Ascletis Announces Positive Topline Results from Its Phase III Open-Label Study of Denifanstat (ASC40), a First-in-Class, Once-Daily Oral FASN Inhibitor for Acne [Accessibility Statement] Skip Navigation- Denifanstat (ASC40), a once-daily oral fatty acid synthase (FASN) inhibitor, demonstrated favorable safety and tolerability in a Phase III open-label study- The exceptional efficacy of denifanstat (ASC40) observed in the Company's previously reported placebo-controlled Phase III trial coupled with a favora ...

Core Insights - Ascletis Pharma Inc. is advancing its investigational drug ASC30, a GLP-1 receptor agonist, into a Phase II study for type 2 diabetes, with topline data expected in Q3 2026 [2][5] Group 1: ASC30 Development - ASC30 has shown a placebo-adjusted weight loss of up to 7.7% in a completed 13-week Phase II study for obesity, demonstrating better gastrointestinal tolerability compared to other treatments [1][3] - The Phase II study for diabetes will evaluate ASC30's efficacy, safety, and tolerability, focusing on changes in HbA1c and body weight among approximately 100 participants [5][6] - ASC30 is designed for once-daily oral administration and has been developed in-house by Ascletis as a first and only investigational small molecule GLP-1R fully biased agonist [4][6] Group 2: Clinical Study Details - The obesity Phase II study involved 125 participants and reported a treatment discontinuation rate due to adverse events of 4.8% [3] - The study for diabetes is randomized, double-blind, and placebo-controlled, with participants assigned to different dosages of ASC30 [5] - The primary endpoint of the diabetes study is the mean change in HbA1c from baseline, with secondary endpoints including fasting blood glucose and body weight changes [5]

Core Insights - Ascletis Pharma Inc. has selected ASC37 injection, a next-generation GLP-1R/GIPR/GCGR triple peptide agonist, for clinical development, with an Investigational New Drug Application (IND) submission to the FDA expected in Q2 2026 [2][5]. Group 1: Product Development - ASC37 has an average observed half-life of approximately 17 days in non-human primate studies, which is 7-fold longer than retatrutide, supporting once-monthly subcutaneous dosing [1][4]. - The in vitro activity of ASC37 is approximately 5-fold, 4-fold, and 4-fold more potent than retatrutide for GLP-1R, GIPR, and GCGR, respectively [1][3]. - ASC37 is engineered for a longer half-life compared to retatrutide, allowing for a subcutaneous injection volume of one milliliter or less, which also provides manufacturing scalability advantages [3][4]. Group 2: Clinical Strategy - The company plans to initiate a Phase I study for ASC37 in the second half of 2026, as part of its strategy to enhance treatment options for obesity [5]. - ASC37 is being developed both as a monotherapy and in combination with ASC36, another peptide agonist, to address cardio-metabolic diseases including obesity and diabetes [5]. Group 3: Technological Innovation - Ascletis utilizes its proprietary Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) and Ultra-Long-Acting Platform (ULAP) technologies to design and optimize multiple once-monthly subcutaneous ultra-long-acting peptides [6][8]. - The ULAP technology allows for precise control over the release of peptides, improving clinical outcomes by reducing peak-to-trough ratios [6].

Core Insights - Ascletis Pharma Inc. announced positive topline results from a Phase I clinical trial for ASC50, an oral small molecule inhibitor targeting IL-17, indicating favorable safety, tolerability, and pharmacokinetics [3][5][7] Group 1: Clinical Trial Results - The Phase I clinical trial was randomized, double-blind, and placebo-controlled, involving 46 healthy participants who received varying doses of ASC50 [3] - ASC50 demonstrated a dose-proportional pharmacokinetic profile from 10 mg to 600 mg, with an elimination half-life ranging from 43 to 104 hours depending on the dose [1][2][8] - All adverse events reported were mild and transient, with no serious adverse events or discontinuations noted during the study [8] Group 2: Target Engagement and Efficacy - Strong target engagement was observed with elevated plasma IL-17A levels persisting until day 7 for higher doses of ASC50 [1][8] - The drug showed higher absolute oral bioavailability and longer half-life compared to another IL-17 inhibitor currently in clinical development [8] Group 3: Future Development - Based on the positive results, ASC50 is advancing to the next phase of clinical development, focusing on multiple ascending doses in participants with mild to moderate plaque psoriasis [5] - ASC50 is positioned as a potential best-in-class oral small molecule IL-17 inhibitor, developed using Artificial Intelligence-assisted Structure-Based Drug Discovery technology [6][7]

Core Insights - Ascletis Pharma Inc. has received FDA clearance for the investigational new drug (IND) application for ASC50, an oral small molecule IL-17 inhibitor aimed at treating mild-to-moderate plaque psoriasis [3][6] - ASC50 shows promising preclinical data, including higher oral exposure, longer half-life, and strong efficacy, positioning it as a potential best-in-class treatment for psoriasis [2][4] Company Overview - Ascletis is an innovative R&D driven biotech company listed on the Hong Kong Stock Exchange, focusing on metabolic and other diseases while addressing unmet medical needs globally [7] - The company utilizes an Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) platform for drug development, with ASC50 being the first oral small molecule candidate in immunology from this platform [6] Clinical Development - The Phase I clinical trial for ASC50 will be a randomized, double-blind, placebo-controlled study conducted at multiple sites in the U.S., with patient dosing expected to start in the third quarter of 2025 [5][6] - Preclinical studies indicate that ASC50 has a lower clearance rate compared to existing oral IL-17 inhibitors currently in clinical development, suggesting a potentially advantageous pharmacokinetic profile [4]