Structure Therapeutics (GPCR) Study result summary

Key study results and efficacy

• Aleniglipron achieved up to 16.3% placebo-adjusted mean weight loss at 44 weeks for 180 mg and 16.0% at 240 mg, with no plateauing observed up to 56 weeks in the open label extension.

• Clinically significant weight loss was achieved across all high-dose groups, with 93% of participants on 180 mg achieving at least 10% weight loss, 61% reaching 15% or greater, and up to 32% achieving 20% or greater.

• Starting at 2.5 mg and titrating slowly led to 6.4%-6.8% weight loss after 20 weeks, supporting the 'start low, go slow' approach.

• Efficacy at 180 mg and 240 mg was comparable, informing dose selection for phase III.

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

Safety and tolerability profile

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

• GI events (nausea, vomiting) were reduced with the lower starting dose and slower titration, with no vomiting events and no discontinuations in the 2.5 mg start group after 20 weeks.

• No drug-induced liver injury, no off-target safety signals, and no QTc prolongation were observed across all studies and dose levels in over 625 participants.

• Tolerability improvements were consistent with the 'start low, go slow' strategy, and learnings will inform phase III protocols.

• Aleniglipron showed a tolerability profile consistent with the GLP-1 receptor agonist class, supporting chronic use.

Study design and next steps

• ACCESS II and open label extension studies included adults with obesity or overweight and at least one comorbidity, with robust efficacy and safety data across over 625 participants.

• Phase III will use a 2.5 mg starting dose with four-week titration steps, evaluating multiple doses up to 240 mg and optimizing tolerability and early weight loss.

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

• Additional data from type 2 diabetes, switch, and body composition studies will further inform phase III design.

• Manufacturing and scalability have been prioritized, enabling potential global reach for oral small molecule therapies.