Inmune Bio Inc. · NASDAQ:INMB
Inmune Bio — Investor Presentation (September 2021)
45 slides from Inmune Bio's investor presentation, Sep 7, 2021
Slide 1: Harnessing the Power of the Innate Immune System
H A R N E SS I N G T H E P O W E R O F T H E I NN A T E I MM U N E S Y S T E M Targeting Innate Immune Dysfunction I N M B INVESTOR PRESENTATION September 2021
Slide 2: Forward Looking Statements
F O R W A R D L OO K I N G S T A T E M E N T S 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
Slide 3: Investment Highlights
▪ Clinical - stage biopharmaceutical company with two therapeutic platforms in Phase 1 and Phase 2 of development ▪ Patented therapies that repair dysfunction of the innate immune system to combat immune diseases including; Alzheimer’s Disease, Cancer, Treatment Resistant Depression and other seriou
Slide 4: Targeting Innate Immune System Dysfunction: Our Strategy
Metabolic Disease Neurological Disease Autoimmune Disease Cardiovascular Disease Pulmonary Disease Infectious Disease 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 1 Furma
Slide 5: An Active Pipeline of Therapies
DN - TNF PLATFORM DISEASE FIELD PRE - CLINICAL PHASE I PHASE II (POC) PIVOTAL EST. NEXT MI L ES T ONE Alzheimer’s Disease CNS P2 data analysis underway 2021 COVID - 19 C y t ok i ne Storm P2 Start 4Q 2021 Treatment Resistant D epre s s i on P2 Start 4Q 2021 NK PRIMING PLATFORM M y e lody s pl a s t
Slide 6: DN-TNF and INKmune: Tip of the Iceberg
▪ Visible programs AD, TRD, ALS ▪ “Out - of - Sight” PD, MS, FTD, LBD, TBI PTSD, autism, bi - polar disease Much, much, more…. ▪ Visible programs High risk MDS; Ovarian Cancer ▪ “Out - of - Sight” AML, MM, lymphoma RCC, Lung, prostate and breast cancer DN - T N F A N D I N K M U N E TIP OF THE ICEBE
Slide 7: Treating Alzheimer's Disease as an Immunologic Disease
f o r A D Treating Alzheimer’s Disease as an Immunologic Disease … not A Neurologic Disease 7
Slide 8: Breaking the Destructive Cycle of Neuroinflammation
f o r A D B R E A K I N G T H E D E S T R U C T I V E C Y C L E O F N E U R O I N F L A MM A T I O N D R I V E N BY G L I A L A C T I V A T I O N Any Drug Therapy Must Stop Nerve Cell Death and Improve Synaptic Dysfunction OU R S T R A TE G Y I N AD s T NF Amyloid plaques Neurofibrillary tangles Beh
Slide 9: XPro Decreases Neuroinflammation
1. XPro Œ decreases neuroinflammation in patients after 12 weeks of therapy 2. Statistically decreased neuroinflammation when measured by: • White Matter Free Water – a validated non - invasive MRI measure of neuroinflammation • Chemokine and cytokine levels in CSF 3. Neuroinflammation controlled sa
Slide 10: XPro Decreases Neuronal Injury and Improves Synaptic Dysfunction
XPro Œ DECREASES Neuronal Injury f o r A D CSF Proteome 20 of 26 Targets Significant (P < 0.0001) 10 XPro Œ IMPROVES Synaptic Dysfunction 222% Contactin - 2 56% Neurogranin 91% V isi n i n - l i k e Protein 1 8 4 % N e urofilam e nt Light Chain Pre - specified Analysis Using tmtCalibrator Œ
Slide 11: Reduction of Neuroinflammation Is Dose-Dependent
f o r A D X P R O 1 5 9 5 R E D U C T I O N O F N E U R O I N F L A MM A T I O N I S DOSE - DEPENDENT CSF following 12 weeks of treatment Olink® Target 48 Cytokine CCL8 OLR1 IL27 IL2 CXCL9 TGFA IL6 TNFSF12 CCL11 HGF FLT3LG IL17F IL7 IL18 CCL13 TNFSF10 CXCL10 IFNG IL10 CCL19 IL15 CCL3 CXCL8 MMP12 CSF
Slide 12: Assessing White Matter Pathology: pTau217 Dose Response
1 2 f o r A D 12 A SS E SS I N G W H I T E M A TT E R P A T H O L O G Y – p T a u 2 1 7 D O S E RESPONSE CSF fol l ow i ng 12 w e e ks of t rea t ment A SS E SS I N G W H I T E M A TT E R P A T H O L O G Y – p T a u 2 1 7 / 1 8 1 CSF fol l owing 12 w e e k s of t r eatment D o se Percent Change over
Slide 13: The Virtual Biopsy: MRI Measures White and Gray Matter Quality
D I SE A SE D Apparent fiber density (AFD) A measure of White matter quality H E A LT H Y D I SE A SE D H E A LT H Y Cortical Disarray Measurement (CDM) A measure of Gray Matter quality f o r A D The Virtual Biopsy – MRI Imaging Can Measure White and Gray Matter Quality 13 N O N - I N V A S I V E M
Slide 14: Improved Biomarkers of Axonal Integrity in AD
