Slide 1: Initial Clinical and Translational Data from Phase 1 Trial of LYL797
Exhibit 99.2 Initial Clinical and Translational Data from Phase 1 Trial of LYL797, an Enhanced ROR1-targeted CAR-T Cell Product Candidate June 26, 2024 1
Slide 2: Forward Looking Statements
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 w
Slide 3: LYL797 Clinical Data Summary and Background
LYL797 Clinical Data Summary and Background Lynn Seely, MD President and Chief Executive Officer 3
Slide 4: LYL797 Initial Clinical Data and Progress Update
LYL797 Initial Clinical Data and Progress Update Dose-Dependent Clinical Activity Observed • 40% Objective Response Rate, including 2 confirmed partial responses, at 150M CAR T cell dose (n=5), the highest dose level cleared to date – Clinical Benefit Rate of 60% at 150M CAR T cell dose and 38% acro
Slide 5: Fred Hutch Study: ROR1 CAR T Cells Exhaustion in Solid Tumors vs CLL
Fred Hutch Cancer Center Study: ROR1 CAR T Cells in Peripheral Blood Samples Demonstrated Increased Markers of Exhaustion in Patients with Solid Tumors Compared to Those with Chronic Lymphocytic Leukemia (CLL) Solid Tumors: Cells Exhaust CLL: Cells Did Not Exhaust CD4 CD8 CD4 CD8 (n=2) (n=3) TIGIT L
Slide 6: LYL797 Designed to Overcome Two Key Barriers to Cell Therapy in Solid Tumors
LYL797 was Designed to Overcome Two Key Barriers to Cell Therapy in Solid Tumors: Lack of T-cell Expansion and Rapid T-cell Exhaustion Lack of durable stemness and cell death Proliferation & cell differentiation Tumor antigen Tumor cell Repeat antigen stimulation T-cell exhaustion – 6 ©2024 Lyell Im
Slide 7: LYL797: Improved Tumor Control and Prolonged Survival In Vivo
LYL797: Improved Tumor Control and Prolonged Survival In Vivo NSCLC (H1975) Xenograft Model LYL797 Reduced Tumor Burden LYL797 Prolonged Survival 6 6 5 x 10 CAR T cells 5 x 10 CAR T cells Genetic Epigenetic Reprogramming Reprogramming c-Jun regulates the Manufacturing protocol AP-1 transcription tha
Slide 8: LYL797: Phase 1 Trial Design
LYL797: Phase 1 Trial Design Patient Population mTPI-2 Dose Escalation Followed by Dose Expansion • Patients with relapsed/refractory TNBC after failure of at least two Dose Escalation Dose Expansion lines of therapy • Patients with relapsed/refractory Dose Level 4 NSCLC after failure of at least on
Slide 9: LYL797: Updated Dose Escalation Design
LYL797: Updated Dose Escalation Design Dose Escalation (mTPI-2) Dose Expansion • No dose-limiting toxicities in patients without lung metastases 6 450 x 10 cells • Pneumonitis observed in some patients with lung metastases TNBC RP2D (N~15) ⎼ Separately escalating cohorts of 6 300 x 10 cells patients
Slide 10: LYL797 Clinical Data Update
LYL797 Clinical Data Update David R. Spigel, MD Chief Scientific Officer Sarah Cannon Research Institute Nashville, TN
Slide 11: Patient Characteristics
Patient Characteristics Predominantly TNBC with Multiple Lines of Prior Therapy 6 6 6 6 6 50 x 10 cells 75 x 10 cells 100 x 10 cells 150 x 10 cells 300 x 10 cells Total n = 8 n = 2 n = 4 n = 5 n = 1 N = 20 Age, mean 54 59 48 48 58 52 Indication, n (%) TNBC 6 (75%) 1 (50%) 3 (75%) 5 (100%) 1 (100%) 1
Slide 12: Dose-Dependent Clinical Activity with 40% ORR at Highest Completed Dose Level
Dose-Dependent Clinical Activity with 40% Objective Response Rate at Highest Completed Dose Level 6 6 6 6 Efficacy evaluable 50 x 10 cells 100 x 10 cells 150 x 10 cells 300 x 10 cells Total patients, n n = 6 n = 4 n = 5* n = 1 N = 16 Patients with CR/PR, n 0 0 2 0 2 Patients with SD, n 1 1 1 1 4 ORR
Slide 13: Best Response for Target Lesions Demonstrating Clinical Activity
Best Response for Target Lesions Demonstrating Clinical Activity 50M cells 100M cells 150M cells 300M cells Change from Baseline (%) Individual Patients 13 ©2024 Lyell Immunopharma, Inc. Data cutoff of 29 May 2024
Slide 14: Clinical Benefit Rate was Dose Dependent
