Updated preliminary data to be presented at the 35th AACR-NCI-EORTC Symposium

更新的初步数据将在第35届AACR-NCI-EORTC研讨会上提交

Company plans to host a conference call on October 13, 2023 at 8:00am EDT

公司计划于2023年10月13日上午8:00召开电话会议

CAMBRIDGE, Mass., Oct. 4, 2023 /PRNewswire/ -- Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, today announced preliminary data from the Phase 1 dose-escalation portion of its ongoing ALKOVE-1 Phase 1/2 clinical trial of NVL-655 for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors as reported in an abstract accepted for presentation at the 35th AACR-NCI-EORTC (ANE) Symposium in Boston, Massachusetts.

马萨诸塞州剑桥市，2023年10月4日/PRNewswire/-Nuvalent，Inc.（纳斯达克股票代码：NUVL），一家临床阶段的生物制药公司，致力于为临床证明的癌症激酶靶标创建精确靶向的疗法，今天宣布了正在进行的NVL-655 ALKOVE-1 1/2期临床试验的1期剂量递增部分的初步数据，用于晚期ALK阳性非小细胞肺癌（NSCLC）和其他实体瘤患者在马萨诸塞州波士顿举行的第35届AACR-NCI-EORTC（ANE）研讨会上接受提交的摘要。

Updated preliminary data will be presented at the conference and during a live webcast and conference call with management on October 13th at 8:00am EDT..

更新的初步数据将于10月13日上午8:00在会议上以及与管理层进行的实时网络广播和电话会议上公布。。

NVL-655 is a novel brain-penetrant ALK-selective tyrosine kinase inhibitor (TKI) created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, brain metastases, and off-target central nervous system (CNS) adverse events associated with tropomyosin receptor kinase (TRK) inhibition that may limit the use of currently available ALK TKIs..

NVL-655是一种新型脑渗透性ALK选择性酪氨酸激酶抑制剂（TKI），旨在同时克服与原发性相关的紧急治疗抵抗，脑转移和脱靶中枢神经系统（CNS）不良事件的临床挑战。肌球蛋白受体激酶（TRK）抑制，可能限制目前可用的ALK TKI的使用。。

NVL-655 is currently being evaluated in the ALKOVE-1 Phase 1/2 clinical trial, a first-in-human study of NVL-655 in patients with advanced ALK-positive NSCLC and other solid tumors (NCT05384626). The Phase 1 dose escalation portion is enrolling ALK-positive NSCLC patients who have previously received at least one ALK TKI and patients with other ALK-positive solid tumors who have been previously treated with at least one prior systemic anticancer therapy.

NVL-655目前正在ALKOVE-1期1/2临床试验中进行评估，这是NVL-655在晚期ALK阳性NSCLC和其他实体瘤患者中的首次人体研究（NCT05384626）。第1阶段剂量递增部分招募先前已接受至少一种ALK TKI的ALK阳性NSCLC患者和先前已用至少一种先前的全身抗癌疗法治疗的其他ALK阳性实体瘤患者。

The primary objectives are to determine the recommended Phase 2 dose (RP2D) and if applicable, the maximum tolerated dose (MTD) of NVL-655 in patients with ALK-positive solid tumors. Additional objectives include characterization of the overall safety, tolerability, and pharmacokinetic profile, and evaluation of the preliminary anti-tumor activity of NVL-655..

主要目标是确定ALK阳性实体瘤患者推荐的2期剂量（RP2D）和NVL-655的最大耐受剂量（MTD）。其他目标包括表征总体安全性，耐受性和药代动力学特征，以及评估NVL-655的初步抗肿瘤活性。。

As of June 12, 2023, 57 patients (54 NSCLC, 3 other solid tumors) received NVL-655 orally at dose levels ranging from 15 to 200 mg once daily in the Phase 1 dose escalation portion of ALKOVE-1.

截至2023年6月12日，57名患者（54名NSCLC，3名其他实体瘤）在ALKOVE-1的1期剂量递增部分以15至200mg的剂量水平口服NVL-655，每日一次。

The patient population was heavily pre-treated and included:

患者人群经过大量预处理，包括：

patients with baseline CNS metastases (51%);

基线CNS转移患者（51%）；

patients with ALK resistance mutations (47%), including compound ALK mutations (32%);

ALK耐药突变患者（47%），包括复合ALK突变（32%）；

patients who had received ≥3 prior ALK TKIs (53%); and,

接受过≥3次ALK TKI的患者（53%）；和，

patients who had received ≥1 2nd generation ALK TKI (alectinib, brigatinib, ceritinib) and the 3rd generation ALK TKI lorlatinib (77%).

接受≥1第二代ALK TKI（alectinib，brigatinib，ceritinib）和第三代ALK TKI lorlatinib（77%）的患者。

Preliminary activity of NVL-655 was demonstrated in this heavily pre-treated patient population as measured by objective response rate (ORR) per RECIST 1.1. Partial responses were observed in 45% (15/33; 8 pending confirmation) of response-evaluable patients with ALK-positive NSCLC who received NVL-655 at doses ranging from 15-150 mg once daily.

