Core Insights - Lyell Immunopharma, Inc. is a clinical-stage company focused on developing next-generation CAR T-cell therapies for cancer patients [1][3] - The company will present at the Goldman Sachs 46th Annual Global Healthcare Conference on June 11, 2025, at 10:00 am ET [1] - A live webcast of the presentation will be available on the company's website, with a replay accessible afterward [2] Company Overview - Lyell Immunopharma is advancing a pipeline of CAR T-cell therapies targeting hematologic malignancies and solid tumors [3] - The company employs various technologies to enhance CAR T cells, aiming for durable tumor cytotoxicity and consistent clinical responses [3] - Key attributes of Lyell's CAR T cells include resistance to exhaustion, maintenance of stemness, and functionality in challenging tumor microenvironments [3]

PART I—FINANCIAL INFORMATION [Item 1. Financial Statements (unaudited)](index=7&type=section&id=Item%201.%20Financial%20Statements%20(unaudited)) This section presents the unaudited condensed consolidated financial statements for the quarter ended March 31, 2025, including balance sheets, statements of operations, and cash flows [Condensed Consolidated Balance Sheets](index=7&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of March 31, 2025, total assets decreased to $429.8 million from $490.9 million, primarily due to a reduction in marketable securities | | March 31, 2025 (in thousands) | December 31, 2024 (in thousands) | | :--- | :--- | :--- | | **Total Current Assets** | $309,178 | $379,594 | | **Total Assets** | $429,798 | $490,859 | | **Total Current Liabilities** | $41,285 | $53,788 | | **Total Liabilities** | $93,277 | $108,035 | | **Total Stockholders' Equity** | $336,521 | $382,824 | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) For Q1 2025, the company reported a net loss of **$52.2 million**, an improvement from **$60.7 million** in Q1 2024, mainly due to a non-recurring impairment in the prior year | | Three Months Ended March 31, 2025 (in thousands) | Three Months Ended March 31, 2024 (in thousands) | | :--- | :--- | :--- | | **Revenue** | $7 | $3 | | **Research and development** | $43,447 | $43,174 | | **General and administrative** | $14,046 | $13,494 | | **Loss from operations** | ($57,367) | ($55,575) | | **Net loss** | ($52,195) | ($60,667) | | **Net loss per common share, basic and diluted** | ($0.18) | ($0.24) | [Condensed Consolidated Statements of Stockholders' Equity](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders'%20Equity) Total stockholders' equity decreased from **$382.8 million** to **$336.5 million** as of March 31, 2025, primarily driven by the net loss for the quarter - The primary driver for the decrease in stockholders' equity during the first quarter of 2025 was the net loss of **$52.2 million**[26](index=26&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities increased to **$54.7 million** in Q1 2025, while net cash provided by investing activities was **$69.5 million**, leading to a **$14.7 million** increase in total cash | Cash Flow Activity (in thousands) | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | **Net cash used in operating activities** | $(54,738) | $(42,016) | | **Net cash provided by investing activities** | $69,466 | $21,994 | | **Net cash provided by financing activities** | $1 | $27 | | **Net increase (decrease) in cash, cash equivalents and restricted cash** | $14,729 | $(19,995) | [Notes to Unaudited Condensed Consolidated Financial Statements](index=13&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) The notes detail accounting policies, the ImmPACT Bio acquisition, collaboration agreements, and an ATM equity offering, confirming sufficient liquidity for the next 12 months - The company believes its available cash, cash equivalents, and marketable securities as of March 31, 2025, will be adequate to fund operations for at least the next 12 months[35](index=35&type=chunk) - Following the acquisition of ImmPACT Bio, a contingent consideration payable of **$6.4 million** was recorded related to potential future equity issuance upon achieving clinical or regulatory milestones[43](index=43&type=chunk) - The company has success payment agreements with Fred Hutch and Stanford, with potential aggregate payments of up to **$200.0 million** each, contingent on the company's stock price reaching certain thresholds[48](index=48&type=chunk)[49](index=49&type=chunk)[53](index=53&type=chunk) - In February 2024, the company entered into an at-the-market (ATM) sales agreement to offer