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Company Overview

We are a clinical-stage immunotherapy company developing a growing pipeline of targeted cancer and infectious disease immunotherapies based on our proprietary Versamune®, Versamune plus IL-12

(PDS0301) and Infectimune™ T cell activating technology platforms.

Our Versamune based products have demonstrated the potential to overcome the limitations of current immunotherapies by inducing, in vivo, large

quantities of high-quality, potent polyfunctional CD4 helper and CD8 killer T cells.

We have developed multiple therapies, based on combinations of Versamune and disease-specific antigens, designed to train the immune system to recognize diseased

cells and effectively attack and destroy them.

We continue to advance our pipeline of candidates to address a wide range of cancers including HPV-positive cancers (anal, cervical, head and neck, penile, vaginal, vulvar) and breast, colon, lung

prostate and ovarian cancers.

Our Infectimune based vaccines have demonstrated the potential to induce, not only robust and durable neutralizing antibody response, but also powerful T cell responses including long-lasting memory T cell responses.

Our infectious disease candidates are of potential interest primarily for use in universal influenza vaccines.

In June 2022, two abstracts were presented at the 2022 American Society of Clinical Oncology Annual Meeting:

Abstract number 6041, PDS0101 a novel type 1 interferon and CD8 T cell

activating immunotherapy in combination with pembrolizumab in subjects with recurrent/metastatic HPV16-positive squamous cell carcinoma (HNSCC) and Abstract number 2518, Phase 2 evaluation of the combination of PDS0101, M9241, now PDS0301, and

bintrafusp alfa with HPV16+ malignancies.

Also in May 2022, we announced expansion of our VERSATILE-002 clinical trial into Europe and in June 2022, we announced the U.S.

Food and Drug Administration (FDA) had granted Fast Track designation to

our lead candidate PDS0101 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab).

The FDA’s Fast Track designation is designed to aid in the development and to expedite the review of drug candidate applications that would

potentially treat serious or life-threatening conditions.

In order to receive Fast Track designation, a product must also demonstrate the potential to address an unmet medical need.

Treatments granted this designation are given the opportunity to

have more frequent meetings with the FDA throughout the entire dug development and review process, with the goal of moving promising new drugs more rapidly through the process.

It also provides the opportunity to submit sections of a New Drug

Application (NDA) or Biologics License Application (BLA) on a rolling basis, where the FDA may review portions of the NDA or BLA as they are received instead of waiting for the entire NDA or BLA submission.

In addition, Fast Track designated

products are eligible for priority review at the time of NDA or BLA submission.

In October 2022, we announced the successful end-of-phase 2 meeting with the FDA, in which we received feedback on a number of points, including guidance on key

elements of the clinical program that will support the submission of a Biologics License Application (BLA).

In July 2022, we announced the presentation of universal flu vaccine preclinical data for PDS0202 at the 41 st American Society of Virology meeting:

Abstract number 3733830, Infectimune™ enhances antibodies elicited by COBRA hemagglutinin influenza vaccine.

We are a clinical-stage immunotherapy company developing a growing pipeline of targeted cancer immunotherapies based on our Versamune® T cell-activator and Versamune® in

combination with our interleukin 12 (IL-12) fused antibody drug conjugate (ADC), PDS01ADC, a tumor targeting immunocytokine.

In addition, we are developing the Infectimune® T cell-activator in infectious diseases.

We believe our investigational targeted immunotherapies have the potential to overcome the limitations of current immunotherapy approaches through effective conversion of the

immune suppressive tumor to an immunogenic microenvironment in addition to the induction of the right type, potency and quantity of tumor-targeting killer (CD8) T cells.

Our Versamune® immunotherapies and Versamune® in combination with

PDS01ADC, are utilized for treatments in oncology, and Infectimune® is utilized for preventive vaccines against infectious agents.

When paired with an antigen, which is a disease-related protein that is recognizable by the immune system,

Versamune® and Infectimune® have both been shown to induce, in vivo, large quantities of high-quality, highly potent polyfunctional disease-specific CD4 helper and CD8 killer T cells, a specific

sub-type of T cell that has shown potential to be more effective at killing infected or target cells.

Infectimune® is also designed to promote the induction of disease-specific neutralizing antibodies.

PDS01ADC is an investigational tumor

targeting IL-12 that we believe may enhance the proliferation, potency and longevity of T cells in the tumor microenvironment and reduces the prevalence of immune suppressive cells and components within the tumor.

We believe that our

proprietary combination of Versamune® and PDS01ADC may enhance the proliferation, potency and longevity of antigen specific multifunctional CD8 T cells in the tumor microenvironment and work synergistically to inhibit or treat cancer.

In November 2022, we announced the presentation of data from two Phase 2 clinical trials at the 37 th

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advanced cervical cancers and Abstract number 695, “Immune correlates associated with clinical benefit in patients with immune checkpoint refractory HPV-associated malignancies treated with triple combination immunotherapy”.

In January 2023, we announced the exclusive global license agreement with Merck KGaA, Darmstadt, Germany for the tumor targeting antibody conjugated IL-12, M9241 (formerly known as NHS-IL-12),

which joined our pipeline as PDS0301.

PDS0301 is a novel investigational tumor-targeting antibody conjugate of Interleukin 12 (IL-12) that enhances the proliferation, potency, infiltration and longevity of T cells in the tumor microenvironment and

is designed to overcome tumor immune suppression utilizing a different mechanism from immune checkpoint inhibitors (ICI).

The ownership of these two assets we believe will streamline the registrational process and a use of the combination of Versamune® and IL-12 is patented by PDS Biotech .

In a Phase 2 National Cancer Institute (NCI)-led clinical trial in ICI refractory patients,

the combination of PDS0101 and PDS0301 administered with an investigational bi-functional ICI resulted in a median overall survival of 21 months, which compares favorably to the historical median survival of 3-4 months seen with checkpoint

inhibitors and best reported median survival to date with systemic therapy of 8.2 months in ICI refractory head and neck cancer.

In February 2023, we announced a successful completion of a Type B meeting with the FDA for the triple combination of PDS0101 and PDS0301 with an FDA-approved immune checkpoint

inhibitor for the treatment of recurrent/metastatic, ICI refractory head and neck cancer that is positive for the human papilloma virus (HPV) type 16.

In recent interactions with the FDA, we confirmed the required contents of a clinical protocol

for the potential registrational trial.

In December 2022, we executed an exclusive global license agreement with Merck KGaA, Darmstadt, Germany for the tumor targeting IL12 fused antibody drug conjugate, M9241, which joined our

pipeline as PDS01ADC.

PDS01ADC is a novel investigational tumor-targeting fusion protein of IL-12 that enhances the proliferation, potency, infiltration and longevity of T cells in the tumor microenvironment and is therefore designed to overcome

the limitations of cytokine therapy, specifically high toxicity and limited therapeutic potential.

The proprietary combination of Versamune® and PDS01ADC is designed to overcome tumor immune suppression utilizing a different mechanism from immune

checkpoint inhibitors (ICI).

The combination of Versamune® and IL-12 to overcome immune suppression is patented by PDS Biotech, and we believe our ownership of both assets will streamline the clinical

development, registrational process and their potential therapeutic use .

In a Phase 2 National Cancer Institute (NCI)-led clinical trial in Immune checkpoint

inhibitor (ICI) resistant patients, the combination of PDS0101 and PDS01ADC administered with an investigational bi-functional ICI resulted in a median overall survival of approximately 20 months.

The historical median survival reported in ICI

resistant HPV-positive cancers when treated with ICIs is 3-4 months and best reported median survival to date with systemic therapy is 8.2 months in ICI resistant head and neck cancer.

In February 2023, we announced a successful completion of a Type B meeting with the FDA for the triple combination of PDS0101 and PDS01ADC with an FDA-approved immune

checkpoint inhibitor for the treatment of recurrent/metastatic, ICI resistant head and neck cancer that is positive for the human papilloma virus (HPV) type 16.

In recent interactions with the FDA, we confirmed the required contents of a clinical

protocol for the potential registrational trial.

In June 2023, an abstract was presented at the 2023 American Society of Clinical Oncology:

Abstract number 6012, “Safety and Efficacy of Immune Checkpoint Inhibitor Naïve Cohort from Study of

PDS0101 and Pembrolizumab in HPV16-Positive Head and Neck Squamous Cell Carcinoma (HNSCC)”.

The abstract was also selected as one of the featured posters reviewed by an expert panel in the Head and Neck Cancer discussion session.

In September 2023, data on our investigational universal flu vaccine, PDS0202, was presented at the 9 th European

Scientific Working Group on Influenza (ESWI) conference.

This data demonstrated broad neutralization across multiple influenza strains in animals and provided protection against infection after challenging animals not previously exposed to flu

with lethal doses of the pandemic H1N1 flu virus.

In October 2023, data demonstrating PDS0101 in combination with standard-of-care (SOC) chemoradiotherapy was associated with a rapid decline in human papillomavirus-positive circulating cell-free

DNA (ctHPV-DNA), a potential predictive biomarker of treatment response.

The data from the IMMUNOCERV Phase 2 clinical trial was featured in an oral presentation at the American Society for Radiation Oncology Annual Meeting.

In October 2023, updated interim data based on an August 2, 2023 cut off from our VERSATILE-002 Phase 2 clinical trial evaluating the combination of PDS0101 in combination with Merck’s anti-PD-1

therapy, Keytruda® (pembrolizumab) which is the FDA-approved standard of care for first-line treatment of recurrent/metastatic head and neck cancer was presented at a Company-sponsored key opinion leader roundtable.

In October 2023, interim safety and immune response data was presented for the first-in-human Phase 1/2 clinical trial evaluating PDS01ADC in combination with current SOC chemotherapy, docetaxel,

to treat metastatic castration sensitive and castration resistant prostate cancer.

The data was featured in an oral presentation at the 11 th Annual Meeting of the

International Cytokine & Interferon Society.

In October 2023, immune response data from a preliminary analysis of a subset of patients in our VERSATILE-002 Phase 2 clinical trial was presented at the European Society for Medical Oncology

Congress 2023.

In November 2023, we announced updated survival data from our NCI-led Phase 2 trial investigating the triple combination of PDS0101, PDS01ADC and an investigational ICI in two groups of advanced

cancer patients with various types of human papillomavirus (HPV) 16-positive cancers.

In November 2023, preclinical data from our NCI-led trial including PDS0101, PDS01ADC and an HDAC inhibitor in ICI-resistant HPV-16 positive cancer was presented during a poster presentation at

the Society for Immunotherapy of Cancer 38 th Annual Meeting.

The challenges to effective immunotherapy

The inability to generate adequate quantities of high-quality killer CD8 T cells, to minimize systemic toxicities, to overcome the immune system’s tolerance of the cancer and to

generate immunological memory, all limit the clinical effectiveness of immunotherapies.

On a fundamental biological or immunological level, one of the most significant challenges facing the industry is the development of simple and easy to

administer therapies that can effectively treat cancer with minimal side effects.

Suboptimal activation of killer CD8 T cells remains a key limitation of immunotherapies.

Potential hurdles exist at various stages of the immunological process,

including poor uptake of the antigen by the dendritic cells as well as inadequate processing and presentation of the tumor antigen into the correct immunological pathways.

The clinical effectiveness of immunotherapy has been limited by two main challenges:

(i) inability to access and convert the tumor to an immunogenic microenvironment, and

(ii) inability to generate adequate quantities of high-quality killer CD8 T cells.

Effective treatments should also minimize systemic toxicities and generate immunological memory.

On a fundamental biological or immunological level, one of the

most significant challenges facing clinicians is the availability of simple and easy to administer therapies that can effectively treat cancer with minimal side effects.

Cancer Immunotherapy

Cancer immunotherapy is a form of cancer treatment that utilizes the power of the body’s own immune system to recognize, attack and eliminate cancer.

Cancer immunotherapy is a form of cancer treatment that utilizes the ability of the body’s own immune system to recognize, attack and eliminate cancer.

The ultimate goal of

cancer immunotherapy is to improve patient quality of life and to extend patient life by slowing down progression of the cancer, shrinkage of the tumors and in some cases eradication of the cancer.

cancer immunotherapy is to improve patient quality of life and to extend patient life by slowing down progression of the cancer, causing shrinkage of the tumors and in some cases eradication of the cancer.

The body’s immune system is a complex,

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challenge remains that cancer cells are able by various mechanisms to evade the immune system’s surveillance, so the body becomes tolerant to them.

An ideal cancer immunotherapy should have the following attributes to maximize the opportunity for clinical effectiveness in patients.

We believe cancer immunotherapy should have the following attributes to maximize the opportunity for clinical effectiveness in patients:

Stimulate both tumor-specific killer and helper T cells within the body

Activate, arm and expand large numbers of T cells that recognize the tumor

Alter or de-camouflage the tumor microenvironment (TME) to make the cancer more visible or susceptible to attack by the immune system

Generate immune memory, so that if the cancer cells return, the immune system can recognize and eliminate them

Minimize immune suppression in the tumor microenvironment (TME) to make the cancer more visible or susceptible to attack by the immune system

Generate immune memory, so that there is a prolonged anti-tumor immune response to treatment

Optimize safety and tolerability by limiting systemic inflammation and toxicity

As stated in the June 2019 issue of The Journal of Immunology , a leading peer-reviewed journal in the field of immunology, our Versamune platform possesses each of these

attributes, inducing potent anti-tumor responses in preclinical studies.

As stated in the June 2019 issue of The Journal of Immunology , a leading peer-reviewed journal in the field of immunology, our Versamune® platform possesses each of

these attributes, inducing potent anti-tumor responses in preclinical studies.

(Gandhapudi, et al., J.

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Journal for ImmunoTherapy of Cancer, May 2020 ).

We believe our

Versamune technology platform is unique in its ability to successfully encompass the mechanistic attributes required to induce a safe and effective anti-cancer immune response.

believe our Versamune® technology platform in combination with our IL-12 antibody drug conjugate, PDS01ADC, is unique in its ability to successfully encompass the mechanistic attributes required to induce a safe and effective anti-cancer immune

response in preclinical data.

How does cancer immunotherapy work?

An important function of the body’s immune system is to scan for proteins not normally expressed in healthy tissue (antigens).

Once an antigen has been identified as foreign,

abnormal or dangerous, the antigen is presented to T cells, a type of white blood cell effective at eliminating cancer cells and infectious agents (e.g.

Once an antigen has been identified as

foreign, abnormal or dangerous, the antigen is presented to T cells, a type of white blood cell effective at eliminating cancer cells and infectious agents (e.g.

bacteria and viruses).

The presentation of an antigen to T cells is implemented primarily in

the lymph nodes by specialized antigen presenting cells known as dendritic cells which are programmed specially to identify foreign antigens, process them and to present them to T cells.

Unique proteins on the surface of dendritic cells, known as

major histocompatibility complex (MHC) molecules, bind to the foreign antigen and display them on the cell surface for recognition by the appropriate T cells.

Then, once presented, a sub-population of T cells known as the CD8 or killer T cells,

are primed and respond to the specific foreign antigen by attacking and killing the cells containing the abnormal protein.

Other T cell sub-populations, such as CD4 or helper T cells, are also critical in regulating immune responses.

The presentation of an antigen to T cells is implemented

primarily in the lymph nodes by specialized antigen presenting cells known as dendritic cells which are programmed specially to identify foreign antigens, process them and to present them to T cells.

Unique proteins on the surface of dendritic

cells, known as major histocompatibility complex (MHC) molecules, bind to the foreign antigen and display them on the cell surface for recognition by the appropriate T cells.

Then, once presented, a sub-population of T cells known as the CD8 or

killer T cells, are primed and respond to the specific foreign antigen by attacking and killing the cells containing the abnormal protein.

Other T cell sub-populations, such as CD4 or helper T cells, are also critical in regulating immune

Cells communicate via chemical signaling.

For an immune response to be triggered and to be effective, important immune signaling pathways must be activated to enable the body

to induce messenger proteins known as cytokines and chemokines.

For an immune response to be triggered and to be effective, important immune signaling pathways must be activated to enable the

body to induce messenger proteins known as cytokines and chemokines.

Some of these cytokines and chemokines serve both to activate and expand T cells and to arm the T cells with the appropriate cancer-killing function.

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tumor-specific T cell populations, most notably CD8 killer cells.

As will be reviewed in more detail in the section below, the ability to promote the induction of therapeutic quantities of high-quality tumor-targeting CD8 killer T cells within a

patient’s own body has been a major limitation of cancer immunotherapy.

As will be reviewed in more detail in the section below, the ability to promote the induction of therapeutic quantities of high-quality tumor-targeting CD8 killer T cells within

a patient’s own body has been a major limitation of cancer immunotherapy.

Production of adequate numbers of high-quality CD8 killer T cells alone, however, is insufficient to eradicate all cancer cells.

One of the difficulties in treating cancer stems

from the fact that cancer cells have the unique ability to evade the immune system;

One of the difficulties in treating cancer

stems from the fact that cancer cells have the unique ability to evade the immune system;

they camouflage themselves or suppress T cell attack by activating immune mechanisms that suppress the ability of T cells to detect or attack them.

They accomplish

this in part by increasing the population of immune suppressive cells, including cells known as regulatory T cells (Treg) as well as other cell types, within the tumor microenvironment.

An effective immunotherapy must overcome the tumor’s immune

suppressive mechanisms in order to successfully locate and attack the cancer cells.

accomplish this in part by increasing the population of immune suppressive cells, including cells known as regulatory T cells (Treg) as well as other cell types, within the tumor microenvironment.

An effective immunotherapy must overcome the

tumor’s immune suppressive mechanisms in order to successfully locate and attack the cancer cells.

Finally, cancers can be difficult to cure because they may recur even after successful initial treatment due to micro-metastatic (hidden) tumors that are not completely

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the immune system’s long-term memory.

To be durable and effective over an extended period after treatment, and to minimize the likelihood of cancer recurrence, an immunotherapy should enhance this immune function as well.

To be durable and effective over an extended period after treatment, and to minimize the likelihood of cancer recurrence, immunotherapy should enhance this immune function as well.

Versamune® Platform

Versamune® has shown the potential to overcome the challenges of immunotherapy

Versamune is a proprietary lipid nanoparticle and T cell activating platform designed to overcome the challenges of current immunotherapy and improve the treatment outcomes of

patients with cancer.

Versamune® is a proprietary lipid nanoparticle and T cell activating platform designed to overcome the challenges of current immunotherapy and improve the treatment outcomes

of patients with cancer.

Versamune® derived products are based on positively charged (cationic) and immune activating lipids that form spherical nanoparticles in aqueous media.

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Cationic lipids are positively charged molecules that have a water-soluble portion (head group) attached to a water insoluble tail.

The water-soluble portion of the molecule has a positive charge

and the water-insoluble portion is made up of hydrocarbon (also called fatty acid) chains.

The nanoparticles, which are coated with a positive charge, are deliberately sized to mimic viruses, facilitating detection by the body’s immune system and

uptake by dendritic cells.

To treat a specific cancer, the unique or overexpressed antigen found on the surface of the cancer cells is manufactured, then mixed with the Versamune nanoparticles to create a pharmaceutical

product for simple subcutaneous injection.

The water-soluble portion of the molecule has a positive

charge and the water-insoluble portion is made up of hydrocarbon (also called fatty acid) chains.

The nanoparticles, which are coated with a positive charge, are deliberately sized to mimic viruses, facilitating detection by the body’s immune

system and uptake by dendritic cells.

To treat a specific cancer, the unique or overexpressed antigen found on the surface of the cancer cells is manufactured, then mixed with the Versamune® nanoparticles to create a

pharmaceutical product for simple subcutaneous injection.

Versamune® has the potential to promote dendritic cell update of antigens

One of the biggest challenges in developing a potent immunotherapy has been dendritic cell uptake.

Versamune is designed specifically to be taken up by dendritic cells in the skin.

One of the biggest challenges in developing a potent immunotherapy is uptake of the immunotherapy by dendritic cells.

Versamune® is designed specifically to be taken up by

dendritic cells in the skin.

As noted, Versamune® nanoparticles are sized comparably to viruses normally taken up as part of the natural function of the dendritic cells, facilitating efficient uptake of the Versamune® based immunotherapy.

Studies evaluating the uptake of

Versamune nanoparticles by dendritic cells and epithelial cells, found almost exclusive uptake by the dendritic cells.

Four hours following a single subcutaneous injection, about 80% of the dendritic cells in the draining lymph node were found to

have taken up the Versamune based immunotherapy.

evaluating the uptake of Versamune® nanoparticles by dendritic cells and epithelial cells, found almost exclusive uptake by the dendritic cells.

Four hours following a single subcutaneous injection, about 80% of the dendritic cells in the

draining lymph node were found to have taken up the Versamune® based immunotherapy.

Versamune® has the potential to promote efficient antigen processing and T cell presentation

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pathway is critical to programming CD8 killer T cells and the MHC class II pathway to programming CD4 helper T cells to recognize tumor antigens.

When Versamune induced maturation occurs, the dendritic cells express costimulatory molecules on their

surface, which facilitate the highly efficient uptake and presentation of antigens to the T cells.

We believe this activity overcomes one of the most significant limitations of current immunotherapy development – the efficient priming of critical

CD8 killer T cells against tumor antigens.

Versamune has been demonstrated to promote presentation of antigens to CD4 helper cells as well.

Versamune has the potential to promote efficient activation and robust expansion of high quality polyfunctional CD8 killer T cells and CD4 helper in Lymph

When Versamune® - induced maturation occurs, the dendritic cells express costimulatory molecules on

their surface, which facilitate the highly efficient uptake and presentation of antigens to the T cells.

We believe this activity overcomes one of the most significant limitations of current immunotherapy development – the efficient priming of

critical CD8 killer T cells against tumor antigens.

Versamune® has been demonstrated to promote presentation of antigens to CD4 helper T cells as well.

Versamune® has the potential to promote efficient activation and robust expansion of high quality polyfunctional CD8 killer T cells and CD4 helper in

Ultimately mature dendritic cells migrate into lymph nodes, small glands located throughout the body containing white blood cells including T cells, where much of the key

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based immunotherapies.

Thus, through the versality of its mechanisms of action, as understood to date, we believe that Versamune may safely promote the efficient and robust expansion in-vivo of large numbers of highly potent (polyfunctional) CD8

killer T cells, both critical factors in developing a successful immunotherapy.

Thus, through the versality of its mechanisms of action, as understood to date, we believe that Versamune® may safely promote the efficient and robust expansion in-vivo of large numbers of highly potent (polyfunctional)

CD8 killer T cells, both critical factors in developing a successful immunotherapy.

Versamune® has the potential to overcome immune suppression

Regulatory T cells (Treg) are a sub-population of white blood cells normally responsible for recognizing normal healthy cells and for preventing autoimmune disease.

however, they are utilized by the cancer cells to suppress immune detection.

Versamune may contribute to significant alteration of the tumor microenvironment by dramatically reducing the Treg to killer CD8 T cell ratio thus making the tumors more

susceptible to destruction by killer T cells.

Preclinical studies have demonstrated that lowering the Treg to CD8 killer T cell ratio with polyfunctional CD8 killer and CD4 helper T cells promotes effective tumor lysis and regression.

a tumor’s immune tolerance and minimizing its ability to evade detection is a significant goal of a successful cancer immunotherapy that together with potent T cell induction may translate to enhanced tumor elimination.

cancer however, they are utilized by the cancer cells to suppress immune detection.

Versamune® may contribute to significant alteration of the tumor microenvironment by dramatically reducing the Treg to killer CD8 T cell ratio thus making the

tumors more susceptible to destruction by killer T cells.

Preclinical studies have demonstrated that lowering the Treg to CD8 killer T cell ratio with polyfunctional CD8 killer and CD4 helper T cells promotes effective tumor lysis and

Overcoming a tumor’s immune tolerance and minimizing its ability to evade detection is a significant goal of successful cancer immunotherapy that together with potent T cell induction may translate to enhanced tumor elimination.

In preclinical studies, Versamune® (R-DOTAP) nanoparticles demonstrated a reduction in the Treg/CD8 T cell ratio

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Using the tumor model, the Versamune® based therapy was unique in its ability to reduce the tumor size and eventually completely regress the tumors.

The results from the Versamune

based treatment are attributed to its ability to induce:

(i) powerful activation of the critical immunological signaling pathways, (ii) robust production of both CD8 killer and CD4 helper T cells, and (iii) the degradation of the tumor’s protective

immune suppression mechanism.

The results from the

Versamune® based treatment are attributed to its ability to induce:

(i) powerful activation of the critical immunological signaling pathways, (ii) robust production of both CD8 killer and CD4 helper T cells, and (iii) the degradation of the

tumor’s protective immune suppression mechanism.

Versamune® has the potential to induce Immune Memory

Memory T cells allow the body to maintain tumor-recognizing and attacking T cells for an extended period after treatment, with the ideal outcome of reducing cancer recurrence.

Memory T cells allow the body to maintain tumor-recognizing and attacking T cells for an extended period after treatment, with the ideal outcome of reducing cancer

Preliminary studies demonstrated that Versamune® protected mice that had experienced tumor regression against tumor reestablishment even when the mice were reinjected with the same tumor cells.

This sustained protection was evidence of immune

This sustained protection was evidence

of immune memory:

persistence of antigen-specific T cells to recognize tumor proteins associated with a particular cancer, as the animals were not protected against establishment of different tumors.

Evidence of the potential for Versamune based

immunotherapies to induce immune memory was also demonstrated in a Phase 1 clinical trial in humans.

Enhancing tumor-specific memory responses to monitor for tumor antigens and eradicate cancer cells well after initial treatment we believe provides potential for significant

durable clinical benefit by possibly reducing the incidence of tumor recurrence and improving survival of patients.

Evidence of the potential for Versamune®

based immunotherapies to induce immune memory was also demonstrated in a Phase 1 clinical trial in humans.

Enhancing tumor-specific memory responses to monitor for tumor antigens and eradicate cancer cells well after initial treatment we believe provides potential for

significant durable clinical benefit by possibly reducing the incidence of tumor recurrence and improving survival of patients.

Today, many cancer immunotherapies produce serious systemic autoimmune effects due to blockage of existing regulatory mechanisms such as the immune checkpoints as well as

inflammatory toxicities due to the increased presence and spikes of cytokines in the blood circulation.

We believe the mechanism of action of Versamune as well as its design have the potential to contribute to the localization of cytokines in the

lymph nodes and specific targeting of CD8 killer T cells to antigens in tumor tissue.

Therefore, the hypothesis is that Versamune based therapies may exhibit an improved and favorable safety profile compared to currently available treatments.

We believe the mechanism of action of Versamune® as well as its design have the potential to contribute to the localization of cytokines in

the lymph nodes and specific targeting of CD8 killer T cells to antigens in tumor tissue.

Therefore, the hypothesis is that Versamune® based therapies may exhibit an improved and favorable safety profile compared to currently available

As noted, Versamune® is injected subcutaneously (under the skin) and its mechanisms of action are localized primarily in the lymph nodes.

Further supporting these observations

are data demonstrating that negligible levels of Versamune induced cytokines were detected in the blood of mice.

