市场是不是应该期待6月下旬的ADA（美国糖尿病学会年会）上，有新的大额BD交易爆发？ 2025年6月2日，翰森制药与美国再生元（Regeneron）共同宣布一项重磅许可合作：再生元以8000万美 元首付款、最高19.3亿美元里程碑付款获得翰森在研GLP-1/GIP双受体激动剂HS-20094在大中华区以外 的全球独家开发与商业化权利。 HS-20094是一款每周皮下注射的候选药物，在超过千例受试者的II期试验中展现出与礼来tirzepatide（全 球唯一获批GLP-1/GIP双激动剂）相近的显著减重和安全数据，目前正于中国开展肥胖症III期和糖尿病 2b期试验。 值得注意的是，这笔交易虽然还是GLP-1/GIP，但对于购买方再生元来说，目的已经非常明确，联用自 己的肌肉保持产品，进入减脂增肌的减肥药2.0时代。 再生元联手翰森：减肥药2.0时代的起点？ 在2025年Q1财报电话会上，再生元管理层明确传递出对肥胖治疗业务的新态度：公司将"致力于通过提 高减肥质量来推进更好的肥胖治疗"，关注点不仅是减轻体重数字，更强调"高质量、持续的减重"。 再生元联合创始人兼首席科学官George Yancopoulos博士 ...

Core Insights - Regeneron Pharmaceuticals announced interim results from the Phase 2 COURAGE trial, showing that approximately 35% of weight loss from semaglutide was due to lean mass loss, and combining it with trevogrumab helped preserve lean mass while increasing fat loss [1][2][3] Group 1: Trial Results - The COURAGE trial demonstrated that combining semaglutide with trevogrumab, with or without garetosmab, preserved 50%-80% of lean mass compared to semaglutide alone while enhancing fat mass loss [1][2] - At the 26-week interim analysis, patients receiving semaglutide alone lost an average of 7.9 lbs of lean mass, while those on the lower-dose and higher-dose combinations lost 3.7 lbs and 4.2 lbs respectively, and the triplet group lost only 2.0 lbs [3][4] - Fat mass loss was significantly higher in combination groups, with the triplet group losing an average of 25.4 lbs, representing an 84.4% change from baseline [3][4] Group 2: Safety and Tolerability - The combination therapies were generally well-tolerated, but the triplet combination had a higher rate of treatment discontinuation due to tolerability issues, with 28.3% of participants discontinuing treatment [1][6] - The overall incidence of treatment-emergent adverse events (TEAEs) was 64.9% for semaglutide monotherapy, increasing to 77.2% in the triplet group [6] Group 3: Future Directions - The full data set from the COURAGE trial is expected to be available later this year, which will provide further insights for optimizing dosing regimens in future trials [2] - Regeneron is focused on developing treatments that improve the quality of weight loss by preserving muscle mass during weight reduction, addressing a significant concern in obesity management [7][8]

Investment Rating - The report maintains a "Positive" investment rating for the industry [1] Core Insights - The report highlights the significant potential of blocking the Activin receptor (ActR) signaling pathway to promote muscle growth, particularly in treating muscle atrophy-related diseases [4][9] - There is a substantial unmet clinical need for muscle-targeted therapies, especially for patients with spinal muscular atrophy (SMA) and those experiencing muscle loss due to aging or weight management [4][29] - The market for muscle-targeted therapies is projected to be large, with current SMA therapies generating approximately $4.5 billion in sales, indicating a significant opportunity for new treatments [4][33] Summary by Sections 1. ActR Pathway - The ActR pathway plays a crucial role in regulating muscle, blood, and bone through members of the TGFβ superfamily, including Myostatin [9] - Blocking the ActR pathway can effectively treat muscle atrophy by inhibiting Myostatin, which negatively regulates muscle growth [4][10] 2. Clinical Applications of ActR Pathway Blockade: Spinal Muscular Atrophy (SMA) - SMA is a genetic neuromuscular disease caused by mutations in the SMN1 gene, leading to severe muscle atrophy and respiratory failure [22][23] - Current SMA therapies primarily target SMN protein, but they have limitations, highlighting the need for combined therapies that also address muscle atrophy [25][29] 3. Clinical Applications of ActR Pathway Blockade: Weight Management - Muscle loss is a significant issue not only in genetic diseases but also in aging populations, with a 1% annual muscle loss in individuals over 60 [36] - The widespread use of GLP-1RA medications has been linked to 25-40% muscle loss in users, creating a demand for therapies that preserve or enhance muscle mass during weight management [36] 4. Targeted ActRII Pathway Drugs - Apitegromab, developed by Scholar Rock, is a monoclonal antibody targeting latent Myostatin, showing promising results in Phase 3 trials for SMA and expected to submit for FDA approval [38][39] - Taldefgrobep, developed by BIOHAVEN, targets active Myostatin but did not meet primary endpoints in its Phase 2 trial for SMA, although it showed trends of benefit in certain subgroups [57][62] - GYM329, developed by Roche, specifically targets latent Myostatin and is currently undergoing clinical trials for various indications, demonstrating potential for muscle mass increase [69]