Crystalline and salt forms of an NLRP3 inhibitor

HK40138748APending Publication Date: 2026-10-09BIOAGE LABS INC
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Patent Information

Application Number
HK62026127446
Authority / Receiving Office
HK · HK
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-09-12
Filing Date
2026-08-12
Publication Date
2026-10-09
Estimated Expiration
2044-09-10

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Abstract

This disclosure provides crystalline forms of an NLRP3 inhibitor, and methods of making and using these forms.
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Description

W O 2 0 2 5 / 0 5 9 1 3 9 A 1 (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (43) International Publication Date (10) International Publication Number WO 2025 / 059139 A1 20 March 2025 (20.03.2025) WIPO PCT (51) International Patent Classification: C07D 471 / 04 (2006.01) A61K 31 / 437 (2006.01) (21) International Application Number: PCT / US2024 / 046141 MA, MD, MG, MK, MN, MU, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, WS, ZA, ZM, ZW. (22) International Filing Date: (84) 11 September 2024 (11.09.2024) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 63 / 582,161 12 September 2023 (12.09.2023) US (71) Applicant: BIOAGE LABS, INC. [US / US]; 1445A S 50th Street, Richmond, California 94804 (US). (72) Inventor; and (71) Applicant: KOTHARI, Sanjeev Hukmichand [US / US]; c / o BIOAGE LABS, INC., 1445A S 50th Street, Richmond, California 94804 (US). (74) Agent: TRINQUE, Brian C.; Lathrop GPM LLP, 28 State Street, Boston, Massachusetts 02109 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AМ, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CV, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT. HN, HR, HU, ID, IL, IN, IQ, IR, IS, IT, JM, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, CV, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SC, SD, SL, ST. SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, ME, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GO, GW. KM, ML, MR, NE, SN, TD, TG). Published: - with international search report (Art. 21(3)) (54) Title: CRYSTALLINE AND SALT FORMS OF AN NLRP3 INHIBITOR Figure 1 10 ,0 00 12 ,0 00 2Theta (Coupled TwoTheta / Theta) WL=1.54060 (57) Abstract: This disclosure provides crystalline forms of an NLRP3 inhibitor, and methods of making and using these forms. 本公開提供了NLRP3抑制劑的結晶形式，以及製備和使用這些形式的方法。 摘要

Claims

CLAIMS1. A crystalline form of 2-ethoxy-3',5'-difluoro-N-((4-(hydroxymethyl)-1 H-pyrazolo[4,3- c]pyridin-7-yl)methyl)-N-methyl-[1,T-biphenyl]-4-carboxamide, or a pharmaceutically acceptable salt or hydrate thereof.

2. The crystalline form of claim 1 , wherein the crystalline form is a monohydrate.

3. The crystalline form of claim 1 , wherein the crystalline form is an anhydrate.

4. The crystalline form of any one of claims 1-3, wherein the crystalline form is a pharmaceutically acceptable salt.

5. The crystalline form of claim 4, wherein the pharmaceutically acceptable salt is selected from the group consisting of hydrochloric acid salt, phosphoric acid salt, and sodium salt.

6. The crystalline form of claim 3, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 7.2, 20.4, and 20.6.

7. The crystalline form of claim 3 or 6, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 7.2, 20.4, 20.6, and 21.6.

8. The crystalline form of any one of claims 3, 6, and 7, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 7.2, 11.1 , 11.8, 20.4, 20.6, and 21.6.

9. The crystalline form of any one of claims 3 and 6-8, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 5.5, 7.2, 11.1, 11.8, 15.3, 20.4, 20.6, 21.6, 26.7, and 30.9.

10. The crystalline form of any one of claims 3 and 6-9 having a DSC thermogram characterized by an endotherm with an onset temperature of 177.3 °C.

11. The crystalline form of claim 2, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 6.5, 12.9, and 16.1.

12. The crystalline form of claim 2 or 11, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 6.5, 11.2, 12.9, and 16.1.

13. The crystalline form of any one of claims 2, 11, and 12, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 6.5, 11.2, 12.9, 16.1, 22.7, 24.8, and 32.6.

