Structure Therapeutics (GPCR) Study result summary

ACCG-2671 (oral amylin/calcitonin receptor agonist) study update

• ACCG-2671 is a first-in-class oral small molecule dual amylin and calcitonin receptor agonist (DACRA) with a six-day half-life, showing no serious adverse events or liver signals in phase I/IIa trials, supporting once-weekly dosing.

• Single ascending dose studies in healthy adults (BMI 26–27) demonstrated dose-proportional pharmacokinetics, rapid absorption, and dose flexibility; mild to moderate, dose-dependent GI events were observed.

• Early target engagement included a 3.3% mean body weight reduction at 10 mg by day 24 and a rapid, consistent 60% reduction in CTX-1 (bone resorption marker), with a 10.7% increase in bone-specific alkaline phosphatase.

• The ongoing phase IIa multiple ascending dose study in participants with obesity explores daily and weekly regimens, titration strategies, safety, tolerability, and bone biomarkers, including as add-on to GLP-1 therapy; topline data expected in 2027.

• No clinically significant changes in calcium, PTH, or vitamin D were observed; further bone health monitoring and imaging are planned for longer-term studies.

Aleniglipron (oral GLP-1 receptor agonist) study results

• ACCESS open-label extension (OLE) study completed with 151 participants continuing up to 72 weeks and transitioning to 180 mg, achieving a 16.2% mean body weight reduction at 72 weeks in the highest dose cohort, with no plateau observed.

• High responder rates: 76.7% achieved ≥10% weight loss, 59.6% ≥15%, and 36.3% ≥20% at week 72; mean absolute losses reached 35.9 and 40.5 pounds in the highest dose groups.

• Significant improvements in cardiometabolic risk factors, including reductions in blood pressure, waist circumference, and up to 64% reduction in hsCRP.

• Optimized tolerability with a start-low, go-slow titration (2.5 mg start), resulting in fewer than 5% discontinuation rates and lower GI adverse events; no drug-induced liver injury or Hy's law cases over 72 weeks.

• Phase III ACCOMPLISH-1 and -2 trials are underway, targeting over 4,700 participants, with 52 weeks at maintenance dose (180 mg) and topline data expected in 2H 2028.

Combination and pipeline strategy

• Combination studies of oral amylin and GLP-1 agonists are planned, leveraging different PK profiles for synergistic efficacy and improved tolerability; the first combination study is set to start at the end of 2026.

• Next-generation amylin (ACCG-3535) will enter the clinic later this year; ongoing SARA amylin discovery program and additional combination programs with GIP and glucagon receptor agonists are in progress.

• $1.3 billion in cash as of June 2026 is expected to fund operations and clinical milestones, including multiple phase III and combination trials, through 2028.

• Upcoming catalysts include aleniglipron data readouts (body composition, Type 2 diabetes, SWITCH trial) and 12-week MAD data for ACCG-2671 in 2027.

• Emphasis on retention strategies, flexible titration, and participant experience to maximize trial completion and data quality.