HER2 mutant non-small cell lung cancer

Well-capitalized with operating runway anticipated into 2027 CAMBRIDGE, Mass., Feb. 27, 2024 /PRNewswire/ -- Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, today highlighted pipeline progress, reiterated key anticipated milestones and reported fourth quarter and full year 2023 financial results. "With our OnTarget 2026 operating plan as a clear guide, the Nuvalent team continues to prove its ability to execute on its goals as demonstrated by the recently announced initiation of the Phase 2 portion of our ALKOVE-1 study for NVL-655 and the receipt of FDA breakthrough therapy designation for NVL-520 based on preliminary data from our ARROS-1 study." said Alexandra Balcom, Chief Financial Officer at Nuvalent. "We now have two global registration-directed studies underway in support of our target of a first approved product in 2026 and we look forward to providing updates on both of our parallel lead programs at medical meetings later this year." "Our ability to deliver on our program goals is interconnected with our ability to build the team and maintain a strong culture centered around our core values of Patient Impact, Empowerment, and Collaboration. In recognition of his leadership and contributions across these areas, we are proud to announce the promotion of Matthew Metivier to Senior Vice President of Human Resources," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "Backed by a dedicated and expert team, and a strong balance sheet, we are well positioned to continue delivering on our planned 2024 milestones across our portfolio of precisely targeted therapies for patients with cancer." Recent Pipeline Progress and Anticipated Milestones ROS1 Program The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation (BTD) to NVL-520 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 (TKIs). NVL-520 was previously granted FDA Orphan Drug Designation for the treatment of ROS1-positive NSCLC. The company expects to share updated data from the ARROS-1 Phase 1/2 trial at a medical meeting in 2024. Enrollment is ongoing in the global Phase 2 portion of the study. ALK Program Nuvalent recently announced the initiation of the Phase 2 portion of the ALKOVE-1 trial of NVL-655 for patients with advanced ALK-positive NSCLC and other solid tumors, following alignment with the FDA on a recommended Phase 2 dose (RP2D) of 150 mg once daily. The Phase 2 portion of the ALKOVE-1 clinical trial is designed to 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. The Phase 2 cohorts are designed with registrational intent for TKI pre-treated patients with ALK-positive NSCLC and to enable preliminary evaluation in patients with ALK-positive NSCLC who are TKI naïve. The company expects to share updated data from the ALKOVE-1 trial at a medical meeting and to outline its broader front-line development strategy for its ALK program in 2024. HER2 Program The company expects to initiate the Phase 1 trial for its HER2 program in 2024. Recent Leadership Promotions Promotion of Matthew Metivier to Senior Vice President of Human Resources: Mr. Metivier brings over 20 years of experience in various human resources leadership roles, specifically within the biotechnology/pharmaceutical industry, with a focus on building companies and guiding organizations through the early development phase to commercial launch. At Nuvalent, Mr. Metivier has built and led our Human Resources capabilities and facilitated our people and culture strategy to ensure we optimize our work environment to attract, retain and develop the talent needed to achieve our mission. Prior to joining Nuvalent, he held leadership roles of increasing responsibility in human resources at Gamida Cell, Ltd, Sage Therapeutics, Inc, and Infinity Pharmaceuticals. Mr. Metivier holds an MBA from Suffolk University with a concentration in Organizational Behavior and a B.A. in Political Science and Business Studies from Providence College. Upcoming Events TD Cowen 44th Annual Health Care Conference: Management will be participating in a fireside chat on Wednesday, March 6, 2024, at 1:30 p.m. ET in Boston, MA. Leerink Global Biopharma Conference 2024: Management will be participating in a fireside chat on Tuesday, March 12, 2024, at 8:00 a.m. ET in Miami, FL. A live webcast of each fireside chat will be available in the Investors section of Nuvalent's website at , and will be archived for 30 days following the conference. Fourth Quarter and Full Year 2023 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $719.9 million as of December 31, 2023. Nuvalent believes these existing cash, cash equivalents and marketable securities to be sufficient to fund its current operating plan into 2027. R&D Expenses: Research and development (R&D) expenses were $35.6 million for the fourth quarter of 2023 and $113.2 million for the year ended December 31, 2023. G&A Expenses: General and administrative (G&A) expenses