Inmune Bio Inc. · NASDAQ:INMB
Inmune Bio — Investor Presentation (June 2019)
65 slides from Inmune Bio's investor presentation, Jun 24, 2019
Slide 1: INMB non-confidential key facts
INMB non-confidential 6.4m Nasdaq Symbol: INMB Shares Outstanding: ~10.5M Share Price 6.18.19: $10.35 Market Cap: ~100M Debt: Je) Largest Shareholder: XNCR Insider Ownership: >50%
Slide 2: Forward-Looking Statements
| Forward-Looking Statements INmunesio 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
Slide 3: Summary
| Summary oe * Clinical stage immunology company - programs in oncology and Alzheimer’s disease + Platforms target “ignored” elements of immunology + Innate immune system + “Resistance” immunology of the Tumor Micro Environment (TME) + Neuroinflammation is a cause of Alzheimer's disease * Large mark
Slide 4: INmune Bio = Innate Immunity
| INmune Bio = Innate Immunity oneoue Our Vision: Become the Leader in Reprograming the Innate Immune System for the Treatment of Disease INMB non-confidential 6.17.19
Slide 5: INMB Target Cells of Innate Immune System
| INMB Target Cells of Innate Immune System 8 INmunesio NK MDSC Microglia
Slide 6: INMB Pipeline & Clinical Status
| INMB Pipeline & Clinical Status ® IemruneRie Pre cli ll INBO3 for Checkpoint Inhibitor resistance (Melanoma and Renal Cell Cancer) INBO3 for trastuzumab resistance (breast ne =» INKmune for Relapse / Minimal Residual Disease (ovarian cancer) INKmune (High-risk MDS - Leukemia) == XPro1595 for Neuro
Slide 7: Pipeline Market Opportunity
| Pipeline Market Opportunity ® * XPro1595 - Alzheimer’s/dementia market* — 5.8 M patients in US — 2019 est cost to care for US AD patients $280B * INKmune - Cancer residual disease market ** — 1,735,350 new cases and 609,640 people will die — Initial targets: Ovarian Cancer and High Risk MDS * INBO
Slide 8: Clinical programs vs Peers
| Clinical programs vs Peers ® PEERS Company Market Clinical Status Symbol Fate Therapeutics Cancer residual disease Phase | FATE Alector Neuro-inflammation Phase | ALEC IFM Tre Resistance to Checkpoint Inhibitors Phase | private Company Market Clinical Status INmuneBio Cancer residual disease Phase
Slide 9: INB03 (for the treatment of Melanoma and Renal Cell Cancer)
\ C4 on % INBO3 (for the treatment of Melanoma and Renal Cell Cancer) def sf _ewewen ) wr u INMB non-confidential 6. 17.18 ——- % ite.
Slide 10: Problem: % of Patients Resistant to CPI
] Problem: 3 of 4 Patients Resistant to CPI Nmunedie 0 . ieee eas par < 9/54 tage IV Melanoma +75 Mpsces o:5% treated with os Ipilimumab P=67~*10-" zz (Wolchok2016) = 8 06 2 a 3 2 04 = 5 a 0.2 0.0 + ° 1 2 3 * a Years MDSC predict resistance to CPI INBO3 targets MDSC Combination therapy should improv
Slide 11: INB03 Development Program
| INBO3 Development Program wm ap Ongoing Phase 1 open- Phase 2 trial in Stage IV label, dose-escalation trial melanoma or RCC* + CPI 12 patients with advanced Patients resistant to CPI solid tumors with with 7 MDSC* biomarkers of chronic 7 inflammation * Treatment*: combo * Treatment: INBO3 sub- th
Slide 12: XPro1595 (for the treatment of Alzheimer's Disease/dementia)
\ C4 on XPro1595 (for the treatment of Alzheimer's Disease/dementia)
Slide 13: Cancer vs. Alzheimer's disease/Dementia
] Cancer vs. Alzheimer’s disease/Dementia wm, U.S. HEALTHCARE COST VS. U.S. VENTURE CAPITAL FUNDING OF NOVEL R&D FOR HIGHLY PREVALENT CHRONIC DISEASES $14 wm — 210 2s Eo ER $8 ee gg $6 es $2 $a $2 Respiratory Heart Disease . e _. @ Psychiatric Diabetes Pail $0 Obesity@ @ Pas $50 $75 $100 $125 $150 $
Slide 14: Neuroinflammation: the "ignored" element of Alzheimer's Disease
Neuroinflammation: the “ignored” ® element of Alzheimer’s Disease INmunedie tau neurofibrillary tangles B amyloid plaques microglial activation Microglial activation — neuro-inflammation — synaptic pruning & neuronal death INMB non-confidential 6.17.19
Slide 15: How do we know anti-TNF therapy prevents AD?
