Summary of Lyell Immunopharma Conference Call Company Overview - **Company**: Lyell Immunopharma (NasdaqGS:LYEL) - **Focus**: Development of next-generation CAR T cell therapies for cancer, including hematologic malignancies and solid tumors [6][7] Key Industry Insights - **Acquisition**: Lyell has acquired exclusive global rights to a novel CAR T cell product candidate, LYLE-273, in clinical development for metastatic colorectal cancer [3][7] - **Market Potential**: Colorectal cancer is the second leading cause of cancer death globally, with a market projected to grow from $6 billion to $12 billion by 2032 [12] - **Clinical Need**: Current therapies for metastatic colorectal cancer have poor outcomes, with overall response rates of less than 6% and median overall survival of less than 12 months [13][20] Clinical Data Highlights - **Phase One Trial Results**: - LYLE-273 showed a 67% overall response rate and an 83% disease control rate in patients with refractory metastatic colorectal cancer [10][20] - The median overall survival was 17 months at dose level one, with data not yet reached at dose level two [31] - The trial included patients who had received 2-6 prior lines of therapy, indicating a high-risk population [25][26] Mechanism of Action - **Target**: Guanylyl cyclase C (GCC) is expressed in 95% of colorectal cancers, making it a promising target for CAR T cell therapy [11][22] - **Enhancements**: LYLE-273 is designed with CD19 CAR expression and controlled cytokine release to improve T cell expansion and infiltration into tumors [22][39] - **Safety Profile**: The therapy has a manageable safety profile, with adverse events primarily including grade one or two cytokine release syndrome (CRS) and diarrhea [27][30] Strategic Rationale - **Pipeline Expansion**: The acquisition of LYLE-273 strengthens Lyell's pipeline in oncology, particularly in solid tumors, which represent over 90% of all cancers [7][47] - **Future Development**: There is potential to explore LYLE-273 in earlier lines of therapy and other GCC-expressing tumors, such as pancreatic cancer [62][76] Financial Terms of Acquisition - **Payment Structure**: ICT received $40 million and 1.9 million shares of Lyell stock, with additional payments based on clinical, regulatory, and commercial milestones [11][47] Future Outlook - **Clinical Trials**: Enrollment in the phase one trial of LYLE-273 continues, with further data expected in 2026 [36][52] - **Manufacturing Capacity**: Lyell operates a manufacturing facility capable of producing over 1,200 doses annually, supporting both clinical and early commercial needs [52] Conclusion - **Optimism for Impact**: The promising initial clinical data for LYLE-273 positions Lyell favorably in the competitive landscape of colorectal cancer therapies, with a focus on delivering significant clinical benefits to patients [52][70]

Lyell Strengthens Next-Generation CAR T-Cell Pipeline with Novel GCC-Targeted Product Candidate for Metastatic Colorectal Cancer Lyell Immunopharma November 10, 2025 Forward Looking Statements Certain matters discussed in this presentation are "forward-looking statements" of Lyell Immunopharma, Inc. (hereinafter referred to as the "Company," "we," "us," or "our") within the meaning of the Private Securities Litigation Reform Act of 1995 (the "PSLRA"). All such written or oral statements made in this present ...

