Claims for Patent: 12,410,184

Summary for Patent: 12,410,184

Title:	Crystalline forms of a menin inhibitor
Abstract:	Described herein are crystalline forms of (S)-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1-(2-(4-(methylsulfonyl)piperazin-1-yl)propyl)-1H-indole-2-carbonitrile or solvate thereof.
Inventor(s):	Roger Paul BAKALE, Craig Michael Bowe, Dipanjan Sengupta, Patricia Andres, Xiaohu Deng
Assignee:	Keystone Pharma Consulting LLC , Kura Oncology Inc
Application Number:	US18/827,512
Patent Claims:	1. A crystalline Form 1 of of (S)-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1-(2-(4-(methylsulfonyl)piperazin-1-yl)propyl)-1H-indole-2-carbonitrile having an X-ray powder diffraction (XRPD) pattern with at least three characteristic peaks selected from 4.1° 2-Theta, 5.4° 2-Theta, 6.6° 2-Theta, 8.2° 2-Theta, 9.5° 2-Theta, 12.3° 2-Theta, 13.1° 2-Theta, 13.9° 2-Theta, 15.9° 2-Theta, 16.4° 2-Theta, 17.0° 2-Theta, 17.5° 2-Theta, 19.7° 2-Theta, and 22.6° 2-Theta. 2. A crystalline Form 1 of (S)-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl) thieno [2,3-d]pyrimidin-4-yl) amino) piperidin-1-yl) methyl)-1-(2-(4-(methylsulfonyl) piperazin-1-yl) propyl)-1H-indole-2-carbonitrile having an X-ray powder diffraction (XRPD) pattern set forth in FIG. 1 . 3. The crystalline Form 1 of claim 1, wherein the crystalline form has an XRPD pattern with at least five characteristic peaks selected from 4.1° 2-Theta, 5.4° 2-Theta, 6.6° 2-Theta, 8.2° 2-Theta, 9.5° 2-Theta, 12.3° 2-Theta, 13.1° 2-Theta, 13.9° 2-Theta, 15.9° 2-Theta, 16.4° 2-Theta, 17.0° 2-Theta, 17.5° 2-Theta, 19.7° 2-Theta, and 22.6° 2-Theta. 4. The crystalline Form 1 of claim 1, wherein the crystalline form has a DSC thermogram set forth in FIG. 2 . 5. The crystalline Form 1 of claim 1, wherein the crystalline form has a DSC thermogram with an endotherm having an onset at about 136° C. and/or a peak at about 149° C. 6. The crystalline Form 1 of claim 1, wherein the crystalline form has a TGA curve set forth in FIG. 3 . 7. A crystalline Form 2 of (S)-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl) thieno [2,3-d]pyrimidin-4-yl) amino) piperidin-1-yl) methyl)-1-(2-(4-(methylsulfonyl) piperazin-1-yl) propyl)-1H-indole-2-carbonitrile having: (a) an X-ray powder diffraction (XRPD) pattern set forth in FIG. 4 ; or (b) an XRPD pattern with at least three characteristic peaks selected from 3.8° 2-Theta, 5.6° 2-Theta, 6.4° 2-Theta, 7.1° 2-Theta, 8.8° 2-Theta, 9.9° 2-Theta, 11.9° 2-Theta, and 14.8° 2-Theta; or (c) (a) and (b). 8. A crystalline Form 3 of (S)-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl) thieno [2,3-d]pyrimidin-4-yl) amino) piperidin-1-yl) methyl)-1-(2-(4-(methylsulfonyl) piperazin-1-yl) propyl)-1H-indole-2-carbonitrile having: (a) an X-ray powder diffraction (XRPD) pattern set forth in FIG. 5 ; or (b) an XRPD pattern with at least three characteristic peaks selected from 7.9° 2-Theta, 9.5° 2-Theta, 11.0° 2-Theta, 15.7° 2-Theta, 16.5° 2-Theta, 18.0° 2-Theta, 19.0° 2-Theta, and 21.9° 2-Theta; or (c) (a) and (b). 9. The crystalline Form 3 of claim 8, wherein the crystalline form has an XRPD pattern with at least five characteristic peaks selected from 7.9° 2-Theta, 9.5° 2-Theta, 11.0° 2-Theta, 15.7° 2-Theta, 16.5° 2-Theta, 18.0° 2-Theta, 19.0° 2-Theta, and 21.9° 2-Theta. 