Crystalline forms of 3-(7-chloro-1h-indazol-5-yl)-2,5-bis(trifluoromethyl)-3h-imidazo[4,5-b]pyridine and their use in the treatment of epilepsy

Abstract

Provided are crystalline forms of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine, pharmaceutical compositions comprising the crystalline form, and their use in treating conditions associated with TARP γ8-dependent AMPA activity, such as epilepsy, epileptic disorders, seizures, seizure disorders, pain, psychiatric diseases, or neurodegenerative diseases.

Description

139260-00120 CRYSTALLINE FORMS OF 3-(7-CHLORO-1H-INDAZOL-5-YL)-2,5- BIS(TRIFLUOROMETHYL)-3H-IMIDAZO[4,5-b]PYRIDINE RELATED APPLICATIONS

[0001] This application claims priority to International Application No. PCT / CN2024 / 072842, filed on January 17, 2024. The entire contents of the foregoing application are expressly incorporated herein by reference. BACKGROUND

[0002] α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are tetrameric, glutamate gated transmembrane ion channels which mediate the majority of fast neurotransmission across synaptic gaps. Thus, inhibition or negative modulation of AMPA receptors is an attractive strategy for therapeutic intervention in CNS disorders characterized by excessive neuronal activity. However, since AMPA receptor activity is so ubiquitous within CNS, general antagonism affects most areas of the CNS, resulting in undesired effects, such as ataxia, sedation, and / or dizziness, which are shared by all known general AMPA receptor antagonists.

[0003] Transmembrane AMPA Receptor Regulatory Proteins (TARPs) are a family of proteins that have been found to associate with and modulate the activity of AMPA receptors. See e.g. Gill and Bredt., Neuropsychopharmacology 201136(1): 362-363. Several TARPs exhibit regiospecific expression in the brain, leading to physiological differentiation of the AMPA receptor activity. For example, TARP γ2-dependent AMPA receptors are primarily localized in the cerebellum and cerebral cortex while TARP γ8-dependent AMPA receptors are localized primarily in the hippocampus.

[0004] Due to the specific localization of these TARPs, there has been an interest in compounds which selectively modulate AMPA assembled with the auxiliary TARP protein in order to avoid or reduce the undesired effect of the general AMPA receptor antagonistsdiscussed above. See e.g., Knopp et al. J Pharmacol Exp Ther. 2019 Jun;369(3):345-363.This specific regulation of the TARP dependent AMPA receptor activity is an attractive therapeutic area of investigation for the treatment of pain, psychiatric diseases, or neurodegenerative diseases.

[0005] Such compounds which selectively inhibit TARP γ8-dependent AMPA activity are described in WO 2016 / 176460. Of these inhibitors, 3-(7-chloro-1H-indazol-5-yl)-2,5- bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine (see Example 270 of WO 2016 / 176460), is one that has potential as a clinical drug candidate. In an effort to further improve upon the 1 ME151785720v.1139260-00120 properties of this compound, as well as to facilitate isolation, bolster large-scale manufacturing, and / or promote formulation develop and long-term storage, the need for alternative forms exists. SUMMARY

[0006] Provided herein are crystalline forms of 3-(7-chloro-1H-indazol-5-yl)-2,5- bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine. In certain aspects Form A was found to be the most stable and the preferred crystalline form based on at least the stability and interconversion experiments described in the Exemplification section below.

[0007] Also provided are pharmaceutical compositions comprising the described crystalline forms as well as methods for their preparation and uses for treating conditions responsive to the modulation of TARP γ8-dependent AMPA receptor activity are also included. BRIEF DESCRIPTION OF THE FIGURES

[0008] Figure 1 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form A of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0009] Figure 2 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form B of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0010] Figure 3 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form C of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0011] Figure 4 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form D of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0012] Figure 5 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form E of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0013] Figure 6 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form F of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0014] Figure 7 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form G of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0015] Figure 8 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form H of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0016] Figure 9 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form I of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0017] Figure 10 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form J of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0018] Figure 11 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form L of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine. 2 ME151785720v.1139260-00120

[0019] Figure 12 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form M of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0020] Figure 13 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form N of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0021] Figure 14 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form O of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0022] Figure 15 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form P of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0023] Figure 16 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form Q of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0024] Figure 17 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form R of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0025] Figure 18 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form S of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0026] Figure 19 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form U of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0027] Figure 20 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form V of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0028] Figure 21 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form W of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0029] Figure 22 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form X of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0030] Figure 23 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form Y of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0031] Figure 24 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form Z of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0032] Figure 25 depicts an X-ray powder diffraction pattern (XRPD) for crystalline Form AA of 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0033] Figure 26 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form A.

[0034] Figure 27 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form B.

[0035] Figure 28 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form C. 3 ME151785720v.1139260-00120

[0036] Figure 29 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form D.

[0037] Figure 30 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form E.

[0038] Figure 31 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form F.

[0039] Figure 32 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form G.

[0040] Figure 33 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form H.

[0041] Figure 34 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form J.

[0042] Figure 35 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form L.

[0043] Figure 36 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form M.

[0044] Figure 37 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form P.

[0045] Figure 38 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form Q.

[0046] Figure 39 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form R.

[0047] Figure 40 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form S.

[0048] Figure 41 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form U.

[0049] Figure 42 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form V.

[0050] Figure 43 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form X.

[0051] Figure 44 depicts differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA) plots for crystalline Form Y.

[0052] Figure 45 is a flow chart which shows the interconversion of the various crystalline forms. 4 ME151785720v.1139260-00120

[0053] Figure 46 depicts an X-ray powder diffraction pattern (XRPD) for 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine prepared as described in WO 2016 / 176460. DETAILED DESCRIPTION A. General Description of Compound Forms

[0054] In embodiments, provided are crystalline Forms A, B, C, D, E, F, G, H, I, J, L, M, N, O, P, Q, R, S, U, V, W, X, Y, Z, or AA of 3-(7-chloro-1H-indazol-5-yl)-2,5- bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine. B. Definitions

[0055] As used herein, the recitation of a range of values is intended to serve as a shorthand method of referring individually to each separate value falling within the range as well as the highest and lowest values that define the range and that each value is incorporated into the specification as if it were individually recited herein, unless expressly stated to the contrary. For example, a range of values from X to Y includes both X and Y and all the values in between X and Y.

[0056] The use of any and all examples, or exemplary language (e.g., “such as” and “e.g.”) provided herein, is intended to better illustrate the disclosure and is not a limitation on the scope of the disclosure unless otherwise claimed. Phrases such as “in one aspect”, “in one embodiment”, “in another aspect”, “in another embodiment”, “in embodiments”, and the like should not be construed as indicating that such elements occur or exist in isolation or that such elements are not shared by other aspects or embodiments of the disclosure. Rather, it should be understood that all aspects and embodiments may be freely combined with any and all other aspects and embodiments of the disclosure as described herein. No language in the specification should be construed as indicating that any non-claimed element is essential to the practice of the disclosure.

[0057] 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine and Compound 1 may be used interchangeably and each refer to the compound having the following chemical structure:. 5 ME151785720v.1139260-00120

[0058] As used herein, “crystalline” refers to a solid form of Compound 1 where there exists long-range atomic order in the positions of the atoms. The crystalline nature of Compound 1 can be confirmed, for example, by examination of the X-ray powder diffraction pattern.

[0059] When used alone, the terms “Form A”, “Form B”, “Form C”, “Form D”, “Form E”, “Form F”, “Form G”, “Form H” ... “Form AA” refer to the crystalline Form A”, “Form B”, “Form C”, “Form D”, “Form E”, “Form F”, “Form G”, “Form H” ... “Form AA” of Compound 1, respectively, as described herein.

[0060] In one embodiment, the crystalline forms described herein are each single crystalline forms. A “single crystalline form” means that the recited compound, i.e., Compound 1, is present as a single crystal or a plurality of crystals in which each crystal has the same crystal form (e.g., Form A, Form B, Form C). Percent by weight of a particular crystal form is determined by the weight of the particular crystal form divided by the sum weight of the particular crystal, plus the weight of the other crystal form(s) present plus the weight of amorphous form, if present, multiplied by 100%. In some instances, crystalline Forms A, B, C, D, E, F, G, H, I, J, L, M, N, O, P, Q, R, S, U, V, W, X, Y, Z, or AA, as described herein are at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% a single crystalline form. “Pure single crystalline form” means that Compound 1 is present as a single crystal or a plurality of crystals in which each crystal has the same crystal form with no other detectable amounts of other crystal forms present and / or amorphous forms.

[0061] As use herein, “substantially free of amorphous form” or “substantially free of amorphous form of the compound” means that the recited compound, i.e., Compound 1 is present in the described crystalline form in which there is no detectable amount of amorphous form of the compound.

[0062] The 2-theta (2Θ) values of the X-ray powder diffraction patterns for the crystalline form described herein may vary slightly from one instrument to another and also depending on variations in sample preparation and batch to batch variation due to factors such as temperature variation, sample displacement, and the presence or absence of an internal standard. Therefore, unless otherwise defined, the XRPD patterns / assignments recited herein are not to be construed as absolute and can vary ± 0.2 degrees. It is well known in the art that this variability will account for the above factors without hindering the unequivocal identification of a crystal form. Unless otherwise specified, the 2-theta values provided herein were obtained using Cu Kα1 radiation. 6 ME151785720v.1139260-00120

[0063] Temperature values, e.g., for DSC peaks herein may vary slightly from one instrument to another and also depending on variations in sample preparation, batch to batch variation, heating rate of the method, and environmental factors. Therefore, unless otherwise defined, temperature values recited herein are not to be construed as absolute and can vary ± 5 degrees or ± 2 degrees.

[0064] “Substantially the same XRPD pattern” or “an X-ray powder diffraction pattern substantially similar to” a defined figure means that for comparison purposes, at least 90%, at least 95%, at least 99%, of the peaks shown are present. It is to be further understood that for comparison purposes some variability in peak intensities from those shown are allowed, such as ± 0.2 degrees.

[0065] The term “amorphous” refers to a solid that is present in a non-crystalline state or form. Amorphous solids are disordered arrangements of molecules and therefore possess no distinguishable crystal lattice or unit cell and consequently have no definable long range ordering. Solid state ordering of solids may be determined by standard techniques known in the art, e.g., by X-ray powder diffraction (XRPD) or differential scanning calorimetry (DSC).

[0066] The term “anhydrous” and “anhydrate” are used interchangeably and mean that the referenced crystalline form has substantially no water in the crystal lattice, e.g., less than 1% by weight as determined by Karl Fisher analysis.

[0067] The terms “subject” and “patient” may be used interchangeably, and means a mammal in need of treatment, e.g., companion animals (e.g., dogs, cats, and the like), farm animals (e.g., cows, pigs, horses, sheep, goats and the like) and laboratory animals (e.g., rats, mice, guinea pigs and the like). Typically, the subject is a human in need of treatment.

