Inmune Bio Inc. · NASDAQ:INMB
Inmune Bio — BIO CEO & Investor Conference Feb 2019
62 slides from Inmune Bio's conference presentation, Feb 8, 2019
Slide 1: INmune Bio - Nasdaq: INMB, February 2019
Nasdaq: INMB February 20197
Slide 2: Forward-Looking Statements
| Forward-Looking Statements pac 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 th
Slide 3: INmune Bio = Innate Immunity
| INmune Bio = Innate Immunity INmunesio Our Vision: Become the Leader in Reprograming the Innate Immune System for the Treatment of Disease. EERE... LS
Slide 4: INMB Target Cells of Innate Immune System
| INMB Target Cells of Innate Immune System ®) INmunesio NK MDSC Microglial
Slide 5: INMB Pipeline
| INMB Pipeline eens Pi Phase II clinical POC INBO3 for CPI resistance INBO3 for trastuzumab resistance INKmune for relapsed/refractory ovarian cancer INKmune for high-risk MDS XPro1595 for Alzheimer’s disease Current Trials Potential Future Programs EE====> ss
Slide 6: INB03
Slide 7: Problem: % of Patients Resistant to CPI
| Problem: 3 of 4 Patients Resistant to CPI INmunesio 9 MDSCs< 5.1% Stage IV Melanoma <> Mbscs< aa j <> MDSCS treated with os Ipilimumab P=6.7%«10" 2 (Woiehok2016) a 8 06 2 Es re 204 2 5 3 0.2 0.0 4 ° 2 2 2 s . Years MDSC predict resistance to CPI Se [6
Slide 8: Why is MDSC Important?
i ® | Why is MDSC Important? poe Lethal cycle of chronic inflammation, immunosuppression, cancer progression and metastasis MDSC Proliferation Immunosuppression in TME
Slide 9: How INB03 Improves CPI Function
i ® | How INBO3 Improves CPI Function ae MDSC “force field” before INBO3 Cancer killing ‘o) T cell after CPI does not kill & cancer cells live cancer cells Oo Za SS) and grow due to MDSC MDSC “force field” after INBO3 ! cancer cells A Cancer killing T I cell after CPI kills —+@ “¢@ killed ei cancer
Slide 10: INB03 Development Program
| INBO3 Development Program Wenunetie Ongoing Phase 1 open- Phase 2 trial in Stage IV label, dose-escalation trial melanoma* + CPI 12 cherie with advan Patients resistant to CPI solid tumors wii i * biomarkers of chronic vith _— inflammation including * Treatment*: combo “4 MDSC therapy INBO3 + CPI
Slide 11: XPro1595
\ i C4 ; +h out a XPro1595 —__—_—_— wri | —wewen " ‘| —i { lll sl
Slide 12: Alzheimer's - an Intractable Problem
| Alzheimer’s - an Intractable Problem INmunesio Alzheimer’s Association awards INmune Bio Part the Cloud Grant - $1M USD translational funding to study XPXro1595 in Alzheimer's disease Goal: Help promising therapies across “Valley of Death” ee : D
Slide 13: Neuroinflammation: the "ignored" Element of Alzheimer's Disease
Neuroinflammation: the “ignored” ® Element of Alzheimer’s Disease WemunERe tau neurofibrillary tangles B amyloid plaques microglial activation Microglial activation = neuroinflammation = synaptic pruning & neuronal death
Slide 14: Neuroinflammation Linked to Every Aspect of Alzheimer's Disease Pathology
| Neuroinflammation Linked to Every Aspect ® of Alzheimer’s Disease Pathology ATURE Abnormal Ab and ~~ ie and processing Astrogliosis Synaptic loss «—— - @- —> Excitotoxicity Neuronal cell heath 2 Srcppression of growth factors
Slide 15: XPro1595 Phase I AD
| xPro1595 Phase I AD oe Biomarker directed trial of patients with inflammation and proven Alzheimer’s Diseases 18 patients in 3 cohorts * Weekly XPro1595 subQ for 3 months * Biomarkers of inflammation at 0,6 and 12 weeks » Endpoints: — Safety — J inflammation blood, CSF, brain and breath — Measures
Slide 16: Novel use of Biomarkers of Inflammation
| Novel use of Biomarkers of Inflammation Blood Inflammatory cytokines and immune profiling ® Wemunetie CSF Inflammatory cytokines and immune profiling
Slide 17: INKmune
\ i C4 ‘ a aa" au aie [NKmune —___— wri | —wewen " ‘| —i { lll Sipe
Slide 18: INKmune to Treat Minimal Residual Disease (MRD)
| INKmune to Treat Minimal Residual Disease (MRD) roan 100: survivors ate 12. 2% LCA om 412 2% LCA ®, 0=0.007 “relapsers” 0 12 24 36 48 60 72 &4 96 108 Months in CR Difference between survivors and relapsers is MRD a—————aaEaEaEeEeEeEeEeE—————EEE |
Slide 19: What is MRD?
