礼来宣布因"战略业务原因"终止一项2b期肥胖试验，该研究在尚未招募任何参与者前即被叫停。该试验原计划评估礼来以19亿美元收 购Versanis获得的资产bimagrumab，既作为单一疗法，也与其主力GLP-1/GIP药物替尔泊肽联合使用。 整理 | GLP1减重宝典内容团队 公司在今年3月提交了试验申请，计划招募180名肥胖或超重并伴有2型糖尿病的成年人。bimagrumab是一种抗体，通过结合激活素II 型A和B受体来阻断激活素和肌生成抑制素信号通路。研究设计了九个分组，分别测试bimagrumab单用或与替尔泊肽联合，后者正是 Mounjaro和Zepbound的活性成分。 据彭博社首次报道，该试验已被取消。早在6月，ClinicalTrials.gov上的试验状态就从"尚未招募"变更为"进行中但未招募"，引发外界 关注。 本周，该试验状态再次更新为"撤回"。礼来表示，此举是基于业务层面的考虑，公司"会常规性地评估研发管线，以最大化每一款产品 的潜力"。 礼来同时强调，bimagrumab仍在进行中的另一项2期试验中被研究，该试验评估其与替尔泊肽单独或联合在肥胖人群中的疗效。该研 究结果预计将在2026 ...

Core Viewpoint - The article highlights the approval of Masitide injection (GLP-1/GCG dual receptor agonist) by the National Medical Products Administration (NMPA) for blood sugar control in adults with type 2 diabetes, based on two pivotal Phase III clinical studies demonstrating its efficacy and safety [2][4]. Clinical Research Shows Significant Efficacy - In the DREAMS-1 and DREAMS-2 studies, Masitide injection outperformed placebo and Dulaglutide 1.5mg in blood sugar control and weight loss, also showing improvements in cardiovascular, liver, and kidney-related indicators [4]. - The safety profile of Masitide was consistent with previous studies and other GLP-1 receptor agonists, with no new safety risks identified, enhancing its market potential as a treatment for type 2 diabetes [4]. International Presentation and Scientific Conferences - The results of the DREAMS-1 study were presented as an oral report at the 2025 ADA Scientific Conference, while the DREAMS-2 study results are set to be disclosed at the 2024 EASD Congress, gaining recognition among Chinese clinical diabetes experts [5]. Other Indications and Future Outlook - Masitide injection has also been approved for long-term weight management in adults with obesity or overweight, with ongoing or completed Phase III clinical studies covering multiple indications, including metabolic-associated fatty liver disease (MAFLD) and obstructive sleep apnea (OSA) with obesity [7]. - The continuous advancement of Masitide's clinical research aims to expand its leadership in the global diabetes and obesity treatment market, potentially benefiting more patients [7].

Core Viewpoint - The article discusses the advancements in GLP-1 drug development, particularly focusing on Eli Lilly's innovative drugs, Tirzepatide and Retatrutide, and their potential applications in treating various conditions, including MASLD [4][6]. Group 1: Clinical Trials and Research - Eli Lilly registered a Phase III clinical trial for Tirzepatide and Retatrutide targeting MASLD, aiming to enroll 4,500 patients, with preliminary results expected by 2030 [4]. - The trial will evaluate the efficacy and safety of Tirzepatide and Retatrutide in treating MASLD, with the primary observation endpoint being the MALO composite endpoint [4]. Group 2: Drug Development and Mechanism - Eli Lilly maintains a leading position in multi-target GLP-1 drug development, with Tirzepatide being the first GLP-1/GIP dual-target agonist and Retatrutide being the first triple-target agonist acting on GLP-1/GIP/GCG [6]. - Retatrutide is currently involved in multiple Phase III studies, including those for obesity and type 2 diabetes, and the new MASLD trial expands its indication exploration [6]. - Additionally, Retatrutide is being evaluated for its potential efficacy in chronic kidney disease (CKD) [6].

