Structure Therapeutics (GPCR) Study result summary

Study Design and Objectives

• ACCESS II was a randomized, double-blind, placebo-controlled study evaluating aleniglipron at 120 mg, 180 mg, and 240 mg for 44 weeks in adults with obesity or overweight and comorbidities, with primary endpoint of percent change in body weight versus placebo.

• Secondary endpoints included proportions achieving ≥5%, ≥10%, and ≥15% weight loss and safety/tolerability.

• The ACCESS OLE and Body Composition studies assessed long-term efficacy, tolerability, and safety, including effects of a 2.5 mg starting dose titration strategy.

• Over 625 participants were treated for up to 56 weeks across all studies.

• An End-of-Phase 2 FDA meeting is scheduled for Q2 2026, with Phase 3 initiation anticipated in the second half of 2026.

Efficacy Results

• Placebo-adjusted mean weight loss at 44 weeks reached 16.3% (39 lbs) at 180 mg and 16.0% (37 lbs) at 240 mg, with no evidence of plateauing; 93% of participants on 180 mg achieved ≥10% weight loss, 61% achieved ≥15%, and up to 32% achieved ≥20%.

• All dose cohorts in ACCESS II met statistical significance versus placebo at 44 weeks (p < 0.0001).

• In the OLE, weight loss continued beyond 36 weeks, reaching up to 16.2% (40.5 lbs) at 56 weeks with 120 mg.

• Clinically significant weight loss was observed at low doses (2.5 mg start), with up to 6.8% reduction at 20 weeks in the Body Composition study.

• No evidence of weight loss plateau was observed up to 56 weeks across studies.

Safety and Tolerability

• AE-related discontinuation rates were low: 3.7% in ACCESS II after re-randomization, 2% in the open label extension, and 3.4% in the body composition study.

• Lower 2.5 mg starting dose and slow titration reduced GI events and AE-related discontinuations to 2.0–3.4%, with most GI events mild and transient.

• No cases of drug-induced liver injury, persistent liver enzyme elevations, or QTc prolongation were reported in over 625 participants.