INmune Bio Inc. · NASDAQ:INMB
INmune Bio — Investor Presentation (July 2023)
56 slides from INmune Bio's investor presentation, July 2023
Slide 1: Harnessing the Power of the Innate Immune System
HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM Two Therapeutic Platforms: XPro™ and INKmune™ Help Repair Innate Immune Dysfunction INMB INVESTOR PRESENTATION July 2023
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
INVESTMENT HIGHLIGHTS Targeting Innate Immune Dysfunction Two platforms INMB XPro™ for CNS INKmune™ for CANCER PRICE(5/9/23) COMMON S/O $8 ~19 M Cap structure Large insider ownership MARKET CAP CASH/DEBT ( 3 /3 1 /2 3 ) ~$145M ~$51M/$15M All common stock, no warrants 52-WEEK RANGE AVG. V
Slide 4: Chronic inflammatory diseases are the most significant cause of death
Chronic Inflammatory diseases have been recognized as the most significant cause of death in the world today, with more than 50% of all deaths being attributable to inflammation-related diseases. 4
Slide 5: Corporate Focus
Corporate Focus Disequilibrium of the innate immune system is a key driver of both cancer, INMB neurodegenerative diseases and many other conditions INmune Bio is developing two novel platform therapies that recalibrate the innate immune system Chronic inflammatory diseases XPro™ DN-TNF selectiv
Slide 6: Pipeline
DEVELOPMENT PIPELINE DN-TNF PLATFORM EST. NEXT DISEASE FIELD PRE-CLINICAL PHASE I PHASE II (POC) PIVOTAL MILESTONE Early Alzheimer’s P2 Data 2024 Treatment Resistant Depression P2 Start 2023 DMD Future pSar DN-TNF Cancer Development and/or Other Partnership NK PRIMING PLATFORM Myelodysplastic P1 Dat
Slide 7: Intellectual Property
INTELLECTUAL PROPERTY DN-TNF PLATFORM Patent exclusivity through 2033 and beyond 47 global patent properties* DN-TNF compositions Use of DN-TNF for treatment of a variety of disease indications Combination therapies NK PRIMING PLATFORM Patent exclusivity through 2036 and beyond 11 glob
Slide 8: Management Team
MANAGEMENT TEAM Broad biotechnology background including legal, intellectual property, drug manufacturing, clinical trial management, FDA approval, Raymond J. Tesi, MD David J. Moss Mark W. Lowdell, PhD drug marketing, finance, CEO/CMO & Chairman of the CFO CSO business development and Board operati
Slide 9: Treating Alzheimer's as an Immunologic Disease
for AD Treating Alzheimer’s as an Immunologic Disease …not a Neurologic Disease 9
Slide 10: Alzheimer's disease burden
Long duration of illness before death, as long as 20 years 121,499 deaths from Alzheimer’s disease in 2019 High burden and stress on family caregivers, especially spouses Total cost of care for Americans age ’ 65 or older with AD: $321 billion
Slide 11: Questions to Answer about INmune Bio's approach to Alzheimer's Disease
Questions to Answer about INmune Bio’s approach to for AD Alzheimer’s Disease Why neuroinflammation? What causes neuroinflammation? Why XPRO™? XPRO results in patients with ADi Next steps in patients with Alzheimer’s Disease 11
Slide 12: Evidence supports neuroinflammation in Alzheimer's
A wealth of evidence supports NEUROINFLAMMATION as a critical driver of the pathogenesis and progression of Alzheimer’s disease
Slide 13: Strong association with immune dysfunction
Large genetic profile study of AD patients demonstrated strong association with immune dysfunction for AD MICROGLIA Genome-wide association study of 71,880 AD cases and 383,378 controls Astroglia Genes associated with AD were strongly expressed in immune-related tissues and cell types, including mic
Slide 14: Strong Evidence Supports Neuroinflammation in Alzheimer's
