Crystalline forms of a TYK2 inhibitor and uses thereof

Abstract

The disclosure is in part directed to crystalline salt forms of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropane carboxamide, pharmaceutical compositions thereof, and methods of use.

Description

Attorney Docket No.: ESK-025WO CRYSTALLINE FORMS OF A TYK2 INHIBITOR AND USES THEREOF CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of, and priority to, U.S. Provisional Patent Application No. 63 / 671,862, filed on July 16, 2024; the content of which is hereby incorporated by reference herein in its entirety. BACKGROUND

[0002] TYK2 is a non-receptor tyrosine kinase member of the Janus kinase (JAKs) family of protein kinases. TYK2 activation has been linked to diseases and disorders such as, for example, autoimmune disorders, inflammatory disorders, proliferative disorders (e.g., cancer), endocrine disorders, and neurological disorders. For example, TYK2 activation has been linked to inflammatory bowel disease (IBD), Crohn's disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, ulcerative colitis, psoriatic arthritis, and systemic sclerosis. TYK2 also plays a role in respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and cystic fibrosis. Accordingly, compounds that inhibit the activity of TYK2 are beneficial, especially those with selectivity over JAK2. Such compounds should deliver a pharmacological response that favorably treats one or more of the conditions described herein without the side-effects associated with the inhibition of JAK2.

[0003] Polymorphism is the ability of a substance to crystallize in more than one crystal lattice arrangement. Crystallization, or polymorphism, can influence many aspects of the solid- state properties of a drug substance. A crystalline substance may differ considerably from an amorphous form, and different crystal modifications of a substance may differ considerably from one another in many respects including solubility, dissolution rate and / or bioavailability. Generally, it is difficult to predict whether a given compound will form any crystalline solid- state forms. It is even more difficult to predict the physical properties of these crystalline solid- state forms. Therefore, it can be advantageous to have a crystalline form of a therapeutic agent for certain formulations and / or for manufacturing processes. 1 IPTS / 128645168.1Attorney Docket No.: ESK-025WO SUMMARY

[0004] The present disclosure is directed, at least in part, to crystalline salt forms of N-(4- ((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide. Also disclosed are crystalline hydrates, anhydrates, hemihydrates, solvates, tautomers and cocrystals of any of the crystalline forms described herein.

[0005] For example, disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.3, for example, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 10.3, 11.3, and 23.9, for example, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 10.3, 11.3, 19.5, 20.3, 23.9, and 24.4, for example, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 10.3, 11.3, 12.1, 13.3, 19.5, 20.3, 23.9, 24.4, and 25.3, for example, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 10.3, 11.3, 12.1, 13.3, 19.5, 20.3, 21.9, 23.9, 24.4, 24.8, 25.3, and 25.9.

[0006] N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide is, for example, a modulator of tyrosine kinase 2 (TYK2), e.g., an inhibitor of TYK2, and is represented by: .

[0007] Further contemplated herein is a pharmaceutical composition comprising a disclosed crystalline salt form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide and a pharmaceutically acceptable excipient, for example, a composition that is formulated for oral 2 IPTS / 128645168.1Attorney Docket No.: ESK-025WO administration. Further contemplated herein is a drug substance comprising at least a detectable amount of a disclosed crystalline salt form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4- triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide. For example, disclosed herein is a drug substance comprising substantially pure crystalline salt form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide.

[0008] Also provided herein is a method of treating a TYK2-mediated disorder in a patient in need thereof, comprising administering to the patient an effective amount of a disclosed crystalline salt form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide.

[0009] For example, provided herein is a method of treating a neuroinflammatory disease, for example, multiple sclerosis, in a patient in need thereof, comprising administering to the patient an effective amount of a disclosed crystalline salt form of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] FIG. 1 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 1).

[0011] FIG. 2 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 1).

[0012] FIG. 3 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 1).

[0013] FIG. 4 depicts the asymmetric unit of the N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 1) single X-ray crystal structure. 3 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0014] FIG. 5 depicts the ORTEP drawing of the N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 1) single X-ray crystal structure.

[0015] FIG. 6 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 2).

[0016] FIG. 7 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 2).

[0017] FIG. 8 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 2).

[0018] FIG. 9 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 4).

[0019] FIG. 10 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 4).

[0020] FIG. 11 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 4).

[0021] FIG. 12 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 5).

[0022] FIG. 13 depicts the differential scanning calorimetry (DSC) profile of (4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 5). 4 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0023] FIG. 14 depicts the thermogravimetric analysis (TGA) profile of (4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 5).

[0024] FIG. 15 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 6).

[0025] FIG. 16 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 6).

[0026] FIG. 17 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 6).

[0027] FIG. 18 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 7).

[0028] FIG. 19 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 7).

[0029] FIG. 20 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 7).

[0030] FIG. 21 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 8).

[0031] FIG. 22 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 8). 5 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0032] FIG. 23 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 8).

[0033] FIG. 24 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 9).

[0034] FIG. 25 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 9).

[0035] FIG. 26 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 9).

[0036] FIG. 27 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 13).

[0037] FIG. 28 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 13).

[0038] FIG. 29 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 13).

[0039] FIG. 30 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen chloride (Form 1).

[0040] FIG. 31 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen chloride (Form 1). 6 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0041] FIG. 32 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen chloride (Form 1).

[0042] FIG. 33 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen chloride (Form 2).

[0043] FIG. 34 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen chloride (Form 2).

[0044] FIG. 35 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen chloride (Form 2).

[0045] FIG. 36 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen chloride (Form 3).

[0046] FIG. 37 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen chloride (Form 3).

[0047] FIG. 38 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen chloride (Form 3).

[0048] FIG. 39 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen sulfate (Form 1).

[0049] FIG. 40 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen sulfate (Form 1). 7 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0050] FIG. 41 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen sulfate (Form 1).

[0051] FIG. 42 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen sulfate (Form 2).

[0052] FIG. 43 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen sulfate (Form 2).

[0053] FIG. 44 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen sulfate (Form 2).

[0054] FIG. 45 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide bis-p-toluenesulfonic acid (Form 1).

[0055] FIG. 46 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide bis-p-toluenesulfonic acid (Form 1).

[0056] FIG. 47 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide bis-p-toluenesulfonic acid (Form 1).

[0057] FIG. 48 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide bis-methanesulfonic acid (Form 1).

[0058] FIG. 49 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide bis-methanesulfonic acid (Form 1). 8 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0059] FIG. 50 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide bis-methanesulfonic acid (Form 1).

[0060] FIG. 51 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide phosphoric acid (Form 1).

[0061] FIG. 52 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide phosphoric acid (Form 1).

[0062] FIG. 53 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide phosphoric acid (Form 1).

[0063] FIG. 54 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hemi-L-tartaric acid (Form 1).

[0064] FIG. 55 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hemi-L-tartaric acid (Form 1).

[0065] FIG. 56 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hemi-L-tartaric acid (Form 1).

[0066] FIG. 57 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide oxalic acid (Form 1).

[0067] FIG. 58 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide oxalic acid (Form 1). 9 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0068] FIG. 59 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide oxalic acid (Form 1).

[0069] FIG. 60 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hemi-maleic acid (Form 1).

[0070] FIG. 61 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hemi-maleic acid (Form 1).

[0071] FIG. 62 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hemi-maleic acid (Form 1).

[0072] FIG. 63 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide citric acid (Form 1).

[0073] FIG. 64 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide citric acid (Form 1).

[0074] FIG. 65 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide citric acid (Form 1).

[0075] FIG. 66 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide citric acid (Form 2).

[0076] FIG. 67 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide citric acid (Form 2). 10 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0077] FIG. 68 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide citric acid (Form 2).

[0078] FIG. 69 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide citric acid (Form 3).

[0079] FIG. 70 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide citric acid (Form 3).

[0080] FIG. 71 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide citric acid (Form 3).

[0081] FIG. 72 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 2P).

[0082] FIG. 73 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 2P).

[0083] FIG. 74 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 2P).

[0084] FIG. 75 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 3P).

[0085] FIG. 76 depicts the differential scanning calorimetry (DSC) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 3P). 11 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0086] FIG. 77 depicts the thermogravimetric analysis (TGA) profile of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 3P).

[0087] FIG. 78 depicts an X-ray powder diffraction (XRPD) pattern of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate (Form 4P). DETAILED DESCRIPTION

[0088] The features and other details of the disclosure will now be more particularly described. Before further description of the present disclosure, certain terms employed in the specification, examples and appended claims are collected here. These definitions should be read in light of the remainder of the disclosure and as understood by a person of skill in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art. Definitions

[0089] The term “crystalline form” refers to a crystal form or modification that can be characterized by analytical methods such as, e.g., X-ray powder diffraction (XRPD) and / or Differential scanning calorimetry (DSC). The crystalline compounds disclosed herein can exist in solvated as well as unsolvated forms with solvents such as water, ethanol, and the like. Unless otherwise indicated or inferred, it is intended that disclosed crystalline compounds include both solvated and unsolvated forms.

[0090] “Treating” includes any effect, e.g., lessening, reducing, modulating, or eliminating, that results in the improvement of the condition, disease, disorder and the like.

[0091] The term “disorder” refers to and is used interchangeably with, the terms “disease,” “condition,” or “illness,” unless otherwise indicated.

[0092] “Pharmaceutically or pharmacologically acceptable” include molecular entities and compositions that do not produce an adverse, allergic or other untoward reaction when administered to an animal, or a human, as appropriate. For human administration, preparations should meet sterility, pyrogenicity, and general safety and purity standards as required by FDA Office of Biologics standards. 12 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0093] The term “pharmaceutically acceptable excipient” or “pharmaceutically acceptable carrier” as used herein refers to any and all solvents, dispersion media, coatings, isotonic and absorption delaying agents, and the like, that are compatible with pharmaceutical administration. The use of such media and agents for pharmaceutically active substances is well known in the art. The compositions may also contain other active compounds providing supplemental, additional, or enhanced therapeutic functions.

[0094] The term “pharmaceutical composition” as used herein refers to a composition comprising at least one compound as disclosed herein formulated together with one or more pharmaceutically acceptable excipients.

[0095] “Individual,” “patient,” or “subject” are used interchangeably and include any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and most preferably humans. The compounds of the present disclosure can be administered to a mammal, such as a human, but can also be administered to other mammals such as an animal in need of veterinary treatment, e.g., domestic animals (e.g., dogs, cats, and the like), farm animals (e.g., cows, sheep, pigs, horses, and the like) and laboratory animals (e.g., rats, mice, guinea pigs, and the like). The mammal treated in the methods of the present disclosure is desirably a mammal in which treatment, for example, of a cancer or a blood disorder is desired. “Modulation” includes antagonism (e.g., inhibition), agonism, partial antagonism and / or partial agonism.

[0096] In the present specification, the terms “effective amount” or “therapeutically effective amount” means the amount of the subject compound that will elicit the biological or medical response of a tissue, system or animal, (e.g., mammal or human) that is being sought by the researcher, veterinarian, medical doctor or other clinician. The compounds of the present disclosure are administered in therapeutically effective amounts to treat a disease. Alternatively, a therapeutically effective amount of a compound is the quantity required to achieve a desired therapeutic and / or prophylactic effect.

[0097] The term “and / or” is used in this disclosure to mean either “and” or “or” unless indicated otherwise. 13 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0098] As used herein, the words “a” and “an” are meant to include one or more unless otherwise specified. For example, the term “an agent” encompasses both a single agent and a combination of two or more agents.

[0099] Where the use of the term “about” is before a quantitative value, the present disclosure also includes the specific quantitative value itself, unless specifically stated otherwise. As used herein, the term “about” refers to a ± 10% variation from the nominal value unless otherwise indicated or inferred. The term “about” in the context of peaks at degrees 2θ means that there is an uncertainty in the measurements of the 2θ of ± 0.2 (expressed in 2θ). Generally, a DSC thermogram may have a variation in the range of ± 2 °C. Therefore, the temperature values should be understood as including values in the range of about ± 2 °C.

[0100] In general, provided herein are crystalline salt forms of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide that are substantially free of any other crystalline forms, unless indicated otherwise. As used herein, “substantially free” or substantially free of any other crystalline forms” means that the disclosed crystalline form contains about 20% or less, about 10% or less, about 5% or less, about 2% or less, or about 1% or less, of any other crystalline forms of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide as measured, for example, by XRPD, or less than about 20%, less than about 10%, less than about 5%, less than about 4%, less than about 3%, less than about 2% or less than about 1%, of any other crystalline forms of N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide as measured, for example, by XRPD. Thus, a disclosed crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide described herein as substantially free of any other crystalline forms would be understood to contain greater than 80% (w / w), greater than 90% (w / w), greater than 95% (w / w), greater than 98% (w / w), or greater than 99% (w / w) of the said crystalline forms of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide. Accordingly, in some embodiments, a disclosed crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4- triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide may contain 14 IPTS / 128645168.1Attorney Docket No.: ESK-025WO from 1% to 20% (w / w), from 5% to 20% (w / w), or from 5% to 10% (w / w) of one or more other crystalline forms of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide.

[0101] Compounds of the disclosure may comprise one or more isotopic substitutions. For example, the disclosure also embraces crystalline salt forms of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide which are identical to those recited herein, except that one or more atoms different from the atomic mass or mass number usually found in nature (e.g.,2H,3H,13C,14C,15N,18O,17O,31P,32P,35S,18F, and36Cl) are replaced by an atom having an atomic mass or mass number usually found in nature (e.g., hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine and chlorine, respectively). Crystalline Forms

[0102] The present disclosure is directed, at least in part, to crystalline salt forms of N-(4- ((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide. Also disclosed are crystalline hydrates, anhydrates, hemihydrates, solvates, tautomers and cocrystals of any of the crystalline forms described herein.

[0103] For example, disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.3 (referred to herein as “Form 1”).

[0104] In one embodiment, the crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.3, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 12.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 19.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak 15 IPTS / 128645168.1Attorney Docket No.: ESK-025WO in degrees 2θ at about 20.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.9, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.4, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 25.3, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 25.9.

[0105] In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 10.3, 11.3, and 23.9. In a further embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 10.3, 11.3, 19.5, 20.3, 23.9, and 24.4. In yet another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 10.3, 11.3, 12.1, 13.3, 19.5, 20.3, 23.9, 24.4, and 25.3. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 10.3, 11.3, 12.1, 13.3, 19.5, 20.3, 21.9, 23.9, 24.4, 24.8, 25.3, and 25.9. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 1. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0106] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 208 °C and a peak of about 209 °C (enthalpy 149.8 J / g). Form 1, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 2.

[0107] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a thermogravimetric analysis (TGA) profile 16 IPTS / 128645168.1Attorney Docket No.: ESK-025WO showing a mass loss of about 0.6 wt. % between about 20 °C to about 120 °C. Form 1, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 3. In certain embodiments, the contemplated crystalline Form 1 is an anhydrous crystalline form.

[0108] In some embodiments, contemplated crystalline Form 1 displays a molar ratio of succinic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 1.0. In some embodiments, the contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate is characterized by the following unit cell parameters: cell dimensions a = 5.59870(10) Å, α = 90º, b = 53.3322(11) Å, β = 98.904(2)º, c = 8.9036(2) Å, γ = 90º; space group = P21 / c; volume = 2626.50(9) Å3; and crystal system = monoclinic. For example, Form 1 may be characterized by the single X-ray co-crystal structures shown in FIG. 4 and FIG. 5.

[0109] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.7, 20.2, and 26.9 (referred to herein as “Form 2”).

[0110] In one embodiment, the crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.3, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.2, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.4, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.9, is 17 IPTS / 128645168.1Attorney Docket No.: ESK-025WO characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 27.8, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 28.0.

[0111] In a further embodiment, crystalline Form 2 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.7, 15.7, 16.2, 20.2, 26.2, and 26.9. In another embodiment, crystalline Form 2 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.7, 15.7, 16.2, 20.2, 26.2, 26.4, 26.9, 27.8, and 28.0. In a further embodiment, crystalline Form 2 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.7, 13.3, 15.7, 16.2, 17.2, 20.2, 21.2, 26.2, 26.4, 26.9, 27.8, and 28.0. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 6. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0112] The contemplated crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 140 °C and a peak of about 146 °C (enthalpy 139.6 J / g), a characteristic endotherm with a peak of about 209 °C, and a characteristic endotherm with a peak of about 210 °C. Form 2, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 7.

[0113] The contemplated crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 1.1 wt. % between about 26 °C to about 100 °C, and a mass loss of about 13.8 wt. % between about 100 °C to about 160 °C. Form 2, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 8.

