Inmune Bio Inc. · NASDAQ:INMB
Inmune Bio — Investor Presentation (January 2020)
48 slides from Inmune Bio's investor presentation, Jan 13, 2020
Slide 1: Response Against Diseases
a, ~~ Response Against Diseases
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
INVESTMENT SUMMARY = Immunology company, advancing through Phase | and Phase II clinical trials = Two platforms with novel approaches to inflammation, neurodegenerative disease and oncology Dominant Negative Tumor Necrosis Factor (DN-TNF) PLATFORM Immune Priming PLATFORM INmuneBio for Carer INmuneBi
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 Mecical Of
Slide 5: Non-Employee Board of Directors
NON-EMPLOYEE BOARD OF DIRECTORS David Szymkowski, PhD David E. Sankowsi leads the immunology group as Vice President of Cell Biology at Xencor Inc where he is focused on translational development of Fe-engineered and bispecific antibodies for the treatment of autoimmune diseases, allergic diseases,
Slide 6: Pipeline
PIPELINE Focused on Developing Therapies that Target the INNATE IMMUNE System DN-TNF PLATFORM DISEASE FIELD PRE-CLINICAL PHASE | PHASE II (POC) PIVOTAL NEXT MILESTONE INmuneBio farCance Trastuzumab Resistance Mid-20 INBO3 ONCOLOGY initiate p2 I WA" NASH Mid-20 LIVNate Gl Initiate p2 eranebio 10 . Al
Slide 7: DN-TNF Platform Technology
INmuneBio DN-TNF PLATFORM TECNOLOGY 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
Slide 8: Chronic Inflammation = Innate Immune Dysfunction
CHRONIC INFLAMMATION = INNATE IMMUNE DYSFUNCTION Innate Immune Dysfunction is a Disease that Causes Various Symptoms —~ Neurodegenerative ian Neuroinflammation “\ | Metaflammation J __Inflamm-aging ~ \ x Pa Cardiovascular Psychiatric metabolism Innate Immune Dysfunction / Autoimmune Diet 775 Infecti
Slide 9: Tumor Necrosis Factor (TNF)
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 Plasma Concentration PRO-INFLAMATORY ANTI-INFLAMATORY Adapted from Andreasen et al 2008 INmuneBio 9
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 Adapted from MacEwan et al 2002 INmuneBio 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 ansmembrane-bound XtmTNF’) GOOD Adapted from MacEwan et al 2002 Negative effects of TNF are a result of sTNF WHEREAS tmTNF PROVIDES IMMUNOSUPPORTIVE AND NEUROPROTECTIVE FUNCTION IMPORTANT TO HOST SUR
Slide 12: The Novel Structure of INMB's DN-TNF Protein
THE NOVEL STRUCTURE OF INMB’S DN-TNF PROTEIN Receptor binding, "small" domain (subunit A) Mutation A145R Receptor binding, “large” domain (subunit C) Receptor binding, "DE loop" domain (subunit A) Mutation Y87H ‘Mutation R31C uration (for 10kD PEGylation) 17 kDal mutated protein +10 kDal Identical t
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 Only “GOOD” tmTNF continues to inflammation “BAD” sTNF with XPRO J bind to TNFR1 and
Slide 14: DN-TNF Does Not Cause Immunosuppression
DN-TNF DOES NOT CAUSE IMMUNOSUPPRESSION 400 Inhibition of 90 transmembrane TNF 80 (genetically with =~ Vehicle 70 mo Etanercept knockout or = 60 =0= DN-TNF pharmacologically with 3 Mice: C57BL/6 (n=6) = Sol-tm TNF KO i § 50 Blologies: 30 mg/kg sc q2w m= inTNF KI etanercept) causes mice x 40 Day-1 to
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: INB03
Slide 17: INMB Conclusions from INB03 Phase I Data
