Lyell Immunopharma, Inc. · NASDAQ:LYEL

Lyell Immunopharma — Investor Presentation (September 2026)

51 slides from Lyell Immunopharma's investor presentation, September 2026

  1. Slide 1: The Future of Cell Therapy — Today

    The Future of Cell Therapy — Today September 2026 ©2026 Lyell Immunopharma, Inc.

  2. Slide 2: Forward-Looking Statements

    Forward-Looking Statements Certain matters discussed in this presentation are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 (the “PSLRA”). All such written or oral statements made in this presentation are forward-looking statements, including

  3. Slide 3: Advancing Next Generation CAR T-Cell Therapies

    Advancing Next Generation CAR T-Cell Therapies Improve outcomes for patients with first-in-class cell therapy innovation for hematologic malignancies and solid tumors CAR, chimeric antigen receptor ©2026 Lyell Immunopharma, Inc. 3

  4. Slide 4: Creating an Industry-Leading Pipeline of Next-Generation CAR T-Cell Therapies

    Creating an Industry-Leading Pipeline of Next-Generation CAR T-Cell Therapies Identify promising targets Arm with enhancements Develop one-time CAR • High tumor expression to designed to improve the T-cell therapies enhance benefit T cell’s ability to fight cancer • Designed to deliver lasting • Low

  5. Slide 5: Lyell Is Well Positioned for Significant Value Creation in the Next 12 to 18 Months

    Lyell Is Well Positioned for Significant Value Creation in the Next 12 to 18 Months Multiple catalysts in multi-billion-dollar markets expected to unlock value Lyell has two potentially first-in-class CAR T-cell programs targeting large markets with significant unmet need • R/R LBCL is a growing $3

  6. Slide 6: Multiple Near-Term Value-Creating Milestones

    Advancing Next Generation CAR T-Cell Therapies Multiple Near-Term Value-Creating Milestones Product Target Target Indications Enhancements Phase 1/2 Pivotal Next Expected Milestones 3L+ Aggressive LBCL • Regenerative Medicine • Additional data from PiNACLE Advanced Therapy pivotal trial in 2H 2026 D

  7. Slide 7: Ronde-Cel for Large B-Cell Lymphoma

    Ronde-Cel for Large B-Cell Lymphoma ©2026 Lyell Immunopharma, Inc. 7

  8. Slide 8: Ronde-Cel is a Dual-Targeting CD19/CD20 CAR T-Cell Product Enriched for Stemlike Phenotype

    Ronde-Cel is a Dual-Targeting CD19/CD20 CAR T-Cell Product Enriched for Stemlike Phenotype (CD62L+ Cells) Ronde-Cel Designed to Achieve High Complete Response Rates and Long Duration of Responses Ronde-cel is a true CD19/CD20 "OR" logic-gated CAR Ronde-cel is manufactured with CD62L enrichment to de

  9. Slide 9: Ronde-Cel is Targeting a Growing Multi-Billion-Dollar Market

    Ronde-Cel is Targeting a Growing Multi-Billion-Dollar Market Ronde-Cel’s Ongoing Clinical Trials Include Patients with Relapsed/Refractory Large B-Cell Lymphoma Projected global sales of currently approved CD19 CAR T-cell products $6 $5 30,000 patients with LBCL in U.S. Worldwide Sales ($bn) $4 ~12,

  10. Slide 10: 3L+ Setting Represents Significant, Underappreciated Opportunity

    3L+ Setting Represents Significant, Underappreciated Opportunity MSKCC and U.S. Medicare Claims Analyses Suggest Substantial Share of 2L Patients May Be 3L+ Memorial Sloan Kettering Medicare Fee-for-Service Retrospective Analysis1 Claims Analysis2 Up to 50% 57% of patients who progress on 1L therapy

  11. Slide 11: Relapsed/Refractory Large B-Cell Lymphoma Third- or Later-Line Setting (3L+)

    Relapsed/Refractory Large B-Cell Lymphoma Third- or Later-Line Setting (3L+) CD19 CAR T-Cell Therapies Have Been Transformative for Patients With LBCL, But Better Therapies Are Needed ©2026 Lyell Immunopharma, Inc. 11

