Fate Therapeutics, Inc. · NASDAQ:FATE
Fate Therapeutics — Investor Presentation (April 2018)
66 slides from Fate Therapeutics's investor presentation, April 2018
Slide 1: Programmed Cellular Immunotherapies Corporate Overview
Better Cells For Better Therapies™ Programmed Cellular Immunotherapies Corporate Overview April 2018 -1-
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding the Company's advancement of and plans related to the Company's product candidates, clinical studies, and rese
Slide 3: Fate Therapeutics Mission
Fate Therapeutics Mission To develop first-in-class cell-based immunotherapies for cancer and immune disorders by programming cell function and fate T cells | CD34+ cells | NK cells induced Pluripotent Cell Platform for off-the-shelf engineered immunotherapies -3-
Slide 4: Proven Role of Cells in Cancer Immunotherapy
Proven Role of Cells in Cancer Immunotherapy Antibody-Dependent Cellular Immune Checkpoint Targeted / Activated Cytotoxicity (ADCC) Blockade Cell Products -4-
Slide 5: Early Innings of Cellular Immunotherapy Development
Early Innings of Cellular Immunotherapy Development Patient-derived CAR T Cells Patient Genetic Engineering Cell Composition Manufacturing Yield Random & Variable Heterogeneous Single Patient per Run How do we Build on Early Successes and Transition From a Personalized Process to the Delivery of an
Slide 6: Better Cells for Better Therapies
Better Cells for Better Therapies™ Our Approach to Cellular Immunotherapy Programmed Donor Cell Products Off-the-Shelf Cell Products Cells from healthy donors with Renewable pluripotent cell line selected traits with engineered functionality Donors iPSC Line Ex vivo cell modulation to Ex vivo expans
Slide 7: First-in-Class Cellular Immunotherapy Pipeline
Fate Therapeutics First-in-Class Cellular Immunotherapy Pipeline PROGRAM PRECLINICAL CLINICAL RIGHTS IMMUNO-ONCOLOGY FATE-NK100 – AML Phase 1 Worldwide FATE-NK100 – Ovarian Phase 1 Worldwide FATE-NK100 – Solid Tumor mAb Combo Phase 1 Worldwide FT500 (iNK Cell) OTS Checkpoint Inhibitor Combination Wo
Slide 8: Immuno-Oncology Programs
Immuno-Oncology Programs -8-
Slide 9: Natural Killer Cells
Natural Killer Cells Unique Properties Enable Off-the-Shelf Cancer Immunotherapy • Effector function is not patient or single-antigen specific • Multi-faceted effector function against tumor cells • Use of mismatched cells has been shown to be well-tolerated / low risk of GvHD _ Inhibitory receptors
Slide 10: Adaptive Memory NK Cells
Adaptive Memory NK Cells A Potent Subset of NK Cells with Unique Anti-tumor Attributes NK NK NK NK NK NK NK NK NK NK NK NK NK NK NKG2C NK Jeffrey S. Miller, MD CD57+ Formation of Adaptive Memory NK Cells Correlated with reduced relapse risk and superior disease-free survival in HCT Unique Subset of
Slide 11: Adaptive Memory NK Cells: Resistance to Checkpoint Pathways
Adaptive Memory NK Cells Resistance to Immune Checkpoint Pathways Retained Proliferation Potential of Adaptive Memory NK Cells NK Cell Proliferation NK Cell Proliferation Conventional NK Cells Adaptive Memory NK Cells - 11 -
Slide 12: FATE-NK100: Realizing the Potential of Adaptive Memory NK Cells
