Lyell Immunopharma, Inc. · NASDAQ:LYEL
Lyell Immunopharma — Investor Presentation (September 2023)
35 slides from Lyell Immunopharma's investor presentation, Sep 11, 2023
Slide 1: Lyell Immunopharma
Exhibit 99.1 DRAFT JPM22 Updated 12-14-21 Lyell Immunopharma September 11, 2023
Slide 2: Forward-looking statements
Forward-looking statements Certain matters discussed in this presentation are “forward-looking statements” of Lyell Immunopharma, Inc, 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 s
Slide 3: Advancing T cell therapies for solid tumors
Advancing T cell therapies for solid tumors Clinical data from two lead programs in 2024 Two clinical programs: wholly-owned, Executing a scalable manufacturing addressing large patient populations strategy LYL797: ROR1 targeted CAR T cell Lyell’s LyFE center producing current clinical supply • 1H20
Slide 4: Developing two types of personalized cell therapy
Lyell is developing two types of personalized cell therapy: Focused on getting the T-cells right OUR GOAL: Reprogram T cells to defeat solid tumors Resist exhaustion Durable cytotoxicity CAR T cells Self-renewal Persistence Metastatic Durable cytotoxicity Tumor- cancer Maintain polyclonality infiltr
Slide 5: Technologies designed to address primary barriers in solid tumors
Lyell’s T-cell reprogramming technologies are designed to address primary barriers to success in solid tumors TO ACHIEVE SUCCESS IN SOLID TUMORS, CELL THERAPY MUST: RESIST EXHAUSTION, Maintain cancer cell killing in the immunosuppressive tumor microenvironment RETAIN FUNCTION ENHANCE DURABLE Increas
Slide 6: Solid tumors drive T cells down a path to exhaustion
Solid tumors drive T cells down a path to exhaustion Solid Hematologic Autologous Infusion Autologous Infusion tumor malignancy CAR T cell CAR T cell Adequate cell Inadequate expansion, expansion, persistence, driven to exhaustion, and tumor killing and lack of durability Tumor cell Lack of T-cell c
Slide 7: Stackable technologies designed to generate potent T cells
Stackable technologies designed to generate potent T cells with durable function GENETIC REPROGRAMMING EPIGENETIC REPROGRAMMING c-Jun NR4A3 Epi-R™ Stim-R™ overexpression knockout c-Jun and NR4A3 regulate the activator Manufacturing protocols that generate protein 1 (AP-1) transcription factor more s
Slide 8: A clinical-stage company with a growing pipeline for solid tumors
A clinical-stage company with a growing pipeline of novel therapies for solid tumors Genetic Epigenetic Product Reprogramming Reprogramming Target Phase 2 / Next Expected Candidate/ Target Preclinical Phase 1 Indications Pivotal Milestone Modality c-Jun NR4A3 Epi-R™ Stim-R™ TNBC LYL797 Initial data
Slide 9: People with cancer need better therapies
People with cancer need better therapies 90% <2 <3 Years Cancer Years most deaths before metastatic cancer caused by cancer progresses solid patients tumors live after diagnosis seer.cancer.gov; Deaths (Estimated 2021); Survival Rates by Time Since Diagnosis, 2000-2017 CDC Nat’l Ctr for Health Stati
Slide 10: Lyell product candidates target large unmet needs
Lyell product candidates target large unmet needs ~500K new cases and ~180K US deaths annually TRIPLE-NEGATIVE NON-SMALL CELL MELANOMA COLORECTAL BREAST CANCER LUNG CANCER CANCER • 15% of breast cancer • 84% of new lung • 80% of all skin • 3rd most common diagnoses in the US cancer diagnoses cancer-
Slide 11: Reprogramming T cells to target aggressive cancers: LYL797
Reprogramming T cells to target aggressive cancers LYL797: A genetically and epigenetically reprogrammed ROR1 CAR T cell product candidate designed for differentiated potency and durability
Slide 12: LYL797 CAR T cell Phase 1 trial design
