Immunitybio, Inc. · NASDAQ:IBRX
Immunitybio — NantKwest — Investor Day (December 2019)
111 slides from Immunitybio's investor day presentation, Dec 2, 2019
Slide 1: The Innate Killing Ability of Natural Killer Cells
THE INNATE KILLING ABILITY OF NATURAL KILLER CELLS Dr. Patrick Soon-Shiong Chairman & CEO December 2, 2019 NantKwest The Benjamin Hotel – New York City NantKwest KOL New York Meeting – December 2, 2019
Slide 2: General Disclaimer and Forward-Looking Statements
GENERAL DISCLAIMER Not all product candidates and/or services referenced in these slides are proprietary to NantKwest or ImmunityBio and may be owned or controlled by third parties, including their affiliates. FORWARD-LOOKING STATEMENTS These slides and the accompanying oral presentation contain for
Slide 3: First in Human, First in Class: Clinical Path to Immunogenic Cell Death
First in Human, First in Class Clinical Path to Immunogenic Cell Death by Natural Killer Cell Activation NK Platforms NK Products in Clinical Development Cryopreserved • haNK Off-the-Shelf Engineered • PD-L1 t-haNK NK-92 • HER2 t-haNK Cryopreserved NK Off-the-Shelf Engineered NK-92 Autologous Cytoki
Slide 4: First in Human, First in Class: Clinical Paths to Immunogenic Cell Death
First in Human, First in Class Clinical Paths to Immunogenic Cell Death by Natural Killer Cell Activation NK Platforms NK Products in Clinical Development Cryopreserved • haNK Off-the-Shelf Engineered • PD-L1 t-haNK NK-92 • HER2 t-haNK Cryopreserved NK Off-the-Shelf Engineered NK-92 Autologous Cytok
Slide 5: Cryopreserved Ready to Use Off-the-Shelf Natural Killer Cells
Cryopreserved Ready to Use Off-the-Shelf Natural Killer Cells Off-the-Shelf NK-92 Cells 2 Billion Cells (2x109) Transfused as an Outpatient Over 30 Minutes First in Human Studies 2017 - 2019 Cryopreserved / Ready-to-Use Phase I / Ib Natural Killer Cell Transfusion Exploratory Completed Dec 2019 ~600
Slide 6: Off-the-Shelf Natural Killer Cells
Off-the-Shelf Natural Killer Cells NantKwest KOL New York Meeting – December 2, 2019
Slide 7: haNK: First in Class Natural Killer Cell Immunotherapy at Clinical Stage
First in Human First in Class Natural Killer Cell Immunotherapy at Clinical Stage haNK High Affinity Tumor Antigen CD-16 (e.g. HER2, PD-L1) IgG1 Antibody (e.g. Herceptin Avelumab) ADCC Killing Off-the-Shelf Tumor Cell Natural Killer Cell NantKwest KOL New York Meeting – December 2, 2019 7
Slide 8: NantKwest KOL New York Meeting – December 2, 2019
NantKwest KOL New York Meeting – December 2, 2019
Slide 9: PD-L1 t-haNK: First in Class Natural Killer Cell Immunotherapy
First in Human First in Class Natural Killer Cell Immunotherapy at Clinical Stage PD-L1 t-haNK PD-L1 Tumor Antigen CAR PD-L1 Direct Targeted Killing Off-the-Shelf Tumor Cell Natural Killer Cell NantKwest KOL New York Meeting – December 2, 2019 9
Slide 10: NantKwest KOL New York Meeting – December 2, 2019
NantKwest KOL New York Meeting – December 2, 2019
Slide 11: First in Human, First in Class: Clinical Paths to Immunogenic Cell Death
First in Human, First in Class Clinical Paths to Immunogenic Cell Death by Natural Killer Cell Activation NK Platforms NK Products in Clinical Development Cryopreserved • haNK Off-the-Shelf Engineered • PD-L1 t-haNK NK-92 • HER2 t-haNK Cryopreserved NK Off-the-Shelf Engineered NK-92 Autologous Cytok
Slide 12: Proprietary Method for Autologous Memory NK Cell Production in 17 Days
