INmune Bio Inc. · NASDAQ:INMB
INmune Bio — Investor Presentation (March 2024)
55 slides from INmune Bio's investor presentation, March 2024
Slide 1: Harnessing the Power of the Innate Immune System
HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM Two Therapeutic Platforms: XPro and INKmune Single Goal: Repair Innate Immune Dysfunction to Treat Disease INMB Investor Presentation March 2024 (rayjay final) 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(3/13/24) COMMON S/O $11.51 ~18 M • Cap structure • Large insider ownership a MARKET C
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 1 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 Ophthalmology pSar DN-TNF Cancer Future Development Orphan indicatio
Slide 6: Anticipated Milestones in 2024 and 2025
Anticipated Milestones in 2024 and 2025 Open Label INKmune mCRPC and AD Open Label Extension Data to be Reported Periodically Topline Complete Data AD FDA End- First enrollment Phase 2 of-Phase II patient AD AD Phase 2 Complete meeting Phase III Fast-Track or data AD AD Break-Through Phase 2 XPro in
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: Phase II Blinded Randomized Trial of XPro in Early Alzheimer's
COMPLETE ENROLLMENT MID 2024-TOPLINE DATA 6 MONTHS LATER PHASE II BLINDED RANDOMIZED OF XPRO IN PATIENTS WITH EARLY ALHEIMER’S DISEASE Primary Endpoint ❑ EMACC a Secondary Endpoints Treatment ❑ CDR, ECog ❑ 2:1 (XPro1595:Placebo) ❑ ADL, NPI ❑ 1 mg/kg XPro1595 weekly subQ ❑ Blood injection ❑ MRI ❑ Saf
Slide 10: Neuroinflammation and TNF Causes Alzheimer's Disease
Neuroinflammation and TNF Causes Alzheimer’s Disease Inflammation, not amyloid or tau, causes AD pathology Tau Tangles Amyloid Beta TNF long associated with AD and predates deposition of 2 amyloid Cognitively normal AD Cognitively normal AD 3 in CSF Tarkowski 2003 co-localized with plaques Astrocyte
Slide 11: 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 12: XPro Safely Prevents Neuroinflammation without Axonal Degeneration
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 13: 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 TNF Neuronal Dysfunction Cognitive TNF Decline Released and Nerve Dementia Cell Death Activated Microglia Axonal Demyelination 1. Chang R, et al. J Cent Nerv Syst Dis. 2
Slide 14: Phase 1b Clinical Trial Design and Results
PHASE 1B CLINICAL TRIAL DESIGN AND RESULTS N=18 : 6 Patients per Cohort 14
Slide 15: Enrichment Criteria 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's MOA Hypothesis: Validation: Patients with elevated biomarkers of ADNI* patients without enrichment had peripheral inflammation have lower WMFW compared to our e
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 XPro decreases whole brain neuroinflammation by 15% after 12 weeks of therapy 1mg/kg XPro (n=6) 16
Slide 17: Non-invasive Virtual Biopsy – Measuring Microstructural Changes
Non-invasive Virtual Biopsy – Measuring Microstructural Changes • Diffusion MRI-DTI imaging can assess microstructural changes within the brain. • Demonstrates structural pathology to located and stage the patient’s disease. • Demonstrates remodeling and repair of effective treatment in “real time.”
