CAMBRIDGE, Mass.--(BUSINESS WIRE)--Scholar Rock (NASDAQ: SRRK), a Phase 3, clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, today announced new data from its Phase 1 DRAGON proof-of-concept trial of SRK-181, a selective inhibitor of latent TGFβ1 activation being developed with the aim of overcoming resistance to checkpoint inhibitor therapy in patients with advanced cancer.

马萨诸塞州剑桥-（BUSINESS WIRE）-Scholar Rock（纳斯达克股票代码：SRRK）是一家专注于治疗蛋白质生长因子发挥重要作用的严重疾病的3期临床阶段生物制药公司，今天宣布了新的数据来自其SRK-181的1期DRAGON概念验证试验，正在开发潜在TGFβ1活化的选择性抑制剂，目的是克服晚期癌症患者对检查点抑制剂治疗的抗性。

These data will be presented in two poster presentations during the Society for Immunotherapy of Cancer's (SITC) 38th Annual Meeting & Pre-Conference being held November 1 – 5th in San Diego..

这些数据将在11月1日至5日在圣地亚哥举行的癌症免疫治疗学会（SITC）第38届年会和会前会议期间以两张海报的形式展示。。

The first poster focuses on the safety, efficacy, and preliminary biomarker data in patients with anti-PD-1 resistant clear cell renal cell carcinoma (ccRCC) in Part A2 (dose escalation) and Part B (dose expansion) of the Phase 1 DRAGON trial. The ccRCC cohort was the focus for that poster, as it was the fastest cohort to achieve enrollment goals.

第一张海报着重于A2部分（剂量递增）和B部分（剂量扩展）中抗PD-1抗性透明细胞肾细胞癌（ccRCC）患者的安全性，有效性和初步生物标志物数据阶段1 DRAGON试验。ccRCC队列是该海报的重点，因为它是实现招生目标的最快队列。

The second poster focuses on preliminary biomarker data from part B of the trial in patients with multiple tumor types..

第二张海报侧重于多种肿瘤类型患者试验B部分的初步生物标志物数据。。

Data presented continues to support proof of concept for SRK-181 in 28 heavily pretreated patients with ccRCC resistant to anti-PD-1. SRK-181 was generally well tolerated and showed promising anti-tumor activity in this patient population. Of 28 evaluable patients in the ccRCC cohort, six patients treated with SRK-181 in combination with pembrolizumab had confirmed partial responses (PRs) and achieved a best tumor reduction of 33% to 93%, with an objective response rate (ORR) of 21.4%.

所提供的数据继续支持SRK-181在28位严重预处理的抗PD-1抗ccRCC患者中的概念验证。SRK-181通常具有良好的耐受性，并且在该患者群体中显示出有希望的抗肿瘤活性。在ccRCC队列中的28名可评估患者中，6名接受SRK-181联合pembrolizumab治疗的患者证实了部分缓解（PR），最佳肿瘤减少33%至93%，客观缓解率（ORR）为21.4%。

In the biomarker analysis for ccRCC, levels of circulating granulocytic myeloid-derived suppressor cells (gMDSC) correlated with clinical activity in ccRCC patients treated with SRK-181 in combination with pembrolizumab. The data cutoff for all analyses was August 29, 2023..

在ccRCC的生物标志物分析中，循环粒细胞骨髓衍生抑制细胞（gMDSC）的水平与用SRK-181联合pembrolizumab治疗的ccRCC患者的临床活性相关。所有分析的数据截止日期是2023年8月29日。。

“The DRAGON trial has successfully delivered on its objective of demonstrating proof of concept for SRK-181 by showing promising anti-tumor activity. These data, along with biomarker results that support proof of mechanism, highlight the immunosuppressive role of TGFβ as a mechanism of anti-PD-1 resistance in patients,” said Jay Backstrom, M.D., M.P.H., President and Chief Executive Officer of Scholar Rock.

“DRAGON试验通过显示有希望的抗肿瘤活性，成功地证明了SRK-181的概念证明，这些数据，以及支持机制证明的生物标志物结果，突出了TGF作为患者抗PD-1耐药机制的免疫抑制作用，”Jay Backstrom，M.D.，M.P.H.说。，Scholar Rock的总裁兼首席执行官。

“We are particularly encouraged by the responses observed in patients with ccRCC who had been treated with multiple lines of therapy before receiving SRK-181.”.

“我们特别鼓舞在接受SRK-181之前接受多种治疗方案治疗的ccRCC患者的反应。”。

Safety data from ccRCC cohort continue to show SRK-181 is generally well tolerated

来自ccRCC队列的安全性数据继续显示SRK-181通常具有良好的耐受性

Safety data from the ccRCC cohort (n=30 patients; part A2: 1 patient on 800mg q3w and 1 patient on 1600mg q3w and Part B: 28 patients on 1500 mg q3w) continue to show SRK-181 has been generally well tolerated when used in combination with pembrolizumab. No dose-limiting toxicities were observed at any dose level, including at 1500 mg q3w in combination with pembrolizumab, the recommended dose selected for Part B..

