Inmune Bio Inc. · NASDAQ:INMB
Inmune Bio — Investor Presentation (August 2021)
47 slides from Inmune Bio's investor presentation, Aug 4, 2021
Slide 1: Harnessing the Power of the Innate Immune System
HARNESSING THE POWER OF THE INN A TE IMMUNE SYSTEM Modulating an Innate Immune Response Against Diseases IN MB CORPORATE PRESENTATION August 2021
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
I N M U N E B I O H I G H L I G H T S C lini c a l - st a g e biopharmaceutical company developing a new class of therapeutics that modulate dysfunction of the innate immune system Third party validation: ▪ Over 65 publications from multiple universities worldwide on both platforms with extensive in
Slide 4: Active Pipeline: Therapies that Target the Innate Immune Response
DN - TNF PLATFORM DISEASE FIELD PRE - CLINICAL PHASE I PHASE II (POC) P I V O T A L EST. NEXT MILESTONE NK PRIMING PLATFORM DISEASE FIELD PRE - CLINICAL PHASE I PHASE II (POC) PIVOTAL NEXT MILESTONE Myelodysplastic Syndrome ONCOLOGY Data 2H 2021 COVID - 19 Cytokine Storm P2 data analysis underway 20
Slide 5: Innate immune system plays a critical and often overlooked role
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 I N NATE I M MUNE D Y SF U NCTI O N Chronic Inflammation drives Innate Immune Dysfunction are the Causes of Many Diseases 1 F
Slide 6: XPro: Treating Alzheimer's disease as an immunologic disease
XPr o ™ Treating Alzheimer’s disease as an immunologic d i sea s e…not a n e u r o l og ic d i sea s e! 6
Slide 7: Proposed Mechanism of Inflammation in AD Pathology
s T NF Amyloid plaques Neurofibrillary tangles Behavioral, Environmental and Genetic factors MICROGLIA Synaptic Dysfunction Nerve Cell Death PROPOSED MECHANISM OF INFLAMMATION IN AD PATHOLOGY Plaques and Tangles are Cogs in the Inflammatory Loop That Perpetuate the Inflammatory Cycle by TNF Cogniti
Slide 8: Phase I Trial a Success: What Did We Learn?
P H A S E I T R I A L A S U CC E S S : W H A T D I D W E L E A R N ? • XPro™ decreases neuroinflammation • Dose response seen by proteomics and MRI • Benefits of decreasing neuroinflammation include improved synaptic function and less neurodegeneration • Xpro™ is well tolerated in patients for up to
Slide 9: Neuroinflammation in White Matter Tracts in AD
N E U R O I N F L A MM A T I O N I N W H I T E M A TT E R T R A C T S I N A D Premotor cortex Broca’s area Wernicke's area Xpro ™ Reduces Neuroinflammation Within the Arcuate Fasciculus (n=6) Xpro ™ Reduces Neuroinflammation within the arcuate fasciculus • The arcuate plays a key role in language pr
Slide 10: XPro Reduced Whole Brain Neuroinflammation (12 Weeks)
XPRO ™ (1 MG/KG; N=6) REDUCED WHOLE BRAIN NEUROINFLAMMATION (12 WEEKS) 0% - 5% - 10 % - 15 % - 20 % - 25 % - 30 % - 35 % - 40 % - 45 % - 50 % M R I C S F Olink® Target 48 Cytokine 10
Slide 11: Benefits of Reducing Neuroinflammation
20 of 26 Targ ets Significant (P < 0.000 1 ) BENEFITS OF REDUCING NEUROINFLAMMATION A prespecified analysis using TMTcalibrator™ revealed significant regulation of AD relevant Neuroinflammatory, neural injury, and synaptic proteins Synaptic Proteins Contactin - 2 – 222% increase Neurogranin – 56% de
Slide 12: Measuring Brain Quality
MEASURING BRAIN QUALITY The virtual Biopsy White Matter Gray Matter D i s e as ed Apparent fiber density (AFD) A measure of White matter quality He a lt h y D i s e as ed He a lt h y Cortical Disarray Measurement (CDM) A measure of Gray Matter quality 12
Slide 13: Measuring Gray Matter Quality (N=1)
