Indaptus Therapeutics, Inc. · NASDAQ:INDP
Indaptus Therapeutics — Investor Presentation (November 2021)
42 slides from Indaptus Therapeutics's investor presentation, Nov 15, 2021
Slide 1: Investor Presentation
nda OTUS November 15, 2021 THERAPEUTICS Investor Presentation
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward‐looking statements with the meaning of the Private Securities Litigation Reform Act. These include statements regarding management’s expectations, beliefs and intentions regarding, among other things, our product development efforts, busi
Slide 3: Current Cancer Immunotherapies: Low Percentage Cures for Most Advanced Cancers
Current Cancer Immunotherapies: Low Percentage Cures for Most Advanced Cancers Gamma‐ TAA Delta Natural Killer T‐Cell T‐Cell Tumor Tumor Natural Killer Cell Dendritic Cell Innate Neutrophil CD8+ T‐Cell Adaptive TAA Macrophage CD4+ T‐Cell Targeted Antibodies IL‐2 and IFN‐α T‐vec/GM‐CSF Checkpoint CAR
Slide 4: 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 5: Goal is Activation of Both Innate and Adaptive Cellular Pathways in Multiple Locations
Goal is Activation of Both Innate and Adaptive Cellular Pathways in Multiple Locations No one has figured out how to do this safely Gamma‐ TAA Delta Natural Killer T‐Cell T‐Cell Innate Natural Killer Cell Dendritic Cell Adaptive Neutrophil CD8+ T‐Cell TAA Macrophage CD4+ T‐Cell Tumor History provide
Slide 6: 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 7: Scientific Knowledge Lagged Behind Clinical Validation
Scientific Knowledge Lagged Behind Clinical Validation • FDA required to certify old and new drugs in 1962 and decided not to grandfather‐in CT as an approved drug in 1963, despite cures, due to variability in clinical response • Pharmaceutical industry abandoned the product – Mechanism of action wa
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 TL
Slide 9: High Levels of TLR4 Agonist Lipopolysaccharide (LPS) Produce I.V. Toxicity
High Levels of TLR4 Agonist Lipopolysaccharide (LPS) Produce I.V. Toxicity • The most prominent danger signal family activates Toll‐like receptors (TLR) Source Danger Signal (TLR Ligand / Agonist) Toll‐Like Receptor Bacteria Lipoproteins, Peptidoglycans TLR2 (1/2, 6/2) Viruses (Bacteria?) Double Str
Slide 10: 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 • Decoy therapeutic is significantly less toxic non‐pathogenic, Gram‐negative bacteria in vivo than untreated bacteria and several live competitor produc
Slide 11: 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 12: 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 Decoy therapeutics are more broadly active of anti‐tumor cytokines and chemokines, than mono‐specific TLR agonists uncoupling toxicity from anti‐tumor activity
Slide 13: Single Agent Activity - Metastatic Mouse Pancreatic Carcinoma
Single Agent Activity ‐ Metastatic Mouse Pancreatic Carcinoma 100 No Decoy Decoy Gem Treatment 5x10^7 2x10^8 No Treatment Median 35 Days 41 Days 75 Days 27 Days 80 Gemcitabine Survival P<0.01 P<0.01 P<0.01 50 mg/kg Log-Rank Test Decoy20 vs. No Treatment Decoy20 Decoy i.v. 2x perBoth week x3 Doses P
Slide 14: Single Agent Activity - Orthotopic Mouse Colorectal Carcinoma
Single Agent Activity ‐ Orthotopic Mouse Colorectal Carcinoma 100 Tumor fragments were sewn onto the 90 cecum wall on Day 0 (7 mice/group) 80 Dose and regimen not optimized Percent Survival 70 Decoy 2x10^8 (i.v. 2x per week x 3) Metastasis 60 Decoy10 2x10^8 • 11 total in 5 sacrificed mice (2x per we