  12. Slide 12: CAR T Treating Physicians Show Historical Willingness to Switch Based on Clinical Data

    CAR T-Cell Therapy Treating Physicians Show Historical Willingness to “Switch” Based on Strength of Clinical Data Differentiated efficacy and safety pivotal data could enable ronde-cel to disrupt LBCL treatment paradigm CD19 CAR T-Cell Therapy Market Share in BCMA CAR T-Cell Therapy Market Share in

  13. Slide 13: Higher Complete Response Rates and Longer Duration of Responses Needed for Patients with LBCL in 3L+

    Higher Complete Response Rates and Longer Duration of Responses Needed for Patients with LBCL in 3L+ Setting Line of Therapy, Overall Complete Median PHASE 1/2 TRIAL Indication, Response Response PFS (Data from ASH 2025) Target Sample Size Rate Rate (months) 3L+, R/R LBCL Ronde-cel CD19/CD20 N = 29

  14. Slide 14: Ronde-Cel Phase 1/2 Trial Multi-Cohort Trial (3L+ LBCL)

    Ronde-Cel Phase 1/2 Trial Multi-Cohort Trial (3L+ LBCL) Patients with Higher-Risk Disease in General Achieve Lower Complete Response Rates Demographics and 3L+ LBCL Patient Population Disease Characteristics N = 37 • Patients with relapsed/refractory DLBCL, PMBCL, 3BFL, and tFL Median (range) age, y

  15. Slide 15: Overall Response Rate of 93% and Complete Response Rate of 76%

    Overall Response Rate of 93% and Complete Response Rate of 76% High Rate of Durable Complete Responses in 3L+ LBCL Cohort Best Overall Response N = 29 (3L+ LBCL) Overall Responses, n (%) 27 (93%) Complete Responses, n (%) 22 (76%) Partial Response, n (%) 5 (17%) Median progression-free survival (mPF

  16. Slide 16: Clinical Trial Design

    Clinical Trial Design A Single-Arm Pivotal Trial in 3L+ CAR T-Cell Naïve Patients; Seamless Expansion of Phase 1/2 Cohort Data readout on track for mid-2027, with BLA submission expected to follow in 2H 2027 Ronde-cel Infusion Enrollment/ Single dose 100 x 106 Leukapheresis CAR T cells Lymphodepleti

  17. Slide 17: Relapse/Refractory Large B-Cell Lymphoma Second-Line Setting (2L)

    Relapse/Refractory Large B-Cell Lymphoma Second-Line Setting (2L) Patient Demographics and Disease Characteristics Impact Outcomes ©2026 Lyell Immunopharma, Inc. 17

  18. Slide 18: Patients with Higher-Risk Disease In General Achieve Lower Complete Response Rates With CD19 CAR T

    Patients with Higher-Risk Disease In General Achieve Lower Complete Response Rates With CD19 CAR T-Cell Therapies Patient Demographics and Disease Characteristics are Critical to Understanding Dataset Outcomes High-risk features in patients with relapsed/refractory LBCL • Primary refractory disease

  19. Slide 19: Higher Complete Response Rates and Longer Duration of Response Needed for Higher-Risk Patients in 2L

    Higher Complete Response Rates and Longer Duration of Response Needed for Higher-Risk Patients with LBCL in 2L Setting Line of Therapy, Overall Complete Median PHASE 1/2 TRIAL Indication Response Response PFS (Data from ASH 2025) Target Sample Size Rate Rate (months) 2L, R/R LBCL Ronde-cel CD19/CD20

  20. Slide 20: High Overall Response Rate in High-Risk Patients with LBCL in 2L Cohort

    High Overall Response Rate in High-Risk Patients with LBCL in 2L Cohort >90% of Patients with Primary Refractory Disease Demographics and 2L Overall Best Overall Response Disease Characteristics N = 24 (2L Overall) N = 18 Median (range) age, years 65 (26, 85) Overall Responses, n (%) 15 (83%) ≥ 75 y

  21. Slide 21: High Overall Response Rate in High-Risk Patients with 2L LBCL Cohort

    High Overall Response Rate in High-Risk Patients with 2L LBCL Cohort High-Risk Characteristics with 94% of Patients with Primary Refractory Disease Data cutoff date: September 5, 2025 (response rates); November 11, 2025 (swimmer plot). Presented at the American Society of Hematology Annual Conferenc

