ASC35
Ascletis Pharma's GLP-1/GIP dual agonist peptide, formulated as a subcutaneous lipid depot intended for once-monthly dosing rather than weekly. Its phase 1 began dosing in August 2026 with tirzepatide as an active comparator, and no human data has been reported.
ASC35 is an experimental weight-loss injection that works on the same two gut-hormone receptors as tirzepatide (Mounjaro and Zepbound). The idea is that it forms a small gel reservoir under the skin so one injection lasts a month instead of a week. It started its first human trial in August 2026 and no results exist yet — everything published about it so far comes from animal studies run by the company.
What is ASC35?
ASC35 is an investigational peptide that activates both the GLP-1 receptor and the GIP receptor — the same dual mechanism as tirzepatide. What distinguishes it is not the pharmacology but the formulation. Ascletis delivers it as a Self-Assembling Lipid Depot, a low-viscosity solution of lipids, biocompatible solvents and drug that is injected through a fine needle and then transforms into a gel-like depot in the tissue, releasing over a month or longer. The company's stated goal is once-monthly subcutaneous dosing where tirzepatide and every approved incretin are weekly. Ascletis now writes ASC35i for the injectable and ASC35o for a separate once-weekly oral peptide version that remains preclinical. The injectable entered its first human study in August 2026 under an FDA investigational new drug application cleared that June. ASC35 is also being developed as half of a co-formulation with the amylin receptor agonist ASC36, which is where the company has placed most of its public emphasis. There is no human data of any kind. There is also no peer-reviewed literature — not one paper mentions ASC35.
What ASC35 Is Investigated For
ASC35 is at the earliest stage of clinical development and should be read accordingly: a phase 1 study that began dosing on 27 August 2026, 84 participants, with completion estimated for June 2027. Nothing has been reported from it. The mechanism is thoroughly validated — tirzepatide established that simultaneous GLP-1 and GIP receptor agonism produces greater weight loss than GLP-1 agonism alone, with about 20.9% mean reduction at 72 weeks in its pivotal obesity trial. What ASC35 proposes to add is interval. Every approved incretin for weight management is dosed weekly; a monthly depot would be a genuine difference for anyone who finds weekly injections the limiting factor, and the phase 1 is designed to test that directly by including a once-weekly tirzepatide arm as active comparator. The supporting evidence is entirely preclinical and entirely from the sponsor. Ascletis reports roughly four-fold greater in vitro potency than tirzepatide at both receptors, an observed half-life of about 14 days in non-human primates, and in a diet-induced obese mouse study at equimolar dosing, 33.6% body-weight reduction against 19.6% for tirzepatide. None of this is peer-reviewed or independently replicated, and sponsor-run head-to-head comparisons against competitor compounds are the weakest form of comparative evidence. Treat the numbers as a hypothesis the phase 1 was designed to start testing.
History & Discovery
ASC35's public record is short and begins more recently than most sources suggest. Ascletis Pharma, a Hangzhou company listed in Hong Kong whose earlier work was in hepatitis C and B, announced ASC35's selection as a clinical candidate on 12 October 2025, describing it as a once-monthly subcutaneous GLP-1/GIP dual peptide agonist discovered in-house through an AI-assisted structure-based drug discovery platform. Nothing public predates that announcement; claims that development began in 2023 or 2024 are not supported by any source. A co-formulation with the amylin receptor agonist ASC36 was announced for clinical development in November 2025. The FDA cleared an investigational new drug application for the ASC35 phase 1 on 23 June 2026, dosing began on 27 August 2026, and the trial was first posted to ClinicalTrials.gov on 25 September 2026. Preclinical data for the ASC36_35 combination was presented at the European Association for the Study of Diabetes meeting in Milan in October 2026, and a once-weekly oral peptide pipeline including ASC35o was disclosed later that month. The programme is notable for being run United States-first — the investigational new drug application, the trial and its single site are all American, with no registered Chinese study. That is a reversal of the pattern many Chinese biotechs follow, and the same approach Ascletis has taken with ASC30.
