Inmune Bio Inc. · NASDAQ:INMB

Inmune Bio — Investor Presentation (March 2023)

55 slides from Inmune Bio's investor presentation, Mar 15, 2023

  1. Slide 1: INMB Investor Presentation March 2023

    I N M B IN V E S T O R PRES E NT A TIO N March 2023 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 Two Therapeutic Platforms: XPro Πand INKmune ΠHe l p Rep a ir Inn a te Immune D ysfunction

  2. 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

  3. Slide 3: INMB Corporate Focus

    I N M B C o r p o r a t e F o c u s 3 x Disequilibrium of the innate immune system is a key driver of both cancer, neurodegenerative diseases and many other conditions x INmune Bio is developing two novel platform therapies that recalibrate the innate immune system XPro  DN - TNF selectively inhibi

  4. Slide 4: Pipeline Development

    4 PIPELINE DEVELOPMENT D N - TNF PL A TFORM DI S E A S E FI E LD PRE - CLINICAL P H AS E I P H AS E I I ( POC) PIVOTAL ES T. N EX T MILESTONE E a rly A lzh e im e r’s P 2 D at a 2024 Treatment Resistant D epre s s i on P 2 S ta r t 2023 pSar D N - TNF DMD Cancer Other Future D evelopm ent and/or Par

  5. Slide 5: Management Team

    MANAGEM E NT T EAM 5 Broad biotechnology background including legal, intellectual property, drug manufacturing, clinical trial management, FDA approval, drug marketing, finance, business development and operations.

  6. Slide 6: Treating Alzheimer's as an Immunologic Disease, not a Neurologic Disease

    f o r A D Treating Alzheimer’s as an Immunologic Disease … not a Neur o lo g ic Disease 6

  7. Slide 7: Alzheimer's disease burden

    ’ 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

  8. Slide 8: Questions to Answer about INmune Bio's approach to Alzheimer's Disease

    8 Q u e s t i o n s t o An s w e r a b o u t I N m u n e B i o ’ s a pp r o a c h t o A l z h e i m e r ’ s D i s e a s e ▪ Why neuroinflammation? ▪ What causes neuroinflammation? ▪ Why XPRO Œ ? ▪ XPRO results in patients with ADi ▪ Next steps in patients with Alzheimer’s Disease f o r A D

  9. Slide 9: Neuroinflammation as a critical driver of Alzheimer's disease

    A wealth of evidence supports NEUROINFLAMMATION as a critical driver of the pathogenesis and progression of Alzheimer’s disease

  10. Slide 10: Genetic study links AD with immune dysfunction

    10 Large genetic profile study of AD patients demonstrated strong association with immune dysfunction f o r A D A s t r o g lia MICROGLIA Genome - wide association study of 71,880 AD cases and 383,378 controls Jansen IE, et al. Nature Genetics . 2019;51:404 – 413 Genes associated with AD were strong

  11. Slide 11: Strong Evidence Supports Neuroinflammation in Alzheimer's

    11 Strong Evidence Supports Neuroinflammation in Alzheimer’s f o r A D Torres - Acosta N, et al. J Alzheimer’s Dis. 2020;78:619 – 626 R IS K O F A L Z H EIME R ’S DISEASE I N P A T EINTS W I T H Rheum a to id A r thritis Ri s k o f g e n e r a l p o p u lation Adap t ed fro m C h o u e t al . 2016 8

  12. Slide 12: Anti-TNF Antibodies Have Serious Limitations; XPro Improves the Brain

    f o r A D 12 An t i - T N F An t i b od i e s H a v e S e r i o u s L i m i t a t i o n s X P R O T M i m p r o v e s t h e b r a i n approved TNF Inhibitors “abuse” the brain Etanercept XPRO No n - s ele c t i v e T N F i nh i b i t o r s ( E t a n e r c e p t ) t h a t b lo c k b ot h t r a n sm e

  13. Slide 13: INmune Bio's AD Program simplified

    f o r A D 13 I N m u n e B i o ’ s A D P r o g r a m s i m p l i f i e d … s T NF Am ylo i d plaqu e s Neu r o f i b r ill a r y t an gles Behavioral, Environmental and G en e t i c f a c t o r s M IC R O GLIA N e r v e C e ll Death Synaptic Dy s f unc t i on Cogni t i v e Decline ▪ Neuroinflammatio

  14. Slide 14: Summary of Successful Phase 1b trial in AD patients

    f o r A D Summary of Successful Phase 1b trial: AD patients with biomarkers of inflammation (ADi) 14 DESIGN ▪ O pe n - l a b el Mul t i ple dosing c oh o r t s ( 0 . 3 , 0. 6 , 1.0 m g/kg) ▪ Weekly XPro1595 Œ SubQ injections for 3 months ▪ Biomarke r s a ssessed a t 0 a nd 12 we eks Inclusion ▪ AD D

