INmune Bio Inc. · NASDAQ:INMB
INmune Bio — Investor Presentation (December 2020)
51 slides from INmune Bio's investor presentation, December 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 Dec 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: INmune Bio Highlights
INMUNE BIO HIGHLIGHTS Clinical-stage Two platforms: biopharmaceutical company ▪ DN-TNF: First selective TNF developing a new class of inhibitor targeting inflammation therapeutics that target without demyelination or dysfunction of the innate immunosuppression immune system ▪ NK Cell Priming: Primes
Slide 4: Active Pipeline
ACTIVE PIPELINE Therapies that Target the INNATE IMMUNE Response DN-TNF PLATFORM DISEASE FIELD PRE-CLINICAL PHASE I PHASE II (POC) PIVOTAL EST. NEXT MILESTONE COVID-19 Cytokine Storm P2 underway – data 2021 Treatment P2 Mid-2021 Resistant Depression Alzheimer’s Jan 2021 P1b data Disease CNS P2 start
Slide 5: Innate Immune Dysfunction
INNATE IMMUNE DYSFUNCTION Chronic Inflammation drives Innate Immune Dysfunction are the Causes of Many Diseases Innate immune system Neurological Cardiovascular plays a critical and Disease Disease often overlooked role in host protection and normal function Infectious Autoimmune Disease Innate Dise
Slide 6: Selective sTNF Neutralizer for Neuroinflammation in Alzheimer's Disease
Selective sTNF Neutralizer for the Treatment of Neuroinflammation in ALZHEIMER’S DISEASE 6
Slide 7: Alzheimer's Disease Driven by Neuroinflammation
ALZHEIMER’S DISEASE (AD) 1250 Driven by Neuroinflammation 1000 affected by AD (millions) Number of Americans 750 Projected cost to US ▪ Characterized by chronic inflammation per year (billions) which drives synaptic loss and neurodegeneration 500 ▪ As of today, there is no treatment for the cognitiv
Slide 8: Innate Immune Dysfunction Damages CNS
INNATE IMMUNE DYSFUNCTION DAMAGES CNS Innate Immune Dysfunction = Chronic Inflammation ▪ Inflammaging wreaks havoc on patients over time and is a central component of aging and age-related diseases1 ▪ Dysregulated innate immune responses are Innate widely recognized as playing a major role in Immune
Slide 9: White Matter Free Water (WMFW)
WHITE MATTER FREE WATER (WMFW) A Validated Biomarker For Neuroinflammation WHITE MATTER FREE WATER ▪ White matter (WM) changes are an early event in the development of AD1 ▪ An elevated WMFW index is a biomarker of neuroinflammation ▪ Higher WMFW is associated with worse scores on a clinical dementi
Slide 10: Phase 1 AD Trial
PHASE 1 AD TRIAL Phase IB trial in Alzheimer’s IMMUNOLOGIC BIOMARKERS patients with biomarkers of inflammation BEHAVIORAL BIOMARKERS OF INFLAMMATION SLEEP DEPRESSION PSYCHOSIS APATHY AGGRESSION DESIGN DISORDERS ▪ 18 patients in 3 cohorts BIOLOGICAL BIOMARKERS OF INFLAMMATION ▪ Weekly XPro1595™ SubQ
Slide 11: XPro1595 Reduces Neuroinflammation
XPRO1595 REDUCES NEUROINFLAMMATION XPro1595 Reduces Neuroinflammation Within the Arcuate Fasciculus XPro1595 Reduces Neuroinflammation XPro1595 Reduces Whole Brain Neuroinflammation within the AF Premotor cortex Broca’s area Wernicke's area The arcuate plays a key role in language processing – the a
Slide 12: TNF and Neuroinflammation Are Validated Targets in AD
TNF and NEUROINFLAMMATION ARE VALIDED TARGETS IN AD Correlation with Changes to Amyloid RISK OF ALZHEIMER’S DISEASE IN MAN Risk of general population Adapted from Chou et al. 2016 8.5M claims Dumont et al Descoteaux Frontiers in Aging Neuroscience 2019 12
