1786-P: BGE-102, a Novel NLRP3 Inhibitor, Demonstrated Robust Anti-Inflammatory Activity in an Ongoing Phase 1 Study in Healthy Volunteers and Participants with Obesity

Introduction and Objective: NLRP3-driven inflammation contributes to metabolic dysfunction, insulin resistance, and cardiovascular risk in obesity and type 2 diabetes. BGE-102 is a potent, structurally novel, orally bioavailable, brain-penetrant small molecule inhibitor of NLRP3 inflammasome. We evaluated safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of BGE-102 in healthy volunteers and participants with obesity. Methods: This randomized, double-blind, placebo-controlled Phase 1 study included single ascending dose (SAD) cohorts in healthy volunteers and participants with obesity (10-120 mg; N=45); multiple ascending dose (MAD) cohorts in healthy volunteers (60 & 120 mg QD, 14 d; N=18); and a MAD cohort in participants with obesity and high-sensitivity C-reactive protein (hsCRP) ≥ 3 mg/L at baseline (120 mg QD, 14 d; N=18). A MAD cohort in participants with obesity and elevated hsCRP is pending. A single-dose food effect cohort was included for patients with obesity. Primary endpoints were safety and tolerability. Secondary endpoints included PK. Exploratory endpoints included ex vivo IL-1β inhibition and hsCRP. Results: BGE-102 was well tolerated with all adverse events mild to moderate and self-resolving; no dose-limiting toxicities occurred. PK showed dose-proportional exposure supporting once-daily dosing. Food had no clinically relevant effect on oral bioavailability. At Day 14, trough plasma concentrations exceeded IL-1β IC90 by ~2× at 60 mg and ~5× at 120 mg. Ex vivo IL-1β suppression at trough was 90% at 60 mg and 98% at 120 mg. In the MAD cohort with obese participants, hsCRP was reduced 86% at Day 14 vs 43% with placebo; 93% of treated participants achieved normal hsCRP (<2 mg/L). Conclusion: BGE-102 was well tolerated and showed sustained IL-1β suppression in treated participants and significant hsCRP reduction in participants with obesity. These results support advancing BGE-102 into proof-of-concept studies for metabolic and inflammatory conditions. Disclosure L. Chen: Employee; Current; BioAge Labs. A. Deshpande: Employee; Current; BioAge Labs. T. Salazar: Employee; Current; BioAge Labs. C. Patil: Employee; Current; BioAge Labs. A. Neale: Employee; Current; BioAge Labs. E. Morgen: Employee; Current; BioAge Labs. Board Member; Current; BioAge Labs. Stock/Shareholder; Current; BioAge Labs. P. Martin: Employee; Current; BioAge Labs. K. Wilhelmsen: Employee; Current; BioAge Labs. K. Fortney: Board Member; Current; BioAge Labs. Employee; Current; BioAge Labs. Stock/Shareholder; Current; BioAge Labs. P. Rubin: Employee; Current; BioAge Labs.