M E ASURI N G GRAY M ATT E R Q U A L ITY ( N=1) B a selin e 3 months 6 months 9 months ▪ Metric: Cortical Disarray Measurement (CDM) ▪ Improvement (Green) within 3 months ( Yellow – no change) ▪ Continued improvement over 9 months ▪ Improvement was observed in brain regions critically involved in De
Slide 14: Measuring White Matter Quality (N=1)
M E ASURI N G W HITE M ATT E R Q U A L ITY ( N=1) B a se li n e 3 months 6 months 9 months ▪ Metric: Apparent Fiber Density (AFD) ▪ Improvement within 3 months (all non - purple color) that peaked at 6 months ▪ Improvement was observed in 31 of 33 fiber bundles associated with AD ▪ The average incre
Slide 15: Assessing Cognition
ASSESSING COGNITION ▪ Challenge: 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 patients of different disease
Slide 16: Apparent Fiber Density – A Non-Invasive Biomarker of Axonal Health
Health White matter AD white matter APPARENT FIBER DENSITY – A NON - INVASIVE BIOMARKER OF AXONAL HEALTH 16
Slide 17: XPro Improves Biomarkers of Axonal Integrity in AD
XPRO™ IMPROVES BIOMARKERS OF AXONAL INTEGRITY IN AD Xpro™ after 3 months: • • • Increase of AFD in 34 of 35 white matter tracts 6 - 12% increase in bundles directly implicated Alzheimer’s bundles Strong correlation with CSF markers 17
Slide 18: Phase 2 Study of XPro in Mild AD with Biomarkers of Inflammation
A PHASE 2, BLINDED, RANDOMIZED, PLACEBO - CONTROLLED, STUDY OF XPRO™ IN MILD AD WITH BIOMARKERS OF INFLAMMATION INCLUSION • 168 patients • 2:1 randomization (112 XPro™ patients vs 56 placebo patients) • 1mg/kg XPro™ once a week for 6 months or placebo • Inclusion criteria • Mild AD - CDR global rati
Slide 19: Why a 6 Month Study with Patients Is Possible
WHY A 6 M O NTH S T UDY WITH 168 PATIENTS IS POSSIBLE Methodology: Analysis of ADNI data base cut by biomarkers of inflammation used as enrollment criteria in Phase I study Findings: Higher inflammation leads to • Faster decline of cognition • Lower variance of ADAS13 Implications for Phase II desig
Slide 20: TNF Biology: Good vs Bad: tmTNF vs sTNF
A d a p t ed f r o m M ac E w a n et al 200 2 T N F B I O L O G Y : Goo d v s B a d : t m T N F v s s T N F 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 (t
Slide 21: XPro: A Precision TNF Inhibitor
Decreases inflammation Y Y I n c r e a se d r i s k of infection Y N I n c r e a se d r i s k of cancer Y N Causes d e m y e li n a t i o n Y N Neuroprotective N Y Enhances n e u r op la s t i c i t y N Y DIFFERENCES: Selective vs . Non - Selective sTNF Inhibition Non - DN Selective TNF X P R O ™ :
Slide 22: How XPro Neutralizes sTNF
see Steed et al., Science , 301, 2003 " la r g e " do m a i n (subunit C) R ecep t o r b i nd i n g , Receptor binding, "small" domain ( s ubun i t A) Receptor binding, ( s ubun i t B) Mutation Y87H Mutation R31C (for 10kD pegylation) Mutation A145R NONGLYCOSYLATED PROTEIN EXPRESSED IN E.COLI DN - T
Slide 23: Current TNF Inhibitors and XPro Are Different
CURRENT TNF INHIBITORS AND XPRO™ ARE DIFFERENT Demyelination is an off - target safety side effect of currently approved anti - TNF therapies EXACERBATED DEMYELINATION R E M YEL IN A T I ON ETANERCEPT Anti - inflammatory AND immunosuppressive DN - TNF Anti - inflammatory NOT immunosuppressive CUPRIZ
Slide 24: Unique Mechanism Expands Market Opportunity
Global TNF inhibitor drug market is estimated to reach $42 billion by 2026 1 UNIQUE MECHANISM EXPANDS MARKET OPPORTUNITY Currently approved TNF inhibitors contraindicated in most markets Estimates from 1 GBI Research, 2 BCC Research , 3 MarketWatch, and 4 ResearchandMarkets.com. Innate Immune D y s