[0114] In some embodiments, contemplated crystalline Form 2 displays a molar ratio of succinic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 1.1. In certain 18 IPTS / 128645168.1Attorney Docket No.: ESK-025WO embodiments, the contemplated crystalline Form 2 is a dichloromethane solvate crystalline form, with 12.4 residual solvent wt. % as determined by1H NMR.

[0115] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.2, 10.6, and 13.7 (referred to herein as “Form 4”).

[0116] In one embodiment, the crystalline Form 4 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 5.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 6.0, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 18.4, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 25.3, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.0.

[0117] In a further embodiment, crystalline Form 4 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.0, 10.2, 10.6, 13.7, 17.9, and 25.3. In another embodiment, crystalline Form 4 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.0, 10.2, 10.6, 11.9, 13.7, 17.9, 22.1, 23.0, and 25.3. In another embodiment, crystalline Form 4 is characterized by a powder X-ray diffraction pattern having at least one or more 19 IPTS / 128645168.1Attorney Docket No.: ESK-025WO characteristic peaks in degrees 2θ at about 5.6, 6.0, 10.2, 10.6, 11.9, 13.7, 17.9, 18.4, 22.1, 23.0, 25.3, and 26.0. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 9. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0118] The contemplated crystalline Form 4 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 214 °C and a peak of about 216 °C (enthalpy 119.5 J / g). Form 4, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 10.

[0119] The contemplated crystalline Form 4 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamidehydrogen succinate may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 3.0 wt. % between about 26 °C to about 170 °C. Form 4, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 11.

[0120] In some embodiments, contemplated crystalline Form 4 displays a molar ratio of succinic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 0.5. In certain embodiments, the contemplated crystalline Form 4 is an anhydrate or hydrate crystalline form.

[0121] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 9.3, 23.9, and 24.2 (referred to herein as “Form 5”).

[0122] In one embodiment, the crystalline Form 5 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 9.3, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.2, is characterized 20 IPTS / 128645168.1Attorney Docket No.: ESK-025WO by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 18.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 18.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.7, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.2, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.5.

[0123] In a further embodiment, crystalline Form 5 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 9.3, 16.2, 21.7, 23.9, 24.2, and 24.5. In another embodiment, crystalline Form 5 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.6, 9.3, 16.2, 18.0, 20.8, 21.7, 23.9, 24.2, and 24.5. In another embodiment, crystalline Form 5 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.6, 9.3, 16.2, 18.0, 18.5, 20.5, 20.8, 21.7, 22.9, 23.9, 24.2, and 24.5. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 12. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0124] The contemplated crystalline Form 5 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with a peak of about 100 °C, a characteristic endotherm with a peak of about 118 °C, a characteristic endotherm with a peak of about 208 °C, and a characteristic endotherm with a peak of about 218 °C. Form 5, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 13. 21 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0125] The contemplated crystalline Form 5 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 6.4 wt. % between about 31 °C to about 150 °C. Form 5, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 14.

[0126] In some embodiments, contemplated crystalline Form 5 displays a molar ratio of succinic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 0.8. In certain embodiments, the contemplated crystalline Form 5 is a hydrate crystalline form.

[0127] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.6, 15.9, and 26.2 (referred to herein as “Form 6”).

[0128] In one embodiment, the crystalline Form 6 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 9.2, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.9, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.4, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at 22 IPTS / 128645168.1Attorney Docket No.: ESK-025WO about 26.2, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 29.2.

[0129] In a further embodiment, crystalline Form 6 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.6, 11.3, 15.9, 17.2, 26.2, and 29.2. In another embodiment, crystalline Form 6 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.6, 9.2, 11.3, 15.1, 15.9, 17.2, 17.9, 26.2, and 29.2. In another embodiment, crystalline Form 6 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.6, 9.2, 11.3, 15.1, 15.9, 16.2, 17.2, 17.9, 21.4, 23.1, 26.2, and 29.2. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 15. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0130] The contemplated crystalline Form 6 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with a peak of about 112 °C, a characteristic endotherm with a peak of about 139 °C, a characteristic endotherm with a peak of about 207 °C, and a characteristic endotherm with a peak of about 215 °C. Form 6, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 16.

[0131] The contemplated crystalline Form 6 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 1.3 wt. % between about 83 °C to about 70 °C, and a mass loss of about 13.1 wt. % between about 70 °C to about 160 °C. Form 6, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 17.

[0132] In some embodiments, contemplated crystalline Form 6 displays a molar ratio of succinic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 0.9. In certain embodiments, the contemplated crystalline Form 6 is a 1,4-dioxane solvate crystalline form, with 13.0 residual solvent wt. % as determined by1H NMR. 23 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0133] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.5, 11.0, and 20.6 (referred to herein as “Form 7”).

[0134] In one embodiment, the crystalline Form 7 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 6.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.5, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 14.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 18.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 18.9, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 25.6, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.1.

[0135] In a further embodiment, crystalline Form 7 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 10.5, 11.0, 14.2, 18.1, 20.6, and 26.1. In another embodiment, crystalline Form 7 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.0, 10.5, 11.0, 14.2, 18.1, 20.6, 24.7, 25.6, and 26.1. In another embodiment, crystalline Form 7 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.0, 10.5, 11.0, 13.1, 14.2, 17.5, 18.1, 18.9, 20.6, 24.7, 25.6, and 26.1. For example, a contemplated crystalline form has a powder X-ray diffraction 24 IPTS / 128645168.1Attorney Docket No.: ESK-025WO pattern shown in FIG. 18. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0136] The contemplated crystalline Form 7 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 215 °C and a peak of about 216 °C (enthalpy 125.5 J / g). Form 7, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 19.

[0137] The contemplated crystalline Form 7 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 1.9 wt. % between about 35 °C to about 150 °C. Form 7, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 20.

[0138] In some embodiments, contemplated crystalline Form 7 displays a molar ratio of succinic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 0.5. In certain embodiments, the contemplated crystalline Form 7 is an anhydrate crystalline form.

[0139] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.0, 10.1, and 10.6 (referred to herein as “Form 8”).

[0140] In one embodiment, the crystalline Form 8 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 6.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.1, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at 25 IPTS / 128645168.1Attorney Docket No.: ESK-025WO about 13.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.3, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.6, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 25.2.

[0141] In a further embodiment, crystalline Form 8 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.0, 10.1, 10.6, 11.9, 17.9, and 20.5. In another embodiment, crystalline Form 8 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.0, 10.1, 10.6, 11.9, 15.6, 17.9, 20.3, 20.5, and 23.6. In another embodiment, crystalline Form 8 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.0, 10.1, 10.6, 11.9, 13.5, 15.6, 17.9, 20.3, 20.5, 22.0, 23.6, and 25.2. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 21. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0142] The contemplated crystalline Form 8 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with a peak of about 205 °C, a characteristic endotherm with a peak of about 214 °C, and a characteristic endotherm with a peak of about 219 °C. Form 8, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 22.

[0143] The contemplated crystalline Form 8 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a thermogravimetric analysis (TGA) profile 26 IPTS / 128645168.1Attorney Docket No.: ESK-025WO showing a mass loss of about 11.5 wt. % between about 29 °C to about 140 °C. Form 8, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 23.

[0144] In some embodiments, contemplated crystalline Form 8 displays a molar ratio of succinic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 0.7. In certain embodiments, the contemplated crystalline Form 8 is an anhydrate crystalline form.

[0145] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.8, 13.6, and 15.7 (referred to herein as “Form 9”).

[0146] In one embodiment, the crystalline Form 9 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.6, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.4, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 19.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.7, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.6, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 27.8.

[0147] In a further embodiment, crystalline Form 9 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.8, 27 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 13.6, 15.7, 17.3, 20.7, and 26.6. In another embodiment, crystalline Form 9 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.8, 13.6, 15.4, 15.7, 17.3, 20.7, 26.0. 26.6, and 27.8. In another embodiment, crystalline Form 9 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.8, 13.6, 15.4, 15.7, 17.3, 19.8, 20.5, 20.7, 22.1, 26.0. 26.6, and 27.8. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 24. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0148] The contemplated crystalline Form 9 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with a peak of about 162 °C, a characteristic endotherm with a peak of about 205 °C, a characteristic endotherm with a peak of about 215 °C, and a characteristic endotherm with a peak of about 219 °C. Form 9, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 25.

[0149] The contemplated crystalline Form 9 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 10.7 wt. % between about 27 °C to about 180 °C. Form 9, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 26.

[0150] In some embodiments, contemplated crystalline Form 9 displays a molar ratio of succinic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 0.5. In certain embodiments, the contemplated crystalline Form 9 is a 1,2-dimethoxyethane solvate crystalline form, with 8.1 residual solvent wt. % as determined by1H NMR.

[0151] Also disclosed herein is a crystalline of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.3, 23.2, and 23.9 (referred to herein as “Form 13”). 28 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0152] In one embodiment, the crystalline Form 13 of N-(4-((3-methoxy-4-(1-(methyl- d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide succinate is characterized by a powder X-ray diffraction pattern that has a peak in degrees 2θ at about 6.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 8.2, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 14.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.6, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.9, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.4.

[0153] In a further embodiment, crystalline Form 13 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 10.3, 11.1, 23.2, 23.6, 23.9, and 24.4. In another embodiment, crystalline Form 13 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 10.3, 11.1, 14.3, 16.1, 22.6, 23.2, 23.6, 23.9, and 24.4. In another embodiment, crystalline Form 13 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.6, 8.2, 10.3, 11.1, 14.3, 16.1, 21.9, 22.6, 23.2, 23.6, 23.9, and 24.4. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 27. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0154] The contemplated crystalline Form 13 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a differential scanning calorimetry (DSC) profile 29 IPTS / 128645168.1Attorney Docket No.: ESK-025WO showing a characteristic endotherm with a peak of about 212 °C, a characteristic endotherm with a peak of about 209 °C, and a characteristic endotherm with a peak of about 218 °C. Form 13, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 28.

[0155] The contemplated crystalline Form 13 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 1.8 wt. % between about 28 °C to about 150 °C. Form 13, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 29.

[0156] In some embodiments, contemplated crystalline Form 13 displays a molar ratio of succinic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 0.7. In certain embodiments, the contemplated crystalline Form 13 is an anhydrate crystalline form.

[0157] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.7, 11.3, and 15.5 (referred to herein as “Form 1”).

[0158] In one embodiment, the crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 9.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.3, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.0, is characterized by a powder X-ray diffraction 30 IPTS / 128645168.1Attorney Docket No.: ESK-025WO pattern that has a characteristic peak in degrees 2θ at about 23.4, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 28.1, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 31.4.

[0159] In a further embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.7, 11.3, 15.5, 23.4, 26.0, and 31.4. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.7, 9.9, 11.3, 15.5, 16.3, 20.0, 23.4, 26.0, and 31.4. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.7, 9.9, 11.3, 15.5, 16.3, 20.0, 20.6, 23.0, 23.4, 26.0, 28.1, and 31.4. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 30. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0160] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 102 °C and a peak of about 116 °C, a characteristic endotherm with an onset of about 216 °C and a peak of about 227 °C, a characteristic endotherm with a peak of about 251 °C, and a characteristic endotherm with a peak of about 267 °C. Form 1, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 31.

[0161] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.1 wt. % between about 75 °C to about 145 °C. Form 1, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 32. 31 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0162] In some embodiments, crystalline Form 1 may be characterized by a dynamic vapor sorption (DVS) profile showing a reversable total mass change of about 7.3 wt.% between about 0% to about 80% relative humidity (RH) at 25 °C. In some embodiments, contemplated crystalline Form 1 displays a molar ratio of hydrochloric acid to N-(4-((3-methoxy-4-(1-(methyl- d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- free base of about 1:1. In certain embodiments, the contemplated Form 1 is an anhydrate crystalline form. In some embodiments, the contemplated crystalline Form 1 displays a rod-like morphology as observed by polarized light microscopy.

[0163] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 9.3, 21.2, and 26.7 (referred to herein as “Form 2”).

[0164] In one embodiment, the crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 8.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 9.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.0, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.5, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.7, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 28.3. 32 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0165] In a further embodiment, crystalline Form 2 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 8.6, 9.3, 15.2, 21.2, 26.7, and 28.3. In another embodiment, crystalline Form 2 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 8.6, 9.3, 10.5, 15.2, 21.2, 22.5, 22.8, 26.7, and 28.3. In another embodiment, crystalline Form 2 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 8.6, 9.3, 10.0, 10.5, 15.2, 16.2, 20.7, 21.2, 22.5, 22.8, 26.7, and 28.3. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 33. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0166] The contemplated crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 120 °C and a peak of about 142 °C, a characteristic endotherm with an onset of about 166 °C and a peak of about 194 °C, and a characteristic endotherm with an onset of about 215 °C and a peak of about 225 °C. Form 2, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 34.

[0167] The contemplated crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 14.3 wt. % between about 50 °C to about 207 °C. Form 2, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 35.

[0168] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.2, 12.8, and 26.0 (referred to herein as “Form 3”).

[0169] In one embodiment, the crystalline Form 3 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.2, is characterized by a powder X-ray diffraction pattern that has a 33 IPTS / 128645168.1Attorney Docket No.: ESK-025WO characteristic peak in degrees 2θ at about 8.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 12.8, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 14.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 14.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.0, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 27.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 28.0, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 29.1.

[0170] In a further embodiment, crystalline Form 3 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.2, 8.5, 12.8, 22.0, 26.0, and 28.0. In another embodiment, crystalline Form 3 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.2, 8.5, 12.8, 14.5, 17.3, 22.0, 23.0, 26.0, and 28.0. In another embodiment, crystalline Form 3 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.2, 8.5, 12.8, 14.5, 14.7, 17.3, 22.0, 23.0, 26.0, 27.7, 28.0, and 29.1. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 36. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0171] The contemplated crystalline Form 3 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 214 °C and a peak of about 226 °C, and a characteristic endotherm with an onset of about 231 °C and a peak of about 253 °C. Form 3, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 37. 34 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0172] The contemplated crystalline Form 3 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride may be characterized by a thermogravimetric analysis (TGA) profile showing negligible mass loss prior to 200 °C. Form 3, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 38.

[0173] In some embodiments, crystalline Form 3 may be characterized by a dynamic vapor sorption (DVS) profile showing a reversable total mass change of about 7.1 wt.% between about 0% to about 80% relative humidity (RH) at 25 °C. In some embodiments, contemplated crystalline Form 3 displays a molar ratio of hydrochloric acid to N-(4-((3-methoxy-4-(1-(methyl- d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 1:1. In certain embodiments, the contemplated crystalline Form 3 is an anhydrate crystalline form. In some embodiments, the contemplated crystalline Form 3 displays a rod-like morphology as observed by polarized light microscopy.

[0174] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.4, 15.0, and 17.7 (referred to herein as “Form 1”).

[0175] In one embodiment, the crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.4, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 8.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.9, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 14.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.5, is characterized by a powder X- 35 IPTS / 128645168.1Attorney Docket No.: ESK-025WO ray diffraction pattern that has a characteristic peak in degrees 2θ at about 25.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 25.9, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 27.5.

[0176] In a further embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.4, 10.9, 14.6, 15.0, 17.7, and 22.0. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.4, 10.9, 14.6, 15.0, 17.7, 21.8, 22.0, 22.5, and 25.9. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.4, 8.3, 10.9, 14.6, 15.0, 17.7, 21.8, 22.0, 22.5, 25.3, 25.9, and 27.5. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 39. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0177] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 178 °C and a peak of about 181 °C, and a characteristic endotherm with an onset of about 199 °C and a peak of about 209 °C. Form 1, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 40.

[0178] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.7 wt. % between about 25 °C to about 170 °C. Form 1, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 41. In certain embodiments, the contemplated crystalline Form 1 is an anhydrate crystalline form.

[0179] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide 36 IPTS / 128645168.1Attorney Docket No.: ESK-025WO hydrogen sulfate, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 8.0, 8.3, and 9.0 (referred to herein as “Form 2”).

[0180] In one embodiment, the crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 5.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 6.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 8.0, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 8.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 9.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.7, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.1, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.5.

[0181] In a further embodiment, crystalline Form 2 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 5.3, 8.0, 8.3, 9.0, 10.8, and 13.0. In another embodiment, crystalline Form 2 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 5.3, 8.0, 8.3, 9.0, 10.8, 13.0, 13.2, 13.7, and 17.1. In another embodiment, crystalline Form 2 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 5.3, 6.8, 8.0, 8.3, 9.0, 10.8, 13.0, 13.2, 13.7, 17.1, 24.1, and 24.5. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 42. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation. 37 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0182] The contemplated crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 76 °C and a peak of about 103 °C, and a characteristic endotherm with an onset of about 194 °C and a peak of about 204 °C. Form 2, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 43.