Slide 18: XPro Decreases Neuroinflammation in AD at 12 Months
PHASE 1b RESULTS – MRI-DTI VIrtual Biopsy XPRO DECREASES NEUROINFLAMMATION IN AD Decrease in Neuroinflammation in AD white matter tracts over 12 months XPro decreases neuroinflammation • Patients with AD have by 45% after 12 months of therapy increasing WMFW Phase Open Label Extension I trial • AD p
Slide 19: XPro Decreases Neurodegeneration and Improves Synaptic Function
Phase 1b Results: CSF PROTEOMICS XPro Decreases Neurodegeneration and Improves Synaptic Function Downstream benefits of decreasing neuroinflammation Synaptic Proteins Contactin-2 +222% increase Neurogranin -56% decrease Neuronal Injury pTau 217 -46% decrease Visinin-like protein 1 (VILIP-1) -91% dec
Slide 20: XPro Promotes Myelin Repair and Improves Axonal Integrity
Phase 1b Results – MRI-DTI Virtual Biopsy XPro Promotes Myelin Repair and Improves Axonal Integrity ✓ XPro improves axonal integrity by 17% in white matter tracts after 12 months of therapy (increased Apparent Fiber Density) ✓ XPro promotes improved myelin by 16% after 12 months of therapy (reduced
Slide 21: Remodeling and Repair of White Matter Tracts After XPro
Phase 1b Results: Changes in Axonal Fiber Density (AFD) in AD White Matter Tracts REMODELING AND REPAIR OF WHITE MATTER TRACTS AFTER XPRO ➢ 65-year-old white male retired due to AD a ➢ Returned to work Improvement after 6 months of within 3 months XPro therapy ➢ Increasing green/blue shows improveme
Slide 22: Alzheimer's Patients in 4-week Phase 1b of XPro
Alzheimer’s Patients in 4-week Phase 1b 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 with the
Slide 23: XPro Attenuates AD-like Pathology 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 24: 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 25: The EMACC Provides an Accurate Cognitive Assessment in Early AD
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 26: 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 27: 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 28: 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 = smaller N’s/shorter duration ▪ Cognitive and f
Slide 29: 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. 29
Slide 30: TNF Biology Is Complicated: Two Ligands with Opposite Effects
TNF BIOLOGY IS COMPLICATED: TWO LIGANDS WITH OPPOSITE EFFECTS 30
Slide 31: 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 32: 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 32
Slide 33: 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 34: 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 35: Off-the-Shelf NK Therapy Converts Resting NK Cells into Cancer Killing Cells
Off-the-Shelf NK Therapy Converts Patient’s Resting NK cells into Cancer Killing memory like NK cells 35
Slide 36: 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 36
Slide 37: Prostate Cancer Incidence and Mortality
PROSTATE CANCER INCIDENCE AND MORTALITY a Rettig 2024 37
Slide 38: 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 38
Slide 39: 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 40: 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 40
Slide 41: INKmune Phase 1 Human Results
INKMUNE PHASE 1 HUMAN RESULTS Safe and well-tolerated as an out-patient Controls disease with excellent QOL 41
Slide 42: CaRe PC Phase I/II Trial 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 43: INKmune MBION12 mCRPC
INKMUNE MBION12 MCRPC Short term safety Immunologic efficacy / long term safety Immunologic efficacy Anti tumor effects Step 1 Step 2 6 patient confirmatory group Low dose 1 1 1 In this example: SRC choses middle dose for pivotal trial Middle dose 1 1 1 6 patients High dose 1 1 1 6 patients 6 patien
Slide 44: Appendix
Appendix
Slide 45: 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
Slide 46: 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 47: 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 47
Slide 48: 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 48
Slide 49: Large Genetic Profile Study of AD Patients Shows 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 50: TNF Increases Early in Life Contributing to Inflammaging
TNF INCREASES EARLY IN LIFE CONTRIBUTING TO INFLAMMAGING Biomarker Concentrations by Age Age • Age is the most important risk factor for AD. • Pro-inflammatory cytokines increase with age • TNF is the master cytokine driving age related chronic inflammation – also known as inflammaging. Parker et al
Slide 51: Dose Response Phase I AD
Dose response Phase I AD • 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 statistically evaluated • Conclusion: Markers of microglial activation, synaptic and axonal dysf
Slide 52: XPro Increased White Matter Volume
Phase 1b Data XPRO INCREASED WHITE MATTER VOLUME a 52
Slide 53: 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 54: Patients with Higher Levels of FW Have Greater Cognitive Decline
Patients with higher levels of FW have greater cognitive decline (ADAS13) over 12 months in ADNI for AD 54
Slide 55: 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