How It Works
ASC35 switches on two gut-hormone receptors at once, GLP-1 and GIP — the same pair tirzepatide targets. Together they increase insulin when blood sugar rises, slow the stomach and reduce appetite. The unusual part is delivery: the liquid turns into a small gel reservoir under the skin after injection and releases the drug slowly, with the aim of one injection a month instead of one a week.
ASC35 is a peptide agonist at both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor. Dual agonism produces additive effects on glucose-dependent insulin secretion, glucagon suppression, gastric emptying and central appetite regulation, and tirzepatide established the clinical validity of the combination. The pharmacological rationale for adding GIP agonism is more contested than the clinical results suggest, and it is worth understanding because it is the live scientific question in this class. GIP receptor agonism appears to attenuate the nausea and emesis caused by GLP-1 receptor activation — demonstrated across mice, rats and musk shrews, where GIP receptor signalling blocked emesis and reduced illness behaviours while preserving reduced food intake and weight loss. That would make GIP agonism a tolerability mechanism as much as an efficacy one. But GIP receptor antagonism conjugated to GLP-1 agonism also produces weight loss in humans, as maridebart cafraglutide has shown, which means two opposite interventions at the same receptor both work. Nobody has reconciled this, and a 2026 review frames it explicitly as a paradox. ASC35's specific receptor pharmacology has not been published. Ascletis reports approximately four-fold greater in vitro potency than tirzepatide at both receptors, without disclosing EC50 values, selectivity ratios or assay conditions. The delivery technology is where the company has said most. The Self-Assembling Lipid Depot is a low-viscosity solution of lipids, biocompatible organic solvents and active ingredient that can be injected through a needle as fine as 29 gauge by pen or autoinjector, forming a gel-like depot in tissue that releases over a month or longer. In non-human primates the observed half-life was about 14 days, which the company reports as roughly six-fold longer than tirzepatide's authorised subcutaneous formulation, with exposure around 70 to 80% greater; the projected human half-life of 30 days or more is an extrapolation from that primate data rather than a measurement. Within the ASC36 co-formulation, reported primate half-lives were up to about 30 days for ASC35 and 33 days for ASC36.
Evidence Snapshot
Human Clinical Evidence
None. A single phase 1 study (NCT07842640) began dosing on 27 August 2026 — randomised, double-blind, placebo-controlled, with single- and multiple-ascending-dose cohorts plus a once-weekly tirzepatide active comparator arm, 84 participants at one US site, estimated completion June 2027. The primary endpoint is adverse events through day 141, with pharmacokinetics and percent change in body weight as secondary endpoints. No dose levels have been disclosed and no results have been reported.
Animal / Preclinical
Company-reported only, and not peer-reviewed. The claims are roughly four-fold greater in vitro potency than tirzepatide at both receptors; an observed half-life of about 14 days in non-human primates with exposure 70 to 80% above tirzepatide; and in diet-induced obese mice dosed at equimolar 3 nmol/kg daily for 14 days, body-weight reduction of 33.6% versus 19.6% for tirzepatide. Sponsor-run comparisons against competitor compounds warrant particular caution.
Mechanistic Rationale
Strong for dual GLP-1/GIP agonism, which tirzepatide validated clinically. Weaker for the specific proposition that a monthly depot delivers equivalent efficacy to weekly dosing — depot formulations trade peak exposure for duration, and whether that trade preserves efficacy and improves tolerability is exactly what has not been tested in humans.
Research Gaps & Open Questions
What the current literature has not yet settled about ASC35:
- 01All human pharmacokinetics. Whether the projected 30-day human half-life is achieved is the single question the programme turns on, and primate-to-human extrapolation of depot formulations is unreliable.
- 02Whether monthly dosing delivers efficacy equivalent to weekly dosing of an established agent. The phase 1 includes a tirzepatide comparator arm, which is unusually informative for a first-in-human study, but it is a phase 1 and not powered for efficacy.