[0183] The contemplated crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 3.2 wt. % between about 38 °C to about 126 °C. Form 2, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 44. In certain embodiments, the contemplated crystalline Form 2 is a hydrate crystalline form. In some embodiments, the contemplated crystalline Form 2 displays a needle-like morphology as observed by polarized light microscopy.

[0184] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis-p-toluenesulfonic acid, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.2, 7.9, and 21.8 (referred to herein as “Form 1”).

[0185] In one embodiment, the crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis-p-toluenesulfonic acid is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.9, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 14.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 19.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.8, is characterized by a powder X-ray diffraction 38 IPTS / 128645168.1Attorney Docket No.: ESK-025WO pattern that has a characteristic peak in degrees 2θ at about 23.6, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 28.6, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 29.2.

[0186] In a further embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.2, 7.9, 14.2, 16.2, 21.8, and 23.6. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.2, 7.9, 14.2, 16.2, 19.9, 21.8, 23.6, 23.7, and 26.1. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.2, 7.9, 14.2, 16.2, 19.9, 20.8, 21.8, 23.6, 23.7, 26.1, 28.6, and 29.2. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 45. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0187] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis-p- toluenesulfonic acid may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 108 °C and a peak of about 120 °C, and a characteristic endotherm with an onset of about 144 °C and a peak of about 188 °C. Form 1, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 46.

[0188] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis-p- toluenesulfonic acid may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 5.4 wt. % between about 53 °C to about 141 °C. Form 1, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 47. In some embodiments, contemplated crystalline Form 1 displays a molar ratio of p-toluenesulfonic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- 39 IPTS / 128645168.1Attorney Docket No.: ESK-025WO propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 2:1. In certain embodiments, the contemplated crystalline Form 1 is a hydrate crystalline form.

[0189] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis-methanesulfonic acid, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.0, 19.2, and 21.0 (referred to herein as “Form 1”).

[0190] In one embodiment, the crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis-methanesulfonic acid is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 9.5, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.4, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 12.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 18.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 19.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.1, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.3, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 29.0.

[0191] In a further embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.0, 10.4, 19.2, 21.0, 21.1, and 29.0. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.0, 9.5, 10.4, 12.6, 19.2, 21.0, 21.1, 26.3, and 29.0. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more 40 IPTS / 128645168.1Attorney Docket No.: ESK-025WO characteristic peaks in degrees 2θ at about 7.0, 9.5, 10.4, 12.6, 18.6, 19.2, 21.0, 21.1, 21.8, 23.3, 26.3, and 29.0. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 48. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0192] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis- methanesulfonic acid may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 106 °C and a peak of about 113 °C, and a characteristic endotherm with an onset of about 154 °C and a peak of about 163 °C. Form 1, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 49.

[0193] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis- methanesulfonic acid may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 6.5 wt. % between about 55 °C to about 141 °C. Form 1, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 50.

[0194] In some embodiments, contemplated crystalline Form 1 displays a molar ratio of methanesulfonic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 2:1. In some embodiments, crystalline Form 1 displays a rod-like morphology as observed by polarized light microscopy. In certain embodiments, the contemplated crystalline Form 1 is a hydrate crystalline form.

[0195] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide phosphoric acid, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.1, 10.2, and 19.6 (referred to herein as “Form 1”).

[0196] In one embodiment, the crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide phosphoric acid is characterized by a powder X-ray diffraction pattern that has a characteristic 41 IPTS / 128645168.1Attorney Docket No.: ESK-025WO peak in degrees 2θ at about 7.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.1, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 18.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 19.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.4, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 25.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 25.8, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 27.4, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 27.9, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 28.9.

[0197] In a further embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.1, 10.2, 19.6, 25.2, 27.4, and 27.9. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.1, 10.2, 13.1, 19.6, 25.2, 25.8, 27.4, 27.9, and 28.9. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.1, 10.2, 13.1, 18.7, 19.6, 21.7, 22.4, 25.2, 25.8, 27.4, 27.9, and 28.9. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 51. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0198] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide phosphoric acid may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with a peak of about 203 °C, and a characteristic endotherm with a peak of about 225 °C. Form 1, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 52. 42 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0199] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide phosphoric acid may be characterized by a thermogravimetric analysis (TGA) profile showing negligible mass loss prior to about 210 °C. Form 1, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 53. In certain embodiments, the contemplated crystalline Form 1 is an anhydrous crystalline form.

[0200] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi-L-tartaric acid, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.1, 7.9, and 13.8 (referred to herein as “Form 1”).

[0201] In one embodiment, the crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi-L-tartaric acid is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.9, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 12.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 14.4, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.3, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.7, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 25.2.

[0202] In a further embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.1, 43 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 7.9, 13.8, 14.4, 15.1, and 20.9. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.1, 7.9, 10.6, 13.8, 14.4, 15.1, 17.4, 20.9, and 21.7. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.1, 7.9, 10.6, 12.2, 13.8, 14.4, 15.1, 17.4, 20.9, 21.2, 21.7, and 25.2. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 54. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0203] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi- L-tartaric acid may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 31 °C and a peak of about 65 °C, a characteristic endotherm with an onset of about 201 °C and a peak of about 204 °C, and a characteristic endotherm with an onset of about 225 °C and a peak of about 229 °C. Form 1, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 55.

[0204] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi- L-tartaric acid may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 2.1 wt. % between about 25 °C to about 52 °C. Form 1, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 56.

[0205] In some embodiments, the contemplated crystalline Form 1 displays a molar ratio of L-tartaric acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 0.5:1. In some embodiments, crystalline Form 1 displays a needle-like morphology as observed by polarized light microscopy. In certain embodiments, the contemplated crystalline Form 1 is a tetrahydrofuran solvate crystalline form, with 2.5% residual solvent wt. % as determined by1H NMR.

[0206] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide 44 IPTS / 128645168.1Attorney Docket No.: ESK-025WO oxalic acid, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 5.4, 7.8, and 11.3 (referred to herein as “Form 1”).

[0207] In one embodiment, the crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide oxalic acid is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 5.4, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.1, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 14.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 19.8, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.4, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.1.

[0208] In a further embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 5.4, 7.8, 11.3, 14.2, 15.7, and 22.4. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 5.4, 7.8, 11.3, 14.2, 15.7, 16.2, 17.6, 22.0, and 22.4. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 5.4, 7.8, 11.1, 11.3, 14.2, 15.7, 16.2, 17.6, 19.8, 22.0, 22.4, and 23.1. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 57. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation. 45 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0209] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide oxalic acid may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 220 °C and a peak of about 226 °C. Form 1, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 58.

[0210] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide oxalic acid may be characterized by a thermogravimetric analysis (TGA) profile showing negligible mass loss prior to about 210 °C. Form 1, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 59.

[0211] In some embodiments, crystalline Form 1 may be characterized by a dynamic vapor sorption (DVS) profile showing a reversable total mass change of about 1.65 wt.% between about 0% to about 80% relative humidity (RH) at 25 °C. In some embodiments, contemplated crystalline Form 1 displays a molar ratio of oxalic acid to N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 1:1. In certain embodiments, the contemplated crystalline Form 1 is an anhydrate crystalline form. In some embodiments, the contemplated crystalline Form 1 displays a needle-like morphology as observed by polarized light microscopy.

[0212] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi-maleic acid, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.8, 8.2, and 25.2 (referred to herein as “Form 1”).

[0213] In one embodiment, the crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi-maleic acid is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 6.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 8.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 9.4, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.7, is 46 IPTS / 128645168.1Attorney Docket No.: ESK-025WO characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.1, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 25.2, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.0.

[0214] In a further embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.8, 8.2, 11.3, 16.7, 21.7, and 25.2. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.8, 8.2, 11.3, 16.7, 20.6, 21.7, 23.1, 25.2, and 26.0. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.8, 8.2, 9.4, 11.3, 16.7, 20.6, 20.8, 21.7, 23.1, 24.7, 25.2, and 26.0. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 60. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0215] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi- maleic acid may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 91 °C and a peak of about 117 °C, a characteristic endotherm with an onset of about 137 °C and a peak of about 142 °C, a characteristic endotherm with an onset of about 148 °C and a peak of about 167 °C, and a characteristic endotherm with an onset of about 220 °C and a peak of about 224 °C. Form 1, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 61.

[0216] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi- maleic acid may be characterized by a thermogravimetric analysis (TGA) profile showing a mass 47 IPTS / 128645168.1Attorney Docket No.: ESK-025WO loss of about 3.5 wt. % between about 59 °C to about 140 °C. Form 1, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 62.

[0217] In some embodiments, contemplated crystalline Form 1 displays a molar ratio of maleic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 0.5:1. In certain embodiments, the contemplated crystalline Form 1 is a tetrahydrofuran solvate crystalline form, with 4.1% residual solvent wt. % as determined by1H NMR.

[0218] Also disclosed herein is aN-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.8, 22.1, and 26.2 (referred to herein as “Form 1”).

[0219] In one embodiment, the crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 6.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 8.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 12.7, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.1, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.6, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 27.0. 48 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0220] In a further embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.8, 20.2, 22.1, 26.2, 26.6, and 27.0. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.8, 12.7, 16.7, 17.0, 20.2, 22.1, 26.2, 26.6, and 27.0. In another embodiment, crystalline Form 1 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 6.8, 8.3, 12.7, 13.0, 15.0, 16.7, 17.0, 20.2, 22.1, 26.2, 26.6, and 27.0. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 63. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0221] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with a peak of about 153 °C, and a characteristic endotherm with an onset of about 220 °C and a peak of about 228 °C. Form 1, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 64.

[0222] The contemplated crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamideacid may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.04 wt. % between about 25 °C to about 110 °C. Form 1, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 65.

[0223] In some embodiments, contemplated crystalline Form 1 displays a molar ratio of citric acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 1:1. In certain embodiments, the contemplated crystalline Form 1 is a tetrahydrofuran solvate crystalline form, with 5.6% residual solvent wt. % as determined by1H NMR.

[0224] Also disclosed herein is a N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.5, 8.9, and 9.3 (referred to herein as “Form 2”). 49 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0225] In one embodiment, the crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 5.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 8.9, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 9.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 14.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 19.7, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.7, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 25.4.

[0226] In a further embodiment, crystalline Form 2 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 5.0, 7.5, 8.9, 9.3, 15.3, and 19.7. In another embodiment, crystalline Form 2 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 5.0, 7.5, 8.9, 9.3, 14.5, 15.3, 19.7, 22.7, and 25.4. In another embodiment, crystalline Form 2 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 5.0, 7.5, 8.9, 9.3, 14.5, 15.3, 15.8, 17.3, 19.7, 22.1, 22.7, and 25.4. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 66. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0227] The contemplated crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid may be characterized by a differential scanning calorimetry (DSC) profile showing a 50 IPTS / 128645168.1Attorney Docket No.: ESK-025WO characteristic endotherm with a peak of about 122 °C, a characteristic endotherm with a peak of about 148 °C, a characteristic exotherm with a peak of about 152 °C, a characteristic endotherm with a peak of about 181 °C, a characteristic exotherm with a peak of about 197 °C, and a characteristic endotherm with a peak of about 228 °C. Form 2, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 67.

[0228] The contemplated crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.4 wt. % between about 25 °C to about 100 °C. Form 2, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 68.

[0229] In some embodiments, contemplated crystalline Form 2 displays a molar ratio of citric acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 1:1. In certain embodiments, the contemplated crystalline Form 2 is an anhydrous crystalline form.

[0230] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.4, 9.3, and 23.6 (referred to herein as “Form 3”).

[0231] In one embodiment, the crystalline Form 3 of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.4, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 9.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 9.7, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 14.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.5, is characterized by a powder X-ray diffraction pattern that has a 51 IPTS / 128645168.1Attorney Docket No.: ESK-025WO characteristic peak in degrees 2θ at about 23.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.9, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.5, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.1.

[0232] In a further embodiment, crystalline Form 3 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.4, 9.3, 9.7, 15.7, 23.6, and 24.3. In another embodiment, crystalline Form 3 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.4, 9.3, 9.7, 11.2, 14.0, 15.7, 23.6, 24.3, and 26.1. In another embodiment, crystalline Form 3 is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.4, 9.3, 9.7, 11.2, 14.0, 15.7, 16.5, 23.6, 23.9, 24.3, 24.5, and 26.1. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 69. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0233] The contemplated crystalline Form 3 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 84 °C and a peak of about 91 °C, a characteristic endotherm with an onset of about 115 °C and a peak of about 126 °C, a characteristic endotherm with an onset of about 182 °C and a peak of about 185 °C, and a characteristic endotherm with an onset of about 230 °C and a peak of about 233 °C. Form 3, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 70.

[0234] The contemplated crystalline Form 3 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 2.5 wt. % between about 25 °C to about 150 °C. Form 3, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 71. 52 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0235] In some embodiments, contemplated crystalline Form 3 displays a molar ratio of citric acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 1:1. In certain embodiments, the contemplated crystalline Form 3 is a hydrate crystalline form.

[0236] Also disclosed herein is a crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.6, 8.0, and 20.0 (referred to herein as “Form 2P”).

[0237] In one embodiment, the crystalline Form 2P of N-(4-((3-methoxy-4-(1-(methyl- d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 7.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 8.0, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.5, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 17.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.1, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.8, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 26.8, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 27.3.

[0238] In a further embodiment, crystalline Form 2P is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.6, 8.0, 13.0, 15.5, 20.0 and 26.8. In another embodiment, crystalline Form 2P is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at 53 IPTS / 128645168.1Attorney Docket No.: ESK-025WO about 7.6, 8.0, 13.0, 15.5, 16.2, 20.0, 20.1, 26.8, and 27.7. In another embodiment, crystalline Form 2P is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 7.6, 8.0, 13.0, 15.5, 16.2, 17.1, 20.0, 20.1, 21.1, 21.8, 26.8, and 27.7. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 72. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0239] The contemplated crystalline Form 2P of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 97 °C and a peak of about 136 °C, and a characteristic endotherm with an onset of about 218 °C and a peak of about 219 °C. Form 2P, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 73.

[0240] The contemplated crystalline Form 2P of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 8.9 wt. % between about 72 °C to about 194 °C. Form 2P, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 74.

[0241] In some embodiments, contemplated crystalline Form 2P displays a molar ratio of succinic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 0.5. In certain embodiments, the contemplated crystalline Form 2P is an ethanol solvate crystalline form, with 7.6% residual solvent wt. % as determined by1H NMR.

[0242] Also disclosed herein is a form of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 23.7, 23.9, and 24.2 (referred to herein as “Form 3P”).

[0243] In one embodiment, the crystalline Form 3P of N-(4-((3-methoxy-4-(1-(methyl- d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide 54 IPTS / 128645168.1Attorney Docket No.: ESK-025WO hydrogen succinate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 9.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.1, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 19.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 20.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 21.4, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.2, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.6.

[0244] In a further embodiment, crystalline Form 3P is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 9.1, 10.1, 11.1, 23.7, 23.9, and 24.2. In another embodiment, crystalline Form 3P is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 9.1, 10.1, 11.1, 13.1, 21.4, 23.7, 23.9, 24.2, and 24.6. In another embodiment, crystalline Form 3P is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 9.1, 10.1, 11.1, 13.1, 16.0, 19.3, 20.0, 21.4, 23.7, 23.9, 24.2, and 24.6. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 75. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0245] The contemplated crystalline Form 3P of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a differential scanning calorimetry (DSC) profile showing a characteristic endotherm with an onset of about 109 °C and a peak of about 115 °C, a characteristic endotherm with a peak of about 211 °C, and a characteristic endotherm with a peak 55 IPTS / 128645168.1Attorney Docket No.: ESK-025WO of about 219 °C. Form 3P, for example, may be characterized by the differential scanning calorimetry profile shown in FIG. 76.

[0246] The contemplated crystalline Form 3P of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate may be characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 2.2 wt. % between about 82 °C to about 145 °C. Form 3P, for example, may be characterized by the thermogravimetric analysis profile shown in FIG. 77.

[0247] In some embodiments, contemplated crystalline Form 3P displays a molar ratio of succinic acid to N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base of about 1.0. In certain embodiments, the contemplated crystalline Form 3P is a tetrahydrofuran solvate crystalline form, with 2.2% residual solvent wt. % as determined by1H NMR.

[0248] Also disclosed herein is aN-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.1, 23.7, and 24.2 (referred to herein as “Form 4P”).

[0249] In one embodiment, the crystalline Form 4P of N-(4-((3-methoxy-4-(1-(methyl- d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 8.0, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 10.1, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 11.1, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 13.2, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 15.9, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 16.6, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 19.3, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 22.4, is characterized by a powder X- ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.4, is characterized 56 IPTS / 128645168.1Attorney Docket No.: ESK-025WO by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 23.7, is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.2, and / or is characterized by a powder X-ray diffraction pattern that has a characteristic peak in degrees 2θ at about 24.6.

