Apitegromab

从韩美药品 HM17321，到口服 GLP-1、三靶点、Amylin 和“保肌肉”组合，再到本周首尔 COEX 的 ADC、TPD、AI 新药大会，2026 年的药圈突然把几条看似不相干的线连到了一起。8 月 24 日，韩国韩美药品（Hanmi Pharm）丢出了一枚相当大的炸弹。公司宣布，将新型肥胖药候选物HM17321授权给罗氏旗下 Genentech。韩国以外的全球开发、生产和商业化权利交给 Genentech，韩美拿到1.9 亿美元不可退还首付款，随着临床、注册和商业化推进，交易总额最高可达到约23 亿美元，约 3.19 万亿韩元，上市后还有额外分级销售提成。(Hanmi Pharmaceutical)韩国股市的反应简单粗暴。韩美药品当天从 41.55 万韩元直接冲到54 万韩元，+29.96%，封死涨停。不过今天，也就是 8 月 25 日，又回落 7.22%，收在 50.1 万韩元。两天合起来看，比单纯喊一句“暴涨 30%”更有意思：市场认可这笔 BD，但也已经开始给这个仍处于早期临床阶段的项目算概率了。(Seoul Economic Daily)先把一个容易被新闻标题带偏的地方说清楚很多报道把 HM17321 写成：“韩美研发出减肥不掉肌肉的新药，成功了。”这句话目前还不能这么说。真正已经成功的，是一笔非常漂亮的技术授权。HM17321 的“减脂同时保存甚至增加肌肉”数据，目前最漂亮的部分仍来自动物实验和非临床研究。它现在正在美国做 Phase 1， 登记的是约 90 名健康受试者和肥胖受试者，进行单次递增剂量和多次递增剂量试验，首先看安全性、耐受性、PK 和 PD。目前页面明确写着No Results Posted。()所以准确的说法应该是：“一个在非临床中显示出选择性减脂、保护肌肉潜力的候选药，在人体疗效出来之前，就被 Genentech 以最高 23 亿美元的交易框架拿走了。”我反而觉得，这比“减肥不掉肌肉成功”更值得琢磨。大药厂买的不是一个已经证明成功的答案，而是一个它认为值得提前下注的问题。HM17321 到底新在哪里？现在大家一说减肥药，条件反射就是 GLP-1。Semaglutide 是 GLP-1，tirzepatide 是 GLP-1/GIP，Lilly 下一代 retatrutide 更进一步，把 GLP-1、GIP、glucagon 三个受体放到了一起。HM17321 偏偏绕开了这条越来越拥挤的高速公路。它是一个长效UCN2，Urocortin-2 类似物，选择性作用于CRFR2，corticotropin-releasing factor receptor 2。也就是说，它属于 non-incretin 路线。韩美公布的肥胖动物模型中，HM17321 在产生类似 semaglutide 的体重下降时，脂肪量下降，而 lean mass 和 muscle mass 反而增加；wire-hanging test 中肌肉功能也得到改善。与 GLP-1 类药物联合时，公司还观察到更明显的脂肪下降和瘦体重保护。(Hanmi Pharmaceutical)这里再插一句药理学上的“扫兴话”。Lean mass 不完全等于 skeletal muscle。DXA 测到的瘦体重还包括水分、器官等成分，所以“lean mass loss”直接翻译成“掉了多少肌肉”并不严谨。但当减重达到 15%、20% 甚至更高时，肌肉量、力量和身体功能确实越来越重要，尤其对老年人、肌少症风险人群以及需要长期治疗的人。于是，减肥药的 KPI 开始变了。以前大家问：能减多少公斤？现在开始问：减掉的到底是什么？这个变化非常重要。减肥药已经打了四轮战争第一轮很好理解：谁减得多。Wegovy 把药物减重带进了 15% 左右的时代，Zepbound 又把上限进一步抬高。现在 Lilly 的 retatrutide 已经进入 Phase 3，今年公布的一项 80 周研究中，最高剂量平均减重达到22.6%；Lilly 计划 2027 年第一季度向 FDA 申报。(Reuters)当减重效果开始逼近减重手术时，“再多减两三个百分点”当然还有价值，但已经不再是唯一战场。第二轮是：谁更方便。2026 年是口服减肥药真正进入商业化的一年。Novo 的 Wegovy 片剂已经进入美国市场，Lilly 的小分子口服 GLP-1orforglipron，商品名 Foundayo又在今年 4 月 1 日获得 FDA 批准。它不需要多肽注射，这件事对生产成本、供应能力和患者接受度都很有杀伤力。(U.S. Food and Drug Administration)Novo 甚至在这个月刚启动新的后期临床，研究 Wegovy 口服制剂能不能用更低的维持剂量。背后的问题已经不只是疗效，还有成本、副作用和长期依从性。(Reuters)第三轮是：谁让病人舒服一点。恶心、呕吐、腹泻这些 GI adverse events，是 incretin 类药物很难绕开的现实。所以 Amylin 突然又热起来了。罗氏现在手里已经有双靶点 GLP-1/GIP 激动剂enicepatide，CT-388，同时又有长效 amylin 类似物petrelintide。两者都在向 Phase 3 推进，罗氏还在做它们的固定剂量组合。罗氏自己的措辞很有意思：enicepatide 可以成为未来组合疗法的backbone。(Roche)翻译成药企语言就是：我不打算只卖一个减肥药，我准备搭积木。第四轮，就是现在最值得注意的：谁能让减掉的更多是脂肪，而不是瘦体重。这正是 HM17321 被罗氏拿走的背景。“保肌肉”已经不是 PPT 概念，人体数据开始出来了今年两篇Nature Medicine很能说明这个趋势。Scholar Rock 的apitegromab是 myostatin 通路抑制抗体。今年公布的 Phase 2 EMBRAZE 试验把它和 tirzepatide 联用。24 周后，两组总体减重差不多，但加 apitegromab 的患者少损失了约1.9 kg lean mass，相当于瘦体重损失减少 54.9%。对照组减掉的体重中有约 30.2% 来自 lean mass，而联合组降到了 14.6%。(Nature)另一条路线是bimagrumab，通过 Activin type II receptor 通路作用。507 人的 Phase 2 研究中，semaglutide 单药 48 周瘦体重下降约 4.7% 到 6.9%，而加入 bimagrumab 后下降只有约 0.8% 到 2.3%。高剂量组合中，减掉的体重约92.3% 来自脂肪，semaglutide 2.4 mg 单药则是 71.1%。(Nature)这两个项目有一个地方反而让 HM17321 的故事更有意思。Apitegromab 和 bimagrumab 是大分子抗体，主要负责“保肌肉”，然后跟 incretin 搭配。HM17321 本身是一条 peptide，而且韩美的目标是同时推动脂肪下降和肌肉改善。韩美还特别提到，肽类属性使其未来有机会和 incretin 做 fixed-dose combination。