharmaceutical composition comprising a therapeutically effective amount of a crystalline form of Compound 1 described herein. In one embodiment, the cells are MTAP-deficient cells. In one embodiment, negatively regulating PRMT5 activity occurs in the presence of bound MTA.

[0095] In particular, for cells lacking MTAP activity, negatively regulating PRMT5 activity can be used to inhibit PRMT5 activity and prevent cell proliferation. Cells can be contacted with a single or multiple doses according to a specific treatment regimen to negatively regulate the desired PRMT5 activity. The degree of PRMT5 inhibition can be monitored in vitro against the intracellular enzyme in the presence and absence of MTA using well-known methods, including the method described in Example B below, to evaluate the effectiveness of the treatment and dosage.

[0096] In another aspect, there is provided a method of treating cancer, comprising administering to a patient suffering from cancer a therapeutically effective amount of a crystalline form of Compound 1 described herein or a pharmaceutical composition comprising a therapeutically effective amount of a crystalline form of Compound 1 described herein. In one embodiment, the cancer is an MTAP-associated cancer.

[0097] The compositions and methods provided herein can be used to treat a wide variety of cancers, including tumors (e.g., prostate cancer, breast cancer, brain cancer, skin cancer, cervical cancer, testicular cancer, etc.). More specifically, cancers that can be treated by the compositions and methods of the present invention include, but are not limited to, tumor types such as astrocytoma, breast cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, gastric cancer, head and neck cancer, hepatocellular carcinoma, laryngeal cancer, lung cancer, oral cancer, ovarian cancer, prostate cancer, thyroid cancer, and sarcoma. More specifically, these compounds can be used to treat the following: cardiac system: sarcoma (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipoma, and teratoma; pulmonary system: bronchogenic carcinoma (squamous cell carcinoma, undifferentiated small cell carcinoma, undifferentiated large cell carcinoma, adenocarcinoma), alveolar (bronchiolopulmonary) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondroitin hamartoma, mesothelioma; digestive system Esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumor, lipoma), small intestine (adenocarcinoma, lymphoma, carcinoid tumor, Kaposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large intestine (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, smooth muscle tumors); genitourinary system: kidney (adenocarcinoma, Wilm's tumor (nephroblastoma), lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testis (seminoma, teratoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, stromal cell carcinoma, fibroma, fibroadenoma, adenomatous tumor, lipoma); liver: liver cancer (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma tumor, hepatic hemangioma; biliary tract: gallbladder cancer, duodenal papilla, bile duct cancer; bone: osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor, chordoma, osteochondroma (squamous cell carcinoma, undifferentiated small cell carcinoma, undifferentiated large cell carcinoma, adenocarcinoma), benign chondroma, chondroblastoma, chondrodysplastic fibroma, osteoid osteoma, and giant cell tumor;Nervous system: skull (osteoma, hemangioma, granuloma, xanthomas, osteitis deformans), meninges (meningioma, meningeal sarcoma, gliomatosis), brain (astrocytoma, medulloblastoma, glioma, ependymoma, embryonal tumor (pinealoma), glioblastoma multiforme, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors), spinal cord neurofibroma, meningioma, glioma, sarcoma); gynecology: uterus (endometrial cancer), cervix (cervical cancer, preneoplastic cervical dysplasia), ovary [ovarian cancer (serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma), granulosa cell tumor, Sertoli-Leydig cell tumor, dysgerminoma, malignant teratoma], vulva (squamous cell carcinoma, carcinoma in situ, adenocarcinoma, fibrosarcoma) tumor, melanoma), granulosa cell tumor, vagina [(clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma)], fallopian tube (cancer); blood system: blood [myeloid leukemia (acute and chronic), acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative disorders, multiple myeloma, myelodysplastic syndrome], Hodgkin's disease, non-Hodgkin's lymphoma (malignant lymphoma); skin: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, dysplastic nevi, lipoma, hemangioma, dermatofibroma, keloid, psoriasis; adrenal gland: neuroblastoma. In certain embodiments, the cancer is diffuse large B-cell lymphoma (DLBCL);

[0098] In one embodiment, the cancer is an MTAP-associated cancer selected from hepatocellular carcinoma, breast cancer, skin cancer, bladder cancer, liver cancer, pancreatic cancer, and head and neck cancer.

[0099] In other embodiments, the cancer is selected from the group consisting of ovarian serous cystadenocarcinoma, lung squamous cell carcinoma, lung adenocarcinoma, mesothelioma, esophageal squamous cell carcinoma, gastric adenocarcinoma, pancreatic ductal adenocarcinoma, renal adenocarcinoma, bladder transitional cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, osteosarcoma, multiple myeloma, astrocytoma, glioma, glioblastoma, uterine sarcoma, acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin's lymphoma, malignant melanoma, endometrial carcinoma, and thyroid carcinoma.

[0100] In other embodiments, the cancer is selected from the group consisting of bladder cancer, bone cancer, brain cancer, blood cancer, breast cancer, colorectal cancer, esophageal cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, mesothelioma, ovarian cancer, pancreatic cancer, skin cancer, thyroid cancer, and uterine cancer.

[0101] The concentration and route of administration to a patient will vary depending on the cancer being treated. The crystalline forms of Compound 1 described herein or pharmaceutical compositions comprising the crystalline forms of Compound 1 described herein may also be co-administered with other anti-neoplastic compounds (e.g., chemotherapy) or used as a pre- or post-surgical adjuvant in combination with other treatments, such as radiation or surgical intervention. [Example]

[0102] The following examples are intended to further illustrate certain embodiments of the present invention and are not intended to limit the scope of the invention.

[0103] Example 1: Decomposition of salts of Compound 1 Compound 1 can be prepared as a gum according to the procedures described in International Publication No. WO2021050915. See Example 16-8.

[0104] The amorphous HCl salt of compound 1 was used for salt decomposition studies on a 500 mg scale. To a 500 mL glass vessel, HCl salt (502 mg) was added, followed by Milli-Q water (41.7 mL). The mixture was stirred to obtain a homogeneous solution. NaHCO3 (saturated solution) (3.3 mL) was added to the solution, and the pH was measured to be 7.28. Dichloromethane (DCM) (50 mL) was added to the solution, and stirring was continued for 30 minutes. The mixture was then transferred to a 1 L separatory funnel, and two distinct phases separated within 10 minutes. The DCM layer was isolated in a 250 mL round-bottom flask and evaporated under reduced pressure at 40 °C. The isolated solid was dried under reduced pressure at 25 °C overnight. The yield was 95% (calculated based on the theoretical weight of the free base). The solid was confirmed to be amorphous by XRD (Figure 8A). The polarized light microscope image in Figure 8B shows the resulting solid. The solid was further characterized by DSC and TGA, as shown in Figure 8C. The solid was confirmed to be the free base with residual DCM by NMR (Figure 8D).