[0250] In a further embodiment, crystalline Form 4P is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 10.1, 11.1, 13.1, 23.4, 23.7, and 24.2. In another embodiment, crystalline Form 4P is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 8.0, 10.1, 11.1, 13.1, 15.9, 16.6, 23.4, 23.7, and 24.2. In another embodiment, crystalline Form 4P is characterized by a powder X-ray diffraction pattern having at least one or more characteristic peaks in degrees 2θ at about 8.0, 10.1, 11.1, 13.1, 15.9, 16.6, 19.3, 22.4, 23.4, 23.7, 24.2, and 24.6. For example, a contemplated crystalline form has a powder X-ray diffraction pattern shown in FIG. 78. In one embodiment, the powder X-ray diffraction pattern of the crystalline form was obtained using Cu Kα radiation.

[0251] In a further embodiment, a pharmaceutical composition comprising a disclosed crystalline salt form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide and a pharmaceutically acceptable excipient is disclosed herein. In another embodiment, a pharmaceutical composition formed from a disclosed crystalline salt form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide disclosed herein.

[0252] In an embodiment, a drug substance comprising at least a detectable amount of a disclosed crystalline salt form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide is disclosed herein. In another embodiment, a drug substance comprising a substantially pure crystalline salt form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide is disclosed herein. Compositions

[0253] Another aspect of the disclosure provides pharmaceutical compositions comprising crystalline compounds as disclosed herein formulated together with a 57 IPTS / 128645168.1Attorney Docket No.: ESK-025WO pharmaceutically acceptable excipient. In particular, the present disclosure provides pharmaceutical compositions comprising crystalline compounds as disclosed herein formulated together with one or more pharmaceutically acceptable excipients. These formulations include those suitable for oral, topical (e.g., transdermal), buccal, ocular, parenteral (e.g., subcutaneous, intramuscular, intradermal, or intravenous) rectal, vaginal, or aerosol administration, although the most suitable form of administration in any given case will depend on the degree and severity of the condition being treated and on the nature of the particular compound being used. For example, disclosed compositions may be formulated as a unit dose, and / or may be formulated for oral, subcutaneous or intravenous administration.

[0254] Exemplary pharmaceutical compositions of this disclosure may be used in the form of a pharmaceutical preparation, for example, in solid, semisolid or liquid form, which contains one or more of the compounds of the disclosure, as an active ingredient, in admixture with an organic or inorganic excipient or excipient suitable for external, enteral or parenteral applications. The active ingredient may be compounded, for example, with the usual non-toxic, pharmaceutically acceptable excipients for tablets, pellets, capsules, suppositories, solutions, emulsions, suspensions, and any other form suitable for use. The active object compound is included in the pharmaceutical composition in an amount sufficient to produce the desired effect upon the process or condition of the disease.

[0255] For preparing solid compositions such as tablets, the principal active ingredient may be mixed with a pharmaceutical excipient, e.g., conventional tableting ingredients such as corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalcium phosphate or gums, and other pharmaceutical diluents, e.g., water, to form a solid preformulation composition containing a homogeneous mixture of a compound of the disclosure. When referring to these preformulation compositions as homogeneous, it is meant that the active ingredient is dispersed evenly throughout the composition so that the composition may be readily subdivided into equally effective unit dosage forms such as tablets, pills and capsules.

[0256] In solid dosage forms for oral administration (capsules, tablets, pills, dragees, powders, granules and the like), the subject composition is mixed with one or more pharmaceutically acceptable excipients, such as sodium citrate or dicalcium phosphate, and / or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, 58 IPTS / 128645168.1Attorney Docket No.: ESK-025WO mannitol, and / or silicic acid; (2) binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and / or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; (5) solution retarding agents, such as paraffin; (6) absorption accelerators, such as quaternary ammonium compounds; (7) wetting agents, such as, for example, acetyl alcohol and glycerol monostearate; (8) absorbents, such as kaolin and bentonite clay; (9) lubricants, such a talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; and (10) coloring agents. In the case of capsules, tablets and pills, the compositions may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like.

[0257] A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared using binder (for example, gelatin or hydroxypropylmethyl cellulose), lubricant, inert diluent, preservative, disintegrant (for example, sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), surface-active or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the subject composition moistened with an inert liquid diluent. Tablets, and other solid dosage forms, such as dragees, capsules, pills and granules, may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceutical-formulating art.

[0258] Compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable, aqueous or organic solvents, or mixtures thereof, and powders. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, nano-suspensions, syrups and elixirs. In addition to the subject composition, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, cyclodextrins and mixtures thereof. 59 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0259] Suspensions, in addition to the subject composition, may contain suspending agents, such as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof.

[0260] Formulations for rectal or vaginal administration may be presented as a suppository, which may be prepared by mixing a subject composition with one or more suitable non-irritating excipients or excipients comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, and which is solid at room temperature, but liquid at body temperature and, therefore, will melt in the body cavity and release the active agent.

[0261] Dosage forms for transdermal administration of a subject composition include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active component may be mixed under sterile conditions with a pharmaceutically acceptable excipient, and with any preservatives, buffers, or propellants which may be required.

[0262] The ointments, pastes, creams and gels may contain, in addition to a subject composition, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof.

[0263] Powders and sprays may contain, in addition to a subject composition, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays may additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane.

[0264] Compositions and compounds of the present disclosure may alternatively be administered by aerosol. This is accomplished by preparing an aqueous aerosol, liposomal preparation or solid particles containing the compound. A non-aqueous (e.g., fluorocarbon propellant) suspension could be used. Sonic nebulizers may be used because they minimize exposing the agent to shear, which may result in degradation of the compounds contained in the subject compositions. Ordinarily, an aqueous aerosol is made by formulating an aqueous solution or suspension of a subject composition together with conventional pharmaceutically acceptable excipients and stabilizers. The excipients and stabilizers vary with the requirements of the particular subject composition, but typically include non-ionic surfactants (Tweens, 60 IPTS / 128645168.1Attorney Docket No.: ESK-025WO Pluronics, or polyethylene glycol), innocuous proteins like serum albumin, sorbitan esters, oleic acid, lecithin, amino acids such as glycine, buffers, salts, sugars or sugar alcohols. Aerosols generally are prepared from isotonic solutions.

[0265] Pharmaceutical compositions of this disclosure suitable for parenteral administration comprise a subject composition in combination with one or more pharmaceutically-acceptable sterile isotonic aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, or sterile powders which may be reconstituted into sterile injectable solutions or dispersions just prior to use, which may contain antioxidants, buffers, bacteriostats, solutes which render the formulation isotonic with the blood of the intended recipient or suspending or thickening agents.

[0266] Examples of suitable aqueous and non-aqueous excipients which may be employed in the pharmaceutical compositions of the disclosure include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils, such as olive oil, and injectable organic esters, such as ethyl oleate and cyclodextrins. Proper fluidity may be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants. For example, crystalline forms provided herein may be milled to obtain a particular particle size, and in at least some embodiments, such crystalline forms may remain substantially stable upon milling.

[0267] Amounts of a crystalline compound as described herein in a formulation may vary according to factors such as the disease state, age, sex, and weight of the individual. Dosage regimens can be adjusted to provide the optimum therapeutic response. For example, a single bolus can be administered, several divided doses may be administered over time or the dose can be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. It is especially advantageous to formulate parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the mammalian subjects to be treated; each unit containing a predetermined quantity of active crystalline compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. 61 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0268] The specification for the dosage unit forms of the disclosure is dictated by and directly dependent on (a) the unique characteristics of the crystalline compound selected and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding such an active crystalline compound for the treatment of sensitivity in individuals.

[0269] Disclosed compositions can be formulated as a solution, microemulsion, liposome, or other ordered structure suitable to high drug concentration. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. In many cases, it is suitable to include isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, or sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, monostearate salts and gelatin.

[0270] A disclosed crystalline compound can be administered in a time release formulation, for example in a composition which includes a slow release polymer. The crystalline compound can be prepared with carriers that will protect the compound against rapid release, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, polylactic acid and polylactic, polyglycolic copolymers (PLG). Many methods for the preparation of such formulations are generally known to those skilled in the art.

[0271] In accordance with an alternative aspect of the disclosure, a disclosed crystalline compound can be formulated with one or more additional compounds that enhance the solubility of the compound. Methods

[0272] The crystalline salt forms disclosed herein are useful for the inhibition of kinase activity of one or more enzymes. In some embodiments the kinase inhibited by the crystalline forms and methods is TYK2. 62 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0273] Provided herein are crystalline salt forms of N-(4-((3-methoxy-4-(1-(methyl-d3)- 1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide that are inhibitors of TYK2 and are therefore useful for treating one or more disorders associated with activity of TYK2 or mutants thereof.

[0274] Provided herein are methods for treating a disease or disorder in a patient in need thereof, wherein the disease or disorder is an autoimmune disorders, inflammatory disorders, proliferative disorders, endocrine disorders, neurological disorders, neuroinflammatory diseases or disorders, or disorders associated with transplantation, comprising administering to the patient an effective amount of a crystalline salt form described herein, or a pharmaceutical composition comprising an effective amount of a disclosed crystalline form.

[0275] In some embodiments, the disease or disorder is a neuroinflammatory disease or disorder. In some embodiments, the neuroinflammatory disease or disorder is, for example, multiple sclerosis. For example, provided herein is a method of treating a neuroinflammatory disease or disorder in a patient in need thereof, comprising administering to the patient an effective amount of a crystalline form described herein, or a pharmaceutical composition comprising an effective amount of a disclosed crystalline form. Also provided herein is a method of treating multiple sclerosis in a patient in need thereof, comprising administering to the patient an effective amount of a crystalline form described herein, or a pharmaceutical composition comprising an effective amount of a disclosed crystalline form.

[0276] In some embodiments, the disease or disorder is an autoimmune disorder. In some embodiments the disease or disorder is selected from type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, psoriasis, Behçet's disease, POEMS syndrome, Crohn's disease, ulcerative colitis, and inflammatory bowel disease.

[0277] In some embodiments, the disease or disorder is an inflammatory disorder. In some embodiments, the inflammatory disorder is rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, psoriasis, hepatomegaly, Crohn's disease, ulcerative colitis, inflammatory bowel disease.

[0278] In some embodiments, the disease or disorder is a proliferative disorder. In some embodiments, the proliferative disorder is cancer. In some embodiments, the disease or disorder is a proliferative disorder. In some embodiments, the proliferative disorder is a hematological 63 IPTS / 128645168.1Attorney Docket No.: ESK-025WO cancer. In some embodiments the proliferative disorder is a leukemia. In some embodiments, the leukemia is a T-cell leukemia. In some embodiments the T-cell leukemia is T-cell acute lymphoblastic leukemia (T-ALL). In some embodiments the proliferative disorder is polycythemia vera, myelofibrosis, essential or thrombocytosis.

[0279] In some embodiments, the disease or disorder is an endocrine disorder. In some embodiments, the endocrine disorder is polycystic ovary syndrome, Crouzon's syndrome, or type 1 diabetes.

[0280] In some embodiments, the disease or disorder is a neurological disorder. In some embodiments, the neurological disorder is Alzheimer's disease.

[0281] In some embodiments the proliferative disorder is associated with one or more activating mutations in TYK2. In some embodiments, the activating mutation in TYK2 is a mutation to the FERM domain, the JH2 domain, or the kinase domain. In some embodiments the activating mutation in TYK2 is selected from G36D, S47N, R425H, V731I, E957D, and R1027H.

[0282] In some embodiments, the disease or disorder is associated with transplantation. In some embodiments the disease or disorder associated with transplantation is transplant rejection, or graft versus host disease.

[0283] In some embodiments the disease or disorder is associated with type I interferon, IL-10, IL-12, or IL-23 signaling. In some embodiments the disease or disorder is associated with type I interferon signaling. In some embodiments the disease or disorder is associated with IL-10 signaling. In some embodiments the disorder is associated with IL-12 signaling. In some embodiments the disease or disorder is associated with IL-23 signaling.

[0284] Provided herein are methods for treating an inflammatory or allergic condition of the skin, for example psoriasis, contact dermatitis, atopic dermatitis, alopecia areata, erythema multiforma, dermatitis herpetiformis, scleroderma, vitiligo, hypersensitivity angiitis, urticaria, bullous pemphigoid, lupus erythematosus, systemic lupus erythematosus, pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, epidermolysis bullosa acquisita, acne vulgaris, and other inflammatory or allergic conditions of the skin. 64 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0285] Provided herein are methods for treating other diseases or conditions, such as diseases or conditions having an inflammatory component, for example, treatment of diseases and conditions of the eye such as ocular allergy, conjunctivitis, keratoconjunctivitis sicca, and vernal conjunctivitis, diseases affecting the nose including allergic rhinitis, and inflammatory disease in which autoimmune reactions are implicated or having an autoimmune component or etiology, including autoimmune hematological disorders (e.g. hemolytic anemia, aplastic anemia, pure red cell anemia and idiopathic thrombocytopenia), systemic lupus erythematosus, rheumatoid arthritis, polychondritis, scleroderma, Wegener granulamatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, Steven-Johnson syndrome, idiopathic sprue, autoimmune inflammatory bowel disease (e.g. ulcerative colitis and Crohn's disease), irritable bowel syndrome, celiac disease, periodontitis, hyaline membrane disease, kidney disease, glomerular disease, alcoholic liver disease, multiple sclerosis, endocrine opthalmopathy, Grave's disease, sarcoidosis, alveolitis, chronic hypersensitivity pneumonitis, multiple sclerosis, primary biliary cirrhosis, uveitis (anterior and posterior), Sjogren's syndrome, keratoconjunctivitis sicca and vernal keratoconjunctivitis, interstitial lung fibrosis, psoriatic arthritis, systemic juvenile idiopathic arthritis, cryopyrin-associated periodic syndrome, nephritis, vasculitis, diverticulitis, interstitial cystitis, glomerulonephritis (with and without nephrotic syndrome, e.g. including idiopathic nephrotic syndrome or minal change nephropathy), chronic granulomatous disease, endometriosis, leptospiriosis renal disease, glaucoma, retinal disease, ageing, headache, pain, complex regional pain syndrome, cardiac hypertrophy, musclewasting, catabolic disorders, obesity, fetal growth retardation, hyperchlolesterolemia, heart disease, chronic heart failure, mesothelioma, anhidrotic ecodermal dysplasia, Behcet's disease, incontinentia pigmenti, Paget's disease, pancreatitis, hereditary periodic fever syndrome, asthma (allergic and non-allergic, mild, moderate, severe, bronchitic, and exercise-induced), acute lung injury, acute respiratory distress syndrome, eosinophilia, hypersensitivities, anaphylaxis, nasal sinusitis, ocular allergy, silica induced diseases, COPD (reduction of damage, airways inflammation, bronchial hyperreactivity, remodeling or disease progression), pulmonary disease, cystic fibrosis, acid-induced lung injury, pulmonary hypertension, polyneuropathy, cataracts, muscle inflammation in conjunction with systemic sclerosis, inclusion body myositis, myasthenia gravis, thyroiditis, Addison's disease, lichen planus, Type 1 diabetes, or Type 2 diabetes, appendicitis, atopic dermatitis, asthma, allergy, blepharitis, bronchiolitis, bronchitis, bursitis, cervicitis, cholangitis, cholecystitis, 65 IPTS / 128645168.1Attorney Docket No.: ESK-025WO chronic graft rejection, colitis, conjunctivitis, Crohn's disease, cystitis, dacryoadenitis, dermatitis, dermatomyositis, encephalitis, endocarditis, endometritis, enteritis, enterocolitis, epicondylitis, epididymitis, fasciitis, fibrositis, gastritis, gastroenteritis, Henoch-Schonlein purpura, hepatitis, hidradenitis suppurativa, immunoglobulin A nephropathy, interstitial lung disease, laryngitis, mastitis, meningitis, myelitis myocarditis, myositis, nephritis, oophoritis, orchitis, osteitis, otitis, pancreatitis, parotitis, pericarditis, peritonitis, pharyngitis, pleuritis, phlebitis, pneumonitis, pneumonia, polymyositis, proctitis, prostatitis, pyelonephritis, rhinitis, salpingitis, sinusitis, stomatitis, synovitis, tendonitis, tonsillitis, ulcerative colitis, uveitis, vaginitis, vasculitis, or vulvitis.

[0286] In some embodiments the inflammatory disease is acute and chronic gout, chronic gouty arthritis, psoriasis, psoriatic arthritis, rheumatoid arthritis, Juvenile rheumatoid arthritis, Systemic juvenile idiopathic arthritis (SJIA), Cryopyrin Associated Periodic Syndrome (CAPS), or osteoarthritis.

