Ascletis Pharma-B (01672) has announced that, following Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA), it has initiated two Phase 1 studies in the United States for obesity treatments. These include a once-monthly to once-quarterly next-generation amylin receptor agonist peptide, ASC36, and a subcutaneous fixed-dose combination (FDC) monthly injection, ASC36_35FDC, which combines ASC36 with the GLP-1R/GIPR dual-target agonist peptide ASC35.

The Phase 1 study for ASC36_35FDC is a randomized, double-blind, placebo-controlled trial designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ASC36_35FDC injections following single and multiple ascending doses in obese (BMI ≥30.0 kg/m²) or overweight (BMI ≥27.0 kg/m²) individuals with weight-related comorbidities. This Phase 1 study will also assess two different FDC formulations: Injection A, conducted in 88 subjects, and Injection B, conducted in another 88 subjects. Both Injections A and B consist of two ultra-long-acting agonist peptides: the amylin receptor agonist peptide ASC36 and the GLP-1R/GIPR dual-target agonist peptide ASC35.

The Phase 1 trial for ASC36 is a randomized, double-blind, placebo-controlled clinical study aimed at evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of ASC36 injections following single and multiple ascending doses in obese (BMI ≥30.0 kg/m²) or overweight (BMI ≥27.0 kg/m²) subjects with weight-related comorbidities. This Phase 1 study will also assess two different formulations: Injection A, conducted in 72 subjects, and Injection B, conducted in another 72 subjects.

"Recent data for eloralintide combined with tirzepatide showed a 29.0% weight reduction at Week 32. However, this regimen requires two weekly injections—one of eloralintide and one of tirzepatide—equating to eight injections per month. In contrast, the potentially first-in-class subcutaneous fixed-dose combination injection ASC36_35FDC, which targets the amylin receptor, GLP-1R, and GIPR, requires just one injection per month. Even more exciting, in head-to-head diet-induced obesity (DIO) rat studies, ASC36_35FDC demonstrated a weight loss effect approximately 51% greater than the eloralintide plus tirzepatide combination (refer to the company's announcement dated November 13, 2025, for more details). These animal models are highly predictive of human efficacy," said Dr. Jinzi J. Wu, Founder, Chairman, and CEO of Ascletis. "As we advance the global Phase III clinical program for the oral small-molecule GLP-1 drug ASC30, I am equally pleased with the significant progress in 2026 for our once-monthly subcutaneous peptide pipeline, marked by the launch of three Phase I studies in the U.S. for ASC35, ASC36, and ASC36_35FDC."

Both ASC36 and ASC35 were independently developed by Ascletis using its structure-based AI-assisted drug discovery (AISBDD) technology. The once-monthly to once-quarterly formulation of ASC36 and the once-monthly combination formulation of ASC36_35FDC are self-assembled lipid depot (SALD) formulations, developed by Ascletis using its proprietary ultra-long-acting drug development platform (ULAP) technology. The SALD formulation is a low-viscosity solution composed of lipids, biocompatible organic solvents, and the active pharmaceutical ingredient (API). This low-viscosity solution can be easily injected into subcutaneous tissue using a pen injector or auto-injector equipped with a needle as fine as 29G (gauge). After subcutaneous injection, the solution transforms into a gel-like depot in the tissue. Under the action of enzymes within the tissue, the depot slowly degrades, controlling the sustained release of the API over a month or longer.

In head-to-head non-human primate studies, the observed half-life of the ASC36 SALD formulation was approximately six times that of eloralintide, supporting once-monthly to once-quarterly subcutaneous dosing in humans. In non-human primate studies, both ASC36 and ASC35 exhibited prolonged observed half-lives within the ASC36_35FDC SALD combination formulation, supporting once-monthly subcutaneous dosing in humans. Preclinical studies have established the superior efficacy of the ASC36 injection and the ASC36_35FDC combination injection. In head-to-head DIO rat studies (highly predictive of human efficacy), the weight loss effect of the amylin receptor-targeting ASC36 monotherapy was relatively improved by approximately 91% and 32% compared to petrelintide monotherapy and eloralintide monotherapy, respectively. In head-to-head DIO rat studies, ASC36_35FDC, targeting the amylin receptor, GLP-1R, and GIPR, showed a weight loss effect relatively improved by approximately 51% compared to the eloralintide plus tirzepatide combination. Both the ASC36 injection and the ASC36_35FDC combination injection exhibit superior physicochemical stability, with no fibrosis-related aggregation or precipitation near neutral pH levels.