NR4A3

Strengthens Lyell’s clinical pipeline with the addition of IMPT-314, a dual-targeting CD19/CD20 CAR T-cell product candidate Data from ImmPACT’s multi-center Phase 1-2 clinical trial of IMPT-314 in patients with large B-cell lymphoma treated in the 3rd line CAR-naïve setting to be presented at a major medical conference later this year; initiation of a pivotal trial for IMPT-314 expected in 2025 Lyell has prioritized its pipeline to focus on next-generation CAR T-cell therapies, including IMPT-314 and LYL119, and is discontinuing development of LYL797, LYL845 and earlier-stage TIL programs Cash runway following the close of the transaction is expected to fund operations into 2027, through important clinical milestones for each pipeline program Lyell will host an investor webcast at 4:30 PM ET today Oct. 24, 2024 -- Lyell Immunopharma, Inc. (Nasdaq: LYEL) announced today that it has entered into a definitive agreement to acquire ImmPACT Bio USA Inc. (“ImmPACT”), a privately-owned clinical-stage biotechnology company. ImmPACT’s lead program, IMPT-314, is a CD19/20-targeting chimeric antigen receptor (CAR) T-cell product candidate that Lyell will continue to develop for hematologic malignancies, including large B-cell lymphoma. IMPT-314 was designed to outperform the efficacy of approved CD19 CAR T-cell therapies via a dual-targeting CAR T-cell design and to improve CAR T-cell persistence by enriching for naïve and central memory T cells during manufacturing. The acquisition of ImmPACT is expected to significantly strengthen Lyell’s clinical-stage pipeline of next- generation CAR T-cell therapies and complement its suite of proprietary technologies designed to generate longer-lasting, functional T cells to achieve more durable outcomes for patients with solid tumors and hematologic malignancies. “Lyell’s vision is to bring meaningful and durable clinical benefit to patients suffering from cancer with our next-generation cell therapies,” stated Lynn Seely, M.D., Lyell’s President and Chief Executive Officer. “The emerging data from ImmPACT’s ongoing Phase 1-2 trial and the Phase 1 clinical data from a published UCLA-sponsored trial suggest the potential of IMPT-314 to have improved complete response rates and duration of response compared to the approved CD19 CAR T-cell therapies in CAR-naïve patients with aggressive B-cell lymphoma. Since licensing this product candidate from UCLA, the team at ImmPACT has made impressive progress in the multi-center IMPT-314 Phase 1-2 clinical program. We look forward to presenting initial data from this program at a major medical conference later this year and initiating a pivotal trial for IMPT-314 in 2025.” “I am incredibly proud of the ImmPACT team and all of their accomplishments in developing next-generation CAR T-cell therapies,” stated Sumant Ramachandra, M.D., Ph.D., Chief Executive Officer of ImmPACT. “This transaction validates our novel science and enhances the potential for this therapy to make a meaningful impact on patients' lives. I am confident that in Lyell, we have found a team that shares our passion for advancing novel science to benefit patients.” ImmPACT licensed its dual-targeting CD19/CD20 CAR T-cell product candidate from the University of California, Los Angeles (UCLA). Phase 1 data in 13 patients with relapsed/refractory (R/R) aggressive non-Hodgkin lymphoma treated in a UCLA-sponsored clinical trial were presented at the 2024 AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy. CAR T-cell naïve patients with R/R diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma after at least two lines of therapy or mantle cell lymphoma, follicular lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma after at least three lines of therapy were evaluated. Autologous T cells were obtained and enriched for CD14-/CD25-/CD62L+ naïve or memory T cells. Twelve out of 13 patients achieved a complete or partial response (92% objective response rate), with ten achieving a confirmed complete response (CR) (77% CR rate). The median progression-free survival was 50.1 months, and median overall survival was not reached with a median follow up of 32 months (range: 5.7 – not estimable). A favorable safety profile was observed. The ongoing Phase 1-2 clinical trial initiated by ImmPACT is a multi-center, open-label clinical trial designed to evaluate the tolerability and clinical benefit of IMPT-314 in patients with R/R aggressive B-cell lymphoma and determine a recommended Phase 2 dose. Initial Phase 1-2 clinical data evaluating IMPT-314 primarily in patients who have received at least two prior lines of therapy for large B-cell lymphoma will be presented at a major medical conference this year. IMPT-314 has received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of R/R aggressive B-cell lymphoma. Lyell expects to initiate a pivotal trial in 2025 for IMPT-314 in patients in the 3rd line setting who have not yet been exposed to CAR T-cell therapy. In connection with the acquisition, Lyell has prioritized its pipeline to focus resources on its most differentiated CAR T-cell clinical programs, including IMPT-314 following the close of the acquisition and LYL119. The enhanced anti-exhaustion technology incorporated into LYL119, including c-Jun overexpression, NR4A3 knockout, Epi-R and Stim R, has the potential to achieve improved efficacy at lower cell doses with an acceptable safety profile. In a validated in vivo preclinical model of non-small cell lung