Indaptus Therapeutics, Inc. · NASDAQ:INDP
Indaptus Therapeutics — Investor Presentation (August 2021)
40 slides from Indaptus Therapeutics's investor presentation, Aug 6, 2021
Slide 1: Indaptus Therapeutics Investor Presentation
* Indaptus August 3, 2021 THERAPEUTICS Investor Presentation
Slide 2: Forward Looking Statement
Forward Looking Statement ‘Ths presentation contin forwardicoting totems with he ming ofthe Price Sere Ligation Reform Act. Ther include ttementseganing management's expeiaons bas ond [prema regarding emang ake hing cur product dvsopman efor, busnarsfandaltndon rete of operations rataiee plan and pr
Slide 3: Indaptus Therapeutics
Indaptus Therapeutics With the ability to harness both the body’s innate and adaptive immune responses, we believe we are uniquely positioned to revolutionize the treatment of cancer and certain infectious diseases. Broad Platform Safety Efficacy cmc IP Inflection Timeline Indaptus tmmunology-based
Slide 4: Current Cancer Immunotherapies: Low Percentage Cures for Most Advanced Cancers
Current Cancer Immunotherapies: Low Percentage Cures for Most Advanced Cancers Dele Natural Killer 2 T-cell Tumor = SO Tumor fe) ent eiccat e fA Innate Neutrophi 08+ T-Cell Adaptive 1, @ 1 S 1 coat teen 1 1 ef “Nn if th wtZ. 12 and IFN saad oon Checkpoint CAR-T Current immunotherapies only cure a ve
Slide 5: Improving Cancer Immunotherapy - Indaptus Assumptions
Improving Cancer Immunotherapy - Indaptus Assumptions + We need innate & adaptive pathway activation in lymphoid organs as well as tumor — Tumors promote an immune-suppressive environment ~ Tumors negatively remodel the entire systemic immune system — Most steps required for innate and adaptive immu
Slide 6: Goal is Activation of Both Innate and Adaptive Cellular Pathways
Goal is Activation of Both Innate and Adaptive Cellular Pathways in Multiple Locations No one has figured out how to do this —y \ 7 2» Same aural ler ee Tell ie Innate Natural Killer Cell \ | Dendrite ce Adaptive ==. Macrophage cD4+ T-Cell Tumor Indaptus History provided a clue about how to do this
Slide 7: World's First Immunotherapy: Clinically Validated and Composed of Killed Bacteria
World’s First Immunotherapy: Clinically Validated and Composed of Killed Bacteria * Coley’s Toxins (CT) — based on observation of regression of cancer in setting of infection — Invented by Dr. William Coley at Memorial Sloan Kettering in NYC in 1894 — Composed of heat-killed bacteria * Coley’s Toxin
Slide 8: Immunological Sciences Caught Up to the Clinic in the 1990's
Immunological Sciences Caught Up to the Clinic in the 1990’s Bacteria Contain Immune System Stimulating Danger Signals + The most prominent danger signal family activates Toll-like receptors (TLR) Source Danger Signal (TLR Ligand / Agonist) Toll-Like Receptor Bacteria Lipoproteins, Peptidoglycans TU
Slide 9: Indaptus has Used Modern Science to Optimize and Re-Invent the Approach
Indaptus has Used Modern Science to Optimize and Re-Invent the Approach Decoy Product Result and Predictions * Start with a single, pure strain of non-pathogenic, Gram-negative bacteria * Reduce LPS-endotoxin level by ~90% * Kill the bacteria and stabilize so they remain intact after i.v. administra
Slide 10: Indaptus Result — Effective, Safe and Patented
Indaptus Result — Effective, Safe and Patented Decoy therapeutics exhibit many unique properties — Single agent anti-tumor activity + tumor eradicating synergy with 5 different existing therapies ~ Reduced toxicity and broad therapeutic index (no increase in toxicity with combinations) ~ Safe induct