INMB CONCLUSIONS FROM INBO3™ PHASE | DATA SAMPLE 11 patients treated Open Label, Biomarker Directed, ENROLLMENT CRITERIA: Dose-escalation Trial In Patients Advanced solid tumors DEMOGRAPHIC Age (median): 54 Gender: 6M/5F . a hsCRP > 4 mg/L With Advanced Solid Tumors And Treatment: INBO3 subQ once a
Slide 18: Trastuzumab Resistance in Breast Cancer
TRASTUZUMAB RESISTANCE IN BREAST CANCER A seldom-discussed problem PROBABILITY OF DISEASE-FREE SURVIVAL 100 = ~20% of women with breast cancer are HER2+ a 75 = ~25% have metastatic disease = ~30% will develop brain metastasis = MUC4 expression predicts ade trastuzumab resistance 255 P=00086 ams | UC
Slide 19: INB03 Reverses Trastuzumab Resistance
INBO3 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 500, T=trastuzumab DN-INBO3 = “7 5 = 400. od = 300 -1 . 5 = ON 8% 8 eo -T z © 166 i = 100. z ° 0 20 30 ‘Time of t
Slide 20: INB03 Reverses Trastuzumab Resistance
INBO3 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 500 ~~ 400 = —E 2 300 -= T+DN s -- DN ro] 5 200 + T € -@ IgG s F 100 0 0 10 20 3
Slide 21: INB03 Phase II Cancer
INBO3 PHASE Il CANCER Modifying the TME To Reverse Resistance To Immunotherapy The Problem: HER2+ BC no effective therapy for brain metastasis The Goal: make “cold” tumors Treatment with INBO3/Drug X = Both drugs cross BBB 12 patients Composite end-point If positive, petition FDA for Break-Through D
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 300 -~@ ic trastuzumab resistance = E-etanercept € we ‘iis (asaaaad = DN—INBO3™ 2 200 Ae DN = Murine model with 3 me DrugX frastucumab resistant 5 100 Me Drug Xe , e =3% © Drug X+DN | INmuneBio 22
Slide 23: INmuneBio
INmuneBio
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 ‘a f y \\ yp - Le \ Nerve Cell Synaptic ( q \ Death Dysfunction “ y Damaged \ Parkinson’s Myelin Affected Neuron NUMBER OF DN-TNF PU
Slide 25: Evidence for TNF in Alzheimer's Disease
EVIDENCE FOR TNF IN ALZHEIMER’S DISEASE Pre-clinical mechanistic studies NEURODEGENERATION EXCITOTOXICITY & OXIDATIVE STRESS REDUCED CLEARANCE OF TOXIC DEBRIS ALTERNATIVE PROCESSING SYNAPSE OF AMYLOID & TAU Loss MICROGLIAL & ASTROGLIA ACTIVATION METABOLIC DYSFUNCTION INmuneBio 25
Slide 26: XPro1595 Attenuates AD Pathology In Vivo
Xpro 1595™ ATTENUATES AD PATHOLOGY IN VIVO and Restores Normal Function Synapse dysfunction Cognitive Impairment Saline Pro? maa “VTS Immune dysfunction (% first block) ‘Swim distance 2345 6 Training block Amyloid pathology Saline | XProt59s Activated Mycloid celts Erain Tcl infiltration Microgia |
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 Amyloid plaques Neurofibrillary tangles «& Synaptic Dysfunction Nerve Cell Death AD pathology is driven by TNF activities that modulate synapses and
Slide 28: TNF Inhibitors Have a Protective Effect Against Developing 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 Rheu
Slide 29: Phase I AD Trial
PHASE 1 AD TRIAL Phase IB trial in Alzheimer’s patients with biomarkers of inflammation DESIGN = 18 patients in 3 cohorts = Weekly XPro1595™ SubQ injections for 3 months = Biomarkers of inflammation at 0, 6, 12 weeks INCLUSION Must have 1 inflammatory biomarker (local lab): = hsCRP>1.5 = ESR>10 = Hb
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 <4) XPRO1595 Anti-inflamma
Slide 31: LIVNate
Slide 32: Three Principles of INMB's NASH Program
