Structure Therapeutics’ oral GLP-1 hit all endpoints in a pair of mid-stage studies evaluating weight loss and safety, sending its stock $GPCR up nearly 55% on Monday morning.
The drug, dubbed GSBR-1290, showed a placebo-adjusted decrease in mean weight of 6.2% after 12 weeks in the Phase 2a study, with 67% of patients seeing at least 6% weight loss and 33% achieving at least 10% weight loss, compared to none for those on placebo.
In a second study investigating a new capsule-to-tablet formulation, patients taking the once-daily drug had a mean weight loss of up to 6.9%, earning a p<0.0001. Only topline data were available in the capsule study, with the company saying it “demonstrated comparable exposure to the prior capsule formulation.”
As is typical for the GLP-1 class, the most common adverse events were gastrointestinal and occurred during the titration part of the study. About 5% of participants in the Phase 2a study discontinued treatment, citing adverse events, as did 11% in the capsule-to-tablet pharmacokinetic trial.
Structure now plans to move its GLP-1 into a 36-week Phase 2b study in the fourth quarter using its tablet formulation. It’s aiming to enroll 300 patients.
“Based on the data that we’ve seen, we have confidence that by extending the exposure will continue expanding and increasing the body weight reduction,” Structure VP of clinical development Blai Coll said during an investor call.
Structure’s CEO Raymond Stevens also reiterated plans to find a partner for the drug.
“We recognize that the obesity and metabolic disease market is very large, and it will require a strategic partner to help us in the late-stage development and commercialization,” Stevens said during the call.
The company is continuing to build out its oral obesity pipeline. It expects to choose an oral amylin small molecule by the end of the year, putting it in the clinic in 2025, and an oral small molecule GIP candidate in the second half of 2025, with plans to enter the clinic in the first half of 2026. Structure also plans to pick a glucagon oral small molecule candidate in the first half of 2026.
Structure is competing with several companies trying to develop well-tolerated and effective oral GLP-1s like Eli Lilly’s orforglipron, which is in Phase 3 trials, and AstraZeneca’s early-stage candidate, ECC5004.
Leerink analysts said Monday that discontinuation rates in Structure’s study were “better” than the ones in Lilly’s orforglipron trials. In Structure’s 36-week Phase 2 obesity trial, up to 21% of patients discontinued treatment. The analysts also noted that Structure’s efficacy was “roughly comparable” to Lilly’s drug.
In the investor call’s presentation, Structure compared the efficacy of its oral treatment to other drugs at 12 weeks, saying orforglipron had 6.5% weight loss, Pfizer’s danuglipron had 6.6% and Novo’s oral semaglutide had 3.7% weight loss.