(Hanmi Pharmaceutical)如果这个机制最终在人身上站得住，罗氏得到的可能不是“另一个减肥药”，而是一块可以插进现有肥胖组合疗法里的新积木。当然，现在必须把“如果”两个字写大一点。Apitegromab 和 bimagrumab 已经有人体 Phase 2 体成分数据，HM17321 还没有。所以 23 亿美元代表的是潜在价值，不是临床成功证明。这也解释了罗氏为什么现在出手从罗氏现有布局看，这笔交易其实相当顺。它已经有负责强力减重的 incretin backbone，有 amylin 去争耐受性和更细分的人群，现在又把一个可能改善 body composition 的 non-incretin UCN2 项目收入囊中。未来肥胖治疗越来越可能不像今天这样：“你用 Wegovy，我用 Zepbound。”而会变得更像高血压或者肿瘤治疗：患者需要减 10% 还是 25%？有没有糖尿病？有没有 MASH？GI 副作用能不能忍？年龄多大？有没有 sarcopenia 风险？停药后怎么维持？然后选择不同 backbone、不同 add-on，甚至不同固定组合。所以我现在越来越不愿意把肥胖药市场简单理解成“GLP-1 市场”。它已经开始变成一个代谢疾病组合治疗市场。这也是为什么 Reuters 在今年总结行业竞争时，除了 Lilly 和 Novo，还不断出现 Roche、Pfizer、AstraZeneca、Zealand、Structure 等名字。这个市场依然由 Lilly 和 Novo 主导，但竞争正在从单一的减重百分比，分化到口服、给药频率、耐受性、体成分以及伴随疾病。分析师预计未来年度市场规模可能达到约1000 亿美元级别。(Reuters)很巧的是，今天首尔 COEX 正好也在发生另一件事8 月 25 日到 27 日，CPHI/Hi Korea 2026正在首尔 COEX 举办。如果最近听韩国药企的人一直说“COEX、ADC、TPD、GLP-1、BD”，大概率说的就是这个会。它并不是一个单独的 ADC 学术会议，更像是把制药、Biotech、CDMO、原料、设备、投资和 Business Development全部塞进一个场馆的产业交流平台。今年共有22 个国家、478 家企业参加，展区覆盖 COEX C Hall、E Hall 和 The Platz。海外预注册参会者比例达到 19.6%，比去年的 14% 明显增加，参会者来源接近 90 个国家。Samsung Biologics、大雄制药、GC 绿十字等韩国企业也在场。(CPhI)更有意思的是今年的议程。以前这种 CPHI 给人的感觉常常是 API、CMO、包装、设备。今年台上的关键词已经变成：ADC、TPD、microneedle、GLP-1、AI drug discovery、open innovation。今天的 bio modality session 直接讨论 ADC、靶向蛋白降解、放射增敏剂等新技术；后面还有 AI 新药研发、创业公司 IR、DIPS Open Innovation，以及企业之间的一对一 matchmaking。(모바일 네이트 뉴스)这其实比“有多少家企业参展”更值得看。ADC 和减肥药明明八竿子打不着，为什么我觉得应该放在一起看？因为从药物发现的角度它们当然完全不同，但从2026 年制药公司的 BD 逻辑来看，两边越来越像。ADC 不再只是“我有一个抗体，再接一个毒素”。大家真正争的是 target、antibody、linker、payload、DAR、内吞、旁观者效应、CMC，以及最后能不能组成一个可以不断扩展的 platform。肥胖药也一样。GLP-1 已经变成 backbone，后面可以接 GIP、glucagon、amylin、myostatin/activin、UCN2，甚至 oral delivery 和 microneedle。真正值钱的东西，越来越不是“我也做了一个 GLP-1”。而是：我手里有没有一块别人没有、但又能插进现有产业链和治疗组合里的积木。HM17321 这次最高 23 亿美元的授权，恰好把这个逻辑展示得很漂亮。一个仍处于 Phase 1 的韩国原创项目，只要机制足够差异化、非临床数据能讲清楚 translational story、专利和 CMC 能继续推进，而且能和大药厂现有 portfolio 拼起来，就可能在非常早的阶段产生巨大的 BD 价值。这也是为什么我觉得这周的 COEX 比单纯看展台有意思。韩美药品前一天告诉大家“什么样的资产可能卖出大价钱”，第二天 COEX 里几百家公司就在展示“下一个这样的资产可能从哪里长出来”。减肥药的下一阶段，我会盯三个问题第一，减重 20% 以后，患者剩下的身体是什么样。第二，停药以后怎么办。第三，能不能针对不同病人，把 incretin、amylin、肌肉通路和其他代谢机制重新组合。因此，HM17321 接下来真正重要的已经不是股价还能不能再涨 30%。我更想看到的是它 Phase 1 的人体 PD 信号，肥胖受试者 12 周给药后的 fat mass 和 lean mass 变化，CRFR2 长期激活的安全窗口，以及它跟 GLP-1/GIP 类药物联用时到底有没有真正的 additive effect。如果动物身上“脂肪掉、肌肉保住甚至增加”的结果能够在人身上复制，那它确实可能打开一条非常漂亮的新路线。如果复制不了，23 亿美元依然只是一个带着大量 milestone 的 23 亿美元。药物研发就是这么残酷，也正因为这样有意思。减肥药第一阶段解决的是“能不能把体重减下来”。第二阶段开始解决“能不能把该减的东西减下来”。坠入爱河的智者觉得，这才是韩美药品这条新闻真正值得记住的地方。本文截至 2026 年 8 月 25 日公开资料整理，仅用于药物研发与产业趋势讨论，不构成医疗或投资建议。

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Scholar Rock (NASDAQ: SRRK), a global biopharmaceutical company dedicated to improving the lives of patients with rare, severe, and debilitating neuromuscular diseases by applying its world-leading platform in myostatin biology, today announced it has successfully removed Catalent Indiana LLC (part of Novo Nordisk) as a commercial fill-finish facility from its apitegromab Biologics License Application (BLA) for the treatment of spinal muscular atrophy (SMA) in the U.S., under