Inmune Bio Inc. · NASDAQ:INMB
Inmune Bio — Investor Presentation (April 2020)
47 slides from Inmune Bio's investor presentation, Apr 9, 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 IN MB INVESTOR PRESENTATION 2Q 20 V1
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 the
Slide 3: Investment Summary
▪ Immunology company, advancing through Phase I and Phase II clinical trials ▪ Two platforms with novel approaches to inflammation, neurodegenerative disease and oncology INB03™ & INKmune™ - Resistance to cancer immunotherapy by altering the TME and triggering NK cells XPro1595™ - Neuroinflammation
Slide 4: Management Team
MANAGEMENT TEAM 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 Chief Medic
Slide 5: Non-Employee Board of Directors
NON - EMPLOYEE BOARD OF DIRECTORS David Szymkowski, PhD 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, allergic dis
Slide 6: Pipeline
DN - TNF PLATFORM DISEASE FIELD PRE - CLINICAL PHASE I PHASE II (POC) PIVOTAL NEXT MILESTONE Trastuzumab Resistance ONCOLOGY NASH GI Alzheimer’s Disease CNS Mid - 20 Initiate p2 Mid - 20 initiate p2 NK PRIMING PLATFORM DISEASE FIELD PRE - CLINICAL PHASE I PHASE II (POC) PIVOTAL NEXT MILESTONE Ovaria
Slide 7: A Selective, Safer, Next Generation TNF Inhibitor
A SELECTIVE, SAFER, NEXT GENERATION TNF INHIBITOR TARGETING MARKETS EXISTING TNF INHIBITORS MUST AVOID DN - TNF PLATFORM TECNOLOGY Pro - inflammatory cytokines are positively associated with age. XPro1595™ can be used in markets such as cancer and neurodegenerative diseases where existing TNF inhibi
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 ▪ sTNF promotes translation of IL6, Lipocalin 2 and other downstream cytokines ▪ Block sTNF and downstream pro - inflammatory cytokines do not occur LCN2 IL 6 ANTI - INFLAMATORY Time Plasma Concentration sTNF 9 PRO - INFLAMATORY Adapted from Andrease
Slide 10: TNF Biology
TNF BIOLOGY Two Ligands and Receptors Mediate a Diverse Set of Outcomes tmTNF sTNF Pro - inflammatory Demyelination Neurodegeneration BAD TNF Prevents immunosuppression Promotes rem yelination Improves immune response to cancer Neuroprotection Improves synaptic function GOOD TNF 10 TNFR1 TNFR2 Inter
Slide 11: Negative Effects of TNF Are a Result of sTNF
Negative effects of TNF are a result of sTNF WHEREAS tmTNF PROVIDES IMMUNOSUPPORTIVE AND NEUROPROTECTIVE FUNCTION IMPORTANT TO HOST SURVIVAL THE BIOLOGY OF CURRENT INHIBITORS Current Inhibitors Are Not Selective and Block Both Forms of TNF Transmembrane - bound (‘tmTNF’) GOOD Soluble TNF (‘sTNF’) BA
Slide 12: The Novel Structure of DN-TNF Protein
THE NOVEL STRUCTURE OF DN - TNF PROTEIN 17 kDal mutated protein +10 kDal linear PEG Identical to human TNF except for 6 amino acid substitutions Once a week dosing by subQ injection 12
Slide 13: How DN-TNF Works: Selective vs. Non-Selective Inhibition
Decreases inflammation Y Y Increased risk of infection Y N Increased risk of cancer Y N Causes demyelination Y N Neuroprotective N Y Enhances neuroplasticity N Y DIFFERENCES: Selective vs. Non - Selective TNF Inhibition Non - Selective DN TNF TNF BIOLOGY. HOW DN - TNF WORKS DN - TNF Neutralizes ONLY
Slide 14: DN-TNF Does Not Cause Immunosuppression
DN - TNF DOES NOT CAUSE IMMUNOSUPPRESSION Inhibition of transmembrane TNF (genetically with knockout or pharmacologically with etanercept) causes mice to die from Listeria infection. DN - TNF treated mice survive. 14 Vehicle Etanercept DN - TNF Sol - tm TNF KO tmTNF KI Days Post - Infection % Surviv
Slide 15: Selective Targeting of TNF Prevents Demyelination
SELECTIVE TARGETING OF TNF PREVENTS DEMYLINATION Non - selective TNF Inhibition Causes Demyelination, DN - TNF Promotes Remyelination EXACERBATED DEMYELINATION REMYELINATION ETANERCEPT Anti - inflammatory AND immunosuppressive DN - TNF Anti - inflammatory NOT immunosuppressive CUPRIZONE Model of Mul