来自ccRCC队列的安全性数据（n=30名患者；部分A2:800mg q3w上的1名患者和1600mg q3w上的1名患者和部分B:1500mg q3w上的28名患者）继续显示SRK-181在使用时通常具有良好的耐受性与pembrolizumab联合使用。在任何剂量水平均未观察到剂量限制性毒性，包括1500 mg q3w联合pembrolizumab（为B部分选择的推荐剂量）。。

One Grade 4 treatment-related adverse event (AE) was observed, dermatitis exfoliative generalized. No Grade 5 treatment-related AEs occurred. Treatment-related serious adverse events were dermatitis exfoliative generalized (1 patient), pemphigoid and rash (both in 1 patient), immune-related hepatitis (1 patient), and diarrhea, nausea, and vomiting (all three in 1 patient)..

观察到一个4级治疗相关不良事件（AE），剥脱性皮炎全身。没有发生5级治疗相关的AE。治疗相关的严重不良事件是剥脱性全身性皮炎（1例），类天疱疮和皮疹（1例），免疫相关性肝炎（1例）和腹泻，恶心和呕吐（1例患者中均有3例）。。

Preliminary results of SRK-181 in ccRCC patients show promising anti-tumor activity

SRK-181在ccRCC患者中的初步结果显示有希望的抗肿瘤活性

The response was assessed by principal investigators based on RECIST 1.1. Out of the 28 ccRCC patients with evaluable responses (defined as all enrolled patients except those who are still on study, but pending post-treatment radiographic evaluation):

主要研究人员根据RECIST 1.1评估了反应。在28例具有可评估反应的ccRCC患者中（定义为除仍在研究中但尚未进行治疗后影像学评估的患者外的所有入选患者）：

Six patients had confirmed PRs (defined as at least a 30% tumor reduction), with best tumor reduction of 33% to 93%, and remained on study for 2.8+ to 16.3+ months (5 of the 6 patients remained on for over 6.5 months).

6名患者确诊PRs（定义为肿瘤减少至少30%），最佳肿瘤减少33%至93%，并且继续研究2.8+至16.3+个月（6名患者中有5名持续超过6.5个月）。

Ten patients had stable disease (SD) (defined as tumors with neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). Five of these patients continued in the study.

10名患者具有稳定的疾病（SD）（定义为既没有足够的收缩以符合PR又没有足够的增加以符合进行性疾病（PD）的肿瘤）。其中五名患者继续进行研究。

The objective response rate (ORR), defined as the percentage of patients with a partial or complete response to therapy, was 21.4% and the disease control rate (DCR), defined as the percentage of patients whose disease shrinks or remains stable over a certain time period, was 57%. In this difficult to treat population, anti-PD-1 retreatment is generally associated with single-digit ORR or no response.1.

客观反应率（ORR），定义为对治疗有部分或完全反应的患者百分比，为21.4%，疾病控制率（DCR），定义为疾病缩小或保持稳定的患者百分比。一段时间，是57%。在这个难以治疗的人群中，抗PD-1再治疗通常与单位数ORR或无反应相关。

Biomarker data support proof of mechanism in multiple tumor types

生物标志物数据支持多种肿瘤类型的机制证明

The biomarker strategy includes measuring effects of SRK-181 on both circulating and tumor immune cells, such as tumor infiltration by CD8+ T cells and reductions in myeloid-derived suppressor cell (MDSC) populations. The analysis included patients from Part B with ccRCC, melanoma, non-small cell lung cancer (NSCLC), or urothelial carcinoma (UC)..

生物标志物策略包括测量SRK-181对循环和肿瘤免疫细胞的影响，例如CD8+T细胞的肿瘤浸润和骨髓衍生抑制细胞（MDSC）群体的减少。分析包括来自B部分的患有ccRCC，黑素瘤，非小细胞肺癌（NSCLC）或尿路上皮癌（UC）的患者。。

Following treatment with SRK-181 and pembrolizumab, circulating MDSC levels decreased below baseline in all patients with PRs (n=7), which included those in the ccRCC, melanoma, and UC cohorts. CD8+ T cells were measured in tumor types for which paired biopsy samples (i.e., samples before and after treatment for individual patients) of sufficient quality were available: UC, melanoma, and NSCLC.