Core Viewpoint - Tirzepatide has gained unprecedented attention as an effective solution for sustainable weight loss, initially developed for treating type 2 diabetes, and has proven effective in controlling blood sugar and aiding weight loss [4] Group 1: Clinical Trial Data - Mounjaro has shown significant results in the SURMOUNT-5 phase 3 clinical trial, where participants lost an average of 50.3 pounds (22.8 kg) over 72 weeks [6] - Experts highlight that Mounjaro is one of the first drugs to effectively combine weight loss and metabolic health improvement, marking a cornerstone in modern obesity treatment [6] Group 2: Mechanism of Action - Mounjaro employs a dual-target mechanism, affecting two key hormones, GIP and GLP-1, which helps patients feel full longer and reduces binge eating impulses [6][7] - This multi-target approach is noted to provide comprehensive support for weight management, leading to better long-term results compared to traditional methods [7] Group 3: Health Benefits Beyond Weight Loss - Tirzepatide has shown improvements in metabolic indicators such as blood pressure, blood lipids, BMI, and waist circumference, which are critical risk factors for cardiovascular diseases [8] - Ongoing SURPASS-CVOT trials aim to clarify the cardiovascular benefits of Tirzepatide compared to other treatments [8] Group 4: Broader Implications - The drug has been approved for treating moderate to severe obstructive sleep apnea (OSA) in obese adults, indicating a close link between obesity and OSA [9] - Positive results from the SUMMIT trial show a 38% reduction in heart failure risk among patients treated with Tirzepatide, along with significant improvements in heart failure symptoms and physical ability [9] - The SYNERGY-NASH study indicates that Tirzepatide can help 73% of patients achieve resolution of metabolic dysfunction-associated fatty liver disease (MAFLD) without worsening fibrosis [9] Group 5: Future Outlook - The impact of obesity extends beyond health, contributing to various complications and economic burdens on society [10] - Effective weight loss interventions can significantly reduce the risk of related conditions, such as type 2 diabetes and sleep apnea, by over 50% for patients without complications [12] - Experts believe that advancements in science may lead to a turning point in the battle against obesity, making weight loss less of a struggle [12]

Core Viewpoint - The article highlights the successful development of ASC30, a long-acting subcutaneous formulation of a small molecule GLP-1 receptor agonist by the company, which shows promise for quarterly dosing in obesity management, addressing an unmet need in long-term weight management [2][5]. Group 1: Product Development - ASC30 is the first and currently the only investigational small molecule GLP-1 receptor agonist that can be developed as an oral tablet taken once daily or a subcutaneous formulation administered monthly or quarterly [5]. - The clinical study in the U.S. demonstrated a 75-day half-life for ASC30, indicating its potential for less frequent dosing [2]. - The treatment showed good tolerability with only mild gastrointestinal reactions, which may enhance patient compliance and quality of life [2]. Group 2: Company Overview - The company focuses on innovative therapies for chronic diseases, particularly in the development of small molecule drugs aimed at sustainable weight control [6]. - ASC30 is a new chemical entity (NCE) with compound patent protection in the U.S. and globally until 2044, excluding any patent extensions [5].

Core Viewpoint - The article discusses the effectiveness of Tirzepatide, a dual agonist of GIP and GLP-1 receptors, in weight loss, highlighting its clinical trial results and personal success stories from various individuals who have used the drug for weight management [6][8][9]. Group 1: Clinical Research Findings - Tirzepatide has shown significant weight loss results comparable to bariatric surgery in the SURMOUNT-1 study, where participants lost an average of 16.1 kg, 22.2 kg, and 23.6 kg in different dosage groups over 72 weeks, compared to a mere 2.4 kg in the placebo group [6]. - The drug operates by reducing food intake and increasing energy expenditure, while also delaying gastric emptying and suppressing appetite [6]. Group 2: Personal Success Stories - Dan Yongping reported a weight loss of 15 pounds (approximately 13.6 kg) after using Tirzepatide for two and a half months, noting improvements in his blood lipid levels without significant side effects [8]. - Whoopi Goldberg shared her experience of losing a substantial amount of weight, stating that she felt the drug was beneficial for those needing assistance with weight management [9][11]. - Lauren Manzo mentioned a weight loss of 30 pounds (approximately 27.2 kg) since starting Tirzepatide, expressing that it has been more effective than other weight loss methods, including surgery [12][13]. - Charles Barkley revealed a weight loss of 65 pounds (approximately 58.9 kg) while using Tirzepatide, emphasizing the drug's effectiveness in his weight loss journey [14][16].

