ASCLETIS-B (01672) announced positive topline results from a 24-week U.S. Phase II study (NCT06679959) evaluating its small molecule GLP-1 receptor agonist ASC30 in a long-acting subcutaneous depot formulation for obesity. The trial enrolled 65 participants across three cohorts, all of whom were either obese or overweight with at least one weight-related comorbidity. Two formulations (A1 and A2) were administered.
The study met its primary endpoint: patients receiving three doses of ASC30 depot formulation A1 (administered once monthly) showed a statistically significant and clinically meaningful mean weight reduction of 6.3% (placebo-adjusted) at week 12. Furthermore, after three monthly doses, formulation A1 demonstrated a placebo-adjusted mean weight loss of 7.5% at week 16.
This Phase II trial was a randomized, double-blind, placebo-controlled, multicenter study conducted in the United States over 24 weeks. It aimed to assess the safety, tolerability, and efficacy of ASC30 in 65 subjects with a BMI ≥ 30 kg/m² or overweight subjects (BMI between 27 kg/m² and 30 kg/m²) with at least one weight-related comorbidity. All participants received subcutaneous injections on day 1, day 29 (week 4), and day 57 (week 8), with no weekly lead-in period required. A maintenance period followed from week 8 to week 24.
The study evaluated two depot formulations (A1 and A2) to assess the potential for both monthly treatment and quarterly maintenance therapy. Formulation A1, previously evaluated in a 12-week Ib single-dose study, showed an observed half-life ranging from 46 to 75 days. Formulation A2 had not been previously tested in humans. In this study, formulation A1 achieved therapeutic drug exposure levels in obese patients, while formulation A2 did not.
The dosing regimen for formulation A1 involved three subcutaneous injections of 400 mg each, administered four weeks apart. Placebo-adjusted mean weight reductions were 2.7% at week 4, 5.5% at week 8, 6.3% at week 12, and 7.5% at week 16. These results indicate that ASC30 depot formulation A1 could support monthly dosing for obesity treatment, with potential for bimonthly administration, without a weekly lead-in.
The study also evaluated the potential of formulation A1 as a maintenance therapy. Efficacy was assessed over a 16-week period following the last dose at week 8. Therapeutic drug exposure was maintained throughout this period. Placebo-adjusted mean weight loss was 5.5% at week 8, 6.4% at week 20 (three months post-last dose), and 5.8% at week 24 (four months post-last dose), supporting its potential as an effective quarterly maintenance regimen.
Both ASC30 depot formulations A1 and A2 demonstrated a favorable safety and tolerability profile consistent with GLP-1 class drugs. No subjects discontinued due to adverse events. All adverse events, including those at the injection site, were mild to moderate in severity. All gastrointestinal adverse events were mild, with no moderate or severe events reported. No liver safety signals were observed, and laboratory tests, vital signs, electrocardiograms, and physical examinations revealed no abnormalities.
"We are highly encouraged by the statistically significant and clinically meaningful weight loss observed in obese patients treated with the long-acting ASC30 subcutaneous depot formulation," said Dr. Jinzi J. Wu, Founder, Chairman, and CEO of ASCLETIS. "ASC30 is the first and only incretin agent with proven efficacy in two Phase II studies that offers flexible dosing: once-daily oral or once-monthly subcutaneous administration for weight loss treatment, and once-quarterly subcutaneous dosing for maintenance. The competitive efficacy and favorable safety profile of the long-acting formulation strengthen our confidence in expanding the clinical development of ASC30 depot, including monthly treatment and quarterly maintenance therapies. Furthermore, data from this 24-week study validate our proprietary Ultra-Long-Acting Platform technology for developing monthly to quarterly therapies for long-term weight management."
ASC30, wholly developed by ASCLETIS, is the first and only small molecule GLP-1 receptor agonist in clinical development that can be administered either once-daily orally or once-monthly to once-quarterly subcutaneously, serving as both a weight loss treatment and a maintenance therapy for long-term weight management.