Exhibit 99.1
A new generation of multi-functional cancer immunotherapies October 2019Products, Clinical Indications
and Scientific Overview
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 activities and timelines and market
opportunities. All statements other than statements of historical facts included in this presentation are forward-looking statements. The words “anticipates,” “may,” “can,” “plans,” “believes,” “estimates,” “expects,” “projects,” “intends,”
“likely,” “will,” “should,” “to be,” and any similar expressions or other words of similar meaning are intended to identify those assertions as forward-looking statements. These forward-looking statements involve substantial risks and
uncertainties that could cause actual results to differ materially from those anticipated.Factors that may cause actual results to differ materially from such forward-looking statements include those identified under the caption “Risk
Factors” in the documents filed with the Securities and Exchange Commission from time to time, including its Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. You are cautioned not to place undue
reliance on these forward-looking statements, which speak only as of the date of this presentation. Except to the extent required by applicable law or regulation, PDS undertakes no obligation to update the forward-looking statements included
in this presentation to reflect subsequent events or circumstances.
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 cancer – overview, preliminary data
Slide 19PDS0103 for MUC-1 cancers – overview, preliminary data Slide 23PDS0104 for melanoma - overview, preliminary data Slide 25Versamune® mechanism of action studies Slide 27Summary of mechanism Slide 53Intellectual property Slide
55Conclusions Slide 56
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 presentation to CD8+ T-cells therefore
resulting in sub-optimal therapeutic benefit The first truly multi-functional immunotherapeutic platformEngineered to promote efficient antigen uptake, processing and presentation to killer and helper T-cellsSuperior levels of in-vivo
tumor-specific killer T-cell inductionSuperior in-vivo induction of high quality/poly-functional T-cellsDemonstrated ability to break tumor immune toleranceSuperior safety and anti-tumor responses Solutions Provided by Versamune® Antigen
– The unique protein associated with the cancer that is not expressed by normal healthy cells and which is recognized by the immune system
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 & positively charged head-groupcoats the
particle surface Water-insolubleFatty acids/hydrocarbon chains
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 susceptible to T-cell
attack Positively charged nano-particles engineered to access critical MHC Class I pathway Activates stimulation of type I interferon (IFN) genes within lymph nodes Significantly increases ratio of killer T-cells to immune-suppressive
regulatory T-cells Induces memory immune response Body generates tumor-attacking T-cells for extended period after treatment Potent poly-functional T-cells De-camouflaged tumor Robust / lasting effect 1 2 3 4 *Mechanism of Action:
Journal of Immunology, Vol. 202, Issue 1215 June 2019
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
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 only work in patients whose immune
systems are already generating tumor attacking CD8 killer T-cells pre-treatmentUsing various tumor-specific proteins (antigens), Versamune® has demonstrated the ability to generate large numbers of CD8 killer T-cells that effectively
recognize and kill the antigen-expressing cancer cells in preclinical and in human clinical studiesBy combining the Versamune®-based immunotherapies with checkpoint inhibitors and other standard of care modalities, PDS plans to generate a new
generation of effective treatments for advanced cancer The immunotherapies are being developed as combination therapies to exploit the demonstrated synergies between the Versamune® technology and checkpoint inhibitors *L. V. Wood et al et
al, Oncoimmunology, 2016, Vol. 5 (8)**S. Gandhapudi et al, Journal of Immunology, 2019 (202), 1215
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 survival over checkpoint inhibitor
therapy** Treatment started UntreatedAnti PD-1 checkpoint inhibitor (CPI)Versamune® + TRP2 AntigenCPI + Versamune® + TRP2 No survivors by Day 18CPI-treated ineffective dueto absence of tumor infiltrating T-cells *Vasievich et al,
Molecular Pharmaceutics 2012, 6, 9(2) 261-8**S. Gandhapudi et al, Journal of Immunology, 2019 (202), 1215 Percentage of CD4+ and CD8+ among all cells in the tumor mass 75nmol TRP2+ Versamune 75nmol TRP2 Versamune® induces
TRP2-specificCD4+ (helper) and CD8+ (killer) T-cells& infiltration into the B16 tumor 7 daysafter a subcutaneous injection*
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 trial the PDS has demonstrated that
the proprietary antigens are effectively recognized by the immune systems of HPV-infected patients. Treatment led to strong HPV-specific killer T-cell responses and clinical benefit. The proprietary Versamune® platform technology which has
demonstrated exceptional ability to train the killer (CD8+) T-cells of the immune system to recognize the specific tumor antigens included in the formulation, and to arm the T-cells with potent ability to specifically attack and kill the
cancer cells expressing the tumor antigen** *L. V. Wood et al et al, Oncoimmunology, 2016, Vol. 5 (8)**S. Gandhapudi et al, Journal of Immunology, 2019 (202), 1215