NantKwest Proprietary Method for Autologous (Cytokine Induced) Memory NK Cell Production in 17 Days Day 1 Day 1 Day 1 Day 17 Day 17 Cryopreservation For Future Uses Single Aliquot For Enrichment Day 1-16 NK Enrichment Autologous Apheresis Autologous Aliquot One Bag GMP-in-a-Box Concentrate Autologou
Slide 13: First in Human, First in Class: Clinical Paths to Immunogenic Cell Death
First in Human, First in Class Clinical Paths to Immunogenic Cell Death by Natural Killer Cell Activation NK Platforms NK Products in Clinical Development Cryopreserved • haNK Off-the-Shelf Engineered • PD-L1 t-haNK NK-92 • HER2 t-haNK Cryopreserved NK Off-the-Shelf Engineered NK-92 Autologous Cytok
Slide 14: IL-15 (N-803) First-in-Class IgG1-Fc IL-15 Cytokine Agonist
IL-15 (N-803) Key Features Composition IL-15 / IL-15RαFc Fusion Protein First-in-Class IgG1-Fc IL-15 Mechanism of Activation and expansion of NK and Cytokine Agonist Action CD8+ T cells, without expansion of Tregs Route of Subcutaneous (systemic) IL-15 N72D mutation enhances Administration Intravesi
Slide 15: Blood Commentary on First-In-Class IL-15 (N-803)
Blood Commentary on First-In-Class IL-15 (N-803) N-803 Mimics an Activated Dendritic Cell N-803 “…in the past, use of IL-15 in clinical trials has been hampered by the limited availability of recombinant human IL-15 (rhIL-15). Additionally, although IV rh1L-15 increased NK and CD8 T-cell numbers, it
Slide 16: Current Clinical Development Status
Current Clinical Development Status 2017 – 2019: First in Human Trials 2020+: Pivotal Trials NantKwest KOL New York Meeting – December 2, 2019 16
Slide 17: Status of Development (2017 - 2020)
First in Human, First in Class Clinical Paths to Immunogenic Cell Death by Natural Killer Cell Activation Status of Development (2017 - 2020) NK Platforms MOA NK Product Indication IND Phase I Phase Ib CD-16 IgG1 haNK Solid Tumors No DLTs First in Human Studies Targeting 2017 - 2019 Phase I / Ib PD-
Slide 18: Key Opinion Leaders
Key Opinion Leaders – December 2, 2019 Topic: Merkel Cell Carcinoma George Ansstas, MD Washington University of Medicine, St. Louis Assistant Professor Department of Medicine, Medical Oncology Topic: PD-L1 t-haNK Clint Allen, MD Johns Hopkins Otolaryngology Consult for the National Institutes of Hea
Slide 19: Status of Development (2017 - 2020)
First in Human, First in Class Clinical Paths to Immunogenic Cell Death by Natural Killer Cell Activation Status of Development (2017 - 2020) NK Platforms MOA NK Product Indication IND Phase I Phase Ib CD-16 IgG1 haNK Solid Tumors No DLTs First in Human Studies Targeting 2017 - 2019 Phase I / Ib PD-
Slide 20: Thank You
Thank You NantKwest KOL New York Meeting – December 2, 2019
Slide 21: Key Opinion Leaders: Merkel Cell Carcinoma
Key Opinion Leaders – December 2, 2019 Topic: Merkel Cell Carcinoma George Ansstas, MD Washington University of Medicine, St. Louis Assistant Professor Department of Medicine, Medical Oncology NantKwest KOL New York Meeting – December 2, 2019 21
Slide 22: Merkel Cell Carcinoma - What is Next?
Merkel Cell Carcinoma - What is Next? George Ansstas, MD Associate Professor Washington University School of Medicine 12/02/2019
Slide 23: Lecture Outlines
Lecture Outlines § Disease overview § Current treatment paradigm § Unmet medical need § Comments on NK recent data (N-803, haNK cells & avelumab in MCC)
Slide 24: Why Is MCC Important?
