MET-097

Hong Kong-based Ascletis Pharma Inc. announced topline results from a US Phase II study of ASC30, a small molecule GLP-1 receptor agonist formulated as a subcutaneous depot injection for obesity. The company reported that the long-acting obesity drug achieved a placebo-adjusted mean weight loss of 7.5% at week 16 after three monthly doses and maintained that effect for four months after the final injection, data that could position the asset as a differentiated entry in a crowded GLP-1 agonist weight loss field. Trial specifics The Ascletis ASC30 Phase II results derive from a randomized, double-blind, placebo-controlled, multi-center 24-week study (NCT06679959) conducted in the US. The trial enrolled 65 participants with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity across three cohorts evaluating two subcutaneous depot GLP-1 formulations, designated A1 and A2. Participants received three monthly 400 mg subcutaneous doses at day 1, week 4, and week 8, with no lead-in weekly injections. A 16-week maintenance period followed the final dose. The study met its primary endpoint: formulation A1 produced a placebo-adjusted mean weight loss of 6.3% at week 12 (p < 0.05 versus placebo). Weight loss continued to 7.5% at week 16 (p < 0.05). During the maintenance period, placebo-adjusted weight loss was 6.4% at week 20 and 5.8% at week 24, four months after the last dose. Formulation A2 did not achieve therapeutic drug exposures in obese patients. The ASC30 clinical trial reported no discontinuations due to adverse events in any arm. All gastrointestinal adverse events were grade 1, and no hepatic safety signals, ECG abnormalities, or laboratory findings of concern were observed. Jinzi Jason Wu, founder and CEO of Ascletis, said the data “reinforce our confidence in expanding clinical development program for ASC30 SQ depot formulation for both once-monthly treatment therapy and once-quarterly maintenance therapy”. Research context ASC30 is a GLP-1 receptor biased agonist, meaning it is designed to preferentially activate certain intracellular signaling pathways downstream of GLP-1R activation. GLP-1R agonism suppresses appetite, delays gastric emptying, and enhances insulin secretion. The biased agonism profile may in principle allow separation of efficacy from class-related gastrointestinal side effects, though this has not been confirmed in comparative studies. Notably, ASC30 is a small molecule rather than a peptide, which enables both oral and injectable formulations from the same compound, a property the company has exploited through its proprietary Ultra-Long-Acting Platform technology to produce depot injections with reported half-lives of 46 to 75 days. The GLP-1R agonist landscape for obesity is densely populated, however, no direct competitor replicates ASC30’s specific profile as a small molecule subcutaneous depot GLP-1 agonist with monthly dosing and no weekly titration. Other molecules with monthly or potentially longer dosing under development include: Amgen’s maridebart cafraglutide (MariTide), a GLP-1R agonist/GIPR antagonist antibody-peptide conjugate dosed monthly, currently Phase II stage (NCT04478708). And Pfizer is developing PF-08653944 (MET-097i), a fully biased GLP-1 receptor agonist licensed from Metsera and currently in the Phase IIb VESPER-3 trial for obesity. The program is exploring a transition from weekly induction dosing to once-monthly maintenance injections, positioning it among a small number of candidates aiming to extend GLP-1 dosing intervals. For Ascletis’s molecule, 7.5% placebo-adjusted weight loss at 16 weeks for ASC30 is modest compared with results from semaglutide and tirzepatide pivotal trials at similar or later timepoints, though cross-trial comparisons are limited by differences in dose titration, duration, and population. The absence of any gastrointestinal adverse events above grade 1 and zero discontinuations are notable in a class where tolerability often constrains dose escalation, but the small sample of 65 participants limits the strength of safety conclusions. Whether ASC30’s maintenance-dosing profile translates into a clinical or commercial advantage will depend on data from larger and longer studies.