Reactive oxygen species 1 positive non-small cell lung cancer

CAMBRIDGE, Mass., April 29, 2025 /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 the publication of a manuscript in Molecular Cancer Therapeutics, 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. The publication, entitled "Zidesamtinib Selective Targeting of Diverse ROS1 Drug-Resistant Mutations," is published online and can be accessed here: "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. 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," said first author Anupong Tangpeerachaikul, Ph.D., Director, Biology at Nuvalent. "With this publication in Molecular Cancer Therapeutics, 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." 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. 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. 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. The crystal structure elucidates zidesamtinib's preclinical affinity for ROS1 G2032R and selectivity for ROS1 over TRK. 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. About Zidesamtinib 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. 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. 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. About 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 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. Forward-Looking Statements 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. 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. 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. 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. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Nuvalent's Annual Report on Form 10-K for the fiscal year ended December 31, 2024, 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. SOURCE Nuvalent, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

CAMBRIDGE, Mass., April 23, 2025 /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 two "Trial in Progress" poster presentations for its novel ALK-selective inhibitor, neladalkib, and novel HER2-selective inhibitor, NVL-330, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting from May 30 – June 5, 2025, in Chicago. Posters will be archived on the Nuvalent website at . The first "Trial in Progress" poster will include background and study design for ALKAZAR (NCT06765109), a global, randomized, controlled Phase 3 trial designed to evaluate neladalkib versus the current standard of care for the treatment of patients with TKI-naïve ALK-positive non-small cell lung cancer (NSCLC). Patients will be randomized 1:1 to receive neladalkib monotherapy or ALECENSA® (alectinib) monotherapy. The company plans to initiate the ALKAZAR trial in the first half of 2025. The second poster will include background and study design for the ongoing HEROEX-1 Phase 1a/1b clinical trial (NCT06521554) evaluating the overall safety and tolerability of NVL-330 for pre-treated patients with HER2-altered NSCLC. Additional objectives include determination of the recommended Phase 2 dose, characterization of NVL-330's pharmacokinetic profile, and preliminary evaluation of anti-tumor activity. Details of the poster presentations are as follows: Title: Neladalkib (NVL-655), a highly selective anaplastic lymphoma kinase (ALK) inhibitor, compared to alectinib in first-line treatment of patients with ALK-positive advanced non-small cell lung cancer: The Phase 3 ALKAZAR study Authors: Sanjay Popat*1, Benjamin J. Solomon2, Thomas E. Stinchcombe3, Geoffrey Liu4, Gilberto Lopes5, Melissa Johnson6, Misako Nagasaka7, Ece Cali Daylan8, Christina Baik9, James D'Olimpio10, Tzu-Chuan Huang11, Alexander Spira12, Daniel Haggstrom13, Benjamin Creelan14, Tina Kehrig15, Junwu Shen15, Rachel DeLaRosa15, Viola W. Zhu15, Alexander Drilon16, Alice T. Shaw17 Abstract Number: TPS8666 Session Title: Lung Cancer—Non-Small Cell Metastatic Session Date and Time: May 31, 2025, from 1:30 p.m.– 4:30 p.m. CDT Poster Board Number: 136b *Presenter, corresponding author; 1Royal Marsden Hospital NHS Foundation Trust and The Institute of Cancer Research, London, UK; 2Peter MacCallum Cancer Centre, Melbourne, Australia; 3Duke Cancer Center, Durham, NC, USA; 4Princess Margaret Hospital, Toronto, ON, Canada; 5Sylvester Comprehensive Cancer Center, Miami, FL, USA; 6Sarah Cannon Research Institute Oncology Partners, Nashville, TN, USA; 7University of California Irvine School of Medicine, Orange, CA, USA; 8Washington University School of Medicine, St. Louis, MO, USA; 9Fred Hutchinson Cancer Center, Seattle, WA, USA; 10Clinical Research Alliance Inc., Westbury, NY, USA; 11University Cancer and Blood Center, LLC, Athens, GA, USA; 12Virginia Cancer Specialists (Fairfax) - USOR, Fairfax, VA, USA; 13Carolinas Medical Center, Charlotte, NC, USA; 14H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA; 15Nuvalent, Inc., Cambridge, MA, USA; 16Memorial Sloan Kettering Cancer Center, New York, NY, USA; 17Dana-Farber Cancer Institute, Boston, MA, USA Title: NVL-330, a selective HER2 tyrosine kinase inhibitor, in patients with advanced or metastatic HER2-altered non-small cell lung cancer: The Phase 1 HEROEX-1 study Authors: Xiuning Le*1, Zofia Piotrowska2, Alexander Spira3, Christina Baik4, Maria Q. Baggstrom5, Gerald Falchook6, Joel Neal7, Shirish Gadgeel8, Gilberto Lopes9, Melissa Johnson10, Jonathan W. Riess11, Danny Nguyen12, Lisa Morelli13, Danieska Sandino13, Steven Margossian13, Vivek Upadhyay13, Fernando C. Santini14 Abstract Number: TPS8665 Session Title: Lung Cancer—Non-Small Cell Metastatic Session Date and Time: May 31, 2025, from 1:30 p.m.