Slide 13: TNF Biology: Good vs Bad: tmTNF vs sTNF
TNF BIOLOGY: Good vs Bad: tmTNF vs sTNF sTNF is well known, tmTNF is unknown, they do very different things… Soluble TNF (‘sTNF’) Transmembrane-bound ▪ Soluble TNF (sTNF): “bad” TNF BAD (‘tmTNF’) GOOD that is known to cause acute and chronic inflammation and cell death ▪ Transmembrane TNF (tmTNF): “
Slide 14: XPro1595: A Precision TNF Inhibitor
XPRO1595: A PRECISION TNF INHIBITOR: DIFFERENCES: XPro1595 neutralizes sTNF while allowing tmTNF to provide the neuroprotective benefits Selective vs. without the safety risks of current anti-TNF therapies Non-Selective sTNF Inhibition Non- DN Selective TNF Decreases “BAD” sTNF with DN-TNF Only “GOO
Slide 15: How XPro1595 Neutralizes sTNF
HOW XPRO1595 NEUTRALIZES sTNF NONGLYCOSYLATED PROTEIN INFLAMMATORY SOLUBLE TNF ELIMINATEED EXPRESSED IN E.COLI No Paracrine Signaling Through Receptors Receptor binding, "small" domain (subunit A) Mutation A145R DN-TNF NEUTRALIZES sTNF WITHOUT EFFECTING tmTNF Immunoprotective Transmembrane TNF Unaff
Slide 16: Current TNF Inhibitors and XPro1595 Are Different
CURRENT TNF INHIBITORS AND XPRO1595 ARE DIFFERENT Demyelination is an off-target safety side effect of currently approved anti-TNF therapies NORMAL CUPRIZONE ETANERCEPT DN-TNF Model of Multiple Sclerosis Anti-inflammatory AND Anti-inflammatory NOT immunosuppressive immunosuppressive EXACERBATED DEMY
Slide 17: Unique Mechanism Expands Market Opportunity
UNIQUE MECHANISM EXPANDS MARKET OPPORTUNITY Currently approved TNF inhibitors contraindicated in most markets Neurological Cardiovascular Disease Disease Global TNF inhibitor drug market is Infectious Autoimmune estimated to reach Disease Innate Disease $42 billion by 20261 Immune Dysfunction Cancer
Slide 18: Targeting Neuroinflammation for Treatment Resistant Depression
Targeting Neuroinglammation for the Treatment of TREATMENT RESISTANT DEPRESSION (TRD) 18
Slide 19: Treatment Resistant Depression (TRD)
TREATMENT RESISTANT DEPRESSION (TRD) The Subset of People Who Have Failed At Least Two Anti Depressants 1 out of 3 MDD patients or 33% Economic toll: Higher Chronic course TNF biology POC studies with anti-TNF of the estimated 7M patients $64B/year comorbidity of MDD in TRD blood CRP predicts respon
Slide 20: TRD Driven by Neuroinflammation
TRD Driven by Neuroinflammation Plasma TNF levels are increased in TRD patients ▪ 20 million adults have major depressive disorder (MDD) per year ▪ One third (~7 million patients) have Treatment Resistant Depression (TRD)1 ▪ Cost of TRD is nearly $64 billion2 Haroon et al., Psychoneuroendocrinology,
Slide 21: INMB Approach: TNF Predicts TRD
INMB APPROACH: TNF PREDICTS TRD Anti-TNF Therapy Improves Depression in Patients With Elevated Inflammatory Biomarkers Anti-TNF treatment reduces depressive symptoms in patients with elevated biomarkers of inflammation 62% 57% 41% 33% Inflammation-associated deficits in reward circuitry mediate the
Slide 22: Phase 2 TRD Trial
PHASE 2 TRD TRIAL Supported by Small Business Innovation Research BIOMARKERS OF INFLAMMATION (SBIR) grant from the National Institutes of Health DESIGN ▪ Six-week double blind placebo-controlled study of XPro1595 MRI ▪ 45 patients in XPro1595 at 1 mg/kg WMFW as measure of neuroinflammation ▪ 45 pati
Slide 23: Targeting Cytokine Storm in COVID-19
Targeting CYTOKINE STORM may Prevent Catastrophic Complications of COVID-19 23
Slide 24: What Brings Patients to the Hospital with COVID-19?