and sell up to **$150.0 million** of its common stock, with no sales made to date[75](index=75&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=30&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides an overview of the company's clinical-stage cell therapy business, financial performance, and liquidity, highlighting the lead program LYL314 and manufacturing strategy [Overview](index=30&type=section&id=Overview) Lyell is a clinical-stage cell therapy company focused on its lead CAR T-cell product candidate, LYL314, for B-cell lymphomas, with a pivotal trial planned for mid-2025 - The company's lead program is LYL314, a dual-targeting CD19/CD20 CAR T-cell product candidate for B-cell lymphomas, acquired from ImmPACT Bio[99](index=99&type=chunk)[107](index=107&type=chunk) - A pivotal trial for LYL314 in 3rd-line+ large B-cell lymphoma is expected to start in mid-2025, with a second pivotal trial in the 2nd-line setting planned by early 2026[102](index=102&type=chunk)[139](index=139&type=chunk) | Best Overall Response (N=17) | Result | | :--- | :--- | | Overall Responses, n (%) | 16 (94%) | | Complete Responses, n (%) | 12 (71%) | | Partial Responses, n (%) | 4 (24%) | | Stable Disease, n (%) | 1 (6%) | - Manufacturing for LYL314 has been transferred to the company's LyFE Manufacturing Center in Bothell, Washington, and the acquired West Hills facility was closed, resulting in a workforce reduction of approximately **73 employees**[139](index=139&type=chunk)[144](index=144&type=chunk) [Results of Operations](index=42&type=section&id=Results%20of%20Operations) Q1 2025 R&D expenses slightly increased to **$43.4 million**, while G&A expenses rose to **$14.0 million**, and net loss decreased to **$52.2 million** due to a non-recurring impairment in Q1 2024 | Expense (in thousands) | Q1 2025 | Q1 2024 | Change | | :--- | :--- | :--- | :--- | | **Research and development** | $43,447 | $43,174 | $273 | | **General and administrative** | $14,046 | $13,494 | $552 | - The slight increase in R&D expenses was primarily due to a **$3.1 million** increase in personnel-related expenses, mainly from severance costs related to the closure of the West Hills manufacturing facility[161](index=161&type=chunk) - The decrease in net loss was largely due to a non-recurring **$13.0 million** impairment of other investments in Q1 2024[160](index=160&type=chunk)[168](index=168&type=chunk) [Liquidity and Capital Resources](index=44&type=section&id=Liquidity%20and%20Capital%20Resources) As of March 31, 2025, the company held **$330.1 million** in cash and marketable securities, deemed sufficient for at least the next 12 months, with an ATM program for future funding - As of March 31, 2025, the company had **$330.1 million** in cash, cash equivalents, and marketable securities[169](index=169&type=chunk) - Management believes existing cash, cash equivalents, and marketable securities will be sufficient to meet working capital and capital expenditure needs for at least the next 12 months[171](index=171&type=chunk) - An at-the-market (ATM) sales agreement is in place for up to **$150.0 million**, with no sales made to date[170](index=170&type=chunk) | Cash Flow Activity (in thousands) | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | **Operating activities** | $(54,738) | $(42,016) | | **Investing activities** | $69,466 | $21,994 | | **Financing activities** | $1 | $27 | [Quantitative and Qualitative Disclosures About Market Risk](index=47&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company's primary market risk is interest rate sensitivity on short-term cash and marketable securities, which is not considered significant, and foreign currency risk is minimal - The primary market risk is interest rate sensitivity on cash and marketable securities, which is not considered significant due to their short-term nature[183](index=183&type=chunk) - Foreign currency exchange risk is not significant as operations are U.S.-based and expenses are in USD[184](index=184&type=chunk) [Controls and Procedures](index=47&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 to internal control over financial reporting during the quarter - Management concluded that disclosure controls and procedures were effective as of March 31, 2025[186](index=186&type=chunk) - No material changes to internal control over financial reporting occurred during the quarter ended March 31, 2025[187](index=187&type=chunk) PART II—OTHER INFORMATION [Legal Proceedings](index=48&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently involved in any material legal proceedings and is unaware of any contemplated actions - The company is not currently party to any material legal proceedings[189](index=189&type=chunk) [Risk Factors](index=48&type=section&id=Item%201A.