Ascletis Pharma has announced recent submissions of 2 Investigational New Drug (IND) applications to the US Food and Drug Administration (FDA) for ASC36, a once-monthly to once-quarterly next-generation peptide amylin receptor agonist and ASC36_35 FDC, a once-monthly injection co-formulation of ASC36 plus peptide GLP-1R/GIPR agonist ASC35, for the treatment of obesity.

Jinzi Jason Wu, PhD, Founder, Chairman and CEO, Ascletis, said, "Eloralintide in combination with tirzepatide recently demonstrated 29 percent weight loss at week 32. However, 2 separate weekly injections are required; 1 for eloralintide and 1 for tirzepatide. In contrast, ASC36_35 FDC, a potentially first-in-class subcutaneous (SQ) injection co-formulation targeting amylin receptor, GLP-1R and GIPR, requires only 1 monthly injection. Equally exciting, ASC36_35 FDC demonstrated approximately 51 percent greater relative body weight reduction compared to the co-administration of eloralintide and tirzepatide in a head-to-head Diet-Induced Obese (DIO) rat study. These animal models are highly predictive of human efficacy."

Both ASC36 and ASC35 were discovered in-house utilising Ascletis' Artificial Intelligence-Assisted Structure-Based Drug Discovery (AISBDD). Both ASC36 once-monthly to once-quarterly formulation and ASC36_35 FDC once-monthly co-formulation are Self-Assembling Lipid Depot (SALD) formulations, developed in-house utilising Ascletis' Ultra-Long-Acting Platform (ULAP) technology.

In head-to-head Non-Human Primate (NHP) studies, ASC36 SALD formulation demonstrated approximately 6-fold longer observed half-life than eloralintide, supporting once-monthly to once-quarterly SQ administration in humans. In NHP studies, ASC36_35 FDC SALD co-formulation demonstrated long observed half-lives for both ASC36 and ASC35, supporting once-monthly SQ administration in humans.

Preclinical studies have established the superior efficacy of ASC36 injection and ASC36_35 FDC injection co-formulation. In head-to-head DIO rat studies, which are highly predictive of human efficacy, ASC36 monotherapy, targeting amylin receptor, demonstrated approximately 91 percent and 32 percent greater relative body weight reduction compared to petrelintide and eloralintide monotherapies, respectively. In head-to-head DIO rat studies, the ASC36_35 co-formulation, targeting 3 targets of amylin receptor, GLP-1R and GIPR, demonstrated approximately 51 percent greater relative body weight reduction compared to the co-administration of eloralintide and tirzepatide.

Both ASC36 injection formulation and ASC36_35 FDC injection co-formulation exhibit excellent chemical and physical stability with no aggregation or precipitation caused by fibrillation at neutral pH.