INmune Bio Inc. · NASDAQ:INMB
INmune Bio — Investor Presentation (March 2023)
55 slides from INmune Bio's investor presentation, March 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 March 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: 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 4: 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 5: 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 6: 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 7: Treating Alzheimer's as an Immunologic Disease, not a Neurologic Disease
for AD Treating Alzheimer’s as an Immunologic Disease …not a Neurologic Disease 7
Slide 8: Alzheimer's burden: deaths, caregivers and cost of care
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 9: 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 9
Slide 10: Neuroinflammation
A wealth of evidence supports NEUROINFLAMMATION as a critical driver of the pathogenesis and progression of Alzheimer’s disease
Slide 11: Genetic study shows association of AD 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 12: 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 12
Slide 13: 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 14: 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 15: Summary of Successful Phase 1b trial in ADi
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 16: XPro decreases neuroinflammation in AD
Phase 1b Data: TARGET ENGAGEMENT XPROTM DECREASES NEUROINFLAMMATION IN AD for AD Inflammatory Cytokines in CSF after 3 months 16
Slide 17: XPro decreases neuroinflammation in AD: free-water
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 18: White Matter Metrics
WHITE MATTER METRICS for AD Health White matter AD white matter 18
Slide 19: Downstream benefits: decreases neurodegeneration, improves synaptic function
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 20: 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 20
Slide 21: 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 22: XPro increased white matter volume
White Matter volumetric analysisWhite Matter volum Phase 1b Data XPRO™ INCREASED WHITE 460000 0.1469 1000 460000 0.1469 1 Total White Matter volume (mm3) 0.1084 (mm3)) 3 Left Entorhinal volume (mm3) volume(mm MATTER VOLUME 440000 440000 900 for AD Mattervolume 420000 420000 800 Entorhinal 400000 400
Slide 23: 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 6 months 9 months green/blue shows improvement in axonal qu
Slide 24: 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 25: 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 25
Slide 26: What is different about XPro Phase 2 program in early AD?
WHAT IS DIFFERENT ABOUT XPROTM PHASE 2 PROGRAM IN EARLY AD? for AD Small and Fast Sensitive Endpoint Enrichment 26
Slide 27: 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 28: Targeting Neuroinflammation for Treatment Resistant Depression (TRD)
Targeting Neuroinflammation for the Treatment of TREATMENT RESISTANT DEPRESSION (TRD) 28
Slide 29: 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 30: 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 TRDpatients1 patients with elevated biomarkers of inflammation2 80 Infliximab (TNF inhibitor) Placebo Responders (%) 60 40 20 0 < 5mg/L > 5mg
Slide 31: 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 32: 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 33: Off-the-Shelf NK Therapy Converts Resting NK cells into Memory-Like NK cells
for Oncology Off-the-Shelf NK Therapy Converts Patient’s Resting NK cells into Cancer Killing memory like NK cells 33
Slide 34: NK cells play a critical role in eliminating cancer cells
Natural Killer (NK) cells play a critical role in eliminating cancer cells in Oncology ✓ NK cells are principal anti-tumor cells in innate immune system ✓ 5-15% of the circulating lymphocytes NK T ✓ Primed NK cells are capable of high cytotoxicity against tumors without prior sensitization cells cel
Slide 35: NK cell cytotoxicity predicts survival in myelodysplastic syndrome
NK cell cytotoxicity is a predictor of survival in myelodysplastic syndrome in Oncology Better NK cytotoxicity Greater NK-mediated correlates with cell function in long- increased survival term survivors % K562 Lysis NO YES Alive >2yrs Tsirogianni M, et al. Leukemia & Lymphoma. 2019;60(10):2457-2463
Slide 36: Why don't NK cells kill cancer cells more effectively?
