GDF11

大会由扬州市人民政府主办，同写意专业策划，以“打造生物医药新质生产力”为主题，邀请众多行业领袖和先锋人物一起取势明道，就如何打造中国医药新质生产力，面向未来创新药如何立项，资本寒冬下的创新药BD与出海，GLP-1&小核酸药物以及抗体药的质量与生产四大主题展开深度研讨，为行业发展提供方向性指引。GLP-1引发的药王争霸赛，创造了前所未有的盛况。有目共睹，第一波“泼天富贵”已被诺和诺德、礼来瓜分殆尽，这两家公司市值纷纷暴涨。礼来市值突破7200亿美元，诺和诺德则在最近FDA批准司美格鲁肽新适应症之后，市值一度接近6000亿。财报显示，2023年诺和诺德司美格鲁肽销售额约211.58亿美元，礼来的度拉糖肽则创造71.3亿美元收入，替尔泊肽获批首年销售额也达到51.63亿美元。从增速来看，替尔泊肽远超司美格鲁肽最初的表现。减重市场的潜力依然在火热挖掘中。“大哥”“二哥”纷纷买厂建厂催产能，明面上，市场占领是当下这两家公司兵刃相接的主要触点。但长期结果还要回归医药市场的本质来看，患者需求是药物“适者生存”的根本法则。目前减重药物存在巨大缺陷——减重往往伴随肌肉减少，且对“骨骼肌和心肺肌都有明显的影响”。有研究显示，司美格鲁肽受试者减掉的体重中近40%为肌肉，而肌肉减少会增加患心血管疾病、骨质疏松症的风险，替尔泊肽也难以避免这一问题，这无疑创造了新的需求。蝴蝶扇动翅膀，增肌剂在无意间被“带飞”，很可能成为减肥药市场的下一个赛点。越来越多的公司开始推进增肌药物试验，有分析师预测，其市场将达到1000亿美元。这些药物最初设计用于构建、保存或再生骨骼肌，以治疗退行性疾病或老化引起的肌肉萎缩。而现在，它们最受关注的用途是，用于和治疗肥胖症的GLP-1激动剂联合进行测试，以抵御减重的副作用。投资者也开始将目光转向减脂增肌。BioAge Labs是该领域中一家代表公司，今年2月13日宣布已完成由Sofinnova Investments领投的1.7亿美元的D轮融资，礼来也选择这家Biotech作为合作伙伴。当然，长远来看，增肌并不总是配角位，在人类抗衰大健康领域还有更广阔的市场，有望带来更多临床和投资机会。1礼来押注ActRII和Apelin相比规规矩矩增产、想要坐稳“减肥一哥”宝座的诺和诺德来说，后来挑战者礼来的翻盘策略更耐人寻味。去年7月，礼来以19.25亿美元高价收购Versanis，获得其ActRIIA/B 单抗Bimagrumab。10月，礼来宣布与BioAge达成合作，将替尔泊肽和BioAge的其口服Apelin受体激动剂Azelaprag联用，进行II期临床试验。本质上这是一件事。礼来正在探索减少脂肪同时防止肌肉流失的产品组合，这家巨头最关注肌肉生长抑制素和艾帕素领域（ActRII受体和Apelin受体靶点）。1997年，科学家发现肌肉生长抑制素 (GDF8) 是骨骼肌大小的关键调节因子。早期研究显示，缺乏肌肉生长抑制素的老鼠和狗，其肌肉质量是野生型的两倍。随后大量研究证实，肌生长抑制素是肌肉质量的主要负调节因子，主要通过激活素II型受体 (ActRII) 发挥作用。包括Activin和GDF11在内的一些ActRII配体，被认为是肌肉质量的负调节剂。它们与肌生长抑制素一起与细胞膜上的ActRIIA或ActRIIB受体结合，ActRIIB最初被认为是肌生长抑制素的主要受体。ActRII在肌肉组织中的生物学机制（图源：Versanis公司官网）Versanis开发的Bimagrumab单抗是该靶点领域的代表者，此前已收获大量积极数据。其在一项针对2型糖尿病的超重或肥胖患者的II临床试验中48周数据显示，相比安慰剂，Bimagrumab治疗组的体重下降了6.5%，造成患者约22%脂肪质量的损失，并增加4.5%的无脂体重。同时，Bimagrumab治疗组在停药12周内并未观察到体重的增加。关于联用效果，一项Bimagrumab和司美格鲁肽联用的动物试验显示，用药2周后，该产品组合导致肥胖小鼠大于30%的脂肪损失，并增加了5%的瘦肉质量。目前，Bimagrumab正在进行临床IIb期BELIEVE研究，评估单药或联合司美格鲁肽48周治疗后在超重或肥胖的成年人中的效果。另一边，牵手礼来的BioAge在今年2月宣布完成1.7亿美元的D轮融资，主要用于推进Azelaprag与替尔泊肽联合治疗肥胖的2期临床试验，预计将于今年年中正式开启。Azelapra是Apelin受体的APJ激动剂，模拟了exerkine Apelin的活性，这是一种在运动后释放的“运动因子”多肽，作用于骨骼肌、心脏和中枢神经系统，调节代谢并促进肌肉再生。BioAge的研究显示，人的一生中，Apelin总体水平会逐渐下降，而Apelin水平较高的人具有更强的身体功能和更长的寿命。在2022年12月对227名65岁或以上老年人进行的一项Ib临床试验中，该药物可以显著预防老年人的肌肉萎缩。BioAge联合创始人、首席执行官Kristen Fortney曾公开表示，Azelaprag和Mounjaro联用的产品组合在I期研究和动物模型中均保留了瘦肉体组织，与单独使用Mounjaro相比，体重减轻了10-15%，有效地“增压”了减肥。不仅能看到减肥效果的放大，还看到了身体成分和功能的改善。巨头的收购与合作，往往预示着下一个热门竞逐标的。礼来的一系列布局似乎正指向，增肌是减肥市场的下一个赛点。2凭借增肌药物中场入局虽然没能赶上第一波东风，但还有机会在减肥市场分一杯羹，再生元、罗氏、辉瑞、阿斯利康等药企纷纷朝增肌药物联用展开动作。