[0105] Example 2: Screening of salts of Compound 1 Using the amorphous free base of Example 1, screening experiments for 64 salts were conducted using 16 acids in four solvent systems, with four blank experiments for each solvent system. Polymorphs of salts of Compound 1 were obtained using the slurry method disclosed herein. In each experiment, approximately 30 mg of the amorphous free base form of Example 1 was mixed with approximately 30 mg of the corresponding acid (e.g., sulfate, tosylate, glutamate, fumarate, glycolate, hippurate, or phosphate) in a 1:1 molar ratio in 0.3–4.4 mL of solvent (based on solubility). After magnetic stirring at room temperature for 4 days, any precipitate was separated by centrifugation. If no precipitation was observed after 4 days at room temperature, the clear solution was stirred at 5°C for 24 hours to induce crystallization. If no solids were still observed, the final clear solution was allowed to slowly evaporate at room temperature for 4 days. The isolated solids were air-dried under ambient conditions before analysis. Table 1 summarizes the experiments performed and the crystalline forms obtained. [Table 1-1] [Table 1-2]

[0106] From Table 1, it can be seen that nine crystalline salts were obtained: sulfate Form A, tosylate Form A, glutamate Form A, fumarate Form A, fumarate Form B, glycolate Form A, glycolate Form B, hippurate Form A, and phosphate Form A. Under the other 22 conditions, solids were successfully isolated, but the solids were characterized as amorphous, poorly crystalline, or the counterion itself. The following examples discuss the characteristics of these nine crystalline salts.

[0107] Example 3: Characterization of Form A of the Crystalline Sulfate Salt of Compound 1 As shown in Table 1, Form A of the sulfate salt of Compound 1 was obtained from a mixture of Compound 1 free base, sulfuric acid, and THF using the slurry method described in Example 2. The resulting solid remained a wet, paste-like substance after air-drying, likely due to its hygroscopic nature. Therefore, DSC / TGA data were not obtained. Figure 1A shows the XRD for the crystalline form of Form A of the sulfate salt of Compound 1.

[0108] Table 2 shows the XRD pattern for the crystalline form of Form A of the sulfate salt of Compound 1 shown in Figure 1A. [Table 2]

[0109] Example 4: Characterization of Form A of the Crystalline Tosylate Salt of Compound 1 As shown in Table 1, Form A of the tosylate salt of Compound 1 was obtained from a mixture of the free base of Compound 1, toluenesulfonic acid, and either THF or EtOAc using the slurry method described in Example 2. The solids were characterized by DSC / TGA and XRPD, as shown in Figures 2A and 2B, respectively. Table 3 summarizes the characterization results of Form A of the tosylate salt of Compound 1. [Table 3]

[0110] Table 4 shows the XRD pattern for the crystalline form of Form A of the tosylate salt of Compound 1 shown in Figure 2B. [Table 4]

[0111] Example 5: Characterization of Form A of the Glutamate Salt of Compound 1 As shown in Table 1, Form A of the glutamic acid salt of Compound 1 was obtained from a mixture of Compound 1 free base, glutamic acid, and acetone / HO (1:1, v / v) using the slurry method described in Example 2. The solid was characterized by DSC / TGA and XRPD, as shown in Figures 3A and 3B, respectively. Table 5 summarizes the characterization results of Form A of the glutamic acid salt of Compound 1. [Table 5]

[0112] Table 6 shows the XRD pattern for the crystalline form of Form A of the glutamate salt of Compound 1 shown in Figure 3B. [Table 6]

[0113] Example 6: Characterization of Forms A and B of the Fumarate Salt of Compound 1 As shown in Table 1, Forms A and B of the fumarate salt of Compound 1 were obtained by the slurry method described in Example 2. Form A of the fumarate salt was obtained from a mixture of Compound 1 free base, fumaric acid, and THF, and Form B of the fumarate salt was obtained from a mixture of Compound 1 free base, fumaric acid, and acetone / HO (1:1, v / v). The solids were characterized by DSC / TGA and XRPD, as shown in Figures 4A, 4B, 4C, and 4D. Table 7 summarizes the characterization results of Forms A and B of the fumarate salt of Compound 1. [Table 7]

[0114] Table 8 shows the XRD pattern for the crystalline form of Form A of the fumarate salt of Compound 1 shown in Figure 4B. [Table 8]

[0115] Table 9 shows the XRD pattern for the crystalline form of Form B of the fumarate salt of Compound 1, shown in Figure 4D. [Table 9]

[0116] Example 7: Characterization of Forms A and B of the Glycolic Acid Salt of Compound 1 As shown in Table 1, Forms A and B of the glycolic acid salt of Compound 1 were obtained by the slurry method described in Example 2. Form A of the glycolic acid salt was obtained from a mixture of Compound 1 free base, glycolic acid, and methanol, and Form B of the glycolic acid salt was obtained from a mixture of Compound 1 free base, glycolic acid, and THF. The resulting solids were characterized by DSC / TGA and XRPD, as shown in Figures 5A, 5B, 5C, and 5D. Table 10 summarizes the characterization results for Forms A and B of the glycolic acid salt of Compound 1. [Table 10]

[0117] Table 11 shows the XRD pattern for the crystalline form of Form A of the glycolic acid salt of Compound 1 shown in Figure 5B. [Table 11]

[0118] Table 12 shows the XRD pattern for the crystalline form of Form B of the glycolic acid salt of Compound 1 shown in Figure 5D. [Table 12]

[0119] Example 8: Characterization of Form A of the Hippurate Salt of Compound 1 As shown in Table 1, Form A of the hippuric acid salt of Compound 1 was obtained from a mixture of the free base of Compound 1, hippuric acid, and THF using the slurry method described in Example 2. The solid was characterized by DSC / TGA and XRPD, as shown in Figures 6A and 6B. Figure 6C shows a polarized light microscope (PLM) image of the resulting solid. Table 13 summarizes the characterization results of Form A of the hippuric acid salt of Compound 1. [Table 13]

[0120] Table 14 shows the XRD pattern for the crystalline form of Form A of the hippuric acid salt of Compound 1 shown in Figure 6B. [Table 14]

[0121] Example 9: Characterization of Form A of the Phosphate Salt of Compound 1 As shown in Table 1, Form A of the phosphate salt of Compound 1 was obtained from a mixture of the free base of Compound 1, phosphoric acid, and methanol using a slurry method similar to that in Example 2. The solid was characterized by DSC / TGA and XRPD, as shown in Figures 7A and 7B, respectively. Table 15 summarizes the characterization of Form A of the phosphate salt of Compound 1. [Table 15]

[0122] Table 16 shows the XRD pattern for the crystalline form of Form A of the phosphate salt of Compound 1 shown in Figure 7B. [Table 16]

