Pds Biotechnology Corporation · NASDAQ:PDSB
Pds Biotechnology — Investor Presentation (October 2019)
57 slides from Pds Biotechnology's investor presentation, Oct 29, 2019
Slide 1: A new generation of multi-functional cancer immunotherapies
A new generation of multi-functional cancer immunotherapies October 2019Products, Clinical Indications and Scientific Overview
Slide 2: Forward-Looking Statements
Forward-Looking Statements 2 This presentation contains forward-looking statements about PDS Biotechnology Corporation (“PDSB”), and its businesses, business prospects, strategies and plans, including but not limited to statements regarding anticipated preclinical and clinical drug development activ
Slide 3: Table of Contents
3 Table of Contents Introduction to the Versamune® -based immunotherapies Slide 3Versamune® Products: Clinical and commercialization strategy Slide 8PDS0101 product: Clinical trials, markets, immunology & efficacy Slide 10Versamune® oncology pipeline – preclinical stage Slide 18PDS0102 for prostate
Slide 4: Versamune Overcomes key Limitations of Immunotherapy
Versamune® Overcomes key Limitations of Immunotherapy 4 Limitations of T-Cell Activators Cancer vaccines have been unsuccessful in generating strong in-vivo killer (CD8+) T-cells necessary for therapeutic benefitAdjuvant technologies have been unsuccessful in facilitating antigen* processing and pre
Slide 5: Introduction to the Versamune Platform Technology
5 Introduction to the Versamune® Platform Technology The proprietary Versamune® platform technology is based on structure-specific positively charged (cationic) and immune activating lipids that form spherical liposomal nanoparticles in aqueous media and are sized to mimic viruses Water-soluble & po
Slide 6: Multi-Functional Versamune Platform Overcomes key Limitations of Immunotherapy
Multi-Functional Versamune® Platform Overcomes key Limitations of Immunotherapy 6 Engineered to promote in-vivo induction of tumor-recognizing and attacking killer (CD8+) T-cells* Trains killer T-cells to recognize & attack cancer Activates powerful T-cells to attack cancer cells Makes tumors more s
Slide 7: Unique Versamune-Based Immunotherapies Present Advantages in Efficacy, Manufacturing, Administration
Unique Versamune®-Based Immunotherapies Present Advantages in Efficacy, Manufacturing, and Administration 7 Vials Versamune® Formulations By Electron Microscopy Vial of Versamune® Vial of Tumor antigens Versamune® Proprietary tumor antigens Mixed Bedside
Slide 8: Versamune Immunotherapies: Clinical Development Strategy
8 Versamune® Immunotherapies: Clinical Development Strategy Checkpoint inhibitors have shown confirmed clinical efficacy and have demonstrated clinical benefit in late stage cancer.Checkpoint inhibitors work by blocking one of the cancer’s key immunological defense mechanisms, and are reported to on
Slide 9: Synergy of Versamune + Tumor Antigen and Checkpoint Inhibitor in B16 Melanoma Model
Synergy of Versamune® + Tumor Antigen and Checkpoint Inhibitor: Demonstrated in Aggressive & Difficult-to Treat B16 Melanoma Model 9 Versamune® + TRP2 (PDS0104) injection demonstrates strong synergy in combination with a checkpoint inhibitor in B16 melanoma – Provides significantly prolonged surviva
Slide 10: PDS0101 Immunotherapy for Advanced HPV-Associated Cancers
10 PDS0101 Immunotherapy for Advanced HPV-Associated Cancers PDS0101 is based on two key components:Proprietary mixture of six HPV16 E6 and E7 multi-epitope peptides designed to address over 90% of the population. HPV16 causes the vast majority of the HPV associated cancers. In a human clinical tria
Slide 11: PDS0101 Phase Combination Trials with Leaders in Immuno-Oncology
PDS0101 Phase 2 Combination Trials with Leaders in Immuno-Oncology 11 11 PDS Product Indication Partner Added Combination Product Study Size PDS0101(HPV-Cancer) Head & neck cancer First line treatment Recurrent/metastatic KEYTRUDA®FDA-approved 96 subjects20 US sites Advanced HPV cancers Confidential
