849-P: Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of an Optimized Dual GLP-1/GIP Receptor Agonist (BGM0504) in Healthy Subjects—A Phase Ia, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study

Background: BGM0504 is an optimized dual GIP and GLP-1 receptor agonist with greater in vitro potency, and similar GLP-1R/GIPR activity ratio as Tirzepatide. Here we report the results of a phase Ia study of BGM0504 in healthy subjects (CTR20230120).

Methods: In a clinical study of 40 healthy subjects, four initially received a single 2.5 mg subcutaneous injection of BGM0504. The remaining 36 were divided into three groups, each receiving two weekly injections at escalating doses: 2.5/5 mg, 5/10 mg, and 10/15 mg, respectively. In each group, 10 subjects were randomly assigned to BGM0504, and 2 received a placebo. The primary endpoints were safety and tolerability. The secondary endpoints included PK and PD.

Results: In the study with 40 healthy subjects, gastrointestinal adverse events like decreased appetite, nausea, abdominal distension, vomiting, and diarrhea were most common, all mild to moderate. The concentration of BGM0504 peaked between 24 to 72 hours post-dosing, with a mean half-life of approximately 4 days, supporting a weekly dosing schedule. BGM0504 showed dose-proportional PK within the tested range, with slightly higher exposures (Cmax and AUC) than Tirzepatide at equivalent doses. Subjects experienced a dose-dependent weight loss ranging from 3.24% to 8.30% by study end, with no significant changes in other PD markers like glycemia, C-peptide, and insulin.

Conclusions: BGM0504 was well tolerated with favorable PK profile and led to evident body weight loss. These data support further clinical developments of BGM0504 for T2DM and obesity. The phase II clinical trials for both T2DM and obesity are ongoing, and available results will be presented.