Structure Therapeutics (NASDAQ:GPCR) shared new top-line results from its ACCESS II clinical program for aleniglipron, an oral small-molecule GLP-1 receptor agonist being developed for chronic weight management. Management also discussed pre-specified interim analyses from the ACCESS open-label extension (OLE) study and a separate body composition study, highlighting what the company described as consistent efficacy across studies and an improving tolerability profile with a lower starting dose and slower titration strategy.
ACCESS II: 44-week efficacy and dose comparison
Chief Medical Officer Dr. Blai Coll reviewed results from the completed Phase II ACCESS II trial, which enrolled 73 participants with obesity or overweight plus at least one comorbidity. Participants started at 5 mg and titrated in four-week steps to 120 mg, then were re-randomized at week 28 to 120 mg, 180 mg, or 240 mg (with a four-week step at 180 mg before reaching 240 mg).
- 13.6% for 120 mg
- 15.3% for 180 mg
- 15.0% for 240 mg
On a placebo-adjusted basis, the company reported a 14.7% reduction for 120 mg, 16.3% for 180 mg, and 16.0% for 240 mg, which management said represented an absolute loss of roughly 33–39 pounds.
Structure Therapeutics also highlighted categorical outcomes in ACCESS II. Dr. Coll said 93% of participants on 180 mg achieved at least 10% weight loss and 61% reached at least 15% weight loss. In an exploratory analysis, 32% of participants receiving 180 mg achieved at least 20% weight loss by week 44.
Tolerability after re-randomization and the 180 mg vs. 240 mg question
In the re-randomization period, Dr. Coll said one participant in the 120 mg group and one in the 180 mg group reported vomiting, while four participants in the 240 mg arm experienced vomiting events beginning at week 37. He said only one participant in the re-randomized cohort discontinued due to an adverse event up to the 240 mg dose.
Overall, the company reported no serious adverse events after re-randomization and a 3.7% discontinuation rate due to adverse events. Dr. Coll also noted that 70%–100% of aleniglipron participants completed the last 12 weeks at target dose with at least 80% compliance, compared with 60% in the placebo arm.
During Q&A, management addressed why 180 mg and 240 mg showed similar efficacy at week 44. Dr. Coll said the efficacy pattern looked “very similar” between the two doses, but tolerability at 180 mg appeared similar to 120 mg, while nausea and vomiting were higher at 240 mg. He characterized ACCESS II as providing “highly valuable data” to help identify a Phase III top dose.
ACCESS open-label extension: weight loss beyond 36 weeks and 2.5 mg start
The company also shared a pre-specified interim analysis from the ACCESS OLE, which enrolled 151 participants who completed 36 weeks in the original ACCESS study and continued into an open-label period. In this OLE, participants previously on active doses were up-titrated to or maintained at 120 mg, while participants previously on placebo crossed over to aleniglipron starting at 2.5 mg and titrated every four weeks.
After a median follow-up of 20 weeks in the OLE (56 weeks total exposure for some continuing participants), Structure reported ongoing weight loss without signs of plateauing. Dr. Coll said participants previously on 120 mg in the double-blind period experienced additional weight loss, reaching about 15.3% to 16.2% at week 56. Placebo crossover participants who started at 2.5 mg and titrated up were reported at about 6.4% weight loss after a median 20 weeks of exposure.
On tolerability, the company highlighted low discontinuations in the OLE and described the placebo crossover group as having low nausea occurrence without a temporal pattern and no reported vomiting events through week 56. Dr. Coll said there were three discontinuations during the open-label period (2% overall) and stated that for placebo crossover participants, there were no discontinuations after a median 20 weeks of follow-up.
Body composition study: early weight loss at lower doses and GI reporting context
Structure also discussed an interim readout from a 71-participant body composition study at 11 U.S. sites, in which 59 participants were randomized to aleniglipron starting at 2.5 mg with four-week titration steps. The company presented data after a median follow-up of 20 weeks, corresponding to the 30 mg titration step.
At that point, the company reported a 6.8% weight loss in aleniglipron-treated participants, while placebo participants fluctuated around a 2% reduction. Dr. Coll said nausea events tended to coincide with titration steps and “taper down over time,” while vomiting was described as very low. Two participants (3.4%) discontinued due to gastrointestinal symptoms at weeks nine and 11.
Dr. Coll cautioned that placebo GI event rates were high in the body composition study, including 33.3% reporting nausea, 8.3% vomiting, and 50% diarrhea. He also said increased awareness of GI events in the GLP-1 class and use of eDiaries could inflate subjective event reporting such as nausea.
Asked about lean mass versus fat mass, management said DEXA collection remains blinded and those data were not yet available.
Safety observations and development plans
Across ACCESS II, the interim OLE analysis, and the body composition study, the company reiterated what it described as an absence of drug-induced liver injury (DILI). Dr. Coll said there were no cases of liver enzyme increases above 10x, and fluctuations in ALT/AST resolved while participants continued on study drug. Management also reiterated prior comments that there were no reported QTc prolongation events and no “off-target safety signals” across dose levels in the overall program dataset described on the call.
Looking ahead, CEO Ray Stevens said the company has an end-of-Phase II meeting with the FDA scheduled in Q2 and remains on track to initiate Phase III in the second half of the year. He said Structure expects multiple additional data readouts throughout 2026, including completion of the ACCESS OLE and readouts from type 2 diabetes, obesity, switch, and body composition studies.
Stevens also discussed the company’s broader metabolic portfolio, including two oral small-molecule amylin receptor agonist programs. He said ACCG-2671 began a Phase I trial in December and Structure anticipates Phase I data in the second half of 2026, while ACCG-3535 is expected to enter the clinic by year-end.
About Structure Therapeutics (NASDAQ:GPCR)
Structure Therapeutics (NASDAQ:GPCR) is a clinical‐stage biotechnology company focused on the discovery and development of oral small‐molecule therapies that target G protein‐coupled receptors (GPCRs). Leveraging advances in structural biology, computational chemistry and medicinal chemistry, the company’s scientific platform is designed to optimize binding interactions and pharmacokinetic properties, with the goal of delivering innovative treatments for metabolic and inflammatory disorders.
The company’s pipeline comprises multiple programs in various stages of preclinical and clinical development.
