以下文章来源于内分泌早知道 ，作者关注内分泌的 内分泌早知道 . 深度分享内分泌用药经验、病例剖析、指南专业解读并紧跟国内外内分泌领域前沿进展，「每医健」旗下内容平台。 核心发现： 1. 全球首次证实：GLP- 1 /GIP双受体激动剂Tir z e pa ti de能有效减少2型糖尿病患者肌肉脂肪沉积，同时保持肌肉量合理变化 2. 5 2周治疗数据显示：患者体重显著降低同时，肌肉脂肪浸润程度明显改善，肌肉量变化与体重下降呈科学匹配 3. 创新研究方法：结合UK Bi oba nk近3000例真实世界数据，为临床结果提供精准参照系 研究价值与发表背景 这项具有里程碑意义的研究源自SURPASS- 3临床试验的MRI亚组分析，最新发表于《柳叶刀·糖尿病与内分泌学》2025年6月刊。研究 团队采用高精度MRI技术，系统对比了Tir z e pa ti de与德谷胰岛素治疗5 2周后，2型糖尿病患者大腿肌肉体积、脂肪浸润程度及标准化Z 分数的动态变化。 研究突破性地引入英国生物库大规模人群数据，首次建立了糖尿病药物治疗与肌肉健康变化的科学评价体系。这不仅为Tir z e p a ti de的 临床优势提供了影像学证 ...

Company Strategy & Market Opportunity - Lilly aims to provide freedom from diabetes, eliminate serious health issues caused by obesity, and reduce cardiovascular deaths[10] - The company estimates a significant addressable market of over 170 million patients by 2030 for obesity and related conditions[13] - Outside of the US, the addressable market is expected to be approximately 1 billion patients[15] Orforglipron Development Program - Orforglipron, a GLP-1 small molecule, has a broad development plan including studies for Type 2 Diabetes, obesity, hypertension, and obstructive sleep apnea[20] - In the ACHIEVE-1 trial, all three doses of orforglipron achieved superiority versus placebo in reducing HbA1c levels in patients with Type 2 Diabetes[27] - ACHIEVE-1 trial data showed significant reductions in HbA1c observed as early as 4 weeks, with approximately 3/4 of patients achieving an ADA HbA1c target of less than 7%, and 2/3 reaching HbA1c ≤6.5%[27] - ACHIEVE-1 trial also demonstrated dose-dependent reduction in body weight, with approximately 2/3 of patients achieving ≥5% weight reduction and approximately 1/3 achieving ≥10% weight reduction[30] - Topline results for ATTAIN-1, an orforglipron trial in obesity, are expected in Q3 2025[39] Retatrutide Development Program - Retatrutide is undergoing global development with the TRIUMPH program for obesity and related complications, and the TRANSCEND program for Type 2 Diabetes[41] - Topline results for TRIUMPH-4, a retatrutide trial in knee osteoarthritis pain and overweight or obesity, are expected in Q4 2025[48] Tirzepatide & Early Phase Pipeline - The SURPASS-CVOT trial is designed to evaluate tirzepatide against dulaglutide in patients with established cardiovascular disease[51] - Eloralintide, a selective amylin receptor agonist, showed weight loss up to 11.3% in Phase 1 trials and is well-tolerated with less than 10% incidence of GI side effects[60]

Group 1: Dividend-Paying Stocks Performance - Dividend-paying stocks in the S&P 500 index delivered an average annualized return of 9.2% over the 50-year period ending in 2024, compared to 4.3% for non-dividend stocks [3] - Novo Nordisk and Constellation Brands are highlighted as dividend-paying stocks that have seen significant price declines but are expected to rebound [4] Group 2: Novo Nordisk Analysis - Novo Nordisk's stock price has dropped over 50% in the past year, yet its earnings per share have increased by 154% over the last five years, indicating strong underlying performance [5] - Analysts project a consensus price target above $97 per share for Novo Nordisk, suggesting a potential 40% increase in the next 12 months [6] - The company has increased total dividends per share by 173% from 2019 to 2024, with a potential yield of 1.8% for investors buying at recent prices [7] - First-quarter sales of its obesity drug, Wegovy, surged by 65% to $2.9 billion, contributing to an overall revenue increase of 18% at constant exchange rates [8] - The main patent for semaglutide, Novo Nordisk's leading drug, does not expire until 2032, allowing for continued market exclusivity [10] Group 3: Constellation Brands Analysis - Constellation Brands' stock has fallen by about one-third in the past year, but analysts expect a rebound with an average price target of $202, implying a 17% gain [11] - The company has consistently raised its dividend since 2015, with a current yield of 2.4% and a 229% increase in dividend payments over the past 10 years [12][13] - Constellation's beer business is gaining market share, and despite potential challenges from new tariffs on imports from Mexico, it remains the sole distributor of popular brands like Modelo and Corona [14][15]