Core Insights - Lyell Immunopharma has acquired global rights to LYL273, a novel CAR T-cell therapy targeting guanylyl cyclase-C (GCC) for metastatic colorectal cancer (mCRC) and other GCC-expressing cancers, enhancing its solid tumor pipeline [1][9] - In a Phase 1 clinical trial, LYL273 demonstrated a 67% overall response rate and an 83% disease control rate in patients with refractory mCRC, indicating promising efficacy and a manageable safety profile [1][4][5] - The acquisition includes an upfront payment of $40 million and potential milestone payments totaling up to $675 million, along with royalties on future net sales [9] Company Developments - The Phase 1 clinical trial data showed that at the highest dose level, 67% of patients achieved an overall response, with one patient experiencing a pathological complete response [4][5] - The treatment-related adverse events were more common at the higher dose level, with cytokine release syndrome occurring in 83% of patients [5][6] - Lyell expects its cash resources to be sufficient to fund operations into 2027, supported by ongoing clinical trials and prudent expense management [10][11] Industry Context - Colorectal cancer is the second leading cause of cancer deaths globally, with a rising incidence among individuals under 55 years old, highlighting the urgent need for innovative therapies like LYL273 [2][7] - The Fast Track designation granted by the U.S. FDA for LYL273 underscores its potential as a significant advancement in treating mCRC, an area with substantial unmet medical needs [7]

Core Insights - Lyell Immunopharma, Inc. is advancing a pipeline of next-generation CAR T-cell therapies, specifically focusing on rondecabtagene autoleucel (ronde-cel) for aggressive large B-cell lymphoma (LBCL) [1][8] - Ronde-cel has received FDA designations as Regenerative Medicine Advanced Therapy (RMAT) and Fast Track for treating relapsed and/or refractory diffuse LBCL in later lines of therapy [1][8] Clinical Data Presentation - New clinical and translational data from the Phase 1/2 trial of ronde-cel will be presented at the 67th American Society of Hematology (ASH) Annual Meeting, highlighting high overall response and complete response rates in high-risk LBCL patients [2][3] - The ongoing PiNACLE trial continues to enroll patients with LBCL in the third- or later-line setting, and a randomized controlled trial comparing ronde-cel to an approved CD19 CAR T-cell therapy is set to begin in the second-line setting [2] Manufacturing and Technology - Ronde-cel is manufactured using a process that enriches for CD62L-positive cells, resulting in enhanced naïve and central memory CAR T cells with improved antitumor activity [4][8] - The Lyell LyFE Manufacturing Center™ has the capacity to produce over 1,200 CAR T-cell doses at full capacity, supporting both ongoing and future clinical trials [8]

Summary of Lyell Immunopharma FY Conference Call Company Overview - **Company**: Lyell Immunopharma (NasdaqGS:LYEL) - **Focus**: Clinical stage oncology company specializing in next-generation cell therapy for cancer, targeting both hematologic malignancies and solid tumors [3][4] Key Initiatives and Pipeline - **Lead Program**: RondaCell, a dual-targeting CD19/20 CAR T cell therapy for relapsed and refractory aggressive large B-cell lymphoma [3][4] - **Clinical Trials**: - Pivotal single-arm study for third-line treatment underway - Phase 3 randomized head-to-head trial launched for second-line treatment [3][4] Competitive Landscape - **RondaCell vs. Existing Therapies**: - RondaCell shows an 88% overall response rate and a 70% complete response rate in patients with relapsed disease, compared to 70% and 50% respectively for currently approved CD19 CARs [4][5] - Duration of complete response is emphasized as a critical metric for success [8][12] Data and Efficacy - **Response Rates**: - RondaCell's complete response rate at six months is 71%, significantly higher than Yescarta's 40% [8][12] - The company aims to demonstrate superior efficacy in harder-to-treat patient populations [10][12] Safety Profile - **Safety Data**: - RondaCell shows lower rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) compared to competitors [16] - 47% to 57% CRS rates for RondaCell versus 80% for Kite/Gilead products [16] Market Potential - **Market Disruption**: - The emergence of CD19/CD20 CAR therapies is expected to disrupt the existing CD19 CAR market, with potential for significant market share capture [17][18] - The company is confident in its product profile and aims to position RondaCell as a best-in-class therapy [18] Trial Design and Regulatory Path - **Pivotal Trials**: - Two pivotal trials are ongoing, with the third-line study being a single-arm study and the second-line study designed as a head-to-head trial against Yescarta and Breyanzi [19][22] - Primary endpoint for the second-line trial is event-free survival [23] Commercial Strategy - **Self-Sufficiency**: - The company believes it can independently commercialize RondaCell, with a manufacturing capacity of up to 1,200 doses per year [27][28] - Open to strategic partnerships but not urgent due to current capital and manufacturing capabilities [28] Future Outlook - **Data Readouts**: - Significant data updates expected by the end of the year for both third-line and second-line trials [30] - Continued data flow anticipated, with a focus on maturing trial results [30][31] Conclusion - Lyell Immunopharma is positioned to potentially redefine treatment paradigms in large B-cell lymphoma with RondaCell, leveraging strong clinical data, a favorable safety profile, and a strategic approach to market entry and commercialization [3][4][18]

