Encouraging preliminary signs of activity observed in heavily pre-treated patients with ALK-positive NSCLC, including in subgroups of patients who have previously received a 2nd generation ALK TKI and lorlatinib, have brain metastases, or have single or compound ALK resistance mutations

鼓励在严重预处理的ALK阳性NSCLC患者中观察到活性的初步迹象，包括先前接受第二代ALK TKI和lorlatinib，脑转移或具有单一或复合ALK抗性突变的患者亚组

Favorable preliminary safety profile is consistent with an ALK-selective, TRK sparing design

有利的初步安全概况与ALK选择性，TRK保留设计一致

Company to host a conference call today, October 13, at 8:00am EDT

公司将于10月13日上午8:00召开电话会议

CAMBRIDGE, Mass., Oct. 13, 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 updated 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.

马萨诸塞州剑桥市，2023年10月13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，致力于为临床证实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期剂量递增部分针对晚期ALK阳性非小细胞肺癌（NSCLC）和其他实体瘤患者的最新初步数据。

These data will be presented today at the 35th AACR-NCI-EORTC (ANE) Symposium in Boston, Massachusetts..

这些数据将于今天在马萨诸塞州波士顿举行的第35届AACR-NCI-EORTC（ANE）研讨会上公布。。

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。。

'Significant advancements have been made with the development of three generations of ALK TKIs, and the five ALK inhibitors that are currently FDA-approved provide important treatment options for patients with advanced ALK fusion-positive cancers. However, some limitations remain with the available therapies, ranging from association with TRK-related neurologic adverse events that can limit adequate coverage of ALK single resistance mutations to the emergence of refractory compound mutations following sequential treatment with ALK TKIs,' said presenting investigator Jessica J.

“随着三代ALK TKIs的发展取得了重大进展，目前FDA批准的五种ALK抑制剂为晚期ALK融合阳性癌症患者提供了重要的治疗选择。然而，现有疗法仍存在一些局限性，从与TRK相关的神经系统不良事件的关联，可能限制ALK单抗性突变的充分覆盖到ALK TKIs顺序治疗后难治性化合物突变的出现，“介绍研究者Jessica J。

Lin, M.D., Assistant Professor of Medicine, Harvard Medical School and Attending Physician, Mass General Cancer Center. 'These preliminary data support the potential for NVL-655 as an ALK-selective inhibitor that may combine, for the first time, potent and selective targeting of diverse ALK fusions and secondary ALK resistance mutations, including single and compound mutations involving G1202R and I1171N, brain penetrance, and the avoidance of TRK inhibition that can be dose limiting.'.

Lin，M.D.，哈佛医学院医学助理教授和Mass General Cancer Center主治医师这些初步数据支持NVL-655作为ALK选择性抑制剂的潜力，该抑制剂可能首次结合有效和选择性靶向多种ALK融合和继发性ALK抗性突变，包括涉及G1202R和I1171N的单一和复合突变，脑外显率和避免可能是剂量限制的TRK抑制。

As of the enrollment and data cut-off date of August 8, 2023 for the preliminary data, 93 patients have been enrolled in the Phase 1 portion of the ALKOVE-1 trial across six evaluated dose levels of NVL-655 ranging from 15 mg once daily (QD) to 200 mg QD. Enrollment in the Phase 1 portion of the trial is ongoing..

截至2023年8月8日的入选和数据截止日期，初步数据显示，93名患者参加了ALKOVE-1试验的第一阶段，评估了NVL-655的6个评估剂量水平，范围从15 mg每日一次（QD）至200毫克QD。正在进行试验的第一阶段部分的注册。。

Preliminary activity data as of the cut-off date were available from 51 heavily pre-treated response-evaluable NSCLC patients. The objective response rate (ORR) by RECIST 1.1 was 39% (20/51) of patients treated at all doses, of which all were partial responses (4 pending confirmation). In the subset of 41 patients treated at dose levels of 50 mg QD or higher, the ORR was 44% (18/41)..