Why Is MCC Important? • ~2500 cases annually in the US; incidence is increasing. • Aggressive course with a disease mortality rate ~45%. 5-year OS for stage IV MCC is < 20% • Pathogenesis: - MCC polyoma virus (MCPyV) in ~80% of MCC tumors - UV-induced damage 1. Bhatia S, et al. Curr Oncol Rep. 2011;
Slide 25: A New Human Virus That Causes Cancer Reported in 2008
A New Human Virus That Causes Cancer Reported in 2008 Schematic of MCPyV Genome[1] Clonal Integration of Sm Polyomavirus in MCC[1] Replication origin al (19 l T a 6-7 ntig 2 93) 56 en P (19 ) § Merkel cell polyomavirus ( 5 V -43 11 8 ) 6-4 29) 3 93 identified by Moore and Chang P V -43 983 5000 5387
Slide 26: Genomic Landscape of MCC
Genomic Landscape of MCC A, Distribution of MCCs with high intermediate, and low TMB (N = 317). Todd C. Knepper et al. Clin Cancer Res 2019;25:596 ©2019 by American Association for Cancer Research 1-5971
Slide 27: Treatment with Immune Checkpoint Inhibitors and Patient Survival
Patient Dichotomous Treatment with immune checkpoint inhibitors and patient survival. Todd C. Knepper et al. Clin Cancer Res 2019;25:5961-5971 ©2019 by American Association for Cancer Research
Slide 28: Radiologic Tumor Response to Pembrolizumab by Viral Status
Radiologic tumor response to pembrolizumab in patients per viral status MCPyV status: • 45 evaluable patients Response rate (%) diameters of target lesions (RECIST 1.1) 100 • Investigator-assessed 90 MCPyV (+) 19/32 (59%) Percent change in sum of tumor 80 exploratory end point 70 MCPyV (-) 9/17 (53%
Slide 29: Patients that Respond to Checkpoint Have Durable Response
Patients that Respond to Checkpoint have an approximate 80% durable response
Slide 30: Major Unmet Needs for MCC Patients
Major Unmet Needs for MCC Pts § PD-1 refractory pts: PD-1 blockade is effective only in a subset of pts (~ 50% of chemotherapy-naive pts[1] and ~ 30% of chemotherapy-treated pts[2]) § Immune-suppressed pts have limited options for treatment § Effective systemic adjuvant therapy is needed for pts at
Slide 31: Metastatic MCC
Metastatic MCC § There is a strong need for rational, biology-driven drug development in MCC for finding effective options in – Pts who do not respond optimally to PD-1 blockade – Pts who cannot receive immunotherapy due to autoimmune disease or systemic immune suppression
Slide 32: MCC: Immune Evasion Mechanisms
Merkel Cell Carcinoma (MCC): Immune evasion mechanisms • Still significant unmet needs in advanced MCC - Intrinsic or acquired resistance to ICI (~50% OF MCC pts) - Ineligibility for ICI therapy (autoimmunity, immunosuppression etc). • Several mechanisms of immune evasion: - Sparse T-cell infiltrate
Slide 33: What are Natural Killer Cells?
Slide 34: Innate Lymphoid Cells
Founding member of Innate lymphoid cells Hee00 ILCa ILC2 ILC3 5-20% of Blood a lym oa =o
Slide 35: Germline DNA Encoded Receptors
Germline DNA encoded receptors: Founding member of inhibitory, activating, and cytokine Innate lymphoid cells e000 er [Feo lies 5-20% of Blood ____ lymphocytes Different from T cells! Do not have: Recombined DNA for antigen-specific activating receptor
Slide 36: What are Natural Killer Cells?
What are Natural Killer Cells? Cytotoxicity (Killing) Founding member of g Granzymes@, Innate lymphoid cells <> ~ @- Perforin © Hee00 ; Fe ILC1a ILC2 ILC3 ) A. LAMP-1 (CD107a) ! Degranulation marker | 5-20% of Blood lymphocytes Cytokine and Chemokine Production Different from T cells! Do not have: (
