The oral small-molecule amylin receptor agonist ASC39 demonstrated amylin selectivity and efficacy similar to eloralintide in preclinical models
- In a head-to-head cyclic adenosine monophosphate (cAMP) activation assay with eloralintide, the oral small-molecule amylin receptor agonist ASC39 exhibited selectivity and activity similar to eloralintide. The EC values for ASC39 and eloralintide on the human amylin type 1 receptor (hAMY1R)50were 21.4 pM and 21.2 pM, respectively. The EC values for ASC39 and eloralintide on the human calcitonin receptor (hCTR)50These values were 846.1 pM and 1,350.8 pM, respectively. The data indicate that, compared to hCTR, both ASC39 and eloralintide demonstrate a higher selectivity for hAMY1R, with comparable levels of preference.
- In a head-to-head diet-induced obesity (DIO) rat study comparing ASC39 with eloralintide, the oral administration efficacy of ASC39 was on par with eloralintide, showing significant placebo-adjusted weight loss of 6.6% for ASC39 and 5.6% for eloralintide.
- An investigational new drug application (IND) for ASC39 oral tablets is expected to be submitted to the U.S. Food and Drug Administration (FDA) in the third quarter of 2026.
Hong Kong, March 17, 2026 -- Ascletis Pharma Inc. (HKEX code: 1672, referred to as 'Ascletis') announced the selection of ASC39, a potent orally active small-molecule amylin receptor agonist with high selectivity for amylin, as the clinical development candidate. Ascletis anticipates submitting an investigational new drug application (IND) to the U.S. Food and Drug Administration (FDA) for ASC39 oral tablets to treat obesity in the third quarter of 2026.
ASC39 features a unique chemical scaffold independently discovered using Ascletis' artificial intelligence-assisted structure-based drug discovery (AISBDD) technology. In a head-to-head cyclic adenosine monophosphate (cAMP) activation assay comparing ASC39 with eloralintide, the EC50 (half-maximal effective concentration) values of ASC39 and eloralintide (an amylin peptide analog) for the human amylin type 1 receptor (hAMY1R) were 21.4 pM and 21.2 pM, respectively. The EC50 values of ASC39 and eloralintide for the human calcitonin receptor (hCTR) were 846.1 pM and 1,350.8 pM, respectively. These data indicate that ASC39 demonstrates high selectivity for hAMY1R over hCTR, with its selectivity for hAMY1R comparable to that of eloralintide. The selectivity of ASC39 and eloralintide for hAMY1R over hCTR was 40-fold and 64-fold, respectively.
In a head-to-head diet-induced obesity (DIO) rat study, daily oral administration of ASC39 showed statistically significant weight loss comparable to eloralintide when compared with obese rats receiving a placebo (see Table 1). Once-daily oral dosing of ASC39 at 5 mg/kg for six consecutive days resulted in a significant placebo-adjusted weight loss of 6.6%. Eloralintide administered subcutaneously every three days at 3 nmol/kg over six days produced a significant placebo-adjusted weight loss of 5.6%, consistent with published data [1].
Table 1. Once-daily oral administration of ASC39 for six consecutive days resulted in statistically significant weight loss, with efficacy comparable to eloralintide.
Notes:
a. Day 1 body weight was set as the baseline.
b. Obese rats: Diet-induced obesity rats.
ASC39 has demonstrated favorable pharmacokinetic properties in rats and non-human primates, supporting once-daily oral dosing in humans.
Dr. Jinzi J. Wu, Founder, Chairman, and CEO of Ascletis, stated:
Ascletis is committed to developing treatment options for obesity patients. To that end, we are pleased to advance our first orally available small molecule selective amylin receptor agonist, similar to eloralintide, into clinical trials later this year. We believe ASC39 may offer efficacy and safety comparable to Eli Lilly and Co's eloralintide, while providing the convenience of a once-daily oral small molecule for patients, along with commercial scalability potential.
ASC39 is a potent, selective oral small-molecule amylin receptor agonist under development both as a monotherapy and in combination with ASC30 (Ascletis' oral small molecule GLP-1 candidate drug, which has met Phase III criteria) for the treatment of metabolic disorders, including obesity. This novel oral small-molecule amylin program enhances Ascletis' existing portfolio of amylin peptide candidates, including ASC36 (a once-monthly to once-quarterly subcutaneous injectable amylin peptide monotherapy), and a fixed-dose combination of ASC36 with ASC35 (a once-monthly subcutaneous injectable GLP-1/GIP peptide).
[1]Briere DA, Qu H, Lansu K, et al. Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept. Mol Metab. 2025;102:102271. doi:10.1016/j.molmet.2025.102271
About Ascletis Pharma Inc.
Ascletis Pharmaceuticals Co., Ltd. is a fully integrated biotechnology company focused on the development and commercialization of best-in-class and first-in-class drugs for the treatment of metabolic diseases. Leveraging its proprietary Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD), Ultra-Long-Acting Platform (ULAP), and Peptide Oral Transport ENhancement Technology (POTENT), Ascletis has independently developed multiple small molecule and peptide candidates, including its core project ASC30, an investigational small-molecule GLP-1R agonist that can be administered either once daily orally or once monthly to once quarterly via subcutaneous injection for weight loss therapy and maintenance therapy for long-term weight management; ASC36, an amylin receptor agonist peptide; ASC35, a once-monthly subcutaneous injectable GLP-1R/GIPR dual-target agonist peptide; ASC37, a GLP-1R/GIPR/GCGR triple-target agonist peptide; and ASC39, a potent, selective oral small-molecule amylin receptor agonist for long-term weight management. Ascletis is listed on the Hong Kong Stock Exchange (1672.HK).
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