Slide 12: HPV-Associated Cancer Annual Incidences – United States
HPV-Associated Cancer Annual Incidences – United States* 12 12 HPV experts project that current HPV preventive vaccines will have little impact on HPV-related cancer incidences over next twenty-plus years** * CDC Data Brief, August 2018 – based on data collected 2011-2015** 2016 Report by Dr. Laurie
Slide 13: PDS0101 Proprietary formulation: Peptide Micelles with Versamune
13 PDS0101 Proprietary formulation: Mixture of Peptide Micelles with Versamune® Promotes Superior CD8+ T-Cell Response Comparison of Micellar vs. Traditional Encapsulation Methods - IFN-γ ELISPOT Shows Superior Potency of the PDS Micellar Approach* DOPC and DOTMA (Lipids covered under Versamune®-cla
Slide 14: Versamune: Superior Antigen Processing & Presentation Promotes Killer T-Cells
Versamune®: Superior Antigen Processing & Presentation Promotes Superior Quantity & Quality Tumor-Attacking Killer T-Cells In-Vivo 14 500 1,000 1,500 2,000 PDS0101* Cytokine/E7* Electroporation# Live Vector Vaccine## # of HPV-Recognizing T-CellsIFN-γ Spot Forming Cells/1X106 Spleen cells Versamune®
Slide 15: PDS0101: Superior Ability to Eliminate HPV-Positive TC-1 Tumors
PDS0101: Promotes Superior Ability to Eliminate HPV-Positive TC-1 Tumors & Generates Sustained (Memory) T-Cell Response 15 In vivo induction of superior quantity & quality of tumor-specific CD4+ and CD8+ T-cells result in complete regression & effective T-cell memory after a single dose* *J. Immunol
Slide 16: Human clinical results: Phase 1/2a Dose Escalating Study
Human clinical results: Phase 1/2a Dose Escalating Study Shows Potent HPV16 CD8+ T-Cell Induction by Granzyme-b ELISPOT Clinical Study DesignOpen-label studyCervical Intraepithelial Neo-plasia (CIN) & high-risk HPV infection3 cohorts, each 3-6 subjectsEvaluated safety, tolerability & T-cell immunoge
Slide 17: PDS0101: Follow-up Data Supports Strong Killer T-Cell Induction, CIN Clearance
PDS0101: Phase 1 Follow-up Data Supports Observed Strong Killer T-Cell Induction Causing Clearance of CIN Lesions in 60% of Evaluable Patients 17 PDS0101 was immunologically active at all three doses resulting in 5 to 73-fold increase in circulating HPV disease-attacking T-cells in 10/12 subjectsCle
Slide 18: Developing Broad Product Pipeline with Leaders in I-O
Developing Broad Product Pipeline with Leaders in I-O 18 Product Indication Partner Combination Status PDS0102(TARP) Prostate and breast cancers Checkpoint Inhibitor Preclinical studies ongoing PDS0103(MUC-1) Ovarian, colorectal, lung, breast cancers TBD Checkpoint Inhibitor Preclinical studies ongo
Slide 19: PDS0102 Immunotherapy for Prostate Cancer
19 PDS0102 Immunotherapy for Prostate Cancer PDS0102 is based on two key components:The novel and proprietary TARP protein, a tumor antigen identified by the National Cancer Institute (NCI) that is expressed in about 90% of prostate cancers at all stages of the disease. In a human clinical trial the
Slide 20: Clinical Development of PDS0102
20 Clinical Development of PDS0102: PDS Biotechnology has signed a collaborative research and development agreement (CRADA 03039) with the National Cancer Institute to co-develop PDS0102 (NCI-patented TARP cancer antigen with R-DOTAP):Checkpoint inhibitors have shown confirmed clinical activity and
Slide 21: PDS0102: R-DOTAP May Provide Superior Anti-TARP Killer T-Cell Response
21 PDS0102: R-DOTAP May Provide Superior In-Vivo Ability to Generate Significantly Enhanced Anti-TARP Killer T-Cell Response* *Ongoing preclinical development at PDS Biotechnology CFA +TARP (1-20) R-DOTAP +TARP (1-20) Number of TARP-Specific T-cells(Interferon-γ spot forming cells per million spleno
Slide 22: Planned PDS0102 Clinical Development Timeline
22 Formulation Optimization GMP ManufacturingPeptide, R-DOTAP First Patient DosedQ4 2020/Q1 2021 Late Q1, 2020 Q3, 2020 Planned PDS0102 Clinical Development Timeline* *Assumes additional funding to support development.
