PART I—FINANCIAL INFORMATION [Item 1. Financial Statements (Unaudited)](index=10&type=section&id=Item%201.%20Financial%20Statements%20(Unaudited)) Nuvalent, Inc.'s unaudited Q1 2025 consolidated financial statements report an $84.6 million net loss and $1.1 billion in cash and marketable securities [Condensed Consolidated Balance Sheets](index=10&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Total assets decreased to $1.11 billion as of March 31, 2025, while total liabilities increased to $94.7 million, driven by changes in cash and accounts payable Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $120,835 | $145,691 | | Marketable securities | $952,390 | $972,611 | | **Total Assets** | **$1,105,806** | **$1,141,752** | | Total current liabilities | $75,034 | $54,020 | | **Total Liabilities** | **$94,749** | **$71,960** | | **Total Stockholders' Equity** | **$1,011,057** | **$1,069,792** | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Net loss increased to $84.6 million in Q1 2025 from $44.5 million in Q1 2024, driven by a significant rise in operating expenses, particularly Research and Development Statement of Operations Highlights (in thousands, except per share data) | Metric | Three Months Ended Mar 31, 2025 | Three Months Ended Mar 31, 2024 | | :--- | :--- | :--- | | Research and development | $74,418 | $38,634 | | General and administrative | $20,394 | $13,954 | | **Total operating expenses** | **$94,812** | **$52,588** | | Loss from operations | ($94,812) | ($52,588) | | **Net loss** | **($84,582)** | **($44,482)** | | Net loss per share | ($1.18) | ($0.69) | [Condensed Consolidated Statements of Cash Flows](index=13&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities increased to $54.8 million in Q1 2025, while investing activities provided $25.4 million, a shift from prior year's cash usage Cash Flow Highlights (in thousands) | Activity | Three Months Ended Mar 31, 2025 | Three Months Ended Mar 31, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | ($54,821) | ($36,087) | | Net cash provided by (used in) investing activities | $25,417 | ($206,771) | | Net cash provided by financing activities | $4,548 | $5,986 | | **Net decrease in cash and cash equivalents** | **($24,856)** | **($236,872)** | [Notes to Condensed Consolidated Financial Statements](index=14&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) Notes detail accounting policies, confirm the company's clinical-stage status with recurring losses, and outline stock-based compensation and segment reporting - The company is a clinical-stage biopharmaceutical company that has incurred recurring losses since inception, with a net loss of **$84.6 million** for Q1 2025. Management believes existing cash, cash equivalents, and marketable securities are sufficient to fund operations for at least 12 months[29](index=29&type=chunk)[31](index=31&type=chunk) - The company operates as a single reportable segment focused on the discovery, development, and commercialization of cancer therapies. The Chief Executive Officer, as the CODM, assesses performance based on consolidated net loss[57](index=57&type=chunk) Direct External Expenses by Program (in thousands) | Program | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Zidesamtinib | ($15,551) | ($10,366) | | Neladalkib | ($28,007) | ($9,731) | | NVL-330 | ($3,961) | ($1,972) | | Discovery programs | ($2,133) | ($2,100) | - Stock-based compensation expense was **$20.4 million** in Q1 2025, up from **$13.9 million** in Q1 2024. As of March 31, 2025, total unrecognized compensation cost was **$190.3 million**, expected to be recognized over a weighted average period of 2.6 years[44](index=44&type=chunk)[46](index=46&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=25&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses clinical program progress for lead candidates, reporting an **$84.6 million** net loss for Q1 2025 due to increased R&D, with **$1.1 billion** in cash expected to fund operations into 2028 - Zidesamtinib (NVL-520): The company expects to report pivotal data for TKI pre-treated patients in H1 2025 and anticipates an NDA submission by mid-2025[67](index=67&type=chunk) - Neladalkib (NVL-655): Pivotal data for TKI pre-treated patients is expected by year-end 2025. A global Phase 3 trial (ALKAZAR) for TKI-naïve patients is planned to start in H1 2025[72](index=72&type=chunk)[73](index=73&type=chunk) - NVL-330: The Phase 1a/1b HEROEX-1 clinical trial is currently enrolling pre-treated patients with advanced HER2-altered NSCLC[75](index=75&type=chunk) Comparison of Operating Expenses (in thousands) | Expense Category | Q1 2025 | Q1 2024 | Change | | :--- | :--- | :--- | :--- | | Research and development | $74,418 | $38,634 | $35,784 | | General and administrative | $20,394 | $13,954 | $6,440 | | **Total operating expenses** | **$94,812** | **$52,588** | **$42,224** | - The **$18.3 million** increase in neladalkib program expenses was primarily due to costs for the ongoing Phase 2 trial, preparation for the Phase 3 ALKAZAR trial, and increased manufacturing costs[94](index=94&type=chunk) - As of March 31, 2025, the company had **$1.1 billion** in cash, cash equivalents, and marketable securities, which is expected to fund operations and capital expenditures into 2028[83](index=83&type=chunk)[97](index=97&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=37&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risk is interest rate sensitivity on its **$1.1 billion** cash and marketable securities, with a 10% rate change not expected to materially impact financial results - The company is exposed to interest rate risk on its cash, cash equivalents (**$120.8 million**), and marketable securities (**$952.4 million**)[114](index=114&type=chunk) - Due to the short-term maturities and low-risk profile of its investments, a **10%** change in market interest rates is not expected to materially impact financial condition or results of operations[115](index=115&type=chunk) [Controls and Procedures](index=37&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of March 31, 2025, with no material changes in internal control over financial reporting during the quarter - Management, including the CEO and CFO, concluded that disclosure controls and procedures were effective as of the end of the reporting period[117](index=117&type=chunk) - No changes in internal control over financial reporting occurred during the most recent fiscal quarter that have materially affected, or are reasonably likely to materially affect, internal controls[118](index=118&type=chunk) PART II—OTHER INFORMATION [Legal Proceedings](index=38&type=section&id=Item%201.%20Legal%20Proceedings) As of March 31, 2025, the company was not involved in any material legal proceedings - As of March 31, 2025, the company was not a party to any material legal proceedings[120](index=120&type=chunk) [Risk Factors](index=38&type=section&id=Item%201A.%20Risk%20Factors) This section outlines significant risks including financial position, product development, regulatory hurdles, reliance on third parties, intellectual property, and stock ownership [Risks related to financial position and need for additional capital](index=38&type=section&id=Risks%20related%20to%20our%20financial%20position%20and%20need%20for%20additional%20capital) The company faces risks from its limited operating history, lack of approved products, recurring net losses, and the need for additional capital to fund future operations - The company has a limited operating history, no products approved for sale, and has not generated any revenue, making it difficult for investors to evaluate its prospects[122](index=122&type=chunk) - Significant net losses have been incurred each period since inception, including **$84.6 million** for Q1 2025, and are expected to continue for the foreseeable future[125](index=125&type=chunk) [Risks related to the discovery, development and commercialization of our product candidates](index=42&type=section&id=Risks%20related%20to%20the%20discovery%2C%20development%20and%20commercialization%20of%20our%20product%20candidates) The company's prospects depend on its lead candidates, facing risks of clinical trial failure, non-predictive early data, and substantial competition from larger pharmaceutical companies - The company's future is substantially dependent on the success of its three lead product candidates: zidesamtinib, neladalkib, and NVL-330[135](index=135&type=chunk) - The outcome of preclinical testing and early clinical trials may not predict the success of later trials, and positive results may not satisfy regulatory requirements[149](index=149&type=chunk) - The company faces substantial competition from major multinational pharmaceutical companies with greater financial resources and established market presence, including approved products for ROS1-positive and ALK-positive NSCLC[180](index=180&type=chunk)[183](index=183&type=chunk)[185](index=185&type=chunk) [Risks related to regulatory approval and other legal compliance matters](index=66&type=section&id=Risks%20related%20to%20regulatory%20approval%20and%20other%20legal%20compliance%20matters) The company faces lengthy, complex, and unpredictable regulatory approval processes, including risks with accelerated pathways, and is subject to stringent laws regarding healthcare fraud and data privacy - The company may be unable to obtain U.S. or foreign regulatory approval for its product candidates, which is a costly, time-consuming, and uncertain process[207](index=207&type=chunk) - Even if accelerated approval is granted, the FDA may withdraw it if confirmatory trials fail to verify clinical benefit or if post-marketing requirements are not met[241](index=241&type=chunk)[242](index=242&type=chunk) - The company is subject to stringent and evolving data privacy laws like GDPR in the EU and various state laws in the U.S., which could impose significant fines and penalties for non-compliance[275](index=275&type=chunk)[277](index=277&type=chunk) [Risks related to our dependence on third parties](index=127&type=section&id=Risks%20related%20to%20our%20dependence%20on%20third%20parties) Nuvalent heavily relies on third parties for clinical trials and manufacturing, increasing risks of poor performance, delays, and supply chain disruptions that could impair development and commercialization - The company depends on third parties like CROs to conduct preclinical studies and clinical trials, and their failure to perform satisfactorily could delay or derail development programs[390](index=390&type=chunk) - Reliance on third-party manufacturers for product supply increases the risk of not having sufficient quality or quantities at an acceptable cost, which could impair development and commercialization[395](index=395&type=chunk) [Risks related to employee matters, managing our growth and other risks related to our business](index=101&type=section&id=Risks%20related%20to%20employee%20matters%2C%20managing%20our%20growth%20and%20other%20risks%20related%20to%20our%20business) Success depends on attracting and retaining skilled personnel, managing organizational growth, and mitigating vulnerabilities to IT failures, security breaches, and external events - Success is highly dependent on the ability to attract and retain highly skilled personnel, including key members of management, in a competitive environment[307](index=307&type=chunk)[308](index=308&type=chunk) - The company will need to manage its growth effectively, as it expects to add significant personnel and expand its operational, financial, and management systems[312](index=312&type=chunk) - Internal computer systems and those of third-party partners are vulnerable to security breaches and cyber-attacks, which could result in significant liabilities and disruption of operations[317](index=317&type=chunk)[318](index=318&type=chunk) [Risks related to our intellectual property](index=111&type=section&id=Risks%20related%20to%20our%20intellectual%20property) Success hinges on obtaining and enforcing patent protection, which is uncertain and vulnerable to challenges, alongside risks of infringing third-party intellectual property leading to costly litigation - The company's ability to successfully commercialize its products depends on obtaining and maintaining patent protection, which is an expensive, complex, and uncertain process[340](index=340&type=chunk)[341](index=341&type=chunk) - The company may become involved in lawsuits to protect its patents or be subject to claims that it is infringing on the intellectual property rights of third parties, which could be expensive and have an adverse effect on the business[355](index=355&type=chunk)[360](index=360&type=chunk) - The company relies on trade secrets and confidentiality agreements to protect proprietary information, but these measures may be breached, and legal remedies may be inadequate[385](index=385&type=chunk) [Risks related to ownership of our common stock](index=137&type=section&id=Risks%20related%20to%20ownership%20of%20our%20common%20stock) Ownership of Class A common stock involves high price volatility, significant control by principal stockholders, and potential impacts from anti-takeover provisions and dual-class stock structure - The market price of the Class A common stock is likely to be highly volatile and subject to wide fluctuations[412](index=412&type=chunk) - Principal stockholders own over **50%** of the capital stock and can exert significant control over matters subject to stockholder approval, including the election of directors[423](index=423&type=chunk) - Anti-takeover provisions in the company's charter and bylaws, along with Delaware law, could discourage or prevent a change in control, potentially depressing the stock price[438](index=438&type=chunk) [Other Information](index=146&type=section&id=Item%205.%20Other%20Information) No directors or officers adopted or terminated Rule 10b5-1 or non-Rule 10b5-1 trading arrangements during Q1 2025 - No directors or officers adopted or terminated a Rule 10b5-1 trading arrangement or a non-Rule 10b5-1 trading arrangement during the quarterly period ended March 31, 2025[444](index=444&type=chunk) [Exhibits](index=147&type=section&id=Item%206.%20Exhibits) This section lists exhibits filed with the Form 10-Q, including CEO and CFO certifications required by the Sarbanes-Oxley Act and XBRL data files - The report includes a list of filed exhibits, such as the company's certificate of incorporation, bylaws, and certifications from the Principal Executive Officer and Principal Financial Officer as required by the Sarbanes-Oxley Act[445](index=445&type=chunk)