cancer, LYL119 achieved tumor control at a 10-fold lower cell dose than LYL797 with more gradual cell expansion to peak, and a substantial increase in the duration of cell killing demonstrated by a repetitive tumor cell killing assay in vitro. Lyell is discontinuing development of LYL797, its ROR1-targeted CAR T-cell product candidate to focus on the Phase 1 clinical trial of its next-generation ROR1-targeted CAR T-cell product candidate LYL119, which is expected to initiate enrollment of patients with platinum-resistant ovarian cancer or relapsed/refractory endometrial cancer this year or early next year. The LYL845 tumor-infiltrating lymphocyte (TIL) program is also being discontinued as the clinical data in patients with advanced melanoma did not meet our rigorous pre-determined criteria for continued development. Its next-generation TIL and rejuvenation programs that are in preclinical development will also be discontinued. Following the close of the transaction, Lyell expects its cash balance will fund operations into 2027, through important clinical milestones for each pipeline program, including initiation of a pivotal trial for IMPT-314, which is expected to start in 2025. Upon closing, Lyell will acquire worldwide rights to ImmPACT’s pipeline, including the next- generation bispecific CD19/CD20 autologous CAR T-cell therapy, currently in clinical development for B-cell lymphoma and autoimmune diseases, and an activating TGF-beta Claudin 18.2 CAR T-cell candidate, which is in preclinical development. Lyell will prioritize the development of IMPT-314 for patients with B-cell lymphoma. Deal terms include upfront consideration payable upon closing the potential transaction of $30 million in cash, subject to certain adjustments, and 37.5 million shares of Lyell common stock. ImmPACT shareholders will also be eligible to receive contingent consideration consisting of 12.5 million shares of Lyell common stock that may be earned upon the achievement of a value-enhancing clinical milestone and a low single-digit royalty on future net sales of the dual-targeting CD19/20 CAR T-cell product in the United States. The proposed transaction, which has been unanimously approved by the Boards of Directors of both companies, is expected to close in the fourth quarter of 2024. The closing of the proposed transaction is subject to expiration of the Hart-Scott-Rodino antitrust waiting period and the satisfaction of other customary closing conditions. Goldman Sachs & Co LLC is acting as sole financial advisor to Lyell in this transaction and Skadden, Arps, Slate, Meagher & Flom LLP is acting as its legal advisor. Cooley LLP is acting as ImmPACT’s legal advisor. Lyell’s management will host an investor conference call and Webcast beginning at 4:30 pm ET today. The Webcast can be accessed here. A replay of the event and presentation materials will be archived on the Investor page of the Lyell Website following the end of the event. Lyell is a clinical-stage company advancing a pipeline of next-generation CAR T-cell therapies for patients with solid tumors or hematologic malignancies. Lyell’s product candidates are enhanced with novel technology designed to generate T cells that resist exhaustion and have qualities of durable stemness in order to drive durable tumor cytotoxicity and achieve consistent and long-lasting clinical response. Lyell is based in South San Francisco, California with facilities in Seattle and Bothell, Washington. To learn more, please visit www.lyell.com. The content above comes from the network. if any infringement, please contact us to modify.

Reported dose-dependent antitumor clinical activity in patients with relapsed/refractory triple-negative breast cancer from the Phase 1 trial of LYL797, a ROR1-targeted Chimeric Antigen Receptor (CAR) T‑cell product candidate enhanced with proprietary anti-exhaustion technology; 40% objective response rate and 60% clinical benefit rate at the highest dose cleared at the time of the initial data report (150 x 106 CAR T cells)Expanded development of LYL797 into four new tumor types, including ROR1+ relapsed/refractory platinum‑resistant ovarian cancer, endometrial cancer, multiple myeloma and chronic lymphocytic leukemiaReceived FDA clearance of an IND for LYL119, a next-generation ROR1-targeted CAR T-cell product candidate incorporating four proprietary technologies designed to enhance the anti-exhaustion capability and persistence of T cellsCash, cash equivalents and marketable securities of $491.1 million as of June 30, 2024 supports advancing diverse pipeline through multiple clinical milestones into 2027 SOUTH SAN FRANCISCO, Calif., Aug. 07, 2024 (GLOBE NEWSWIRE) -- Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors or hematologic malignancies, today reported financial results and business highlights for the second quarter ended June 30, 2024. “We are pleased that initial data from our Phase 1 trial of LYL797 demonstrated dose-dependent clinical activity and that LYL797 CAR T cells expanded, infiltrated solid tumors and killed cancer cells in patients. Based on these promising initial data, we have expanded the cancer indications under evaluation in this trial to include patients with ovarian and endometrial cancers, and we plan to file an IND to initiate a new trial evaluating LYL797 in multiple myeloma and chronic lymphocytic leukemia,” said Lynn Seely, M.D., Lyell’s President and CEO. “In addition, our IND for LYL119, a next generation ROR1-targeted CAR T‑cell