OBESITY INTHE US, 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 that
Slide 33: Three Cycles of Inflammation Lead to NASH
THREE CYCLES OF INFLAMMATION LEAD TO NASH Steatohepatitis Peripheral Inflammation (NASH) _, Regional Inflammation ag Lipotoxicity netveton P i eo” heathy vee fatty bver Intestinal Inflammation LIVNate™ REDUCES INSULIN RESISTANCE With No Weight Change 19 SH 3 5 S = HB Neutiv = 2 Control 8 £ g 2 a Con
Slide 34: STAM Model
STAM MODEL LIVNate™ Reduces Hepatocyte Death and Fibrosis /7 Vivo With No Change in Total Body Weight sTEATOSIs weiSamaon BALLOONING n 0 1 2 3 0 1 2 3 0 1 2 va Control 2 4 1 - - - 1 6 3 3 1 Pa LIVNate™ © 4 @) - .-f.. @) 3 . NAS (mean + SD) FIBROSIS SCORE Control 44+0.8 Parameter (mean +SD) Control L
Slide 35: NASH Trial Design
NASH TRIAL DESIGN Phase Ila Biomarker Directed Trial Phase Ila 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-week
Slide 36: INKmune
Slide 37: Immune Priming Technology
INmuneBio IMMUNE PRIMING TECNOLOGY 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. INKm
Slide 38: INKmune Treats Residual Disease
INKmune™ TREATS RESIDUAL DISEASE INMUNEBIO so, igh Risk MOS INmuneBio for Ovarian Cancer INKmune” INKmune’ 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
Slide 39: NK Cells Determine Relapse or Survival Through Their Ability to Target MRD
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
INKmune™ PRIMING’S BROAD MARKET APPLICATIONS FOR MULTIPLE CONDITIONS INKmune™ CELLS PRIME NK RELAPSE DUE TO MRD ), CELLS TO ELIMINATE MRD A Yam: oS y e rNK Cell Cancer Cell pp AE TpNK Cell Dead-Cancer Cell @, INKmune” Tumor cells down-regulate ( cy) ~] A INKmune™ provides surface molecules which es
Slide 41: INKmune Primed NK Cells
INKmune™ PRIMED NK CELLS Kill Resistant Ovarian Cancer Cells /7 Vitro Human ovarian cancer cells plus patient’s own NK cells Human ovarian cancer cells with patient’s NK cells after INKmune treatment BROAD THERAPEUTIC PLATFORM INKmune™ TPNK Are Active Against Many Types of Cancers v Blood cancers: A
Slide 42: TpNK Therapy in Two Phase I 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 oe oe 1. Prolonged remissions with exc
Slide 43: High-Risk MDS Clinical Study Objectives
HIGH-RISK MDS CLINICAL STUDY OBJECTIVES A Phase | 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 To evaluate the safety and tolerability of INKmune when given intravenously (i.v.) Secondary To
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 1. To evaluate the safety and tolerability of INKmune when
Slide 45: DN-TNF Patents / NK 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 2035 use for treatment of cancer (issued in US) Future 2039 ae i P Usefor treatment GANESH Additional IP file
Slide 46: Our Objectives Completed and Moving Forward
OUR OBJECTIVES COMPLETED AND MOVING FORWARD OBJECTIVE NASDAQ Listing Feb 4, 2019 $1 Million Park the Cloud Award — Alzheimer's Association Feb 19, 2019 Initial Data on INBO3 Phase 1 3Q, 2019 Announce LIVNate for NASH 3Q, 2019 Final INBO3 Phase 1 Readout and Datalock 4Q, 2019 XPro1595 First Patient E
Slide 47: Summary
SUMMARY INM Bnasdaq = ‘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 hu
Slide 48: Contact Us
~ CONTACT US j INmuni 4 1200 ct Str. Suite 525 lla, CA 92037 (898 ( dmoss@inmuneb www.inmunebio.con