[0123] List of Items of Implementation Embodiment 1.6. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile sulfate having an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 6°±0.2. Embodiment 2. The crystalline form of embodiment 1, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 10.9°±0.2°. Embodiment 3. The crystalline form of embodiment 1, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 20.4°±0.2°. Embodiment 4. The crystalline form of embodiment 1, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 22.9°±0.2°. Embodiment 5. The crystalline form of embodiment 1, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 6.6°±0.2°, 10.9°±0.2°, 20.4°±0.2°, and 22.9°±0.2°. Embodiment 6. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile sulfate having an X-ray powder diffraction pattern as shown in Figure 1A. Embodiment 7. The crystalline form of any one of embodiments 1-3, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile sulfate. Embodiment 8. The crystalline form of any one of embodiments 1-7, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile sulfate. Embodiment 9. A pharmaceutical composition comprising the crystalline form of any one of embodiments 1-8 and a pharmaceutically acceptable carrier. Embodiment 10. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate having a differential scanning calorimetry (DSC) endothermic peak temperature within 55°C ± 2%. Embodiment 11. The crystalline form of embodiment 10, having an endothermic DSC peak temperature within 55°C ± 1%. Embodiment 12. The crystalline form of embodiment 10, having an endothermic DSC peak temperature within 55°C ± 0.5%. Embodiment 13. The crystalline form of embodiment 10, wherein the crystalline form has an endothermic DSC peak temperature within 163°C ± 2%. Embodiment 14. The crystalline form of embodiment 13, having an endothermic DSC peak temperature within 163°C ± 1%. Embodiment 15. The crystalline form of embodiment 13, having an endothermic DSC peak temperature within 163°C ± 0.5%. Embodiment 16. The crystalline form of embodiment 10, wherein the crystalline form has an exothermic DSC peak temperature within 247°C ± 2%. Embodiment 17. The crystalline form of embodiment 16, wherein the exothermic DSC peak temperature is within 247°C ± 1%. Embodiment 18. The crystalline form of embodiment 16, wherein the exothermic DSC peak temperature is within 247°C ± 0.5%. Embodiment 19. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate having an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 4.4°±0.2°. Embodiment 20. The crystalline form of embodiment 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 5.2°±0.2°. Embodiment 21. The crystalline form of embodiment 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 8.2°±0.2°. Embodiment 22. The crystalline form of embodiment 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 13.1°±0.2°. Embodiment 23. The crystalline form of embodiment 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 15.9°±0.2°. Embodiment 24. The crystalline form of embodiment 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 16.5°±0.2°. Embodiment 25. The crystalline form of embodiment 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 4.4°±0.2°, 5.2°±0.2°, 8.2°±0.2°, 13.1°±0.2°, 15.9°±0.2°, and 16.5°±0.2°. Embodiment 26. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate, having an X-ray powder diffraction pattern as shown in Figure 2B. Embodiment 27. The crystalline form of any one of embodiments 10 to 26, wherein the crystalline form is a hydrate, solvate, or anhydrate. Embodiment 28. The crystalline form of any one of embodiments 10-27, wherein the crystalline form has a thermogravimetric analysis (TGA) plot showing a mass loss of about 2.7% when heated from about 25°C to about 150°C. Embodiment 29. The crystalline form of any one of embodiments 10-28, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate. Embodiment 30. The crystalline form of any one of embodiments 10-29, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate. Embodiment 31. A pharmaceutical composition comprising the crystalline form of any one of embodiments 10 to 30 and a pharmaceutically acceptable carrier. Embodiment 32. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate having a differential scanning calorimetry (DSC) endothermic peak temperature within 51°C ± 2%. Embodiment 33. The crystalline form of embodiment 32, having an endothermic DSC peak temperature within 51°C ± 1%. Embodiment 34. The crystalline form of embodiment 32, having an endothermic DSC peak temperature within 51°C ± 0.5%. Embodiment 35. The crystalline form of embodiment 32, wherein the crystalline form has an endothermic DSC peak temperature within 94°C ± 2%. Embodiment 36. The crystalline form of embodiment 25, having an endothermic DSC peak temperature within 94°C ± 1%. Embodiment 37. The crystalline form of embodiment 25, having an endothermic DSC peak temperature within 94°C ± 0.5%. Embodiment 38. The crystalline form of embodiment 32, wherein the crystalline form has an endothermic DSC peak temperature within 174°C ± 2%. Embodiment 39. The crystalline form of embodiment 38, having an endothermic DSC peak temperature within 174°C ± 1%. Embodiment 40. The crystalline form of embodiment 38, having an endothermic DSC peak temperature within 174°C ± 0.5%. Embodiment 41. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate having an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 9.9°±0.2°. Embodiment 42. The crystalline form of embodiment 41, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 14.3°±0.2°. Embodiment 43. The crystalline form of embodiment 41, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 16.9°±0.2°. Embodiment 44. The crystalline form of embodiment 41, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 22.4°±0.2°. Embodiment 45. The crystalline form of embodiment 41, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 24.6°±0.2°. Embodiment 46. The crystalline form of embodiment 41, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 25.2°±0.2°. Embodiment 47. The crystalline form of embodiment 41, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 9.9°±0.2°, 14.3°±0.2°, 16.9°±0.2°, 22.4°±0.2°, 24.6°±0.2°, and 25.2°±0.2°. Embodiment 48. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate having an X-ray powder diffraction pattern as shown in Figure 3B. Embodiment 49. The crystalline form of any one of embodiments 32 to 48, wherein the crystalline form is a hydrate or a solvate. Embodiment 50. The crystalline form of any one of embodiments 32-49, wherein the crystalline form has a thermogravimetric analysis (TGA) plot showing a mass loss of about 6.5% when heated from about 25°C to about 150°C. Embodiment 51. The crystalline form of any one of embodiments 32-50, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate. Embodiment 52. The crystalline form of any one of embodiments 32-51, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate. Embodiment 53. A pharmaceutical composition comprising the crystalline form of any one of embodiments 32-52 and a pharmaceutically acceptable carrier. Embodiment 54. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate having a differential scanning calorimetry (DSC) endothermic peak temperature within 36°C ± 2%. Embodiment 55. The crystalline form of embodiment 54, having an endothermic DSC peak temperature within 36°C ± 1%. Embodiment 56. The crystalline form of embodiment 54, having an endothermic DSC peak temperature within 36°C ± 0.5%. Embodiment 57. The crystalline form of embodiment 54, wherein the crystalline form has an endothermic DSC peak temperature within 256°C ± 2%. Embodiment 58. The crystalline form of embodiment 57, having an endothermic DSC peak temperature within 256°C ± 1%. Embodiment 59. The crystalline form of embodiment 57, having an endothermic DSC peak temperature within 256°C ± 0.5%. Embodiment 60. