Structure Therapeutics (GPCR) Study Update summary

Study design and objectives

• Phase II-A/2a obesity studies evaluated GSBR-1290, an oral GLP-1 receptor agonist, in overweight or obese adults (BMI ≥27–40, age 18–75) over 12 weeks, with 64 participants randomized to GSBR-1290 or placebo.

• Capsule-to-tablet PK studies assessed safety, tolerability, and pharmacokinetics of new tablet formulations in 54 participants, with similar baseline demographics across cohorts.

• Primary endpoints included safety, tolerability, and percent change in body weight at 12 weeks; secondary endpoints included PK comparability and dose proportionality.

• Studies used rapid weekly titration to 120 mg, with balanced baseline characteristics across groups.

Efficacy results

• GSBR-1290 achieved statistically significant, clinically meaningful placebo-adjusted mean weight loss of 6.2% in phase II-A/2a and up to 6.9% in PK/tablet studies at 12 weeks (p<0.0001).

• 67% of participants on GSBR-1290 lost at least 6% body weight, and 33% lost at least 10% at 12 weeks; no placebo participants achieved ≥5% weight loss.

• Weight loss curves showed early separation from placebo and no plateauing at 12 weeks.

• Tablet and capsule formulations showed comparable efficacy and proportional PK exposure.

• Efficacy compares favorably to other oral GLP-1 receptor agonists in cross-trial analysis.

Safety and tolerability

• Over 200 patients treated with GSBR-1290; no serious adverse events, drug-induced liver injury, or permanent liver enzyme elevations observed.

• Most adverse events were mild or moderate, primarily gastrointestinal (nausea, vomiting, constipation), with incidence decreasing over time.

• AE-related discontinuations were low (5% in phase II-A/2a, 11% in PK study); no study discontinuations due to liver function abnormalities.

• Liver enzyme elevations were transient and not drug-related.

• Improved tolerability observed at lower starting doses and slower titration.