Slide 37: Inhibitory and Activating Receptors
Inhibitory Receptor (iKIR) Activating Receptor
Slide 38: Inhibitory and Activating Receptors
Inhibitory Receptor (iKIR) Activating Receptor
Slide 39: Inhibitory HLA Class I Receptor
Inhibitory HLA Class | Receptor (iKIR) c Activating Receptor
Slide 40: Inhibitory HLA Class I Receptor
Inhibitory HLA Class | Receptor (iKIR) Response NoNK | Heajth | Activating ~ aNKR Receptor Ligands
Slide 41: Infection and Disease Activating Ligands
R aoe ie) HLA Class | Infection €ceptor (1 eH : | Disease | ~ aNKR Ligands Activating Receptor
Slide 42: Missing Self
Missing Self (HLA Mismatch) Inhibitory Infection Receptor (iKIR) nd Sd Disease Activating - aNKR Receptor — Ligands
Slide 43: Missing Self
Missing Self (HLA Mismatch) Inhibitory Infection Receptor (iKIR) He ea Disecse | 8 y Malignant ~ aNKR ransformatio Ligands Abnormal Self Activating Receptor
Slide 44: NK cell multipotential function
Slide 45: Communicate
Communicate — Recruit IFN-y”s °° 49 / TNF, GM-CSF Signal Danger: <3. MIPta
Slide 46: Communicate
Communicate IFN-y° ne cru °°. / TNF, GM-CSF Signal Danger: ;5- MIPta
Slide 47: Communicate
Communicate . ee IFN-° 6 Recruit. V/n hice SS Signal Danger:
Slide 48: Communicate
Communicate ee * Recruit . Signal Danger*4¥-" MiP ia *” Kill Cancer (Single Cell Killing)
Slide 49: Communicate
Communicate os 2 * , : IFNy" 6 Recruit oo (ine hese SS, Signal Danger: 4x. MIP1a Kill Cancer (Single Cell Killing)
Slide 50: Cytokines enable functionality, survival, proliferation
enable functionality, survival, proliferation, metabolism, inhibitory/activating receptors
Slide 51: Cytokines enable functionality, survival, proliferation
enable functionality, survival, proliferation, metabolism, inhibitory/activating receptors Infection %
Slide 52: Cytokines enable functionality, survival, proliferation
enable functionality, survival, proliferation, metabolism, inhibitory/activating receptors Infection 1%
Slide 53: Cytokines enable functionality, survival, proliferation
enable functionality, survival, proliferation, metabolism, inhibitory/activating receptors ° e Danger, , e TNF, GM- : ee “CSE ° Infection
Slide 54: Cytokines enable functionality, survival, proliferation
enable functionality, survival, proliferation, metabolism, inhibitory/activating receptors Recruit Chemokines MIP-1a, MIP-1B ‘6 Infection RANTES * a
Slide 55: Cytokines enable functionality, survival, proliferation
enable functionality, survival, proliferation, metabolism, inhibitory/activating receptors Recruit Chemokines MIP-10, MIP-1B v6 Infection RANTES m7 a Expand
Slide 56: Cytokines enable functionality, survival, proliferation
enable functionality, survival, proliferation, metabolism, inhibitory/activating receptors Recruit Chemokines : aa ee P farm Infection Arm Death Receptors: TRAIL FASL Expand
Slide 57: Cytokines enable functionality, survival, proliferation
enable functionality, survival, proliferation, metabolism, inhibitory/activating receptors Recruit Chemokines : MIP-10, MIP-18 Sé Infection RANTES Arm ie Check point Arm Death Receptors: TRAIL FASL Expand
Slide 58: Phase II Trial of Activated Natural Killer Cells (NCT02465957)
Innate Immunity: Phase II Trial of Activated Natural Killer Cells (NCT02465957) Response With aNK Cell Therapy in a Pt With MCC Refractory to Chemotherapy, RT, and PD-1 Blockade Bhatia S, et al. SITC 2016. Abstract 45.