截至截止日期的初步活动数据可从51名严重预处理的可评估反应的NSCLC患者获得。RECIST 1.1的客观缓解率（ORR）为所有剂量治疗患者的39%（20/51），其中全部为部分缓解（4例待确认）。在以50mg QD或更高剂量水平治疗的41名患者的子集中，ORR为44%（18/41）。。

To evaluate key target characteristics of NVL-655, activity was examined in subgroups of the 51 response-evaluable patients treated at all doses, including:

为了评估NVL-655的关键目标特征，在所有剂量下治疗的51位反应可评估患者的亚组中检查了活性，包括：

Patients with any history of CNS metastases (ORR 52%, 15/29);

有任何中枢神经系统转移史的患者（ORR 52%，15/29）；

Patients with any ALK resistance mutation (ORR 54%, 15/28), including those with compound ALK mutations (ORR 56%, 9/16) and those with ALK G1202R single or compound mutations (ORR 71%, 12/17);

具有任何ALK抗性突变（ORR 54%，15/28）的患者，包括具有复合ALK突变的患者（ORR 56%，9/16）和具有ALK G1202R单突变或复合突变的患者（ORR 71%，12/17）；

The most heavily pre-treated of patients, after receiving ≥3 prior ALK TKIs including at least one 2nd generation (2G) ALK TKI (alectinib, brigatinib, or ceritinib) plus lorlatinib, and prior chemotherapy (ORR 42%, 8/19); and,

在接受≥3个先前的ALK TKI（包括至少一个第二代（2G）ALK TKI（alectinib，brigatinib或ceritinib）加lorlatinib）和之前的化疗（ORR 42%，8/19）；和，

Lorlatinib-naïve patients who had received at least one 2G +/- 1G ALK TKI (ORR 71%, 5/7).

接受至少一种2G+/-1G ALK TKI（ORR 71%，5/7）的Lorlatinib初治患者。

Preliminary pharmacokinetic (PK) analyses were available for dose levels 15 mg QD to 150 mg QD. Treatment with NVL-655 resulted in exposure above target efficacy thresholds in both the periphery and in the CNS. These preliminary PK data suggest that dose levels of 50 mg QD and above may provide increased coverage of single and compound mutations in the CNS.

初步药代动力学（PK）分析可用于15mg QD至150mg QD的剂量水平。用NVL-655治疗导致在外周和CNS中暴露高于目标功效阈值。这些初步的PK数据表明，剂量水平为50 mg QD及以上可能会增加CNS中单个和复合突变的覆盖率。

Preliminary pharmacodynamic analysis showed that NVL-655 induced clearance of diverse ALK resistance mutation alleles across a wide dose range..

初步药效学分析表明，NVL-655在很宽的剂量范围内诱导了多种ALK耐药突变等位基因的清除。。

As of the cut-off date for the preliminary data, 67% (34/51) of response-evaluable patients remained on treatment with NVL-655 with duration of treatment up to 12 months (median duration of treatment of 3.4 months). All patients with tumor response continued on treatment without disease progression.

截至初步数据的截止日期，67%（34/51）的应答可评估患者仍在接受NVL-655治疗，治疗时间长达12个月（中位治疗时间为3.4个月）。所有具有肿瘤反应的患者继续接受治疗而没有疾病进展。

NVL-655 was well-tolerated with a preliminary safety profile that was favorable and consistent with its ALK-selective, TRK sparing design..

NVL-655耐受性良好，初步安全性良好，与其ALK选择性TRK保留设计相符。。

'We are excited to present the first look at the safety and clinical activity of NVL-655 from our ALKOVE-1 clinical trial, which we believe supports the potential for NVL-655 to address each key area of its desired target product profile,' said Christopher Turner, M.D., Chief Medical Officer of Nuvalent.

