Core Viewpoint - Ascletis Pharma Inc. announced positive topline results from a Phase III open-label study of denifanstat (ASC40), a first-in-class oral fatty acid synthase (FASN) inhibitor for treating moderate-to-severe acne vulgaris, indicating a potential breakthrough in acne treatment [1] Group 1: Study Results - Denifanstat (ASC40) demonstrated a favorable safety and tolerability profile in a Phase III open-label study involving 240 patients, with most treatment-emergent adverse events (TEAEs) being mild (grade 1) or moderate (grade 2) [1] - No grade 3 or 4 adverse events or serious adverse events (SAEs) related to denifanstat (ASC40) were reported, and no deaths occurred during the study [1] Group 2: Mechanism of Action - The mechanism of action for denifanstat (ASC40) includes direct inhibition of sebum production by inhibiting de novo lipogenesis (DNL) in human sebocytes and reducing inflammation by decreasing cytokine secretion and Th17 differentiation [1] - This unique mechanism sets denifanstat (ASC40) apart from most other acne treatments, which do not address the underlying cause of acne [1] Group 3: Regulatory Progress - The New Drug Application for denifanstat (ASC40) for acne has been accepted by the China National Medical Products Administration, indicating progress towards commercialization [1] Group 4: Company Overview - Ascletis Pharma Inc. is a fully integrated biotechnology company focused on developing and commercializing potential best-in-class and first-in-class therapeutics for metabolic diseases [1] - The company utilizes proprietary technologies such as Artificial Intelligence-assisted Structure-Based Drug Discovery (AISBDD) and Ultra-Long-Acting Platform (ULAP) to develop multiple drug candidates, including small molecules and peptides [1]

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]