1823-P: Long-Term Safety and Efficacy of HTD1801 in Patients with Type 2 Diabetes: Two Phase 3 Open-Label Extensions

Introduction and Objective: HTD1801 is an anti-inflammatory metabolic modulator (AIMM) that activates AMPK and inhibits the NLRP3 inflammasome. In two 24-week, double-blind (DB), placebo-controlled Phase 3 studies, HTD1801, administered as monotherapy (SYMPHONY-1) or as add-on to metformin (SYMPHONY-2), significantly reduced HbA1c versus placebo in patients with type 2 diabetes (T2D). Open-label extensions (OLE) evaluated longer-term efficacy and safety. Methods: After the DB phase, patients originally randomized to HTD1801 continued active treatment; those originally randomized to placebo switched to HTD1801. 817 patients from SYMPHONY-1 (n=383) and SYMPHONY-2 (n=498) entered the OLE. Durability of metabolic control was assessed as change from baseline to Week 52. Safety was evaluated through Week 52. Results: In both studies, HbA1c reductions achieved during the DB phase were durable among patients continuing HTD1801 (-1.2% and -1.1% in SYMPHONY-1 and 2, respectively). Patients who switched from placebo to HTD1801 had mean HbA1c reductions of -1.3% and -1.2%, respectively. Improvements in LDL-C, hs-CRP, and eGFR were sustained. Long-term safety through 52 weeks was consistent with the DB period. Conclusion: HTD1801 showed sustained cardiovascular-kidney-metabolic benefits and consistent safety through 52 weeks, supporting its potential as a well-tolerated, effective therapy for patients with T2D. Disclosure Y. Luo: None. J. Ma: None. Z. Cheng: None. S. Gan: None. K. Liu: Employee; Current; HighTide Therapeutics Inc. M. Yu: Employee; Current; HighTide Therapeutics Inc. L. MacConell: Employee; Current; HighTide Therapeutics Inc. L. Liu: Employee; Current; HighTide Therapeutics Inc. L. Ji: None.