14. The crystalline form of any one of claims 2 and 11-13 having a DSC thermogram characterized by an endotherm with an onset temperature of 139.6 °C.

15. The crystalline form of any one of claims 1-5, wherein the crystalline form is 2- ethoxy-3',5'-difluoro-N-((4-(hydroxymethyl)-1H-pyrazolo[4,3-c]pyridin-7-yl)methyl)-N-methyl- [1,1'-biphenyl]-4-carboxamide hydrochloric acid salt.

16. The crystalline form of claim 15, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 12.3, 18.1, and 18.

217. The crystalline form of claim 15 or 16, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 12.3, 12.8, 18.1, 18.2, and 28.7.

18. The crystalline form of any one of claims 15-17, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 12.3, 12.8, 18.1, 18.2, 26.0, and 28.7.

19. The crystalline form of any one of claims 15-18 having a DSC thermogram characterized by an endotherm with an onset temperature of 218.3 °C.

20. The crystalline form of any one of claims 1-5, wherein the crystalline form is 2- ethoxy-3',5'-difluoro-N-((4-(hydroxymethyl)-1H-pyrazolo[4,3-c]pyridin-7-yl)methyl)-N-methyl- [1,1'-biphenyl]-4-carboxamide phosphoric acid salt.

21. The crystalline form of claim 20, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 3.1 , 9.2, and 16.4.

22. The crystalline form of claim 20 or 21, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 3.1, 9.2, 11.7, 13.9, 15.4, 16.4, and 24.7.

23. The crystalline form of any one of claims 20-22, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 3.1, 9.2, 11.7, 13.9, 15.4, 16.4, 18.1, 19.0, 16.4, and 24.7.

24. The crystalline form of any one of claims 20-23 having a DSC thermogram characterized by an endotherm with an onset temperature of 223.9 °C.

25. The crystalline form of any one of claims 1-5, wherein the crystalline form is 2- ethoxy-3',5'-difluoro-N-((4-(hydroxymethyl)-1H-pyrazolo[4,3-c]pyridin-7-yl)methyl)-N-methyl- [1,1'-biphenyl]-4-carboxamide sodium salt.

26. The crystalline form of claim 25, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 10.3, 21.1, and 25.8.

27. The crystalline form of claim 25 or 26, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 10.3, 17.3, 20.6, 21.1, 23.3, and 25.8.

28. The crystalline form of any one of claims 25-27, wherein the crystalline form is characterized by an XRPD diffractogram having peaks expressed in degrees-2-theta at angles (± 0.2 degrees) of 10.3, 14.9, 17.2, 17.3, 18.8, 20.6, 20.0, 21.1, 23.3, and 25.8.

29. A crystalline form of a pharmaceutically acceptable salt of 2-ethoxy-3',5'-difluoro-N- ((4-(hydroxymethyl)-1H-pyrazolo[4,3-c]pyridin-7-yl)methyl)-N-methyl-[1,1'-biphenyl]-4- carboxamide, wherein the pharmaceutically acceptable salt is selected from the group consisting of hydrochloric acid salt, phosphoric acid salt, and sodium salt.

30. A pharmaceutical composition comprising the crystalline form of any of claims 1-29 and a pharmaceutically acceptable carrier.

31. A method of inhibiting NLRP3 inflammasome in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the crystalline form of any one of claims 1-29, or the pharmaceutical composition of claim 30.

32. A method of treating inflammation in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the crystalline form of any one of claims 1-29, or the pharmaceutical composition of claim 30.

33. A method of treating inflammaging in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the crystalline form of any one of claims 1-29, or the pharmaceutical composition of claim 30.

34. A method of treating cryopyrin-associated periodic syndrome (CAPS) in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the crystalline form of any one of claims 1-29, or the pharmaceutical composition of claim 30.

35. A method of treating a disease or disorder of the inner ear in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the crystalline form of any one of claims 1-29, or the pharmaceutical composition of claim 30.

36. The method of claim 35, wherein the disease or disorder of the inner ear is selected from the group consisting of hearing loss, hearing impairment, vertigo, Meniere’s disease, and tinnitus.