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 that support the potential of SRK-439, a highly selective investigational antimyostatin antibody, to increase lean mass and lower fat mass gain when taken with metformin.

马萨诸塞州剑桥市。-（商业新闻短讯）--Scholar Rock（纳斯达克：SRRK），一家晚期生物制药公司，专注于推进脊髓性肌萎缩症（SMA），心脏代谢紊乱和其他蛋白质生长因子起基础作用的严重疾病的创新治疗，今天宣布了新的临床前数据，支持SRK-439的潜力，SRK-439是一种高度选择性的研究性抗肌球蛋白抗体，与二甲双胍一起服用可增加瘦体重和降低脂肪量。

These data will be presented by Melissa Fulham, Ph.D., of Scholar Rock, at the ObesityWeek conference in San Antonio, Texas on November 5..

这些数据将由学者岩（Scholar Rock）的梅丽莎·富勒姆（MelissaFulham）博士在11月5日于德克萨斯州圣安东尼奥举行的肥胖周（ObesityWeek）会议上提交。。

“These new data build upon a robust body of evidence demonstrating the potential of selective myostatin inhibition as an important therapeutic approach,” said Jay Backstrom, M.D., MPH, President and Chief Executive Officer at Scholar Rock. “These latest SRK-439 data support our hypothesis that a highly selective approach to targeting myostatin inhibition could have positive effects on body composition in people living with obesity and associated comorbidities like diabetes, and also underscore the value within Scholar Rock’s platform.

Scholar Rock总裁兼首席执行官Jay Backstrom医学博士说：“这些新数据建立在大量证据的基础上，证明选择性肌肉生长抑制素抑制作为一种重要治疗方法的潜力。”。“这些最新的SRK-439数据支持我们的假设，即针对肌肉生长抑制素抑制的高度选择性方法可能对肥胖和糖尿病等相关合并症患者的身体成分产生积极影响，也强调了Scholar Rock平台的价值。

We are looking forward to providing more updates on the exciting advancements in our cardiometabolic program, including our Phase 2 EMBRAZE trial topline data in the second quarter of 2025.”.

我们期待着提供更多关于我们心脏代谢计划令人兴奋的进展的最新信息，包括2025年第二季度的第二阶段EMBRAZE试验topline数据。”。

Preclinical study design

临床前研究设计

The research study tested a murine equivalent of SRK-439 in a diet-induced obesity (DIO) mouse model. All mice were given a high-fat diet, followed by either metformin (50 mg/kg daily) or control (water) for four weeks. Following that four-week period, mice in metformin and control groups were given either an IgG control antibody (10 mg/kg weekly) or SRK-439 (10 mg/kg weekly for younger mice and 3 mg/kg weekly for older mice) for another four weeks.

该研究在饮食诱导的肥胖（DIO）小鼠模型中测试了SRK-439的小鼠等效物。所有小鼠均接受高脂肪饮食，然后服用二甲双胍（每日50 mg/kg）或对照（水）四周。在这四周之后，给予二甲双胍和对照组的小鼠IgG对照抗体（每周10 mg/kg）或SRK-439（年轻小鼠每周10 mg/kg，老年小鼠每周3 mg/kg）另外四周。

To assess whether effects were persistent across age ranges, this study design was repeated in two age groups: both young (10-week-old) and mature (22-week-old) DIO mice..

为了评估不同年龄段的影响是否持续，在两个年龄组中重复了这项研究设计：年轻（10周龄）和成熟（22周龄）DIO小鼠。。

Quantitative nuclear magnetic resonance (qNMR) was used to analyze change in lean mass at baseline, after four weeks of metformin treatment, and every two weeks following treatment with SRK-439 or IgG control.

