Ascletis Pharma Inc. (HKEX: 1672) announced positive topline data from the ASC47-103 trial, showing its muscle-preserving weight loss drug candidate ASC47 in combination with semaglutide delivered superior results compared to semaglutide alone.
The trial demonstrated better gastrointestinal (GI) tolerability, significant body weight reduction, and evidence supporting the use of once-monthly ASC47 as a potential maintenance therapy.
Key Clinical Highlights
- GI Tolerability: Vomiting occurred in only 6.7% of patients receiving ASC47 + semaglutide, compared to 57.1% on semaglutide monotherapy.
- Weight Loss:
- 30 mg ASC47 + semaglutide: 56.2% greater relative reduction in body weight vs. semaglutide alone.
- 60 mg ASC47 + semaglutide: 15.1% greater relative reduction.
- Pooled analysis: 31.6% greater relative reduction across cohorts vs. semaglutide alone. - Maintenance Effect: At day 57 (four weeks post-treatment), weight rebound was significantly lower in the ASC47 groups compared to semaglutide alone.
- LDL-C Reduction: 30 mg and 60 mg ASC47 showed meaningful decreases in LDL-C compared to semaglutide alone.
About the ASC47-103 Trial
- Design: Randomized, double-blind, placebo-controlled.
- Location: United States.
- Participants: 28 adults with obesity (BMI ≥ 30 kg/m²).
- Treatment Duration: Four weeks, with six weeks of follow-up.
- Cohorts:
- 10 mg ASC47 + semaglutide
- 30 mg ASC47 + semaglutide
- 60 mg ASC47 + semaglutide
- Placebo + semaglutide
The 10 mg dose showed no added weight loss benefits, with data indicating insufficient target engagement at thyroid hormone receptor beta (THRβ).
Safety Profile
- Well tolerated across all dose groups.
- No serious adverse events (SAEs) reported.
- No thyroid-related adverse events observed.
- Telemetry, ECG, and thyroid function tests were within normal ranges.
- Adverse events: Primarily mild (Grade 1–2).
Scientific Context
- Half-life: ASC47 demonstrated an observed half-life of ~30 days, enabling once-monthly dosing.
- Pharmacokinetics: Profiles of ASC47 and semaglutide remained consistent when combined, suggesting no need for dose adjustment.
- Preclinical validation: Data align with earlier diet-induced obese mouse models, where ASC47 combined with semaglutide showed synergistic effects.
Leadership Perspective
Dr. Jinzi Jason Wu, Founder, Chairman, and CEO, Ascletis:
“This is the first study to evaluate an adipose-targeted THRβ agonist with an incretin drug in obesity. The synergy delivered up to a 56.2% improvement in efficacy and a substantial boost in GI tolerability. These proof-of-concept results will inform our Phase IIb designs for obesity and metabolic dysfunction-associated steatohepatitis (MASH).”
Next Steps
Pending discussions with the U.S. FDA and other regulators, Ascletis plans Phase IIb combination studies that may include:
- Once-monthly ASC47 (30 mg and 60 mg) + ASC35 (a GLP-1R/GIPR peptide agonist).
- Once-daily oral ASC47 + ASC30 (an oral GLP-1R agonist).
About Ascletis Pharma
Ascletis is a Hong Kong-listed biotechnology company (1672.HK) focused on metabolic diseases. Using its AI-Assisted Structure-Based Drug Discovery (AISBDD) platform and Ultra-Long-Acting Platform (ULAP), the company develops both small-molecule and biologic drug candidates, including ASC30, an oral GLP-1R agonist for chronic weight management.
Key Takeaway: The ASC47 + semaglutide combo achieved stronger weight reduction, improved tolerability, and reduced rebound, positioning it as a promising next-generation obesity therapy.
