Core Insights - Nuvalent, Inc. has promoted Henry Pelish, Ph.D., to Chief Scientific Officer, reflecting his significant contributions to the company and its mission in cancer therapy development [1][7] - Dr. Pelish has been with Nuvalent since 2018, overseeing the development of key investigational drugs and has over 15 years of experience in cancer biology and chemistry [2][7] - The company focuses on creating targeted therapies for cancer, specifically for clinically proven kinase targets, and aims to address limitations of existing treatments [7] Company Overview - Nuvalent, Inc. is a clinical-stage biopharmaceutical company that develops precisely targeted therapies for cancer [1][7] - The company leverages expertise in chemistry and structure-based drug design to create innovative small molecules that can overcome resistance and minimize adverse events [7] - Nuvalent is advancing a robust pipeline, including investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, along with multiple discovery-stage research programs [7]

Core Viewpoint - Nuvalent's NVL-655 has received FDA's Breakthrough Therapy Designation for treating locally advanced or metastatic ALK+ non-small cell lung cancer (NSCLC), indicating its potential to be a significant therapy for patients who have developed resistance to existing treatments [1][6]. Company Background - Nuvalent is a clinical-stage biopharmaceutical company focused on developing targeted kinase therapies for oncology, particularly NSCLC [26]. - The company has a pipeline that includes kinase agents for ROS1-positive, ALK-positive, and HER2-altered NSCLC, along with undisclosed discovery-stage candidates [3]. Pipeline Overview - NVL-655 is designed as a brain-penetrant ALK selective TKI, aiming to overcome tumor resistance to ALK inhibitor therapy and reduce CNS adverse events [4][17]. - The drug has shown a 71% objective response rate in lorlatinib-native populations, indicating its potential effectiveness [7]. - The ALKOVE-1 Phase II trial is currently ongoing, with expectations for updated trial data to be presented at a medical conference later this year [21]. Market Potential - The U.S. NSCLC market is projected to grow from approximately $11.4 billion in 2023 to $76.3 billion by 2030, with the ALK+ NSCLC patient population expected to represent 2%-7% of all NSCLC patients [10]. - NVL-655 could potentially generate annual sales of $1.6 billion to $2.12 billion by capturing 30%-40% of the ALK+ NSCLC market [11]. Financial Outlook - Analysts estimate that NVL-655 could achieve peak sales of around $2.6 billion, contributing to a valuation of Nuvalent between $10.4 billion and $13 billion, translating to a share price of approximately $161 to $201 [12]. - The company had about $691.8 million in cash and equivalents at the end of Q1, which is expected to sustain operations into 2027 [17]. Competitive Landscape - NVL-655 aims to differentiate itself from existing therapies by potentially offering a better safety profile and effectiveness in patients with CNS metastases, a common issue in ALK+ NSCLC [20][24]. - The drug's ability to target both the original and mutated forms of the ALK gene positions it favorably against current treatments [26].

Company Overview - Nuvalent, Inc. is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for cancer, specifically targeting clinically proven kinase targets [3] - The company leverages expertise in chemistry and structure-based drug design to develop innovative small molecules aimed at overcoming resistance and minimizing adverse events [3] - Nuvalent is advancing a robust pipeline with investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, along with multiple discovery-stage research programs [3] Upcoming Events - James Porter, Ph.D., CEO, and Alexandra Balcom, CFO, will participate in a fireside chat at the 2024 Jefferies Global Healthcare Conference on June 5, 2024, at 4:30 p.m. ET in NYC [1] - A live webcast of the event will be available on the company's website and archived for 30 days following the presentation [2]

Core Insights - Nuvalent, Inc. has received FDA breakthrough therapy designation for NVL-655, aimed at treating patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with two or more ALK tyrosine kinase inhibitors (TKIs) [1][4][5] Group 1: Drug Development and Clinical Trials - NVL-655 is a novel brain-penetrant ALK-selective TKI designed to address treatment resistance, brain metastases, and off-target CNS adverse events associated with existing therapies [3][6] - The breakthrough therapy designation is based on preliminary safety and activity data from the Phase 1 portion of the Phase 1/2 ALKOVE-1 clinical trial, which is currently ongoing [5][6] - The company plans to provide updates from the ALKOVE-1 trial at a medical meeting in the second half of 2024 [4][5] Group 2: Market Context and Patient Needs - ALK rearrangements occur in approximately 5% of metastatic NSCLCs, with up to 40% of these patients presenting with brain metastases at diagnosis [2] - About 50% of patients develop resistance mutations after treatment with existing first- or second-generation ALK TKIs, highlighting the need for new treatment options [2][4] - There is currently no clear standard of care for patients who have been treated with two or more ALK TKIs, indicating a significant unmet medical need [2][4] Group 3: Company Overview - Nuvalent, Inc. focuses on creating targeted therapies for cancer, leveraging expertise in chemistry and structure-based drug design to develop innovative small molecules [7] - 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 [7]

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from _____________ to _____________ Commission File Number: 001-40671 NUVALENT, INC. (Exact Name of Registrant as Specified in its Charter) Delawar ...

Exhibit 99.1 Nuvalent Highlights Pipeline Progress, Reiterates Key Anticipated Milestones, and Reports First Quarter 2024 Financial Results Updates from the ongoing Phase 1/2 ARROS-1 and ALKOVE-1 clinical trials expected at a medical meeting in the second half of 2024 Strong financial position with operating runway anticipated into 2027 Recent Pipeline Progress and Anticipated Milestones ROS1 Program ALK Program HER2 Program • Nuvalent presented new preclinical data at the American Association for Cancer Re ...