Core Insights - The healthcare sector is highlighted as having significant growth opportunities, particularly in the weight loss drug market and gene editing technologies [2][4]. Group 1: Weight Loss Drug Market - Eli Lilly is positioned to potentially lead the GLP-1 agonist market, currently holding approximately 35% market share, while Novo Nordisk leads with 65% [4]. - The GLP-1 market is projected to grow to a $150 billion opportunity over the next decade, representing a tenfold increase from last year's sales [4]. - Eli Lilly is developing two promising drugs: Orforglipron, an oral GLP-1 pill, and Retatrutide, which targets multiple hormones and is in phase 3 studies [5][6]. - Analysts anticipate Eli Lilly will achieve 32% annualized earnings growth over the long term, despite a high price-to-earnings (P/E) ratio of nearly 65 [7][8]. Group 2: Gene Editing Technology - CRISPR Therapeutics is advancing its commercialization efforts for Casgevy, a therapy for sickle cell disease and beta-thalassemia, which is the first CRISPR-based treatment to receive FDA approval [10]. - The company has five additional therapies in clinical trials, indicating potential for significant growth if successful [11]. - Analysts project CRISPR Therapeutics will achieve $173 million in revenue next year, with an enterprise value of $2.2 billion, suggesting a reasonable price for the stock given its potential [12].

Summary of China GLP-1 Market Update Industry Overview - **Industry**: China Pharma and Biotech, specifically focusing on the GLP-1 market - **Key Products**: Semaglutide (Ozempic, Wegovy) and Tirzepatide Core Insights 1. **Sales Performance**: - Semaglutide sales in China increased by **110% QoQ** in 1Q25 after a **49% QoQ** decline in 4Q24, indicating easing supply constraints. However, YoY growth has slowed from over **100%** to **19%** [1][6][7] - The Chinese market contributes only **2-4%** of global GLP-1 sales, significantly lagging behind the US market, which accounts for **70-80%** [6][15] 2. **Pricing Trends**: - A **5-7%** price decline for Semaglutide has resumed in 2025 after stabilization in late 2024. Hospital pricing fell by **7-8% QoQ** in 1Q25 [2][23][33] - Tirzepatide is priced **2-3 times** higher than Semaglutide, with monthly costs ranging from **CNY 3,000 to CNY 4,000** [26][38] 3. **Market Segmentation**: - The GLP-1 market in China is segregated into hospital pricing (lower, NRDL-covered) and retail pricing (higher, not covered by insurance) [22][28] - New GLP-1 drugs like Wegovy and Tirzepatide are expected to remain outside of NRDL coverage, maintaining higher retail prices [22][29] 4. **Competitive Landscape**: - The market is becoming increasingly competitive with **7 domestic players** showing weight loss efficacy over **15%** [3] - United Laboratories has entered an exclusive licensing agreement with Novo Nordisk for UBT251, a new GLP-1 drug, with potential milestone payments up to **CNY 1.8 billion** [49] 5. **Clinical Trials and Efficacy**: - Recent trials show promising results for various GLP-1 drugs, with weight loss efficacy ranging from **9.5% to 19.8%** in different studies [50][51] - Notable results include Raynovent's RAY1225 showing **15.1%** weight loss in a Phase 2 trial and BrightGene's BGM0504 reporting up to **19.8%** weight loss [50] Additional Important Insights - **Supply Constraints**: Despite recent improvements in supply, Tirzepatide continues to face shortages, affecting its availability in online pharmacies [29][25] - **Long-term Pricing Outlook**: The expectation is that domestic supply of new GLP-1 drugs will drive prices down significantly in the long term, potentially to **CNY 300/month** [2] - **Investment Ratings**: Companies like Hansoh, Innovent, and Jiangsu Hengrui are rated as Outperform, while CSPC is rated as Market-Perform [5] This summary encapsulates the key points from the conference call regarding the current state and future outlook of the GLP-1 market in China, highlighting both opportunities and challenges within the industry.

