Interleukin-12 (IL-12) KOL Roundtable NASDAQ: PDSB |

Interleukin-12 (IL-12) KOL Roundtable NASDAQ: PDSB | April 21, 2023

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result of various factors, including, without limitation: the Company's ability to protect its intellectual property rights; the Company's anticipated capital requirements, including the Company's anticipated cash runway and the Company's

current expectations regarding its plans for future equity financings; the Company's dependence on additional financing to fund its operations and complete the development and commercialization of its product candidates, and the risks that

raising such additional capital may restrict the Company's operations or require the Company to relinquish rights to the Company's technologies or product candidates; the Company's limited operating history in the Company's current line of

business, which makes it difficult to evaluate the Company's prospects, the Company's business plan or the likelihood of the Company's successful implementation of such business plan; the timing for the Company or its partners to initiate the

planned clinical trials for PDS0101, PDS0203 and other Versamune and Infectimune based product candidates; the future success of such trials; the successful implementation of the Company's research and development programs and collaborations,

including any collaboration studies concerning PDS0101, PDS0203 and other Versamune and Infectimune based product candidates and the Company's interpretation of the results and findings of such programs and collaborations and whether such

results are sufficient to support the future success of the Company's product candidates; the success, timing and cost of the Company's ongoing clinical trials and anticipated clinical trials for the Company's current product candidates,

including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including the Company's ability to fully fund its disclosed clinical trials, which assumes no material changes to our currently projected

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the final results of the Company's ongoing clinical trials; the timing of and the Company's ability to obtain and maintain U.S. Food and Drug Administration or other regulatory authority approval of, or other action with respect to, PDS0101,

PDS0203 and other Versamune and Infectimune based product candidates; any Company statements about its understanding of product candidates mechanisms of action and interpretation of preclinical and early clinical results from its clinical

development programs and any collaboration studies; and other factors, including legislative, regulatory, political and economic developments not within the Company's control, including unforeseen circumstances or other disruptions to normal

business operations arising from or related to COVID-19. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with

statements that are included herein and elsewhere, including the risk factors included in the Company's annual and periodic reports filed with the SEC. The forward-looking statements are made only as of the date of this press release and,

except as required by applicable law, the Company undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or

otherwise. Versamune is a registered trademark, and Infectimune is a trademark of PDS Biotechnology Corporation.KEYTRUDA is a registered trademark of Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclaimer PDS Biotech is hosting this roundtable Each panelist is speaking at

the request of PDS Biotech Information presented is consistent with FDA guidelines

Introducing our Panel Dr. James Gulley Co-Director of the Center for

Immuno-Oncology National Cancer Institute Dr. Jeffrey Schlom Co-Director of the Center for Immuno-Oncology National Cancer Institute

Today's Agenda 5 Welcome and Introductions Dr. Lauren V. Wood History of IL-12

and NHS-IL12/PDS0301 Dr. James Gulley Preclinical and Mechanistic Studies of NHS-IL12/PDS0301 Dr. Jeffrey Schlom Clinical Studies of NHS-IL12/PDS0301 Dr. James Gulley Panel Discussion Moderated by Dr. Lauren V. Wood Closing

Remarks Dr. Lauren V. Wood

History of IL-12 and NHS-IL12 / PDS0301 Dr. James Gulley

Investigations elucidate the mechanisms of IL-12 anti-tumor activity Modified

from Trinchieri G, Nature Reviews Immunology 2003 DC IL-12 Antigen processing & presentation

1994: Early clinical development of IL-12 Day 1 Test dose 15 Cycle

1 19 35 Cycle 2 40 Tumor measurement 50 Schema of Phase 1: Day 1 Cycle 1 (dosed at MTD) 5 Schema of Phase 2: 500 ng/kg defined as the MTD Explanation: Mouse and monkey data show that the test dose' in the phase one trial reduced

the toxicity of subsequent daily administrations - clinical trials allowed to resume Severe toxicity in all patients; two patient deaths; trial stopped - Source: Leonard J et al, Blood 1997, Atkins M et al, Clin Ca Res 1997

IL-12 de-sensitization in patients is associated with counter-induction of

IL-10 The first dose of IL-12 increases production of Th1 cytokines such as IFN- and TNF- Frequent, repeated dosing was associated with declining IFN- and TNF- levels, and a persistent elevation of the Th2 cytokine, IL-10 IL-10 is a

negative regulator of IL-12 activity Repeated administration also increased serum levels of soluble IFN- receptor IL-10 1st dose 7th dose IFN- Source: Portielje J, Clin Can Res 2003

After well over a decade in the clinic, recombinant IL-12 has failed due to

limited efficacy and toxicity Phase 2 Selected Phase I Limited efficacy observed in RCC and melanoma Promising activity against lymphomas Immunomodulatory effects clearly demonstrated Toxicities problematic, tolerability improved with

s.c. delivery Frequent, repeated dosing causes a de-sensitization effect that limits efficacy