10. The crystalline Form 3 of claim 8, wherein the crystalline form has a DSC thermogram set forth in FIG. 6A. 11. The crystalline Form 3 of claim 8, wherein the crystalline form has a DSC thermogram with an endotherm having an onset at about 117° C. and/or a peak at about 135° C. 12. The crystalline Form 3 of claim 8, wherein the crystalline form has a TGA curve set forth in FIG. 6B. 13. The crystalline Form 3 of claim 8, wherein the crystalline form is an ethanol solvate. 14. A crystalline Form 4 of (S)-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl) thieno [2,3-d]pyrimidin-4-yl) amino) piperidin-1-yl) methyl)-1-(2-(4-(methylsulfonyl) piperazin-1-yl) propyl)-1H-indole-2-carbonitrile having: (a) an X-ray powder diffraction (XRPD) pattern set forth in FIG. 7 ; or (b) an XRPD pattern with at least three characteristic peaks selected from 8.1° 2-Theta, 9.4° 2-Theta, 10.8° 2-Theta, 13.5° 2-Theta, 15.7° 2-Theta, 16.3° 2-Theta, 17.5° 2-Theta, 18.3° 2-Theta, 18.7° 2-Theta, 20.1° 2-Theta, 21.6° 2-Theta, 21.8° 2-Theta, 25.2° 2-Theta, and 25.7° 2-Theta; or (c) (a) and (b). 15. The crystalline Form 4 of claim 14, wherein the crystalline form has an XRPD pattern with at least five characteristic peaks selected from 8.1° 2-Theta, 9.4° 2-Theta, 10.8° 2-Theta, 13.5° 2-Theta, 15.7° 2-Theta, 16.3° 2-Theta, 17.5° 2-Theta, 18.3° 2-Theta, 18.7° 2-Theta, 20.1° 2-Theta, 21.6° 2-Theta, 21.8° 2-Theta, 25.2° 2-Theta, and 25.7° 2-Theta. 16. The crystalline Form 4 of claim 14, wherein the crystalline form has a DSC thermogram set forth in FIG. 8 . 17. The crystalline Form 4 of claim 14, wherein the crystalline form has a DSC thermogram with an endotherm having an onset at about 127° C. and/or a peak at about 138° C. 18. A crystalline Form 5 of (S)-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl) thieno [2,3-d]pyrimidin-4-yl) amino)piperidin-1-yl) methyl)-1-(2-(4-(methylsulfonyl) piperazin-1-yl) propyl)-1H-indole-2-carbonitrile having: (a) an X-ray powder diffraction (XRPD) pattern set forth in FIG. 9 ; or (b) an XRPD pattern with at least three characteristic peaks selected from 7.9° 2-Theta, 8.5° 2-Theta, 9.6° 2-Theta, 11.1° 2-Theta, 15.8° 2-Theta, 16.9° 2-Theta, 18.4° 2-Theta, 19.1° 2-Theta, 22.1° 2-Theta, 25.5° 2-Theta, and 27.4° 2-Theta; or (c) (a) and (b). 19. The crystalline Form 5 of claim 18, wherein the crystalline form has an XRPD pattern with at least five characteristic peaks selected from 7.9° 2-Theta, 8.5° 2-Theta, 9.6° 2-Theta, 11.1° 2-Theta, 15.8° 2-Theta, 16.9° 2-Theta, 18.4° 2-Theta, 19.1° 2-Theta, 22.1° 2-Theta, 25.5° 2-Theta, and 27.4° 2-Theta. 20. The crystalline Form 5 of claim 18, wherein the crystalline form has a DSC thermogram set forth in FIG. 10 . 21. The crystalline Form 5 of claim 18, wherein the crystalline form has a DSC thermogram with an endotherm having an onset at about 122° C. and/or a peak at about 132° C. 22. The crystalline Form 5 of claim 18, wherein the crystalline form has a DVS curve set forth in FIG. 11 . 23. The crystalline Form 5 of claim 18, wherein the crystalline form is an anhydrate. 24. A pharmaceutical composition comprising a crystalline form of (S) -4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethythieno [2,3-d]pyrimidin-4-y1) amino) piperidin-1-yl) methyl)-1-(2-(4-(methylsulfonyl) piperazin-1-yl) propyl)-1H-indole-2-carbonitrile, wherein the crystalline form is: (a) a crystalline Form 1 having an X-ray powder diffraction (XRPD) pattern with at least three characteristic peaks selected from 4.1° 2-Theta, 5.4° 2-Theta, 6.6° 2-Theta, 8.2° 2-Theta, 9.5° 2-Theta, 12.3° 2-Theta, 13.1° 2-Theta, 13.9° 2-Theta, 15.9° 2-Theta, 16.4° 2-Theta, 17.0° 2-Theta, 17.5° 2-Theta, 19.7° 2-Theta, and 22.6° 2-Theta; or (b) a crystalline Form 2 having