• ASC36_35 FDC, a once-monthly subcutaneous (SQ) injection co-formulation of ASC36 and ASC35, is a potentially first-in-class drug candidate targeting three validated targets of amylin receptor, GLP-1R and GIPR.
• ASC36_35 FDC demonstrated approximately 51% 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.
• ASC36 is a potentially first-in-class once-monthly to once-quarterly SQ injection targeting amylin receptor.
• ASC36 monotherapy demonstrated approximately 91% and 32% greater relative body weight reduction compared to petrelintide and eloralintide monotherapies, respectively, in head-to-head DIO rat studies.

Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") announces recent submissions of two Investigational New Drug (IND) applications to the U.S. 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.

"Eloralintide in combination with tirzepatide recently demonstrated 29.0% weight loss at week 32^[1]. However, two separate weekly injections are required; one for eloralintide and one 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 one monthly injection," said Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis, "Equally exciting, ASC36_35 FDC demonstrated approximately 51% 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 utilizing 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 utilizing 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% and 32% 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 three targets of amylin receptor, GLP-1R and GIPR, demonstrated approximately 51% 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.