f o r A D AFD in Arcurate Fasciculus (% Change) ▪ Increase of AFD in 34 of 35 white matter tracts ▪ 6 - 12% increase in bundles directly implicated in AD ▪ Strong correlation with CSF markers I M P R O V E D B I O M A R K E R S O F A X O N A L I N T E G R I T Y I N A F XPRO Œ AFTER 3 MONTHS Cross Se
Slide 15: Longitudinal Apparent Fiber Density
0 3 6 9 12 15 18 21 24 - 10 0 - 5 5 15 10 20 Fiber Density in AD bundles (% change) XPro1595 1 mg/kg ADNI database N = 36 N = 6 N = 5 N = 5 N = 3 +17% f o r A D LONGITUDINAL APPARENT FIBER DENSITY Xpro ΠRESULTS Visit (months) 15
Slide 16: Longitudinal Free Water
0 3 6 9 12 15 18 21 24 - 60 - 50 - 30 - 40 - 20 - 10 30 20 10 0 Free - water in AD bundles (% change) XPro1595 1 mg/kg ADNI database N = 36 N = 6 N = 5 N = 5 N = 3 f o r A D L O N G I T U D I N A L F R E E W A T E R Xpro ΠRESULTS - 46% Visit (months) 16
Slide 17: Longitudinal Radial Diffusivity
f o r A D L O N G I T U D I N A L R A D I A L D I FF U S I V I T Y Xpro ΠRESULTS - 16% 17
Slide 18: Increase in White Matter Volume
f o r A D I N C R E A S E I N W H I T E M A TT E R V O L U M E (MACROSTRUCTURE) Xpro ΠRESULTS 18 0 12 3 6000 0 4 4000 0 4 2000 0 4 0000 0 3 8000 0 4 6000 0 3 6 9 V isit ( m o nt h s ) Total White Matter volume (mm 3 ) 0 . 146 9 0 12 5 00 0 5 50 0 6 00 0 6 50 0 3 6 9 Visit (months) Left Inferior Tem
Slide 19: Summary of Phase 1 MRI Results
In Alzheimer’s Disease bundles over a 12 - month period: 1) XPro1595 reduces FreeWater by 46% (neuroinflammation) 2) XPro1595 increases Apparent Fiber Density by 17% (axon integrity) 3) XPro1595 reduces tissue Radial Diffusivity by 16% (remyelination) x Confirmed by CSF inflammatory & tau markers f
Slide 20: Phase 1b Mild AD Patients With Neuroinflammation Had Best Response
f o r A D Phase 1b Mild AD Patients With Neuroinflammation On Xpro Œ Had Best Response ▪ Phase I study: small N, disease heterogeneity (mild, moderate and severe), short time period, no placebo group ▪ Assessments administered: ▪ Cognitive: MMSE, Verbal Fluency Test, Digit Symbol Coding ▪ Neuropsych
Slide 21: Phase 2 Trial Design Rationale
▪ INCLUSION Mild AD with biomarkers of inflammation ▪ SIZE - 200 patients 2:1 randomization (134 XPro Œ vs 66 placebo) ▪ DOSE 1 mg/kg/week subQ ▪ DU R A TION – 6 m o n t h s ▪ COGNITION END - POINT - EMACC Phase I inclusion criteria selected for patients with neuroinflammation Patients with mild AD
Slide 22: Phase 2 Blinded, Randomized, Placebo-Controlled Trial in Mild AD
INCLUSION ▪ 200 patients 2:1 randomization (134 XPro Œ patients vs 66 placebo patients) ▪ 1mg/kg XPro Œ once a week for 6 months or placebo ▪ Inclusion criteria Mild AD - CDR global: 0.5 or 1 MMSE>21 Two or more biomarkers of inflammation CRP>1.5 mg/L ESR>10 sec HgbA1c>6% ApoE4 positive EN D - P O I
Slide 23: Selective vs. Non-Selective sTNF Inhibition
NON - Selective S e l ec t i v e DN TNF Decreases inflammation Y Y Increased risk o f i n f e c t i o n Y N Increased risk o f c an c e r Y N Causes demyelination Y N Neuroprotective N Y Enhances neuroplasticity N Y The Benefits of INMB’s Selective vs. Non - Selective sTNF Inhibition Adapted from Ma
Slide 24: How XPro Neutralizes sTNF
see Steed et al., Science , 301, 2003 Soluble TNF Function Eliminated No inflammatory signaling f o r A D Nonglycosylated Protein Expressed in E. Coli DN - TNF Can Not Neutralize tmTNF receptors not blocked so tmTNF biology preserved H O W X P r o ΠN E U T R A L I ZE S s T N F And importantly leave
Slide 25: Approved TNF Inhibitors Should Not Be Used in CNS
EXACERBATED DEMYELINATION REMYELINATION XPro ΠPROMOTES R E M Y E L I N A T I O N ETANERCEPT A n t i - i nf l amma t o r y AND immunosuppressive DN - TNF Anti - inflammatory NOT immunosuppressive CUPRIZONE Model of Multiple Sclerosis NORMAL Cuprizone model of demyelination in mice: Prober 2017 https
Slide 26: Off-the-Shelf NK Therapy in Oncology
Off - the - Shelf NK Therapy Producing memory like NK cells from Patient’s Own NK cells in Their Circulation (ie: in vivo) f o r Oncolo g y 26
Slide 27: NK Recognition and Binding to Tumor Cells
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 to tumor cell 4. NK cell kills tumor cell 1. NK recognizes RESISTANT tumor cell 3 . NK forms Unstable immune synapse with tumor cell - NO ACTIVA
