Fate Therapeutics, Inc. · NASDAQ:FATE
Fate Therapeutics — Investor Presentation (May 2017)
54 slides from Fate Therapeutics's investor presentation, May 2017
Slide 1: Programmed Cellular Immunotherapies Corporate Overview
Better Cells For Better Therapies™ Programmed Cellular Immunotherapies Corporate Overview May 2017 - 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 therapeutic and market potential of the Company’s product candidates and engineered pluripotent cell pla
Slide 3: Mission
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: Why Use Cells as the Therapeutic Modality?
Why Use Cells as the Therapeutic Modality? Proven Role of Immune Cells in Fighting Cancer Antibody-Dependent Cellular Immune Checkpoint Targeted / Activated Cytotoxicity (ADCC) Blockade Cell Products Indirect Cell Therapy Direct - 4 -
Slide 5: Better Cells for Better Therapies: Our Approach to Cellular Immunotherapy
Better Cells for Better Therapies™ Our Approach to Cellular Immunotherapy Programmed Donor Cell Products iPSC-derived Cell Products Cells from healthy donors with Renewable pluripotent cell lines selected traits with engineered functionality Donors iPSC Cell Line Ex vivo cell modulation to Ex vivo
Slide 6: Pioneering First-in-Class Product Candidates
Pioneering First-in-Class Product Candidates IMMUNO-ONCOLOGY IMMUNO-REGULATION • FATE-NK100 first-in-class adaptive memory • ProTmune™ next-generation graft to prevent NK cell cancer immunotherapy leading life-threatening HCT complications – Multi-faceted anti-tumor activity, persistence
Slide 7: Immuno-Oncology Programs
Immuno-Oncology Programs - 7 -
Slide 8: Natural Killer (NK) Cells
Natural Killer (NK) Cells Unique Properties & Emerging Role in Cancer Immunotherapy • Multi-faceted effector function against tumor cells – Direct killing of tumor cells through release of cytotoxic granules – Trigger adaptive immune response (e.g., T cells) through cytokine production – Engage and
Slide 9: Adaptive Memory NK Cells
Adaptive Memory NK Cells A specific sub-population of NK cells with adaptive immune and memory-like properties that arises in response to CMV infection Heightened effector function Checkpoint resistant Persistence Jeffrey S. Miller, MD CD8+ T cell-like epigenetic profile Clonal expansion NK NK NK
Slide 10: FATE-NK100: Realizing the Potential of Adaptive Memory NK Cells
FATE-NK100 Realizing the Potential of Adaptive Memory NK Cells mono 7-Day NK 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
Slide 11: FATE-NK100: Potent Direct Cellular Cytotoxicity
FATE-NK100 Potent Direct Cellular Cytotoxicity KG1 AML Cell Line Patient-Derived Primary AML Blasts % Tumor Killing % Tumor Killing Log(E:T) Ratio Log(E:T) Ratio FATE-NK100 O/N Cytokine-induced E:T = Effector (NK) to Target (Tumor) - 11 -
Slide 12: FATE-NK100: Elevated Cytokine Production
FATE-NK100 Elevated Cytokine Production Cytokine Release Cytokine Release Activating Signal Activating Signal FATE-NK100 O/N Cytokine-induced - 12 -
Slide 13: FATE-NK100: Augmented ADCC Effector Function
FATE-NK100 Augmented ADCC Effector Function Exploiting CD16 IgG antibody-binding receptor in combination with FDA-approved mAbs for solid tumors SKOV3 (Ovarian Cancer) Line Luc-SKOV3 Tumor Image Analysis Day 21 Herceptin Herceptin Tumor Killing % Tumor Killing + Herceptin FATE-NK100 FATE-NK100
Slide 14: FATE-NK100: Increased Resistance to Immune Checkpoints
FATE-NK100 Increased Resistance to Immune Checkpoints Immune Checkpoint Receptor PD1 Cell-Surface Expression FATE-NK100 O/N Cytokine-induced - 14 -
Slide 15: FATE-NK100: Tumor Cell-Specific Cytotoxicity
FATE-NK100 Tumor Cell-Specific Cytotoxicity Multiplex Killing Assay K562 Lines % Specific Killing Allogeneic PB Mononuclear Cells Log(E:T) Ratio FATE-NK100 O/N Cytokine-induced - 15 -
Slide 16: FATE-NK100: Potential Therapeutic Applications Across Cancer