“我们很高兴从我们的ALKOVE-1临床试验中首次看到NVL-655的安全性和临床活性，我们认为这支持NVL-655解决其所需目标产品概况的每个关键领域的潜力，”Nuvalent首席医疗官Christopher Turner博士说。

'Across a wide dose range, NVL-655 demonstrated activity in a heavily pre-treated patient population that uniquely includes patients in the post-lorlatinib setting, with a favorable preliminary safety profile consistent with its ALK-selective, TRK sparing design. Importantly, all patients with tumor response remained on treatment without disease progression as of the data cut-off date, suggesting the potential for durable responses even in this late line population.'.

“在广泛的剂量范围内，NVL-655在严重预处理的患者群体中表现出活性，其独特地包括在lorlatinib后环境中的患者，具有与其ALK选择性TRK保留设计一致的有利的初步安全性。重要的是，截至数据截止日期，所有肿瘤反应患者仍在接受治疗而无疾病进展，这表明即使在这一晚期人群中也有可能获得持久的反应。

Dr. Turner continued, 'Ultimately, we view the ability to keep patients on therapeutically relevant dose levels as a key indicator of the potential for NVL-655 to drive clinically meaningful durable responses when used earlier in the treatment paradigm. In earlier lines of therapy, potent activity against ALK as well as single or compound ALK resistance mutations in both the periphery and the brain has the potential to delay or prevent the emergence of both treatment resistance and CNS progression.

特纳博士继续说：“最终，我们认为将患者保持在治疗相关剂量水平的能力作为NVL-655在治疗范式早期使用时推动临床上有意义的持久反应的潜力的关键指标。在早期的治疗方案中，针对ALK的有效活性以及外周和大脑中的单一或复合ALK抗性突变具有延迟或阻止治疗抗性和CNS进展的出现的潜力。

Furthermore, selective inhibition of wild-type ALK and its resistance variants may minimize TRK-related CNS adverse events and other off-target toxicities that can be dose limiting. We believe that the preliminary characteristics of NVL-655 observed in this heavily pre-treated patient population support its opportunity as a potential best-in-class therapy that can move up the treatment paradigm to deliver deep and durable responses for patients with ALK-positive cancers.'.

此外，选择性抑制野生型ALK及其抗性变体可以使TRK相关的CNS不良事件和可能是剂量限制的其他脱靶毒性最小化。我们相信NVL-655在这个严重预处理的患者群体中观察到的初步特征支持其作为潜在的一流疗法的机会，其可以提升治疗范例以为患者提供深度和持久的反应ALK阳性癌症“。

'With today's data, Nuvalent has presented preliminary proof-of-concept data for both of its novel parallel lead programs in ROS1 and ALK-positive cancers in just over 5 years since the company's inception,' said James Porter, Ph.D., Chief Executive Officer at Nuvalent. 'We believe this achievement is a testament to the dedication of the Nuvalent team, and to our approach of collaboration with leading physician-scientists, identification of medical needs stemming from the limitations of existing therapies, and focused application of our innovative chemistry and deep expertise in structure-based drug design to develop precisely targeted therapies according to well-defined target product profiles.'.

“根据今天的数据，Nuvalent在公司成立后的短短5年内为其在ROS1和ALK阳性癌症中的新型平行铅项目提供了初步的概念验证数据，”Nuvalent首席执行官James Porter博士说我们相信这一成就证明了Nuvalent团队的奉献精神，以及我们与领先的医师科学家合作的方法，确定了现有疗法局限性带来的医疗需求，并将我们的创新化学和深度专业知识集中应用于基于结构的药物设计，以根据明确定义的目标产品概况开发精确靶向治疗。

Dr. Porter continued, 'Most importantly, we recognize that this achievement is made possible by the patients, caregivers, and investigators who are participating in the ALKOVE-1 trial and offer our sincere gratitude. We look forward to discussions with investigators and regulators on the selection of a recommended Phase 2 dose (RP2D) and the transition to the planned Phase 2 portion of ALKOVE-1 for patients with lorlatinib-naïve and lorlatinib-treated ALK-positive NSCLC.