Core Insights - The global market for GLP-1 drugs is rapidly expanding, with sales expected to exceed $50 billion in 2024, driven by the success of drugs like semaglutide, which generated $16.632 billion in sales in the first half of the year, surpassing competitors [1][10] - The Hong Kong market is witnessing significant interest in GLP-1 drug stocks, exemplified by the 270% surge in shares of Sinovant Biopharma during its IPO and a fourfold increase in shares of Pague Biopharma over three months, indicating strong investor enthusiasm for this sector [1][2] - Pague Biopharma is positioning itself as a challenger to established pharmaceutical giants like Novo Nordisk, with its core product PB-119 recently having its registration application accepted, and promising clinical data emerging for its other candidate PB-718 [1][5] Company Developments - Pague Biopharma has developed a proprietary platform (HECTOR®) for drug discovery, which includes a drug molecule design platform that enhances the stability and efficacy of compounds while reducing research costs [4] - The company is focusing on the development of PB-718, a dual receptor agonist targeting GLP-1 and GCGR, which shows potential for significant metabolic improvements and addresses the complex mechanisms of MASH, a previously challenging area for drug development [5][6] - Recent clinical trial results for PB-718 demonstrated a 57.14% reduction in liver fat content over 18 weeks, outperforming semaglutide's results in a similar context, suggesting PB-718 could offer a valuable treatment option for patients [7][8] Market Context - The MASH patient population is projected to reach 486 million by 2030, with a market potential of $100 billion, highlighting a significant unmet medical need [6] - The competitive landscape for GLP-1 drugs is intensifying, with Eli Lilly's tirzepatide showing strong growth and capturing a larger market share compared to Novo Nordisk's offerings, indicating a shift in market dynamics [10][11] - Pague Biopharma's innovative products, including PB-718 and the GLP-1 receptor agonist PB-119, are expected to enhance the company's market position and valuation, with the potential to become a leading player in the GLP-1 space [9][14] Investment Outlook - The ongoing innovation in the pharmaceutical sector, particularly in the GLP-1 market, is expected to drive significant valuation increases for companies like Pague Biopharma, which is well-positioned to capitalize on the growing demand for effective treatments [14] - The recent trends in the Hong Kong stock market, coupled with favorable macroeconomic conditions, suggest a strong potential for continued investment in the biotech sector, particularly for companies with robust product pipelines [14]

Investment Rating - The report gives a "Buy" rating for the company, with a target price of 16.16 HKD [6]. Core Insights - The company is positioned as a leader in the antibiotic industry, with a diversified business model that includes intermediates, active pharmaceutical ingredients, and formulations, which is expected to drive a new growth cycle [1][10]. - The innovative pipeline is showing promising results, particularly with UBT251, which has successfully partnered with a global leader in diabetes treatment, Novo Nordisk, indicating strong potential for future revenue [2][23]. - The company is expected to achieve a compound annual growth rate (CAGR) of 8.0% in its formulation business from 2024 to 2027, driven by various factors including the expansion of its animal health business and the approval of new insulin products [3][4]. Summary by Sections 1. Antibiotic Industry Leadership - The company has over 30 years of experience in the pharmaceutical industry, starting with antibiotic formulations and expanding into a fully integrated business model covering intermediates, active ingredients, and formulations [10]. - The company has established a strong cash flow from its core business, which supports its innovative transformation strategy [1][14]. 2. Innovative Pipeline - UBT251, a self-developed GLP-1/GIP/GCG three-target drug, has shown significant weight loss results in clinical trials, with a 15.1% reduction in weight over 12 weeks in the highest dosage group [22][40]. - The partnership with Novo Nordisk includes a potential total income of up to 2 billion USD, with an upfront payment of 200 million USD and milestone payments [23][24]. 3. Formulation Business - The formulation business is expected to grow steadily, with a projected CAGR of 8.0% from 2024 to 2027, supported by the expansion of animal health production and new insulin product approvals [3][4]. - The company’s insulin products have achieved significant market presence, with a 52.5% growth rate in basic volume [3]. 4. Intermediates and Active Pharmaceutical Ingredients - The intermediates and active pharmaceutical ingredients business is expected to see a CAGR of -7.0% from 2024 to 2027, primarily due to price fluctuations in key products [3]. - Despite short-term price declines, the long-term outlook remains stable due to a consolidated market structure [3]. 5. Financial Forecast - The company is projected to achieve net profits of 2.78 billion, 2.13 billion, and 2.27 billion RMB from 2025 to 2027, with corresponding growth rates of 4.5%, -23.4%, and 6.9% [4][5].