product candidate designed with four technologies to generate T cells with even greater capacity to resist exhaustion, has been cleared by the FDA, and we expect to report initial clinical data from the Phase 1 trial in the second half of 2025. We remain on track to report initial clinical data from our lead TIL program in the second half of this year. Our strong cash position enables us to advance multiple product candidates through critical clinical milestones and fund operations into 2027.” Second Quarter Updates and Recent Business Highlights Lyell is advancing four wholly-owned product candidates. Two product candidates, LYL797 and LYL845, are in Phase 1 clinical development, and LYL119 is entering Phase 1 clinical development. A second-generation tumor infiltrating lymphocyte (TIL) product candidate is in preclinical development. LYL797 – A ROR1-targeted CAR T-cell product candidate enhanced with anti-exhaustion technology designed for improved tumor infiltration and tumor cell killing Enrollment in the Phase 1 clinical trial of LYL797 is ongoing. The study was initiated in patients with relapsed/refractory triple-negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC). Based on the initial clinical data that demonstrated dose-dependent anti-tumor activity, the trial has been expanded to include patients with platinum-resistant ovarian or endometrial cancers and an investigational new drug (IND) application is expected to be submitted in the second half of this year to initiate a second Phase 1 clinical trial of LYL797 in multiple myeloma and chronic lymphocytic leukemia (CLL).Initial clinical and translational data from the Phase 1 clinical trial of LYL797 were reported in June 2024. The initial dataset of 20 patients (16 patients with TNBC and four patients with NSCLC) demonstrated dose-dependent antitumor clinical activity and the ability of LYL797 CAR T cells to proliferate, infiltrate tumors and kill cancer cells in patients with relapsed/refractory disease. Patients with TNBC treated with LYL797 had an objective response rate (ORR) of 40% and a clinical benefit rate (CBR) of 60% at the 150 x 106 CAR T cell dose level, with a CBR of 38% across all dose levels evaluable at the time data were reported. Common treatment-related adverse events (TRAE) in patients without lung metastases included Grade 1 and 2 cytokine release syndrome (CRS) and headache, and the expected cytopenia from lymphodepletion. There were no reports of immune effector cell‑associated neurotoxicity syndrome (ICANS) attributed to LYL797. Pneumonitis occurred in some patients with lung metastases, including the index patient who experienced Grade 5 respiratory failure on Day 41. All patients are now given dexamethasone prophylaxis and dose escalation is continuing separately and more gradually in patients with lung involvement. No dose‑limiting toxicities have been reported in patients without lung involvement.Updated data from the ongoing Phase 1 trial in solid tumor indications, including the initiation of dose expansion, are expected in late 2024 – early 2025. LYL845 – A TIL product candidate epigenetically reprogrammed using Lyell’s proprietary Epi-R manufacturing protocol, designed for differentiated potency and durability Enrollment in the Phase 1 clinical trial of LYL845 is ongoing. The trial is designed to include patients with relapsed or refractory metastatic or locally advanced melanoma, NSCLC and colorectal cancer.Initial clinical and translational data from the Phase 1 trial of LYL845 in patients with advanced melanoma are expected in the second half of 2024. LYL119 – A next-generation ROR1-targeted CAR T-cell product candidate incorporating four stackable and complementary anti-exhaustion technologies designed for enhanced potency LYL119 is a ROR1-targeted CAR T-cell product enhanced with four novel genetic and epigenetic reprogramming technologies: c-Jun overexpression, NR4A3 knockout, Epi-R manufacturing protocol and Stim‑RTM T-cell activation technology.An IND application for LYL119 has received clearance from the U.S. Food and Drug Administration (FDA).The Phase 1 trial is designed as an open‑label dose‑escalation and ‑expansion trial in patients with ROR1‑positive solid tumors and will initially enroll patients with ROR1‑positive platinum‑resistant ovarian cancer or endometrial cancer. It is estimated that approximately 50% of patients with ovarian cancer and approximately 50% of patients with endometrial cancer have ROR1‑positive tumors.Initial clinical data are expected in the second half of 2025. Second Quarter Financial Results Lyell reported a net loss of $45.8 million for the second quarter ended June 30, 2024, compared to a net loss of $63.9 million for the same period in 2023. Non‑GAAP net loss, which excludes non-cash stock-based compensation, non‑cash expenses related to the change in the estimated fair value of success payment liabilities and certain non-cash investment gains and charges, was $39.1 million for the second quarter ended June 30, 2024, compared to $45.6 million for the same period in 2023. GAAP and Non-GAAP Operating Expenses Research and development (R&D) expenses were $40.3 million for the second quarter ended June 30, 2024, compared to $47.5 million for the same period in 2023. The decrease in second quarter 2024 R&D expenses of $7.2 million was primarily driven by a decrease in personnel-related expenses associated with Lyell’s November 2023 reduction in workforce. Non‑GAAP R&D