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate having an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 4.3°±0.2°. Embodiment 61. The crystalline form of embodiment 60, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 6.0°±0.2°. Embodiment 62. The crystalline form of embodiment 60, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 9.8°±0.2°. Embodiment 63. The crystalline form of embodiment 60, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 19.6°±0.2°. Embodiment 64. The crystalline form of embodiment 60, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 25.0°±0.2°. Embodiment 65. The crystalline form of embodiment 60, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 4.3°±0.2°, 6.0°±0.2°, 9.8°±0.2°, 19.6°±0.2°, and 25.0°±0.2°. Embodiment 66. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate having an X-ray powder diffraction pattern as shown in Figure 4B. Embodiment 67. The crystalline form of any one of embodiments 54 to 66, wherein the crystalline form is a hydrate or a solvate. Embodiment 68. The crystalline form of any one of embodiments 54-67, wherein the crystalline form has a thermogravimetric analysis (TGA) plot showing a mass loss of about 7.0% when heated from about 25°C to about 150°C. Embodiment 69. The crystalline form of any one of embodiments 54 to 68, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate. Embodiment 70. The crystalline form of any one of embodiments 54-69, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate. Embodiment 71. A pharmaceutical composition comprising the crystalline form of any one of embodiments 54 to 70 and a pharmaceutically acceptable carrier. Embodiment 72. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate having a differential scanning calorimetry (DSC) endothermic peak temperature within 259°C ± 2%. Embodiment 73. The crystalline form of embodiment 72, having an endothermic DSC peak temperature within 259°C ± 1%. Embodiment 74. The crystalline form of embodiment 72, having an endothermic DSC peak temperature within 259°C ± 0.5%. Embodiment 75. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate having an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 3.6°±0.2°. Embodiment 76. The crystalline form of embodiment 75, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 14.3°±0.2°. Embodiment 77. The crystalline form of embodiment 75, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 20.6°±0.2°. Embodiment 78. The crystalline form of embodiment 75, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 23.7°±0.2°. Embodiment 79. The crystalline form of embodiment 58, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 25.3°±0.2°. Embodiment 80. The crystalline form of embodiment 75, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 26.9°±0.2°. Embodiment 81. The crystalline form of embodiment 75, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 3.6°±0.2°, 14.3°±0.2°, 20.6°±0.2°, 23.7°±0.2°, 25.3°±0.2°, and 26.9°±0.2°. Embodiment 82. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate having an X-ray powder diffraction pattern as shown in Figure 4D. Embodiment 83. The crystalline form of any one of embodiments 72 to 82, wherein the crystalline form is a hydrate or a solvate. Embodiment 84. The crystalline form of any one of embodiments 72-83, wherein the crystalline form has a thermogravimetric analysis (TGA) plot showing a mass loss of about 3.9% when heated from about 25°C to about 150°C. Embodiment 85. The crystalline form of any one of embodiments 72-84, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate. Embodiment 86. The crystalline form of any one of embodiments 72-85, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate. Embodiment 87. A pharmaceutical composition comprising the crystalline form of any one of embodiments 72 to 86 and a pharmaceutically acceptable carrier. Embodiment 88. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate having a differential scanning calorimetry (DSC) endothermic peak temperature within 36°C ± 2%. Embodiment 89. The crystalline form of embodiment 88, having an endothermic DSC peak temperature within 36°C ± 1%. Embodiment 90. The crystalline form of embodiment 88, having an endothermic DSC peak temperature within 36°C ± 0.5%. Embodiment 91. The crystalline form of embodiment 88, wherein the crystalline form has an exothermic DSC peak temperature within 119°C ± 2%. Embodiment 92. The crystalline form of embodiment 91, having an exothermic DSC peak temperature within 119°C ± 1%. Embodiment 93. The crystalline form of embodiment 91, wherein the exothermic DSC peak temperature is within 119°C ± 0.5%. Embodiment 94. The crystalline form of embodiment 88, wherein the crystalline form has an exothermic DSC peak temperature within 161°C ± 2%. Embodiment 95. The crystalline form of embodiment 94, wherein the exothermic DSC peak temperature is within 161°C ± 1%. Embodiment 96. The crystalline form of embodiment 94, wherein the exothermic DSC peak temperature is within 161°C ± 0.5%. Embodiment 97. The crystalline form of embodiment 88, wherein the crystalline form has an endothermic DSC peak temperature within 253°C ± 2%. Embodiment 98. The crystalline form of embodiment 97, having an endothermic DSC peak temperature within 253°C ± 1%. Embodiment 99. The crystalline form of embodiment 97, having an endothermic DSC peak temperature within 253°C ± 0.5%. Embodiment 100. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate having an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 9.8°±0.2°. Embodiment 101. The crystalline form of embodiment 100, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 15.3°±0.2°. Embodiment 102. The crystalline form of embodiment 100, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 16.1°±0.2°. Embodiment 103. The crystalline form of embodiment 100, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 25.0°±0.2°. Embodiment 104. The crystalline form of embodiment 100, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 9.8°±0.2°, 15.3°±0.2°, 16.1°±0.2°, and 25.0°±0.2°. Embodiment 105. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate having an X-ray powder diffraction pattern as shown in Figure 5B. Embodiment 106. The crystalline form of any one of embodiments 88 to 105, wherein the crystalline form is a hydrate or a solvate. Embodiment 107. The crystalline form of any one of embodiments 88-106, wherein the crystalline form has a thermogravimetric analysis (TGA) plot showing a mass loss of about 2.1% when heated from about 25°C to about 150°C. Embodiment 108. The crystalline form of any one of embodiments 88 to 107, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate. Embodiment 109. The crystalline form of any one of embodiments 88 to 108, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate. Embodiment 110. A pharmaceutical composition comprising the crystalline form of any one of embodiments 88 to 109 and a pharmaceutically acceptable carrier. Embodiment 111. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate having a differential scanning calorimetry (DSC) endothermic peak temperature within 56°C ± 2%. Embodiment 112. The crystalline form of embodiment 111, having an endothermic DSC peak temperature within 56°C ± 1%. Embodiment 113. The crystalline form of embodiment 111, having an endothermic DSC peak temperature within 56°C ± 0.5%. Embodiment 114. The crystalline form of embodiment 111, wherein the crystalline form has an endothermic DSC peak temperature within 138°C ± 2%. Embodiment 115. The crystalline form of embodiment 114, having an endothermic DSC peak temperature within 138°C ± 1%. Embodiment 116. The crystalline form of embodiment 114, having an endothermic DSC peak temperature within 138°C ± 0.5%. Embodiment 117. The crystalline form of embodiment 111, wherein the crystalline form has an exothermic DSC peak temperature within 259°C ± 2%. Embodiment 118. The crystalline form of embodiment 117, having an exothermic DSC peak temperature within 259°C ± 1%. Embodiment 119. The crystalline form of embodiment 117, having an exothermic DSC peak temperature within 259°C ± 0.5%. Embodiment 120. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate having an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 2.9°±0.2°. Embodiment 121. The crystalline form of embodiment 120, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 5.8°±0.2°. Embodiment 122. The crystalline form of embodiment 120, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 8.4°±0.2°. Embodiment 123. The crystalline form of embodiment 120, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 10.2°±0.2°. Embodiment 124. The crystalline form of embodiment 120, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 27.0°±0.2°. Embodiment 125. The crystalline form of embodiment 120, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 2.9°±0.2°, 5.8°±0.2°, 8.4°±0.2°, 10.2°±0.2°, and 27.0°±0.2°. Embodiment 126. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate having an X-ray powder diffraction pattern as shown in Figure 5D. Embodiment 127. The crystalline form of any one of embodiments 111 to 126, wherein the crystalline form is a hydrate, solvate, or anhydrate. Embodiment 128. The crystalline form of any one of embodiments 111-127, wherein the crystalline form has a thermogravimetric analysis (TGA) plot showing a mass loss of about 1.3% when heated from about 25°C to about 150°C. Embodiment 129. The crystalline form of any one of embodiments 111 to 128, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate. Embodiment 130. The crystalline form of any one of embodiments 111 to 129, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate. Embodiment 131. A pharmaceutical composition comprising the crystalline form of any one of embodiments 111 to 130 and a pharmaceutically acceptable carrier. Embodiment 132. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate having a differential scanning calorimetry (DSC) endothermic peak temperature within 36°C ± 2%. Embodiment 133. The crystalline form of embodiment 132, having an endothermic DSC peak temperature within 36°C ± 1%. Embodiment 134. The crystalline form of embodiment 132, having an endothermic DSC peak temperature within 36°C ± 0.5%. Embodiment 135. The crystalline form of embodiment 132, wherein the crystalline form has an endothermic DSC peak temperature within 177°C ± 2%. Embodiment 136. The crystalline form of embodiment 135, having an endothermic DSC peak temperature within 177°C ± 1%. Embodiment 137. The crystalline form of embodiment 135, having an endothermic DSC peak temperature within 177°C ± 0.5%. Embodiment 138. The crystalline form of embodiment 132, wherein the crystalline form has an endothermic DSC peak temperature within 208°C ± 2%. Embodiment 139. The crystalline form of embodiment 138, having an endothermic DSC peak temperature within 208°C ± 1%. Embodiment 140. The crystalline form of embodiment 138, having an endothermic DSC peak temperature within 208°C ± 0.5%. Embodiment 141. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate having an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 3.2°±0.2°. Embodiment 142. The crystalline form of embodiment 141, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 19.1°±0.2°. Embodiment 143. The crystalline form of embodiment 141, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 20.8°±0.2°. Embodiment 144. The crystalline form of embodiment 141, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 27.4°±0.2°. Embodiment 145. The crystalline form of embodiment 141, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 3.2°±0.2°, 19.1°±0.2°, 20.8°±0.2°, and 27.4°±0.2°. Embodiment 146. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate having an X-ray powder diffraction pattern as shown in Figure 6B. Embodiment 147. The crystalline form of any one of embodiments 132 to 146, wherein the crystalline form is a hydrate, solvate, or anhydrate. Embodiment 148. The crystalline form of any one of embodiments 132-147, wherein the crystalline form has a thermogravimetric analysis (TGA) plot showing a mass loss of about 2.7% when heated from about 25°C to about 150°C. Embodiment 149. The crystalline form of any one of embodiments 132 to 148, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate. Embodiment 150. The crystalline form of any one of embodiments 132 to 149, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate. Embodiment 151. A pharmaceutical composition comprising the crystalline form of any one of embodiments 132 to 150 and a pharmaceutically acceptable carrier. Embodiment 152. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate having a differential scanning calorimetry (DSC) endothermic peak temperature within 36°C ± 2%. Embodiment 153. The crystalline form of embodiment 152, having an endothermic DSC peak temperature within 36°C ± 1%. Embodiment 154. The crystalline form of embodiment 152, having an endothermic DSC peak temperature within 36°C ± 0.5%. Embodiment 155. The crystalline form of embodiment 152, wherein the crystalline form has an endothermic DSC peak temperature within 82°C ± 2%. Embodiment 156. The crystalline form of embodiment 155, having an endothermic DSC peak temperature within 82°C ± 1%. Embodiment 157. The crystalline form of embodiment 155, having an endothermic DSC peak temperature within 82°C ± 0.5%. Embodiment 158. The crystalline form of embodiment 152, wherein the crystalline form has an endothermic DSC peak temperature within 162°C ± 2%. Embodiment 159. The crystalline form of embodiment 158, having an endothermic DSC peak temperature within 162°C ± 1%. Embodiment 160. The crystalline form of embodiment 158, having an endothermic DSC peak temperature within 162°C ± 0.5%. Embodiment 161. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate having an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 6.6°±0.2°. Embodiment 162. The crystalline form of embodiment 161, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 17.0°±0.2°. Embodiment 163. The crystalline form of embodiment 161, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 18.9°±0.2°. Embodiment 164. The crystalline form of embodiment 161, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 20.4°±0.2°. Embodiment 165. The crystalline form of embodiment 161, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 22.9°±0.2°. Embodiment 166. The crystalline form of embodiment 161, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 6.6°±0.2°, 17.0°±0.2°, 18.9°±0.2°, 20.4°±0.2°, and 22.9°±0.2°. Embodiment 167. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate having an X-ray powder diffraction pattern as shown in Figure 7B. Embodiment 168. The crystalline form of any one of embodiments 152 to 167, wherein the crystalline form is a hydrate or a solvate. Embodiment 169. The crystalline form of any one of embodiments 152-168, wherein the crystalline form has a thermogravimetric analysis (TGA) plot showing a mass loss of about 2.2% when heated from about 25°C to about 150°C. Embodiment 170. The crystalline form of any one of embodiments 152 to 169, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate. Embodiment 171. The crystalline form of any one of embodiments 152 to 170, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate. Embodiment 172. A pharmaceutical composition comprising the crystalline form of any one of embodiments 152 to 171 and a pharmaceutically acceptable carrier. Embodiment 173. A method of treating cancer in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising the crystalline form of any one of embodiments 1-8, 10-30, 32-52, 54-70, 72-86, 88-109, 111-130, 132-150, or 152-171, or the crystalline form of any one of embodiments 9, 31, 53, 71, 87, 110, 131, 151, or 172. Embodiment 174. The method of embodiment 173, wherein the cancer is an MTAP-associated cancer. Embodiment 175. The method of embodiment 173, wherein the cancer is selected from the group consisting of ovarian serous cystadenocarcinoma, lung squamous cell carcinoma, lung adenocarcinoma, mesothelioma, esophageal squamous cell carcinoma, gastric adenocarcinoma, pancreatic ductal adenocarcinoma, renal adenocarcinoma, bladder transitional cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, osteosarcoma, multiple myeloma, astrocytoma, glioma, glioblastoma, uterine sarcoma, acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin's lymphoma, malignant melanoma, endometrial carcinoma, and thyroid carcinoma. Embodiment 176. The method of embodiment 173, wherein the cancer is selected from the group consisting of bladder cancer, bone cancer, brain cancer, blood cancer, breast cancer, colorectal cancer, esophageal cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, mesothelioma, ovarian cancer, pancreatic cancer, skin cancer, thyroid cancer and uterine cancer.