近日，再生元重申了2024年进入减肥赛道的计划——公司将开始测试其防止肌肉流失药物与司美格鲁肽的组合，预计在今年年中开始一项II期研究，测试一系列不同剂量和组合的司美格鲁肽、trevogrumab（一种抗肌肉生长抑制素抗体）和garetosmab（一种抗激活素a抗体）。Garetosmab（REGN 2477）是一种全人IgG4单克隆抗体，可特异性抑制激活素A (activin A)。Garetosmab可用于进行性骨化性纤维发育不良 。再生元称，预计将于5月开展Garetosmab和司美格鲁肽的联用试验，探索提高减肥质量且停药不反弹的解决方案。此外，这家公司还在推进基于遗传学的肥胖研究，重点关注GPR75靶点，而资料显示GPR75基因与肥胖显著相关。再生元正在通过内部和外部的组合开发，拓展siRNA/小核酸、小分子和抗体等多种GPR75靶点的疗法。罗氏也有凭借增肌药物联用入局减肥市场的想法，自去年的收购案之后，在一些公开发言中均有透露。去年年底，罗氏以超30亿美金收购了Carmot Therapeutics，一次获得了3款GLP类药物。该公司希望将抗肌肉生长抑制素抗体RO7204239与肠促胰岛素治疗相结合。RO7204239最初被测试用于增强脊髓性肌萎缩症患者的肌肉，但罗氏首席执行官Thomas Schinecker表示，该药物在弥补GLP-1缺陷方面能够发挥重要作用。辉瑞于2022年以116亿美元收购的Biohaven，同样也在推进增肌药物和司美格鲁肽的联合使用。目前，Biohaven正在进行taldefgrobep alfa（一种肌肉生长抑制素抑制剂）的临床III期试验，以改善脊髓性肌萎缩症的肌肉质量。肥胖小鼠模型中，该药物被证明成功地在减肥期间保持肌肉质量，促使Biohaven在II期试验中将其与司美格鲁肽联合使用。阿斯利康同样正在积极探索增肌降脂联合疗法。该公司去年以1.85亿美元收购了诚益生物口服GLP-1药物的非中国权利，并打算将其与AZD6234结合试验。还有一些靶点机制同样展现出增肌潜力。例如，mTORC1（雷帕霉素复合体1的机制靶点），参与肌肉再生。mTORC1激活可促进肌肉生长，但如果持续受到刺激，它也会通过激活蛋白酶体降解来诱导肌肉分解。长期的雷帕霉素治疗对老化的骨骼肌具有积极的作用，可以保持肌肉的大小、功能和神经肌肉连接（NMJ）完整性。此外，有研究人员希望通过刺激肌肉干细胞、调整细胞外基质的硬度等变量或改造细胞外囊泡来提供治疗，从而促进肌肉再生。Immunis和Juvena Therapeutics针对这一机制进行研究，专注于肌肉干细胞分泌成分，包括生长因子、细胞因子、趋化因子和细胞外基质成分。分泌蛋白会促进运动后的增殖，或增强细胞相互作用以加速伤口愈合，但它会随着年龄的增长而显著下降。Biophytis则重点关注与年龄相关的肌肉减少症和杜氏肌营养不良等神经肌肉疾病之间的共同途径。其主要候选药物是ruvembri（BIO101），是一款针对MAS受体的小分子药物。MAS受体存在于心肺和骨骼肌中。MAS激活下游AKT和AMPK激酶通路，分别刺激蛋白质合成和能量产生。相比海外的热火初起，国内还未形成增肌药物潮流。港股上市公司来凯医药可以说是最先作出反应的一家，本月上旬，该公司宣布其减脂增肌药物LAE102已完成中美双报。值得注意的是，目前全球在研ActRII药物中，Bimagrumab和LAE102是目前唯二开发肥胖适应症的候选药物。翰森制药也有意在ActRII受体靶点方向展开布局，2021年12月翰森药业曾以2000万美元加高达1.705亿美元里程碑从Keros引入KER-050，该药物家族蛋白是血红细胞和血小板生成以及肌肉和骨骼生长、修复和维护的主要调节因子，具备增肌药物潜力。3不可限量的消费和抗衰市场除了作为减肥“伴侣”外，增肌药物真正的蓝海市场在塑形消费和人类抗衰领域。从消费市场来看，增肌与减脂需求并驾齐驱，且随着审美观念的转变，增肌或将囊括更多潜在消费群体。同时，从广泛的人类抗衰领域来看，抗衰老将是一个必选项。研究显示，从30岁开始，人类每十年平均会失去3-8%的肌肉质量，60岁以后这种情况会加速。在老年群体中，肌肉流失或肌肉减少症会导致活动能力下降，并与跌倒、虚弱和心血管疾病有关。梅奥诊所Robert和Arlene Kogod表示，针对肌肉减少症最关键的问题在于，它通常被视为衰老和长期不动的症状，而不是一种独立的疾病。现阶段，肌肉减少症的标准干预措施包括力量训练和营养咨询，以确保患者摄入足够的蛋白质。从理论上讲，这种方法是有效的。但是，在有其他慢性病、炎症、受伤或行动不便的患者身上，并不总是奏效，因此需要有效药物的干预。随着全球人口老龄化加剧和抗衰老理念的普及，越来越多的消费者开始关注抗衰老措施。调查显示，59.2%的人在20-30岁就对衰老产生焦虑，95.3%的人在50岁之前对衰老产生焦虑。因此，有分析师表示，抗衰老市场潜力甚至更高于减肥。而增肌药物横跨减肥抗衰两大市场，显然前景可期。参考文献：1.Arnold, C. After obesity drugs’ success, companies rush to preserve skeletal muscle. Nat Biotechnol 42, 351–353 (2024).2.各公司官网更多优质内容，欢迎关注↓↓↓