Further supporting these

observations are data demonstrating that negligible levels of Versamune® induced cytokines were detected in the blood of mice.

Very low quantities of Versamune® were detected in the blood or in any organ outside of the lymph nodes.

Additionally, Versamune is broken down (hydrolyzed) in the body into fatty acids and excreted, showing in these preliminary studies that it could mitigate the potential for

short- or long-term accumulation of the nanoparticles.

These preclinical observations have been confirmed by early clinical data documenting that this localized and highly specific cascade of immune activity was associated with an absence of

significant systemic toxicity at all doses tested.

In a Phase 1 clinical trial designed to evaluate safety, all patients had transient swelling and redness at the injection site due to initiation of the immunological cascade at the injection site

which cleared completely within 3-7 days and no dose-limiting toxicities or long-term safety concerns were observed.

Similarly, in our ongoing Phase 2 trials in combination with other treatments, no dose-limiting toxicities or long-term safety

concerns were attributed to PDS0101 since three of the four studies were initiated in 2020.

In choosing and designing a Versamune based therapy for development, careful attention is paid to selecting specific, appropriate antigens because, as described above, Versamune

induces a strong T cell response to the antigen.

All of the antigens currently being evaluated in combination with Versamune are present primarily in cancer cells which should therefore result in tumor-specific T cell attack, thereby minimizing

off-target toxicity and potential destruction of healthy cells and tissue.

Additionally, Versamune® is broken down (hydrolyzed) in the body into fatty acids and excreted, showing in these preliminary studies that it could mitigate the potential

for short- or long-term accumulation of the nanoparticles.

These preclinical observations have been confirmed by early clinical data documenting that this localized, and highly specific cascade of immune activity was associated with an absence

of significant systemic toxicity at all doses tested.

In a Phase 1 clinical trial designed to evaluate safety, all patients had transient swelling and redness at the injection site due to initiation of the immunological cascade at the injection

site which cleared completely within 3-7 days and no dose-limiting toxicities or long-term safety concerns were observed.

Similarly, in our ongoing Phase 2 trials in combination with other treatments, no dose-limiting toxicities or long-term

safety concerns were attributed to PDS0101 since three of the four studies were initiated in 2020.

In choosing and designing a Versamune® based therapy for development, careful attention is paid to selecting specific, appropriate antigens because, as described above,

Versamune® induces a strong T cell response to the antigen.

All the antigens currently being evaluated in combination with Versamune® are present primarily in cancer cells which should therefore result in tumor-specific T cell attack, thereby

minimizing off-target toxicity and potential destruction of healthy cells and tissue.

Versamune® has the potential to minimize circulating tumor DNA (ctDNA)

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highly potent (polyfunctional) CD8 killer T cells.

In MD Anderson led Phase 2 clinical trial, IMMUNOCERV, where the ctHPV 16 DNA biomarker measured in certain patients decreased in the blood by Day 170 (T5) as HPV16-specific killer T cells

In an MD Anderson led Phase 2 clinical trial, IMMUNOCERV, where the ctHPV 16 DNA biomarker measured in certain patients decreased in the blood by Day 170 (T5) as HPV16-specific killer T cells

proliferated in the tumor microenvironment as seen in a representative patient in the chart below.

Versamune®’ s potential as a cancer immunotherapy platform

The potential ability of Versamune to modulate and enhance numerous critical steps required for an effective immune response may provide additional opportunities to treat a variety

Further, its diverse mechanisms of action together with its favorable safety profile suggest therapeutic promise when used in combination with other treatment modalities or immunotherapies such as immune checkpoint inhibitors as well as

in the single-agent monotherapy setting.

The potential ability of Versamune® to modulate and enhance numerous critical steps required for an effective immune response may provide additional opportunities to treat a

variety of cancers.

as well as in the single-agent monotherapy setting.

Human Papillomavirus (HPV)-Related Cancers

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PDS0101 is our lead Versamune ® based immunotherapy.

PDS0101 combines Versamune with a mixture of short proteins (peptides) derived from the cancer-causing HPV16 viral protein.

PDS0101 combines Versamune® with a mixture of short proteins (peptides) derived from the cancer-causing HPV16

viral protein.

HPV16 is the most pervasive and difficult to treat HPV amongst the 13 different high-risk, cancer-causing HPV types.

In a preclinical study in the most widely utilized animal HPV-cancer tumor model, PDS0101 uniquely induced complete regression of the tumors after a single sub-cutaneous injection.

As a result of these data, a Phase 1 open-label,

dose-escalation, proof of concept study of PDS0101 in women with cervical intraepithelial neoplasia (CIN) infected with high-risk HPV types.

The data demonstrated that PDS0101 was immunologically active at all three doses studied, confirmed

induction of high levels of active HPV-specific CD8 killer T cells, and was associated with clinical regression of the cervical lesions that often occurred rapidly.

These results suggest that PDS0101 activated the critical mechanisms in

humans resulting in potent T cells which target and effectively kill human HPV-positive cancer cells.

All patients who experienced regression remained disease-free over the 2-year retrospective evaluation period, suggesting potential

durability or memory of the immune response.

The clinical data were presented at the 34 th Annual Society for the Immunotherapy of Cancer

Conference in November 2019 (Wood, et al., 2019).

Based on these encouraging preclinical and human data, PDS0101 is being studied in multiple Phase 2 clinical studies in various HPV-related cancers one sponsored by the Company in

collaboration Merck and three investigator-initiated trials being conducted by the National Cancer Institute (NCI), MD Anderson Cancer Center and Mayo Clinic.

We believe the data presented from these Phase 2 clinical studies in 2022

demonstrated favorable results.

In a preclinical study in the most widely utilized animal HPV-cancer tumor model, PDS0101 uniquely induced

complete regression of the tumors after a single sub-cutaneous injection.

As a result of this data, a Phase 1 open-label, dose-escalation, proof of concept study of PDS0101 in women with cervical intraepithelial neoplasia (CIN) infected with

high-risk HPV types.

The data demonstrated that PDS0101 was immunologically active at all three doses studied, confirmed induction of high levels of active HPV-specific CD8 killer T cells, and was associated with clinical regression of the

cervical lesions that often occurred rapidly.

These results suggest that PDS0101 activated the critical mechanisms in humans resulting in potent T cells which target and effectively kill human HPV-positive cancer cells.

All patients who

experienced regression remained disease-free over the 2-year retrospective evaluation period, suggesting potential durability or memory of the immune response.

The clinical data was presented at the 34 th Annual Society for the Immunotherapy of Cancer Conference in November 2019 (Wood, et al., 2019).

Based on this encouraging preclinical and human data, PDS0101 is being studied in multiple Phase 2

clinical trials in various HPV-related cancers one sponsored by the Company in collaboration with Merck and three investigator-initiated trials being conducted by the National Cancer Institute (NCI), MD Anderson Cancer Center and Mayo Clinic.

We believe the data presented from these Phase 2 clinical trials in 2022 demonstrated favorable results.

T cell receptor gamma Alternate Reading frame Protein (TARP)-Related Cancers

The TARP antigen is strongly associated with prostate and breast cancers.

450,000 patients are projected to be diagnosed with prostate or breast cancer this year.

450,000 patients are projected to be diagnosed with prostate or breast cancer this

Approximately 90% of prostate cancers and 50% of breast cancers overexpress the TARP tumor antigen.

In a human clinical trial, the NCI demonstrated that its proprietary TARP antigens were effectively recognized by the immune system in prostate

cancer patients with PSA biochemical recurrence leading to a notable reduction in tumor growth rate.

In preclinical studies, a dramatically enhanced TARP-specific killer T cell response was observed when our designed TARP antigens were combined

with Versamune.

In a human clinical trial, the NCI demonstrated that its proprietary TARP antigens were effectively recognized by the immune system in

prostate cancer patients with PSA biochemical recurrence leading to a notable reduction in tumor growth rate.

In preclinical studies, a dramatically enhanced TARP-specific killer T cell response was observed when our designed TARP antigens were

combined with Versamune®.

As discussed further below, in November 2021, we entered into the NCI Patent License Agreement with the U.S.

Department of Health and Human Services, as represented by the NCI of the National Institutes of Health (NIH).

obtained a nonexclusive worldwide license to the patent rights for NCI’s TARP to develop and commercialize TARP peptide-based therapies in combination with our Versamune technology for the treatment of acute myeloid leukemia, prostate and breast

Department of Health and Human Services, as represented by the NCI of the National Institutes of Health

We obtained a nonexclusive worldwide license to the patent rights for NCI’s TARP to develop and commercialize TARP peptide-based therapies in combination with our Versamune® technology for the treatment of acute myeloid leukemia,

prostate and breast cancers.

Preclinical development is ongoing.

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Versamune® based therapy in combination with novel, highly immunogenic, agonist epitopes of the MUC1 oncogenic C-terminal region to treat ovarian, breast, colorectal and lung cancers.

In preclinical studies, a dramatically enhanced MUC1-specific

killer T cell response was observed when the novel antigens were combined with Versamune.

In preclinical studies, a dramatically enhanced

MUC1-specific killer T cell response was observed when the novel antigens were combined with Versamune®.

Preclinical development is ongoing.

Versamune® has demonstrated immunological compatibility with a wide array of tumor and pathogenic antigens.

While our current oncology pipeline pairs Versamune with 4 different tumor

antigens, to address over 10 cancer types, more than 75 tumor antigens have been identified and reported.

We believe that Versamune could work well with a wide range of identified tumor antigens and neoantigens.

We are exploring the expansion of

our Versamune based pipeline by pairing the technology with multiple tumor antigens to potentially develop additional product candidates.

Versamune based immunotherapies plus PDS0301 (IL-12) Platform as a cancer immunotherapy platform

PDS0301 (formerly known as NHS-IL-12 and M9241) is a novel investigational antibody conjugated (IgG1), tumor-targeting interleukin 12 (IL-12) immune-cytokine that enhances the

proliferation, potency and longevity of T cells in the tumor microenvironment.

Together with Versamune based immunotherapies PDS0301 works synergistically to promote a targeted T cell attack against cancers.

As with Versamune, PDS0301 is given by

a simple subcutaneous injection.

Clinical data suggests the addition of PDS0301 to Versamune based immunotherapies may demonstrate significant disease control by shrinking tumors and/or prolonging life.

PDS0301 monotherapy has shown activation of an immune response and correlation with clinical benefit in metastatic solid tumors

We believe PDS0301 monotherapy promotes therapeutically relevant immune responses, and stronger immune activation has been observed at higher doses.

While our current oncology pipeline pairs Versamune® with 4

different tumor antigens, to address over 10 cancer types, more than 75 tumor antigens have been identified and reported.

We believe that Versamune® has the potential to work well with a wide range of identified tumor antigens and neoantigens,

and we are exploring the expansion of our Versamune® based pipeline by pairing the technology with multiple tumor antigens to potentially develop additional product candidates.

Versamune® based immunotherapies plus PDS01ADC as a cancer immunotherapy platform

PDS01ADC (formerly known as PDS0301/NHS-IL-12/M9241) is a novel investigational antibody conjugated (IgG1), tumor-targeting interleukin 12 (IL-12)

immune-cytokine that enhances the proliferation, potency and longevity of T cells in the tumor microenvironment.

Together with Versamune® based immunotherapies PDS01ADC works synergistically to overcome immune suppression and simultaneously

promote a targeted T cell attack against cancer.

As with Versamune®, PDS01ADC is given by a simple subcutaneous injection.

Clinical data suggests the addition of PDS01ADC to Versamune® based immunotherapies may demonstrate significant disease

control by shrinking tumors and/or prolonging life.

In a completed Phase 2 clinical trial conducted by NCI, evaluating PDS0101 and PDS01ADC in combination with M7824 (Bintrafusp alfa), survival

data for ICI naïve patients from the trial indicated that 75% (6/8) of these patients were still alive at 36 months, and the median overall survival (OS) has not yet been reached.

Published data on standard-of-care ICIs report 30-50% of these

patients typically remain alive at 12 months, and less than 30% of the patients remain alive at 24 months.

In the ICI resistant group, the 12-month OS rate was 72% and the triple combination achieved a median OS of approximately 20 months.

PDS01ADC monotherapy has shown activation of an immune response and correlation with clinical benefit in metastatic solid tumors

We believe PDS01ADC monotherapy promotes therapeutically relevant immune responses, and stronger immune activation has been observed at higher doses.

An analysis of patients at

baseline and after PDS0301 monotherapy treatment documented in the graphs below.

baseline and after PDS01ADC monotherapy treatment documented in the graphs below.

Interferon-gamma is associated with the induction of natural killer (NK) cells and T cells.

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International Immunopharmacology 116 (2023) 109736 ).

PDS0301 is differentiated from other IL-12s

PDS0301 is a novel immune-cytokine fusion protein composed of two molecules of IL-12 fused to each of the heavy-chains of a human IGg1 antibody.

The IGg1 antibody targets the

DNA/histones exposed in necrotic areas of solid tumors, thus delivering the IL-12 into the tumor and limiting its systemic accumulation.

As seen in the chart below, PDS0301 shows low accumulation in blood circulation potentially promoting safety.

PDS01ADC is differentiated from other IL-12 treatments

PDS01ADC is a novel investigational immune-cytokine fusion protein composed of two molecules of IL-12 fused to each of the two heavy-chains of a human IGg1 antibody.

IGg1 antibody targets the DNA/histones exposed in necrotic areas of solid tumors, thus delivering the IL-12 into the tumor and limiting its systemic accumulation.

As seen in the chart below, PDS01ADC (PDS0301) shows low accumulation in blood

circulation potentially promoting safety.

Infectimune® has potential as an infectious disease vaccine platform

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It has been formulated to activate the immune system to induce rapid and longer-lasting neutralizing antibody responses for improved protection against infectious pathogens.

We believe it has the potential to induce T

cell responses including memory T cell responses to provide the immune system with long-term memory and potential sustained protection against infectious pathogens over an extended period of time that may exceed traditional antibody-based

Preclinical studies suggest that it has

the potential to induce T cell responses including memory T cell responses to provide the immune system with long-term memory and potential sustained protection against infectious pathogens over an extended period of time that may exceed

traditional antibody-based protection.

We believe it could provide safe and effective vaccines that are well tolerated by healthy individuals.

Universal influenza vaccine

According to the World Health Organization,

influenza causes 3 to 5 million cases and approximately 290,000 to 650,000 deaths each year.

Due to the existence of multiple strains of flu, a new seasonal flu vaccination is usually developed to provide protection against the strains

predicted to be prevalent in an upcoming flu season.

As a result, the protective efficacy of the current vaccines varies widely from season to season.

We are developing a new generation of flu vaccines with the potential to provide

long-lasting, and broad protection against multiple strains of the virus.

We believe that the successful development of a universal flu vaccine could eliminate the need to create a vaccine to protect against each year’s predicted variants.

Our Infectimune platform is combined with computationally optimized broadly reactive antigen (COBRA) to potentially provide longer lasting, more effective response to the influenza vaccine.

The preclinical work is complete, and we are

working to obtain nondilutive financing to fund the next steps in development.

In the fourth quarter of 2021, we entered into a Patent License Agreement with the University of Georgia (UGA) which provides a nonexclusive license to the

patent rights for UGA’s COBRA antigens to develop and commercialize a universal influenza vaccine worldwide.

According to the World Health Organization, influenza causes 3 to 5 million cases and approximately 290,000 to 650,000 deaths each year.

Due to the existence of multiple

strains of flu, a new seasonal flu vaccination is usually developed to provide protection against the strains predicted to be prevalent in an upcoming flu season.

As a result, the protective efficacy of the current vaccines varies widely from

season to season.

We are developing a new generation of flu vaccines with the potential to provide long-lasting, and broad protection against multiple strains of the virus.

We believe that the successful development of a universal flu vaccine

could eliminate the need to create a vaccine to protect against each year’s predicted variants.

Our Infectimune® platform is combined with computationally optimized broadly reactive antigen (COBRA) to potentially provide longer lasting, more

effective response to the influenza vaccine.

In the fourth quarter of 2021, we entered into a Patent License Agreement with the University of Georgia (UGA) which provides a nonexclusive license to the patent rights for UGA’s COBRA antigens to

develop and commercialize a universal influenza vaccine worldwide.

The UGA Patent License Agreement includes customary milestone payments and royalties.

Initiation of preclinical work is dependent

on obtaining nondilutive financing.

In February 2023, we announced preclinical Infectimune™ publication in peer reviewed jour nal Viruses showin g unique induction of high levels of multifunctional CD4+ T cells capable of broadly protective

functions compared to leading commercial vaccine technologies (Henson TR et al.

Viruses 2023, 15 , 538).

In February 2023, we announced a second preclinical Infectimune™ publication in peer reviewed journal Viruses showing complete protection in animal studies with PDS0202 a novel recombinant protein-based Universal flu vaccine (Gandhapudi SK et al.

In February 2023, we announced preclinical Infectimune® publication in peer reviewed journal Viruses showing unique induction of high levels of multifunctional CD4+ T cells capable of broadly protective functions compared to leading commercial vaccine technologies (Henson TR et al.

Viruses 2023, 15 , 538).

PDS0201 combines the utility of the Versamune

platform with bacillus Mycobacterium tuberculosis (M.

tuberculosis) antigens.

Tuberculosis (TB) is the leading cause of death from a single infectious agent and is caused by the M.

tuberculosis, which is spread when people who are sick

with TB expel bacteria into the air.

About a quarter of the world’s population is infected with M.

tuberculosis and thus at risk of developing TB disease.

It has been reported that a total of 1.5 million people died from TB in 2020.

Worldwide, TB is one of the top 10 causes of death and the leading cause from a single infectious agent (above HIV/AIDS).

It is estimated that 10 million people fell ill with TB worldwide 5.7 million men, 3.2 million women and 1.1

million children.

There were cases in all countries and age groups.

Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat.

The World Health Organization (WHO) estimates that there were 484,000 new

cases with resistance to rifampicin – the most effective first-line drug, of which 78% had MDR-TB.

WHO has identified TB as a global priority and is focused on eradication of the disease.

The only licensed vaccine for prevention of TB

disease was developed almost 100 years ago.

PDS0201 is currently in preclinical development.

SARS-CoV-2 vaccine

Our Infectimune platform based COVID-19 vaccine combines our nanoparticle technology with a SARS-CoV-2 recombinant protein derived from the spike (S) protein.

Notably, the protein

in this fully synthetic vaccine includes conserved and non-mutating regions of the virus.

The vaccine has demonstrated strong potential in preclinical studies to efficiently promote the induction of killer CD8 and helper CD4 helper T cells that

recognize and induce immune responses against such non-mutating regions of the virus.

The protein also includes regions of the spike protein that result in the induction of neutralizing antibodies.

In February 2023, PDS Biotech announced the publication of Infectimune based vaccines preclinical studies demonstrating complete protection against sickness after lethal challenge

with live SARS-CoV-2 (Gandhapudi SK et al.

Also in February 2023, we announced a second preclinical Infectimune® publication in peer reviewed journal Viruses showing complete protection in animal studies with PDS0202, a novel recombinant investigational protein-based universal flu vaccine (Gandhapudi SK et al.

Viruses 2023, 15 , 432).

Versamune Development Strategy

The unique combination of high potency and excellent safety of the Versamune platform observed in preclinical studies was corroborated in the successfully-completed 12-patient

PDS0101 monotherapy Phase 1/2a clinical trial.

Oncology Development Strategy

The unique combination of high potency and favorable safety profile of the Versamune® platform observed in preclinical studies was corroborated in the successfully completed

12-patient PDS0101 monotherapy Phase 1/2a clinical trial.

All patients were infected with cancer causing (high risk) strains of HPV, which are less likely to spontaneously regress.

In September 2019, we reported retrospective clinical outcome data from

Despite most of the patients being infected with multiple HPV strains including or excluding HPV 16, regression was seen in 8 out of 10 patients, with complete regression of pre-cancerous lesions documented in 6 out of 10 patients at

their first post-treatment evaluation, which occurred within 1-3 months of completing treatment.

In addition, the fact that no disease recurrence occurred over the two-year evaluation period strongly suggested a robust and durable therapeutic

immune response due to the induction of T cells by PDS0101 administration that were clinically active.

As a result of this information and the documentation in the trial of PDS0101’s ability to generate potent and biologically active CD8 T cells

in-vivo , we focused our clinical strategy on areas of more severe unmet medical need in which PDS0101 is combined with other immune-modulating agents, including immune checkpoint inhibitors and standard of

care e.g., chemoradiotherapy, to provide improved clinical benefit to patients.

We believe that rational design of combination

immunotherapies using complementary agents that promote synergy with each other and reduce the potential for compounded toxicity will substantially enhance the potential for combination therapies to deliver improved clinical benefit for

cancer patients.

Based on our data, Versamune appears to activate an appropriate combination of immunological pathways to promote strong CD8 T cell induction while also altering the tumor microenvironment to make tumors more susceptible

to T cell attack, which we believe makes it an ideal complement to immune checkpoint inhibitors and other immune-modulating agents by enhancing their potency as part of combination therapies.

In addition, the differences in mechanism of

action between Versamune and checkpoint inhibitors, as well as the initial demonstrated safety profile of Versamune, suggests that these combinations may be potentially much better tolerated by patients than other combination therapies

involving immune checkpoint inhibitors and other cancer treatments such as immune-cytokines and chemotherapy.

VERSATILE-002:

PDS0101 + KEYTRUDA ®

In November 2020, our VERSATILE-002 Phase 2 clinical trial evaluating the combination of PDS0101 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA ® (pembrolizumab) which is the FDA-approved standard of care for first-line treatment of recurrent/ metastatic head and neck cancer opened and is actively recruiting patients.

trial will evaluate the efficacy and safety of this therapeutic combination as a first-line treatment in patients with recurrent or metastatic head and neck cancer and high-risk human papillomavirus-16 (HPV16) infection.

In this PDS Biotech-sponsored trial, patients whose cancer has returned or spread following initial treatment, will be able to avoid chemotherapy and take this combination of two

immuno-therapy drugs.

Enrolling patients with more functional immune systems that have not been compromised by extensive chemotherapy may allow improved efficacy of the combination.

Patients in the trial will receive a total of 5 cycles of

combination therapy in the context of standard of care KEYTRUDA ® therapy administered every three weeks until disease progression.

The primary endpoint of

VERSATILE-002 is the objective response rate – or ORR – at six months following initiation of treatment.

There are two cohorts in the trial.

Cohort 1 is for patients that are yet to be treated with an immune checkpoint inhibitor (ICI naïve) and

cohort 2 which consists of patients that have failed immune checkpoint inhibitor therapy (ICI refractory).

In February 2022, we announced we had achieved the preliminary efficacy milestone of at least four or more objective responses of the first 17 patients in the ICI naïve arm that

allowed that arm to proceed to full enrollment.

We also announced detailed preliminary safety data which showed that the combination is well tolerated without evidence of enhanced or significant toxicity in the first 18 patients in the ICI naïve

We have completed enrollment in Stage 1 of the ICI refractory arm and are waiting for sufficient follow up to conduct the futility analysis.

In June 2022, we announced additional preliminary efficacy and safety data from this trial at the ASCO Annual Meeting (Weiss J et al.

J Clin Oncol 40, 2022 (suppl 16;

The abstract provided preliminary data on 19 patients (safety) with available imaging data for 17 of the 19 patients (efficacy).

Highlights from the abstract were as follows:

Response rates thus far (tumor shrinkage greater than 30%) seen in 7/17 (41.2%) patients in comparison to the published results of approximately 19% for approved ICI, used as monotherapy for recurrent or

metastatic head and neck cancer, with 2 of the 7 having complete responses (CR)

Stable disease (SD) was reported in 6/17 (35.3%) patients, with 4 of the 6 (67%) experiencing tumor shrinkage of less than 30%

Clinical efficacy (ORR + SD) was seen in 13/17 (76.5%) patients

Progressive/ongoing disease was reported in 4/17 (23.5%) patients

Patients had received a median of 4/5 doses of PDS0101 (range 1-5) and 9/35 doses of KEYTRUDA® (range 1-18)

There were no treatment-related adverse events greater than or equal to Grade 3 (N=19)

No patients required dose interruption or reduction on the combination treatment

No patients discontinued the combination treatment

At 9 months of follow up (median not yet achieved):

Progression free survival (PFS) rate was 55.2%

Overall survival (OS) rate was 87.2%

In May 2022, we announced the expansion of this trial into Europe and in June 2022, as described above, we received Fast Track designation for PDS0101 in combination with

pembrolizumab.

In August 2022, we announced our independent Data Monitoring Committee (DMC) met and evaluated data from the first 43 patients and noted there were no Grade 3 or greater

treatment-related adverse events attributed to the combination.

The DMC recommended continuing the trial with no modifications.

In October 2022, we announced an end-of-phase 2 meeting with the FDA for PDS0101 in combination with KEYTRUDA ® .

We are currently evaluating the guidance on the key elements of the clinical program that will support the submission of a Biologics License Application for PDS0101.

In September 2019, we reported retrospective clinical outcome

data from this trial.

patients at their first post-treatment evaluation, which occurred within 1-3 months of completing treatment.

In addition, the fact that no disease recurrence occurred over the two-year evaluation period strongly suggested a robust and durable

therapeutic immune response due to the induction of T cells by PDS0101 administration that were clinically active.

As a result of this information and the documentation in the trial of PDS0101’s ability to generate potent and biologically

active CD8 T cells in-vivo , we focused our clinical strategy on areas of more severe unmet medical need in which PDS0101 is combined with other immune-modulating agents, including immune checkpoint

inhibitors and standard of care e.g., chemoradiotherapy, to provide improved clinical benefit to patients.

We believe that rational design of combination immunotherapies using complementary agents that promote synergy with each other and reduce the potential for compounded

toxicity will substantially enhance the potential for combination therapies to deliver improved clinical benefit for cancer patients.

Based on our data, Versamune® appears to activate an appropriate combination of immunological pathways to

promote strong CD8 T cell induction while also altering the tumor microenvironment to make tumors more susceptible to T cell attack, which we believe makes it an ideal complement to immune checkpoint inhibitors and other immune-modulating

agents by enhancing their potency as part of combination therapies.

In addition, the differences in mechanism of action between Versamune® and checkpoint inhibitors, as well as the initial demonstrated safety profile of Versamune®, suggests

that these combinations may be potentially much better tolerated by patients than other combination therapies involving immune checkpoint inhibitors and other cancer treatments such as immune-cytokines and chemotherapy.

Clinical Candidate Pipeline

National Cancer Institute:

PDS0101+ M9241 (now PDS0301) +Bintrafusp Alfa

In June 2020, the first patient was dosed under a PDS0101 Cooperative Research and Development Agreement (CRADA), in the NCI led Phase 2 investigator-initiated trial

evaluating PDS0101 with an IgG1 IL-12 (M9241), now PDS0301, and M7824 (Bintrafusp Alfa), which is owned by EMD Serono (Merck KGaA) in patients with advanced/refractory HPV-associated cancers who have failed prior treatment.

In February 2021, we

announced that the NCI’s Phase 2 clinical trial of PDS0101 for the treatment of advanced/refractory HPV-associated cancers achieved its preliminary objective response target in patients naïve to immune checkpoint inhibitors (ICI) which allowed

for full enrollment of approximately 20 patients in this group.