Strong Evidence Supports Neuroinflammation in Alzheimer’s for AD RISK OF ALZHEIMER’S DISEASE IN PATEINTS WITH Rheumatoid Arthritis Risk of general population Adapted from Chou et al. 2016 8.5M claims Torres-Acosta N, et al. J Alzheimer’s Dis. 2020;78:619–626 14
Slide 15: Headline: TNF Inhibitor Prevent Alzheimers
HEADLINE: “TNF INHIBITOR PREVENT ALZHEIMERS” for AD 15
Slide 16: TNF increases early in life
TNF increases early in life Pro-inflammatory cytokines are linearly and positively associated with AGE 30 age. Age alone accounts for the substantial portion (>80%)of explained variance for TNF, TNFR-I, TNFR-II. Adapted from Parker et al. 2008 16
Slide 17: Anti-TNF Antibodies Have Serious Limitations
Anti-TNF Antibodies Have Serious Limitations XPROTM improves the brain for AD approved TNF Inhibitors “abuse” the brain Etanercept XPRO Myelin Axons Non-selective TNF inhibitors (Etanercept) that block both transmembrane TNF and soluble TNF cause demyelination (yellow arrow) and axonal degeneration
Slide 18: INmune Bio's AD Program simplified
INmune Bio’s AD Program simplified… for AD Neuroinflammation is a cause of AD Soluble TNF causes neuroinflammation XPro neutralizes soluble TNF to reduce neuroinflammation Cognitive Decline Amyloid plaques Nerve Cell Neurofibrillary tangles Death Behavioral, MICROGLIA Environmental Synaptic an
Slide 19: Summary of Successful Phase 1b trial in AD
Summary of Successful Phase 1b trial: AD for AD patients with biomarkers of inflammation (ADi) DESIGN Open-label Multiple dosing cohorts (0.3, 0.6, 1.0 mg/kg) Weekly XPro1595™ SubQ injections for 3 months Biomarkers assessed at 0 and 12 weeks Inclusion AD Diagnosis At least one biomarkers
Slide 20: XPro decreases neuroinflammation in AD
Phase 1b Data: TARGET ENGAGEMENT XPROTM DECREASES NEUROINFLAMMATION IN AD for AD Inflammatory Cytokines in CSF after 3 months 20
Slide 21: White Matter Metrics
WHITE MATTER METRICS for AD Health White matter AD white matter 21
Slide 22: XPro decreases neuroinflammation in AD
RESULT OF PHASE I TRIAL XPRO DECREASES NEUROINFLAMMATION IN AD for AD Decrease in Neuroinflammation in white matter tracts over 12 months XPro decreases neuroinflammation over 12 months in patients with AD 30 Free-water in AD bundles (% change) 20 10 0 -10 XPro1595 1 mg/kg -20 ADNI database N = 36 -
Slide 23: Downstream benefits of XPro treatment
Phase 1b Data: CSF PROTEOMICS DOWNSTREAM BENEFITS OF XPRO™ TREATMENT: DECREASES for AD NEURODEGENERATION AND IMPROVES SYNAPTIC FUNCTION Synaptic Proteins Contactin-2 – 222% increase Neurogranin – 56% decrease Neuronal Injury Visinin-like protein 1 (VILIP-1) – 91% decrease Neurofilament light (NFL) –
Slide 24: A traditional biomarker of AD: pTau217/181
RESULT OF PHASE I TRIAL – p-tau217 as a biomarker of AD A “traditional” biomarker of AD – pTau217/181 CSF following 12 weeks of treatment with XPro1595 (1 mg/kg) for AD p<0.0001 p<0.01 Phospho-tau is a biomarker of neurodegeneration Phospho-tau217 correlates best with cognitive dysfunction 24
Slide 25: Downstream benefits of XPro in patients with ADi
Phase 1b Data THE “DOWNSTREAM” BENEFITS OF XPROTM IN PATIENTS for AD WITH ADI XPRO improves axonal integrity in white matter tracts (increased AFD) XPRO promotes remyelination/myelin repair (RD) 12 month AFD improvement 1mg/kg 12 month RD improvement 1mg/kg 20 Fiber Density in AD bundles (% chan
Slide 26: XPro increased white matter volume
Phase 1b Data XPRO™ INCREASED WHITE 460000 0.1469 Total White Matter volume (mm3) MATTER VOLUME 440000 for AD 420000 400000 380000 360000 0 3 6 9 12 Visit (months) 0.0839 6500 0.0381 0.1226 Left Inferior Temporal 6000 3 volume (mm ) 5500 5000 0 3 6 9 12 Visit (months) INMB AD Non-confidential 1.5.22
Slide 27: Remodeling of white matter tracts after XPro