- 03Tolerability. The hypothesis that gradual depot release reduces gastrointestinal events is plausible and entirely untested.
- 04Dose levels, which have not been disclosed for any cohort.
- 05Whether the preclinical potency advantage over tirzepatide is real. It is a sponsor-run comparison, unreplicated and unpublished, and head-to-head claims generated by one company about another's drug are the weakest comparative evidence there is.
- 06Whether ASC35o, the oral version, is the same molecule as the injectable. The company's naming does not consistently distinguish them.
- 07The co-formulation. ASC36_35FDC was announced as having begun phase 1 in August 2026 but has no trial registration on ClinicalTrials.gov, so its status cannot be independently verified.
- 08Immunogenicity, which matters for any peptide held in tissue for a month and is not addressed in any public material.
Forms & Administration
Subcutaneous injection of a Self-Assembling Lipid Depot formulation, intended for once-monthly administration. The solution is low-viscosity and deliverable by pen or autoinjector through a needle as fine as 29 gauge, forming a gel-like depot after injection. The phase 1 study tests a formulation designated 'Injection B', described in the trial record as an investigational once-monthly formulation — implying an 'Injection A' that has not been separately registered or described. A separate once-weekly oral peptide version, ASC35o, is preclinical with an investigational new drug application guided for late 2026. No dose levels have been disclosed for any formulation.
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.
Typical Range
Not disclosed. The phase 1 tests four single-ascending-dose and four multiple-ascending-dose cohorts, labelled only as dose levels in the trial registration.
Frequency
Once monthly by subcutaneous injection — the design intent of the depot formulation and the reason the programme exists.
Timing Considerations
Time of day
Not applicable — a monthly depot makes time-of-day irrelevant
Relative to meals
No relationship established
Relative to exercise
Not tied to exercise timing.
The practical timing question for a monthly depot is not when in the day but how consistently the interval is kept, and whether trough exposure at the end of a month remains therapeutic. That is one of the things the multiple-ascending-dose cohorts are designed to characterise.
Cycle Length
Chronic and indefinite would be anticipated for weight management, as for all incretin agonists, but nothing has been established.
Protocol Notes
No dosing information exists outside the trial protocol, and the protocol does not disclose dose levels. What can be said concerns the delivery rather than the dose. The depot is a low-viscosity solution injectable through a needle as fine as 29 gauge, which matters because thick, slow-to-inject depot formulations are unpleasant and have historically limited this approach. After injection the solution forms a gel-like reservoir in the tissue and releases over a month or longer, with an observed half-life of about 14 days in non-human primates and a projected human half-life of 30 days or more. That projection is the central uncertainty of the programme. A monthly interval only works if human pharmacokinetics match the primate extrapolation, and depot formulations are notoriously species-dependent. The phase 1 is structured to answer exactly this — single-ascending-dose cohorts with long follow-up to characterise the release profile before multiple-ascending-dose cohorts begin, with the primary safety endpoint extending to day 141 precisely because a monthly depot has to be observed for months, not weeks.
ASC35 is an investigational drug in a first-in-human phase 1 trial. It is not approved anywhere, no dose has been established, and it is not available outside that trial.
Timeline of Effects
Onset
Not characterised in humans. A depot formulation releases gradually by design, so onset would be expected to be slower than a conventional subcutaneous injection — part of the rationale for better tolerability, since the gastrointestinal effects of incretins track the rate of rise in exposure as much as the absolute level. Whether that holds is untested.
Peak Effect
Not characterised in humans. In non-human primates the observed half-life was about 14 days; the human projection of 30 days or more is an extrapolation. The phase 1's multiple-ascending-dose cohorts and day-141 follow-up are designed to establish where steady state sits on a monthly interval.
After Discontinuation
Prolonged, and this is the formulation's defining practical consequence. If the projected half-life of 30 days or more is borne out, exposure would persist for several months after a final injection — there is no way to stop a depot once it is in the tissue. For a drug used chronically in weight management that may be unimportant; for pregnancy, surgery, or an adverse event requiring withdrawal it is a real constraint, and it is the trade-off accepted in exchange for twelve injections a year instead of fifty-two.