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 Large Pharma Two NovelImmunotherapies (Superior results in phase 1 studies) 30 subjects1 US site (NCI) Cervical cancerStage IIb-IVa To be announced Chemo-radiotherapy (Standard of care) 33 subjects1 US site * These
clinical studies are expected to be initiated with current funding All clinical trials to be initiated in Q1 2020Interim data expected within 18 months of start
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 Markowitz, Epidemiologist, U.S. Centers
for Disease Control and Prevention Female Male 100% = 24,391 100% = 18,280 Annual Incidence~43,000 HPV-associated cancersTrial: PDS0101 + 2 immunotherapiesCervical cancerMost common HPV-cancer in women Incidence steadyTrial: PDS0101 +
Chemoradiotherapy (SOC)Oropharyngeal (head & neck) cancers Most common HPV-cancer in menIncidence increasingTrial: PDS0101 + Keytruda (SOC)
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®-class) formulated using a weakly immunogenic
HPV antigen: CD8+ T-cell response of DOTMA and DOEPC vastly superior to the clinical-stage adjuvant Montanide (ISA Pharma – HPV competitor) The micellar peptides without Versamune® generate a very weak CD8+ T-cell response even less than seen
with Montanide IFN-γ Spots per 106 Splenocytes *Patent covers compositions of micellar antigens and cationic lipidsUS patent prosecution on-going; Patents issued in EU and JP
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® (R-DOTAP)
induces approx. 10-fold higher number of potent/polyfunctional T-cells vs. competition *J. Immunology, 2019 (202), 1215Studies in TC-1 tumor model with other immunotherapies reported in: #Vaccine 2009, January 14, 27 (3): 431;##Journal for
Immunotherapy of Cancer, 2013 (1) 15 Polyfunctional/mostpotent killer T-cells (4-Adjuvant Combination) (Positive Control) 40.78% 18.9% 16.55% 40.5%
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. Immunology, 2019 (202),
1215**Studies in TC-1 tumor model with other immunotherapies reported in: Vaccine 2009, January 14, 27 (3): 431; Science Translational Medicine 2016, 13 April, Vol 8 Issue 334; Vaccine 2009, August 3, 27 (33): 5706 Single treatment
dose 50 55 60 80 Inject TC-1 Tumor Cells Top competitors such as live vectorsTLR agonist adjuvants, electroporationonly slow down TC-1 tumor growth (delay death)**
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 immunogenicity 14x 24x Total T-Cells
26x Over 20-Fold Increase in HPV-Specific CD8+ T-Cell ResponsesVersus Pre-Treatment Levels at Recommended Clinical Doses 16 Days Dosage Unlike PDS0101, no T-cell activating technology or immunotherapy has demonstrated the ability to
induce in-vivo in humans, quantifiable amounts of granzyme-b inducing antigen-specific CD8+ T-cells in circulating blood
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 subjectsClearance of the CIN (lesion regression) was
observed in 60% of evaluable patients across the three tested doses, as early as 1-3 months after treatment in some patients Dose Cohort Evaluable Patients* Clearance of Lesions 12 Months Post Treatment** N = N = % of
Evaluable 1mg 3 of 3 2 67% 3mg 2 of 3 1 50% 10mg 5 of 6 3 60% Total 10 6 60% *Two of twelve patients were not evaluable: one patient, who demonstrated a strong immune response, was lost to follow up and another received LEEP
excision therapy (standard of care) **Two of ten evaluable patients who had clearance of CIN by cytology were not considered as clinical responders: one patient regressed from CIN to atypical squamous cells of undetermined
significance (ASCUS) with detectable virus, and the other showed consistent disease elimination by cytology, but showed residual disease by colposcopy
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 ongoing PDS0104(Melanoma) Melanoma TBD Checkpoint Inhibitor Preclinical studies ongoing
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 NCI demonstrated that the antigen was
effectively recognized by the immune system in prostate cancer patients with PSA biochemical recurrence leading to a reduction in tumor growth rate*The proprietary Versamune® platform technology which has demonstrated exceptional ability to
train the killer (CD8+) T-cells of the immune system to recognize the specific tumor antigens included in the formulation, and to arm the T-cells with potent ability to specifically attack and kill the cancer cells expressing the tumor
antigen** *L. V. Wood et al et al, Oncoimmunology, 2016, Vol. 5 (8)**S. Gandhapudi et al, Journal of Immunology, 2019 (202), 1215
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 have demonstrated strong potential
in on-going prostate cancer trials.In on going preclinical studies R-DOTAP, has demonstrated the ability to significantly enhance the immune system’s ability to generate TARP-recognizing killer T-cellsProstate cancer patients treated with a
TARP-based immunotherapy (no R-DOTAP) showed generation of TARP recognizing T-cells and reduction in tumor growth rate* *L. V. Wood et al et al, Oncoimmunology, 2016, Vol. 5 (8)
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 splenocytes) PRE-CLINICAL
OPTIMIZATION STUDIES: TARP-Specific T-cell Induction after 2 injections of R-DOTAP + TARP (1-20) IFN-γ ELISPOT Study Range of observed T-cell responsesWith Versamune® + TARP(1-20) 100 spots/million cellsStrong T-cell response level CFA
– Complete Freund’s Adjuvant a highly potent immune activator not used in humans due to potentially lethal toxicity
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.