| what is MRD? us * Residual disease is the cancer that is left behind after treatment Two types: — Overt: visible by imaging studies — Minimal (MRD): invisible by imaging studies NK cells are responsible for eliminating MRD Problem: patient’s NK cells are inert Solution: |NKmune primes the patient’
Slide 20: Ovarian cancer cells with NK cells before and after INKmune
SN cancer cell —, Lo O Human ovarian cancer cells plus patient's Human ovarian cancer cells with patient's own NK cells NK cells after INKmune treatment _ a 6
Slide 21: INKmune Clinical Trial
| INKmune Clinical Trial nee INKmune causes in vivo priming so patient's NK cells can kill their cancer by targeting naturally occurring tumor antigens Phase 1/2 study in relapsed/ refractory CaOva Platinum resistant/refractory patients with residual disease » Treatment: INKmune -6 doses » Endpoints
Slide 22: Investment Opportunity
| Investment Opportunity ® Imaal + Public clinical stage immunology company with programs in oncology and neurodegenerative disease + Platforms target “ignored” elements of immunology + Innate immune system + MDSC - “protector” cells of the TME + Neuroinflammation as a cause of Alzheimer's disease +
Slide 23: INmune Bio = Innate Immunity
z o4 ren !Nmune Bio = Innate Immunity - re || =a ll |
Slide 24: Milestones
| Milestones ® iNmunedie © February 1, 2019 - IPO closed (7) February 4, 2019 —- NASDAQ Capital Markets listing (a) Feb19 — Part the Cloud award — Alzheimer’ Assoc O Mar19 - initial data on INBO3 Phase | ro) May19 — first patient enrolled INKmune CaOva O May19 - initiate INBO3 combination trial ° Ju
Slide 25: Sum-of-Parts Market Opportunity
| Sum-of-Parts Market Opportunity iNmunenie INMB pipeline address 3 market * Alzheimer’s Disease/dementia market (US) —5.5M patients * Cancer residual disease market (US) — 1,735,350 new cases and 609,640 people will die * Resistance to CPI market — Combination therapy has the potential of improving
Slide 26: Experienced Leadership
| Experienced Leadership Management RJ Tesi, MD Chief Executive Officer & Chief Medical Officer Mark Lowdell, PhD Chief Scientific Officer David Moss Chief Financial Officer Board of Directors J. Kelly Ganjei CEO of Cognate Timothy Schroeder CEO and Founder of CTI David Szymkowski, PhD VP of Cell Bi
Slide 27: Intellectual Property
| Intellectual Property ® INmenekie INB03/XPro1595 INKmune » 2021 -composition-of- matter (licensed from * 2035 — use for treatment Xencor) of cancer » 2032 —Methods for treatment of neurologic disease » Multiple filings in process 2035 — use for treatment of cancer (licensed from University of Pitt
Slide 28: INB03/XPro1595 MOA Appendix
Slide 29: XPro1595/INB03: Selective Inhibitor of Soluble TNF (sTNF)
XPro1595/INBO3: Selective Inhibitor of ® Soluble TNF (sTNF) Wenunetie 17kDal non-glycosylated protein attached Nearly identical to to 10 kDal linear PEG with 18 hour half life human TNF protein — 2 mutations produce mechanism-of- action Excellent CMC amd PK properties — Qweek patient administration
Slide 30: How XPro1595/INB03 Neutralizes sTNF
| How XPro159/INBO3 Neutralizes sTNF ® Normal sTNF activity 4 a 2 + v 9 3 Inflammation os VY > vov > Active TNF ER Neon XPro1595 TNFR ge No sTNF activity ed v + ™ YY = = NO _ Vv Inflammation “ gy Heterotrimers Active TNF Inactive cannet hind _ heterotrimers
Slide 31: Why is XPro1595/INB03 Different?