expenses, which exclude non-cash stock-based compensation and non-cash expenses related to the change in the estimated fair value of success payment liabilities for the second quarter ended June 30, 2024, were $37.2 million, compared to $41.6 million for the same period in 2023. The decrease in second quarter 2024 non-GAAP R&D expenses was primarily driven by a decrease in personnel-related expenses.General and administrative (G&A) expenses were $12.3 million for the second quarter ended June 30, 2024, compared to $19.0 million for the same period in 2023. The decrease in second quarter 2024 G&A expenses was primarily driven by decreases in non-cash stock-based compensation. Non‑GAAP G&A expenses, which exclude non-cash stock‑based compensation, for the second quarter ended June 30, 2024, were $7.8 million, compared to $10.1 million for the same period in 2023. The decrease in second quarter 2024 non-GAAP G&A expenses was primarily driven by a decrease in personnel-related expenses associated with Lyell’s November 2023 reduction in workforce. A discussion of non-GAAP financial measures, including reconciliations of the most comparable GAAP measures to non‑GAAP financial measures, is presented below under “Non-GAAP Financial Measures.” Cash, cash equivalents and marketable securities Cash, cash equivalents and marketable securities as of June 30, 2024, were $491.1 million, compared to $562.7 million as of December 31, 2023. Lyell believes that its cash, cash equivalents and marketable securities balances will be sufficient to meet working capital and capital expenditure needs into 2027. About Lyell Immunopharma, Inc. Lyell is a clinical-stage T-cell reprogramming company advancing a diverse pipeline of cell therapies, including three product candidates in or entering Phase 1 clinical development for patients with solid tumors or hematologic malignancies. Lyell’s product candidates are enhanced with novel anti-exhaustion technology designed to address barriers that limit consistent and long-lasting responses to cell therapy for solid tumors: T-cell exhaustion and lack of durable stemness, which includes the ability to persist and self-renew to drive durable tumor cytotoxicity. Lyell applies its proprietary ex vivo genetic and epigenetic reprogramming technology to address these barriers to develop new medicines with improved durable clinical outcomes. Lyell is based in South San Francisco, California with facilities in Seattle and Bothell, Washington. To learn more, please visit www.lyell.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding: the continued clinical progress of the LYL797 trials; Lyell’s plans to enroll patients with platinum-resistant ovarian cancer and endometrial cancer in the LYL797 trial; Lyell’s plans to submit an IND for LYL797 to initiate a new trial evaluating LYL797 in patients with multiple myeloma or chronic lymphocytic leukemia and the timing thereof; Lyell’s development plans for LYL119 and the effectiveness of any technologies incorporated into LYL119; the ability of Lyell’s anti-exhaustion technology to address barriers that limit consistent and long-lasting responses to cell therapy for solid tumors: T‑cell exhaustion and lack of durable stemness, and for its reprogramming technology to address these barriers to develop new medicines with improved durable clinical outcomes; Lyell’s anticipated progress, business plans, business strategy and clinical trials; Lyell’s advancement of its pipeline and its research, development and clinical capabilities; the potential clinical benefits and therapeutic potential of Lyell’s product candidates; the advancement of Lyell’s technology platform; Lyell’s expectation that its financial position and cash runway will support advancement of its pipeline through multiple clinical milestones into 2027; expectations around enrollment and the timing of initial and updated clinical and translational data from Lyell’s Phase 1 trials for LYL797, LYL845 and LYL119; and other statements that are not historical fact. These statements are based on Lyell’s current plans, objectives, estimates, expectations and intentions, are not guarantees of future performance and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, but are not limited to, risks and uncertainties related to: the effects of macroeconomic conditions, including any geopolitical instability and actual or perceived changes in interest rates and economic inflation; Lyell’s ability to submit planned INDs or initiate or progress clinical trials on the anticipated timelines, if at all; Lyell’s limited experience as a company in enrolling and conducting clinical trials, and lack of experience in completing clinical trials; Lyell’s ability to manufacture and supply its product candidates for its clinical trials; the nonclinical profiles of Lyell’s product candidates or technology not translating in clinical trials; the potential for results from clinical trials to differ from nonclinical, early clinical, preliminary or expected results; significant adverse events, toxicities or other undesirable side effects associated with Lyell’s product candidates; the significant uncertainty associated with Lyell’s product candidates ever receiving any regulatory approvals; Lyell’s ability to obtain, maintain or protect intellectual property rights related to its product candidates; implementation of Lyell’s strategic plans for its business and product candidates; the sufficiency of Lyell’s capital resources and