[0068] As used herein, the terms “treatment,” “treat,” and “treating” refer to reversing, alleviating, delaying the onset of, or inhibiting the progress of a disease or disorder, or one or more symptoms thereof, as described herein. In some aspects, treatment may be administered after one or more symptoms have developed, i.e., therapeutic treatment. In other aspects, treatment may be administered in the absence of symptoms. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of symptoms and / or in light of exposure to a particular organism, or other susceptibility factors), i.e., prophylactic treatment. Treatment may also be continued after symptoms have resolved, for example to delay their recurrence.

[0069] The term “pharmaceutically acceptable carrier” refers to a non-toxic carrier, adjuvant, or vehicle that does not destroy the pharmacological activity of the compound with which it is formulated. Pharmaceutically acceptable carriers, adjuvants or vehicles that may 7 ME151785720v.1139260-00120 be used in the compositions described herein include, but are not limited to, ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat.

[0070] The term “effective amount” or “therapeutically effective amount” refers to an amount of a crystalline form described herein that will elicit a desired or beneficial biological or medical response of a subject e.g., a dosage of between 0.01 - 100 mg / kg body weight / day. C. Exemplary Forms

[0071] In embodiments, provided herein is a crystalline Form A of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0072] In embodiments, the crystalline Form A is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 12.3, 12.9, 13.7, 22.0, 24.5, and 25.2. In embodiments, the crystalline Form A is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 12.3, 12.9, 13.7, 22.0, 24.5, and 25.2. In embodiments, the crystalline Form A is characterized by X-ray powder diffraction peaks at 2Θ angles 12.3, 12.9, 13.7, 22.0, 24.5, and 25.2. In embodiments, the crystalline Form A is characterized by an X-ray powder diffraction peak at 2Θ angle 13.7 and at least three additional X-ray powder diffraction peaks at 2Θ angles selected from 12.3, 12.9, 22.0, 24.5, and 25.2. In embodiments, the crystalline Form A is characterized by an X-ray powder diffraction peak at 2Θ angle 13.7 and at least four additional X-ray powder diffraction peaks at 2Θ angles selected from 12.3, 12.9, 22.0, 24.5, and 25.2. In embodiments, the crystalline Form A is characterized by X-ray powder diffraction peaks at 2Θ angles 12.3, 12.9, 13.7, 22.0, 24.5, and 25.2. In embodiments, the crystalline Form A is characterized by X-ray powder diffraction peaks at a 2Θ angles 13.7 and 33.6 and at least three additional X-ray powder diffraction peaks at 2Θ angles selected from 12.3, 12.9, 22.0, 24.5, and 25.2. In embodiments, the crystalline Form A is characterized by X-ray powder diffraction peaks at a 2Θ angles 13.7 and 33.6 and at least four additional X-ray powder diffraction peaks at 2Θ angles selected from 12.3, 12.9, 22.0, 24.5, and 25.2. In embodiments, the crystalline Form A is characterized by X-ray powder diffraction peaks at 2Θ angles 12.3, 12.9, 13.7, 22.0, 24.5, 25.2, and 33.6. In embodiments, the crystalline Form A is characterized by X-ray powder 8 ME151785720v.1139260-00120 diffraction peaks at 2Θ angles 12.3, 12.9, 13.7, 20.3, 21.2, 22.0, 24.5, 25.2, 26.6, and 33.6. In embodiments, the crystalline Form A is characterized by X-ray powder diffraction peaks at 2Θ angles 12.3, 12.9, 13.7, 20.3, 21.2, 21.9, 24.5, 24.7, 25.2, and 26.6. In embodiments, the crystalline Form A is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, at least sixteen, at least seventeen, at least eighteen, at least nineteen, at least twenty, at least twenty-one, at least twenty-two, at least twenty-three, at least twenty-four, at least twenty-five, at least twenty- six, at least twenty-seven, at least twenty-eighth, at least twenty-nine, at least thirty, at least thirty-one, at least thirty-two, at least thirty-three, at least thirty-four, or at least thirty-five X- ray powder diffraction peaks at 2Θ angles selected from those in Table 1. In embodiments, the crystalline Form A is characterized by an X-ray powder diffraction substantially similar to Figure 1. Table 19 ME151785720v.1139260-00120

[0073] In embodiments, provided herein is a crystalline Form B of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0074] In embodiments, the crystalline Form B is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 9.0, 11.6, 12.1, 16.4, and 19.2. In embodiments, the crystalline Form B is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 9.0, 11.6, 12.1, 16.4, and 19.2. In embodiments, the crystalline Form B is characterized by X-ray powder diffraction peaks at 2Θ angles 9.0, 11.6, 12.1, 16.4, and 19.2. In embodiments, the crystalline Form B is characterized by X-ray powder diffraction peaks at 2Θ angles 9.0, 11.6, 12.1, 15.5, 16.4, 19.2, 19.8, 20.6, 24.1, and 25.2. In embodiments, the crystalline Form B is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least eleven X-ray powder diffraction peaks at 2Θ angles selected from those in Table 2. In embodiments, the crystalline Form B is characterized by an X-ray powder diffraction substantially similar to Figure 2. Table 210 ME151785720v.1139260-00120

[0075] In embodiments, provided herein is a crystalline Form C of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0076] In embodiments, the crystalline Form C is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 17.6, 24.2, 24.4, 25.6. In embodiments, the crystalline Form C is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 17.6, 24.2, 24.4, and 25.6. In embodiments, the crystalline Form C is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 17.6, 24.2, 24.4, and 25.6. In embodiments, the crystalline Form C is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 12.8, 17.6, 19.7, 22.3, 24.2, 24.4, 25.6, 25.9, 30.2. In embodiments, the crystalline Form C is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, at least sixteen, at least seventeen, at least eighteen, at least nineteen, at least twenty, at least twenty-one, at least twenty-two, at least twenty-three, at least twenty-four, or at least twenty- five X-ray powder diffraction peaks at 2Θ angles selected from those in Table 3. In embodiments, the crystalline Form C is characterized by an X-ray powder diffraction substantially similar to Figure 3. Table 311 ME151785720v.1139260-00120

[0077] In embodiments, provided herein is a crystalline Form D of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0078] In embodiments, the crystalline Form D is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 10.8, 14.5, 19.2, 25.3, and 29.2. In embodiments, the crystalline Form D is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 10.8, 14.5, 19.2, 25.3, and 29.2. In embodiments, the crystalline Form D is characterized by X-ray powder diffraction peaks at 2Θ angles 10.8, 14.5, 19.2, 25.3, and 29.2. In embodiments, the crystalline Form D is characterized by X-ray powder diffraction peaks at 2Θ angles 10.8, 14.5, 19.2, 19.4, 23.7, 25.3, 25.7, 26.9, 29.2, 32.8. In embodiments, the crystalline Form D is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, or at least fourteen X-ray powder diffraction peaks at 2Θ angles selected from those in Table 4. In embodiments, the crystalline Form D is characterized by an X-ray powder diffraction substantially similar to Figure 4. Table 412 ME151785720v.1139260-00120 32.8032 7.31

[0079] In embodiments, provided herein is a crystalline Form E of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0080] In embodiments, the crystalline Form E is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 14.4, 15.1, 17.2, 21.8, and 24.3. In embodiments, the crystalline Form E is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 14.4, 15.1, 17.2, 21.8, and 24.3. In embodiments, the crystalline Form E is characterized by X-ray powder diffraction peaks at 2Θ angles 14.4, 15.1, 17.2, 21.8, and 24.3. In embodiments, the crystalline Form E is characterized by X-ray powder diffraction peaks at 2Θ angles 14.4, 15.1, 17.2, 21.8, 22.9, 23.824.3, 24.8, 29.0, and 29.9. In embodiments, the crystalline Form E is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, at least sixteen, at least seventeen, at least eighteen, or at least nineteen X-ray powder diffraction peaks at 2Θ angles selected from those in Table 5. In embodiments, the crystalline Form E is characterized by an X-ray powder diffraction substantially similar to Figure 5. Table 513 ME151785720v.1139260-00120

[0081] In embodiments, provided herein is a crystalline Form F of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0082] In embodiments, the crystalline Form F is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 18.6, 19.4, 23.4, 26.9, and 30.1. In embodiments, the crystalline Form F is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 18.6, 19.4, 23.4, 26.9, and 30.1. In embodiments, the crystalline Form F is characterized by X-ray powder diffraction peaks at 2Θ angles 18.6, 19.4, 23.4, 26.9, and 30.1. In embodiments, the crystalline Form F is characterized by X-ray powder diffraction peaks at 2Θ angles 13.5, 14.5, 16.1, 18.6, 19.4, 23.4, 24.6, 25.3, 26.9, and 30.1. In embodiments, the crystalline Form F is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten X-ray powder diffraction peaks at 2Θ angles selected from those in Table 6. In embodiments, the crystalline Form F is characterized by an X-ray powder diffraction substantially similar to Figure 6. Table 6

[0083] In embodiments, provided herein is a crystalline Form G of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0084] In embodiments, the crystalline Form G is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 7.4, 14.9, 16.8, 17.4, and 22.4. In embodiments, the crystalline Form G is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 7.4, 14.9, 16.8, 17.4, and 22.4. In embodiments, the crystalline Form G is characterized by X-ray powder diffraction peaks at 2Θ angles 7.4, 14 ME151785720v.1139260-00120 14.9, 16.8, 17.4, and 22.4. In embodiments, the crystalline Form G is characterized by X-ray powder diffraction peaks at 2Θ angles 7.4, 10.6, 12.4, 14.9, 15.9, 16.8, 17.4, 18.8, and 22.4. In embodiments, the crystalline Form G is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, or at least nine X-ray powder diffraction peaks at 2Θ angles selected from those in Table 7. In embodiments, the crystalline Form G is characterized by an X-ray powder diffraction substantially similar to Figure 7. Table 7

[0085] In embodiments, provided herein is a crystalline Form H of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0086] In embodiments, the crystalline Form H is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 14.3, 17.5, 19.5, and 24.8. In embodiments, the crystalline Form H is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 14.3, 17.5, 19.5, and 24.8. In embodiments, the crystalline Form H is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 14.3, 17.5, 19.5, and 24.8. In embodiments, the crystalline Form H is characterized by X-ray powder diffraction peaks at 2Θ angles 9.7, 11.7, 12.7, 14.3, 17.5, 18.6, 19.5, 22.0, 23.1, and 24.8. In embodiments, the crystalline Form H is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, or at least fourteen X-ray powder diffraction peaks at 2Θ angles selected from those in Table 8. In embodiments, the crystalline Form H is characterized by an X-ray powder diffraction substantially similar to Figure 8. 15 ME151785720v.1139260-00120 Table 8