波特博士继续说：“最重要的是，我们认识到参与ALKOVE-1试验的患者，护理人员和研究人员可以实现这一成就，并衷心感谢。我们期待与研究者和监管机构讨论选择推荐的2期剂量（RP2D）以及向lorlatinib-naïve和lorlatinib治疗的ALK阳性NSCLC患者过渡到ALKOVE-1计划的2期部分。

We also look forward to using the preliminary data to guide discussions with physicians regarding potential development strategies for patients with TKI-naïve ALK-positive NSCLC as we work towards our goal of bringing new treatment options to all patients with ALK-positive cancers.'.

我们也期待使用初步数据指导与医生讨论TKI初治ALK阳性NSCLC患者的潜在发展策略，因为我们致力于为所有ALK阳性癌症患者提供新治疗方案的目标。

NVL-655 First-in-Human Preliminary Phase 1 Data

NVL-655首次在人体初步阶段1数据

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 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 and intracranial activity of NVL-655..

主要目标是确定ALK阳性实体瘤患者的RP2D和NVL-655的最大耐受剂量（MTD）（如果适用）。其他目标包括表征NVL-655的总体安全性，耐受性和药代动力学特征，以及初步抗肿瘤活性和颅内活性的评估。。

As of the enrollment and data cut-off date of August 8, 2023 for the preliminary data, 93 patients were enrolled in the Phase 1 portion of the ALKOVE-1 trial, of which 91 patients had ALK-positive NSCLC and 58% (54/93) had a history of CNS metastases.

截至2023年8月8日的入选和数据截止日期为初步数据，93名患者参加了ALKOVE-1试验的第一阶段，其中91名患者为ALK阳性NSCLC，58%（54/93）有中枢神经系统转移史。

The patient population was heavily pre-treated:

患者人群经过大量预处理：

100% (93/93) had received a 2G ALK TKI or lorlatinib;

100%（93/93）已接受2G ALK TKI或lorlatinib；

77% (72/93) had received two or more ALK TKIs, including a 2G ALK TKI and lorlatinib;

77%（72/93）接受了两种或两种以上的ALK TKI，包括2G ALK TKI和lorlatinib；

44% (41/93) had received three or more ALK TKIs, including a 2G ALK TKI and lorlatinib; and,

44%（41/93）接受了三种或更多种ALK TKI，包括2G ALK TKI和lorlatinib；和，

46% (43/93) had an identified secondary ALK mutation, including 26% (24/93) with any compound ALK mutation.

46%（43/93）具有确定的继发性ALK突变，包括26%（24/93）具有任何复合ALK突变。

Preliminary Activity Analysis

初步活动分析

As of the cut-off date for the preliminary data, patients were treated in six NVL-655 dose cohorts of 15 mg, 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg QD. Fifty-one patients with NSCLC were response-evaluable by investigator assessment with duration of treatment up to 12 months (median duration of treatment of 3.4 months)..

截至初步数据的截止日期，患者接受了6个NVL-655剂量组的15 mg，25 mg，50 mg，100 mg，150 mg和200 mg QD治疗。51名NSCLC患者通过研究者评估进行反应评估，治疗持续时间长达12个月（中位治疗时间为3.4个月）。。

Key findings include early anti-tumor activity in ALK-positive NSCLC patients, including partial responses (RECIST 1.1) in:

主要发现包括ALK阳性NSCLC患者的早期抗肿瘤活性，包括部分反应（RECIST 1.1）：

Heavily pre-treated patients: An ORR of 39% (20/51) was observed in response-evaluable patients, and all patients with tumor response continued on treatment without disease progression as of the data cut-off date.

严重预处理的患者：在响应可评估的患者中观察到ORR为39%（20/51），并且截至数据截止日期，所有具有肿瘤响应的患者继续治疗而没有疾病进展。

For dose levels of 50 mg or greater, which may provide increased coverage of single and compound mutations in the CNS, an ORR of 44% (18/41) was observed.