FATE-NK100 Realizing the Potential of Adaptive Memory NK Cells NK mono 7-Day Apheresis mono NK Ex Vivo Modulation NK NK NK NK NK NK NK mono NK NK NK NK T & B Cell Depletion FT1238 + Cytokine mono Feeder-free CMV+ Donor Day 0 Day 0 – Post-Depletion Day 7 – Programming 99 0.20 CD56 (NK cells) 0.51 0.2
Slide 13: FATE-NK100: Unique and Differentiated Properties
FATE-NK100 Unique and Differentiated Properties of Adaptive Memory NK Cells ↑ NK cell product purity, potency and consistency ↑ NK cell maturation during product manufacture (↑CD57, ↑KIR, ↓NKG2A, ↓TIGIT) ↑ Tumor necrosis factor (TNF) and interferon (IFN)-γ cytokine production ↑ Direct cytotoxicity a
Slide 14: FATE-NK100: Multi-pronged Clinical Development Strategy
FATE-NK100 Launch of Multi-pronged Clinical Development Strategy • Single IV infusion; accelerated dose-escalation; up to 3 dose levels VOYAGE • 10-patient expansion at MTD Refractory / • Key read-outs: NK cell persistence; anti-leukemia activity; CRs Relapsed AML • Advanced through first two dose c
Slide 15: The VOYAGE Study: Initial Clinical Observations
FATE-NK100 The VOYAGE Study: Initial Clinical Observations • Single IV infusion; accelerated dose-escalation; up to 3 dose levels VOYAGE • 10-patient expansion at MTD Refractory / • Key read-outs: NK cell persistence; anti-leukemia activity; CRs Relapsed AML • Advanced through first two dose cohorts
Slide 16: The APOLLO Study: Initial Clinical Observations
FATE-NK100 The APOLLO Study: Initial Clinical Observations • Single IP infusion; accelerated dose-escalation; up to 3 dose levels APOLLO • 10-patient expansion at MTD Recurrent Ovarian • Key read-outs: NK cell persistence; ORR by RECIST • Advanced through first two dose cohorts with no DLTs Dose Coh
Slide 17: Advantages of an Off-the-Shelf Cell Product Paradigm
Cell-based Cancer Immunotherapy Advantages of an Off-the-Shelf Cell Product Paradigm Key Features Today Tomorrow Cell Source Patient / Donor Cells Master Cell Line Genetic Engineering Random & Variable Precise & Complete Manufacturing Patient-specific Off-the-Shelf Product Consistency Heterogeneous
Slide 18: Human Induced Pluripotent Stem Cells
Human Induced Pluripotent Stem Cells Renewable Source for Off-the-Shelf Cell Products A Single Human Induced Pluripotent Cell Unlimited Self- On-Demand Immune Renewal Cell Derivation Robust Expansion Master Cell Capacity Banking Precise, Single-Cell Cell Line Engineering Validation Multi-faceted Fun
Slide 19: iPSC Product Platform
iPSC Product Platform Fate Therapeutics’ Transformative Approach to Cancer Immunotherapy (Engineered) Single Pluripotent Stem Cell Single • Renewable iPSC Clone • Propensity to differentiate into 200+ cell types Expansion & Banking Working Cell Banks Unlimited Supply of Master Cell Clonal iPSC Maste
Slide 20: Off-the-Shelf NK- and T-Cell Products: Collaborations
Off-the-Shelf NK- and T-Cell Products Collaborations with Top Investigators and Leading Centers 59th American Society of Hematology (ASH) Annual Meeting December 9-12, 2017 in Atlanta, Georgia Clinical Translation of Pluripotent Engineered Human iPSCs with Generation of Clonal Antigen Specific Cell-
Slide 21: Off-the-Shelf NK Cell Products
