Inmune Bio Inc. · NASDAQ:INMB
Inmune Bio — Investor Presentation (November 2020)
51 slides from Inmune Bio's investor presentation, Nov 12, 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 Nov 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: INmune Bio Highlights
INMUNE BIO HIGHLIGHTS 3 Clinical - stage biopharmaceutical company developing a new class of therapeutics that target dysfunction of the innate immune system Two platforms : ▪ DN - TNF: First selective TNF inhibitor targeting inflammation without demyelination or immunosuppression ▪ NK Cell Priming:
Slide 4: 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 Treatment Resistant Depression Alzheimer’s Disease CNS P2 Mid - 2021 P2 underway – data 2021 NK PRIMING PLATFORM DISEASE FIELD PRE - CLINICAL PHASE I PHASE II (POC) PIVOTAL NEX
Slide 5: Innate immune dysfunction and chronic inflammation cause many diseases
Innate immune system plays a critical and often overlooked role in host protection and normal function 50% of all deaths are attributable to inflammation - related diseases 1 5 INNATE IMMUNE DYSFUNCTION Chronic Inflammation drives Innate Immune Dysfunction are the Causes of Many Diseases 1 Furman et
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
7 ALZHEIMER’S DISEASE (AD) Driven by Neuroinflammation ▪ Characterized by chronic inflammation which drives synaptic loss and neurodegeneration ▪ As of today, there is no treatment for the cognitive decline of AD Adapted from Alzheimer’s Association “Changing the Trajectory of Alzheimer's Disease: H
Slide 8: Innate Immune Dysfunction Damages the CNS
▪ Inflammaging wreaks havoc on patients over time and is a central component of aging and age - related diseases 1 ▪ Dysregulated innate immune responses are widely recognized as playing a major role in the development of neurodegeneration including AD ▪ Targeting glial activation may prevent much o
Slide 9: White Matter Free Water: A Validated Biomarker for Neuroinflammation
9 WHITE MATTER FREE WATER (WMFW) A Validated Biomarker For Neuroinflammation ▪ White matter (WM) changes are an early event in the development of AD 1 ▪ An elevated WMFW index is indicative of neuroinflammation and higher WMFW is associated with worse scores on a clinical dementia rating (CDR) based
Slide 10: 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 w SubQ injections for 3 months ▪ Biomar
Slide 11: XPro1595 Reduces Neuroinflammation
XPRO1595 REDUCES NEUROINFLAMMATION Premotor cortex Broca’s area Wernicke's area The arcuate plays a key role in language processing – the ability to understand or express speech – critical to AD XPro1595 Reduces Neuroinflammation Within the Arcuate Fasciculus 11 XPro1595 Reduces Whole Brain Neuroinf
Slide 12: TNF and Neuroinflammation Are Validated Targets in AD
Dumont et al Descoteaux Frontiers in Aging Neuroscience 2019 TNF and NEUROINFLAMMATION ARE VALIDED TARGETS IN AD Correlation with Changes to Amyloid 12 RISK OF ALZHEIMER’S DISEASE IN MAN Risk of general population Adapted from Chou et al. 2016 8.5M claims
Slide 13: TNF Biology: Good vs Bad, tmTNF vs sTNF
13 Adapted from MacEwan et al 2002 TNF BIOLOGY : Good vs Bad: tmTNF vs sTNF sTNF is well known, tmTNF is unknown, they do very different things… ▪ Soluble TNF ( sTNF ): “bad” TNF that is known to cause acute and chronic inflammation and cell death ▪ Transmembrane TNF ( tmTNF ): “good” TNF improves t
Slide 14: Selective vs Non-Selective sTNF 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 May improve cognitive function N Y DIFFERENCES: Selective vs. Non - Selective sTNF Inhibition Non - Selective DN TNF 14 Adapted from MacEw
Slide 15: How XPro1595 Neutralizes sTNF
see Steed et al., Science , 301, 2003 Receptor binding, Receptor binding, "small" domain (subunit A) Receptor binding, (subunit B) Mutation Y87H (subunit C) Mutation R31C (for 10kD pegylation) "large" domain Mutation A145R NONGLYCOSYLATED SMALL HOMOTRIMERIC PROTEIN EXPRESSED IN E.COLI DN - TNF NEUTR
