ASCLETIS-B(01672): The oral small molecule glucagon-like peptide-1 receptor agonist ASC39 has shown similar pancreatic selectivity and efficacy to eloralintide in preclinical models.

ASCLETIS-B (01672) announced that the company's board of directors has selected the highly effective orally available small molecule pancreatic polypeptide receptor agonist ASC39, which is selective for insulin, as a candidate drug for clinical development. Galilee is expected to submit an Investigational New Drug Application (IND) for ASC39 oral tablets for the treatment of obesity to the Food and Drug Administration (FDA) in the third quarter of 2026. ASC39 has a unique chemical scaffold discovered independently by Galilee using Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) technology. In a head-to-head experiment of ASC39 with eloralintide in cyclic adenosine monophosphate (cAMP) activation, the EC50 (half maximal effective concentration) of ASC39 and eloralintide (an insulin analog) for the human pancreatic polypeptide type 1 receptor (hAMY1R) were 21.4 pM and 21.2 pM, respectively. The EC50 of ASC39 and eloralintide for the human calcitonin receptor (hCTR) were 846.1 pM and 1,350.8 pM, respectively. These data suggest that compared to hCTR, ASC39 has a high selectivity for hAMY1R, and ASC39's selectivity for hAMY1R is comparable to that of eloralintide. The selectivity of ASC39 and eloralintide for hAMY1R was 40-fold and 64-fold higher, respectively, compared to hCTR. In a head-to-head diet-induced obesity (DIO) study in rats, daily oral administration of ASC39 showed statistically significant weight loss compared to obese rats receiving a placebo, with results similar to eloralintide (see Table 1). Daily oral administration of ASC39 at a dose of 5 mg/kg for 6 consecutive days resulted in a significant placebo-corrected weight loss of 6.6%. Subcutaneous injection of eloralintide at a dose of 3 nmol/kg every three days for 6 consecutive days showed a significant placebo-corrected weight loss of 5.6%, consistent with published data. "Galilee is committed to developing treatment options for obese patients," said Dr. Wu Jinzi, founder, chairman, and CEO of Galilee. "We are pleased to advance the first selective small molecule pancreatic polypeptide receptor agonist similar to eloralintide into clinical trials later this year. We believe that ASC39 may offer efficacy and safety similar to Eli Lilly's eloralintide, while providing the convenience of once-daily oral small molecule dosing for patients and commercial scalability potential." ASC39 is a highly effective orally available small molecule pancreatic polypeptide receptor agonist selective for insulin, being developed both as a monotherapy and in combination with ASC30 (a Galilee oral small molecule GLP-1 candidate with Phase III conditions) for the treatment of metabolic diseases including obesity. This novel oral small molecule insulin project strengthens Galilee's existing portfolio of pancreatic polypeptide candidates, including ASC36 (a monthly to quarterly subcutaneously injected pancreatic polypeptide monotherapy) and a fixed-dose combination of ASC36 and ASC35 (a monthly subcutaneous injection of GLP-1/GIP polypeptide).