定量核磁共振（qNMR）用于分析基线时，二甲双胍治疗四周后以及用SRK-439或IgG对照治疗后每两周瘦体重的变化。

Changes in body composition in the presence or absence of metformin

存在或不存在二甲双胍时身体成分的变化

The group that received SRK-439 on the background of metformin showed a significant increase in lean mass versus the group receiving metformin alone, and this result was consistent across age groups. Key findings supporting the potential for SRK-439 in advancing healthier weight management include:

在二甲双胍背景下接受SRK-439的组与单独接受二甲双胍的组相比，瘦体重显着增加，并且该结果在各年龄组之间是一致的。支持SRK-439促进更健康体重管理潜力的主要发现包括：

Young animals treated with SRK-439 and metformin demonstrated a 2-fold increase in lean mass over the duration of the study compared to the lean mass increase in the metformin group and in IgG controls (31.6% increase from baseline vs. 15.1%, p<0.0001).

与二甲双胍组和IgG对照组的瘦体重增加相比，用SRK-439和二甲双胍治疗的年轻动物在研究期间瘦体重增加了2倍（比基线增加31.6%，比15.1%，p<0.0001）。

In older metformin-treated animals, the increase in lean mass in the SRK-439 treated animals compared to IgG controls was 50-fold (10.2% lean mass increase from baseline versus 0.2% in IgG controls, p<0.0001), owing primarily to the limited lean mass growth in the IgG control group over the duration of the study due to the age of the animals..

在老年二甲双胍治疗的动物中，与IgG对照组相比，SRK-439治疗动物的瘦体重增加了50倍（从基线到IgG对照组瘦体重增加了10.2%，而IgG对照组瘦体重增加了0.2%，p<0.0001），这主要是由于IgG对照组在研究期间由于动物的年龄而瘦体重增长有限。。

In young mice, the combination treatment of SRK-439 and metformin also resulted in lower fat mass gain (68.2% increase from baseline) than metformin alone (114% increase from baseline; p<0.05).

在年轻小鼠中，SRK-439和二甲双胍的联合治疗也比单独使用二甲双胍（从基线增加114%；p＜0.05）导致较低的脂肪量增加（从基线增加68.2%）。

In older mice, SRK-439 showed a trend toward reduced fat mass gain when combined with metformin, as compared to metformin alone (10.6% increase from baseline vs 18.4%; not statistically significant).

。

“These new preclinical data show that selectively inhibiting myostatin in combination with metformin increased lean mass—and this effect was robust even in the older treatment group that was more weight stable,” said Mo Qatanani, PhD, Chief Scientific Officer at Scholar Rock. 'In addition, we observed that when we combined SRK-439 and metformin in younger mice, the effect of lowering fat mass gain was greater than with either therapy alone.

Scholar Rock首席科学官Mo Qatanani博士说：“这些新的临床前数据表明，选择性抑制肌肉生长抑制素联合二甲双胍可以增加瘦体重，即使在体重更稳定的老年治疗组中，这种效果也很明显。”此外，我们观察到，当我们在年轻小鼠中联合使用SRK-439和二甲双胍时，降低脂肪量增加的效果大于单独使用任何一种疗法。

Taken together, this is compelling evidence suggesting that SRK-439 has the potential to improve body composition and contribute to healthier weight management in the context of both obesity and type 2 diabetes. These exciting data advance the science of obesity research and continue to differentiate Scholar Rock’s pipeline and anti-myostatin programs.”.

综上所述，这是令人信服的证据，表明SRK-439有可能在肥胖和2型糖尿病的背景下改善身体成分并有助于更健康的体重管理。这些令人兴奋的数据推进了肥胖研究的科学，并继续区分学者洛克的管道和抗肌肉生长抑制素计划。”。

Poster Presentation Information

海报展示信息

Title: SRK-439 Selectively Inhibits Myostatin to Promote Healthy Body Composition During Metformin Therapy

标题：在二甲双胍治疗期间，SRK-439选择性抑制肌肉生长抑制素以促进健康的身体成分

Presentation type: Poster presentation

展示类型：海报展示

Presenter: Melissa Fulham, Ph.D., Senior Scientist II, Scholar Rock

主持人：梅丽莎·富勒姆博士，高级科学家II，学者洛克

Date and time: Tuesday, November 5, 2024, 2:30 PM CT

Date and time: Tuesday, November 5, 2024, 2:30 PM CT

Location: Henry B. González Convention Center, San Antonio, TX

地点：德克萨斯州圣安东尼奥市亨利·冈萨雷斯会议中心

For conference information, visit https://obesityweek.org/.