Common Questions
How is ASC35 different from tirzepatide?
Same receptor targets, different molecule, and a completely different dosing interval. Tirzepatide is a once-weekly peptide; ASC35 is formulated as a subcutaneous lipid depot intended for once-monthly administration, which is the entire reason the programme exists. The phase 1 study makes the comparison explicit by including a once-weekly tirzepatide arm as an active comparator alongside the ascending-dose cohorts. On potency, Ascletis reports roughly four-fold greater in vitro activity at both receptors and a 33.6% versus 19.6% body-weight reduction in diet-induced obese mice at equimolar dosing over 14 days — company-generated preclinical comparisons that have not been peer-reviewed or replicated independently.
Is ASC35 being developed for type 2 diabetes?
No, and this is worth stating plainly because the dual-agonist class is so closely associated with diabetes. Every Ascletis communication describes ASC35 as being for obesity and chronic weight management, and the phase 1 trial registration lists chronic weight management as its only condition. More tellingly, the study excludes anyone with a prior diagnosis of type 1 or type 2 diabetes. Diabetes is the indication for ASC30, Ascletis's oral GLP-1 agonist, which has a dedicated phase 2 and a diabetes-inclusive phase 3 — not for ASC35.
What is a Self-Assembling Lipid Depot?
A formulation strategy rather than a change to the molecule, and the distinction matters. Long-acting peptides are usually made long-acting by chemistry — attaching a fatty acid so the peptide binds albumin, which is how semaglutide and tirzepatide achieve weekly dosing. Ascletis's approach instead keeps the peptide and changes what it is dissolved in: a low-viscosity solution of lipids, biocompatible organic solvents and drug, injectable through a needle as fine as 29 gauge, which transforms into a gel-like depot in the tissue after injection and releases slowly. The company calls the underlying technology its Ultra-Long-Acting Platform. In non-human primates the observed half-life was about 14 days, roughly six times that reported for tirzepatide's subcutaneous formulation, with a projected human half-life of 30 days or more — a projection, not a measurement.
What is ASC36_35FDC?
A fixed-dose co-formulation of ASC35 with ASC36, Ascletis's amylin receptor agonist, in a single once-monthly injection — and arguably the more important programme of the two. Combining an incretin with an amylin analogue is the strategy behind CagriSema, which pairs semaglutide with cagrilintide and reported 20.4% weight loss at 68 weeks; doing it in one monthly depot rather than a weekly injection is the differentiation Ascletis is pursuing. The company reported preclinical data at the European Association for the Study of Diabetes meeting in October 2026 showing the combination outperformed ASC35 alone in rats and non-human primates, with half-lives supporting monthly and potentially quarterly dosing. It announced phase 1 initiation in August 2026, though no trial registration for the combination has appeared on ClinicalTrials.gov.
Can I get ASC35?
No. It is in a single phase 1 study at one site in Baltimore, Maryland, recruiting 84 participants with obesity or overweight, and is not available any other way. Anything sold online as ASC35 is not ASC35 — the compound has never been outside a clinical supply chain, no sequence has been published, and there is no peer-reviewed literature on it at all.
Who ASC35 Is NOT For
- •All use outside the clinical trial. ASC35 has no established dose, no human safety data and no legal supply route.
- •Pregnancy and breastfeeding — excluded from the trial and particularly consequential for a depot formulation that cannot be withdrawn.
- •Children and adolescents — the programme enrols adults aged 18 to 65.
- •Type 1 or type 2 diabetes, which is a trial exclusion criterion rather than a safety finding, but means no data will exist in that population from this study.
- •Personal or family history of medullary thyroid carcinoma, or multiple endocrine neoplasia type 2 — a class consideration inherited from approved incretin agonists.
- •History of pancreatitis.
- •Clinically significant gastroparesis or gastric-emptying abnormality.
