Hong Kong, China, October 26, 2026
Ascletis Pharma Inc. announced that it has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for ASC39, an investigational oral small-molecule selective amylin receptor agonist being developed for the treatment of obesity. The candidate is designed to activate the human amylin 1 receptor (hAMY1R) while limiting activity at the human calcitonin receptor (hCTR), a selectivity profile the company aims to translate into potential efficacy and tolerability advantages. According to Ascletis, preclinical studies demonstrated receptor selectivity comparable to eloralintide, an amylin-targeting peptide, and encouraging weight-loss activity in an animal model of obesity. The company plans to initiate a Phase 1 clinical trial in the fourth quarter of 2026, subject to the relevant regulatory process. The IND submission represents a development milestone for Ascletis as it expands its obesity portfolio beyond incretin-based medicines and advances oral small-molecule approaches to chronic weight management.
ASC39 Shows Selective Amylin Receptor Activity
ASC39 was discovered in-house using Ascletis’ Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) technology. In laboratory testing that compared receptor activation, ASC39 demonstrated an EC50 of 21.4 picomolar at the human amylin 1 receptor, similar to the 21.2 picomolar value reported for eloralintide. At the human calcitonin receptor, ASC39 had an EC50 of 846.1 picomolar, compared with 1,350.8 picomolar for eloralintide. Based on these results, Ascletis reported that ASC39 was approximately 40-fold more selective for hAMY1R than hCTR, while eloralintide was approximately 64-fold selective in the same comparison. These findings suggest that the small molecule can preferentially activate the intended amylin receptor in preclinical assays. The company believes that selective amylin receptor activity could be an important factor in developing obesity medicines with a favourable balance of efficacy and tolerability. However, receptor activity measured in laboratory systems does not establish how the medicine will perform in people, and human studies will be required to assess its safety, pharmacological behaviour and potential weight-management effects.
Animal Study Reports Promising Weight-Loss Activity
In a diet-induced obese rat model, once-daily oral administration of ASC39 at 5 mg/kg for six consecutive days produced a placebo-adjusted weight reduction of 6.6%, according to the company. Ascletis also reported favourable pharmacokinetic profiles in rats and non-human primates, supporting its development as a potential once-daily oral medicine. These findings provide an early basis for clinical investigation, but they should not be interpreted as evidence of equivalent weight loss in humans. The study was conducted in animals over a short period, and the effects of the candidate in people—including the appropriate dose, duration of treatment, tolerability and sustainability of weight reduction—remain unknown. The planned Phase 1 study is expected to provide the first clinical information on ASC39 in humans. Early clinical development will typically focus on safety, tolerability and pharmacokinetics before efficacy can be established in larger patient studies. ASC39 remains an investigational candidate and has not been approved for obesity treatment.
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Ascletis Expands Its Oral Obesity Drug Pipeline
Ascletis is developing ASC39 both as a potential standalone therapy and in combination with ASC30, its oral small-molecule GLP-1 receptor agonist. The company is also exploring fixed-dose combinations designed to engage multiple metabolic pathways. Amylin is a hormone involved in appetite regulation and meal-related satiety, while GLP-1 receptor signalling is another established area of research in obesity treatment. Combining these mechanisms could provide an alternative strategy for chronic weight management, although the benefits and risks of any combination must be demonstrated in clinical trials. Ascletis’ broader metabolic disease portfolio includes small molecules and peptide-based candidates, with research programmes directed at oral and longer-acting formulations. The company said ASC39 expands its development efforts beyond the incretin class and may offer a differentiated approach among oral amylin-targeting drug candidates. The FDA IND submission allows the company to pursue clinical development, but it does not represent FDA approval or confirmation of clinical efficacy. Upcoming Phase 1 findings will be important in determining whether ASC39 can progress into studies designed to evaluate weight loss and long-term safety in people living with obesity.
Source: Ascletis Pharma press release