%20Risk%20Factors) This section outlines significant risks including financial condition, limited operating history, reliance on unproven product candidates, manufacturing complexities, competition, regulatory hurdles, and intellectual property protection - The company is a clinical-stage entity with a history of substantial losses and anticipates incurring substantial and increasing net losses for the foreseeable future[193](index=193&type=chunk) - The company will require substantial additional capital to achieve its goals, and failure to obtain it could force delays or termination of product development[200](index=200&type=chunk) - The company's product candidates are based on novel, unproven technologies, making development time, cost, and regulatory approval difficult to predict[214](index=214&type=chunk) - The company faces risks in manufacturing complex cell therapies, including challenges with the recent transfer of LYL314 manufacturing to its LyFE facility and the closure of its Los Angeles facility[243](index=243&type=chunk)[247](index=247&type=chunk) - The company received a Nasdaq notification for non-compliance with the **$1.00** minimum bid price requirement and may be delisted if compliance is not regained, with a reverse stock split being considered[403](index=403&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=93&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reports no unregistered sales of equity securities during the period - None[428](index=428&type=chunk) [Defaults Upon Senior Securities](index=93&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) Not applicable - Not applicable[429](index=429&type=chunk) [Mine Safety Disclosures](index=93&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) Not applicable - Not applicable[430](index=430&type=chunk) [Other Information](index=93&type=section&id=Item%205.%20Other%20Information) During the first quarter of 2025, no directors or executive officers adopted or terminated a Rule 10b5-1 trading arrangement - No directors or executive officers adopted or terminated a Rule 10b5-1 trading plan in Q1 2025[431](index=431&type=chunk) [Exhibits](index=94&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including certifications by the Principal Executive Officer and Principal Financial Officer - Lists exhibits filed with the report, including officer certifications under Rules 13a-14(a) and 15d-14(a), and Section 1350[434](index=434&type=chunk)

[Business Highlights](index=1&type=section&id=Business%20Highlights) Lyell Immunopharma reported significant progress in its clinical development for the first quarter of 2025, primarily centered on its lead CAR T-cell therapy candidate, LYL314 - The FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to **LYL314** for treating relapsed/refractory diffuse large B-cell lymphoma (LBCL) in the third- or later-line setting[2](index=2&type=chunk)[5](index=5&type=chunk)[6](index=6&type=chunk) - Manufacturing of **LYL314** clinical supply has been successfully transferred to Lyell's **LyFE Manufacturing Center** following FDA clearance of an IND amendment[3](index=3&type=chunk)[6](index=6&type=chunk)[9](index=9&type=chunk) - Lyell plans to initiate a pivotal trial for **LYL314** in third- or later-line LBCL by **mid-2025** and a second pivotal trial in the second-line setting by **early 2026**[3](index=3&type=chunk)[6](index=6&type=chunk) - New clinical data for **LYL314**, including more mature third-line and initial second-line data, will be presented at the International Conference on Malignant Lymphoma in **June 2025**[3](index=3&type=chunk)[6](index=6&type=chunk)[9](index=9&type=chunk) [LYL314 Program Updates](index=1&type=section&id=LYL314%20Program%20Updates) LYL314 is a next-generation CAR T-cell product candidate designed to improve response rates and durability for LBCL - **LYL314** is a next-generation, autologous, dual-targeting (CD19/CD20) CAR T-cell product candidate designed to improve response rates and durability compared to existing CD19-targeted therapies for LBCL[2](index=2&type=chunk)[5](index=5&type=chunk) - Initial data from a Phase 1/2 trial presented in December 2024 showed a **94% overall response rate (ORR)** and a **71% complete response (CR) rate** in 17 efficacy-evaluable patients[9](index=9&type=chunk) - In a safety population of 23 