FATE-NK100 Potential Therapeutic Applications Across Cancer Multifaceted Functionality Creates Opportunities Across Liquid and Solid Tumors - 16 -
Slide 17: FATE-NK100: Launch of Multi-pronged Clinical Development Strategy
FATE-NK100 Launch of Multi-pronged Clinical Development Strategy • IV infusion;; accelerated dose-escalation;; up to 4 dose levels VOYAGE • 10-patient expansion at MTD Refractory / • Key read-outs: rates of CR and MRD;; NK cell persistence Relapsed AML • Open for enrollment at UMN;; initial dat
Slide 18: FATE-NK100: First-in-Class Adaptive Memory NK Cell Product Candidate
FATE-NK100 First-in-Class Adaptive Memory NK Cell Product Candidate • Builds on compelling clinical results with conventional NK cell therapies – Compelling safety profile – Shown to be effective in treating AML and preventing relapse • FATE-NK100 has demonstrated unprecedented NK cell functiona
Slide 19: Ushering in an Off-the-Shelf Cell Product Paradigm
Ushering in 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 Homogeneous Therapeutic Funct
Slide 20: Human Induced Pluripotent Stem Cells: Renewable Source for Off-the-Shelf Products
Human Induced Pluripotent Stem Cells Renewable Source for Off-the-Shelf Cell Products Using Engineered Pluripotent Cell Lines to Create NK Cells and T Cells A Single Human Induced Pluripotent Cell Unlimited Self- On-Demand Immune Renewal Cell Derivation Robust Expansion Master Cell Capacity Bank
Slide 21: Off-the-Shelf Cell Products Derived From Renewable Engineered Pluripotent Cell Lines
Off-the-Shelf Cell Products Derived From Renewable Engineered Pluripotent Cell Lines Human Pluripotent Precise Multi-Gene Engineering Renewable Engineered Cells Pluripotent Cell Line Single-cell Clonal Selection Off-the-Shelf | Homogeneous | Cell Products iT Cells iNK Cells iCD34+ Cells Other
Slide 22: Off-the-Shelf iNK Cell Cancer Immunotherapy: Potent Direct Cellular Cytotoxicity
Off-the-Shelf iNK Cell Cancer Immunotherapy Potent Direct Cellular Cytotoxicity SKOV3 (Ovarian Cancer) Killing Assay Overnight Primed NK Cells FATE-NK100 Off-the-Shelf iNK Cells (donor 1) Off-the-Shelf iNK Cells (donor 2) Tumor Killing - 22 -
Slide 23: Engineered hnCD16 iNK Cell Product Candidate
Engineered hnCD16 iNK Cell Product Candidate Off-the-Shelf Cornerstone Approach for Solid Tumors 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 affini
Slide 24: hnCD16 iNK: CD16 is Expressed and Continuously Maintained
Engineered hnCD16 iNK Cell Product Candidate CD16 is Expressed and Continuously Maintained Conventional NK Cells hnCD16 iNK Cells CD16 Shedding Frequency of NK Cells Frequency of NK Cells CD16 Shedding Control (homeostasis in culture) Treated with TACE / ADAM inhibitor (inhibits CD16 cleavage) Activ
Slide 25: hnCD16 iNK: From a Single iPSC to a Clonal Effector Cell Population
Engineered hnCD16 iNK Cell Product Candidate From a Single iPSC to a Clonal Effector Cell Population Renewable Engineered Engineered hnCD16 iNK Pluripotent Cell Line Cells for ADCC CD16 CD16 hiPSCs CD56 (NK cells) 1 iPSC 1x106 hnCD16 iNKs Clonal Expansion 1M iPSCs 1x1012 hnCD16 iNKs - 25 -
Slide 26: hnCD16 iNK: Augmented ADCC Response
Engineered hnCD16 iNK Cell Product Candidate Augmented ADCC Response Cytokine Release Unstimulated (left) vs. Anti-CD16 Stimulation (right) Cord blood NKs Peripheral blood NKs IFNγ IFNγ TNFα TNFα Enhanced Cytokine hnCD16 iNKs Release IFNγ TNFα - 26 -
Slide 27: hnCD16 iNK: In Vitro ADCC for Solid Tumors
Engineered hnCD16 iNK Cell Product Candidate 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 im e (h o u r s
Slide 28: hnCD16 iNK: Enhanced ADCC in Combination with Herceptin
Engineered hnCD16 iNK Cell Product Candidate Enhanced ADCC in Combination with Herceptin Herceptin + Untreated Herceptin hnCD16-iNK Luc-SKOV3 (Ovarian Cancer) Tumor Image Analysis D4 Initiation of treatment @ Day 5 D18 D39 - 28 -