Summary of Lyell Immunopharma FY Conference Call Company Overview - **Company**: Lyell Immunopharma (NasdaqGS:LYEL) - **Industry**: Biotechnology, specifically focused on oncology and CAR T cell therapy - **Key Product**: RONDACELL, a dual-targeting CD19/CD20 CAR T cell therapy for aggressive relapse refractory large B-cell lymphoma [2][3] Core Points and Arguments - **Clinical Focus**: Lyell Immunopharma is dedicated to developing next-generation CAR T cell therapies for both hematologic malignancies and solid tumors [2] - **Lead Program**: RONDACELL is currently in pivotal clinical trials, including a single-arm trial in the third-line setting and a randomized controlled trial in the second-line setting [2][6] - **Unique Selling Proposition**: - RONDACELL targets both CD19 and CD20, reducing the chance of antigen escape and increasing the likelihood of complete responses [3][4] - The manufacturing process selects for naïve T cells, which are believed to provide better durability and response rates [4][28] - **Trial Design**: The second-line trial, known as Pinnacle head-to-head, will compare RONDACELL against existing therapies (axicabtagene ciloleucel or Breyanzi) with a primary endpoint of event-free survival [7][9] Key Data and Expectations - **Response Rates**: Recent data showed an 88% overall response rate and a 72% complete response rate in the third-line setting, significantly better than existing CD19 CAR therapies [15][16] - **Enrollment Plans**: The company plans to enroll 200 patients per arm in the head-to-head trial, with expectations to begin patient enrollment by early 2026 [9][10] - **Market Opportunity**: Approximately 30,000 patients in the U.S. with DLBCL, with about 12,000 progressing to second-line therapy, representing a significant market potential [24] Financials and Funding - **Cash Position**: Lyell has $347 million in cash, sufficient to support operations through mid-2027, although additional funding will be needed for the second-line pivotal study [48][50] - **Recent Financing**: A recent PIPE financing raised up to $100 million, with structured tranches based on performance milestones [51] Competitive Landscape - **Market Share**: Yescarta holds about 52% of the market share in the CD19 CAR T space, with Breyanzi slightly behind [23] - **Competitive Edge**: Lyell believes its dual-targeting approach and safety profile will allow it to capture market share from existing therapies [38][39] - **Intellectual Property**: The company claims a dominant IP position dating back to 2014, which is crucial for maintaining competitive advantage [44] Safety and Manufacturing - **Safety Profile**: RONDACELL has shown a favorable safety profile, with lower rates of cytokine release syndrome (CRS) and neurotoxicity compared to competitors [30][32] - **Manufacturing Capacity**: The Bothell, Washington facility can produce approximately 1,200 doses per year, supporting both clinical and potential commercial needs [33] Future Directions - **Solid Tumor Program**: Lyell is developing a solid tumor CAR T therapy, with an IND submission planned for 2026 [45] - **AI Utilization**: The company is exploring AI applications primarily in R&D to enhance efficiency and effectiveness [56][58] Regulatory Environment - **Focus on FDA**: The company is closely monitoring FDA regulations as it prepares for pivotal trials and BLA submissions [59][60] Conclusion Lyell Immunopharma is positioned to disrupt the CAR T cell therapy market with its innovative dual-targeting approach, strong clinical data, and robust manufacturing capabilities, while also navigating a competitive landscape and regulatory challenges effectively.

Core Viewpoint - Lyell Immunopharma has initiated the PiNACLE - H2H Phase 3 trial to evaluate its dual-targeting CAR T-cell therapy, rondecabtagene autoleucel (ronde-cel), against existing CD19-targeting therapies for relapsed or refractory large B-cell lymphoma [1][10] Group 1: Trial Details - The PiNACLE - H2H trial is a head-to-head randomized controlled trial comparing ronde-cel to either lisocabtagene maraleucel (liso-cel) or axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory large B-cell lymphoma [1][10] - The trial aims to enroll approximately 400 patients and will assess event-free survival as the primary endpoint [10] - Ronde-cel is designed to target B cells expressing either CD19, CD20, or both, with a focus on improving complete response rates and duration of responses compared to existing therapies [5][6] Group 2: Product Information - Ronde-cel has received Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations from the FDA for the treatment of patients with relapsed or refractory large B-cell lymphoma [7] - The manufacturing process of ronde-cel aims to produce a higher proportion of naïve and central memory T cells, enhancing its antitumor activity [6][8] - The company is also conducting a single-arm pivotal trial (PiNACLE) for ronde-cel in the third-line or later setting, expected to enroll around 120 patients [10] Group 3: Expert Collaboration - A Steering Committee of distinguished lymphoma experts has been established to guide the trial's design and execution [2][3] - Experts involved include members from prominent institutions such as the University of Chicago and the Moffitt Cancer Center [4][10] - The collaboration aims to provide robust clinical data to support the potential benefits of ronde-cel over existing therapies [2][3]

