Inmune Bio Inc. · NASDAQ:INMB
Inmune Bio — Investor Presentation (July 2020)
44 slides from Inmune Bio's investor presentation, Jul 30, 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 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 the
Slide 3: 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 First dominant - negative protein to enter clinic selectively targeting inflammation
Slide 4: Pipeline: Therapies Targeting the Innate Immune System
DN - TNF PLATFORM DISEASE FIELD PRE - CLINICAL PHASE I PHASE II (POC) PIVOTAL EST. NEXT MILESTONE Trastuzumab Resistance ONCOLOGY NASH GI Alzheimer’s Disease CNS COVID - 19 1H - 21 Initiate p2 1H - 21 initiate p2 NK PRIMING PLATFORM DISEASE FIELD PRE - CLINICAL PHASE I PHASE II (POC) PIVOTAL NEXT MI
Slide 5: DN-TNF Platform Technology
NEXT GENERATION TNF INHIBITOR - SAFER AND SELECTIVE TO TARGET MARKETS EXISTING TNF INHIBITORS MUST AVOID DN - TNF PLATFORM TECNOLOGY 5
Slide 6: 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 6 PRO - INFLAMATORY Adapted from Andrease
Slide 7: Biology of Current TNF Inhibitors
Negative effects of TNF are a result of sTNF WHEREAS tmTNF PROVIDES IMMUNOSUPPORTIVE AND NEUROPROTECTIVE FUNCTION IMPORTANT TO HOST SURVIVAL THE BIOLOGY OF CURRENT TNF INHIBITORS Current Inhibitors Are Not Selective and Block Both Forms of TNF Transmembrane - bound (‘tmTNF’) GOOD Soluble TNF (‘sTNF’
Slide 8: Selective vs. Non-Selective TNF 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 9: Selective Targeting Prevents Immunosuppression and Demyelination
9 Days Post - Infection % Survival FUNCTIONAL tmTNF PREVENTS IMMUNOSUPPRESSION SELECTIVE TARGETING PREVENTS DEMYLINATION Non - selective TNF Inhibition Causes Demyelination, DN - TNF Promotes Remyelination CUPRIZONE Model of Multiple Sclerosis REMYELINATION ETANERCEPT Anti - inflammatory AND immunos
Slide 10: Alzheimer's Disease Clinical Trial
Clinical Trial to Test Neuroinflammation as the Common Denominator of ALZHEIMER’S DISEASE 10
Slide 11: sTNF: A Validated Target in Alzheimer's Disease
RISK OF ALZHEIMER’S DISEASE IN MAN Risk of general population Adapted from Chou et al. 2016 8.5M claims Despite positive AD activity, non - selective TNF inhibitors increase the risk of cancer, infection, and MS AD risk is not reduced by other anti - inflammatory treatments 11 sTNF A VALIDATED TARGE
Slide 12: Phase 1 AD Trial
IMMUNOLOGIC BIOMARKERS BEHAVIORAL BIOMARKERS OF INFLAMMATION SLEEP DISORDERS DEPRESSION PSYCHOSIS APATHY AGGRESSION Inflammation & Neurodegeneration ( Roche NeuroTool kit ) BIOLOGICAL BIOMARKERS OF INFLAMMATION DESIGN ▪ 18 patients in 3 cohorts ▪ Weekly XPro1595™ SubQ injections for 3 months ▪ Bioma
Slide 13: White Matter Free Water Biomarker
WHITE MATTER FREE WATER A Biomarker For Neuroinflammation Free water = edema/swelling = inflammation
Slide 14: White Matter Free Water Biomarker for Neuroinflammation
WHITE MATTER FREE WATER: 14 From Dumont 2019 White Matter Free Water A Biomarker For Neuroinflammation WMFW - sex and age matched NC and AD subjects AD Normal aging
Slide 15: Neuroinflammation Increases 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 Safe White Matter Mask Arcuate fasciculus Uncinate fasciculus , Inferior fronto - occipital fasciculus , Splenium of the corpus callosum , Inferior longitudinal fasciculus Inferior longitudinal fasciculus , Uncinate fasciculus Measures Whole brain inflamma
Slide 17: XPro1595 Reduces Whole Brain Neuroinflammation
XPRO1595 REDUCES WHOLE BRAIN NEUROINFLAMMATION
Slide 18: XPro1595 Reduces Neuroinflammation
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 neuroinfl
Slide 21: COVID-19 Clinical Trial
21 Clinical Trial to Determine if Targeting Soluble TNF (sTNF) may Prevent Catastrophic Complications of COVID - 19
Slide 22: Blunting Cytokine Storm and Hyperinflammation