LYL797 CAR T cell Phase 1 trial design • Patient population CLINICAL TRIAL DESIGN (mTPI-2) – Relapsed/Refractory TNBC patients who have Dose Escalation Dose Expansion failed two lines of therapy The RP2D – Relapsed/Refractory NSCLC patients who have Dose Level 4 moves failed one line of therapy forw
Slide 13: ROR1 is highly expressed in many human cancers
ROR1 is highly expressed in many human cancers and correlates with a poor prognosis ROR1 expression ~60% ~40% Triple-negative Non-small cell breast cancer lung cancer ~50% ~95% Chronic Ovarian cancer lymphocytic leukemia In previous clinical trials and a non-human primate ROR1 CAR T cell toxicity st
Slide 14: ROR1 assay and screening program
Lyell’s ROR1 assay and screening program support current and future clinical trials Screening data with Lyell’s assay consistent with ROR1 expression in the literature TRIPLE-NEGATIVE BREAST CANCER 53% ROR1+ N=77 • 15% of breast cancer diagnoses/year • ~40,000 new cases / ~10,000 deaths 33% ROR1+ NO
Slide 15: LYL797 supported by robust preclinical data
LYL797 clinical program supported by robust preclinical data ROR1 CAR T cell + c-Jun + Epi-R Key differentiators • Tumor reduction, enhanced cytokine production and tumor infiltration in aggressive NSCLC syngeneic animal model with c-Jun • Stem-like phenotype, durability and enhanced cytotoxicity wi
Slide 16: Preclinical efficacy of c-Jun ROR1 CAR T cells in NSCLC
Superior preclinical efficacy demonstrated with c-Jun overexpressing ROR1 CAR T cells in aggressive NSCLC model Lymphodepletion and • Syngeneic Kras/p53 model that recapitulates human NSCLC NSCLC tumor-bearing mice CAR T cell +/- c-JUN • Also recapitulates the barriers in treating human NSCLC with t
Slide 17: Epi-R technology produces T cells that resist exhaustion
Epi-R™ technology produces transcriptionally distinct populations of T cells that resist exhaustion and maintain cytotoxicity Distinct gene expression profile of Epi-R expanded cells Epi-R expanded cells demonstrate prolonged vs. standard preparation cytotoxicity after removal from Epi-R conditions
Slide 18: LYL797 prolongs survival in NSCLC xenograft model
LYL797 combines c-Jun and Epi-R™ reprogramming technologies to prolong survival in NSCLC (H1975) xenograft model LYL797 reduces tumor burden LYL797 prolongs survival 2500 100 2000 *** 1500 50 1000 500 **** 0 0 2500 2500 0 10 20 30 40 50 60 0 10 20 30 40 50 60 Conventional Mock Conventional mock Conv
Slide 19: Novel stackable technologies: LYL119
Novel stackable technologies designed to improve potency and durability LYL119: Innovative ROR1 CAR T cell product candidate designed for enhanced cytotoxicity
Slide 20: LYL119 incorporates novel stackable technologies
LYL119 incorporates novel stackable technologies designed to improve potency and durability ROR1 CAR T cell + c-Jun + NR4A3 KO + Epi-R + Stim-R Key Differentiators • Combining NR4A3 knockout and c-Jun overexpression further reduces T cell exhaustion and enhances cytotoxicity – Reducing NR4A expressi
Slide 21: Stim-R technology mediates precise signal presentation
Stim-R technology mediates precise signal-molecule presentation during T-cell activation • Stim-R technology mimics physiologic presentation: – Multiple signals presented in precise densities and stoichiometries – Controlled presentation of both soluble and surface signals Stim-R technology is a pro
Slide 22: LYL119 eliminated H1975 xenograft tumors
Peripheral blood CD3+CAR+ numbers LYL119 is potent and eliminated H1975 (NSCLC) xenograft Peripheral blood CD3+CAR+ numbers 0.4e6 CAR T cells 8 10 0.4e6 CAR T cells 8 tumors even at low doses of CAR T cells 10 6 ** * 10 ** * 6 ** * Robust CAR T cells expansion10 Elimination of xenograft tumors at **
Slide 23: Harnessing tumor-infiltrating lymphocytes: LYL845
Harnessing tumor-infiltrating lymphocytes to fight cancer LYL845: A novel epigenetically reprogrammed TIL product candidate designed for differentiated potency and durability
