INmune Bio Inc. · NASDAQ:INMB
INmune Bio — Investor Presentation (September 2021)
45 slides from INmune Bio's investor presentation, September 2021
Slide 1: Harnessing the Power of the Innate Immune System
HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM Targeting Innate Immune Dysfunction INMB INVESTOR PRESENTATION September 2021
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 Highlights
FOLLOW US INVESTMENT HIGHLIGHTS ▪ Clinical-stage biopharmaceutical company with two therapeutic platforms in Phase 1 and Phase 2 of development INMB ▪ Patented therapies that repair dysfunction of the innate immune system to combat immune diseases including; Alzheimer’s Disease, Cancer, Treatment Re
Slide 4: Targeting Innate Immune System Dysfunction
OUR STRATEGY TARGETING INNATE IMMUNE SYSTEM DYSFUNCTION The human immune system undergoes aging-related changes, which progress to a state of Innate immune system plays a immunosenescence and chronic inflammation. Chronic inflammation leads to age related critical and often overlooked role diseases
Slide 5: An Active Pipeline of Therapies That Target the Innate Immune Response
DEVELOPMENT AN ACTIVE PIPELINE OF THERAPIES THAT TARGET THE INNATE IMMUNE RESPONSE UPCOMING EVENTS ▪ P1 AD Data 3Q 2021 DN-TNF PLATFORM EST. NEXT DISEASE FIELD PRE-CLINICAL PHASE I PHASE II (POC) PIVOTAL MILESTONE ▪ P2 AD Start 4Q 2021 ▪ P2 TRD Initiation 4Q 2021 Alzheimer’s P2 data analysis Disease
Slide 6: DN-TNF and INKmune: Tip of the Iceberg
TIP OF THE ICEBERG DN-TNF AND INKMUNE ▪ Visible programs AD, TRD, ALS ▪ “Out-of-Sight” PD, MS, FTD, LBD, TBI PTSD, autism, bi-polar disease Much, much, more…. ▪ Visible programs High risk MDS; Ovarian Cancer ▪ “Out-of-Sight” AML, MM, lymphoma RCC, Lung, prostate and breast cancer 6
Slide 7: Treating Alzheimer's Disease as an Immunologic Disease
for AD Treating Alzheimer’s Disease as an Immunologic Disease …not A Neurologic Disease 7
Slide 8: Breaking the Destructive Cycle of Neuroinflammation Driven by Glial Activation
OUR STRATEGY IN AD BREAKING THE DESTRUCTIVE CYCLE OF for AD NEUROINFLAMMATION DRIVEN BY GLIAL ACTIVATION Any Drug Therapy Must Stop Nerve Cell Death and Improve Synaptic Dysfunction Amyloid plaques Nerve Cell Neurofibrillary tangles Death Cognitive Behavioral, MICROGLIA Decline Environmental Synapti
Slide 9: XPro Decreases Neuroinflammation in AD
TARGET ENGAGEMENT RESULTS FROM PHASE I TRIAL XPRO DECREASES NEUROINFLAMMATION IN AD for AD 1. XPro™ decreases neuroinflammation in patients after 12 weeks of therapy 2. Statistically decreased neuroinflammation when measured by: • White Matter Free Water – a validated non-invasive MRI measure of XPr
Slide 10: Benefits of Reducing Neuroinflammation
DOWNSTREAM EFFECTS OF TARGET ENGAGEMENT RESULTS FORM PHASE I TRAIL BENEFITS OF REDUCING NEUROINFLAMATION for AD Significant Regulation of AD Relevant Neuroinflammatory, Neural Injury, and Synaptic Proteins CSF Proteome 20 of 26 Targets Significant (P < 0.0001) Pre-specified Analysis Using tmtCalibra
Slide 11: XPro1595 Reduction of Neuroinflammation Is Dose-Dependent
XPRO1595 REDUCTION OF NEUROINFLAMMATION IS for AD DOSE-DEPENDENT CSF following 12 weeks of treatment CSF Inflammation Composite Olink® Target 48 Cytokine CCL8 OLR1 IL27 IL2 CXCL9 TGFA IL6 TNFSF12 CCL11 HGF FLT3LG IL17F Percent Change IL7 IL18 CCL13 TNFSF10 CXCL10 IFNG IL10 CCL19 IL15 CCL3 CXCL8 MMP1
