CAMBRIDGE, Mass.

马萨诸塞州剑桥市

,

，

April 29, 2025

2025年4月29日

/PRNewswire/ --

/美通社/ --

Nuvalent, Inc.

努瓦莱特公司

(Nasdaq:

（纳斯达克：

NUVL

NUVL

), a clinical-stage biopharmaceutical company focused on creating

），一家专注于创造的临床阶段生物制药公司

precisely

准确地

targeted therapies for clinically proven kinase targets in cancer, today announced the publication of a manuscript in

针对癌症中经过临床验证的激酶靶点的靶向疗法，今天宣布在一份手稿中发布

Molecular Cancer Therapeutics

分子癌症治疗学

, a journal of the American Association for Cancer Research, which supports the rational molecular design of zidesamtinib, its novel and selective ROS1 inhibitor. Zidesamtinib is currently being evaluated in the ongoing ARROS-1 Phase 1/2 trial for patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) and other solid tumors, which is designed with registrational intent for tyrosine kinase inhibitor (TKI) pre-treated and TKI-naïve patients with advanced ROS1-positive NSCLC..

，美国癌症研究协会期刊，支持齐德萨替尼的合理分子设计，这是一种新型且选择性的ROS1抑制剂。齐德萨替尼目前正在正在进行的ARROS-1 1/2期试验中进行评估，用于治疗晚期ROS1阳性非小细胞肺癌（NSCLC）和其他实体瘤患者，该试验旨在为酪氨酸激酶抑制剂（TKI）预处理和TKI初治的晚期ROS1阳性非小细胞肺癌患者提供注册意图。

The publication, entitled 'Zidesamtinib Selective Targeting of Diverse ROS1 Drug-Resistant Mutations,' is published online and can be accessed here:

标题为“Zidesamtinib选择性靶向各种ROS1耐药突变”的出版物已在线发布，可以在这里访问：

http://doi.org/10.1158/1535-7163.MCT-25-0025

http://doi.org/10.1158/1535-7163.MCT-25-0025

'Zidesamtinib was specifically designed with the goal of addressing the combined medical needs of treating tumors that have developed resistance, treating brain metastases and avoiding off-target adverse events. Structural studies play a critical role in the development and optimization of novel therapeutics, particularly when aiming to solve for multiple, and at times competing, challenges.

‘Zidesamtinib 的设计目标是满足治疗已产生耐药性的肿瘤、治疗脑转移以及避免脱靶不良事件的综合医疗需求。结构研究在新型疗法的开发和优化中起着至关重要的作用，尤其是在旨在解决多个有时相互矛盾的挑战时。

To date, structural studies for ROS1-positive cancers have been hindered by a lack of ROS1 G2032R crystal structures, despite G2032R being the most commonly occurring ROS1 resistance mutation,' .

迄今为止，尽管G2032R是ROS1最常见的耐药突变，但ROS1阳性癌症的结构研究因缺乏ROS1 G2032R晶体结构而受到阻碍。

said first author Anupong Tangpeerachaikul, Ph.D., Director, Biology at Nuvalent.

Nuvalent生物学总监、第一作者Anupong Tangpeerachaikul博士表示。

'With this publication in

‘随着这份出版物的发布

Molecular Cancer Therapeutics

分子癌症治疗学

, we are pleased to have shared what is, to our knowledge, the first structure of ROS1 G2032R, or any ROS1 mutation, offering a framework for understanding ROS1 TKI activity against these important drivers of disease progression. This structure further illustrates the intentional design of zidesamtinib and adds to the growing body of preclinical data supporting its ROS1-selective and TRK-sparing design.'.

，我们很高兴分享了据我们所知是ROS1 G2032R或任何ROS1突变的第一个结构，为理解ROS1 TKI对抗这些重要的疾病进展驱动因子的活性提供了框架。该结构进一步展示了齐德萨替尼的有意设计，并增加了支持其ROS1选择性和TRK保留设计的越来越多的临床前数据。'

The manuscript explores the activity of zidesamtinib and other approved or investigational ROS1 TKIs at clinically relevant concentrations against ROS1 resistance mutations, including the most commonly occurring resistance mutation, ROS1 G2032R, in preclinical mutagenesis screens and an intracranial ROS1 G2032R xenograft model.

手稿探讨了齐德萨替尼和其他已批准或研究中的ROS1 TKIs在临床相关浓度下对ROS1耐药突变的活性，包括最常见的耐药突变ROS1 G2032R，在临床前诱变筛选和颅内ROS1 G2032R异种移植模型中的情况。

Findings presented in the manuscript show that, at clinically relevant concentrations, zidesamtinib suppressed on-target resistance in ENU mutagenesis screens simulating first-line and later-line treatment and inhibited ROS1 G2032R brain tumors more effectively than the other ROS1 TKIs evaluated. This favorable preclinical activity suggests the potential for zidesamtinib to delay tumor progression, both peripherally and intracranially..

