Structure Therapeutics (GPCR) Study Update summary

Study design and objectives

• Phase 2b ACCESS and supplementary studies evaluated efficacy, safety, and tolerability of Eleniglipron/Aleniglipron in adults with obesity or overweight plus comorbidities, using doses up to 240 mg over 36–44 weeks, with alternative titration schemes and exploratory studies at higher doses.

• Participants were randomized to active drug (45, 90, 120 mg) or placebo, with a 5 mg starting dose and four-week titration steps; key endpoints included percent body weight reduction and secondary metabolic outcomes.

• Over 500 participants were treated across all studies, including open-label extension and body composition studies using a lower 2.5 mg starting dose to improve tolerability.

• Studies addressed weight loss durability, higher dosing, and improved tolerability with lower starting dose.

• Phase 3 program is planned to start mid-2026, with an FDA meeting in early 2026 to finalize design.

Efficacy and weight loss outcomes

• At 36 weeks, placebo-adjusted mean weight loss was 8.2% (45 mg), 9.8% (90 mg), and 11.3% (120 mg), with up to 15.3% at 240 mg in exploratory studies; all doses achieved statistical significance on primary and key secondary endpoints.

• No evidence of weight loss plateau through 44 weeks; weight loss continued in open-label extension.

• Over 70% of participants on 120 mg lost at least 10% of body weight, and nearly 40% lost at least 15%.

• Clinically meaningful improvements in systolic blood pressure (-6.4 to -7.5 mmHg) and HbA1c (-0.28% to -0.37%) were observed, even in participants without diabetes.

Safety and tolerability

• GI-related adverse events (nausea, vomiting) were most common, peaking early and mostly mild to moderate, with overall AE-related discontinuation rates of 7.7% to 13.3% (mean 10.4%) in Phase 2b.

• No AE-related discontinuations occurred at higher doses (180/240 mg) after titration in ACCESS II and in studies using a 2.5 mg starting dose.

• No cases of drug-induced liver injury, persistent liver enzyme elevations, or QTc prolongation were observed in over 500 patients.