In addition, based on promising results in the ICI naïve arm, the trial was amended to allow enrollment of a separate cohort of ICI-refractory patients for assessment of safety and

activity of the triple combination.

Preliminary efficacy assessment of the triple combination in this added group of 20 ICI refractory patients is ongoing.

The NCI recently achieved the intended enrollment objective of 30 patients in the ICI

refractory arm of the trial.

The trial has enrolled 45 patients and enrollment in the trial will continue until the total enrollment of 56 patients is achieved.

Preclinical study results arising from this CRADA were recently published in the Journal for ImmunoTherapy of Cancer, Immunomodulation to

enhance the efficacy of an HPV therapeutic vaccine (Journal for ImmunoTherapy of Cancer 2020;8:e000612.

doi:10.1136/ jitc-2020-000612) , indicating that PDS0101 generated both HPV-specific T cells

and an associated antitumor response when used as a monotherapy.

When PDS0101 was combined with two other novel clinical-stage anti-cancer agents, Bintrafusp Alfa and M9241, now PDS0301, the preclinical data suggested that all three therapeutic

agents worked synergistically to provide superior tumor T cell responses and subsequent tumor regression when compared to any of the agents alone or the 2-component combinations.

If the published preclinical data demonstrating powerful activity

of the triple combination is successfully confirmed in the ongoing Phase 2 trial, this triple combination could form the basis of a unique platform providing improved cancer treatments across multiple cancers.

In June 2021, at the American Society of Clinical Oncology (ASCO) conference the NCI announced interim data in this trial which included, data in both ICI naïve and refractory

patients (Strauss J et al.

J Clin Oncol 39, 2021 [suppl 15;

abstr 2502]).

In the ICI naïve group 83% (5/6) of patients had an objective response, and 1 subject had achieved a complete response with no

evidence of disease.

100% of the ICI naïve patients were alive at a median duration of 8 months.

In the ICI refractory group 42% (5/12) of patients had an objective response, and 1 subject had achieved a complete response with no evidence of

10/12 (83%) of ICI refractory patients were alive at a median duration of 8 months.

An update provided in January 2022 showed as of December 31, 2021, that >40 subjects had been recruited into the trial and 30 HPV16-positive

patients had been evaluated.

The median survival of all patients (3:1 ICI refractor to naïve) was 12 months and progressing.

The historical survival of ICI naïve and ICI refractory advanced HPV-associated cancers when treated with ICI are 7-11

months and 3-4 months, respectively, best reported median survival to date with systemic therapy of 8.2 months in ICI refractory head and neck cancer.

Versamune® PDS0101+ PDS01ADC (formerly known as PDS0301/M9241/NHS-IL-12) +Bintrafusp Alfa

In June 2020, the first patient was dosed under a Cooperative Research and Development Agreement (CRADA), in the NCI led Phase 2 investigator-initiated trial evaluating our product candidates

PDS0101 and PDS01ADC in combination with M7824 (Bintrafusp alfa), a bi-functional immune checkpoint inhibitor (ICI) which is owned by EMD Serono (Merck KGaA) in patients with advanced HPV-positive cancers who have failed prior treatment.

February 2021, the NCI’s Phase 2 clinical trial of PDS0101 for the treatment of advanced HPV-positive cancers had achieved its preliminary objective response target in patients naïve to check point inhibitors which allowed for full enrollment of

approximately 20 patients in this group.

In addition, based on promising results in the ICI naïve arm, the trial was amended to allow enrollment of a separate cohort of IC -resistant patients for assessment of safety and activity of the triple

The trial has been closed for enrollment.

Preliminary efficacy assessment of the triple combination in this added group of 29 ICI resistant patients has been completed and evaluation of long-term patient survival is ongoing.

Preclinical study results arising from this CRADA were published in the Journal for ImmunoTherapy of Cancer, Immunomodulation to enhance the efficacy of an HPV

therapeutic vaccine (Journal for ImmunoTherapy of Cancer2020;8:e000612.

Doi:10.1136/ jitc-2020-000612), and indicate that PDS0101 generated both HPV-specific T cells and an associated antitumor response when used as a monotherapy.

When PDS0101 was combined with the two other novel clinical-stage anti-cancer agents, Bintrafusp Alfa and M9241 (which

is now owned by us and referred to as PDS01ADC), the preclinical data suggested that all three therapeutic agents worked synergistically to provide superior tumor T cell responses and subsequent tumor

regression when compared to any of the agents alone or the 2-component combinations.

The published preclinical data demonstrating powerful activity of the triple combination appears to be corroborated in

the Phase 2 trial, and this triple combination could form the basis of a unique platform providing improved cancer treatments across multiple cancers.

In June 2022, at the 2022 ASCO Annual Meeting, the NCI provided an update to the preliminary data presented at the 2021 meeting (Strauss J et al.

1 unchanged sentence

abstr 2518]).

This included data from 30 patients and highlights were as follows:

This included data from 30 HPV16-positive patients and highlights were as follows:

Objective response (OR = > 30% tumor reduction) was seen in 88% (7/8) of patients with ICI naive disease;

4/7 (57%) patients’ responses are ongoing (median 17 months).

With ICI refractory patients:

PDS0301 dosing appears to affect response rates, with 5/8 (63%) patients receiving PDS0301 at 16.8 mcg/kg achieving an OR compared to 1/14 (7%) patients who received PDS0301 at

8 mcg/kg achieving an OR;

4/6 (67%) patients’ responses are ongoing (median 12 months).

Tumor reduction was seen in 45% (10/22) of patients with ICI-refractory disease, including patients receiving high or low dose PDS0301.

In ICI refractory patients treated with high or low dose PDS0301, survival outcomes were similar (p=0.96 by Kaplan Meier analysis).

4/7 (57%) patients’ responses were ongoing (median 17 months).

With ICI resistant patients:

PDS01ADC dosing appeared to affect response rates, with 5/8 (63%) patients receiving PDS01ADC at 16.8 mcg/kg achieving an OR compared to 1/14 (7%) patients who received PDS01ADC

at 8 mcg/kg achieving an OR;

4/6 (67%) patients’ responses were ongoing (median 12 months).

Tumor reduction was seen in 45% (10/22) of patients with ICI resistant disease, including patients receiving high or low dose PDS01ADC.

In ICI resistant patients treated with high or low dose PDS01ADC, survival outcomes were similar (p=0.96 by Kaplan Meier analysis).

At a median of 12 months of follow up 17/22 (77%) of patients were alive.

4 unchanged sentences

There were no grade 5 treatment-related AEs.

We believe the study results to date strongly suggest, in agreement with the published preclinical studies, that all 3 drugs contribute to the clinical outcomes.

In September 2022, we announced, in agreement with the NCI, that the ICI refractory patients had been selected as the preferred treatment group in the on-going PDS0101-based

triple combination therapy in advanced HPV-positive cancers and the trial was closed to further enrollment given the ICI refractory arm has been fully recruited.

In October 2022, we announced expanded interim data as follows:

We believe the trial results to date strongly suggest, in agreement with the published preclinical studies, that all 3 drugs contribute to the clinical outcomes.

In September 2022, we determined, in agreement with the NCI, to select the ICI resistant patients as the preferred treatment group in the on-going PDS0101-based triple

combination therapy in advanced HPV-positive cancers and the trial was closed to further enrollment given the ICI resistant arm had been fully recruited.

In October 2022, we presented additional interim data as follows:

Survival data:

66% (19/29) of HPV16-positive ICI refractory patients in the cohort were alive at a median follow up of 16 months.

66% (19/29) of HPV16-positive ICI resistant patients in the cohort were alive at a median follow up of 16 months.

Safety profile:

3 unchanged sentences

75% (6/8) were alive at a median follow up of 25 months and 38% (3/8) of responders had a complete response.

In December 2022, we announced expanded interim data as follows:

Median OS is 21 months in 29 checkpoint inhibitor refractory patients who received the triple combination.

The reported historical median OS in patients with ICI refractory disease is 3-4 months seen

with checkpoint inhibitors and best reported median survival to date with systemic therapy of 8.2 months in ICI refractory head and neck cancer .

In ICI naïve subjects, 75% remain alive at a median follow-up of 27 months.

As a result, median OS has not yet been reached.

Historically median OS for similar patients with platinum experienced ICI naïve disease is 7-11 months.

Objective response rate (ORR) in ICI refractory patients who received the optimal dose of the triple combination is 63% (5/8).

In December 2022, we presented interim data as follows:

Median OS was 21 months in 29 checkpoint inhibitor resistant patients who received the triple combination.

The reported historical median OS in patients with ICI resistant disease is 3-4 months seen with

checkpoint inhibitors and best reported median survival to date with systemic therapy of 8.2 months in ICI resistant head and neck cancer.

In ICI naïve subjects, 75% remained alive at a median follow-up of 27 months.

As a result, median OS had not yet been reached.

Historically, observed median OS for similar patients with platinum

experienced ICI naïve disease is 7-11 months.

Objective response rate (ORR) in ICI resistant patients who received the optimal dose of the triple combination is 63% (5/8).

In current approaches ORR is reported to be less than 10%.

ORR in ICI naïve patients with the triple combination is 88%.

In current approaches ORR is reported to be less than 25% with FDA-approved ICIs in HPV-associated cancers.

Safety data have not changed since October’s update.

48% (24/50) of patients experienced Grade 3 (moderate) treatment-related adverse events (AEs), and 4% (2/50)

patients experienced Grade 4 (severe) AEs, compared with approximately 70% of patients receiving the combination of ICIs and chemotherapy reporting Grade 3 and higher treatment-related AEs.

In February 2023, we announced the successful completion of a Type B meeting with the FDA for the combination therapy of PDS0101, PDS0301, and an FDA-approved immune

checkpoint inhibitor for the treatment of recurrent/metastatic HPV-positive ICI-refractory head and neck cancer.

We confirmed the required contents of the study design for a potential registration of the combination.

ORR in ICI naïve patients with the triple combination was reported as 88%.

In current approaches, ORR is reported to be less than 25% with FDA-approved ICIs in HPV-positive cancers.

Safety data had not changed since October’s update.

48% (24/50) of patients experienced Grade 3 (moderate) treatment-related adverse events (AEs), and 4% (2/50) patients experienced Grade 4 (severe) AEs,

compared with approximately 70% of patients receiving the combination of ICIs and chemotherapy reporting Grade 3 and higher treatment-related AEs.

In February 2023, we announced the successful completion of a Type B meeting with the FDA for the combination therapy of PDS0101, PDS01ADC, and an FDA-approved immune

checkpoint inhibitor for the treatment of recurrent/metastatic HPV-positive ICI-resistant head and neck cancer.

We confirmed the required contents of the trial design for a potential registrational trial of the combination.

In November 2023, we released updated interim survival data as follows:

75% of ICI naïve patients remain alive at 36 months;

published median OS in similar patients is 7-11 months

12-month survival rate in ICI resistant patients was 72%

Median OS in ICI resistant HPV-positive patients is approximately 20 months;

published median OS is 3.4 months

VERSATILE-002:

PDS0101 + Keytruda®

In November 2020, our VERSATILE-002 Phase 2 clinical trial evaluating the combination of PDS0101 in combination with Merck’s anti-PD-1 therapy, Keytruda® (pembrolizumab) which is the

FDA-approved standard of care for first-line treatment of recurrent/ metastatic head and neck cancer commenced.

Enrollment in stage 2 of 2 for the ICI naïve arm and the ICI resistant arms are complete.

The clinical trial was designed to

evaluate the efficacy and safety of this therapeutic combination as a first and second line treatment in patients with recurrent or metastatic head and neck cancer and high-risk human papillomavirus-16 (HPV16) infection.

In this PDS Biotech-sponsored trial patients whose cancer had returned following initial treatment or spread were treated with the combination of PDS0101 and Keytruda®

to evaluate if the addition of PDS0101 might improve the efficacy reported in published studies of Keytruda® alone.

Patients in the trial received a total of 5 cycles of combination therapy in the

context of standard of care Keytruda® therapy which was administered every three weeks until disease progression.

The primary endpoint of VERSATILE-002 is the objective response rate (ORR) at six months

following initiation of treatment.

There are two cohorts in the trial.

Cohort 1 is for patients who have yet to be treated with an immune checkpoint inhibitor (ICI naïve) and cohort 2 which consists of

patients who have failed immune checkpoint inhibitor therapy (ICI resistant).

In February 2022, we achieved the preliminary efficacy milestone of at least four or more objective responses among the first 17 patients in the ICI naïve arm, allowing that arm to proceed to

full enrollment.

We also announced detailed preliminary safety data which showed that the combination was well tolerated without evidence of enhanced or significant toxicity in the first 18 patients in the ICI naïve arm.

We also completed enrollment in Stage 1 of the ICI resistant arm and were awaiting sufficient follow-up to conduct the futility analysis .

In May 2022, we expanded this trial into Europe and in June 2022, we received Fast Track designation from the U.S.

FDA for PDS0101 in combination with pembrolizumab.

In June 2022, we presented additional preliminary efficacy and safety data from this trial at the ASCO Annual Meeting (Weiss J et al.

J Clin Oncol 40, 2022

abstr 6041)) .

The abstract provided preliminary data on 19 patients (safety) with available imaging data for 17 of the 19 patients (efficacy).

Data on 17 patients was presented.

Highlights from the abstract were as follows:

Confirmed and unconfirmed objective response rates (ORR) thus far (tumor shrinkage greater than 30%) was seen in 7/17 (41.2%) patients with 2 of the 7 having complete responses (CR).

Published results state ORR of approximately 19% for

approved ICIs, used as monotherapy for recurrent or metastatic head and neck cancer.

Stable disease (SD) was reported in 6/17 (35.3%) patients, with 4 of the 6 (67%) experiencing tumor shrinkage of less than 30%

Clinical efficacy (ORR + SD) was seen in 13/17 (76.5%) patients

Progressive/ongoing disease was reported in 4/17 (23.5%) patients

Patients had received a median of 4/5 doses of PDS0101 (range 1-5) and 9/35 doses of Keytruda® (range 1-18)

There were no treatment-related adverse events greater than or equal to Grade 3 (N=19)

No patients required dose interruption or reduction on the combination treatment

No patients discontinued the combination treatment

At 9 months of follow up (median not yet achieved):

Progression free survival (PFS) rate was 55.2%

Overall survival (OS) rate was 87.2%

No control or comparative studies have been conducted between ICIs and PDS0101

In August 2022, our independent Data Monitoring Committee (DMC) met and evaluated data from 43 patients and noted there were no Grade 3 or greater treatment-related adverse events attributed to

the combination.

The DMC recommended continuing the trial with no modifications.

In October 2022, we announced the results of an end-of-phase 2 meeting with the FDA for PDS0101 in combination with Keytruda®.

We have completed the plan for the Phase 3 clinical program that

will support the submission of a BLA for PDS0101 and have submitted it to the FDA.

In December 2022, we completed the first stage of enrollment in the ICI resistant arm.

Cohort follow-up is in progress that will permit a futility analysis to determine

progression to stage 2 enrollment is in progress.

In May 2023, we completed enrollment in the ICI naïve arm.

We filed our amended Investigational New Drug (IND) application with the FDA in the third quarter of 2023.

October 2023, we received feedback from the FDA on the amended IND.

Later in October, as part of business development discussions, we received insights from potential business partners on the Phase 3 clinical protocol.

In June 2023, an abstract was presented at the 2023 American Society of Clinical Oncology:

Abstract number 6012, Safety and Efficacy of Immune

Checkpoint Inhibitor (ICI) Naïve Cohort from Study of PDS0101 and Pembrolizumab in HPV16-Positive Head and Neck Squamous Cell Carcinoma (HNSCC).

The abstract was also selected as one of the featured posters to be reviewed by an expert panel in

the Head and Neck Cancer discussion session.

Data on 34 patients was presented.

The data from the abstract is as follows:

Estimated 12-month overall survival rate was 87.1%.

Published results are 36-50% with approved ICIs used alone.

Median progression-free survival was 10.4 months (95% CI 4.2, 15.3).

Published results are median PFS of 2-3 months for approved ICIs when used as monotherapy in patients with similar PD-L1 levels.

A disease control rate (disease stabilization or tumor shrinkage) of 70.6% (24/34)

Confirmed and unconfirmed objective response rate is 41.2% (14/34 patients), which is identical to the preliminary response rate data PDS Biotech previously reported at ASCO 2022 (7/17 patients).

To date, these responses have been

confirmed in 9 of the 34 patients (26.5%), including one complete response.

15/34 patients (44.1%) had stable disease.

9/34 patients (26.5%) had progressive disease.

4/48 (8.3%) of patients had a Grade 3 treatment-related adverse event (TRAE).

No Grade 4 or higher TRAEs were observed.

In October 2023, at a key opinion roundtable updated interim data was presented based on an August 2, 2023 cut off from our VERSATILE-002 Phase 2 clinical trial evaluating PDS0101 in combination with Merck’s

anti-PD-1 therapy, Keytruda® (pembrolizumab) which is an FDA-approved standard of care for first-line treatment of recurrent/ metastatic head and neck cancer.

Data on 52 patients was presented.

The data from the roundtable based on investigator

assessment was as follows:

Highlights from the ICI naïve cohort include:

24-month overall survival rate is 74%;

published 24-month survival rate of less than 30% for approved ICI.

12-month OS rate is 80%;

published results of 30-50% with approved ICIs.

Tumor shrinkage seen in 60% (31/52) of patients.

Confirmed overall response rate is 27% (14/52) to date.

Median progression-free survival is 8.1 months to date;

published results of 2-3 months PFS with approved ICIs.

13% (8/62) of patients experienced Grade 3 treatment-related adverse events (TRAE) and 0% (0/62) experienced Grade 4 or 5 TRAE;

published results report 13-17% Grade 3-5 TRAE with approved ICI monotherapy.

60% (33/55) of patients have CPS score of 1-19 (who generally have a weaker response to Keytruda®), and 40% (22/55) have CPS score >20 (who generally have a higher response to Keytruda®).

Highlights form the ICI refractory cohort include:

The 12-month OS rate is 56%.

The published median 12-month OS rate is 17% with no salvage chemotherapy following tumor progression on ICI (ICI Resistant).

0% (0/21) confirmed ORR suggests that PDS0101’s impact on survival does not appear to be dependent on tumor shrinkage.

4% (1/25) of patients experienced Grade 3 TRAE and 0% (0/21) patients experienced Grade 4 and 5 TRAE.

MD Anderson Cancer Center (IMMUNOCERV):

PDS0101+ Chemoradiotherapy

In October 2020, another PDS0101 Phase 2 IIT was initiated with The University of Texas MD Anderson Cancer Center and is actively recruiting patients.

This clinical trial is

investigating the safety and anti-tumor efficacy of PDS0101 in combination with standard-of-care chemo-radiotherapy, or CRT, and their correlation with critical immunological biomarkers in patients with locally advanced cervical cancer.

believe that Versamune has strong T cell induction has the potential to enhance efficacy of the current standard of care CRT treatment in this indication.

Enrollment rate in this trial had been negatively impacted by the COVID-19 pandemic and

enrollment is on-going.

In November 2022, we announced data from this trial was included in a poster presentation at the 2022 SITC Annual Meeting which included the following:

In October 2020, a PDS0101 Phase 2 IIT was initiated with The University of Texas MD Anderson Cancer Center and is actively recruiting patients.

This clinical trial is investigating the safety

and anti-tumor efficacy of PDS0101 in combination with standard-of-care chemo-radiotherapy, or CRT, and their correlation with critical immunological biomarkers in patients with locally advanced cervical cancer.

We believe that Versamune® has

strong T cell induction with the potential to enhance efficacy of the current standard of care CRT treatment in this indication.

In November 2022, data from this trial was included in a poster presentation at the 2022 SITC Annual Meeting which included the following:

9 of the 17 patients had completed a Day 170 post-treatment Positron Emission Tomography, Computed Tomography (PET CT) scan to assess the status of the cancer.

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generated by the treatment is positively correlated with tumor cell death, suggesting cytotoxic CD8 T cells are important mediators of antigen-specific immunity.

The data affirm that PDS0101 activates Type 1 interferon pathway in humans, mimicking the mechanism previously demonstrated in preclinical studies in animal models.

Toxicity of PDS0101 remains limited to low-grade local injection site reactions.

In October 2023, data demonstrated that PDS0101 in combination with standard-of-care (SOC) chemoradiotherapy was associated with a rapid decline in human papillomavirus circulating cell-free DNA

(ctHPV-DNA), a potential predictive biomarker of treatment response.

The data from the IMMUNOCERV Phase 2 clinical trial was featured in an oral presentation at the American Society for Radiation Oncology Annual Meeting which included the

Earlier and greater proportion of ctDNA clearance with PDS0101 plus chemoradiation (CRT) vs.

SOC CRT alone (81.3% clearance after 3 weeks vs.

30.3% with SOC (p=0.0018), and 91.7% of clearance at 5 weeks vs.

53.1% with SOC (p=0.0179).

Baseline ctDNA levels correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node involvement;

100% of patients treated with PDS0101 had cancer that had spread to the lymph nodes.

PDS0101 Monotherapy and in combination with Keytruda®

In February 2022 we announced the initiation of an Investigator-Initiated Trial (ITT), MC200710, for PDS0101 alone or in combination with the immune checkpoint inhibitor, KEYTRUDA ® , in patients with HPV-associated oropharyngeal cancer (HPV(+)OPSCC) at high risk of recurrence.

In February 2022, we initiated an Investigator-Initiated Trial (ITT), MC200710, for PDS0101 alone or in combination with the immune checkpoint inhibitor, Keytruda® , in patients with HPV-positive oropharyngeal cancer (HPV(+)OPSCC) at high risk of recurrence.

The trial is being led by Drs.

David Routman, Katharine Price, Kathryn

Van Abel, and Ashish Chintakuntlawar at Mayo Clinic, a nationally and internationally recognized center of excellence for the treatment of head and neck cancers.

We believe that this trial not only broadens our addressable patient population of

those affected by the increasing incidence of HPV(+)OPSCC, but also allows us to better understand the activity of PDS0101 alone or in combination with KEYTRUDA ® in

earlier stages of disease.

David Routman, Katharine Price, Kathryn Van Abel, and Ashish Chintakuntlawar at Mayo

Clinic, a nationally and internationally recognized center of excellence for the treatment of head and neck cancers.

We believe that this trial not only broadens our addressable patient population of those affected by the increasing incidence

of HPV(+)OPSCC, but also allows us to better understand the activity of PDS0101 alone or in combination with Keytruda® in earlier stages of disease.

This trial is currently open for enrollment.

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PDS0101 has been shown to induce killer T cells that target and kill HPV-positive cancers, either alone or in combination with ICIs in preclinical studies, and in combination in clinical studies of patients with advanced

recurrent/metastatic HPV-associated cancers.

recurrent/metastatic HPV-positive cancers.

This trial will explore whether PDS0101 with or without checkpoint inhibition may increase HPV-specific anti-tumor responses, potentially resulting in tumor shrinkage, pathologic regression, and

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PDS0102 is designed to treat TARP-associated cancers, including acute myeloid leukemia (AML), prostate and breast cancer.

In our preclinical work, the administration of PDS0102, the Versamuine+TARP antigen combination led to the induction of

In our preclinical work, in the administration of PDS0102, the Versamune®+TARP antigen combination led to the induction of

large numbers of tumor targeted killer T cells.

In addition, the TARP tumor antigen alone has already been studied at the NCI in men with prostate cancer and been shown to be safe, immunogenic with slowing tumor growth rates (NCT00972309).

evaluating the next steps in the clinical development of PDS0102 and are seeking nondilutive financings to move to human trials.

In April 2020, the above mentioned, PDS-NCI CRADA was expanded beyond PDS0101 to include clinical and preclinical development of PDS0103.

In April 2020, the above mentioned CRADA between PDS Biotech and the NCI was expanded beyond PDS0101 to include clinical and preclinical development of PDS0103.

PDS0103 is an investigational

immunotherapy owned by us and designed to treat cancers associated with the mucin 1, or MUC1, oncogenic protein.

immune therapy owned by us and designed to treat cancers associated with the mucin-1, or MUC1, oncogenic protein.

These include cancers such as ovarian, breast, colorectal and lung cancers.

PDS0103 combines Versamune with novel highly immunogenic

agonist epitopes of MUC1 developed by the NCI and licensed by PDS.

PDS0103 is currently in late preclinical development.

MUC1 is highly expressed in several types of cancer

and has been shown to be associated with drug resistance and poor disease prognosis in breast, colorectal, lung and ovarian cancers, for which PDS0103 is being developed.

Expression of MUC1 is often associated with poor disease prognosis,

due in part to drug resistance.

In preclinical studies, and similarly to PDS0101, PDS0103 demonstrated the ability to generate powerful MUC1-specific CD8 killer T cells.

In the first quarter of 2022, we held a pre-IND meeting with the FDA

Our primary goal is commercialization of PDS0101, and allocation of resources to implement an earlier than planned start of a registrational trial may delay PDS0103 initiation .

PDS0103 combines Versamune® with novel highly

immunogenic agonist epitopes of MUC1 developed by the NCI and licensed by us.

PDS0103 is currently in the tech transfer and clinical scale up and manufacturing stage.

MUC1 is highly expressed in several types of cancer and has been shown to be associated with drug resistance and poor disease prognosis in breast, colorectal, lung and ovarian cancers, for which

PDS0103 is being developed.

Expression of MUC1 is often associated with poor disease prognosis, due in part to drug resistance.

In preclinical studies, and similarly to PDS0101, PDS0103 demonstrated the ability to generate powerful MUC1-specific

CD8 killer T cells.

In the first quarter of 2022, we held a pre-IND meeting with the FDA on PDS0103, and we are prepared to submit our IND package by the second half of 2024.

IL-12 Oncology Immunocytokine Pipeline

PDS01ADC has been designed to overcome the limitations of cytokine therapy as explained above, and based on extensive preclinical studies performed at the NCI evaluating PDS01ADC as a

monotherapy and also in combinations with established standard of care treatments for cancer, we believe that PDS01ADC has significant potential as a cytokine therapy independent of Versamune®.

Based on the informative preclinical studies, a

number of ITT Phase 2 trials are currently in progress at the NCI, some of which are outlined below:

Phase 2 Study Evaluating ICI Naïve and Resistant Patients with HPV-positive malignancies treated with PDS01ADC, PDS0101 and bintrafusp alfa.

A Phase 2 Study Evaluating T-Cell Clonality After Stereotactic Body Radiation Therapy Alone and in Combination with the Immunocytokine PDS01ADC in Localized High and Intermediate Risk Prostate Cancer Treated with Androgen Deprivation

A Phase 1/2 Study of PDS01ADC in Combination with Docetaxel in Adults with Metastatic Castration Sensitive and Castration Resistant Prostate Cancer

Phase 1/2 of PDS01ADC going forward as a Monotherapy in Advanced Kaposi Sarcoma

Phase 1/2 of PDS01ADC in Combination of with a Histone Deacetylase (HDAC) Inhibitor in ICI resistant MUC1-positive colon and bladder cancers among others

In October 2023, interim safety and immune response data was presented for the first-in-human Phase 1/2 clinical trial evaluating PDS01ADC in combination with current SOC chemotherapy,

docetaxel, to treat metastatic castration sensitive and castration resistant prostate cancer.