在用SRK-181和pembrolizumab治疗后，所有PR患者（n=7）的循环MDSC水平均低于基线水平，其中包括ccRCC，黑素瘤和UC队列中的患者。在肿瘤类型中测量CD8+T细胞，其中可获得足够质量的配对活检样品（即，个体患者治疗前后的样品）：UC，黑素瘤和NSCLC。

In those patients (n=8), SRK-181 treatment was associated with an increase in CD8+ T cell infiltration into tumors. These findings were consistent with preclinical data showing that treatment with SRK-181 and anti-PD-(L)1 therapy decreased circulating MDSC levels and increased CD8+ T cell infiltration into tumors, which correlated with tumor response and survival benefit..

在那些患者（n=8）中，SRK-181治疗与CD8+T细胞浸润到肿瘤中的增加有关。这些发现与临床前数据一致，表明用SRK-181和抗PD-（L）1疗法治疗可降低循环MDSC水平并增加CD8+T细胞向肿瘤的浸润，这与肿瘤反应和生存获益相关。。

The results will be presented at the SITC 38th Annual Meeting in two poster presentations, details of which can be found below. The posters will be made available in the Publications & Posters section of Scholar Rock’s website following the conference.

结果将在SITC第38届年会上以两个海报展示形式呈现，详情见下文。会议结束后，海报将在Scholar Rock网站的出版物和海报部分发布。

Title: Establishing Proof of Mechanism in Patients: Preliminary Biomarker Data of SRK-181 (a latent TGFβ1 inhibitor) from DRAGON Study

题目：建立患者机制的证据：DRAGON研究中SRK-181（一种潜在的TGFβ1抑制剂）的初步生物标志物数据

Presentation Type: Poster 726

演示类型：海报726

Presenter: Susan Henry, PhD, Senior Director, Translational Sciences, Scholar Rock, Inc.

主持人：Susan Henry博士，Scholar Rock公司转化科学高级主任。

Location: Exhibit Halls A and B1, San Diego Convention Center

地点：圣地亚哥会议中心A大厅和B1大厅

Date/Time: November 4, 11:55 AM – 1:25 PM PST and 7 – 8:30 PM PST

日期/时间：11月4日，太平洋标准时间上午11:55-下午1:25和太平洋标准时间下午7:30

Title: Safety, Efficacy, and Biomarker Results of SRK-181, a Latent TGFβ1 Inhibitor, in Anti-PD-1 Resistant Metastatic ccRCC Patients

题目：SRK-181（一种潜在的TGFβ1抑制剂）在抗PD-1耐药转移性ccRCC患者中的安全性，有效性和生物标志物结果

Presentation Type: Poster 666

演示类型：海报666

Presenter: Timothy Yap, MBBS, PhD, FRCP, Medical Oncologist and Physician-Scientist; and Associate Professor, Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center

主持人：Timothy Yap，MBBS，博士，FRCP，医学肿瘤学家和医师科学家；德克萨斯大学MD安德森癌症中心研究癌症治疗学系副教授

Location: Exhibit Halls A and B1, San Diego Convention Center

地点：圣地亚哥会议中心A大厅和B1大厅

Date/Time: November 4, 11:55 AM – 1:25 PM PST and 7 – 8:30 PM PST

日期/时间：11月4日，太平洋标准时间上午11:55-下午1:25和太平洋标准时间下午7:30

For conference information, visit https://www.sitcancer.org/2023/home

有关会议信息，请访问https://www.sitcancer.org/2023/home

(1) Pal, et al. The Lancet. 2023; 15;402(10397):185-195.

（1） Pal等人，“柳叶刀”。2023; 15;402(10397):185-195.

About SRK-181

关于SRK-181

SRK-181 is a selective inhibitor of TGFβ1 activation being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies, in advanced cancer. TGFβ1 is the predominant TGFβ isoform expressed in many human tumor types. Based on analyses of various human tumors that are resistant to anti-PD-(L)1 therapy, data suggest that TGFβ1 is a key contributor to the immunosuppressive tumor microenvironment, excluding and preventing entry of cytotoxic T cells into the tumor, thereby inhibiting anti-tumor immunity.

SRK-181是TGFβ1活化的选择性抑制剂，正在开发用于克服晚期癌症中对检查点抑制剂疗法（例如抗PD-（L）1抗体）的主要抗性。TGFβ1是在许多人类肿瘤类型中表达的主要TGFβ同种型。基于对抗PD-（L）1疗法具有抗性的各种人类肿瘤的分析，数据表明TGFβ1是免疫抑制性肿瘤微环境的关键因素，排除和阻止细胞毒性T细胞进入肿瘤，从而抑制抗肿瘤免疫。

(2) SRK-181 specifically targets the latent TGFβ1 isoform in a context-independent manner, designed to enable complete inhibition of TGFβ1 in all compartments within the tumor microenvironment. Scholar Rock believes that SRK-181 has the potential to overcome this immune cell exclusion and induce tumor regression when administered in combination with anti-PD-(L)1 therapy while potentially avoiding toxicities associated with non-selective TGFβ inhibition.