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 immunogenicity and also induce significantly
higher avidity T-cells compared to native MUC-1. These antigens have been licensed by PDS from the NCI for the four indications above.*The proprietary Versamune® platform technology which has demonstrated exceptional ability to train the
killer (CD8+) T-cells of the immune system to recognize the specific tumor antigens included in the formulation, and to arm the T-cells with potent ability to specifically attack and kill the cancer cells expressing the tumor
antigen** *Jochems et al, 2014 Cancer Immunol Immunother 63, 161 -174**S. Gandhapudi et al, Journal of Immunology, 2019 (202), 1215
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 agonist emulsion clinical-stage
adjuvantIFA-Cyt – Multi-adjuvant emulsion: Incomplete Freund’s adjuvant + IL12 + GM-CSF + HBV helper peptide V1A-Specific T-Cells V2A-Specific T-Cells Mice receiving R-DOTAP+MUC1 showed strong responses to both V1A and V2A antigens.
The potent combination adjuvant IFA-Cyt generated an equivalent quantity of T-cells only to V2A. However, R-DOTAP+MUC1 also generated > 2X poly-functional (higher quality) CD8+ T-cells compared to both IFA-Cyt and Montanide (data not
shown)
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.* Excellent synergy with checkpoint
inhibitors has also been demonstrated in on-going preclinical development studies.**The proprietary Versamune® platform technology which has demonstrated exceptional ability to train the killer (CD8+) T-cells of the immune system to recognize
the specific tumor antigens included in the formulation, and to arm the T-cells with potent ability to specifically attack and kill the cancer cells expressing the tumor antigen** *Vasievich et al, Molecular Pharmaceutics 2012, 6, 9(2)
261-8**S. Gandhapudi et al, Journal of Immunology, 2019 (202), 1215
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 cells in the tumor mass
75nmol TRP2+ Versamune 75nmol TRP2 Versamune® induces TRP2-specificCD4+ (helper) and CD8+ (killer) T-cells& infiltration into the B16 tumor 7 daysafter a subcutaneous injection*
Versamune® Mechanisms of Action 27
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 bydendritic cells of the immune
system Versamune® facilitates processing ofthe cancer protein by the immune system Versamune® promotespresentation of processedprotein to killer T-cells Activated immune cells migrateto lymph nodes to present proteinto T-cells
(training of T-cells occurs) *The antigen is a protein that can be recognized by the immune system, and that is uniquely associated with or overexpressed by the particular cancer of interest. TARP is associated with prostate and breast
cancers.
