INmune Bio Inc. · NASDAQ:INMB
INmune Bio — Investor Presentation (January 2020)
48 slides from INmune Bio's investor presentation, January 2020
Slide 1: Harnessing the Power of the Innate Immune System
HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM Modulating an Innate Immune Response Against Diseases INMB INVESTOR PRESENTATION January 2020
Slide 2: Forward Looking Statements
FORWARD LOOKING STATEMENTS This presentation contains “forward-looking statements” Forward-looking statements reflect our current view about future events. When used in this presentation, the words “anticipate,” “believe,” “estimate,” “expect,” “future,” “intend,” “plan,” or the negative of these te
Slide 3: Investment Summary
Nasdaq INVESTMENT SUMMARY INMB Cash (9/30/19) $7.4 Million ▪ Immunology company, advancing through Phase I and Phase II clinical trials Debt ▪ Two platforms with novel approaches to inflammation, neurodegenerative disease and oncology $0 Common Shares Dominant Negative Tumor Necrosis Factor (DN-TNF)
Slide 4: Management Team
MANAGEMENT TEAM TEAM PEDEGREE Raymond J. Tesi, MD, CEO/CMO & Chairman of the Board Dr. Tesi has been our President, Chief Executive Officer and acting Chief Medical Officer since the formation of the Company in September 2015. From November 2011 to May 2015, Dr. Tesi was CEO, President and Acting Ch
Slide 5: Non-Employee Board of Directors
NON-EMPLOYEE BOARD OF DIRECTORS David Szymkowski, PhD BOARD PEDEGREE David E. Szymkowski leads the immunology group as Vice President of Cell Biology at Xencor Inc where he is focused on translational development of Fc-engineered and bispecific antibodies for the treatment of autoimmune diseases, al
Slide 6: Pipeline
PIPELINE Focused on Developing Therapies that Target the INNATE IMMUNE System DN-TNF PLATFORM DISEASE FIELD PRE-CLINICAL PHASE I PHASE II (POC) PIVOTAL NEXT MILESTONE Trastuzumab Resistance Mid-20 ONCOLOGY initiate p2 NASH Mid-20 GI Initiate p2 Alzheimer’s Disease Mid-20 CNS Complete p1 IMMUNE PRIMI
Slide 7: DN-TNF Platform
DN-TNF PLATFORM T EC N OLOGY A SELECTIVE, SAFER, NEXT GENERATION TNF INHIBITOR TARGETING MARKETS EXISTING TNF INHIBITORS MUST AVOID Pro-inflammatory cytokines are positively associated with age. XPro1595™ can be used in markets such as cancer and neurodegenerative diseases where existing TNF inhibit
Slide 8: Chronic Inflammation = Innate Immune Dysfunction
CHRONIC INFLAMMATION = INNATE IMMUNE DYSFUNCTION Innate Immune Dysfunction is a Disease that Causes Various Symptoms 8
Slide 9: Tumor Necrosis Factor (TNF): The Master Cytokine
TUMOR NECROSIS FACTOR (TNF) The “Master” Cytokine LCN2 PRO-INFLAMATORY IL 6 ANTI-INFLAMATORY ▪ sTNF promotes translation of IL6, Lipocalin 2 and other sTNF Plasma Concentration downstream cytokines ▪ Block sTNF and downstream pro- inflammatory cytokines do not occur Time Adapted from Andreasen et al
Slide 10: TNF Biology
