Ascletis Pharma said the FDA has cleared its Investigational New Drug application for ASC35, a once‑monthly subcutaneously administered GLP‑1 receptor/GIP receptor dual peptide agonist being developed for the treatment of obesity. The decision allows the company to begin a Phase I clinical trial in adults with obesity or overweight and weight‑related comorbidities.
The Phase I study is a randomized, double‑blind, placebo‑controlled trial designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ASC35 after single and multiple ascending doses in 84 participants. Eligible subjects will have a body mass index of at least 30 kg/m², or at least 27 kg/m² with weight‑related comorbidities. The trial has two parts: a single‑ascending‑dose arm testing once‑monthly ASC35 in a Self‑Assembling Lipid Depot (SALD) formulation, and a multiple‑ascending‑dose arm that will compare once‑monthly ASC35 SALD head‑to‑head against the FDA‑approved once‑weekly tirzepatide formulation.
ASC35 was discovered and developed in‑house using Ascletis’ AI‑assisted, structure‑based drug discovery technology and formulated with the company’s Ultra‑Long‑Acting Platform into the SALD depot. The SALD formulation is a low‑viscosity solution composed of lipids, biocompatible organic solvents and the active ingredient, designed for subcutaneous injection with a fine 29‑gauge needle. After injection, the solution forms a gel‑like depot in subcutaneous tissue that slowly degrades under the action of local enzymes, releasing the peptide over a period of about one month or longer.
In nonclinical work, the once‑monthly ASC35 SALD formulation showed an observed half‑life in non‑human primates roughly six times longer than that of subcutaneous tirzepatide in its authorized formulation, along with a flatter pharmacokinetic profile that the company suggests could translate into improved gastrointestinal tolerability in humans. In head‑to‑head primate studies, systemic exposure after intravenous and subcutaneous administration of ASC35 was approximately 80% and 70% higher, respectively, than for tirzepatide at comparable dosing.
A diet‑induced obese mouse study using equal molar concentrations of ASC35 and tirzepatide, in a model described as predictive of human efficacy, showed ASC35 achieving 71% greater relative efficacy on weight‑loss endpoints. In vitro, ASC35 was about four times more potent than tirzepatide at both GLP‑1 and GIP receptors, and Ascletis said the totality of preclinical data indicates that ASC35 is more efficient on a per‑milligram peptide basis. The company plans to advance ASC35 and other once‑monthly to once‑quarterly injectable peptides as part of a broader obesity pipeline.
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