  22. Slide 22: Clinical Trial Design

    Clinical Trial Design Phase 3 Head-to-Head CAR T-Cell Randomized Controlled Trial in 2L LBCL Arm A: Response Assessments: 1:1 Randomization Enrollment & Optional Bridging Ronde-cel Day 28, Month 3, then every 3 months for 18 months Lymphodepletion (200 / arm) Apheresis Therapy Day 28 Month 3 Month 6

  23. Slide 23: Optimized Development Strategy Creates Multiple Catalysts for Potential Near-Term Value Creation

    Optimized Development Strategy Creates Multiple Catalysts for Potential Near-Term Value Creation Ronde-cel clinical development plan Fast-to-Market Leave-No-Doubt Pivotal trial supporting potential for Superiority Trial Design full or accelerated approval in First-of-its kind Phase 3 head-to-head 3L

  24. Slide 24: Ronde-Cel Safety Data

    Ronde-Cel Safety Data ©2026 Lyell Immunopharma, Inc. 24

  25. Slide 25: Lower Rates of High Grade ICANS and CRS Needed to Enable Increased Use of CAR T-Cell Therapy

    Lower Rates of High Grade ICANS and CRS Needed to Enable Increased Use of CAR T-Cell Therapy in Outpatient Setting Line of Therapy, Grade ≥ 3 PHASE 1/2 TRIAL Indication, Cytokine Grade ≥ 3 Neurotoxicity1 (Data from EHA 2026) Target Sample Size Release Syndrome1 3L+ and 2L LBCL Ronde-Cel CD19/CD20 (N

  26. Slide 26: Dexamethasone Prophylaxis Reduced Grade ≥ 3 ICANS

    Dexamethasone Prophylaxis Reduced Grade ≥ 3 ICANS Adverse Events of Interest (3L+ and 2L Cohorts) Adverse Event, n (%) Adverse Event, n (%) No No Prophylaxis Prophylaxis Prophylaxis Prophylaxis N = 44 N = 64 N = 44 N = 64 CRS 30 (68%) 44 (69%) IEC-HS / HLH Grade 1 13 (30%) 36 (56%) Grade 1 or 2 1 (2

  27. Slide 27: Ronde-Cel Expansion Was Robust in Patients With or Without Dexamethasone Prophylaxis

    Ronde-Cel Expansion Was Robust in Patients With or Without Dexamethasone Prophylaxis Higher CAR T-Cell Expansion is Associated with Better CAR T-Cell Response CAR T-Cell Expansion With or Without Dexamethasone Prophylaxis Prophylaxis Median ddPCR Copies/g DNA No Prophylaxis All Patients • No signif

  28. Slide 28: Robust and Scalable Manufacturing for Ronde-Cel

    Robust and Scalable Manufacturing for Ronde-Cel Competitive Median Vein-to-Site Time of 16 Days LyFE Manufacturing CenterTM Built for Scale • State-of-the-art facility in Bothell, Washington designed specifically to enable commercial readiness • > 1,200 CAR T-cell doses/year • Fully electronic syste

  29. Slide 29: Ronde-Cel Well Positioned to Potentially Redefine the Standard of Care for R/R LBCL

    Ronde-Cel Well Positioned to Potentially Redefine the Standard of Care for Relapsed/Refractory Large B-Cell Lymphoma Potential First-in-Class Efficacy Two pivotal trials ongoing Ronde-cel CAR-T cell Improved Safety Robust Profile for Inpatient & Scalable Use, with Potential Manufacturing for Outpati

  30. Slide 30: LYL273 for Metastatic Colorectal Cancer

    LYL273 for Metastatic Colorectal Cancer ©2026 Lyell Immunopharma, Inc. 30

  31. Slide 31: Colorectal Cancer Is the Second Leading Cause of Cancer Deaths Worldwide and a $6+ Billion Market

    Colorectal Cancer Is the Second Leading Cause of Cancer Deaths Worldwide and is a Large and Growing $6+ Billion Market A common cancer that is often diagnosed late: Worldwide Projected Net Sales $Billions (CRC) $14 • Over 150,000 new cases and more than 50,000 deaths expected in the U.S. in 2025 $12