Clinical Trials and Data - Topline pivotal data for zidesamtinib in TKI pre-treated ROS1-positive NSCLC population expected in the first half of 2025, supporting NDA submission by mid-year 2025[2] - Initiation of ALKAZAR Phase 3 trial for neladalkib planned for the first half of 2025, with pivotal data anticipated by year-end 2025[2][4] - Enrollment ongoing in HEROEX-1 Phase 1a/1b trial for NVL-330, a novel HER2-selective inhibitor[8] - New preclinical data for neladalkib presented at AACR Annual Meeting, demonstrating suppression of resistance in mutagenesis screens[10] Financial Performance - Cash, cash equivalents, and marketable securities totaled $1.1 billion as of March 31, 2025, expected to fund operations into 2028[17] - R&D expenses for Q1 2025 were $74.4 million, while G&A expenses were $20.4 million[17] - Net loss for Q1 2025 was $84.6 million, with a net loss per share of $1.18[17][22] - Total operating expenses for Q1 2025 were $94.8 million, compared to $52.6 million in Q1 2024[22] - Total assets as of March 31, 2025, were $1.1 billion, with total liabilities of $94.7 million[24] Leadership Changes - Leadership team strengthened with promotions of Ruth Adams, Joshua Horan, and Jessie Lin to Senior Vice President roles[4][11]