（2） SRK-181以上下文无关的方式特异性靶向潜在的TGFβ1同种型，旨在使肿瘤微环境内的所有区室中的TGFβ1完全抑制。Scholar Rock认为，当与抗PD-（L）1疗法联合给药时，SRK-181有可能克服这种免疫细胞排斥并诱导肿瘤消退，同时可能避免与非选择性TGFβ抑制相关的毒性。

The DRAGON Phase 1 proof-of-concept clinical trial (NCT04291079) in patients with locally advanced or metastatic solid tumors is ongoing. The trial is currently enrolling and dosing patients in multiple proof of concept cohorts conducted in parallel, including urothelial carcinoma (UC), cutaneous melanoma (MEL), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and clear cell renal cell carcinoma (ccRCC).

DRAGON 1期概念验证临床试验（NCT04291079）正在进行中，用于局部晚期或转移性实体瘤患者。该试验目前正在招募和给予患者多个概念验证队列，包括尿路上皮癌（UC），皮肤黑色素瘤（MEL），非小细胞肺癌（NSCLC），头颈部鳞状细胞癌（HNSCC）和透明细胞肾细胞癌（ccRCC）。

SRK-181 is an investigational product candidate and its efficacy and safety have not been established. SRK-181 has not been approved for any use by the FDA or any other regulatory agency..

SRK-181是一种研究候选产品，其功效和安全性尚未确定。SRK-181尚未被FDA或任何其他监管机构批准用于任何用途。。

2) Martin et al., Sci. Transl. Med. 12: 25 March 2020

2） Martin等人，科学。Transl。Med.12:2020年3月25日

About Scholar Rock

关于学者岩石

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，为需求未得到满足的严重疾病患者发现，开发和提供改变生活的疗法。作为转化生长因子β（TGFβ）细胞蛋白超家族生物学的全球领导者，并以学者rock与蛋白质结构的视觉相似性命名，临床阶段公司专注于推进蛋白质生长因子的创新治疗。基础。

Over the past decade, the company 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，该公司创建了一条管道，有可能提高神经肌肉疾病，心脏代谢紊乱，癌症以及生长因子靶向药物可以发挥变革作用的其他疾病的护理标准。。

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）中的肌肉靶向治疗提供临床概念验证的公司。这种释放根本不同的治疗方法的承诺是由专有平台的广泛应用所驱动的，该平台开发了新型单克隆抗体以非常高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 the company’s approach at ScholarRock.com and follow @ScholarRock and on LinkedIn..

通过在传统疗法历史上未得到解决的疾病空间中利用尖端科学，Scholar Rock每天都在为患者创造新的可能性。了解更多关于公司在ScholarRock.com上的方法，并关注@ScholarRock和LinkedIn。。

Availability of Other Information About Scholar Rock

有关学者岩石的其他信息的可用性

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，我们使用我们的公司网站www.scholarrock.com与我们的投资者和公众进行沟通，包括但不限于公司披露，投资者演示和常见问题解答，证券交易委员会文件，新闻稿，公共电话会议记录和网络广播记录，以及Twitter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..

我们在我们的网站或Twitter或LinkedIn上发布的信息可能被视为材料信息。因此，我们鼓励投资者，媒体和其他有兴趣查看我们定期在那里发布的信息。根据1933年“证券法”（经修订），我们的网站或社交媒体的内容不得被视为包含在任何文件中。。

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

ScholarRock®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, and progress and indication selection and development timing, 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”含义范围内的“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对其增长的期望，战略，进度和指示选择和发展时机，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内表现的能力，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”，“将会”，“应该”，“期望”，“计划”，“预期”，“相信”，“估计”，“项目”，“意图”，“未来”，“潜力”或“继续”之类的词语，以及其他类似的表达方式旨在识别此类前瞻性陈述。所有这些前瞻性陈述均基于管理层对未来事件的当前预期，并受到若干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陈述中提出或暗示的结果产生重大不利影响。

These risks and uncertainties include, without limitation, that clinical data, including the results from the Phase 2 clinical trial of apitegromab, or Part B of the Phase 1 clinical trial of SRK-181, and are not predictive of, may be inconsistent with, or more favorable than, data generated from future 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 the expected timeline, the data generated from Scholar Rock’s nonclinical and preclinical studies and clinical trials, and Scholar Rock’s ab.

这些风险和不确定性包括但不限于临床数据，包括apitegromab的2期临床试验结果，或SRK-181的1期临床试验的B部分，并且不能预测，可能与相同产品候选物的未来临床试验产生的数据不一致或更有利，Scholar Rock能够在预期的时间表上提供识别和开发产品候选人所需的财务支持，资源和专业知识，Scholar Rock的非临床和临床前研究和临床试验以及Scholar Rock的ab所产生的数据。