  32. Slide 32: Standard of Care Therapies in 3L+ mCRC Do Not Achieve Meaningful Response Rates or Survival Benefit

    Standard of Care Therapies in 3L+ mCRC Do Not Achieve Meaningful Response Rates or Survival Benefit A Response Rate of > 20% Would Represent a Meaningful Improvement to Current Standard of Care Overall Disease Response Rate Control Rate mPFS mOS Treatment (CR + PR) (CR + PR + SD) (months) (months) L

  33. Slide 33: LYL273, a Potentially Transformative Clinical-Stage Program, in Colorectal Cancer

    LYL273, a Potentially Transformative Clinical-Stage Program, in Colorectal Cancer High response rates and manageable safety profile in relapsed/refractory (R/R) metastatic colorectal cancer (mCRC) LYL273 exhibits significant anti-tumor activity in patients with R/R mCRC with a manageable safety prof

  34. Slide 34: Proof-of-Concept Case Study

    Proof-of-Concept Case Study Compelling Clinical Responses in Chinese Patients Published in JAMA Oncology Led to the Initiation of an FDA-Cleared Clinical Trial in the U.S. • 48-year-old woman diagnosed with mCRC Baseline Month 3 - Surgical resection and four prior lines of chemotx - Multiple courses

  35. Slide 35: LYL273 is a GCC-Targeted CAR T-Cell Product Candidate Armed with Enhancements

    LYL273 is a GCC-Targeted CAR T-Cell Product Candidate Armed with Enhancements to Improve CAR T-Cell Expansion and Cancer Cell Killing Guanylyl Cyclase C (GCC) Arming Technologies CD19 CAR Arming • Jump starts CAR T-cell activation and expansion upon GCC scFv CD19 scFv infusion by engaging B cells Co

  36. Slide 36: Phase 1 Clinical Trial Design

    Phase 1 Clinical Trial Design A Phase 1 Multicenter Trial Evaluating the Safety and Efficacy of LYL273 in Patients with Relapsed/Refractory (R/R) Metastatic Colorectal Cancer (mCRC) Enrollment/ LYL273 Infusion Screening Lymphodepletion Post-infusion DLT Leukapheresis Single day of Flu/Cy monitoring

  37. Slide 37: Baseline Patient Demographics and Disease Characteristics

    Baseline Patient Demographics and Disease Characteristics Dose Level 1 Dose Level 2 Overall Characteristics (N = 6) (N = 6) (N = 12) Age, year Median (range) 46 (39-52) 53 (46-57) 49 (39-57) Sex, n, % Male 3 (50%) 3 (50%) 6 (50%) Female 3 (50%) 3 (50%) 6 (50%) Prior Therapies Median prior lines, n (

  38. Slide 38: Best Overall Response Rates

    Best Overall Response Rates Dose Level 1 Dose Level 2 (1 x 106 CAR T cells/kg) (2 x 106 CAR T cells/kg) Total Best Overall Response N=6 N=6 N = 12 Overall Response Rate n (%) 2 (33%) 4 (67%) 6 (50%) Complete Response 0 1 (17%)* 1 (8%)* Partial Response 2 (33%) 3 (50%) 5 (42%) Stable Disease 3 (50%)

  39. Slide 39: LYL273: High Overall Response Rates in Patients with R/R Metastatic Colorectal Cancer

    LYL273: High Overall Response Rates in Patients with Relapsed/Refractory Metastatic Colorectal Cancer Tumor Reduction: Best Overall Response Swimmer Plot of Each Patient’s Response Pt 09: Censored after receiving radiation to slightly enlarging lesions (non PD) Pt 11: Resolution of target lesions an

  40. Slide 40: Manageable Safety Profile

    Manageable Safety Profile Treatment-Related Adverse Events Adverse Events of Interest, N (%) Dose Dose Dose Dose Level 1 Level 2 Level 1 Level 2 CRS (N = 6) (N = 6) Diarrhea/Colitis (N = 6) (N = 6) Grade 1 4 (67%) 4 (67%) Grade 1 2 (33%) 2 (33%) Grade 2 2 (33%) 1(17%) Grade 2 1 (17%) 2 (33%) Grade 3