  15. Slide 15: XPro decreases neuroinflammation in AD

    X P R O T M D E C R E A S E S N E U R O I N F L A M M A T I O N I N A D Inflammatory Cytokines in CSF after 3 months P h a se 1 b D a t a: T A R G E T ENG A G E MENT f o r A D 15

  16. Slide 16: XPro decreases neuroinflammation in AD over 12 months

    XPRO DECREASES NEUROINFLAMMATION IN AD D e cr e ase in N eu r oinflam m ation in whit e matter tra c ts over 12 months RE S U L T OF P H A S E I TRIAL XPro decreases neuroinflammation over 12 months in patients with AD - 60 - 30 - 40 - 50 - 20 - 10 30 20 10 0 Fr e e - w a te r i n A D bun d l es ( %

  17. Slide 17: White Matter Metrics

    W H I T E M A TT E R M E T R I C S f o r A D Hea l th Whi t e matter 17 AD wh i te matter

  18. Slide 18: Downstream benefits: decreases neurodegeneration and improves synaptic function

    D O W N S T R E A M B E N E F I T S OF X P R O Ρ T R E A T M E N T : D E C R E A S E S NEURODEGENERATION AND IMPROVES SYNAPTIC FUNCTION Phase 1b Data: CSF PROTEOMICS f o r A D Synaptic Proteins Contactin - 2 – 222% increase Neurogranin – 56% decrease Neuronal Injury Visinin - like protein 1 (VILIP -

  19. Slide 19: p-tau217 as a biomarker of AD

    f o r A D RESULT OF PHASE I TRIAL – p - tau217 as a biomarker of AD A “ t r a d i t i on a l ” b i o m a r k e r o f A D – p T a u 2 1 7 / 1 8 1 CSF following 12 weeks of treatment with XPro1595 (1 mg/kg) p<0.0001 p<0.01 Phospho - tau is a biomarker of neurodegeneration Phospho - tau217 correlates b

  20. Slide 20: Downstream benefits of XPro in patients with AD

    0 3 6 18 21 24 - 10 0 - 5 5 20 15 10 9 12 15 V i s i t ( m on t hs ) Fiber Density in AD bundles (% change) XPro1595 1 mg/kg ADNI database N = 36 N = 6 N = 5 N = 5 N = 3 12 month AFD improvement 1mg/kg 12 month RD improvement 1mg/kg T H E “ D O W N S T R E A M ” B E N E F I T S O F X P R O T M I N P

  21. Slide 21: XPro increased white matter volume

    XPR O ΠINCREASED WHITE MATTER VOLUME 0 1 2 5 00 0 5 50 0 6 00 0 6 50 0 3 6 9 Visit (months) Left Inferior Temporal volume (mm 3 ) 0.0839 0.0381 0.1226 INMB AD Non - confidential 1.5.22 f o r A D 21 Phase 1b Data

  22. Slide 22: Remodeling of white matter tracts after XPro

    R E M O D E L I N G O F W H I T E M A TT E R T R A C T S A F T E R X P R O TM Phase 1b Data: CHANGES IN AFD IN AD WHITE MATTER TRACTS IN MAN Baseline 3 months 6 months 9 months ▪ 65 - year - old white male retired due to AD ▪ Returned to work after 6 months of XPro therapy ▪ Increasing green/blue sh

  23. Slide 23: Clinical Benefit in Phase I trial

    Clinical Benefit in Pha s e I t rial 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 patients of di

  24. Slide 24: Correlation between decreased neuroinflammation and improved cognition

    Correlation bet w een decreased neuroinflam m ation and i m proved cognition R 2 = 0.4 to 0.6 CSF cytokines by OLINK platform INMB AD Non - confidential 1.5.22 f o r A D 24

  25. Slide 25: Phase 2 randomized placebo-controlled study in early Alzheimer's

    25 f o r A D All patients canenroll in a 12 - month open - label extension A randomized, placebo - controlled, double - blind study of XPro1595 in patients with Early Alzheimer's Disease with biomarkers of inflammation − A t l e a s t o n e n i f l a m m a t o ry b i o m a r k e r : − CRP > 1.5 − E

  26. Slide 26: Statistical power: why XPro trials are short and small

    f o r A D S t a t i s t i c a l P o w e r : w h y X P R O c l i n i c a l t r i a l s a r e d e s i g n e d t o b e s h o r t a n d s m a l l • Patients with neuroinflammation have faster cognitive decline that patients without neuroinflammation • Enrichment strategy selects patients with neuroinfla

