Structure Therapeutics Reports Positive Data From Oral Amylin And GLP-1 Programs

(RTTNews) - Structure Therapeutics Inc. (GPCR) reported positive clinical data from its two lead oral small-molecule programs, ACCG-2671, an investigational dual amylin and calcitonin receptor agonist, and aleniglipron, an oral GLP-1 receptor agonist, for chronic weight management.

In the Phase 1/2a single-ascending-dose (SAD) study, ACCG-2671 demonstrated a terminal half-life of approximately six days, supporting the potential for once-weekly dosing.

The trial enrolled 31 healthy adults without obesity who received single doses of 1, 2, 5 or 10 mg of ACCG-2671 or placebo.

ACCG-2671 was generally well tolerated, with no serious adverse events, no drug-related treatment-emergent adverse events leading to treatment discontinuation and no cases of drug-induced liver injury.

Exploratory findings showed evidence of target engagement, with participants receiving a single 10 mg dose experiencing a 3.3% mean reduction in body weight at Day 24.

The candidate also produced an approximately 60% reduction in CTX-1, a biomarker of bone resorption, across active dose cohorts at Day 2.

Dose-related gastrointestinal events emerged at higher doses, with nausea and vomiting reported in the 5 mg and 10 mg cohorts.

These findings informed the starting doses and gradual titration strategies for the multiple-ascending-dose (MAD) study.

Structure has begun dosing participants in the 12-week MAD portion of the Phase 1/2a trial.

The randomized, placebo-controlled study will evaluate multiple doses and titration regimens, including daily and weekly dosing, in participants living with obesity.

The MAD study will also include a cohort receiving a stable dose of an injectable GLP-1 receptor agonist to assess ACCG-2671 in combination with GLP-1 therapy.

Topline data from the MAD portion are expected in the first half of 2027.

Separately, Structure reported 72-week results from the ACCESS open-label extension (OLE) study of aleniglipron.

Participants originally assigned to the 45 mg, 90 mg and 120 mg dose groups who continued into the OLE and were titrated up to 180 mg achieved weight reductions of 11.6%, 14.4% and 16.2%, respectively, at Week 72.

The company said there was no evidence of a weight-loss plateau at the two highest dose levels.

More than one-third of participants in the highest 90 mg and 120 mg dose cohorts achieved more than 20% body weight reduction, with mean absolute weight losses of 35.9 pounds and 40.5 pounds, respectively.

Participants who originally received placebo and crossed over to aleniglipron in the OLE started at a lower 2.5 mg dose and achieved a 9.0%, or 22.7-pound, weight reduction after 36 weeks of treatment.

The lower 2.5 mg starting dose and gradual four-week titration were associated with improved gastrointestinal tolerability compared with the 5 mg starting dose used in the double-blind portion of ACCESS.

Fewer than 5% of participants discontinued aleniglipron due to treatment-emergent adverse events during the OLE.

No cases of drug-induced liver injury were reported, while observed liver-enzyme elevations resolved without treatment discontinuation.

Aleniglipron is currently being evaluated in the Phase 3 ACCOMPLISH program, consisting of two randomized, double-blind, placebo-controlled trials.

ACCOMPLISH-1 is enrolling up to 3,600 adults with obesity or overweight and at least one weight-related comorbidity, while ACCOMPLISH-2 is enrolling up to 1,100 adults with obesity or overweight and type 2 diabetes.

Participants in both trials will receive placebo or 45 mg, 90 mg or 180 mg maintenance doses of aleniglipron following a 2.5 mg starting dose and four-week dose escalations.

Topline data from the Phase 3 ACCOMPLISH program are expected in the second half of 2028.

Structure also expects additional aleniglipron data in the fourth quarter of 2026 from a Phase 2 body-composition study, a Phase 2 trial in type 2 diabetes and the Phase 1 SWITCH study evaluating transition from injectable GLP-1 therapy to once-daily oral aleniglipron.

ACCG-2671 is an investigational oral small-molecule dual amylin and calcitonin receptor agonist being developed as a potential first-in-class oral amylin therapy for obesity and related metabolic diseases.

Aleniglipron, also known as GSBR-1290, is an investigational once-daily oral small-molecule GLP-1 receptor agonist being developed for chronic weight management and type 2 diabetes.

Structure Therapeutics is developing a pipeline of oral small-molecule therapies for chronic metabolic conditions, leveraging its structure-based drug discovery platform and focusing on treatments designed to offer scalable manufacturing and greater convenience compared with injectable therapies.

GPCR closed Friday's trade at $47.3. In the premarket trading, the stock is trading up 1.39% at $48.00.