[0124] While the invention has been described in relation to particular embodiments thereof, it will be understood that the invention is capable of further modifications, and this application is generally intended to cover such modifications, uses, or adaptations of the invention as fall within the scope of the appended claims, in accordance with the principles of the invention, including departures from the present disclosure as may be applicable to the essential features hereinabove described, which are within known or customary practice in the art to which this invention pertains.

Claims

1. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile sulfate having an X-ray powder diffraction (XRPD) pattern including a peak at a 2θ angle of 6.6°±0.

2.

2. 2. The crystalline form of claim 1, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 10.9°±0.2°.

3. 2. The crystalline form of claim 1, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 20.4°±0.2°.

4. 2. The crystalline form of claim 1, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 22.9°±0.2°.

5. 2. The crystalline form of claim 1, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 6.6°±0.2°, 10.9°±0.2°, 20.4°±0.2°, and 22.9°±0.2°.

6. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile sulfate, having a powder X-ray diffraction pattern as shown in Figure 1A.

7. 4. The crystalline form of any one of claims 1 to 3, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile sulfate.

8. 8. The crystalline form of any one of claims 1 to 7, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile sulfate.

9. A pharmaceutical composition comprising the crystalline form of any one of claims 1 to 8 and a pharmaceutically acceptable carrier.

10. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate having a differential scanning calorimetry (DSC) endothermic peak temperature within 55°C ± 2%.

11. 11. The crystalline form of claim 10, having an endothermic DSC peak temperature within 55°C ± 1%.

12. 11. The crystalline form of claim 10, having an endothermic DSC peak temperature within 55°C ± 0.5%.

13. 11. The crystalline form of claim 10, wherein the crystalline form has an endothermic DSC peak temperature within 163°C ± 2%.

14. 14. The crystalline form of claim 13, having an endothermic DSC peak temperature within 163°C ± 1%.

15. 14. The crystalline form of claim 13, having an endothermic DSC peak temperature within 163°C ± 0.5%.

16. 11. The crystalline form of claim 10, wherein the crystalline form has an exothermic DSC peak temperature within 247°C ± 2%.

17. 17. The crystalline form of claim 16, having an exothermic DSC peak temperature within 247°C ± 1%.

18. 17. The crystalline form of claim 16, having an exothermic DSC peak temperature within 247°C ± 0.5%.

19. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate, having an X-ray powder diffraction (XRPD) pattern containing a peak at a 2θ angle of 4.4°±0.2°.

20. 20. The crystalline form of claim 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 5.2°±0.2°.

21. 20. The crystalline form of claim 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 8.2°±0.2°.

22. 20. The crystalline form of claim 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 13.1°±0.2°.

23. 20. The crystalline form of claim 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 15.9°±0.2°.

24. 20. The crystalline form of claim 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 16.5°±0.2°.

25. 20. The crystalline form of claim 19, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 4.4°±0.2°, 5.2°±0.2°, 8.2°±0.2°, 13.1°±0.2°, 15.9°±0.2°, and 16.5°±0.2°.

26. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate, having a powder X-ray diffraction pattern as shown in Figure 2B.

27. 27. The crystalline form of any one of claims 10 to 26, wherein the crystalline form is a hydrate, solvate or anhydrate.

28. 28. The crystalline form of any one of claims 10-27, wherein the crystalline form has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 2.7% when heated from about 25°C to about 150°C.

29. 29. The crystalline form of any one of claims 10-28, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate.

30. 30. The crystalline form of any one of claims 10-29, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile tosylate.

31. 31. A pharmaceutical composition comprising the crystalline form of any one of claims 10 to 30 and a pharmaceutically acceptable carrier.

32. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate having a differential scanning calorimetry (DSC) endothermic peak temperature within 51°C ± 2%.

33. 33. The crystalline form of claim 32, having an endothermic DSC peak temperature within 51°C ± 1%.

34. 33. The crystalline form of claim 32, having an endothermic DSC peak temperature within 51°C ± 0.5%.

35. 33. The crystalline form of claim 32, wherein the crystalline form has an endothermic DSC peak temperature within 94°C ± 2%.

36. 36. The crystalline form of claim 35, having an endothermic DSC peak temperature within 94°C ± 1%.

37. 36. The crystalline form of claim 35, having an endothermic DSC peak temperature within 94°C ± 0.5%.

38. 33. The crystalline form of claim 32, wherein the crystalline form has an endothermic DSC peak temperature within 174°C ± 2%.

39. 39. The crystalline form of claim 38, having an endothermic DSC peak temperature within 174°C ± 1%.

40. 39. The crystalline form of claim 38, having an endothermic DSC peak temperature within 174°C ± 0.5%.

41. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate having an X-ray powder diffraction (XRPD) pattern containing peaks at 2θ angles of 9.9°±0.2°.

42. 42. The crystalline form of claim 41, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 14.3°±0.2°.

43. 42. The crystalline form of claim 41, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 16.9°±0.2°.

44. 42. The crystalline form of claim 41, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 22.4°±0.2°.

45. 42. The crystalline form of claim 41, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 24.6°±0.2°.

46. 42. The crystalline form of claim 41, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 25.2°±0.2°.

47. 42. The crystalline form of claim 41, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 9.9°±0.2°, 14.3°±0.2°, 16.9°±0.2°, 22.4°±0.2°, 24.6°±0.2°, and 25.2°±0.2°.

48. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate, having a powder X-ray diffraction pattern as shown in Figure 3B.

49. 49. The crystalline form of any one of claims 32 to 48, wherein the crystalline form is a hydrate or a solvate.

50. 50. The crystalline form of any one of claims 32-49, wherein the crystalline form has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 6.5% when heated from about 25°C to about 150°C.

51. 51. The crystalline form of any one of claims 32-50, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate.

52. 52. The crystalline form of any one of claims 32-51, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glutamate.

53. 53. A pharmaceutical composition comprising the crystalline form of any one of claims 32 to 52 and a pharmaceutically acceptable carrier.

54. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate having a differential scanning calorimetry (DSC) endothermic peak temperature within 36°C ± 2%.

55. 55. The crystalline form of claim 54, having an endothermic DSC peak temperature within 36°C ± 1%.

56. 55. The crystalline form of claim 54, having an endothermic DSC peak temperature within 36°C ± 0.5%.

57. 55. The crystalline form of claim 54, wherein the crystalline form has an endothermic DSC peak temperature within 256°C ± 2%.

58. 58. The crystalline form of claim 57, having an endothermic DSC peak temperature within 256°C ± 1%.

59. 58. The crystalline form of claim 57, having an endothermic DSC peak temperature within 256°C ± 0.5%.

60. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate having an X-ray powder diffraction (XRPD) pattern containing a peak at a 2θ angle of 4.3°±0.2°.

61. 61. The crystalline form of claim 60, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 6.0°±0.2°.

62. 61. The crystalline form of claim 60, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 9.8°±0.2°.

63. 61. The crystalline form of claim 60, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 19.6°±0.2°.

64. 61. The crystalline form of claim 60, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 25.0°±0.2°.

65. 61. The crystalline form of claim 60, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 4.3°±0.2°, 6.0°±0.2°, 9.8°±0.2°, 19.6°±0.2°, and 25.0°±0.2°.

66. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate, having a powder X-ray diffraction pattern as shown in Figure 4B.

67. 67. The crystalline form of any one of claims 54 to 66, wherein the crystalline form is a hydrate or a solvate.

68. 68. The crystalline form of any one of claims 54-67, wherein the crystalline form has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 7.0% when heated from about 25°C to about 150°C.

69. 69. The crystalline form of any one of claims 54-68, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate.

70. 70. The crystalline form of any one of claims 54-69, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate.

71. 71. A pharmaceutical composition comprising the crystalline form of any one of claims 54 to 70 and a pharmaceutically acceptable carrier.

72. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate having a differential scanning calorimetry (DSC) endothermic peak temperature within 259°C ± 2%.

73. 73. The crystalline form of claim 72, having an endothermic DSC peak temperature within 259°C ± 1%.

74. 73. The crystalline form of claim 72, having an endothermic DSC peak temperature within 259°C ± 0.5%.

75. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate having an X-ray powder diffraction (XRPD) pattern containing a peak at a 2θ angle of 3.6°±0.2°.

76. 76. The crystalline form of claim 75, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 14.3°±0.2°.

77. 76. The crystalline form of claim 75, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 20.6°±0.2°.

78. 76. The crystalline form of claim 75, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 23.7°±0.2°.

79. 59. The crystalline form of claim 58, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 25.3°±0.2°.

80. 76. The crystalline form of claim 75, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 26.9°±0.2°.

81. 76. The crystalline form of claim 75, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 3.6°±0.2°, 14.3°±0.2°, 20.6°±0.2°, 23.7°±0.2°, 25.3°±0.2°, and 26.9°±0.2°.

82. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate, having a powder X-ray diffraction pattern as shown in Figure 4D.

83. 83. The crystalline form of any one of claims 72 to 82, wherein the crystalline form is a hydrate or a solvate.

84. 84. The crystalline form of any one of claims 72-83, wherein the crystalline form has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 3.9% when heated from about 25°C to about 150°C.

85. 85. The crystalline form of any one of claims 72-84, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate.

86. 86. The crystalline form of any one of claims 72-85, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile fumarate.

87. 87. A pharmaceutical composition comprising the crystalline form of any one of claims 72 to 86 and a pharmaceutically acceptable carrier.

88. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate having a differential scanning calorimetry (DSC) endothermic peak temperature within 36°C ± 2%.

89. 89. The crystalline form of claim 88, having an endothermic DSC peak temperature within 36°C ± 1%.

90. 89. The crystalline form of claim 88, having an endothermic DSC peak temperature within 36°C ± 0.5%.

91. 89. The crystalline form of claim 88, wherein the crystalline form has an exothermic DSC peak temperature within 119°C ± 2%.

92. 92. The crystalline form of claim 91, having an exothermic DSC peak temperature within 119°C ± 1%.

93. 92. The crystalline form of claim 91, having an exothermic DSC peak temperature within 119°C ± 0.5%.

94. 89. The crystalline form of claim 88, having an exothermic DSC peak temperature within 161°C ± 2%.

95. 95. The crystalline form of claim 94, having an exothermic DSC peak temperature within 161°C ± 1%.

96. The crystal according to claim 94, wherein the exothermic DSC peak temperature is within 161°C ± 0.5%.

97. 89. The crystalline form of claim 88, wherein the crystalline form has an endothermic DSC peak temperature within 253°C ± 2%.

98. 98. The crystalline form of claim 97, having an endothermic DSC peak temperature within 253°C ± 1%.

99. 98. The crystalline form of claim 97, having an endothermic DSC peak temperature within 253°C ± 0.5%.

100. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate having an X-ray powder diffraction (XRPD) pattern containing a peak at a 2θ angle of 9.8°±0.2°.

101. 101. The crystalline form of claim 100, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 15.3°±0.2°.

102. 101. The crystalline form of claim 100, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 16.1°±0.2°.

103. 101. The crystalline form of claim 100, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 25.0°±0.2°.

104. 101. The crystalline form of claim 100, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 9.8°±0.2°, 15.3°±0.2°, 16.1°±0.2°, and 25.0°±0.2°.

105. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate, having a powder X-ray diffraction pattern as shown in Figure 5B.

106. 106. The crystalline form of any one of claims 88-105, wherein the crystalline form is a hydrate or a solvate.

107. 107. The crystalline form of any one of claims 88-106, wherein the crystalline form has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 2.1% when heated from about 25°C to about 150°C.

108. 108. The crystalline form of any one of claims 88-107, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate.

109. 109. The crystalline form of any one of claims 88-108, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate.

110. 110. A pharmaceutical composition comprising the crystalline form of any one of claims 88-109 and a pharmaceutically acceptable carrier.

111. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate having a differential scanning calorimetry (DSC) endothermic peak temperature within 56°C ± 2%.

112. 112. The crystalline form of claim 111, having an endothermic DSC peak temperature within 56°C ± 1%.

113. 112. The crystalline form of claim 111, having an endothermic DSC peak temperature within 56°C ± 0.5%.

114. 112. The crystalline form of claim 111, wherein the crystalline form has an endothermic DSC peak temperature within 138°C ± 2%.

115. 115. The crystalline form of claim 114, having an endothermic DSC peak temperature within 138°C ± 1%.

116. 115. The crystalline form of claim 114, having an endothermic DSC peak temperature within 138°C ± 0.5%.

117. 112. The crystalline form of claim 111, wherein the crystalline form has an exothermic DSC peak temperature within 259°C ± 2%.

118. 118. The crystalline form of claim 117, having an exothermic DSC peak temperature within 259°C ± 1%.

119. 118. The crystalline form of claim 117, having an exothermic DSC peak temperature within 259°C ± 0.5%.

120. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate having an X-ray powder diffraction (XRPD) pattern containing peaks at 2θ angles of 2.9°±0.2°.

121. 121. The crystalline form of claim 120, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 5.8°±0.2°.

122. 121. The crystalline form of claim 120, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 8.4°±0.2°.

123. 121. The crystalline form of claim 120, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 10.2°±0.2°.

124. 121. The crystalline form of claim 120, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 27.0°±0.2°.