背景GLP-1药物作为降糖减肥的重要药物类别，近年来备受关注并取得显著发展。以司美格鲁肽、替尔泊肽为代表的重磅单品频出，重点布局2型糖尿病、肥胖等患者基数较大的慢性病领域，全球年销售额快速攀升。市场研究机构数据显示，2020年全球GLP-1类药物市场规模约131亿美元，主要由诺和诺德和礼来占领，两家公司合计占比95%左右，也让礼来和诺和诺德登上了全球前二大市值药企，两者市值分别为7189.2亿美元、5493.95亿美元。未来长效GLP-1类药物市场规模将快速扩增，预计2025年全球GLP-1类药物市场规模将增至282亿美元，2030年增至407亿美元。图1.全球GLP-1类药物市场规模然而GLP-1类药物并非完美无缺，目前存在一定的局限性，比如需要长期服药，停药会发生反弹；另外，GLP-1类药物在减重过程中，除了能让患者失去脂肪，还会失去肌肉。俨然GLP-1类药物的竞争逐渐趋向白热化，在GLP-1之后，有哪些新的减重靶点值得关注？礼来近20亿美金大手笔押注的减重新靶点ActRII在闪闪发光。ActRII靶点概述激活素Ⅱ型受体（Activin type Ⅱ Receptor，即ActRⅡ，包括ActRⅡA和ActRⅡB）是转化生长因子β（TGF-β）受体家族的成员，是包括活化素A(Activin A)和活化素B(Activin B)及BMP7、BMP9、BMP10、GDF1、GDF8(myostatin)、 GDF11和Nodal在内的其他TGF-β家族成员的II型受体。 ActRⅡ存在于脂肪和肌肉细胞中。在脂肪细胞中，激活素通过ActRⅡ进行脂质存储，这是肥胖的重要驱动因素，阻断该信号通路，则可促进脂肪代谢；在肌肉细胞中，ActRⅡ受体传导的信号通路能够抑制肌肉生长并导致其萎缩，阻断骨骼肌中的激活素信号可以抑制这种萎缩，并可以促进肌肉质量的增加，帮助肥胖患者在减肥的同时改善身体成分和代谢。ActRII受体传导信号的活化会导致肌肉萎缩和脂肪组织中脂肪的累积，因此靶向此通路有望在驱动脂肪流失的同时，增加患者身体的肌肉组成，能够发挥双重作用，解决了GLP-1的痛点问题。ActRII靶点在研格局目前从全球来看，ActRII靶点的竞争格局十分良好，在研相关药物较多，但适应症以血液病、肺动脉高压、癌症为主，表现形式以ActRIIA/B融合蛋白为主；真正进入临床研究的、以肥胖为适应症的ActRII抗体，仅有礼来的Bimagrumab和来凯医药的LAE102。图2. ActRII在研格局来源：药研网✦  礼来|Bimagrumab2023年7月，礼来以19.25亿美金收购了Versanis公司，将其ActRIIA/B 单抗 Bimagrumab纳入囊中。而 Bimagrumab 的显著特点就在于：只减脂肪、不减肌肉。Bimagrumab最早是诺华制药开发治疗病理性肌肉丧失和无力的药物，但最终在临床试验阶段被砍掉。随后Versanis通过融资从诺华手里拿下该药授权，并将其推上减重赛道临床开发。图3. Bimagrumab作用机制来源:Versanis官网在Versanis的在研管道中，Bimagrumab也是最受关注的是一款单克隆抗体药物，直接对脂肪细胞产生作用，通过阻断II型激活素受体和肌肉生长抑制素，能够同时减少脂肪质量并保持肌肉质量。由于作用机制不同，Bimagrumab也不会有GLP-1药物“影响食欲”的副作用。据Ⅱ期试验数据，Bimagrumab 相比安慰剂表现出优异的减重控糖且肌肉量稳定的结果（第 48 周时全身脂肪量，治疗组和对照组分别为-20.5% 和-0.5%；瘦体重 3.6%vs-0.8%；Hb1Ac 水平-0.76%vs0.04%；体重-6.5%vs-0.8%）。此外，患者在停止治疗12周内并未观察到体重的增加。目前为止，观察到的bimagrumab的副作用包括肌肉痉挛和腹泻，它们发生在治疗早期，且大多为轻度。图4&5. Bimagrumab 2期临床结果目前，Bimagrumab 联用司美格鲁肽治疗肥胖症的 Ⅱb 临床 BELIEVE 研究已完成患者入组，顶线数据有望于 2024 年读出。✦  莱凯医药LAE102礼来的收购，让产业再次开始关注 ActRII 信号通路在增肌减重上的潜力。除bimagrumab外，全球范围内ActRII单抗仅来凯医药的LAE-102进入临床阶段。图6. 来凯医药部分管线|来源：官网LAE102是一种强效、选择性单克隆抗体，针对肌肉再生具有调控作用的新靶点ActRIIA。在临床前研究中，LAE102已显示出增加骨骼肌并减少白色脂肪的效果，是一种潜在的、用于肥胖和其他代谢性疾病适应症开发的候选药物。在肥胖小鼠模型中，LAE102与GLP-1的联合疗法显示出协同增效作用，有效加大减脂效果，同时避免肌肉流失，有望实现高质量减脂结果。去年5月，来凯医药宣布其自主研发的抗肿瘤潜在新药 LAE102 抗体获得 FDA 临床试验批准。今年2月28日，来凯医药宣布，CDE已受理了LAE102在肥胖症的新药临床试验申请(IND)，潜在用于治疗成人肥胖或代谢性疾病患者。图7. CDE官网✦  翰森药业KER-050除了来凯医药之外，翰森药业也留意到了激活素（ActRII）受体靶点带来的广谱疾病治疗的机会。2021年12月，翰森药业以2000万美金加高达1.705亿美元里程碑从Keros引入KER-050，获得了该产品在中国内地、香港和澳门地区的独家权益。KER-050（HS-20106）是一种“工程化的配体捕获体”，由经修饰的TGF-β受体（即激活素受体IIA型）配体结合区域与人源抗体的Fc区域融合而成，用于治疗骨髓增生异常综合征（MDS）和骨髓纤维化患者血细胞减少等领域患者。据ClinicalTrials网站，KER-050正在被开发用于治疗骨髓增生异常综合征（MDS）和骨髓纤维化（MF）患者，相关临床试验均已进展至2期临床阶段。