Ascletis’ ASC47 Combo with Semaglutide Shows 56% Greater Weight Loss, Better GI Safety

Topline Data from ASC47-103 (NCT06972992)
Ascletis Pharma (HKEX: 1672) announced results from its U.S. Phase I/IIa ASC47-103 study evaluating ASC47, an adipose-targeted, ultra-long-acting thyroid hormone receptor beta (THRβ) agonist, in combination with semaglutide (0.5 mg weekly) in people with obesity (BMI ≥ 30).

• On day 29, a single 30 mg ASC47 injection plus semaglutide achieved a 56.2% greater relative body weight reduction vs semaglutide alone (N=6 vs N=7).
• 60 mg ASC47 combo showed a 15.1% additional reduction (N=9 vs N=7).
• Pooled analysis (N=15 vs N=7): 31.6% greater relative reduction.
• Semaglutide monotherapy group showed 2.5% weight loss, consistent with literature.
• LDL-C reduction significant in 30 mg and 60 mg cohorts.

Rebound Control & Long Half-Life

• ASC47 depot formulation demonstrated an observed half-life up to 30 days.
• On day 57 (4 weeks post-discontinuation):
  • 30 mg ASC47 + semaglutide: 157.1% greater relative weight reduction vs semaglutide monotherapy.
  • 60 mg ASC47 + semaglutide: 110.4% greater relative reduction.
  • Pooled analysis: 129.9% greater relative reduction.
• Supports once-monthly ASC47 as a maintenance therapy.

GI Safety Advantage

• Vomiting incidence: 6.7% with ASC47 combo vs 57.1% with semaglutide alone.
• No thyroid-related adverse events; ECG and telemetry normal.

Next Steps
The study is the first to evaluate an adipose-targeted THRβ agonist with an incretin in obesity, delivering both synergistic efficacy and better tolerability.

• Planned Phase IIb studies may test once-monthly ASC47 (30 mg/60 mg) in combination with ASC35 (GLP-1R/GIPR agonist) and oral ASC47 with oral ASC30.

Reference

• Ascletis Pharma Inc. “Ascletis Announces ASC47 in Combination with Semaglutide Demonstrated Up to 56.2% Greater Relative Reduction in Body Weight…” PR Newswire, Sept 21, 2025