Re-thinking IL-12 immunotherapy A strategy for success with NHS-IL12

(PDS0301): NHS-IL12 targets IL-12 delivery to the tumor, increasing exposure at the tumor site while reducing systemic exposure Further improved tolerability due to the reduced potency of NHS-IL12 NHS-IL12 is a large macromolecule (~250 kDa)

with a longer PK than rIL-12, providing efficacious exposure with a single s.c. dose, eliminating the need for frequent dosing Administration by s.c. route will promote lymphatic absorption of the large NHS-IL12 molecule, promoting IL-12

effects at draining lymph nodes prior to systemic distribution Monitor the IL-10/IFN- axis to guide the establishment of optimal dose schedules in the clinic

NHS-IL12 - Molecule Overview Molecule Composition M9241 (NHS-IL12) is an

immuno-cytokine comprised of two IL-12 heterodimers each fused to one of the H-chains of the IgG NHS76 (fully human) antibody It is a complex molecule with several glycosylation sites IL-12 has been genetically modified to eliminate a

proteolytic cleavage site (p40 clipping resistant) The junction region between the IL-12 and NHS76 has been de-immunized. Molecule Characteristics NHS76 targets regions of tumor necrosis where cell membrane integrity has been lost and DNA

has become exposed. It has affinity for both single- and double-stranded DNA Tolerability is further increased by administering NHS-IL12 by the s.c. route of administration to achieve a slow, sustained release into the bloodstream and

enhance lymphatic absorption No ADCC or CDC activity in vitro

MOA: Innate & Adaptive Immunity Driving Force Distinct Mechanisms for IL-12

as a Tumor Targeting Therapy Induces differentiation of na ve CD4+ T-cells to the Th1 phenotype Increases the proliferation and lytic capacity of CD8+ cytotoxic T cells and NK cells Promotes IFN- production via NK & T-cells Increases

the production of IP-10 (interferon-inducible protein 10) and MIG (monokine induced by interferon gamma) which then mediates an anti-angiogenic effect Enhances antigen-presentation through paracrine upregulation of MHC class I and II

expression Source: Lasek et al 2014

Effector programing of CD8+ T-cells dependent on APC in TME CD8+ T cells in

tumor-draining lymph nodes maintain a TCF1+ stem-like program Tumor-specific CD8+ T cells migrate to the tumor in the stem-like state CD8+ T cells only acquire the canonical effector program within the tumor Effector program acquisition

requires co-stimulation in the tumor microenvironment Source: Prokhnevska Kissick et al. CD8+ T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor. Immunity Dec

Kinetic Analysis of Tumor Localization Following s.c. Administration of

AF750-labeled NHS-muIL12 and BC1-muIL12 15 chTNT is a mouse/human chimeric Ab 131I-chTNT is a targeted radiotherapeutic Image at right shows biodistribution of 131I-chTNT in a patient with lung cancer. 131I-chTNT is licensed in China for

advanced lung cancer treatment NHS-76 is a fully human 2nd generation TNT antibody 131I-chTNT targeting to lung tumor

Preclinical and Mechanistic Studies of NHS-IL12/PDS0301 Dr. Jeffrey Schlom

Components of Effective Cancer Immunotherapy Source: Schlom and Gulley. JAMA,

Potential of IL-12 as an anti-cancer therapy: Bridges host innate and adaptive

immunity Produced by activated APCs (macrophages, DCS, neutrophils, B cells) Drives Th1 differentiation of helper T cells Promotes IFN- production via NK & T cells Increases proliferation and lytic capacity of NK, NKT, and CD8+ T

cells Stimulates further IL-12 production in DCs & enhances antigen presentation Upregulates IP-10/CXCL10 & MIG/CXCL9 - mediate an anti-angiogenic effect - drive infiltration of CD8+ T cells Clinically, recombinant human IL-12

has a narrow therapeutic index and its systemic administration can result in significant toxicity Image: Del Vecchio, et al. Cancer Res, 2020 Exploiting Immunotherapy Combinations With NHS-IL12/PDS0301

Tumor Localization Kinetics of AF750-labeledNHS-muIL12 and BC1-muIL12 (sc)

MC38 LLC Antitumor Effect of NHS-muIL12 vs. muIL12 (sc) Fallon Schlom, Greiner. Oncotarget, 2014; Greiner Schlom. Immunotargets Ther., 2021

The Combination of PDS0101, NHS-IL12 and Bintrafusp alfa Reduced Tumor Volume and

Increased T-cell Clonality in TC-1-bearing Mice Source: Smalley Rumfield Schlom, Jochems. J Immunother Cancer. 2020

