ASCLETIS-B Submits Two IND Applications to US FDA for Obesity Treatments: Monthly Peptide Amylin Receptor Agonist ASC36 and ASC36_35 Combination Monthly Injection

ASCLETIS-B (01672) has announced it recently submitted two Investigational New Drug (IND) applications to the U.S. Food and Drug Administration (FDA).

The applications are for a next-generation, once-monthly to once-quarterly peptide amylin receptor agonist, ASC36, and for ASC36_35 FDC, a once-monthly injectable fixed-dose combination of ASC36 with the peptide GLP-1R/GIPR agonist ASC35, both intended for the treatment of obesity.

"Recent data for eloralintide combined with tirzepatide showed a 29.0% weight reduction at week 32. However, that regimen requires two weekly injections, one of eloralintide and another of tirzepatide," said Dr. Jinzi J. Wu, Founder, Chairman, and CEO of Ascletis.

"In contrast, the potential first-in-class, subcutaneous fixed-dose combination ASC36_35 FDC, which targets the amylin receptor, GLP-1R, and GIPR, requires only a once-monthly injection."

"Equally exciting, in a head-to-head diet-induced obesity (DIO) rat study, the ASC36_35 FDC demonstrated approximately a 51% relative improvement in weight loss compared to eloralintide combined with tirzepatide. These animal models are highly predictive of human efficacy."

Both ASC36 and ASC35 were independently developed by Ascletis using its structure-based AI-assisted drug discovery (AISBDD) technology.

The once-monthly to once-quarterly ASC36 formulation and the once-monthly ASC36_35 FDC combination formulation are both Self-Assembled Lipid Depot (SALD) formulations developed using the company's proprietary Ultra-Long-Acting Platform (ULAP) technology.

In a head-to-head non-human primate study, the ASC36 SALD formulation showed an observed half-life approximately 6 times that of eloralintide, supporting once-monthly to once-quarterly subcutaneous dosing in humans.

In non-human primate studies, both ASC36 and ASC35 within the ASC36_35 FDC SALD formulation exhibited long observed half-lives, supporting once-monthly subcutaneous dosing in humans.

Preclinical studies established the superior efficacy of the ASC36 injection and the ASC36_35 FDC combination injection.

In a head-to-head DIO rat study (highly predictive of human efficacy), ASC36 monotherapy targeting the amylin receptor showed approximately a 91% and 32% relative improvement in weight loss compared to petrelintide monotherapy and eloralintide monotherapy, respectively.

In a head-to-head DIO rat study, the ASC36_35 combination, targeting three receptors (amylin, GLP-1R, and GIPR), demonstrated approximately a 51% relative improvement in weight loss compared to eloralintide combined with tirzepatide.

The ASC36 injection and ASC36_35 FDC combination injection possess favorable physicochemical stability, with no aggregation or precipitation due to fibrillation near neutral pH.

Building on the recent milestone achieved with the ASC35 SALD monthly formulation, the company has now submitted these two INDs for the ASC36 monthly injection and the ASC36_35 combination monthly injection.

The announcement also noted that Ascletis has received IND clearance from the U.S. FDA for a Phase I clinical trial of its once-monthly subcutaneous ASC35 for obesity, highlighting the company's strong clinical development execution and the potential of its ULAP technology.