[0087] In embodiments, provided herein is a crystalline Form I of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0088] In embodiments, the crystalline Form I is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 7.9, 10.6, 12.3, 18.6, and 19.0. In embodiments, the crystalline Form I is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 7.9, 10.6, 12.3, 18.6, and 19.0. In embodiments, the crystalline Form I is characterized by X-ray powder diffraction peaks at 2Θ angles 7.9, 10.6, 12.3, 18.6, and 19.0. In embodiments, the crystalline Form I is characterized by X-ray powder diffraction peaks at 2Θ angles 7.9, 10.6, 12.3, 12.8, 13.3, 16.6, 18.6, 19.0.22.9, and 25.2. In embodiments, the crystalline Form I is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, at least sixteen, or at least seventeen X-ray powder diffraction peaks at 2Θ angles selected from those in Table 9. In embodiments, the crystalline Form I is characterized by an X-ray powder diffraction substantially similar to Figure 9. Table 916 ME151785720v.1139260-00120

[0089] In embodiments, provided herein is a crystalline Form J of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0090] In embodiments, the crystalline Form J is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 9.5, 9.8, 14.0, 21.1, and 29.5. In embodiments, the crystalline Form J is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 9.5, 9.8, 14.0, 21.1, and 29.5. In embodiments, the crystalline Form J is characterized by X-ray powder diffraction peaks at 2Θ angles 9.5, 9.8, 14.0, 21.1, and 29.5. In embodiments, the crystalline Form J is characterized by X-ray powder diffraction peaks at 2Θ angles 7.0, 9.5, 9.8, 12.8, 14.0, 19.6, 21.1, 28.3, 29.3, and 29.5. In embodiments, the crystalline Form J is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, at least sixteen, at least seventeen, at least eighteen, at least nineteen, at least twenty, at least twenty-one, or at least twenty-two X-ray powder diffraction peaks at 2Θ angles selected from those in Table 10. In embodiments, the crystalline Form J is characterized by an X-ray powder diffraction substantially similar to Figure 10. Table 1017 ME151785720v.1139260-00120

[0091] In embodiments, provided herein is a crystalline Form L of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0092] In embodiments, the crystalline Form L is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 9.5, 10.9, 14.2, 16.3, and 24.7. In embodiments, the crystalline Form L is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 9.5, 10.9, 14.2, 16.3, and 24.7. In embodiments, the crystalline Form L is characterized by X-ray powder diffraction peaks at 2Θ angles 9.5, 10.9, 14.2, 16.3, and 24.7. In embodiments, the crystalline Form L is characterized by X-ray powder diffraction peaks at 2Θ angles 9.5, 10.9, 13.8, 14.2, 16.3, 21.3, 24.7, 25.2, 27.2, and 28.7. In embodiments, the crystalline Form L is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten X-ray powder diffraction peaks at 2Θ angles selected from those in Table 11. In embodiments, the crystalline Form L is characterized by an X-ray powder diffraction substantially similar to Figure 11. Table 1118 ME151785720v.1139260-00120

[0093] In embodiments, provided herein is a crystalline Form M of 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0094] In embodiments, the crystalline Form M is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 8.8, 17.7, 24.6, 26.6, and 30.8. In embodiments, the crystalline Form M is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 8.8, 17.7, 24.6, 26.6, and 30.8. In embodiments, the crystalline Form M is characterized by X-ray powder diffraction peaks at 2Θ angles 8.8, 17.7, 24.6, 26.6, and 30.8. In embodiments, the crystalline Form M is characterized by X-ray powder diffraction peaks at 2Θ angles 6.7, 8.8, 14.2, 17.7, 20.9, 22.0, 24.6, 25.8, 26.6, and 30.8. In embodiments, the crystalline Form M is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, at least sixteen, at least seventeen, or at least eighteen X-ray powder diffraction peaks at 2Θ angles selected from those in Table 12. In embodiments, the crystalline Form M is characterized by an X-ray powder diffraction substantially similar to Figure 12. Table 1219 ME151785720v.1139260-00120

[0095] In embodiments, provided herein is a crystalline Form N of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0096] In embodiments, the crystalline Form N is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 9.1, 9.4, 18.2, 18.8, and 24.1. In embodiments, the crystalline Form N is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 9.1, 9.4, 18.2, 18.8, and 24.1. In embodiments, the crystalline Form N is characterized by X-ray powder diffraction peaks at 2Θ angles 9.1, 9.4, 18.2, 18.8, and 24.1. In embodiments, the crystalline Form N is characterized by X-ray powder diffraction peaks at 2Θ angles 9.1, 9.4, 14.8, 18.2, 18.8, 19.4, 23.3, 24.1, 27.2, and 29.7. In embodiments, the crystalline Form N is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least eleven X-ray powder diffraction peaks at 2Θ angles selected from those in Table 13. In embodiments, the crystalline Form N is characterized by an X-ray powder diffraction substantially similar to Figure 13. Table 13

[0097] In embodiments, provided herein is a crystalline Form O of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine. 20 ME151785720v.1139260-00120

[0098] In embodiments, the crystalline Form O is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 12.8, 17.6, 19.5, and 25.7. In embodiments, the crystalline Form O is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 12.8, 17.6, 19.5, and 25.7. In embodiments, the crystalline Form O is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 12.8, 17.6, 19.5, and 25.7. In embodiments, the crystalline Form O is characterized by X-ray powder diffraction peaks at 2Θ angles 9.7, 11.7, 12.8, 17.6, 18.6, 19.5, 22.0, 23.9, 25.7, and 30.1. In embodiments, the crystalline Form O is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, or at least thirteen X-ray powder diffraction peaks at 2Θ angles selected from those in Table 14. In embodiments, the crystalline Form O is characterized by an X-ray powder diffraction substantially similar to Figure 14. Table 14

[0099] In embodiments, provided herein is a crystalline Form P of 3-(7-chloro-1H-indazol- 5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0100] In embodiments, the crystalline Form P is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 12.9, 17.6, 25.1, and 30.3. In embodiments, the crystalline Form P is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 12.9, 17.6, 25.1, and 30.3. In embodiments, the crystalline Form P is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 12.9, 17.6, 25.1, and 30.3. In embodiments, the crystalline Form P is characterized by X-ray 21 ME151785720v.1139260-00120 powder diffraction peaks at 2Θ angles 11.7, 12.9, 14.4, 17.6, 19.8, 22.3, 23.3, 25.1, 25.9, and 30.3. In embodiments, the crystalline Form P is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, or at least sixteen X-ray powder diffraction peaks at 2Θ angles selected from those in Table 15. In embodiments, the crystalline Form P is characterized by an X-ray powder diffraction substantially similar to Figure 15. Table 15

[0101] In embodiments, provided herein is a crystalline Form Q of 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0102] In embodiments, the crystalline Form Q is characterized by at least three X- ray powder diffraction peaks at 2Θ angles selected from 11.7, 17.6, 19.8, 24.3, and 25.2. In embodiments, the crystalline Form Q is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 17.6, 19.8, 24.3, and 25.2. In embodiments, the crystalline Form Q is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 17.6, 19.8, 24.3, and 25.2. In embodiments, the crystalline Form Q is characterized by X-ray powder diffraction peaks at 2Θ angles 11.0, 11.7, 12.9, 16.6, 17.6, 19.8, 24.3, 25.2, 25.9, and 30.4. In embodiments, the crystalline Form Q is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at 22 ME151785720v.1139260-00120 least ten, at least eleven, at least twelve, at least thirteen, or at least fourteen X-ray powder diffraction peaks at 2Θ angles selected from those in Table 16. In embodiments, the crystalline Form Q is characterized by an X-ray powder diffraction substantially similar to Figure 16. Table 16

[0103] In embodiments, provided herein is a crystalline Form R of 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0104] In embodiments, the crystalline Form R is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 5.7, 11.3, 13.4, 17.0, and 28.5. In embodiments, the crystalline Form R is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 5.7, 11.3, 13.4, 17.0, and 28.5. In embodiments, the crystalline Form R is characterized by X-ray powder diffraction peaks at 2Θ angles 5.7, 11.3, 13.4, 17.0, and 28.5. In embodiments, the crystalline Form R is characterized by X-ray powder diffraction peaks at 2Θ angles 5.7, 11.3, 12.5, 13.4, 17.0, 23.8, 24.4, 25.2, 28.5, and 32.9. In embodiments, the crystalline Form R is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, or at least fourteen X-ray powder diffraction peaks at 2Θ angles selected from those in Table 17. In embodiments, the crystalline Form R is characterized by an X-ray powder diffraction substantially similar to Figure 17. 23 ME151785720v.1139260-00120 Table 17

[0105] In embodiments, provided herein is a crystalline Form S of 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0106] In embodiments, the crystalline Form S is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 8.2, 10.9, 13.6, 17.1, and 19.1. In embodiments, the crystalline Form S is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 8.2, 10.9, 13.6, 17.1, and 19.1. In embodiments, the crystalline Form S is characterized by X-ray powder diffraction peaks at 2Θ angles 8.2, 10.9, 13.6, 17.1, and 19.1. In embodiments, the crystalline Form S is characterized by X-ray powder diffraction peaks at 2Θ angles 8.2, 10.9, 13.6, 16.4, 17.1, 19.1, 19.5, 21.9, 22.8, and 24.6. In embodiments, the crystalline Form S is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, at least sixteen, at least seventeen, at least eighteen, or at least nineteen X-ray powder diffraction peaks at 2Θ angles selected from those in Table 18. In embodiments, the crystalline Form S is characterized by an X-ray powder diffraction substantially similar to Figure 18. 24 ME151785720v.1139260-00120 Table 18

[0107] In embodiments, provided herein is a crystalline Form U of 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0108] In embodiments, the crystalline Form U is characterized by at least three X- ray powder diffraction peaks at 2Θ angles selected from 12.0, 12.6, 21.4, 24.7, and 25.3. In embodiments, the crystalline Form U is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 12.0, 12.6, 21.4, 24.7, and 25.3. In embodiments, the crystalline Form U is characterized by X-ray powder diffraction peaks at 2Θ angles 12.0, 12.6, 21.4, 24.7, and 25.3. In embodiments, the crystalline Form U is characterized by X-ray powder diffraction peaks at 2Θ angles 12.0, 12.6, 16.6, 18.4, 19.5, 20.6.21.4, 23.8, 24.7, and 25.3. In embodiments, the crystalline Form U is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, or at least fourteen X-ray powder diffraction peaks at 2Θ angles selected from those in Table 19. In embodiments, the crystalline Form U is characterized by an X-ray powder diffraction substantially similar to Figure 19. 25 ME151785720v.1139260-00120 Table 19