Core Insights - Nuvalent, Inc. is focused on advancing its pipeline of targeted therapies for cancer, with pivotal data for zidesamtinib and neladalkib expected in 2025 to support New Drug Application submissions [1][2][5] Pipeline and Business Highlights - The company anticipates pivotal data for zidesamtinib in TKI pre-treated ROS1-positive NSCLC in the first half of 2025, with an NDA submission expected by mid-2025 [1][5] - The ALKAZAR Phase 3 trial for neladalkib is set to begin in the first half of 2025, targeting front-line ALK-positive NSCLC [1][6] - Pivotal data for neladalkib in TKI pre-treated ALK-positive NSCLC is expected by the end of 2025 [1][5] Leadership Promotions - Nuvalent has strengthened its leadership team with key promotions: Ruth Adams to Senior Vice President of Clinical Operations, Dr. Joshua Horan to Senior Vice President of Chemistry, and Jessie Lin to Senior Vice President of Corporate Strategy and Portfolio Management [2][12] Financial Results - As of March 31, 2025, the company reported cash, cash equivalents, and marketable securities totaling $1.1 billion, sufficient to fund operations into 2028 [13][19] - Research and development expenses for Q1 2025 were $74.4 million, while general and administrative expenses were $20.4 million, resulting in a net loss of $84.6 million for the quarter [13][18]

