INmune Bio Inc. · NASDAQ:INMB
INmune Bio — Investor Presentation (April 2024)
53 slides from INmune Bio's investor presentation, April 2024
Slide 1: Harnessing the Power of the Innate Immune System
HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM Immunology & Inflammation Focus : Two Therapeutic Platforms INMB Investor Presentation April 2024 v2 Nasdaq
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: Large Insider Ownership and All Common Capital Structure
Large Insider Ownership and All Common Capital Structure Targeting Innate Immune Dysfunction INMB • Material Clinical Data in 2024/2025 Nasdaq • Data from two biologic platforms in the clinic in 2024 and 2025 PRICE(3/28/24) COMMON S/O $11.63 ~18.0M • Cap structure • Large insider ownership a MARKET
Slide 4: Investment Snapshot
Investment Snapshot De-Risked, Phase 2 Leader in a Neuroinflammation Neuroinflammation Experienced Team Significant Near Two Product Asset with plays a key role in with Track Record of and Long-Term Platforms Driving a Substantial Clinical with next generation nearly all CNS Success Leading in Miles
Slide 5: Development Pipeline
DEVELOPMENT PIPELINE DESEASE FIELD PRE-CLINICAL PHASE I PHASE II (POC) PIVOTAL EST.NEXT DN-TNF PLATFORM MILESTONE Early Alzheimer’s Full enrollment mid-2024 Disease Topline Data 6m later Treatment Resistant Depression P2 Start 2024 EST.NEXT NK PRIMING PLATFORM DESEASE FIELD PRE-CLINICAL PHASE I/II P
Slide 6: Anticipated Milestones in 2024 and 2025
Anticipated Milestones in 2024 and 2025 Key Upcoming Clinical & Regulatory Milestones EVENT EXPECTED TIMING Complete Phase 2 AD enrollment Mid 2024 6m from Last Patient Topline Phase 2 AD data Enrolled a End of Phase 2 FDA Meeting AD Mid 2025 Pre-clinical Anti-AB and XPro Data 2H 2024 Initiate Phase
Slide 7: Neuroinflammation
The Match that lights the Fire... NEUROINFLAMMATION is a critical driver of the pathogenesis and progression of Alzheimer’s disease 7
Slide 8: Decades of data connects TNF and neuroinflammation with AD
Decades of data connects TNF and neuroinflammation with AD PubMed 2023: >1500 papers on neuroinflammation and AD “Current evidence suggests that neuroinflammation has a vital role in the pathogenesis and progression of Alzheimer’s disease.” — Leng F, Edison P. Nature Reviews Neurology. 2020 “In Alzh
Slide 9: TNF Drives Neuroinflammation and Risk of AD
TNF Drives Neuroinflammation and Risk of AD Tau Tangles Amyloid Beta TNF inhibitors reduce risk of developing AD +800% Cognitively AD Cognitively AD normal normal Rheumatoid Arthritis Astrocytes Microglia Risk of general population Rheumatoid Arthritis -60% + Anti-TNF treatment Cognitively AD Cognit
Slide 10: TNF Increases Early in Life Contributing to Inflammaging
TNF INCREASES EARLY IN LIFE CONTRIBUTING TO INFLAMMAGING and TNF LONG ASSOCIATED WITH AD AND PREDATES DEPOSITION OF AMYLOID Biomarker Concentrations by Age 2 3 in CSF Tarkowski 2003 co-localized with plaques Dickson 1997 Age • Age is the most important risk factor for AD. in blood Fillit 1991 4 core
Slide 11: XPro Safely Prevents Neuroinflammation without Axonal Degeneration and Demyelination
XPRO Safely Prevents Neuroinflammation without Axonal Degeneration and Demyelination Etanercept XPro • Currently approved non-selective TNF inhibitors (eg: Etanercept) block both trans-membrane TNF and soluble TNF, leading to demyelination (yellow arrow) and axonal degeneration Myelin (white arrows)
Slide 12: TNF Plays a Central Role in Neuroinflammation and AD
TNF Plays a Central Role in Neuroinflammation and AD Pub MED: >1500 papers published on Neuroinflammation and AD Synaptic ↑Aβ Loss sTNF Axonal Degneration Cognitive TNF Decline Released and Nerve Dementia Cell Death Activated Microglia Axonal Demyelination 1. Chang R, et al. J Cent Nerv Syst Dis. 20
Slide 13: Phase 1b Clinical Trial Design and Results
PHASE 1B CLINICAL TRIAL DESIGN AND RESULTS N=18 : 6 Patients per Cohort 13
