Ascletis' industry-leading once-weekly oral peptide pipeline covers all four validated targets, with multiple first-in-class fixed-dose combinations.

-     ASC36o, a once-weekly oral amylin receptor peptide agonist, is the most advanced drug candidate of Ascletis' once-weekly oral peptide pipeline and its Phase I study has started in the U.S.

-     ASC36o demonstrated a half-life of approximately 7 days and oral bioavailability of 6% to 8% in non-human primates (NHPs), supporting once-weekly oral administration.

-     Using ASC36o as a cornerstone, Ascletis has developed two first-in-class once-weekly oral peptide fixed-dose combinations (FDCs), ASC36_37o FDC (amylin/GLP-1/GIP/GCG) and ASC36_35o FDC (amylin/GLP-1/GIP).

-     Ascletis' once-weekly oral peptide pipeline was developed by its Peptide Oral Transport ENhancement Technology (POTENT) that increased oral bioavailability through both gastric and intestinal absorption and reduced within-subject and between-subject variability.

Ascletis Pharma Inc. announced positive preclinical data demonstrating the long half-lives and superior bioavailability of its industry-leading once-weekly oral peptide pipeline.

The industry's most comprehensive once-weekly oral peptide pipeline

The foundation of Ascletis' industry-leading once-weekly oral peptide pipeline (Table 1) for the treatment of obesity and other metabolic diseases is a first-in-class once-weekly oral amylin receptor peptide agonist ASC36o (tablet) which is currently in a Phase I study in the U.S. The topline human pharmacokinetic (PK) data of ASC36o are expected by the end of 2026. At steady state in non-human primates (NHPs), ASC36o tablets reached a half-life of up to 167 hours (approximately 7 days) and oral bioavailability of 6% to 8%. In a head-to-head diet-induced obesity (DIO) rat study comparing ASC36 to eloralintide and petrelintide, ASC36 demonstrated 32% and 91%, respectively, greater body weight reduction.

Table 1. Ascletis' once-weekly oral peptide pipeline covers all four validated targets, alone and in combination:

Notes:

FDC: fixed-dose combination; R: receptor; GLP-1R: glucagon-like peptide 1 receptor; GIPR: gastric inhibitory polypeptide receptor; GCGR: glucagon receptor; FDA: the U.S. Food and Drug Administration; IND: Investigational New Drug.

First-in-class once-weekly oral fixed-dose combination (FDC) peptides

Ascletis' two FDC oral peptides combine its amylin receptor agonist with incretin agonists in a single once-weekly pill:

• ASC36_37o FDC (tablet), a once-weekly oral quadruple peptide agonist (amylin receptor + GLP-1R/GIPR/GCGR)
• ASC36_35o FDC (tablet), a once-weekly oral triple peptide agonist (amylin receptor + GLP-1R/GIPR)

In NHPs, combining the peptides extended the half-lives beyond that observed with the single agent. The half-life of ASC36o increased from approximately 7 days as monotherapy to approximately 8.8 days in an FDC of ASC36_35o, and approximately 8.3 days in an FDC of ASC36_37o. ASC36o oral bioavailability also rose, from 6% to 8% alone to ≥10% in both FDCs (Table 2).

Furthermore, the Company's pipeline includes a once-weekly oral GLP-1/GIP/GCG triple peptide agonist, ASC37o, and a once-weekly oral GLP-1/GIP dual peptide agonist, ASC35o (Table 1). This pipeline gives Ascletis a unique competitive position to significantly expand the population that can be treated with oral agents.

Industry-leading oral bioavailability across our once-weekly oral peptide pipeline

All five of Ascletis' once-weekly oral peptides/fixed-dose combinations utilize Ascletis proprietary Peptide Oral Transport Enhancement Technology (POTENT). In both dogs and NHPs, POTENT increases oral bioavailability through absorption in both the stomach and the intestines. POTENT also significantly reduces within-subject and between-subject variability after oral dosing. This technology allowed for oral bioavailability of Ascletis' once-weekly oral peptides of up to > 10% at the steady state, with half-lives up to approximately 8.8 days in NHPs (Table 2). These high rates of oral bioavailability combined with extremely long half-lives allows for commercially viable once-weekly dosing of its oral peptides.

Table 2. Half-life and bioavailability of oral peptide pipeline at steady state in NHPs

Notes:

NHPs: non-human primates; FDC: fixed-dose combination; approx.: approximately.

"With the start of our U.S. Phase I study, our once-weekly oral peptide platform has crossed another milestone." said Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis, "Our two FDC tablets are, to our knowledge, the first once-weekly oral fixed-dose combinations of peptides. Together with ASC37o and ASC35o, they give Ascletis what we believe is the most comprehensive once-weekly oral peptide pipeline in the industry, covering all four validated targets: amylin, GLP-1, GIP and GCG receptors. Our POTENT platform increased absorption in both the stomach and the intestine and reduced variability within and between animal subjects, and our unique combinations improved both even further. We look forward to the topline human PK data of ASC36o (tablet) and the submission of Investigational New Drug applications (INDs) for our four additional once-weekly oral peptide programs by year-end."