– 4:30 p.m. CDT Poster Board Number: 136a *Presenter, corresponding author; 1University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Massachusetts General Hospital, Boston, MA, USA; 3NEXT Oncology, Fairfax, VA, USA; 4Fred Hutchinson Cancer Center, Seattle, WA, USA; 5Washington University School of Medicine, St. Louis, MO, USA; 6Sarah Cannon Research Institute at HealthONE, Denver, CO, USA; 7Stanford Cancer Institute, Stanford, CA, USA; 8Henry Ford Cancer Institute, Detroit, MI, USA; 9Sylvester Comprehensive Cancer Center, Miami, FL, USA; 10Sarah Cannon Research Institute Oncology Partners, Nashville, TN, USA; 11University of California Davis, Davis Comprehensive Cancer Center, Sacramento CA, USA; 12City of Hope-Lennar, Irvine, CA, USA; 13Nuvalent, Inc., Cambridge, MA, USA; 14Memorial Sloan Kettering Cancer Center, New York, NY, USA About Neladalkib Neladalkib is a novel brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. Neladalkib is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R. In addition, neladalkib 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/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. Neladalkib has received breakthrough therapy designation for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with 2 or more ALK tyrosine kinase inhibitors and orphan drug designation for ALK-positive NSCLC. About NVL-330 NVL-330 is a novel brain-penetrant HER2-selective tyrosine kinase inhibitor designed to address the combined medical need of treating HER2-mutant tumors, including those with HER2 exon 20 insertion mutations, avoiding treatment related adverse events due to off-target inhibition of wild-type EGFR, and treating brain metastases. About 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 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. Forward-Looking Statements 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 presentations; the potential benefits and effects of Nuvalent's product development candidates; the potential of Nuvalent's pipeline programs, including zidesamtinib, neladalkib and NVL-330; Nuvalent's research and development programs for the treatment of cancer; and risks and uncertainties associated with drug development. 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. 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. 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: 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 operations; the timing and outcome of Nuvalent's planned interactions with regulatory authorities; and risks related to obtaining, maintaining, and protecting Nuvalent's intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Nuvalent's Annual Report on Form 10-K for the fiscal year ended December 31, 2024, 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. SOURCE Nuvalent, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

SHANGHAI & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Apr. 21, 2025-- Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) today announced that China’s National Medical Products Administration (NMPA) has accepted the supplemental New Drug Application (sNDA) for repotrectinib for the treatment of adult patients with solid tumors that harbor a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. The application is intended for patients whose disease is locally advanced or metastatic, or where surgical resection is likely to result in severe morbidity, and who have either progressed following prior therapies or have no satisfactory alternative treatment options. “NTRK fusion-positive tumors represent a significant therapeutic challenge, particularly in the setting of acquired resistance to existing TRK tyrosine kinase inhibitors (TKIs),” said Dr. Rafael Amado, M.D., President, Head of Global Research and Development at Zai Lab. “There are no approved treatments for NTRK-positive cancers for both TKI-naïve and TKI-pretreated patients in China. Repotrectinib has the potential to become a next-generation TKI that can be used across a broad range of NTRK fusion-positive solid tumors in both settings.” In February 2025, China’s NMPA granted priority review to repotrectinib for the treatment of adult patients