Slide 16: DN-TNF Options in Immuno-Oncology
DN - TNF Options in Immuno - Oncology for Treatment of Resistance to Immunotherapies 16
Slide 17: Conclusions from INB03 Phase I Data
SAMPLE 11 patients treated DEMOGRAPHIC Age (median): 54 Gender: 6M/5F DISEASE Ovary, Mesothelioma; RCC, Lung; Prostate; Colon, Cholangial, other PREVIOUS LINES OF THERAPY 3 (range:2 - 5) INB03 DURATION 74 days (21 - 119d) • No drug related SAE • All discontinuation due to disease progression PHASE I
Slide 18: Trastuzumab Resistance in Breast Cancer
▪ ~20% of women with breast cancer are HER2+ ▪ ~25% have metastatic disease ▪ ~30% will develop brain metastasis ▪ MUC4 expression predicts trastuzumab resistance PROBABILITY OF DISEASE - FREE SURVIVAL 18 TRASTUZUMAB RESISTANCE IN BREAST CANCER A seldom - discussed problem
Slide 19: INB03 Reverses Trastuzumab Resistance
INB03 ™ REVERSES TRASTUZUMAB RESISTANCE Decreases MUC 4 Expression – MUC4 Expression Causes Steric Hinderance to Trastuzumab INB03 OVERCOMES TRASTUZUMAB RESISTANCE IN JIMT - 1 TUMORS T - trastuzumab DN - INB03 Schillaci - SABCS2018 MUC4 BLOCKS TRASTUZUMAB BINDING INB03 DECREASES MUC4 EXPRESSION 19
Slide 20: INB03 Reverses Trastuzumab Resistance: Modifies TME
INB03 ™ REVERSES TRASTUZUMAB RESISTANCE Modifies immunology of TME and DECREASES MYELOID CELLS, INCREASES NK CELLS IN VIVO I g G T D N T + D N 0 20 40 60 % C D 1 1 b / C D 4 5 + * * FEWER MYELOID CELLS from Schillaci 2018 T =trastuzumab DN =INB03 JIMT - 1 BREAST CANCER INTO NUDE MOUSE MORE ACTIVATED
Slide 21: INB03 Phase II Cancer
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 Break - Through Designation ▪ If positive, consider adding CPI 21 INB03 ™ PH
Slide 22: Drug X Indicated in Women with HER2+ BC
Drug X+DN Drug X+E Drug X ▪ Drug X used as second line in women with trastuzumab resistance ▪ E – etanercept ▪ DN – INB03™ ▪ Murine model with trastuzumab resistant HE2+ BC 22 DRUG X INDICATED IN WOMEN WITH HER2 + BC DN E IgG Time Tumor Volume (mm 3 )
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
MULTIPLE SCLEROSIS ALZHEIMER’S DISEASE PARKINSON’S DISEASE Synaptic Dysfunction Nerve Cell Death Parkinson’s Affected Neuron Damaged Myelin NUMBER OF DN - TNF PUBLICATIONS FOR EACH DISEASE DEMONSTRATING DISEASE - MODIFYING ACTIVITY 6 5 5 24 CENTRAL ROLE OF INFLAMMATION IN NEURODEGENERATION Inflammat
Slide 25: Proposed Mechanism of Inflammation in AD Pathology
TNF Amyloid plaques Neurofibrillary tangles MICROGLIA Synaptic Dysfunction Nerve Cell Death AD pathology is driven by TNF activities that modulate synapses and drive cell death 25 PROPOSED MECHANISM OF INFLAMMATION IN AD PATHOLOGY Plaques and Tangles are Cogs in the Inflammatory Loop That Perpetuate
Slide 26: XPro1595 Attenuates AD Pathology In Vivo
26 Xpro 1595 ™ ATTENUATES AD PATHOLOGY IN VIVO and Restores Normal Function
Slide 27: TNF Inhibitors Have a Protective Effect Against Alzheimer's
RISK OF ALZHEIMER’S DISEASE Risk of general population Adapted from Chou et al. 2016 8.5M claims ANTI - TNFS PROTECT AGAINST AD & DEMENTIA Adapted from Zhou et al. 2016 56M claims Despite positive AD activity, non - selective TNF inhibitors increase the risk of cancer, infection, and MS AD risk is n
Slide 28: Peripheral XPro1595 Decreases Central Neuroinflammation
28 • Reporter in brain “lights up” with neuroinflammation caused by LPS • subQ XPro1595 eliminates neuroinflammation within 3 hours Peripheral XPro1595 ™ DECREASES Central NEUROINFLAMMATION
Slide 29: Phase 1 AD Trial
IMMUNOLOGIC BIOMARKERS BEHAVIORAL BIOMARKERS OF INFLAMMATION SLEEP DISORDERS DEPRESSION PSYCHOSIS APATHY AGGRESSION MRI CSF Breath Blood FreeWater content of white matter (Imeka) Inflammation & Neurodegeneration ( Roche NeuroTool kit ) Volatile Organic Compounds Inflammation & Neurodegeneration ( Ro
Slide 30: Combination Therapy Is the Future for AD