  41. Slide 41: Safety Update for LYL273

    Safety Update for LYL273 June 8, 2026 ©2026 Lyell Immunopharma, Inc. 41

  42. Slide 42: Safety Update for Patients With and Without GI Prophylaxis

    Safety Update for Patients With and Without GI Prophylaxis GI prophylaxis and standardized safety management plan were added to mitigate LYL273 adverse events GI prophylaxis was added to the protocol to mitigate diarrhea and colitis • Infliximab, vedolizumab and budesonide after infusion and prior t

  43. Slide 43: Updated Safety Data for LYL273 With and Without GI Prophylaxis

    Updated Safety Data for LYL273 With and Without GI Prophylaxis LYL273 has a Manageable Safety Profile Grade ≥ 2 diarrhea/colitis decreased from 55% to 10% with GI prophylaxis Adverse Events of Interest No GI GI Prophylaxis Prophylaxis N=9 N = 10 CRS, % Grade 2 33 0 Grade ≥ 3 0 0 ICANS, % Grade 2 11

  44. Slide 44: LYL273 has a Manageable Safety Profile at Dose Level 2

    LYL273 has a Manageable Safety Profile at Dose Level 2 No Grade ≥ 3 CRS, ICANS, or Diarrhea/Colitis Reported for Patients Receiving GI Prophylaxis Optimization of GI prophylaxis and safety management plan ongoing as recommended Phase 2 dose determined Dose Level 1 Dose Level 2 (1 x 106 CAR T cells/k

  45. Slide 45: No Difference Observed in GCC-CAR Cell Expansion Kinetics With or Without GI Prophylaxis

    No Difference Observed in GCC-CAR Cell Expansion Kinetics Between Patients With or Without GI Prophylaxis Both peak and overall exposure for GCC CAR T-cell expansion are similar with and without GI prophylaxis at Dose Levels 1 and 2 With Prophylaxis GCC CAR copies per μg of gDNA Without Prophylaxis

  46. Slide 46: LYL273 Has a Manageable Safety Profile With GI Prophylaxis

    LYL273 Has a Manageable Safety Profile With GI Prophylaxis Grade ≥2 diarrhea/colitis decreased from 55% to 10% with GI prophylaxis • Based on new safety data and cell expansion kinetics, Lyell has amended the Phase 1 trial to enable seamless expansion into a pivotal single-arm Phase 1/2 trial, pendi

  47. Slide 47: Trial Overview

    Trial Overview A Phase 1/2 Multicenter Trial Evaluating the Safety and Efficacy of LYL273 in Patients with Relapsed/Refractory (R/R) Metastatic Colorectal Cancer (mCRC) Patient Population: Adult patients with R/R mCRC Phase 1, N ≈ 95 Dose Escalation, N ≈ 18 - 24 For 84 treated Dose escalation DL 1:

  48. Slide 48: LYL273 Automated Manufacturing Process Fits Seamlessly into the LyFE Manufacturing Center Footprint

    LYL273 Automated Manufacturing Process Fits Seamlessly into the LyFE Manufacturing CenterTM Footprint LyFE capable of commercial launch, can supply > 1,200 CAR T-cell doses/year • Miltenyi CliniMACS Prodigy® closed, automated manufacturing system for LYL273 • Standardized 7-day manufacturing process

  49. Slide 49: Cash Runway into Q3 2027 Through Multiple Expected Clinical Milestones

    Cash Runway into Q3 2027 Through Multiple Expected Clinical Milestones ~$228 million* at the end of Q2 2026 Ronde-cel Dual-Targeting CD19/CD20 CAR T-Cell Therapy for Aggressive LBCL ✓ Reported more mature data in 3L+ and initial data in 2L in June (ICML) Mid-2025 ✓ Initiated pivotal trial in 3L+ Lat

  50. Slide 50: Lyell Immunopharma is Well Positioned for Success

    Lyell Immunopharma is Well Positioned for Success Two clinical-stage programs, one in pivotal trials First pivotal trial read-out mid-2027 Multi-billion-dollar commercial opportunities Manufacturing facility with commercial launch capability Multiple clinical milestones over the next 12 to 18 months

  51. Slide 51: The Future of Cell Therapy – Today

    The Future of Cell Therapy – Today For more information, please contact ir@lyell.com ©2026 Lyell Immunopharma, Inc.

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