- •Known hypersensitivity to the compound, to incretin analogues generally, or to the lipid and solvent excipients of the depot formulation.
Drug & Supplement Interactions
No interaction data exists and none can, at this stage. The relevant considerations are class-level inferences. Incretin agonists slow gastric emptying, which can alter the absorption of co-administered oral drugs — most consequentially for narrow-therapeutic-index medicines and oral contraceptives. With conventional weekly agents this effect is largest during dose escalation; how it behaves under a monthly depot with gradual release is unknown and is one of the more interesting open questions about this formulation. Combination with insulin or sulfonylureas raises hypoglycaemia risk, since the incretin's insulinotropic effect is glucose-dependent while the partner drug's is not — though as a peptide given to people explicitly without diabetes, that scenario does not currently arise for ASC35. As a peptide, ASC35 would be expected to be degraded by peptidases rather than cytochrome P450 enzymes, so pharmacokinetic interactions through metabolic competition are unlikely. The excipients are a less familiar question: a lipid and organic-solvent depot is a different exposure from a simple aqueous peptide solution, and what it does to local tissue or to co-administered injectables has not been described.
Safety Profile
Common Side Effects
Cautions
- • Investigational and at the earliest clinical stage. No efficacy or safety result in humans exists.
- • All preclinical efficacy and pharmacokinetic figures are company-reported, not peer-reviewed, and include head-to-head comparisons against competitor drugs run by the sponsor — the weakest form of comparative evidence.
- • Standard GLP-1 and GIP class precautions apply by inference, including the thyroid C-cell tumour warning carried by approved agents in this class, pancreatitis and gallbladder events. These are inferences from the class, not findings about ASC35.
- • A depot designed to release over a month or more cannot be withdrawn if an adverse event, pregnancy or surgery intervenes. For a first-in-human programme this is a meaningful difference from a weekly injection, and it is why single-ascending-dose cohorts precede multiple-ascending-dose cohorts with long follow-up.
- • No dose levels have been disclosed for any cohort, so nothing can be said about the exposure range being tested.
What We Don't Know
Essentially everything clinical: tolerability, the dose range, whether the projected 30-day human half-life is achieved, and whether monthly exposure produces the same efficacy as weekly dosing of an established agent. Beyond that, two structural questions. Whether a depot releasing over a month can avoid the concentration peaks that drive nausea, or whether the slow onset simply moves the problem. And whether 'ASC35' in the oral programme is the same molecule as the injectable — the company's own naming is not consistent on this point.
Legal Status
United States
Investigational. ASC35 is not FDA-approved and is available only through its phase 1 trial. The FDA cleared the investigational new drug application on 23 June 2026 and dosing began on 27 August 2026.
International
Investigational everywhere, with no approval or registration anywhere. The development programme is United States-first: the investigational new drug application, the trial and its single site are all American, and no Chinese registration trial for ASC35 has been identified despite the sponsor being a Chinese company.
Sports & Competition
Not named on the WADA Prohibited List — GLP-1 and GIP receptor agonists as a class appear nowhere on the 2027 List, and the metabolic modulators of S4.4 cover AMPK activators, PPARδ agonists, Rev-erbα agonists, insulins and insulin mimetics rather than incretins. S0 nonetheless applies: it prohibits at all times any pharmacological substance not addressed elsewhere on the List and with no current approval by any governmental regulatory health authority for human therapeutic use, naming drugs under clinical development among its examples. ASC35 is in phase 1 and approved nowhere, so it is prohibited under S0. That status would change on approval, at which point it would be treated as approved incretins are — not prohibited.
Regulatory status changes over time. Verify current local rules with a qualified professional.
Myths & Misconceptions
Myth
ASC35 is a weekly injection like tirzepatide.
Reality
It is designed to be monthly, and that is the whole point of the programme. The phase 1 trial's official title specifies a once-monthly formulation, and the study's active comparator is once-weekly tirzepatide — the comparison is explicitly monthly against weekly. Describing ASC35 as weekly erases its only meaningful differentiation from a drug already on the market.