Slide 15: Decoy Synergizes With NSAID to Safely Eradicate Mouse HCC
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 i.v. for 7 weeks / Start treatment at 103 mm3 4,000 4,000 Decoy Decoy Tumor Volume (mm3) Tumor Volume (mm3) 3,000
Slide 16: Combination With Anti-PD-1 Produces 100% Complete Responses With HCC
Combination With Anti‐PD‐1 Checkpoint Therapy Produces 100% Complete Responses With Hepatocellular Carcinoma 3,500 Control Control (6 mice per Indomethacin All group) animals also received NSAID 3,000 Decoy 2x10^8 Indomethacin i.v. 1xDecoy10 + 2x10^8 per week x6 x6 1x/week Mean Tumor Volume (mm3 ± S
Slide 17: Synergistic Eradication of Murine HCC Exhibits Very Wide Therapeutic Index
Synergistic Eradication of Murine HCC Exhibits a Very Wide Decoy Therapeutic Index (≥33‐fold) All animals also received a non‐steroidal anti‐inflammatory drug (NSAID) No Treatment (6 mice per group) 3x107 Decoy 1x108 Decoy 4,000 1,000 1,000 Tumor Volume (mm3) Tumor Volume (mm3) Tumor Volume (mm3) 3,
Slide 18: Cured Mice Re-Challenged with Fresh HCC Tumor Cells Reject the Tumors
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 Naïve Mice were Challenged HCC Tumor Cells on Day 91 on the Opposite Flank with the Same Tumor Cells as the Cured from the
Slide 19: 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 + LDC and 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 20: Decoy Technology Also Regresses Human Tumor Xenografts
Decoy Technology Also Regresses Human Tumor Xenografts Treat 5 mice per group 2x per week for 3 weeks / Start treatment at 173 mm3 5,000 Mean Tumor Volume (mm3 ± SEM) Rituximab 2x per week i.p. x 3 NHL standard of care 4,000 Control Control LDC(20 mg/kg) LDC 3,000 Decoy (2x10^8) Decoy10 (2x10^8) Con
Slide 21: 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 4,000 4,000 5 tumor-regressed mice from last slide 5 naïve mice each each injected s.c. on opposite flank with injected s.c. wi
Slide 22: Decoy Technology Platform: Potential Anti-Viral Utility
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 hav
Slide 23: Indaptus Clinical Development Plan
Indaptus Clinical Development Plan 2021 2022 2022 2023 2023 2024 2024 2025 2025 2026 Q3/4 Q1/2 Q3/4 Q1/2 Q3/4 Q1/2 Q3/4 Q1/2 Q3/4 Q1/2 Dose Escalation Single Ascending Doses Expansion Multiple Doses All Comers Then Focus Ph1b Combination Checkpoint / Targeted Abs / Chemo? 23
Slide 24: Target Indications Include 6 of the World's 12 Deadliest Cancers
Target Indications Include 6 of the World’s 12 Deadliest Cancers 12 Deadliest Cancers World-Wide (Decoy Targets) % of Yearly % of Yearly Deaths Cases High Unmet Medical Need 1 Lung 18.4 11.6 2 Colorectal 9.0 10.0 3 Stomach 8.2 5.7 4 Liver 8.2 4.7 Percent five‐year survival 5 Breast 6.6 11.6 for pati
Slide 25: 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. Chairman Michael J. Newman, Ph.D. Founder, CSO, Director Decoy Biosystems Jeffrey Meckler CEO, Director Anthony J. Maddaluna Director W. Brad Hayes Director Brian O’Ca
Slide 26: Thank you.
Thank you. 26
Slide 27: Appendix
Appendix 27
Slide 28: There are No Intrinsically "Bad" Cytokines/Chemokines
There are No Intrinsically “Bad” Cytokines/Chemokines Good or Bad Depends on Time, Place, Amount and How Long Cytokines and Chemokines Responsive Immune Cell Type: Inducing Migration, Activation, All Participate in Maturation and/or Proliferation Anti-Tumor Immune Responses GM-CSF, IL-1β, IL-4, IL-1
Slide 29: How Can Bacterial Danger Signals Activate Anti-Tumor Immunity?