对于50mg或更高的剂量水平，其可以提供CNS中单个和化合物突变的增加的覆盖率，观察到44%（18/41）的ORR。

In patients who have likely exhausted all available treatment options (≥3 prior ALK TKIs including a 2G ALK TKI and lorlatinib), the observed ORR was 40% (10/25) regardless of prior chemotherapy and 42% (8/19) with prior chemotherapy.

在可能用尽所有可用治疗方案的患者中（≥3个先前的ALK TKI，包括2G ALK TKI和lorlatinib），观察到的ORR为40%（10/25），无论之前的化疗如何，42%（8/19）之前的化疗。

Patients with ALK single or compound resistance mutations: An ORR of 54% (15/28) was observed in patients with any ALK resistance mutation, including an ORR of 56% (9/16) in patients with compound ALK mutations, and an ORR of 71% (12/17) in patients with ALK G1202R single or compound mutations.

ALK单一或复合耐药突变患者：任何ALK耐药突变患者的ORR为54%（15/28），其中复合ALK突变患者的ORR为56%（9/16），ALK G1202R单一或复合突变患者的ORR为71%（12/17）。

Patients with CNS metastases: An ORR of 52% (15/29) was observed in patients with any history of CNS metastases. All patients with tumor response who had a history of CNS disease continued on treatment without CNS progression.

中枢神经系统转移患者：有中枢神经系统转移病史的患者ORR为52%（15/29）。所有有中枢神经系统疾病史的肿瘤反应患者继续接受治疗，无中枢神经系统进展。

Lorlatinib-naïve patients: Of patients who received at least one 2G +/- 1G ALK TKI and had not previously received lorlatinib, 5 of 7 (71%) responded.

未接受Lorlatinib治疗的患者：接受至少一种2G+/-1G ALK TKI且以前未接受Lorlatinib治疗的患者中，7例中有5例（71%）有反应。

Preliminary Safety, Pharmacokinetic, and Pharmacodynamic Analysis

初步安全性，药代动力学和药效学分析

A favorable preliminary safety profile was observed with NVL-655 treatment in the 93 patients enrolled across the dose-escalation portion of ALKOVE-1, consistent with an ALK-selective, TRK-sparing design. Most treatment-related adverse events (TRAEs) were low-grade and manageable, with the highest incidence of TRAEs being ALT increase (19%, 18/93 any grade; 6%, 6/93 ≥ Grade 3), AST increase (18%, 17/93 any grade; 4%, 4/93 ≥ Grade 3), and nausea (10%, 9/93 of which all were Grade 1 or 2).

NVL-655治疗在ALKOVE-1剂量递增部分招募的93名患者中观察到有利的初步安全性，与ALK选择性TRK保留设计一致。大多数治疗相关不良事件（TRAEs）是低级别和可控的，TRAEs发生率最高的是ALT升高（19%，任何级别18/93；6%，6/93≥3级），AST升高（18%，17/93任何等级；4%，4/93≥3级）和恶心（10%，9/93均为1级或2级）。

TRAEs requiring dose modification were infrequent, with 2% (2/93) discontinuations and 5% (5/93) dose reductions. There was one dose-limiting toxicity of transient asymptomatic Grade 4 CPK increase at the 200 mg QD dose level. An MTD was not reached, and the preliminary overall safety profile was consistent with avoidance of TRK-related neurotoxicities..

需要改变剂量的TRAEs不常见，停药2%（2/93），剂量减少5%（5/93）。在200 mg QD剂量水平下，短暂的无症状4级CPK增加存在一种剂量限制性毒性。未达到MTD，初步的总体安全性与避免TRK相关的神经毒性一致。。

The observed favorable preliminary safety profile allowed for achievement of NVL-655 exposure levels above target CNS efficacy thresholds for ALK, ALK single and compound G1202R mutations, and other recalcitrant ALK single mutations such as I1171N. Favorable PK and low intra-cohort patient PK variability were observed, with dose-proportional exposure and a half-life that is supportive of once daily dosing.