[0287] In some embodiments the inflammatory disease is a Th1 or Th17 mediated disease. In some embodiments the Th17 mediated disease is selected from Systemic lupus erythematosus, Multiple sclerosis, and inflammatory bowel disease (including Crohn's disease or ulcerative colitis).

[0288] In some embodiments the inflammatory disease is Sjogren's syndrome, allergic disorders, osteoarthritis, conditions of the eye such as ocular allergy, conjunctivitis, keratoconjunctivitis sicca, vernal conjunctivitis, or diseases affecting the nose such as allergic rhinitis.

[0289] For example, disclosed herein is a method of inhibiting a TYK2 enzyme in a patient or biological sample, comprising contacting said patient or biological sample with a therapeutically effective amount of a crystalline form described herein, or a pharmaceutical composition comprising an effective amount of a disclosed crystalline form.

[0290] Also disclosed herein is method of inhibiting TYK2 activity in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a crystalline form described herein, or a pharmaceutical composition comprising an effective amount of a disclosed crystalline form. In some embodiments, inhibiting TYK2 activity is associated with treating a disease or disorder selected from the group consisting of, e.g., Crohn's 66 IPTS / 128645168.1Attorney Docket No.: ESK-025WO disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, ulcerative colitis, psoriatic arthritis, multiple sclerosis, and systemic sclerosis.

[0291] Further disclosed herein is a TYK2-mediated disorder in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a crystalline form described herein, or a pharmaceutical composition comprising an effective amount of a disclosed crystalline form. In some embodiments, a contemplated TYK2-mediated disorder may be, for example, an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, a neuroinflammatory disease or disorder, or a disorder associated with transplantation. In other embodiments, a contemplated disorder is associated with type I interferon, IL-10, IL-12, or IL-23 signalling.

[0292] For example, provided herein is a method of treating one or more of: Crohn's disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, ulcerative colitis, psoriatic arthritis, multiple sclerosis, and systemic sclerosis in a patient in need thereof, comprising administering to the patient an effective amount of a crystalline form described herein, or a pharmaceutical composition comprising an effective amount of a disclosed crystalline form.

[0293] In particular, in certain embodiments, the disclosure provides a method of treating the above medical indications comprising administering to a patient in need thereof an effective amount of a crystalline form described herein, or a pharmaceutical composition comprising an effective amount of a disclosed crystalline form. In certain other embodiments, the disclosure provides a method of treating the above medical conditions in a patient in need thereof, comprising orally, subcutaneously, or intravenously administering to the patient a composition comprising a crystalline form described herein, or a pharmaceutical composition comprising an effective amount of a disclosed crystalline form.

[0294] The crystalline compounds disclosed herein can be used as a medicament or pharmaceutically acceptable composition, e.g., in the form of pharmaceutical preparations for oral, enteral, parenteral, or topical administration, and the contemplated methods disclosed herein may include administering orally, enterally, parenterally, or topically a disclosed crystalline compound, or a composition comprising or formed from such a disclosed crystalline compound. For example, a disclosed crystalline form may be capable of controlling one or more pharmacokinetic properties (e.g., a longer or shorter release profile) when administered by a 67 IPTS / 128645168.1Attorney Docket No.: ESK-025WO certain route (e.g., oral) or in a certain formulation, as compared to a different route (e.g., subcutaneous) or other formulation e.g., a formulation having the amorphous form. In one embodiment, a disclosed crystalline form may afford substantial reproducibility from one formulation to another. EXAMPLES

[0295] The compounds and crystalline forms described herein can be prepared in a number of ways based on the teachings contained herein and synthetic procedures known in the art. The following non-limiting examples illustrate the disclosure. Instruments and Methods

[0296] PANalytical X-ray powder diffractometers were used for XRPD analysis. The XRPD parameters are listed in Table 1. TABLE 1 XRPD XRPD Parameters (Reflection Mode) (Variable Temperature model)

[0297] TGA data were collected using a TA Discovery TGA5500 / TGA550 from TA Instruments. DSC was performed using a TA Discovery DSC2500 / DSC250 from TA Instruments. Detailed parameters used are listed in Table 2. 68 IPTS / 128645168.1Attorney Docket No.: ESK-025WO TABLE 2 Parameters TGA DSC Method Ram Ram

[0298] DVS was measured via a SMS (Surface Measurement Systems) DVS Intrinsic Plus. The relative humidity at 25 °C was calibrated against deliquescence point of LiCl, Mg(NO3)2 and KCl. The DVS test parameters are listed in Table 3. TABLE 3 Parameters Value )Example 1

[0299] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate was prepared as followed. A slurry of 5 g of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4- triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide, free base, and succinic acid (1.3 equiv) in THF was stirred at 50 °C for 1 hour, then at room temperature for 5 days. The solids were filtered and dried at 40 °C under vacuum for 3 hours, and then 69 IPTS / 128645168.1Attorney Docket No.: ESK-025WO further dried at room temperature under vacuum overnight. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 1.

[0300] The XRPD pattern of crystalline Form 1 is shown in FIG. 1. Characteristic peaks include one or more of the peaks shown in Table 4. TABLE 4 Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%] 33533 15479 2635 11570 IPTS / 128645168.1Attorney Docket No.: ESK-025WO Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%] 25.9312 1093.88 3.44 8.15

[0301] FIG. 2 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 1. As shown in FIG. 2, crystalline Form 1 shows a characteristic endotherm with an onset of about 208 °C and a peak of about 209 °C (enthalpy 149.8 J / g).

[0302] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.6 wt. % between about 20 °C to about 120 °C (FIG. 3).

[0303] Crystalline Form 1 displayed a molar ratio of succinic acid to N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 1.0. Form 1 was observed to be an anhydrate crystalline form.

[0304] When mixed with the pharmaceutical excipient microcrystalline cellulose (1:2 API:excipient molar ratio), Form 1 was observed to be chemically and physicaly stable after being exposed under the condition of 40 °C / 75%RH (open) at least 8 weeks, with no observed 71 IPTS / 128645168.1Attorney Docket No.: ESK-025WO change in polymorphic form. When mixed with the pharmaceutical excipient microcrystalline cellulose (1:2 API:excipient molar ratio), Form 1 was also observed to be chemically and physicaly stable after being exposed under the condition of 40 °C / 75%RH (open) at least 8 weeks, with no observed change in polymorphic form.

[0305] The approximate solubility of Form 1 was measured in solvents at RT. For each experiment, approximately 2 mg of sample was added into a 3 mL glass vial. Solvents were then added stepwise and sonicated or oscillated. Addition of solvent was stopped when the solids dissolved or the total volume reached 1.0 mL. Crystalline Form 1 displayed a solubility of < 1.8 mg / mL in MeOH, a solubility of < 2.0 mg / mL in EtOH at RT, a solubility of < 2.0 mg / mL in IPA at RT, a solubility between about 2.3 mg / mL and about 5.8 mg / mL in acetone at RT, a solubility of < 2.1 mg / mL in MIBK at RT, a solubility of < 1.9 mg / mL in EtOAc at RT, a solubility of < 2.0 mg / mL in IPAc at RT, a solubility of < 1.9 mg / mL in MTBE at RT, a solubility between about 1.8 mg / mL and about 4.5 mg / mL in 1,4-dioxane at RT, a solubility between about 5.5 mg / mL and about 11.0 mg / mL in THF at RT, a solubility of < 1.9 mg / mL in 2-MeTHF at RT, a solubility of < 2.0 mg / mL in MeCN at RT, a solubility of < 2.4 mg / mL in CHCl3 at RT, a solubility of < 2.0 mg / mL in CH2Cl2 at RT, a solubility of < 2.4 mg / mL in n- heptane at RT, a solubility of < 2.1 mg / mL in toluene at RT, a solubility of > 46.0 mg / mL in DMAc at RT, a solubility between about 10.0 mg / mL and about 20.0 mg / mL in DMSO at RT, a solubility of > 38.0 mg / mL in NMP at RT, and a solubility of < 2.0 mg / mL in H2O at RT.

[0306] Single crystals of Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol- 3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate were grown and analyzed by single crystal X-ray analysis. A 3 mL glass vial was charged with 20.1 mg of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base, and 5.8 mg of succinic acid (molar ratio of base / acid = 1:1). The solids were taken up in THF (0.5 mL) to produce a suspension. The 3 mL vial was enclosed in a 10 mL Teflon lined hydrothermal autoclave. The autoclave was then placed in an oven to conduct solvothermal synthesis by running a heating and cooling program consisting of warming from room temperature to 80 °C over 5 hours, maintaining a temperature of 80 °C for 12 hours, then cooling from 80 °C to 25 °C over 46 hours. After the heating and cooling program was completed, rod-like single crystals were observed. A single crystal with suitable size was isolated and analyzed by single-crystal X-ray diffraction. 72 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0307] The crystal system of the single crystal was monoclinic and P21 / c space group. The unit cell dimensions were determined as {a = 5.59870(10) Å, b = 53.3322(11) Å, c = 8.9036(2) Å, α = 90º, β = 98.904(2) º, γ = 90º, V = 2626.50(9) Å3}. Other crystallographic data and the refinement parameters are listed in Table 5. TABLE 5 Temperature299.27(18)Wavelength Cu / Kα(λ = 154184 Å) 2]

[0308] FIG. 4 depicts the asymmetric unit of the N-(4-((3-methoxy-4-(1-(methyl-d3)-1H- 1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 1) single X-ray co-crystal structure. As shown in FIG. 4, the 73 IPTS / 128645168.1Attorney Docket No.: ESK-025WO asymmetric unit of the succinate Form 1 single crystal structure was comprised of one protonated N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide cation (+1 charge) and one hydrogen succinate anion (-1 charge), indicating that Form 1 was a salt form. In addition, there was no water molecule, or any other solvent molecule in the crystal structure, which indicated that Form 1 was an anhydrate. FIG. 5 depicts the ORTEP diagram of the X-ray crystal structure of Form 1. Example 2

[0309] Crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate was prepared as followed. A sample of 20 mg of crystalline Form 1 of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate was suspended in CH2Cl2 (0.5 mL) in an HPLC vial. The suspension was stirred at room temperature for 6 days. The solids were isolated by centrifugation and air-dried at room temperature for 2 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 2.

[0310] The XRPD pattern of crystalline Form 2 is shown in FIG. 6. Characteristic peaks include one or more of the peaks shown in Table 6. TABLE 6 Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%]74 IPTS / 128645168.1Attorney Docket No.: ESK-025WO Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%] 21.1669 540.90 4.20 9.85

[0311] FIG. 7 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 2. As shown in FIG. 7, crystalline Form 2 shows a characteristic endotherm with an onset of about 140 °C and a peak of about 146 °C (enthalpy 139.6 J / g), a characteristic endotherm with a peak of about 209 °C, and a characteristic endotherm with a peak of about 210 °C.

[0312] Crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate 75 IPTS / 128645168.1Attorney Docket No.: ESK-025WO displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 1.1 wt. % between about 26 °C to about 100 °C, and a mass loss of about 13.8 wt. % between about 100 °C to about 160 °C (FIG. 8).

[0313] Crystalline Form 2 displayed a molar ratio of succinic acid to N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 1.1. Form 2 was observed as a dichloromethane solvate crystalline form, with 12.4 residual solvent wt. % as determined by1H NMR. Example 3

[0314] Crystalline Form 4 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate was prepared as followed. A sample of 20 mg of crystalline Form 1 of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate was suspended in MeOH (0.5 mL) in an HPLC vial. The suspension was stirred at room temperature for 6 days. The solids were isolated by centrifugation and air-dried at room temperature for 2 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 4.

[0315] The XRPD pattern of crystalline Form 4 is shown in FIG. 9. Characteristic peaks include one or more of the peaks shown in Table 7. TABLE 7 Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%]76 IPTS / 128645168.1Attorney Docket No.: ESK-025WO Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%] 15.8062 81.14 5.61 2.17

[0316] FIG. 10 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 4. As shown in FIG. 10, crystalline Form 4 shows a characteristic endotherm with an onset of about 214 °C and a peak of about 216 °C (enthalpy 119.5 J / g).

[0317] Crystalline Form 4 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 3.0 wt. % between about 26 °C to about 170 °C (FIG. 11).

[0318] Crystalline Form 4 displayed a molar ratio of succinic acid to N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- 77 IPTS / 128645168.1Attorney Docket No.: ESK-025WO yl)cyclopropanecarboxamide, free base of about 0.5. Form 4 was observed to be an anhydrate or hydrate crystalline form. Example 4

[0319] Crystalline Form 5 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate was prepared as followed. A sample of 20 mg of crystalline Form 1 of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate was suspended in THF (0.5 mL) in an HPLC vial. The suspension was stirred at room temperature for 6 days. The solids were isolated by centrifugation and air-dried at room temperature for 2 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 5.

[0320] The XRPD pattern of crystalline Form 5 is shown in FIG. 12. Characteristic peaks include one or more of the peaks shown in Table 8. TABLE 8 Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%]78 IPTS / 128645168.1Attorney Docket No.: ESK-025WO Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%] 18.9101 281.65 4.69 2.62

[0321] FIG. 13 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 5. As shown in FIG. 13, crystalline Form 5 shows a characteristic endotherm with a peak of about 100 °C, a characteristic endotherm with a peak of about 118 °C, a characteristic endotherm with a peak of about 208 °C, and a characteristic endotherm with a peak of about 218 °C. 79 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0322] Crystalline Form 5 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 6.4 wt. % between about 31 °C to about 150 °C (FIG. 14).

[0323] Crystalline Form 5 displayed a molar ratio of succinic acid to N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 0.8. Form 5 was observed to be a hydrate crystalline form. Example 5

[0324] Crystalline Form 6 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate was prepared as followed. A sample of 20 mg of crystalline Form 1 of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate was suspended in 1,4-dioxane (0.5 mL) in an HPLC vial. The suspension was stirred at room temperature for 6 days. The solids were isolated by centrifugation and air-dried at room temperature for 2 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 6.

[0325] The XRPD pattern of crystalline Form 6 is shown in FIG. 15. Characteristic peaks include one or more of the peaks shown in Table 9. TABLE 9 Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%]80 IPTS / 128645168.1Attorney Docket No.: ESK-025WO Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%] 15.9243 1671.52 5.57 18.38

[0326] FIG. 16 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 6. As shown in FIG. 16, crystalline Form 6 shows a characteristic endotherm with a peak of about 112 °C, a characteristic endotherm with a peak of about 139 °C, a characteristic endotherm with a peak of about 207 °C, and a characteristic endotherm with a peak of about 215 °C.

[0327] Crystalline Form 6 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate displayed a thermogravimetric analysis (TGA) profile showing a 1.3 wt. % between about 83 °C 81 IPTS / 128645168.1Attorney Docket No.: ESK-025WO to about 70 °C, and a mass loss of about 13.1 wt. % between about 70 °C to about 160 °C (FIG. 17).

[0328] Crystalline Form 6 displayed a molar ratio of succinic acid to N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 0.9. Form 6 was observed to be a 1,4-dioxane solvate crystalline form, with 13.0 residual solvent wt. % as determined by1H NMR. Example 6

[0329] Crystalline Form 7 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate was prepared as followed. A sample of 20 mg of crystalline Form 1 of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate was suspended in acetone (0.5 mL) in an HPLC vial. The suspension was stirred at room temperature for 6 days. The solids were isolated by centrifugation and air-dried at room temperature for 2 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 7.

[0330] The XRPD pattern of crystalline Form 7 is shown in FIG. 18. Characteristic peaks include one or more of the peaks shown in Table 10. TABLE 10 Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%]82 IPTS / 128645168.1Attorney Docket No.: ESK-025WO Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%] 18.4692 123.20 4.80 1.02

[0331] FIG. 19 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 7. As shown in FIG. 19, crystalline Form 7 shows a characteristic endotherm with an onset of about 215 °C and a peak of about 216 °C (enthalpy 125.5 J / g).

[0332] Crystalline Form 7 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 1.9 wt. % between about 35 °C to about 150 °C (FIG. 20).

[0333] Crystalline Form 7 displayed a molar ratio of succinic acid to N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- 83 IPTS / 128645168.1Attorney Docket No.: ESK-025WO yl)cyclopropanecarboxamide, free base of about 0.5. Form 7 was observed to be an anhydrate crystalline form. Example 7

[0334] Crystalline Form 8 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate was prepared as followed. A sample of 20 mg of crystalline Form 3 of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate was suspended in acetone (0.5 mL) in an HPLC glass vial. The suspensions were then heated to 50 °C and equilibrated for about 2 hours, then filtered to a new vial using a filter (PTFE, pore size of 0.45 μm). The filtrate was slowly cooled to 5 °C at a rate of 0.1 °C / min and then kept at 5 °C. The solids were collected and analyzed by XRPD, which indicated that the cooled material was crystalline with a pattern consistent with Form 8.