Slide 14: Enrichment Criteria used to select patients with AD due to Neuroinflammation
Enrichment Criteria used to select patients with AD due to Neuroinflammation Using simple biomarkers to match patient’s disease with XPRO MOA Peripheral Inflammation cause Central Inflammation • Patients with elevated biomarkers of peripheral inflammation have increased risk of AD due to neuroinflam
Slide 15: XPro Crosses the BBB to Neutralize sTNF in Brain
XPro Crosses the BBB to Neutralize sTNF in Brain Phase I CSF from 1mg/kg patients • In OLINK assay, sTNF cross reacts with XPro • CSF XPro level is a measure of CNS XPro level 6.5 Log increase in CSF TNF • Methodology: • Baseline sTNF level at time 0 6.0 • Repeat sTNF level after 12 weeks XPRO 1mg/k
Slide 16: XPro Decreases Neuroinflammation in AD Patients
Phase 1b Results: TARGET ENGAGEMENT XPRO DECREASES NEUROINFLAMMATION IN AD Patients Decreased Inflammatory Cytokines in CSF after 3 months at 1mg/kg/QW dose 16
Slide 17: XPro Has a Significant Effect on the Regulation of AD Related Biomarkers
Phase 1b Results: CSF PROTEOMICS XPro has a Significant Effect on the Regulation of AD Related Biomarkers Downstream Benefits of Decreasing Neuroinflammation 17
Slide 18: Functional Change in AD Patients after 4 weeks of XPro
Functional Change in AD Patients after 4 weeks of XPro Pilot study of 7 moderate to severe AD Patients; 1 mg/kg once a week subQ EEG Alpha Power after 4 weeks of Resting alpha-band power XPro1595 treatment in EEG is a broad measure Week 4 of brain network connectivity, which is Baseline attenuated w
Slide 19: CSF proteome changes after XPro predicts EEG functional response
CSF proteome changes after XPro predicts EEG functional response Phase I patients at 3 months 1mg/kg/QW A comprehensive analysis of the CSF proteome affected by 3 months of XPro treatment for AD is in progress. Top-level results show a high concentration of synaptic proteins (24%) among the group wi
Slide 20: Structural Benefit: XPro Increased White Matter Volume
Phase 1b Data Structural Benefit: XPro Increased White Matter Volume a 20
Slide 21: XPro Attenuates AD-like Pathology and Restores Normal Function in Animal Models
XPro Attenuates AD-like Pathology and Restores Normal Function in Animal Models Findings in Phase I studies precisely matched findings in animal studies Immune Dysfunction Amyloid Pathology a Synaptic Dysfunction Nerve Cell 1. Ekert JO, et al. Int J Geriatr Psychiatry. 2017;33:688–694 Death 2. Kalov
Slide 22: 6 Month Randomized, Placebo-Controlled Study of XPro in Early Alzheimer's
A 6 MONTH, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND STUDY OF XPRO IN PATIENTS WITH EARLY ALZHEIMER’S DISEASE WITH BIOMARKERS OF INFLAMMATION Primary Endpoint ❑ EMACC a Secondary Endpoints Treatment ❑ CDR, ECog ❑ 2:1 (XPro1595:Placebo) ❑ ADL, NPI ❑ 1 mg/kg XPro1595 weekly subQ ❑ Blood injection ❑
Slide 23: The EMACC provides an accurate cognitive assessment in Early Alzheimer's Disease
EMACC: Early/ Mild Alzheimer’s Cognitive Composite Why use EMACC as our primary endpoint? The EMACC provides an accurate cognitive assessment in patients with Early Alzheimer’s Disease Measure what matters! ▪ Traditional endpoints (CDR/ADAS-Cog) optimized for cognitive changes that occur in moderate
Slide 24: XPro Phase II Trial uses Conservative Statistical Plan Based on CDR-SB
XPro Phase II Trial uses Conservative Statistical Plan Based on CDR-SB • Both lecanemab and donanemab Phase III statistically positive at 6 months • Effects size of XPro at 6 months is “same” as anti- a amyloid • Conclusion: XPro needs to be as good as lecanemab or better for a positive study Placeb
Slide 25: Summary: Phase 2 XPro for AD
Summary: Phase 2 XPro for AD ENROLLMENT TO COMPLETE MID 2024 WITH TOP LINE DATA APPROXIMATELY 6 MONTHS FROM LAST ENROLLMENT ▪ Enriching for patients that have AD with inflammation (ADi) ▪ ADi patients have faster progressing disease with less variance derisks clinical trial design ▪ Cognitive and fu