need for additional capital to achieve its goals; and other risks, including those described under the heading “Risk Factors” in Lyell’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the Securities and Exchange Commission (SEC) on February 28, 2024, and the Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, being filed with the SEC today. Forward-looking statements contained in this press release are made as of this date, and Lyell undertakes no duty to update such information except as required under applicable law. Lyell Immunopharma, Inc.Unaudited Selected Consolidated Financial Data(in thousands) Statement of Operations Data: Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Revenue$13 $27 $16 $92 Operating expenses: Research and development(1) 40,261 47,471 83,435 92,101 General and administrative 12,256 19,030 25,750 38,309 Other operating income, net (976) (569) (2,066) (1,857)Total operating expenses 51,541 65,932 107,119 128,553 Loss from operations (51,528) (65,905) (107,103) (128,461)Interest income, net 6,364 5,264 13,183 9,761 Other (expense) income, net (645) (326) 445 774 Impairment of other investments — (2,923) (13,001) (12,923)Total other income (loss), net 5,719 2,015 627 (2,388)Net loss$(45,809) $(63,890) $(106,476) $(130,849) (1)Lyell’s success payment liability was recognized at fair value as Fred Hutch had provided the requisite service obligation to earn the potential success payment consideration under the continued collaboration. The change in the estimated fair value of Fred Hutch success payment liabilities beginning in Q1 2023 was recognized within other (expense) income, net in the unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss. The change in the estimated fair value of Stanford success payment liabilities was recognized within research and development expenses in the unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss. Balance Sheet Data: As of June 30, 2024 As of December 31, 2023 Cash, cash equivalents and marketable securities$491,119 $562,729Property and equipment, net$93,096 $102,654Total assets$654,142 $750,029Total stockholders’ equity$566,501 $654,952 Non-GAAP Financial Measures To supplement our financial results and guidance presented in accordance with U.S. generally accepted accounting principles (GAAP), we present non-GAAP net loss, non-GAAP R&D expenses and non-GAAP G&A expenses. Non‑GAAP net loss and non-GAAP R&D expenses exclude non-cash stock-based compensation expense and non-cash expenses related to the change in the estimated fair value of success payment liabilities from GAAP net loss and GAAP R&D expenses. Non-GAAP net loss further adjusts non‑cash investment gains and charges, as applicable. Non‑GAAP G&A expenses exclude non-cash stock-based compensation expense from GAAP G&A expenses. We believe that these non-GAAP financial measures, when considered together with our financial information prepared in accordance with GAAP, can enhance investors’ and analysts’ ability to meaningfully compare our results from period to period, and to identify operating trends in our business. We have excluded stock-based compensation expense, changes in the estimated fair value of success payment liabilities and non-cash investment gains and charges from our non‑GAAP financial measures because they are non-cash gains and charges that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. We also regularly use these non-GAAP financial measures internally to understand, manage and evaluate our business and to make operating decisions. These non-GAAP financial measures are in addition to, and not a substitute for or superior to, measures of financial performance prepared in accordance with GAAP. In addition, these non-GAAP financial measures have no standardized meaning prescribed by GAAP and are not prepared under any comprehensive set of accounting rules or principles and, therefore, have limits in their usefulness to investors. We encourage investors to carefully consider our results under GAAP, as well as our supplemental non-GAAP financial information, to more fully understand our business. Lyell Immunopharma, Inc.Unaudited Reconciliation of GAAP to Non-GAAP Net Loss(in thousands) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Net loss - GAAP$(45,809) $(63,890) $(106,476) $(130,849)Adjustments: Stock-based compensation expense 8,284 14,223 17,439 28,105 Impairment of other investments — 2,923 13,001 12,923 Change in the estimated fair value of success payment liabilities (1,534) 1,105 (566) (603)Net loss - Non-GAAP(1)$(39,059) $(45,639) $(76,602) $(90,424) (1)There was no income tax effect related to the adjustments made to calculate non-GAAP net loss because of the full valuation allowance on our net U.S. deferred tax assets for all periods presented. Lyell Immunopharma, Inc.Unaudited Reconciliation of GAAP to Non-GAAP Research and Development Expenses(in thousands) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Research and development - GAAP$40,261 $47,471 $83,435 $92,101 Adjustments: Stock-based compensation expense (3,865) (5,279) (7,657) (9,891)Change in the estimated fair value of success payment liabilities(1) 793 (605) 268 3 Research and development - Non-GAAP$37,189 $41,587 $76,046 $82,213 (1)Lyell’s success payment liability was recognized at fair value as Fred Hutch had provided the requisite service obligation to earn the potential success payment consideration under the continued collaboration. The change in the estimated