| How do we know anti-TNF therapy ® prevents AD? INmuneeie 1 2 800% 60% 1. Risk of AD in RA patients 8 times higher* 2. Risk of AD in RA patients treated with anti- TNF therapy is 0.4* Anti-TNF is the only DMARD that decreases risk of AD! * In RA patients compared to patients without RA fr
Slide 16: XPro1595 Clinical Development Supported by the Alzheimer's Association
| XPro1595 Clinical Development Supported ® by the Alzheimer’s Association Namaste Alzheimer’s Association awards INmune Bio Part the Cloud Grant - $1M USD translational funding to study XPro1595 in Alzheimer's disease INMB non-confidential 6.17.19
Slide 17: XPro1595 Development Program
| XPro1595 Development Program wm ap Phase | 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 neuro-inflammation measured in:
Slide 18: INKmune (for the treatment of Ovarian Cancer and high risk MDS)
\ 4 on % INKmune (for the treatment oh Ovarian Cancer and high risk MDS) P |i ye « ewewen " er : INMB non-confidential 6. 17.18 ——- % ite.
Slide 19: Problem INKmune Addresses: Minimal Residual Disease (MRD)
Problem INKmune Addresses: Minimal Residual ® Disease (MRD) Fearne survivors ate 12.2% LCA we 412 2% LCA, : . 0=0.007 “relapsers” + 1 1 or 0 12 94 96 48 60 72 &4 96 108 Months inCR Difference between survivors and relapsers is MRD INMB non-confidential 6.17.19 [19 |
Slide 20: Ovarian cancer cells with patient NK cells before and after INKmune
cancer cell —_, cancer cell rae Wg" arin Human ovarian cancer cells plus patient's Human ovarian cancer cells with patient's own NK cells NK cells after INKmune treatment INMB non-confidential 6.17.19
Slide 21: INKmune Clinical Trial
| INKmune Clinical Trial ® 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: INmune Bio = Innate Immunity
PAE Sal on a. !Nmune Bio = Innate Immunity — = —
Slide 23: Milestones
| Milestones nn oeve © February 1, 2019 — IPO closed (7) February 4, 2019 - NASDAQ Capital Markets listing (3) Feb19 — Part the Cloud award — Alzheimer’ Assoc (eo) 3Q19 — first patient enrolled XPro1595 AD trial (e) 3Q19 — initial data on INBO3 Phase | re) 4Q19 — first patient enrolled INKmune CaOva
Slide 24: 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 B
Slide 25: Intellectual Property
wo | Intellectual Property IN cy INB03/XPro1595 INKmune 2021 — composition-of- matter (licensed from 2035 — use for treatment Xencor) of cancer 2032 — Methods for Multiple filings in process treatment of neurologic disease 2035 — use for treatment of cancer (licensed from University of Pittsburgh) C
Slide 26: INB03/XPro1595 MOA Appendix
Slide 27: XPro1595/INB03: Selective Inhibitor of Soluble TNF (sTNF)
XPro1595/INBO3: Selective Inhibitor of ® Soluble TNF (sTNF) Wmuneaio . . 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 administ
Slide 28: How XPro1595/INB03 Neutralizes sTNF
| How XPro159/INBO3 Neutralizes sTNF ® Normal sTNF activity 9o+ % > Je => Inflammation os VY vov Active TNF TNER sTNF bind XPro1595, TNFR A] ) °) No sTNF activity 4 Vv NO + > => V v aac es 2° BOL ) Heterotrimers Active TNF Inactive aE pind heterotrimers INMB non-confidential 6.17.19
Slide 29: Why is XPro1595/INB03 Different?