Myth
ASC35 is being developed for type 2 diabetes as well as obesity.
Reality
Only obesity. The trial registration lists chronic weight management as its sole condition and excludes anyone with a prior diagnosis of type 1 or type 2 diabetes. Ascletis's diabetes asset is ASC30, which has a completed phase 2 in type 2 diabetes and a diabetes-inclusive phase 3. The assumption that any GLP-1/GIP dual agonist must be a diabetes drug comes from tirzepatide's history, not from anything about ASC35.
Myth
The preclinical numbers show ASC35 is more effective than tirzepatide.
Reality
They show that in Ascletis's own mice. A 33.6% versus 19.6% body-weight reduction in diet-induced obese mice at equimolar dosing, and roughly four-fold greater in vitro potency, are company-generated figures that have not been peer-reviewed, published in full, or replicated by anyone else. Sponsor-run head-to-head comparisons against a competitor's marketed drug are the least reliable form of comparative evidence, and rodent weight-loss magnitude has repeatedly failed to predict human results in this class.
Myth
ASC35 is approved in China, or will be approved there first.
Reality
It is approved nowhere and its development is United States-led. The investigational new drug application was cleared by the FDA, the phase 1 is a US trial at a single site in Baltimore, and no Chinese registration trial exists. The assumption that a Chinese sponsor must be pursuing a domestic-first pathway does not hold here — it is the same US-first approach Ascletis has taken with ASC30, which is now in global phase 3.
Myth
There is published research on ASC35.
Reality
There is none. A search of PubMed returns no record of ASC35 in any form — not a paper, not a case report, not a conference proceeding indexed as literature. Everything known about the molecule comes from company announcements, one conference oral presentation, and the trial registration. That is normal for a compound at this stage, and it is also why nothing about it should be treated with the confidence that a published result would earn.
Published Research
10 studiesEffectiveness, Safety and Pharmacokinetics of BGM0504, a Dual GLP-1/GIP Receptor Agonist, in Chinese Adults With Overweight or Obesity Without Diabetes: A Phase 2 Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial
Ji L et al., Diabetes Obes Metab 2026. The closest published analogue to ASC35 — a China-originated GLP-1/GIP dual agonist with peer-reviewed phase 2 human data, reporting weight reductions of 10.68%, 16.07% and 18.33% at 5, 10 and 15 mg over 24 weeks. A useful reference point for what this class delivers once it clears peer review, which ASC35 has not yet had to do.
The Paradox and Future of GLP-1/GIP Combination Therapies: Efficacy and Mechanisms
Davies I et al., Annual Review of Nutrition 2026. The best current account of the unresolved question at the centre of this class — that the GIP receptor agonist tirzepatide and the GIP receptor antagonist maridebart cafraglutide both produce beneficial metabolic effects, so the direction of GIP targeting that matters is genuinely unsettled.
Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity
Novel GLP-1-based Medications for Type 2 Diabetes and Obesity
Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight
A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings
Tirzepatide Once Weekly for the Treatment of Obesity
GIP Receptor Agonism Attenuates GLP-1 Receptor Agonist-Induced Nausea and Emesis in Preclinical Models
LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept
Phase I study of ASC35 injection, once-monthly formulation, in adults with obesity or overweight (NCT07842640)
The only primary-source record of ASC35 in humans. Randomised, double-blind, placebo-controlled single- and multiple-ascending-dose study, 84 participants, dosing began 27 August 2026 at a single site in Baltimore, completion estimated June 2027. Two details settle common misconceptions: the multiple-ascending-dose section includes a once-weekly tirzepatide active comparator arm, and the eligibility criteria exclude anyone with a prior diagnosis of type 1 or type 2 diabetes — confirming this is an obesity programme, not a diabetes one.
Quick Facts
- Class
- GLP-1 / GIP Dual Receptor Agonist
- Tier
- D
- Evidence
- Preliminary
- Safety
- Limited Data
- Updated
- Oct 2026
- Citations
- 10PubMed
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Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.