Slide 23: PDS0103 Immunotherapy for Breast, Colon, Lung & Ovarian Cancers
23 PDS0103 Immunotherapy for Breast, Colon, Lung & Ovarian Cancers PDS0103 is based on two key components:The novel and proprietary peptide agonist epitopes of the MUC-1 oncoprotein, developed and patented by the National Cancer Institute (NCI). The novel analogs provide significantly higher immunog
Slide 24: PDS0103: R-DOTAP May Provide Superior Anti-MUC1 Killer T-Cell Response
24 PDS0103: R-DOTAP May Provide Superior In-Vivo Ability to Generate Significantly Enhanced Anti-MUC1 Killer T-Cell Response* *Ongoing preclinical development at PDS Biotechnology**P < 0.05 R-DOTAP + MUC1 Antigens (V1A, V2A, C1A, C2A)Sucrose + MUC1 Antigens (V1A, V2A, C1A, C2A) Montanide – LTR agoni
Slide 25: PDS0104 Immunotherapy for Melanoma
25 PDS0104 Immunotherapy for Melanoma PDS0104 is based on two key components:Well established melanoma antigens including TRP-2 modified according to PDS’ patented micellar approach. Excellent ability to break immune tolerance in the highly immunosuppressive B16 tumor model has been demonstrated.* E
Slide 26: Pre-clinical Metastatic Melanoma: PDS0104 TRP2-Specific CD8+ T-Cells
26 Pre-clinical Metastatic melanoma (Lung metastases): Single injection of Versamune® + melanoma-specific antigen leads to potent T-cell attack against tumors PDS0104: Potent TRP2-Specific CD8+ T-Cells Break Immune Tolerance in Difficult-To-Treat B16 Melanoma Percentage of CD4+ and CD8+ among all ce
Slide 27: Versamune Mechanisms of Action
Versamune® Mechanisms of Action 27
Slide 28: R-DOTAP + Antigens: Addressing Limitations of Immuno-Oncology
R-DOTAP+ Antigens*: Addressing Limitations of Immuno-Oncology 28 1. SUPERIOR IN-VIVO TRAINING OF THE BODY’S SOLDIERS (KILLER T-CELLS) TO RECOGNIZE THE ENEMY (TUMOR CELLS) Injection SiteInitiation of the immunological events Versamune® design & size promotes high uptake of the immunotherapy bydendrit
Slide 29: The Potency of Versamune: SubQ Injection Initiates Immunological Cascade
29 R-DOTAP nanoparticles S-DOTAP nanoparticles The POTENCY of Versamune®: SubQ injection Initiates a Powerful & Targeted Cascade of Critical Immunological Events First ever demonstration of effect of lipid enantiomeric specificity on immune activation is shown in the histology of the injection site*
Slide 30: Targeting Specificity of Versamune: Taken up by Dendritic Cells
The Targeting SPECIFICITY of Versamune®: Designed to be Taken up Predominantly by Dendritic Cells 30 Dendritic cells (DC) or epithelial cell line (TC1) incubated with DQ-OVA (fluoresces UPON UPTAKE & PROCESSING) alone or with VARYING DOSES OF R-DOTAP Plot shows the fluorescent intensity – R-DOTAP pr
Slide 31: Targeting Specificity of Versamune: Dendritic Cell Uptake and Migration
The Targeting SPECIFICITY of Versamune®: Designed to be Taken up Predominantly by Dendritic Cells 31 Subcutaneous injection of Mice with Versamune® + HPV leads to high uptake by dendritic cells (DC) & subsequent activation and migration to lymph nodes* Mice were injected with Versamune®/HPV containi
Slide 32: Versamune Promotes Superior Antigen Processing and Presentation
32 Versamune® Promotes Superior Antigen Processing and Presentation R-DOTAP induced protein uptake and processing(green fluorescence) R-DOTAP induced peptide accumulation in endosome(red fluorescence) R-DOTAP+DQ-OVA DQ-OVA Confocal microscopy: Incubation of fluorescent DQ-OVA with human THP1 monocyt
Slide 33: Versamune Overcomes Limitations of Adjuvants to Promote Antigen Processing
33 Versamune® Overcomes Limitations of Adjuvants to Promote Antigen Processing and Endosome Accumulation Flow Cytometry: Incubation of fluorescent DQ-OVA (OVA) with mouse bone marrow derived dendritic cells with R-DOTAP or the TLR-agonist LPS shows enhanced uptake, processing and endosomal accumulat
Slide 34: Superior Antigen Presentation by Versamune: In-Vivo Antigen Presentation
34 Adoptive transfer mice were produced using CFSE labeled DO11.10 T cells (TCR transgenic, class II restricted, OVA specific) or OT1 T cells (TCR transgenic, class I restricted, OVA specific). Mice were immunized 24h later subcutaneously with 0.25 μg (OT1) or 1μg (DO11.10) whole OVA alone or mixed