| Why is Xpro1595/INBO3 Different? ® Normal TNF Biology INBO3 does not neutralize tmTNF TNFR1 TNFR2 oe > C> < INBO3 als aed ioor ° - TNF sTNF — tmTNF = ots (bad) (good) tmTNF binds TNFR with normal function Approved TNF inhibitors XPro1595/INBO3 TNFR1 TNFR2 TNFR1 TNFR2 T tmJNF sTF tmTNF as impor (ba
Slide 30: Precision Therapy: Targets sTNF not tmTNF
] Precision Therapy: Targets sTNF not tmTNF Soluble TNF Trans-membrane TNF Caspase activity ea ~=INB03 os “etanercept infximad os -*-adalimumab evehicle esé& 3 2 4 6 4G Log [anti-TNF (g/ml) ® INeuneRle Inflammatory soluble TNF eliminated: No paracrine signaling through receptors e@.% INBO3 soITNF (r
Slide 31: Expected Dose: 1mg/kg/week
® | Expected Dose: 1mg/kg/week preety Repeat Dose Modeling of XENP1595 in Humans 1mg/kg Administered SC Every 5, 7, or 10 Days 10 a E > — 2 1 - : 2.4yg/ml 4.3ygiml 7 oe a 0.5,:g/ml = 01+ t) 5 10 15 20 25 30 Time (day) Allometric scaling of cyno PK data suggests weekly dosing of 1 mg/kg SC in humans
Slide 32: Manufacturing
| Manufacturing Nmunenie + INBO3 was engineered for single, site-specific clean pegylation (10kD PEG/monomer x 3 monomers) + Unpegylated XENPS580 is produced through E. coli expression + INBO3 is a nonglycosylated small (17 kD monomer) & stable homotrimeric protein, with superior manufacturing vs. m
Slide 33: \ a4
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Slide 34: Different Approach to Immuno-oncology
| Different Approach to Immuno-oncology Adaptive Innate immunity Immunity Most I/O companies ® Inamunedle cells Effector Protector cells + Effector cells: T and NK cells + Protector cells: MDSC, TAM, TAN, Treg, CAF 5
Slide 35: Eligibility vs Response to CPI - US
Eligibility vs Response to CPI - US * 44% US cancer patients eligible for CPI * 29% of cancer patients who receive CPI respond JAMA2019
Slide 36: INB03 Targets Resistant to Checkpoint Inhibitors
| INBO3 Targets Resistant to Checkpoint Inhibitors INmuneeie * Myeloid-derived suppressor cells US CPI 2018 (MDSC) predict resistance to Checkpoint Inhibitors (CPI) ¢ INBO3 targets MDSC * Addition of INBO3 should increase number of patients responding to CPI Only 27% of patients that receive CPI res
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 1.0 treated with 7 MDSCs > 9. Ipilimumab = os (Wolchok2016) a B06 2 a 3 204 2 5 a ° N IV Melanom: —7 MOSCs< Stage IV Melanoma Sar eae P=67%10-" INmune
Slide 38: INB03 to Treat Resistance to CPI
| INBO3 to Treat Resistance to CPI ® 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 | trial i
Slide 39: How does INB03 Inhibit MDSC to Kill Tumor?