PDS0301 (NHS-IL12) Accumulates in Tumors and Promotes PDS0101 Induced CD8 and CD4

T Cell Infiltration and Expansion in Tumors - Maximum T Cell Accumulation in Tumor with All Three Agents 21 PBS Control PDS0301 (NHS-IL12) PDS0101 vaccine PDS0101 + PDS0301 PDS0101 + PDS0301 + checkpoint inhibitor

Hypothesis: Necrosis-inducing Agents Will Increase NHS-IL12 Targeting to the Tumor

and Increase Immune Activation Day 17 Docetaxel causes necrosis in a dose-specific manner Tumoral NHS-IL12

Anti-tumor Activity of Docetaxel + NHS-IL12

Docetaxel and NHS-IL-12 Combination Therapy Independent of PD-L1 Tumor

Expression MC38-PD-L1 KO: MC38 cells were co-transfected recombinant Cas9 and a RNA targeting murine PD-L1 PD-L1 negative cells were cloned and used in subsequent studies Model of Primary Checkpoint Resistance Cells made and characterized

by Dr. Duane Hamilton

FDA-approved HDACi Indication Vorinostat Cutaneous T cell

lymphoma Romidepsin Cutaneous & peripheral T cell lymphoma Belinostat Peripheral T cell lymphoma Tucidinostat Cutaneous T cell lymphoma Panobinostat Multiple myeloma HDACi in solid tumors Exploiting Immunotherapy Combinations

With HDAC Inhibition Source: Hontecillas-Prieto,et al. Front Genet., 2020

Exploiting Immunotherapy Combinations with NHS-IL12 ABSTRACT

Days Post-Tumor Implant Tumor Volume (mm3) EMT6 (BrCa) NHS-IL12 PBS ENT CR:

0/5 1/7 0/7 3/7 7/7 0/7 Days Post-Tumor Implant Tumor Rechallenge Survival Kristin Hicks ENT+NHS-rmIL12 rmIL-12 ENT+rmIL-12 Entinostat plus NHS-IL12 Source: Hicks Schlom, Gameiro. Nat Commun, 2021 Exploiting Immunotherapy

Combinations with NHS-IL12

79% TGI: 100% 63% Cures: 40% 100% 20% Can NHS-IL12 Plus Entinostat Overcome

PD-1/-L1 Refractory Tumors Due to Defects in APM/IFN Signaling? Source: Minnar...Schlom, Gameiro. J Immunother Cancer, 2022

M2 to M1 shift Activated CD8+

TILs Increased CD8/Tregs TC-1/a9 CMT.64 RVP3 TC-1/a9 TME NHS-IL12 Synergizes with Entinostat to Suppress PD1/ PDL1 Refractory Tumors

Components of Effective Cancer Immunotherapy Source: Schlom and Gulley. JAMA,

Clinical Studies of NHS-IL12 / PDS0301 Dr. James Gulley

Source: Clinical Cancer Research, 2019 Tumor targeted cytokine (binds DNA in

areas of necrosis) Demonstrated safety and biologic activity MTD 16.8 mg/kg s.c. every 28 days NCI Phase 1: First in Human (FIH) Study NCT01417546

NCI Phase 1: FIH Study Phase I Study Design (Open Label) Assess the safety, PK

and immune impact 3+3 dose-escalation in solid tumors (SAD & MAD portions) Dosing Schedule: Q4W s.c. administration 6 week DLT period Primary Objective MTD Secondary Objectives PK of subcutaneously administered

NHS-IL12 Immunogenicity To determine immune response, including frequency of immune cell subtypes infiltrating tumor tissue (CD8 memory/effector cells, CD4 memory/effector cells, Tregs, NK cells, DCs), and activation of T lymphocytes against

relevant tumor-associated antigens as measured by tetramer and/or ELISPOT analysis Dose Level* (mcg/kg) # of pts Tumor Types # of pts Treatment duration (MD), # of cycles Tumor Types 0.1 3 Kaposi, Breast, Transitional 0.5 3 CRC

(n=2), Mesothelioma 1.0 4 CRC (n=4) 2.0 4 CRC (n=2), Rectal, Pancreatic 4 1, 1, 4, 5 NSCLC (n=3), Renal 4.0 3 CRC, Gallbladder, Lung 4 2, 2, 2, 9 Rectal, Pancreatic, Gallbladder, Prostate 8.0 3 Pancreatic, NEC lung, Esoph

(sq) 3 3, 5, 6 CRC (n=2), Pancreatic 12.0 2 Adeno Ca (tongue), Breast 4 1, 3, 3, 14 Prostate (n=2), Thymoma, Anal 16.8 (MTD) 17 1, 1, 2, 2, 2, 2, 2, 2, 3, 4, 6 PDAC, Ovarian (n=3), Breast, Adeno Ca intestinal, Prostate (n=3),