Structure Therapeutics Reports Positive Topline Data from its Phase 2a Obesity Study and Capsule to Tablet PK Study for its Oral Non-Peptide Small Molecule GLP-1 Receptor Agonist GSBR-1290

GSBR-1290 Overview - GSBR-1290 is an orally-available small molecule agonist of the GLP-1 receptor, targeting type 2 diabetes mellitus (T2DM) and obesity [1] - Designed as a biased GPCR agonist, selectively activating the G-protein signaling pathway [1] - Phase 2a study completed in participants with obesity or overweight and T2DM with BMI ≥27 [1] - Phase 2b study in obesity expected to start in Q4 2024, with Phase 2 development plan in T2DM to be determined in H2 2024 [1] - Next-generation combination GLP-1R candidates are also in development, including GIP, amylin, glucagon, and apelin oral small molecules [1] Clinical Trial Results - GSBR-1290 achieved a placebo-adjusted mean weight loss of 6.2% (p<0.0001) in the Phase 2a obesity study and up to 6.9% (p<0.0001) in the capsule to tablet PK study at 12 weeks [3][7] - 67% of GSBR-1290-treated participants achieved ≥6% weight loss, and 33% achieved ≥10% weight loss at Week 12, compared to 0% for placebo [7] - The tablet formulation demonstrated comparable exposure to the capsule formulation, supporting dose proportional exposure and once-daily dosing [7] - GSBR-1290 showed generally favorable safety and tolerability, with low AE-related study discontinuations (5% in Phase 2a and 11% in PK study) [7] Future Development Plans - Phase 2b obesity study expected to begin in Q4 2024, using the tablet formulation and including approximately 300 participants [8] - IND submission to the FDA planned for Q3 2024 to support trials in chronic weight management [8] - The company anticipates using the tablet formulation for future studies, starting with the Phase 2b obesity study [10] Market and Industry Context - By 2030, the global prevalence of obesity is expected to reach 1 billion, highlighting the need for oral treatments that are scalable, stable, and cost-effective [6] - GSBR-1290 has the potential to become a best-in-class oral small molecule GLP-1RA and an ideal backbone for future combination therapeutics for obesity and related diseases [6] Company Background - Structure Therapeutics is a clinical-stage biopharmaceutical company focused on developing innovative oral small molecule treatments for metabolic and cardiopulmonary conditions [11] - The company utilizes a structure-based drug discovery platform to develop GPCR-targeted therapies, aiming to overcome the limitations of traditional biologic and peptide therapies [11]