Off-the-Shelf NK Cell Products Three Product Candidates Undergoing IND-Enabling Activities • Clonal master iPSC line • NK differentiation FT500 • Homogenous cell product Master iPSC Line + hnCD16 • hnCD16 insertion • Clonal master iPSC line • NK differentiation FT516 • Homogeneous cell product Engin
Slide 22: FT500 Manufacturing
FT500 Manufacturing Robust Differentiation Protocol for iPSC-derived NK Cell Production 1 iPSC 100 CD34s 5L Grex Large clonal population of NK cells in a single production run capable of yielding hundreds of doses of homogeneous drug product for off-the-shelf delivery to patients - 22 -
Slide 23: FT500 Biological Properties
FT500 Biological Properties Comparative Gene Expression Analysis vs. Peripheral Blood NKs iNK iPSC 50 iPSC iNK Round 1 iCD34+ iNK Round 2 -50 PC 2 Fibroblast 50 100 0.0 iCD34+ iReg iNK Round 3 CD14+ 50 Adult NK CD33+ iProT CD7- Adult NK Round 1 iProT CD7+ Fibroblast iProT CD7+ Adult NK Round 2 iProT
Slide 24: FT500 Cell Potency
FT500 Cell Potency iPSC-derived vs. Peripheral Blood NK Cells SKOV3 (Ovarian Cancer) Killing Assay Overnight Primed NK Cells Off-the-Shelf iNK Cells Off-the-Shelf iNK Cells Tumor Killing - 24 -
Slide 25: FT500 Purity
FT500 Purity No Residual iPSCs in FT500 Cell Product • Determination made analyzing a set of master pluripotency genes (NANOG, OCT4, SOX2, REX1) highly expressed in iPSCs but not in background of NK cells No iPSCs detected at the resolution of 1 in 2 million during multiple iNK cell manufacturing ru
Slide 26: FT500 Production
FT500 Production Technology Transfer to MCT cGMP Facility 1x106 iPSCs delivers 1x1012 NK cells during 44 day manufacturing process Molecular and Cellular Therapeutics 33,000 sf, free-standing, FT500 state-of-the-art GMP facility 1x109 Cryopreserved Cells - 26 -
Slide 27: FT500 in Combination with Checkpoint Inhibitors
FT500 in Combination with Checkpoint Inhibitors Synergy with T Cells to Infiltrate and Destroy 3D Tumor Mass - 27 -
Slide 28: FT500 Proposed FIH Study
FT500 Proposed FIH Study Multiple Cycles of FT500 + Checkpoint Inhibitor Dosed Weekly Screening Window: Refractory Solid Tumors -14 --------One Cycle-------- Checkpoint Inhibitor Given per SOC dose and frequency until disease progression - 28 -
Slide 29: FT516 Engineered hnCD16+ NK Cell Product Candidate
FT516 Engineered hnCD16+ NK Cell Product Candidate For Combination with Monoclonal Antibody Therapy Engineered high-Affinity non-Cleavable CD16 Fc Receptor FDA-approved Monoclonal Antibodies Modified form of CD16a IgG antibody-binding receptor resists shedding upon activation hnCD16 + High affinity
Slide 30: FT516: Augmented In Vitro ADCC for Solid Tumors
FT516 Engineered hnCD16+ NK Cell Product Candidate Augmented In Vitro ADCC for Solid Tumors SKOV3 (Ovarian) A549 (Lung) 125 125 (HER2hi/EGFRhi) (HER2lo/EGFRhi) 100 100 Tumor Killing Tumor Killing 75 75 50 50 25 25 0 0 0 6 12 18 24 30 36 42 48 54 60 66 72 78 0 6 12 18 24 30 36 42 48 54 60 66 72 78 T
Slide 31: FT516: In Vivo POC
FT516 Engineered hnCD16+ NK Cell Product Candidate In Vivo POC Untreated Herceptin Herceptin + FT516 Luc-SKOV3 (Ovarian Cancer) Tumor Image Analysis D4 Initiation of treatment @ Day 5 D18 D39 - 31 -
Slide 32: FT538 Engineered hnCD16+ / CD38-null NK Cell Product
