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 that the first participants were dosed in the Phase 2 EMBRAZE proof-of-concept trial, designed to assess the safety and efficacy of apitegromab, an investigational, highly selective myostatin inhibitor, to preserve lean muscle mass in individuals living with obesity and on background therapy of a GLP-1 receptor agonist (GLP-1 RA).

马萨诸塞州剑桥市。-（商业新闻短讯）--Scholar Rock（纳斯达克：SRRK）是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，第一批参与者在第二阶段EMBRAZE概念验证试验中服用了药物，该试验旨在评估apitegromab（一种研究性高选择性肌肉生长抑制素抑制剂）的安全性和有效性，以保持肥胖患者的瘦肌肉质量，并对GLP-1受体激动剂（GLP-1 RA）进行背景治疗。

The trial will also evaluate the effects of apitegromab on the durability of weight loss upon withdrawal of GLP-1 RA therapy. The results from this trial will inform the development of SRK-439, a novel investigational selective myostatin inhibitor optimized for the treatment of cardiometabolic disorders, including obesity..

该试验还将评估阿匹曲单抗对停止GLP-1 RA治疗后体重减轻持久性的影响。该试验的结果将为SRK-439的开发提供信息，SRK-439是一种新型的研究性选择性肌肉生长抑制素抑制剂，可用于治疗包括肥胖在内的心脏代谢紊乱。。

The Company also presented new preclinical data that support the potential of SRK-439 to increase lean mass and contribute to a favorable body composition following withdrawal from GLP-1 RA treatment. These data were presented by Melissa Fulham, PhD, of Scholar Rock, at the American Diabetes Association’s 84th Scientific Sessions on June 23rd in Orlando, Florida..

该公司还提供了新的临床前数据，这些数据支持SRK-439在退出GLP-1 RA治疗后增加瘦体重并有助于改善身体成分的潜力。这些数据由Scholar Rock的Melissa Fulham博士于6月23日在佛罗里达州奥兰多举行的美国糖尿病协会第84届科学会议上提交。。

“We are happy to share the exciting news that we’ve dosed the first participants in our EMBRAZE clinical trial ahead of schedule and to have new preclinical data with SRK-439, our highly selective anti-myostatin, featured at the American Diabetes Association Scientific Sessions,” said Jay Backstrom, M.D., MPH, President and Chief Executive Officer at Scholar Rock.

Scholar Rock总裁兼首席执行官Jay Backstrom医学博士说：“我们很高兴与大家分享一个令人兴奋的消息，即我们提前给EMBRAZE临床试验的首批参与者服用了药物，并获得了SRK-439的新临床前数据，SRK-439是我们高度选择性的抗肌生长抑制素，在美国糖尿病协会科学会议上发挥了重要作用。”。

“SRK-439 preclinical data to date have demonstrated preservation of lean mass with GLP-1 RA-induced weight loss, attenuation of fat mass regain following GLP-1 RA withdrawal, and greater potency compared to an anti-ACTRII antibody. Together, these data continue to support a best-in-class potential for healthy weight loss management and could be transformative for the management of weight loss.

“迄今为止，SRK-439临床前数据已经证明，GLP-1 RA诱导的体重减轻可以保持瘦体重，GLP-1 RA停药后脂肪量恢复的减弱，以及与抗ACTRII抗体相比更大的效力。总之，这些数据继续支持健康减肥管理的最佳潜力，并可能对减肥管理产生变革。

We are looking forward to providing additional updates on our cardiometabolic program as we advance SRK-439, as well as the EMBRAZE trial.”.

随着我们推进SRK-439以及EMBRAZE试验，我们期待着为我们的心脏代谢计划提供更多更新。”。

Preclinical experimental design

临床前实验设计

For the preclinical research study, the Company tested a murine equivalent of SRK-439 in a diet-induced obesity (DIO) mouse model. Mice were given either a high-fat diet plus semaglutide (0.04 mg/kg, daily) and an IgG control antibody (weekly, 10 mg/kg), or a high-fat diet plus semaglutide (0.04 mg/kg, daily) in combination with weekly injections of SRK-439 (10 mg/kg).