Slide 35: Versamune: Overcoming the Limitations of Immuno-Oncology
Versamune®: Overcoming the Limitations of Immuno-Oncology 35 Confirmed mechanistic property of Versamune® – Efficient antigen cross presentation overcomes key limitations of competing approachesEfficient uptake by dendritic cells at site of injection and migration to lymph nodes leads to very low sy
Slide 36: R-DOTAP + Antigens: Activation and Expansion of Primed T-Cells
R-DOTAP + Antigens: Addressing Limitations of Immuno-Oncology 36 2. SUPERIOR ACTIVATION AND EXPANSION/PROLIFERATION OF THE PRIMED ANTIGEN-SPECIFIC HELPER (CD4) AND KILLER (CD8) T-CELLS Lymph NodesLocalized immune activation and expansion Versamune® activates theType I interferon (IFN I) pathway Acti
Slide 37: Versamune Upregulates Type I Interferon Genes
37 Versamune® Upregulates Type I Interferon Genes for Effective CD8+ T-Cell Induction & Activation Activated dendritic cells from the lymph nodes after a single injection of R-DOTAP were analyzed for gene expression. The study identified expression of Interferon–alpha 1 (IFNα1) and interferon-beta 1
Slide 38: Versamune Induces CD8+ T-Cells Primarily Via Type I Interferon
38 Versamune® Induces Superior Levels of Antigen Specific CD8+ T-Cells Primarily Via Type I Interferon Induction Versamune® uniquely activates a specific immunological pathway that promotes effective CD8 T-cell induction Evaluation of HPV-specific CD8+ T-cell response (Wild Type mice) (Type I IFN de
Slide 39: Type I Interferons Upregulated Via Activation of the Myd88 Pathway
39 Specificity of the Versamune® Effect: Type I Interferons are Upregulated Via Activation of the Myd88 Pathway R-DOTAP mediates its CTL-inducing effects by activating type I IFN in a Myd88-dependent manner. The T-cell responses were eliminated only in Myd88 or IFNAR (Type 1 IFN) knockout mice, but
Slide 40: Versamune Induces Activation and Maturation of Human Dendritic Cells
40 Mechanism of Immune Activation: Versamune® Induces Activation and Maturation of Human Dendritic cells The cationic lipids R-DOTAP (R-D) and S-DOTAP (S-D) and a positive control (PC) known to induce maturation of dendritic cells were incubated with human dendritic cells from donors and compared wi
Slide 41: Versamune Upregulates Critical Danger Signals in Human Cells
41 Mechanism of Immune Activation: Versamune® Upregulates Critical “Danger Signals” in Human Cells In an independent NCI study R-DOTAP showed strong induction of cytokines and chemokines as well as the upregulation of important “danger signals”. Danger signals released by cells provide signals neces
Slide 42: Sustained Activity of Versamune: Prolonged Chemokine Induction in Lymph Nodes
42 Versamune®-activated dendritic cells migrate to the LN. Upregulation of type I interferons results in, elevated chemokine levels which persist for several days after a subcutaneous injection – LN localization promotes superior CD8+ T-cell activation & proliferation Sustained activity of Versamune
Slide 43: Localized Immune Responses and Negligible Systemic Cytokines
43 Negligible increases above baseline in systemic cytokine levels with R-DOTAP or PDS0101Localized cytokine induction in lymph nodes results in superior potency and safety Unique mechanism of Versamune® IMMUNE ACTIVATION: Localized Immune Responses & Negligible Systemic Cytokines CCL2
Slide 44: Chemokine-Induced T-Cell Infiltration into Lymph Nodes Persists
44 Elevated T-cell levels persist in LNs for greater than 7 days after 1 subcutaneous injection Sustained activity of Versamune®: Chemokine-Induced T-Cell Infiltration into Lymph Nodes Persists For Several Days
Slide 45: Versamune: Superior Antigen Processing & Presentation Promotes Killer T-Cells
Versamune®: Superior Antigen Processing & Presentation Promotes Superior Quantity & Quality Tumor-Attacking Killer T-Cells In-Vivo 45 500 1,000 1,500 2,000 PDS0101* Cytokine/E7* Electroporation# Live Vector Vaccine## # of HPV-Recognizing T-CellsIFN-γ Spot Forming Cells/1X106 Spleen cells Versamune®
Slide 46: Versamune Upregulates CD69 on T-Cells to Sequester in Lymph Nodes