Clinical Benefit Rate was Dose Dependent n = 1 • Clinical benefit rate is defined as SD, PR or CR as best response n = 5 n = 5 • Several patients had additional Clinical observations of clinical benefit Benefit Rate (%) including weight gain, decreased pain and improved n = 4 n = 4 liver function te
Slide 15: Treatment Related Adverse Events
Treatment Related Adverse Events: All Dose-Limiting Toxicities in Patients with Lung Involvement and Prior to Implementing Dexamethasone Prophylaxis 6 6 6 6 6 Safety Evaluable 50 x 10 cells 75 x 10 cells 100 x 10 cells 150 x 10 cells 300 x 10 cells Patients With: n = 7 n = 1 n = 4 n = 5 n = 1 TRAEs
Slide 16: Pneumonitis has a Predictable Onset and is Treatable
Pneumonitis has a Predictable Onset and is Treatable • Pneumonitis does not appear to be related to on-target, off-tumor toxicity; we believe it is related to local cytokine production due to underlying lung disease • The onset is predictable(generally 4 – 10 days after treatment) • It has been effe
Slide 17: Case Report of LYL797 Clinical Activity: Metastatic TNBC
Case Report of LYL797 Clinical Activity Patient with metastatic triple-negative breast cancer with confirmed partial response following LYL797 after having failed 3 prior lines of treatment % Change from Screening to Baseline 51-year-old female previously treated with Best % Change from Baseline (1)
Slide 18: Case Report of LYL797 Clinical Activity: Metastatic NSCLC
Case Report of LYL797 Clinical Activity Patient with metastatic non-small cell lung cancer with stable disease for 6 4 months following LYL797 at a dose of 50 x 10 cells • 49-year-old male diagnosed with metastatic NSCLC and treated with XRT then (1) carbo/pemetrexed and pembrolizumab, (2) a novel I
Slide 19: Confirmed Partial Responses in Patients with Progression Before Baseline
Confirmed Partial Responses in Patients Who had Progression in their Target Lesions Between Screening and Baseline % Change from Screening to Baseline % Change from Screening to Baseline Best % Change from Baseline Best % Change from Baseline % Change in % Change in Sum of Sum of Diameters Diameters
Slide 20: LYL797 Translational Science
LYL797 Translational Science Gary Lee, PhD Chief Scientific Officer
Slide 21: LYL797 Translational Data: Key Findings
LYL797 Translational Data: Key Findings Expansion • LYL797 CAR T-cell expansion observed in the peripheral blood from all patients (n=11) CAR T Cell Phenotype • LYL797 cells had low exhaustion markers and a significant proportion of cells with the desired stem-like and effector-memory phenotype (n=6
Slide 22: LYL797 CAR T-cell Expansion Observed in Peripheral Blood
LYL797 CAR T-cell Expansion Observed in Peripheral Blood Samples from All Treated Patients Peak Expansion Between Days 8 and 11 100000 6 DL 1 50 x 10 cells (n = 5) DL 1 DL 1A 6 100 x 10 cells (n = 1) DL 1A DL 2 Median Peak PK 10000 6 DL 2 150 x 10 cells (n = 5) 1000 Median peak PK = 11,251 copies/µg
Slide 23: Lower Percent TIGIT+ Cells in Infusion Products and Peripheral Blood
Infusion Products and LYL797 in Day 11 Peripheral Blood Samples Had Significantly Lower Percent TIGIT+ Cells (Exhaustion Marker) Fred Hutch Cancer Center: Solid Tumor Patients LYL797 CAR T Cell Data 100 100 100 80 80 80 60 60 60 + + + % TIGIT % TIGIT % TIGIT 40 CAR T cells CAR T cells CAR T cells 40
Slide 24: LYL797 Exhaustion Profile Comparable to CD19 CAR PBMC Samples
LYL797 Cells Had an Exhaustion Profile More Comparable to Published Data from CD19 CAR PBMC Samples than Exhausted TNBC TIL Samples mRNA by RNAseq/ transcriptomic analyses Exhaustion related gene set consistent among multiple tumor types (N = 18 genes) LYL797 PublicStudy1 PublicStudy2 Exhausted TILs
Slide 25: Stem-like and Effector-memory Phenotype in LYL797 Cells
LYL797 Cells from Day 11 and Day 22 PBMC Samples Had a Significant Proportion of Cells with Stem-like and Effector-memory Phenotype * mRNA by RNAseq/ transcriptomic analyses LYL797 Compared to CD19 CAR * LYL797 from Day 11 PBMC Samples Stem-like Phenotype Stem-like Effector memory Stem-like Effector