有关会议信息，请访问https://obesityweek.org/.

The slides from the presentation are available in the Publications & Posters section of Scholar Rock’s website.

演讲中的幻灯片可在学者洛克网站的出版物和海报部分找到。

About EMBRAZE

关于EMBRAZE

EMBRAZE is a randomized, double-blind, placebo-controlled, Phase 2 proof-of-concept trial evaluating the efficacy, safety and pharmacokinetics of apitegromab in adults with a body mass index (BMI) of >27 (overweight) or a BMI of >30 (obese) and taking a GLP-1 RA (tirzepatide or semaglutide). The target enrollment of EMBRAZE is 100 subjects aged 18-65 who are overweight or obese without diabetes.

EMBRAZE是一项随机，双盲，安慰剂对照的2期概念验证试验，评估阿哌曲单抗在体重指数（BMI）>27（超重）或BMI>30（肥胖）且服用GLP-1 RA（tirzepatide或semaglutide）的成年人中的疗效，安全性和药代动力学。EMBRAZE的目标招募对象是100名年龄在18-65岁之间的超重或肥胖且无糖尿病的受试者。

As part of the study design, the treatment period is 24 weeks, and all subjects will receive a GLP-1 RA. In addition, all subjects will be randomized 1:1 to receive either apitegromab or placebo by intravenous (IV) infusion every four weeks during the 24-week treatment period. The primary endpoint is change from baseline at Week 24 in lean mass assessed by dual-energy X-ray absorptiometry.

作为研究设计的一部分，治疗期为24周，所有受试者将接受GLP-1 RA。此外，在24周的治疗期间，所有受试者将以1:1的比例随机接受apitegromab或安慰剂，每四周静脉（IV）输注一次。主要终点是通过双能X射线吸收测定法评估的瘦体重从第24周的基线变化。

Secondary endpoints include additional weight loss measures, safety and tolerability, and pharmacokinetic outcomes. Exploratory endpoints at Weeks 24 and 32 include cardiometabolic parameters (e.g. HbA1c), body composition, and physical function..

次要终点包括额外的减肥措施，安全性和耐受性以及药代动力学结果。第24周和第32周的探索性终点包括心脏代谢参数（例如HbA1c），身体成分和身体机能。。

About SRK-439

关于SRK-439

SRK-439 is a novel, preclinical, investigational myostatin inhibitor that binds to pro- and latent myostatin with high affinity and is selective for myostatin (i.e., no GDF11 or Activin-A binding), and is initially being developed for the treatment of cardiometabolic disorders, including obesity. Based on preclinical data, SRK-439 has the potential to support healthier weight management by preserving lean mass during weight loss.

SRK-439是一种新型的临床前研究性肌生长抑制素抑制剂，以高亲和力与促肌生长抑制素和潜伏性肌生长抑制素结合，对肌生长抑制素具有选择性（即无GDF11或激活素a结合），最初用于治疗心脏代谢紊乱，包括肥胖。根据临床前数据，SRK-439有可能通过在减肥过程中保持瘦体重来支持更健康的体重管理。

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..

SRK-439的有效性和安全性尚未确定，并且SRK-439尚未被FDA或任何其他监管机构批准用于任何用途。。

About Apitegromab

关于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 to demonstrate clinical proof-of-concept in spinal muscular atrophy (SMA).

Apitegromab是一种通过选择性结合骨骼肌中肌生长抑制素的前体和潜伏形式来抑制肌生长抑制素活化的研究性全人单克隆抗体。。

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.

肌肉生长抑制素是生长因子TGFβ超家族的成员，主要由骨骼肌细胞表达，其基因的缺失与包括人类在内的多种动物的肌肉质量和力量增加有关。Scholar Rock认为，阿匹曲单抗对肌肉生长抑制素的前体和潜在形式的高度选择性靶向可能会导致SMA患者运动功能的临床意义改善。

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) has 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..