▪ Cytokine storm caused by increase expression of sTNF, IL1, and IL6 ▪ sTNF significantly elevated in blood of patients ▪ Neutralizing sTNF should decrease expression of IL1 and IL6 ▪ Ideal therapy has 5 characteristics: ▪ Safe and well tolerated ▪ Not immunosuppressive ▪ Easy to use ▪ Rapid onset ▪
Slide 23: Why sTNF and Why Quellor
▪ Stops inflammation ▪ Not immunosuppressive ▪ Rapid onset ▪ No contra - indications ▪ Easy to use ▪ Safe and well tolerated ▪ Crosses BBB (Blood Brain Barrier) 23 WHY s TNF AND WHY ? IS NOT IMMUNOSUPPRESSIVE Approved cytokine inhibitors (anti - TNF/IL6/IL1) are immunosuppressive ▪ QUELLOR does not
Slide 24: Phase II Trial: 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; diabet
Slide 25: DN-TNF Options in Immuno-Oncology
DN - TNF Options in Immuno - Oncology for Treatment of Resistance to Immunotherapies 25
Slide 26: 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 26 TRASTUZUMAB RESISTANCE IN BREAST CANCER I g G T D N T + D N 0 20 40 60 % C D 1 1 b / C D 4 5 +
Slide 27: INB03 Reverses Trastuzumab Resistance
INB03 REVERSES TRASTUZUMAB RESISTANCE 1 st – It Modifies immunology of TME and DECREASES MYELOID CELLS, INCREASES NK CELLS IN VIVO 2 nd – It Decreases MUC4 Expression – MUC4 Expression resistance to Trastuzumab and promotes metastasis T - trastuzumab DN - INB03 Schillaci - NYAS2020 MUC4 BLOCKS TRAST
Slide 28: 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 29: Phase II in HER2+ Metastatic Breast Cancer
29 Twofer1: PHASE II IN HER2+ METASTATIC BREAST CANCER Step 1: eliminating MUC4 and modifying the TME GOAL: IMPROVE RESPONSE TO IMMUNOTHERAPY Modifying the TME To Reverse Resistance To Immunotherapy ▪ Metastatic HER2+ breast cancer resistant to immunotherapy ▪ Trastuzumab resistant ▪ Immune checkpoi
Slide 30: Liver Fibrosis and Inflammation
Addressing the Link Between Liver Fibrosis, the Innate Immune Cells of the Liver and Inflammation, a Pleiotropic Approach 30
Slide 31: 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 32: LIVNate Reduces Hepatocyte Death and Fibrosis
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 33: 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
Slide 34: Natural Killer Cells Clear Residual Disease
Natural Killer cells are responsible for clearing residual disease 34
Slide 35: NK Cells Determine Relapse or Survival
NK CELLS DETERMINE RELAPSE OR SURVIVAL THROUGH THEIR ABILITY TO TARGET RESIDUAL DISEASE ▪ 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 resti
Slide 36: 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 37: 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 38: 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) Primary 1. To evaluate the safety and tolerability of INKmune when given intravenously 38 Exploratory 1.
Slide 39: 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 Primary 1. To evaluate the safety and tolerability of INKmune when given intraperitoneally 39 Explo
Slide 40: DN-TNF and NK 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 2040 use for immune mediated complications from COVID - 19/CRS 40 NK PATENTS* 2035 use for treatment
Slide 41: Milestones and Future Catalysts
41 Q1 Q2 2019 Q3 Q4 Q1 Q2 2020 2H 1H 2021 2H NASDAQ Listing $1 Million Park the Cloud Award – Alzheimer’s Association Initial Data on INB03 Phase 1 $1 Million Park the Cloud Award – Alzheimer’s Association INB03 Phase 1 Readout XPro1595 First Patient Enrolled in Phase 1 AD Trial $500,000 ALS Associa
Slide 42: 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 43: 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 44: Contact Us
CONTACT US 44 HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM INMB INmune Bio Inc. 1200 Prospect Str. Suite 525 La Jolla, CA 92037 (858) 964 - 3720 www.inmunebio.com