INmune Bio Inc. · NASDAQ:INMB
INmune Bio — Investor Presentation (August 2020)
45 slides from INmune Bio's investor presentation, August 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 CORPORATE PRESENTATION Aug 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
INVESTMENT SUMMARY ▪ Immunology company, advancing through Phase I and Phase II clinical trials ▪ Catalyst rich programs with multiple readouts in 2020 and 2021 ▪ Two platforms with novel approaches targeting the innate immune system DOMINANT NEGATIVE TUMOR NECROSIS FACTOR (DN-TNF) PLATFORM First do
Slide 4: 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 EST. NEXT MILESTONE Trastuzumab Resistance 1H-21 ONCOLOGY initiate p2 NASH 1H-21 GI Initiate p2 Alzheimer’s Disease 2H-20 CNS Complete p1 COVID-19 3
Slide 5: DN-TNF Platform: Next Generation TNF Inhibitor
DN-TNF PLATFORM T EC N OLOGY NEXT GENERATION TNF INHIBITOR -SAFER AND SELECTIVE TO TARGET MARKETS EXISTING TNF INHIBITORS MUST AVOID 5
Slide 6: 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 downstream cytokines sTNF Plasma Concentration ▪ Block sTNF and downstream pro- inflammatory cytokines do not occur Time Adapted from Andreasen et al
Slide 7: The Biology of Current TNF Inhibitors
THE BIOLOGY OF CURRENT TNF 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
Slide 8: TNF Biology. How DN-TNF Works
TNF BIOLOGY. HOW DN-TNF WORKS DIFFERENCES: DN-TNF Neutralizes ONLY Soluble TNF and Leaves 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 to
Slide 9: Functional tmTNF Prevents Immunosuppression; Selective Targeting
FUNCTIONAL tmTNF PREVENTS SELECTIVE TARGETING IMMUNOSUPPRESSION PREVENTS DEMYLINATION Non-selective TNF Inhibition Causes Immunosuppression Non-selective TNF Inhibition Causes Demyelination, DN-TNF Promotes Remyelination CUPRIZONE Model of Multiple Sclerosis % Survival ETANERCEPT DN-TNF Anti-inflamm
Slide 10: Clinical Trial to Test Neuroinflammation in Alzheimer's Disease
Clinical Trial to Test Neuroinflammation as the Common Denominator of ALZHEIMER’S DISEASE 10
Slide 11: sTNF a Validated Target in Alzheimer's Disease
sTNF A VALIDATED TARGET IN ALZHEIMERS DISEASE RISK OF ALZHEIMER’S DISEASE IN MAN Risk of general population Adapted from Chou et al. 2016 8.5M claims AD risk is not reduced by other anti-inflammatory treatments Despite positive AD activity, non-selective TNF inhibitors increase the risk of cancer, i
Slide 12: 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 13: White Matter Free Water
WHITE MATTER FREE WATER A Biomarker For Neuroinflammation Free water = edema/swelling = inflammation
Slide 14: White Matter Free Water: A Biomarker for Neuroinflammation
WHITE MATTER FREE WATER: A Biomarker For Neuroinflammation White Matter Free Water WMFW - sex and age matched NC and AD subjects Normal aging AD From Dumont 2019 14
Slide 15: Neuroinflammation Continues to Increase Over Time
NEUROINFLAMMATION CONTINUES TO INCREASE OVER TIME AND CORRELATES WITH CHANGES TO AMYLOID Dumont et al Descoteaux Frontiers in Aging Neuroscience 2019
Slide 16: Neuroinflammation – Free Water White Matter
NEUROINFLAMMATION – FREE WATER WHITE MATTER Measures Whole brain inflammation Measure Inflammation in specific white matter tracts Inferior longitudinal fasciculus, Uncinate fasciculus Arcuate fasciculus Uncinate fasciculus, Inferior fronto-occipital fasciculus, Safe White Matter Mask Splenium of th
