AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
A Phase 1 Study of BGE-102, a Novel Oral NLRP3 Inhibitor, in Healthy Volunteers and Participants with Obesity and Elevated High-Sensitivity C-Reactive Protein
By Chen L, Deshpande A, Salazar T et al.
Introduction/Background: High-sensitivity C-reactive protein (hsCRP) is among the strongest predictors of major adverse cardiovascular events (MACE) and a clinically actionable cardiovascular (CV) risk factor. NLRP3 inflammasome activation drives the IL-1β → IL-6 → CRP cascade, IL-18 release, and pyroptosis in atherosclerotic CV disease. CANTOS validated the IL-1β arm: among participants reaching on-treatment hsCRP <2 mg/L with the IL-1β antibody canakinumab, MACE was reduced 25% independent of LDL-C. Targeting NLRP3 upstream could therefore address residual inflammatory risk with an oral therapy. BGE-102 is a structurally novel, potent, orally available, brain-penetrant NLRP3 inhibitor with a distinct binding site. We report the full Phase 1 dataset for BGE-102 in healthy volunteers and participants with obesity and elevated hsCRP. Methods: BGE-102 was evaluated in a randomized, double-blind, placebo-controlled Phase 1 study comprising 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 and 120 mg QD х 14 days; N=18); and MAD cohorts in participants with obesity (BMI 32-42) and baseline hsCRP >3 mg/L (60 mg QD х 21 days and 120 mg QD х 14 days; N=41: 60 mg N=19, 120 mg N=14, placebo N=8). We assessed pharmacokinetics (PK), safety/tolerability, ex vivo IL-1β suppression, and inflammatory biomarkers (hsCRP, IL-6, fibrinogen). Results: BGE-102 was well tolerated across all doses: all treatment-emergent adverse events were mild or moderate and self-limited, with no serious adverse events, no discontinuations, and no clinically meaningful laboratory, vital sign, or ECG changes. PK was dose-proportional with no clinically relevant food effect. Plasma trough concentrations at both doses exceeded the ex vivo IL-1β IC90, producing 90% (60 mg) and 98% (120 mg) IL-1β suppression at Day 14 trough and supporting once-daily dosing. In participants with obesity and elevated baseline hsCRP, BGE-102 reduced hsCRP by a median of 86% at Day 21 (60 mg) and Day 14 (120 mg) versus –34% and –43% with placebo, respectively. Normalization of hsCRP (<2 mg/L) was achieved by 87% (13/15) of 60 mg participants at Day 21 and 93% (13/14) of 120 mg participants at Day 14, with 60% (9/15) and 71% (10/14) reaching ≤1 mg/L, respectively. Parallel declines were observed in plasma IL-6 (55-78%) and fibrinogen (19-30%). Conclusions: BGE-102 lowered hsCRP at both 60 mg and 120 mg, with concordant decreases in IL-6 and fibrinogen, a favorable safety profile, and once-daily dosing. Normalization of hsCRP in the majority of treated participants supports BGE-102 as a potential best-in-class oral NLRP3 inhibitor for reductions in inflammatory biomarkers of cardiovascular risk and motivates the ongoing QUELL-CV Phase 2 dose-ranging proof-of-concept trial in elevated-risk participants.