guidance from FDA. FDA review of the BLA is progressing well with the Company’s alternate fill-finish facility, and Scholar Rock continues to expect an FDA approval decision by the September 30, 2026 Prescription Drug User Fee Act (PDUFA) date. Scholar Rock also announced that, following the August 7, 2026 customer notification that FDA classified the Catalent Indiana April 2026 general site inspection as Official Action Indicated (OAI), the Company has withdrawn its apitegromab Marketing Authorisation Application (MAA) via written procedure with the Committee for Medicinal Products for Human Use (CHMP), which concluded on August 20, 2026. Scholar Rock will remove Catalent Indiana as a commercial fill-finish facility from the apitegromab MAA and resubmit the application with the alternate fill-finish facility to facilitate the most expeditious path to a CHMP opinion. In addition, Scholar Rock announced that it is now on track to submit a Japanese New Drug Application (JNDA) for apitegromab for the treatment of children and adults with SMA by year end 2026, following alignment with Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) that no additional clinical studies are required. This alignment is based on PMDA’s assessment of the ability of apitegromab to meet the criteria as described in recent guidelines on core conditions for filing without Japanese clinical data. “We are very pleased with the continued constructive and collaborative engagement we have with regulators both in the U.S. and Europe and look forward to commencing our US launch in Q3 pending FDA approval,” said David L. Hallal, Board Chair and Chief Executive Officer of Scholar Rock. “In line with our ambition to serve patients with SMA in up to 50 countries around the world, we are also thrilled to announce that we now have alignment with PMDA in Japan to submit our apitegromab JNDA for the treatment of children and adults with SMA by year end. Together, our regulatory advancements reinforce our commitment to act with urgency on behalf of the SMA community globally.” In Japan, clinical studies in the Japanese population are typically required to support a JNDA filing. Scholar Rock engaged with PMDA regarding recent guidelines allowing JNDA submissions for specific orphan and rare disease drugs without domestic Japanese clinical trial data. The core conditions include a pivotal trial successfully completed outside of Japan, impractical patient recruitment due to small target patient populations, and available scientific and clinical evidence strongly indicating favorable benefit-risk profile for Japanese patients. Based on these criteria, the PMDA has agreed that an apitegromab JNDA may be filed without clinical data in Japanese patients. Scholar Rock’s alternate fill-finish facility for apitegromab is a U.S.