2845-LB: Safety, Pharmacokinetics, and Weight Loss Effects of the Oral GLP-1/GIP Dual Agonist BGM0504 in Healthy and Overweight or Obese Adults: A Phase 1 Multiple-Ascending Dose Study

Introduction and Objective: To evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the oral formulation of BGM0504 in Chinese population. Methods: This Phase 1, double-blind, randomized, placebo-controlled, multiple-ascending-dose study evaluated once-daily oral BGM0504. Participants were randomized in a 4:1 ratio (BGM0504:placebo) across five cohorts (n=15 per cohort) and treated for 28 days. Cohort 1 enrolled healthy participants receiving 10 mg daily (10 mg × 28 days). Cohorts 2-5 enrolled non-diabetic overweight or obese adults with dose-escalation regimens: Cohort 2, 20 mg (10 mg × 7 days, 20 mg × 21 days); Cohort 3, 40 mg (10 mg × 7 days, 20 mg × 7 days, 40 mg × 14 days); Cohort 4, 60 mg (20 mg × 7 days, 40 mg × 7 days, 60 mg × 14 days); Cohort 5, 80 mg (20 mg × 7 days, 40 mg × 7 days, 60 mg × 7 days, 80 mg × 7 days). The primary endpoint was safety and tolerability. Results: A total of 75 subjects were randomized. All participants completed the study. Consistent with the incretin class, the most frequently reported treatment-emergent adverse events (TEAEs) among BGM0504-treated subjects were gastrointestinal events, including nausea (approximately 5-50%) and vomiting (approximately 10-30%). Most TEAEs were mild and resolved spontaneously; no serious adverse events were reported. Decreased appetite was observed in approximately 40-75% of BGM0504-treated subjects. Plasma BGM0504 exhibited a half-life of approximately 100 hours, with a median Tmax of approximately 1 hour after oral administration. A dose-dependent increase in systemic exposure was observed. A dose-response signal was also observed for body weight reduction, ranging from approximately −1% to −5.5% at Day 28. Conclusion: Daily oral BGM0504 was generally well tolerated across all dose levels. The safety, tolerability, PK, and PD findings from this study support further clinical evaluation of oral BGM0504 as a potential treatment for obesity. Disclosure J. Yuan: Employee; Current; BrightGene BioMedical. D. Xie: Employee; Current; BrightGene BioMedical. Y. Huang: Employee; Current; BrightGene BioMedical. H. Ding: Employee; Current; BrightGene BioMedical. S. Chen: Employee; Current; BrightGene BioMedical. X. Jiang: Consultant; Current; BrightGene BioMedical.