[0335] The XRPD pattern of crystalline Form 8 is shown in FIG. 21. Characteristic peaks include one or more of the peaks shown in Table 11. TABLE 11 Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%]84 IPTS / 128645168.1Attorney Docket No.: ESK-025WO Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%] 20.5469 825.07 4.32 8.57

[0336] FIG. 22 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 8. As shown in FIG. 22, crystalline Form 8 shows a characteristic endotherm with a peak of about 205 °C, a characteristic endotherm with a peak of about 214 °C, and a characteristic endotherm with a peak of about 219 °C.

[0337] Crystalline Form 8 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 11.5 wt. % between about 29 °C to about 140 °C (FIG. 23).

[0338] Crystalline Form 8 displayed a molar ratio of succinic acid to N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 0.7. Form 8 was observed to be an anhydrate crystalline form. Example 8 85 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0339] Crystalline Form 9 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate was prepared as followed. A sample of 20 mg of crystalline Form 1 of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate was mixed with 1,2-dimethoxyethane (0.5 mL) in a glass vial to form a suspension. The suspension was placed into a biochemical incubator of 50 °C for heating and cooling temperature cycles as follows: heating to 50 °C in 7.5 hours; then holding at 50 °C for 2 hours; then cooling to 5 °C at a rate of 0.1 °C / min and then holding at 5 °C for 1 hr. The temperature cycle was repeated 8 times. The solids were isolated by centrifugation and air-dried at room temperature for 2 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 9.

[0340] The XRPD pattern of crystalline Form 9 is shown in FIG. 24. Characteristic peaks include one or more of the peaks shown in Table 12. TABLE 12 Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%]86 IPTS / 128645168.1Attorney Docket No.: ESK-025WO Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%] 22.6744 491.54 3.92 2.10

[0341] FIG. 25 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 9. As shown in FIG. 25, crystalline Form 9 shows a characteristic endotherm with a peak of about 162 °C, a characteristic endotherm with a peak of about 205 °C, a characteristic endotherm with a peak of about 215 °C, and a characteristic endotherm with a peak of about 219 °C.

[0342] Crystalline Form 9 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate 87 IPTS / 128645168.1Attorney Docket No.: ESK-025WO displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 10.7 wt. % between about 27 °C to about 180 °C (FIG. 26).

[0343] Crystalline Form 9 displayed a molar ratio of succinic acid to N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 0.5. Form 9 was observed to be a 1,2- dimethoxyethane solvate crystalline form, with 8.1 residual solvent wt. % as determined by1H NMR. Example 9

[0344] Crystalline Form 13 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate was prepared as followed. A sample of 20 mg of crystalline Form 5 of N-(4-((3-methoxy-4-(1- (methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide hydrogen succinate was heated to 170 °C and then cooled to room temperature. XRPD analysis indicated that the cooled material was crystalline with a pattern consistent with Form 13.

[0345] The XRPD pattern of crystalline Form 13 is shown in FIG. 27. Characteristic peaks include one or more of the peaks shown in Table 13. TABLE 13 Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%]88 IPTS / 128645168.1Attorney Docket No.: ESK-025WO Pos. [°2θ] Height [cts] d-spacing [Å] Rel. Int. [%] 15.1903 172.68 5.83 4.80

[0346] FIG. 28 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 13. As shown in FIG. 28, crystalline Form 13 shows a characteristic endotherm with a peak of about 212 °C, a characteristic endotherm with a peak of about 209 °C, and a characteristic endotherm with a peak of about 218 °C.

[0347] Crystalline Form 13 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate 89 IPTS / 128645168.1Attorney Docket No.: ESK-025WO displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 1.8 wt. % between about 28 °C to about 150 °C (FIG. 29).

[0348] Crystalline Form 13 displayed a molar ratio of succinic acid to N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 0.7. Form 13 was observed to be an anhydrate crystalline form. Example 10

[0349] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride was prepared as followed. HCl (1.1 equiv) was dissolved in 3 mL of ethanol / water (v / v 95 / v) at 50 °C. N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base (210 mg) was added to the solution. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional one day at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 24 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 1.

[0350] The XRPD pattern of crystalline Form 1 is shown in FIG. 30. Characteristic peaks include one or more of the peaks shown in Table 14. TABLE 14 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]90 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 16.256 5.44836 170.151 1.4 17.489 5.06687 49.0786 0.2

[0351] FIG. 31 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 1. As shown in FIG. 31, crystalline Form 1 shows a characteristic endotherm with an onset of about 102 °C and a peak of about 116 °C, a characteristic endotherm with an onset of about 91 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 216 °C and a peak of about 227 °C, a characteristic endotherm with a peak of about 251 °C, and a characteristic endotherm with a peak of about 267 °C.

[0352] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.1 wt. % between about 75 °C to about 145 °C (FIG. 32).

[0353] Crystalline Form 1 displayed a dynamic vapor sorption (DVS) profile showing a reversable total mass change of about 7.3 wt.% between about 0% to about 80% relative humidity (RH) at 25 °C, and a reversable total mass change of about 7.57% between about 0% to about 80% relative humidity (RH) at 25 °C. The moisture uptake process was reversed with hysteresis upon subsequently decreasing RH from 90% to 0%. The XRPD of Form 1 had no change after completion of 0% to 90% to 0% RH cycling in DVS.

[0354] Crystalline Form 1 displayed a molar ratio of hydrochloric acid to N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 1:1. Form 1 displayed a rod-like morphology as observed by polarized light microscopy. Form 1 was observed to be an anhydrate crystalline form.

[0355] Crystalline Form 1 was also observed to be chemically and physically stable after being exposed under the condition of 40 °C / 75%RH (open) for at least 14 days, with no observed change in polymorphic form. Crystalline Form 1 converted to Form 3 after 4 months at 20 °C to 25 °C (closed). Example 11

[0356] Crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride was prepared as followed. HCl (2.1 equiv) was dissolved in tetrahydrofuran (1 mL) at 50 °C. N- (4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin- 2-yl)cyclopropanecarboxamide, free base (25 mg) was added to the solution at 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional three days at room temperature. The solids were collected by filtration and dried under vacuum 92 IPTS / 128645168.1Attorney Docket No.: ESK-025WO at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 2.

[0357] The XRPD pattern of crystalline Form 2 is shown in FIG. 33. Characteristic peaks include one or more of the peaks shown in Table 15. TABLE 15 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%] 774 1141271 793 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 26.195 3.39927 94.1449 9.9 26.693 3.33693 307.514 73.9

[0358] FIG. 34 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 2. As shown in FIG. 34, crystalline Form 2 shows a characteristic endotherm with an onset of about 120 °C and a peak of about 142 °C, a characteristic endotherm with an onset of about 166 °C and a peak of about 194 °C, and a characteristic endotherm with an onset of about 215 °C and a peak of about 225 °C.

[0359] Crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 14.3 wt. % between about 50 °C to about 207 °C. (FIG. 35). Example 12

[0360] Crystalline Form 3 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride was prepared as followed. HCl (1.1 equiv) was dissolved in 9.4 mL of ethanol / water (v / v 95 / 5). N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base (670 mg) was added to the solution at 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional three days at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 5 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 3.

[0361] The XRPD pattern of crystalline Form 3 is shown in FIG. 36. Characteristic peaks include one or more of the peaks shown in Table 16. 94 IPTS / 128645168.1Attorney Docket No.: ESK-025WO TABLE 16 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%] 4563 1934855 844003 19

[0362] FIG. 37 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 3. As shown in FIG. 37, crystalline Form 3 shows a characteristic endotherm with an onset of about 214 °C and a peak of about 226 °C, and a characteristic endotherm with an onset of about 231 °C and a peak of about 253 °C.

[0363] Crystalline Form 3 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride 95 IPTS / 128645168.1Attorney Docket No.: ESK-025WO displayed a thermogravimetric analysis (TGA) profile showing negligible mass loss prior to 200 °C. (FIG. 38).

[0364] Crystalline Form 3 displayed a dynamic vapor sorption (DVS) profile showing a reversable total mass change of about 7.1 wt.% between about 0% to about 80% relative humidity (RH) at 25 °C, and a reversable total mass change of about 7.3% between about 0% to about 80% relative humidity (RH) at 25 °C. The moisture uptake process was reversed with hysteresis upon subsequently decreasing RH from 90% to 0%. The XRPD of Form 3 had no change after completion of 0% to 90% to 0% RH cycling in DVS.

[0365] Crystalline Form 3 displayed a molar ratio of hydrochloric acid to N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 1:1. Form 3 displayed a rod-like morphology as observed by polarized light microscopy. Form 3 was observed to be an anhydrate crystalline form. Example 13

[0366] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate was prepared as followed. H2SO4(0.6 equiv) was dissolved in 1 mL of tetrahydrofuran. N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base (25 mg) was added to the solution at 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional three days at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 1.

[0367] The XRPD pattern of crystalline Form 1 is shown in FIG. 39. Characteristic peaks include one or more of the peaks shown in Table 17. TABLE 17 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]96 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 10.929 8.08886 222.426 2.7 14.608 6.05893 324.741 4.0

[0368] FIG. 40 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 1. As shown in FIG. 40, crystalline Form 1 shows a characteristic endotherm with an onset of about 178 °C and a peak of about 181 °C, and a characteristic endotherm with an onset of about 199 °C and a peak of about 209 °C.

[0369] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.7 wt. % between about 25 °C to about 170 °C (FIG. 41). Form 1 was observed to be an anhydrate crystalline form. Example 14

[0370] Crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate was 97 IPTS / 128645168.1Attorney Docket No.: ESK-025WO prepared as followed. H2SO4(0.6 equiv) was dissolved in 1 mL of ethanol / water (v / v 95 / 5). N- (4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin- 2-yl)cyclopropanecarboxamide, free base (25 mg) was added to the solution at 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional four days at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 2.

[0371] The XRPD pattern of crystalline Form 2 is shown in FIG. 42. Characteristic peaks include one or more of the peaks shown in Table 18. TABLE 18 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]98 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 19.109 4.64068 60.1148 1.5 19.744 4.49294 213.664 11.2

[0372] FIG. 43 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 2. As shown in FIG. 40, crystalline Form 2 shows a characteristic endotherm with an onset of about 76 °C and a peak of about 103 °C, and a characteristic endotherm with an onset of about 194 °C and a peak of about 204 °C.

[0373] Crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 3.2 wt. % between about 38 °C to about 126 °C (FIG. 44). Form 2 was observed to be an anhydrate crystalline form. Form 2 displayed a needle-like morphology as observed by polarized light microscopy. 99 IPTS / 128645168.1Attorney Docket No.: ESK-025WO Example 15

[0374] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis-p-toluenesulfonic acid was prepared as followed. p-Toluenesulfonic acid (1.1 equiv) was dissolved in 1 mL of tetrahydrofuran. N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)- 5-propionylpyridin-2-yl)cyclopropanecarboxamide, free base (25 mg) was added to the solution at 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional three days at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 1.

[0375] The XRPD pattern of crystalline Form 1 is shown in FIG. 45. Characteristic peaks include one or more of the peaks shown in Table 19. TABLE 19 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]100 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 26.069 3.41536 138.635 7.6 28.563 3.12261 119.116 6.4

[0376] FIG. 46 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 1. As shown in FIG. 46, crystalline Form 1 shows a characteristic endotherm with an onset of about 108 °C and a peak of about 120 °C, and a characteristic endotherm with an onset of about 144 °C and a peak of about 188 °C.

[0377] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis-p-toluenesulfonic acid displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 5.4 wt. % between about 53 °C to about 141 °C (FIG. 47).

[0378] Crystalline Form 1 displayed a molar ratio of p-toluenesulfonic acid to N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 2:1. Form 1 was observed to be a hydrate crystalline form. Example 16

[0379] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis-methanesulfonic acid was prepared as followed. Methanesulfonic acid (1.1 equiv) was dissolved in 1 mL of tetrahydrofuran. N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)- 5-propionylpyridin-2-yl)cyclopropanecarboxamide, free base (25 mg) was added to the solution at 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional three days at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 1.

[0380] The XRPD pattern of crystalline Form 1 is shown in FIG. 48. Characteristic peaks include one or more of the peaks shown in Table 20. 101 IPTS / 128645168.1Attorney Docket No.: ESK-025WO TABLE 20 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%] 7023 1257673 299212 1000102 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 34.906 2.56829 74.9466 1.1 36.002 2.49264 60.991 0.7

[0381] FIG. 49 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 1. As shown in FIG. 49, crystalline Form 1 shows a characteristic endotherm with an onset of about 106 °C and a peak of about 113 °C, and a characteristic endotherm with an onset of about 154 °C and a peak of about 163 °C.

[0382] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis-methanesulfonic acid displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 6.5 wt. % between about 55 °C to about 141 °C (FIG. 50).

[0383] Crystalline Form 1 displayed a molar ratio of methanesulfonic acid to N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 2:1. Form 1 was observed to be a hydrate crystalline form. Crystalline Form 1 displayed a rod-like morphology as observed by polarized light microscopy. Example 17

[0384] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide phosphoric acid was prepared as followed. Phosphoric acid (0.7 equiv) was dissolved in 1 mL of tetrahydrofuran. N- (4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin- 2-yl)cyclopropanecarboxamide, free base (25 mg) was added to the solution at 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional three days at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 1.

[0385] The XRPD pattern of crystalline Form 1 is shown in FIG. 51. Characteristic peaks include one or more of the peaks shown in Table 21. 103 IPTS / 128645168.1Attorney Docket No.: ESK-025WO TABLE 21 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%] 6116 1443887 715195 20104 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 25.849 3.44402 165.038 9.7 26.504 3.36030 108.958 5.4

[0386] FIG. 52 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 1. As shown in FIG. 52, crystalline Form 1 shows a characteristic endotherm with a peak of about 203 °C, and a characteristic endotherm with a peak of about 225 °C.

[0387] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide phosphoric acid displayed a thermogravimetric analysis (TGA) profile showing negligible mass loss prior to about 210 °C (FIG. 53).

[0388] Crystalline Form 1 displayed a molar ratio of phosphoric acid to N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 2:1. Form 1 was observed to be an anhydrous crystalline form. Example 18

[0389] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi-L-tartaric acid was prepared as followed. L-tartaric acid (1.1 equiv) was dissolved in 1 mL of tetrahydrofuran. N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base (25 mg) was added to the solution at 105 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional three days at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 1.

[0390] The XRPD pattern of crystalline Form 1 is shown in FIG. 54. Characteristic peaks include one or more of the peaks shown in Table 22. TABLE 22 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]106 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 26.396 3.37379 64.8833 1.1 27.888 3.19666 65.0327 1.0

[0391] FIG. 55 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 1. As shown in FIG. 55, crystalline Form 1 shows a characteristic endotherm with an onset of about 31 °C and a peak of about 65 °C, a characteristic endotherm with an onset of about 201 °C and a peak of about 204 °C, and a characteristic endotherm with an onset of about 225 °C and a peak of about 229 °C.

[0392] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi-L-tartaric acid displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 2.1 wt. % between about 25 °C to about 52 °C (FIG. 56).

[0393] Crystalline Form 1 displayed a molar ratio of L-tartaric acid to N-(4-((3- methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 0.5:1. Form 1 was observed to be a tetrahydrofuran solvate crystalline form, with 2.5% residual solvent wt. % as determined by1H NMR. Crystalline Form 1 displays a needle-like morphology as observed by polarized light microscopy. Example 19

[0394] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide oxalic acid was prepared as followed. Neat oxalic acid (1.1 equiv) was dissolved in 8 mL of ethyl acetate at 50 °C. N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base (210 mg) was added to the solution at 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional one day at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 1. 107 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0395] The XRPD pattern of crystalline Form 1 is shown in FIG. 57. Characteristic peaks include one or more of the peaks shown in Table 23. TABLE 23 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%] 5447 1621003 152471 355108 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 25.730 3.45959 66.2 0.6 26.746 3.33044 183.292 3.4

[0396] FIG. 58 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 1. As shown in FIG. 58, crystalline Form 1 shows a characteristic endotherm with an onset of about 220 °C and a peak of about 226 °C.

[0397] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide oxalic acid displayed a thermogravimetric analysis (TGA) profile showing negligible mass loss prior to about 210 °C (FIG. 59).

[0398] Crystalline Form 1 displayed a dynamic vapor sorption (DVS) profile showing a reversable total mass change of about 1.65 wt.% between about 0% to about 80% relative humidity (RH) at 25 °C, and a reversable total mass change of about 2.74% between about 0% to about 80% relative humidity (RH) at 25 °C. The moisture uptake process was reversed with 109 IPTS / 128645168.1Attorney Docket No.: ESK-025WO hysteresis upon subsequently decreasing RH from 90% to 0%. The XRPD of Form 1 had no change after completion of 0% to 90% to 0% RH cycling in DVS.

