ASCLETIS-B (01672) has announced its board of directors' decision to select ASC39, a potent and selective oral small molecule amylin receptor agonist, as a candidate for clinical development. The company anticipates submitting an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) in the third quarter of 2026 for ASC39 oral tablets targeting obesity treatment. ASC39 features a unique chemical scaffold discovered using the company's proprietary AI-assisted structure-based drug discovery (AISBDD) technology.

In head-to-head cyclic adenosine monophosphate (cAMP) activation assays comparing ASC39 with eloralintide, the EC50 (half maximal effective concentration) values for the human amylin type 1 receptor (hAMY1R) were 21.4 pM for ASC39 and 21.2 pM for eloralintide (an amylin peptide analog). For the human calcitonin receptor (hCTR), the EC50 values were 846.1 pM for ASC39 and 1,350.8 pM for eloralintide. These results indicate that ASC39 exhibits high selectivity for hAMY1R over hCTR, with a selectivity profile comparable to eloralintide. Specifically, ASC39 demonstrated 40-fold greater selectivity for hAMY1R over hCTR, while eloralintide showed 64-fold greater selectivity.

In a head-to-head study using diet-induced obese (DIO) rats, daily oral administration of ASC39 resulted in statistically significant body weight reduction compared to placebo-treated obese rats, achieving efficacy equivalent to eloralintide. Administration of 5 mg/kg ASC39 once daily for six days produced a significant placebo-adjusted body weight reduction of 6.6%. Subcutaneous injection of 3 nmol/kg eloralintide every three days over six days resulted in a significant placebo-adjusted body weight reduction of 5.6%, consistent with published data.

"We are committed to developing treatments for patients with obesity," stated Dr. Jinzi J. Wu, Founder, Chairman, and CEO of ASCLETIS. "We are pleased to advance the first oral small molecule selective amylin receptor agonist with eloralintide-like properties into clinical studies later this year. We believe ASC39 may offer efficacy and safety similar to Eli Lilly's eloralintide, combined with the convenience of once-daily oral dosing and potential for commercial scalability."

ASC39 is being developed both as a monotherapy and in combination with ASC30, an oral small molecule GLP-1 receptor agonist candidate with Phase III-ready status, for the treatment of metabolic diseases including obesity. This novel oral amylin program strengthens ASCLETIS's existing portfolio of amylin peptide candidates, which includes ASC36, a subcutaneous amylin peptide monotherapy amenable to monthly or quarterly dosing, and a fixed-dose combination of ASC36 with ASC35, a once-monthly subcutaneous GLP-1/GIP dual agonist peptide.