Slide 25: INKmune: Provides essential signals to patients' NK cells
Provides essential signals to patients’ NK cells to target and kill tumor cells. INKmune ™ is not antigen - specific so there is no need to identify the specific tumor antigen 25
Slide 26: Residual Disease Is the Cause of Cancer Relapse
RESIDUAL DISEASE IS THE CAUSE OF CANCER RELAPSE ▪ Prevention of relapse key to survival and death in patients with cancer ▪ Relapse is caused by residual cancer cells ▪ NK cells, not T cells, are responsible for finding and targeting residual cancer cells to provide long lasting remission ▪ Patients
Slide 27: INKmune Advantages
27 27 INKmune A D V AN T A G E S: x Universal — Potentially effective in blood cancer and solid tumors x Off - the - shelf therapy x Easy to use 1. NK recognizes tumor cell 3. NK forms stable immune synapse with tumor cell and NK ligands send activating signals to the NK cell 2. NK makes strong bond
Slide 28: How Does INKmune Work?
INKmune A D V AN T A G E S: x Universal — Potentially effective in blood cancer and solid tumors x Off - the - shelf therapy x Easy to use H O W DOES INKmun e ™ W O R K ? INKmune a multi - dimensional “pseudokine” Resting NK don’t bind/kill resistant tumor cells Priming with IL - 15 promotes NK kill
Slide 29: INKmune MoA #1: Increases Avidity of NK Cell Binding
INKmune: a multi - dimensional “pseudokine” MoA #1 – INKmune increases avidity of NK cell binding to tumor cells r N K c e l l s ( g r e e n ) a d d ed t o r e s i s t a n t t u m o r c e ll s I N K m un e p r i m e d NK c e l l s a dded t o r e s i s t a n t t u m o r c e l l s L o w f o rc e c a u
Slide 30: INKmune MoA #2: Differentiates Resting NK to Memory-Like NK Cells
0 5000 10000 15000 N K p 8 0 F e M I 0 1000 2000 3000 4000 5000 N K p 4 6 M e F I 0 2000 4000 6000 8000 N K p4 4 M e F I 0 20000 40000 60000 80000 N K p3 0 M e F I 2000 2500 3000 3500 C D2 5 M e F I INKmune: a multi - dimensional “pseudokine” MoA #2 – INKmune differentiates resting NK to “memory - l
Slide 31: High-Risk Myelodysplastic Syndrome (MDS)
31 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 32: INKmune Phase I Study in High-Risk MDS
I N K m un e ™ P H A SE 1 S T U D Y Phase I Trial in High - Risk MDS 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
Slide 33: INKmune First in Human Trial – MDS/AML Data
INKmune First in Human Trial – MDS/AML Day 15 Data - First Patient Treated with INKmune IV IV INKmune Activates and Matures NK Cells for Two Weeks and Counting …. INKmune activates all types of cytolytic NK cells 1st patient INKmune induces NK proliferation in vivo 1st patient 1 1 1 2 1 3 1 4 1 5 0
Slide 34: NK Competitive Landscape
NK Competitive Landscape 1 8 p r o gr a m s an d c o un t i n g … The Variables • Cytokines - single or multiple as a therapeutic or as part of cell therapy • NK cell source – autologous, allogeneic, iPSC, cord blood • Genetically engineered – CAR or cytokine • Off - the - Shelf or patient specific
Slide 35: XPro: Targeting Neuroinflammation for Treatment Resistant Depression
XPr o ™ Targeting Neuroinflammation for the Treatment of TREATMENT RESISTANT DEPRESSION (TRD) 35
Slide 36: 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 co m o r b i d i ty C hron i c c our se of MDD T NF b i o l o g y in TRD POC studies with anti - TNF blo
Slide 37: TRD Driven by Neuroinflammation
37 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. Psychiatry Serv 2014. 2 Ionescu, et al. Dialogues Clin Neurosci .