[0109] In embodiments, provided herein is a crystalline Form V of 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0110] In embodiments, the crystalline Form V is characterized by at least three X- ray powder diffraction peaks at 2Θ angles selected from 10.8, 14.4, 19.4, 25.9, and 28.9. In embodiments, the crystalline Form V is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 10.8, 14.4, 19.4, 25.9, and 28.9. In embodiments, the crystalline Form V is characterized by X-ray powder diffraction peaks at 2Θ angles 10.8, 14.4, 19.4, 25.9, and 28.9. In embodiments, the crystalline Form V is characterized by X-ray powder diffraction peaks at 2Θ angles 10.8, 14.4, 18.6, 18.9, 19.4, 22.7, 25.0, 25.9, 28.9, and 32.7. In embodiments, the crystalline Form V is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, at least sixteen, or at least seventeen X-ray powder diffraction peaks at 2Θ angles selected from those in Table 20. In embodiments, the crystalline Form V is characterized by an X-ray powder diffraction substantially similar to Figure 20. Table 2026 ME151785720v.1139260-00120

[0111] In embodiments, provided herein is a crystalline Form W of 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0112] In embodiments, the crystalline Form W is characterized by at least three X- ray powder diffraction peaks at 2Θ angles selected from 6.7, 7.1, 7.9, 13.5, and 14.2. In embodiments, the crystalline Form W is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 6.7, 7.1, 7.9, 13.5, and 14.2. In embodiments, the crystalline Form W is characterized by X-ray powder diffraction peaks at 2Θ angles 6.7, 7.1, 7.9, 13.5, and 14.2. In embodiments, the crystalline Form W is characterized by X-ray powder diffraction peaks at 2Θ angles 6.7, 7.1, 7.9, 11.4, 13.5, 14.2, 15.7, 17.3, 21.4, and 28.6. In embodiments, the crystalline Form W is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, or at least twelve X-ray powder diffraction peaks at 2Θ angles selected from those in Table 21. In embodiments, the crystalline Form W is characterized by an X-ray powder diffraction substantially similar to Figure 21. Table 2127 ME151785720v.1139260-00120

[0113] In embodiments, provided herein is a crystalline Form X of 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0114] In embodiments, the crystalline Form X is characterized by at least three X- ray powder diffraction peaks at 2Θ angles selected from 7.1, 7.9, 11.0, 14.2, and 24.7. In embodiments, the crystalline Form X is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 7.1, 7.9, 11.0, 14.2, and 24.7. In embodiments, the crystalline Form X is characterized by X-ray powder diffraction peaks at 2Θ angles 7.1, 7.9, 11.0, 14.2, and 24.7. In embodiments, the crystalline Form X is characterized by X-ray powder diffraction peaks at 2Θ angles 7.1, 7.9, 11.0, 14.2, 15.8, 16.5, 21.4, 24.7, and 32.0. In embodiments, the crystalline Form X is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, or at least nine X-ray powder diffraction peaks at 2Θ angles selected from those in Table 22. In embodiments, the crystalline Form X is characterized by an X-ray powder diffraction substantially similar to Figure 22. Table 22

[0115] In embodiments, provided herein is a crystalline Form Y of 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine). 28 ME151785720v.1139260-00120

[0116] In embodiments, the crystalline Form Y is characterized by at least three X- ray powder diffraction peaks at 2Θ angles selected from 7.1, 7.4, 7.8, 11.7, or 14.8. In embodiments, the crystalline Form Y is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 7.1, 7.4, 7.8, 11.7, or 14.8. In embodiments, the crystalline Form Y is characterized by X-ray powder diffraction peaks at 2Θ angles 7.1, 7.4, 7.8, 11.7, or 14.8. In embodiments, the crystalline Form Y is characterized by X-ray powder diffraction peaks at 2Θ angles 7.1, 7.4, 7.8, 11.7, 17.7, 14.0, 14.8, 19.3, 24.4, and 26.2. In embodiments, the crystalline Form Y is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or at least eleven X-ray powder diffraction peaks at 2Θ angles selected from those in Table 23. In embodiments, the crystalline Form Y is characterized by an X-ray powder diffraction substantially similar to Figure 23. Table 23

[0117] In embodiments, provided herein is a crystalline Form Z of 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0118] In embodiments, the crystalline Form Z is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 7.6, 8.0, 10.1, 14.2, and 15.9. In embodiments, the crystalline Form Z is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 7.6, 8.0, 10.1, 14.2, and 15.9. In embodiments, the crystalline Form Z is characterized by X-ray powder diffraction peaks at 2Θ angles 7.6, 8.0, 10.1, 14.2, and 15.9. In embodiments, the crystalline Form Z is characterized by X-ray powder diffraction peaks at 2Θ angles 7.6, 8.0, 10.0, 13.2, 14.2, 15.2, 15.9, 19.8, and 30.7. In 29 ME151785720v.1139260-00120 embodiments, the crystalline Form Z is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, or at least nine X-ray powder diffraction peaks at 2Θ angles selected from those in Table 24. In embodiments, the crystalline Form Z is characterized by an X-ray powder diffraction substantially similar to Figure 24. Table 24

[0119] In embodiments, provided herein is a crystalline Form AA of 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine.

[0120] In embodiments, the crystalline Form AA is characterized by at least three X- ray powder diffraction peaks at 2Θ angles selected from 8.1, 10.8, 13.5, 17.0, and 19.0. In embodiments, the crystalline Form AA is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 8.1, 10.8, 13.5, 17.0, and 19.0. In embodiments, the crystalline Form AA is characterized by X-ray powder diffraction peaks at 2Θ angles 8.1, 10.8, 13.5, 17.0, and 19.0. In embodiments, the crystalline Form AA is characterized by X- ray powder diffraction peaks at 2Θ angles 8.1, 10.8, 13.5, 16.2, 17.0, 19.0, 19.4, 21.7, 23.0, and 24.8. In embodiments, the crystalline Form AA is characterized by at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, at least sixteen, at least seventeen, at least eighteen, at least nineteen, at least twenty, at least twenty-one, at least twenty-two, at least twenty-three, at least twenty-four, at least twenty-five, at least twenty-six, at least twenty-seven, at least twenty-eighth, at least twenty- nine, or at least thirty X-ray powder diffraction peaks at 2Θ angles selected from those in Table 25. In embodiments, the crystalline Form AA is characterized by an X-ray powder diffraction substantially similar to Figure 25. 30 ME151785720v.1139260-00120 Table 25Uses, Formulation, and Administration

[0121] The crystalline forms and compositions described herein are generally useful for modulating the activity of AMPA receptor. In embodiments, the crystalline forms and compositions described herein are useful in the inhibition of TARP γ8-dependent AMPA receptor activity. In embodiments, the crystalline forms and compositions described herein are negative AMPA allosteric modulators.

[0122] In some aspects, the crystalline forms and pharmaceutical compositions described herein are useful in treating a condition associated with AMPA receptor function. In some 31 ME151785720v.1139260-00120 aspects, the crystalline forms and pharmaceutical compositions described herein are useful in treating a condition associated with TARP γ8-dependent AMPA receptor function. Thus, provided herein are methods of treating a condition associated with AMPA receptor function or TARP γ8-dependent AMPA receptor function, comprising administering to a subject in need thereof a therapeutically effective amount of a crystalline form described herein or a pharmaceutical composition comprising a disclosed crystalline form.

[0123] Also provided is the use of a crystalline form described herein, or a pharmaceutical composition comprising a disclosed crystalline form, for the manufacture of a medicament for treating a condition associated with AMPA receptor function or TARP γ8- dependent AMPA receptor function. Also provided is a crystalline form described herein or a pharmaceutical composition comprising a disclosed crystalline form for use in treating a condition associated with AMPA receptor or TARP γ8-dependent AMPA receptor function.

[0124] In some aspects, the crystalline forms and pharmaceutical compositions described herein are useful in treating epilepsy, epilepsy disorders, seizures, seizure disorders, pain, a psychiatric disorder, or a neurodegenerative disease in a subject in need thereof. In some aspects, the crystalline forms and pharmaceutical compositions described herein are useful in treating epilepsy or seizures. In some aspects, the crystalline forms and pharmaceutical compositions described herein are useful in treating focal onset epilepsy or focal onset seizures. Thus, provided herein are methods of treating pain, a psychiatric disorder, or a neurodegenerative disease, comprising administering to a subject in need thereof a therapeutically effective amount of a crystalline form described herein or a pharmaceutical composition comprising a disclosed crystalline form. Also provided is the use of a crystalline form described herein, or a pharmaceutical composition comprising a disclosed crystalline form, for the manufacture of a medicament for treating pain, a psychiatric disorder, or a neurodegenerative disease. Also provided is a crystalline form described herein or a pharmaceutical composition comprising a disclosed crystalline form for use in treating pain, bipolar disorder, a psychiatric disease, or a neurodegenerative disease.

[0125] In some aspects the epilepsy, epilepsy disorder, seizures, or seizure disorder is focal onset epilepsy or focal onset seizures, absence epilepsy, early infantile developmental end epileptic encephalopathy, childhood absence epilepsy, childhood epilepsy centrotemporal spiked (benign Roland epilepsy), Dravet syndrome, epilepsy eyelid myoclonia jeavons syndrome, epilepsy of infancy with migrating focal seizure, epilepsy myoclonic absences, developmental / epileptic encephalopathy with spike wave activation in sleep, fired febrile infection-related epilepsy syndrome, Hypothalamic hamartoma, indantile spasms (west 32 ME151785720v.1139260-00120 syndrome), juvenile myoclonic epilepsy, Lennox-Gastaut syndrome (LGS), myoclonic epilepsy in infancy, Panayiotopoulos syndrome, progressive myoclonic epilepsies, Rasmussen’s encephalitis, reflex epilepsies, self-limited familial and non-familial neonatal infant seizures, self-limited late onset occipital epilepsy Gastaut syndrome, epilepsy generalized tonic clonic seizures alone, genetic epilepsy with febrile seizure plus, juvenile absence epilepsy, myoclonic atonic epilepsy doose syndrome, developmental and epileptic encephalopathy (DEE), frontal lobe epilepsy, temporal lobe epilepsy (TLE), neocortal epilepsy, or sleep-related hypermotor epilepsy, absence seizures, atonic seizures, atypical absence seizures, clonic seizures, epileptic or infantile spasms, eclampsia, febrile seizures, focal bilateral tonic clonic seizures (secondarily generalized seizures), focal aware seizures (simple partial seizures), focal impaired awareness seizures (complex partial seizures), gelastic and dacrystic seizures, myoclonic seizures, drug-resistant seizures, new terms seizure classification, tonic-clonic seizures, or tonic seizures. In some aspects, the pain is a neuropathic pain, acute pain, or inflammatory pain. In some embodiments the psychiatric disease is bipolar disorder, acute mania, acute depression, major depressive disorder, or post- traumatic stress disorder (PTSD). In some aspects, the neurodegenerative disease is Alzheimer’s disease.

[0126] In some aspects, the pharmaceutical compositions are administered orally.