对于临床前研究，该公司在饮食诱导肥胖（DIO）小鼠模型中测试了小鼠等效的SRK-439。给予小鼠高脂饮食加semaglutide（每天0.04 mg/kg）和IgG对照抗体（每周10 mg/kg），或高脂饮食加semaglutide（每天0.04 mg/kg）每周注射SRK-439（10 mg/kg）。

Following four weeks of treatment, semaglutide was withdrawn from both treatment groups and mice remained on either the IgG control antibody weekly or on SRK-439. Treatment continued for another four weeks, for a total of eight weeks in the study. Quantitative nuclear magnetic resonance (qNMR) was used to analyze change in lean mass at two weeks and again at four weeks of semaglutide treatment, and every two weeks after that until the end of the subsequent four-week withdrawal period..

。在研究中，治疗又持续了四周，总共持续了八周。定量核磁共振（qNMR）用于分析semaglutide治疗两周和四周时瘦体重的变化，此后每两周分析一次，直到随后的四周停药期结束。。

Changes in body composition after semaglutide withdrawal

停用semaglutide后身体成分的变化

The group that received SRK-439 maintained more favorable body composition than the group receiving IgG antibody. Key findings supporting the potential for SRK-439 in advancing healthier weight management include:

接受SRK-439的组比接受IgG抗体的组保持更有利的身体组成。支持SRK-439促进更健康体重管理潜力的主要发现包括：

Administration with SRK-439 attenuated the loss of lean mass during semaglutide treatment and significantly increased lean mass after semaglutide discontinuation as compared to IgG control;

与IgG对照相比，SRK-439给药减轻了semaglutide治疗期间瘦体重的损失，并且在停用semaglutide后瘦体重显着增加；

SRK-439 administration also attenuated the fat mass rebound after semaglutide discontinuation as compared to that in IgG control + semaglutide mice; and

与IgG对照+semaglutide小鼠相比，SRK-439给药也减弱了semaglutide停药后的脂肪量反弹；和

Body composition, i.e. proportion of lean mass or fat mass to total body weight, was more favorable in mice receiving SRK-439 as compared to IgG control: Mice administered SRK-439 had higher relative lean mass (65.8%) and lower relative fat mass (18.0%) at the end of the withdrawal period compared to IgG control (57.1% lean mass and 28.7% fat mass)..

与IgG对照组相比，接受SRK-439的小鼠的身体组成，即瘦体重或脂肪量占总体重的比例更有利：与IgG对照组（57.1%瘦体重和28.7%脂肪量）相比，服用SRK-439的小鼠在停药期结束时具有更高的相对瘦体重（65.8%）和更低的相对脂肪量（18.0%）。。

Shown below are results for body composition at baseline (6 days before semaglutide treatment), the end of semaglutide treatment (at 4 weeks), and at the end of the semaglutide withdrawal period (at 8 weeks):

如下所示为基线（semaglutide治疗前6天），semaglutide治疗结束（4周）和semaglutide停药期结束（8周）时的身体成分结果：

Endpoint (units)

端点（单位）

IgG control + semaglutide

IgG对照+semaglutide

SRK-439 + semaglutide

SRK-439+信号肽

P value

P值

Absolute lean mass (g) at baseline

基线时的绝对瘦质量（g）

24.8

24.8

25.5

25.5

n.s.

n、 s。

Absolute lean mass (g) at 4 weeks

4周时的绝对瘦体重（g）

22.3

22.3

26.4

26.4

P<0.001

P<0.001

Absolute lean mass (g) at 8 weeks

8周时的绝对瘦体重（g）

25.1

25.1

29.4

29.4

P<0.0001

P<0.0001

Absolute fat mass (g) at baseline

11.8

11.8

10.3

10.3

n.s.