Slide 59: Pembrolizumab Rechallenge Led to Durable CR
Despite radiologic CR, residual MCC was detected on biopsy. Pembrolizumab re- challenge led to durable CR, ongoing at 3 yrs August 2016 July 2019 Pembrolizumab 2015 2016 2017 2018 2019 Ongoing CR Oct Pembro Neutron 2014 RT RT+IFN+ TLR-4 QUILT-3.009: Pembrolizumab imiquimod agonist+RT aNK
Slide 60: Patient 02-02: Immune Cell Infiltration Increased After aNK
Patient 02-02: Immune cell infiltration in the TME is increased after aNK Monotherapy Nuclei CD8 H&E Pre 1.8 4.5 Months from Start of Therapy
Slide 61: Patient 02-02: Immune Response Gene Expression Increased
Patient 02-02: Immune response-related gene expression is increased in the TME after aNK monotherapy IFN-g-responsive gene expression Pre 1.8 4.5 Months from Start of Therapy
Slide 62: QUILT-3.009: Conclusions
QUILT-3.009: Conclusions § aNK monotherapy and aNK+N-803 were well-tolerated, with no treatment-related SAEs or grade ≥3 AEs. § Promising clinical activity was observed with aNK monotherapy and with aNK+N-803 [ORR of 29% (2 of 7 patients); 1 pt with SD]. – 1 patient (aNK monotherapy) experienced a r
Slide 63: QUILT-3.063 Study Design
QUILT-3.063: A PHASE 2 STUDY OF COMBINATION THERAPY WITH AN IL-15 SUPERAGONIST (N-803), OFF-THE-SHELF CD16-TARGETED NATURAL KILLER CELLS (HANK), AND AVELUMAB WITHOUT CYTOTOXIC CHEMOTHERAPY IN SUBJECTS WITH MERKEL CELL CARCINOMA (MCC) THAT HAS PROGRESSED ON OR AFTER TREATMENT WITH A CHECKPOINT INHIBI
Slide 64: Study Objectives
Study Objectives § Primary – Evaluate safety of Avelumab, haNK™, and N-803 in subjects with progressed MCC on or after checkpoint inhibitor therapy. – Determine efficacy of Avelumab, haNK™, and N-803 in subjects with progressed MCC on or after checkpoint inhibitor therapy. – ORR using RECIST 1.1 bas
Slide 65: Planned Enrollment
Planned Enrollment § 15-20 US sites. § Up to 43 subjects. – Initially 18 subjects enrolled; ≤ 2 subjects confirmed response, enrollment terminated; otherwise additional 25 subjects enrolled in second stage. – 52 subjects screened to reach max target. – Number includes replacement subjects. § Utilize
Slide 66: Study Treatment Schema
Study Treatment Schema § Combination therapy administered: – Day 1, every 2 weeks: Avelumab via IV, haNK™ via IV – Day 1, every 3 weeks: N-803 SC injection. § Treatment for up to 2 years. § Treatment discontinued if experience PD, unacceptable toxicity, withdraw consent, or not longer in patient’s b
Slide 67: haNK Program: Enhanced Antibody Killing (ADCC)
haNK Program Enhanced Antibody Killing (ADCC) IgG1 CD16 Binding antibody haNK Program Innate Direct Killing • Over 200 doses administered in Avelumab combination with avelumab • Cryopreservation storage Universal Off the Shelf • Off the Shelf ready to use Activated Natural Avelumab Killer Cell • Bri
Slide 68: Investigational Product: haNK
Investigational Product – haNK™ NK-92 [CD16.158V, ER IL-2] haNK = HIGH AFFINITY NATURAL KILLER CELLS § NK (Natural Killer) cells provide a rapid defense response to virus-infected cells and tumor cells. § NK cells are activated and regulated by cytokines including IL- 2 and IL-15. § haNK Cells – NK
Slide 69: Investigational Product: N-803
Investigational Product – N-803 N-803; IL15 Superagonist Fusion Complex § N-803 is an IL-15 stimulator (IL = interleukin → cytokine → brings about cell to cell communication ) § IL-15 promotes NK and T cell expansion and activation without expanding immunosuppressive regulatory T cells. § Administer
Slide 70: Combination Therapy Summary
Combination Therapy Summary Route Approved or Intended Mechanism of Action in of Composition Investigation MCC Admin al . N-803 Protein Complex Activation and proliferation of NK and Mutated IL-15 / IL-15Rα CD8+ T cells, without proliferation of SubQ Investigational (IL-15RαFc) Fc Tregs Natural Kill
Slide 71: Thank You
Thank You
Slide 72: Key Opinion Leaders: PD-L1 t-haNK