The data was featured in an oral presentation at the 11 th Annual

Meeting of the International Cytokine & Interferon Society.

Data presented as follows:

Decrease in PSA levels was seen in all patients at all three tested doses of PDS01ADC, and 61% of patients had at least a 60% decrease in PSA levels.

All doses of the combination were well-tolerated with one patient experiencing Grade 4 neutropenia.

Administration of the combination was associated with decreases in T reg cells and increases in activated natural killer (NK) cells, memory CD8 T cells, proliferating CD4 and CD8 T cells and cytokines INF-γ and Interleukin 10

The changes in immune responses with the combination were independent of the PDS01ADC dose.

We are working closely with the NCI to determine the best pathway forward for the prioritized PDS01ADC studies, as well as evaluating the use of PDS01ADC in combination with other Versamune®

based clinical candidates.

Infectimune® Development Strategy

Based on the promising data recently announced with the universal seasonal flu vaccine and the current focus of the NIAID in developing more effective flu vaccines, we have

decided to opportunistically focus our near-term infectious disease activities to align with the interests of the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) program.

This will involve development of a universal seasonal

flu vaccine and the potential development of a universal pandemic influenza vaccine based on similar computationally designed antigens as have shown promise with Infectimune.

In July 2022, we announced the presentation of universal flu vaccine preclinical data for PDS0202 at the 41 st American Society of Virology meeting:

We believe that the key differentiating attributes of the Infectimune® platform technology are strong induction of CD8 and CD4 T cells as well as antibodies which can be leveraged to improve

treatment and preventive options in several infectious disease indications.

In January 2022, we presented preclinical data on our universal flu program sponsored by the National Institute of Allergy and Infectious Disease (NIAID) demonstrating the potential of the

Infectimune® technology with computationally designed influenza proteins developed by the laboratory of Dr.

Ted Ross at the University of Georgia to generate broadly protective anti-influenza immune responses across multiple strains of influenza

This data has provided a unique opportunity to highlight Infectimune®’s potentially transformative utility in the development of more broadly effective and longer lasting protective vaccines.

Current preventive and prophylactic

vaccine approaches and technologies predominantly focus on creating strong induction of antibody responses.

However, the induction of T cell responses, in addition to antibody responses, provides more durable and broad protection against

infectious diseases.

Based on the data with the universal seasonal flu vaccine in animals and the current focus of the NIAID in developing more effective flu vaccines, we have decided to focus our near-term

infectious disease activities to align with the interests of the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVICs) program.

This will involve development of a universal seasonal flu vaccine and the potential development of a

universal pandemic influenza vaccine, which is based on similar computationally designed antigens that have shown promise with Infectimune®.

In July 2022, universal flu vaccine preclinical data for PDS0202 at the 41 st American Society of Virology meeting:

Abstract number 3733830, Infectimune® enhances antibodies elicited by COBRA hemagglutinin influenza vaccine.

We are evaluating the next steps in the clinical development and funding for

We are evaluating the next steps in the clinical development and funding for PDS0202.

The results for Infectimune® based vaccines were published in two separate articles in the peer reviewed journal Viruses in February

preclinical studies demonstrating complete protection against sickness after lethal challenge with live SARS-CoV-2 or influenza viruses (Gandhapudi SK et al.

Viruses 2023, 15 , 432) and 2.

Dramatically enhanced CD4 T cell responses to recombinant influenza proteins compared to leading commercial vaccine adjuvants (Henson TR et al.

2023, 15 , 538).

In September 2023, data on our investigational universal flu vaccine, PDS0202, were presented at the 9 th European

Scientific Working Group on Influenza (ESWI) conference.

These data demonstrated active neutralization across multiple influenza viruses in animals and provided protection against infection and weight loss after challenging with high doses of

H1N1 viruses not previously exposed to flu.

Universal Flu

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Ted Ross and licensed from the University of Georgia.

PDS0202 preclinical development was supported by an agreement with the

NIAID CIVICs, program, with a goal of progressing into a human clinical trial with nondilutive financing.

PDS0202 preclinical development was supported by an agreement with

the NIAID CIVICs, program, with a goal of progressing into a human clinical trial with nondilutive financing.

Preclinical development studies were performed at three sites:

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Medicine, and the CIVICs Center for Influenza Vaccine Research for High-Risk Populations.

The data produced in the preclinical showed significant levels of hemagglutinin inhibition (HAI) titer levels when utilizing PDS0202 as compared to COBRA

antigens alone ranging from 28x to 62x on various strains of the H1N1 influenza virus.

The preclinical data also showed all animals in the control group when challenged by the flu virus became sick and died while all animals treated with either a 3mcg (high

dose) or .012mcg (low dose) of PDS0102 remained alive and healthy.

We are seeking nondilutive financing for the next stage of clinical development.

PDS0203 is being designed with the goal to potentially provide long-term and broad protection against infection from COVID-19 and its potential mutations, based on the understood

potential of Infectimune to prime the immune system to generate both antibodies for near term protection and T cell responses for long term protection against pathogens.

Preclinical data of studies performed at the University of Kentucky

indicates that PDS0203 elicits the induction of highly active and potent virus-specific CD8 killer and CD4 helper T cells within 14 days of treatment.

The study also showed induction of the long-lasting virus-specific memory T cells necessary

for longer term protection.

A 30-45-fold increase in COVID-19 specific T cells was observed by Day 14 when compared to the vaccine without Versamune.

These preclinical studies also indicated induction of strong anti-SARS-CoV-2 neutralizing

antibodies within 14 days, with a 20-25-fold increase when compared to the vaccine without Versamune.

As previously noted, the results highlighted above for Infectimune based PDS0202 and PDS0203 were published in the peer reviewed journal Viruses

in February 2023:

preclinical studies demonstrating complete protection against sickness after lethal challenge with live SARS-CoV-2 or influenza viruses (Gandhapudi SK et al.

Viruses 2023, 15 , 432) and dramatically enhanced CD4 T cell responses to recombinant influenza proteins compared to leading commercial vaccine adjuvants (Henson TR et al.

2023, 15 , 538).

Since our inception we have devoted substantially all our resources to developing our Versamune and Infectimune platforms and our Versamune and Infectimune based products, advancing preclinical programs, conducting clinical trials, manufacturing PDS0101 for clinical trials, and providing general and administrative support.

We have funded

our operations primarily from the issuance of common stock.

The data produced in the preclinical studies showed significant levels of hemagglutinin inhibition (HAI) titer levels when utilizing PDS0202 as compared

to COBRA antigens alone ranging from 28x to 62x on various strains of the H1N1 influenza virus.

The preclinical data also showed all animals in the control group, when challenged by the flu virus became sick and died while all animals treated with either a 3mcg (high dose) or .012mcg (low dose) of PDS0102

remained alive and healthy.

Clinical Development Strategy

Since our inception we have devoted substantially all our resources to developing our Versamune® and Infectimune® platforms, and products derived thereof, as well as

PDS01ADC, advancing preclinical programs, conducting clinical trials, manufacturing PDS0101 and PDS01ADC for clinical trials, and providing general and administrative support.

We have funded our operations primarily from the issuance of common

We have not generated any product revenue to date.

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Our future funding requirements will depend on many factors, including the following:

the timing and costs of our planned clinical trials;

the timing and costs of our planned preclinical studies of our Versamune, Versamune plus PDS0301 and Infectimune based products;

the timing and costs of our planned clinical trials and manufacturing of our clinical products;

the timing and costs of our planned preclinical studies of our lead program of Versamune® PDS0101 in combination with PDS01ADC and an immune checkpoint inhibitor, as well as other earlier-stage programs;

the outcome, timing and costs of seeking regulatory approvals;

ability to repay debt financings including interest payments;

the ability to repay debt financings including interest payments;

the terms and timing of any future collaborations, licensing, consulting or other arrangements that we may enter into;

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the extent to which we license or acquire other products and technologies.

Development Pipeline

Our current program development pipeline is shown below:

We are led by a team of executives and directors with significant experience in drug discovery, development and commercialization.

Our founder and CEO Frank Bedu-Addo has been

responsible for developing and launching products for KBI BioPharma Inc., Schering-Plough, Merck, Elan Corporation, and the National Cancer Institute.

Our other co-founder and Chief Scientific Officer, Dr.

Gregory Conn has more than 35 years of

drug-development experience, including development of antiviral and anticancer drugs through to commercialization.

Our Chief Medical Officer, Dr.

Wood has over 30 years of translational clinical research experience and held senior

positions at the National Cancer Institute Center for Cancer Research.

Our Chief Financial Officer, Matthew Hill has over 25 years of experience in finance and held prior roles as Chief Financial Officer and in operational leadership roles at

several public life science companies.

We are supported by scientific leaders in the field of vaccine development and oncology.

Lisa Rohan, one of our founders, is Chair of the Scientific Advisory Board.

professor in the department of Pharmaceutical Sciences at the University of Pittsburgh where she also holds appointments in the Department of Obstetrics, Gynecology and Reproductive Sciences in the School of Medicine and the Clinical Translational

Science Institute.

Mark Einstein, Professor and Chair in the Department of OB/ GYN & Women’s Heath at Rutgers University Medical School is an expert in HPV-related pathogenesis, therapy and prevention of lower anogenital tract and

gynecologic cancers.

He is an active leader for management guidelines and translating clinical study and translational data for the World Health Organization, American Cancer Society, Society of Gynecologic Oncology and the American College of

Obstetrics and Gynecology.

Gross, Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center.

Jon Wigginton, President, Research and Development Bright Peak Therapeutics and former

President of Society for Immunotherapy of Cancer.

Professor Leaf Huang, one of our founders, is a Distinguished Professor of Pharmaco-engineering and Molecular Pharmaceutics at the Eshelman School of Pharmacy, University of North Carolina at Chapel

Hill pioneered the liposome design and manufacture of cationic lipid vector nanoparticles as a delivery system for cDNA, mRNA, siRNA, proteins and peptides for tumor growth inhibition and for vaccines in treating cancer and infectious diseases.

Olivera Finn is a Distinguished Professor of Immunology at the University of Pittsburgh School of Medicine and she discovered the MUC1 antigen.

Our Principal Investigator for the PDS0101 Head and Neck Trial with KEYTRUDA ® for first-line treatment of recurrent/ metastatic Head and Neck Cancer is Dr.

Jared Weiss, Associate Professor of Medicine, University of North Carolina Lineberger

Comprehensive Cancer Center, who is an expert in head and neck thoracic oncology with a focus on immunotherapeutic approaches for these diseases.

The following table

sets forth certain information about our executive officers as of the date of the filing of this Annual Report:

Frank Bedu-Addo, Ph.D.

President, Chief Executive Officer, Principal Executive Officer and Director

Chief Scientific Officer

Shepard, M.D.

Chief Medical Officer

Lars Boesgaard

Chief Financial Officer, Principal Financial Officer and Principal Accounting Officer

Spencer Brown

Senior Vice President, General Counsel, Chief Compliance Officer

Frank Bedu-Addo, Ph.D.

Bedu-Addo has served as director, President and Chief Executive Officer of PDS Biotech since March 2019.

Bedu-Addo is a veteran biotech executive with experience

successfully starting and growing biotechnology organizations.

He has been responsible for the oversight, development and implementation of both operational and drug development strategies in both large organizations and emerging biotechnology

Bedu-Addo was a member of the senior executive team at KBI BioPharma, Inc.

As Vice President of Drug Development, he oversaw all operations including business development, drug development/manufacturing and profit and loss.

Before his tenure at KBI, he successfully started and managed Cardinal Health’s East Coast biotechnology drug development and manufacturing operations.

Prior to Cardinal Health, Dr.

Bedu-Addo was an Associate Director at Akzo-Nobel, Senior

Scientist at Elan (The Liposome Co.), and Principal Scientist at Schering-Plough.

In these positions, he contributed to the development of numerous drugs, including antiviral and anticancer products.

Bedu-Addo obtained both his M.S.

Chemical Engineering and Ph.D.

in Pharmaceutics from the University of Pittsburgh.

Conn was a founding member of the PDS Biotech team in 2005 as Chief Scientific Officer and continues to serve PDS Biotech in that role.

He has more than 35 years of

drug-development expertise, including development of antiviral and anticancer drugs through to commercialization.

He is a graduate of the Albert Einstein College of Medicine, where he obtained both his M.S.

and Ph.D., discovering novel

angiogenic molecules in the human brain.

Conn started his pharmaceutical career at Merck, Sharpe, and Dohme, where he continued his work on novel angiogenic factors, discovering and characterizing the VEGF family of growth factors, work

which led to the development and commercialization of the anti-cancer drug Avastin.

He was later a leading scientist at Regeneron Pharmaceuticals, where he established and headed various groups in the Cell and Molecular Biology and Drug

Discovery departments.

Conn subsequently became a Director in the Process Development department at Covance Biotechnology Services Inc., a contract research and development and drug manufacturing organization, where he supervised the

analytical development teams responsible for drug characterization, method development and drug stability studies, and program teams responsible for developing drug manufacturing processes.

Conn has expertise across all phases of the drug

development process, including FDA and regulatory requirements, and is the co-inventor of eight drug patents.

Shepard, M.D.

Shephard has served as Chief Medical Officer of PDS Biotech since January 2024.

Shepard is a board-certified medical oncologist and hematologist with more than 30

years of experience in the pharmaceutical industry.

His experience spans multiple therapeutic areas and includes operational and strategic product development from Phases 1 through 4 and diverse disciplines of medical affairs and product

commercialization.

Prior to joining PDS Biotech, Dr.

Shepard was Chief Medical Officer, Senior Vice President and Head of the Global Medical Affairs Oncology Business Group at Eisai Pharmaceutical Company from March 2017 to August 2023.

Shepard previously held leadership roles including Senior Vice President & Head, Global Medical Affairs at Baxter International Inc., Senior Vice President, Global Medical Affairs at Takeda Pharmaceuticals International and Vice President,

Clinical and Scientific Affairs at Boehringer Ingelheim Pharmaceuticals, Inc.

Before his pharmaceutical industry career, Dr.

Shepard served as a staff physician in the Department of Hematology and Medical Oncology at the Cleveland Clinic

Foundation, where he supervised numerous studies in oncology and symptom control.

He has been published in more than 50 medical publications.

Shepard holds a bachelor’s degree from Cornell University and earned his medical degree from the

University of Cincinnati Medical School.

He completed his internship and internal medicine residency at Case Western Reserve University and fellowships in hematology and oncology at the University of Chicago Hospitals and Clinics.

Lars Boesgaard

Boesgaard has served as our Chief Financial Officer since December 2023.

Boesgaard has had a career spanning more than 25 years in healthcare and has deep capital

markets and investor relations experience with global clinical and commercial-stage pharmaceutical and biotechnology companies.

He has prepared and executed corporate transactions and built financial frameworks for rapidly growing

organizations.

Boesgaard served as CFO of AM-Pharma B.V.

from September 2021 to August 2023.

Boesgaard also served as CFO of Columbia Care from August 2018 to August 2021, where he completed key transactions including an IPO/reverse

merger resulting in a $120 million capital infusion and raising $200 million in public equity and debt offerings.

Boesgaard was also previously the Vice President, CFO of Roka Bioscience from November 2015 to July 2018 and held several

other senior finance positions with publicly traded companies including Insulet Corporation, Alexion Pharmaceuticals and Novo Nordisk A/S.

Boesgaard holds a Bachelor of Science in Business Administration from the Copenhagen Business School

and a Master of Business Administration from the Richard Ivey School of Business, Western University, Ontario, Canada.

Spencer Brown

Brown has served as Senior Vice President, General Counsel of PDS Biotech since June 2022.

He was appointed as Compliance Officer in October 2023.

Brown previously

served as Vice President, Legal Affairs from January 2018 to January 2022 and as Senior Vice President, Legal Affairs and Compliance Officer from January 2022 to May 2022, for Aclaris Therapeutics, Inc.

Prior to joining Aclaris

Therapeutics, Inc., Mr.

Brown worked nearly eight years at GE Healthcare as Senior Commercial Counsel for the Life Sciences Core Imaging business in Princeton, New Jersey.

Prior to that, Mr.

Brown spent almost ten years at AstraZeneca

Pharmaceuticals in Wilmington, Delaware where he provided legal support for most of the company’s therapeutic areas at some point during his tenure.

Brown has over two decades of in-house experience in the pharmaceutical industry.

began his legal career as an associate at Skadden, Arps, Slate, Meagher & Flom.

Brown earned his bachelor’s degree at Princeton University and obtained his juris doctorate degree from the University of Pennsylvania Carey School of Law.

We are also supported by scientific leaders in the field of vaccine development and oncology.

Lisa Rohan, one of our founders, is Chair of the Scientific

Advisory Board.

She is a professor in the department of Pharmaceutical Sciences at the University of Pittsburgh where she also holds appointments in the Department of Obstetrics, Gynecology and Reproductive Sciences in the School of Medicine

and the Clinical Translational Science Institute.

Mark Einstein, Professor and Chair in the Department of OB/ GYN & Women’s Heath at Rutgers University Medical School is an expert in HPV-related pathogenesis, therapy and prevention of

lower anogenital tract and gynecologic cancers.

He is an active leader for management guidelines and translating clinical study and translational data for the World Health Organization, American Cancer Society, Society of Gynecologic Oncology

and the American College of Obstetrics and Gynecology.

Gross, Professor and Director of Clinical Research, Department of Head and Neck Surgery, Division of Surgery, The University of

Texas MD Anderson Cancer Center.

Jon Wigginton, President, Research and Development Bright Peak Therapeutics and former President of Society for Immunotherapy of Cancer.

Olivera Finn is a Distinguished Professor of Immunology at the

University of Pittsburgh School of Medicine and she discovered the MUC1 antigen.

Our Principal Investigator for the PDS0101 Head and Neck Trial with Keytruda® for first-line treatment of recurrent/

metastatic Head and Neck Cancer is Dr.

Jared Weiss, Associate Professor of Medicine, University of North Carolina Lineberger Comprehensive Cancer Center, who is an expert in head and neck thoracic oncology with a focus on immunotherapeutic

approaches for these diseases.

Facilities & Manufacturing and Commercial Scale Up

Product candidates using our Versamune, Versamune plus PDS0301 and Infectimune development platforms are manufactured using a readily scalable, fill-finish process with

well-defined and reproducible operations.

We do not own or operate cGMP compliant manufacturing facilities to produce any of our product candidates and we do not have plans to develop our own manufacturing operations in the foreseeable future.

currently rely on third-party contract manufacturing organizations to produce the amounts of our product candidates necessary for our preclinical research and clinical studies.

As part of the manufacture and design process for our product

candidates, we rely on internal, scientific and manufacturing know-how and trade secrets and the know-how and trade secrets of third-party manufacturers.

We currently employ internal resources to manage our manufacturing contractors.

Product candidates using our Versamune®, Versamune® in combination with PDS01ADC and Infectimune® development platforms are manufactured using a readily scalable,

fill-finish process with well-defined and reproducible operations.

We do not own or operate cGMP compliant manufacturing facilities to produce any of our product candidates and we do not have plans to develop our own manufacturing operations in

the foreseeable future.

We currently rely on third-party contract manufacturing organizations to produce the amounts of our product candidates necessary for our preclinical research and clinical studies.

As part of the manufacture and design

process for our product candidates, we rely on internal, scientific and manufacturing know-how and trade secrets and the know-how and trade secrets of third-party manufacturers.

We currently employ internal resources to manage our manufacturing

Our research and development activities are located at the Princeton Innovation Center BioLabs, 303A College Road East, Princeton, NJ 08540, which provides first-rate

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All animal toxicology and efficacy testing are done via third-party contracts and collaborations to provide maximum flexibility and to minimize operational costs and overhead.

This approach allows for

independent validation of our data, and we believe it has historically been a cost-efficient way to progress our development programs.

This approach allows

for independent validation of our data, and we believe it has historically been a cost-efficient way to progress our development programs.

We do not intend to incur the costs of building, staffing and maintaining manufacturing facilities in the near term.

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operations expertise, including past senior executive management roles in contract drug development and manufacturing.

Our management team plans to utilize its expertise and knowledge to identify suitable alternative contract manufacturers who will

be capable of efficiently manufacturing our products.

For our lead product candidate, PDS0101, we continue to progress our ongoing Phase 2 clinical trials.

Our management team plans to utilize its expertise and knowledge to identify suitable alternative contract manufacturers who

will be capable of efficiently manufacturing our products.

For our Versamune® PDS0101 and PDS01ADC product candidate, we continue to progress our ongoing Phase 2 clinical trials.

This process is described further under “U.S.

Product Development Process.”

The final protocols for all Phase 2 clinical trials were submitted to the FDA prior to trial initiation and information for all three trials are on www.clinicaltrials.gov.

To conform to the FDA electronic Common Technical Document format

requirement and submission of the cGMP material that will be used in the Phase 2 trials for PDS0101, we submitted a Chemistry, Manufacturing, and Controls amendment to our IND application, related to our Phase 2 studies with PDS0101 to the FDA in

In addition, the next step for PDS0101, in our most advanced Phase 2 clinical trial, VERSATILE-002, will be transitioning into Phase 3 clinical development called VERSATILE-003,

where we plan to file an amended IND in the third quarter 2023 to enter into a registrational trial by the end of the year.

Product Development Process.” The final protocols for all Phase 2 clinical trials were submitted to the FDA prior to trial initiation and information for all three trials are on www.clinicaltrials.gov.

To conform to the FDA electronic Common

Technical Document format requirement and submission of the cGMP material that will be used in the Phase 2 trials for PDS0101, we submitted a Chemistry, Manufacturing, and Controls amendment to our IND application, related to our Phase 2

studies with PDS0101 to the FDA in 2020.

We anticipate that we would seek marketing authorization from the FDA for our product candidates through the Biologics License Application pathway, under Section 351(a) of

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Product Development Process.”

For our earlier stage, preclinical product candidates PDS0102 and PDS0103, we plan to work to develop data with the goal of progressing to an IND submission in 2023 and progressing

For our earlier stage, preclinical product candidate PDS0103, we plan to work to develop data with the goal of progressing to an IND submission in 2024 and progressing

clinical development to first-in-human trials with these products.

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Intellectual Property

We seek to maintain high barriers to entry around our product candidates and the markets in which they are utilized by using a multiple layered approach to our patents,

patent applications, substantial know-how and trade secrets related to the Versamune, Versamune plus PDS0301, and Infectimune platforms.

We strive to protect and enhance the proprietary technology, inventions and improvements that are

commercially important to our business, including seeking, maintaining, and defending patent rights.

We also rely on trade secrets relating to our platforms and on know-how, continuing technological innovation to develop, strengthen and maintain

its proprietary position in the vaccine field.

We seek to maintain high barriers to entry around our product our product candidates and the markets in which they are utilized by using a multiple layered approach to our

patents, patent applications, substantial know-how and trade secrets related to our platforms.

We strive to protect and enhance our proprietary technology, inventions and improvements that are commercially important to our business, including

seeking, maintaining, and defending patent rights.

We also rely on trade secrets relating to our platforms and on know-how, continuing technological innovation to develop, strengthen and maintain its proprietary position in the vaccine field.

In addition, we rely on regulatory protection afforded through data exclusivity, market exclusivity and patent term extensions where available.

We also utilize trademark protection for our company

name and we expect to do so for products and/or services as they are marketed.

We have developed numerous patents and patent applications and owns substantial know-how and trade secrets related to our Versamune platform.

As of December 31, 2022, PDS holds

seven (7) U.S.

patents with granted claims directed to its platform technology and nineteen (19) pending U.S.

patent applications.

These issued patents will expire in 2026, 2029, 2031 and 2033.

Should the more recently submitted patent applications

currently in prosecution be issued, these will expire in 2033 through 2043 assuming no patent term extensions are granted.

As of March 1, 2023, PDS holds seventy-one (71) issued foreign patents and thirty-eight (38) pending or published foreign

We also utilize trademark protection for our company name and we expect to do so for products and/or

services as they are marketed.

We have developed numerous patents and patent applications and own substantial know-how and trade secrets related to our Versamune® platform.

As of March 1, 2024, PDS Biotech

holds thirteen (13) U.S.

patents with granted claims directed to its platform technology and twenty-four (24) pending U.S.

patent applications.

Most of our international issued patents are issued in multiple countries including Europe, Japan and Australia, and all of which cover compositions of matter and methods of use related to its platform technology.

patents will expire in 2028-2037, or later if patent term extension applies.

Most recently, the USPTO allowed two (2) applications methods of use related to our Versamune platform technology which when granted will run until November 2036.

Included in the patents above is a patent protecting the use of Versamune plus PDS0301.

These issued patents will expire in 2026 to 2037.

Should the more recently submitted patent

applications currently in prosecution be issued, these will expire in 2033 through 2043 assuming no patent term extensions are granted.

As of March 1, 2024, PDS Biotech holds seventy-four (74) issued foreign patents and forty-four (44) pending or

published foreign patent applications.

These issued patents will expire in 2028 through 2037, or later if patent term extension applies.

Included in the patents above is a patent protecting the use of Versamune® in combination with IL-12.

Licensed Patents

We have an exclusive worldwide license from Merck & Cie to (R)-DOTAP and its crystal forms, manufacturing methods, and pharmaceutical compositions using the compounds.,

which are owned by Merck Patent GmbH, for use in our immunotherapy compositions and immunotherapies.

Merck & Cie has informed us that it has rights to license these patent families through an intra-company agreement with Merck Patent GmbH.

These licensed patents are significant to the Versamune, Versamune plus PDS0301 and Infectimune platforms, as they are directed to an important ingredient utilized in the Versamune product.

We have licensed patented antigens from the US government for use worldwide in our cationic lipid immunotherapies.

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These patents are directed to immunogenic peptides and peptide derivatives for the treatment of prostate and breast cancer treatment and multi-epitope TARP peptide vaccines and uses thereof.

These antigens are

incorporated in PDS0102 with Versamune.

These antigens

are incorporated in PDS0102 with Versamune®.

We have licensed novel and highly immunogenic agonist epitopes of mucin-1 (“MUC1”) developed by the National Cancer Institute.

MUC1 is highly expressed in multiple solid tumors and has been shown to be

associated with drug resistance and poor disease prognosis in breast, colorectal, lung and ovarian cancers, for which PDS0103 is being developed.

We have granted patents and are pursuing additional patents that cover compositions and methods of

use of cationic lipid immunotherapies with each of the licensed technologies.

We entered into a non-exclusive agreement to license COBRA universal influenza antigens with the University of Georgia Research Foundation to develop, manufacture and use COBRA

antigens in a clinical trial for a universal influenza vaccine worldwide.

MUC1 is highly expressed in multiple solid tumors and has been shown to

be associated with drug resistance and poor disease prognosis in breast, colorectal, lung and ovarian cancers, for which PDS0103 is being developed.

We have granted patents and are pursuing additional patents that cover compositions and

methods of use of cationic lipid immunotherapies with each of the licensed technologies.