。Apitegromab尚未被FDA或任何其他监管机构批准用于任何用途。。

About Scholar Rock

关于学者岩

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.

Scholar Rock是一家生物制药公司，为严重疾病患者发现、开发和提供改变生活的疗法，这些患者的需求尚未得到满足。作为细胞蛋白转化生长因子β（TGFβ）超家族生物学的全球领导者，该公司以学者摇滚与蛋白质结构的视觉相似性而命名，临床阶段公司专注于推进蛋白质生长因子为基础的创新治疗。

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..

在过去的十年中，学者洛克（Scholar Rock）创建了一条管道，有可能提高神经肌肉疾病、心脏代谢紊乱、癌症和其他生长因子靶向药物可以发挥变革作用的疾病的护理标准。。

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.

这种解锁根本不同的治疗方法的承诺是由专利平台的广泛应用所推动的，该平台开发了新型单克隆抗体，以非凡的选择性调节蛋白质生长因子。学者洛克（Scholar Rock）每天都在利用传统疗法无法解决的疾病领域的尖端科学，为患者创造新的可能性。

Learn more about our approach at ScholarRock.com and follow @ScholarRock and on LinkedIn..

在ScholarRock.com了解更多有关我们的方法的信息，并关注@ScholarRock和LinkedIn。。

Availability of Other Information About Scholar Rock

学者岩其他信息的可用性

Investors and others should note that we communicate with our investors and the public using our company website www.scholarrock.com, 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.

投资者和其他人应该注意，我们使用公司网站www.scholarrock.com与投资者和公众进行沟通，包括但不限于公司披露、投资者介绍和常见问题解答、证券交易委员会备案、新闻稿、公开电话会议记录和网络广播记录，以及推特和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..

我们在网站、推特或LinkedIn上发布的信息可能被视为重要信息。因此，我们鼓励投资者、媒体和其他有兴趣的人定期审查我们在那里发布的信息。我们网站或社交媒体的内容不应被视为通过引用纳入1933年《证券法》修订版下的任何备案中。。

Scholar Rock® is a registered trademark of Scholar Rock, Inc.

Scholar Rock®是Scholar Rock，Inc.的注册商标。

Forward-Looking Statements

前瞻性声明

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 for apitegromab, and indication selection and development timing, including the timing of any regulatory submissions, the therapeutic potential, clinical benefits and safety of any product candidates, expectations regarding timing, success and data announcements of current ongoing preclinical and clinical trials, its cash runway, expectations regarding the achievement of important milestones, 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.

本新闻稿包含1995年《私人证券诉讼改革法案》所指的“前瞻性声明”，包括但不限于关于Scholar Rock未来期望、计划和前景的声明，包括但不限于Scholar Rock对其阿替格洛单抗临床试验的增长、战略、进展和时间安排的期望，以及适应症选择和开发时间安排，包括任何监管提交的时间安排，任何候选产品的治疗潜力、临床益处和安全性，对当前正在进行的临床前和临床试验的时间安排、成功和数据公告的期望，其现金跑道，对实现重要里程碑的期望，任何候选产品以与早期非临床试验一致的方式在人体中表现的能力，以及临床前或临床试验数据，及其候选产品和专有平台的潜力。

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.

使用诸如“可能”、“可能”、“可能”、“将要”、“应该”、“期望”、“计划”、“预期”、“相信”、“估计”、“项目”、“打算”、“未来”、“潜力”或“继续”等词语以及其他类似表达旨在识别此类前瞻性陈述。所有此类前瞻性声明均基于管理层当前对未来事件的预期，并受到许多风险和不确定性的影响，这些风险和不确定性可能导致实际结果与此类前瞻性声明中规定或暗示的结果存在重大不利差异。

These risks and uncertainties include, without limitation, whether the results from the Phase 3 SAPPHIRE trial will be sufficient to support regulatory approval, that the full results from the Phase 3 SAPPHIRE trial may differ from the topline data, tha.

这些风险和不确定性包括但不限于，第三阶段SAPPHIRE试验的结果是否足以支持监管部门的批准，第三阶段SAPPHIRE试验的全部结果可能与topline数据tha不同。