| How does INBO3 Inhibit MDSC to Kill Tumor? ,,, ® Step1 INBO3 binds TNFR Step7 increased tumor killing Step 2 TNER inhibits pSTAT3 Step 6 Recruitment of CD8+ TIL to tumor Step 3 Stops differentiation and proliferation of myeloid cells to MDSC Step 4 Decrease MDSC in TME decreases TAM and Treg Step
Slide 40: INB03: Step Process for Improved Survival
| INBO3: 2 Step Process for Improved Survival wm ap MCA fibrosarcoma model in mice MDSC in tumor ‘CD8+ lymphocytes 4112 day survival 1 in tumor 1 » ° “ : ; 2 2 7 10 ? ‘ * . +: = i Ro 4 - bal 4 . . l] ° ° | a control etanercept INBO3 etanercept ing03 control B03 Decreased sTNF tmTNF promotes ene decr
Slide 41: Alzheimer's Disease Appendix
Slide 42: XPro1595 to Treat Alzheimer's Disease
| XPro1595 to Treat Alzheimer’s Disease ® 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: entering Ph
Slide 43: Inflammation: the Third Horseman of Alzheimer's Pathology
| Inflammation: the Third Horseman of Alzheimer’s Pathology TANGLE AMYLOID Neurofibrillary tangles AB accumulation Neuronal cell death Disease Pathology INFLAMMATION Reactive microglia
Slide 44: Problem XPro1595 Addresses: Neuroinflammation
Problem XPro1595 Addresses: ® Neuroinflammation, Linked to Every Aspect _ ""**!° of Alzheimer’s Disease Patholoav Abnormal Ab and Tau Betis and processing Astrogliosis Synaptic loss q«—— - @- ——> Excitotoxicity Neuronal cell deat a7 SSE a ression of growth factors XPro1595 is a protein biologic that
Slide 45: Inflammation in Alzheimer's Disease
| Inflammation in Alzheimer’s Disease ® Neurodegeneration Reduced clearance ‘Synapse loss of toxic debris Alternative processing Excitotoxi “ of Amyloid and tau ‘Suppression of Microglial activation growth factors ec Infection | Stress Environment ee, §6=6le
Slide 46: XPro1595 Attenuates Alzheimer's Pathology and Restores Normal Function
| XPro1595 Attenuates Alzheimer’s Pathology and : ww wp Restores Normal Function [ea au sgn el, ose 2007 01. Amyloid pathology 02. Synapse dysfunction Saline xPro™* saline = Ty Actwated Myeloidcalls Brain Teal intitrtion ifa Efficacy has been shown in 3xTgAD, 5xFAD, TgCRND8 and aged mice
Slide 47: Phase 1b Biomarker Directed, Proof of Biology Study
| Phase 1b Biomarker Directed, Proof of ® Biology Study in Mild to Moderate AD Patients" ; ssi sate) ¥ BlodtsCRP 22mg © Blood ntanmaion SEY 2 Bod ntanmaion Brain inflammation Eas Brain inflammation i Imaging (MRI) O Imaging (MRI) ee O Imaging (MRI) Cognition de D Cognition O Psychiatric symptoms rae
Slide 48: Novel use of Biomarkers of Inflammation
| Novel use of Biomarkers of Inflammation ® Imuneeie Blood CSF Inflammatory Inflammatory cytokines and cytokines and immune profiling immune profiling
Slide 49: INKmune Appendix
Slide 50: INKmune to Treat Residual Disease
| INKmune to Treat Residual Disease ® Residual disease is the cause of relapse and death in a majority of patients Problem: cancer remains after treatment Solution: eliminate residual disease Drug: INKmune Target: patient’s NK cells Status: entering Phase I/II trial in women with relapse/refractory
Slide 51: What is MRD?