n、 s。

Absolute fat mass (g) at 4 weeks

5.9

5.9

3.8

3.8

n.s.

n、 s。

Absolute fat mass (g) at 8 weeks

8周时的绝对脂肪量（g）

12.7

12.7

8.3

8.3

n.s.

n、 s。

Relative lean mass (%) at 8 weeks

8周时的相对瘦体重（%）

57.1%

57.1%

65.8%

65.8%

P<0.001

P<0.001

Relative fat mass (%) at 8 weeks

8周时的相对脂肪量（%）

28.7%

28.7%

18.0%

18.0%

P<0.01

P<0.01

“These new preclinical data provide compelling evidence that SRK-439 contributed to lean muscle preservation during GLP-1 RA-induced weight loss and attenuated fat mass rebound following discontinuation of semaglutide,” said Mo Qatanani, PhD, Chief Scientific Officer at Scholar Rock. “Mice receiving SRK-439 treatment had significantly more lean mass at the end of the semaglutide withdrawal period.

Scholar Rock首席科学官Mo Qatanani博士说：“这些新的临床前数据提供了令人信服的证据，表明SRK-439在GLP-1 RA诱导的体重减轻过程中有助于保持瘦肌肉，并在停用semaglutide后减轻了脂肪量反弹。”。“接受SRK-439治疗的小鼠在semaglutide停药期结束时有明显更多的瘦体重。

These exciting data continue to support the differentiated profile of SRK-439 and its potential to contribute to healthier weight management and long-term metabolic benefits during and after GLP-1 RA treatment.”.

这些令人兴奋的数据继续支持SRK-439的差异化特征及其在GLP-1 RA治疗期间和之后为更健康的体重管理和长期代谢益处做出贡献的潜力。”。

For conference information, visit https://professional.diabetes.org/scientific-sessions.

有关会议信息，请访问https://professional.diabetes.org/scientific-sessions.

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。它是第一个在脊髓性肌萎缩症（SMA）中证明临床概念验证的肌肉靶向治疗候选者。

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. The efficacy and safety of apitegromab have not been established and apitegromab has not been approved for any use by the FDA or any other regulatory agency..

美国食品和药物管理局（FDA）已授予快速通道，孤儿药和罕见儿科疾病名称，欧洲药品管理局（EMA）已授予apitegromab优先药物（PRIME）和孤儿药品名称，用于治疗SMA。阿替格玛的有效性和安全性尚未确定，阿替格玛尚未被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。。

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.

Scholar Rock是唯一一家为脊髓性肌萎缩症（SMA）的肌肉靶向治疗提供临床概念验证的公司。这种解锁根本不同的治疗方法的承诺是由专有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。

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..

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。在ScholarRock.com上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。根据修订后的《1933年证券法》，我们网站或社交媒体的内容不得被视为通过引用纳入任何备案中。。

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 its preclinical programs, including SRK-439, and indication selection and development timing, including the therapeutic potential, clinical benefits and safety thereof, expectations regarding timing, success and data announcements of current ongoing preclinical and clinical trials, 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未来的期望、计划和前景的声明，包括但不限于Scholar Rock对其阿替格单抗及其临床前项目（包括SRK-439）临床试验的增长、战略、进展和时机的期望，以及适应症选择和开发时机，包括其治疗潜力、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机、成功和数据公告的期望，任何候选产品以与早期非临床、临床前或临床试验数据一致的方式在人体中表现的能力，以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产生重大不利差异。

These risks and uncertainties include, without limitation, that preclinical and clinical data, including the results from the Phase 2a clinical trial of apitegromab, or its preclinical data with respect to SRK-439, are not predictive of, may be inconsistent with, or more favorable than, data generated from future or ongoing clinical trials of t.

这些风险和不确定性包括但不限于临床前和临床数据，包括阿哌曲单抗2a期临床试验的结果，或其关于SRK-439的临床前数据，不能预测，可能与未来或正在进行的t临床试验产生的数据不一致或更有利。