手稿中展示的研究结果表明，在临床相关浓度下，齐德萨替尼在模拟一线和后线治疗的ENU诱变筛选中抑制了靶向耐药，并且比其他评估的ROS1 TKI更有效地抑制了ROS1 G2032R脑肿瘤。这一良好的临床前活性表明，齐德萨替尼有潜力延缓肿瘤的外周和颅内进展。

In addition, the manuscript details the first crystal structure of ROS1 G2032R in complex with zidesamtinib, which further supports zidesamtinib's molecular design and provides structural insights into how the ROS1 G2032R mutation affects TKI binding. Zidesamtinib was designed with the goal of being active against ROS1 and ROS1 resistance mutations while avoiding the inhibition of the structurally related tropomyosin receptor kinase (TRK) family in the central nervous system (CNS), which has been associated with neurological adverse events that can be dose limiting.

此外，该手稿详细介绍了ROS1 G2032R与齐德萨替尼复合物的第一个晶体结构，这进一步支持了齐德萨替尼的分子设计，并提供了关于ROS1 G2032R突变如何影响TKI结合的结构见解。齐德萨替尼的设计目标是针对ROS1和ROS1耐药突变具有活性，同时避免抑制与中枢神经系统（CNS）中结构相关的原肌球蛋白受体激酶（TRK）家族，该家族与可能限制剂量的神经系统不良事件有关。

The crystal structure elucidates zidesamtinib's preclinical affinity for ROS1 G2032R and selectivity for ROS1 over TRK..

晶体结构阐明了齐德萨替尼对ROS1 G2032R的临床前亲和力以及对ROS1优于TRK的选择性。

The company expects to report pivotal clinical data for TKI pre-treated patients with advanced ROS1-positive NSCLC from the ARROS-1 Phase 1/2 trial in the first half of 2025 in support of an anticipated New Drug Application submission by mid-year 2025, with an initial target indication of TKI pre-treated patients with advanced ROS1-positive NSCLC..

公司预计将在2025年上半年报告来自ARROS-1 I/II期试验的TKI预处理的晚期ROS1阳性非小细胞肺癌患者的关键临床数据，以支持预计在2025年年中提交的新药申请，初始目标适应症为TKI预处理的晚期ROS1阳性非小细胞肺癌患者。

About Zidesamtinib

关于齐德萨替尼

Zidesamtinib is a novel brain-penetrant ROS1-selective inhibitor created with the aim to overcome limitations observed with currently available ROS1 inhibitors. Zidesamtinib is designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with treatment-emergent ROS1 mutations such as G2032R.

Zidesamtinib 是一种新型的可穿透大脑的 ROS1 选择性抑制剂，旨在克服目前可用的 ROS1 抑制剂所观察到的局限性。Zidesamtinib 的设计使其在对现有 ROS1 抑制剂产生耐药性的肿瘤中仍然有效，包括出现治疗相关 ROS1 突变（如 G2032R）的肿瘤。

In addition, zidesamtinib is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and to drive deep, durable responses for patients across all lines of therapy.

此外，齐德萨替尼设计用于穿透中枢神经系统 (CNS)，以改善脑转移患者的治疗选择，并避免抑制结构相关的原肌球蛋白受体激酶 (TRK) 家族。这些特性共同有可能避免与双重 TRK/ROS1 抑制剂相关的 TRK 相关中枢神经系统不良事件，并为各线治疗的患者带来深度且持久的反应。

Zidesamtinib has received breakthrough therapy designation for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ROS1 tyrosine kinase inhibitors and orphan drug designation for ROS1-positive NSCLC..

Zidesamtinib 已获得突破性疗法认定，用于治疗先前接受过两种或更多种 ROS1 酪氨酸激酶抑制剂治疗的 ROS1 阳性转移性非小细胞肺癌（NSCLC）患者，并获得了 ROS1 阳性 NSCLC 的孤儿药认定。

About Nuvalent

关于Nuvalent

Nuvalent, Inc. (Nasdaq:

努瓦莱特公司（纳斯达克：

NUVL

NUVL

) is a clinical-stage biopharmaceutical company focused on creating

）是一家临床阶段的生物制药公司，专注于创造

precisely

确切地

targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets. Leveraging deep expertise in chemistry and structure-based drug design, we develop innovative small molecules that have the potential to overcome resistance, minimize adverse events, address brain metastases, and drive more durable responses.

针对癌症患者的靶向治疗，旨在克服现有疗法在临床上已证明的激酶靶点的局限性。凭借在化学和基于结构的药物设计方面的深厚专业知识，我们开发创新的小分子，有望克服耐药性、减少不良反应、应对脑转移并实现更持久的治疗效果。

Nuvalent is advancing a robust pipeline with investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, and multiple discovery-stage research programs..

Nuvalent正在推进一条强大的研发管线，其中包括针对ROS1阳性、ALK阳性和HER2改变的非小细胞肺癌的研究候选药物，以及多个处于发现阶段的研究项目。

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, as amended, including, without limitation, implied and express statements regarding Nuvalent's strategy, business plans, and focus; the expected timing of data announcements and FDA submissions; the clinical development program for and potential effects of zidesamtinib; the potential of Nuvalent's pipeline programs, including zidesamtinib; the implications of data readouts and presentations; Nuvalent's research and development programs for the treatment of cancer; and risks and uncertainties associated with drug development.