图9. KER-050相关临床试验来源：ClinicalTrials结语对于国内的创新药企业来说，减重新靶点ActRII是能够获得MNC补全代谢领域布局的热门方向，也是全新的方向，存在巨大的机会。参考资料：1.https://www.laekna.com/new/342.htm2.https://classic.clinicaltrials.gov/3.https://www.cde.org.cn/4.https://www.versanisbio.com/细胞系产品查询投稿丨商务合作转载丨加交流群往期推荐一国产GLP-1药企递交IPO招股书，估值约8.3亿元人民币超40亿美元：上海Argo与Novartis达成多项目RNAi独家合作17 亿美元！强生与LegoChem就Trop2 靶向ADC的达成许可协议完整版：2023 全年药企裁员汇总点击下方“药研网”，关注更多精彩内容

Preclinical findings presented at Keystone Symposia show lean mass preservation, fat mass loss, and improved glucose metabolism Scholar Rock’s novel myostatin inhibitor, SRK-439, is part of its growing, industry-leading portfolio of innovative, highly selective anti-myostatin treatments under development CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Scholar Rock (NASDAQ: SRRK), a late-stage biopharmaceutical company focused on advancing innovative treatments for spinal muscular atrophy (SMA), cardiometabolic disorders, and other serious diseases where protein growth factors play a fundamental role, today announced new preclinical data showing the potential of SRK-439 to preserve lean mass and improve metabolic health as part of healthy weight loss. These data showed that SRK-439 maintained lean mass and improved fat mass loss when used in combination with a GLP-1 receptor agonist (GLP-1 RA; in separate experiments with semaglutide and liraglutide) in diet-induced obesity (DIO) mice. SRK-439 treatment also led to incremental lowering of fasting glucose beyond the levels seen with semaglutide alone. Detailed results were presented by Melissa Fulham, PhD, of Scholar Rock, at the Keystone Symposia’s Obesity: Causes and Consequences meeting in Vancouver, BC, Canada on February 5. “These preclinical data showing that SRK-439 preserves lean mass and improves fat mass loss provide compelling scientific rationale to study SRK-439 in combination with GLP-1 RA therapies for healthy weight loss management,” said Jay Backstrom, M.D., MPH, President and CEO of Scholar Rock. “We believe that preserving lean muscle mass through our highly selective approach to myostatin inhibition in combination with GLP-1 RA therapy has the potential to transform the management of weight loss. We look forward to initiating our proof-of-concept study with apitegromab in combination with GLP-1 RA therapy in obesity as we also continue to advance SRK-439 to clinic.” In