WHAT BRINGS PATIENTS TO THE HOSPITAL WITH COVID-19? Problem Hypothesis Solution At time of hospitalization , the Focusing on the Cytokine Targeting the Master Cytokine Storm is making Storm, not the virus, should Cytokine with QUELLOR patients sick, mot the virus... make patients better should tame
Slide 25: TNF is the Master of the Cytokine Storm
TNF is the “MASTER” of the Cytokine Storm ▪ Block sTNF and downstream pro- inflammatory cytokines should decrease Cytokine Storm Pathology ▪ Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality 25 Adapted from Karki et al 2020
Slide 26: TNF Causes Endothelial Cell Activation
TNF CAUSES ENDOTHELIAL CELL ACTIVATION The Real “Villain” in COVID-19 ▪ TNF activates endothelial cells ▪ Up-regulation of Tissue Factor promotes coagulopathy ▪ Blood clots contribute to pulmonary, renal, CNS and cardiovascular disease McGonagle et al Lancet Rheumatol., 2020 26
Slide 27: Phase 2 Trial: Treating Pulmonary Complications of COVID-19
PHASE 2 TRIAL: Treating Pulmonary Complications of COVID-19 GOAL: PREVENT PROGRESSION TO CATASTROPHIC COMPLICATIONS DESIGN ▪ SOC vs SOC+Quellor™ 1mg/kg subQ day 1 and 7 (if in hospital) ▪ Patient discharged based on clinical status or First 100 patients final study visit day 28 “proof-of-concept” to
Slide 28: INKmune Provides Essential Signals to Patients' NK Cells
Provides essential signals to patients’ NK cells to target and kill tumor cells. INKmune™ is not antigen-specific so there is no need to identify the specific tumor antigen 28
Slide 29: Residual Disease Is the Cause of Cancer Relapse
RESIDUAL DISEASE IS THE CAUSE OF CANCER RELAPSE Difference Between Survival and Relapse is NK Failure to Eradicate Residual Disease Cancer survivors ▪ Prevention of relapse can be the difference between survival and death in patients with cancer >12% NK killing ▪ Relapse is caused by hidden residual
Slide 30: INKmune Is a Biologic System to Prime Resting NK Cells
INKmune™ IS A BIOLOGIC SYSTEM TO DELIVER ESSENTIAL PRIMING SIGNALS TO PATIENTS’ RESTING NK CELLS INKmune™ CELLS PRIME NK CELLS RELAPSE DUE TO RESIDUAL DISEASE TO ELIMINATE RESIDUAL DISEASE INKmune ADVANTAGES: Priming ✓Universal—Potentially S1 effective in blood cancers Triggering S2 and solid tumors
Slide 31: High-Risk Myelodysplastic Syndrome (MDS)
HIGH-RISK MYELODYSPLASTIC SYNDROME (MDS) ▪ MDS is an incurable disease ▪ One-third of all MDS cases evolve to become acute myeloid leukemia (AML) ▪ Survival for patients with high-risk MDS is dismal ▪ Patients with high-risk MDS have functionally defective NK cells 1 ▪ Level of NK dysfunction is pre
Slide 32: INKmune Phase 1 Study
INKmune™ PHASE 1 STUDY GOAL: EVALUATE SAFETY & TOLERABILITY Phase I Trial in High-Risk MDS OF INKmune™ IN HIGH-RISK MDS DESIGN ▪ Open-label dose escalation study of intravenous INKmune enrolling 9 patients INCLUSION First in human ▪ Patients with MDS with excess blasts trial of INKmune ENDPOINTS ▪ P
Slide 33: Milestones and Future Catalysts
MILESTONES AND FUTURE CATALYSTS Interim readout Phase 2 AD INB03 Phase 1 showing decreases initiation NASDAQ Readout Listing neuroinflammation $500,000 Initial Data on ALS Expanded P1 readout INB03 Phase 1 Association $25 M award Capital Raise Phase 2 2019 2020 2021 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 1H 2H Pha
Slide 34: DN-TNF Patents and NK Patents
DN-TNF PATENTS* NK PATENTS* 2024 2035 pegylated DN-TNF (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 allow
Slide 35: 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 35
Slide 36: Appendix
APPENDIX 36
Slide 37: Management Team
MANAGEMENT TEAM TEAM PEDEGREE Raymond J. Tesi, M.D. CEO/CMO & Chairman of the David J. Moss Board CFO The Phoenix Partners Mark W. Lowdell, Ph.D., FRCPath, FRSB, Christopher J. Barnum, Ph.D. Joshua S. Schoonover, Esq. CSO Director of Neuroscience Assoc. General Counsel 37
Slide 38: White Matter Free Water
WHITE MATTER FREE WATER A Biomarker For Neuroinflammation Free water = edema/swelling = inflammation
Slide 39: 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 40: DN-TNF Options in Immuno-Oncology
DN-TNF Options in Immuno-Oncology for Treatment of Resistance to Immunotherapies 40
Slide 41: 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 42: 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 43: 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 44: Goal: Improve Response to Immunotherapy; Phase II in HER2+ 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 HER2+ breast cancer ▪ Metastatic MUC4+/HER2+ breast cancer resistant to immunotherapy on tr
Slide 45: 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 45
Slide 46: 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 47: 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 48: 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 49: 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 50: Two Hypotheses Behind NK Immunotherapy
TWO HYPOTHESIS BEHIND NK IMMUNOTHERAPY Difference Between Survival and Relapse is NK Failure to Eradicate Residual Disease • Cancer patient NK cells are terminally defective and must be replaced with NK from healthy donors • Nanktwest • Fate • Takeda • Glycostem • Cancer patient NK cells can be enha
Slide 51: Refractory Ovarian Cancer Clinical Trial
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