本新闻稿包含1995年《私人证券诉讼改革法案》（经修订）所指的前瞻性声明，包括但不限于关于Nuvalent的战略、业务计划和重点的明示或暗示声明；数据公告和FDA提交的预期时间；齐德萨替尼的临床开发计划及其潜在效果；Nuvalent管线项目（包括齐德萨替尼）的潜力；数据解读和展示的含义；Nuvalent针对癌症治疗的研发计划；以及与药物开发相关的风险和不确定性。

The words 'may,' 'might,' 'will,' 'could,' 'would,' 'should,' 'expect,' 'plan,' 'anticipate,' 'aim,' 'goal,' 'intend,' 'believe,' 'expect,' 'estimate,' 'seek,' 'predict,' 'future,' 'project,' 'potential,' 'continue,' 'target' or the negative of these terms and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

“可能”、“也许”、“将”、“可以”、“会”、“应该”、“预期”、“计划”、“预期”、“目标”、“目的”、“打算”、“相信”、“估计”、“寻求”、“预测”、“未来”、“项目”、“潜力”、“继续”、“目标”这些词语或其否定形式以及类似的词语或表达旨在识别前瞻性陈述，尽管并非所有前瞻性陈述都包含这些识别词语。

Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. You should not place undue reliance on these statements or the scientific data presented..

药物开发和商业化涉及高度风险，只有少数研发计划能成功实现产品的商业化。你不应过分依赖这些声明或所提供的科学数据。

Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties, and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation: risks that Nuvalent may not fully enroll its clinical trials or that enrollment will take longer than expected; unexpected concerns that may arise from additional data, analysis, or results obtained during preclinical studies and clinical trials; the risk that results of earlier clinical trials may not be predictive of the results of later-stage clinical trials; the risk that data from our clinical trials may not be sufficient to support registration and that Nuvalent may be required to conduct one or more additional studies or trials prior to seeking registration of our product candidates; the occurrence of adverse safety events; risks that the FDA may not approve our potential products on the timelines we expect, or at all; risks of unexpected costs, delays, or other unexpected hurdles; risks that Nuvalent may not be able to nominate drug candidates from its discovery programs; the direct or indirect impact of public health emergencies or global geopolitical circumstances on the timing and anticipated timing and results of Nuvalent's clinical trials, strategy, and future operations, including the ARROS-1trial; the timing and outcome of Nuvalent's planned interactions with regulatory authorities; and risks related to obtaining, maintaining, and protecting Nuvalent's intellectual property.

本新闻稿中的任何前瞻性声明均基于管理层的当前预期和信念，并受到多种风险、不确定性和重要因素的影响，这些因素可能导致实际事件或结果与此新闻稿中包含的任何前瞻性声明所表达或暗示的内容存在重大差异，包括但不限于：Nuvalent可能无法完全招募其临床试验参与者，或招募时间比预期更长的风险；在临床前研究和临床试验期间从额外数据、分析或结果中可能出现意外问题的风险；早期临床试验结果可能无法预测后期临床试验结果的风险；我们临床试验的数据可能不足以支持注册，且Nuvalent可能需要在寻求产品候选物注册之前进行一项或多项额外研究或试验的风险；发生不良安全事件的风险；FDA可能不会按照我们预期的时间表批准我们的潜在产品，甚至完全不批准的风险；意外成本、延迟或其他未预料障碍的风险；Nuvalent可能无法从其发现计划中提名药物候选物的风险；公共卫生紧急事件或全球地缘政治局势对Nuvalent临床试验（包括ARROS-1试验）策略及未来运营的时机及其预期时间和结果的直接或间接影响；Nuvalent与监管机构计划互动的时机和结果；以及与获取、维护和保护Nuvalent知识产权相关的风险。

These and other risks and uncertainties are described in greater detail in the section entitled 'Risk Factors' .

这些以及其他风险和不确定性在“风险因素”部分中有更详细的描述。

December 31, 2024

2024年12月31日

, as well as any prior and subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Nuvalent's views only as of today and should not be relied upon as representing its views as of any subsequent date. Nuvalent explicitly disclaims any obligation to update any forward-looking statements..

以及之前和之后向证券交易委员会提交的任何文件。此外，任何前瞻性陈述仅代表Nuvalent截至今日的观点，不应被视为代表其在任何后续日期的观点。Nuvalent明确声明不承担更新任何前瞻性陈述的义务。

SOURCE Nuvalent, Inc.

来源：Nuvalent公司

WANT YOUR COMPANY'S NEWS

想要你公司的新闻

FEATURED ON PRNEWSWIRE.COM?

荣登PRNEWSWIRE.COM？

440k+

44万+

Newsrooms &

新闻编辑室 &

Influencers

影响者

9k+

9k+

Digital Media

数字媒体

Outlets

插座

270k+

27万+

Journalists

记者

Opted In

已选择加入

GET STARTED

开始使用