| Why is Xpro1595/INBO3 Different? meee Normal TNF Biology INBO3 does not neutralize tmTNF TNFR1 om oe > iY tmTNF binds TNFR with normal function Approved TNF inhibitors XPro1595/INBO3 TNFR1 TNFR2 TNFR1 TNFR2 T tmJNF sTF tmTNF 0G impr (bad) (good) Prevent function of Neutralizes sTNF allowing TNF an
Slide 32: Precision Therapy: Targets sTNF not tmTNF
| Precision Therapy: Targets sTNF not tmTNF Inflammatory soluble TNF eliminated: No paracrine signaling through receptors ® L é oF) 2 ~) 3 ‘solTNF 2 INBos 3 cecombrantor _(Scnae = shy ) Physiological) No paver 2 ae ae eT a Log [anti TNF (yo/mi) wo Immunoprotective transmembrane TNF unaffected: Z All
Slide 33: Expected Dose: 1mg/kg/week
| Expected Dose: 1mg/kg/week nee Repeat Dose Modeling of XENP1595 in Humans ‘mg/kg Administered SC Every 5, 7, or 10 Days 3 XENP1595 (ug/mL) 2.4ug/ml ine =" 0.5j.g/mi bie 01+ oO 5 10 15 20 25 30 Time (day) Allometric scaling of cyno PK data suggests weekly dosing of 1 mg/kg SC in humans will sustain
Slide 34: Manufacturing
| Manufacturing ® RP-HPLC of INBO3 \ + INBO3 was engineered for single, site-specific clean pegylation (10kD PEG/monomer x 3 monomers) + Unpegylated XENPS560 is produced through E. | _ coli expression | + INBO3 is a nonglycosylated small (17 kD monomer) & stable homotrimeric protein, with superior m
Slide 35: MDSC Appendix
Slide 36: Different Approach to Immuno-oncology
| Different Approach to Immuno-oncology ® Adaptive Innate ae Immunity Most I/O companies cells Effector Protector cells + Effector cells: T and NK cells + Protector cells: MDSC, TAM, TAN, Treg, CAF Bl
Slide 37: MDSC Predict Resistance to CPI
| MDSC Predict Resistance to CPI * INBO3 targets MDSC * CPI +INBO3 should overcome MDSC based resistance by eliminating MDSC so CPI become effective Stage IV Melanoma —F MDSCs<5.1% 20 - si «#™ MDSCs < 9.5% treated with 7 MDSCs > 9.5% Ipilimumab (n=209) e & (Wolehok2016) P=67% 10" 2° a Survival proba
Slide 38: INB03 to Treat Resistance to CPI
| INBO3 to Treat Resistance to CPI INmunesio Resistance to checkpoint inhibitors is a growing problem in the care of cancer patients * Problem: 3 of 4 patients resistant to CPI * Solution: eliminate cause resistance ¢ Drug: INBO3 * Target: myeloid derived suppressor cells (MDSC) * Status: in Phase |
Slide 39: How does INB03 Inhibit MDSC to Kill Tumor?
