ASC36

What is ASC36?

ASC36 is an investigational amylin receptor agonist peptide for chronic weight management. Amylin is co-secreted with insulin after meals and signals satiety through the area postrema, slows gastric emptying and suppresses postprandial glucagon — a mechanism distinct from and complementary to GLP-1, which is why amylin analogues are the most watched class in obesity after the incretins. The page previously described ASC36 as a single weekly injection; that is wrong on both counts. Ascletis develops it as two products. ASC36i is a subcutaneous Self-Assembling Lipid Depot intended for once-monthly to once-quarterly dosing, and ASC36o is a once-weekly oral tablet built on a separate oral-peptide delivery technology. Both began phase 1 trials in autumn 2026 — the injectable on 28 September, the tablet on 13 October — and neither has reported any human data. The engineering claim worth attention is stability. Ascletis states that ASC36 shows no fibrillation at neutral pH, meaning it does not aggregate into the amyloid structures that human amylin notoriously forms. That is what allows co-formulation with the company's GLP-1/GIP dual agonist ASC35 in a single monthly injection, which is where the programme's commercial emphasis sits.

What ASC36 Is Investigated For

ASC36 has no human data. Both phase 1 studies are recruiting with 2027 completion dates, and no doses have been disclosed for any cohort. Everything known about the molecule is company-reported preclinical work, and there is no peer-reviewed literature mentioning it at all. The class it joins is, however, crowded and moving fast — faster than this page previously reflected. Cagrilintide combined with semaglutide produced 20.4% weight loss at 68 weeks in REDEFINE 1 and is under FDA review. Petrelintide reported 9.8% at 28 weeks in a phase 2 with gastrointestinal tolerability similar to placebo apart from mild nausea during escalation, and has moved into phase 3. Eloralintide, the most selective agent in the class, reported 20% weight loss at 48 weeks in a Lancet phase 2 and is in multiple phase 3 trials. A selective amylin agonist is no longer a novel proposition; what ASC36 proposes to add is dosing interval and route. Ascletis's preclinical claims are specific: a depot half-life of about 15 days in non-human primates, roughly three times petrelintide's; 10.01% versus 5.25% body-weight reduction against petrelintide in diet-induced obese rats at equimolar dosing; and for the oral tablet, 13.2% weight reduction in primates after seven days of once-daily dosing with oral bioavailability of 6 to 8%. These are sponsor-run comparisons against competitors' compounds, unpublished and unreplicated, and the company's own chief executive has described the animal models as highly predictive of human efficacy — a marketing claim rather than a finding.

History & Discovery

ASC36's public record begins on 30 October 2025, when Ascletis Pharma announced it had selected the compound as a development candidate, describing it as an amylin receptor peptide agonist discovered in-house through an AI-assisted structure-based drug discovery platform and formulated as a slow-release subcutaneous depot. Claims that development began in 2024 are not supported by any public source. The company had earlier been known for hepatitis C and B antivirals rather than metabolic disease. The announced preclinical package compared ASC36 directly against competitors: an observed depot half-life of about 15 days in non-human primates, three times petrelintide's, and 10.01% versus 5.25% body-weight reduction against petrelintide in diet-induced obese rats over seven days at equimolar dosing. A co-formulation with the GLP-1/GIP dual agonist ASC35 was announced for clinical development in November 2025. Investigational new drug applications for both the ASC36 injection and the ASC36_35 combination were submitted to the FDA in July 2026 and cleared the following month, announced on 10 August 2026. Dosing in the injectable phase 1 actually began on 28 September 2026, and the oral tablet study — announced on 8 September with primate data showing 13.2% weight reduction over seven days of once-daily dosing and oral bioavailability of 6 to 8% — began dosing on 13 October 2026. Both were first posted to ClinicalTrials.gov on 23 October 2026. The gap between announcement and actual trial start is worth noting whenever company dates and registry dates disagree: the registry records when participants were dosed. Like Ascletis's other metabolic assets, ASC36 is being developed United States-first, under US investigational new drug applications with US-only sites and no registered Chinese trial.

How It Works

Amylin is a hormone released from the pancreas alongside insulin after you eat. It tells the brain you have had enough, slows the stomach emptying and stops the liver releasing extra sugar. ASC36 is a synthetic, long-lasting version of that signal. One formulation is injected and designed to keep working for a month or more; the other is a tablet.

