Ascletis Files Dual FDA INDs for Ultra‑Long‑Acting Obesity Therapies Targeting Amylin, GLP‑1, and GIP

Hong Kong-based Ascletis Pharma has submitted two Investigational New Drug (IND) applications to the U.S. Food and Drug Administration for experimental obesity therapies built on its ultra-long-acting peptide platform. The filings cover ASC36, a next-generation amylin receptor agonist formulated for once-monthly to once-quarterly subcutaneous administration, and ASC36_35, a once-monthly fixed-dose combination (FDC) that combines ASC36 with the company’s dual GLP-1/GIP receptor agonist ASC35.

If approved for clinical development, ASC36_35 could become the first co-formulated monthly injectable therapy to simultaneously target three validated metabolic pathways: the amylin receptor, glucagon-like peptide-1 receptor (GLP-1R), and glucose-dependent insulinotropic polypeptide receptor (GIPR). The dual IND submissions follow the recent FDA clearance of ASC35 to enter a Phase I clinical trial as a once-monthly obesity treatment.

Long-acting peptide platform targets multiple metabolic pathways

Amylin receptor agonists have emerged as a promising complement to incretin-based therapies by enhancing satiety, slowing gastric emptying, and supporting sustained weight reduction. Combining amylin signaling with GLP-1 and GIP receptor activation has attracted growing interest as developers seek greater efficacy while reducing treatment burden.

Both ASC36 and ASC35 were discovered using Ascletis’ artificial intelligence-assisted structure-based drug discovery platform. The candidates also incorporate the company’s Self-Assembling Lipid Depot (SALD) formulation technology within its Ultra-Long-Acting Platform (ULAP), which enables slow drug release following subcutaneous injection.

In non-human primate studies, the ASC36 SALD formulation demonstrated an observed half-life approximately six times longer than eloralintide, supporting monthly to quarterly dosing. The ASC36_35 co-formulation also maintained prolonged half-lives for both peptide components, supporting once-monthly administration.

Preclinical studies show enhanced weight-loss potential

Ascletis reported favorable efficacy across multiple head-to-head diet-induced obese (DIO) rat studies.

ASC36 monotherapy produced approximately 91% greater relative body weight reduction than petrelintide and approximately 32% greater reduction than eloralintide. Meanwhile, the ASC36_35 fixed-dose combination demonstrated approximately 51% greater relative body weight reduction than co-administered weekly eloralintide and tirzepatide.

The company also reported that both formulations remained chemically and physically stable at neutral pH without aggregation or fibrillation, characteristics that may support long-term injectable administration.

Simplifying obesity treatment through less frequent dosing

Founder, Chairman and Chief Executive Officer Dr. Jinzi Jason Wu said the company believes a single monthly injection could provide a practical alternative to combination regimens that currently require separate weekly injections. He also highlighted the superior weight-loss results observed in preclinical comparisons with eloralintide plus tirzepatide, noting that diet-induced obese rat models have historically shown strong predictive value for clinical obesity research.

Path Forward

The IND submissions represent another step in Ascletis’ expanding obesity pipeline following the recent FDA clearance of ASC35. Pending regulatory review, the company plans to initiate clinical evaluation of ASC36 and ASC36_35 to assess their safety, pharmacokinetics and weight-loss potential in humans. Together, the programs strengthen Ascletis’ strategy to develop long-acting obesity therapies that combine multiple validated metabolic targets with less frequent dosing schedules.

Reference

Ascletis Submits Two IND Applications to the U.S. FDA for the Treatment of Obesity: ASC36 Once-Monthly Injection, a Peptide Amylin Receptor Agonist, and ASC36_35 FDC Once-Monthly Injection, a Co-Formulation of ASC36 Plus Peptide GLP-1R/GIPR Agonist ASC35