We entered into a non-exclusive agreement to license COBRA universal influenza antigens with the University of Georgia Research Foundation to develop, manufacture and use

COBRA antigens in a clinical trial for a universal influenza vaccine worldwide.

These antigens are developed by Dr.

Ted Ross at the University of Georgia.

We believe that the combination of these antigens with our proprietary Infectimune technology,

representing PDS0202, has the potential to induce a broad immune response as a universal flu vaccine, based on preclinical development studies performed to date.

Exclusive License Agreement

We believe that the combination of these antigens with our proprietary Infectimune®

technology, represented by PDS0202, has the potential to induce a broad immune response as a universal flu vaccine, based on preclinical development studies performed to date.

Exclusive License Agreements

On December 30, 2022, we entered into a License Agreement (the “Merck KGaA License”), with Merck KGaA, Darmstadt, Germany, pursuant to which Merck KGaA, Darmstadt, Germany

granted us an exclusive (even as to Merk KGaA), worldwide, sublicensable, milestone and royalty-bearing right and license to certain patent rights and certain related data (the “Licensed Technology”) to develop, manufacture, use, commercialize

and otherwise exploit any product containing NHS-IL12 fusion protein known as M9241 (the “Compound”).

Merck KGaA, Darmstadt, Germany retains the right under the Licensed Technology in connection with certain existing collaborations between Merck

KGaA, Darmstadt, Germany and academic institutions to allow such academic institutions to exercise their rights granted under such collaborations.

We agreed to use commercially reasonable efforts to develop, manufacture and commercialize at least

one pharmaceutical preparation, substance, or formulation, comprising or employing, the Compound (the “Product”).

In consideration for the rights granted by Merck KGaA, Darmstadt, Germany, we (i) made a one-time up-front cash payment of $5.0 million to Merck KGaA, Darmstadt, Germany, and

(ii) entered into a Share Transfer Agreement dated December 30, 2022 (the “Share Transfer Agreement”), pursuant to which we issued 378,787 shares of our common stock (the “Shares”) to Merck KGaA, Darmstadt, Germany in a private placement for an

aggregate value of $5.0 million, as measured by the closing price of our common stock on the Nasdaq Capital Market as of December 30, 2022.

granted us an exclusive (even as to Merck KGaA), worldwide, sublicensable, milestone and royalty-bearing right and license to certain patent rights and certain related data (the “Licensed Technology”) to develop, manufacture, use, commercialize

and otherwise exploit any product containing NHS-IL12 fusion protein formerly known as M9241, now PDS01ADC (the “Compound”).

Merck KGaA, Darmstadt, Germany retains the right under the Licensed Technology in connection with certain existing

collaborations between Merck KGaA, Darmstadt, Germany and academic institutions to allow such academic institutions to exercise their rights granted under such collaborations.

We agreed to use commercially reasonable efforts to develop,

manufacture and commercialize at least one pharmaceutical preparation, substance, or formulation, comprising or employing, the Compound (the “Product”).

In consideration for the rights granted by Merck KGaA, Darmstadt, Germany, we (i) made a one-time up-front cash payment of $5.0 million to Merck KGaA, Darmstadt, Germany,

and (ii) entered into a Share Transfer Agreement dated December 30, 2022 (the “Share Transfer Agreement”), pursuant to which we issued 378,787 shares of our common stock (the “Shares”) to Merck KGaA, Darmstadt, Germany in a private placement

for an aggregate value of $5.0 million, as measured by the closing price of our common stock on the Nasdaq Capital Market as of December 30, 2022.

Pursuant to the Merck KGaA License Agreement, we agreed to make (i) development and first commercial sale milestone payments totaling up to $11 million upon the achievement

of certain milestones, including the dosing of the fifth patient in a Phase 3 trial of the Product and first commercial sale of the Product for a first and second indications in a major market, and (ii) up to $105 million upon achieving certain

of certain milestones, including the dosing of the fifth patient in a Phase 3 trial of the Product and first commercial sale of the Product for a first and second indication in a major market, and (ii) up to $105 million upon achieving certain

aggregate sales levels of the Product.

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(i) ten years after the first commercial sale of a Product in a given country;

and (ii) the expiration or invalidation of the licensed patents covering the Compound or Product in

such country (collectively, the “Royalty Term”).

The royalty rate is subject to reduction in that event that a Product is not covered by a valid patent claim, a biosimilar to the Compound or the Product comes on the market in a particular

country, or if we obtain a license to any intellectual property owned or controlled by a third-party which but for such license would be infringed by making, using or selling the Compound.

and (ii) the expiration or invalidation of the licensed patents covering the Compound or Product

in such country (collectively, the “Royalty Term”).

The royalty rate is subject to reduction in that event that (i) a Product is not covered by a valid patent claim, (ii) a biosimilar to the Compound or the Product comes on the market in a

particular country, or (iii) we obtain a license to any intellectual property owned or controlled by a third-party in order to ensure that we are not infringing intellectual property owned or controlled by such third-party by making, using or

selling the Compound.

The Merck KGaA License Agreement will expire on a product-by-product and country-by-country basis upon expiration of the last-to-expire Royalty Term for such Product.

expiration (but not earlier termination), we will have a fully paid-up, royalty-free, non-exclusive, transferable, perpetual and irrevocable license under the licensed patent rights and related data to develop, manufacture, use, commercialize and

otherwise exploit the Compound.

and otherwise exploit the Compound.

Either party may terminate the Merck KGaA License Agreement for the other party’s material breach following a cure period.

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and technological advances, especially where they do not believe patent protection is appropriate or obtainable.

Trade secret protection depends in part on confidentiality agreements with employees, consultants, outside scientific collaborators,

sponsored researchers and other advisors that prohibit disclosure of designated proprietary information.

Trade secret protection depends in part on confidentiality agreements with employees, consultants, outside scientific

collaborators, sponsored researchers and other advisors that prohibit disclosure of designated proprietary information.

Trade secrets can be difficult to protect.

Confidentiality agreements may not succeed in preventing a person or parties from disclosing

confidential information, and in that event the rights of the trade secret holder are subject to the viability of an adequate remedy at law, typically under state law modeled on the Uniform Trade Secrets Protection Act, to stop, mitigate or

compensate for the unauthorized disclosure of confidential information.

Confidentiality agreements may not succeed in preventing a person or parties

from disclosing confidential information, and in that event the rights of the trade secret holder are subject to the viability of an adequate remedy at law, typically under state law modeled on the Uniform Trade Secrets Protection Act, to stop,

mitigate or compensate for the unauthorized disclosure of confidential information.

Costly and time-consuming litigation could be necessary to enforce and determine the scope of the proprietary rights.

Finally, there is always at least some risk that

others may independently discover the trade secrets and proprietary information .

Finally, there is always at least some

risk that others may independently discover the trade secrets and proprietary information .

Material License Agreements and Research and Development Agreements

Patent License Agreements with National Institutes of Health.

Effective January 5, 2015, we entered into a Patent License Agreement (the “Patent License Agreement”) as Amended by First Amendment to Patent License Agreement (“First

Amendment”) of August 5, 2015, with an agency within the Department of Health and Human Services (“HHS”), pursuant to which NIH granted PDS a nonexclusive license to certain patent rights for the development of a therapeutic cancer vaccine

specifically in combination with PDS’s proprietary Versamune technology for ovarian, breast, colon and lung cancers.

The Patent License Agreement expires when the last licensed patent expires if the Patent License Agreement is not terminated

prior to that date.

NIH may terminate the Patent License Agreement if PDS is in default in the performance of any material obligation under the Patent License Agreement.

PDS may unilaterally terminate the Patent License Agreement in any country

or territory upon sixty (60) days written notice.

Under the Patent License Agreement and First Amendment PDS agreed to pay NIH:

(a) a noncreditable, nonrefundable royalty in the amount of $30,000 upon execution of the Patent

License Agreement;

(b) a noncreditable, nonrefundable royalty in the amount of $60,000 upon execution of the First Amendment to Patent License Agreement (c) a nonrefundable minimum annual royalty of $5,000;

(d) earned royalties of two percent (2%)

on net sales, reducible by a half percent (0.5%) for any earned royalties PDS must pay to third parties;

Effective January 5, 2015, we entered into a Patent License Agreement (the “Patent License Agreement”) as Amended by the First Amendment to Patent License Agreement (“First

Amendment”) of August 5, 2015, with an agency within the Department of Health and Human Services (“HHS”), pursuant to which NIH granted PDS Biotech a nonexclusive license to certain patent rights for the development of a therapeutic cancer

vaccine specifically in combination with PDS Biotech’s proprietary Versamune® technology for ovarian, breast, colon and lung cancers.

The Patent License Agreement expires when the last licensed patent expires if the Patent License Agreement is

not terminated prior to that date.

NIH may terminate the Patent License Agreement if PDS Biotech is in default in the performance of any material obligation under the Patent License Agreement.

PDS Biotech may unilaterally terminate the Patent

License Agreement in any country or territory upon sixty (60) days written notice.

Under the Patent License Agreement and First Amendment we agreed to pay NIH:

(a) a non-creditable, non-refundable royalty in the amount of $30,000 upon execution of the

Patent License Agreement;

(b) a non-creditable, non-refundable royalty in the amount of $60,000 upon execution of the First Amendment to Patent License Agreement (c) a non-refundable minimum annual royalty of $5,000;

(d) earned royalties of two

percent (2%) on net sales, reducible by a half percent (0.5%) for any earned royalties PDS Biotech must pay to third parties;

(e) benchmark royalties as follows:

(i) $25,000 upon successful completion of each Phase 2 Clinical Studies of a licensed product for breast,

colon, lung or ovarian cancer within each licensed territory;

(ii) $50,000 upon initiation of the first Phase 3 Clinical Trial of a licensed product for breast, colon, lung or ovarian cancer within each licensed territory;

(iii) $750,000 upon the

first commercial sale in the licensed territory utilizing and/or directed to licensed product(s) and/or licensed process(es) within the licensed patent rights for breast, colon, lung or ovarian cancer;

and (f) additional sublicensing royalties for

each sublicense required to be approved by NIH of four percent (4%) on the fair market value of any consideration received for granting such sublicense.

(i) $25,000 upon successful completion of each Phase 2 Clinical Studies of a

licensed product for breast, colon, lung or ovarian cancer within each licensed territory;

(ii) $50,000 upon initiation of the first Phase 3 Clinical Trial of a licensed product for breast, colon, lung or ovarian cancer within each licensed

(iii) $750,000 upon the first commercial sale in the licensed territory utilizing and/or directed to licensed product(s) and/or licensed process(es) within the licensed patent rights for breast, colon, lung or ovarian cancer;

additional sublicensing royalties for each sublicense required to be approved by NIH of four percent (4%) on the fair market value of any consideration received for granting such sublicense.

Effective as November 5, 2021, we entered into a Patent License Agreement (the “NCI Patent License Agreement”) with the U.S.

Department of Health and Human Services, as represented

by NCI of NIH.

Pursuant to the NCI Patent License Agreement, we obtained a nonexclusive, worldwide license to the patent rights for TARP to develop and commercialize TARP peptide-based therapies in combination with the Versamune technology and any

other of our proprietary technologies for prostate and breast cancers and Acute Myeloid Leukemia.

The NCI Patent License Agreement expires when the last licensed patent expires if the Patent License Agreement is not terminated prior to that date.

Department of Health and Human Services, as

represented by NCI of NIH.

technology and any other of our proprietary technologies for prostate and breast cancers and Acute Myeloid Leukemia.

The NCI Patent License Agreement expires when the last licensed patent expires if the Patent License Agreement is not terminated

prior to that date.

NCI may terminate the Patent License Agreement if we are in default in the performance of any material obligation under the Patent License Agreement.

We may unilaterally terminate the NCI Patent License Agreement in any country or territory upon

sixty (60) days written notice.

Under the NCI Patent License Agreement, we agreed to pay NCI certain non-creditable, nonrefundable license issue royalties, unreimbursed patent expenses for the licensed patent rights, a nonrefundable minimum annual

royalty, earned royalties as a percentage of net sales and benchmark royalties.

We may unilaterally terminate the NCI Patent License Agreement in any

country or territory upon sixty (60) days written notice.

Under the NCI Patent License Agreement, we agreed to pay NCI certain non-creditable, nonrefundable license issue royalties, unreimbursed patent expenses for the licensed patent rights, a

nonrefundable minimum annual royalty, earned royalties as a percentage of net sales and benchmark royalties.

DOTAP Chloride Enantiomer License Agreement with Merck Eprova AG.

Effective November 1, 2008, we entered into a DOTAP Chloride Enantiomer License (the “DOTAP License Agreement”) with Merck Eprova AG (“EPRO”), pursuant to which we obtained an

exclusive license from EPRO technology to undertake development of products relating to the R-enantiomer and S-enantiomer of DOTAP Chloride for worldwide commercialization in a composition and method of inducing an immune response in a subject by

administering at least one cationic lipid with or without an antigen.

The DOTAP License Agreement expires on a licensed product-by-licensed product and country-by-country basis until the expiration of the obligation to pay royalties applicable to

such licensed product in such country.

We have the right to unilaterally terminate the DOTAP License Agreement (in its entirety or on a licensed product-by-licensed product or country-by-country basis) at any time for any reason upon prior written

Effective November 1, 2008, we entered into a DOTAP Chloride Enantiomer License (the “DOTAP License Agreement”) with Merck Eprova AG (“EPRO”), pursuant to which we obtained

an exclusive license from EPRO technology to undertake development of products relating to the R-enantiomer and S-enantiomer of DOTAP Chloride for worldwide commercialization in a composition and method of inducing an immune response in a subject

by administering at least one cationic lipid with or without an antigen.

The DOTAP License Agreement expires on a licensed product-by-licensed product and country-by-country basis until the expiration of the obligation to pay royalties applicable

to such licensed product in such country.

written notice.

Cooperative Research and Development Agreement for Intramural-PHS Clinical Research with The U.S.

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technology in a non-cellular vaccine platform.

The term of the CRADA is five (5) years, starting February 2, 2016.

Pursuant to Appendix A, PDS agreed to provide up to $1,000,000 but no less than $500,000 during the first year of

the CRADA and up to $1,000,000 but no less than $750,000 per year for the remaining years of the CRADA for NCI to use in connection with acquiring technical, statistical, and administrative support for the clinical research activities, as well as

to pay for supplies and travel expenses and, upon consent of the parties, to acquire support for a postdoctoral research fellow to conduct additional preclinical studies.

The CRADA may be terminated by either party at any time by mutual written

Either party may unilaterally terminate the CRADA at any time by providing sixty (60) days written notice.

If we terminate prior to the completion of all approved or active study protocol(s) pursuant to the CRADA, we must supply enough

study test product to complete these study protocol(s) unless termination is for safety reasons.

If the CRADA is mutually or unilaterally terminated by us before its expiration, we must pay non-cancellable obligations for personnel for a period of

six (6) months after the termination date or until the expiration date of the CRADA, whichever is sooner.

If we suspend development on the test article without the transfer of its active development efforts, assets, and obligations to a third party

within ninety (90) days of discontinuation, NCI may continue development.

In such event, we must transfer all information necessary to enable NCI to contract for the manufacture of the test article and grant NCI a nonexclusive, irrevocable,

worldwide, paid-up license regarding same.

Cost Reimbursement Agreement with University of Kentucky Research Foundation - I.

with University of Kentucky Research Foundation - I.

Effective November 1, 2015, we entered into an annual Research Agreement (the “Cost Reimbursement Agreement”) with the University of Kentucky Research Foundation (“UKRF”), pursuant

to which UKRF agreed to test PDS’s preclinical and clinical-stage formulations based on HPV, TARP, MUC1, Melanoma antigens as specified more fully in the statement of work.

The Cost Reimbursement Agreement has been renewed annually, and was renewed

on July 1, 2021, for an anticipated cost of $404,502.

Cost Reimbursement Agreement with University of Kentucky Research Foundation

Effective November 1, 2015, we entered into an annual Research Agreement (the “Cost Reimbursement Agreement”) with the University of Kentucky Research Foundation (“UKRF”),

pursuant to which UKRF agreed to test PDS Biotech’s preclinical and clinical-stage formulations based on HPV, TARP, MUC1, Melanoma antigens as specified more fully in the statement of work.

The cost reimbursement agreement has been renewed

annually, and was renewed on June 30, 2023, for an anticipated cost of $628,171.

The agreement terminates on June 30, 2024, unless extended by written mutual agreement of parties or is terminated by one of the parties.

Either party may terminate the Cost Reimbursement

Agreement for any reason with thirty (30) days written notice.

Either party may terminate

the Cost Reimbursement Agreement for any reason with thirty (30) days written notice.

Cost Reimbursement and Sponsored Agreement with University of Kentucky Research Foundation - II.

Effective November 1, 2015, we entered into an annual Research Agreement (the “Cost Reimbursement Agreement”) with the University of Kentucky Research Foundation (“UKRF”),

pursuant to which UKRF agreed to test PDS’s preclinical and clinical-stage formulations based on HPV, TARP, MUC1, Melanoma antigens as specified more fully in the statement of work.

The Cost Reimbursement Agreement has been renewed annually, and

was renewed on July 1, 2021, for an anticipated cost of $13,998.

pursuant to which UKRF agreed to test PDS Biotech’s preclinical and clinical-stage formulations based on HPV, TARP, MUC1, Melanoma antigens as specified more fully in the statement of work.

The cost reimbursement agreement has been renewed

annually, and was renewed on June 30, 2023, for an anticipated cost of $13,897.

The agreement terminates on June 30, 2024, unless extended by written mutual agreement of parties or is terminated by one of the parties.

Either party may terminate the Cost

Reimbursement Agreement for any reason with thirty (30) days written notice.

Either party may terminate

the Cost Reimbursement Agreement for any reason with thirty (30) days written notice.

Clinical Trial Collaboration and Supply Agreement with MSD International GmbH.

Effective May 19, 2017, we entered into a Clinical Trial Collaboration and Supply Agreement (the “CTCSA”) with MSD International GmbH (“Merck”) pursuant to which we and Merck

agreed to collaborate in a Phase 2 clinical trial to evaluate the safety, and preliminary efficacy of the concomitant and/or sequenced administration of the combination of a Merck compound (i.e., pembrolizumab, a humanized anti-human PD-1

Effective May 19, 2017, we entered into a Clinical Trial Collaboration and Supply Agreement (the “CTCSA”) with MSD International GmbH (“Merck”) pursuant to which we and

Merck agreed to collaborate in a Phase 2 clinical trial to evaluate the safety, and preliminary efficacy of the concomitant and/or sequenced administration of the combination of a Merck compound (i.e., pembrolizumab, a humanized anti-human PD-1

monoclonal antibody) and our compound (i.e., PDS0101, a cationic lipid-based therapeutic vaccine combining HPV peptides) in treatment of patients with recurrent or metastatic head and neck cancer and high-risk human papillomavirus-16 (HPV 16)

The term of the CTCSA commenced on May 19, 2017 and will continue until the earlier of (i) delivery of the final study report and (ii) Study Completion (i.e., upon database lock of the Study results), or until terminated by either

In the event the CTCSA is terminated by Merck upon a material breach by PDS, PDS must reimburse Merck for its direct manufacturing costs, such as manufacturing fees, raw materials, direct labor, freight and duty, factory overhead costs and

its indirect manufacturing costs, such as allocations of indirect factory overhead and site support costs.

This agreement was amended on October 28, 2019 to reflect the trial will be for first in line treatment of disease.

On October 28, 2019, we entered into an amendment to the clinical trial collaboration agreement with Merck to evaluate the combination of our lead Versamune based immunotherapy,

PDS0101, with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in a Phase 2 clinical trial.

The modification to the clinical trial design to evaluate PDS0101 in combination with KEYTRUDA® as first-line treatment comes as a result of Merck’s

approval by the FDA on June 10, 2019 for first line treatment of patients with metastatic or unresectable recurrent HNSCC using KEYTRUDA® in combination with platinum and fluorouracil (FU) for all patients and as a single agent for patients whose

tumors express PD-L1 as determined by an FDA-approved test.

The trial was initiated in November of 2020 to evaluate the efficacy and safety of the combination as a first-line treatment in patients with recurrent or metastatic head and neck cancer

and high-risk human papillomavirus-16 (HPV16) infection.

The term of the CTCSA commenced on May 19, 2017 and will continue until the earlier of (i) delivery of the final trial report and (ii) study completion (i.e., upon database lock of the trial results), or until terminated by either

In the event the CTCSA is terminated by Merck upon a material breach by PDS Biotech, PDS Biotech must reimburse Merck for its direct manufacturing costs, such as manufacturing fees, raw materials, direct labor, freight and duty, factory

overhead costs and its indirect manufacturing costs, such as allocations of indirect factory overhead and site support costs.

This agreement was amended on October 28, 2019 to reflect that the trial will be for first in line treatment of

On October 28, 2019, we entered into an amendment to the clinical trial collaboration agreement with Merck to evaluate the combination of our lead Versamune® based

immunotherapy, PDS0101, with Merck’s anti-PD-1 therapy, Keytruda® (pembrolizumab), in a Phase 2 clinical trial.

The modification to the clinical trial design to evaluate PDS0101 in combination with Keytruda® as first-line treatment comes as a

result of Merck’s approval by the FDA on June 10, 2019 for first line treatment of patients with metastatic or unresectable recurrent HNSCC using Keytruda® in combination with platinum and fluorouracil (FU) for all patients and as a single agent

for patients whose tumors express PD-L1 as determined by an FDA-approved test.

The trial was initiated in November of 2020 to evaluate the efficacy and safety of the combination as a first-line treatment in patients with recurrent or metastatic

head and neck cancer and high-risk human papillomavirus-16 (HPV16) infection.

Other Research and Development Agreements

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Department of Health and Human Services.

Effective April 22, 2019, PDS entered into a Cooperative Research and Development Agreement (the “ CRADA ”) with the U.S.

Effective April 22, 2019, we entered into a Cooperative Research and Development Agreement (the “ CRADA ”) with the U.S.

Department of

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Research Plan.

Under the agreement, PDS will collaborate with the NCI’s Genitourinary Malignancies Branch (GMB) and Laboratory of Tumor Immunology and Biology (LTIB) with plans to conduct a Phase 2 clinical trial evaluating PDS0101 with novel

immune-modulating agents M7824 and NHS-IL12 being studied at NCI as part of a CRADA with EMD serono (Merck KGaA).

Under the agreement, we will collaborate with the NCI’s Genitourinary Malignancies Branch (“GMB”) and Laboratory of Tumor Immunology and Biology (“LTIB”) with plans to conduct a Phase 2 clinical trial evaluating PDS0101 with

novel immune-modulating agents M7824 and NHS-IL12 being studied at NCI as part of a CRADA with EMD Serono (“Merck KGaA”).

The Phase 2 clinical trial was initiated in June of 2020.

The CRADA also involves preclinical evaluation of PDS0101 in combination

with other therapeutic modalities upon the mutual agreement of both parties.

In April 2020, this agreement was amended to include PDS0103, in preclinical and clinical development for treatment of ovarian, breast, colorectal and lung cancers.

The CRADA also involves preclinical evaluation of PDS0101 in

combination with other therapeutic modalities upon the mutual agreement of both parties.

In April 2020, this agreement was amended to include PDS0103, in preclinical and clinical development for treatment of ovarian, breast, colorectal and lung

The term of the CRADA is five (5) years, starting April 22, 2019.

Pursuant to Appendix A, we agreed to provide $110,000 annually, the first payment of which is to be made on the

first anniversary the of the CRADA Effective date or upon the initiation of a Phase 2 clinical trial as the NIH Clinical Center, whichever comes first for NCI to use in connection with acquiring technical, statistical, and administrative support

Pursuant to Appendix A, we agreed to provide $110,000 annually, the first payment of which is to be made on

the first anniversary of the CRADA Effective date or upon the initiation of a Phase 2 clinical trial as the NIH Clinical Center, whichever comes first for NCI to use in connection with acquiring technical, statistical, and administrative support

for the clinical research activities, as well as to pay for supplies and travel expenses and infrastructure costs.

The CRADA may be terminated by either party at any time by mutual written consent.

Either party may unilaterally terminate the CRADA

at any time by providing sixty (60) days written notice.

If we terminate prior to the completion of all approved or active study protocol(s) pursuant to the CRADA, we must supply enough study test product to complete these study protocol(s) unless

termination is for safety reasons.

If the CRADA is mutually or unilaterally terminated by PDS before its expiration, we must pay non-cancellable obligations for personnel for a period of six (6) months after the termination date or until the

expiration date of the CRADA, whichever is sooner.

If we suspend development on the test article without the transfer of its active development efforts, assets, and obligations to a third party within ninety (90) days of discontinuation, NCI may

continue development.

In such event, we must transfer all information necessary to enable NCI to contract for the manufacture of the test article and grant NCI a nonexclusive, irrevocable, worldwide, paid-up license regarding same.

Either party may unilaterally terminate the

CRADA at any time by providing sixty (60) days written notice.

If we terminate prior to the completion of all approved or active study protocol(s) pursuant to the CRADA, we must supply enough study test product to complete these study protocol(s)

unless termination is for safety reasons.

If the CRADA is mutually or unilaterally terminated by PDS Biotech before its expiration, we must pay non-cancellable obligations for personnel for a period of six (6) months after the termination date or

until the expiration date of the CRADA, whichever is sooner.

If we suspend development on the test article without the transfer of its active development efforts, assets, and obligations to a third party within ninety (90) days of

discontinuation, NCI may continue development.

In such event, we must transfer all information necessary to enable NCI to contract for the manufacture of the test article and grant NCI a nonexclusive, irrevocable, worldwide, paid-up license

regarding same.

Option to License with the University of Georgia Research Foundation of Georgia Research Foundation

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This agreement allows us to develop, manufacture and use COBRA antigens in a clinical trial for a universal influenza vaccine worldwide.

The term of the agreement extends twelve months after initiation of first Phase 1 clinical trial

and may be extended upon agreement of the parties.

The term of the agreement extends twelve months after initiation of the first Phase 1 clinical

trial and may be extended upon agreement of the parties.

We may convert the option to a full agreement any time prior to the conclusion of the term.

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We are aware of various

established companies, including major pharmaceutical companies, broadly engaged in immunotherapies and vaccines in research and development that may compete directly with the products we are developing including Jansen Pharmaceuticals (part of

J&J), Sanofi-Aventis, GlaxoSmithKline plc, Merck and Pfizer, among others.

In addition, there are many development-stage biotechnology companies in various immunotherapy and vaccine development including, but not limited to Inovio, Advaxis,

Kite Pharma, Hookipa, Moderna, ZIOPHARM Oncology, Heat Biologics, Harpoon Therapeutics, Oncosec Medical, BioNTech, Osivax, Medicago, Vaxart, and Flugen.

If one or more of these companies is successful in developing their technologies, it could

materially impact our business.

While we believe that the Versamune, Versamune plus PDS0301 and Infectimune platforms provide us with competitive advantages, we face competition from many different sources,

including biotechnology and pharmaceutical companies, academic institutions, government agencies, as well as public and private research institutions.