Slide 28: INKmune Pseudokine: Memory-Like NK Cells
A M U L T I - D I M E N S I O N A L “ P S E U D O K I N E ” Moa #2 – InkMUNE Œ Differentiates Resting NK to “Memory - Like” NK Cells Cytokine cocktail (IL - 12/15/18) drives resting NK to memory - like NK (SciTranslMed 2016; Romee,Fenheger, et al) 0 5000 10000 15000 NK G 2 C M e F I 0 10000 20000 30
Slide 29: INKmune First in Human Trial: MDS/AML
i n Onco l o g y INKmune First in Human Trial – MDS/AML Day 29 Data - First Patient treated with INKmune IV IV INKmune activates and matures NK cells for one month and counting…. INKmune activates all types of cytolytic NK cells INKmune induces NK proliferation in vivo 1st patient 0 5 1 0 1 5 2 0 0
Slide 30: Relapse Prevention and High-Risk MDS
▪ 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 with better functioning NK cells have longer su
Slide 31: INKmune Increases Avidity of NK Cell Binding
rNK Cells (Green) Added To Resistant Tumor Cells INKmune ΠPrimed NK Cells added to resistant tumor cells Low force causes break of immune synapse and NK collect in clusters Increasing force fails to break immune synapse and NK remain bound to tumor cells 0 200 800 1000 400 600 rForce (pN) 4 0 2 0 0
Slide 32: How Does INKmune Work?
Resting NK don’t bind/kill resistant tumor cells Priming with IL - 15 promotes NK killing INKmune - primed NK form intensely strong bonds to tumor cells and kill them INKmune Œ AD V AN T AGE S : Universal, potentially effective in blood cancers and solid tumors Off - the - shelf therapy Easy to use
Slide 33: INKmune Phase 1 Study 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 I NK M U N E ΠP H A S E 1 S T U D Y Phase I Trial in High - Risk MDS i n O
Slide 34: NK Cell Therapy Comparison
T H E V ARIABLES ▪ 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 manufacturing ▪ A unique, stable cell line, not an NK cell ▪ >1
Slide 35: Targeting Neuroinflammation for Treatment Resistant Depression
f o r T R D Targeting Neuroinflammation for TREATMENT RESISTANT DEPRESSION (TRD) 35
Slide 36: Treatment Resistant Depression
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 c o m orbid ity Chronic course of MDD TNF biology in TRD POC studies with anti - TNF blood CRP predicts response Symptoms affected anhedonia,
Slide 37: TRD Is Driven by Inflammation
▪ 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 Haroon et al., P s y c h o neu r o e nd o c r i n o l ogy , 2018. Plasma TNF levels are increased in TRD patients T H
Slide 38: TNF Predicts TRD: Anti-TNF Improves Depression
Treatment Response (≥50 reduction in HAM - D - 17 at any point during treatment) Miller 2011 Anti - tnf Treatment Reduces Depressive Symptoms In Patients With Elevated Biomarkers of Inflammation Inflammation - associated deficits in reward circuitry mediate the relationship between CRP and anhedonia
Slide 39: TRD Phase 2 Trial
DESIGN Six - week double blind placebo - controlled study of Xpro Π45 patients in Xpro Πat 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 >3 mg/L Anhedonia ENDPOINTS Primary: I
Slide 40: COVID-19 Complications
f o r C O VI D - 1 9 Comp li c a ti on s Targ e ting CYT O KINE STORM may P revent Catastrophic Complications of COVID - 19 40
Slide 41: Cytokine Storm Hypothesis in 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 BL E M SOLUTION HYPOTHESIS The dysregulated innate immu
Slide 42: TNF Is the Master of the Cytokine Storm
f o r C O V I D - 19 42 Adapted from Karki et al 2020 ▪ Block sTNF and downstream pro - inflammatory cytokines should decrease ▪ Synergism of TNF - α and IFN - γ triggers inflammatory cell death, tissue damage, and mortality T N F I S T H E “ M A S T E R ” O F T H E C Y T O K I N E S T O R M
Slide 43: COVID-19 Phase 2 Trial
DESIGN SOC vs SOC+Quellor Œ 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% One or more medical/demographic comorbidities: age ≥ 60; hypertension, cardio
Slide 44: COVID-19 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: 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 (858) 964 - 3720 I N M B www.inmunebio.com 45