TNF BIOLOGY Two Ligands and Receptors Mediate a Diverse Set of Outcomes sTNF tmTNF Pro-inflammatory Lymphoid organ development Demyelination Myelination Neurodegeneration Immunity to infection Neuroprotection TNFR1 TNFR2 Internalization Adapted from MacEwan et al 2002 10
Slide 11: The Biology of Current Inhibitors
THE BIOLOGY OF CURRENT INHIBITORS Current Inhibitors Are Not Selective and Block X Both Forms of TNF Negative effects of TNF are a result of sTNF WHEREAS tmTNF XX Soluble TNF (‘sTNF’) Transmembrane-bound PROVIDES BAD (‘tmTNF’) GOOD IMMUNOSUPPORTIVE AND NEUROPROTECTIVE FUNCTION IMPORTANT TO HOST SURV
Slide 12: The Novel Structure of INMB's DN-TNF Protein
THE NOVEL STRUCTURE OF INMB’S DN-TNF PROTEIN 17 kDal mutated protein +10 kDal Identical to human TNF except for 6 amino acid Once a week dosing by subQ linear PEG substitutions injection 12
Slide 13: TNF Biology. How Our DN-TNF Works
TNF BIOLOGY. HOW OUR DN-TNF WORKS DIFFERENCES: DN-TNF Neutralizes ONLY Soluble TNF and Leave Transmembrane TNF Selective vs. and the Receptors Functional Non-Selective TNF Inhibition Non- DN Selective TNF Decreases Y Y “BAD” sTNF with DN-TNF Only “GOOD” tmTNF continues to inflammation does not bind
Slide 14: DN-TNF Does Not Cause Immunosuppression
DN-TNF DOES NOT CAUSE IMMUNOSUPPRESSION Inhibition of transmembrane TNF (genetically with Vehicle Etanercept knockout or DN-TNF pharmacologically with % Survival Sol-tm TNF KO tmTNF KI etanercept) causes mice to die from Listeria infection. DN-TNF treated mice survive. Days Post-Infection 14
Slide 15: Selective Targeting of TNF Prevents Demyelination
SELECTIVE TARGETING OF TNF PREVENTS DEMYLINATION Non-selective TNF Inhibition Causes Demyelination, DN-TNF Promotes Remyelination NORMAL CUPRIZONE ETANERCEPT DN-TNF Model of Multiple Sclerosis Anti-inflammatory AND Anti-inflammatory NOT immunosuppressive immunosuppressive EXACERBATED DEMYELINATION R
Slide 16: DN-TNF Options in Immuno-Oncology
DN-TNF Options in Immuno-Oncology for Treatment of Resistance to Immunotherapies 16
Slide 17: INMB Conclusions from INB03 Phase I Data
INMB CONCLUSIONS FROM INB03™ PHASE I DATA SAMPLE 11 patients treated Open Label, Biomarker Directed, ENROLLMENT CRITERIA: Dose-escalation Trial In Patients Advanced solid tumors hsCRP > 4 mg/L DEMOGRAPHIC With Advanced Solid Tumors And Treatment: INB03 subQ once a week Elevated Markers Of Inflammati
Slide 18: Trastuzumab Resistance in Breast Cancer
TRASTUZUMAB RESISTANCE IN BREAST CANCER A seldom-discussed problem PROBABILITY OF DISEASE-FREE SURVIVAL ▪ ~20% of women with breast cancer are HER2+ ▪ ~25% have metastatic disease ▪ ~30% will develop brain metastasis ▪ MUC4 expression predicts trastuzumab resistance 18
Slide 19: INB03 Reverses Trastuzumab Resistance
INB03 REVERSES TRASTUZUMAB RESISTANCE 1st – It Modifies immunology of TME and DECREASES MYELOID CELLS, INCREASES NK CELLS IN VIVO JIMT-1 BREAST CANCER INTO NUDE MOUSE FEWER MYELOID CELLS * T=trastuzumab DN=INB03 60 * + % CD 11b /C D 45 40 20 0 T N G N D Ig D T+ MORE ACTIVATED NK CELLS from Schillaci
Slide 20: INB03 Reverses Trastuzumab Resistance