[0127] A specific dosage and treatment regimen for any particular patient will depend upon a variety of factors, including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, rate of excretion, drug combination, and the judgment of the treating physician and the severity of the particular disease being treated. The amount of a compound described herein in the composition will also depend upon the particular compound in the pharmaceutical composition. EXEMPLIFICATION Abbreviations 2-MeTHF = 2-methyltetrahydrofuran BuOH = 1-butanol DCM = CH2Cl2= dichloromethane DMAc = N,N-dimethylacetamide DMSO = dimethylsulfoxide EtOAc = EA = ethyl acetate EtOH = ethanol 33 ME151785720v.1139260-00120 H2O = water IPAc = isopropyl acetate IPA = isopropyl alcohol MeCN = ACN = CH3CN = acetonitrile MeOH = CH3OH = methanol MIBK = 4-methyl-2-pentanone MTBE = methyl tert-butyl ether NMP = N-Methylpyrrolidone THF = tetrahydrofuran XRPD = X-ray powder diffraction pattern UPLC = ultra-performance liquid chromatography DSC = differential scanning calorimetry TGA = thermo gravimetric analysis RT = room temperature Cu = copper kV = kilo Volts Å = angstroms mA = milli-Amps

[0128] The representative examples that follow are intended to help illustrate the present disclosure, and are not intended to, nor should they be construed to, limit the scope of the invention.

[0129] 3-(7-chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine, was prepared according to the procedures described in Example 270 of WO 2016 / 176460. For example, a solution of 2-chloro-3-nitro-6-(trifluoromethyl)pyridine and 7-chloro-1H- indazol-5-amine (1 eq.) in dimethylformamide (~5 mL per mmol) was heated at 110 °C. After 3 h, sodium dithionite (4 eq.) was added to the mixture was allowed to stir at 110 °C for 5 h. The reaction was diluted with water (~35 mL per mmol) and allowed to stir for 20 min where precipitate formed. The reaction was filtered and the solid was washed with H2O and oven dried at 45 °C to give N2-(7-chloro-1H-indazol-5-yl)-6-(trifluoromethyl)pyridine-2,3- diamine as a solid. Subsequently, a solution of N2-(7-chloro-1H-indazol-5-yl)-6- (trifluoromethyl)pyridine-2,3-diamine in trifluoroacetic acid (~4 mL per mmol) was stirred at 70 °C for 16 h. The reaction was concentrated in vacuo, diluted with sat. sodium bicarbonate (~25 mL per mmol) and extracted with ethyl acetate (EtOAc) (~20 mL per mmol 34 ME151785720v.1139260-00120 x 3). The organic layers were combined, dried over sodium sulfate and concentrated in vacuo. Purification with flash chromatography (SiO2, EtOAc / hexanes) afforded 3-(7-chloro-1H- indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine as a solid.

[0130] The X-ray powder diffraction for 3-(7-chloro-1H-indazol-5-yl)-2,5- bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine made by this process is shown in Figure 46, where amorphous material was observed.

[0131] XRPD samples were analyzed using PANalytical X-ray powder diffract meters with the parameters listed below:

[0132] TGA data was collected using TA Discovery 5500 / 550 TGA from TA Instruments. DSC was performed using TA Discovery 2500 / 250 DSC from TA Instruments. The parameters for the TGA and DSC instruments are listed below:

[0133] DVS was measured via a SMS (Surface Measurement Systems) DVS Intrinsic Plus using the parameters below. The relative humidity at 25 ºC were calibrated against deliquescence point of LiCl, Mg(NO3)2, and KCl.35 ME151785720v.1139260-00120

[0134] UPLC tests were completed on a Waters H-Class UPLC using the parameters listed below:

[0135] The preparation of the biological solvents used in the experiments is described below:36 ME151785720v.1139260-00120Form A

[0136] Form A was prepared by the procedure below. Acetone (1V) and purified water (2V) were added to a reaction flask. To this flask was added more acetone (2V) and 3-(7- chloro-1H-indazol-5-yl)-2,5-bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridine, followed by the 0.5V acetone wash of the addition funnel. The reaction mixture was stirred at RT until clear. Afterwards, water (0.75) was added dropwise over ~30 minutes. Then the reaction mixture was heated to 50oC and stirred for 3 hour at 50oC, cooled to RT and stirred at 2 hours at RT. Afterwards, water (3.75 V) is added dropwise over ~4.5 hr then stirred at 3 hr at RT. The reaction is then filtered and the solid collected and dried under vacuum at 50oC for at least 8 hours.

[0137] The XRPD pattern of Form A is shown in Figure 1. The TGA / DSC curves are shown in Figure 26, which showed a weight loss of 0.14% up to 150 ºC and one endotherm at 225.2 ºC (peak). Variable XRPD results showed no change for Form A after N2 purge for 20 min, heated to 150oC and cooled to 30oC, which showed Form A to be an anhydrate. Form B

[0138] Form B was obtained via anti-solvent addition of starting material in a Toluene / n- Heptane system. The XRPD pattern of Form B is shown in Figure 2. The TGA / DSC curves are shown in Figure 27, which showed a two-step weight loss of 1.59% up to 80 ºC and 8.71% from 80 ºC to 150 ºC and two endotherms at 115.9 and 224.2 ºC (peak). Form C

[0139] Form C was obtained via slurring Form A in MeOH with temperature cycling (50 ºC~5 ºC, 0.1 ºC / min, 2 cycles). The XRPD pattern of Form C is shown in Figure 3. The TGA / DSC curves are shown in Figure 28, which showed a two-step weight loss of 0.33% up to 50 ºC and 4.54% from 50 ºC to 150 ºC and two endotherms at 102.6 and 224.8 ºC (peak). Form D 37 ME151785720v.1139260-00120

[0140] Form D was obtained via slurring Form A in EtOH / n-Heptane (1:1, v / v) with temperature cycling (50 ºC~5 ºC, 0.1 ºC / min, 2 cycles). The XRPD pattern of Form D is shown in Figure 4. The TGA / DSC curves are shown in Figure 29, which showed a weight loss of 7.94% up to 150 ºC and two endotherms at 97.0 and 224.7 ºC (peak). Form E

[0141] Form E was obtained via slurring Form A in CHCl3with temperature cycling (50 ºC~5 ºC, 0.1 ºC / min, 4 cycles). The XRPD pattern of Form E is shown in Figure 5. The TGA / DSC curves are shown in Figure 30, which showed a two-step weight loss of 0.63% up to 90 ºC and 12.20% from 90 ºC to 150 ºC and two endotherms at 107.3 and 224.4 ºC (peak). Form F

[0142] Form F was obtained via a slow evaporation of Form A in MTBE. The XRPD pattern of Form F is shown in Figure 6. The TGA / DSC curves are shown in Figure 31, which showed a weight loss of 1.17% up to 150 ºC and one endotherm at 224.8 ºC (peak). The small TGA weight loss and small residual solvent content showed Form F to be an anhydrate. Form G

[0143] Form G was obtained via a slow evaporation of Form A in CHCl3. The XRPD pattern of Form G is shown in Figure 7. The TGA / DSC curves are shown in Figure 32, which showed a weight loss of 0.65% up to 150 ºC and one endotherm at 224.9 ºC (peak). The small TGA weight loss and small residual solvent content showed Form G to be an anhydrate. Form H

[0144] Form H was obtained via a slow evaporation of Form A in MeOH / DCM (1:1, v / v) at RT. The XRPD pattern of Form H is shown in Figure 8. The TGA / DSC curves are shown in Figure 33, which showed a two-step weight loss of 3.65% up to 60 ºC and 6.14% from 60 ºC to 150 ºC and three endotherms at 77.2, 106.9 and 224.9 ºC (peak). Form I

[0145] Form I was obtained via a slow evaporation of Form A in ACN / H2O. The XRPD pattern of Form I is shown in Figure 9. Form J

[0146] Form J was obtained via a slow cooling of Form A in IPA. The XRPD pattern of Form J is shown in Figure 10. The TGA / DSC curves are shown in Figure 34, which showed a two-step weight loss of 0.71% up to 50 ºC and 9.56% from 50 ºC to 150 ºC and two endotherms at 71.6 and 225.1 ºC (peak). 38 ME151785720v.1139260-00120 Form L

[0147] Form L was obtained via a slow cooling of Form A in IPA followed by drying at RT. The XRPD pattern of Form L is shown in Figure 11. The TGA / DSC curves are shown in Figure 35, which showed a weight loss of 6.46% up to 150 ºC and two endotherms at 87.6 and 224.2 ºC (peak). Form M

[0148] Form M was obtained via a solution vapor diffusion of Form A in a 1,4- Dioxane / n-Hexane system at RT. The XRPD pattern of Form M is shown in Figure 12. The TGA / DSC curves are shown in Figure 36, which showed a two-step weight loss of 15.01% up to 70 ºC, and 11.83% from 70 ºC to 150 ºC and three endotherms at 70.6, 95.3 and 224.8 ºC (peak). Form N

[0149] Form N was obtained via a solution vapor diffusion of Form A in a DMAc / H2O system at RT. The XRPD pattern of Form N is shown in Figure 13. Form O

[0150] Form O was obtained via a slow cooling of Form A in MeOH. The XRPD pattern of Form O is shown in Figure 14. Form P

[0151] Form P was obtained via a slow evaporation of Form A in MeOH / DCM (1:1, v / v) at RT followed by drying at RT. The XRPD pattern of Form P is shown in Figure 15. The TGA / DSC curves are shown in Figure 37, which showed a two-step weight loss of 1.02% up to 60 ºC and 3.93% from 60 ºC to 150 ºC, and two endotherms at 104.5 and 224.7 ºC (peak). Form Q

[0152] Form Q was obtained via slurring Form A in MeOH with temperature cycling (50 ºC~5 ºC, 0.1 ºC / min, 2 cycles) followed by drying at RT. The XRPD pattern of Form Q is shown in Figure 16. The TGA / DSC curves are shown in Figure 38, which showed a two- step weight loss of 1.38% up to 50 ºC and 4.52% from 50 ºC to 150 ºC., and two endotherms at 99.3 and 224.8 ºC (peak). Form R

[0153] Form R was obtained via a solution vapor diffusion of Form A in a 1,4- Dioxane / n-Hexane system at RT. The XRPD pattern of Form R is shown in Figure 17. The TGA / DSC curves are shown in Figure 39, which showed a two-step weight loss of 0.91% up to 80 ºC, and 2.90% from 80 ºC to 150 ºC and two endotherms at 86.6 and 224.9 ºC (peak). Form S 39 ME151785720v.1139260-00120

[0154] Form S was obtained via a slow cooling of Form A in ACN / H2O (1:1, v / v) followed by drying at RT. The XRPD pattern of Form S is shown in Figure 18. The TGA / DSC curves are shown in Figure 40, which showed a weight loss of 1.40% up to 150 ºC and two endotherms at 88.9 and 224.1 ºC (peak). Form U

[0155] Form U was obtained via heating Form B to 130 oC and cooling to 30 oC. TheXRPD pattern of Form U is shown in Figure 19. The TGA / DSC curves are shown in Figure 41, which showed a weight loss of 1.45% up to 150 ºC and one endotherm at 224.7 ºC (peak). The small TGA weight loss and small residual solvent content showed Form U to be an anhydrate. Form V