were $10.9 million for the fourth quarter of 2023 and $36.2 million for the year ended December 31, 2023. Net Loss: Net loss was $38.3 million for the fourth quarter of 2023 and $126.2 million for the year ended December 31, 2023. About OnTarget 2026 OnTarget 2026 delineates Nuvalent's 3-year operating plan towards bringing new, potential best-in-class medicines to patients with cancer. As part of this plan announced in January 2024, Nuvalent outlined the following anticipated milestones throughout 2024, leading to the company's first potential pivotal data in 2025 and first potential approved product in 2026: 2024: Execute on Global Registrational Strategies Progress the Phase 2 portion of its ARROS-1 trial of NVL-520 in patients with advanced ROS1-positive NSCLC with registrational intent; Initiate the Phase 2 portion of its ALKOVE-1 trial of NVL-655 in patients with advanced ALK-positive NSCLC with registrational intent; Launch the front-line development strategy for its ALK program; Present interim data from its ongoing ARROS-1 and ALKOVE-1 clinical trials at medical meetings; and, Initiate the Phase 1 trial for its HER2 program. 2025: First Pivotal Data 2026: First Approved Product 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-positive 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 period over which Nuvalent estimates its cash, cash equivalents and marketable securities will be sufficient to fund its future operating expenses and capital expenditure requirements; Nuvalent's estimate of its cash, cash equivalents and marketable securities as of December 31, 2023; the expected timing of data announcements, clinical trial initiations and FDA product approvals, including the projections in our OnTarget 2026 operating plan; the preclinical and clinical development programs for NVL-520, NVL-655 and NVL-330; the potential clinical effect of NVL-520 and NVL-655; the potential benefits of NVL-330; the design and enrollment of the ARROS-1 and ALKOVE-1 trials, including their intended pivotal registration-directed design; the potential of Nuvalent's pipeline programs, including NVL-520, NVL-655 and NVL-330; the implications of 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 ARROS-1 and ALKOVE-1 trials; 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 the ARROS-1 or ALKOVE-1 trials 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; 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; risks that Nuvalent may not achieve the goals and milestones set forth in its OnTarget 2026 operating plan; 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-1 and ALKOVE-1 trials; 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 Quarterly Report on Form 10-Q for the quarterly period ended September 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. Nuvalent explicitly disclaims any obligation to update any forward-looking statements. SOURCE Nuvalent, Inc.

CAMBRIDGE, Mass., Feb. 27, 2024 /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 that the U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation (BTD) to NVL-520 for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) who have been previously treated with two or more ROS1 tyrosine kinase inhibitors (TKIs). ROS1 rearrangements occur in up to approximately 3% of metastatic NSCLCs. At the time of diagnosis, up to 40% of these patients present with accompanying brain metastases, and approximately 40% of patients develop resistance mutations following current front-line treatment. There remains no clear standard of care for patients who have been previously treated with two or more ROS1 TKIs. NVL-520 is a novel brain-penetrant ROS1-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 inhibition of the structurally-related tropomyosin receptor kinase (TRK) family that may limit the use of currently available ROS1 TKIs. "In line with our commitment to bringing new potential best-in-class medicines to patients with cancer as quickly as possible, we are always looking for opportunities to further accelerate our programs," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "We're very encouraged by today's announcement of FDA breakthrough therapy designation for NVL-520, as it recognizes the continued need for innovation for patients with ROS1-positive NSCLC who have exhausted available therapies. We look forward to providing an update from the ARROS-1 trial of NVL-520 at a medical meeting later this year." BTD is designed to expedite the development and review of therapies intended to treat a serious or life-threatening condition and whose preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over existing available therapies. Under the designation, the FDA provides intensive guidance, organizational commitment involving senior managers, and eligibility for rolling review and other actions to expedite review. The BTD for NVL-520 is based on the preliminary safety and activity of NVL-520 in