January, Scholar Rock announced that the U.S. Food and Drug Administration cleared the company’s Investigational New Drug (IND) application for its Phase 2 proof-of-concept trial of apitegromab to treat obesity in patients taking a GLP-1 RA. Trial initiation is on track for mid-2024, and data from the apitegromab Phase 2 trial are expected in mid-2025. In parallel, Scholar Rock is developing SRK-439, a novel investigational selective myostatin inhibitor, optimized for the treatment of obesity. Selectivity and affinity: SRK-439 works by selectively binding to the pro- and latent forms of myostatin, as confirmed through in vitro ELISA testing that shows SRK-439 does not bind to closely related TGFβ family members GDF11 and Activin A, both of which, if inhibited, have potentially detrimental effects outside of the muscle. The studies confirmed that SRK-439 binds to latent myostatin with 0.579 nM affinity. This selectivity and affinity, along with favorable developability characteristics and durable pharmacokinetics suggests that SRK-439 could be suitable for dosing in a subcutaneous formulation and in a low dose volume in a population of adults with obesity. Changes in body weight, lean mass, and fat mass: Quantitative nuclear magnetic resonance (qNMR) was used to analyze body composition in DIO mice in two separate experiments. In the first, mice received either liraglutide, 0.06 mg/kg daily, or liraglutide, at the same dose, plus SRK-439 in either a 0.3, 1.0, or 3.0 mg/kg weekly dose. In the second experiment, DIO mice received either semaglutide, 0.04 mg/kg daily or semaglutide, at the same dose, plus SRK-439 in either a 0.1, 0.3, 1.0, or 3.0 mg/kg weekly dose. Total body weight, lean mass, and fat mass were assessed. As expected, both liraglutide and semaglutide reduced body weight in DIO mice compared to baseline. SRK-439 diminished the GLP-1 RA-driven lean mass loss in combination with semaglutide (–7.55% to –1.43% change from baseline in lean mass) and with liraglutide (1.98% to 5.55% from baseline). These results were dose-dependent: lean mass was preserved more as the dose of SRK-439 increased. SRK-439 also improved fat mass loss (–36.60% to –46.32% from baseline with semaglutide; –17.31% to –19.04% from baseline with liraglutide). Results below are shown for the 3 mg/kg dose group of SRK-439 as compared to the IgG