[0156] Form V was obtained via slurring Form A in EtOH in RT. The XRPD pattern of Form V is shown in Figure 20. The TGA / DSC curves are shown in Figure 42, which showed a two-step weight loss of 2.96% up to 90 ºC and 8.98% from 90 ºC to 150 ºC, and three endotherms at 73.8, 105.0 and 224.5 ºC (peak). Form W

[0157] Form W was obtained via a fast cooling of Form A in BuOH. The XRPD pattern of Form W is shown in Figure 21. Form X

[0158] Form X was obtained via fast cooling Form A in BuOH followed by drying at RT. The XRPD pattern of Form X is shown in Figure 43. The TGA / DSC curves are shown in Figure 47, which showed a two-step weight loss of 4.89% up to 70 ºC and 6.31% from 70 ºC to 150 ºC, and two endotherms at 79.9 and 224.5 ºC (peak). Form Y

[0159] Form Y was obtained via evaporation of Form A in BuOH at RT. The XRPD pattern of Form Y is shown in Figure 23. The TGA / DSC curves are shown in Figure 44, which showed a two-step weight loss of 2.14% up to 70 ºC and 12.55% from 70 ºC to 150 ºC, and two endotherms at 83.9 and 224.4 ºC (peak). Form Z

[0160] Form Z was obtained via fast cooling Form A in IPA The XRPD pattern of Form Z is shown in Figure 24. Form AA

[0161] Form AA was obtained from Form S via N2purge for 20 min. The XRPD pattern of Form AA is shown in Figure 25. 40 ME151785720v.1139260-00120 Summary of Polymorph Results / Properties

[0162] The crystalline forms above were obtained via a variety of polymorph screens, a summary of which is shown below. As can be seen, Form A is the most prevalent form obtained during the screening process, especially for the slurry and temperature cycling experiments, indicating that Form A is the most stable and preferred polymorph.

[0163] Vapor-solid diffusion experiments were conducted using 8 different solvents. Approximately 20 mg of Form A was weighed into a 3-mL vial, which was placed into a 20- mL vial with 4 mL of volatile solvent. The 20-mL vial was sealed with a cap and kept at RT for 8 days allowing solvent vapor to interact with sample. The solids were tested by XRPD and the results summarized in the table below.*: The sample was clear after 8 days, and the solid was obtained after evaporation.

[0164] Vapor-solution experiments were conducted using 11 different solvents. Approximately 20 mg of Form A was dissolved in 0.2 to 1.5 mL of appropriate solvent to obtain a clear solution in a 3-mL vial. This solution was then placed into a 20-mL vial with 4 mL of volatile solvent. The 20-mL vial was sealed with a cap and kept at RT allowing sufficient time for organic vapor to interact with the solution. The obtained solids were tested by XRPD and the results summarized in the table below:41 ME151785720v.1139260-00120*: The sample was clear after 8 days, and the solid was obtained after evaporation.

[0165] Slow cooling experiments were conducted in 7 solvent systems.20 to 60 mg of Form was suspended in 0.8 to 1.4 mL of solvent in a 3-mL glass vial at RT. The suspension was then heated to 50 ºC, equilibrated for about 3 hrs and filtered to a new vial. Filtrates were slowly cooled down to 5 ºC at a rate of 0.1 ºC / min. The obtained solids were kept isothermal at 5 ºC and then solids were tested by XRPD. The clear samples were transferred to -20 ºC. The clear samples or sample with little solid were transferred to RT for evaporation. The results are summarized in the table below:*: Little solid was obtained at 5 ºC and -20 ºC, and the solid was obtained via evaporation at RT. #: Clear solution was obtained at 5 ºC, and the solid was obtained at -20 ºC.

[0166] For the slurry at RT experiments, 20 to 60 mg of Form A was suspended in 0.5 mL of solvent in an HPLC glass vial. After the suspension was stirred magnetically (1000 rpm) for 3 days at RT, the remaining solids were centrifuged for XRPD analysis. The results are summarized in the table below:42 ME151785720v.1139260-00120*: Clear solution was obtained via slurry at RT for 16 hrs, additional Form A was added, and suspension was obtained via slurry at RT for 2 days.

[0167] For the slurry at 50oC, 20 to 60 mg of Form A was suspended in 0.5 mL of solvent in an HPLC glass vial. After the suspension was stirred (1000 rpm) for about 3 days at 50 ºC, the remaining solids were centrifuged for XRPD analysis. The results are summarized in the table below:*: Clear solution or little solid was obtained via slurry at 50 ºC for 16 hrs, additional starting material (829117-01-A) was added, and suspension was obtained via slurry at 50 ºC for 2 days.

[0168] Temperature cycling experiments were completed for 12 different solvents. About 20 mg of Form A was suspended in 0.5 mL of solvent in an HPLC glass vial. After heating- cooling (50 ºC to 5 ºC, 0.1 ºC / min) was performed for the suspension for 2 cycles, the remaining solids were centrifuged for XRPD analysis. The results are summarized in the table below:43 ME151785720v.1139260-00120*: Clear solution was obtained via temperature cycling (50 ºC~5 ºC, 0.1 ºC / min, 2 cycles). Additional starting material (829117-01-A) was added, and suspension was obtained via temperature cycling (50 ºC~5 ºC, 0.1 ºC / min, 2 cycles).

[0169] Slow evaporation experiments were performed with 14 different solvent conditions. About 20 mg of Form A was dissolved in 0.2-1.7 mL of solvent in a 3 mL glass vial. The resulting solution was subjected to slow evaporation at RT with vials sealed and poked with 4 pinholes. The remaining solids were isolated and analyzed by XRPD, the results of which are summarized in the table below:

[0170] Grinding experiments were performed with or without solvent addition. Approximately 20 mg of Form A was weighed into the mortar.20 μL solvent was optionally added into the mortar. The solids were ground for 3 to 5 min then isolated for XRPD analysis. The results are summarized in the table below: 44 ME151785720v.1139260-00120

[0171] A total of 18 anti-solvent addition experiments were carried out. About 20 mg of Form A was dissolved in 0.2 to 1.5 mL solvent to obtain a clear solution and the solution was magnetically stirred (~1000 rpm) followed by addition of anti-solvent until precipitate appeared or the total amount of anti-solvent reached 10.0 mL. The samples without precipitate were transferred to slurry at 5 ºC and then transferred to slurry at -20 ºC. The clear sample or sample with little solid was transferred to RT for evaporation. The solids were isolated for XRPD analysis. The results are summarized in the table below:*: Clear solution was obtained via slurry at RT and 5 ºC. The sample was a little turbid at -20 ºC, and was transferred to evaporate at RT. #: Clear solution was obtained via slurry at RT. Solid was obtained via slurry at 5 ºC. Interconversion Studies

[0172] Several interconversion studies were completed in an effort to test the stability of the various forms. The results of these studies are shown in the flow chart in Figure 45. As can be seen, Form A was discovered to be the preferred form to which all forms eventually converted. This was something that could not be predicted, particularly given the many 45 ME151785720v.1139260-00120 crystalline forms that were identified and the fact that the initial material as described in WO 2016 / 176460 was substantially amorphous, as described above.

[0173] For the first experiment, 2 to 90 mg of Form A was weighed into four separate UPLC vials, by addition of 0.5 mL solvent and slurry at RT or 50 ºC for 4 hours. After slurry, the samples were filtered with 0.45 μm PTFE filter. The filtrates were transferred into the UPLC vials containing approximately 5 mg of Forms A, F, G, and U followed by slurry at RT or 50 ºC. The results of this experiment are summarized in the table below, and showed that Form A was obtained as a result of all experiments, indicating the Form A is the most thermodynamically stable form.

[0174] For the second experiment 5 to 210 mg of Form A was weighed into six separate UPLC vials followed by addition of 0.5 mL solvent and slurry at RT for 4 hours. After slurry, the samples were filtered with 0.45 μm PTFE filter. The filtrates were transferred into the UPLC vials containing ~5 mg of Forms A, D, L, P, Q, and S followed by slurry at RT. The results of this experiment are summarized in the table below, and showed that Form A was obtained as a result of all experiments, indicating the Form A is the most thermodynamically stable form.Further Evaluation of Form A

[0175] To evaluate the hygroscopicity of Form A, a DVS isotherm plot was collected at 25 ºC between 0%RH and 95%RH and XRPD characterization was performed for the sample after DVS test. The water uptake of Form A at 25 ºC / 80 %RH was 0.0347%, which was non- hygroscopic. After the DVS test, no form change was observed for Form A. 46 ME151785720v.1139260-00120

[0176] The solubility and stability of Form A was tested in a variety of representative biological solvents at RT. Approximately 5 mg of Form A was added into 1.0 mL of the solvents followed by slurring at 500 rpm at 37oC for 24 hours, after which the sample was centrifuged and filtered. The resultant solid was analyzed by XRPD, which showed no form change. The results of the solubility test are shown in the table below:

[0177] In order to further evaluate the stability of Form A, Form A was placed under the conditions of 60 ºC for 24 hrs, 25ºC / 60 %RH and 40 ºC / 75 %RH for 1 week. The physical and chemical stability were evaluated by XRPD and UPLC purity, respectively. No UPLC purity change and no form change was observed. These data further show the impressive unexpected stability of Form A.

[0178] While we have described a number of embodiments, it is apparent that our basic examples may be altered to provide other embodiments that utilize the compounds and methods of this invention. Therefore, it will be appreciated that the scope of this invention is to be defined by the appended claims rather than by the specific embodiments that have been represented by way of example.

[0179] The contents of all references (including literature references, issued patents, published patent applications, and co-pending patent applications) cited throughout this application are hereby expressly incorporated herein in their entireties by reference. Unless otherwise defined, all technical and scientific terms used herein are accorded the meaning commonly known to one with ordinary skill in the art. 47 ME151785720v.1

Claims

139260-00120 CLAIMS What is claimed is:

1. A crystalline Form A, Form B, Form C, Form D, Form E, Form F, Form G, Form H, Form I, Form J, Form L, Form M, Form N, Form O, Form P, Form Q, Form R, Form S, Form U, Form V, Form W, Form X, Form Y, Form Z, or Form AA of a compound having the following structural formula:.

2. The crystalline Form A of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 12.3, 12.9, 13.7, 22.0, 24.5, and 25.

2.

3. The crystalline Form A of claim 1 or 2, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 12.3, 12.9, 13.7, 22.0, 24.5, and 25.

2.

4. The crystalline Form A of any one of claims 1 to 3, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 12.3, 12.9, 13.7, 22.0, 24.5, and 25.

2.

5. The crystalline Form A of claim 1, wherein said crystalline form is characterized by an X-ray powder diffraction peak at 2Θ angle 13.7 and at least three additional X-ray powder diffraction peaks at 2Θ angles selected from 12.3, 12.9, 22.0, 24.5, and 25.