ASC36 activates amylin receptors, which are not standalone proteins but heterodimers of the calcitonin receptor with one of three receptor activity-modifying proteins, producing the AMY1R, AMY2R and AMY3R subtypes. The downstream pharmacology is canonical for the class: central anorectic signalling through the area postrema and connected brainstem and hypothalamic circuits, slowed gastric emptying, and suppression of postprandial glucagon. The pharmacologically consequential variable in this class is selectivity, and it is exactly what has not been disclosed for ASC36. Agents differ in how much they engage the calcitonin receptor relative to the amylin receptor subtypes, and that difference appears to determine tolerability rather than efficacy. Eloralintide preferentially activates human AMY1R — twelve-fold over the calcitonin receptor and eleven-fold over AMY3R — and induced significantly less conditioned taste avoidance in rats than the non-selective cagrilintide. The open question across the field is whether reduced food intake on these drugs reflects physiological satiation or aversive signalling, with receptor selectivity, exposure kinetics and downstream circuit recruitment all implicated. Ascletis describes ASC36 only as an amylin receptor agonist and has published no selectivity data, so it cannot be placed on that spectrum. The stability engineering is better documented. Native human amylin aggregates readily into amyloid fibrils; this is how islet amyloid polypeptide was discovered, and aggregated amylin is cytotoxic and implicated in beta-cell loss in type 2 diabetes. Every amylin analogue has to solve this — pramlintide's acidic formulation is a direct consequence, and petrelintide's development paper describes chemical-stability optimisation enabling formulation at about neutral pH as the central achievement. Ascletis reports that ASC36 shows no fibrillation around neutral pH and no aggregation or precipitation either alone or co-formulated, which is what makes a single-injection combination with the GLP-1/GIP dual agonist ASC35 feasible. Duration comes from formulation rather than from chemical modification of the peptide. The injectable uses a Self-Assembling Lipid Depot — a low-viscosity solution of lipids, solvents and drug that forms a gel-like depot in tissue after subcutaneous injection — with a reported observed half-life of about 15 days in non-human primates, which the company states is roughly three times petrelintide's and six times eloralintide's. The oral tablet uses a separate delivery technology, with reported primate absolute bioavailability of 8% at 10 mg and 6% at 25 mg and elimination half-lives of 116 and 167 hours respectively.

Evidence Snapshot

Research Gaps & Open Questions

What the current literature has not yet settled about ASC36:

• 01ASC36's receptor selectivity across AMY1R, AMY2R, AMY3R and the calcitonin receptor. This is the single most informative missing number — it determines whether ASC36 resembles the selective eloralintide or the non-selective cagrilintide, and selectivity appears to drive tolerability rather than efficacy in this class.
• 02All human pharmacokinetics, and specifically whether the 15-day primate depot half-life translates into a workable monthly or quarterly human interval.
• 03Whether the oral formulation's 6 to 8% primate bioavailability produces useful human exposure, and at what dose.
• 04The actual oral dosing interval, which the company's pipeline and its own filings describe inconsistently as once-weekly and once-daily.
• 05Tolerability. Nausea is the limiting effect for this class and nothing is known about ASC36's profile.
• 06Whether the sponsor's preclinical superiority claims over petrelintide and eloralintide are real. They are unpublished, unreplicated, sponsor-run comparisons against competitors' compounds, and rodent weight-loss magnitude has a poor record of predicting human results.
• 07Immunogenicity of a depot-resident peptide, which the injectable trial measures and nothing public addresses.
• 08The co-formulation's status. ASC36_35FDC was announced as having entered phase 1 in August 2026 but has no ClinicalTrials.gov registration, so it cannot be independently verified.
• 09Body composition. No lean-mass data exists, and it is a standard question for the class — amylin agonists are of interest partly because of a hypothesis that they preserve lean mass better than incretins, which has not been established.

Forms & Administration

Two formulations in parallel first-in-human development. ASC36i is a subcutaneous Self-Assembling Lipid Depot intended for once-monthly to once-quarterly dosing; its phase 1 tests two distinct depot formulations, designated A and B, across single- and multiple-ascending-dose cohorts. ASC36o is an oral tablet, described by the company as designed for once-weekly administration, whose phase 1 includes a food-effect assessment. Neither is commercially available and no dose levels have been disclosed for either. A fixed-dose co-formulation with the GLP-1/GIP dual agonist ASC35, given as a single monthly injection, was announced as having entered phase 1 in August 2026 but has no trial registration on ClinicalTrials.gov.

Dosing & Protocols

The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.

ASC36 is an investigational drug in first-in-human phase 1 trials in both its formulations. It is not approved anywhere, no dose has been established, and it is not available outside those trials.

Timeline of Effects

Common Questions

Who ASC36 Is NOT For

Drug & Supplement Interactions

No interaction data exists for ASC36 and none can at this stage. The considerations below are class-level. The interaction that matters most for amylin analogues is with insulin. Pramlintide, the only approved amylin analogue, carries a boxed warning for severe hypoglycaemia when used with insulin, and its label requires insulin dose reduction at initiation. ASC36's trials exclude people with diabetes, so the scenario does not arise in the current programme, but it would become central if the compound were ever developed in that population. Slowed gastric emptying is the second consideration, shared with the incretins: it can delay or reduce absorption of co-administered oral drugs, which matters most for narrow-therapeutic-index medicines and oral contraceptives. Pramlintide's label advises separating oral medications where rapid absorption matters. How a monthly depot with gradual release behaves in this respect, as opposed to a weekly injection with distinct peaks, is unknown and is one of the more interesting unanswered questions about the formulation. As a peptide, ASC36 would be expected to be cleared by peptidase degradation rather than cytochrome P450 metabolism, making classical pharmacokinetic interactions unlikely. The lipid and organic-solvent excipients of the depot are a less familiar exposure, and nothing has been published about them.

Safety Profile

Legal Status

Regulatory status changes over time. Verify current local rules with a qualified professional.

Myths & Misconceptions