Core Insights - Lyell Immunopharma, Inc. announced positive clinical data for LYL314, a CAR T-cell therapy for relapsed/refractory large B-cell lymphoma (LBCL), showing an 88% overall response rate and a 72% complete response rate in patients treated in the third- or later-line setting [1][3][4] Clinical Data Summary - In a Phase 1/2 trial, 25 patients in the 3L+ setting demonstrated an 88% overall response rate and a 72% complete response rate, with 71% of those achieving complete response remaining so at ≥ 6 months [1][3][4] - The efficacy evaluable population included 36 patients, with a median follow-up of 9 months for 3L+ patients and 5 months for 2L patients [2][3] - Among 51 CAR T-naive patients, 70% of those with primary refractory disease achieved a complete response [4] Safety Profile - The safety profile of LYL314 was manageable for outpatient administration, with no Grade ≥ 3 cytokine release syndrome reported and low rates of Grade 1 (22%) and Grade 2 (35%) adverse events [3][5] - Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 6% (Grade 1), 2% (Grade 2), and 14% (Grade ≥ 3) of patients, with a median resolution time of 5 days [5] Ongoing Trials - The pivotal single-arm PiNACLE trial is currently underway, targeting approximately 120 patients with relapsed/refractory LBCL in the third- or later-line setting [6][12] - The trial aims to evaluate the overall response rate as the primary endpoint [12] Regulatory Designations - LYL314 has received Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations from the FDA for the treatment of relapsed/refractory aggressive B-cell lymphoma [11] Manufacturing and Technology - LYL314 is designed to target B cells expressing either CD19 or CD20, utilizing a proprietary manufacturing process to enhance T-cell activity [10][9] - The Lyell LyFE Manufacturing Center™ has the capacity to produce over 1,200 CAR T-cell doses at full capacity [13]

Financial Data and Key Metrics Changes - The company is in a strong capital position to advance pivotal studies without the need for immediate capital raising [10] - The current market for CAR T therapies is approximately $3 billion annually, with expectations to grow significantly [46] Business Line Data and Key Metrics Changes - The lead program, Lyle 314, has shown a 94% overall response rate and a 71% complete response rate in ongoing trials [5][19] - The company is expanding its focus from solid tumors to include hematologic malignancies, indicating a strategic shift [11] Market Data and Key Metrics Changes - The CD19 market is projected to grow from $3 billion to $5 billion over the next few years, highlighting significant commercial opportunities [14] - The competitive landscape includes existing CD19 CAR therapies, with a focus on demonstrating superior efficacy and safety [29] Company Strategy and Development Direction - The company aims to develop next-generation cell therapies that provide long-term disease-free periods for cancer patients [3] - The acquisition of Impact Bio and its lead asset is part of a broader strategy to enhance capabilities in hematologic malignancies [11][12] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the FDA's openness to cell therapies, which could facilitate future approvals [44] - The company is focused on executing its pivotal trial and is optimistic about the potential for its lead product to penetrate the market effectively [49] Other Important Information - The company has successfully transitioned the manufacturing process from an academic setting to its own facility, enhancing production capabilities [15] - The company is preparing for commercial launch with a manufacturing capacity of approximately 1,200 doses per year [46] Q&A Session Summary Question: What is the strategy behind the acquisition of Impact Bio? - The acquisition was driven by the desire to expand into hematologic malignancies and capitalize on the potential of the lead asset [11][12] Question: How does the company plan to differentiate its product in a competitive market? - The company aims to show superior efficacy and safety compared to existing CD19 CAR therapies, which is critical for market penetration [29][30] Question: What are the expectations for the upcoming data presentation at the International Conference of Malignant Lymphoma? - The focus will be on demonstrating durability of response, particularly the maintenance of complete responses beyond six months [18][19] Question: How is the company preparing for manufacturing and commercialization? - The company has a robust manufacturing facility capable of supporting both clinical and early commercial needs, with plans for potential expansion [46][47] Question: Are there plans for further acquisitions or partnerships? - The company is open to exploring additional opportunities but will maintain a disciplined approach given current market conditions [51]

Core Insights - Lyell Immunopharma, Inc. has appointed new leaders to strengthen its clinical and commercial capabilities as it advances its CAR T-cell therapy pipeline [1][2][6] Leadership Appointments - Mark J. Bachleda, PharmD, MBA has been appointed as an independent member of the Board of Directors, bringing extensive experience in cell therapy and commercial leadership [3][6] - David Shook, MD has been appointed as Chief Medical Officer, recognized for his pioneering work in cell therapy and experience in leading clinical development for CAR NK cell products [4][6] - Mark Meltz, JD has been appointed as General Counsel and Corporate Secretary, with over two decades of experience in legal and business roles within life sciences [5][7] - Jarrad Aguirre, MD, MBA has been appointed as Senior Vice President of Medical Affairs, previously co-founding a digital health company and holding leadership roles in other biotech firms [8][6] Strategic Focus - The company is preparing to advance LYL314 towards approval for patients with aggressive large B-cell lymphoma, indicating a focus on late-stage clinical trials and potential commercial launch [2][9] - The new leadership team is expected to enhance operational excellence and contribute to the rapid advancement of LYL314, an autologous CD19/CD20 CAR T-cell therapy [2][6]

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].