control group in each experiment (IgG + semaglutide or IgG + liraglutide), with the full results available on the poster in the Posters and Presentations section of the Scholar Rock website. Experiment 1: Liraglutide Experiment 2: Semaglutide IgG Control SRK-439 (3mg/kg) IgG Control SRK-439 (3mg/kg) Change in Lean Mass from Baseline –4.5% (n=8; p<0.0001) 5.6% (n=8; p<0.0001) –11.3% (n=8; P<0.0001) –1.4% (n=8; p<0.0001) Change in Fat Mass from Baseline 0.4% (n=8; p<0.001) –18.6% (n=8; ns) –36.6% (n=8; ns) –37.99 (n=8; ns) Changes in fasting glucose Fasting glucose was measured on Day 18 of the study in DIO mice that had received treatment with either semaglutide or semaglutide in combination with SRK-439. Mean fasting glucose levels were lower in mice receiving SRK-439, with results for 0.3, 1.0, and 3.0 mg/kg reaching significance compared to semaglutide + IgG control alone (103.0 – 107.8 mg/dL; p<0.05). For conference information, visit . The poster is available in the Publications & Posters section of Scholar Rock’s website. About SRK-439 SRK-439 is a novel, preclinical, investigational myostatin inhibitor that has high in vitro affinity for pro- and latent myostatin and maintains myostatin specificity (i.e., no GDF11 or Activin-A binding), and is initially being developed for the treatment of obesity. Based on preclinical data, SRK-439 has the potential to support healthier weight management by preserving lean mass. The efficacy and safety of SRK-439 have not been established and SRK-439 has not been approved for any use by the FDA or any other regulatory agency. About Scholar Rock Scholar Rock is a biopharmaceutical company that discovers, develops, and delivers life-changing therapies for people with serious diseases that have high unmet need. As a global leader in the biology of the transforming growth factor beta (TGFβ) superfamily of cell proteins and named for the visual resemblance of a scholar rock to protein structures, the clinical-stage company is focused on advancing innovative treatments where protein growth factors are fundamental. Over the past decade, Scholar Rock has created a pipeline with the potential to advance the standard of care for neuromuscular disease, cardiometabolic disorders, cancer, and other conditions where growth factor-targeted drugs can play a transformational role. Scholar Rock