Key Opinion Leaders – December 2, 2019 Topic: PD-L1 t-haNK Clint Allen, MD Johns Hopkins Otolaryngology Consult for the National Institutes of Health Associate Professor of Otolaryngology Head and Neck Surgery NantKwest KOL New York Meeting – December 2, 2019 51
Slide 73: Why we should be focused on developing NK cellular therapies
Why we should be focused on developing NK cellular therapies Clint T. Allen, MD, FACS Chief, Translational Tumor Immunology Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD Associate Professor, Otolaryngology-Head and Neck Surgery
Slide 74: Discussion topics
Discussion topics • What is the scientific rationale for the development of NK cell-based immunotherapy when we have so many options for T cell-based immunotherapy? • What advantages might NK cellular therapy have over T cell-based cellular therapy? 53
Slide 75: Genomic instability leads to subclones with different mutations
Genomic instability leads to subclones of cells within a tumor that have different mutations 54
Slide 76: Subclones lose genes required for T cell killing
Subclones of tumor cells within an individual cancer lose genes required for T cell killing Tumor cells require HLA expression and proper antigen processing to be detected and killed by T cells Examples of mutated or lost genes: Class I or class II HLA alleles Antigen processing machinery genes IFN
Slide 77: NK cells can still detect and kill tumor cells invisible to T cells
NK cells can still detect and kill tumor cells invisible to T cells NK cells require neither HLA nor antigen to detect and kill a tumor cell Figures adapted from PMID: 27755997 56
Slide 78: NK cellular therapy is feasible as an off the shelf product
NK cellular therapy is feasible as an “off the shelf” product haNK Engineered autologous T cells (high-affinity NK cell) Adapted from PMID 24329789 57
Slide 79: Immunosuppressive myeloid cells
Another major mechanism of tumor immune escape: Immunosuppressive myeloid cells Myeloid cells express very high levels of PD-L1 58
Slide 80: The next NK cellular therapy product: PD-L1 t-haNKs
The next NK cellular therapy product: PD-L1 t-haNKs haNK cells that express a chimeric antigen receptor that targets PD-L1 These cells have two major mechanisms of killing: 1) Direct NK killing 2) PD-L1 specific killing 59
Slide 81: PD-L1 t-haNKs efficiently kill PD-L1+ tumor cells
PD-L1 t-haNKs efficiently kill PD-L1+ tumor cells Tumor cell killing is increased when cell surface PD-L1 is increased and decreased by ~80% when PD-L1 is deleted. 60 Confidential - unpublished
Slide 82: PD-L1 t-haNKs deplete immunosuppressive cells in tumor-bearing mice
Treatment of tumor-bearing mice with PD-L1 t-haNKs depletes immunosuppressive cells Immune cells within the tumor that have high PD-L1 expression (macrophages and MDSC) are selectively reduced and good effector immune cells are increased. 61 Confidential - unpublished
Slide 83: PD-L1 t-haNK treatment cured 30% of mice
PD-L1 t-haNK treatment cured 30% of mice bearing resistant MOC1 tumors Anti-tumor effect in mice is lost in PD-L1 knockout tumors or when T cells depleted Confidential - unpublished 62
Slide 84: PD-L1 t-haNKs deplete immunosuppressive cells from patient blood
PD-L1 t-haNKs deplete immunosuppressive cells from the blood of cancer patients Human immune cells that have high PD-L1 expression (macrophages and MDSC) are selectively reduced 63 Confidential - unpublished
Slide 85: First in Human Phase I PD-L1 t-haNK Safely Administered
First in Human Phase I PD-L1 t-haNK Safely Administered to First 6 Patients Without SAE or DLT as Outpatient 64
Slide 86: Conclusions
Conclusions • Curing most patients with heterogeneous tumors with T cell-based immunotherapy alone is unlikely • NK-based immunotherapy is likely to be additive or synergistic with T cell-based immunotherapy • The availability of NK cellular therapies such as haNKs or t.haNKs add a valuable tool to
Slide 87: Thank you