2.

6. The crystalline Form A of claim 1 or 5, wherein said crystalline form is characterized by an X-ray powder diffraction peak at 2Θ angle 13.7 and at least four additional X-ray powder diffraction peaks at 2Θ angles selected from 12.3, 12.9, 22.0, 24.5, and 25.

2. 48 ME151785720v.1139260-00120 7. The crystalline Form A of any one of claims 1, 5, or 6, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 12.3, 12.9, 13.7, 22.0, 24.5, and 25.

2.

8. The crystalline Form A of claim 1, wherein said crystalline form is characterized by X-ray powder diffraction peaks at a 2Θ angles 13.7 and 33.6 and at least three additional X- ray powder diffraction peaks at 2Θ angles selected from 12.3, 12.9, 22.0, 24.5, and 25.

2.

9. The crystalline Form A of claim 1 or 8, wherein said crystalline form is characterized by X-ray powder diffraction peaks at a 2Θ angles 13.7 and 33.6 and at least four additional X-ray powder diffraction peaks at 2Θ angles selected from 12.3, 12.9, 22.0, 24.5, and 25.

2.

10. The crystalline Form A of claim any one of claims 1, 8, or 9, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 12.3, 12.9, 13.7, 22.0, 24.5, 25.2, and 33.

6.

11. The crystalline Form A of any one of claims 1 to 10, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 12.3, 12.9, 13.7, 20.3, 21.2, 22.0, 24.5, 25.2, 26.6, and 33.

6.

12. The crystalline Form A of claim 1, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 12.3, 12.9, 13.7, 20.3, 21.2, 21.9, 24.5, 24.7, 25.2, and 26.

6.

13. The crystalline Form A of any one of claims 1 to 12, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 1.

14. The crystalline Form B of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 9.0, 11.6, 12.1, 16.4, and 19.

2.

15. The crystalline Form B of claim 1 or 14, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 9.0, 11.6, 12.1, 16.4, and 19.

2. 49 ME151785720v.1139260-00120 16. The crystalline Form B of any one of claims 1, 14, or 15, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 9.0, 11.6, 12.1, 16.4, and 19.

2.

17. The crystalline Form B of any one of claims 1, or 14 to 16, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 9.0, 11.6, 12.1, 15.5, 16.4, 19.2, 19.8, 20.6, 24.1, and 25.

2.

18. The crystalline Form B of any one of claims 1 or 14 to 17, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 2.

19. The crystalline Form C of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 17.6, 24.2, 24.4, 25.

6.

20. The crystalline Form C of claim 1 or 19, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 17.6, 24.2, 24.4, and 25.

6.

21. The crystalline Form C of any one of claims 1, 19, or 20, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 17.6, 24.2, 24.4, and 25.

6.

22. The crystalline Form C of any one of claims 1 or 19 to 21, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 12.8, 17.6, 19.7, 22.3, 24.2, 24.4, 25.6, 25.9, 30.

2.

23. The crystalline Form C of any one of claims 1 or 19 to 22, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 3.

24. The crystalline Form D of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 10.8, 14.5, 19.2, 25.3, and 29.

2. 50 ME151785720v.1139260-00120 25. The crystalline Form D of claim 1 or 24, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 10.8, 14.5, 19.2, 25.3, and 29.

2.

26. The crystalline Form D of any one of claims 1, 24, or 25, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 10.8, 14.5, 19.2, 25.3, and 29.

2.

27. The crystalline Form D of any one of claims 1 or 24 to 26, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 10.8, 14.5, 19.2, 19.4, 23.7, 25.3, 25.7, 26.9, 29.2, 32.

8.

28. The crystalline Form D of any one of claims 1 or 24 to 27, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 4.

29. The crystalline Form E of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 14.4, 15.1, 17.2, 21.8, and 24.

3.

30. The crystalline Form E of claim 1 or 29, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 14.4, 15.1, 17.2, 21.8, and 24.

3.

31. The crystalline Form E of any one of claims 1, 29, or 30, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 14.4, 15.1, 17.2, 21.8, and 24.

3.

32. The crystalline Form E of any one of claims 1 or 29 to 31, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 14.4, 15.1, 17.2, 21.8, 22.9, 23.824.3, 24.8, 29.0, and 29.

9.

33. The crystalline Form E of any one of claims 1 or 29 to 32, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 5. 51 ME151785720v.1139260-00120 34. The crystalline Form G of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 7.4, 14.9, 16.8, 17.4, and 22.

4.

35. The crystalline Form G of claim 1 or 34, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 7.4, 14.9, 16.8, 17.4, and 22.

4.

36. The crystalline Form G of any one of claims 1, 34, or 35, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 7.4, 14.9, 16.8, 17.4, and 22.

4.

37. The crystalline Form G of any one of claims 1 or 34 to 36, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 7.4, 10.6, 12.4, 14.9, 15.9, 16.8, 17.4, 18.8, and 22.

4.

38. The crystalline Form G of any one of claims 1 or 34 to 37, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 7.

39. The crystalline Form H of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 14.3, 17.5, 19.5, and 24.

8.

40. The crystalline Form H of claim 1 or 39, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 14.3, 17.5, 19.5, and 24.

8.

41. The crystalline Form H of any one of claims 1, 39, or 40, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 14.3, 17.5, 19.5, and 24.

8. 52 ME151785720v.1139260-00120 42. The crystalline Form H of any one of claims 1 or 39 to 41, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 9.7, 11.7, 12.7, 14.3, 17.5, 18.6, 19.5, 22.0, 23.1, and 24.

8.

43. The crystalline Form H of any one of claims 1 or 39 to 42, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 8.

44. The crystalline Form I of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 7.9, 10.6, 12.3, 18.6, and 19.

0.

45. The crystalline Form I of claim 1 or 44, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 7.9, 10.6, 12.3, 18.6, and 19.

0.

46. The crystalline Form I of any one of claims 1, 44, or 45, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 7.9, 10.6, 12.3, 18.6, and 19.

0.

47. The crystalline Form I of any one of claims 1 or 44 to 46, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 7.9, 10.6, 12.3, 12.8, 13.3, 16.6, 18.6, 19.0.22.9, and 25.

2.

48. The crystalline Form I of any one of claims 1 or 44 to 47, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 9.

49. The crystalline Form J of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 9.5, 9.8, 14.0, 21.1, and 29.

5.

50. The crystalline Form J of claim 1 or 49, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 9.5, 9.8, 14.0, 21.1, and 29.

5. 53 ME151785720v.1139260-00120 51. The crystalline Form J of any one of claims 1, 49, or 50, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 9.5, 9.8, 14.0, 21.1, and 29.

5.

52. The crystalline Form J of any one of claims 1 or 49 to 51, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 7.0, 9.5, 9.8, 12.8, 14.0, 19.6, 21.1, 28.3, 29.3, and 29.

5.

53. The crystalline Form J of any one of claims 1 or 49 to 52, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 10.

54. The crystalline Form L of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 9.5, 10.9, 14.2, 16.3, and 24.

7.

55. The crystalline Form L of claim 1 or 54, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 9.5, 10.9, 14.2, 16.3, and 24.

7.

56. The crystalline Form L of any one of claims 1, 54, or 55, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 9.5, 10.9, 14.2, 16.3, and 24.

7.

57. The crystalline Form L of any one of claims 1 or 54 to 56, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 9.5, 10.9, 13.8, 14.2, 16.3, 21.3, 24.7, 25.2, 27.2, and 28.

7.

58. The crystalline Form L of any one of claims 1 or 54 to 57, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 11.

59. The crystalline Form M of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 8.8, 17.7, 24.6, 26.6, and 30.

8. 54 ME151785720v.1139260-00120 60. The crystalline Form M of claim 1 or 59, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 8.8, 17.7, 24.6, 26.6, and 30.

8.

61. The crystalline Form M of any one of claims 1, 59, or 60, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 8.8, 17.7, 24.6, 26.6, and 30.

8.

62. The crystalline Form M of any one of claims 1 or 59 to 61, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 6.7, 8.8, 14.2, 17.7, 20.9, 22.0, 24.6, 25.8, 26.6, and 30.

8.

63. The crystalline Form M of any one of claims 1 or 59 to 62, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 12.

64. The crystalline Form N of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 9.1, 9.4, 18.2, 18.8, and 24.

1.

65. The crystalline Form N of claim 1 or 64, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 9.1, 9.4, 18.2, 18.8, and 24.

1.

66. The crystalline Form N of any one of claims 1, 64, or 65, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 9.1, 9.4, 18.2, 18.8, and 24.

1.

67. The crystalline Form N of any one of claims 1 or 64 to 66, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 9.1, 9.4, 14.8, 18.2, 18.8, 19.4, 23.3, 24.1, 27.2, and 29.

7.

68. The crystalline Form N of any one of claims 1 or 64 to 67, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 13. 55 ME151785720v.1139260-00120 69. The crystalline Form O of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 12.8, 17.6, 19.5, and 25.

7.

70. The crystalline Form O of claim 1 or 69, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 12.8, 17.6, 19.5, and 25.

7.

71. The crystalline Form O of any one of claims 1, 69, or 70, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 12.8, 17.6, 19.5, and 25.

7.

72. The crystalline Form O of any one of claims 1 or 69 to 71, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 9.7, 11.7, 12.8, 17.6, 18.6, 19.5, 22.0, 23.9, 25.7, and 30.

1.

73. The crystalline Form O of any one of claims 1 or 69 to 72, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 14.

74. The crystalline Form P of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 12.9, 17.6, 25.1, and 30.

3.

75. The crystalline Form P of claim 1 or 74, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 12.9, 17.6, 25.1, and 30.

3.

76. The crystalline Form P of any one of claims 1, 74, or 75, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 12.9, 17.6, 25.1, and 30.

3.

77. The crystalline Form P of any one of claims 1 or 74 to 76, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 12.9, 14.4, 17.6, 19.8, 22.3, 23.3, 25.1, 25.9, and 30.

3. 56 ME151785720v.1139260-00120 78. The crystalline Form P of any one of claims 1 or 74 to 77, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 15.

79. The crystalline Form Q of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 17.6, 19.8, 24.3, and 25.

2.

80. The crystalline Form Q of claim 1 or 79, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 11.7, 17.6, 19.8, 24.3, and 25.

2.

81. The crystalline Form Q of any one of claims 1, 79, or 80, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 11.7, 17.6, 19.8, 24.3, and 25.

2.

82. The crystalline Form Q of any one of claims 1 or 79 to 81, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 11.0, 11.7, 12.9, 16.6, 17.6, 19.8, 24.3, 25.2, 25.9, and 30.

4.

83. The crystalline Form Q of any one of claims 1 or 79 to 82, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 16.

84. The crystalline Form R of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 5.7, 11.3, 13.4, 17.0, and 28.

5.

