ASCLETIS-B (01672) Announces Positive Preclinical Data for Its Most Comprehensive Once-Weekly Oral Peptide Pipeline for the Treatment of Obesity

ASCLETIS-B (01672) Announces Positive Preclinical Data for Its Most Comprehensive Once-Weekly Oral Peptide Pipeline for the Treatment of Obesity ASCLETIS-B (01672) announced that its industry-leading once-weekly oral peptide pipeline has obtained positive preclinical data, demonstrating long half-life and superior bioavailability. Ascletis' 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 study in the United States. Topline human pharmacokinetic (PK) data for ASC36o are expected by the end of 2026. In non-human primates (NHP) at steady state, the half-life of ASC36o oral tablet reached 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 with eloralintide and petrelintide, with relative improvements in weight loss of 32% and 91%, respectively. Ascletis' two 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 quadruple agonist peptide (amylin receptor + GLP-1R/GIPR/GCGR). ASC36_35o FDC (tablet), a once-weekly oral triple agonist peptide (amylin receptor + GLP-1R/GIPR). In non-human primates, peptide combination extended the half-life beyond the levels observed with monotherapy. The half-life of ASC36o was extended from approximately 7 days as monotherapy to approximately 8.8 days in the ASC36_35o FDC and approximately 8.3 days in the ASC36_37o FDC. The oral bioavailability of ASC36o was also improved, from 6% to 8% as monotherapy to 10% in both FDCs. In addition, the Company's pipeline includes the once-weekly oral GLP-1/GIP/GCG triple agonist peptide ASC37o and the once-weekly oral GLP-1/GIP dual agonist peptide ASC35o. This pipeline gives Ascletis a unique competitive position, enabling substantial expansion of the population eligible for oral drug treatment. All five of Ascletis' once-weekly oral peptides/fixed-dose combinations utilize Ascletis' proprietary oral peptide delivery enhancement technology (POTENT). In dogs and non-human primates, POTENT improved oral bioavailability through dual absorption in the stomach and intestine. POTENT also significantly reduced intra- and inter-subject variability after oral administration. This technology enables Ascletis' once-weekly oral peptides to achieve oral bioavailability of up to more than 10% at steady state and a half-life of up to approximately 8.8 days in non-human primates. The combination of these high oral bioavailability levels and ultra-long half-lives provides commercial feasibility for once-weekly dosing of its oral peptides. "With the launch of the U.S. Phase I study, our once-weekly oral peptide platform has crossed another milestone," said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis. "To our knowledge, our two FDC tablets are 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- and inter-subject variability in test animals, and our unique combination formulations further improve both metrics. We look forward to obtaining topline human PK data for ASC36o (tablet) by the end of the year, and to submitting investigational new drug (IND) applications for our other four once-weekly oral peptide programs."