Structure Therapeutics (GPCR) Study Update summary

Program Overview and Study Design

• GSBR-1290 is an oral, nonpeptide small molecule GLP-1R agonist developed for obesity and related metabolic conditions, aiming for best-in-class efficacy and safety, with manufacturing scalability for up to 120 million patients.

• The Phase IIb ACCESS program includes two randomized, double-blind, placebo-controlled studies (ACCESS and ACCESS II), enrolling over 300 adults with BMI ≥30 or ≥27 with comorbidities.

• ACCESS uses a 'low and slow' titration approach over 36 weeks, with doses up to 120 mg, while ACCESS II explores higher doses (180 and 240 mg) to establish the maximum tolerated dose.

• Both studies use a four-week titration schedule to optimize tolerability and minimize GI-related adverse events.

• Topline data from both studies are expected in Q4 2025, supporting rapid progression to phase III in 2026.

Efficacy, Safety, and Dose Rationale

• GSBR-1290 demonstrated 6.2–6.9% placebo-adjusted weight loss at 12 weeks, with over 10% weight loss in 34% of participants and a clean safety profile with no liver toxicity.

• Adverse event-related discontinuations ranged from 5–11%, and pharmacokinetics support once-daily dosing with no food effect.

• Higher doses are expected to yield greater efficacy, with dose proportionality and a wide safety margin observed up to 120 mg.

• Modeling suggests a 1.5–2% additional weight loss at higher doses compared to 120 mg, and the design allows for down titration based on tolerability.

• The primary endpoint is percent change in body weight at 36 weeks; secondary endpoints include safety, tolerability, and pharmacokinetics.

Pipeline, Strategic Positioning, and Future Directions

• GSBR-1290 is positioned as a backbone for a metabolic franchise, with plans for fixed-dose combinations and expansion into indications like type 2 diabetes, heart failure, and sleep apnea.

• The oral small molecule franchise includes amylin, GIPR, GCGR, and APJR programs, with multiple catalysts anticipated through 2026.

• The amylin program is the most advanced among pipeline assets, with a development candidate announcement expected by year-end.

• Cash reserves of $915.3 million as of September 30, 2024, support ongoing and future development.

• The company is focused on late-stage development partnerships but is currently prioritizing phase II execution.