Investors are always looking for stocks that are poised to beat at earnings season and Nuvalent, Inc. (NUVL) may be one such company. The firm has earnings coming up pretty soon, and events are shaping up quite nicely for their report.That is because Nuvalent is seeing favorable earnings estimate revision activity as of late, which is generally a precursor to an earnings beat. After all, analysts raising estimates right before earnings — with the most up-to-date information possible — is a pretty good indic ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION FORM 10-K Washington, D.C. 20549 (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, 2023 OR Commission file number: 001-40671 NUVALENT, INC. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) One Broadway, 14 Floor th Cambridge, MA 02142 (Address of principal executive offices) (Zip Code) (857) 357-7000 ☐ TRA ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q For the quarterly period ended September 30, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from _____________ to _____________ Commission File Number: 001-40671 NUVALENT, INC. (Exact Name of Registrant as Specified in its Charter) Delaware 81-5112298 (State or other jurisdiction of incorporation or organization) One Broadway, 14 Floo ...

Financial Performance - Total current assets decreased to $436,992,000 as of June 30, 2023, down from $477,991,000 as of December 31, 2022, representing a decline of approximately 8.5%[22] - Net loss for the six months ended June 30, 2023, was $54,282,000, compared to a net loss of $36,015,000 for the same period in 2022, reflecting a 50.8% increase in losses[23] - Cash and cash equivalents decreased significantly to $70,872,000 as of June 30, 2023, from $241,806,000 as of December 31, 2022, indicating a reduction of approximately 70.7%[22] - Total stockholders' equity decreased to $421,153,000 as of June 30, 2023, down from $462,978,000 as of December 31, 2022, a decline of about 9%[22] - Comprehensive loss for Q2 2023 was $30,325,000, compared to $18,579,000 in Q2 2022, indicating a year-over-year increase of 63.5%[23] - Net cash used in operating activities for the six months ended June 30, 2023, was $46.5 million, up from $29.0 million in the same period of 2022, indicating a 60% increase in cash outflow[112][113] - The company reported a net cash decrease of $170.9 million in cash and cash equivalents during the first half of 2023, compared to an increase of $7.4 million in the same period of 2022[28] - The accumulated deficit as of June 30, 2023, was $214.4 million, reflecting ongoing significant net losses since inception[136] Research and Development - Research and development expenses for Q2 2023 were $25,922,000, an increase of 91% compared to $13,558,000 in Q2 2022[23] - The company incurred stock-based compensation expenses of $11.2 million for the six months ended June 30, 2023, up from $4.7 million in the prior year, reflecting a 140% increase[28] - Direct research and development expenses for NVL-655 increased by $3.2 million in Q2 2023, primarily due to higher clinical and manufacturing costs[100] - The company is advancing its lead product candidates, NVL-520 and NVL-655, in clinical development, with ongoing Phase 1 trials for both[84] - NVL-520 is being evaluated in the ARROS-1 clinical trial for ROS1-positive non-small cell lung cancer (NSCLC), with preliminary data showing it was well-tolerated and demonstrated objective responses in heavily pre-treated patients[74] - NVL-655 is being evaluated in the ALKOVE-1 clinical trial for ALK-positive NSCLC, with preliminary dose-escalation data expected to be reported in Q4 2023[77] - The company has initiated IND-enabling studies for its newest product candidate, NVL-330, a HER2-selective inhibitor designed to treat tumors driven by HER2 mutations[79] Capital and Funding - The company raised $247.9 million in a follow-on public offering on November 3, 2022, selling 7,895,522 shares at a price of $33.50 per share[33] - The company expects its existing cash, cash equivalents, and marketable securities to be sufficient to fund operating expenses for at least 12 months from the date of the financial statements[35] - The existing cash, cash equivalents, and marketable securities are projected to fund operations into the second half of 2025, but additional capital will be needed for product candidates' development and commercialization[89] - The company anticipates needing to raise additional capital to complete the development and commercialization of its product candidates, as existing resources will not suffice for regulatory approval[118][119] Clinical Trials and Regulatory Risks - The company has not yet commercialized any product candidates and does not expect to generate revenue in the foreseeable future[109] - The company must demonstrate safety and efficacy through extensive clinical studies before obtaining marketing approval for its product candidates[153] - The regulatory approval process for product candidates is lengthy and unpredictable, with potential changes in approval policies that could delay marketing[167] - The company faces risks related to the discovery and development of targeted therapeutics for cancer-associated genomic alterations, which may not lead to marketable products[151] - The company may incur unplanned costs and delays in seeking marketing approval if additional clinical trials are required[150] - The company is subject to numerous foreign regulatory requirements, which can complicate the approval process and introduce additional risks[214] Competition and Market Challenges - The company faces significant competition in the oncology field, including from major pharmaceutical companies and emerging biotech firms, which may impact its ability to recruit patients for clinical trials[186] - Patient enrollment for clinical trials may be hindered by competition from other ongoing trials and the specific eligibility criteria that limit the patient population[180] - The addressable patient population for the company's product candidates may be smaller than estimated, affecting potential profitability[202] - Coverage and reimbursement from third-party payors are essential for the commercialization of products, and unfavorable practices could hinder sales[203] - The company faces significant risks related to product liability, which could adversely affect its business and financial condition if sufficient insurance coverage is not obtained[210]