Slide 12: Assessing White Matter Pathology – pTau 217/181
ASSESSING WHITE MATTER for AD PATHOLOGY – pTau 217/181 CSF following 12 weeks of treatment ASSESSING WHITE MATTER Percent Change over 12 Weeks PATHOLOGY – pTau 217 DOSE RESPONSE CSF following 12 weeks of treatment 12 12
Slide 13: Non-Invasive Measurement of CNS Pathology
QUANTIFYING CNS BENEFITS OF DECREASED NEUROINFLAMMATION RESULTS FORM PHASE I TRIAL NON-INVASIVE MEASUREMENT OF CNS PATHOLOGY for AD The Virtual Biopsy – MRI Imaging Can Measure White and Gray Matter Quality DISEASED HEALTHY DISEASED HEALTHY Apparent fiber density (AFD) Cortical Disarray Measurement
Slide 14: Apparent Fiber Density (AFD)
TARGETING WHITE MATTER TO TREAT CNS DISEASE RESULTS FROM PHASE I TRIAL APPARENT FIBER DENSITY (AFD) Non-invasive Biomarker of White Matter Disease for AD Cross Section of Healthy White Matter Cross Section of diseased AD White Matter - Loosely Spaced Neurons by Extracellular Water Increase in extrac
Slide 15: Longitudinal Apparent Fiber Density
Xpro™ RESULTS LONGITUDINAL APPARENT FIBER DENSITY for AD 20 Fiber Density in AD bundles (% change) +17% 15 10 XPro1595 1 mg/kg 5 ADNI database N = 36 0 -5 N=6 N=5 N=5 N=3 -10 0 3 6 9 12 15 18 21 24 Visit (months) 15
Slide 16: Longitudinal Free Water
Xpro™ RESULTS LONGITUDINAL FREE WATER for AD 30 Free-water in AD bundles (% change) 20 10 0 -10 XPro1595 1 mg/kg -20 ADNI database N = 36 -30 -40 -50 -46% N=6 N=5 N=5 N=3 -60 0 3 6 9 12 15 18 21 24 Visit (months) 16
Slide 17: Longitudinal Radial Diffusivity
Xpro™ RESULTS LONGITUDINAL RADIAL DIFFUSIVITY for AD -16% 17
Slide 18: Increase in White Matter Volume
Xpro™ RESULTS INCREASE IN WHITE MATTER VOLUME for AD (MACROSTRUCTURE) White Matter volumetric an White Matter volumetric analysis 460000 0.1469 1000 (mm3) (mm ) 3 460000 1000 Left Entorhinal volume (mm3) 0.1469 Total White Matter volume (mm3) 440000 0.1084 volumevolume 900 440000 900 420000 White Ma
Slide 19: Summary
SUMMARY for AD ✓ White matter microstructure degenerates with Alzheimer’s Disease ✓ Neuroinflammation as well as axon & myelin disruption ✓ Non-invasive advanced MRI & Imeka tools quantify where & how white matter is disrupted and rescued In Alzheimer’s Disease bundles over a 12-month period: 1) XPr
Slide 20: Cognition Results Encouraging but Anecdotal
WHAT IS NOT MEASURED? RESULTS FROM PHASE I TRIAL COGNITION RESULTS ENCOURAGING BUT ANECDOTAL for AD Trial Did Not Include a Placebo Group Phase 1b Mild AD Patients With Neuroinflammation On Xpro™ Had Best Response Mild AD patients had greatest improvement in cognition had the largest reduction in ne
Slide 21: Phase 1 Trial Informed Dose, Duration and Design
DATA DRIVEN TRIAL DESIGN LEARNINGS FROM PHASE I TRIAL PHASE 1 TRIAL INFORMED DOSE, DURATION AND DESIGN for AD ▪ INCLUSION Mild AD with biomarkers of inflammation Phase I inclusion criteria selected for patients with neuroinflammation ▪ SIZE - 200 patients 2:1 randomization (134 XPro™ vs 66 placebo)
Slide 22: Phase 2 Blinded, Randomized, Placebo-Controlled in Mild AD