[0399] Crystalline Form 1 displayed a molar ratio of oxalic acid to N-(4-((3-methoxy-4- (1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 1:1. Form 1 displayed a needle-like morphology as observed by polarized light microscopy. Form 1 was observed to be an anhydrate crystalline form.

[0400] Crystalline Form 1 was observed to be chemically and physically stable after being exposed under the condition of 40 °C / 75%RH (open) for at least 14 days, with no observed change in polymorphic form. Crystalline Form 1 was also observed to be chemically and physically stable at 20 °C to 25 °C (closed) for at least 3 months, with no observed change in polymorphic form. Example 20

[0401] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi-maleic acid was prepared as followed. Maleic acid (1.1 equiv) was dissolved in 1 mL of tetrahydrofuran. N-(4- ((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base (25 mg) was added to the solution at 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional three days at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 1.

[0402] The XRPD pattern of crystalline Form 1 is shown in FIG. 60. Characteristic peaks include one or more of the peaks shown in Table 24. TABLE 24 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]110 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 8.843 9.99192 60.2819 8.8 9.433 9.36820 68.2346 12.6

[0403] FIG. 61 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 1. As shown in FIG. 61, crystalline Form 1 shows a characteristic endotherm with an onset of about 91 °C and a peak of about 117 °C, a characteristic endotherm with an onset of about 137 °C and a peak of about 142 °C, a characteristic endotherm with an onset of about 148 °C and a 111 IPTS / 128645168.1Attorney Docket No.: ESK-025WO peak of about 167 °C, and a characteristic endotherm with an onset of about 220 °C and a peak of about 224 °C.

[0404] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi-maleic acid displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 3.5 wt. % between about 59 °C to about 140 °C (FIG. 62).

[0405] Crystalline Form 1 displayed a molar ratio of maleic acid to N-(4-((3-methoxy-4- (1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 0.5:1. Form 1 was observed to be a tetrahydrofuran solvate crystalline form, with 4.1% residual solvent wt. % as determined by1H NMR. Example 21

[0406] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid was prepared as followed. Citric acid (1.1 equiv) was dissolved in 1 mL of tetrahydrofuran. N-(4- ((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base (25 mg) was added to the solution at 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional three days at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 1.

[0407] The XRPD pattern of crystalline Form 1 is shown in FIG. 63. Characteristic peaks include one or more of the peaks shown in Table 25. TABLE 25 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]112 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 9.380 9.42096 70.3111 1.0 10.085 8.76384 204.908 5.8113 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 28.640 3.11441 145.073 2.6 29.478 3.02776 112.577 1.8

[0408] FIG. 64 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 1. As shown in FIG. 64, crystalline Form 1 shows a characteristic endotherm with a peak of about 153 °C, and a characteristic endotherm with an onset of about 220 °C and a peak of about 228 °C.

[0409] Crystalline Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.04 wt. % between about 25 °C to about 110 °C (FIG. 65).

[0410] Crystalline Form 1 displayed a molar ratio of citric acid to N-(4-((3-methoxy-4- (1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 1:1. Form 1 was observed to be a tetrahydrofuran solvate crystalline form, with 5.6% residual solvent wt. % as determined by1H NMR. Example 22

[0411] Crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid was prepared as followed. Citric acid (1.1 equiv) was dissolved in 1 mL of dichloromethane. N-(4- ((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base (25 mg) was added at room temperature. The solution was stirred for an additional four days at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 2. 114 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0412] The XRPD pattern of crystalline Form 2 is shown in FIG. 66. Characteristic peaks include one or more of the peaks shown in Table 26. TABLE 26 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%] 5048 1749331 165004 39115 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 26.019 3.42179 99.9958 2.2 26.845 3.31835 97.6032 2.4

[0413] FIG. 67 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 2. As shown in FIG. 67, crystalline Form 2 shows a characteristic endotherm with a peak of about 122 °C, a characteristic endotherm with a peak of about 148 °C, a characteristic exotherm with a peak of about 152 °C, a characteristic endotherm with a peak of about 181 °C, a characteristic exotherm with a peak of about 197 °C, and a characteristic endotherm with a peak of about 228 °C.

[0414] Crystalline Form 2 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.4 wt. % between about 25 °C to about 100 °C (FIG. 68).

[0415] Crystalline Form 2 displayed a molar ratio of citric acid to N-(4-((3-methoxy-4- (1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 1:1. Form 2 was observed to be an anhydrous crystalline form. Example 23

[0416] Crystalline Form 3 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid was prepared as followed. Citric acid (1.1 equiv) was dissolved in 1 mL of ethanol / water (v / v 95 / 5). N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base (25 mg) was added at 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional four days at room temperature. The solids were collected by filtration and dried under vacuum at 116 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 3.

[0417] The XRPD pattern of crystalline Form 3 is shown in FIG. 69. Characteristic peaks include one or more of the peaks shown in Table 27. TABLE 27 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%] 22 1 1 7 4 712 1117 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 23.365 3.80424 128.762 5.2 23.610 3.76526 288.201 15.5

[0418] FIG. 70 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 3. As shown in FIG. 70, crystalline Form 3 shows a characteristic endotherm with an onset of about 84 °C and a peak of about 91 °C, a characteristic endotherm with an onset of about 115 °C and a peak of about 126 °C, a characteristic endotherm with an onset of about 182 °C and a peak of about 185 °C, and a characteristic endotherm with an onset of about 230 °C and a peak of about 233 °C.

[0419] Crystalline Form 3 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 2.5 wt. % between about 25 °C to about 150 °C (FIG. 71). 118 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0420] Crystalline Form 3 displayed a molar ratio of citric acid to N-(4-((3-methoxy-4- (1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 1:1. Form 3 was observed to be a hydrate crystalline form. Example 24

[0421] Crystalline Form 2P of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate was prepared as followed. Succinic acid (1.1 equiv) was dissolved in 1 mL of ethanol / water (v / v 95 / 5). N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base (25 mg) was added at 50 °C. The solution was stirred at 50 °C for 1 hour, cooled to room temperature, and stirred for an additional four days at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 2P.

[0422] The XRPD pattern of crystalline Form 2P is shown in FIG. 72. Characteristic peaks include one or more of the peaks shown in Table 28. TABLE 28 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]119 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 17.061 5.19301 289.845 4.4 19.226 4.61283 96.6736 1.0

[0423] FIG. 73 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 2P. As shown in FIG. 73, crystalline Form 2P shows a characteristic endotherm with an onset of about 97 °C and a peak of about 136 °C, and a characteristic endotherm with an onset of about 218 °C and a peak of about 219 °C. 120 IPTS / 128645168.1Attorney Docket No.: ESK-025WO

[0424] Crystalline Form 2P of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 8.9 wt. % between about 72 °C to about 194 °C (FIG. 74).

[0425] Crystalline Form 2P displayed a molar ratio of succinic acid to N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 0.5. Form 2P was observed to be an ethanol solvate crystalline form, with 7.6% residual solvent wt. % as determined by1H NMR. Example 25

[0426] Crystalline Form 3P of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate was prepared as followed. Succinic acid (1.2 equiv) was dissolved in 8 mL of tetrahydrofuran. N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base (80 mg) was added at 50 °C. The solution was stirred at 50 °C for 1 hour and cooled to room temperature. A 358 mg mixture of Form 1 of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate, succinic acid (0.1. equiv, and N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5- propionylpyridin-2-yl)cyclopropanecarboxamide, free base was added to the suspension and stirred for an additional three days at room temperature. The solids were collected by filtration and dried under vacuum at 40 °C for 3 hours. XRPD analysis indicated that the dried material was crystalline with a pattern consistent with Form 3P.

[0427] The XRPD pattern of crystalline Form 3P is shown in FIG. 75. Characteristic peaks include one or more of the peaks shown in Table 29. TABLE 29 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]121 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 10.060 8.78545 1128.94 38.2 11.084 7.97640 849.27 28.1122 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 25.085 3.54703 291.434 5.4 25.732 3.45937 306.892 6.3

[0428] FIG. 76 depicts the differential scanning calorimetry (DSC) profile of crystalline Form 3P. As shown in FIG. 76, crystalline Form 3P shows a characteristic endotherm with an onset of about 109 °C and a peak of about 115 °C, a characteristic endotherm with a peak of about 211 °C, and a characteristic endotherm with a peak of about 219 °C.

[0429] Crystalline Form 3P of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate displayed a thermogravimetric analysis (TGA) profile showing a mass loss of about 2.2 wt. % between about 82 °C to about 145 °C (FIG. 77).

[0430] Crystalline Form 3P displayed a molar ratio of succinic acid to N-(4-((3-methoxy- 4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2- yl)cyclopropanecarboxamide, free base of about 1.0. Form 3P was observed to be a tetrahydrofuran solvate crystalline form, with 2.2% residual solvent wt. % as determined by1H NMR. Example 26

[0431] Crystalline Form 4P of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3- yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate 123 IPTS / 128645168.1Attorney Docket No.: ESK-025WO was prepared as followed. Crystalline Form 3P of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4- triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate was subject to heating from room temperature to 135 °C at a rate of 10 °C / minute. XRPD analysis indicated that the cooled material was crystalline with a pattern consistent with Form 3P.

[0432] The XRPD pattern of crystalline Form 4P is shown in FIG. 78. Characteristic peaks include one or more of the peaks shown in Table 30. TABLE 30 Pos. [°2θ] d-spacing [Å] Height [cts] Rel. Int. [%]124 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 20.108 4.41240 301.202 6.0 20.772 4.27284 222.899 3.1INCORPORATION BY REFERENCE

[0433] All publications and patents mentioned herein, including those items listed below, are hereby incorporated by reference in their entirety for all purposes as if each individual publication or patent was specifically and individually incorporated by reference. In case of conflict, the present application, including any definitions herein, will control. EQUIVALENTS

[0434] While specific embodiments of the subject disclosure have been discussed, the above specification is illustrative and not restrictive. Many variations of the disclosure will become apparent to those skilled in the art upon review of this specification. The full scope of 125 IPTS / 128645168.1Attorney Docket No.: ESK-025WO the disclosure should be determined by reference to the claims, along with their full scope of equivalents, and the specification, along with such variations.

[0435] Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in this specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure.

[0436] What is claimed is: 126 IPTS / 128645168.1

Claims

Attorney Docket No.: ESK-025WO CLAIMS 1. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 1), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.

3.

2. The crystalline form of claim 1, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 10.3, 11.3, and 23.

9.

3. The crystalline form of claim 1 or 2, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 10.3, 11.3, 19.5, 20.3, 23.9, and 24.

4.

4. The crystalline form of any one of claims 1-3, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 10.3, 11.3, 12.1, 13.3, 19.5, 20.3, 23.9, 24.4, and 25.

3.

5. The crystalline form of any one of claims 1-4, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 10.3, 11.3, 12.1, 13.3, 19.5, 20.3, 21.9, 23.9, 24.4, 24.8, 25.3, and 25.

9.

6. The crystalline form of any one of claims 1-5, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

7. The crystalline form of any one of claims 1-6, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 208 °C and a peak of about 209 °C.

8. The crystalline form of any one of claims 1-7, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.6 wt. % between about 20 °C to about 120 °C.

9. The crystalline form of any one of claims 1-8, wherein the crystalline form is an anhydrate crystalline form.

10. The crystalline form of any one of claims 1-9, wherein the molar ratio of succinic acid to N- (4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2-yl)amino)-5-propionylpyridin- 2-yl)cyclopropanecarboxamide, free base is about 1.

0. 127 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 11. The crystalline form of any one of claims 1-10, characterized by the following unit cell parameters: cell dimensions a = 5.59870(10) Å, α = 90º b = 53.3322(11) Å, β = 98.904(2)ºc = 8.9036(2) Å, γ = 90º; space group = P21 / c; volume = 2626.50(9) Å3; and crystal system = monoclinic.

12. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 2), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.7, 20.2, and 26.

9.

13. The crystalline form of claim 12, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.7, 15.7, 16.2, 20.2, 26.2, and 26.

9.

14. The crystalline form of claim 12 or 13, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.7, 15.7, 16.2, 20.2, 26.2, 26.4, 26.9, 27.8, and 28.

0.

15. The crystalline form of any one of claims 12-14, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.7, 13.3, 15.7, 16.2, 17.2, 20.2, 21.2, 26.2, 26.4, 26.9, 27.8, and 28.

0.

16. The crystalline form of any one of claims 12-15, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

17. The crystalline form of any one of claims 12-16, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 140 °C and a peak of about 146 °C, a characteristic endotherm with a peak of about 209 °C, and a characteristic endotherm with a peak of about 210 °C. 128 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 18. The crystalline form of any one of claims 12-17, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 1.1 wt. % between about 26 °C to about 100 °C, and a mass loss of about 13.8 wt. % between about 100 °C to about 160 °C.

19. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 4), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.2, 10.6, and 13.

7.

20. The crystalline form of claim 19, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.0, 10.2, 10.6, 13.7, 17.9, and 25.

3.

21. The crystalline form of claim 19 or 20, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.0, 10.2, 10.6, 11.9, 13.7, 17.9, 22.1, 23.0, and 25.

3.

22. The crystalline form of any one of claims 19-21, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 5.6, 6.0, 10.2, 10.6, 11.9, 13.7, 17.9, 18.4, 22.1, 23.0, 25.3, and 26.

0.

23. The crystalline form of any one of claims 19-22, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

24. The crystalline form of any one of claims 19-23, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 214 °C and a peak of about 216 °C.

25. The crystalline form of any one of claims 19-24, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 3.0 wt. % between about 26 °C to about 170 °C.

26. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 5), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 9.3, 23.9, and 24.

2. 129 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 27. The crystalline form of claim 26, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 9.3, 16.2, 21.7, 23.9, 24.2, and 24.

5.

28. The crystalline form of claim 26 or 27, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.6, 9.3, 16.2, 18.0, 20.8, 21.7, 23.9, 24.2, and 24.

5.

29. The crystalline form of any one of claims 26-28, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.6, 9.3, 16.2, 18.0, 18.5, 20.5, 20.8, 21.7, 22.9, 23.9, 24.2, and 24.

5.

30. The crystalline form of any one of claims 26-29, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

31. The crystalline form of any one of claims 26-30, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with a peak of about 100 °C, a characteristic endotherm with a peak of about 118 °C, a characteristic endotherm with a peak of about 208 °C, and a characteristic endotherm with a peak of about 218 °C.

32. The crystalline form of any one of claims 26-31, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 6.4 wt. % between about 31 °C to about 150 °C.

33. The crystalline form of any one of claims 26-32, wherein the crystalline form is a hydrate crystalline form.

34. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 6), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.6, 15.9, and 26.

2.

35. The crystalline form of claim 34, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.6, 11.3, 15.9, 17.2, 26.2, and 29.

2.

36. The crystalline form of claim 34 or 35, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.6, 9.2, 11.3, 15.1, 15.9, 17.2, 17.9, 26.2, and 29.

2. 130 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 37. The crystalline form of any one of claims 34-36, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.6, 9.2, 11.3, 15.1, 15.9, 16.2, 17.2, 17.9, 21.4, 23.1, 26.2, and 29.

2.

38. The crystalline form of any one of claims 34-37, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

39. The crystalline form of any one of claims 34-38, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with a peak of about 112 °C, a characteristic endotherm with a peak of about 139 °C, a characteristic endotherm with a peak of about 207 °C, and a characteristic endotherm with a peak of about 215 °C.

40. The crystalline form of any one of claims 34-39, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 1.3 wt. % between about 83 °C to about 70 °C, and a mass loss of about 13.1 wt. % between about 70 °C to about 160 °C.

41. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 7), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.5, 11.0, and 20.

6.

42. The crystalline form of claim 41, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.5, 11.0, 14.2, 18.1, 20.6, and 26.

1.

43. The crystalline form of claim 41 or 42, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.0, 10.5, 11.0, 14.2, 18.1, 20.6, 24.7, 25.6, and 26.

1.

44. The crystalline form of any one of claims 41-43, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.0, 10.5, 11.0, 13.1, 14.2, 17.5, 18.1, 18.9, 20.6, 24.7, 25.6, and 26.

1.

45. The crystalline form of any one of claims 41-44, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation. 131 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 46. The crystalline form of any one of claims 41-45, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 215 °C and a peak of about 216 °C.

47. The crystalline form of any one of claims 41-46, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 1.9 wt. % between about 35 °C to about 150 °C.

48. The crystalline form of any one of claims 41-47, wherein the crystalline form is an anhydrate crystalline form.

49. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 8), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.0, 10.1, and 10.

6.

50. The crystalline form of claim 49, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.0, 10.1, 10.6, 11.9, 17.9, and 20.