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* SC injection of the active
enantiomer (R-DOTAP) results in activation of type I interferons and induces monocyte infiltration to injection site SC injection of the weakly biologically active enantiomer (S-DOTAP) results in low infiltration of monocytes to the
injection site *Compositions of R-DOTAP to induce immune responses covered by US patent # 9,789,129. Also patented in EU, JP, AUS, TW, CA, RU, IN, IL
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 promotes uptake of antigens
almost exclusively by the dendritic cells, the primary antigen presenting cells of the immune system
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 containing fluorescent NBD-labelled
DOTAP. Draining lymph node cells were analyzed by flow cytometry. The number of mature dendritic cells (CD11c+) cells increased more than 2.5-fold at 4 hours (A and B). NBD-positive cells demonstrated high levels of CD86 (C and D) indicating
that SC injection of Versamune® induced DC activation. Other cell types showed no NBD uptake (E and F) demonstrating that Versamune® is mainly taken up by DC (~80%) and induces migration of activated DC to the draining lymph node, resulting
in effective DC-T cell interactions and superior priming of T-cells. *Cancer Immunol Immunother 2008, 57 (4) 517-30
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 monocytes with R-DOTAP shows dramatic
uptake, processing and endosomal accumulation in presence of R-DOTAP – Facilitates entry into cytoplasm and cross-presentation to CD8+ T-cells
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 accumulation over OVA only with R-DOTAP
(Upper right quadrant)
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 with 4mM R-DOTAP immediately prior to
injection. Draining LN cells were analyzed 3 days later by flow cytometry measuring CFSE fluorescence on gated TCR transgenic T cells. Histograms are representative of three to four mice per group. CFSE bright cells (far right peak) represent
undivided cells. Each cell division (proliferation) results in a 50% reduction of CFSE intensity and a left-ward shift of the peaks High levels of antigen-specific CD8+/killer T-cells High levels of antigen-specific CD4+/helper
T-cells superior antigen presentation by Versamune®: Promotes In-Vivo Antigen Presentation Via MHC Class I (CD8) & Class II (CD4) Effective antigen processing and endosomal entry results in robust in-vivo T-cell responses
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 systemic bioavailability (~5%) and
promotes most effective T-cell interactions and immune responsesEfficient dendritic cell uptake and ability to process and present proteins and peptides into the class I pathway overcomes limitations of live vectors (DNA/RNA),
electroporation, TLR-agonist adjuvants etc. Ability to promote antigen processing and endosomal entry overcomes limitations of current adjuvant-based cancer vaccines Summary/Advantage: Potent in-vivo ANTIGEN PROCESSING and Efficient priming
of antigen-specific CD4+ and CD8+ 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 Activation of Type I IFN
inducescritical cytokines & chemokines Cytokines and chemokinesprovide killer T-cell activation & expansion Trained and armed T-cells invade tumors
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 (IFBβ1) as well as a pattern
of cytokines and chemokines characteristic of a type I IFN response including the chemokine CxCl10 known to be critical for activation of killer T-cells. Abbreviated from S. Gandhapudi et al, Journal of Immunology, 2019 (202),
1215 CxCl10 IFNα1 IFNβ1 Expression relative to PBS treatment 0 5 10 Relative expression of key genes in the lymph nodes after injection of R-DOTAP known to highly important in the ability of the immune system to generate CD8 T-cells
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 deficient mice) * * CFA:
Compete Freund’s Adjuvant** Statistically significant difference from Versamune® in WT mice P<0.05
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 not in wild type mice (WT), STING or
TRIF knockout mice
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 with the untreated negative controls (NC).
Both R-DOTAP and S-DOTAP are seen to induce activation and maturation of dendritic cells resulting in expression of both CD83 and CD86.
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 necessary to activate the immune
response.Cytokines evaluated/induced – IL1α, IL1β, IL5, TNF-α, IL10Chemokines evaluated/induced – IL8, CCL2 (MCP-1), CCL3, CCL4, CCL5 (Rantes)Danger signals – MMP-1, MMP-7, MMP-9
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®: Prolonged & Localized Induction
of Chemokines in Draining Lymph Nodes (LN) CCL2 (MCP-1) is a chemokine that is of clinical importance in the generation of robust T-cell responses
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
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
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® (R-DOTAP)
induces approx. 10-fold higher number of potent/polyfunctional T-cells vs. competition *J. Immunology, 2019 (202), 1215Studies in TC-1 tumor model with other immunotherapies reported in: #Vaccine 2009, January 14, 27 (3): 431;##Journal for
Immunotherapy of Cancer, 2013 (1) 15 Polyfunctional/mostpotent killer T-cells (4-Adjuvant Combination) (Positive Control) 40.78% 18.9% 16.55% 40.5%