Phase 1b Data: CHANGES IN AFD IN AD WHITE MATTER TRACTS IN MAN REMODELING OF WHITE MATTER TRACTS AFTER XPROTM for AD Baseline 3 months 65-year-old white male retired due to AD Returned to work after 6 months of XPro therapy Increasing 9 months green/blue 6 months shows improvement in axonal qu
Slide 28: Clinical Benefit in Phase I trial
Clinical Benefit in Phase I trial Disclaimer: small N, disease status heterogeneity, short time period for AD Assessments administered: Cognitive: MMSE, Verbal Fluency Test, Digit Symbol Coding Neuropsychiatric Inventory Bristol Activities of Daily Living Scale To compare across patients o
Slide 29: Correlation between decreased neuroinflammation and improved cognition
Correlation between decreased for AD neuroinflammation and improved cognition R2 = 0.4 to 0.6 CSF cytokines by OLINK platform INMB AD Non-confidential 1.5.22 29
Slide 30: Randomized Placebo-Controlled Study of XPro1595 in Early Alzheimer's
A 6 month, Randomized, Placebo-Controlled, Double-Blind Study of XPro1595 in Patients with Early Alzheimer’s Disease with Biomarkers of Inflammation Baseline Week 6 Week 12 Week 18 Week 24 Key enrollment criterion Cognition EMACC Cognition EMACC Cognition Early AD (50-85 yrs) (N=201) F
Slide 31: Statistical Power: why XPro trials are short and small
Statistical Power: why XPRO clinical trials are for AD designed to be short and small • Patients with neuroinflammation have faster cognitive decline than patients without neuroinflammation • Enrichment strategy selects patients with neuroinflammation • Goal of XPRO therapy is to prevent cognitive d
Slide 32: Targeting Neuroinflammation for Treatment Resistant Depression
Targeting Neuroinflammation for the Treatment of TREATMENT RESISTANT DEPRESSION (TRD) 32
Slide 33: Treatment Resistant Depression (TRD)
TREATMENT RESISTANT DEPRESSION (TRD) for TRD Frustrations of psychiatric drug development THE PROBLEM Drug development in psychiatry is a “one size fits all” approach MDD, TRD and Inflammation 200+ ways to be diagnosed with depression There are 200+ symptom combinations that will lead to a dep
Slide 34: Why sTNF is the right Target
TREATMENT RESISTANT DEPRESSION (TRD) Why sTNF is the right Target for TRD Plasma TNF levels are increased Anti-TNF treatment reduces depressive symptoms in in TRD patients1 patients with elevated biomarkers of inflammation2 80 Infliximab (TNF inhibitor) Placebo 60 Responders (%) 40 20 0 < 5mg/L > 5m
Slide 35: A biomarker of neuroinflammatory depression
A biomarker of neuroinflammatory depression for TRD VmPFC Patients with higher levels of blood CRP (>3mg/L) had lower Functional Connectivity between the ventral striatum (VS) and a cluster in ventromedial prefrontal cortex (vmPFC) compared to those with CRP <1 mg/L; a region of the brain that subse
Slide 36: 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 37: Off-the-Shelf NK Therapy Converts Resting NK Cells
for Oncology Off-the-Shelf NK Therapy Converts Patient’s Resting NK cells into Cancer Killing memory like NK cells 37
Slide 38: Goal of INKmune NK cell priming program in cancer
Goal of INKmune NK cell priming program in cancer in Oncology Novel technology with strong patent protection Off-the-shelf program with scalable manufacturing Clinical trials in liquid and solid tumors Ambitious goal: be leader in solid tumors Timeline: top-line Phase II data EOY24 38
Slide 39: Why don't NK cells kill tumor cells more effectively?
Why don’t NK cells kill tumor cells more effectively? in Oncology 1. INSUFFICIENT ACTIVATION Resting NK cells are not sufficiently activated 2. TUMOR-MEDIATED INHIBITION Tumors release factors that inhibit NK cell activity NK activators resting NK tumor primed NK (rNK) (tpNK) Karvouni M, et al. Fron
Slide 40: Why NK cells, why INKmune, why Prostate Cancer?
