ASCLETIS-B (01672) announced that its small molecule glucagon-like peptide-1 receptor (GLP-1R) agonist ASC30's ultra-long-acting subcutaneous depot formulation for weight maintenance demonstrated a 75-day apparent half-life (observed half-life) in obese subjects (body mass index (BMI) ≥ 30 kg/m²) in a US Phase Ib clinical study (NCT06679959). This data supports ASC30 as a maintenance therapy for long-term weight management with quarterly dosing. The ASC30 weight maintenance formulation was developed using ASCLETIS's Ultra-Long-Acting Platform (ULAP).

Following a single subcutaneous injection of ASC30 weight maintenance formulation (100 mg) in 8 obese subjects, the time to reach peak plasma concentration (Cmax) of ASC30 was 17 days (median) post-dosing. Approximately 75 days after administration, ASC30 plasma concentration decreased to fifty percent (50%) of the Cmax value, indicating an apparent half-life of 75 days.

"Weight maintenance therapy represents a significant unmet medical need in long-term weight management," stated Dr. Jinzi Wu, Founder, Chairman and CEO of ASCLETIS. "For example, after patients achieve their weight loss goals using weekly incretin medications for a period of time, they tend to prefer switching to a quarterly dosing regimen to maintain their weight. Based on superior pharmacokinetic parameters including ultra-long half-life and good safety profile, we believe ASC30's quarterly dosing regimen has the potential to help patients maintain weight without rebound. ASC30's ultra-long-acting subcutaneous depot formulation for weight maintenance is the fastest progressing quarterly-dosed incretin drug in clinical development and represents a potential breakthrough in the quarterly maintenance treatment field for long-term weight management patients, potentially improving patient compliance and quality of life."

Good tolerability is crucial for weight maintenance therapy. During the 12-week period following a single subcutaneous injection of ASC30 weight maintenance formulation (100 mg), the incidence rates of vomiting, nausea, diarrhea, and constipation in ASC30-treated patients (N=8) were 0.0%, 0.0%, 12.5%, and 12.5%, respectively, while in placebo group patients (N=16), the rates were 0.0%, 12.5%, 6.3%, and 0.0%, respectively.

The good gastrointestinal (GI) tolerability of ASC30 weight maintenance formulation is attributed to its slow rate of reaching Cmax and maintaining approximately a 2.5:1 peak-to-trough plasma concentration ratio (Cmax to Ctrough ratio) during the 12-week post-dosing period. ASC30's trough plasma concentration (Ctrough) occurred 84 days post-dosing.

In the Phase Ib study, no serious adverse events (SAE) were reported, and no Grade 3 or higher adverse events (AE) were observed. Among obese subjects treated with 100 mg ASC30, GI-related AEs were infrequent and only Grade 1. No elevation in liver enzymes (including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBL)) occurred. Laboratory tests, vital signs, ECGs (electrocardiograms, including heart rate-corrected QT interval (QTc)), and physical examinations showed no abnormalities.

ASC30's ultra-long-acting subcutaneous depot formulation exhibits dose-proportional pharmacokinetic characteristics, supporting both weight loss treatment and maintenance therapy. The ASC30 ultra-long-acting subcutaneous depot formulation for weight loss treatment, also developed using ASCLETIS's ULAP, is currently undergoing a Phase IIa study (NCT06679959) in the US as a once-monthly weight loss therapy for obese populations (BMI ≥ 30 kg/m²) or overweight populations with at least one weight-related comorbidity (27 kg/m² ≤ BMI < 30 kg/m²). Topline data from the Phase IIa study of ASC30 weight loss treatment formulation is expected in the first quarter of 2026.

The ASC30 weight loss treatment formulation demonstrated a 46-day apparent half-life in obese subjects, supporting once-monthly dosing for obesity treatment. Based on the characteristics of small molecules, peptides, and proteins/antibodies, ASCLETIS can design various release constants (k) for subcutaneous depot drugs through its proprietary ULAP technology, achieving precise sustained release of subcutaneously injected drugs within predetermined dosing intervals, thereby reducing peak-to-trough plasma concentration ratios and improving clinical efficacy.

ASC30, independently developed by ASCLETIS, is the first and only small molecule GLP-1R biased agonist that can be administered both once-daily orally and once-monthly to once-quarterly subcutaneously, serving as both weight loss treatment and weight maintenance therapy for long-term weight management.