Core Insights - Eli Lilly's experimental drug Bimagrumab, when combined with Novo Nordisk's GLP-1 weight loss drug Wegovy, shows superior weight loss results while preserving muscle mass [1][2] - The combination therapy resulted in a 22.1% weight reduction over 48 weeks, with 92.8% of the weight loss coming from body fat, compared to a 15.7% reduction and 71.8% fat loss with Wegovy alone [1] - Morgan Stanley expresses optimism about the combination therapy's efficacy and safety, noting improvements in various cardiovascular metabolic indicators [2] Company Analysis - Morgan Stanley highlights that the combination therapy's safety and tolerability are better than expected, with mild muscle cramps occurring in about 60% of patients, and transient increases in ALT and lipase levels [2] - Eli Lilly is conducting a Phase II trial for Bimagrumab combined with Tirzepatide for obesity and/or type 2 diabetes, with data expected in April and October 2026 [2][3] - The stock rating for Eli Lilly is "Overweight" with a 12-month target price of $1,133, representing a 46% upside from the closing price of $778.08 on June 24 [3] Industry Insights - The combination therapy may be particularly beneficial for older patients on GLP-1 medications, who are more prone to muscle loss [3] - The concept of "sarcopenic obesity" is identified as a significant indication for the combination therapy, with interest in its application for metabolic-associated fatty liver disease (MASH) and osteoarthritis [3] - Potential upside risks for Eli Lilly's stock include better-than-expected performance of oral GLP-1 drug Orforglipron and positive results from Tirzepatide studies [4]

Investment Rating - The industry investment rating is "Positive" (maintained) [1] Core Insights - The report highlights recent positive developments in the high-quality weight loss sector, particularly focusing on myostatin pathway clinical trial results from Regeneron and Scholar Rock, which demonstrate significant reductions in lean body mass loss when combined with GLP-1 medications [4][12] - The pharmaceutical and biotechnology sector experienced a decline of 4.35% in the third week of June 2025, underperforming the CSI 300 index by 3.9 percentage points, ranking 29th among 31 sub-industries [5][16] - The report emphasizes the potential of Activin receptor drugs, such as Eli Lilly's Bimagrumab and Lai Kai's LAE-102, to retain lean body mass and even promote muscle gain, with promising safety and pharmacokinetic data [4][12] Summary by Sections 1. Recent Developments in Weight Loss Sector - Regeneron's myostatin antibody Trevogrumab combined with semaglutide showed a 50.8% reduction in lean body mass loss over 24 weeks, compared to a 7.9 lbs loss with semaglutide alone [4][12] - Scholar Rock's myostatin antibody Apitegromab combined with Tirzepatide demonstrated a 54.9% reduction in lean body mass loss [4][12] 2. Market Performance - The pharmaceutical and biotechnology sector's decline of 4.35% in June's third week was the largest among all sectors, with the vaccine sector experiencing the smallest drop of 0.4% [5][21] - Other sub-sectors, such as blood products and medical consumables, also faced declines, with the largest drop seen in other biological products at 6.7% [5][21] 3. Recommended Stocks - Recommended stocks include major pharmaceutical and biotechnology companies such as Heng Rui Medicine, East China Medicine, and Innovent Biologics, among others [6]

