Ascletis Pharma Inc. （股份代號：1672） 香港交易及結算所有限公司及香港聯合交易所有限公司對本公告的內容概不負責，對其準確性 或完整性亦不發表任何聲明，並明確表示，概不就因本公告全部或任何部分內容所產生或因依 賴該等內容而引致的任何損失承擔任何責任。 歌禮製藥有限公司 （於開曼群島註冊成立的有限公司） － 在飲食誘導肥胖(DIO)小鼠模型中，低劑量ASC47與新型GLP-1R/GIPR雙受 體激動劑多肽ASC31聯用治療14天後，小鼠體重下降44.8%。 － 在DIO小鼠模型中，低劑量ASC47與ASC31聯用的療效（減重44.8%）優於低 劑量ASC47與替爾泊肽聯用（減重38.1%），療效差異具有統計學顯著性。 該DIO小鼠研究旨在對比低劑量ASC47（9 mg/kg，皮下）聯合ASC31（3 nmol/kg， 皮下）與低劑量ASC47（9 mg/kg，皮下）聯合替爾泊肽（3 nmol/kg，皮下）的減 重療效，治療期為14天。結果顯示，ASC47聯合ASC31治療DIO小鼠平均減重 44.8%，比ASC47聯合替爾泊肽(38.1%)多減重17.6%（ p =0.02）。 「我們的 ...

Core Viewpoint - The company reported significant revenue growth and advancements in its drug pipeline, particularly in obesity treatment, indicating strong research and development capabilities and a commitment to addressing unmet clinical needs [1][2]. Financial Performance - Total revenue reached RMB 104 million, representing a year-on-year increase of 111.4% [1] - Research and development costs amounted to RMB 147 million, up 10.9% year-on-year [1] - Loss attributable to equity shareholders was RMB 87.95 million, a decrease of 32.5% compared to the previous year [1] - Loss per share was 9.14 cents [1] Drug Development Progress - ASC30, an oral medication for obesity, showed a significant average weight reduction of 6.5% after 28 days in a U.S. Phase Ib study, positioning it as a potential best-in-class treatment for obesity [1] - The company rapidly enrolled 125 participants in a U.S. Phase IIa study for ASC30, demonstrating efficient execution in clinical trials [2] - ASC30 also showed a 36-day half-life in a single subcutaneous injection study, supporting less frequent dosing [2] - ASC47, another obesity treatment, exhibited a 40-day half-life and has completed participant enrollment for a study combining it with semaglutide [2] - ASC50, an oral IL-17 inhibitor, has entered Phase I clinical trials with initial dosing completed [2] - ASC40, a daily oral FASN inhibitor for acne treatment, demonstrated statistically significant improvements in all primary and secondary endpoints in a Phase III study, indicating its potential for a breakthrough in acne treatment [2] Research and Development Commitment - The achievements highlight the company's strong R&D capabilities and commitment to developing best-in-class and first-in-class drugs to meet long-term clinical needs [2]

Core Viewpoint - The company reported a significant increase in other income and a reduction in R&D expenses, while also showing a decrease in losses, indicating a positive trend in financial performance and ongoing development of promising drug candidates [1][2][3] Financial Performance - The company achieved other income of RMB 19.908 million for the six months ending June 30, 2025, representing a year-on-year increase of 40.7% [1] - R&D expenses amounted to RMB 105 million, a decrease of 16.61% year-on-year [1] - The net loss for the period was RMB 130 million, which is a 9.79% reduction compared to the previous year [1] - As of June 30, 2025, the company had current assets of RMB 762 million, including cash and cash equivalents of RMB 677 million, indicating strong financial reserves for future R&D projects [1] Drug Development - LAE102, a monoclonal antibody targeting ActRIIA, has shown potential for muscle regeneration and weight control, with successful completion of the single ascending dose part of Phase I clinical trials for obesity treatment in China by the end of 2024 [1] - The company initiated a Phase III clinical trial (AFFIRM-205) in May 2024 for LAE002 (afuresertib), an oral AKT inhibitor, in combination with Fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer patients [2] - The Phase III trial is a multi-center, randomized, double-blind, placebo-controlled study aimed at evaluating the anti-tumor efficacy and safety of the combination therapy, with plans to complete subject enrollment by Q4 2025 and submit a New Drug Application (NDA) in H1 2026 [2] - The company has submitted an IND application for LAE103 to the FDA as of June 30, 2025, with plans to initiate Phase I clinical trials in the second half of 2025 [3]