-based facility producing numerous commercial products with a strong track record of regulatory compliance, including recent successful FDA and EMA inspections. Robust supply of apitegromab commercial vials from the alternate fill-finish facility is available to support the global launch of apitegromab following regulatory approvals. About Apitegromab Apitegromab is an investigational fully human monoclonal antibody inhibiting myostatin activation by selectively binding the pro- and latent forms of myostatin in the skeletal muscle. It is the first muscle-targeted treatment candidate in spinal muscular atrophy (SMA) to demonstrate clinical success in a pivotal Phase 3 clinical trial. Myostatin, a member of the TGFβ superfamily of growth factors, is expressed primarily by skeletal muscle cells, and the absence of its gene is associated with an increase in muscle mass and strength in multiple animal species, including humans. Scholar Rock believes that its highly selective targeting of pro- and latent forms of myostatin with apitegromab may lead to a clinically meaningful improvement in motor function in patients with SMA. The U.S. Food and Drug Administration (FDA) has granted Fast Track, Orphan Drug and Rare Pediatric Disease designations, and the European Medicines Agency (EMA) granted Priority Medicines (PRIME) and Orphan Medicinal Product designations, to apitegromab for the treatment of SMA. Apitegromab has not been approved for any use by the FDA or any other regulatory agency. About Scholar Rock Scholar Rock is a late-stage biopharmaceutical company focused on developing and commercializing apitegromab for children and adults with spinal muscular atrophy (SMA) and other rare, severe and debilitating neuromuscular diseases. As a global leader in myostatin biology, a field focused on proteins that regulate muscle mass, the biopharmaceutical company is named for the visual resemblance of a scholar rock to protein structures. Our commitment to unlock fundamentally different treatment approaches is powered by broad application of a proprietary platform, which has developed novel monoclonal antibodies to modulate protein growth factors with extraordinary selectivity. Scholar Rock works every day to create new possibilities for patients through its highly innovative anti-myostatin program, including opportunities in additional rare neuromuscular diseases. Learn more at ScholarRock.com and follow @ScholarRock on X and on LinkedIn. Scholar Rock® is a registered trademark of Scholar Rock, Inc. Availability of Other Information About Scholar Rock Investors and others should note that we communicate with our investors and the public using our company website, including, but not limited to, company disclosures, investor presentations and FAQs, Securities and Exchange Commission filings, press releases, public conference call transcripts and webcast transcripts, as well as on X (formerly known as Twitter) and LinkedIn. The information that we post on our website, X, or LinkedIn could be deemed to be material information. As a result, we encourage investors, the media and others interested to review the information that we post there on a regular basis. The contents