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 current therapies but not of XPro1595 EXACERBATED DEMYELINATION REMYELINATION ETANERCEPT Anti - inflammatory AND immunosuppressive DN - TNF Anti - inflammatory NOT immunosuppressive CUPRIZONE Mod
Slide 17: Unique MOA Means Expanded Market Opportunity
Global TNF inhibitor drug market is estimated to reach $42 billion by 2026 1 17 UNIQUE MOA MEANS EXPANDED MARKET OPPORTUNITY Current TNF inhibitors contraindicated in most markets Estimates from 1 GBI Research, 2 BCC Research , 3 MarketWatch, and 4 ResearchandMarkets.com. Innate Immune Dysfunction C
Slide 18: Selective sTNF Neutralization in Treatment Resistant Depression
Selective sTNF Neutralization for the Treatment of Neuroinflammation in 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% of the estimated 7M patients Economic toll: $64B/year Higher comorbidity Chronic course of MDD TNF biology in TRD POC studies with anti - TNF blood CRP predicts resp
Slide 20: TRD Driven by Neuroinflammation
20 TRD Driven by Neuroinflammation ▪ 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 billion 2 1 Mrazek, et al. Psychiatr Serv 2014. 2 Ionescu, et al. Dialogues Clin Neurosci . 2
Slide 21: TNF Predicts TRD; Anti-TNF Improves Depression
Haroon et al., Psychoneuroendocrinology , 2018. Plasma TNF levels are increased in TRD patients INMB APPR OACH: TNF PREDICTS TRD Anti - TNF Therapy Improves Depression in Patients With Elevated Inflammatory Biomarkers 21 Treatment Response ( ≥ 50 reduction in HAM - D - 17 at any point during treatme
Slide 22: Phase 2 TRD Trial
Functional connectivity between motivation and reward centers in brain BIOMARKERS OF INFLAMMATION DESIGN ▪ Six - week double blind placebo - controlled study of XPro1595 ▪ 45 patients in XPro1595 at 1 mg/kg ▪ 45 patients in placebo control group ▪ Biomarkers of inflammation at 0, 2, 6 weeks INCLUSIO
Slide 23: Targeting sTNF to Prevent Complications of COVID-19 Cytokine Storm
23 Clinical Trial to Determine if Targeting Soluble TNF (sTNF) may Prevent Catastrophic Complications of COVID - 19 due to Cytokine Storm
Slide 24: What Brings Patients to the Hospital with COVID-19?
24 WHAT BRINGS PATIENTS TO THE HOSPITAL WITH COVID - 19? Cytokine Storm is making patients sick. At time of admission viral titer is decreasing Blunting the effects of Cytokine Storm will make patients better Target the Master Cytokine of the Cytokine Storm with QUELLOR Problem Solution Hypothesis T
Slide 25: TNF: The Master Cytokine of Cytokine Storm
TUMOR NECROSIS FACTOR (TNF) The “Master” Cytokine of Cytokine Storm 25 ▪ sTNF promotes translation of IL6, IL1 and other downstream cytokines ▪ Block sTNF and downstream proinflammatory cytokines should decrease LCN2 IL - 6 ANTI - INFLAMATORY Time Plasma Concentration sTNF PRO - INFLAMATORY
Slide 26: Endothelial Cell Activation in COVID-19
ENDOTHELIAL CELL ACTIVATION The Real “Villain” in COVID - 19 ▪ Up - regulation of ICAM/VCAM allows migration of immune cells from blood vessel to tissue ▪ Up - regulation of Tissue Factor promotes coagulopathy ▪ Up - regulates Neurophilin - 1 - a receptor binding required for COVID - 19 entry to cel
Slide 27: Phase 2 Trial: Pulmonary Complications of COVID-19
PHASE 2 TRIAL: Treating Pulmonary Complications of COVID - 19 27 27 DESIGN ▪ SOC vs SOC+Quellor w 1mg/kg subQ day 1 and 7 (if in hospital) ▪ Patient discharged based on clinical status or final study visit day 28 ▪ 360 patients randomized 1:1 INCLUSION ▪ COVID - 19 infection with room air SaO2<94% ▪
Slide 28: INKmune Primes NK Cells to Kill Tumor Cells
