Lyell(LYEL) - 2025 Q2 - Quarterly Results

Business Overview and Recent Highlights This section provides an overview of Lyell Immunopharma's strategic vision, clinical progress with LYL314, and advancements in its preclinical pipeline Company Introduction and Strategic Vision Lyell Immunopharma is a late-stage clinical company focused on advancing next-generation CAR T-cell therapies for cancer, with LYL314 as its lead program for relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) - Lyell Immunopharma is a late-stage clinical company advancing next-generation CAR T-cell therapies for patients with cancer, with LYL314 as its lead clinical program for R/R large B-cell lymphoma (LBCL)[2] - LYL314, a CD19/CD20 CAR T-cell therapy, is believed to disrupt the therapeutic landscape by delivering meaningfully increased complete response rates and improved durability over currently approved CD19 CAR T-cell therapies[3] - A recent private placement with well-respected investors significantly de-risks the business, extends the cash runway into mid-2027, and enables focus on rapidly advancing LYL314's clinical development[3] LYL314 Clinical Program Updates LYL314, a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate, is designed to increase complete response rates and prolong the duration of response - LYL314 is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of response compared to approved CD19-targeted CAR T-cell therapies for LBCL[5] - LYL314 has been granted Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations by the FDA for the treatment of R/R diffuse LBCL in the 3L+ setting[5] - The PiNACLE pivotal trial for LYL314 in 3L+ LBCL has been initiated, and a pivotal trial in the 2L setting is on track to begin by early 2026[3][6] PiNACLE Pivotal Trial (3L+ LBCL) The PiNACLE trial is a single-arm pivotal study evaluating LYL314 in approximately 120 CAR T-cell therapy naive patients with R/R LBCL in the 3L+ setting - PiNACLE is a single-arm pivotal trial evaluating LYL314 at a dose of 100 x 10^6 CAR T cells in approximately 120 CAR T-cell therapy naive patients with R/R LBCL in the 3L+ setting[5][7] - The primary endpoint of the PiNACLE trial is the overall response rate, including an evaluation of duration of response[7] - Data from the PiNACLE trial is expected to form the basis of a Biologics License Application submission to the FDA in 2027 for patients with R/R LBCL receiving treatment in the 3L+ setting[10] Phase 1/2 Trial (2L LBCL) & Future Plans The Phase 1/2 trial continues to enroll CAR T-cell therapy naive patients in the 2L setting, with a Phase 3 trial expected by early 2026 - The Phase 1/2 trial continues to enroll CAR T-cell therapy naive patients receiving treatment in the 2L setting, with more mature data expected to be presented in late 2025[5][10] - A Phase 3 randomized controlled trial of LYL314 is expected to be initiated by early 2026 in patients receiving treatment in the 2L setting with R/R LBCL[10] Regulatory Designations LYL314 has been granted Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations by the FDA for R/R diffuse LBCL in the 3L+ setting - The FDA has granted LYL314 Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations for the treatment of R/R diffuse LBCL in the 3L+ setting, providing benefits like increased communication with the FDA[5] Clinical Data Presentation Highlights Positive new clinical data from the Phase 1/2 trial of LYL314 demonstrated high rates of durable complete responses and a manageable safety profile - Positive new clinical data demonstrating high rates of durable complete responses from the Phase 1/2 trial of LYL314 for the treatment of aggressive large B-cell lymphoma were presented[6][10] LYL314 Phase 1/2 Efficacy Data (as of April 15, 2025) | Patient Cohort | N (efficacy-evaluable) | Median Follow-up | Overall Response Rate | Complete Response Rate | Durable CR (≥ 6 months) | | :-------------- | :--------------------- | :--------------- | :-------------------- | :--------------------- | :---------------------- | | 3L+ LBCL | 25 | 9 months | 88% (22/25) | 72% (18/25) | 71% (10/14) | | 2L LBCL (initial) | 11 | 5 months | 91% (10/11) | 64% (7/11) | 100% (3/3) | - LYL314 demonstrated a manageable safety profile appropriate for outpatient administration, with low rates of Grade 1 (22%) or Grade 2 (35%) cytokine release syndrome (CRS) and no deaths related to LYL314 administration[10] Preclinical Pipeline and Technology Lyell is advancing next-generation fully-armed CAR T-cell product candidates designed to overcome T-cell exhaustion and immune suppression - Lyell is advancing next-generation fully-armed CAR T-cell product candidates, each including multiple technologies, designed to overcome T-cell exhaustion and lack of durable stemness, as well as immune suppression within the hostile tumor microenvironment[8] - The first IND for a fully-armed CAR T-cell product candidate with an undisclosed target for solid tumors is