Slide 11: Decoy Treatment Does Not Impair Anti-Tumor Cytokine/Chemokine Induction
Decoy Treatment Does Not Impair Anti-Tumor Cytokine/Chemokine Induction Despite being less toxic, Decoy therapeutics induce similar amounts eye ee eee cts acl ‘of anti-tumor cytokines and chemokines, Nica nuapentitttmeedse ‘uncoupling toxicity from anti-tumor activity = ° Secretion by = = = ren by t
Slide 12: Single Agent Activity - Metastatic Mouse Pancreatic Carcinoma
Single Agent Activity - Metastatic Mouse Pancreatic Carcinoma Indaptus Percent Survival 100 No Decoy Decoy Treatment | 5x10°7 2x10%8 “© No Trestment Median a 35 Days 41Days 75 Days 80 oe Survival Ys peool | POOL = POOL © some Decoy iv. 2x per week x3 Desay 604 sx1087 Desay * 2008 4 40 Decoy 20108 20
Slide 13: Single Agent Activity - Orthotopic Mouse Colorectal Carcinoma
Single Agent Activity - Orthotopic Mouse Colorectal Carcinoma ‘100 ‘Tumor fragments were sewn onto the cecum wall on Day 0 (7 mice/group) a Dose and regimen not optimized z 3 w © Decoy 2x10"8 iv. 2xper week x3) z Metastasis 5 6. * 11 total in 5 sacrificed mice a * Oin mouse sacrificed on Day 118 = 9
Slide 14: Decoy Synergizes With a Non-Steroidal Anti-Inflammatory Drug (NSAID)
Decoy Synergizes With a Non-Steroidal Anti-Inflammatory Drug (NSAID) to Safely Eradicate Subcutaneous Mouse Hepatocellular Carcinomas (HCC) Treat 6 mice per group with Decoy 2x per week iv. for 7 weeks / Start treatment at 103 mm? Decoy : Decoy Vente Pome 20% Dk NSAIDS reduce Days Ate Tumor Cel impl
Slide 15: Combination With Anti-PD-1 Checkpoint Therapy Produces 100% Complete Responses
Combination With Anti-PD-1 Checkpoint Therapy Produces 100% Complete Responses With Hepatocellular Carcinoma > Control All animals also received NSAID = 3000 z -w- Decoy 2x10°8 Lv. 1x per week x6 ates 2 agq9 | ANIHPD-1 10 mgikg ip. 2x per week x2 Teck: = Decoy — Decoy + anti-PD-1 pe 2 2,000 E ‘Start
Slide 16: Synergistic Eradication of Murine HCC
Synergistic Eradication of Murine HCC Exhibits a Very Wide Decoy Therapeutic Index (233-fold) All animals also received a non-steroidal ant-inflammatory drug (NSAID) No Treatment (6 mice per group) 3x10” Decoy ‘txt0® Decoy Tm i= “018% To “4.10% Fe j j ‘tumors were sil at _ fe a eames i fe ue ‘aye tr
Slide 17: Mice Cured by Decoy + NSAID + Anti-PD-1 and Re-Challenged
Mice Cured by Decoy + NSAID + Anti-PD-1 and Re-Challenged with Fresh HCC Tumor Cells Reject the Tumors (Immunological Memory) Eleven Cured Mice were Re-Challenged with Fresh Six Naive Mice were Challenged HCC Tumor Cells on Day 91 on the Opposite Flank with the Same Tumor Cells as the Cured from the
Slide 18: Decoy Produces Similar Results in Multiple Mouse Models
Decoy Produces Similar Results in Multiple Mouse Models Decoy Therapeutic Synergizes with Low-Dose Chemotherapy (LDC) to Mice Cured by Decoy + LDCand Re-Challenged with Fresh NHL ‘Safely Induce Regression of s.c. Mouse Non-Hodgkin's Lymphoma (NHL) “Tumor Cells Reject the Tumors (Immunological Memory
Slide 19: Decoy Technology Also Regresses Human Tumor Xenografts
Decoy Technology Also Regresses Human Tumor Xenografts ‘Treat § mice per group 2x per week for 3 weeks / Start treatment at 173 mm* 5,000 Riturimab 2x per week ip. x2 NHL standard of care 4,000 = Wwe 3,000 Decoy (2x10"8) 2,000 ituximab (100 ug) -® Decoy + LDC. Decoy +LDC + Rituxmab Decoy +LD¢ Mean T
Slide 20: Decoy Technology can Induce Immunological Memory Via the Innate Immune System
