Ascletis Pharma completes dosing in U.S. ASC47-semaglutide study for obesity treatment

Ascletis Pharma Inc. (HKEX: 1672) has completed dosing of all 28 participants in its U.S.-based ASC47-103 clinical study evaluating a once-monthly injectable thyroid hormone receptor beta (THRβ) agonist, ASC47, in combination with semaglutide for the treatment of obesity. The randomized, double-blind, placebo-controlled study is designed to assess safety, tolerability, and preliminary efficacy at day 29. Enrollment was completed in under two months since the trial began in May 2025, underscoring strong patient and investigator interest in next-generation combination therapies for weight management. Topline results are expected in the fourth quarter of 2025, which could provide an early indication of the drug’s potential to compete with or complement established GLP-1 receptor agonists.

The Hong Kong-listed biotechnology company has positioned this combination study as a cornerstone of its obesity drug pipeline. Its rapid enrollment reflects a broader market interest in differentiated weight-loss solutions, especially as GLP-1 monotherapies face scrutiny over long-term muscle mass loss and adherence issues due to weekly injections.

What are the key design features of the ASC47-103 study and how does it integrate semaglutide with THRβ modulation?

The ASC47-103 study (NCT06972992) is being conducted in the United States and targets adults with obesity (BMI ≥30 kg/m²) who do not have type 2 diabetes. Participants are divided into three cohorts receiving single ascending doses of ASC47 at 10 mg, 30 mg, or 60 mg, or a placebo, delivered via subcutaneous injection. In parallel, each participant is administered four once-weekly doses of semaglutide at 0.5 mg. The primary objective is to evaluate safety and tolerability, while secondary endpoints focus on body weight reduction and other efficacy signals by day 29.

The study design reflects Ascletis Pharma’s strategy to test a low-dose GLP-1 regimen in combination with ASC47’s adipose-targeting properties. By optimizing dose synergy, the company aims to achieve clinically meaningful weight loss while reducing the gastrointestinal side effects typically associated with higher GLP-1 doses.

How does ASC47 differ from existing GLP-1 therapies and what makes it a potential market disruptor?

ASC47 is an adipose-targeted, ultra-long-acting small molecule THRβ agonist developed entirely in-house by Ascletis Pharma. Its pharmacokinetic profile, featuring a half-life of up to 40 days as demonstrated in an earlier Phase Ib study (NCT06427590), supports once-monthly dosing. Unlike GLP-1 receptor agonists that primarily act through appetite suppression and delayed gastric emptying, ASC47 is designed to directly target adipose tissue, leading to more pronounced fat mass reduction while preserving lean muscle mass.

Preclinical evidence from diet-induced obese mouse models showed that ASC47 achieved a 63.5% reduction in fat mass, outperforming semaglutide’s 39.6% and tirzepatide’s 50.4%. Moreover, a combination of low-dose ASC47 with semaglutide resulted in a 56.7% greater reduction in body weight compared to semaglutide monotherapy while preserving muscle composition. These differentiated attributes have sparked analyst interest, as the current obesity treatment market is increasingly focused on therapies that balance efficacy with muscle preservation.

What are institutional investors and analysts saying about Ascletis Pharma’s obesity pipeline prospects?

Institutional sentiment toward Ascletis Pharma’s obesity pipeline has been cautiously optimistic. Analysts have noted that combining THRβ agonism with GLP-1 modulation could address the unmet need for muscle-preserving weight-loss therapies. While semaglutide and tirzepatide have set a high efficacy benchmark, both drugs have been associated with lean mass reduction, which limits their long-term use in specific patient populations such as older adults or those with sarcopenia risks.

Market observers have also pointed out that Ascletis Pharma’s rapid enrollment in the ASC47-103 study reflects the strong demand for novel obesity treatments in clinical settings. However, institutional investors remain focused on the forthcoming Q4 2025 topline data, which will determine whether ASC47’s preclinical promise translates into human efficacy.

How does this clinical milestone align with Ascletis Pharma’s broader strategy and financial outlook?

The ASC47-103 study is part of Ascletis Pharma’s broader obesity and metabolic disease pipeline, which also includes ASC30, a small molecule GLP-1 receptor agonist being developed as a once-daily oral tablet and once-monthly injectable. By leveraging its proprietary Artificial Intelligence-Assisted Structure-Based Drug Discovery (AISBDD) Platform and Ultra-Long-Acting Platform (ULAP), the Hong Kong-based biotechnology firm aims to establish a differentiated position in a crowded obesity market dominated by injectable biologics.

From a financial perspective, Ascletis Pharma has yet to disclose half-yearly revenue details for 2025, but investor attention has already shifted toward potential value inflection points in its metabolic franchise. Market activity following clinical updates suggests a growing expectation that positive ASC47 data could strengthen the company’s competitive positioning, attract licensing or partnership discussions, and drive medium-term valuation gains.

What is the expected timeline for next steps and how could it impact the company’s market position?

Topline results from the ASC47-103 study are expected in the fourth quarter of 2025. If the safety and preliminary efficacy data align with preclinical outcomes, Ascletis Pharma is likely to advance into a multiple ascending dose Phase II trial by early 2026. Analysts believe that a successful readout could not only accelerate this transition but also position the company as a credible competitor to established players in the obesity treatment market, particularly in Asia where monthly dosing regimens may offer strong adherence advantages.

The company’s progress will be closely watched by institutional investors, as the obesity treatment market continues to expand and competition intensifies among both established GLP-1 developers and emerging biotech challengers.