85. The crystalline Form R of claim 1 or 84, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 5.7, 11.3, 13.4, 17.0, and 28.

5.

86. The crystalline Form R of any one of claims 1, 84, or 85, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 5.7, 11.3, 13.4, 17.0, and 28.

5. 57 ME151785720v.1139260-00120 87. The crystalline Form R of any one of claims 1 or 84 to 86, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 5.7, 11.3, 12.5, 13.4, 17.0, 23.8, 24.4, 25.2, 28.5, and 32.

9.

88. The crystalline Form R of any one of claims 1 or 84 to 87, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 17.

89. The crystalline Form S of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 8.2, 10.9, 13.6, 17.1, and 19.

1.

90. The crystalline Form S of claim 1 or 89, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 8.2, 10.9, 13.6, 17.1, and 19.

1.

91. The crystalline Form S of any one of claims 1, 89, or 90, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 8.2, 10.9, 13.6, 17.1, and 19.

1.

92. The crystalline Form S of any one of claims 1 or 89 to 91, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 8.2, 10.9, 13.6, 16.4, 17.1, 19.1, 19.5, 21.9, 22.8, and 24.

6.

93. The crystalline Form S of any one of claims 1 or 89 to 92, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 18.

94. The crystalline Form U of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 12.0, 12.6, 21.4, 24.7, and 25.

3.

95. The crystalline Form U of claim 1 or 94, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 12.0, 12.6, 21.4, 24.7, and 25.

3. 58 ME151785720v.1139260-00120 96. The crystalline Form U of any one of claims 1, 94, or 95, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 12.0, 12.6, 21.4, 24.7, and 25.

3.

97. The crystalline Form U of any one of claims 1 or 94 to 96, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 12.0, 12.6, 16.6, 18.4, 19.5, 20.6.21.4, 23.8, 24.7, and 25.

3.

98. The crystalline Form U of any one of claims 1 or 94 to 97, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 19.

99. The crystalline Form V of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 10.8, 14.4, 19.4, 25.9, and 28.

9.

100. The crystalline Form V of claim 1 or 99, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 10.8, 14.4, 19.4, 25.9, and 28.

9.

101. The crystalline Form V of any one of claims 1, 99, or 100, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 10.8, 14.4, 19.4, 25.9, and 28.

9.

102. The crystalline Form V of any one of claims 1 or 99 to 101, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 10.8, 14.4, 18.6, 18.9, 19.4, 22.7, 25.0, 25.9, 28.9, and 32.

7.

103. The crystalline Form V of any one of claims 1 or 99 to 102, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 20.

104. The crystalline Form W of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 6.7, 7.1, 7.9, 13.5, and 14.

2. 59 ME151785720v.1139260-00120 105. The crystalline Form W of claim 1 or 104, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 6.7, 7.1, 7.9, 13.5, and 14.

2.

106. The crystalline Form W of any one of claims 1, 104, or 105, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 6.7, 7.1, 7.9, 13.5, and 14.

2.

107. The crystalline Form W of any one of claims 1 or 104 to 106, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 6.7, 7.1, 7.9, 11.4, 13.5, 14.2, 15.7, 17.3, 21.4, and 28.

6.

108. The crystalline Form W of any one of claims 1 or 104 to 107, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 21.

109. The crystalline Form X of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 7.1, 7.9, 11.0, 14.2, and 24.

7.

110. The crystalline Form X of claim 1 or 109, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 7.1, 7.9, 11.0, 14.2, and 24.

7.

111. The crystalline Form X of any one of claims 1, 109, or 110, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 7.1, 7.9, 11.0, 14.2, and 24.

7.

112. The crystalline Form X of any one of claims 1 or 109 to 111, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 7.1, 7.9, 11.0, 14.2, 15.8, 16.5, 21.4, 24.7, and 32.

0.

113. The crystalline Form X of any one of claims 1 or 109 to 112, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 22. 60 ME151785720v.1139260-00120 114. The crystalline Form Y of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 7.1, 7.4, 7.8, 11.7, or 14.

8.

115. The crystalline Form Y of claim 1 or 114, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 7.1, 7.4, 7.8, 11.7, or 14.

8.

116. The crystalline Form Y of any one of claims 1, 114, or 115, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 7.1, 7.4, 7.8, 11.7, or 14.

8.

117. The crystalline Form Y of any one of claims 1 or 114 to 116, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 7.1, 7.4, 7.8, 11.7, 17.7, 14.0, 14.8, 19.3, 24.4, and 26.

2.

118. The crystalline Form Y of any one of claims 1 or 114 to 117, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 23.

119. The crystalline Form Z of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 7.6, 8.0, 10.1, 14.2, and 15.

9.

120. The crystalline Form Z of claim 1 or 119, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 7.6, 8.0, 10.1, 14.2, and 15.

9.

121. The crystalline Form Z of any one of claims 1, 119, or 120, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 7.6, 8.0, 10.1, 14.2, and 15.

9. 61 ME151785720v.1139260-00120 122. The crystalline Form Z of any one of claims 1 or 119 to 121, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 7.6, 8.0, 10.0, 13.2, 14.2, 15.2, 15.9, 19.8, and 30.

7.

123. The crystalline Form Z of any one of claims 1 or 119 to 122, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 24.

124. The crystalline Form AA of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 8.1, 10.8, 13.5, 17.0, and 19.

0.

125. The crystalline Form AA of claim 1 or 124, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 8.1, 10.8, 13.5, 17.0, and 19.

0.

126. The crystalline Form AA of any one of claims 1, 124, or 125, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 8.1, 10.8, 13.5, 17.0, and 19.

0.

127. The crystalline Form AA of any one of claims 1 or 124 to 126, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 8.1, 10.8, 13.5, 16.2, 17.0, 19.0, 19.4, 21.7, 23.0, and 24.

8.

128. The crystalline Form AA of any one of claims 1 or 124 to 127, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 25.

129. The crystalline Form F of claim 1, wherein said crystalline form is characterized by at least three X-ray powder diffraction peaks at 2Θ angles selected from 18.6, 19.4, 23.4, 26.9, and 30.

1.

130. The crystalline Form F of claim 1 or 129, wherein said crystalline form is characterized by at least four X-ray powder diffraction peaks at 2Θ angles selected from 18.6, 19.4, 23.4, 26.9, and 30.

1. 62 ME151785720v.1139260-00120 131. The crystalline Form F of any one of claims 1, 129, or 130, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 18.6, 19.4, 23.4, 26.9, and 30.

1.

132. The crystalline Form F of any one of claims 1 or 129 to 131, wherein said crystalline form is characterized by X-ray powder diffraction peaks at 2Θ angles 13.5, 14.5, 16.1, 18.6, 19.4, 23.4, 24.6, 25.3, 26.9, and 30.

1.

133. The crystalline Form F of any one of claims 1 or 129 to 132, wherein the crystalline form is characterized by an X-ray powder diffraction substantially similar to Figure 6.

134. The crystalline Form A, Form B, Form C, Form D, Form F, Form E, Form G, Form H, Form I, Form J, Form L, Form M, Form N, Form O, Form P, Form Q, Form R, Form S, Form U, Form V, Form W, Form X, Form Y, Form Z, or Form AA, of any one of claims 1 to 133, wherein the crystalline form is at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% a single crystalline form.

135. The crystalline Form A, Form B, Form C, Form D, Form F, Form E, Form G, Form H, Form I, Form J, Form L, Form M, Form N, Form O, Form P, Form Q, Form R, Form S, Form U, Form V, Form W, Form X, Form Y, Form Z, or Form AA, of any one of claims 1 to 134, wherein the crystalline form is substantially free from amorphous form of the compound.

136. A pharmaceutical composition comprising the crystalline Form A, Form B, Form C, Form D, Form E, Form F, Form G, Form H, Form I, Form J, Form L, Form M, Form N, Form O, Form P, Form Q, Form R, Form S, Form U, Form V, Form W, Form X, Form Y, Form Z, or Form AA of any one of claims 1 to 135; and a pharmaceutically acceptable carrier.

137. A method of treating a condition responsive to the modulation of TARP γ8-dependent AMPA receptor activity in a subject, the method comprising administering to the subject an effective amount of the crystalline Form A, Form B, Form C, Form D, Form E, Form F, Form G, Form H, Form I, Form J, Form L, Form M, Form N, Form O, Form P, Form Q, Form R, 63 ME151785720v.1139260-00120 Form S, Form U, Form V, Form W, Form X, Form Y, Form Z, or Form AA of any one of claims 1 to 135, or the pharmaceutical composition of claim 136.

138. The method of claim 137, wherein the condition responsive to the inhibition of TARP γ8-dependent AMPA receptor activity is epilepsy, epileptic disorders, seizures, seizure disorders, pain, a psychiatric disorder, or a neurodegenerative disease.

139. The method of claims 138, wherein the condition responsive to the inhibition of TARP γ8-dependent AMPA receptor activity is focal onset epilepsy or focal onset seizures, absence epilepsy, early infantile developmental end epileptic encephalopathy, childhood absence epilepsy, childhood epilepsy centrotemporal spiked (benign Roland epilepsy), Dravet syndrome, epilepsy eyelid myoclonia jeavons syndrome, epilepsy of infancy with migrating focal seizure, epilepsy myoclonic absences, developmental / epileptic encephalopathy with spike wave activation in sleep, fired febrile infection-related epilepsy syndrome, Hypothalamic hamartoma, indantile spasms (west syndrome), juvenile myoclonic epilepsy, Lennox-Gastaut syndrome (LGS), myoclonic epilepsy in infancy, Panayiotopoulos syndrome, progressive myoclonic epilepsies, Rasmussen’s encephalitis, reflex epilepsies, self-limited familial and non-familial neonatal infant seizures, self-limited late onset occipital epilepsy Gastaut syndrome, epilepsy generalized tonic clonic seizures alone, genetic epilepsy with febrile seizure plus, juvenile absence epilepsy, myoclonic atonic epilepsy doose syndrome, developmental and epileptic encephalopathy (DEE), frontal lobe epilepsy, temporal lobe epilepsy (TLE), neocortal epilepsy, or sleep-related hypermotor epilepsy, absence seizures, atonic seizures, atypical absence seizures, clonic seizures, epileptic or infantile spasms, eclampsia, febrile seizures, focal bilateral tonic clonic seizures (secondarily generalized seizures), focal aware seizures (simple partial seizures), focal impaired awareness seizures (complex partial seizures), gelastic and dacrystic seizures, myoclonic seizures, drug- resistant seizures, new terms seizure classification, tonic-clonic seizures, tonic seizures, neuropathic pain, acute pain, inflammatory pain, bipolar disorder, acute mania, acute depression, major depressive disorder, post-traumatic stress disorder (PTSD), or Alzheimer’s disease.

140. The method of claims 138, wherein the condition responsive to the inhibition of TARP γ8-dependent AMPA receptor activity is focal onset epilepsy or focal onset seizures. 64 ME151785720v.1