COMBINATION THERAPY IS THE FUTURE FOR AD MILD COGNITIVE IMPAIRMENT MILD ALZHEIMER’S MODERATE ALZHEIMER’S SEVERE ALZHEIMER’S Duration : 7 Years Duration : 2 Years Duration : 2 Years Duration : 2 Years 30 Aducanumab Anti - AB Strategies XPro1595™ Strategies Combine to Provide Therapies Throughout
Slide 31: Liver Fibrosis and Innate Immune Cells: Pleiotropic Approach
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
THREE PRINCIPLES OF INMB’s NASH PROGRAM OBESITY IN THE U.S. Obesity increases the risk of dementia and NASH. XPro1595 has been shown to reverse both in vivo. Tansey, et. Al. 1. NASH is a complex pleiotropic disease with metabolic, biochemical, immunologic and intestinal elements that combine to caus
Slide 33: Three Cycles of Inflammation Lead to NASH
THREE CYCLES OF INFLAMMATION LEAD TO NASH LIVNate™ REDUCES INSULIN RESISTANCE 25 27 29 31 33 35 37 39 41 43 B a s e l i n e W e e k 1 W e e k 2 W e e k 3 W e e k 4 W e e k 5 W e e k 6 W e e k 7 W e e k 8 W e e k 9 W e e k 1 0 w e e k 1 1 w e e k 1 2 w e e k 1 3 B o d y W e i g h t ( g ) Control/Sali
Slide 34: LIVNate Reduces Hepatocyte Death and Fibrosis In Vivo
0 1 2 3 0 1 2 3 0 1 2 Control 2 4 1 - - - 1 6 3 3 1 LIVNate™ 4 4 - - - - 5 3 8 - - HEPATOCYTE BALLOONING LOBULAR INFLAMMATION STEATOSIS Control 4.4 ц 0.8 LIVNate™ 2.9 ц 0.8 NAS (mean ц SD) Parameter (mean ц SD) Control LIVNate™ Sirus Red positive area (%) 0.96 ц 0.29 0.69 ц 0.23 FIBROSIS SCORE n 7 8
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” a
Slide 36: Natural Killer Cells Clear Residual Disease
Natural Killer cells are responsible for clearing residual disease 36
Slide 37: NK Priming Technology: INKmune
A BIOLOGIC SYSTEM THAT ALLOWS FOR THE DELIVERY OF ESSENTIAL PRIMING SIGNALS TO PATIENTS’ RESTING NK CELLS NK PRIMING TECNOLOGY 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 not ant
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
Slide 39: NK Cells Determine Relapse or Survival
NK CELLS DETERMINE RELAPSE OR SURVIVAL THROUGH THEIR ABILITY TO TARGET MRD ▪ Patients who relapse have NK cells that do not target the MRD which survives chemotherapy ▪ Patients who survive have NK cells that can see and target MRD and provide long lasting remissions ▪ Circulating resting NK cells a
Slide 40: INKmune Cells Prime NK Cells to Eliminate MRD
S1 S2 rNK Cell = Resting NK Cell TpNK Cell = tumor - primed NK Cell INKmune™ provides missing signals to the NK cells to initiate NK killing of tumor cells INKmune™ CELLS PRIME NK CELLS TO ELIMINATE MRD S2 Tumor cells down - regulate surface molecules which prime NK cell activity, “evading” NK cell
Slide 41: INKmune Primed NK Cells
INKmune™ PRIMED NK CELLS Human ovarian cancer cells plus patient’s own NK cells Human ovarian cancer cells with patient’s NK cells after INKmune treatment Modified from Lowdell et al 2007 & 2011 BROAD THERAPEUTIC PLATFORM x Blood cancers: AML, MM, lymphoma x Solid tumors: breast, ovary, prostate, re
Slide 42: 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 1. To evaluate the safety and tolerability of INKmune when given intravenously (i.v.)
Slide 43: 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 1. To evaluate the safety and tolerability of INKmu
Slide 44: DN-TNF Patents
DN - TNF PATENTS 2021 composition - of - matter (licensed from Xencor) 2032 Methods for treatment of neurologic disease 2035 use for treatment of cancer (issued in US) 2039 use for treatment of NASH DN - TNF Platform Therapies 44 NK Patents 2035 use for treatment of cancer 2039 INB16 composition - o
Slide 45: 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 46: Summary
SUMMARY ▪ 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 bot
Slide 47: Contact Us
CONTACT US 47 HARNESSING THE POWER OFTHE INNATE IMMUNE SYSTEM INMB INmune Bio Inc. 1200 Prospect Str. Suite 525 La Jolla, CA 92037 (858) 964 - 3720 dmoss@inmunebio.com www.inmunebio.com