Slide 17: XPro1595 Reduces Whole Brain Neuroinflammation
XPRO1595 REDUCES WHOLE BRAIN NEUROINFLAMMATION
Slide 18: XPro1595 Reduces Neuroinflammation Within the Arcuate Fasciculus
XPro1595 reduces neuroinflammation within the
Slide 19: Arcuate Fasciculus
Arcuate Fasciculus Premotor cortex Broca’s area Wernicke's area The arcuate plays a key role in language processing – the ability to understand or express speech
Slide 20: Summary
SUMMARY ▪ Neuroinflammatory biomarkers assessed by free water white matter in 6 AD patients ▪ N=3 at 0.3 mg/kg of XPro1595 ▪ N=3 at 1.0 mg/kg of XPro1595 ▪ Dose-dependent reduction in whole brain neuroinflammation (“safe mask free water”) ▪ A more focused analysis shows a 40.6% reduction neuroinflam
Slide 21: Clinical Trial in COVID-19 Complications
Clinical Trial to Determine if Targeting Soluble TNF (sTNF) may Prevent Catastrophic Complications of COVID-19 21
Slide 22: Blunting Cytokine Storm and Hyperinflammation
BLUNTING CYTOKINE STORM AND HYPERINFLAMMATION TNF levels elevated in COVID-19 Patients ▪ Cytokine storm caused by increase expression of sTNF, 250 IL1, and IL6 ▪ sTNF significantly elevated in blood of patients 200 ▪ Neutralizing sTNF should decrease expression of IL1 and IL6 150 ▪ Ideal therapy has
Slide 23: Endothelial Cell Inflammation: the Real Villain in C19?
Endothelial cell inflammation: the real “villain” in C19? • sTNF activates endothelial cells to upregulate Tissue Factor • Tissue Factor causes blood clots • Clots can block blood vessels in: • Lungs • Kidneys • Brain • Heart • more From McGonagle Lancet 2020 23 BTIG FireSide Chat August 10, 2020
Slide 24: Why sTNF and Why Is It Not Immunosuppressive
WHY sTNF AND IS NOT IMMUNOSUPPRESSIVE WHY ? Approved cytokine inhibitors (anti-TNF/IL6/IL1) are immunosuppressive ▪ Stops inflammation ▪ QUELLOR does not compromise immune response to viral infection ▪ Not immunosuppressive ▪ QUELLOR improves immune response to bacterial infection including M. tuber
Slide 25: Phase II Trial: Treating Pulmonary Complications of COVID-19
PHASE II TRIAL: Treating Pulmonary Complications of COVID-19 Goal: Prevent progression to catastrophic complications ▪ Enrollment criteria: COVID-19 infection with room air SaO2<94% ▪ One or more medical/demographic comorbidities: age≥60; hypertension, cardiovascular disease, BMI≥30; diabetes, Black
Slide 26: DN-TNF Options in Immuno-Oncology
DN-TNF Options in Immuno-Oncology for Treatment of Resistance to Immunotherapies 26
Slide 27: INB03 Changes TME In Vivo: Trastuzumab Resistance in Breast Cancer
TRASTUZUMAB RESISTANCE INB03 CHANGES TME IN VIVO IN BREAST CANCER PROBABILITY OF DISEASE-FREE SURVIVAL JIMT-1 BREAST CANCER INTO NUDE MOUSE FEWER MYELOID CELLS ▪ ~20% of women * with breast cancer are 60 * HER2+ + % CD 11b /C D 45 40 ▪ ~25% have metastatic 20 disease ▪ ~30% will 0 develop brain T N
Slide 28: INB03 Reverses Trastuzumab Resistance
INB03 REVERSES TRASTUZUMAB RESISTANCE 1st – It Modifies immunology of TME and DECREASES MYELOID CELLS, INCREASES NK CELLS IN VIVO 2nd – It Decreases MUC4 Expression – MUC4 Expression resistance to Trastuzumab and promotes metastasis Model of Metastasis: Downregulation of MUC4 MUC4 BLOCKS TRASTUZUMAB
Slide 29: Conclusions from INB03 Phase I Data