patients, **LYL314** was well-tolerated, with **no Grade 3 or greater cytokine release syndrome (CRS)** reported. Grade 3 ICANS occurred in **13% of patients** and resolved quickly[9](index=9&type=chunk) [Preclinical Pipeline and Manufacturing](index=2&type=section&id=Preclinical%20Pipeline%20and%20Manufacturing) The company's preclinical pipeline focuses on fully-armed CAR T-cell candidates and robust manufacturing capabilities - The preclinical pipeline focuses on fully-armed CAR T-cell candidates designed to overcome T-cell exhaustion and the hostile tumor microenvironment in solid tumors[7](index=7&type=chunk) - The first Investigational New Drug (IND) application for a fully-armed CAR T-cell product candidate targeting solid tumors is expected in **2026**[9](index=9&type=chunk) - The **LyFE Manufacturing Center** has the capacity to produce over **1,000 CAR T-cell therapy doses per year**, sufficient for pivotal trials and potential commercial launch[9](index=9&type=chunk) [Financial Results](index=2&type=section&id=Financial%20Results) For Q1 2025, Lyell reported a GAAP net loss of **$52.2 million**, a decrease from Q1 2024, with **$330.1 million** cash expected to fund operations into 2027 [Financial Performance Summary](index=2&type=section&id=Financial%20Performance%20Summary) Key financial metrics for Q1 2025 show a reduced net loss and stable operating expenses Q1 2025 Key Financial Metrics (GAAP) | Metric | Q1 2025 (in millions) | Q1 2024 (in millions) | Change | | :--- | :--- | :--- | :--- | | Net Loss | $52.2 | $60.7 | Decreased $8.5 | | R&D Expenses | $43.4 | $43.2 | Increased $0.2 | | G&A Expenses | $14.0 | $13.5 | Increased $0.5 | - The decrease in net loss was primarily driven by a **$13.0 million impairment expense** recognized in Q1 2024 that did not recur in Q1 2025[8](index=8&type=chunk) - Cash, cash equivalents, and marketable securities totaled **$330.1 million** as of March 31, 2025, which is expected to fund operations into **2027**[6](index=6&type=chunk)[12](index=12&type=chunk) Net Loss Comparison (in millions) | Metric | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | GAAP Net Loss | $(52.2) | $(60.7) | | Non-GAAP Net Loss | $(46.3) | $(37.5) | Operating Expenses Comparison (in millions) | Expense Category | Q1 2025 (GAAP) | Q1 2024 (GAAP) | Q1 2025 (Non-GAAP) | Q1 2024 (Non-GAAP) | | :--- | :--- | :--- | :--- | :--- | | R&D Expenses | $43.4 | $43.2 | $41.1 | $38.9 | | G&A Expenses | $14.0 | $13.5 | $10.4 | $8.1 | - The increase in R&D expenses was mainly due to a **$3.1 million rise in personnel costs**, including severance from a facility closure[15](index=15&type=chunk) - The increase in G&A expenses was driven by a **$2.4 million rise in personnel costs** from higher headcount and severance expenses[15](index=15&type=chunk) - Cash, cash equivalents, and marketable securities decreased from **$383.5 million** at year-end 2024 to **$330.1 million** at the end of Q1 2025[12](index=12&type=chunk)[18](index=18&type=chunk) [Selected Consolidated Financial Data](index=4&type=section&id=Selected%20Consolidated%20Financial%20Data) Detailed unaudited financial statements provide a comprehensive view of the company's Q1 2025 performance and balance sheet Unaudited Selected Consolidated Statement of Operations Data (in thousands) | | Three Months Ended March 31, | | | :--- | :--- | :--- | | | **2025** | **2024** | | Revenue | $7 | $3 | | Total operating expenses | $57,374 | $55,578 | | Loss from operations | $(57,367) | $(55,575) | | Net loss | $(52,195) | $(60,667) | Unaudited Selected Balance Sheet Data (in thousands) | | As of March 31, 2025 | As of December 31, 2024 | | :--- | :--- | :--- | | Cash, cash equivalents and marketable securities | $330,126 | $383,541 | | Total assets | $429,798 | $490,859 | | Total stockholders' equity | $336,521 | $382,824 | [Non-GAAP Financial Measures and Reconciliations](index=5&type=section&id=Non-GAAP%20Financial%20Measures%20and%20Reconciliations) Non-GAAP financial measures provide a clearer view of core operational performance by excluding specific non-cash items - The company uses non-GAAP measures to enhance comparability by excluding non-cash items like stock-based compensation, changes in fair value of success payment liabilities, and non-cash investment charges[19](index=19&type=chunk) Reconciliation of GAAP to Non-GAAP Net Loss (in thousands) | | Three Months Ended March 31, | | | :--- | :--- | :--- | | | **2025** | **2024** | | Net loss - GAAP | $(52,195) | $(60,667) | | Stock-based compensation expense | $6,024 | $9,155 | | Impairment of other investments | — | $13,001 | | Net loss - Non-GAAP | $(46,296) | $(37,543) | Reconciliation of GAAP to Non-GAAP R&D and G&A Expenses (in thousands) | Expense | GAAP (Q1 2025) | Non-GAAP (Q1 2025) | GAAP (Q1 2024) | Non-GAAP (Q1 2024) | | :--- | :--- | :--- | :--- | :--- | | R&D | $43,447 | $41,059 | $43,174 | $38,857 | | G&A | $14,046 | $10,410 | $13,494 | $8,131 |