® | How does INBO3 Inhibit MDSC to Kill Tumor? wrunesie Step 2 TNFR inhibits pSTAT3 Step 3 Stops differentiation and proliferation of myeloid Step1 cells to MDSC INBO3 binds TNFR Step 4 Decrease MDSC in TME decreases as TAM and Treg ep increased tumor killing Step 5 Increased Step 6 Recruitment of C
Slide 40: INB03: Step Process for Improved Survival
| INBO3: 2 Step Process for Improved Survival MCA fibrosarcoma model in mice VMDSC in tumor TL control etanercept 1NBO3 % cells Decreased sTNF decreases differentiation and proliferation of MDSC ¢CD8+ lymphocytes in tumor ry fl a etanercept B03 tmTNF promotes NK/DC crosstalk that recruits CD+8 TILs
Slide 41: Alzheimer's Disease Appendix
Slide 42: XPro1595 to Treat Alzheimer's Disease
| XPro1595 to Treat Alzheimer’s Disease INmunesio AD is an expanding, expensive and intractable disease that defies a therapeutic solution * Problem: synaptic pruning and nerve cell death * Solution: reduce neuroinflammation ¢ Drug: XPro1595 * Target: activated glial cells in the brain * Status: ent
Slide 43: Inflammation: the Third Horseman of Alzheimer's Pathology
Inflammation: the Third Horseman of ® Alzheimer’s Pathology ANTENERE TANGLE Neurofibrillary tangles Neuronal cell death AMYLOID AB accunulation Disease n Pathology INFLAMMATION Reactive microglia
Slide 44: Inflammation in Alzheimer's Disease
| Inflammation in Alzheimer’s Disease wn ooue Neurodegeneration Reduced clearance ‘Synapse loss of toxic debris ‘Alternative processing Excitotoxicit 'y of Amyiold and tau Suppression of Microglial activat roglial activation growth factors ee :
Slide 45: XPro1595 Attenuates Alzheimer's Pathology and Restores Normal Function
| XPro1595 Attenuates Alzheimer’s Pathology and ® Restores Normal Function ANmunERIe 01. Amyloid pathology 02. Synapse dysfunction Saline xPro' Saline we TY recanos \/~ T= Efficacy has been shown in 3xTgAD, 5xFAD, TgCRND8 and aged mice
Slide 46: Phase 1b Biomarker Directed, Proof of Biology Study in Mild to Moderate AD
Phase 1b Biomarker Directed, Proof of Biology Study in Mild to Moderate AD Patients" a sate 2 sate ¥ Blood hsCRP > 2mg/L Q Blood inflammation O Safety a Blood infernmation Brain ntanmat 1 Biood intanmation Sei ran nfammaton peer ran eitammation imaging (Mt) ous i imageg (HR Cognition OQ Coonton ms C
Slide 47: INKmune Appendix
Slide 48: INKmune to Treat Residual Disease
| INKmune to Treat Residual Disease INmunesio Residual disease is the cause of relapse and death in a majority of patients Problem: cancer remains after treatment * Solution: eliminate residual disease Drug: |NKmune Target: patient’s NK cells * Status: entering Phase I/II trial in women with relapse
Slide 49: Tumor not Immune System Cause of Relapse
| Tumor not Immune System Cause of Relapse meee Relapser Survivor NK cells NK cells i=) * Relapser NK cells kill survivors AML. * Survivor NK cells can not kill relapser AML. Conclusion: AML mutates to evade NK cell killing.