Core Insights - Nuvalent, Inc. announced the publication of a manuscript in Molecular Cancer Therapeutics, detailing the design and efficacy of zidesamtinib, a selective ROS1 inhibitor for treating advanced ROS1-positive non-small cell lung cancer (NSCLC) and other solid tumors [1][2][4] Company Overview - Nuvalent, Inc. is a clinical-stage biopharmaceutical company focused on developing targeted therapies for cancer, specifically addressing limitations of existing treatments for kinase targets [6] - The company is advancing a pipeline that includes investigational candidates for ROS1-positive, ALK-positive, and HER2-altered NSCLC, along with multiple discovery-stage research programs [6] Product Development - Zidesamtinib is designed to target tumors resistant to current ROS1 inhibitors, including those with the G2032R mutation, and aims to penetrate the central nervous system (CNS) while avoiding TRK-related adverse events [5] - The ongoing ARROS-1 Phase 1/2 trial is evaluating zidesamtinib in TKI pre-treated and TKI-naïve patients, with pivotal clinical data expected in the first half of 2025 [4][5] Research Findings - The manuscript presents the first crystal structure of ROS1 G2032R in complex with zidesamtinib, providing insights into how this mutation affects TKI binding and supporting the drug's design [3] - Preclinical studies indicate that zidesamtinib effectively suppresses on-target resistance and inhibits ROS1 G2032R brain tumors more effectively than other ROS1 TKIs, suggesting its potential to delay tumor progression [2][3]