  27. Slide 27: Targeting Neuroinflammation for Treatment Resistant Depression

    Targeting Neuroinflammation for the Treatment of TREATM E NT RESISTANT DEPR E SSION (TRD) 27

  28. Slide 28: Treatment Resistant Depression

    TREATMENT RESI S TA N T DEPRE S SI O N ( T R D ) ▪ There are 200+ symptom combinations that will lead to a depression diag n os i s ▪ No Biomarker s ▪ High p l a c e b o res ponse ▪ Drug development failure rate in psychiatry i n Pha se II: 35% i n Phas e III: 6 5 % ▪ Effect i veness of approv ed d

  29. Slide 29: Why sTNF is the right target

    TREATMENT RESI S TA N T DEPRE S SI O N ( T R D ) Why sTNF is the right Tar g et f o r T R D 1 H a r oo n e t a l . , P syc honeu r oendo cr inology , 2018 2 Raison CL, et al. JAMA Psychiatry. 2013;70(1):31 - 41 P l asm a TN F l e v e l s a r e i nc r ease d i n TR D p at i e n ts 1 c o m bined < 5mg

  30. Slide 30: A biomarker of neuroinflammatory depression

    A biomarker of neuroinflammatory depression f o r T R D Felger et al., Mol Psychiatry, 2016 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

  31. Slide 31: Phase 2 TRD trial design

    BIOMA RKERS OF I N F L A MM A T I O N D E S I G N ▪ S i x - w ee k d o u b l e b l i n d p l a c e b o - c o n t r o ll e d s t u d y o f X P r o 1 5 9 5 ▪ 4 5 p a t i e n t s i n X P r o 1 5 9 5 a t 1 m g / k g ▪ 4 5 p a t i e n t s i n p l a c e b o c o n t r o l gr o u p ▪ B i o m a r k e r s o f

  32. Slide 32: Off-the-Shelf NK Therapy Converts Patient's Resting NK cells into Cancer Killing memory-like NK cells

    Off - th e - Shelf NK Th erapy Conver t s Patien t ’s Resting NK cells in t o Cancer Kill i ng me m ory like NK cells f o r Oncolo g y 32

  33. Slide 33: NK cells play a critical role in eliminating cancer cells

    33 N a t u r a l K i ll e r ( N K ) c e ll s p l a y a c r i t i c a l r o l e i n e l i m i n a t i n g c a n c e r c e ll s i n Onco l o g y i n Onco l o g y A n t i - T u m or Cytotoxic Immunity x NK cells are principal anti - tumor cells in innate immune system x 5 - 15% of the circulating lymph

  34. Slide 34: NK cell cytotoxicity predicts survival in myelodysplastic syndrome

    34 NK cell cytotoxicity is a predictor of survival in m y e l o d y s p l a s t i c s y n d r o m e i n Onco l o g y i n Onco l o g y Alive >2yrs % K562 Lysis NO YES Tsirogianni M, et al. Leukemia & Lymphoma. 2019;60(10):2457 - 2463. Greater NK - mediated cell function in long - term survivors Bette

  35. Slide 35: Why don't NK cells kill cancer cells more effectively?

    35 Why don’t NK cel s kil cancer cells more effectively? i n Onco l o g y i n Onco l o g y Karvouni M, et al. Front Immunol. 2022;13:825979 resting NK (rNK) tumor primed NK (tpNK) 1. INSUFFICIENT ACTIVATION Resting NK cells are not sufficiently activated by NK - resistant cancer cells 2. TUMOR - MED

  36. Slide 36: Many NK cell-based immunotherapy approaches are being tested

    36 Many NK cell - based immunotherapy approaches are being tested i n Onco l o g y i n Onco l o g y 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

  37. Slide 37: NK cell immunotherapies have serious limitations

    Several NK cell - based immunotherapies have serious limitations i n Onco l o g y i n Onco l o g y 37 ᤵ 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) ᤵ

  38. Slide 38: Re-equilibrating the immune system in cancer

    Re - equilibrating the immune system in cancer i n Onco l o g y i n Onco l o g y 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. 38

  39. Slide 39: How does INKmune prime NK cells to kill cancer cells?

    How does INKmune Πprime NK cells to kill cancer cells? i n Onco l o g y i n Onco l o g y 39 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 c

  40. Slide 40: INKmune stimulates differentiation of resting NK cells to memory-like NK cells

    40 INKmune Πstimulates differentiation of resting NK cells to m e m o r y - l i k e N K c e ll s i n Onco l o g y i n Onco l o g y INKmune - primed NK cells (TpNK) are phenotypically comparable to cytokine - induced memory - like NK cells 0 5000 10000 NK G 2 C I F e M 0 10000 20000 30000 40000 NK G