Any products that we may commercialize will have to compete with existing products and

therapies as well as new products and immunotherapies that may become available in the future.

We anticipate that it will face intense and increasing competition as new immunotherapies enter the market and advanced technologies become available.

PDS Biotech expects any

products that it develops and commercializes to compete based on, among other things, efficacy, safety, convenience of administration and delivery, price, availability of therapeutics, the level of generic competition and the availability of

Innovative Medicine (part of Johnson & Johnson), Sanofi-Aventis, GlaxoSmithKline plc, Merck and Pfizer, among others.

In addition, there are many development-stage biotechnology companies in various immunotherapy and vaccine development

including, but not limited to Merus N.V., F-Star Therapeutics, Inovio, Kite Pharma, Hookipa, Moderna, ZIOPHARM Oncology, Heat Biologics, Harpoon Therapeutics, BioNTech, Osivax, Medicago, Vaxart, and Flugen.

If one or more of these companies is

successful in developing their technologies, it could materially impact our business.

While we believe that the Versamune®, Versamune® in combination with PDS01ADC and Infectimune® platforms provide us with competitive advantages, we face competition from

many different sources, including biotechnology and pharmaceutical companies, academic institutions, government agencies, as well as public and private research institutions.

Any products that we may commercialize will have to compete with

existing products and therapies as well as new products and immunotherapies that may become available in the future.

We anticipate that we will face intense and increasing competition as new immunotherapies enter the market and advanced technologies become available.

We expect any

products that we develop and commercialize to compete based on, among other things, efficacy, safety, convenience of administration and delivery, price, availability of therapeutics, the level of generic competition and the availability of

reimbursement from government and other third-party payors.

PDS Biotech’s competitors may obtain FDA or other regulatory approval for their products more rapidly than it may obtain approval for its products, which could result in our competitors

establishing a strong market position before it is able to enter the market.

Our competitors may obtain FDA or other regulatory approval for their products more rapidly than us and may obtain approval for their products, which could result in our competitors

establishing a strong market position before we are able to enter the market.

In addition, our ability to compete may be affected in many cases by insurers or other third-party payors seeking to encourage the use of generic products.

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Federal, state and local government authorities in the United States and in other countries extensively regulate, among other things, the research, development, testing,

manufacturing, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, post-approval monitoring and reporting, marketing and export and import of biological and pharmaceutical products such as

those we are developing.

as those we are developing.

Our product candidates must be approved by the FDA before they may be legally marketed in the United States and by the appropriate foreign regulatory agency before they may be legally marketed in foreign countries.

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the market, product seizures, total or partial suspension of production or distribution injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties.

Any agency or judicial enforcement action could

have a material adverse effect on PDS.

Any agency or judicial enforcement action

could have a material adverse effect on PDS Biotech.

The process required by the FDA before a biological drug product may be marketed in the United States generally involves the following:

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submission to the FDA of an investigational new drug application, or an IND, which must become effective before human clinical studies may begin;

approval by an independent institutional review board, or IRB, representing each clinical site before each clinical may be initiated;

approval by an independent institutional review board, or IRB, representing each clinical site before each clinical trial may be initiated;

performance of adequate and well-controlled human clinical studies according to the FDA’s regulations commonly referred to as good clinical practice, or GCP, and any additional requirements for the protection of human research subjects

and their health information, to establish the safety and efficacy of the proposed biological product for its intended use;

submission to the FDA of a Biologics License Application, or BLA, for marketing approval that meets applicable requirements to ensure the continued safety, purity, and potency/efficacy of the product that is the subject of the BLA based

on results of nonclinical testing and clinical studies (including among other things clinical data, chemistry, and manufacturing and controls (CMC) data);

based on results of nonclinical testing and clinical studies (including among other things clinical data, chemistry, and manufacturing and controls (CMC) data);

review by an FDA advisory committee, where appropriate or if applicable;

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investigator-initiated trial, the sponsor may be an investigator who is conducting the trial.

In addition, the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and

plans for clinical trials, among other things, are submitted to the FDA as part of an IND.

In addition, the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature

and plans for clinical trials, among other things, are submitted to the FDA as part of an IND.

The FDA requires a 30-day waiting period after the filing of each IND before clinical trials may begin.

This waiting period is designed to allow the FDA to

review the IND to determine whether human research subjects will be exposed to unreasonable health risks.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions regarding the proposed

clinical studies and places the study on a clinical hold within that 30-day time period.

This waiting period is designed to allow the

FDA to review the IND to determine whether human research subjects will be exposed to unreasonable health risks.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions regarding the

proposed clinical studies and places the study on a clinical hold within that 30-day time period.

In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical study can begin.

The FDA may also impose clinical holds

on a biological product candidate at any time before or during clinical studies due to safety concerns or non-compliance.

If the FDA imposes a clinical hold, studies may not recommence without FDA authorization and then only under terms authorized

Accordingly, PDS cannot be sure that submission of an IND will result in the FDA allowing clinical studies to begin, or that, once begun, issues will not arise that suspend or terminate such studies.

The FDA may also impose

clinical holds on a biological product candidate at any time before or during clinical studies due to safety concerns or non-compliance.

If the FDA imposes a clinical hold, studies may not recommence without FDA authorization and then only under

terms authorized by the FDA.

Accordingly, PDS Biotech cannot be sure that submission of an IND will result in the FDA allowing clinical studies to begin, or that, once begun, issues will not arise that suspend or terminate such studies.

Following commencement of a clinical trial under an IND, the FDA may also place a clinical hold or partial clinical hold on that trial.

A clinical hold is an order issued by the FDA to the sponsor

to delay a proposed clinical investigation or to suspend an ongoing investigation.

A clinical hold is an order issued by the FDA to the

sponsor to delay a proposed clinical investigation or to suspend an ongoing investigation.

A partial clinical hold is a delay or suspension of only part of the clinical work requested under the IND.

For example, a specific protocol or part of a protocol is

not allowed to proceed, while other protocols may do so.

For example, a specific protocol or part of a

protocol is not allowed to proceed, while other protocols may do so.

No more than 30 days after imposition of a clinical hold or partial clinical hold, the FDA will provide the sponsor a written explanation of the basis for the hold.

Following issuance of a

clinical hold or partial clinical hold, an investigation may only resume after the FDA has notified the sponsor that the investigation may proceed.

The FDA will base that determination on information provided by the sponsor correcting the

deficiencies previously cited or otherwise satisfying the FDA that the investigation can proceed.

issuance of a clinical hold or partial clinical hold, an investigation may only resume after the FDA has notified the sponsor that the investigation may proceed.

The FDA will base that determination on information provided by the sponsor

correcting the deficiencies previously cited or otherwise satisfying the FDA that the investigation can proceed.

A sponsor may choose, but is not required, to conduct a foreign clinical study under an IND.

When a foreign clinical study is conducted under an IND, all IND requirements must be met unless waived.

When a foreign clinical study is conducted under an IND, all IND requirements must be met unless

When the foreign clinical study is not conducted under an IND, the sponsor must ensure that the study complies with certain FDA regulatory requirements in order to use the study as support for an IND or application for marketing approval.

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The GCP requirements encompass both ethical and data integrity standards for clinical studies.

The FDA’s regulations are intended to help ensure the protection of human subjects

enrolled in non-IND foreign clinical trials, as well as the quality and integrity of the resulting data.

The FDA’s regulations are intended to help ensure the protection of human

subjects enrolled in non-IND foreign clinical trials, as well as the quality and integrity of the resulting data.

They further help ensure that non-IND foreign studies are conducted in a manner comparable to that required for IND studies.

If a marketing

application is based solely on foreign clinical data, the FDA requires that the foreign data be applicable to the U.S.

marketing application is based solely on foreign clinical data, the FDA requires that the foreign data be applicable to the U.S.

population and U.S.

medical practice;

the studies must have been performed by clinical investigators of recognized competence;

the studies must have been performed by clinical investigators of recognized

and the FDA must be able to validate the data through an on-site inspection or other appropriate means, if the FDA deems such an inspection to be necessary.

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The IRB must review and approve, among other things, the study protocol and informed consent information to be provided to study subjects.

IRB must operate in compliance with FDA regulations.

An IRB must operate in compliance with FDA regulations.

An IRB can suspend or terminate approval of a clinical trial at its institution, or an institution it represents, if the clinical trial is not being conducted in accordance with the IRB’s

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amendments to previously submitted clinical trials.

Further, an independent IRB for each institution participating in the clinical trial must review and approve the plan for any clinical trial, its informed consent form, and other communications to

study subjects before the clinical trial commences at that site.

Further, an independent IRB for each institution participating in the clinical trial must review and approve the plan for any clinical trial, its informed consent form, and other communications

to study subjects before the clinical trial commences at that site.

The IRB must continue to oversee the clinical trial while it is being conducted, including any changes to the study plans.

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This group provides

authorization for whether or not a trial may move forward at designated check points based on access that only the group maintains to available data from the study.

authorization for whether or not a trial may move forward at designated check points based on access that only the group maintains to available data from the trial.

Suspension or termination of development during any phase of clinical trials can

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subject safety, including stopping rules that assure a clinical trial will be stopped if certain adverse events should occur.

Each protocol and any amendments to the protocol must be submitted to the FDA as part of the IND and require IRB approval.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

Each protocol and any amendments to the protocol must be submitted to the FDA as part of the IND and require IRB

Human clinical trials are typically conducted in four sequential phases that may overlap or be combined:

The biological product is initially introduced into healthy human subjects and tested for safety.

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Although these are the typical phases of progression, and characteristics of the phases of a clinical development program, certain expedited programs allow for variations that could support a

marketing application based on surrogate endpoints, intermediate clinical endpoints, or single-arm as opposed to comparative or placebo-controlled studies (for example, FDA could rely on well-controlled Phase 2 studies for evidence of effectiveness

under certain circumstances).

effectiveness under certain circumstances).

In December 2022, with the passage of the Food and Drug Omnibus Reform Act, or FDORA, Congress required sponsors to develop and submit a diversity action plan for each Phase 3 clinical trial or

any other “pivotal study” of a new drug or biological product.

These plans are meant to encourage the enrollment of more diverse patient populations in late-stage clinical trials of FDA-regulated products.

Specifically, action plans must include

the sponsor’s goals for enrollment, the underlying rationale for those goals, and an explanation of how the sponsor intends to meet them.

During all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical activities, clinical data, and clinical trial investigators.

Annual progress

reports detailing the results of the clinical trials must be submitted to the FDA.

Written IND safety reports must be promptly submitted to the FDA and the investigators of potential safety risks, from clinical trials or any other source, including

for serious and unexpected adverse events and serious and unexpected suspected adverse reactions, any findings from other studies suggesting a significant risk in humans exposed to the drug, tests in laboratory animals or in vitro testing that

suggest a significant risk for human subjects, or any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

The sponsor must submit an IND safety report within

15 calendar days after the sponsor determines that the information qualifies for reporting.

The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible but no later than within

seven calendar days after the sponsor’s initial receipt of the information.

progress reports detailing the results of the clinical trials must be submitted to the FDA.

Written IND safety reports must be promptly submitted to the FDA and the investigators of potential safety risks, from clinical trials or any other

source, including for serious and unexpected adverse events and serious and unexpected suspected adverse reactions, any findings from other studies suggesting a significant risk in humans exposed to the drug, tests in laboratory animals or in

vitro testing that suggest a significant risk for human subjects, or any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

The sponsor must submit an IND

safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting.

The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction as soon as possible but

no later than within seven calendar days after the sponsor’s initial receipt of the information.

Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, if at all.

The FDA, the sponsor or its data safety monitoring

board, or DSMB, which receives special access to unblinded data during the clinical trial, may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects are being exposed to an unacceptable

health risk or no demonstration of efficacy.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the biological

product has been associated with unexpected serious harm to subjects.

The FDA, the sponsor or its

data safety monitoring board, or DSMB, which receives special access to unblinded data during the clinical trial, may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects are being

exposed to an unacceptable health risk or no demonstration of efficacy.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s

requirements or if the biological product has been associated with unexpected serious harm to subjects.

The FDA will typically inspect one or more clinical sites to assure compliance with GCP and the integrity of the clinical data submitted.

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and other jurisdictions have similar laws that may apply.

Concurrently with clinical trials, companies usually complete additional studies and must also develop additional information about the physical characteristics of the biological product as well as

finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

To help reduce the risk of the introduction of adventitious agents with use of biological products, the PHSA emphasizes the importance

of manufacturing controls for products whose attributes cannot be precisely defined.

The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other criteria, the sponsor must develop

methods for testing the identity, strength, quality, potency and purity of the final biological product.

Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the biological

product candidate does not undergo unacceptable deterioration over its shelf life.

Concurrently with clinical trials, companies usually complete additional studies and must also develop additional information about the physical characteristics of the biological product as well

as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

To help reduce the risk of the introduction of adventitious agents with use of biological products, the PHSA emphasizes the

importance of manufacturing controls for products whose attributes cannot be precisely defined.

The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other criteria, the sponsor

must develop methods for testing the identity, strength, quality, potency and purity of the final biological product.

Additionally, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the

biological product candidate does not undergo unacceptable deterioration over its shelf life.

Review and Approval Processes

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non-orphan indication.

Within 60 days following submission of the application, the FDA reviews a BLA submitted to determine if it is substantially complete before the agency accepts it for filing.

FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission and may request additional information.

Within 60 days following submission of the application, the FDA reviews a BLA submitted to determine if it is substantially complete before the agency accepts it for

The FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission and may request additional information.

In this event, the BLA must be resubmitted with the additional information.

The resubmitted

application also is subject to review before the FDA accepts it for filing.

resubmitted application also is subject to review before the FDA accepts it for filing.

Once the submission is accepted for filing, the FDA begins an in-depth substantive review of the BLA.

The FDA has agreed to specified performance goals in the review

process of BLAs.

The FDA has agreed to specified performance goals in

the review process of BLAs.

Most such applications are meant to be reviewed within ten months from the filing date, and most applications for “priority review” products are meant to be reviewed within six months of the filing date.

The review process and

the PDUFA goal date may be extended by the FDA for three additional months to consider new information or clarification provided by the applicant to address an outstanding deficiency identified by the FDA following the original submission.

process and the PDUFA goal date may be extended by the FDA for three additional months to consider new information or clarification provided by the applicant to address an outstanding deficiency identified by the FDA following the original

The FDA reviews the BLA to determine, among other things, whether the proposed product is safe, potent, and/or effective for its intended use, and has an acceptable purity

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The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

During the biological product approval process, the FDA also will determine whether a Risk Evaluation and Mitigation Strategy, or REMS, is necessary to assure the safe use of the

biological product.

To determine whether a REMS is needed, the FDA will consider the size of the population likely to use the product, seriousness of the disease, expected benefit of the product, expected duration of treatment, and seriousness of

known or potential adverse events.

During the biological product approval process, the FDA also will determine whether a Risk Evaluation and Mitigation Strategy, or REMS, is necessary to assure the safe use

of the biological product.

seriousness of known or potential adverse events.

REMS can include medication guides, physician communication plans for healthcare professionals, and elements to assure safe use, or EYASU.

EYASU may include, but are not limited to, special training or

certification for prescribing or dispending, dispensing only under certain circumstances, special monitoring, and the use of patient registries.

The FDA may require a REMS before approval or post-approval if it becomes aware of a serious risk

associated with the use of a product.

EYASU may include, but are not limited to, special

training or certification for prescribing or dispending, dispensing only under certain circumstances, special monitoring, and the use of patient registries.

The FDA may require a REMS before approval or post-approval if it becomes aware of a

serious risk associated with the use of a product.

If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS.

The FDA will not approve a BLA without a REMS, if required.

The requirement for a REMS can materially affect the

potential market and profitability of a product.

The requirement for a REMS can materially

affect the potential market and profitability of a product.

Before approving a BLA, the FDA will typically inspect the facilities at which the product is manufactured.

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associated with a BLA submission, including component manufacturing, finished product manufacturing, and control testing laboratories.

The FDA will not approve the product unless it is satisfied that the manufacturing establishments and processes

supporting the BLA meet the appropriate requirements and comply with the applicable regulations (including cGMP requirements and adequate assurance for consistent commercial production of the product within required specifications).

Additionally,

before approving a BLA, the FDA will typically conduct a pre-approval inspection of regulated participants in clinical trials (for example, the sponsor, investigators responsible for specific sites, and CROs) to assure that the clinical trials

were conducted in compliance with the IND and GCP requirements.

To assure cGMP and GCP compliance, an applicant must incur significant expenditure of time, money and effort in the areas of training, record keeping, production, and quality

Notwithstanding the submission of relevant data and information, the FDA may ultimately decide that the BLA does not satisfy its regulatory criteria for approval and deny approval.

Data obtained from clinical studies are not always conclusive and the FDA may interpret data differently than PDS interprets the same data.

If the agency decides not to approve the BLA in its present form, the FDA will issue a complete response

letter that describes all of the specific deficiencies in the BLA identified by the FDA.

The deficiencies identified may be minor, for example, requiring labeling changes, or major, for example, requiring additional clinical studies.

Additionally,

the complete response letter may include recommended actions that the applicant might take to place the application in a condition for approval.

If a complete response letter is issued, the applicant may either resubmit the BLA, addressing all of

the deficiencies identified in the letter, or withdraw the application.

Even if the submission is re-submitted with additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

The FDA will not approve the product unless it is satisfied that the manufacturing establishments and

processes supporting the BLA meet the appropriate requirements and comply with the applicable regulations (including cGMP requirements and adequate assurance for consistent commercial production of the product within required specifications).

Additionally, before approving a BLA, the FDA will typically conduct a pre-approval inspection of regulated participants in clinical trials (for example, the sponsor, investigators responsible for specific sites, and CROs) to assure that the

clinical trials were conducted in compliance with the IND and GCP requirements.

To assure cGMP and GCP compliance, an applicant must incur significant expenditure of time, money and effort in the areas of training, record keeping, production,

and quality control.

Notwithstanding the submission of relevant data and information, the FDA may ultimately decide that the BLA does not satisfy its regulatory criteria for approval and deny

Data obtained from clinical studies are not always conclusive and the FDA may interpret data differently than PDS Biotech interprets the same data.

If the agency decides not to approve the BLA in its present form, the FDA will issue a

complete response letter that describes all of the specific deficiencies in the BLA identified by the FDA.

The deficiencies identified may be minor, for example, requiring labeling changes, or major, for example, requiring additional clinical

Additionally, the complete response letter may include recommended actions that the applicant might take to place the application in a condition for approval.

If a complete response letter is issued, the applicant may either resubmit the

BLA, addressing all of the deficiencies identified in the letter, or withdraw the application.

Even if the submission is re-submitted with additional information, the FDA ultimately may decide that the application does not satisfy the regulatory

criteria for approval.

If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited,

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studies, designed to further assess a biological product’s safety and effectiveness, and testing and surveillance programs to monitor the safety of approved products that have been commercialized.

The FDA may prevent or limit further marketing of

a product based on the results of post-market studies or surveillance programs.

After approval, many types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to

further testing requirements and FDA review and approval.

In addition, under the Pediatric Research Equity Act, a BLA or supplement to a BLA for a new indication, dosage form, dosage regimen, or route of administration must contain data

that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and

The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data

requirements.

The FDA may prevent or limit further marketing

of a product based on the results of post-market studies or surveillance programs.

After approval, many types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject

to further testing requirements and FDA review and approval.

In addition, under the Pediatric Research Equity Act, a BLA or supplement to a BLA for a new indication, dosage form, dosage regimen, or route of administration must contain

data that is adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is

safe and effective.

pediatric data requirements.

Fast track, breakthrough therapy and priority review designations

The FDA is authorized to designate certain products for expedited review if they are intended to address an unmet medical need in the treatment of a serious or life-threatening

disease or condition.

The FDA is authorized to designate certain products for expedited review if they are intended to address an unmet medical need in the treatment of a serious or

life-threatening disease or condition.

These programs are referred to as fast track designation, breakthrough therapy designation and priority review designation.

In May 2014, the FDA published a final Guidance for Industry titled “Expedited Programs for Serious

Conditions-Drugs and Biologics,” which provides guidance on the FDA programs that are intended to facilitate and expedite development and review of new product candidates as well as threshold criteria generally applicable to concluding that a

product candidate is a candidate for these expedited development and review programs.

In May 2014, the FDA published a final Guidance for Industry titled “Expedited

Programs for Serious Conditions-Drugs and Biologics,” which provides guidance on the FDA programs that are intended to facilitate and expedite development and review of new product candidates as well as threshold criteria generally applicable to

concluding that a product candidate is a candidate for these expedited development and review programs.

Specifically, the FDA may designate a product for fast track review if it is intended, whether alone or in combination with one or more other products, for the treatment of a

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The FDA may take certain actions with respect to breakthrough therapies, including holding meetings with the sponsor throughout the development process;

providing timely advice to the product sponsor

regarding development and approval;

providing timely advice to the product

sponsor regarding development and approval;

involving more senior staff in the review process;

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and taking other steps to design the clinical trials in an efficient manner.

Third, the FDA may designate a product for priority review if it is a product that treats a serious condition and, if approved, would provide a significant improvement in safety or

effectiveness.

Third, the FDA may designate a product for priority review if it is a product that treats a serious condition and, if approved, would provide a significant improvement in

safety or effectiveness.

The FDA determines, on a case-by-case basis, whether the proposed product represents a significant improvement when compared with other available therapies.

Significant improvement may be illustrated by evidence of increased

effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment-limiting product reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, and evidence of safety and

effectiveness in a new subpopulation.

A priority designation is intended to direct overall attention and resources to the evaluation of such applications, and to shorten the FDA’s goal for taking action on a marketing application from ten months to

Significant improvement may be illustrated by evidence of

increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment-limiting product reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, and evidence of

safety and effectiveness in a new subpopulation.

A priority designation is intended to direct overall attention and resources to the evaluation of such applications, and to shorten the FDA’s goal for taking action on a marketing application from

ten months to six months.

Accelerated approval pathway

The FDA may grant accelerated approval to a drug for a serious or life-threatening condition that provides meaningful therapeutic advantage to patients over existing treatments

based upon a determination that the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.

The FDA may also grant accelerated approval for such a condition when the product has an effect on an intermediate

clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality, or IMM, and that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account

the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments.

Drugs granted accelerated approval must meet the same statutory standards for safety and effectiveness as those granted traditional

For the purposes of accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to

predict clinical benefit, but is not itself a measure of clinical benefit.

The FDA may grant accelerated approval to a drug for a serious or life-threatening condition that provides meaningful therapeutic advantage to patients over existing

treatments based upon a determination that the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.

The FDA may also grant accelerated approval for such a condition when the product has an effect on an

intermediate clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality, or IMM, and that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking

into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments.

Drugs granted accelerated approval must meet the same statutory standards for safety and effectiveness as those granted

traditional approval.

For the purposes of accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is

thought to predict clinical benefit, but is not itself a measure of clinical benefit.

Surrogate endpoints can often be measured more easily or more rapidly than clinical endpoints.

An intermediate clinical endpoint is a measurement of a therapeutic effect

that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on IMM.

The FDA has limited experience with accelerated approvals based on intermediate clinical endpoints, but has indicated that such endpoints

generally may support accelerated approval where the therapeutic effect measured by the endpoint is not itself a clinical benefit and basis for traditional approval, if there is a basis for concluding that the therapeutic effect is reasonably

likely to predict the ultimate clinical benefit of a drug.

The accelerated approval pathway is most often used in settings in which the course of a disease is long and an extended period of time is required to measure the intended clinical

benefit of a drug, even if the effect on the surrogate or intermediate clinical endpoint occurs rapidly.

Thus, accelerated approval has been used extensively in the development and approval of drugs for treatment of a variety of cancers in which

the goal of therapy is generally to improve survival or decrease morbidity and the duration of the typical disease course requires lengthy and sometimes large trials to demonstrate a clinical or survival benefit.

The accelerated approval pathway is contingent on a sponsor’s agreement to conduct, in a diligent manner, additional post-approval confirmatory studies to verify and describe the

drug’s clinical benefit.

As a result, a drug candidate approved on this basis is subject to rigorous post-marketing compliance requirements, including the completion of Phase 4 or post-approval clinical trials to confirm the effect on the clinical

An intermediate clinical endpoint is a measurement of a

therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on IMM.

The FDA has limited experience with accelerated approvals based on intermediate clinical endpoints, but has indicated

that such endpoints generally may support accelerated approval where the therapeutic effect measured by the endpoint is not itself a clinical benefit and basis for traditional approval, if there is a basis for concluding that the therapeutic

effect is reasonably likely to predict the ultimate clinical benefit of a drug.

The accelerated approval pathway is most often used in settings in which the course of a disease is long and an extended period of time is required to measure the intended

clinical benefit of a drug, even if the effect on the surrogate or intermediate clinical endpoint occurs rapidly.

Thus, accelerated approval has been used extensively in the development and approval of drugs for treatment of a variety of cancers

in which the goal of therapy is generally to improve survival or decrease morbidity and the duration of the typical disease course requires lengthy and sometimes large trials to demonstrate a clinical or survival benefit.

The accelerated approval pathway is contingent on a sponsor’s agreement to conduct, in a diligent manner, additional post-approval confirmatory studies to verify and describe

the drug’s clinical benefit.

clinical endpoint.

Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing studies, would allow the FDA to withdraw the drug from the market on an expedited basis.

All promotional materials for drug candidates

approved under accelerated regulations are subject to prior review by the FDA.

Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time

period for FDA review or approval will not be shortened.

In addition, the manufacturer of an investigational drug for a serious or life-threatening disease is required to make available, such as by posting on its website, its policy on responding

to requests for expanded access.

Furthermore, fast track designation, breakthrough therapy designation, accelerated approval and priority review do not change the standards for approval and may not ultimately expedite the development or approval

All promotional materials for drug

candidates approved under accelerated regulations are subject to prior review by the FDA.

Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the

time period for FDA review or approval will not be shortened.

In addition, the manufacturer of an investigational drug for a serious or life-threatening disease is required to make available, such as by posting on its website, its policy on

responding to requests for expanded access.

or approval process.

Post-Approval Requirements

Any products for which PDS receives FDA approvals are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, reporting of

adverse experiences with the product, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, and complying with FDA promotion and advertising requirements, which include, among others,

standards for direct-to-consumer advertising, restrictions on promoting products for uses or in patient populations that are not described in the product’s approved uses or consistent with the approved labeling, known as ‘off-label’ use,

limitations on industry-sponsored scientific and educational activities, and requirements for promotional activities involving the internet.

Although physicians may prescribe legally available products for off-label uses, if the physicians deem

to be appropriate in their professional medical judgment, manufacturers may not market or promote such off-label uses.

Recent court decisions have impacted the FDA’s enforcement activity regarding off-label promotion in light of First Amendment

considerations;

Any products for which PDS Biotech receives FDA approvals are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements,

reporting of adverse experiences with the product, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, and complying with FDA promotion and advertising requirements, which include,

among others, standards for direct-to-consumer advertising, restrictions on promoting products for uses or in patient populations that are not described in the product’s approved uses or consistent with the approved labeling, known as

‘off-label’ use, limitations on industry-sponsored scientific and educational activities, and requirements for promotional activities involving the internet.