Slide 26: 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. 26
Slide 27: TNF Biology Is Complicated: Two Ligands with Opposite Effects
TNF BIOLOGY IS COMPLICATED: TWO LIGANDS WITH OPPOSITE EFFECTS 27
Slide 28: 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 ▪ Soluble TNF (sTNF): “bad” TNF that is known to cause acute and chronic inflammation and cell death ▪ Transmembrane TNF (tmTNF): “good” TNF
Slide 29: Side Effects of Non-Selective TNF Blockade Are All from Blocking tmTNF
SAFETY SIDE EFFECTS OF NON-SELECTIVE TNF BLOCKADE ARE ALL FROM BLOCKING TMTNF 29
Slide 30: 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 soluble TNF ▪ Soluble TNF (sTNF): “bad” TNF that is known to cause acute and chronic inflammation and cell death ▪ Transmembrane TNF (tmTNF): “good” TNF improves the immune
Slide 31: XPro Unique Mechanism of Action
XPRO UNIQUE MECHANISM OF ACTION Xpro1595 freely exchanges with soIuble TNF tmTNF homotrimers are anchored to the cell monomers to form inactive heterotrimers membrane, XPro1595 cannot exchange Inflammatory soluble TNF eliminated: Immuno protective transmembrane TNF No paracrine signaling through rec
Slide 32: CSF Proteome Dose Response Phase I AD
CSF Proteome Dose Response Phase I AD Confirms CSF inflammatory cytokine dose response that 1mg/kg/QW is optimal dose • Unbiased analysis of CSF proteome using Proteome Sciences TMT Calibrator technology • 35,443 distinct peptide sequences associated with 4,966 protein groups were quantified • and s
Slide 33: Off-the-Shelf NK Therapy Converts Resting NK Cells into Memory-like NK Cells
Off-the-Shelf NK Therapy Converts Patient’s Resting NK cells into Cancer Killing memory like NK cells 33
Slide 34: INKmune NK Cell Priming Program in Cancer
INKMUNE NK CELL PRIMING PROGRAM IN CANCER ➢ Novel technology with strong patent protection ➢ Off-the-shelf program with scalable a manufacturing ➢ Focus on solid tumors ➢ Timeline: o Select patient level data 2H24 o Phase II data 2H25 34
Slide 35: Prostate Cancer Incidence and Mortality
PROSTATE CANCER INCIDENCE AND MORTALITY a Rettig 2024 35
Slide 36: Monthly Median OS Benefit of Drugs Approved for mCRPC
MONTHLY MEDIAN OS BENEFIT OF DRUGS APPROVED FOR MCRPC Agent Sipuleucel-T Abiraterone Enzalutamide Median OS Post-doc: 4.6 Post-doc: 4.8 a benefit (Months) 4.1 Pre-doc: 4.0 Pre-doc: 4.0 Docetaxel Cabazitaxel Radium-223 PSMA RLT Olaparib 2.4 2.4 3.6 5.3 2.3 Rettig 2024 36
Slide 37: INKmune to Activate Resting NK Cells in mCRPC
INKmune to Activate Resting NK Cells in mCRPC • Prostate cancer immune infiltrate cells are resting NK cells not T cells • Is lack of T cell infiltrate why PDL1 and a TIGIT fail in mCRPC? • NK cells in mCRPC are resting NK cells that do not kill tumor • INKmune goal: convert resting NK cells to canc
Slide 38: INKmune Primed NK Cells Produce Cancer Killing Memory Like NK Cells
INKMUNE PRIMED NK CELLS PRODUCE CANCER KILLING MEMORY LIKE NK CELLS INKmune induces a unique NK cell that survives in a hostile TME to kill tumor cells 38
Slide 39: INKmune Phase 1 Human Results
INKMUNE PHASE 1 HUMAN RESULTS Safe and well-tolerated as an out-patient Controls disease with excellent QOL 39
Slide 40: CaRe PC Phase I/II Trial Design of INKmune in mCRPC
CaRe PC – a modified Bayesian design Phase I/II trial testing multiple doses of INKmune in men with mCRPC Step 1 - 3X3 dose escalation “run-in” to demonstrate • Short-term safety (28 days) • short-term immunologic efficacy a Step 2 - simultaneous testing of multiple doses to • Demonstrate long-term
Slide 41: INKmune mBION12 mCRPC
INKmune mBION12 mCRPC Short term safety Immunologic efficacy / long term safety Immunologic efficacy Anti tumor effects Step 1 Step 2 Optional Step 3 Low dose 1 1 1 Complete 6 patient confirmatory group 27-30 patients treated at 8 US Middle dose 1 1 1 6 patients 6 patients sites High dose 1 1 1 6 pa
