Ascletis Announces FDA IND Submission of ASC39, an Oral Small Molecule Selective Amylin Receptor Agonist for the Treatment of Obesity

- ASC39, an oral small molecule selective amylin receptor agonist, demonstrated eloralintide-like amylin selectivity and efficacy in preclinical models.

- ASC39 demonstrated eloralintide-like selectivity for human amylin 1 receptor (hAMY1R) over human calcitonin receptor (hCTR) (40-fold), supporting the potential for best-in-class efficacy and tolerability.

- ASC39 is differentiated from other oral small molecule amylin programs in development, which are non-selective dual amylin and calcitonin receptor agonists.

- The Company anticipates initiating a Phase I trial in the fourth quarter of 2026.

HONG KONG, Oct. 25, 2026 /PRNewswire/ -- Ascletis Pharma Inc. (HKEX: 1672, "Ascletis") today announces the submission of an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) for ASC39 oral tablets, an oral small molecule selective amylin receptor agonist, for the treatment of obesity.

ASC39 has a unique chemical scaffold that was discovered in-house utilizing Ascletis' Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) technology. In a head-to-head cyclic adenosine monophosphate (cAMP) activation assay comparing ASC39 to eloralintide, EC₅₀ (half maximal effective concentration) for human amylin 1 receptor (hAMY1R) was 21.4 pM and 21.2 pM for ASC39 and eloralintide (a selective amylin peptide analog), respectively. EC₅₀ for human calcitonin receptor (hCTR) was 846.1 pM and 1,350.8 pM for ASC39 and eloralintide, respectively. These data indicate that ASC39 is highly selective for hAMY1R over hCTR with comparable selectivity to eloralintide. ASC39 and eloralintide were 40-fold and 64-fold, respectively, more selective for hAMY1R over hCTR.

In a head-to-head diet-induced obese (DIO) rat study, compared with placebo (vehicle)-treated obese rats, once-daily oral administration of 5 mg/kg ASC39 for 6 consecutive days produced significant placebo-adjusted weight loss of 6.6% (press release). ASC39 demonstrated favorable pharmacokinetic profiles in rats and non-human primates (NHPs), supporting once-daily oral dosing in humans.

"ASC39 is the only oral small molecule amylin receptor agonist in development designed to be selective for the amylin receptor over the calcitonin receptor, replicating the pharmacology of eloralintide rather than that of non-selective dual agonists. We believe amylin selectivity will be a key driver of both efficacy and tolerability in chronic weight management." said Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis, "Following the advancement of ASC30, our Phase III incretin drug candidate, the IND submission of ASC39, a non-incretin drug candidate, marks another significant milestone for Ascletis and expands our oral metabolic disease portfolio beyond the incretin class."

ASC39, a potent and amylin-selective oral small molecule amylin receptor agonist, is being developed as a monotherapy and in combination with ASC30, Ascletis' oral small molecule, currently in two pivotal global Phase III studies, for the treatment of metabolic diseases including obesity. This new oral small molecule selective amylin receptor agonist is in addition to Ascletis' current amylin peptide portfolio that includes ASC36, a once-quarterly subcutaneous and once-weekly oral amylin agonist peptide.

About Ascletis Pharma Inc.

Ascletis Pharma Inc. is a fully integrated biotechnology company focused on the development and commercialization of potentially best-in-class and first-in-class therapeutics to treat metabolic diseases. Utilizing its proprietary Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) and Ultra-Long-Acting Platform (ULAP) technologies as well as Peptide Oral Transport ENhancement Technology (POTENT), Ascletis has developed multiple drug candidates in-house, including both small molecules and peptides, such as its lead program, ASC30, a once-daily oral small molecule GLP-1R agonist for chronic weight management and diabetes; ASC30_48FDC, a once-daily oral small molecule dual agonist, a fixed-dose combination of ASC30 (GLP-1R agonist) and ASC48 (GIPR agonist), ASC30_48_39FDC, a once-daily oral small molecule triple agonist, a fixed-dose combination of ASC30 (GLP-1R agonist), ASC48 (GIPR agonist) and ASC39 (amylin receptor agonist (SARA)), ASC39, an eloralintide-like potent selective amylin receptor agonist (SARA) once-daily oral small molecule, ASC30_39FDC, a once-daily oral small molecule dual agonist, a fixed-dose combination of ASC30 (GLP-1R agonist) and ASC39 (amylin receptor agonist (SARA)), ASC36i, an amylin receptor peptide agonist, designed for once-monthly to once-quarterly subcutaneous administration, ASC36_35i FDC, a triple peptide agonist, a fixed-dose combination of ASC36 (amylin receptor agonist) and ASC35 (GLP-1R/GIPR agonist), designed for once-monthly to once-quarterly subcutaneous administration, ASC35i, a GLP-1R/GIPR dual peptide agonist, designed for once-monthly to once-quarterly subcutaneous administration, ASC37i, a GLP-1R/GIPR/GCGR triple peptide agonist, designed for once-monthly to once-quarterly subcutaneous administration, ASC36_37i FDC, a quadruple peptide agonist, a fixed-dose combination of ASC36 (amylin receptor agonist) and ASC37 (GLP-1R/GIPR/GCGR agonist), designed for once-monthly to once-quarterly subcutaneous administration, ASC36o, an amylin receptor peptide agonist, designed for once-weekly oral administration, ASC36_37o FDC, a quadruple peptide agonist, a fixed-dose combination of ASC36 (amylin receptor agonist) and ASC37 (GLP-1R/GIPR/GCGR agonist), designed for once-weekly oral administration, ASC36_35o FDC, a triple peptide agonist, a fixed-dose combination of ASC36 (amylin receptor agonist) and ASC35 (GLP-1R/GIPR agonist), designed for once-weekly oral administration, ASC37o, a GLP-1R/GIPR/GCGR triple peptide agonist, designed for once-weekly oral administration, ASC35o, a GLP-1R/GIPR dual peptide agonist, designed for once-weekly oral administration, for chronic weight management. Ascletis is listed on the Hong Kong Stock Exchange (1672.HK).

For more information, please visit www.ascletis.com. 

Contact：

Peter Vozzo
ICR Healthcare
443-231-0505 (U.S.)
[email protected]

Ascletis Pharma Inc. PR and IR Teams
+86-181-0650-9129 (China)
[email protected]
[email protected] 

SOURCE Ascletis Pharma Inc.