Core Insights - Lyell Immunopharma, Inc. reported financial results and business highlights for Q1 2025, focusing on its lead clinical program LYL314, a CAR T-cell therapy for relapsed and/or refractory large B-cell lymphoma (LBCL) [1][2][3] Financial Performance - The company reported a net loss of $52.2 million for Q1 2025, an improvement from a net loss of $60.7 million in Q1 2024, primarily due to the absence of impairment expenses recognized in the prior year [8][18] - Cash, cash equivalents, and marketable securities totaled $330.1 million as of March 31, 2025, down from $383.5 million at the end of 2024, which is expected to support operations into 2027 [12][19] Clinical Development - LYL314 has received RMAT designation from the FDA, indicating its potential to address significant unmet needs in aggressive LBCL [4][5] - The company plans to present new clinical data for LYL314 at the International Conference on Malignant Lymphoma in June 2025, with pivotal trials expected to start in mid-2025 for the third- or later-line setting and early 2026 for the second-line setting [2][5][6] Research and Development - R&D expenses for Q1 2025 were $43.4 million, slightly up from $43.2 million in Q1 2024, driven by increased personnel costs related to workforce reductions [15][18] - The company is advancing a pipeline of next-generation CAR T-cell therapies, with a focus on overcoming T-cell exhaustion and enhancing durability in hostile tumor environments [7][13] Manufacturing Capabilities - The LyFE Manufacturing Center in Bothell, Washington, is now producing clinical supplies for LYL314 following successful technology transfer and FDA clearance [5][9] - The facility has the capacity to manufacture over 1,000 CAR T-cell therapy doses per year, supporting ongoing and planned pivotal trials [9][19]

Core Insights - Lyell Immunopharma, Inc. is advancing a pipeline of next-generation CAR T-cell therapies for cancer patients, with new clinical data for LYL314 to be presented at the ICML 2025 [1][2] - LYL314 is a dual-targeting CD19/CD20 CAR T-cell product candidate specifically for aggressive large B-cell lymphoma, having received FDA designations for advanced therapy and fast track [2] Company Overview - Lyell is a clinical-stage company focused on CAR T-cell therapies for hematologic malignancies and solid tumors, employing technologies to enhance CAR T-cell durability and efficacy in challenging tumor environments [3] Presentation Details - The presentation on LYL314 will occur on June 18, 2025, at 5:40 pm CEST, featuring Dr. Akil Merchant from Cedars-Sinai Medical Center [5]

Core Viewpoint - Lyell Immunopharma, Inc. has received Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA for its next-generation CAR T-cell therapy, LYL314, aimed at treating adult patients with relapsed and/or refractory large B-cell lymphoma after two or more prior lines of therapy [1][2][7] Group 1: RMAT Designation and Clinical Data - The RMAT designation provides benefits similar to Fast Track and Breakthrough Therapy designations, facilitating early interactions with the FDA [2][6] - LYL314 is a dual-targeting CD19/CD20 CAR T-cell product candidate designed to enhance complete response rates and prolong response duration compared to existing CD19-targeted therapies [1][8] - Initial data from the Phase 1/2 trial showed a 94% overall response rate (16 out of 17 patients) and a 71% complete response rate by three months, with a median follow-up of 6.3 months [3][4] Group 2: Future Clinical Developments - Additional clinical updates from the Phase 1/2 trial are expected in 2025, including more mature data from patients in the 3rd or later line setting and initial data from the 2nd line setting [4][7] - Two pivotal programs for LYL314 are planned, one for patients in the 3rd or later line setting expected to start in mid-2025 and another for the 2nd line setting anticipated to begin by early 2026 [4][9] Group 3: Company Overview - Lyell Immunopharma is focused on advancing a pipeline of next-generation CAR T-cell therapies for hematologic malignancies and solid tumors, utilizing technologies to enhance CAR T-cell durability and efficacy [10]