INB03 REVERSES TRASTUZUMAB RESISTANCE 2nd – It Decreases MUC 4 Expression – MUC4 Expression Causes Steric Hinderance to Trastuzumab MUC4 BLOCKS TRASTUZUMAB BINDING INB03 OVERCOMES TRASTUZUMAB RESISTANCE IN JIMT-1 TUMORS INB03 DECREASES MUC4 EXPRESSION T-trastuzumab DN- INB03 Schillaci-SABCS2018 20
Slide 21: INB03 Phase II Cancer
INB03 PHASE II CANCER Modifying the TME To Reverse Resistance To Immunotherapy The Problem: HER2+ BC no effective therapy for brain metastasis The Goal: make “cold” tumors “hot!” ▪ Treatment with INB03/Drug X ▪ Both drugs cross BBB ▪ 12 patients ▪ Composite end-point ▪ If positive, petition FDA for
Slide 22: Drug X Indicated in Women with HER2+ BC
DRUG X INDICATED IN WOMEN WITH HER2 + BC ▪ Drug X used as second line in women with IgG trastuzumab resistance E Tumor Volume (mm3) ▪ E – etanercept DN ▪ DN – INB03™ ▪ Murine model with Drug X trastuzumab resistant Drug X+E HE2+ BC Drug X+DN Time 22
Slide 23: Chronic TNF Therapy Can Reduce Incidence of Alzheimer Disease
Chronic TNF Therapy Can Reduce Incidence of Alzheimer Disease (AD) 23
Slide 24: Central Role of Inflammation in Neurodegeneration
CENTRAL ROLE OF INFLAMMATION IN NEURODEGENERATION Inflammation is Associated with Many Neurological Diseases MULTIPLE SCLEROSIS ALZHEIMER’S DISEASE PARKINSON’S DISEASE Nerve Cell Synaptic Death Dysfunction Damaged Parkinson’s Myelin Affected Neuron NUMBER OF DN-TNF PUBLICATIONS FOR EACH DISEASE DEMO
Slide 25: Evidence for TNF in Alzheimer's Disease
EVIDENCE FOR TNF IN ALZHEIMER’S DISEASE Pre-clinical mechanistic studies NEURODEGENERATION EXCITOTOXICITY & REDUCED CLEARANCE OXIDATIVE STRESS OF TOXIC DEBRIS SYNAPSE ALTERNATIVE PROCESSING LOSS OF AMYLOID & TAU sTNF MICROGLIAL & ASTROGLIA ACTIVATION METABOLIC DYSFUNCTION 25
Slide 26: XPro1595 Attenuates AD Pathology In Vivo
Xpro 1595™ ATTENUATES AD PATHOLOGY IN VIVO and Restores Normal Function 26
Slide 27: Proposed Mechanism of Inflammation in AD Pathology
PROPOSED MECHANISM OF INFLAMMATION IN AD PATHOLOGY Plaques and Tangles are Cogs in the Inflammatory Loop That Perpetuate the Inflammatory Cycle by TNF Synaptic Dysfunction Amyloid plaques Neurofibrillary tangles MICROGLIA Nerve Cell Death TNF AD pathology is driven by TNF activities that modulate sy
Slide 28: TNF Inhibitors Have a Protective Effect Against Alzheimer's
TNF INHIBITORS HAVE A PROTECTIVE EFFECT AGAINST DEVELOPING ALZHEIMERS DISEASE Inflammation is Associated with the Following Conditions and Diseases PFIZER INTERNAL REVIEW OF RISK OF ALZHEIMER’S ANTI-TNFS PROTECT AGAINST CLAIMS DATA DISEASE AD & DEMENTIA TNF inhibition → 64% reduction in AD risk Risk
Slide 29: Phase 1 AD Trial
PHASE 1 AD TRIAL IMMUNOLOGIC BIOMARKERS Phase IB trial in Alzheimer’s patients with biomarkers of inflammation BEHAVIORAL BIOMARKERS OF INFLAMMATION SLEEP DISORDERS DEPRESSION PSYCHOSIS APATHY AGGRESSION DESIGN BIOLOGICAL BIOMARKERS OF INFLAMMATION ▪ 18 patients in 3 cohorts ▪ Weekly XPro1595™ SubQ
Slide 30: Combination Therapy Is the Future for AD