fair value of Fred Hutch success payment liabilities beginning in Q1 2023 was recognized within other (expense) income, net in the unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss. The change in the estimated fair value of Stanford success payment liabilities was recognized within research and development expenses in the unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss. Lyell Immunopharma, Inc.Unaudited Reconciliation of GAAP to Non-GAAP General and Administrative Expenses(in thousands) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 General and administrative - GAAP$12,256 $19,030 $25,750 $38,309 Adjustments: Stock-based compensation expense (4,419) (8,944) (9,782) (18,214)General and administrative - Non-GAAP$7,837 $10,086 $15,968 $20,095 Contact:Ellen RoseSenior Vice President, Communications and Investor Relationserose@lyell.com

Expect to share initial clinical and translational data from the Phase 1 trial of LYL797, a ROR1-targeted CAR T‑cell product candidate, this quarter On track to report initial clinical data from the Phase 1 trial of LYL845, an epigenetically enhanced TIL product candidate, in the second half of 2024 IND for second generation ROR1-targeted CAR T-cell product candidate on track for submission this quarter Cash, cash equivalents and marketable securities of $526.3 million as of March 31, 2024 supports advancing diverse pipeline through multiple clinical milestones into 2027 SOUTH SAN FRANCISCO, Calif., May 06, 2024 (GLOBE NEWSWIRE) -- Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors today reported financial results and business highlights for the first quarter ended March 31, 2024. “The initial clinical and translational data from the Phase 1 trial of LYL797, our lead CAR T-cell product candidate, will provide the first insights into our ability to reprogram ROR1 CAR T cells that can expand, infiltrate solid tumors and kill cancer cells in patients,” said Lynn Seely, M.D., Lyell’s President and CEO. “Our strong cash position is expected to fund operations through multiple milestones into 2027, including initial clinical data from our lead TIL program in the second half of this year, and to the continued advancement of multiple product candidates with potential to offer better options for patients with cancer.” First Quarter Updates and Recent Business Highlights Lyell is advancing four wholly-owned product candidates. Two product candidates, LYL797 and LYL845 are in Phase 1 clinical development. Two additional product candidates, LYL119, a ROR1-targeted Chimeric Antigen Receptor (CAR) T‑cell product candidate and a second-generation tumor infiltrating lymphocyte (TIL) product candidate, are in preclinical development. LYL797 – A ROR1-targeted CAR T-cell product candidate genetically reprogrammed to overexpress c-Jun and epigenetically reprogrammed using Lyell’s proprietary Epi-R™ manufacturing protocol designed for differentiated potency and durability Enrollment in the Phase 1 clinical trial of LYL797 is ongoing. The study includes patients with relapsed or refractory triple-negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC). Initial data from at least 20 patients from the Phase 1 clinical trial of LYL797 are expected this quarter. LYL845 – A TIL product candidate epigenetically reprogrammed using Lyell’s proprietary Epi-R manufacturing protocol, designed for differentiated potency and durability Enrollment in the Phase 1 clinical trial of LYL845 is ongoing. The study includes patients with relapsed or refractory metastatic or locally advanced melanoma, NSCLC and colorectal cancer. Initial clinical and translational data from the Phase 1 trial of LYL845 are expected in the second half of 2024. LYL119 – A ROR1-targeted CAR T-cell product candidate incorporating Lyell’s four stackable and complementary reprogramming technologies designed for enhanced cytotoxicity LYL119 is a ROR1-targeted CAR T-cell product enhanced with Lyell’s four novel genetic and epigenetic reprogramming technologies: c-Jun overexpression, NR4A3 knockout, Epi-R manufacturing protocol and Stim‑R™ T-cell activation technology. An investigational new drug (IND) application for LYL119 is expected to be submitted this quarter. Presented a poster with new nonclinical data on LYL119 at the American Association for Cancer Research (AACR) Annual Meeting 2024. In this study, LYL119, compared to ROR1 CAR T cells reprogrammed with only two or three technologies, demonstrated reduced CAR T‑cell exhaustion, enhanced CAR T‑cell function, enhanced proliferation capacity and sustained antitumor activity in a mouse xenograft tumor model across a 10-fold dose range, including at very low cell doses. In addition, following repeated rounds of tumor cell killing, LYL119 displayed reduced expression of exhaustion-related gene signatures and retained unique cell subsets characterized by upregulation of memory and effector-associated gene signatures. First Quarter Financial Results Lyell reported a net loss of $60.7 million for the first quarter ended March 31, 2024, compared to a net loss of $67.0 million for the same period in 2023. Non‑GAAP net loss, which excludes non-cash stock-based compensation, non‑cash expenses related to the change in the estimated fair value of success payment liabilities and certain non-cash investment gains and charges, was $37.5 million for the first quarter ended March 31, 2024, compared to $44.8 million for the same period in 2023. GAAP and Non-GAAP Operating Expenses