PHASE 2 BLINDED, RANDOMIZED, PLACEBO-CONTROLLED for AD IN MILD AD WITH BIOMARKERS OF INFLAMMATION INCLUSION END-POINTS ▪ 200 patients ▪ Primary: EMACC* 2:1 randomization (134 XPro™ Internatonal Shopping List Test- Immediate recall patients vs 66 placebo patients) Digit Span Forward and Backward Cate
Slide 23: Selective TNF Inhibitor of Soluble TNF
SELECTIVE TNF INHIBITOR OF SOLUBLE TNF for AD Not Competing with Currently Approved TNF Inhibitors or Biosimilars DN-TNF Neutralizes ONLY sTNF and Leaves The Benefits of INMB’s Selective vs. Non- tmTNF and TNF Receptors Free to Function Selective sTNF Inhibition whereas existing TNF inhibitors block
Slide 24: How XPro Neutralizes sTNF
HOW XPro™ NEUTRALIZES sTNF for AD And importantly leaves tmTNF and TNF receptors alone. sTNF and tmTMF Do Very Different Things… Nonglycosylated Protein Soluble TNF Function Eliminated Expressed in E. Coli No inflammatory signaling DN-TNF Can Not Neutralize tmTNF receptors not blocked so tmTNF biolo
Slide 25: Approved TNF Inhibitors Should Not Be Used in CNS
APPROVED TNF INHIBITORS SHOULD NOT BE for AD USED IN CNS Demyelination Is An Off-Target Safety Side Effect of Currently Approved TNF Therapies NORMAL CUPRIZONE ETANERCEPT DN-TNF Model of Multiple Sclerosis Anti-inflammatory AND Anti-inflammatory NOT immunosuppressive immunosuppressive EXACERBATED DE
Slide 26: Off-the-Shelf NK Therapy for Oncology
for Oncology Off-the-Shelf NK Therapy Producing memory like NK cells from Patient’s Own NK cells in Their Circulation (ie: in vivo) 26
Slide 27: NK Recognition and Binding to Tumor Cells Is Essential for Cancer Cell Killing
NK RECOGNITION AND BINDING TO TUMOR CELLS in Oncology IS ESSENTIAL FOR CANCER CELL KILLING INKmune™ Advantages 1. NK recognizes tumor 2. NK makes strong bond 3. NK forms stable immune 4. NK cell kills tumor cell UNIVERSAL cell to tumor cell synapse with tumor cell and Potentially NK ligands send act
Slide 28: A Multi-Dimensional Pseudokine
A MULTI-DIMENSIONAL “PSEUDOKINE” in Oncology Moa #2 – InkMUNE™ Differentiates Resting NK to “Memory-Like” NK Cells Cytokine cocktail (IL-12/15/18) drives resting NK to memory-like NK (SciTranslMed 2016; Romee,Fenheger, et al) Inkmune Generates Memory-like NK Cells with a Single Pseudokine CD16 CD94
Slide 29: INKmune First in Human Trial – MDS/AML
INKmune First in Human Trial – MDS/AML Day 29 Data - First Patient treated with INKmune IV in Oncology IV INKmune activates and matures NK cells for one month and counting…. INKmune activates all types INKmune induces NK of cytolytic NK cells proliferation in vivo 1st patient 1st patient 20 200 150
Slide 30: Residual Disease Causes Cancer Relapse
RESIDUAL DISEASE CAUSES CANCER RELAPSE in Oncology Difference Between Survival and Relapse is NK Failure to Eradicate Residual Disease ▪ Prevention of relapse key to survival and Leukemia “Survivors” death in patients with cancer Disease-free Survival ▪ Relapse is caused by residual cancer cells “Hi
Slide 31: A Multi-Dimensional Pseudokine
A MULTI-DIMENSIONAL “PSEUDOKINE” in Oncology MoA #1 – INKmune™ Increases Avidity of NK Cell Binding to Tumor Cells rNK Cells (Green) Added INKmune™ Primed NK Cells Avidity of tumor cell binding by resting and To Resistant Tumor Cells added to resistant tumor cells primed NK cells SK-OV-3 (n=3) 5 min
Slide 32: How Does INKmune Work?