COMBINATION THERAPY IS THE FUTURE FOR AD XPro1595™ Strategies Combine to Provide Therapies Throughout Stages of AD MILD COGNITIVE MILD MODERATE SEVERE IMPAIRMENT ALZHEIMER’S ALZHEIMER’S ALZHEIMER’S Duration : 7 Years Duration : 2 Years Duration : 2 Years Duration : 2 Years XPRO1595 Anti-inflammato
Slide 31: Addressing the Link Between Liver Fibrosis and Inflammation
Addressing the Link Between Liver Fibrosis, the Innate Immune Cells of the Liver and Inflammation, a Pleiotropic Approach 31
Slide 32: Three Principles of INMB's NASH Program
OBESITY IN THE U.S. THREE PRINCIPLES OF INMB’s NASH PROGRAM 1. NASH is a complex pleiotropic disease with metabolic, biochemical, immunologic and intestinal elements that combine to cause hepatocyte death and fibrosis 2. Drugs with that target multiple pathologies may have an advantage over drugs th
Slide 33: Three Cycles of Inflammation Lead to NASH
THREE CYCLES OF INFLAMMATION LEAD TO NASH Regional Inflammation LIVNate™ REDUCES INSULIN RESISTANCE With No Weight Change 43 41 Body Weight (g) 39 37 43 35 Control/Saline 33 41 Control/XPro1595 Body Weight (g) 31 HSHF/Saline 39 HSHF/XPro1595 29 27 37 25 35 W i ne W k1 W k2 W k3 W k4 W k5 W k6 W k7 W
Slide 34: STAM Model
STAM MODEL LIVNate™ Reduces Hepatocyte Death and Fibrosis In Vivo With No Change in Total Body Weight LOBULAR HEPATOCYTE STEATOSIS INFLAMMATION BALLOONING n 0 1 2 3 0 1 2 3 0 1 2 7 Control 2 4 1 - - - 1 6 3 3 1 8 LIVNate™ 4 4 - - - - 5 3 8 - - NAS (mean ± SD) FIBROSIS SCORE Control 4.4 ± 0.8 Paramet
Slide 35: NASH Trial Design
NASH TRIAL DESIGN Phase IIa Biomarker Directed Trial Phase IIa open label trial ▪ Patients with F2/3 NASH by non-invasive studies with >10% fat in liver ▪ Treatment with LIVNate™ 1mg/kg SQ for 12 weeks ▪ PIFF and non-invasive biomarkers at 0, 6 and 12 weeks ▪ Open label so biomarkers “visible” at 6-
Slide 36: Natural Killer Cells Are Responsible for Clearing Residual Disease
Natural Killer cells are responsible for clearing residual disease 36
Slide 37: Immune Priming Technology
IMMUNE PRIMING T EC N OLOGY A BIOLOGIC SYSTEM THAT ALLOWS FOR THE DELIVERY OF ESSENTIAL PRIMING SIGNALS TO PATIENTS’ RESTING NK CELLS INKmune™ Immune Priming drugs helps NK cells target and kill the tumor cell by providing the missing signaling necessary to identify and lyse tumor cells. INKmune is
Slide 38: INKmune Treats Residual Disease
INKmune™ TREATS RESIDUAL DISEASE Minimal Residual Disease (MRD) is the cause of relapse and death in the majority of cancer patients Problem Cancer remains after treatment Solution Eliminate residual disease to reduce relapse Drug INKmune Target Patient’s own NK cells Status Entering Phase I trial i
Slide 39: NK Cells Determine Relapse or Survival Through MRD Targeting
NK CELLS DETERMINE RELAPSE OR SURVIVAL THROUGH THEIR ABILITY TO TARGET MRD DIFFERENCE BETWEEN SURVIVORS AND ▪ Patients who relapse have NK cells that do not target the RELAPSERS IS NK FAILURE TO ERADICATE MRD MRD which survives chemotherapy ▪ Patients who survive have NK cells that can see and targe
