Ascletis Pharma-B (01672) has announced that its industry-leading once-weekly oral peptide pipeline has yielded positive preclinical data, demonstrating a long half-life and superior bioavailability.
The company's industry-leading once-weekly oral peptide pipeline for the treatment of obesity and other metabolic diseases is anchored by the first-in-class once-weekly oral amylin receptor agonist peptide ASC36o (tablet), which is currently undergoing Phase I clinical studies in the United States. Topline human pharmacokinetic (PK) data for ASC36o are expected before the end of 2026.
In non-human primates (NHP) under steady-state conditions, the oral tablet of ASC36o achieved a half-life of up to 167 hours (approximately 7 days) with oral bioavailability of 6% to 8%. In a head-to-head diet-induced obesity (DIO) rat study, ASC36 demonstrated superior weight loss efficacy compared to eloralintide and petrelintide, with relative improvements in weight reduction of 32% and 91%, respectively.
Ascletis's two fixed-dose combination (FDC) oral peptides combine an amylin receptor agonist with an incretin agonist in a once-weekly tablet (single tablet): ASC36_37o FDC (tablet), a once-weekly oral quad-target agonist peptide (amylin receptor + GLP-1R/GIPR/GCGR); and ASC36_35o FDC (tablet), a once-weekly oral triple-target agonist peptide (amylin receptor + GLP-1R/GIPR). In non-human primates, the peptide combination extended the half-life beyond that observed with monotherapy. The half-life of ASC36o was extended from approximately 7 days as monotherapy to approximately 8.8 days in ASC36_35o FDC and approximately 8.3 days in ASC36_37o FDC. The oral bioavailability of ASC36o was also improved, rising from 6% to 8% as monotherapy to at least 10% in both FDC formulations.
In addition, the company's pipeline includes the once-weekly oral GLP-1/GIP/GCG triple-target agonist peptide ASC37o and the once-weekly oral GLP-1/GIP dual-target agonist peptide ASC35o. This pipeline gives Ascletis a unique competitive position, enabling a substantial expansion of the patient population suitable for oral drug treatment.
All five of Ascletis's once-weekly oral peptides/fixed-dose combinations utilize the company's proprietary oral peptide delivery enhancement technology (POTENT). In both dogs and non-human primates, POTENT improved oral bioavailability through dual absorption in the stomach and intestine. POTENT also significantly reduced intra-subject and inter-subject variability following oral administration. This technology enables Ascletis's once-weekly oral peptides to achieve oral bioavailability of over 10% and a half-life of up to approximately 8.8 days at steady state in non-human primates. The combination of these high oral bioavailability levels and ultra-long half-lives provides commercial viability for once-weekly dosing of its oral peptides.
"With the Phase I study underway in the United States, our once-weekly oral peptide platform has crossed another milestone," said Dr. Wu Jinzi, founder, chairman of the board and chief executive officer of Ascletis. "To our knowledge, our two FDC tablets are among the first once-weekly oral peptide fixed-dose combinations. Together with ASC37o and ASC35o, Ascletis has thereby built what we believe is the industry's most comprehensive once-weekly oral peptide pipeline, fully covering the four validated targets of amylin, GLP-1, GIP and glucagon receptors. Our POTENT platform promotes dual absorption in the stomach and intestine and reduces intra-subject and inter-subject variability in test animals, while our unique combination formulations further improve both of these metrics. We look forward to obtaining topline human PK data for ASC36o (tablet) before the end of the year, as well as submitting new drug clinical trial (IND) applications for our other four once-weekly oral peptide programs."
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