Decoy Technology can Induce Immunological Memory Via the Innate Immune System ‘Tumor Cell Re-Challenge Cell Culture-Matched Tumor Challenge ‘on Day 74 of Naive Mice on Day 74 5 tumorregressed mice from last slide {2ch injested sc. on opposte tank with ‘naive mice each injected 5c with © soca | fresh
Slide 21: Decoy Technology Platform
Decoy Technology Platform Potential utility as anti-viral therapy - Hepatitis B Virus (HBV), HIV and Others HBV is a chronic liver infection affecting 257 million people world-wide — Only 2% treated with current therapies / Major cause of cirrhosis and HCC / 887,000 deaths per year Cytokines have st
Slide 22: Indaptus Clinical Development Plan
Indaptus Clinical Development Plan Pca 2022 2023 2024 2025 we oh an a a ao aaa Dose Escalation Expansion (~2 tumors) Phib Combination Checkpoint / Tergeted Abs /Chemo Key Milestones 1) Determine MTD / Recommended Ph2 dose / Possible efficacy 2) Single agent efficacy 3) Combination efficacy Indaptus
Slide 23: Target Indications Include Some of the World's Deadliest Cancers
Target Indications Include 6 of the World’s 12 Deadliest Cancers 12 Deadliest Cancers World-Wide (DESSyiTargetS) We of Yearly % of Yearly Deaths Cases Indaptus High Unmet Medical Need Percent five-year survival ._| for patients with metastatic disease 3% -17% Source: American Cancer Society 23
Slide 24: Experienced Management and Board of Directors
Experienced Management and Board of Directors Leadership experience in new modalities and early development Roger J. Pomerantz, M.D. Michael J. Newman, Ph.D. Jeffrey Meckler Anthony J. Maddaluna W. Brad Hayes Brian O'Callaghan Hila Karah Hoonmo Lee Indaptus Chairman Founder, CSO, Director CEO, Direc
Slide 25: Thank you.
Thank you.
Slide 26: Appendix
Appendix
Slide 27: There are No Intrinsically "Bad" Cytokines/Chemokines
Indaptus There are No Intrinsically “Bad” Cytokines/Chemokines Good or Bad Depends on Time, Place, Amount and How Long Cytokines and Chemokines Inducing Migration, Activation, Maturation and/or Proliferation GM-CSF, IL-1, IL-4, IL-12, IL-15, IFN-y IL-2, 1L-12, 1L-18, TNF-a IL-AB, IL-8, IFN-y, MIP-ta
Slide 28: How Can Bacterial Danger Signals Activate Anti-Tumor Immunity?
How Can Bacterial Danger ignals Activate Anti-Tumor Immunity? Most Steps Required for Innate and Adaptive Cellular Immune Responses are Non-Specific Indaptus innat oe \ctivation roliferat Kango | | Usasicdnaal fee Raieelecend Dendritic Cell Innate Cellular Immune Response Adaptive Cellular Immune Re
Slide 29: Toll-Like Receptor (TLR) Agonists from Bacteria Directly Activate Immune Cells
Toll-Like Receptor (TLR) Agonists from Bacteria Directly Activate Immune Cells and Indirectly Activate by Inducing Secretion of Cytokines and Chemokines Macrophage Neutrophil Natural Killer Cell Natural Killer T-Cell “ve mie ED) Effector hes. A exam cn inion af / cytokines and chemokines IAB, IL2, I
Slide 30: Patented Decoy Treatment Kills Bacteria and Significantly Reduces LPS-Endotoxin Activity
Patented Decoy Treatment Kills Bacteria and Significantly Reduces LPS-Endotoxin Activity and In Vivo Pyrogenicity NoTreatment 100% 44.7 Units / 10° Bacteria 3x10* Bacteria Decoy 0 3.6 Units / 10° Bacteria 9x10° Bacteria : 97% reduction Change induced Killed all rosea t reac igpgeaiest! | ERESHD incr
Slide 31: Decoy Therapeutic Synergizes with Human PBMCs to Kill Human Breast Carcinoma Cells
Decoy Therapeutic Synergizes with Human PBMCs to Kill Human Breast Carcinoma Cells In Vitro 20000. = 70000: No Addition Decoy10 PBMC — Decoy +PBMC 7 Days in Culture Killed, non-pathogenic Decoy therapeutic is not intrinsically toxic to tumor cells (broad dose-response not shown), but can activate im
