Ascletis Pharma Inc. (HKEX: 1672) has unveiled ASC35, a next-generation GLP-1/GIP dual peptide agonist designed for once-monthly subcutaneous dosing in obesity treatment.
The company expects to file an IND with the U.S. FDA in Q2 2026.
Engineered for Potency and Duration
Discovered through Ascletis’ AI-Assisted Structure-Based Drug Discovery (AISBDD) and Ultra-Long-Acting Platform (ULAP), ASC35 combines extended half-life with high potency.
- In vitro, ASC35 was ~4× more potent than tirzepatide for both GLP-1R and GIPR activation.
- In non-human primate (NHP) studies, ASC35’s half-life was ~14 days — 6× longer than tirzepatide.
- ASC35 showed 70–80% higher drug exposure (AUC) than tirzepatide via both I.V. and S.Q. routes.
These results support once-monthly dosing in humans with sub-1 mL injection volumes—a strong patient convenience advantage.
Translating Preclinical Data to Human Potential
The NHP-to-human pharmacokinetic scaling suggests ASC35 may achieve a 30-day half-life or longer in humans. Its flatter PK profile could also mean fewer gastrointestinal side effects, a common issue with current incretin therapies.
Superior Weight Loss in Preclinical Models
In head-to-head DIO mouse studies, ASC35 outperformed tirzepatide significantly:
|
Group |
Dosing |
Total Body Weight Change |
Relative weight loss vs Tirzepatide |
|
Vehicle |
SQ, QD |
+0.4% |
- |
|
ASC35 |
-3 nmol/kg, SQ, QD |
-33.6% (p<0.0001 vs vehicle) |
+71% (p<0.0001) |
|
Tirzepatide |
3 nmol/kg, SQ, QD |
-19.6% (p<0.0001 vs vehicle) |
- |
“The preclinical characterization of ASC35 suggests best-in-class efficacy with once-monthly dosing and a more flexible titration schedule.”
- Dr. Jinzi Jason Wu, Founder, Chairman and CEO of Ascletis.
Expanding the Metabolic Pipeline
Ascletis plans to develop ASC35 both as a monotherapy and in combinations for obesity, diabetes, and metabolic dysfunction-associated steatohepatitis (MASH).
Planned combinations include:
- ASC35 + ASC36: GLP-1R/GIPR dual agonist + amylin receptor agonist
- ASC35 + ASC47: GLP-1R/GIPR dual agonist + THRβ agonist for adipose targeting
Both ASC36 and ASC47 are once-monthly injectable peptides developed on the ULAP platform.
The Bigger Picture
With superior half-life, bioavailability, and potency, ASC35 positions Ascletis at the forefront of next-generation incretin therapeutics, aiming to challenge weekly GLP-1s like tirzepatide with a monthly, longer-acting alternative.