NIH Collaborators: Nikki Schmitt, MD (NIDCD) Nyall London, MD, PhD (NIDCD) Carter Van Waes, MD, PhD (NIDCD) Translational Tumor Immunology Program Team: Christian Hinrichs, MD (ETIB, NCI) Paul Clavijo, PhD Claudia Palena, PhD (LTIB, NCI) Jay Friedman, PhD Jim Hodge, PhD (LTIB, NCI) Sreeni Gunti, PhD
Slide 88: Key Opinion Leaders: Triple Negative Breast Cancer
Key Opinion Leaders – December 2, 2019 Topic: Triple Negative Breast Cancer (TNBC) Chaitali Nangia, MD CSSIFM & Hoag Hospital Newport Beach Medical Oncologist 67
Slide 89: NANT Cancer Vaccine: Triple-Negative Breast Cancer
NANT Cancer Vaccine Triple-Negative Breast Cancer Chaitali Nangia MD Associate Professor Chan Soon-Shiong Institute for Medicine (CSSIFM) Immune Oncology Clinic December 2, 2019 NantKwest KOL Meeting - December 2, 2019 - Unpublished 68 68
Slide 90: Study Design
Study Design Phase 1b Trial for patients with relapsed or refractory metastatic TNBC Beyond First line SOC therapy • Low-dose metronomic chemoradiation therapy and immunotherapy activating NK and T-Cells • haNK cells: off-the-shelf high-affinity natural killer cells • Avelumab: Anti-PD-L1IgG1 antibo
Slide 91: Phase Ib Trial: Patient Population
Phase Ib Trial: Patient Population – Advance Disease • 9 Patients enrolled between 3/2018 to present • Most patients were third line of therapy or greater Lines of Therapy Received Patients Enrolled 1 1 2 4 3 2 4 2 NantKwest KOL Meeting - December 2, 2019 - Unpublished 70
Slide 92: Durable Efficacy Results in Advanced TNBC
Durable Efficacy Results in Advanced TNBC Early Efficacy: • Median PFS 13.7 months (Historical PFS in 2nd Line or Greater: 2-3 Months) • 7 / 9 patients treated show a DCR, disease control rate (CR + PR* + SD) of 78% • 6 / 9 patients show overall response rate (PR + CR) of 67% • 2 / 9 patients show a
Slide 93: Percent Change in Size of Target Lesion from Baseline
Percent Change in Size of Target Lesion from Baseline ORR: PR* + CR: 6 / 9 (67%) 90% CR: 2 / 9 (22%) Disease Control: 7 / 9 (78%) * Confirmed and Unconfirmed PR 40% 20% +20% Progression 16% -10% -25% -29% -31% -33% -34% -30% Partial Response -30% -60% -71% -82% -100% -110% NantKwest KOL Meeting - De
Slide 94: Early Signs of Efficacy in Relapsed Metastatic TNBC
Early Signs of Efficacy in Relapsed (3rd line) Metastatic Triple Negative Breast Cancer Best Response by Resist 1.1 80% ORR: PR* + CR: 6 / 9 (67%) X Patient #2 CR: 2 / 9 (22%) Deceased 60% Disease Control: 7 / 9 (78%) * Confirmed and Unconfirmed PR 40% % Change from Baseline 20% 20% Progression Pati
Slide 95: Safety
Safety • All patients received therapy in the outpatient setting • No patients experienced cytokine release syndrome • No SAE or hospitalizations attributable to immunotherapy • All patients experienced at least 1 Grade >3 treatment related AE (mostly cytopenias due to chemotherapy) • Grade 3 AEs fo
Slide 96: Case Study #1: Patient 01, Durable Partial Response
Case Study #1: Patient 01: 57 Year-Old Female with 3rd Line TNBC Demonstrating Durable Partial Response Exceeding 400 Days 80% ORR: PR* + CR: 6 / 9 (67%) X Patient #2 CR: 2 / 9 (22%) Deceased 60% Disease Control: 7 / 9 (78%) * Confirmed and Unconfirmed PR 40% % Change from Baseline 20% 20% Progressi
Slide 97: Case Study #1: Patient 01 Timeline
Case Study #1: Patient 01: 57 Year-Old Female with 3rd Line TNBC Demonstrating Durable Partial Response Exceeding 400 Days First Observation of Partial Response July 10, 2018 Durable Partial Presented Day 105 1st-Line Relapsed as 3rd-Line Response Exceeding Doxorubicin TNBC NANT Cancer 400 days Cyto
Slide 98: Case Study #1: 71% Tumor Reduction by RECIST 1.1
Case Study #1: Patient 01: 57 Year-Old Female with 3rd Line TNBC Demonstrating Durable Partial Response Exceeding 400 Days 71% Tumor Reduction by RECIST 1.1 3/19/2018 11/05/2018 77
Slide 99: Case Study #2: Patient 04
Case Study #2: Patient 04: 51 Year-Old Female with 3rd Line Metastatic TNBC Approaching Complete Response Post Progression 80% ORR: PR* + CR: 6 / 9 (67%) X Patient #2 CR: 2 / 9 (22%) Deceased 60% Disease Control: 7 / 9 (78%) * Confirmed and Unconfirmed PR 40% % Change from Baseline 20% 20% Progressi