Although physicians may prescribe legally available products for off-label uses, if

the physicians deem to be appropriate in their professional medical judgment, manufacturers may not market or promote such off-label uses.

Recent court decisions have impacted the FDA’s enforcement activity regarding off-label promotion in

light of First Amendment considerations;

however, there are still significant risks in this area in part due to the potential False Claims Act exposure.

Further, the FDA has not materially changed its position on off-label promotion following legal setbacks on First

Amendment grounds and the DOJ has consistently asserted in FCA briefings that “speech that serves as a conduit for violations of the law is not constitutionally protected.”

Further, the FDA has not materially changed its position on off-label promotion following

legal setbacks on First Amendment grounds and the DOJ has consistently asserted in FCA briefings that “speech that serves as a conduit for violations of the law is not constitutionally protected.”

After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval.

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process are strictly regulated, and depending on the significance of the change, may require prior FDA approval before being implemented.

Other types of changes to the approved product, such as adding new indications and claims, are also subject

to further FDA review and approval.

The Drug Supply Chain Security Act, or DSCSA imposes obligations on manufacturers of prescription biopharmaceutical products for commercial distribution, regulating the distribution

of the products at the federal level, and sets certain standards for federal or state registration and compliance of entities in the supply chain (manufacturers and repackagers, wholesale distributors, third-party logistics providers, and

Other types of changes to the approved product, such as adding new indications and claims, are also

subject to further FDA review and approval.

The Drug Supply Chain Security Act, or DSCSA imposes obligations on manufacturers of prescription biopharmaceutical products for commercial distribution, regulating the

distribution of the products at the federal level, and sets certain standards for federal or state registration and compliance of entities in the supply chain (manufacturers and repackagers, wholesale distributors, third-party logistics

providers, and dispensers).

The DSCSA preempts certain previously enacted state pedigree laws and the pedigree requirements of the Prescription Drug Marketing Act, or PDMA.

Trading partners within the drug supply chain must now ensure certain product tracing

requirements are met that they are doing business with other authorized trading partners;

and they are required to exchange transaction information, transaction history, and transaction statements.

Product identifier information (an aspect of the

product tracing scheme) is also now required.

Trading partners within the drug supply chain must now ensure certain

product tracing requirements are met that they are doing business with other authorized trading partners, and they are required to exchange transaction information, transaction history, and transaction statements.

Product identifier information

(an aspect of the product tracing scheme) is also now required.

The DSCSA requirements, development of standards, and the system for product tracing have been and will continue to be phased in over a period of years.

The distribution of product samples continues to

be regulated under the PDMA, and some states also impose regulations on drug sample distribution.

Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product

reaches the market.

Later discovery of previously unknown problems with a product, including AEs of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to

the approved labeling to add new safety information;

The distribution of product

samples continues to be regulated under the PDMA, and some states also impose regulations on drug sample distribution.

Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the

product reaches the market.

revisions to the approved labeling to add new safety information;

imposition of post-market studies or clinical trials to assess new safety risks;

or imposition of distribution or other restrictions under a REMS program.

Other potential consequences include,

among other things:

Other potential

consequences include, among other things:

restrictions on the marketing or manufacturing of the product, including total or partial suspension of production, complete withdrawal of the product from the market or product recalls;

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injunctions or the imposition of civil or criminal penalties.

In addition, the distribution of prescription drug products is subject to the Prescription Drug Marketing Act, or PDMA, which regulates the distribution of drugs and drug samples at

the federal level, and sets minimum standards for the registration and regulation of drug distributors by the states.

Both the PDMA and state laws limit the distribution of prescription drug product samples and impose requirements to ensure

accountability in distribution.

In addition, the distribution of prescription drug products is subject to the Prescription Drug Marketing Act, or PDMA, which regulates the distribution of drugs and drug

samples at the federal level, and sets minimum standards for the registration and regulation of drug distributors by the states.

Both the PDMA and state laws limit the distribution of prescription drug product samples and impose requirements to

ensure accountability in distribution.

Failure to comply with any of the FDA’s requirements could result in significant adverse enforcement actions.

These include a variety of administrative or judicial sanctions, such

as refusal to approve pending applications, license suspension or revocation, withdrawal of an approval, imposition of a clinical hold or termination of clinical trials, warning letters, untitled letters, modification of promotional materials or

labeling, product recalls, product seizures or detentions, refusal to allow imports or exports, total or partial suspension of production or distribution, debarment, injunctions, fines, consent decrees, corporate integrity agreements, refusals of

government contracts and new orders under existing contracts, exclusion from participation in federal and state healthcare programs, restitution, disgorgement or civil or criminal penalties, including fines and imprisonment.

It is also possible

that failure to comply with the FDA’s requirements relating to the promotion of prescription drugs may lead to investigations alleging violations of federal and state healthcare fraud and abuse and other laws, as well as state consumer protection

These include a variety of administrative or judicial sanctions,

such as refusal to approve pending applications, license suspension or revocation, withdrawal of an approval, imposition of a clinical hold or termination of clinical trials, warning letters, untitled letters, modification of promotional

materials or labeling, product recalls, product seizures or detentions, refusal to allow imports or exports, total or partial suspension of production or distribution, debarment, injunctions, fines, consent decrees, corporate integrity

agreements, refusals of government contracts and new orders under existing contracts, exclusion from participation in federal and state healthcare programs, restitution, disgorgement or civil or criminal penalties, including fines and

imprisonment.

It is also possible that failure to comply with the FDA’s requirements relating to the promotion of prescription drugs may lead to investigations alleging violations of federal and state healthcare fraud and abuse and other laws, as

well as state consumer protection laws.

Any of these sanctions could result in adverse publicity, among other adverse consequences.

The FDA also may require post-marketing testing, known as Phase 4 testing, and surveillance to monitor the effects of an approved product.

Discovery of previously unknown problems

with a product or the failure to comply with applicable FDA requirements can have negative consequences, including adverse publicity, judicial or administrative enforcement, warning letters from the FDA, mandated corrective advertising or

communications with doctors, and civil or criminal penalties, among others.

Discovery of previously unknown

problems with a product or the failure to comply with applicable FDA requirements can have negative consequences, including adverse publicity, judicial or administrative enforcement, warning letters from the FDA, mandated corrective advertising

or communications with doctors, and civil or criminal penalties, among others.

Newly discovered or developed safety or effectiveness data may require changes to a product’s approved labeling, including the addition of new warnings and

contraindications, and also may require the implementation of other risk management measures.

Also, new government requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could delay

or prevent regulatory approval of its product candidates under development.

Also, new government requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could

delay or prevent regulatory approval of its product candidates under development.

Regulatory Exclusivities Applicable to Biologics and Related Matters

Abbreviated Licensure Pathway for Biosimilars :

The Biologics Price Competition and Innovation Act of 2009 (BPCIA) amended the PHSA to create an abbreviated approval pathway

for “biosimilar” biologics, that is, those shown to be highly similar to an already-FDA-licensed reference biologic.

The abbreviated approval process for biosimilars under the BPCIA is similar in concept to the Abbreviated New Drug Application

(“ANDA”) for generic small molecule drugs established by the Drug Price Competition and Patent Term Restoration Act of 1984 (“Hatch-Waxman”) amendments to the FDCA.

As with Hatch-Waxman, the goal of the BPCIA was to increase access to

lower-priced versions of drugs, while balancing the need to continue incentivizing innovation in drug development.

The Biologics Price Competition and Innovation Act of 2009 (BPCIA) amended the PHSA to create an abbreviated approval

pathway for “biosimilar” biologics, that is, those shown to be highly similar to an already-FDA-licensed reference biologic.

The abbreviated approval process for biosimilars under the BPCIA is similar in concept to the Abbreviated New Drug

Application (“ANDA”) for generic small molecule drugs established by the Drug Price Competition and Patent Term Restoration Act of 1984 (“Hatch-Waxman”) amendments to the FDCA.

As with Hatch-Waxman, the goal of the BPCIA was to increase access

to lower-priced versions of drugs, while balancing the need to continue incentivizing innovation in drug development.

Biosimilarity is defined to mean that the proposed biologic is highly similar to the reference product notwithstanding minor

differences in clinically inactive components and that there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity and potency of the product.

Further, a biosimilar may be

determined to be “interchangeable” with the reference product, in which case the biosimilar may be substituted for the reference product under state substitution laws, similar to the way generic small molecule drugs are substituted.

standard of interchangeability requires a showing that the biosimilar is expected to produce the same clinical result as the reference biologic in any given patient, and further that the risk to the patient in terms of safety, purity, and/or

potency pf switching between the biosimilar and the reference product is no more than using the reference product without switching.

Further, a biosimilar may

be determined to be “interchangeable” with the reference product, in which case the biosimilar may be substituted for the reference product under state substitution laws, similar to the way generic small molecule drugs are substituted.

higher standard of interchangeability requires a showing that the biosimilar is expected to produce the same clinical result as the reference biologic in any given patient, and further that the risk to the patient in terms of safety, purity,

and/or potency of switching between the biosimilar and the reference product is no more than using the reference product without switching.

Regulatory Exclusivities Applicable to Biologics Under the BPCIA :

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periods of time during which competing biosimilars or interchangeable biosimilars may not be approved or may not be marketed.

Once its BLA is approved (“date of first licensure) the reference biologic is entitled to a period of four years after

its date of first licensure during which time FDA is prohibited from accepting a marketing application that would seek approval of any products that are biosimilar to the branded product.

In addition, the reference biologic is entitled to a

period of 12 years after its date of first licensure during which time FDA is prohibited from approving marketing applications for any products that are biosimilar to the branded product.

In addition, the first interchangeable biosimilar may be

entitled to a period of one year after its date of first licensure, or other periods keyed to the outcome of patent litigation if instituted, during which FDA is prohibited from finding that any other biosimilars are interchangeable to the same

reference biologic.

Once its BLA is approved (“date of first licensure”) the reference biologic is entitled to a period of four years

after its date of first licensure during which time FDA is prohibited from accepting a marketing application that would seek approval of any products that are biosimilar to the branded product.

In addition, the reference biologic is entitled

to a period of 12 years after its date of first licensure during which time the FDA is prohibited from approving marketing applications for any products that are biosimilar to the branded product.

In addition, the first interchangeable

biosimilar may be entitled to a period of one year after its date of first licensure, or other periods keyed to the outcome of patent litigation if instituted, during which the FDA is prohibited from finding that any other biosimilars are

interchangeable to the same reference biologic.

The reference biologic may also be entitled to regulatory exclusivity under other statutory provisions that apply to biologics and small molecule drugs.

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A company must request orphan product designation before submitting an NDA.

If the request is granted, the FDA will disclose the identity of the therapeutic agent

and its potential use.

If the request is granted, the FDA will disclose the identity of the therapeutic

agent and its potential use.

Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

Among the other benefits of orphan drug designation are tax credits for certain research and

an exemption from the NDA or BLA application fee.

Among the other benefits of orphan drug designation are tax credits for certain

research and an exemption from the NDA or BLA application fee.

The FDA may revoke orphan drug designation, and if it does, it will publicize that the drug is no longer designated as an orphan drug.

If the sponsor of a product with orphan designation receives the first FDA approval for that drug for the disease or condition for which it has such designation or for a select

indication or use within the rare disease or condition for which it was designated, the product generally will receive orphan product exclusivity.

Orphan product exclusivity means that the FDA may not approve any other applications for the same

product for the same indication for seven years, except in certain limited circumstances.

If a drug or drug product designated as an orphan product ultimately receives marketing approval for an indication broader than what was designated in its

orphan product application, it may not be entitled to exclusivity.

Orphan drug exclusivity, however, could also block the approval of one of our therapeutic candidates for seven years if a competitor obtains orphan drug designation and FDA

approval of the same therapeutic candidate for the same condition or disease as our orphan-designated drug.

Orphan exclusivity will not bar approval of another product under certain circumstances, including if a subsequent product with the same active ingredient for the same indication

is shown to be clinically superior to the approved product on the basis of greater efficacy or safety, or providing a major contribution to patient care, or if the company with orphan drug exclusivity is not able to meet market demand.

the FDA may approve more than one product for the same orphan indication or disease as long as the products contain different active ingredients.

Moreover, competitors may receive approval of different products for the indication for which the

orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity.

If the sponsor of a product with orphan designation receives the first FDA approval for that drug for the disease or condition for which it has such designation or for a

select indication or use within the rare disease or condition for which it was designated, the product generally will receive orphan product exclusivity.

Orphan product exclusivity means that the FDA may not approve any other applications for

the same product for the same indication for seven years, except in certain limited circumstances.

If a drug or drug product designated as an orphan product ultimately receives marketing approval for an indication broader than what was

designated in its orphan product application, it may not be entitled to exclusivity.

Orphan drug exclusivity, however, could also block the approval of one of our therapeutic candidates for seven years if a competitor obtains orphan drug

designation and FDA approval of the same therapeutic candidate for the same condition or disease as our orphan-designated drug.

Orphan exclusivity will not bar approval of another product under certain circumstances, including if a subsequent product with the same active ingredient for the same

indication is shown to be clinically superior to the approved product on the basis of greater efficacy or safety, or providing a major contribution to patient care, or if the company with orphan drug exclusivity is not able to meet market

Further, the FDA may approve more than one product for the same orphan indication or disease as long as the products contain different active ingredients.

Moreover, competitors may receive approval of different products for the

indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity.

In addition, as the FDA has interpreted the Orphan Drug Act, even if a previously approved same drug does not have unexpired orphan exclusivity, a demonstration of clinical

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multiple legal challenges to this FDA interpretation, and in August 2017, Congress amended the orphan drug provisions of the FDCA through enactment of the FDA Reauthorization Act of 2017 to codify FDA’s longstanding interpretation.

Section 527 of

the FDCA now expressly provides that if a sponsor of an orphan-designated drug that is otherwise the same as an already approved drug for the same rare disease or condition is seeking orphan exclusivity, FDA shall require such sponsor, to

demonstrate that such drug is clinically superior to any already approved or licensed drug that is the same drug in order to obtain orphan drug exclusivity.

of the FDCA now expressly provides that if a sponsor of an orphan-designated drug that is otherwise the same as an already approved drug for the same rare disease or condition is seeking orphan exclusivity, the FDA shall require such sponsor,

to demonstrate that such drug is clinically superior to any already approved or licensed drug that is the same drug in order to obtain orphan drug exclusivity.

In September 2021, the United States Court of Appeals for the Eleventh Circuit decided in Catalyst Pharmaceuticals, Inc.

FDA’s interpretation of orphan drug exclusivity “for the same drug for the same disease or condition” as meaning the same “use or indication” was inappropriately narrow.

This decision had the potential to significantly broaden the scope of orphan

drug exclusivity for drugs that receive marketing approval for orphan indications that are narrower than their orphan-designated conditions in the United States.

On January 24, 2023, the FDA issued a statement to address the uncertainty created

by the circuit court’s decision in Catalyst .

This notification announced that, at this time, in matters beyond the scope of that court order (i.e., ordering the FDA to set aside its approval of the

specific drug at issue), the FDA intends to continue to apply its existing regulations tying orphan-drug exclusivity to the uses or indications for which the orphan drug was approved.

We cannot guarantee which rules and interpretations will be

governing going forward in different situations, that the FDA will maintain this current position, or that other judicial actions will not impact the FDA’s application of the Orphan Drug Act.

the FDA’s interpretation of orphan drug exclusivity “for the same drug for the same disease or condition” as meaning the same “use or indication” was inappropriately narrow.

This decision had the potential to significantly broaden the scope of

orphan drug exclusivity for drugs that receive marketing approval for orphan indications that are narrower than their orphan-designated conditions in the United States.

On January 24, 2023, the FDA issued a statement to address the uncertainty

created by the circuit court’s decision in Catalyst .

This notification announced that, at this time, in matters beyond the scope of that court order (i.e., ordering the FDA to set aside its approval of

the specific drug at issue), the FDA intends to continue to apply its existing regulations tying orphan drug exclusivity to the uses or indications for which the orphan drug was approved.

We cannot guarantee which rules and interpretations will

be governing going forward in different situations, that the FDA will maintain this current position, or that other judicial actions will not impact the FDA’s application of the Orphan Drug Act.

Pediatric Study Requirements and Pediatric Exclusivity :

Under the Best Pharmaceuticals for Children Act (BPCA), a sponsor qualifies for “pediatric exclusivity” if it complies

with a Written Request (WR) issued by FDA for pediatric studies.

Under the Best Pharmaceuticals for Children Act (BPCA), a sponsor qualifies for “pediatric exclusivity” if it

complies with a Written Request (WR) issued by FDA for pediatric studies.

The sponsor may apply to FDA to issue a WR.

Pediatric exclusivity operates by adding six months of exclusivity on to the end of the latest-expiring form of exclusivity and may apply

to patent rights or to FDA regulatory exclusivities.

Pediatric exclusivity operates by adding six months of exclusivity to the end of the latest-expiring form of exclusivity and

may apply to patent rights or to FDA regulatory exclusivities.

To qualify for pediatric exclusivity, at least one of those rights must still be currently in force at the time FDA approves the pediatric studies.

Under the Pediatric Research Equity Act of 2003, an NDA, BLA, or supplement thereto must contain data that are adequate to assess the safety and effectiveness of the drug product

for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

With enactment of the Food and Drug Administration Safety

and Innovation Act of 2012 (FDASIA), sponsors must also submit pediatric study plans prior to the assessment data.

Under the Pediatric Research Equity Act of 2003, an NDA, BLA, or supplement thereto must contain data that is adequate to assess the safety and effectiveness of the drug

product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

With enactment of the Food and Drug

Administration Safety and Innovation Act of 2012 (FDASIA), sponsors must also submit pediatric study plans prior to the assessment data.

Those plans must contain an outline of the proposed pediatric study or studies the applicant plans to conduct, including study objectives and design, any deferral or waiver

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request an amendment to the plan at any time.

The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in

adults, or full or partial waivers from the pediatric data requirements.

The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for

use in adults, or full or partial waivers from the pediatric data requirements.

Additional requirements and procedures relating to deferral requests and requests for extension of deferrals are contained in FDASIA.

Unless otherwise required by regulation,

the pediatric data requirements do not apply to products with orphan designation.

Unless otherwise required by

regulation, the pediatric data requirements do not apply to products with orphan designation.

Patent Term Extensions :

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period, plus the time between the submission date of an NDA and the ultimate approval date less any time the applicant did not act with due diligence during the period.

Patent term restoration cannot be used to extend the remaining term of a patent

past a total of 14 years from the product’s approval date.

Only one patent applicable to an approved drug product is eligible for the extension, only those claims covering the approved drug, a method for using it, or a method for manufacturing it

may be extended, and the application for the extension must be submitted prior to the expiration of the patent in question.

A patent that covers multiple drugs for which approval is sought can only be extended in connection with one of the

Patent term restoration cannot be used to extend the remaining term of a

patent past a total of 14 years from the product’s approval date.

Only one patent applicable to an approved drug product is eligible for the extension, only those claims covering the approved drug, a method for using it, or a method for

manufacturing it may be extended, and the application for the extension must be submitted prior to the expiration of the patent in question.

A patent that covers multiple drugs for which approval is sought can only be extended in connection with

one of the approvals.

The USPTO reviews and approves the application for any patent term extension or restoration in consultation with the FDA.

Similar provisions are available in Europe and other foreign jurisdictions to extend the term of a patent that

covers an approved drug.

Similar provisions are available in Europe and other foreign jurisdictions to extend the term of a

patent that covers an approved drug.

In the future, if and when our products receive FDA approval, we expect to apply for patent term extensions on patents covering those products.

We plan to seek patent term extensions to any of our issued patents in any

jurisdiction where these are available, however there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and if granted, the length

of such extensions.

We plan to seek patent term extensions to any of our issued

patents in any jurisdiction where these are available, however there is no guarantee that the applicable authorities, including the FDA in the United States, will agree with our assessment of whether such extensions should be granted, and if

granted, the length of such extensions.

For more information regarding the risks related to our intellectual property, see “Risk Factors—Risks Related to Our Intellectual Property.”

Healthcare Laws and Compliance Requirements

In the United States, PDS’s activities are potentially subject to regulation, either directly or indirectly, by various federal, state and local authorities in addition to the

FDA, including but not limited to, the Centers for Medicare and Medicaid Services, or CMS, other divisions of the U.S.

In the United States, PDS Biotech’s activities are potentially subject to regulation, either directly or indirectly, by various federal, state and local authorities in

addition to the FDA, including but not limited to, the Centers for Medicare and Medicaid Services, or CMS, other divisions of the U.S.

Department of Health and Human Services, for instance the Office of Inspector General (OIG), the U.S.

Department of Justice

(DOJ), and individual U.S.

Department of Justice (DOJ), and individual U.S.

Attorney offices within the DOJ, and state and local governments.

For example, sales, marketing and scientific/educational grant programs must comply with the anti-fraud and abuse provisions of the Social Security Act,

the criminal provisions of the Health Insurance Portability and Accountability Act of 1996 (HIPAA), the federal Anti-Kickback Statute, the federal false claims laws, the physician payment transparency laws, and similar state laws, each as

For example, sales, marketing and scientific/educational grant programs must comply with the anti-fraud and abuse provisions of

the Social Security Act, the criminal provisions of the Health Insurance Portability and Accountability Act of 1996 (HIPAA), the federal Anti-Kickback Statute, the federal false claims laws, the physician payment transparency laws, and similar

state laws, each as amended.

The compliance and enforcement landscape, and related risk, is informed by government enforcement precedent and settlement history, Advisory Opinions, and Special Fraud Alerts.

Our approach to compliance may evolve over time in light of

these types of developments.

Our approach to compliance may evolve

over time in light of these types of developments.

The federal Anti-Kickback Statute prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting or receiving any

remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any item or service reimbursable under Medicare, Medicaid or

other federal healthcare programs.

or other federal healthcare programs.

The term remuneration has been interpreted broadly to include anything of value.

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practices that involve remuneration that may be alleged to be intended to induce prescribing, purchasing or recommending may be subject to scrutiny if they do not qualify for an exception or safe harbor.

Failure to meet all of the requirements of

a particular applicable statutory exception or regulatory safe harbor, however, does not make the conduct per se illegal under the Anti-Kickback Statute.

Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on

a cumulative review of all of its facts and circumstances.

PDS’s practices may not in all cases meet all of the criteria for protection under a statutory exception or regulatory safe harbor.

The lack of uniform court interpretation of the

Anti-Kickback Statute combined with emerging, novel enforcement theories, makes compliance with the law difficult.

The potential safe harbors available are subject to change through legislative and regulatory action, and we may decide to adjust

our business practices or be subject to heightened scrutiny as a result.

Violations of the federal Anti-Kickback Statute can result in significant criminal fines, exclusion from participation in Medicare and Medicaid and follow-on civil

litigation, among other things, for both entities and individuals.

Failure to meet all of the requirements

of a particular applicable statutory exception or regulatory safe harbor, however, does not make the conduct per se illegal under the Anti-Kickback Statute.

Instead, the legality of the arrangement will be evaluated on a case-by-case basis

based on a cumulative review of all of its facts and circumstances.

PDS Biotech’s practices may not in all cases meet all of the criteria for protection under a statutory exception or regulatory safe harbor.

The lack of uniform court

interpretation of the Anti-Kickback Statute combined with emerging, novel enforcement theories, makes compliance with the law difficult.

The potential safe harbors available are subject to change through legislative and regulatory action, and

we may decide to adjust our business practices or be subject to heightened scrutiny as a result.

Violations of the federal Anti-Kickback Statute can result in significant criminal fines, exclusion from participation in Medicare and Medicaid and

follow-on civil litigation, among other things, for both entities and individuals.

Additionally, the intent standard under the Anti-Kickback Statute was amended by the Affordable Care Act to a stricter standard such that a person or entity no longer needs

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connection with the delivery of or payment for healthcare benefits, items or services.

The civil monetary penalties statute imposes penalties against any person or entity that, among other things, is determined to have presented or caused to be presented a claim to a

federal health program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent.

The Federal Civil Monetary Penalties Law authorizes the imposition of substantial civil monetary

penalties against an entity, such as a pharmaceutical manufacturer, that engages in activities including, among others (1) knowingly presenting, or causing to be presented, a claim for services not provided as claimed or that is otherwise false or

fraudulent in any way;

The civil monetary penalties statute imposes penalties against any person or entity that, among other things, is determined to have presented or caused to be presented a

claim to a federal health program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent.

The Federal Civil Monetary Penalties Law authorizes the imposition of substantial civil

monetary penalties against an entity, such as a pharmaceutical manufacturer, that engages in activities including, among others (1) knowingly presenting, or causing to be presented, a claim for services not provided as claimed or that is

otherwise false or fraudulent in any way;

(2) arranging for or contracting with an individual or entity that is excluded from participation in federal healthcare programs to provide items or services reimbursable by a federal healthcare program;

(3) violations of the

federal Anti-Kickback Statute;

(3) violations of the federal Anti-Kickback Statute;

or (4) failing to report and return a known overpayment.

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Other companies have been prosecuted for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, and thus non-reimbursable,

HIPAA created new federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud or to obtain, by means of false or

fraudulent pretenses, representations or promises, any money or property owned by, or under the control or custody of, any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or

HIPAA created new federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud or to obtain, by means of false

or fraudulent pretenses, representations or promises, any money or property owned by, or under the control or custody of, any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or

covering up by trick, scheme or device, a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

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several states, apply regardless of the payor, even extending to self-pay items and services.

PDS may be subject to data privacy and security regulations by both the federal government and the states in which it conducts its business.

We are not a covered entity under

HIPAA and have not functioned as a business associate under HIPAA that would cause the HIPAA Security Rule and provisions of the Privacy Rule to apply directly to us as a business associate.

To the extent that we ever function in a business

associate capacity, HIPAA, as amended by the HITECH Act, and its respective implementing regulations, including the final omnibus rule published on January 25, 2013, imposes requirements relating to the privacy, security and transmission of

individually identifiable health information.

Following enactment of the HITECH Act, HIPAA’s privacy and security standards now directly apply to business associates of covered entities that receive or obtain protected health information in

connection with providing a service on behalf of a covered entity.

HITECH also created four new tiers of civil monetary penalties, gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to

enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

In addition, state laws govern the privacy and security of health information in specified circumstances, many of which differ from

each other in significant ways, and may apply more broadly thus complicating compliance efforts (for example, California recently enacted legislation — the California Consumer Privacy Act, or CCPA — which went into effect on January 1, 2020 and

among other things, creates new data privacy obligations for covered companies and provides new privacy rights to California residents, including the right to opt out of certain disclosures of their information, and creates a private right of

action with statutory damages for certain data breaches.

PDS Biotech may be subject to data privacy and security regulations by both the federal government and the states in which it conducts its business.

We are not a covered

entity under HIPAA and have not functioned as a business associate under HIPAA that would cause the HIPAA Security Rule and provisions of the Privacy Rule to apply directly to us as a business associate.