Core Viewpoint - The company reported a significant increase in other income due to government subsidies, while R&D expenses decreased, leading to a reduced loss compared to the previous year [1][2]. Financial Performance - Other income reached RMB 19.908 million, a year-on-year increase of 40.7% [1] - R&D expenses amounted to RMB 105 million, a decrease of 16.61% year-on-year [1] - The loss for the period was RMB 130 million, a reduction of 9.79% compared to the previous year [1] - As of June 30, 2025, current assets totaled RMB 762 million, with cash and cash equivalents at RMB 677 million, indicating strong financial reserves for future R&D projects [1] Clinical Development - LAE102, a monoclonal antibody targeting ActRIIA, has shown potential for muscle preservation and weight control, with successful completion of the single ascending dose part of Phase I clinical trials for obesity treatment in China by December 2024 [1] - The company initiated a Phase III clinical trial (AFFIRM-205) in May 2024 for LAE002 (afuresertib) in combination with Fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer patients [2] - The Phase III trial is a multi-center, randomized, double-blind, placebo-controlled study aimed at evaluating the efficacy and safety of the combination therapy, with plans to complete subject enrollment by Q4 2025 and submit a New Drug Application (NDA) in H1 2026 [2] - The company is in discussions with potential partners to accelerate the regulatory approval and commercialization of LAE002 and LAE001 [2] Future Plans - The IND application for LAE103 was submitted to the FDA by the end of June 2025, with plans to initiate Phase I clinical trials in the second half of 2025 [3] - The company aims to evaluate the efficacy and safety of monoclonal antibodies targeting ActRIIA and ActRIIB through the Phase I clinical study of LAE103 [3] - Plans are also in place to advance LAE123 to Phase I clinical trials in 2026 [3]

Core Viewpoint - The stock of Gilead Sciences-B (01672) rose over 6%, reaching 15.46 HKD, following the announcement of promising results from a study on its obesity treatment candidate ASC47 combined with teriparatide [1] Group 1: Drug Development - ASC47 is a novel, fat-targeting, once-monthly subcutaneous thyroid hormone receptor β (THRβ) selective small molecule agonist developed by the company [1] - The study involved DIO mice and compared the efficacy of low-dose ASC47 (9 mg/kg, single dose) combined with teriparatide (3 nmol/kg, subcutaneous, daily) against teriparatide monotherapy [1] - Results showed that the combination therapy led to an average weight loss of 38.1% in mice, compared to 20.4% for the teriparatide monotherapy, indicating an 87% greater weight reduction with the combination [1] Group 2: Comparative Efficacy - In comparison, the combination of low-dose ASC47 with semaglutide resulted in a weight loss that was 55% greater than semaglutide monotherapy, indicating that the efficacy of ASC47 combined with teriparatide is superior [2] - The statistical significance of the difference in efficacy between ASC47 combined with semaglutide and teriparatide was noted (p=0.006) [2]

智通财经APP讯，歌礼制药-B(01672)发布公告，同类首创的治疗肥胖症的减重不减肌候选药物ASC47与 替尔泊肽联用在饮食诱导肥胖(DIO)小鼠研究中显示出令人鼓舞的疗效结果。 该DIO小鼠研究旨在对比低剂量ASC47(9mg/kg，单次给药)联合替尔泊肽(3nmol/kg，皮下，每日一次)与 替尔泊肽单药疗法(3nmol/kg，皮下，每日一次)的疗效。DIO小鼠的治疗期为14天。结果显示，低剂量 ASC47联合替尔泊肽的疗效优于替尔泊肽单药疗法，联合用药的小鼠平均总体重下降38.1%，替尔泊肽 单药治疗的小鼠则为20.4%，ASC47联合替尔泊肽比替尔泊肽单药疗法多减重87%(表1)。相比之下，在 DIO小鼠研究中，联合司美格鲁肽与司美格鲁肽单药疗法相比多减重55%，即低剂量ASC47联合司美格 鲁肽的疗效弱于联合替尔泊肽的疗效，具有统计学显著性(p=0.006)。 低剂量ASC47与替尔泊肽联用使肥胖小鼠身体成分恢复至健康非肥胖小鼠的水平。治疗结束时，经低剂 量ASC47与替尔泊肽联用治疗的肥胖小鼠的总肌肉量占总体重的百分比(60.4%)与健康非肥胖小鼠 (62.0%)相当，意味着实现健康减重。替尔泊 ...

Ascletis Pharma Inc. 歌禮製藥有限公司 （於開曼群島註冊成立的有限公司） 香港交易及結算所有限公司及香港聯合交易所有限公司對本公告的內容概不負責，對其準確性 或完整性亦不發表任何聲明，並明確表示，概不就因本公告全部或任何部分內容所產生或因依 賴該等內容而引致的任何損失承擔任何責任。 | 表1. 低劑量ASC47與替爾泊肽聯用療效勝過與司美格魯肽聯用 | | --- | | | | 總體重 | 聯用與單藥相比， | | --- | --- | --- | --- | | 組別 | 給藥 | 相對基線的變化 | 增加的減重效果 | | 經替爾泊肽治療的 | 替爾泊肽， | | | | 肥胖小鼠 | 3 nmol/kg， | -20.4% | – | | | SQ，QD | | | | 經低劑量ASC47與 | ASC47， | | | | 替爾泊肽聯用治 | 9 mg/kg， | | | | 療的肥胖小鼠 | SQ，單次給藥 | -38.1% | | | | + | （ <0.0001 vs替爾 p | 87% | | | 替爾泊肽， | 泊肽單藥療法） | | | | 3 nmol/kg， ...