heavily pretreated patients with advanced ROS1-positive NSCLC in the Phase 1 portion of the Phase 1/2 ARROS-1 clinical trial. Enrollment in the Phase 2 portion of the trial is ongoing, and the company expects to share updated data from the trial at a medical meeting in 2024. About NVL-520 NVL-520 is a novel brain-penetrant ROS1-selective inhibitor created with the aim to overcome limitations observed with currently available ROS1 inhibitors. NVL-520 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, NVL-520 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. NVL-520 has received orphan drug designation for ROS1-positive non-small cell lung cancer (NSCLC) and is currently being investigated in the ARROS-1 trial (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced ROS1-positive NSCLC and other solid tumors. 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-positive 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 product approvals; the clinical development program for NVL-520; the potential clinical effect of NVL-520; the design and enrollment of the ARROS-1 trial, including its intended pivotal registration-directed design; the potential of Nuvalent's pipeline programs, including NVL-520; 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," "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 the ARROS-1 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; 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; 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-1 trial; the timing and outcome of Nuvalent's planned interactions with regulatory authorities; 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 Quarterly Report on Form 10-Q for the quarterly period ended September 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. Nuvalent explicitly disclaims any obligation to update any forward-looking statements. SOURCE Nuvalent, Inc.

AstraZeneca is looking to make up some ground after a rather shaky start to 2024, announcing a flurry of positive lung cancer news on Monday, including that the FDA has agreed to review datopotamab deruxtecan (dato-DXd) for second-line, locally advanced or metastatic non-squamous lung cancer patients.While the focus on the non-squamous population is not a major surprise given results from the supporting Phase III trial, the FDA's decision to go ahead and accept the application without overall survival (OS) data in hand might come as a bit of welcome news for investors. Susan Galbraith, who heads oncology R&D at AstraZeneca, said the TROP2-directed antibody-drug conjugate (ADC) could offer patients "an effective and tolerable alternative to conventional chemotherapy."Recall that AstraZeneca and its partner Daiichi Sankyo reported results from the TROPION-Lung01 study showing a modest progression-free survival (PFS) benefit of less than one month and no OS benefit with dato-DXd in the overall population, compared to docetaxel. However, certain groups in the trial performed better; non-squamous patients who make up about 75% of NSCLC patients had a PFS extension of 1.9 months, or a 37% reduction in the risk of disease progression or death, while those with some actionable genomic alterations, particularly EGFR, saw a benefit of 4.2 months.Non-squamous patients on dato-DXd also showed a "numerically favourable OS trend," the companies said. By contrast, there was no PFS benefit with dato-DXd among patients with squamous NSCLC, who also appeared to fare worse than the docetaxel arm. TROPION-Lung01 is ongoing and OS will be assessed at final analysis. In a recent note, Macquarie analysts said they "continue to believe the TROPION-Lung01 overall survival data will be positive."There were also several cases of interstitial lung disease (ILD) deaths in the trial, including four among non-squamous patients.PDUFA data in Q4AstraZeneca and Daiichi Sankyo anticipate a decision in the fourth quarter, and if approved, dato-DXd could become the first TROP2-directed ADC used in lung cancer treatment. When the TROPION-Lung01 data were detailed late last year, BMO Capital markets analysts highlighted one key opinion leader (KOL) as saying that an approval in patients with non-squamous histology would be sufficient for using dato-DXd over chemotherapy if the PFS benefit seen in TROPION-Lung01 remains consistent.The drug is a follow up to the companies' ADC Enhertu (fam-trastuzumab deruxtecan-nxki), which is approved for several caner types including HER2-mutant metastatic non-small-cell lung cancer (NSCLC) in 2022. Galbraith noted that regulatory discussions are ongoing around the world, while a parallel submission for dato-DXd is underway in the US in breast cancer based on the Phase III TROPION-Breast01 trial.AstraZeneca and Daiichi Sankyo are looking to expand Enhertu's label for use as a pan-tumour ADC. The FDA recently granted a priority review for that filing based on data from the ongoing Phase II DESTINY-PanTumor02 study.