ASCLETIS-B (01672) has initiated two Phase I studies for the treatment of obesity in the United States.

ASCLETIS-B (01672) announced that following the approval of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA), it has initiated two Phase I studies in the United States to treat obesity: the once-monthly to once-quarterly next-generation incretin receptor agonist peptide ASC36, and the subcutaneous fixed-dose combination (FDC) injection ASC36_35FDC, which contains ASC36 and the dual-target agonist peptide ASC35 for GLP-1R/GIPR. The Phase I study of ASC36_35FDC is a randomized, double-blind, placebo-controlled trial aimed at evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of the ASC36_35FDC injection in obese subjects (Body Mass Index (BMI) 30.0 kg/m) or overweight subjects (BMI 27.0 kg/m) with weight-related comorbidities, after single and multiple escalating doses. This Phase I study will also assess two different fixed-dose combination (FDC) formulations: injection A with 88 subjects and injection B with 88 subjects. Both injections A and B consist of two ultra-long-acting agonist peptides: the incretin receptor agonist peptide ASC36 and the dual-target agonist peptide ASC35. The Phase I trial of ASC36 is also a randomized, double-blind, placebo-controlled clinical trial designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the ASC36 injection in obese (BMI 30.0 kg/m) or overweight subjects (BMI 27.0 kg/m) with weight-related comorbidities, after single and multiple escalating doses. This Phase I study will evaluate two different formulations as well: injection A involving 72 subjects and injection B involving 72 subjects. Recent data on the combination of Eloralintide and Tirzepatide showed a weight reduction of 29.0% at week 32. However, this regimen requires two injections per week, one of Eloralintide and another of Tirzepatide, which amounts to eight injections per month. In contrast, the subcutaneous fixed-dose combination injection ASC36_35FDC, which is expected to be a first-in-class targeting incretin receptors, GLP-1R, and GIPR, requires only one injection per month. Even more encouraging, in head-to-head studies using diet-induced obese (DIO) rats, ASC36_35FDC showed approximately a 51% greater weight loss effect compared to the combination of Eloralintide and Tirzepatide (for more information, please refer to our announcement dated November 13, 2025). These animal models have high predictive value for human efficacy, said Dr. Wu Jinzi, the founder, chairman of the board, and CEO of the company. As we initiate the global Phase III clinical program for the oral GLP-1 small molecule ASC30, I am equally pleased with our significant progress expected in 2026 for the monthly subcutaneous peptide regimen, as we have launched three Phase I studies in the United States: 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 monthly to quarterly formulation of ASC36 and the monthly FDC formulation of ASC36_35FDC are both self-assembling lipid depot (SALD) formulations, developed by Ascletis using its proprietary ultra-long-acting drug development platform (ULAP) technology. SALD formulations are low-viscosity solutions composed of lipids, biocompatible organic solvents, and active pharmaceutical ingredients (API). This low-viscosity solution can be easily injected subcutaneously using an injection pen or autoinjector equipped with a fine 29G needle. After subcutaneous injection, the solution transforms into a gel-like depot in the tissue. Under the action of enzymes within the tissue, the depot gradually degrades, controlling the release of the API for a month or longer. In head-to-head studies in non-human primates, the observed half-life of ASC36 SALD formulation was approximately six times that of Eloralintide, supporting monthly to quarterly subcutaneous dosing in humans. In studies with non-human primates, both ASC36 and ASC35 in the ASC36_35FDC SALD combination formulation exhibited a longer observed half-life, supporting monthly subcutaneous dosing in humans. Preclinical studies have established the superior efficacy of ASC36 injection and ASC36_35FDC combination injection. In head-to-head DIO rat studies (which are highly predictive of human efficacy), the ASC36 monotherapy targeting incretin receptors showed approximately 91% and 32% greater weight loss effects compared to petrelintide monotherapy and Eloralintide monotherapy, respectively. In head-to-head DIO rat studies, ASC36_35FDC, targeting the incretin receptors, GLP-1R, and GIPR, demonstrated approximately a 51% greater weight loss effect compared to the combination of Eloralintide and Tirzepatide. Both ASC36 injection and ASC36_35FDC combination injection exhibit excellent physicochemical stability, with no aggregation or precipitation due to fibrillation near neutral pH.