Core Insights - Scholar Rock's Phase 2 EMBRAZE trial results indicate that apitegromab combined with tirzepatide can significantly preserve lean mass during weight loss, with a notable reduction in lean mass loss compared to tirzepatide alone [1][2][3] Group 1: Trial Results - The trial showed that 30% of the weight loss from tirzepatide was attributed to lean mass loss, while the addition of apitegromab reduced this to 14.6% [3][4] - Patients receiving the apitegromab-tirzepatide combination lost 12.3% of their body weight, compared to 13.4% for those on tirzepatide with placebo [4] - The combination therapy resulted in a higher quality of weight loss, with patients losing 85% fat and 15% lean mass, compared to 70% fat and 30% lean mass in the placebo group [4] Group 2: Market Reaction - Following the positive trial results, Scholar Rock's stock price increased by 18%, reaching $36.77 [6]

Skye Bioscience (SKYE) Q1 2025 Earnings Call May 08, 2025 04:30 PM ET Speaker0 Ladies and gentlemen, thank you for standing by. My name is JL, and I will be your conference operator today. At this time, I would like to welcome everyone to the Sky BioScience First Quarter Fiscal twenty twenty five Earnings Call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. I would now like to turn the conference over to Bernie He ...

Financial Data and Key Metrics Changes - Scholar Rock reported an outstanding year in 2024, with significant progress towards regulatory milestones for apitegromab, including the submission of the BLA in the U.S. in January and the upcoming MAA submission in the EU in March [6][36]. - The company anticipates a transformative year in 2025, with plans for a potential launch of apitegromab in the U.S. in Q4 2025 and in the EU in 2026 [37]. Business Line Data and Key Metrics Changes - The SAPPHIRE study demonstrated that apitegromab plus standard-of-care resulted in a 1.8% improvement in the Hammersmith Functional Motor scale compared to placebo, with 30% of patients achieving a 3-point or greater improvement [9][10]. - The cardiometabolic program is on track to share top-line data from the EMBRAZE study in Q2, with the IND filing for SRK-439 planned for Q3 [8][35]. Market Data and Key Metrics Changes - Approximately two-thirds of the 10,000 individuals living with SMA in the U.S. and 35,000 globally have received SMA-targeted therapy, indicating a significant market opportunity for apitegromab as a muscle-targeted therapy [14][15]. - The current market for GLP-1 receptor agonists is projected to generate over $100 billion in sales, highlighting the potential impact of Scholar Rock's cardiometabolic programs [22]. Company Strategy and Development Direction - Scholar Rock aims to establish a neuromuscular franchise starting with SMA, with plans to expand treatment to other neuromuscular disorders [37]. - The company is focused on building a strong commercial team and infrastructure to support the launch of apitegromab, including outreach to payers and scaling the customer-facing team [19][20]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of apitegromab to transform the standard of care for SMA, emphasizing the importance of addressing progressive muscle weakness [12][15]. - The company is optimistic about the EMBRAZE study and the potential for SRK-439 to enhance weight management therapies by preserving lean muscle mass [35][36]. Other Important Information - Scholar Rock has initiated a disease education campaign called "Life Takes Muscle" to raise awareness about the impacts of muscle weakness in SMA [16][17]. - The company is preparing to offer home infusion services at launch to enhance patient support [19]. Q&A Session Summary Question: Discussion on SAPPHIRE data presentation - Management highlighted the importance of presenting additional data points at the MDA conference, focusing on the consistency and impact across age groups and endpoints [42][43]. Question: Insights on obesity and lean mass preservation - Management clarified that a 20% to 40% improvement in lean mass is considered clinically meaningful, and they are looking for trends in the EMBRAZE study to inform the development of SRK-439 [41][47]. Question: Exploration of additional neuromuscular indications - Management is actively engaging experts to explore adjacent neuromuscular indications and is assessing the unmet need and technical success probability for potential studies [60][63]. Question: Implications of FDA guidance on obesity trials - Management noted that the FDA's guidance reinforces the importance of assessing lean mass loss and that they will continue to follow this closely while developing SRK-439 [69][71]. Question: Comparison of SRK-439 and apitegromab - Management expressed confidence in the profile of SRK-439, indicating it may have greater affinity for the target and could potentially offer advantages in dosing and efficacy [80][82]. Question: Initial payer discussions and pricing strategy - Payers have shown receptiveness to Scholar Rock's innovation, and management expects access to be reflective of the value apitegromab brings to SMA treatment [85][86]. Pricing details are not yet disclosed but are expected to align with other SMA treatments [89].