an XRPD pattern with at least three characteristic peaks selected from 3.8° 2-Theta, 5.6° 2-Theta, 6.4° 2-Theta, 7.1° 2-Theta, 8.8° 2-Theta, 9.9° 2-Theta, 11.9° 2-Theta, and 14.8° 2-Theta; or (c) a crystalline Form 3 having an XRPD pattern with at least three characteristic peaks selected from 7.9° 2-Theta, 9.5° 2-Theta, 11.0° 2-Theta, 15.7° 2-Theta, 16.5° 2-Theta, 18.0° 2-Theta, 19.0° 2-Theta, and 21.9° 2-Theta; or (d) a crystalline Form 4 having an XRPD pattern with at least three characteristic peaks selected from 8.1° 2-Theta, 9.4° 2-Theta, 10.8° 2-Theta, 13.5° 2-Theta, 15.7° 2-Theta, 16.3° 2-Theta, 17.5° 2-Theta, 18.3° 2-Theta, 18.7° 2-Theta, 20.1° 2-Theta, 21.6° 2-Theta, 21.8° 2-Theta, 25.2° 2-Theta, and 25.7° 2-Theta; or (e) a crystalline Form 5 having an XRPD pattern with at least three characteristic peaks selected from 7.9° 2-Theta, 8.5° 2-Theta, 9.6° 2-Theta, 11.1° 2-Theta, 15.8° 2-Theta, 16.9° 2-Theta, 18.4° 2-Theta, 19.1° 2-Theta, 22.1° 2-Theta, 25.5° 2-Theta, and 27.4° 2-Theta; or (f) any combination thereof; and a pharmaceutically acceptable excipient. 25. A method of treating a disease or condition characterized by the interaction of menin with MLL in a subject comprising administering to the subject a therapeutically effective amount of the crystalline Form 1 of claim 1, wherein the disease or condition comprises a hematologic malignancy, a solid tumor cancer, or diabetes. 26. The method of claim 25, wherein the hematological malignancy is leukemia, myelodysplastic syndrome, or myelodysplastic/myeloproliferative neoplasm. 27. The method of claim 26, wherein the leukemia is acute myeloid leukemia or acute lymphoblastic leukemia. 28. The method of claim 25, wherein the solid tumor cancer is prostate cancer, breast cancer, liver cancer, or brain tumor. 29. A crystalline Form 1 of (S)-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl) thieno [2,3-d] pyrimidin-4-yl) amino) piperidin-1-yl) methyl)-1-(2-(4-(methylsulfonyl) piperazin-1-yl) propyl)-1H-indole-2-carbonitrile having a DSC thermogram set forth in FIG. 2 . 30. A crystalline Form 1 of (S)-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl) thieno [2,3-d] pyrimidin-4-yl) amino) piperidin-1-yl) methyl)-1-(2-(4-(methylsulfonyl) piperazin-1-yl) propyl)-1H-indole-2-carbonitrile having a DSC thermogram with an endotherm having an onset at about 136° C. and/or a peak at about 149° C. 31. The crystalline Form 1 of claim 1, wherein the crystalline form has a purity and the purity of the crystalline form is no less than about 95%. 32. A method of treating an acute myeloid leukemia (AML) or an acute lymphoblastic leukemia (ALL) in a subject comprising administering to the subject a therapeutically effective amount of a crystalline Form 1 of (S)-4-methyl-5-((4-((2-(methylamino)-6-(2,2,2-trifluoroethyl) thieno [2,3-d] pyrimidin-4-yl) amino) piperidin-1-yl) methyl)-1-(2-(4-(methylsulfonyl) piperazin-1-yl) propyl)-1H-indole-2-carbonitrile having an X-ray powder diffraction (XRPD) pattern with at least three characteristic peaks selected from 4.1° 2-Theta, 5.4° 2-Theta, 6.6° 2-Theta, 8.2° 2-Theta, 9.5° 2-Theta, 12.3° 2-Theta, 13.1° 2-Theta, 13.9° 2-Theta, 15.9° 2-Theta, 16.4° 2-Theta, 17.0° 2-Theta, 17.5° 2-Theta, 19.7° 2-Theta, and 22.6° 2-Theta. 33. The method of claim 32, wherein the AML is menin-dependent AML, KMT2A-rearranged AML, or NPM 1-mutant AML. 34. The method of claim 32, wherein the ALL is KMT2A-rearranged ALL. 35. The crystalline Form 1 of claim 1, wherein the crystalline form is an anhydrate.