expected in 2026[8] Corporate and Financial Updates This section details recent corporate developments, including a private placement and cash runway extension, alongside the second quarter 2025 financial performance Corporate Developments Lyell recently completed a private placement, securing gross proceeds of up to approximately $100 million, extending its cash runway into mid-2027 - Lyell entered into a securities purchase agreement for a private placement with certain institutional and other accredited investors, for gross proceeds of up to approximately $100 million[6][9] - Net proceeds from the private placement, together with existing cash, cash equivalents, and marketable securities, are expected to advance two pivotal-stage clinical trials of LYL314 as well as working capital for other general corporate purposes[11] Private Placement Lyell entered into a securities purchase agreement for a private placement with gross proceeds of up to approximately $100 million, with an initial closing of $50 million - In July, Lyell entered into a securities purchase agreement for a private placement for gross proceeds of up to approximately $100 million[9] - The initial closing of approximately $50 million of common stock at a price of $13.32 per share occurred on July 25, 2025[9] Cash Position and Runway Lyell's pro-forma cash position of approximately $347 million, inclusive of private placement proceeds, is expected to extend its cash runway into mid-2027 Cash, Cash Equivalents and Marketable Securities (in thousands) | Date | Amount | | :--------------- | :----------- | | June 30, 2025 | $296,849 | | December 31, 2024 | $383,541 | - Pro-forma cash of approximately $347 million, inclusive of the initial proceeds from the private placement, is expected to support advancing the pipeline into mid-2027 through key clinical milestones[6][14] Second Quarter 2025 Financial Results Lyell reported a GAAP net loss of $42.7 million for Q2 2025, a decrease from $45.8 million in Q2 2024, primarily due to reduced stock-based compensation - Lyell reported a net loss of $42.7 million for Q2 2025, a $3.1 million decrease compared to $45.8 million for Q2 2024, primarily due to a decrease in stock-based compensation expense[12] - Non-GAAP net loss decreased to $37.8 million for Q2 2025, compared to $39.1 million for Q2 2024, primarily due to lower interest income[12] GAAP Net Loss Lyell's GAAP net loss for Q2 2025 was $42.7 million, an improvement from $45.8 million in Q2 2024, mainly due to reduced stock-based compensation GAAP Net Loss (in thousands) | Period | 2025 | 2024 | Change | | :---------------------- | :---------- | :---------- | :---------- | | Three Months Ended June 30 | $(42,684)$ | $(45,809)$ | $(3,125)$ | - The $3.1 million decrease in net loss was primarily due to a $3.3 million decrease in stock-based compensation expense resulting from lower headcount and the reduced value of new equity awards[12] GAAP Operating Expenses Research and development expenses decreased by $5.4 million to $34.9 million in Q2 2025, while general and administrative expenses decreased by $2.5 million to $9.8 million GAAP Operating Expenses (in thousands) | Expense Category | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Change (YoY) | | :--------------- | :------------------------------- | :------------------------------- | :----------- | | R&D Expenses | $34,857 | $40,261 | $(5,404)$ | | G&A Expenses | $9,786 | $12,256 | $(2,470)$ | - The decrease in R&D expenses was primarily due to a $2.9 million reduction in research activities, collaborations, and outside services, and a $2.4 million decrease in personnel-related expenses[17] - The decrease in G&A expenses was primarily due to a $1.7 million decrease in stock-based compensation expense and a $0.8 million decrease in outside services, mainly legal expenses[17] Company Information and Outlook This section provides an overview of Lyell Immunopharma's mission and technology, along with important forward-looking statements regarding future plans and risks About Lyell Immunopharma, Inc. Lyell is a late-stage clinical company advancing next-generation CAR T-cell therapies for hematologic malignancies and solid tumors, utilizing technologies to enhance durable tumor cytotoxicity - Lyell is a late-stage clinical company advancing a pipeline of next-generation CAR T-cell therapies for patients with hematologic malignancies and solid tumors[15] - Lyell utilizes a suite of technologies to endow CAR T cells with attributes needed to drive durable tumor cytotoxicity and high rates of long-lasting clinical responses, including the ability to resist exhaustion, maintain qualities of durable stemness, and function in the hostile tumor microenvironment[15] - The Lyell LyFE Manufacturing Center™ has commercial launch capability and can manufacture more than 1,200 CAR T-cell doses at full capacity[15] Forward-Looking Statements This section outlines Lyell's future plans, including