Slide 38: INMB Approach: TNF Predicts TRD
I N M B A PP R O A C H : T N F P R E D I C T S T R D Anti - TNF Therapy Improves Depression in Patients With Elevated Inflammatory Biomarkers Treatment Response ( ≥ 50 reduction in HAM - D - 17 at any point during treatment) Miller 2011 62% 57% 41% 33% Anti - TNF treatment reduces depressive symptom
Slide 39: Phase 2 TRD Trial: Biomarkers of Inflammation
BIOMARKERS OF INFLAMMATION DESIGN ▪ Six - week double blind placebo - controlled study of Xpro™ ▪ 45 patients in Xpro™ at 1 mg/kg ▪ 45 patients in placebo control group ▪ Biomarkers of inflammation at 0, 2, 6 weeks INCLUSION ▪ Failed 2 courses of antidepressants ▪ C - reactive protein (CRP) levels >
Slide 40: Targeting Cytokine Storm May Prevent Catastrophic Complications of COVID-19
Tar g eti n g CY T O KINE ST ORM m ay Preve n t Catastrophic Complications of COVID - 19 40
Slide 41: What Brings Patients to the Hospital with COVID-19?
WHAT BRINGS PATIENTS TO THE HOSPITAL WITH COVID - 19? At time of hospitalization , the Cytokine Storm is making patients sick, mot the virus... Focusing on the Cytokine Storm, not the virus, should make patients better Targeting the Master Cytokine with QUELLOR should tame the Cytokine Storm P r o b
Slide 42: TNF Is the Master of the Cytokine Storm
TNF is the “MASTER” of the Cytokine Storm A dapted from Karki et al 2020 42 Cytokine Storm Pathology ▪ Block sTNF and downstream pro - inflammatory cytokines should decrease ▪ Synergism of TNF - α and IFN - γ triggers inflammatory cell death, tissue damage, and mortality
Slide 43: Phase 2 Trial: Treating Pulmonary Complications of COVID-19
P H A S E 2 T R I A L : Treating Pulmonary Complications of COVID - 19 DESIGN ▪ SOC vs SOC+Quellor™ 1mg/kg subQ day 1 and 7 (if in hospital) ▪ Patient discharged based on clinical status or final study visit day 28 ▪ 366 patients randomized 1:1 INCLUSION ▪ COVID - 19 infection with room air SaO2<94%
Slide 44: Quellor Phase 2 Trial: Next Steps
• Changing landscape: • Regulatory – FDA not awarding EUA for therapies • Clinical – C19 less lethal, SOC changing, geography challenging • What we are doing: • Declared Phase II trial complete after 76 patients • Performing data base lock and analysis • Schedule end - of - Phase II meeting with FDA
Slide 45: DN-TNF and INKmune: Tip of the Iceberg
D N - T N F A N D I N K M U N E Tip of the Iceberg • XPRO™ • Visible programs • AD, TRD, ALS • “Out - of - Sight” • PD, MS, FTD, LBD, TBI • PTSD, autism, bi - polar disease • Much, much, more…. • INKmune™ • Visible programs • High risk MDS; Ovarian Cancer • “Out - of - Sight” • AML, MM, lymphoma • R
Slide 46: 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 NK PATENTS* 2035 use for treatment of cancer
Slide 47: Contact Us
HARNESSING THE POWER OF THE INNATE IMMUNE SYSTEM CONTACT US INmune Bio Inc. 980 N. Federal Hwy, Suite 110 Boca Raton, FL 33432 ( 8 58 ) 96 4 - 3720 I N M B www.inmunebio.com 47