Slide 100: Case Study #2: Patient 04 Timeline
Case Study #2: Patient 04: 51 Year-Old Female with 3rd Line Metastatic TNBC Approaching Complete Response Post Progression First Observation of Partial Response Post Study • Patient Had a 31% Genomics analysis 3rd-Line Partial response in 1st-Line 2rd-Line NANT Cancer target lesion masses showed PIK
Slide 101: Case Study #2: Patient 04 Scans
Case Study #2: Patient 04: 51 Year-Old Female with 3rd Line Metastatic TNBC Approaching Complete Response Post Progression Partial Response Nearing Pre-Study Scan On Study Complete Response 1.56 cm by 2.12 cm 1.52 cm by 1.83 cm Off Study Sept 2018 Dec 2018 Sept 2019 Durable Partial Response – 292 Da
Slide 102: Case Study #3: Patient 08
Case Study #3: Patient 08: 53-Year Old Female with 3rd-Line TNBC Demonstrating Durable Complete Response – 12 Months and Ongoing 80% ORR: PR* + CR: 6 / 9 (67%) X Patient #2 CR: 2 / 9 (22%) Deceased 60% Disease Control: 7 / 9 (78%) * Confirmed and Unconfirmed PR 40% % Change from Baseline 20% 20% Pro
Slide 103: Case Study #3: Patient 08 Timeline
Case Study #3: Patient 08: 53-Year Old Female with 3rd-Line TNBC Demonstrating Durable Complete Response – 12 Months and Ongoing Complete Response Presented Ongoing for 1 Year 3rd-Line 1st-Line 2nd-Line NANT Cancer NANT Cancer Vaccine Trial Doxorubicin Vaccine Trial CR achieved January 2019 Cytoxan
Slide 104: Case Study #3: Patient 08 Scans
Case Study #3: Patient 08: 53-Year Old Female with 3rd-Line TNBC Demonstrating Durable Complete Response – 12 Months and Ongoing Pre-Treatment Scan Complete Response Oct 2018 Dec 2018 Durable Complete Response (12 Months and Ongoing) NantKwest KOL Meeting - December 2, 2019 - Unpublished 83
Slide 105: Case Study #4: Patient 09
Case Study #4: Patient 09: 53 Year Old Female with 4th-Line TNBC With Durable Complete Response (11 Months & Ongoing) 80% ORR: PR* + CR: 6 / 9 (67%) X Patient #2 CR: 2 / 9 (22%) Deceased 60% Disease Control: 7 / 9 (78%) * Confirmed and Unconfirmed PR 40% % Change from Baseline 20% 20% Progression Pa
Slide 106: Case Study #4: Patient 09 Timeline
Case Study #4: Patient 09: 53 Year Old Female with 4th-Line TNBC With Durable Complete Response (11 Months & Ongoing) Complete Response 5th-Line 6th-Line 1st-Line 2nd-Line 3rd-Line Abraxane CR observed Herceptin Started NCV January 2019 Taxotere Surgery 4th-Line + on Ongoing CR to Carboplatin follow
Slide 107: Case Study #4: Patient 09 Scans
Case Study #4: Patient 09: 53 Year Old Female with 4th-Line TNBC With Durable Complete Response (11 Months & Ongoing) Pre-Treatment Scan Large Peri-Aortic Mass with Cardiac Tamponade Complete Response Nov 2018 July 2019 Durable Complete Response (11 Months and Ongoing) NantKwest KOL Meeting - Decemb
Slide 108: Case Study #4: Patient 09 Lung Mass Scans
Case Study #4: Patient 09: 53 Year Old Female with 4th-Line TNBC With Durable Complete Response (11 Months & Ongoing) Pre-Treatment Scan Large Apical Lung Mass Complete Response Nov 2018 July 2019 Durable Complete Response (11 Months and Ongoing) NantKwest KOL Meeting - December 2, 2019 - Unpublishe
Slide 109: haNK Cell Infusion Experience
Natural Killer Cell haNK Cell Infusion Experience Total: 547 infusions of haNK given to date TNBC: 224 haNK infusions given to date • Early signs of efficacy with favorable PFS, ORR and Duration of Response • Durable complete remissions • All patients were in an outpatient setting • Zero incidence o
Slide 110: Future Direction: Phase II Randomized TNBC Neoadjuvant Schema
Future Direction: Phase II Exploratory Randomized TNBC Neoadjuvant Schema Investigator Initiated Trial Week 1 Week 2 Week 3 Day 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Arm 1 Cyclophosphamide (50 mg PO BID) Cyclophosphamide (50 mg PO BID) - Rest Period - N=29 Aldoxorubicin (150 mg/m2 IV
Slide 111: Q&A Session
Q&A Session December 2, 2019 The Benjamin Hotel – New York City