Provides essential signals to patients’ NK cells to target and kill tumor cells. INKmune ʳ 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 ▪ Prevention of relapse can be the difference between survival and death in patients with cancer ▪ Relapse is caused by hidden residual cancer cells ▪ The innate immune
Slide 30: Two Hypotheses Behind NK Immunotherapy
• 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 enhanced to mediate autologous tumor killing • Rituximab / Herceptin etc • IL15RA • Ex - vivo activated/expanded NK cells • INm
Slide 31: INKmune Cells Prime NK Cells to Eliminate Residual Disease
Provides the innate signals necessary to prime a patient’s resting NK cells, empowering the immune system to eliminate residual cancer cells INKmune Œ CELLS PRIME NK CELLS TO ELIMINATE RESIDUAL DISEASE Tumor cells down - regulate surface molecules which prime NK cell activity, thus evading NK cell k
Slide 32: High-Risk Myelodysplastic Syndrome (MDS)
32 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 dysfunc
Slide 33: INKmune Phase 1 Study Design in High-Risk MDS
INKmune ʳ PHASE 1 STUDY DESIGN ▪ Open - label dose escalation study of intravenous INKmune enrolling 9 patients INCLUSION ▪ Patients with MDS with excess blasts ENDPOINTS ▪ Primary: Evaluate the safety and tolerability of INKmune when given intravenously ▪ Secondary: ▪ Assess the change in [or effec
Slide 34: Milestones and Future Catalysts
34 2019 Q1 Q2 Q3 Q4 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 Association award Phase 2 Trial
Slide 35: DN-TNF and NK Patents
DN - TNF PATENTS* 2024 pegylated DN - TNF (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 35 NK PATENTS* 2035 use for treatment of can
Slide 36: Contact Us
CONTACT US 36 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
Slide 37: Appendix
APPENDIX 37
Slide 38: Management Team
MANAGEMENT TEAM The Phoenix Partners TEAM PEDEGREE 38 Raymond J. Tesi, M.D. CEO/CMO & Chairman of the Board David J. Moss CFO Mark W. Lowdell , Ph.D., FRCPath , FRSB, CSO Christopher J. Barnum, Ph.D. Director of Neuroscience Joshua S. Schoonover, Esq. Assoc. General Counsel
Slide 39: White Matter Free Water: A Biomarker for Neuroinflammation
Free water = edema/swelling = inflammation WHITE MATTER FREE WATER A Biomarker For Neuroinflammation
Slide 40: 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 41: DN-TNF Options in Immuno-Oncology
DN - TNF Options in Immuno - Oncology for Treatment of Resistance to Immunotherapies 41
Slide 42: 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 42 TRASTUZUMAB RESISTANCE IN BREAST CANCER FEWER MYELOID CELLS JIMT - 1 BREAST CANCER INTO NUDE MO
Slide 43: 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 44: 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 45: Phase II in HER2+ Metastatic Breast Cancer
45 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 46: 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 46
Slide 47: Three Cycles of Inflammation Lead to NASH
THREE CYCLES OF INFLAMMATION LEAD TO NASH LIVNate ʳ 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/Sal
Slide 48: LIVNate Reduces Hepatocyte Death and Fibrosis In Vivo
0 1 2 3 0 1 2 3 0 1 2 Control 2 4 1 - - - 1 6 3 3 1 LIVNate Œ 4 4 - - - - 5 3 8 - - HEPATOCYTE BALLOONING LOBULAR INFLAMMATION STEATOSIS Control 4.4 ц 0.8 LIVNate Œ 2.9 ц 0.8 NAS (mean ц SD) Parameter (mean ц SD) Control LIVNate Œ Sirus Red positive area (%) 0.96 ц 0.29 0.69 ц 0.23 FIBROSIS SCORE N
Slide 49: 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 Œ 1mg/kg SQ treatment with for 12 weeks ▪ PIFF and non - invasive biomarkers at 0, 6 and 12 weeks ▪ Open label so biomarkers “visibl
Slide 50: 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 51: Refractory Ovarian Cancer Clinical Phase 1 Study
REFRACTORY OVARIAN CANCER CLINICAL Phase 1 Open - label Study of Intraperitoneal INKmune ʳ 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 51 Expl