Structure Therapeutics Inc. (NASDAQ: GPCR) has commenced dosing in its Phase 2b ACCESS clinical study, evaluating GSBR-1290, an oral small molecule glucagon-like peptide-1 (GLP-1) receptor agonist, for the treatment of obesity. The trial, a randomized, double-blind, placebo-controlled study, will assess the efficacy and safety of multiple doses of GSBR-1290, up to 120 mg, over a 36-week period in approximately 220 adult participants living with obesity, or overweight with a weight-related comorbidity.
ACCESS and ACCESS II Trial Designs
The Phase 2b ACCESS study is complemented by a second study, the Phase 2 ACCESS II trial, which will evaluate higher doses of GSBR-1290 (180 mg and 240 mg) over 36 weeks in approximately 82 adult participants with similar inclusion criteria. Both trials employ a "low and slow" titration approach, starting at 5mg of GSBR-1290 (or placebo) with a 4-week titration schedule, designed to optimize tolerability and maximize weight loss. Topline data from both ACCESS and ACCESS II studies are anticipated in the fourth quarter of 2025.
The primary endpoint for the ACCESS study is the percent change in body weight from baseline to week 36. Secondary endpoints include assessments of safety, tolerability, and pharmacokinetics of GSBR-1290.
Rationale for Oral GLP-1 Agonist
Raymond Stevens, Ph.D., Founder and CEO of Structure Therapeutics, stated, "We have designed the ACCESS and ACCESS II studies to generate a robust dataset to determine the target doses to move into Phase 3 clinical development with the goal of bringing GSBR-1290 to patients as rapidly as possible. In addition to its very competitive efficacy and tolerability profile, as an oral, nonpeptide small molecule GLP-1R agonist, we believe GSBR-1290 offers attractive manufacturing scalability advantages over peptide-based GLP-1R therapies."
Potential Impact on Obesity Treatment
The development of an oral GLP-1 receptor agonist like GSBR-1290 could provide a significant advantage over injectable therapies, potentially improving patient compliance and accessibility. The obesity market is substantial, with significant unmet needs for effective and convenient treatments. GSBR-1290's potential manufacturing scalability could also lead to lower production costs compared to peptide-based therapies.
Blai Coll, M.D., Ph.D., Chief Medical Officer of Structure Therapeutics, added, "Our 36-week ACCESS study is designed to assess multiple therapeutic doses of GSBR-1290 with a start low and go slow 4-week titration approach to optimize tolerability and increase the likelihood of maximizing weight loss. Based on the data from our earlier studies, clean safety profile and proportional exposure of GSBR-1290, we are also initiating the ACCESS II study to evaluate higher doses of GSBR-1290."
Structure Therapeutics is also developing next-generation oral small molecules, including amylin receptor agonists and other combination GLP-1 receptor agonist candidates.