Core Insights - Nuvalent, Inc. is presenting two "Trial in Progress" posters for its novel ALK-selective inhibitor neladalkib and HER2-selective inhibitor NVL-330 at the 2025 ASCO Annual Meeting [1][2][3] Group 1: Neladalkib - Neladalkib is being evaluated in the ALKAZAR Phase 3 trial, which is a global, randomized, controlled study comparing neladalkib to ALECENSA® for TKI-naïve ALK-positive non-small cell lung cancer (NSCLC) [2][4] - The ALKAZAR trial is set to initiate in the first half of 2025, with a 1:1 randomization for patients to receive either neladalkib monotherapy or ALECENSA® monotherapy [2] - Neladalkib is designed to penetrate the brain and remain effective against tumors that have developed resistance to existing ALK inhibitors, including those with specific mutations [4][6] Group 2: NVL-330 - NVL-330 is currently being assessed in the HEROEX-1 Phase 1a/1b clinical trial, focusing on safety and tolerability for pre-treated patients with HER2-altered NSCLC [3][5] - The trial aims to determine the recommended Phase 2 dose and evaluate the pharmacokinetic profile and preliminary anti-tumor activity of NVL-330 [3] - NVL-330 is designed to treat HER2-mutant tumors while minimizing adverse events related to off-target inhibition of wild-type EGFR and addressing brain metastases [5][6] Group 3: Company Overview - Nuvalent, Inc. is a clinical-stage biopharmaceutical company focused on developing targeted therapies for cancer, aiming to overcome limitations of existing treatments [6] - The company is advancing a robust pipeline that includes investigational candidates for ROS1-positive, ALK-positive, and HER2-altered NSCLC, along with multiple discovery-stage research programs [6]

CAMBRIDGE, Mass., April 1, 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 that James Porter, Ph.D., Chief Executive Officer, and Alexandra Balcom, Chief Financial Officer, will participate in a fireside chat during the Stifel 2025 Virtual Targeted Oncology Forum on Tuesday, April 8, 2025, at 2:30 p.m. ET. A live webcast will be available in the Inve ...

CAMBRIDGE, Mass., March 25, 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 upcoming poster presentations further characterizing the preclinical profiles of its novel ALK-selective inhibitor, neladalkib, and novel ROS1-selective inhibitor, zidesamtinib, at the American Association for Cancer Research (AACR) Annual Meeting 2025 from April 25-30, 2025, ...

CAMBRIDGE, Mass., Feb. 28, 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 that James Porter, Ph.D., Chief Executive Officer, and Alexandra Balcom, Chief Financial Officer, will participate in fireside chats during the following March investor conferences: TD Cowen 45th Annual Health Care Conference on Wednesday, March 5, 2025 at 9:50 a.m. ET in Bos ...

Table of Contents Commission file number: 001-40671 _____________________________________________________ NUVALENT, INC. UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 _____________________________________________________ FORM 10-K _____________________________________________________ (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF T ...

Exhibit 99.1 Nuvalent Outlines Pipeline and Business Progress, Reiterates Key Anticipated Milestones, and Reports Fourth Quarter and Full Year 2024 Financial Results Topline pivotal data expected in 2025 for both TKI pre-treated ROS1-positive and TKI pre-treated ALK-positive NSCLC populations First NDA submission planned for mid-year 2025 towards potential first approval in 2026 for zidesamtinib in TKI pre-treated ROS1-positive NSCLC population Development strategies in place for TKI-naïve populations, incl ...