Structure reports early oral amylin data and 72-week aleniglipron weight-loss results

Structure Therapeutics reported clinical results September 8 across two investigational oral small-molecule programs for chronic weight management: the single-ascending-dose portion of ACCG-2671's Phase 1/2a study and the 72-week open-label extension of the Phase 2b ACCESS trial of aleniglipron. The disclosures are clinical development updates, not FDA approval, NDA acceptance, or Phase 3 topline results. Structure describes the amylin findings as the first reported clinical data for an oral small-molecule amylin receptor agonist; that is a company claim.

ACCG-2671: small single-dose cohorts and exploratory weight findings

ACCG-2671 is an investigational oral, non-peptide dual amylin and calcitonin receptor agonist (DACRA). Its single-dose study evaluated safety, tolerability, pharmacokinetics and exploratory pharmacodynamics in 31 healthy adults without obesity, using 1, 2, 5 or 10 mg doses or placebo. Structure reported rapid absorption, with peak concentration at 1–1.5 hours, dose-proportional exposure and an approximately six-day terminal half-life, supporting further evaluation of daily and weekly dosing. A single 10 mg dose in six participants was associated with mean body-weight reduction of 3.3% at Day 24. That small, exploratory observation does not establish registrational efficacy. The CTX-1 bone-resorption biomarker decreased approximately 60% on Day 2 across active-dose cohorts.

Gastrointestinal events increased at higher single doses

The company reported no serious adverse events, no drug-related treatment-emergent adverse events (TEAE) leading to discontinuation and no drug-induced liver injury in the ACCG-2671 single-dose portion. No nausea or vomiting occurred in the placebo, 1 mg or 2 mg cohorts. At 5 mg, nausea occurred in four of five participants and vomiting in three of five; gastrointestinal events were reported in all six participants at 10 mg. Dosing has begun in the randomized, placebo-controlled multiple-ascending-dose portion, which tests 84 days of treatment across five cohorts of participants living with obesity. It evaluates titration and daily and weekly regimens, including a cohort receiving stable injectable GLP-1 receptor agonist therapy. The company expects topline data in the first half of 2027.

Aleniglipron extension reports weight loss through 72 weeks

Aleniglipron is an investigational once-daily oral, non-peptide selective GLP-1 receptor agonist. Its prespecified 36-week ACCESS extension evaluated longer-term safety, tolerability and durability of weight loss through 72 weeks. Of eligible participants completing the initial 36-week double-blind period, 87% entered the extension. According to Structure, participants originally randomized to 45 mg, 90 mg and 120 mg who continued into the extension and dosed up to 180 mg achieved weight loss of 11.6%, 14.4% and 16.2%, respectively, at Week 72. These are results in extension participants grouped by their original treatment arms, not results from fixed 180 mg treatment for the full period. The company reported no evidence of a weight-loss plateau in the two highest original-dose groups, while noting that titration to 180 mg after Week 60 left relatively limited exposure to that dose by Week 72.

Extension tolerability and the remaining milestones

Participants crossing from placebo started aleniglipron at 2.5 mg and achieved 9.0% weight loss, or 22.7 pounds, after 36 weeks on treatment. Structure reported extension discontinuations due to treatment-emergent adverse events (TEAE) in fewer than 5% of participants and improved gastrointestinal tolerability with the 2.5 mg starting dose versus the 5 mg start in double-blind ACCESS. The company reported no drug-induced liver injury or off-target safety signals; observed liver-enzyme elevations resolved without discontinuation. Phase 3 ACCOMPLISH enrollment is ongoing after initiation in August 2026. ACCOMPLISH-1 plans up to 3,600 adults with obesity or overweight and at least one weight-related comorbidity; ACCOMPLISH-2 plans up to 1,100 adults with obesity or overweight and type 2 diabetes. Topline results are expected in the second half of 2028. Additional company-expected fourth-quarter 2026 readouts include Phase 2 body-composition and type 2 diabetes studies and the Phase 1 SWITCH study. Those future studies have no results in this disclosure.