Why don’t NK cells kill cancer cells more effectively? 1. INSUFFICIENT ACTIVATION in Oncology Resting NK cells are not sufficiently activated by NK-resistant cancer cells 2. TUMOR-MEDIATED INHIBITION Tumors release factors that inhibit NK cell activity Activated NK cells can kill cancer cells effect
Slide 37: Many NK cell-based immunotherapy approaches are being tested
Many NK cell-based immunotherapy approaches are being tested in Oncology 1. Adoptive NK cellular therapy 2. Cytokine activation ex-vivo and in-vivo 3. Chimeric antigen receptor (CAR-NK) 4. mAb inhibition of NK inhibitor receptors 5. Checkpoint inhibitors Paul S, Lal G. Front Immunol. 2017;8:1124 37
Slide 38: Several NK cell-based immunotherapies have serious limitations
Several NK cell-based immunotherapies have serious limitations in Oncology ❌ Poor activation of NK cells by single cytokine signal → suboptimal efficacy ❌ Toxic side effects (in vivo cytokine therapy) ❌ Requirement for lymphopenia → risk of infection (adoptive transfer) ❌ Short-lived therapeutic per
Slide 39: Re-equilibrating the immune system in cancer: INKmune
Re-equilibrating the immune system in cancer in Oncology INKmune™ • Is a proprietary cell line that when given directly to patients delivers essential priming signals to ”turn on” NK cells to become tumor killing memory-like NK cells. 39
Slide 40: How does INKmune prime NK cells to kill cancer cells?
How does INKmune™ prime NK cells to kill cancer cells? in Oncology INKmune™: 1. Robustly activates resting NK to tpNK cells via multiple signals similar to using a combination of at least 3 cytokines in combination (IL-12, IL-15, IL-18) 2. Increases avidity of binding of tpNK cells to tumor target c
Slide 41: INKmune stimulates differentiation of resting NK cells to memory-like NK cells
INKmune™ stimulates differentiation of resting NK cells to in Oncology memory-like NK cells INKmune Generates Memory-Like NK Cells Without Use of IL-12, IL-15 and IL-18 INKmune-primed CD16 CD16 CD94 CD94 NKG2A NKG2A NKG2D NKG2D NKG2C NKG2C NK cells (TpNK) are 20000 80000 30000 15000 40000 phenotypic
Slide 42: INKmune Increases Avidity of NK Cell Binding to Tumor Cells
INKmune™ Increases Avidity of NK Cell Binding to Tumor Cells in Oncology Avidity of tumor cell binding by resting and primed NK cells • rNK bind weakly to NK- SK-OV-3 (n=3) 5 min resistant SKOV-3 ovarian 100 cancer cells and do not lyse % NK Cells Bound resting NK 80 TpNK - INKmune primed NK them. N
Slide 43: INKmune priming allows NK to kill NK-resistant tumor cells in hypoxia
INKmune™ priming allows NK to kill NK-resistant tumor cells in Oncology even in the hypoxia of the TME • SKOV-3 tumor cells establish active growth in 1% O2 for 24h before addition of rNK cells • 12h later, INKmune is added to 50% of cultures (light green) • RNK cells do not lyse SKOV-3 • The SKOV-3
Slide 44: INKmune improves NK fitness
INKmune™ improves NK fitness by activating critical genes and pathways for enhanced NK function / survival in Oncology INB16 upregulates 522 genes distinct from IL2 – including CD70, CXCL10, Stat5 INB16 upregulates 1461 proteins distinct from IL15 – including TIMM29, USP20 Target cell lysis proteins
Slide 45: INKmune Phase 1 study: First patient to have completed treatment
INKmune™ Phase 1 study: First patient to have completed treatment in Oncology Persistence of activated tumor-killing memory-like NK cells in blood at 119 days 45
Slide 46: But is INKmune safe?
But is INKmune™ safe? in Oncology 1. Does not require lymphopenia be induced first unlike adoptive transfer of NK cells 2. Does not have side effects associated with cytokine therapy since it does not contain cytokines 3. Activation of NK cells has been very well tolerated 4. No SAE/R reported despi
Slide 47: cGMP Manufacturing – Doable vs Practical
cGMP MANUFACTURING – DOABLE VS PRACTICAL…. in Oncology Many NK Manufacturing Approaches MFG Process 2 INKmune™ 500 liter bioreactor 500 liter bioreactor 1 batch = 15,000 patient doses Billions of iPSC CLP + differentiating cytokines DRUG PRODUCT Billions of iPSC-NK + gene editing (x1 x2 x3 x4???) DR
Slide 48: Thank you
Thank you HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM 48
Slide 49: What causes immune dysfunction
What causes immune dysfunction 49
Slide 50: TNF biology is complicated: two ligands with opposite effects
TNF biology is complicated: two ligands with opposite effects 50 50
Slide 51: 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 52: Safety side effects of non-selective TNF blockade are from blocking tmTNF
Safety side effects of non-selective TNF blockade are all from blocking tmTNF Consequences of blocking tmTNF: ▪ Infection ▪ Cancer ▪ Demyelination 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 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 54: 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 54
Slide 55: XPro unique Mechanism of Action
XPRO unique Mechanism of Action 55