Ascletis Pharma announced that its ultra-long-acting subcutaneous (SQ) depot maintenance formulation of small molecule GLP-1 receptor (GLP-1R) agonist, ASC30, demonstrated an observed half-life of 75 days in participants with obesity (BMI ≥ 30 kg/m²) in a U.S. Phase Ib clinical study (NCT06679959). This finding supports once-quarterly administration as a potential maintenance therapy for chronic weight management. The ASC30 maintenance formulation was developed using Ascletis’ proprietary Ultra-Long-Acting Platform (ULAP).

In the study, a single 100 mg SQ injection of ASC30 in eight participants with obesity achieved a median time to maximum concentration (Cmax) of 17 days post-dose. The time for concentrations to decline to 50% of Cmax was approximately 75 days, confirming the ultra-long-acting profile.

During the 12-week period following administration, ASC30 demonstrated favorable gastrointestinal tolerability, attributed to its gradual rise to Cmax and a peak-to-trough ratio of approximately 2.5:1. Incidences of nausea, vomiting, diarrhea, and constipation were low and comparable to placebo. No serious adverse events were reported, and no Grade 3 or higher adverse events were observed. Laboratory results, vital signs, ECGs (including QTc intervals), and physical examinations showed no abnormalities.

ASC30’s ultra-long-acting SQ depot formulations have shown dose-proportional pharmacokinetics supporting both treatment and maintenance regimens. In addition to the maintenance formulation, the once-monthly treatment formulation of ASC30 is currently being evaluated in a U.S. Phase IIa study in participants with obesity or overweight with weight-related comorbidities. Topline data from this study are expected in the first quarter of 2026. The treatment formulation previously demonstrated an observed half-life of 46 days, supporting once-monthly administration.

Through its ULAP technology, Ascletis can design customized release rates of small molecules, peptides, and proteins/antibodies in SQ depots, optimizing drug release profiles to improve efficacy, tolerability, and patient convenience.

Discovered and developed in-house by Ascletis, ASC30 is the first and only investigational small molecule GLP-1R biased agonist designed for both oral once-daily dosing and long-acting SQ dosing (once-monthly to once-quarterly) for the treatment and maintenance of chronic weight management.