Slide 32: Tumor-Eradicating Combinations Transform "Cold" HCC Tumors to "Hot"
Tumor-Eradicating Combinations Transform “Cold” HCC Tumors to “Hot” Fold increase in Tumor Inflammation Signature Score (TIS) Treatment Effects on Tumor Volume: ‘SGoldt va “Hat! Temor: (RNA prepared on Day 8 for NanoString Analysis) = 800 NT 016 i 3 “NSAID 1.68 0/6 ane “e Decoy 161 0/6 3 + aPD-1 230
Slide 33: Systemic Administration of Decoy Therapy, NSAID and Anti-PD-1 Induces Cytokine Immune Pathways
Systemic Administration of Decoy Therapy, NSAID and Anti-PD-1 Induces Cytokine Immune Pathways in HCC Tumors o Cg SP A SP PF A MK aE ey NanoString 770 gene expression analysis: \Indaptus
Slide 34: Systemic Administration of Decoy Therapy, NSAID and Anti-PD-1 Induces Chemokine Immune Pathways
Systemic Administration of Decoy Therapy, NSAID and Anti-PD-1 Induces Chemokine Immune Pathways in HCC Tumors Zo gt ot PAP PM A ME NanoString 770 gene expression analysis: ‘Chemokines and Receptors in tumor ‘Mice with 200 mm? tumors were treated for 1 week before ‘tumor removal and RNA isolationiana
Slide 35: Systemic Administration of Decoy Therapy, NSAID and Anti-PD-1 Induces Innate Immune Pathways
Systemic Administration of Decoy Therapy, NSAID and Anti-PD-1 Induces Innate Immune Pathways in HCC Tumors Ms “ ‘NanoString 770 gene expression analysis: Innate Immune response in tumor ‘Mice with 200 mm? tumors were treated for 1 week before ‘tumor removal and RNA isolation/analysis {Each horzentl
Slide 36: Systemic Administration of Decoy Therapy, NSAID and Anti-PD-1 Induces Adaptive Immune Pathways
Systemic Administration of Decoy Therapy, NSAID and Anti-PD-1 Induces Adaptive Immune Pathways in HCC Tumors \Indaptus ‘NanoString 70 gene expression analysis: for 1 week before ‘tumor removal and RNA isolation/analysis oe face fe ie Each horizontal row represents | adiferent adaptive pathway gene
Slide 37: NHL Tumors That Regrow After Sub-Optimal Decoy + LDC Treatment are Sensitive to Retreatment
Indaptus NHL Tumors That Regrow After 1 or 2 Weeks of Sub-Optimal Decoy + LDC Treatment are Sensitive to Optimal Retreatment 3,000 tumorsregresed O2Y End nd and then regrew 2 ‘Same eght mice retrsteg ford weeks ‘th 3108 Decoy ‘FDC staring day 50 Eight mie ested with suboptimal Decoy ose or only eate
Slide 38: High Percentage Eradication of s.c. NHL by Decoy + LDC Requires NK Cells and T Cells
High Percentage Eradication of s.c. NHL by Decoy + LDC Requires NK Cells and CD4+ and CD8+ T Cells ‘Treat all groups (6 mice per group) with iv. Decoy + LDC for 2 weeks / Start treatment at “200 mm? 4,500 +-Decoy + Le — (cD 4+ and CDe+ =-98% Depletion of NK Cells Day 70 no durable OR “100% Depletion
Slide 39: Frequently Asked Question
Indaptus Frequently Asked Question Q) Humans are more sensitive than mice to the toxic effects of TLR agonists such as LPS. Does this mean that the Decoy product will be too toxic in humans? A) Humans are also more sensitive than mice to anti-tumor cytokine induction by TLR agonists, so if there is
Slide 40: Decoy Therapy Induces Human PBMCs to Secrete Higher Levels of Anti-Tumor Cytokines Than Mouse PBMCs
Indaptus Decoy Therapy Induces Human PBMCs to Secrete ~100 to 3,500 Times Higher Levels of Anti-Tumor Cytokines Compared to Mouse PBMCs Based on 48 hour in vitro (full) dose responses carried out in triplicate Fold increase in sensitivity of human PBMCs, relative to mouse PBMCS. 2,383 405 3,453 100,
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