ASC39
Low EvidenceASC39 is Ascletis Pharma's investigational once-daily oral small-molecule amylin-selective amylin receptor agonist for obesity. In head-to-head preclinical assays it matched Eli Lilly's injectable peptide eloralintide on amylin-receptor potency, selectivity over the calcitonin receptor, and weight loss in diet-induced obese rats. Ascletis plans to file a U.S. FDA IND for ASC39 - and for a fixed-dose combination with its oral GLP-1 agonist ASC30 - in the third quarter of 2026.
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
Preclinical / IND-enabling as of mid-2026. Selected as a clinical development candidate in early 2026; Ascletis plans to submit a U.S. FDA IND for ASC39 oral tablets (and for the ASC30_39 fixed-dose combination) for obesity in Q3 2026. No IND cleared and no human trials begun as of July 2026. Not approved in any jurisdiction.
Effective: 2026
View FDA SourceWhy 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
| Study Type | Model | Outcome | Link |
|---|---|---|---|
| Preclinical (in vitro) | Human amylin 1 receptor and calcitonin receptor cAMP activation assays (head-to-head vs eloralintide) | ASC39 EC50 at human amylin 1 receptor 21.4 pM vs 21.2 pM for eloralintide; EC50 at human calcitonin receptor 846.1 pM vs 1,350.8 pM for eloralintide - comparable amylin-receptor potency and similar/greater selectivity over the calcitonin receptor | Source |
| Preclinical (in vivo) | Diet-induced obese (DIO) rats, oral dosing (head-to-head vs eloralintide) | Significant placebo-adjusted weight loss of 6.6% for ASC39 vs 5.6% for eloralintide | Source |
| Preclinical (combination) | ASC30_39 fixed-dose combination tablet, oral dosing in dogs | Excellent oral bioavailability, high drug exposure and half-life up to 12 hours; good compatibility, room-temperature stability and small pill size supporting a once-daily single-pill GLP-1-plus-amylin regimen | Source |
| Company / development | Ascletis Pharma obesity pipeline | ASC39 selected as clinical development candidate in early 2026; U.S. FDA IND for ASC39 oral tablets and for the ASC30_39 fixed-dose combination planned for Q3 2026 | Source |
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Safety & Cautions
- Preclinical / IND-enabling only - no human safety or efficacy data yet, and no IND cleared as of July 2026
- Cross-species translation is uncertain: eloralintide-matching potency and weight loss in rats and cell assays may not reproduce in humans
- Human tolerability of an amylin-selective oral agonist (nausea, vomiting, GI effects) is unproven
- Human weight-loss magnitude, durability and lean-mass benefit are unknown
- Combination (ASC30_39 FDC) benefit and safety are likewise unproven in people
- Not available outside eventual clinical trials; not FDA-approved and not a compounding-eligible peptide
- Any 'ASC39' offered by a vendor is unverified - it is a proprietary investigational small molecule
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Citations
- [1] Ascletis - Oral Small Molecule Amylin Receptor Agonist ASC39 Demonstrated Eloralintide-like Amylin Selectivity and Efficacy in Preclinical Models (Mar 17, 2026) PubMed
- [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] Ascletis Reinforces Its Differentiated Obesity Portfolio at ADA 2026 - ASC30 Clinical Data and Preclinical Findings from ASC37 and ASC39 (June 2026) PubMed
- [4] BioWorld - Ascletis Pharma selects ASC-39 as clinical development candidate PubMed
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Related Peptides
Cagrilintide
High EvidenceA long-acting amylin analog studied for appetite regulation; NDA filed for CagriSema (cagrilintide + semaglutide) combination in December 2025, with FDA review expected in 2026.
Eloralintide
Medium EvidenceA selective, long-acting amylin receptor agonist in Phase 3 trials for obesity, offering a GLP-1-independent weight loss mechanism with up to 20.1% weight loss in Phase 2.
Amycretin
Medium EvidenceA unimolecular GLP-1 and amylin receptor dual agonist in Phase 3 trials, available in both subcutaneous and oral formulations, with up to 22% weight loss in Phase 1b/2a.
Petrelintide
Medium EvidenceA long-acting amylin analog in late-stage clinical development for chronic weight management, designed to deliver double-digit weight loss with a tolerability profile comparable to placebo.
ASC30
Low EvidenceAn oral once-daily small-molecule GLP-1 receptor agonist developed by Ascletis Pharma, showing 5.4–7.7% placebo-adjusted weight loss at 13 weeks in Phase 2, with in vitro potency 2–3x greater than orforglipron.
ALV-200
Low EvidenceALV-200 is Alveus Therapeutics' highly selective amylin receptor 3 (AMYR3) peptide agonist in IND-enabling development for obesity, designed to capture amylin's weight-loss and lean-mass-preserving benefits while avoiding the nausea and aversion tied to calcitonin-receptor activation. It is engineered for once-weekly dosing.