Slide 24: LYL845 TIL Phase 1 trial design
LYL845 TIL Phase 1 trial design • Patient population CLINICAL TRIAL DESIGN (mTPI-2) – Relapsed and/or refractory metastatic or Dose Expansion* Dose Escalation locally advanced solid tumors: (Melanoma) – Melanoma RP2D moves LYL845 Melanoma – Non-small cell lung cancer forward to Dose Level 2 (N = ~ 1
Slide 25: LYL845: A novel and differentiated TIL product candidate
LYL845: A novel and differentiated TIL product candidate Control TIL Key differentiators Standard TIL expansion protocol • Phenotypes (stemness markers and cytotoxic cells) associated with clinical responses LYL845 Tumor Lyell Epi-R protocol comprises: tissue • Proprietary media • Preserved polyclon
Slide 26: LYL845 enriched for cells associated with improved outcomes
LYL845 is enriched for cells with characteristics associated with improved clinical outcomes Increased % of cytotoxic cells Increased % of stem-like T cells Control LYL845 Krishna et al., Science Dec. 2020 Patel et al., SITC 2022 26 PROPRIETARY * is p<.05 ** is p<.01 *** is p<.001 **** is p<.0001 %
Slide 27: LYL845 preserves predicted tumor reactive clones
LYL845 TIL preserve ~94% of predicted tumor reactive clones to enable targeting of heterogeneous solid tumors LYL845 T-Cell preparations LYL845 TIL clinical scale runs Malignant tumor tissue 100 75 50 HIGH Bioinformatics EXHAUSTED FREQUENCY 25 analysis CLONES CLONES 0 Donor Check for preservation of
Slide 28: In vivo efficacy superior with LYL845 TIL
In vivo efficacy is superior with LYL845 TIL using our Epi-R process compared to TIL using standard conditions in novel model In this study: No TIL 2500 • Two refractory melanoma donor Standard TIL samples were collected. 2000 • Samples were split processed to generate TIL products using either 1500
Slide 29: Epi-R P2 shortens product delivery time
Epi-R P2 is a new manufacturing process designed to shorten product delivery time to patients • Compared to Epi-R, Epi-R P2: – Does not compromise yield, stemness phenotype or tumor reactive clones – Reliably produces 10+ billion cells in substantially shorter manufacturing time • Expect to implemen
Slide 30: Epi-R and Epi-R P2 show comparable product profiles
Epi-R and Epi-R P2 processes demonstrate comparable product profiles across CD8 cells Comparable % of stem-like T cells Comparable % of cytotoxic cells NS Epi-R P1 Epi-R P2 Epi-R P1 Epi-R P2 Epi-R P1 Epi-R P2 N=21 include metastatic melanoma, lung cancer and colorectal cancers 30 PROPRIETARY % CD8+
Slide 31: Epi-R P2 preserves and expands tumor reactive TIL
Epi-R P2 preserves and allows expansion of tumor reactive TIL 100000 In this study: • T-cell receptor (TCR) sequencing 10000 was performed across Day 0 tumor, 1000 and TIL samples to assess retention of tumor reactive clones in products 100 • T cell clones that are more highly 10 represented in the
Slide 32: Manufacturing
Manufacturing
Slide 33: Advancing manufacturing strategy to deliver for the future
Advancing manufacturing strategy to deliver for the future • Automated manufacturing processes to rapidly and cost- • Currently producing Phase 1 clinical supply effectively scale to meet anticipated patient demand for • Capabilities include CAR T cell, TIL and GMP vector our CAR T-cell product cand
Slide 34: Advancing T cell therapies for solid tumors
Advancing T cell therapies for solid tumors Clinical data from two lead programs in 2024 Two clinical programs: wholly-owned, Executing a scalable manufacturing addressing large patient populations strategy LYL797: ROR1 targeted CAR T cell Lyell’s LyFE center producing current clinical supply • 1H20
Slide 35: It's all about the cells
IT’S ALL ABOUT | THECELLS..
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