Slide 29: hnCD16 iNK: Maintaining Inherent NK Cell Properties
Engineered hnCD16 iNK Cell Product Candidate Maintaining Inherent NK Cell Properties iN K s ( h n C D 1 6 iP S C L in e ) Minimal Reactivity to 80 Allogeneic PBMCs while 70 Cytotoxic to Transformed Cells % S p e c ific K illin g 60 50 40 iNK + K562 (Measurement of Tumor Cytotoxicity) 30 iNK + PBMCs
Slide 30: hiPSC Platform Versatility
hiPSC Platform Versatility “Backbone” iPSC Line for Incorporating Other Functionality Engineered CAR19 iNK Cells CD19+ Lymphoma Cell Line Other Functionality q Tumor-targeting strategies q CARs / TCRs q Improved persistence q Cell autonomy CAR19 iNK q Overcoming histocompatibility (HvG) q Ada
Slide 31: Off-the-Shelf iT Cell Cancer Immunotherapy: Memorial Sloan Kettering Collaboration
Off-the-Shelf iT Cell Cancer Immunotherapy Memorial Sloan Kettering Collaboration “Engineering therapeutic attributes into pluripotent cell lines is a breakthrough approach to renewably generate potent T-cell immunotherapies. This unique Dr. Michel Sadelain, MD, PhD approach offers the prospect f
Slide 32: Sadelain / Memorial Sloan Kettering Collaboration: Creating Engineered T Cells
Sadelain / Memorial Sloan Kettering Collaboration Creating Engineered T Cells Master Engineered CAR Pluripotent Cell Lines Parental hiPSC Pool CAR-hiPSC Clonal CAR-hiPSC line Empty CAR T-Cell Differentiation - 32 -
Slide 33: Our Foundational Intellectual Property
Renewable Engineered Pluripotent Cell Platform Our Foundational Intellectual Property Over 60 Issued Patents and 90 Pending Applications • Exclusive licenses from pioneers in the induced pluripotent cell field – Drs. Rudolf Jaenisch (Whitehead Institute) and Sheng Ding (TSRI) • OCT4-based generatio
Slide 34: Off-the-Shelf Immuno-Oncology Partners
Off-the-Shelf Immuno-Oncology Partners R&D and Translational Therapeutic Collaborations Jeffrey S. Miller, MD Kalle Malmberg, Dan Kaufman, Michel Sadelain, MD, PhD MD PhD MD PhD Engineered iNK Cells FATE-NK100 Engineered iT Cells Off-the-shelf NK-Cell Therapy First-in-Class Adaptive Memory
Slide 35: Immuno-Regulatory Programs
Immuno-Regulatory Programs - 35 -
Slide 36: ProTmune: Transforming the Curative Potential of Allogeneic HCT
ProTmune™ Transforming the Curative Potential of Allogeneic HCT A Next-Generation Hematopoietic Cell Graft to Prevent Life-Threatening Complications in Allogeneic HCT Patients • HCT performed with curative intent – Orphan hematologic malignancies (e.g., AML, ALL) – Rare genetic disorders (e.g., β-
Slide 37: Pathophysiology of T-Cell Mediated HCT Complications
Pathophysiology of T-Cell Mediated HCT Complications Life-Threatening GvHD, Viral Infections & Relapse Tissue Damage Cytokine Storm IL-6 IL-1β TNF-α T Cells IFN-ᵞ Donor Conditioned Patient Donor Allo-reactive Assault on Immunosuppressive T-cell Activation Patient Tissue Agents Host APCs Tc17
Slide 38: ProTmune: Attenuation of Graft-versus-Host Disease
ProTmune™ Attenuation of Graft-versus-Host Disease In Vivo Efficacy of ProTmune GvHD Survival ProTmune ProTmune p = 0.0005 p < 0.0001 Murine Allogeneic Acute GvHD Model (8 studies) - 38 -
Slide 39: ProTmune: Maintenance of Graft-versus-Leukemia
ProTmune™ Maintenance of Graft-versus-Leukemia In Vivo Efficacy of ProTmune Leukemic Cell Clearance ProTmune ProTmune (T-cell depleted) ProTmune Murine Allogeneic GvL Model (6 studies) - 39 -
Slide 40: ProTmune: Highly-Differentiated Approach for Significant Unmet Need
ProTmune™ Highly-Differentiated Approach for Significant Unmet Need FATE Bellicum Kiadis Pharma Incyte Abbvie ProTmune™ BPX-501 ATIR™ Jakafi® Imbruvica® Product Small molecule Engineered T cells Photo-depleted JAK 1 and JAK 2 Bruton's tyrosine Description modulated HCT w/ CaspaCIDe T cells inhibi
Slide 41: ProTmune: PROTECT Study in mPB HCT for Hematologic Malignancies