Research and development (R&D) expenses were $43.2 million for the first quarter ended March 31, 2024, compared to $44.6 million for the same period in 2023. The decrease in first quarter 2024 R&D expenses of $1.5 million was primarily driven by a decrease in personnel-related expenses associated with Lyell’s November 2023 reduction in workforce. Non‑GAAP R&D expenses, which exclude non-cash stock-based compensation and non-cash expenses related to the change in the estimated fair value of success payment liabilities for the first quarter ended March 31, 2024, were $38.9 million, compared to $40.6 million for the same period in 2023. The decrease in first quarter 2024 non-GAAP R&D expenses was primarily driven by a decrease in personnel-related expenses. General and administrative (G&A) expenses were $13.5 million for the first quarter ended March 31, 2024, compared to $19.3 million for the same period in 2023. The decrease in first quarter 2024 G&A expenses was primarily driven by decreases in non-cash stock-based compensation. Non‑GAAP G&A expenses, which exclude non-cash stock‑based compensation, for the first quarter ended March 31, 2024, were $8.1 million, compared to $10.0 million for the same period in 2023. The decrease in 2024 non-GAAP G&A expenses was primarily driven by a decrease in personnel-related expenses associated with Lyell’s November 2023 reduction in workforce. A discussion of non-GAAP financial measures, including reconciliations of the most comparable GAAP measures to non‑GAAP financial measures, is presented below under “Non-GAAP Financial Measures.” Cash, cash equivalents and marketable securities Cash, cash equivalents and marketable securities as of March 31, 2024, were $526.3 million, compared to $562.7 million as of December 31, 2023. Lyell believes that its cash, cash equivalents and marketable securities balances will be sufficient to meet working capital and capital expenditure needs into 2027. About Lyell Immunopharma, Inc. Lyell is a clinical-stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors. Lyell is currently enrolling a Phase 1 clinical trial evaluating a ROR1-targeted CAR T-cell therapy in patients with relapsed refractory triple-negative breast cancer and non-small cell lung cancer (NSCLC) and a second Phase 1 clinical trial evaluating reprogrammed tumor infiltrating lymphocytes (TIL) in patients with advanced melanoma, NSCLC and colorectal cancer. The technologies powering its product candidates are designed to address barriers that limit consistent and long-lasting responses to cell therapy for solid tumors: T-cell exhaustion and lack of durable stemness, which includes the ability to persist and self-renew to drive durable tumor cytotoxicity. Lyell is applying its proprietary ex vivo genetic and epigenetic reprogramming technologies to address these barriers in order to develop new medicines with improved durable clinical outcomes. Lyell is based in South San Francisco, California with facilities in Seattle and Bothell, Washington. To learn more, please visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding: Lyell’s anticipated progress, business plans, business strategy and clinical trials; Lyell’s advancement of its pipeline and its research, development and clinical capabilities; the potential clinical benefits and therapeutic potential of Lyell’s product candidates; the advancement of Lyell’s technology platform; Lyell’s expectation that its financial position and cash runway will support advancement of its pipeline through multiple clinical milestones into 2027; Lyell’s plans to submit an IND for LYL119 and the timing thereof; expectations around enrollment and the timing of initial clinical and translational data from Lyell’s Phase 1 trials for LYL797 and LYL845; and other statements that are not historical fact. These statements are based on Lyell’s current plans, objectives, estimates, expectations and intentions, are not guarantees of future performance and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, but are not limited to, risks and uncertainties related to: the effects of geopolitical instability; macroeconomic conditions, including actual or perceived changes in interest rates and economic inflation; Lyell’s ability to submit planned INDs or initiate or progress clinical trials on the anticipated timelines, if at all; Lyell’s limited experience as a company in enrolling and conducting clinical trials, and lack of experience in completing clinical trials; Lyell’s ability to manufacture and supply its product candidates for its clinical trials; the nonclinical profiles of Lyell’s product candidates or technology not translating in clinical trials; the potential for results from clinical trials to differ from nonclinical, early clinical, preliminary or expected results; significant adverse events, toxicities or other undesirable side effects associated with Lyell’s product candidates; the significant uncertainty associated with Lyell’s product candidates ever receiving any regulatory approvals; Lyell’s ability to obtain, maintain or protect intellectual property rights related to its product candidates; implementation of Lyell’s strategic plans for its business and product candidates; the sufficiency of Lyell’s capital resources and need for additional capital to achieve its goals; anticipated benefits and financial impact of Lyell’s workforce restructuring; and other risks, including those described under the heading “Risk Factors” in