FT538 Engineered hnCD16+ / CD38-null NK Cell Product For Combination with Darzalex for Multiple Myeloma FT538 • hnCD16 insertion • CD38 knock-out CD16 • Single cell selected • Master iPSC line generated • NK differentiation Renewable Engineered Master Pluripotent Cell Line CD38 • CD38 is expressed a
Slide 33: Off-the-Shelf T Cell Products: Memorial Sloan Kettering Collaboration
Off-the-Shelf T Cell Products Memorial Sloan Kettering Collaboration Dr. Michel Sadelain, MD, PhD Director, Center for Cell Engineering Memorial Sloan Kettering Cancer Center - 33 -
Slide 34: The Sadelain Roadmap
Off-the-Shelf T Cell Products The Sadelain Roadmap “Engineering therapeutic attributes into pluripotent cell lines is a breakthrough approach to renewably generate potent T-cell immunotherapies. This unique approach offers the prospect for off-the-shelf delivery of T-cell therapies with enhanced saf
Slide 35: Ex Vivo Generation of CAR19+ CD8αβ+ T Cells
Ex Vivo Generation of CAR19+ CD8αβ+ T Cells Generation from Clonal Engineered Master iPSC Line Clonal CAR19 Master hiPSC Line CAR19-iT cells CAR+ Master Parental hiPSC CAR+ hiPSC Pool Pluripotent Cell Line CAR19 CAR19 • Clonal (from a single cell) CD3 • Pluripotent • Renewable (unlimited source) • H
Slide 36: iPSC-Derived CAR19+ CD8αβ+ T Cells
iPSC-Derived CAR19+ CD8αβ+ T Cells Global Gene Expression Comparison vs. Primary T Cells - 36 -
Slide 37: FT819 CAR19 TCR-null T Cell Product Candidate
FT819 CAR19 TCR-null T Cell Product Candidate Generated from Clonal Engineered Master iPSC Line TCR Disruption TRAC-encoded CAR Expression Complete Elimination of TCR - 37 -
Slide 38: FT819: In Vitro CAR19 Cytokine Production and Antigen Specificity
FT819 CAR19 TCR-null T Cell Product Candidate In Vitro CAR19 Cytokine Production and Antigen Specificity - 38 -
Slide 39: FT819: In Vitro CD16 ADCC Activity
FT819 CAR19 TCR-null T Cell Product Candidate In Vitro CD16 ADCC Activity to Overcome Antigen Escape - 39 -
Slide 40: Immuno-Regulatory Programs
Immuno-Regulatory Programs - 40 -
Slide 41: ProTmune: Transforming the Curative Potential of Allogeneic HCT
ProTmune™ Transforming the Curative Potential of Allogeneic HCT A Next-Generation Hematopoietic Cell Graft to Prevent Acute Graft-versus-Host Disease ProTmune™ • Allogeneic HCT performed with curative intent Small molecule programmed – Orphan hematologic malignancies (e.g., AML, ALL, MDS) mobilized
Slide 42: Acute Graft-vs-Host Disease: Incidence Rates
Acute Graft-vs-Host Disease High Incidence Rates during First 100 Days post-HCT mPB, MAC, no TBI BM, MAC, TBI mPB, RIC, TBI mPB, MAC, TBI ~ 60% BM, RIC BM, MAC, no TBI Jagasia et al., Blood, 2011 87 CIBMTR centers ~ 60% Historical Incidence Rate (Grade 2–4) - 42 -
Slide 43: Pathophysiology of Acute GvHD
Pathophysiology of Acute GvHD Tissue Damage Cytokine Storm IL-6 IL-1β TNF-α IFN-ᵞ Conditioned T Cells Patient Donor Donor Allo-reactive Assault on Immunosuppressive T-cell Activation Patient Tissue Agents Host APCs Tc17 IL-12 Th17 Severe Infections Tc1 Acute GvHD (gut, liver, skin) ~70% D100 cumulat
Slide 44: Severe Acute GvHD Causes Mortality
Acute Graft-vs-Host Disease Severe Acute GvHD Causes Mortality G1 G0 G2 G3 G4 Years since Transplantation - 44 -
Slide 45: ProTmune: The Next-Generation Hematopoietic Cell Graft
ProTmune™ The Next-Generation Hematopoietic Cell Graft ProTmune™ - 45 -
