Structure’s obesity portfolio impresses on GLP-1 and amylin fronts in dual data drop

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Structure Therapeutics’ oral GLP-1 candidate aleniglipron showed 72-week efficacy “in line” with Novo Nordisk’s oral Wegovy, BMO Capital Markets wrote in a note to investors. Meanwhile, Structure’s amylin and calcitonin receptor agonist ACCG-2671 showed “impressive” target engagement in a Phase 1 trial of healthy volunteers, according to Leerink Partners.

Structure Therapeutics is working to stake its claim in the obesity space Tuesday, reporting positive data from its two lead assets, an oral GLP-1 and a dual amylin and calcitonin receptor agonist.

“Summer vacation may be coming to an end, but Structure’s dual-data update turns up the heat in oral obesity race,” BMO Capital Markets analysts quipped in a note to investors.

Structure’s aleniglipron, an oral weight loss asset, showed 72-week efficacy “in line” with Novo Nordisk’s Wegovy pill, “besting” Eli Lilly’s recently launched Foundayo, BMO wrote on Tuesday. Trial participants receiving the 180-mg dose of Structure’s pill saw up to up to 16.2% weight loss “with no evidence of a plateau in weight loss,” according to the biotech’s press release.

A 36-mg dose of Foundayo elicited 12.4% weight loss at 72 weeks in the Phase 3 ATTAIN-1 trial, BMO noted, while the Wegovy pill at 25 mg showed 16.6% weight reduction at 64 weeks in the Phase 3 OASIS-4 trial.

Additionally, less than 5% of participants across all dose groups discontinued treatment with aleniglipron due to adverse events, Structure said, with no off-target safety signals observed.

Leerink Partners added in a Tuesday morning note that the results “support potential best-in-class efficacy.”

Structure kicked off the Phase 3 ACCOMPLISH program in August, with topline data expected in the second half of 2028, according to Leerink.

Meanwhile, Structure’s ACCG-2671, an oral small molecule that acts as a dual amylin and calcitonin receptor agonist (DACRA) “demonstrated a long half-life of approximately 6 days supporting potential once-weekly dosing” in a Phase 1/2a single ascending dose study of healthy participants without obesity, according to the announcement. A single 10-mg dose of the therapy generated 3.3% mean reduction in body weight, “as well as an encouraging decrease in CTX-1,” which the company explained is a biomarker of bone resorption relevant to bone health.

“ACCG-2671 represents the first reported clinical data for an oral small molecule amylin receptor agonist, and we believe its initial observed clinical profile is quite unique,” Structure CEO Raymond Stevens said in a statement.

Other lower dose treatment arms—1 and 5 mg—saw weight reduction of 0.9% and 1.2% respectively, while participants who received a 2-mg dose of ACCG-2671 gained 0.1% body weight, BMO noted.

Leerink Partners in a Tuesday morning note called the candidate’s target engagement in the trial “impressive,” while noting that high rates of dose-related gastrointestinal adverse events were reported, “with nausea and vomiting occurring in 60-100% participants treated with higher [5 mg and 10 mg] doses.” The study did not include any titration, the analyst said.

Heather McKenzie is senior editor at BioSpace and curator of the ClinicaSpace newsletter. She is an award-winning journalist specializing in rare disease and neuroscience, in addition to her extensive coverage of the FDA and regulatory science. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.
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