Lyell’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the Securities and Exchange Commission (SEC) on February 28, 2024, and the Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, being filed with the SEC today. Forward-looking statements contained in this press release are made as of this date, and Lyell undertakes no duty to update such information except as required under applicable law. Lyell Immunopharma, Inc. Unaudited Selected Consolidated Financial Data (in thousands) Statement of Operations Data: Three Months Ended March 31, 2024 2023 Revenue $ 3 $ 65 Operating expenses: Research and development(1) 43,174 44,630 General and administrative 13,494 19,279 Other operating income, net (1,090 ) (1,288 ) Total operating expenses 55,578 62,621 Loss from operations (55,575 ) (62,556 ) Interest income, net 6,819 4,497 Other income, net(1) 1,090 1,100 Impairment of other investments (13,001 ) (10,000 ) Total other loss, net (5,092 ) (4,403 ) Net loss $ (60,667 ) $ (66,959 ) (1) Lyell’s success payment liability was recognized at fair value as Fred Hutch had provided the requisite service obligation to earn the potential success payment consideration under the continued collaboration. The change in the estimated fair value of Fred Hutch success payment liabilities beginning in Q1 2023 was recognized within other income, net in the unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss. Balance Sheet Data: As of March 31, 2024 As of December 31, 2023 Cash, cash equivalents and marketable securities $ 526,300 $ 562,729 Property and equipment, net $ 97,836 $ 102,654 Total assets $ 694,220 $ 750,029 Total stockholders’ equity $ 603,157 $ 654,952 Non-GAAP Financial Measures To supplement our financial results and guidance presented in accordance with U.S. generally accepted accounting principles (GAAP), we present non-GAAP net loss, non-GAAP R&D expenses and non-GAAP G&A expenses. Non‑GAAP net loss and non-GAAP R&D expenses exclude non-cash stock-based compensation expense and non-cash expenses related to the change in the estimated fair value of success payment liabilities from GAAP net loss and GAAP R&D expenses. Non-GAAP net loss further adjusts non‑cash investment gains and charges, as applicable. Non‑GAAP G&A expenses exclude non-cash stock-based compensation expense from GAAP G&A expenses. We believe that these non-GAAP financial measures, when considered together with our financial information prepared in accordance with GAAP, can enhance investors’ and analysts’ ability to meaningfully compare our results from period to period, and to identify operating trends in our business. We have excluded stock-based compensation expense, changes in the estimated fair value of success payment liabilities and non-cash investment gains and charges from our non‑GAAP financial measures because they are non-cash gains and charges that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. We also regularly use these non-GAAP financial measures internally to understand, manage and evaluate our business and to make operating decisions. These non-GAAP financial measures are in addition to, and not a substitute for or superior to, measures of financial performance prepared in accordance with GAAP. In addition, these non-GAAP financial measures have no standardized meaning prescribed by GAAP and are not prepared under any comprehensive set of accounting rules or principles and, therefore, have limits in their usefulness to investors. We encourage investors to carefully consider our results under GAAP, as well as our supplemental non-GAAP financial information, to more fully understand our business. Lyell Immunopharma, Inc. Unaudited Reconciliation of GAAP to Non-GAAP Net Loss (in thousands) Three Months Ended March 31, 2024 2023 Net loss - GAAP $ (60,667 ) $ (66,959 ) Adjustments: Impairment of other investments 13,001 10,000 Stock-based compensation expense 9,155 13,882 Change in the estimated fair value of success payment liabilities 968 (1,708 ) Net loss - Non-GAAP(1) $ (37,543 ) $ (44,785 ) (1) There was no income tax effect related to the adjustments made to calculate non-GAAP net loss because of the full valuation allowance on our net U.S. deferred tax assets for all periods presented. Lyell Immunopharma, Inc. Unaudited Reconciliation of GAAP to Non-GAAP Research and Development Expenses (in thousands) Three Months Ended March 31, 2024 2023 Research and development - GAAP $ 43,174 $ 44,630 Adjustments: Stock-based compensation expense (3,792 ) (4,612 ) Change in the estimated fair value of success payment liabilities(1) (525 ) 608 Research and development - Non-GAAP $ 38,857 $ 40,626 (1) Lyell’s success payment liability was recognized at fair value as Fred Hutch had provided the requisite service obligation to earn the potential success payment consideration under the continued collaboration. The change in the estimated fair value of Fred Hutch success payment liabilities beginning in Q1 2023 was recognized within other income, net in the unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss. Lyell Immunopharma, Inc. Unaudited Reconciliation of GAAP to Non-GAAP General and Administrative Expenses (in thousands) Three Months Ended March 31, 2024 2023 General and administrative - GAAP $ 13,494 $ 19,279 Adjustments: Stock-based compensation expense (5,363 ) (9,270 ) General and administrative - Non-GAAP $ 8,131 $ 10,009 Contact: Ellen Rose Senior Vice President, Communications and Investor Relations erose@lyell.com