观察到的有利的初步安全性概况允许实现高于针对ALK，ALK单一和化合物G1202R突变以及其他顽固性ALK单一突变如I1171N的目标CNS功效阈值的NVL-655暴露水平。观察到良好的PK和较低的队列内患者PK变异性，剂量成比例的暴露和支持每日一次给药的半衰期。

This preliminary PK data suggest that dose levels of 50 mg QD or greater may provide increased coverage of single and compound mutations in the CNS..

该初步PK数据表明，剂量水平为50 mg QD或更高可能会增加CNS中单个和复合突变的覆盖率。。

Preliminary pharmacodynamic findings by centrally confirmed ctDNA analysis showed that treatment with NVL-655 induced clearance of diverse ALK resistance mutation alleles across a wide dose range. Notably, 100% clearance was observed in 14 of 16 patients with centrally confirmed single or compound ALK G1202R or I1171X (X = N or T) mutations, of which 13 had received prior lorlatinib..

通过中心确认的ctDNA分析的初步药效学发现显示，用NVL-655处理诱导在宽剂量范围内清除多种ALK抗性突变等位基因。值得注意的是，在16例经中央确认的单一或复合ALK G1202R或I1171X（X=N或T）突变的患者中，有14例观察到100%清除率，其中13例先前接受过lorlatinib。。

Combined with the favorable preliminary activity observed as of the data cut-off date, these data suggest that NVL-655 has opportunity as a potential best-in-class therapy that may be able to move up the treatment paradigm for patients with ALK-positive NSCLC.

结合截至数据截止日期观察到的有利的初步活动，这些数据表明NVL-655有机会成为潜在的一流疗法，可能能够为ALK阳性NSCLC患者提供治疗范例。

The ALKOVE-1 clinical trial is continuing to enroll patients in the Phase 1 portion of the trial and is focused on further characterizing the safety, PK, and pharmacodynamic profiles, determining the RP2D, and if applicable, the MTD of NVL-655. Upon RP2D selection, the trial is designed to transition directly into the Phase 2 portion, which will evaluate the safety and activity of NVL-655 in several expansion cohorts of patients defined based on the number and type of prior anti-cancer therapies they have received.

ALKOVE-1临床试验正在继续在试验的第一阶段招募患者，重点是进一步表征安全性，PK和药效学特征，确定RP2D以及NVL-655的MTD（如果适用）。在选择RP2D后，该试验旨在直接过渡到阶段2部分，这将评估NVL-655在几个扩展队列患者中的安全性和活性，这些患者根据之前接受的抗癌治疗的数量和类型进行定义。

The Phase 2 cohorts are intended to support potential registration in patients with ALK-positive NSCLC who are both lorlatinib-naïve and lorlatinib-treated..

第二阶段队列旨在支持接受lorlatinib-naïve和lorlatinib治疗的ALK阳性NSCLC患者的潜在登记。。

In addition to the planned Phase 2 cohorts, Nuvalent intends to use these preliminary data in patients with heavily pre-treated ALK-positive NSCLC to guide discussions with physicians that will inform development strategies in TKI-naïve ALK-positive NSCLC.

除了计划的第二阶段队列外，Nuvalent还打算将这些初步数据用于严重预处理的ALK阳性NSCLC患者，以指导与医生的讨论，这些讨论将为TKI初治ALK阳性NSCLC的发展策略提供信息。

Webcast and Conference Call Information

网络广播和电话信息

A conference call with management will be held today 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.

今天上午8点与管理层召开电话会议。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 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; the implications of the data readouts and presentations; timing and content of potential discussions with regulators and investigators; the design and timing of the planned Phase 2 portion of the ALKOVE-1 trial; 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；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；数据读数和演示文稿的影响；与监管机构和调查人员进行潜在讨论的时间和内容；ALKOVE-1试验计划阶段2部分的设计和时间安排；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 Nuvalent'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日结束的季度期间的Nuvalent季度报告表格10-Q中的“风险因素”部分以及之前和之后与证券交易委员会。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 a.

Nuvalent明确拒绝更新a的任何义务。

SOURCE Nuvalent, Inc.

来源Nuvalent，Inc。