Core Insights - Ascletis Pharma Inc. has received Investigational New Drug (IND) clearance from the U.S. FDA for its Phase II study of ASC30, an oral small molecule GLP-1 receptor agonist for type 2 diabetes [2][5] - The Phase II study will evaluate the efficacy, safety, and tolerability of ASC30 over 13 weeks, with enrollment expected to begin in Q1 2026 [2][3] Group 1: Phase II Study for Diabetes - The Phase II study is a 13-week, randomized, double-blind, placebo-controlled, multi-center trial involving approximately 100 participants with type 2 diabetes [2][3] - Primary endpoint includes mean change from baseline in HbA1c, while secondary endpoints include changes in fasting blood glucose and body weight [2][3] - Participants will be randomly assigned to receive either ASC30 at doses of 40 mg, 60 mg, or 80 mg, or matching placebo tablets [2][3] Group 2: ASC30 Efficacy in Obesity - A recently completed Phase II study for ASC30 demonstrated placebo-adjusted weight loss of 7.7% in participants with obesity or overweight [3] - The study showed statistically significant and clinically meaningful weight reductions of 5.4%, 7.0%, and 7.7% for doses of 20 mg, 40 mg, and 60 mg, respectively [3] - ASC30 exhibited better gastrointestinal tolerability compared to other treatments, with a total treatment discontinuation rate due to adverse events of 4.8% [3] Group 3: Company Overview - Ascletis Pharma Inc. is a fully integrated biotechnology company focused on developing therapeutics for metabolic diseases [5] - The company utilizes proprietary technologies such as Artificial Intelligence-Assisted Structure-Based Drug Discovery and Ultra-Long-Acting Platform to develop drug candidates [5] - ASC30 is part of a broader pipeline that includes other candidates targeting chronic weight management and metabolic diseases [5]

Core Viewpoint - Ascletis Pharma Inc. has selected ASC37 oral tablets as a clinical development candidate for obesity treatment, leveraging its proprietary Peptide Oral Transport ENhancement Technology (POTENT) to achieve significantly higher oral bioavailability compared to existing treatments [4][5][6]. Group 1: Product Development - ASC37 oral tablets achieved an average absolute oral bioavailability of 4.2%, which is approximately 9-, 30-, and 60-fold higher than semaglutide, tirzepatide, and retatrutide, respectively, in head-to-head non-human primate (NHP) studies [6]. - The drug exposure of ASC37, measured by the area under the curve (AUC), was approximately 57-fold greater than that of retatrutide in NHP studies [2][6]. - The average observed half-life of ASC37 oral tablets was approximately 56 hours, supporting once daily and less frequent oral dosing [2][7]. Group 2: Clinical Development Timeline - The company plans to submit an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (FDA) for ASC37 oral tablets in the second quarter of 2026 [3][4]. - A conference call will be hosted by the company in Mandarin on December 1, 2025, to discuss further developments [3][9]. Group 3: Technological Innovation - ASC37 is developed using Ascletis' Artificial Intelligence-Assisted Structure-Based Drug Discovery (AISBDD) and is a GLP-1R, GIPR, and GCGR triple peptide agonist, demonstrating in vitro activity that is approximately 5-, 4-, and 4-fold more potent than retatrutide for GLP-1R, GIPR, and GCGR, respectively [5][8]. - The selection of ASC37 for clinical development highlights the company's strong R&D capabilities and commitment to addressing unmet needs in obesity treatment [8]. Group 4: Company Overview - Ascletis Pharma Inc. is a fully integrated biotechnology company focused on developing and commercializing therapeutics for metabolic diseases, utilizing proprietary technologies including AISBDD and POTENT [10]. - The company has developed multiple drug candidates, including ASC30, ASC36, ASC35, and ASC37, targeting chronic weight management [10].

Core Insights - Ascletis Pharma Inc. has announced the co-formulation of ASC36, a once-monthly amylin receptor agonist, and ASC35, a once-monthly GLP-1R/GIPR dual agonist, for clinical development targeting obesity [5][6] Pharmacokinetics and Efficacy - The co-formulation of ASC36 and ASC35 demonstrated a comparable pharmacokinetic profile to the individual dosing of ASC36 and ASC35 in non-human primate studies, supporting once-monthly subcutaneous administration [7] - ASC36 monotherapy showed approximately 32% greater relative body weight reduction compared to eloralintide monotherapy in diet-induced obese (DIO) rat studies, while ASC35 monotherapy exhibited approximately 71% greater relative body weight reduction compared to tirzepatide monotherapy in DIO mouse studies [2][8] - The co-formulation of ASC36 and ASC35 resulted in approximately 51% greater relative body weight reduction compared to the co-formulation of eloralintide and tirzepatide in DIO rat studies [3][9] Stability and Formulation - The co-formulation of ASC36 and ASC35 exhibited excellent chemical and physical stability, with no aggregation or precipitation at neutral pH, which is crucial for maintaining potency and reducing immunogenicity risks [6][3] Regulatory and Future Plans - The company plans to submit an Investigational New Drug Application (IND) to the U.S. FDA for the co-formulation of ASC36 and ASC35 in the second quarter of 2026 [4][5] - A conference call is scheduled for November 13, 2025, to discuss further developments [12] Technological Advancements - Ascletis utilized its proprietary Artificial Intelligence-Assisted Structure-Based Drug Discovery (AISBDD) and Ultra-Long-Acting Platform (ULAP) technologies to develop ASC36 and ASC35, enabling the design of multiple once-monthly subcutaneous ultra-long-acting peptides [6][11]