| What is MRD? wm ap Residual disease is the cancer that is left behind after treatment Two types: — Overt: visible by imaging studies — Minimal (MRD): invisible by imaging studies Natural Killer (NK) cells are responsible for eliminating MRD Problem: patient’s NK cells are inert Solution: INKmune p
Slide 52: Tumor not Immune System Cause of Relapse
| Tumor not Immune System Cause of Relapse wm ap Relapser Survivor NK cells NK cells x -f Te] you sa ¢ Relapser NK cells kill survivors AML. ¢ Survivor NK cells can not kill relapser AML. Conclusion: AML mutates to evade NK cell killing. INMB non-confidential 6.17.19
Slide 53: Relapse due to MRD; INKmune primes NK cells
® INS Relapse due to MRD A INKmune primes NK ! cells to eliminate MRD ee Lb TPNK Cell Dead-Cancer Cell | Relapse due to Minimal Residual Disease INK Cell Cancer down- regulates S1, “evading” NK cells, allowing cancer to grow INKmune artificially replaces S1 allowing the NK to ‘engage and kill cancer
Slide 54: INKmune: "universal" Cancer Therapy
| INKmune: “universal” Cancer Therapy nn oeve INKmune TpNK are active against many types of cancers: * Blood cancers: AML, MM, lymphoma * Solid tumors: breast, ovary, prostate, renal, lung ~{-- % specific lysis 8 8 8 8 % Specific lysis, Bess 8 Ba CLL
Slide 55: Results with 1st-Generation TpNK Therapy
| Results with 15t-Generation TpNK Therapy ww ap AML Phase 1 INMURERIE 2 Phase 1 clinical trials; 20 patients with high-risk AML using ex vivo, personalized TpNK therapy Clinical Results — Prolonged remissions with excellent TpNK quality of life — Put chemo-resistant disease into therapy made = remi
Slide 56: Biomarker - Patient Selection
| Biomarker - Patient Selection na ooae INKmune pNK target tumor and NOT normal cells 5 % Specific lysis aL CLEC Autologous INKmune pNK cells lyse primary MM cells irespective of prior treatment Eo eSPEarIC LYSIS tf + a Dexamethasone Dexamethasone Am J Hematology; 86:967-973 MB non-confidential 9 |
Slide 57: INKmune Development Program
| INKmune Development Program ® 2"d.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 Patients wi
Slide 58: NK cells and INKmune in Ovarian Cancer
| NK cells and INKmune in Ovarian Cancer invemente J Patient ascites NK cells kill SKOV3 SKOV3 killing by NK cells from healthy donor (HD) or CaOva patient ascites 100: * * 2 3 \ \ 2 6 60 x 5 2 40 r & = 20 S 0 & ‘a ‘a ‘J ‘es o ‘a FPP SS SS SS ww oF FF +IL2 primed NK SE SIF ey cells do not Kill CT or
Slide 59: INKmune MOA
| INKmune MOA ® IemruneRie INB16 vs cytokine priming — Differential protele expression @16h cb16 Colour Key cDS4 (ICAM-1) cp62t < 75% Decrease D184 (CXCR4) D226 (DNAM-1) D244 (284) No change D314 (NKG2D) D335 (NKp46) D337 (NKp30) $ 75% Increase Nkpg0 + Paradoxical decrease (not loss) in ligand expre
Slide 60: INKmune Primed NK Cell Killing Assay
| INKmune Primed NK Cell Killing Assay NuneBio Real-Time Cytolysis Plot NK 1:1 NK 2:1 ——NK 5:1 NK 20:1 TP-NK 1:1 TP-NK 2:1 ~—TP-NK 5:1 240 360 480 600 no mo Time (hr Post-Treatment) INMB non-confidential 6.17.19 | co |
Slide 61: INKmune MOA
| INKmune MOA THTTTTTTTerTs orererenrerrenrerrrtert ZOURUELURUERORUENURCENG| INB16 g _ y: cD16 g NK JT a <—osxll INMB non-confidential 6.17.19 IemruneRie LF, ibe ue i i jul iJ Lf vo Lowdell2007
Slide 62: INB16 vs LAK Priming - Gene Expression Profiles
| INB16 vs LAK Priming - 412 Gene Expression Profiles INmunsRie 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
Slide 63: INB03 HER2/MUC4 Appendix
Slide 64: Trastuzumab Resistance in Breast Cancer
| Trastuzumab Resistance in Breast Cancer wm ap * ~30% of women with breast cancer are HER2+ * 30% - 50% patients have 1° or 2° resistance to trastuzumab * MUC4 expression predicts trastuzumab resistance Disease-free survival probability (%) 100 4 P= 0.0086 s=e= MUC4 negativen= 31 ‘mmm MUC4 posttive
Slide 65: INB03 overcomes trastuzumab resistance in JIMT-1 tumors
INBO3 overcomes trastuzumab resistance in JIMT-1 tumors 500, 400. i Seo 200: x 5 oN $ om. ~T H + ue F 100. ° INBO3 decreases MUC4 expression ° cry % 30 ‘Time of treatment (days) ey a Fa eye woos ——of wrx ‘Ttrastuzumab bd ¢ DN- INBO3 = Schlloc 48052018 Teasturumab INMB non-confidential 6.17.19 ss |