[Special Note Regarding Forward-Looking Statements](index=5&type=section&id=Special%20Note%20Regarding%20Forward-Looking%20Statements) This section highlights forward-looking statements in the 10-Q report, subject to risks and uncertainties that could cause actual results to differ materially [Overview of Forward-Looking Statements](index=5&type=section&id=Overview%20of%20Forward-Looking%20Statements) This section highlights forward-looking statements in the 10-Q report, subject to risks and uncertainties that could cause actual results to differ materially - The report contains forward-looking statements about future results, financial position, business strategy, product candidates, clinical trials, R&D costs, regulatory approvals, and commercialization plans[12](index=12&type=chunk) - These statements involve known and unknown risks, uncertainties, and other important factors that may cause actual results to be materially different from those expressed or implied[12](index=12&type=chunk) - Key forward-looking statements include the sufficiency of cash to fund operations, accuracy of expense estimates, scope and results of LYL314 development, timing of regulatory approvals, commercialization plans, market opportunities, reliance on third parties, and intellectual property protection[13](index=13&type=chunk)[16](index=16&type=chunk) [PART I—FINANCIAL INFORMATION](index=7&type=section&id=PART%20I%E2%80%94FINANCIAL%20INFORMATION) This part presents the unaudited condensed consolidated financial statements and management's discussion and analysis [Item 1. Financial Statements (unaudited)](index=7&type=section&id=Item%201.%20Financial%20Statements%20(unaudited)) This section presents Lyell Immunopharma's unaudited condensed consolidated financial statements, including balance sheets, operations, equity, cash flows, and detailed notes [Condensed Consolidated Balance Sheets](index=7&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) Balance sheets show decreased total assets and equity from December 2024 to June 2025, due to reduced marketable securities and increased accumulated deficit Balance Sheet Summary (in thousands) | ASSETS (in thousands) | June 30, 2025 | December 31, 2024 | | :---------------------- | :------------ | :---------------- | | Cash and cash equivalents | $98,804 | $105,597 | | Marketable securities | $177,986 | $264,930 | | Total current assets | $282,214 | $379,594 | | Total assets | $385,453 | $490,859 | | LIABILITIES AND STOCKHOLDERS' EQUITY (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------------------------------------- | :------------ | :---------------- | | Total current liabilities | $36,903 | $53,788 | | Total liabilities | $86,530 | $108,035 | | Total stockholders' equity | $298,923 | $382,824 | | Accumulated deficit | $(1,439,985) | $(1,345,106) | - Total assets decreased by approximately **$105.4 million** from December 31, 2024, to June 30, 2025, primarily due to a reduction in marketable securities[19](index=19&type=chunk) - Total stockholders' equity decreased by approximately **$83.9 million**, largely driven by an increase in accumulated deficit[19](index=19&type=chunk) [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) The company reported a reduced net loss for Q2 and YTD June 2025, driven by lower operating expenses and increased other income, net Statements of Operations and Comprehensive Loss Summary (in thousands, except per share amounts) | (in thousands, except per share amounts) | 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 | | Research and development | $34,857 | $40,261 | $78,304 | $83,435 | | General and administrative | $9,786 | $12,256 | $23,832 | $25,750 |\ | Total operating expenses | $47,148 | $51,541 | $104,522 | $107,119 | | Net loss | $(42,684) | $(45,809) | $(94,879) | $(106,476) | | Net loss per common share, basic and diluted | $(2.89) | $(3.59) | $(6.42) | $(8.36) | - Net loss for the three months ended June 30, 2025, was **$(42.7) million**, a decrease from $(45.8) million in the prior year period[24](index=24&type=chunk) - Net loss for the six months ended June 30, 2025, was **$(94.9) million**, an improvement from $(106.5) million in the prior year period, driven by lower operating expenses and higher other income, net[24](index=24&type=chunk) [Condensed Consolidated Statements of Stockholders' Equity](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders'%20Equity) Stockholders' equity decreased from December 2024 to June 2025 due to net loss, partially offset by stock-based compensation; a 1-for-20 reverse stock split was effected Stockholders' Equity Summary (in thousands) | (in thousands) | Balance as of Dec 31, 2024 | Net Loss | Stock-based Compensation | Issuance of Common Stock | Balance as of Jun 30, 2025 | | :------------- | :------------------------- | :------- | :----------------------- | :----------------------- | :------------------------- | | Total Stockholders' Equity | $382,824 | $(94,879) | $11,028 | $184 | $298,923 | - Total stockholders' equity decreased from **$382.8 million** at December 31, 2024, to **$298.9 million** at June 30, 2025[27](index=27&type=chunk) - The company effected a **1-for-20 reverse stock split** on May 30, 2025, retroactively adjusting all historical per share data and share counts[41](index=41&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=12&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities increased for the six months ended June 30, 2025, while cash provided by investing activities also increased due to marketable securities maturities Cash Flows Summary (in thousands) | (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------- | :----------------------------- | :----------------------------- |\ | Operating activities | $(89,196) | $(80,110) | | Investing activities | $82,113 | $67,001 | | Financing activities | $184 | $889 | | Net decrease in cash, cash equivalents and restricted cash | $(6,899) | $(12,220) | | Cash, cash equivalents and restricted cash at end of period | $100,388 | $133,711 | - Net cash used in operating activities was **$89.2 million** for the six months ended June 30, 2025, compared to $80.1 million in the prior year, reflecting a higher net loss and a decrease in accrued liabilities[188](index=188&type=chunk)[189](index=189&type=chunk) - Net cash provided by investing activities increased to **$82.1 million** in 2025 from $67.0 million in 2024, primarily due to net maturities and purchases of marketable securities[190](index=190&type=chunk) [Notes to Unaudited Condensed Consolidated Financial Statements](index=14&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) The notes provide detailed explanations of the company's financial statements, covering organization, accounting policies, contingent liabilities, and recent events [1. Organization](index=14&type=section&id=1.%20Organization) Lyell Immunopharma is a late-stage clinical cell therapy company developing next-generation autologous CAR T-cell product candidates for hematologic malignancies and solid tumors, with LYL314 as its lead - Lyell Immunopharma, Inc. is a late-stage clinical cell therapy company developing proprietary next-generation autologous CAR T-cell product candidates[37](index=37&type=chunk) - The lead product candidate, LYL314, is a dual-targeting CD19/CD20 CAR T-cell therapy in a pivotal clinical trial for large B-cell lymphoma (3L+) and a Phase 1/2 study (2L)[37](index=37&type=chunk) [2. Summary of Significant Accounting Policies](index=14&type=section&id=2.%20Summary%20of%20Significant%20Accounting%20Policies) This section outlines the basis of presentation for the unaudited condensed consolidated financial statements, detailing the 1-for-20 reverse stock split and affirming liquidity for the next 12 months - The company effected a **1-

[Business Overview and Recent Highlights](index=1&type=section&id=Business%20Overview%20and%20Recent%20Highlights) 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](index=1&type=section&id=Company%20Introduction%20and%20Strategic%20Vision) 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](index=2&type=chunk) - **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](index=3&type=chunk) - 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](index=3&type=chunk) [LYL314 Clinical Program Updates](index=1&type=section&id=LYL314%20Clinical%20Program%20Updates) 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](index=5&type=chunk) - **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](index=5&type=chunk) - 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](index=3&type=chunk)[6](index=6&type=chunk) [PiNACLE Pivotal Trial (3L+ LBCL)](index=1&type=section&id=PiNACLE%20Pivotal%20Trial%20(3L%2B%20LBCL)) 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](index=5&type=chunk)[7](index=7&type=chunk) - The primary endpoint of the PiNACLE trial is the overall response rate, including an evaluation of duration of response[7](index=7&type=chunk) - 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](index=10&type=chunk) [Phase 1/2 Trial (2L LBCL) & Future Plans](index=1&type=section&id=Phase%201/2%20Trial%20(2L%20LBCL)%20%26%20Future%20Plans) 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](index=5&type=chunk)[10](index=10&type=chunk) - 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](index=10&type=chunk) [Regulatory Designations](index=1&type=section&id=Regulatory%20Designations) 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](index=5&type=chunk) [Clinical Data Presentation Highlights](index=1&type=section&id=Clinical%20Data%20Presentation%20Highlights) 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](index=6&type=chunk)[10](index=10&type=chunk) 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](index=10&type=chunk) [Preclinical Pipeline and Technology](index=2&type=section&id=Preclinical%20Pipeline%20and%20Technology) 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](index=8&type=chunk) - The first IND for a fully-armed CAR T-cell product candidate with an undisclosed target for solid tumors is expected in **2026**[8](index=8&type=chunk) [Corporate and Financial Updates](index=2&type=section&id=Corporate%20and%20Financial%20Updates) This section details recent corporate developments, including a private placement and cash runway extension, alongside the