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 Inflammation 3
Slide 30: Phase II in HER2+ Metastatic Breast Cancer
GOAL: IMPROVE RESPONSE TO Twofer1: PHASE II IN HER2+ IMMUNOTHERAPY METASTATIC BREAST CANCER Modifying the TME To Reverse Resistance To Step 1: eliminating MUC4 and modifying the TME Immunotherapy ▪ Metastatic MUC4+/HER2+ breast cancer on trastuzumab based ▪ Metastatic HER2+ breast cancer immunothera
Slide 31: Liver Fibrosis, Innate Immune Cells and Inflammation
Addressing the Link Between Liver Fibrosis, the Innate Immune Cells of the Liver and Inflammation, a Pleiotropic Approach 31
Slide 32: Three Cycles of Inflammation Lead to NASH
THREE CYCLES OF INFLAMMATION LEAD TO NASH PERIPHERAL INFLAMMATION STEATOHEPATITIS (NASH) Obesity Insulin Resistance LOCAL INFLAMMATION Lipotoxicity Innate Immune Activation REGIONAL INFLAMMATION Intestinal Inflammation Mesenteric Fat Healthy Liver Fatty Liver LIVNate™ REDUCES INSULIN RESISTANCE With
Slide 33: 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 34: 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 with LIVNate™ 1mg/kg SQ treatment with for 12 weeks ▪ PIFF and non-invasive biomarkers at 0, 6 and 12 weeks ▪ Open label so biomarkers “visible” at
Slide 35: Natural Killer Cells Clear Residual Disease
Natural Killer cells are responsible for clearing residual disease 35
Slide 36: NK Cells Determine Relapse or Survival
NK CELLS DETERMINE RELAPSE OR SURVIVAL THROUGH THEIR ABILITY TO TARGET RESIDUAL DISEASE 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
Slide 37: INKmune Provides Missing Priming Signal
INKmune™ PROVIDES MISSING PRIMING SIGNAL 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 prime NK cell activity, missing
Slide 38: INKmune Primed NK Cells Broad Therapeutic Platform
INKmune™ PRIMED NK CELLS BROAD THERAPEUTIC PLATFORM Kill Resistant Ovarian Cancer Cells In Vitro INKmune™ PRIMED NK 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 Huma
Slide 39: High-Risk MDS Clinical Study
HIGH-RISK MDS CLINICAL STUDY 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) ▪ MDS is an incurable disease ▪ No agent is approved for second-line therapy, which means there is a significant un
Slide 40: Refractory Ovarian Cancer Clinical Study
REFRACTORY OVARIAN CANCER CLINICAL Phase 1 Open-label Study of Intraperitoneal INKmune™ in Patients with Relapsed Platinum-resistant, Platinum-refractory, or Platinum-Intolerant Ovarian Cancer ▪ Refractory CaOva is an incurable disease ▪ Despite optimal surgery and paclitaxel–carboplatin chemotherap
Slide 41: DN-TNF Patents and 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 use for treatment of NASH 2040 Broad Platforms
Slide 42: Future Catalysts
FUTURE CATALYSTS XPro1595 Phase 1 INB03 Combination Phase 2 Data AD Trial Breast Cancer Trial INB03 Phase 1 NASDAQ Readout Listing $500,000 INKmune First Patient Initial Data on ALS INB03 Phase 1 Ovarian Cancer Association award Q1 Q2 2019 Q3 Q4 Q1 Q2 2020 2H 1H 2021 2H $1 Million Park the XPro1595
Slide 43: 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 44: 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 45: Contact Us
HARNESSING THE POWER CONTACT US OF THE INNATE IMMUNE SYSTEM INmune Bio Inc. 1200 Prospect Str. Suite 525 La Jolla, CA 92037 INMB (858) 964-3720 www.inmunebio.com 45