ASC39

What It Is

ASC39 is an oral, once-daily small-molecule agonist of the amylin receptor being developed by Ascletis Pharma (HKEX: 1672) for obesity. Amylin is a pancreatic hormone co-secreted with insulin that promotes satiety, slows gastric emptying, and - unlike some appetite pathways - tends to preserve lean mass during weight loss, making it one of the most clinically validated non-GLP-1 targets in obesity medicine. Amylin signals through the calcitonin receptor (CTR) and through the amylin receptors AMY1/AMY2/AMY3 (each the calcitonin receptor paired with a receptor-activity-modifying protein, RAMP1/2/3). The current amylin front-runners are almost all peptides given by subcutaneous injection - cagrilintide, petrelintide and Eli Lilly's selective agonist eloralintide - so a potent oral small molecule that reproduces their pharmacology would be a meaningful differentiator, both as a standalone pill and as a combination partner. ASC39 is designed to be that molecule: an 'eloralintide-like' amylin-selective agonist delivered as a once-daily tablet. Ascletis has reported head-to-head preclinical data that put ASC39 essentially on par with eloralintide. In cyclic-AMP (cAMP) activation assays, ASC39's half-maximal effective concentration (EC50) at the human amylin 1 receptor was 21.4 pM versus 21.2 pM for eloralintide, while its EC50 at the human calcitonin receptor was 846.1 pM versus 1,350.8 pM for eloralintide - indicating comparable potency at the amylin receptor and similar (indeed marginally greater) selectivity away from the calcitonin receptor, which is the receptor most linked to amylin-associated nausea and food aversion. In diet-induced obese (DIO) rats, oral ASC39 produced significant placebo-adjusted weight loss of 6.6%, compared with 5.6% for eloralintide in the same study. Ascletis presented these findings at the American Diabetes Association (ADA) 2026 Scientific Sessions (New Orleans, June 5-8, 2026) alongside clinical data for its oral GLP-1 agonist ASC30 and preclinical data for its triple agonist ASC37. Ascletis selected ASC39 as a clinical development candidate in early 2026 and expects to submit a U.S. FDA Investigational New Drug (IND) application for ASC39 oral tablets in obesity in the third quarter of 2026. In parallel, the company selected a fixed-dose combination, ASC30_39 FDC, that pairs ASC39 with ASC30 (a Phase III-ready once-daily oral small-molecule GLP-1 receptor agonist reported to cause about half the vomiting of orforglipron under weekly titration) into a single once-daily tablet; in a head-to-head dog study the combination tablet showed excellent oral bioavailability, high drug exposure and a half-life of up to 12 hours, along with good compatibility, room-temperature stability and a small pill size. An IND for the ASC30_39 FDC is likewise planned for the third quarter of 2026. ASC39 reflects two converging 2026 themes in obesity drug development: the 'amylin renaissance,' in which amylin-based, lean-mass-sparing mechanisms are pursued as the next pillar beyond GLP-1, and the race to move these mechanisms from weekly injections into convenient oral small molecules.

Regulatory Status

Why Researchers Study It

ASC39 is watched because it tests whether the amylin pathway - one of the most validated non-GLP-1 obesity mechanisms, and one prized for sparing lean mass - can be captured in a convenient oral small molecule rather than a weekly injection. Ascletis has reported preclinical potency, calcitonin-receptor selectivity and weight loss essentially matching Eli Lilly's injectable peptide eloralintide, so ASC39 serves as a proof-of-concept that oral chemistry can reproduce best-in-class amylin peptide pharmacology. It is also a building block for combination therapy: paired with the oral GLP-1 agonist ASC30 in the ASC30_39 fixed-dose tablet, it could enable an all-oral GLP-1-plus-amylin regimen, the oral analog of the injectable CagriSema/MariTide combination strategy. Finally, it is a leading example of the 2026 'amylin renaissance' and the broader push to convert injectable obesity biology into once-daily pills.

Proposed Mechanisms

• Agonizes the amylin receptor (calcitonin receptor paired with RAMP proteins) to promote satiety, slow gastric emptying and reduce food intake
• Amylin-selective: comparable potency at the human amylin 1 receptor (EC50 ~21.4 pM) with substantially weaker activity at the human calcitonin receptor (EC50 ~846 pM), the receptor linked to amylin-related nausea and aversion
• Aims to preserve lean mass during weight loss, a hallmark attributed to amylin-pathway signaling
• Formulated as a once-daily oral small-molecule tablet rather than a subcutaneous peptide injection
• Designed as a combination partner with the oral GLP-1 agonist ASC30 (ASC30_39 fixed-dose combination) for additive weight loss in a single pill

Evidence Snapshot

Commonly Discussed Benefits

Safety & Cautions

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Citations

1. [1] Ascletis - Oral Small Molecule Amylin Receptor Agonist ASC39 Demonstrated Eloralintide-like Amylin Selectivity and Efficacy in Preclinical Models (Mar 17, 2026) PubMed
2. [2] Ascletis Announces Fixed-Dose Combination of ASC30 (oral GLP-1R agonist) and ASC39 (oral amylin-selective agonist) for Clinical Development (Apr 7, 2026) PubMed
3. [3] Ascletis Reinforces Its Differentiated Obesity Portfolio at ADA 2026 - ASC30 Clinical Data and Preclinical Findings from ASC37 and ASC39 (June 2026) PubMed
4. [4] BioWorld - Ascletis Pharma selects ASC-39 as clinical development candidate PubMed

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