  41. Slide 41: INKmune increases avidity of NK cell binding to tumor cells

    41 INKmune ΠIncreases Avidity of NK Cell Binding to Tumor Cells i n Onco l o g y i n Onco l o g y 0 20 0 80 0 100 0 400 600 rForce (pN) 0 2 0 4 0 6 0 8 0 % N K C e l l s B ou n d A v i d ity of tu m or ce ll b i n d i n g by re s ti n g a nd pri m e d NK ce l ls SK - OV - 3 (n=3) 5 min 100 resting

  42. Slide 42: INKmune priming allows NK to kill NK-resistant tumor cells in hypoxia

    i n Onco l o g y INKmune Œ priming allows NK to kill NK - resistant tumor cells e v e n i n t h e h y p o x i a o f t h e T M E • 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 n

  43. Slide 43: INKmune improves NK fitness by activating critical genes and pathways

    I N K m u n e Πi m p r o v e s N K f i t n e s s by activating critical genes and pathways for enhanced NK function / survival i n Onco l o g y i n Onco l o g y INB16 upregulates 522 genes distinct from IL2 Рincluding CD70, CXCL10, Stat5 INB16 upregulates 1461 proteins distinct from IL15 Рincludi

  44. Slide 44: INKmune Phase 1 study: first patient completed treatment

    INKmune ΠPhase 1 study: First patient to have completed treatment i n Onco l o g y Persistence of activated tumor - killing memory - like NK cells in blood at 119 days 44

  45. Slide 45: But is INKmune safe?

    B u t i s I N K m u n e Πs a f e ? i n Onco l o g y i n Onco l o g y 45 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 we

  46. Slide 46: cGMP Manufacturing – Doable vs Practical

    cGMP MANUFACTURING – DOABLE VS PRACTICAL…. i n Onco l o g y IN K mu n e Ρ 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???) MFG Process 2 500 liter bioreactor DRUG PRODUCT Many NK Ma

  47. Slide 47: Thank you

    Thank you 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 47

  48. Slide 48: Neurodegenerative

    Neurodegenerative Psychiatric [inflammatory a, ition \ Metaflami inflamm-aging ~~ ‘metabolism Cardiovascular Innate 7 Immune tL a Dysfunction fo ™ cancer Autoimmune ) Diet Infection” Stress tniury ” * emvieonment

  49. Slide 49: TNF biology is complicated: two ligands with opposite effects

    49 T N F b i o l o g y i s c o m p l i c a t e d : t w o l i g a n d s w i t h o pp o s i t e e ff e c t s 49

  50. Slide 50: XPro is very different from currently available drugs

    Adapted from MacEwan et al 2002 XPRO is very different from currently available drugs Precise neutralization of the TNF ligand that drives disease Approved TNF inhibitors block both cytokines ▪ So l uble TNF ( s T N F ): “ba d ” TNF th a t is k n o w n t o c a u s e acu t e a n d chronic inflammatio

  51. Slide 51: Safety side effects of non-selective TNF blockade

    51 Safety side effects of non - selective TNF blockade are all from b l o c k i n g t m T N F Co n seq u enc e s of b l ocking tmTNF: ▪ Infection ▪ Cancer ▪ Demyelination 51

  52. Slide 52: XPro is very different from currently available drugs

    Adapted from MacEwan et al 2002 XPRO is very different from currently available drugs Precise neutralization of the TNF ligand that drives disease ▪ So l uble TNF ( s T N F ): “ba d ” TNF th a t is k n o w n t o c a u s e acu t e a n d chronic inflammation and cell death ▪ Transmembrane TNF (tmTNF):

  53. Slide 53: XPro1595: a selective inhibitor of only soluble TNF

    St e e d e t a l 20 0 3 XPro1595 is id e n t ical to t h e h u man so l uble TNF mono m er wi t h the exce p t i on of mu t a t io n s in the recep t or bindi n g do m ain a n d ano t h e r for p e gyla tio n . 53 XPro1595: a selective inhibitor of ONLY soluble TNF XPRO: a TNF inhibitor designed to

  54. Slide 54: XPro unique Mechanism of Action

    XPRO unique M e c h a n i s m o f A c t i o n 54

  55. Slide 55: Successful Phase 1b trial: AD patients with biomarkers of inflammation

    Suc c essful Phase 1b trial: AD p a tients with biomarkers of inf l ammat i on ( A Di) DESIGN ▪ O pe n - l a b el Mul t i ple dosing c oh o r t s ( 0 . 3 , 0. 6 , 1.0 m g/kg) ▪ Weekly XPro1595 Œ SubQ injections for 3 months ▪ B i o marke r s a sses s ed a t 0 a nd 12 w e eks Inclusion ▪ AD Di a gn o

INmune Bio — Investor Presentation (March 2023) on 6ix