with advanced solid tumors that have an NTRK gene fusion. About Repotrectinib Repotrectinib is a next-generation tyrosine kinase inhibitor targeting the ROS1 and NTRK oncogenic drivers. Patients with solid tumors, including NSCLC, harboring ROS1 and NTRK gene fusions treated with approved targeted therapies often develop resistance mutations that limit binding of these drugs to their target. Ultimately, this leads to shortened duration of response and tumor progression. Repotrectinib is the first next-generation ROS1 and TRK TKI uniquely designed to improve durability of benefit, including in the brain, and to address acquired resistance. In June 2024, AUGTYRO (repotrectinib) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a NTRK gene fusion, are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy. In May 2024, AUGTYRO was approved by the NMPA for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small-cell lung cancer (NSCLC). It was approved by the FDA for this indication in November 2023. Zai Lab has an exclusive license agreement with Turning Point Therapeutics, Inc. (a Bristol Myers Squibb company) to develop and commercialize AUGTYRO in Greater China (mainland China, Hong Kong, Taiwan, and Macau, collectively). About NTRK-Positive Solid Tumors NTRK-positive advanced malignancies are life-threatening with poor prognoses and represent an area of significant unmet medical need in adult and pediatric patients. Existing targeted therapies have demonstrated clinical benefits but are limited by the duration of response due to the emergence of acquired resistance mutations.1 In China, there was no approved treatment option for NTRK-positive cancers that was studied in both TKI-naïve and TKI-pretreated patients across solid tumors. 1 Harada G, Santini FC, Wilhelm C, Drilon A, et al. NTRK fusions in lung cancer: From biology to therapy. Lung Cancer. 2021;161:108-113. About Zai Lab Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) is an innovative, research-based, commercial-stage biopharmaceutical company based in China and the United States. We are focused on discovering, developing, and commercializing innovative products that address medical conditions with significant unmet needs in the areas of oncology, immunology, neuroscience, and infectious disease. Our goal is to leverage our competencies and resources to positively impact human health. For additional information about Zai Lab, please visit www.zailaboratory.com or follow us at https://x.com/ZaiLab_Global. Zai Lab Forward-Looking Statements This press release contains forward-looking statements relating to our future expectations, plans, and prospects, including, without limitation, statements relating to our prospects and plans for developing and commercializing repotrectinib in Greater China, the potential benefits of repotrectinib, and the potential treatment of NTRK-positive solid tumors. These forward-looking statements may contain words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would,” and other similar expressions. Such statements constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not statements of historical fact or guarantees or assurances of future performance. Forward-looking statements are based on our expectations and assumptions as of the date of this press release and are subject to inherent uncertainties, risks, and changes in circumstances that may differ materially from those contemplated by the forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including but not limited to (1) our ability to successfully commercialize and generate revenue from our approved products, (2) our ability to obtain funding for our operations and business decisions, (3) the results of our clinical and pre-clinical development of our product candidates, (4) the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approvals of our product candidates, (5) risks related to doing business in China, and (6) other factors identified in our most recent annual and quarterly reports and in other reports we have filed with the U.S. Securities and Exchange Commission. We anticipate that subsequent events and developments will cause our expectations and assumptions to change, and we undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as may be required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Our SEC filings can be found on our website at www.zailaboratory.com and the SEC’s website at www.sec.gov. View source version on businesswire.com: https://www.businesswire.com/news/home/20250421607809/en/ For more information, please contact: Investor Relations: Christine Chiou / Lina Zhang +1 (917) 886-6929 / +86 136 8257 6943 christine.chiou1@zailaboratory.com / lina.zhang@zailaboratory.com Media: Shaun Maccoun / Xiaoyu Chen +1 (857) 270-8854 / +86 185 0015 5011 shaun.maccoun@zailaboratory.com / xiaoyu.chen@zailaboratory.com Source: Zai Lab Limited