125. 121. The crystalline form of claim 120, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 2.9°±0.2°, 5.8°±0.2°, 8.4°±0.2°, 10.2°±0.2°, and 27.0°±0.2°.

126. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate, having a powder X-ray diffraction pattern as shown in Figure 5D.

127. 127. The crystalline form of any one of claims 111 to 126, wherein the crystalline form is a hydrate, solvate or anhydrate.

128. 128. The crystalline form of any one of claims 111-127, wherein the crystalline form has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 1.3% when heated from about 25°C to about 150°C.

129. 129. The crystalline form of any one of claims 111-128, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate.

130. 130. The crystalline form of any one of claims 111-129, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile glycolate.

131. 131. A pharmaceutical composition comprising the crystalline form of any one of claims 111-130 and a pharmaceutically acceptable carrier.

132. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate having an endothermic peak temperature within 36°C ± 2%.

133. 133. The crystalline form of claim 132, having an endothermic DSC peak temperature within 36°C ± 1%.

134. 133. The crystalline form of claim 132, having an endothermic DSC peak temperature within 36°C ± 0.5%.

135. 133. The crystalline form of claim 132, wherein the crystalline form has an endothermic DSC peak temperature within 177°C ± 2%.

136. 136. The crystalline form of claim 135, having an endothermic DSC peak temperature within 177°C ± 1%.

137. 136. The crystalline form of claim 135, having an endothermic DSC peak temperature within 177°C ± 0.5%.

138. 133. The crystalline form of claim 132, wherein the crystalline form has an endothermic DSC peak temperature within 208°C ± 2%.

139. 139. The crystalline form of claim 138, having an endothermic DSC peak temperature within 208°C ± 1%.

140. 139. The crystalline form of claim 138, having an endothermic DSC peak temperature within 208°C ± 0.5%.

141. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate having an X-ray powder diffraction (XRPD) pattern containing peaks at 2θ angles of 3.2°±0.2°.

142. 142. The crystalline form of claim 141, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 19.1°±0.2°.

143. 142. The crystalline form of claim 141, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 20.8°±0.2°.

144. 142. The crystalline form of claim 141, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 27.4°±0.2°.

145. 142. The crystalline form of claim 141, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 3.2°±0.2°, 19.1°±0.2°, 20.8°±0.2°, and 27.4°±0.2°.

146. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate, having a powder X-ray diffraction pattern as shown in Figure 6B.

147. 147. The crystalline form of any one of claims 132-146, wherein the crystalline form is a hydrate, solvate, or anhydrate.

148. 148. The crystalline form of any one of claims 132-147, wherein the crystalline form has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 2.7% when heated from about 25°C to about 150°C.

149. 149. The crystalline form of any one of claims 132-148, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate.

150. 150. The crystalline form of any one of claims 132-149, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile hippurate.

151. 151. A pharmaceutical composition comprising the crystalline form of any one of claims 132-150 and a pharmaceutically acceptable carrier.

152. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate having a differential scanning calorimetry (DSC) endothermic peak temperature within 36°C ± 2%.

153. 153. The crystalline form of claim 152, having an endothermic DSC peak temperature within 36°C ± 1%.

154. 153. The crystalline form of claim 152, having an endothermic DSC peak temperature within 36°C ± 0.5%.

155. 153. The crystalline form of claim 152, wherein the crystalline form has an endothermic DSC peak temperature within 82°C ± 2%.

156. 156. The crystalline form of claim 155, having an endothermic DSC peak temperature within 82°C ± 1%.

157. 156. The crystalline form of claim 155, having an endothermic DSC peak temperature within 82°C ± 0.5%.

158. 153. The crystalline form of claim 152, wherein the crystalline form has an endothermic DSC peak temperature within 162°C ± 2%.

159. 159. The crystalline form of claim 158, having an endothermic DSC peak temperature within 162°C ± 1%.

160. 159. The crystalline form of claim 158, having an endothermic DSC peak temperature within 162°C ± 0.5%.

161. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate having an X-ray powder diffraction (XRPD) pattern containing peaks at 2θ angles of 6.6°±0.2°.

162. 162. The crystalline form of claim 161, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 17.0°±0.2°.

163. 162. The crystalline form of claim 161, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 18.9°±0.2°.

164. 162. The crystalline form of claim 161, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 20.4°±0.2°.

165. 162. The crystalline form of claim 161, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising a peak at a 2θ angle of 22.9°±0.2°.

166. 162. The crystalline form of claim 161, wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern comprising peaks at 2θ angles of 6.6°±0.2°, 17.0°±0.2°, 18.9°±0.2°, 20.4°±0.2°, and 22.9°±0.2°.

167. A crystalline form of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate having a powder X-ray diffraction pattern as shown in Figure 7B.

168. 168. The crystalline form of any one of claims 152-167, wherein the crystalline form is a hydrate or a solvate.

169. 169. The crystalline form of any one of claims 152-168, wherein the crystalline form has a thermogravimetric analysis (TGA) plot that exhibits a mass loss of about 2.2% when heated from about 25°C to about 150°C.

170. 170. The crystalline form of any one of claims 152-169, wherein the crystalline form has a purity of at least 97% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate.

171. 171. The crystalline form of any one of claims 152-170, wherein the crystalline form has a purity of at least 98% by weight of 2-(4-(4-(aminomethyl)-1-oxo-1,2-dihydrophthalazin-6-yl)-1-methyl-1H-pyrazol-5-yl)-4-chloro-6-cyclopropoxy-3-fluorobenzonitrile phosphate.

172. 172. A pharmaceutical composition comprising the crystalline form of any one of claims 152-171 and a pharmaceutically acceptable carrier.

173. 13. A method of treating cancer in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising the crystalline form of any one of claims 1-8, 10-30, 32-52, 54-70, 72-86, 88-109, 111-130, 132-150 or 152-171, or the crystalline form of any one of claims 9, 31, 53, 71, 87, 110, 131, 151 or 172.

174. The method of claim 173, wherein the cancer is an MTAP-associated cancer.

175. 174. The method of claim 173, wherein the cancer is selected from the group consisting of ovarian serous cystadenocarcinoma, lung squamous cell carcinoma, lung adenocarcinoma, mesothelioma, esophageal squamous cell carcinoma, gastric adenocarcinoma, pancreatic ductal adenocarcinoma, renal adenocarcinoma, bladder transitional cell carcinoma, hepatocellular carcinoma, cholangiocarcinoma, osteosarcoma, multiple myeloma, astrocytoma, glioma, glioblastoma, uterine sarcoma, acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin's lymphoma, malignant melanoma, endometrial carcinoma, and thyroid carcinoma.

176. 174. The method of claim 173, wherein the cancer is selected from the group consisting of bladder cancer, bone cancer, brain cancer, blood cancer, breast cancer, colorectal cancer, esophageal cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, mesothelioma, ovarian cancer, pancreatic cancer, skin cancer, thyroid cancer and uterine cancer.

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