Slide 46: ProTmune: Ex Vivo Small Molecule Modulation of Donor T Cells
ProTmune™ Ex Vivo Small Molecule Modulation of Donor T Cells Striking the Balance between GvHD and GvL Attenuated T-Cell Response to Cytokine Signaling (IL-6) Naïve T Cells Memory T Cells - 46 -
Slide 47: PROTECT Phase 1/2 Study: Phase 1 Safety
ProTmune™ PROTECT Phase 1/2 Study for Prevention of Acute GvHD Phase 1 Stage: Day 28 Safety Assessment Allogeneic HCT Setting • Matched unrelated donor (MUD) mPB HCT with myeloablative conditioning • Hematologic malignancies include ALL, AML & MDS • Standard-of-care GvHD prophylactic (Methotrexate /
Slide 48: PROTECT Phase 1 Day 100 Efficacy Data
ProTmune™ PROTECT Phase 1 Day 100 Efficacy Data # maximum grade GvHD - 48 -
Slide 49: PROTECT Phase 2 Stage Design
ProTmune™ PROTECT Phase 1/2 Study for Prevention of Acute GvHD Phase 2 Stage: 60 Subjects, Double-blinded, Randomized, Controlled Currently Enrolling at 14 U.S. Centers Fast Track Designation Controlled, Blinded ProTmune Cell Graft (n=30) Randomized, Primary Endpoint Day 100 Cumulative Incidence of
Slide 50: ProTmune: Next-Generation Graft to Prevent Acute GvHD
ProTmune™ Next-Generation Graft to Prevent Acute GvHD • Preventive approach to address leading cause of early morbidity and mortality – 40 to 80% of patients undergoing allogeneic HCT experience acute GvHD – Death directly attributable to acute GvHD or its treatment occurs in 10 to 20% of patients –
Slide 51: ToleraCyte: Tolerizing the Immune System for Autoimmune Diseases
ToleraCyte™ Tolerizing the Immune System for Autoimmune Diseases A First-in-Class Immunoregulatory CD34+ ToleraCyte™ Cell Product Candidate to Induce Small molecule programmed Immune Tolerance CD34+ cells • Autoimmune disorders result from malfunction of the body’s natural defense systems – Adaptive
Slide 52: ToleraCyte: Small Molecule Programmed CD34+ Cell Product
ToleraCyte™ Small Molecule Programmed CD34+ Cell Product Ex vivo modulation of CD34+ cells with two small molecules induces the expression of genes involved in cell migration and immune regulation Vehicle ToleraCyte Fold Change (mRNA) - 52 -
Slide 53: Immuno-Regulatory CD34+ Cell Therapy: Proof-of-Principle in Type 1 Diabetes
Immuno-Regulatory CD34+ Cell Therapy Collaborator Established Proof-of-Principle in Type 1 Diabetes Paolo Fiorina, MD, PhD Hyperglycemic Mice Assistant Professor of Pediatrics, Adoptive Transfer of PD-L1+ Hematopoietic Cells Harvard Medical School • Extensive investigation into T-cell destruction of
Slide 54: Durable Disease Correction in T1D Mouse Model
Immuno-Regulatory CD34+ Cell Therapy Durable Disease Correction in T1D Mouse Model Blood Glucose Levels Hyperglycemic Mouse Small Molecules No Treatment Vehicle-Treated HSPCs Programmed HSPCs Untreated (n=5) pLK cells (n=8) 600 600 600 500 500 500 n=5 n=5 n=8 Glycemia (mg/dl) 400 400 400 300 300 300
Slide 55: Disease Attenuation in EAE Mice (Multiple Sclerosis)
Immuno-Regulatory CD34+ Cell Therapy Disease Attenuation in EAE Mice (Multiple Sclerosis) Programmed HSPCs attenuate loss of motor function in EAE Mice Loss of Motor Function - 55 -
Slide 56: ToleraCyte: Programmed CD34+ Cell Product for Autoimmunity