Core Insights - Ascletis Pharma Inc. is set to present data from its Phase Ib clinical study of the oral GLP-1 receptor agonist ASC30 at the 61st EASD Annual Meeting in Vienna, Austria [1][2] - The company is on track to report topline data from a Phase IIa clinical study of ASC30 in participants with obesity or overweight by the fourth quarter of 2025 [1] Group 1: Clinical Study and Presentation - The 28-day multiple ascending dose study of ASC30 demonstrated superior weight loss in participants with obesity [2] - The short oral discussion will take place on September 16, 2025, from 12:00 to 13:00 CEST, with presentation number 827 [2] Group 2: Product Information - ASC30 is a new chemical entity (NCE) with unique properties allowing for both oral tablet and subcutaneous injection administration, protected by U.S. and global patents until 2044 [3] Group 3: Company Overview - Ascletis Pharma Inc. focuses on developing and commercializing therapeutics for metabolic diseases, utilizing its proprietary AI-assisted drug discovery platform [5] - The company is listed on the Hong Kong Stock Exchange under the ticker 1672.HK [5]

Core Insights - Ascletis Pharma Inc. announced promising efficacy results from a study combining ASC47, a muscle-preserving weight loss drug candidate, with tirzepatide in diet-induced obese (DIO) mice [3][9] Group 1: Efficacy Results - The combination of ASC47 low dose with tirzepatide resulted in an 87% greater reduction in body weight compared to tirzepatide monotherapy, with average total body weight reductions of 38.1% versus 20.4% respectively [1][5] - ASC47 low dose combined with tirzepatide demonstrated a statistically significant increase in efficacy compared to ASC47 low dose combined with semaglutide, achieving 87% weight loss versus 55% [1][5] Group 2: Body Composition Restoration - The combination therapy restored the body composition of obese mice to levels similar to healthy non-obese mice, with total muscle mass percentages of 60.4% for the combination group compared to 62.0% for healthy controls [2][8] - Tirzepatide monotherapy did not restore body composition to healthy levels, indicating the potential superiority of the ASC47 and tirzepatide combination [8] Group 3: Drug Properties - ASC47 is a first-in-class, adipose-targeted, once-monthly subcutaneously injected thyroid hormone receptor beta (THRβ) selective small molecule agonist, developed in-house by Ascletis [4] - The drug's unique properties allow for high drug concentrations in adipose tissue, which may contribute to its efficacy in weight loss [4]

Core Insights - Ascletis Pharma Inc. has completed enrollment for its 13-week Phase IIa study of ASC30, a small molecule oral GLP-1 receptor agonist aimed at treating obesity, with 125 participants enrolled in just over one month [2][3]. Group 1: Study Details - The Phase IIa study is randomized, double-blind, placebo-controlled, and multi-center, focusing on participants with obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m² but < 30 kg/m²) who have at least one weight-related comorbidity [3][4]. - Two oral formulations of ASC30 are being evaluated: formulation 1 (ASC30 tablets) and formulation 2 (ASC30 tablets A1), with a primary endpoint of mean percentage body weight change from baseline at Week 13 [3][4]. - The study protocol starts with a low dose of 1 mg for both formulations, with weekly titrations to maintenance doses of 20 mg and 40 mg for formulation 1, and 20 mg, 40 mg, and 60 mg for formulation 2 [3]. Group 2: Product Information - ASC30 is a first and only investigational small molecule GLP-1R biased agonist, designed for both once-daily oral and once-monthly subcutaneous injection dosing options for obesity treatment [4][5]. - The compound has U.S. and global patent protection until 2044, ensuring its exclusivity in the market [5]. Group 3: Company Overview - Ascletis Pharma Inc. is a fully integrated biotechnology company focused on developing and commercializing therapeutics for metabolic diseases, utilizing proprietary platforms for drug discovery [6]. - The company is listed on the Hong Kong Stock Exchange under the ticker 1672.HK [6].

Core Insights - Ascletis Pharma Inc. has initiated a 12-week Phase IIa study in the U.S. for its once-monthly subcutaneous (SQ) depot formulation of the small molecule GLP-1 receptor agonist ASC30, targeting participants with obesity or overweight and at least one weight-related comorbidity [3][6] - The ASC30 formulation has demonstrated a 36-day half-life in a Phase Ib study, supporting its monthly administration [4][5] - Topline data from the Phase IIa study is expected in the first quarter of 2026 [2][6] Company Overview - Ascletis Pharma Inc. is a biotechnology company focused on developing and commercializing therapeutics for metabolic diseases, utilizing its proprietary Artificial Intelligence-Assisted Structure-Based Drug Discovery (AISBDD) Platform and Ultra-Long-Acting Platform (ULAP) [9][10] - ASC30 is a unique investigational GLP-1R biased small molecule agonist that can be administered both orally and subcutaneously, with patent protection until 2044 [8][10] Study Details - The Phase IIa study is randomized, double-blind, placebo-controlled, and multi-center, involving approximately 65 participants with obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m² but < 30 kg/m²) [6] - The study consists of three cohorts with different doses to evaluate safety, tolerability, and efficacy [6] Technical Insights - The ultra-long-acting SQ depot formulation of ASC30 has a peak-to-trough ratio of less than 2:1, which is critical for achieving acceptable tolerability for SQ dosing of incretin drugs [2][5] - ASC30 is the only once-a-month incretin in clinical development with a half-life greater than the intended dosing interval, which is essential for optimal tolerability [5]