5.

51. The crystalline form of claim 49 or 50, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.0, 10.1, 10.6, 11.9, 15.6, 17.9, 20.3, 20.5, and 23.

6.

52. The crystalline form of any one of claims 49-51, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.0, 10.1, 10.6, 11.9, 13.5, 15.6, 17.9, 20.3, 20.5, 22.0, 23.6, and 25.

2.

53. The crystalline form of any one of claims 49-52, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

54. The crystalline form of any one of claims 49-53, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with a peak of about 205 °C, a characteristic endotherm with a peak of about 214 °C, and a characteristic endotherm with a peak of about 219 °C. 132 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 55. The crystalline form of any one of claims 49-54, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 11.5 wt. % between about 29 °C to about 140 °C.

56. The crystalline form of any one of claims 49-55, wherein the crystalline form in an anhydrate crystalline form.

57. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 9), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.8, 13.6, and 15.

7.

58. The crystalline form of claim 57, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.8, 13.6, 15.7, 17.3, 20.7, and 26.

6.

59. The crystalline form of claim 57 or 58, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.8, 13.6, 15.4, 15.7, 17.3, 20.7, 26.

0. 26.6, and 27.

8.

60. The crystalline form of any one of claims 57-59, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.8, 13.6, 15.4, 15.7, 17.3, 19.8, 20.5, 20.7, 22.1, 26.

0. 26.6, and 27.

8.

61. The crystalline form of any one of claims 57-60, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

62. The crystalline form of any one of claims 57-61, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with a peak of about 162 °C, a characteristic endotherm with a peak of about 205 °C, a characteristic endotherm with a peak of about 215 °C, and a characteristic endotherm with a peak of about 219 °C.

63. The crystalline form of any one of claims 57-62, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 10.7 wt. % between about 27 °C to about 180 °C.

64. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 13), 133 IPTS / 128645168.1Attorney Docket No.: ESK-025WO characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.3, 23.2, and 23.

9.

65. The crystalline form of claim 64, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.3, 11.1, 23.2, 23.6, 23.9, and 24.

4.

66. The crystalline form of claim 64 or 65, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.3, 11.1, 14.3, 16.1, 22.6, 23.2, 23.6, 23.9, and 24.

4.

67. The crystalline form of any one of claims 64-66, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.6, 8.2, 10.3, 11.1, 14.3, 16.1, 21.9, 22.6, 23.2, 23.6, 23.9, and 24.

4.

68. The crystalline form of any one of claims 64-67, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

69. The crystalline form of any one of claims 64-68, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with a peak of about 212 °C, a characteristic endotherm with a peak of about 209 °C, and a characteristic endotherm with a peak of about 218 °C.

70. The crystalline form of any one of claims 64-69, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 1.8 wt. % between about 28 °C to about 150 °C.

71. The crystalline form of any one of claims 64-70, wherein the crystalline form is an anhydrate crystalline form.

72. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride (Form 1), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.7, 11.3, and 15.5, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

73. The crystalline form of claim 72, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.7, 11.3, 15.5, 23.4, 26.0, and 31.

4. 134 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 74. The crystalline form of claim 72 or 73, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.7, 9.9, 11.3, 15.5, 16.3, 20.0, 23.4, 26.0, and 31.

4.

75. The crystalline form of any one of claims 72-74, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 102 °C and a peak of about 116 °C, a characteristic endotherm with an onset of about 216 °C and a peak of about 227 °C, a characteristic endotherm with a peak of about 251 °C, and a characteristic endotherm with a peak of about 267 °C.

76. The crystalline form of any one of claims 72-75, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.1 wt. % between about 75 °C to about 145 °C.

77. The crystalline form of any one of claims 72-76, wherein the crystalline form is an anhydrate crystalline form.

78. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride (Form 2), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 9.3, 21.2, and 26.7, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

79. The crystalline form of claim 78, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 8.6, 9.3, 15.2, 21.2, 26.7, and 28.

3.

80. The crystalline form of claim 78 or 79, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 8.6, 9.3, 10.5, 15.2, 21.2, 22.5, 22.8, 26.7, and 28.

3.

81. The crystalline form of any one of claims 78-80, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 120 °C and a peak of about 142 °C, a characteristic endotherm with an onset of about 166 °C and a peak of about 194 °C, and a characteristic endotherm with an onset of about 215 °C and a peak of about 225 °C. 135 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 82. The crystalline form of any one of claims 78-81, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 14.3 wt. % between about 50 °C to about 207 °C.

83. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen chloride (Form 3), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.2, 12.8, and 26.0, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

84. The crystalline form of claim 83, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.2, 8.5, 12.8, 22.0, 26.0, and 28.

0.

85. The crystalline form of claim 83 or 84, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.2, 8.5, 12.8, 14.5, 17.3, 22.0, 23.0, 26.0, and 28.

0.

86. The crystalline form of any one of claims 83-85, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 214 °C and a peak of about 226 °C, and a characteristic endotherm with an onset of about 231 °C and a peak of about 253 °C.

87. The crystalline form of any one of claims 83-86, wherein the crystalline form is an anhydrate crystalline form.

88. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate (Form 1), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.4, 15.0, and 17.7, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

89. The crystalline form of claim 88, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.4, 10.9, 14.6, 15.0, 17.7, and 22.

0. 136 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 90. The crystalline form of claim 88 or 89, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.4, 10.9, 14.6, 15.0, 17.7, 21.8, 22.0, 22.5, and 25.

9.

91. The crystalline form of any one of claims 88-90, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 178 °C and a peak of about 181 °C, and a characteristic endotherm with an onset of about 199 °C and a peak of about 209 °C.

92. The crystalline form of any one of claims 88-91, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.7 wt. % between about 25 °C to about 170 °C.

93. The crystalline form of any one of claims 88-92, wherein the crystalline form is an anhydrate crystalline form.

94. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen sulfate (Form 2), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 8.0, 8.3, and 9.0, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

95. The crystalline form of claim 94, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 5.3, 8.0, 8.3, 9.0, 10.8, and 13.

0.

96. The crystalline form of claim 94 or 95, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 5.3, 8.0, 8.3, 9.0, 10.8, 13.0, 13.2, 13.7, and 17.

1.

97. The crystalline form of any one of claims 94-96, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 76 °C and a peak of about 103 °C, and a characteristic endotherm with an onset of about 194 °C and a peak of about 204 °C. 137 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 98. The crystalline form of any one of claims 94-97, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 3.2 wt. % between about 38 °C to about 126 °C.

99. The crystalline form of any one of claims 94-98, wherein the crystalline form is a hydrate crystalline form.

100. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis-p-toluenesulfonic acid (Form 1), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.2, 7.9, and 21.8, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

101. The crystalline form of claim 100, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.2, 7.9, 14.2, 16.2, 21.8, and 23.

6.

102. The crystalline form of claim 100 or 101, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.2, 7.9, 14.2, 16.2, 19.9, 21.8, 23.6, 23.7, and 26.

1.

103. The crystalline form of any one of claims 100-102, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 108 °C and a peak of about 120 °C, and a characteristic endotherm with an onset of about 144 °C and a peak of about 188 °C.

104. The crystalline form of any one of claims 100-103, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 5.4 wt. % between about 53 °C to about 141 °C.

105. The crystalline form of any one of claims 100-104, wherein the crystalline form is a hydrate crystalline form.

106. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide bis-methanesulfonic acid (Form 1), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ 138 IPTS / 128645168.1Attorney Docket No.: ESK-025WO at about 7.0, 19.2, and 21.0, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

107. The crystalline form of claim 106, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.0, 10.4, 19.2, 21.0, 21.1, and 29.

0.

108. The crystalline form of claim 106 or 107, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.0, 9.5, 10.4, 12.6, 19.2, 21.0, 21.1, 26.3, and 29.

0.

109. The crystalline form of any one of claims 106-108, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 106 °C and a peak of about 113 °C, and a characteristic endotherm with an onset of about 154 °C and a peak of about 163 °C.

110. The crystalline form of any one of claims 106-109, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 6.5 wt. % between about 55 °C to about 141 °C.

111. The crystalline form of any one of claims 106-110, wherein the crystalline form is a hydrate crystalline form.

112. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide phosphoric acid (Form 1), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.1, 10.2, and 19.6, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

113. The crystalline form of claim 112, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.1, 10.2, 19.6, 25.2, 27.4, and 27.

9.

114. The crystalline form of claim 112 or 113, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.1, 10.2, 13.1, 19.6, 25.2, 25.8, 27.4, 27.9, and 28.

9. 139 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 115. The crystalline form of any one of claims 112-114, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with a peak of about 203 °C, and a characteristic endotherm with a peak of about 225 °C.

116. The crystalline form of any one of claims 112-115, wherein the crystalline form is an anhydrate crystalline form.

117. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi-L-tartaric acid (Form 1), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.1, 7.9, and 13.8, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

118. The crystalline form of claim 117, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.1, 7.9, 13.8, 14.4, 15.1, and 20.

9.

119. The crystalline form of claim 117 or 118, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.1, 7.9, 10.6, 13.8, 14.4, 15.1, 17.4, 20.9, and 21.

7.

120. The crystalline form of any one of claims 117-119, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 31 °C and a peak of about 65 °C, a characteristic endotherm with an onset of about 201 °C and a peak of about 204 °C, and a characteristic endotherm with an onset of about 225 °C and a peak of about 229 °C.

121. The crystalline form of any one of claims 117-120, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 2.1 wt. % between about 25 °C to about 52 °C.

122. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide oxalic (Form 1), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 5.4, 7.8, and 11.3, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation. 140 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 123. The crystalline form of claim 122, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 5.4, 7.8, 11.3, 14.2, 15.7, and 22.

4.

124. The crystalline form of claim 122 or 123, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 5.4, 7.8, 11.3, 14.2, 15.7, 16.2, 17.6, 22.0, and 22.

4.

125. The crystalline form of any one of claims 122-124, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 220 °C and a peak of about 226 °C.

126. The crystalline form of any one of claims 122-125, wherein the crystalline form is an anhydrate crystalline form.

127. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hemi-maleic acid (Form 1), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.8, 8.2, and 25.2, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

128. The crystalline form of claim 127, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.8, 8.2, 11.3, 16.7, 21.7, and 25.

2.

129. The crystalline form of claim 127 or 128, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.8, 8.2, 11.3, 16.7, 20.6, 21.7, 23.1, 25.2, and 26.

0.

130. The crystalline form of any one of claims 127-129, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 91 °C and a peak of about 117 °C, a characteristic endotherm with an onset of about 137 °C and a peak of about 142 °C, a characteristic endotherm with an onset of about 148 °C and a peak of about 167 °C, and a characteristic endotherm with an onset of about 220 °C and a peak of about 224 °C.

131. The crystalline form of any one of claims 127-130, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 3.5 wt. % between about 59 °C to about 140 °C. 141 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 132. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid (Form 1), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.8, 22.1, and 26.2, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

133. The crystalline form of claim 132, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.8, 20.2, 22.1, 26.2, 26.6, and 27.

0.

134. The crystalline form of claim 132 or 133, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 6.8, 12.7, 16.7, 17.0, 20.2, 22.1, 26.2, 26.6, and 27.

0.

135. The crystalline form of any one of claims 132-134, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with a peak of about 153 °C, and a characteristic endotherm with an onset of about 220 °C and a peak of about 228 °C.

136. The crystalline form of any one of claims 132-135, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.04 wt. % between about 25 °C to about 110 °C.

137. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid (Form 2), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.5, 8.9, and 9.3, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

138. The crystalline form of claim 137, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 5.0, 7.5, 8.9, 9.3, 15.3, and 19.

7.

139. The crystalline form of claim 137 or 138, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 5.0, 7.5, 8.9, 9.3, 14.5, 15.3, 19.7, 22.7, and 25.

4.

140. The crystalline form of any one of claims 137-139, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with a peak of about 122 °C, a characteristic endotherm with a peak of about 148 °C, a characteristic exotherm with a peak of 142 IPTS / 128645168.1Attorney Docket No.: ESK-025WO about 152 °C, a characteristic endotherm with a peak of about 181 °C, a characteristic exotherm with a peak of about 197 °C, and a characteristic endotherm with a peak of about 228 °C.

141. The crystalline form of any one of claims 137-140, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 0.4 wt. % between about 25 °C to about 100 °C.

142. The crystalline form of any one of claims 137-141, wherein the crystalline form is an anhydrate crystalline form.

143. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide citric acid (Form 3), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.4, 9.3, and 23.6, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

144. The crystalline form of claim 143, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.4, 9.3, 9.7, 15.7, 23.6, and 24.

3.

145. The crystalline form of claim 143 or 144, characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.4, 9.3, 9.7, 11.2, 14.0, 15.7, 23.6, 24.3, and 26.

1.

146. The crystalline form of any one of claims 143-145, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 84 °C and a peak of about 91 °C, a characteristic endotherm with an onset of about 115 °C and a peak of about 126 °C, a characteristic endotherm with an onset of about 182 °C and a peak of about 185 °C, and a characteristic endotherm with an onset of about 230 °C and a peak of about 233 °C.

147. The crystalline form of any one of claims 143-146, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 2.5 wt. % between about 25 °C to about 150 °C.

148. The crystalline form of any one of claims 143-147, wherein the crystalline form is an anhydrate crystalline form.

149. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 2P), 143 IPTS / 128645168.1Attorney Docket No.: ESK-025WO characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 7.6, 8.0, and 20.0, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

150. The crystalline form of claim 149, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 7.6, 8.0, 13.0, 15.5, 20.0 and 26.

8.

151. The crystalline form of claim 149 or 150, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 7.6, 8.0, 13.0, 15.5, 16.2, 20.0, 20.1, 26.8, and 27.

7.

152. The crystalline form of any one of claims 149-151, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 97 °C and a peak of about 136 °C, and a characteristic endotherm with an onset of about 218 °C and a peak of about 219 °C.

153. The crystalline form of any one of claims 149-152, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 8.9 wt. % between about 72 °C to about 194 °C.

154. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 3P), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 23.7, 23.9, and 24.2, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

155. The crystalline form of claim 154, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 9.1, 10.1, 11.1, 23.7, 23.9, and 24.

2.

156. The crystalline form of claim 154 or 155, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 9.1, 10.1, 11.1, 13.1, 21.4, 23.7, 23.9, 24.2, and 24.

6.

157. The crystalline form of any one of claims 154-156, characterized by a differential scanning calorimetry (DSC) profile having a characteristic endotherm with an onset of about 109 °C and a 144 IPTS / 128645168.1Attorney Docket No.: ESK-025WO peak of about 115 °C, a characteristic endotherm with a peak of about 211 °C, and a characteristic endotherm with a peak of about 219 °C.

158. The crystalline form of any one of claims 154-157, characterized by a thermogravimetric analysis (TGA) profile showing a mass loss of about 2.2 wt. % between about 82 °C to about 145 °C.

159. A crystalline form of N-(4-((3-methoxy-4-(1-(methyl-d3)-1H-1,2,4-triazol-3-yl)pyridin-2- yl)amino)-5-propionylpyridin-2-yl)cyclopropanecarboxamide hydrogen succinate (Form 4P), characterized by a powder X-ray diffraction pattern having a characteristic peak in degrees 2θ at about 10.1, 23.7, and 24.2, wherein the powder X-ray diffraction pattern was obtained using Cu Kα radiation.

160. The crystalline form of claim 159, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 10.1, 11.1, 13.1, 23.4, 23.7, and 24.

2.

161. The crystalline form of claim 159 or 160, characterized by a powder X-ray diffraction pattern having characteristic peaks in degrees 2θ at about 8.0, 10.1, 11.1, 13.1, 15.9, 16.6, 23.4, 23.7, and 24.

2.

162. A pharmaceutical composition comprising a crystalline form of any one of claims 1-161, and a pharmaceutically acceptable excipient.

163. A pharmaceutical composition formed from the crystalline form of any one of claims 1- 161.

164. A method of inhibiting TYK2 activity in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a crystalline form of any one of claims 1-161, or the pharmaceutical composition of claim 162 or 163.

165. A method of treating a TYK2-mediated disorder in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a crystalline form of any one of claims 1-161, or the pharmaceutical composition of claim 162 or 163.

166. A method of treating a neuroinflammatory disease in a patient in need thereof, comprising administering to the patient an effective amount of a crystalline form of any one of claims 1-161, or the pharmaceutical composition of claim 162 or 163. 145 IPTS / 128645168.1Attorney Docket No.: ESK-025WO 167. The method of claim 166, wherein the neuroinflammatory disease is multiple sclerosis.

168. A method of treating multiple sclerosis in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a crystalline form of any one of claims 1-161, or the pharmaceutical composition of claim 162 or 163. 146 IPTS / 128645168.1

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