46 Versamune® Upregulates CD69 on T-Cells to Sequester in Lymph Nodes for Enhanced Dendritic Cell Interaction & Superior Priming Elevated upregulation of Type I Interferons results in CD69 induction and facilitates dendritic cell - T-cell interactions in the draining lymph nodes (R-DOTAP superior to
Slide 47: R-DOTAP/HPV More Effective than S-DOTAP/E7 in Killing HPV-E7 Positive Target
47 R-DOTAP/HPV More Effective than S-DOTAP/E7 in Killing In Vivo HPV-E7 Positive Target After a Subcutaneous Injection* S-DOTAP/HPV killing efficacy was suppressed in the presence of a tumor. R-DOTAP/HPV killing efficacy was independent of the presence of a tumor P > 0.05No difference P < 0.05Statis
Slide 48: Versamune: Overcoming the Limitations of Immuno-Oncology
Versamune®: Overcoming the Limitations of Immuno-Oncology 48 Confirmed mechanistic property of Versamune® – Specific and localized induction of type 1 IFNs overcomes key limitations of competing approachesActivation of type I interferons coupled with efficient antigen cross presentation promotes pow
Slide 49: Altering the Tumor Microenvironment to Break Immune Tolerance
49 3. ABILITY TO ALTER THE TUMOR MICROENVIRONMENT TO MINIMIZE THE TUMOR’S IMMUNE SUPPRESSIVE CAPABILITY AND TO BREAK IMMUNE TOLERANCE Tumor SiteActivated T-cells perform killing functions R-DOTAP+ Antigens: Addressing Limitations of Immuno-Oncology Potent killer and helperT-cells migrate into tumors
Slide 50: Lowering Treg to CD8+ T-Cell Ratio Makes Tumors Susceptible to Killing
50 Significant lowering of the Treg to CD8+ T-Cell ratio causes the tumors to be much less immuno-suppressive and thus more susceptible to killing by T-cells BREAKING IMMUNE TOLERANCE WITH Versamune®: R-DOTAP + HPV Antigens Significantly Alters the Tumor Microenvironment Legend: A – HPV16 antigen; R
Slide 51: Lowering Treg to CD8+ Ratio Promotes Tumor Lysis and Regression
51 Lowering of the Treg to CD8+ T-Cell ratio with the right phenotype of polyfunctional CD8 and CD4 T-cells promotes effective tumor lysis and regression (PDS0101) (PDS0101+GMCSF) potency of Versamune®: Versamune® + HPV Antigens Significantly Alters the Tumor Microenvironment Formulations containing
Slide 52: Versamune: Overcoming the Limitations of Immuno-Oncology
Versamune®: Overcoming the Limitations of Immuno-Oncology 52 Confirmed mechanistic properties of Versamune® – Promoting induction of the preferred T-cell phenotype to significantly alter the tumor microenvironmentVersamune® promotes antigen-specific CD8+ T-cells versus the immuno-suppressive regulat
Slide 53: Versamune Summary Flow Chart: Multi-Functional Mechanisms
Versamune® Summary Flow Chart: The Multi-Functional Mechanisms That Lead to Effective Anti-Tumor Response 53 Activates the Type I Interferon (IFN) pathway Recruits immune cells to injection siteEnhanced uptake of cancer-specific protein antigen by dendritic cells (DCs) of the immune systemActivated
Slide 54: Strong Positioning of Versamune in Immuno-Oncology
Strong Positioning of Versamune® in Immuno-Oncology by Overcoming Key Limitations 54 The Promise of Versamune® Design and composition facilitates uptakeComposition allows for efficient antigen cross-presentationLipid structure allows for powerful antigen-specific T-cell induction via localized activ
Slide 55: PDS-Owned Intellectual Property (Versamune-Related Products)
PDS-Owned Intellectual Property (Versamune® -Related Products) 55 Versamune® and associated patents 100% owned by PDSFive issued US patents valid through 2034Acquired PDS patent #1 covers the use of specific cationic lipids to induce an immune responseIssued PDS patent #2 covers compositions and use
Slide 56: Summary and Conclusions
Summary and Conclusions 56 Powerful T-cell activating immunotherapy platform 1 Versatile platform with potential to transform first-line therapy of late-stage cancers 2 Validated superior pre-clinical and clinical data supported by partnerships with both pharmaceutical companies and the NCI 3 Planne
Slide 57: A new generation of multi-functional cancer immunotherapies
A new generation of multi-functional cancer immunotherapies October 2019Products, Clinical Indications and Scientific Overview
PDS Biotechnology — Investor Presentation (October 2019) on 6ix