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 S-DOTAP) Wild Type miceIFN
knock out mice
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 < 0.05StatisticallyDifferent P <
0.05StatisticallyDifferent P < 0.05StatisticallyDifferent P > 0.05No difference Tumor-bearingUntreated Tumor-freeR-DOTAP/HPV Tumor-bearingR-DOTAP/HPV Tumor-freeS-DOTAP/HPV Tumor-bearingS-DOTAP/HPV % Specific Killing of
HPV-Positive Cells after 20 hours NP – HPV-negative targets(Left peaks) E7 – HPV-positive targets(Right peaks) *Cancer Immunol Immunother 2011, 60 (5) 629-638
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 powerful poly-functional
antigen-specific CD8+ T-cell responsesAbility to generate sustained T-cell responses targeted specifically at antigens overcomes limitations of live vectors (immune response against live agents)Ability to specifically activate the type 1 IFN
pathway overcomes limitations of live vectors and adjuvants which often induce non-specific immune activation leading to weaker anti-tumor effectsAbility to generate localized and non-systemic immune responses overcomes limitations of cancer
vaccines resulting in safer and more powerful T-cell responses Summary/Advantage: Potent in-vivo induction of polyfunctional CD8 T-cells
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 The ratio of
immune-suppressive Treg cells to active CD8 T-cells is drastically reduced Altered microenvironmentmakes tumors more susceptibleto killing by T-cells Effective killing of tumor cells
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 – R-DOTAP; G – GM-CSF
adjuvant/cytokine; S – sucrose; N – Naïve/untreatedRF9 – The HPV16 amino acid sequence recognized by CD8+ T-cells, TIL – Tumor infiltrating lymphocytes/T-cells The % of CD8+ T-cells in the tumor thatspecifically recognize the HPV16
antigen.In R-DOTAP-based formulations it is almost 50% vs <5% with the cytokine GM-CSF. The ratio of immune-suppressive regulatory T-cellsto HPV-specific CD8+ T-cells. In R-DOTAP-based formulations only, the ratio is < 1.
**P<0.05 **P<0.05
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 R-DOTAP nanoparticles (Versamune®)
result in dramatically lowered Treg/CD8 T-cell ratios as well as high quantity and quality T-cells, making them much more effective in inducing an effective anti-tumor immune response and effective killing of the tumor cells, thus inducing
regression of large established TC-1 tumors.Adjuvants including GM-CSF, Montanide, CpG, CFA are all unable to induce regression of the TC-1 tumors
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 regulatory T-cell (Treg) phenotype A dramatic
decrease in the ratio of Tregs to CD8+ T-cells within the tumor limits immune suppression and facilitates effective killing of tumor cellsOvercomes the limitations of cancer vaccines which tend to favor CD4+ T-cell responses and also
upregulate the Treg population in the tumors Summary/Advantage: Reduces tumor immune suppression
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 DCs produce chemokines &
cytokines DCs and Versamune® transport protein to draining lymph nodes Mature and activates DCsInduce stimulation of Type I IFN genesChemokine induced recruitment of T cells into lymph nodes Enhanced presentation of the antigen to CD8+
killer T-cellsActivation and proliferation of potent multi-cytokine inducing/polyfunctional CD4+ & CD8+ T-cells CD4+ & CD8+ T cells enter tumor microenvironment.Significantly decreased ratio of Tregs to killer-T cells Altered tumor
microenvironment facilitates killer T-cell induced killing of the tumor cells leading to tumor regression Enhanced CD4+ and CD8+ T-cell migration to tumor sites Versamune®:(R-enantiomer of a positively charged lipid) Injection Site T-cell
priming in lymph nodes Tumor micro-environment
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 activation of type 1 interferonsLimited
systemic toxicities allows for ideal combination therapy T-cell Activating Technologies Delivery Technologies Checkpoint Inhibitors Ex-Vivo Cell Based PDS BiotechVersamune® Adjuvants, cytokines Live viruses, bacteria,
electroporation Anti-PD1, anti-PD-L1, anti-CTLA-4 CAR-T Train killer T-cells to recognize tumor antigen X ✓ X NA ✓✓ Activate and multiply trained killer T-cells ✓ ✓ X ✓✓✓ ✓✓ Unblock tumor’s defenses X X ✓✓ X ✓ Induce
memory T-cell response ✓ ✓ X X ✓✓
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 of any cationic lipid to activate MAP
kinaseIssued PDS patent #3 covers compositions and use of R-DOTAP to induce immune responseIssued PDS patent #4 covers micellar antigen + cationic lipids compositions (US still ongoing) Issued PDS patent #5 covers compositions of R-DOTAP with
GM-CSF to reduce immune suppressive myeloid derived suppressor cells in the tumor10 total patent families – provides possible protection of products through 2038Patents cover compositions/formulations and methods of use IP strategy intended
to provide multiple layers of technology & product protection
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 Planned Phase 2 clinical studies in
areas of high unmet need in combination with standard of care and promising clinical stage therapy 4
A new generation of multi-functional cancer immunotherapies October 2019Products, Clinical Indications
and Scientific Overview