NVL-655的初步活性在这个严重预处理的患者群体中得到证实，如通过每个RECIST 1.1的客观响应率（ORR）所测量的。45%（15/33；8待确认）的ALK阳性非小细胞肺癌患者接受NVL-655剂量范围为15-150 mg，每日一次，部分缓解。

An ORR of 65% (11/17) was observed in patients with baseline ALK resistance mutations, and an ORR of 41% (12/29) was observed in patients post-lorlatinib, including cases with compound resistance mutations. Early indicators of CNS activity were also observed..

在基线ALK耐药突变患者中观察到ORR为65%（11/17），在lorlatinib后患者（包括复合耐药突变患者）中观察到ORR为41%（12/29）。还观察到中枢神经系统活动的早期指标。。

Preliminary pharmacokinetic analysis demonstrated dose-proportional exposure, and preliminary pharmacodynamic analysis showed reductions, including clearance, of ALK fusion and mutation variants in ctDNA.

初步药代动力学分析显示剂量比例暴露，初步药效学分析显示ctDNA中ALK融合和突变变体的减少，包括清除。

NVL-655 was well-tolerated and treatment-related adverse events (TRAEs) were generally mild. The most frequent TRAEs were nausea (12%), transaminase elevation (12%), fatigue (9%), and constipation (7%). Grade ≥3 TRAEs were transaminase elevation (n=2), CPK elevation (n=1), and fatigue (n=1). An MTD was not identified and Phase 1 was ongoing to determine the RP2D..

NVL-655耐受性良好，治疗相关不良事件（TRAEs）一般较轻。最常见的TRAEs是恶心（12%），转氨酶升高（12%），疲劳（9%）和便秘（7%）。≥3级TRAEs为转氨酶升高（n=2），CPK升高（n=1）和疲劳（n=1）。尚未确定MTD，并且正在进行第1阶段以确定RP2D。。

'We are strongly encouraged by these preliminary safety and clinical activity data from the Phase 1 portion of our ALKOVE-1 clinical trial, which demonstrate the potential for NVL-655 to achieve its target product profile of potent and selective targeting of ALK fusions and secondary ALK single and compound resistance mutations, brain penetrance, and the avoidance of TRK inhibition,' said Christopher Turner, M.D., Chief Medical Officer of Nuvalent.

'我们受到来自ALKOVE-1临床试验第一阶段的初步安全性和临床活性数据的强烈鼓舞，这些数据证明NVL-655有可能实现其有效和选择性靶向ALK融合蛋白的目标产品概况和继发性ALK单一和复合抗性突变，脑外显率和避免TRK抑制，“Nuvalent首席医疗官Christopher Turner博士说。

'We look forward to presenting an update to this data at the AACR-NCI-EORTC Symposium later this month.'.

“我们期待本月晚些时候在AACR-NCI-EORTC研讨会上介绍这些数据的最新情况。”。

Details for the presentation are as follows:

演示文稿的详细信息如下：

Title: Safety and preliminary activity of the selective ALK inhibitor NVL-655 in patients with ALK fusion-positive solid tumorsAbstract Number: 35177Poster Number: B154Session: Poster Session BSession Date and Time: Friday, October 13, 12:30 pm-4:00 pm EDTPresenting Author: Jessica J Lin, Massachusetts General Hospital (MGH), Boston, MA.

题目：选择性ALK抑制剂NVL-655在ALK融合阳性实体瘤患者中的安全性和初步活性摘要编号：35177海报编号：B154会议：海报会议b会议日期和时间：星期五，10月13日，12:30 pm-4:00 pm ED提交作者：马萨诸塞州波士顿麻省总医院（MGH）Jessica J Lin。

Webcast and Conference Call Information

网络广播和电话信息

A conference call with management will be held on October 13th at 8:00 am EDT.  To access the call, please dial +1 (866) 652-5200 (domestic) or +1 (412) 317-6060 (international) at least 10 minutes prior to the start time and ask to be joined to the Nuvalent call. Accompanying slides and a live video webcast will be available in the Investors section of the Nuvalent website at https://investors.nuvalent.com/events.

与管理层的电话会议将于10月13日上午8:00举行。要访问电话，请在开始时间前至少10分钟拨打+1（866）652-5200（家庭电话）或+1（412）317-6060（国际电话），并要求加入Nuvalent电话。随附的幻灯片和实时视频网络广播将在Nuvalent网站的投资者部分提供https://investors.nuvalent.com/events.

A replay and accompanying slides will be archived on the Nuvalent website for 30 days..

重播和随附的幻灯片将在Nuvalent网站上存档30天。。

About NVL-655

关于NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M ('GRLM'), G1202R / G1269A ('GRGA'), or G1202R/L1198F ('GRLF').

NVL-655是一种新型的脑渗透性ALK选择性抑制剂，旨在克服目前可用的ALK抑制剂所观察到的局限性。NVL-655被设计为在对第一代，第二代和第三代ALK抑制剂产生抗性的肿瘤中保持活性，包括具有溶剂前沿G1202R突变或化合物突变G1202R/L1196M（'GRLM'）的肿瘤，G1202R/G1269A（'GRGA'）或G1202R/L1198F（'GRLF'）。

NVL-655 has been designed for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients.