How Can Bacterial Danger Signals Activate Anti-Tumor Immunity? Most Steps Required for Innate and Adaptive Cellular Immune Responses are Non-Specific Tumor Tumor Non-Specific Specific Innate Cellular Immune Response Cell Killing of Innate Cell Migration Activation Proliferation Recognition Tumor Cel
Slide 30: TLR Agonists from Bacteria Directly and Indirectly 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 TLR TAA TLR Innate TLR TLR Effector TLR TLR TLR TLR Example anti-tumor/anti-viral c
Slide 31: 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 Pyrogenicity Live LPS Endotoxin Activity Treatment Threshold Bacteria (LAL Assay) (Rabbit Assay) No Treatment 100% 44.7 Units / 106 Bacteria 3x104 Bacteria Decoy 0 3.6 Units / 106 Bacter
Slide 32: Decoy Therapeutic Synergizes with Human PBMCs to Kill Breast Carcinoma Cells
Decoy Therapeutic Synergizes with Human PBMCs to Kill Human Breast Carcinoma Cells In Vitro 80000 70000 Tumor Cells Per Well (+/- SEM) 60000 50000 40000 30000 20000 10000 0 No Addition Decoy10 PBMC Decoy + PBMC 7 Days in Culture 1 Killed, non-pathogenic Decoy therapeutic is not intrinsically toxic t
Slide 33: 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) “Cold” vs. “Hot” Tumor SEM) 0/6 1.68 0/6 1.61 0/6 Tumor Volume (mm3 2.30 0/6 2.21 2/6 2.92 1 to 2 / 6 3.60 2/6 5.89 5 to 6 / 6 Number of long-term regressions (6 mice per gro
Slide 34: Induces Cytokine Immune Pathways in HCC Tumors
Systemic Administration of Decoy Therapy, NSAID and Anti-PD-1 Induces Cytokine Immune Pathways in HCC Tumors NanoString 770 gene expression analysis: Cytokines and Log base 2 scale Receptors in tumor Mice with 200 mm3 tumors were treated for 1 week before Each horizontal row represents a different t
Slide 35: Induces Chemokine Immune Pathways in HCC Tumors
Systemic Administration of Decoy Therapy, NSAID and Anti-PD-1 Induces Chemokine Immune Pathways in HCC Tumors NanoString 770 gene expression analysis: Chemokines and Receptors in tumor Mice with 200 mm3 tumors were treated for 1 week before Each horizontal row represents a different tumor removal an
Slide 36: Induces Innate Immune Pathways in HCC Tumors
Systemic Administration of Decoy Therapy, NSAID and Anti-PD-1 Induces Innate Immune Pathways in HCC Tumors NanoString 770 gene expression analysis: Innate Immune response in tumor Mice with 200 mm3 tumors were treated Each horizontal row represents for 1 week before a different innate pathway gene t
Slide 37: Induces Adaptive Immune Pathways in HCC Tumors
Systemic Administration of Decoy Therapy, NSAID and Anti-PD-1 Induces Adaptive Immune Pathways in HCC Tumors NanoString 770 gene expression analysis: Adaptive Immune response in tumor Mice with 200 mm3 tumors were treated Each horizontal row represents for 1 week before a different adaptive pathway
Slide 38: NHL Tumors That Regrow are Sensitive to Optimal Retreatment
NHL Tumors That Regrow After 1 or 2 Weeks of Sub-Optimal Decoy + LDC Treatment are Sensitive to Optimal Retreatment 3,000 Tumors regressed Day End 2nd 50 treatment and then regrew Same eight mice retreated for 2 weeks 2,500 with 3x10^8 Decoy + LDC starting day 50 Tumor Volume (mm3) 2,000 1,500 Eight
Slide 39: Eradication of s.c. NHL Requires NK Cells and CD4+ and CD8+ 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 i.v. Decoy + LDC for 2 weeks / Start treatment at ~200 mm3 4,500 Deplete Decoy10 + LDC + LDC 4,000 CD4+ and CD8+ Mean Tumor Volume (mm3 ± SEM) 98% Depletion of
Slide 40: Frequently Asked Question
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 a therape
Slide 41: Decoy Therapy Induces Human PBMCs to Secrete Higher Levels of Cytokines
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 100,000 2,393 105 3,453 429 Cy
Slide 42: Bacterial "Danger Signals" Approved to Prevent or Treat Early Stage Cancer
Bacterial “Danger Signals” Approved to Prevent or Treat Early Stage Cancer Bacillus Calmette-Guérin (BCG) (Sanofi/Merck) • Tuberculosis vaccine (1921) made from live, attenuated Mycobacterium bovis • Approved for superficial bladder cancer via local (intravesical) administration Picibanil™ (OK-4
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