767-P: A Phase 1b/2a Study of the Safety and Tolerability of GSBR-1290, a Novel Oral Small Molecule Glucagon-Like Peptide 1 Receptor Agonist (GLP-1RA), in Healthy Overweight/Obese Volunteers (HOV) and Participants with Type 2 Diabetes Mellitus (T2DM)

Introduction: GSBR-1290 is a novel, oral, non-peptide GLP-1RA and a potential alternative to injectable or oral peptides used for the treatment of T2DM and obesity. These studies were designed to evaluate the safety, tolerability, and efficacy of GSBR-1290. Methods: Phase 1b: The safety and tolerability of multiple ascending doses of GSBR-1290 (5-90mg) and its effects on body weight (BW) were investigated in 24 HOV over 4 weeks. Phase 2a: The effects of GSBR-1290 on safety, tolerability, HbA1c, glucose, and BW were investigated in 54 participants with T2DM (45 and 90mg) over 12 weeks and in an interim 8-week analysis of 40 HOV (120mg). Results: Phase 1b: There were no study discontinuations (d/c) due to adverse events (AEs). Most AEs were mild and GI-related, consistent with GLP-1RAs. BW was significantly reduced (up to 4.9% placebo-adjusted, p=0.013) over 4 weeks. Phase 2a T2DM: Two participants d/c from the study due to an AE (1 attributed to study drug: 2.8% d/c rate). Placebo-adjusted HbA1c (45 mg: -1.01%, p=0.008; 90 mg: -1.02%, p=0.001), BW (45 mg: -3.51%, p=0.0019; 90 mg: -3.26%, p=0.0013), and plasma glucose (45 mg: -2.70, p=0.01; 90 mg: -2.50, p=0.0008) were significantly reduced at day 84. Phase 2a Obesity: There were no study d/c due to AEs. Placebo-adjusted BW decreased though day 56 (120 mg: -4.74%; p0.0001). Complete 12-week results from the cohort of 24 additional participants will be available at presentation. For all phase 2a, AEs were mild-moderate and GI-related, with no SAEs related to GSBR-1290. Conclusions: GSBR-1290 demonstrated favorable safety and tolerability in this Phase 1b/2a study in participants with T2DM and in HOV. GSBR-1290 demonstrated clinical benefits in lowering BW, blood glucose, and HbA1c. These data provide clinical proof-of-concept of GSBR-1290 and support further clinical development in T2DM and obesity. Disclosure B. Coll: Employee; Structure Therapeutics, Inc. J. Zhang: Employee; Structure Therapeutics, Inc. L. Chen: Employee; Structure Therapeutics, Inc. L. Ibarra: Employee; Structure Therapeutics, Inc. H. Yue: Employee; Structure Therapeutics, Inc. A. Barth: Employee; Structure Therapeutics, Inc. M.A. Bach: Employee; Structure Therapeutics, Inc. Funding Structure Therapeutics, Inc