second quarter 2025 financial performance [Corporate Developments](index=2&type=section&id=Corporate%20Developments) 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](index=6&type=chunk)[9](index=9&type=chunk) - 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](index=11&type=chunk) [Private Placement](index=2&type=section&id=Private%20Placement) 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](index=9&type=chunk) - The initial closing of approximately **$50 million** of common stock at a price of **$13.32 per share** occurred on **July 25, 2025**[9](index=9&type=chunk) [Cash Position and Runway](index=1&type=section&id=Cash%20Position%20and%20Runway) 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](index=6&type=chunk)[14](index=14&type=chunk) [Second Quarter 2025 Financial Results](index=3&type=section&id=Second%20Quarter%202025%20Financial%20Results) 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](index=12&type=chunk) - 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](index=12&type=chunk) [GAAP Net Loss](index=3&type=section&id=GAAP%20Net%20Loss) 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](index=12&type=chunk) [GAAP Operating Expenses](index=3&type=section&id=GAAP%20Operating%20Expenses) 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](index=17&type=chunk) - 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](index=17&type=chunk) [Company Information and Outlook](index=3&type=section&id=Company%20Information%20and%20Outlook) 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.](index=3&type=section&id=About%20Lyell%20Immunopharma,%20Inc.) 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](index=15&type=chunk) - 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](index=15&type=chunk) - The Lyell LyFE Manufacturing Center™ has commercial launch capability and can manufacture more than **1,200 CAR T-cell doses** at full capacity[15](index=15&type=chunk) [Forward-Looking Statements](index=3&type=section&id=Forward-Looking%20Statements) 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](index=16&type=chunk)[18](index=18&type=chunk) - Lyell expects its financial position and cash runway to support advancement of its pipeline into **mid-2027** through key clinical milestones[18](index=18&type=chunk) - 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](index=18&type=chunk) [Unaudited Selected Consolidated Financial Data](index=5&type=section&id=Unaudited%20Selected%20Consolidated%20Financial%20Data) 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](index=5&type=section&id=Statement%20of%20Operations%20Data) 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](index=5&type=section&id=Balance%20Sheet%20Data) 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](index=6&type=section&id=Non-GAAP%20Financial%20Measures%20and%20Reconciliations) 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](index=22&type=chunk) - 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](index=22&type=chunk) [Non-GAAP Net Loss Reconciliation](index=6&type=section&id=Non-GAAP%20Net%20Loss%20Reconciliation) 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](index=7&type=section&id=Non-GAAP%20Research%20and%20Development%20Expenses%20Reconciliation) 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](index=7&type=section&id=Non-GAAP%20General%20and%20Administrative%20Expenses%20Reconciliation) 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 |

Core Viewpoint - Lyell Immunopharma is advancing its lead CAR T-cell therapy, LYL314, which targets relapsed and/or refractory large B-cell lymphoma, showing promising clinical results and securing funding to support its development through mid-2027 [2][5][11]. Financial Results - For Q2 2025, Lyell reported a net loss of $42.7 million, a decrease from a net loss of $45.8 million in Q2 2024, primarily due to reduced stock-based compensation expenses [11][15]. - Cash, cash equivalents, and marketable securities as of June 30, 2025, were approximately $297 million, down from $384 million at the end of 2024, but expected to be sufficient to support operations into mid-2027 [13][19]. Clinical Development - LYL314 is currently in the pivotal PiNACLE trial for patients with relapsed and/or refractory large B-cell lymphoma in the third-line or later setting, with plans to initiate a second pivotal trial for the second-line setting by early 2026 [2][4][9]. - The Phase 1/2 trial data presented showed an overall response rate of 88% in the 3L+ cohort and 91% in the 2L cohort, with complete response rates of 72% and 64%, respectively [9]. Business Highlights - The company completed a private placement for gross proceeds of up to approximately $100 million, which will extend its cash runway and support the advancement of its clinical programs [5][8]. - LYL314 has received Regenerative Medicine Advanced Therapy (RMAT) and Fast Track designations from the FDA, facilitating more frequent communication regarding its development [4][9]. Pipeline and Future Plans - Lyell is advancing a pipeline of next-generation CAR T-cell therapies, with plans to submit an Investigational New Drug (IND) application for a solid tumor candidate in 2026 [7][14]. - An update on the progress of the PiNACLE trial is expected in late 2025, with data anticipated to support a Biologics License Application submission to the FDA in 2027 [9].