Ascletis Begins Phase I Studies of Amylin Agonist ASC36 and Its GLP-1/GIP Co-Formulation for Obesity

Ascletis Pharma has initiated two phase 1 clinical studies in the US for the treatment of obesity, following recent Investigational New Drug (IND) clearances from the FDA for both candidates.¹ The first study evaluates ASC36, a once-monthly to once-quarterly amylin receptor peptide agonist administered subcutaneously. The second evaluates ASC36_35FDC, a once-monthly fixed-dose combination (FDC) injection co-formulating ASC36 with ASC35, the company's peptide GLP-1R/GIPR dual agonist.¹ Ascletis describes both candidates as potentially first-in-class within their respective categories.¹

What is the design of the two phase 1 studies?

Both phase 1 studies are randomized, double-blind, placebo-controlled trials evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics following single and multiple ascending doses, enrolling participants with obesity (BMI ≥30.0 kg/m²) or overweight (BMI ≥27.0 kg/m²) with weight-related comorbidities.¹ The ASC36 study evaluates two formulations, designated Injection A and Injection B, in 72 participants each. The ASC36_35FDC study similarly evaluates two FDC formulations, Injection A and Injection B, in 88 participants each.¹

How do ASC36 and ASC36_35FDC work?

ASC36 targets the amylin receptor, a pathway distinct from the incretin hormones (GLP-1 and GIP) that underlie most currently marketed obesity therapies. Amylin is co-secreted with insulin by pancreatic beta cells and acts on receptors in the brainstem to promote satiety, slow gastric emptying, and suppress food intake, a mechanism increasingly viewed as complementary to, rather than redundant with, GLP-1 receptor agonism.² ASC36_35FDC combines this amylin-targeting activity with ASC35's dual GLP-1R/GIPR agonism in a single injection, giving the co-formulation activity across three validated metabolic targets: amylin receptor, GLP-1R, and GIPR.¹ Both candidates use Ascletis' Self-Assembling Lipid Depot (SALD) formulation technology, a low-viscosity solution of lipids, biocompatible organic solvents, and active pharmaceutical ingredient that can be injected subcutaneously through a fine needle as thin as 29 gauge; once administered, the solution transforms into a gel-like depot that slowly degrades under tissue enzymes, releasing drug over a month or longer.¹ In head-to-head non-human primate studies, ASC36's SALD formulation demonstrated approximately 6-fold longer observed half-life than eloralintide, supporting once-monthly to once-quarterly dosing in humans.¹

How does this compare to existing amylin/GLP-1 combination approaches?

Ascletis has positioned ASC36_35FDC against eloralintide combined with tirzepatide, citing a company-reported 29.0% week-32 weight loss figure for that combination that Ascletis attributes to an Eli Lilly abstract accepted for, but not yet presented at, EASD 2026; this figure has not been independently verified.¹ In a head-to-head diet-induced obese (DIO) rat study, Ascletis reported that ASC36_35FDC demonstrated approximately 51% greater relative body weight reduction compared to co-administration of eloralintide and tirzepatide, a regimen requiring two separate weekly injections, or eight per month, versus one monthly injection for the Ascletis co-formulation.¹ Separately, in head-to-head diet-induced obeseDIO rat studies, ASC36 monotherapy demonstrated approximately 91% and 32% greater relative body weight reduction compared to petrelintide and eloralintide monotherapies, respectively.¹ All of these comparative figures come from preclinical animal-model studies rather than human clinical data.

What did company leadership say?

Jinzi Jason Wu, PhD, founder, chairman, and chief executive officer of Ascletis, said in a company press release, "Eloralintide in combination with tirzepatide recently demonstrated 29.0% weight loss at week 32. However, two separate weekly injections are required; one for eloralintide and one for tirzepatide. This translates into eight injections per month. In contrast, ASC36_35FDC, a potentially first-in-class SQ, FDC injection which targets amylin receptor, GLP-1R and GIPR, requires only one injection per month. More exciting, ASC36_35FDC demonstrated approximately 51% greater relative body weight reduction compared to the co-administration of eloralintide and tirzepatide in a head-to-head DIO rat study. These animal models are highly predictive of human efficacy," said Wu. "As we have initiated a global Phase III program for the oral small molecule GLP-1, ASC30, I am equally pleased with our significant progress in 2026 on our once-monthly SQ peptide pipeline, evidenced by initiation of three Phase I studies in the U.S. — ASC35, ASC36 and ASC36_35FDC."¹

What else is in Ascletis' obesity pipeline?

ASC36 and ASC36_35FDC join a considerably broader Ascletis metabolic disease portfolio spanning both oral small-molecule and injectable peptide franchises.¹ The company's lead program, ASC30, is a once-daily oral small-molecule GLP-1R agonist already in a global phase 3 program for chronic weight management and diabetes.¹ ASC35, the GLP-1R/GIPR dual peptide agonist used in the ASC36_35FDC combination, received its own IND clearance and began phase 1 development earlier in 2026.³ Beyond these, Ascletis lists a range of additional fixed-dose combination candidates across the same target classes, including ASC30_48FDC and ASC30_48_39FDC (oral small-molecule GLP-1R/GIPR and GLP-1R/GIPR/amylin combinations), ASC39 (an oral small-molecule amylin receptor agonist), ASC37 (a GLP-1R/GIPR/GCGR triple peptide agonist), and ASC36_37FDC (a once-monthly subcutaneous quadruple peptide agonist combining ASC36 with ASC37).¹ Ascletis has not disclosed an expected timeline for initial phase 2 data readouts from either study announced today.

References

1. Ascletis announces initiation of two Phase I studies in U.S. for the treatment of obesity: ASC36 once-monthly injection, an amylin receptor peptide agonist, and ASC36_35FDC once-monthly injection, a co-formulation of ASC36 and GLP-1R/GIPR peptide agonist ASC35. News release. PR Newswire. August 10, 2026. Accessed August 10, 2026.
2. Boyle CN, Lutz TA, Le Foll C. Amylin - its role in the homeostatic and hedonic control of eating and recent developments of amylin analogs to treat obesity. Mol Metab. 2018;8:203-210. doi:10.1016/j.molmet.2017.11.009
3. Ascletis announces U.S. FDA IND clearance for Phase I study of once-monthly subcutaneously administered GLP-1R/GIPR dual peptide agonist, ASC35, for the treatment of obesity. News release. PR Newswire. June 23, 2026. Accessed August 10, 2026.