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].

Core Insights - Metsera, Inc. has released positive topline data from the Phase 1 clinical trial of MET-233i, an ultra-long-acting amylin analog, showing significant weight loss and favorable tolerability [1][3] Group 1: Clinical Trial Results - MET-233i demonstrated a mean placebo-subtracted weight loss of up to 8.4% at Day 36, with individual responses reaching as high as 10.2% [1][5] - The drug exhibited a 19-day observed half-life, supporting the potential for once-monthly dosing [1][5] - Gastrointestinal adverse events were mild and primarily occurred in the first week of dosing, indicating rapid tolerance onset [5] Group 2: Dosing and Administration - The trial evaluated single doses from 0.15 mg to 2.4 mg and multiple doses from 0.15 mg to 1.2 mg given weekly over five weeks [2] - Anticipated starting doses of 0.15 mg and 0.3 mg showed tolerability results comparable to placebo [5] Group 3: Future Developments - Metsera plans to advance MET-233i as a monotherapy and in combination with MET-097i, with topline data from ongoing trials expected in late 2025 [3][5] - The company is also preparing to report topline clinical data from its ultra-long-acting GIP receptor agonist, MET-034i, in combination with MET-097i, anticipated in late 2025 [3][4] Group 4: Market Reaction - Following the announcement, Metsera's stock increased by 13.24%, reaching $31.13 [4]

Group 1 - The core focus of the news is the progress of LAE102, a monoclonal antibody developed by the company for the treatment of obesity, with the first patient dosing completed in a Phase I clinical trial in the US [1][2] - The Phase I clinical trial is expected to complete its primary research phase by September 2025, while a multi-dose escalation study is ongoing in China, with preliminary data expected by the end of September 2025 [1] - The company has partnered with Eli Lilly to accelerate the global clinical development of LAE102, retaining global rights to the drug [2] Group 2 - LAE102 targets ActRIIA, a receptor important for muscle regeneration and fat metabolism, showing potential to increase muscle and reduce fat in preclinical models [1] - The combination of LAE102 with GLP-1 receptor agonists may further enhance fat reduction and significantly decrease muscle loss associated with GLP-1 receptor agonist treatment, positioning LAE102 as a high-quality weight control candidate [1]

Core Viewpoint - The article highlights the fragmented nature of the U.S. healthcare system, particularly in the context of obesity treatment and the introduction of GLP-1 drugs like Ozempic and Wegovy, which have transformed the understanding of obesity from a matter of willpower to a chronic disease linked to various serious health conditions [2][4]. Group 1: Access to GLP-1 Drugs - Access to GLP-1 drugs is severely limited for many patients due to inconsistent insurance coverage, complex pre-approval processes, and opaque drug benefit management networks [4][5]. - The high out-of-pocket cost for these drugs can exceed $1,000 per month, making them unaffordable for most individuals [4]. - The rise of compounded drugs, produced by loosely regulated supply chains, poses safety and efficacy risks as patients seek more affordable options [5]. Group 2: Impact on Healthcare Providers - The pressure from compounded drugs has led original drug manufacturers like Eli Lilly and Novo Nordisk to offer lower-cost options and telehealth services [5]. - Access to medical services is often dictated by complex insurance standards rather than patient needs or medical expertise, undermining the authority of healthcare providers [5][6]. - The bureaucratic nature of the system forces doctors to adjust diagnoses to meet arbitrary insurance criteria, which can delay necessary interventions [5]. Group 3: Systemic Issues and Public Sentiment - Efforts to regulate and lower the cost of GLP-1 drugs have been limited, with the pharmaceutical industry maintaining high prices and insurance companies reluctant to provide broad coverage [6]. - Millions of Americans seeking obesity treatment face a dilemma between financial stability and health, highlighting a critical flaw in the healthcare system [6]. - The article argues that unless the systemic flaws in healthcare are addressed, the cycle of high costs, poor outcomes, and growing public anger will continue [6].

Core Viewpoint - Septerna (SEPN.US) experienced a significant pre-market surge of 63%, reaching $10.97 with a trading volume of $65.44 million, indicating strong investor interest in the company's developments in GPCR-targeted therapies [2]. Group 1: Company Developments - Septerna is focused on developing therapies targeting G protein-coupled receptors (GPCRs), which are crucial for the absorption of chemical substances through cell membranes [2]. - Two companies are planning to initiate four potential small molecule therapy development projects targeting specific GPCRs, marking a notable collaboration in the pharmaceutical industry [4]. - Novo Nordisk is known for its weight loss drug Wegovy and is working to solidify its position in the rapidly growing obesity treatment market, projected to reach $150 billion [6]. Group 2: Market Context - GPCRs influence a wide range of physiological processes, including metabolism, secretion, cell growth, and immune responses, highlighting their importance in therapeutic development [3]. - The recent collaboration in the obesity sector follows a significant deal in March, where Roche announced plans to invest up to $5.3 billion with Zealand Pharma to develop and commercialize its obesity candidate drug [4].

Group 1 - The core viewpoint of the articles highlights Novo Nordisk's strong financial performance in Q1 2025, with significant sales growth driven by its diabetes and obesity treatment products, particularly in the Greater China region [1] - In Q1 2025, Novo Nordisk's sales increased by 19% in Danish kroner and 18% at constant exchange rates (CER), reaching 78.1 billion Danish kroner, while operating profit grew by 22% in Danish kroner and 20% at CER, totaling 38.8 billion Danish kroner [1] - Sales in the Greater China region saw a remarkable increase of 25% in Danish kroner and 22% at CER, primarily driven by the growth in obesity and diabetes treatment products [1] Group 2 - The sales of GLP-1 products for type 2 diabetes in mainland China grew by 28% in Danish kroner and 26% at CER, reflecting strong performance of the product NovoTide® [1] - Novo Nordisk holds a leading position in the GLP-1 market for diabetes treatment in China, with a market share of 80.9% [1] - The sales in the rare disease segment in the Greater China region surged by 157% at CER, mainly due to growth in the rare blood disease sector [1] Group 3 - For the full year 2025, the company projects a sales growth rate of 13-21% at CER and an operating profit growth rate of 16-24% [1] - The company anticipates that the growth rates in Danish kroner will be 3 and 5 percentage points lower than those at CER, respectively [1] Group 4 - In the U.S. market, the penetration of branded GLP-1 drugs has been lower than expected, prompting Novo Nordisk to combat illegal drug compounding and expand product accessibility [2] - There are approximately 1 billion individuals with obesity globally, yet only a few million are receiving treatment, indicating a significant market opportunity for Novo Nordisk as it continues to pursue the global launch of Wegovy® [2]

Core Insights - The company will present research results on its obesity candidate drug ASC47 at the 32nd European Congress on Obesity [1] - The oral presentation is scheduled for May 13, 2025, and the poster presentation will take place on May 14, 2025, in Malaga, Spain [1] - ASC47 is a thyroid hormone receptor β selective small molecule agonist that targets fat and is designed for subcutaneous injection with a long duration of action [1] - The drug achieves dose-dependent high drug concentrations in adipose tissue [1] - The FDA has approved the clinical trial application for ASC47 in combination with semaglutide for the treatment of obesity [1]