Slide 40: INKmune Priming's Broad Market Applications
INKmune™ PRIMING’S BROAD MARKET APPLICATIONS FOR MULTIPLE CONDITIONS INKmune™ CELLS PRIME NK RELAPSE DUE TO MRD CELLS TO ELIMINATE MRD Priming S1 Triggering S2 S2 S2 Triggering S2 rNK Cell Cancer Cell TpNK Cell Dead-Cancer Cell Tumor cells down-regulate surface molecules which INKmune™ provides prim
Slide 41: INKmune Primed NK Cells Broad Therapeutic Platform
INKmune™ PRIMED NK CELLS BROAD THERAPEUTIC PLATFORM Kill Resistant Ovarian Cancer Cells In Vitro INKmune™ TPNK Are Active Against Many Types of Cancers ✓ Blood cancers: AML, MM, lymphoma Human ovarian cancer cells plus ✓ Solid tumors: breast, ovary, prostate, renal, lung patient’s own NK cells Human
Slide 42: TpNK Therapy in Two Phase 1 AML Trials
TPNK THERAPY IN TWO PHASE 1 AML TRIALS Prolonged Remission In Patients 2x Phase 1 Clinical Trials 20 patients with high-risk AML/MDS using personalized TpNK therapy (rNK primed with INKmune ex-vivo and delivered for a single i.v. infusion) Clinical Results TpNK 1. Prolonged remissions with excellent
Slide 43: High-Risk MDS Clinical Study Objectives
HIGH-RISK MDS CLINICAL STUDY OBJECTIVES A Phase I Open-Label Dose Escalation Study of Intravenous INKmune™ in Patients with Myelodysplastic Syndrome with Excess Blasts (MDS-EB-1/2 - MDS-CMML 1/2) Primary Secondary Exploratory 1. To evaluate the safety 1. To assess the change in [or effect upon] numb
Slide 44: Refractory Ovarian Cancer Clinical Study Objectives
REFRACTORY OVARIAN CANCER CLINICAL STUDY OBJECTIVES Phase 1 Open-label and Phase 2 Randomized Study of Intraperitoneal INKmune™ in Patients with Relapsed Platinum-resistant, Platinum-refractory, or Platinum-Intolerant Ovarian Cancer Primary Secondary Exploratory 1. To evaluate the safety 1. To asses
Slide 45: DN-TNF Patents
DN-TNF PATENTS NK Patents 2021 2035 composition-of-matter (licensed from Xencor) use for treatment of cancer 2032 2039 Methods for treatment of neurologic disease INB16 composition-of-matter Future 2035 use for treatment of cancer (issued in US) 2039 use for treatment of NASH Additional IP filed and
Slide 46: Our Objectives Completed and Moving Forward
OUR OBJECTIVES COMPLETED AND MOVING FORWARD OBJECTIVE Date NASDAQ Listing Feb 4, 2019 $1 Million Park the Cloud Award – Alzheimer’s Association Feb 19, 2019 Initial Data on INB03 Phase 1 3Q, 2019 Announce LIVNate for NASH 3Q, 2019 Final INB03 Phase 1 Readout and Datalock 4Q, 2019 XPro1595 First Pati
Slide 47: Summary
SUMMARY INMB ▪ Two platforms target a wide variety of diseases in humans ▪ First dominant-negative TNF therapeutic drug targeting the master cytokine of inflammation TNF ▪ Novel approach in signaling the patients own NK cells to target residual disease ▪ Extensive data both in animals and humans on
Slide 48: Contact Us
HARNESSING THE POWER CONTACT US OFTHE INNATE IMMUNE SYSTEM INmune Bio Inc. 1200 Prospect Str. Suite 525 La Jolla, CA 92037 INMB (858) 964-3720 [email protected] www.inmunebio.com 48