Core Viewpoint - The World Health Organization (WHO) is set to release new guidelines for the treatment of adult obesity using GLP-1 receptor agonists (GLP-1 RAs), marking a significant shift in its approach to addressing the global obesity crisis [1][3]. Group 1: Guidelines and Recommendations - The guidelines aim to clarify the clinical indications, applications, and management pathways for GLP-1 RAs in treating adult obesity, potentially being the first formal recommendation of weight-loss medications by WHO [1][3]. - An independent development group (GDG) composed of experts from various fields is leading the guideline formulation to ensure high standards of scientific validity and applicability [1]. Group 2: Obesity as a Global Health Crisis - WHO has defined obesity as a global health crisis, with over 1 billion people affected worldwide, and approximately 70% of these individuals living in low- and middle-income countries (LMIC) [5]. - The rising prevalence of obesity is linked to various chronic diseases, with about 90% of obese patients having at least one comorbid condition [1][5]. Group 3: GLP-1 Drugs and Market Potential - GLP-1 drugs are gaining recognition for their dual ability to lower blood sugar and control weight, with a projected increase in potential user coverage from 4% in 2023 to 12% by 2025 [3]. - WHO plans to include GLP-1 receptor agonists in the Essential Medicines List (EML), emphasizing their safety, efficacy, and affordability, particularly for low- and middle-income countries [3][4]. Group 4: Accessibility and Cost Concerns - WHO highlights the need to improve the accessibility of weight-loss medications in LMICs, where most obese patients reside [4]. - The initial high cost of GLP-1 drugs, exceeding $1,000 per month, poses a significant barrier for many patients, despite some price reductions in certain markets [5][7].

Core Viewpoint - The company has completed a randomized, double-blind, placebo-controlled study assessing the safety, tolerability, and preliminary efficacy of ASC47 in obese subjects without type 2 diabetes, with results expected in Q4 2025 [1] Group 1: Product Overview - ASC47 is a long-acting subcutaneous thyroid hormone receptor β selective small molecule agonist developed by the company, designed to target fat tissue and achieve high drug concentrations in adipose tissue in a dose-dependent manner [1] - In a diet-induced obesity mouse model, ASC47 demonstrated a significant ability to reduce fat compared to semaglutide and tirzepatide, with notable statistical significance [1] Group 2: Clinical Study Insights - The study involved 28 subjects, and ASC47 showed a half-life of up to 40 days in a Phase Ib study of obese subjects [1] - In head-to-head comparisons in a diet-induced obesity mouse model, low-dose ASC47 combined with semaglutide resulted in a 56.7% greater weight reduction compared to semaglutide alone, without muscle loss [1]

Core Viewpoint - The STEP 5 trial demonstrates that semaglutide 2.4 mg is effective for long-term weight management in obese adults without type 2 diabetes, showing significant and sustained weight loss over a two-year period [2][3][4]. Group 1: Trial Overview - STEP 5 is a phase 3b randomized, double-blind, placebo-controlled trial involving 304 adults with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) [3][4]. - Participants were assigned to receive either weekly subcutaneous injections of 2.4 mg semaglutide or a placebo, alongside a low-calorie diet and increased physical activity, for 104 weeks [3][4]. - The primary endpoint was the percentage change in weight and the proportion of participants achieving a weight loss of ≥5% by week 104 [3]. Group 2: Weight Loss Results - The semaglutide group experienced a weight loss of -15.2%, compared to -2.6% in the placebo group [4]. - 77.1% of participants in the semaglutide group lost at least 5% of their body weight, while only 34.4% in the placebo group achieved this [4]. Group 3: Safety and Side Effects - Common adverse events associated with semaglutide included nausea, diarrhea, vomiting, constipation, and abdominal pain [6]. - The safety profile of semaglutide in STEP 5 was consistent with previous trials, with 5.9% of patients discontinuing treatment due to adverse events [6]. Group 4: Health Improvements - Significant improvements were observed in waist circumference (-14.4 cm in the semaglutide group vs. -5.2 cm in the placebo group) and systolic blood pressure (-5.7 mmHg vs. -1.6 mmHg) [7]. - Semaglutide also improved various metabolic health markers, including HbA1c, fasting blood glucose, and lipid profiles [7]. Group 5: STEP Trial Context - The STEP program is a comprehensive phase 3 clinical development plan for semaglutide, involving approximately 4,500 overweight or obese adults across multiple trials [8].