Core Viewpoint - Novartis' stock price has increased by 32% since the beginning of the year, with a market capitalization exceeding $240 billion, reaching a historical high. However, the company has not participated in the PD-1 craze or engaged in fierce competition in popular fields like GLP-1 or ADC [2] Group 1: Market Position and Strategy - Novartis has conducted an in-depth evaluation regarding entering the obesity treatment market but believes that the current GLP-1, GIP, and GIPR drug market will continue to be dominated by Eli Lilly and Novo Nordisk, who are rapidly advancing new generation drug development [4] - The CEO of Novartis, Vas Narasimhan, stated that even with slightly differentiated new products, it would be challenging to break through in the current competitive landscape, as high rebate barriers and mature product portfolios will be established by the time follower drugs are launched [4] - Despite not fully abandoning the obesity treatment direction, Novartis is advancing early-stage research projects exploring truly differentiated new pathways, including evaluating longer-acting drug forms such as biologics or siRNA drugs [4] Group 2: Market Potential and Competitors - The obesity drug market is expected to reach $130 billion, with many pharmaceutical companies actively entering the field. Evaluate's latest report indicates that Novo Nordisk's CagriSema project is currently regarded as the most valuable R&D project in the industry [5] - Following closely is Eli Lilly's orforglipron, a new generation oral GLP-1 agonist. Although Novo Nordisk and Eli Lilly have first-mover advantages, Evaluate believes that new entrants with sufficient differentiation still have opportunities to establish a foothold in this field [5]

Investment Rating - The report initiates coverage with a "Buy" rating for the company [4][9]. Core Viewpoints - The company specializes in chronic metabolic diseases and is steadily advancing its transition from generic to innovative drug development. It has a robust product portfolio and a clear strategy to enhance its innovative drug pipeline [8][9]. - The market for GLP-1 drugs is expanding, with the company positioned favorably in the clinical development of its innovative drug DYX116, which targets multiple pathways [2][8]. - The company is expected to achieve significant revenue growth, with projected net profits of 192 million, 218 million, and 200 million yuan for 2025, 2026, and 2027 respectively, indicating a strong growth trajectory [3][9]. Summary by Sections 1. Company Overview - The company has a deep-rooted presence in the chronic metabolic disease market, having been established in 2004 and transitioning from generics to innovative drug development since 2023. It has developed a comprehensive product matrix covering diabetes and cardiovascular diseases [21][24]. 2. Market Dynamics - The chronic metabolic disease market is characterized by a growing patient population due to aging and lifestyle changes. The government is increasingly focused on chronic disease prevention, indicating long-term market expansion potential [54][59]. 3. Diabetes Product Line - The company has a systematic approach to diabetes treatment, with a market size of approximately 34.3 billion yuan in 2023. The introduction of new drugs is expected to enhance its market share, particularly in the innovative drug segment [8][9]. 4. Hypertension Strategy - The company focuses on combination therapies and unmet needs in the hypertension market, which was valued at around 67.6 billion yuan in 2023. Its flagship product, Bo Kai Qing, has maintained a strong market position [8][9]. 5. Financial Projections - The company forecasts a steady increase in revenue, with total revenue expected to reach 1.065 billion yuan in 2025, reflecting a year-on-year growth rate of 22.6% [3][9]. 6. Investment Analysis - The company's current market valuation suggests a price-to-earnings (PE) ratio of 22 for 2025, significantly lower than the industry average of 41, indicating potential for valuation improvement as innovative drug data becomes available [9][10].