clinical trial initiations and regulatory submissions, while acknowledging inherent risks and uncertainties - Forward-looking statements include expectations for LYL314 pivotal trial initiation by early 2026, BLA submission in 2027, and an IND for a solid tumor CAR T-cell candidate in 2026[16][18] - Lyell expects its financial position and cash runway to support advancement of its pipeline into mid-2027 through key clinical milestones[18] - These statements are not guarantees of future performance and inherently involve significant risks and uncertainties, including those related to clinical trial progression, manufacturing, regulatory approvals, and capital resources, which could cause actual results to differ materially[18] Unaudited Selected Consolidated Financial Data This section presents unaudited consolidated financial data, including statements of operations, balance sheet information, and reconciliations of non-GAAP financial measures Statement of Operations Data This section presents unaudited consolidated statement of operations data for the three and six months ended June 30, 2025, and 2024, detailing revenue, expenses, and net loss Statement of Operations Data (in thousands) | Item | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------ | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Revenue | $8 | $13 | $15 | $16 | | R&D Expenses | $34,857 | $40,261 | $78,304 | $83,435 | | G&A Expenses | $9,786 | $12,256 | $23,832 | $25,750 | | Loss from operations | $(47,140)$ | $(51,528)$ | $(104,507)$ | $(107,103)$ | | Interest income, net | $3,276 | $6,364 | $7,138 | $13,183 | | Net loss | $(42,684)$ | $(45,809)$ | $(94,879)$ | $(106,476)$ | Balance Sheet Data This section provides unaudited consolidated balance sheet data as of June 30, 2025, and December 31, 2024, highlighting cash, assets, and stockholders' equity Balance Sheet Data (in thousands) | Item | As of June 30, 2025 | As of December 31, 2024 | | :--------------------------------- | :------------------ | :---------------------- | | Cash, cash equivalents and marketable securities | $296,849 | $383,541 | | Property and equipment, net | $39,115 | $48,200 | | Total assets | $385,453 | $490,859 | | Total stockholders' equity | $298,923 | $382,824 | Non-GAAP Financial Measures and Reconciliations This section explains and reconciles non-GAAP financial measures by excluding non-cash items to enhance comparability and identify operating trends - Non-GAAP financial measures (net loss, R&D expenses, G&A expenses) are presented to supplement GAAP results, excluding non-cash stock-based compensation, changes in estimated fair value of success payment liabilities, and non-cash investment gains/charges[22] - These non-GAAP measures are used internally to understand, manage, and evaluate the business, and are believed to enhance investors' and analysts' ability to compare results and identify operating trends[22] Non-GAAP Net Loss Reconciliation The reconciliation shows Lyell's non-GAAP net loss for Q2 2025 was $37.8 million, an improvement from $39.1 million in Q2 2024, primarily due to adjustments for stock-based compensation Unaudited Reconciliation of GAAP to Non-GAAP Net Loss (in thousands) | Item | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------ | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Net loss - GAAP | $(42,684)$ | $(45,809)$ | $(94,879)$ | $(106,476)$ | | Stock-based compensation expense | $5,004 | $8,284 | $11,028 | $17,439 | | Change in the estimated fair value of success payment liabilities | $(115)$ | $(1,534)$ | $(240)$ | $(566)$ | | Impairment of other investments | — | — | — | $13,001 | | Net loss - Non-GAAP | $(37,795)$ | $(39,059)$ | $(84,091)$ | $(76,602)$ | Non-GAAP Research and Development Expenses Reconciliation Non-GAAP R&D expenses for Q2 2025 were $32.6 million, a decrease from $37.2 million in Q2 2024, after adjusting for non-cash items Unaudited Reconciliation of GAAP to Non-GAAP Research and Development Expenses (in thousands) | Item | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development - GAAP | $34,857 | $40,261 | $78,304 | $83,435 | | Stock-based compensation expense | $(2,295)$ | $(3,865)$ | $(4,683)$ | $(7,657)$ | | Change in the estimated fair value of success payment liabilities | — | $793 | — | $268 | | Research and development - Non-GAAP | $32,562 | $37,189 | $73,621 | $76,046 | Non-GAAP General and Administrative Expenses Reconciliation Non-GAAP G&A expenses for Q2 2025 were $7.1 million, a decrease from $7.8 million in Q2 2024, after adjusting for stock-based compensation Unaudited Reconciliation of GAAP to Non-GAAP General and Administrative Expenses (in thousands) | Item | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | General and administrative - GAAP | $9,786 | $12,256 | $23,832 | $25,750 | | Stock-based compensation expense | $(2,709)$ | $(4,419)$ | $(6,345)$ | $(9,782)$ | | General and administrative - Non-GAAP | $7,077 | $7,837 | $17,487 | $15,968 |