ToleraCyte™ Small Molecule Programmed CD34+ Cell Product for Autoimmunity • Builds on clinical precedent for CD34+ cell therapy – Use of patient- and donor-sourced CD34+ cells has well-established safety record • Unique immuno-regulatory mechanism of action – T-cell targeting approach through enhanc
Slide 57: Myeloid-Derived Suppressor Cells (MDSCs)
Myeloid-Derived Suppressor Cells (MDSCs) Immuno-Regulatory Cells With Unique Properties • Defined as immature myeloid cells with potent suppressive activity – CD33+/CD11b+, CD14+/CD66+, HLA-DRlow • Suppressive activity occurs through diverse mechanisms of action – ARG, iNOS, IL10, Gal9, CD73, TGFb –
Slide 58: MDSCs: Advantages Relative to Other Immuno-Regulatory Cell Types
Myeloid-Derived Suppressor Cells (MDSCs) Advantages Relative to Other Immuno-Regulatory Cell Types Cell Type Cell Feature T Regs MSCs HSCs MDSCs Multiple anti-inflammatory mechanisms ● ● ● ● Able to induce long-term tolerance ● ● ● ● Antigen agnostic activation - ● ● ● Homing to site of inflammation
Slide 59: FT300: iPSC-derived MDSC Product
FT300 iPSC-derived MDSC Product Feature Benefit Anti-inflammatory activity triggered by Efficacy across a variety of autoimmune local inflammatory environment (antigen diseases (antigen independent MOA) independent) MDSC’s capable of homing to site of Systemic “IV” delivery with efficacy in the infl
Slide 60: FT300 In Vitro Activity: T-Cell Proliferation
FT300 In Vitro Activity Potent Suppressor of T-Cell Proliferation Across HLA Barriers CD4+ CD8+ N o r m a liz e d e x p a n s io n N o r m a liz e d e x p a n s io n 100 100 *** *** 50 50 0 0 0 1 -1 1 -2 1 -4 0 1 -1 1 -2 1 -4 Activated T Cells FT300 + Activated T Cells * * Segmented by ratio of FT30
Slide 61: FT300 In Vitro Activity: T-Cell Cytokine Release
FT300 In Vitro Activity Potent Suppressor of T-Cell Cytokine Release Across HLA Barriers IFNg 100 TNFa 80 IL-2 40 T c e lls * ** CD4+ ** ** + 50 40 ** of C D 4 20 ** * * % 0 0 0 40 40 50 T c e lls * CD8+ * ** + * of C D 8 20 20 25 ** * ** % 0 0 0 N o 0 1 -1 1 -2 1 -4 N o 0 1 -1 1 -2 1 -4 N o 0 1 -1
Slide 62: FT300 In Vivo Functionality
FT300 In Vivo Functionality Suppression of T Cells and Disease Activity in GvHD Model NSG Disease Severity % T Cells 8 50 + % H um an C D 45 P<0.0001 S c o re 6 V H D Score iv *** 4 GvHD 25 2 G T Cells * 7.5 x 106 0 0 20 40 * Injected to induce Days 0 D a ys GvHD + Survival % Regulatory T Cells FT30
Slide 63: Financial Summary
‘4 Fate THERAPEUTICS -63-
Slide 64: Financial Summary: Three Months Ended December 31, 2017
Fate Therapeutics Financial Summary Three Months Ended December 31, 2017 Revenue $1.0M R&D Expense $9.9M G&A Expense $3.4M Operating Expense, Adjusted 1 $11.9M Cash & Cash Equivalents $101.0M Employees 80 Total Shares Outstanding 2 66.9M [1] Excludes $0.9M in stock-based compensation expense and $0.
Slide 65: First-in-Class Cellular Immunotherapy Pipeline
Fate Therapeutics First-in-Class Cellular Immunotherapy Pipeline PROGRAM PRECLINICAL CLINICAL RIGHTS IMMUNO-ONCOLOGY FATE-NK100 – AML Phase 1 Worldwide FATE-NK100 – Ovarian Phase 1 Worldwide FATE-NK100 – Solid Tumor mAb Combo Phase 1 Worldwide FT500 (iNK Cell) OTS Checkpoint Inhibitor Combination Wo
Slide 66: Better Cells For Better Therapies
Better Cells For Better Therapies™ - 66 -
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