Claims for Patent: 12,070,449

Summary for Patent: 12,070,449

Title:	Methods of treating TTR amyloidosis using AG10
Abstract:	Described herein are methods for treating transthyretin (TTR) amyloidosis in a subject. The methods include specific dosing regimens that have great efficacy in treating the subjects and that are well tolerated in subjects
Inventor(s):	Uma Sinha, Satish Rao
Assignee:	Eidos Therapeutics Inc
Application Number:	US17/332,359
Patent Claims:	1. A method of treating transthyretin amyloidosis (ATTR) cardiomyopathy in a subject in need thereof, the method comprising orally administering to a subject in need thereof a total daily dosage of about 1,600 milligrams (mg) of Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form, wherein Compound 1 has the Formula: wherein Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form is administered twice daily. 2. The method of claim 1, wherein administration of Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form improves and/or reduces the decline in a six-minute walk test compared to subjects who did not receive treatment with Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form. 3. The method of claim 1, wherein the subject maintains about the same six minute walking distance as prior to treatment with Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form. 4. The method of claim 1, wherein the ATTR cardiomyopathy is wild-type ATTR cardiomyopathy (ATTRwt-CM). 5. The method of claim 1, wherein the ATTR cardiomyopathy is variant ATTR cardiomyopathy (ATTRv-CM). 6. The method of claim 5, wherein the ATTRv-CM is characterized by a transthyretin (TTR) protein that comprises a valine to isoleucine mutation at position 122 (V122I). 7. The method of claim 5, wherein the ATTRv-CM is characterized by a transthyretin (TTR) protein that comprises a threonine to proline mutation at position 49 (T49P) ), a valine to methionine mutation at position 30 (V30M), a threonine to alanine mutation at position 60 (T60A), a proline to serine mutation at position 24 (P24S), an aspartic acid to alanine mutation at position 38 (D38A), or a leucine to histidine mutation at position 58 (L58H). 8. A method of slowing the progression of transthyretin amyloidosis (ATTR) cardiomyopathy in a subject in need thereof, the method comprising orally administering to a subject in need thereof a total daily dosage of about 1,600 milligrams (mg) of Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form, wherein Compound 1 has the Formula: wherein Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form is administered twice daily. 9. The method of claim 1, wherein the administration of Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form decreases the frequency of cardiovascular-related hospitalizations as compared to subjects who did not receive treatment with Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form. 10. The method of claim 1, wherein the administration of Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form decreases mortality as compared to subjects who did not receive treatment with Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form. 11. The method of claim 10, wherein mortality is reduced by about 6% as compared to subjects who did not receive treatment with Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form after 30 months of administration. 12. The method of claim 10, wherein mortality is reduced by about 10% as compared to subjects who did not receive treatment with Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form after 30 months of administration. 13. The method of claim 10, wherein mortality is reduced by about 24% as compared to subjects who did not receive treatment with Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form after 30 months of administration. 14. The method of claim 10, wherein Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form is in HCl salt form. 15. The method of claim 1, wherein the administration of Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form increases transthyretin (TTR) blood serum concentration relative to a baseline level. 16. The method of claim 1, wherein the administration of Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form increases transthyretin (TTR) blood serum concentration by at least 10% relative to a baseline level after 28 days of treatment. 17. The method of claim 1, wherein the administration of Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form decreases serum blood levels of N-terminal pro-brain natriuretic peptide (N-terminal pro-BNP). 18. The method of claim 17, wherein serum blood levels of N-terminal pro-BNP of the subject decreases at least 10% after 30 months of administration as compared to a baseline level of N-terminal pro-BNP in the subject prior to treatment with Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form. 19. The method of claim 1, wherein the administration of Compound 1 in HCl salt form or an equivalent amount of Compound 1 in freebase or in a different salt form improves, stabilizes or delays worsening in the Kansas City Cardiomyopathy Questionnaire (KCCQ) classification of subjects. 20. The method of claim 19, wherein subjects have an average improvement of at least one level in the Kansas City Cardiomyopathy Questionnaire (KCCQ) classification of subjects.