of our website or social media shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended. Forward-Looking Statements This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Scholar Rock’s future expectations, plans and prospects, including without limitation, Scholar Rock’s expectations regarding its growth, strategy, progress and timing of its clinical trials and development programs for apitegromab, including the timing of any regulatory submissions, decisions and anticipated approvals; the therapeutic potential, clinical benefits and safety of any product candidates; expectations regarding actions by any regulatory authority, including the FDA, EMA or PMDA; the expected timing and outcome of FDA review of the accepted BLA for apitegromab by the September 30, 2026 PDUFA action date; expectations regarding timing and outcome of EMA review and MAA approval; expectations regarding the availability and timing of commercial supply of apitegromab from the Company’s fill-finish facility; expectations regarding commercial launch timing and readiness; expectations regarding the timing and submission of a JNDA; and the potential of its product candidates and proprietary platform. The use of words such as “may,” “might,” “could,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify such forward-looking statements. All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, without limitation, whether preclinical and clinical data, including the results from the Phase 3 SAPPHIRE trial and any results from ongoing or future clinical trials, including the Phase 2 OPAL clinical trial, the Phase 2 FORGE trial and the Phase 1 clinical trial of SRK-439, will be sufficient to support regulatory approval or further development; whether the updated BLA, including an alternate fill finish facility, will be sufficient to support regulatory approval; Scholar Rock’s ability to manage expenses or provide the financial support, resources and expertise necessary to identify and develop product candidates on the expected timeline; information provided or decisions made by regulatory authorities; competition from third parties that are developing products for similar uses; Scholar Rock’s ability to obtain, maintain and protect its intellectual property; and Scholar Rock’s dependence on third parties for development and manufacture of product candidates, as well as those risks more fully discussed in the section entitled “Risk Factors” in Scholar Rock’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2026, as well as discussions of potential risks, uncertainties, and other important factors in Scholar Rock’s subsequent filings with the Securities and Exchange Commission. Any forward-looking statements represent Scholar Rock’s views only as of today and should not be relied upon as representing its views as of any subsequent date. All information in this press release is as of the date of the release, and Scholar Rock undertakes no duty to update this information unless required by law.