Slide 42: Appendix
Appendix
Slide 43: Statistical Power: Why XPro Clinical Trials Are Short and Small
STATISTICAL POWER: WHY XPRO CLINICAL TRIALS ARE SHORT AND SMALL ➢ Enrichment strategy selects patients with neuroinflammation ➢ Patients with neuroinflammation have faster cognitive decline with lower variance than patients without neuroinflammation resulting in steeper decline of placebo group ➢ Th
Slide 44: Large Genetic Profile Study of AD Patients Shows Association with Immune Dysfunction
Large Genetic Profile Study Of AD Patients Demonstrated Strong Association With Immune Dysfunction 60% of the genes up-regulated in AD are expressed in immunologically active cells of the brain including microglia and astroglia Genome-wide association study of 71,880 AD cases and 383,378 controls Ja
Slide 45: TNF Drives Amyloid Pathology and Risk of AD
TNF Drives Amyloid Pathology and Risk of AD TNF inhibitors reduce • Neuroinflammation predates formation of amyloid risk of developing AD • TNF drives formation of amyloid plaque • Chronic treatment with TNF inhibitors prevents AD +800% Rheumatoid Arthritis Risk of general population Rheumatoid Arth
Slide 46: Total Addressable Market: XPro in AD
Total Addressable Market: XPro in AD ✓ Early AD = MCI + mild AD ✓ > 40% of Early AD patients have Total Addressable Market: US XPRO for AD neuroinflammation MCI patients -US 7M ✓ XPro Total Addressable Market in US = 4.3M Total AD patients – US* 6.7M ✓ XPro estimated market opportunity mild AD patie
Slide 47: Clinical Benefit in Phase I Trial: Stable Disease
CLINICAL BENEFIT IN PHASE I TRIAL: stable disease Disclaimer: small N, disease status heterogeneity, short time period ➢ Assessments administered: ❖ Cognitive: MMSE, Verbal Fluency Test, Digit Symbol Coding ❖ Neuropsychiatric Inventory ❖ Bristol Activities of Daily Living Scale ➢ To compare across p
Slide 48: Correlation between decreased neuroinflammation and improved cognition
Correlation between decreased neuroinflammation for AD and improved cognition R2 = 0.4 to 0.6 CSF cytokines by OLINK platform INMB AD Non-confidential 1.5.22 48
Slide 49: 1mg/kg/QW XPro Adequate Dose to Neutralize sTNF in CNS
1mg/kg/QW XPRO adequate dose to neutralize >99.99% sTNF in CNS Phase I CSF from 1mg/kg patients XPRO level in CSF after 3 • Maximum dose determined by drug level at trough month therapy • Trough level must be >2logs higher than CNS TNF level 6.5 Log increase in CSF TNF • XPRO 1mg/kg/QW has trough le
Slide 50: Biomarker of Neurodegeneration in AD – pTAU 217/181
RESULT OF PHASE I TRIAL – p-tau217 as a sensitive and specific biomarker of AD BIOMARKER OF NEURODEGENERATION IN AD – pTAU 217/181 CSF following 3 months of therapy with XPro (1 mg/kg) a Phospho-tau is a biomarker of neurodegeneration Phospho-tau217 correlates best with cognitive dysfunction 50
Slide 51: XPro Improves EEG Alpha Power Following 4 Weeks of Treatment
XPro Improves EEG Alpha Power Following 4 Weeks of Treatment EEG is a biomarker of brain function that can be used as a measure of target engagement The study evaluated the feasibility of using a portable EEG device to collect quality EEG data when used by the patients at home. EEG was assessed in s
Slide 52: Intellectual Property Suite
INTELLECTUAL PROPERTY SUITE Patent Ref. Biologic Exclusivity Exclusivity DN-TNF PLATFORM **# years from Marketing NK PRIMING PLATFORM Authorization, 10 issued patents 31 global patent properties varies by jurisdiction: 10 global patent properties 5 issued patents 21 pending apps • Compositions 5 pen
Slide 53: Management Team
MANAGEMENT TEAM Broad biotechnology background including legal, intellectual property, drug Raymond J. Tesi, MD David J. Moss Mark W. Lowdell, PhD a CEO/CMO & Chairman of the Board CFO CSO manufacturing, clinical trial management, FDA approval, drug marketing, finance, business development and opera