HOW DOES INKMUNE™ WORK? in Oncology Resting NK don’t bind/kill resistant tumor cells INKmune-primed NK form intensely strong bonds to tumor cells and kill them Priming with IL-15 promotes NK killing INKmune™ ADVANTAGES: ▪ Universal, potentially effective in blood cancers and solid tumors ▪ Off-the-s
Slide 33: INKmune Phase 1 Study
INKMUNE™ PHASE 1 STUDY in Oncology Phase I Trial in High-Risk MDS GOAL DESIGN Evaluate Safety and Open-label dose escalation study of Tolerability of INKmune™ in intravenous INKmune enrolling 9 patients High-Risk MDS INCLUSION FIRST IN HUMAN TRIAL OF INKMUNE™ Patients with MDS with excess blasts END
Slide 34: NK Competitive Landscape
NK COMPETITIVE LANDSCAPE in Oncology 18 Programs and Counting… THE VARIABLES ▪ A unique, stable cell line, not an NK cell ▪ Cytokines - single or multiple as a therapeutic or ▪ >180 unique genes induced in resting NK cells as part of cell therapy ▪ ↑NK survival = persistence ▪ NK cell source – ▪ ↑ N
Slide 35: Targeting Neuroinflammation for Treatment Resistant Depression
for TRD Targeting Neuroinflammation for TREATMENT RESISTANT DEPRESSION (TRD) 35
Slide 36: Treatment Resistant Depression (TRD)
TREATMENT RESISTANT DEPRESSION (TRD) for TRD The Subset of People Who Have Failed At Least Two Anti Depressants 1 out of 3 MDD Economic Higher Chronic course TNF biology POC studies with anti-TNF patients or 33% of the toll: comorbidity of MDD in TRD blood CRP predicts response estimated 7M patients
Slide 37: TRD Is Driven by Inflammation
TRD IS DRIVEN BY INFLAMMATION for TRD 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., Psychoneuroendocrin
Slide 38: TNF Predicts TRD
TNF PREDICTS TRD for 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 Inflammation-associated deficits in reward circuitry Treatment Response (≥50 reduction i
Slide 39: Phase 2 TRD Trial
PHASE 2 TRD TRIAL for TRD Supported by Small Business Innovation Research (SBIR) grant from the National Institutes of Health DESIGN BIOMARKERS OF INFLAMMATION Six-week double blind placebo-controlled study of Xpro™ MRI 45 patients in Xpro™ at 1 mg/kg WMFW as measure of neuroinflammation 45 patients
Slide 40: Targeting Cytokine Storm in COVID-19 Complications
for COVID-19 Complications Targeting CYTOKINE STORM may Prevent Catastrophic Complications of COVID-19 40
Slide 41: What Brings Patients to the Hospital with COVID-19?
WHAT BRINGS PATIENTS TO THE HOSPITAL for COVID-19 WITH COVID-19? PROBLEM HYPOTHESIS SOLUTION At time of hospitalization , the Focusing on the Cytokine Targeting the Master Cytokine Cytokine Storm is making patients Storm, not the virus, should with QUELLOR should tame sick, mot the virus... make pat
Slide 42: TNF Is the Master of the Cytokine Storm
TNF IS THE “MASTER” OF THE CYTOKINE STORM for COVID-19 ▪ Block sTNF and downstream pro- inflammatory cytokines should decrease ▪ Synergism of TNF-α and IFN-γ triggers inflammatory cell death, tissue damage, and mortality Adapted from Karki et al 2020 42
Slide 43: Phase 2 Trial
PHASE 2 TRIAL for COVID-19 Treating Pulmonary Complications of COVID-19 DESIGN GOAL SOC vs SOC+Quellor™ 1mg/kg subQ day 1 and 7 (if in hospital) Prevent Progression to Patient discharged based on clinical status or final study visit day 28 Catastrophic Complications 366 patients randomized 1:1 First
Slide 44: Quellor Phase 2 Trial: Next Steps
QUELLOR PHASE 2 TRIAL: NEXT STEPS for COVID-19 Treating Pulmonary Complications of COVID-19 ▪ Changing landscape: ▪ Regulatory – FDA not awarding EUA for therapies ▪ Clinical – C19 less lethal, SOC changing, geography challenging ▪ What we are doing: ▪ Declared Phase II trial complete after 76 patie
Slide 45: Harnessing the Power of the Innate Immune System
HARNESSING THE POWER CONTACT US OF THE INNATE IMMUNE SYSTEM INmune Bio Inc. 980 N. Federal Hwy, Suite 110 Boca Raton, FL 33432 INMB (858) 964-3720 www.inmunebio.com 45