Financial Performance and Capital Needs - The company has incurred substantial losses since inception and anticipates continuing to incur significant net losses for the foreseeable future [175]. - As of December 31, 2024, the company had approximately $383.5 million in cash, cash equivalents, and marketable securities, expected to meet capital needs into 2027 [186]. - The company may require substantial additional capital to achieve its goals, and failure to obtain necessary capital could delay or terminate product development efforts [185]. - The financial markets have experienced volatility, which could adversely affect the company's ability to secure financing and impact its growth strategy [209]. - Adverse developments in the financial services industry, such as bank failures, could impact the company's liquidity and operations [211]. - The company has not experienced adverse impacts from recent bank failures but remains cautious about potential liquidity concerns in the broader financial services industry [212]. Product Development and Clinical Trials - The company is focused on the clinical development of its product candidate IMPT-314, currently in Phase 1/2 clinical development [194]. - The company has not yet demonstrated the ability to successfully complete clinical trials or obtain regulatory approvals necessary for commercialization [194]. - The current clinical data for IMPT-314 in Phase 1/2 trials are limited, and prior results may not predict future outcomes [197]. - Patient enrollment and retention in clinical trials are critical; delays in these areas could adversely affect research and development efforts and financial results [257]. - Competition for patient enrollment in clinical trials is significant, particularly from companies with approved CAR T-cell therapies, which may limit the number of eligible patients [258]. - The company faces challenges in recruiting patients and investigators for clinical trials due to various factors, including the proximity of patients to clinical sites and the perceived risks of the product candidates [266]. - The company is currently in Phase 1/2 clinical development for its product candidate IMPT-314, with no products approved for commercial sale yet [267]. - Delays in patient enrollment for clinical trials may increase costs and slow down product development, potentially jeopardizing revenue generation [263]. - The company has not yet fully enrolled or completed any clinical trials required for the approval of its product candidates, leading to potential delays [283]. Regulatory and Compliance Challenges - The company plans to work closely with the FDA for regulatory approval, but the process may be complex and time-consuming, potentially increasing development costs [198]. - Regulatory approval for product candidates is uncertain and may take many years, with the FDA requiring substantial evidence from well-controlled clinical trials [269]. - The FDA's approval process is lengthy and unpredictable, which may hinder the commercialization of product candidates [296]. - Compliance with extensive regulatory requirements is necessary for manufacturing and distribution, which may incur significant expenses [301]. - The company may face penalties or product recalls if regulatory compliance issues arise [302]. - Changes in healthcare policies and regulations may impact the ability to obtain approval for or commercialize product candidates [314]. - Disruptions at the FDA due to funding shortages and workforce reductions could hinder the timely development and approval of new products, negatively impacting the company's business [320]. Manufacturing and Operational Risks - The company has built its own manufacturing facility in Bothell, Washington, designed to support nonclinical and clinical development product candidates [216]. - The acquisition of ImmPACT includes a manufacturing facility in Los Angeles, California, which is critical for the production of IMPT-314 [216]. - Manufacturing facilities are subject to ongoing inspections by the FDA and other regulatory authorities, and failure to comply could lead to significant delays in product availability [217]. - The complexity of manufacturing cellular therapies requires significant expertise and capital investment, with risks associated with scaling for advanced clinical trials [220]. - The company faces risks related to product loss due to low cell viability, contamination, and equipment failure, which could delay programs [222]. - Manufacturing operations may be adversely affected by natural