Slide 50: Relapse due to Minimal Residual Disease
| Relapse due to Minimal Residual Disease pac Relapse due to MRD ZA INKmune primes NK cells to eliminate MRD oa: INK Cell Cancer Cell ae TpNK Cell _Dead-Cancer Cell Cancer down- regulates S1, “evading” NK INKmune artificially cells, allowing replaces S1 cancer to grow allowing the NK to ‘engage and
Slide 51: INKmune: "universal" Cancer Therapy
® | INKmune: “universal” Cancer Therapy INmunesio INKmune TpNK are active against many types of cancers: Blood cancers: AML, MM, lymphoma » Solid tumors: breast, ovary, prostate, E renal, lung 7 0. : v 4 3 & 60. ' 2 7 5 a” YY sal. * : go 3 ft 3 aa ou pot en gi 10. * ee ea - eo wt SF rr aha wr we we
Slide 52: Results with 1st-Generation TpNK Therapy
| Results with 15t-Generation TpNK Therapy ® AML Phase 1 INmunesio 2 Phase 1 clinical trials; 20 patients with high-risk AML using ex vivo, personalized TpNK therapy Clinical Results — Prolonged remissions with excellent Tp NK quality of life — Put chemo-resistant disease into therapy made = remissi
Slide 53: Biomarker Patient Selection
Fr ne ; ® | Biomarker Patient Selection wmunesle INKmune pNK target tumor and NOT normal cells, 4 % Specific lysis ‘Autologous INKmune pNK cells lyse primary IMM cells respective of prior treatment pr00%8 swsecancuvss
Slide 54: INKmune Development Program
® | INKmune Development Program iNmunenie 2"4_.generation TpNK causes in vivo priming so patient's NK cells can kill their cancer by targeting naturally occurring tumor antigens Phase 1/2 study in relapsed/ Phase 1/2 dose-finding study refractory CaOva in high-risk MDS Platinum resistant/refractory
Slide 55: NK cells and INKmune in Ovarian Cancer
| NK cells and INKmune in Ovarian Cancer rc ® SKOV3 killing by NK cells from healthy donor (HD) or CaOva patient ascites 100- * * 2 5 || |] \ \ 3 60- x“ 6 2 40 s 2 2 0. EL PS PO 2 CO Oo SS ) S S So Ss So | Patient ascites ww e ee ro ee ro ro *IL2 primed NK NK cells kill ros e ae Fe K Sa cells do not
Slide 56: INKmune MOA
| INKmune MOA e INB16 vs cytokine priming — Differential protein expression @16h oe Colour Key (CD54 (ICAM-1) p62 $ 75% Decrease cD184 (CXCR4) D226 (DNAM-1) D244 (2B4) No change D314 (NKG2D) D335 (NKp46) ¢D337 (NKp30) $ 75% Increase NKp80 * Paradoxical decrease (not loss) in ligand expression associ
Slide 57: INKmune Primed NK Cell Killing Assay
| INKmune Primed NK Cell Killing Assay meen INKmune Real-Time Cytolysis Plot added NK added = = ad 0 no pry Time (hr Post-Treatment) a: 6S
Slide 58: INKmune MOA
| INKmune MOA TTPTTETTT TTS Peeererneene reereeettT TT INB16 INmenekie 1 3 Wipf Ly i Sihfi Lowdeli2007
Slide 59: INB16 vs LAK Priming - Gene Expression Profiles
| INB16 vs LAK Priming - 412 Gene ( Expression Profiles Wenunetle INB16 ALCAM - NK cell migration and adhesion STATS — “molecular switch” essential for NK killing CD70- CD27L and NCR for B cell tumours VEGFA - survival signal for NK CXCL10 — chemoattractant for NK cells | OF
Slide 60: INB03 HER2/MUC4 Appendix
Slide 61: Trastuzumab Resistance in Breast Cancer
| Trastuzumab Resistance in Breast Cancer ).5,. + ~30% of women with breast cancer & are HER2+ Fa * 30% - 50% patients 8 have 1° or 2° 3 , 5 resistance to 5 trastuzumab 8 . = P= 0.0086 * MUC4 expression = MUD negativen=31 . ‘== MUC4 posttiven= 47 predicts Fal trastuzumab 0 2 40 6 resistance Time (mo
Slide 62: INB03 Reverses Trastuzumab Resistance
® | INBO3 Reverses Trastuzumab Resistance mmunesie INBO3 overcomes trastuzumab resistance in JIMT-1 tumors MUC4 blocks trastuzumab binding seo. ag too ‘ TON 0 ar ; ON 20 -T H = 46 2 re. °. ty % % 30 ‘Time of treatment (days) Ttrastuzumab DN- INBO3 ‘Schiloc:SABCS2018