Slide 26: Detection of LYL797 CAR T Cell Infiltration in On-study Tumor Biopsies
Detection of LYL797 CAR T Cell Infiltration in All Evaluable (N=9) On-study Tumor Biopsies (Days 21-30) In situ detection of CAR-specific T cells using anti-ROR1 scFv mRNA in situ hybridization (ISH) assay T cell receptor ROR1 CAR T Nucleus 6 Data cutoff of 29 May 2024; Patient 18; TNBC; 100 x 10 ce
Slide 27: CAR T Cell Infiltration in Patient with Confirmed Partial Response
LYL797 CAR T Cell Infiltration in Patient with Confirmed Partial Response (Patient 8) T cell receptor ROR1 CAR T Nucleus 6 Data cutoff of 29 May 2024; Patient 8; TNBC; 150 x 10 cells; Day 28 tumor biopsy of lung CAR, chimeric antigen receptor; H&E: Hematoxylin & Eosin; mISH: multiplex fluorescent in
Slide 28: Persistent CAR T Cell Infiltration >4 Months Post-infusion
Persistent LYL797 CAR T Cell Infiltration Observed in Tumor Sample >4 months Post-infusion (Patient 8) Lymph node resected at time of surgery with no evidence of disease T cell receptor ROR1 CAR T Nucleus 6 Data cutoff of 29 May 2024; Patient 8; TNBC; 150 x 10 cells; 2nd post-LYL797 infusion tumor b
Slide 29: Tumor Biopsies Consistent with T Cell-mediated Tumor Lysis
Multiple Tumor Biopsies Had Features Consistent with T Cell-mediated Tumor Lysis Including T Cell-rich Inflammation with Scattered Tumor Cells Scattered tumor cells with lymphocytic cells Fibrous stroma Patient 3, TNBC Patient 5, TNBC Patient 8, TNBC 6 6 50 x 10 cells, Day 26 liver biopsy 6 150 x 10
Slide 30: LYL797 Data Summary
LYL797 Data Summary LYL797 CAR T cells had dose-dependent clinical activity and expanded, infiltrated, persisted and killed tumor cells in patients with TNBC ü 40% ORR and 60% CBR at 150M cells; dose escalation continuing ü No significant safety signal related to LYL797 observed in patients without
Slide 31: Next Steps for ROR1 CAR T Cell Program
Next Steps for ROR1 CAR T Cell Program Demonstrated clinical activity supports expanded development of LYL797 and LYL119 LYL797 • Select Recommended Phase 2 Dose for LYL797 expansion cohort(s) • Generate data at higher dose levels expected to achieve more durable responses • Dose escalate with stero
Slide 32: LYL119: Incorporates Novel Stackable Technologies
LYL119: Incorporates Novel Stackable Technologies Designed to Improve Potency Anti-ROR1 CAR ™ c-Jun Epi-R Overexpression Patient LYL119 T cells ™ NR4A3 Stim-R Knockout Tumor cells CAR, chimeric antigen receptor; NR4A3, The nuclear receptor 4A3; ROR1, receptor tyrosine kinase-like orphan receptor 1 3
Slide 33: LYL119 Demonstrated More Potent Anti-tumor Activity In Vivo
LYL119, Next-generation ROR1-targeted CAR T, Demonstrated More Potent Anti-tumor Activity In Vivo Significantly Improved Elimination of Significantly Improved Animal Xenograft Tumors at the Lower Survival at the Lower 6 6 0.1 x 10 CAR T-cell Dose 0.1 x 10 CAR T-cell Dose 6 1 x 10 CAR T cells 6 0.1 x
Slide 34: ROR1 is Highly Expressed in Many Malignancies
ROR1 is Highly Expressed in Many Malignancies Expression associated with a poor prognosis in solid tumors Solid Tumor Indications in Development TNBC NSCLC Endometrial Ovarian ROR1 Expression 51%* 35%* ~50% ~50% ~40K new cases ~200K new cases ~68K new cases ~20K new cases US Incidences ~10K deaths ~
Slide 35: Upcoming Potential Milestones
Upcoming Potential Milestones Balance sheet of $526M* provides cash runway into 2027, through multiple clinical milestones LYL797 ROR1 CAR T cell + c-Jun + Epi-R q Begin enrolling patients with ovarian or endometrial cancers q Submit IND for trial in patients with multiple myeloma or CLL 2H24 q Clin
Slide 36: With Thanks
With Thanks Our gratitude to patients, caregivers, investigators, clinical site teams and Lyell employees for their contributions to advance innovative cell therapies to people with cancer 36 ©2024 Lyell Immunopharma, Inc.
Slide 37: Q&A
(Lyell Q&A