disasters, equipment failures, and health epidemics, impacting business operations [226]. - The company maintains insurance coverage for property damage and business interruption, but it may not be sufficient to cover all potential losses [229]. - Reliance on third-party manufacturers poses risks, including potential delays in development and commercialization if they fail to meet regulatory standards [230]. - Specialty raw materials required for product candidates may not be available on acceptable terms, leading to potential delays in manufacturing [234]. Intellectual Property and Competitive Landscape - The ability to obtain and maintain sufficient intellectual property protection is crucial for the commercialization of product candidates, as inadequate protection could erode competitive advantages [338]. - The patentability and enforceability of patents in the biotechnology field are uncertain, which may affect the company's ability to secure necessary patents for its product candidates [339]. - The company faces risks regarding the validity and enforceability of its patents, which may be challenged by third parties, potentially jeopardizing commercialization efforts [340]. - The company may seek licenses from third parties for intellectual property rights, but there is no guarantee of obtaining these licenses on commercially reasonable terms [341]. - The lifespan of patents is generally 20 years from the first effective filing date, which may not be sufficient to protect the company's products from competition [346]. - The company may struggle to protect its intellectual property rights globally, as enforcement varies significantly across jurisdictions [347]. - The company may face costly and time-consuming litigation if accused of infringing third-party intellectual property rights, which could delay development and commercialization efforts [351]. Workforce and Operational Challenges - The company has implemented workforce reductions in late 2023 and early 2025, which may lead to operational challenges and loss of expertise [203]. - The company faces intense competition for skilled personnel in its operational regions, which may hinder its ability to attract and retain qualified employees [199]. - The company relies on third parties for clinical trials and research, and failure of these parties to perform satisfactorily could harm regulatory approval and commercialization efforts [237]. - The company relies on third parties, including CROs, for conducting clinical trials, which may lead to delays and increased costs due to budget negotiations and management focus required for switching or adding CROs [238]. Market and Economic Factors - The Inflation Reduction Act of 2022 extends enhanced subsidies for individuals purchasing health insurance coverage in the ACA marketplaces through plan year 2025 [314]. - The Medicare Drug Price Negotiation Program will begin to take effect progressively in fiscal year 2023, with the first ten drugs selected for price negotiations announced on August 15, 2024 [315]. - Cost containment reforms in the healthcare industry may adversely affect the company's operations, particularly in obtaining coverage and adequate reimbursement for product candidates [319]. - The U.S. Supreme Court's June 2024 decision may lead to increased regulatory uncertainty and inconsistent judicial interpretations affecting the FDA's regulations [306].

Financial Performance - Lyell reported a net loss of $191.9 million for Q4 2024, compared to a net loss of $52.9 million in Q4 2023, and a full-year net loss of $343.0 million versus $234.6 million in 2023[9] - Revenue for Q4 2024 was $11,000, a decrease of 15.4% compared to $13,000 in Q4 2023[17] - Non-GAAP net loss for Q4 2024 was $45,867,000, compared to $43,938,000 in Q4 2023, indicating a slight increase of 4.4%[21] - Total operating expenses for Q4 2024 were $201,158,000, significantly higher than $59,521,000 in Q4 2023, primarily due to acquired in-process research and development expenses of $87,184,000[17] - Operating expenses for Q4 2024 included $87.2 million in acquired in-process research and development expenses and a $51.3 million impairment charge for long-lived assets[15] Cash and Assets - The company has cash, cash equivalents, and marketable securities of $383.5 million as of December 31, 2024, down from $562.7 million at the end of 2023, which is expected to support operations into 2027[12] - Cash, cash equivalents, and marketable securities decreased to $383,541,000 as of December 31, 2024, down from $562,729,000 in 