WHY NK CELLS, WHY INKmune, WHY Prostate Cancer? Why NK cells? NK cells are central to immune surveillance against cancer and “innately” kill cancer cells NKs help expand the immune response (recruit T cells to the TME) Why Prostate Cancer? No improvement in survival of mCRPC for >10 years. No
Slide 41: TpNK fitter than cytokine primed NK
TpNK “fitter” than cytokine primed NK Only INKmune induces changes which protect NK in TME rNK LAK-15 CIML-NK INKMUNE-TpNK Change in mitochondrial survival proteins following priming 3 TpNK Log change from rNK (Average Log ratio) 2 CIML IL15 1 0 proteomics -1 -2 QRSL1 GATB GATC RARS2 GFM2 HARS1 HARS
Slide 42: INKmune Phase 1 study: AML/MDS
INKmune™ Phase 1 study: AML/MDS in Oncology Persistence of activated tumor-killing memory-like NK cells in blood at 119 days INKmune induces memory-like NK cells with enhanced NKG2D+ NKcells INKmune activated tumor- lysis of In NK-sensitive and NK-resistant cells vitro Tumor Killing assay killing NK
Slide 43: Prostate Cancer Incidence and Mortality
Prostate Cancer Incidence and Mortality Prostate 2018 2019 2020 2021 2022 Cancer Incidence 164,690 174,650 191,930 248,530 268,490 Mortality 29,430 31,620 33,330 34,130 34,500 Incidence: Prostate vs. Breast Cancer 350,000 300,000 250,000 200,000 150,000 Breast Cancer 100,000 Prostate Cancer 50,000 0
Slide 44: Timeline of Drug Development in mCRPC
Timeline of Drug Development in mCRPC 2013: Radium 223 2010: Cabazitaxel 2017: Pembrolizumab 2022: PSMA radioligand 2004: Docetaxel 2012: Enzalutamide (post-chemo) 2004 2010 2012 2014 2016 2018 2020 2022 2010: Sipuleucel-T 2013: Abiraterone 2020: PARPi (olaparib, (pre-chemo) rucaparib) 2011: Abirate
Slide 45: Monthly Median OS Benefit of Drugs Approved for mCRPC
Monthly Median OS Benefit of Drugs Approved for mCRPC Radium- PSMA Agent Sipuleucel-T Abiraterone Enzalutamide Docetaxel Cabazitaxel Olaparib 223 RLT Median OS Post-doc: 4.6 Post-doc: 4.8 benefit 4.1 2.4 2.4 3.6 5.3 2.3 Pre-doc: 4.4 Pre-doc: 4.0 (months)
Slide 46: mCRPC mBOIN12 – a two step trial
mCPRC mBOIN12 – a two step trial • Step 1: 3X3 dose escalation “run-in” to demonstrate: • short-term safety (28 days) • short-term immunologic efficacy • Step 2: simultaneous testing of multiple doses to: • Demonstrate long-term safety (6 month) • Demonstrate proof-of-biology (POB = anti-tumor effec
Slide 47: INKmune mBOIN12 mCRPC
INKmune mBION12 mCRPC long term safety Short term safety Immunologic efficacy Immunologic efficacy Anti tumor effects Step 1 Step 2 low dose 1 1 1 6 patient confirmatory group In this example: SRC choses middle dose for pivotal trial middle dose 1 1 1 6 patients 6 patients high dose 1 1 1 6 patients
Slide 48: XPro and INKmune: Tip of the Iceberg
TIP OF THE ICEBERG XPROTM AND INKMUNE Visible programs AD, TRD “Out-of-Sight” Parkinson’s Disease, MS, dementia, traumatic brain injury PTSD, autism, bi-polar disease Much, much, more…. Visible programs High risk MDS; Prostate Cancer “Out-of-Sight” Renal, NPC pSar-DN-TNF pSar-DN-
Slide 49: Investment Highlights
INVESTMENT HIGHLIGHTS Targeting Innate Immune Dysfunction Two platforms INMB XPro™ for CNS INKmune™ for CANCER PRICE(5/9/23) COMMON S/O $8 ~19 M Cap structure Large insider ownership MARKET CAP CASH/DEBT ( 3 /3 1 /2 3 ) ~$145M ~$51M/$15M All common stock, no warrants 52-WEEK RANGE AVG. V
Slide 50: Thank you
Thank you HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM 50
Slide 51: XPro: a TNF inhibitor designed to treat neurologic disease
XPRO: a TNF inhibitor designed to treat neurologic disease XPro1595: a selective inhibitor of ONLY soluble TNF XPro1595 is identical to the human soluble TNF monomer with the exception of mutations in the receptor binding domain and another for pegylation. Steed et al 2003 51
Slide 52: TNF biology is complicated: two ligands with opposite effects
TNF biology is complicated: two ligands with opposite effects 52 52
Slide 53: XPro is very different from currently available drugs
XPRO is very different from currently available drugs Precise neutralization of the TNF ligand that drives disease Approved TNF inhibitors block both cytokines X X Soluble TNF (‘sTNF’) Transmembrane-bound Soluble TNF (sTNF): “bad” TNF BAD (‘tmTNF’) GOOD that is known to cause acute and chronic inf
Slide 54: Safety side effects of non-selective TNF blockade
Safety side effects of non-selective TNF blockade are all from blocking tmTNF Consequences of blocking tmTNF: Infection Cancer Demyelination 54 54
Slide 55: XPro is very different from currently available drugs
XPRO is very different from currently available drugs Precise neutralization of the TNF ligand that drives disease XPro blocks solTNF X 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 T
Slide 56: XPro unique Mechanism of Action
XPRO unique Mechanism of Action 56