ProTmune™ PROTECT Study in mPB HCT for Hematologic Malignancies Design • Multi-center, open-label Phase 1/2 clinical trial in US and EU • Matched unrelated donor (MUD) mPB HCT with myeloablative conditioning – Standard of care GvHD prophylactic (Methotrexate / Tacrolimus) – No prophylactic CMV the
Slide 42: ProTmune: Next-Generation Graft to Prevent Life-threatening HCT Complications
ProTmune™ Next-Generation Graft to Prevent Life-threatening HCT Complications • Highly-differentiated therapeutic paradigm – Optimize biological properties of donor hematopoietic cells ex vivo using small molecules – Easily integrates into current clinical practice – Avoids costly and time-consu
Slide 43: 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 – Adaptiv
Slide 44: Immunoregulatory CD34+ Cell Therapy: Proof-of-Principle in Type 1 Diabetes
Immunoregulatory CD34+ Cell Therapy Proof-of-Principle in Type 1 Diabetes Paolo Fiorina, MD, PhD Assistant Professor of Pediatrics, Harvard Medical School Hyperglycemic Mice Adoptive Transfer of PD-L1+ Hematopoietic Cells • Extensive investigation into T-cell destruction of pancreatic beta cells
Slide 45: Immunoregulatory CD34+ Cell Therapy: Checking Autoreactive T Cells
Immunoregulatory CD34+ Cell Therapy Checking Autoreactive T Cells • Small molecule-programmed functionality of ToleraCyte includes: – Enhanced trafficking to sites of T-cell proliferation – Inhibiting T-cell effector function through expression / secretion of potent immunosuppressive factors (e.g
Slide 46: Mechanism of Immune Tolerance Induction
Immunoregulatory CD34+ Cell Therapy Mechanism of Immune Tolerance Induction pCD34+ cells differentiate into immune pCD34+ cells induce T-cell anergy tolerogenic dendritic cells expressing (as assessed upon re-stimulation PD-L1 and IDO1 in absence of pCD34+ cells) In Vitro CD34+ Cell Differentiati
Slide 47: Durable Disease Correction in T1D Mouse Model
Immunoregulatory CD34+ Cell Therapy Durable Disease Correction in T1D Mouse Model Blood Glucose Levels Hyperglycemic Mouse No Treatment Untreated (n=5) Vehicle-Treated HSPCs Programmed HSPCs pLK cells (n=8) 600 600 600 500 500 500 n=5 n=5 n=8 Glycemia (mg/dl) 400 400 400 300 300 300 200 Normoglycem
Slide 48: Delayed Onset of Disease in T1D Mouse Model
Immunoregulatory CD34+ Cell Therapy Delayed Onset of Disease in T1D Mouse Model Untreated (n=20) Single Administration Programmed (n=25) - 48 -
Slide 49: ToleraCyte: First-in-Class CD34+ Cell Product Candidate for Autoimmunity
ToleraCyte™ First-in-Class CD34+ Cell Product Candidate for Autoimmunity • Builds on clinical precedent suggesting role of CD34+ cells in regulating autoreactive T cells – Sustained benefits across autoimmune disorders (e.g,, T1D, MS, scleroderma) seen in HCT setting – Use of patient- and donor-
Slide 50: Financial Summary & Milestones
Financial Summary & Milestones - 50 -
Slide 51: Financial Summary
Financial Summary Three Months Ended March 31, 2017 Revenue $1.0M R&D Expense $8.0M G&A Expense $3.0M Adjusted Operating Expense 1 $9.6M Cash & Cash Equivalents $82.3M Employees 66 Total Shares Outstanding 2 55.5M [1] Excludes $0.9M in stock-based compensation expense and $0.5M in Juno-related res
Slide 52: Top Investors
Top Investors Investor Amount 1 % TSO Redmile Group 2 15,516,803 28.0% Franklin Advisers 6,076,879 10.9% Fidelity Management 4,391,885 7.9% EcoR1 Capital 2,537,026 4.6% ARCH Venture Partners 2,473,187 4.5% Venrock 2,473,187 4.5% Polaris Venture Partners 2,473,187 4.5% BVF Partners 1,945,245 3.5% Kin
Slide 53: First-in-Class Cellular Immunotherapy Pipeline
First-in-Class Cellular Immunotherapy Pipeline PROGRAM PRECLINICAL CLINICAL RIGHTS IMMUNO-ONCOLOGY FATE-NK100 – AML Worldwide FATE-NK100 – Solid Tumor mAb Combo Worldwide FATE-NK100 – Ovarian Worldwide Engineered hnCD16 iNK OTS Worldwide Engineered CAR iT Cell OTS Worldwide Ex Vivo T-Cell Mod
Slide 54: Better Cells For Better Therapies
Better Cells For Better Therapies™ - 54 -