NVL-655专为中枢神经系统的渗透性而设计，可改善脑转移患者的治疗选择。NVL-655已在临床前研究中观察到选择性抑制野生型ALK及其对结构相关的原肌球蛋白受体激酶（TRK）家族的抗性变体，以潜在地避免用双重TRK/ALK抑制剂观察到的TRK相关CNS不良事件并为患者提供更持久的反应。

NVL-655 is currently being investigated in the ALKOVE-1 clinical trial (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors..

NVL-655目前正在ALKOVE-1临床试验（NCT05384626）中进行研究，这是一项针对晚期ALK阳性非小细胞肺癌（NSCLC）和其他实体瘤患者的首次人体1/2期临床试验。。

About Nuvalent

关于Nuvalent

Nuvalent, Inc. (Nasdaq: NUVL) is a clinical-stage biopharmaceutical company focused on creating precisely 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.

Nuvalent，Inc.（纳斯达克股票代码：NUVL）是一家临床阶段的生物制药公司，致力于为癌症患者创造精确的靶向治疗，旨在克服现有治疗方法对临床证实的激酶靶点的局限性。利用化学和基于结构的药物设计方面的深入专业知识，我们开发出具有克服耐药性，减少不良事件，解决脑转移并推动更持久反应的创新小分子。

Nuvalent is advancing a robust pipeline with parallel lead programs in ROS1-positive and ALK-positive non-small cell lung cancer (NSCLC), a program in HER2 Exon 20 Insertion positive cancers, and multiple discovery-stage research programs. We routinely post information that may be important to investors on our website at www.nuvalent.com. Follow us on Twitter (@nuvalent) and LinkedIn..

Nuvalent正在推进一个强大的管道，在ROS1阳性和ALK阳性非小细胞肺癌（NSCLC），HER2外显子20插入阳性癌症计划和多个发现阶段研究计划中并行领导计划。我们经常在我们的网站www.nuvalent.com上发布对投资者可能重要的信息。在Twitter（@nuvalent）和LinkedIn上关注我们。。

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; the preclinical and clinical development programs for NVL-655; the potential clinical effect of NVL-655; the design and enrollment of the ALKOVE-1 clinical trial; the potential of NVL-655; Nuvalent's research and development programs for the treatment of cancer; and risks and uncertainties associated with drug development.

本新闻稿包含经修订的1995年“私人证券诉讼改革法”含义范围内的前瞻性声明，包括但不限于关于Nuvalent战略，业务计划和重点的默示和明示的声明；数据公告的预期时间；NVL-655的临床前和临床开发计划；NVL-655的潜在临床效果；ALKOVE-1临床试验的设计和注册；NVL-655的潜力；Nuvalent的癌症治疗研究和开发计划；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”，“可能”，“将会”，“可能”，“将会”，“应该”，“期望”，“计划”，“预期”，“目标”，“目标”，“意图”，“相信”，“期望”，“估计”，“寻求”，“预测”，“未来”，“项目”，“潜在”，“继续”，“目标”或这些术语和类似词语或表达的否定词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。

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，并且只有少数研究和开发计划导致产品商业化。您不应过分依赖这些陈述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 the ALKOVE-1 clinical trial or that enrollment will take longer than expected; unexpected concerns that may arise from additional data, analysis, or results obtained during preclinical studies or clinical trials, including ALKOVE-1; the occurrence of adverse safety events; 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 ALKOVE-1 clinical trial; 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当前的期望和信念，并受到许多风险，不确定性和重要因素的影响，这些风险，不确定性和重要因素可能导致实际事件或结果与任何前瞻性声明所表达或暗示的实质性差异本新闻稿中包含的声明，包括，但不限于：Nuvalent可能无法完全注册ALKOVE-1临床试验或注册时间将超出预期的风险；在临床前研究或临床试验（包括ALKOVE-1）期间获得的额外数据，分析或结果可能引起意想不到的担忧；不良安全事件的发生；意外成本，延误或其他意外障碍的风险；Nuvalent可能无法从其发现计划中提名候选药物的风险；突发公共卫生事件或全球地缘政治情况对Nuvalent临床试验，策略和未来运作（包括ALKOVE-1临床试验）的时间安排和预期时间以及结果的直接或间接影响；Nuvalent计划与监管机构互动的时间和结果；以及与获取，维护和保护Nuvalent知识产权有关的风险。

These and other risks and uncertainties are described in greater detail in the section entitled 'Risk Factors' in the Company's Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2023, 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.

这些和其他风险和不确定性在2023年6月30日结束的季度期间公司季度报告表格10-Q中的“风险因素”部分以及之前和之后向证券提交的任何文件中有更详细的描述。和交易所。此外，任何前瞻性陈述仅代表截至今天的Nuvalent观点，不应依赖于截至任何后续日期的观点。

Nuvalent explicitly disclaims any obligation to update an.

Nuvalent明确拒绝任何更新an的义务。

SOURCE Nuvalent, Inc.

来源Nuvalent，Inc。