is the only company to show clinical proof-of-concept for a muscle-targeted treatment in spinal muscular atrophy (SMA). This commitment to unlocking fundamentally different therapeutic approaches is powered by broad application of a proprietary platform, which has developed novel monoclonal antibodies to modulate protein growth factors with extraordinary selectivity. By harnessing cutting-edge science in disease spaces that are historically under-addressed through traditional therapies, Scholar Rock works every day to create new possibilities for patients. Learn more about our approach at ScholarRock.com and follow @ScholarRock and on LinkedIn. 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 Twitter and LinkedIn. The information that we post on our website or on Twitter 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. Scholar Rock® is a registered trademark of Scholar Rock, Inc. 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, results and timing of its clinical trials for apitegromab and its preclinical programs, including SRK-439, the ability of any product candidate to perform in humans in a manner consistent with earlier nonclinical, preclinical or clinical trial data, 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, that preclinical data are not predictive of, may be inconsistent with, or more favorable than, data generated from future or ongoing clinical trials of the same product candidates; Scholar Rock’s ability to provide the financial support, resources and expertise necessary to identify and develop product candidates on their expected timelines; the data generated from Scholar Rock’s nonclinical and preclinical studies and clinical trials; 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; Scholar Rock’s dependence on third parties for development and manufacture of product candidates including, without limitation, to supply any clinical trials; Scholar Rock’s ability to manage expenses and to obtain additional funding when needed to support its business activities and establish and maintain strategic business alliances and new business initiatives, and the impacts of public health pandemics such as COVID-19 on business operations and expectations, 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 September 30, 2023, 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.