2023[18] - Total assets decreased to $490,859,000 as of December 31, 2024, from $750,029,000 in 2023, a decline of 34.5%[18] Research and Development - Research and development (R&D) expenses for Q4 2024 were $48.7 million, an increase from $47.0 million in Q4 2023, while full-year R&D expenses decreased to $171.6 million from $182.9 million[15] - Research and development expenses on a GAAP basis for 2024 were $171,603,000, down from $182,945,000 in 2023, a decrease of 6.2%[23] - The ongoing Phase 1/2 trial of IMPT-314 is designed to evaluate tolerability and clinical benefit, with more mature data expected to be shared in mid-2025[10] - IMPT-314, a next-generation dual-targeting CAR T-cell product candidate, is in Phase 1/2 clinical development for relapsed or refractory aggressive large B-cell lymphoma, with an overall response rate of 94% reported in initial data from 23 patients[10] - A new IND submission for a next-generation solid tumor CAR T-cell product candidate is expected in 2026, utilizing proprietary anti-exhaustion technology[3] - The pivotal trial for IMPT-314 in the 3rd line and later setting is expected to be initiated in mid-2025, with a second pivotal trial in the 2nd line setting anticipated by early 2026[6] General and Administrative Expenses - General and administrative (G&A) expenses for Q4 2024 were $14.5 million, compared to $13.2 million in Q4 2023, with full-year G&A expenses decreasing to $52.0 million from $67.0 million[15] - General and administrative expenses on a GAAP basis for 2024 were $52,041,000, a decrease of 22.5% from $66,983,000 in 2023[26] Impairment and Acquisitions - The company recognized impairment of long-lived assets amounting to $51,297,000 in Q4 2024[17] - The company acquired ImmPACT Bio, which strengthened its clinical pipeline with the addition of IMPT-314[6] Future Outlook - The company plans to continue focusing on research and development to enhance its product pipeline and market position[19]

Core Insights - Lyell Immunopharma is advancing its pipeline of next-generation CAR T-cell therapies, particularly focusing on IMPT-314, a dual-targeting CD19/CD20 CAR T-cell product candidate for aggressive large B-cell lymphoma [2][3][5] Financial Performance - For the fourth quarter of 2024, Lyell reported a net loss of $191.9 million, compared to a net loss of $52.9 million in the same period of 2023 [10] - The total net loss for the year ended December 31, 2024, was $343.0 million, up from $234.6 million in 2023 [10] - Cash, cash equivalents, and marketable securities stood at $383.5 million as of December 31, 2024, down from $562.7 million a year earlier, which is expected to support operations into 2027 [14] Clinical Development - IMPT-314 is currently in a Phase 1/2 clinical trial for relapsed or refractory aggressive large B-cell lymphoma, with initial data showing a 94% overall response rate and a 71% complete response rate at three months [6][7] - The company plans to initiate pivotal trials for IMPT-314 in the third-line and later setting by mid-2025 and in the second-line setting by early 2026 [2][12] Research and Development - Research and development expenses for the fourth quarter of 2024 were $48.7 million, slightly up from $47.0 million in the same quarter of 2023 [11] - The annual R&D expenses decreased to $171.6 million in 2024 from $182.9 million in 2023, primarily due to reduced personnel-related costs following a workforce reduction [11][13] Corporate Strategy - The acquisition of ImmPACT Bio has strengthened Lyell's clinical pipeline, particularly with the addition of IMPT-314 [5] - The company is focused on advancing next-generation CAR T-cell product candidates and plans to submit a new IND for a solid tumor CAR T-cell product candidate in 2026 [2][12]

Group 1 - Lyell Immunopharma, Inc. is a clinical-stage company focused on developing next-generation CAR T-cell therapies for cancer patients [1][2] - The company utilizes advanced technologies to enhance CAR T cells, enabling them to resist exhaustion and function effectively in challenging tumor microenvironments [2] - Upcoming investor conferences include the H.C. Wainwright 3rd Annual Cell Therapy Virtual Conference on February 25 and TD Cowen's 45th Annual Health Care Conference on March 3 [3] Group 2 - The company is headquartered in South San Francisco, California, with additional facilities in West Hills, California, and Seattle and Bothell, Washington [2] - A live webcast of the presentations will be available on the company's website, with replays accessible afterward [1]