To the extent that we ever function in

a business associate capacity, HIPAA, as amended by the HITECH Act, and its respective implementing regulations, including the final omnibus rule published on January 25, 2013, imposes requirements relating to the privacy, security and

transmission of individually identifiable health information.

Following enactment of the HITECH Act, HIPAA’s privacy and security standards now directly apply to business associates of covered entities that receive or obtain protected health

information in connection with providing a service on behalf of a covered entity.

HITECH also created four new tiers of civil monetary penalties, gave state attorneys general new authority to file civil actions for damages or injunctions in

federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

In addition, state laws govern the privacy and security of health information in specified circumstances, many

of which differ from each other in significant ways, and may apply more broadly thus complicating compliance efforts (for example, California recently enacted legislation — the California Consumer Privacy Act, or CCPA-which went into effect on

January 1, 2020 and among other things, creates new data privacy obligations for covered companies and provides new privacy rights to California residents, including the right to opt out of certain disclosures of their information, and creates

a private right of action with statutory damages for certain data breaches).

The CCPA was recently amended by the California Privacy Rights Act, or CPRA, expanding certain consumer rights such as the right to know.

It remains unclear what, if any, additional

modifications will be made to these laws by the California legislature or how these laws will be interpreted and enforced.

The potential effects of the CCPA and CPRA and implementing regulations are significant and may cause us to incur

substantial costs and expenses to comply.

Even for entities that are not deemed “covered entities” or “business associates” under HIPAA, according to the United States Federal Trade Commission, or the FTC, failing to take

appropriate steps to keep consumers’ personal information secure constitutes unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act, or the FTCA, 15 USC § 45(a).

It remains unclear what, if

any, additional modifications will be made to these laws by the California legislature or how these laws will be interpreted and enforced.

The potential effects of the CCPA and CPRA and implementing regulations are significant and may cause us

to incur substantial costs and expenses to comply.

Even for entities that are not deemed “covered entities” or “business associates” under HIPAA, according to the United States Federal Trade Commission, or the FTC, failing to

take appropriate steps to keep consumers’ personal information secure constitutes unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act, or the FTCA, 15 USC § 45(a).

The FTC expects a

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The FTC’s guidance for appropriately securing consumers’ personal information is similar to what is required by the HIPAA Security Rule.

The FTC’s authority

under Section 5 is concurrent with HIPAA’s jurisdiction and with any action taken under state law.

authority under Section 5 is concurrent with HIPAA’s jurisdiction and with any action taken under state law.

Additionally, the Federal Physician Payments Sunshine Act under the Affordable Care Act, and its implementing regulations, require that certain manufacturers of drugs,

devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with certain exceptions, report information related to certain payments or other transfers of value made

or distributed to physicians and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians and teaching hospitals and to report annually certain ownership and investment interests held by

physicians and their immediate family members.

Failure to submit timely, accurately, and completely the required information may result in civil monetary penalties of up to an aggregate of $150,000 per year and up to an aggregate of $1 million

per year for “knowing failures”.

In 2022 the Sunshine Act reporting will be extended to payments and transfers of value to physician assistants, nurse practitioners, and other mid-level practitioners (with reporting requirements going into effect

in 2022 for payments made in 2021).

Certain states also mandate implementation of compliance programs, impose restrictions on pharmaceutical manufacturer marketing practices and/or require the tracking and reporting of gifts, compensation and

other remuneration to healthcare providers and entities.

In order to distribute products commercially, PDS must also comply with state laws that require the registration of manufacturers and wholesale distributors of drug and biological

products in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state.

Several states have enacted legislation

requiring pharmaceutical and biotechnology companies to establish marketing compliance programs, file periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, clinical studies and other activities, and/or

register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing certain physician prescribing data to pharmaceutical and biotechnology companies for use in sales and marketing, and to prohibit

certain other sales and marketing practices.

All of PDS’s activities are potentially subject to federal and state consumer protection and unfair competition laws.

We expect that one or more of our products, if approved, may be eligible for coverage under Medicare, the federal health care program that provides health care benefits to the

aged and disabled, including coverage for outpatient services and supplies, such as certain drug products, that are medically necessary to treat a beneficiary’s health condition.

made or distributed to physicians and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians and teaching hospitals and to report annually certain ownership and investment interests held

by physicians and their immediate family members.

Failure to timely, accurately, and completely submit the required information may result in civil monetary penalties of up to an aggregate of $150,000 per year and up to an aggregate of $1

million per year for “knowing failures”.

into effect in 2022 for payments made in 2021).

Certain states also mandate implementation of compliance programs, impose restrictions on pharmaceutical manufacturer marketing practices and/or require the tracking and reporting of gifts,

compensation and other remuneration to healthcare providers and entities.

In order to distribute products commercially, PDS Biotech must also comply with state laws that require the registration of manufacturers and wholesale distributors of drug

and biological products in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state.

Several states have enacted

legislation requiring pharmaceutical and biotechnology companies to establish marketing compliance programs, file periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, clinical studies and other

activities, and/or register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing certain physician prescribing data to pharmaceutical and biotechnology companies for use in sales and

marketing, and to prohibit certain other sales and marketing practices.

All of PDS Biotech’s activities are potentially subject to federal and state consumer protection and unfair competition laws.

We expect that one or more of our products, if approved, may be eligible for coverage under Medicare, the federal health care program that provides health care benefits to

the aged and disabled, including coverage for outpatient services and supplies, such as certain drug products, that are medically necessary to treat a beneficiary’s health condition.

In addition, one or more of our products, if approved, may be

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The Medicaid Drug Rebate Program requires pharmaceutical manufacturers to enter into and have in effect a national rebate

agreement with the Secretary of the Department of Health and Human Services and pay quarterly rebates based on utilization of a manufacturer’s covered outpatient drugs under the program as a condition for states to receive federal matching funds

for a manufacturer’s covered outpatient drugs furnished to Medicaid patients and in order for payment to be available for a manufacturer’s drugs under Medicare Part B.

Pharmaceutical manufacturers are also required to participate in the 340B Drug

Pricing Program in order for payment to be available for a manufacturer’s drugs under Medicaid and Medicare Part B.

Under the 340B Drug Pricing Program, a manufacturer must charge no more than the 340B “ceiling price” for its covered outpatient

drugs purchased by statutorily defined covered entities that participate in the program.

In addition, federal law requires that, in order for payment to be available for a manufacturer’s drugs under Medicaid and Medicare Part B, as well as to be purchased by certain

federal agencies and grantees, it must also participate in the Department of Veterans Affairs (“VA”) Federal Supply Schedule (“FSS”) pricing program.

To participate, manufacturers are required to enter into an FSS contract and other agreements

with the VA for their covered drugs.

Under these agreements, manufacturers must make their covered drugs available to the “Big Four” federal agencies— the VA, the Department of Defense (“DoD”), the Public Health Service (including the Indian

Health Service), and the Coast Guard—at pricing that is capped pursuant to a statutory federal ceiling price, or FCP, formula.

The FCP is based on a weighted average non-federal average manufacturer price, which manufacturers are required to

report on a quarterly and annual basis to the VA.

Further, pursuant to regulations issued by the DoD to implement Section 703 of the National Defense Authorization Act for Fiscal Year 2008, manufacturers may enter into an agreement with the

Defense Health Agency (DHA) under which they agree to honor “Big Four” pricing for their covered drugs when they are dispensed to TRICARE beneficiaries by TRICARE retail network pharmacies.

funds for a manufacturer’s covered outpatient drugs furnished to Medicaid patients and in order for payment to be available for a manufacturer’s drugs under Medicare Part B.

Pharmaceutical manufacturers are also required to participate in the

340B Drug Pricing Program in order for payment to be available for a manufacturer’s drugs under Medicaid and Medicare Part B.

Under the 340B Drug Pricing Program, a manufacturer must charge no more than the 340B “ceiling price” for its covered

outpatient drugs purchased by statutorily defined covered entities that participate in the program.

In addition, federal law requires that, in order for payment to be available for a manufacturer’s drugs under Medicaid and Medicare Part B, as well as to be purchased by

certain federal agencies and grantees, it must also participate in the Department of Veterans Affairs (“VA”) Federal Supply Schedule (“FSS”) pricing program.

To participate, manufacturers are required to enter into an FSS contract and other

agreements with the VA for their covered drugs.

the Indian Health Service), and the Coast Guard—at pricing that is capped pursuant to a statutory federal ceiling price, or FCP, formula.

The FCP is based on a weighted average non-federal average manufacturer price, which manufacturers are

required to report on a quarterly and annual basis to the VA.

Further, pursuant to regulations issued by the DoD to implement Section 703 of the National Defense Authorization Act for Fiscal Year 2008, manufacturers may enter into an agreement

with the Defense Health Agency (DHA) under which they agree to honor “Big Four” pricing for their covered drugs when they are dispensed to TRICARE beneficiaries by TRICARE retail network pharmacies.

As part of the requirements to participate in these government programs, many pharmaceutical manufacturers must calculate and report certain price reporting metrics to the

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with these price reporting and rebate payment obligations, when applicable, could negatively impact our financial results.

Civil monetary penalties can be applied if a manufacturer is found to have knowingly submitted any false price information

to the government, if a manufacturer is found to have made a misrepresentation in the reporting of its average sales price, or if a manufacturer fails to submit the required price data on a timely basis.

Such conduct also could be grounds for CMS

to terminate a manufacturer’s Medicaid drug rebate agreement, in which case federal payments may not be available under Medicaid or Medicare Part B for a manufacturer’s covered outpatient drugs and may provide a basis for other potential

liability under other federal laws such as the False Claims Act.

Civil monetary penalties can be applied if a manufacturer is found to have knowingly submitted any false price

information to the government, if a manufacturer is found to have made a misrepresentation in the reporting of its average sales price, or if a manufacturer fails to submit the required price data on a timely basis.

Such conduct also could be

grounds for CMS to terminate a manufacturer’s Medicaid drug rebate agreement, in which case federal payments may not be available under Medicaid or Medicare Part B for a manufacturer’s covered outpatient drugs and may provide a basis for other

potential liability under other federal laws such as the False Claims Act.

Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs.

It is possible that

governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations, guidance, case law or other applicable law.

If our operations are found to be in violation of any of these laws or any

other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, individual imprisonment, exclusion from participation in federal health care programs, such as

Medicare and Medicaid, disgorgement, reputational harm, additional oversight and reporting obligations pursuant to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with applicable laws and regulations,

and the curtailment or restructuring of our operations, any of which could adversely affect our ability to market our products, if approved, and adversely impact our financial results.

Although effective compliance programs can mitigate the risk

of investigation and prosecution for violations of these laws and regulations, these risks cannot be eliminated entirely.

Any action against us for an alleged or suspected violation could cause us to incur significant legal expenses and could

divert our management’s attention from the operation of our business, even if our defense is successful.

If any of the physicians or other healthcare providers or entities with whom we expect to do business is found not to be in compliance with

applicable laws, it may be costly to us in terms of money, time and resources, and they may be subject to criminal, civil or administrative sanctions, including exclusions from government-funded healthcare programs.

possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations, guidance, case law or other applicable law.

If our operations are found to be in violation of any of

these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, individual imprisonment, exclusion from participation in federal health care

programs, such as Medicare and Medicaid, disgorgement, reputational harm, additional oversight and reporting obligations pursuant to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with applicable

laws and regulations, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to market our products, if approved, and adversely impact our financial results.

Although effective compliance

programs can mitigate the risk of investigation and prosecution for violations of these laws and regulations, these risks cannot be eliminated entirely.

Any action against us for an alleged or suspected violation could cause us to incur

significant legal expenses and could divert our management’s attention from the operation of our business, even if our defense is successful.

If any of the physicians or other healthcare providers or entities with whom we expect to do business

is found not to be in compliance with applicable laws, it may be costly to us in terms of money, time and resources, and they may be subject to criminal, civil or administrative sanctions, including exclusions from government-funded healthcare

The scope and enforcement of each of these laws is uncertain and subject to rapid change in the current environment of healthcare reform, especially in light of the lack of

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prosecutions, convictions and settlements in the industry.

Ensuring that business arrangements with third parties comply with applicable healthcare laws, as well as responding to possible investigations by government authorities, can be time- and

resource-consuming and can divert management’s attention from the business, even if investigators ultimately find that no violation has occurred.

If PDS operations are found to be in violation of any of the federal and state healthcare laws described above or any other governmental regulations that apply to it, PDS may be

subject to penalties, including without limitation, civil, criminal and/or administrative penalties;

Ensuring that business arrangements with third parties comply with applicable healthcare laws, as well as responding to possible investigations by government authorities, can be time-

and resource-consuming and can divert management’s attention from the business, even if investigators ultimately find that no violation has occurred.

If PDS Biotech operations are found to be in violation of any of the federal and state healthcare laws described above or any other governmental regulations that applies to

it, PDS Biotech may be subject to penalties, including without limitation, civil, criminal and/or administrative penalties;

disgorgement;

exclusion from participation in government programs, such as Medicare and Medicaid;

private “qui tam”

actions brought by individual whistleblowers in the name of the government, or refusal to allow it to enter into government contracts;

private “qui tam” actions brought by individual whistleblowers in the name of the government, or refusal to allow it to enter into government contracts;

contractual damages;

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administrative burdens;

diminished profits and future earnings;

curtailment or restructuring of its operations;

any of which could adversely affect PDS’s ability to operate its business and its results of operations.

In addition to the laws discussed above, we may see more stringent state and federal privacy legislation in the future, as the increased cyber-attacks during the COVID-19 pandemic

have heightened attention to data privacy and security in the U.S.

profits and future earnings;

and the curtailment or restructuring of its operations;

any of which could adversely affect PDS Biotech’s ability to operate its business and its results of operations.

In addition to the laws discussed above, we may see more stringent state and federal privacy legislation in the future, as the increased instances of cyber-attacks have

heightened attention to data privacy and security in the U.S.

and other jurisdictions.

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Coverage, Pricing and Reimbursement

Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which PDS obtains regulatory approval.

In the United States and markets in

other countries, sales of any products for which PDS receives regulatory approval for commercial sale will depend, in part, on the extent to which third-party payors provide coverage, and establish adequate reimbursement levels for such products.

Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which PDS Biotech obtains regulatory approval.

In the United States

and markets in other countries, sales of any products for which PDS Biotech receives regulatory approval for commercial sale will depend, in part, on the extent to which third-party payors provide coverage, and establish adequate reimbursement

levels for such products.

In the United States, third-party payors include federal and state healthcare programs, private managed care providers, health insurers and other organizations.

The process for determining whether a third-party payor will provide coverage for a

product may be separate from the process for setting the price of a product or for establishing the reimbursement rate that such a payor will pay for the product.

Third-party payors may limit coverage to specific products on an approved list, also

known as a formulary, which might not include all of the FDA-approved products for a particular indication.

Third-party payors are increasingly challenging the price, examining the medical necessity and reviewing the cost-effectiveness of medical

products, therapies and services, in addition to questioning their safety and efficacy.

PDS may need to conduct expensive pharmaco-economic studies in order to demonstrate the medical necessity and cost-effectiveness of its tablet product

candidates, in addition to the costs required to obtain the FDA approvals.

PDS’s product candidates may not be considered medically necessary or cost-effective.

A payor’s decision to provide coverage for a product does not imply that an adequate

reimbursement rate will be approved.

No uniform policy requirement for coverage and reimbursement exists among third-party payors in the United States, which causes significant uncertainty related to the insurance coverage and reimbursement of

newly approved products, and the procedures which may utilize such newly approved products.

Further, one payor’s determination to provide coverage for a product does not assure that other payors will also provide coverage for the product.

The process for determining whether a third-party payor

will provide coverage for a product may be separate from the process for setting the price of a product or for establishing the reimbursement rate that such a payor will pay for the product.

Third-party payors may limit coverage to specific

products on an approved list, also known as a formulary, which might not include all of the FDA-approved products for a particular indication.

Third-party payors are increasingly challenging the price, examining the medical necessity, and

reviewing the cost-effectiveness of medical products, therapies and services, in addition to questioning their safety and efficacy.

PDS Biotech may need to conduct expensive pharmaco-economic studies in order to demonstrate the medical necessity

and cost-effectiveness of its product candidates, in addition to the costs required to obtain the FDA approvals.

PDS Biotech’s product candidates may not be considered medically necessary or cost-effective.

A payor’s decision to provide coverage

for a product does not imply that an adequate reimbursement rate will be approved.

No uniform policy requirement for coverage and reimbursement exists among third-party payors in the United States, which causes significant uncertainty related to

the insurance coverage and reimbursement of newly approved products, and the procedures which may utilize such newly approved products.

Further, one payor’s determination to provide coverage for a product does not assure that other payors will

also provide coverage for the product.

Therefore, coverage and reimbursement can differ significantly from payor to payor and health care provider to health care provider.

As a result, the coverage determination process is often a time-consuming and costly process that requires the

provision of scientific and clinical support for the use of new products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.

Adequate third-party

reimbursement may not be available to enable PDS to maintain price levels sufficient to realize an appropriate return on its investment in product development.

As a result, the coverage determination process is often a time-consuming

and costly process that requires the provision of scientific and clinical support for the use of new products to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the

first instance.

Adequate third-party reimbursement may not be available to enable PDS Biotech to maintain price levels sufficient to realize an appropriate return on its investment in product development.

Different pricing and reimbursement schemes exist in other countries.

Some jurisdictions operate positive and negative list systems under which products may only be marketed

once a reimbursement price has been agreed.

To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical studies that compare the cost-effectiveness of a particular product candidate to currently

available therapies.

Some jurisdictions operate positive and negative list systems under which products may only be

marketed once a reimbursement price has been agreed.

To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical studies that compare the cost-effectiveness of a particular product candidate to

currently available therapies.

Other countries allow companies to fix their own prices for medicines, but monitor and control company profits.

The downward pressure on health care costs has become very intense.

As a result, increasingly high barriers are

being erected to the entry of new products.

As a result, increasingly high

barriers are being erected to the entry of new products.

In addition, in some countries, cross-border imports from low-priced markets exert a commercial pressure on pricing within a country.

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adequate coverage and reimbursement or require onerous prior approvals or other restricted access.

In addition, emphasis on managed care in the United States has increased and PDS expects the pressure on healthcare pricing will continue to

In addition, emphasis on managed care in the United States has increased and PDS Biotech expects the pressure on healthcare pricing will continue

Coverage policies and third-party reimbursement rates may change at any time.

Even if favorable coverage and reimbursement status is attained for one or more products for which PDS receives regulatory approval, less favorable coverage

policies and reimbursement rates may be implemented in the future.

There may be significant delays in obtaining coverage and reimbursement for newly approved products, and coverage may be more limited than the purposes for which the product is

approved by the FDA.

Moreover, eligibility for coverage and reimbursement does not imply that a product, or the procedures which utilize such product, will be paid for in all cases or at a rate which the health care providers who purchase those

products will find cost effective.

Additionally, we expect pricing pressures in connection with the sale of any of our product candidates due to the trend toward managed healthcare, the increasing influence of health maintenance organizations, and

additional legislative changes.

We cannot be sure that coverage and reimbursement will be available for any product that we commercialize, or the procedures which utilize such product, and, if reimbursement is

available, what the level of reimbursement will be.

Even if favorable coverage and reimbursement status is attained for one or more products for which PDS Biotech receives regulatory approval, less favorable

coverage policies and reimbursement rates may be implemented in the future.

There may be significant delays in obtaining coverage and reimbursement for newly approved products, and coverage may be more limited than the purposes for which the product

is approved by the FDA.

those products will find cost effective.

Additionally, we expect pricing pressures in connection with the sale of any of our product candidates due to the trend toward managed healthcare, the increasing influence of health maintenance

organizations, and additional legislative changes.

We cannot be sure that coverage and reimbursement will be available for any product that we commercialize, or the procedures which utilize such product, and, if reimbursement

is available, what the level of reimbursement will be.

Coverage and reimbursement may impact the demand for, or the price of, any product candidate for which we obtain marketing approval.

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In recent years, there have been numerous initiatives on the federal and state levels in the United States for comprehensive reforms.

In the United States and some foreign

jurisdictions, there have been and continue to be a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate

post-approval activities and affect our ability, or the ability of our future collaborators, to effectively sell any drugs for which we, or they, obtain marketing approval.

We expect that current laws, as well as other healthcare reform measures

that may be adopted in the future, may result in more rigorous coverage criteria and additional downward pressure on the price that we, or our future collaborators, may receive for any approved drugs.

For example, the Patient Protection and

Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, “PPACA”) has substantially changed and continues to impact healthcare financing and delivery by both government payors and private insurers.

the PPACA provisions of importance to the pharmaceutical industry, in addition to those otherwise described above, are the following:

an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents, apportioned among these entities according to their market share in certain

federal programs identified in the PPACA;

In the United States and some foreign jurisdictions, there have been and continue to be a number of legislative and regulatory changes and proposed changes regarding the

healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability, or the ability of our future collaborators, to effectively sell any drugs for

which we, or they, obtain marketing approval.

We expect that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and additional downward pressure on the

price that we, or our future collaborators, may receive for any approved drugs.

For example, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, “PPACA”) has

substantially changed and continues to impact healthcare financing and delivery by both government payors and private insurers.

Among the PPACA provisions of importance to the pharmaceutical industry, in addition to those otherwise described

above, are the following:

an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents, apportioned among these entities according to their market share in

certain federal programs identified in the PPACA;

expansion of beneficiary eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to certain individuals with income at or below 138% of the federal

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annual reporting of certain information regarding drug samples that manufacturers and distributors provide to licensed practitioners.

The framework of the PPACA continues to evolve as a result of executive, legislative, regulatory, and administrative developments that have challenged the law and contribute to

legal uncertainty that could affect the profitability of our products.

While Congress has not enacted legislation to comprehensively repeal the PPACA, legislation affecting the PPACA has been signed into law, including the elimination, effective

January 1, 2019, of the tax-based shared responsibility payment imposed by the PPACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year, which is commonly referred to as the “individual mandate.” In

December 2018, a federal district court in Texas ruled that the PPACA’s individual mandate, without the penalty that was eliminated effective January 1, 2019, was unconstitutional and could not be severed from the PPACA.

As a result, the court

ruled the remaining provisions of the PPACA were also invalid.

The Fifth Circuit Court of Appeals affirmed the district court’s ruling that the individual mandate was unconstitutional, but it remanded the case back to the district court for

further analysis of whether the mandate could be severed from the PPACA (i.e., whether the entire PPACA was therefore also unconstitutional).

The framework of the PPACA continues to evolve as a result of executive, legislative, regulatory, and administrative developments that have challenged the law and

contribute to legal uncertainty that could affect the profitability of our products.

While the United States Congress has not enacted legislation to comprehensively repeal the PPACA, legislation affecting the PPACA has been signed into law,

including the elimination, effective January 1, 2019, of the tax-based shared responsibility payment imposed by the PPACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year, which is commonly

referred to as the “individual mandate.” In December 2018, a federal district court in Texas ruled that the PPACA’s individual mandate, without the penalty that was eliminated effective January 1, 2019, was unconstitutional and could not be

severed from the PPACA.

As a result, the court ruled the remaining provisions of the PPACA were also invalid.

The Fifth Circuit Court of Appeals affirmed the district court’s ruling that the individual mandate was unconstitutional, but it

remanded the case back to the district court for further analysis of whether the mandate could be severed from the PPACA (i.e., whether the entire PPACA was therefore also unconstitutional).

On June 17, 2021, the U.S.

Supreme Court dismissed this challenge without specifically ruling on the

constitutionality of the PPACA.

Effective January 1, 2019, the Bipartisan Budget Act of 2018, among other things, further amended portions of the Social Security Act implemented as part of the PPACA to increase

from 50% to 70% the point-of-sale discount that pharmaceutical manufacturers participating in the Coverage Gap Discount Program must provide to eligible Medicare Part D beneficiaries during the coverage gap phase of the Part D benefit, commonly

referred to as the “donut hole,” and to reduce standard beneficiary cost sharing in the coverage gap from 30% to 25% in most Medicare Part D plans.

In addition, the Further Consolidated Appropriations Act of 2020, signed into law December 20,

2019, fully repealed the PPACA’s “Cadillac Tax” on certain high-cost employer-sponsored insurance plans (for tax years beginning after December 31, 2019), the annual fee imposed on certain health insurance providers based on market share (for

calendar year 2021), and the medical device excise tax on non-exempt medical devices (for sales after December 31, 2019).

Supreme Court dismissed

this challenge without specifically ruling on the constitutionality of the PPACA.

Effective January 1, 2019, the Bipartisan Budget Act of 2018, among other things, further amended portions of the Social Security Act implemented as part of the PPACA to

increase from 50% to 70% the point-of-sale discount that pharmaceutical manufacturers participating in the Coverage Gap Discount Program must provide to eligible Medicare Part D beneficiaries during the coverage gap phase of the Part D benefit,

commonly referred to as the “donut hole,” and to reduce standard beneficiary cost sharing in the coverage gap from 30% to 25% in most Medicare Part D plans.

In addition, the Further Consolidated Appropriations Act of 2020, signed into law

December 20, 2019, fully repealed the PPACA’s “Cadillac Tax” on certain high-cost employer-sponsored insurance plans (for tax years beginning after December 31, 2019), the annual fee imposed on certain health insurance providers based on market

share (for calendar year 2021), and the medical device excise tax on non-exempt medical devices (for sales after December 31, 2019).

In the future, there may be additional challenges and/or amendments to the PPACA.

It remains to be seen precisely what any

new legislation will provide, when or if it will be enacted, and what impact it will have on the availability and cost of healthcare items and services, including drug products.

It remains to be seen

precisely what any new legislation will provide, when or if it will be enacted, and what impact it will have on the availability and cost of healthcare items and services, including drug products.

In addition, other legislative changes have been proposed and adopted since the PPACA was enacted.

For example, the Budget Control Act of 2011, among other things, resulted in

reductions in payments to Medicare providers of 2% per fiscal year, which went into effect on April 1, 2013 and, due to subsequent legislation, will remain in effect through 2031, with the exception of a temporary suspension of the payment

reduction from May 1, 2020 through March 31, 2022 due to the coronavirus pandemic.

Sequestration will start again on April 1, 2022.

From April 1, 2022 to June 30, 2022, payment for Medicare fee-for-service claims will be adjusted downwards by 1%;

beginning on July 1, 2022, the payment will be adjusted downwards by 2%.

In addition, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set

at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.

Further, the American Taxpayer Relief Act of 2012, among other things, reduced CMS payments to several providers,

including hospitals, and increased the statute of limitations period for the government to recover Medicare overpayments to providers from three to five years.

These legislative changes may result in additional reductions in Medicare and other

healthcare funding and otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.

For example, the Budget Control Act of 2011, among other things, resulted

in reductions in payments to Medicare providers of 2% per fiscal year, which went into effect on April 1, 2013 and, due to subsequent legislation, will remain in effect through 2031, with the exception of a temporary suspension of the payment

reduction which occurred from May 1, 2020 through March 31, 2022 due to the coronavirus pandemic.

Sequestration started again on April 1, 2022.

From April 1, 2022 to June 30, 2022, payment for Medicare fee-for-service claims was adjusted

downwards by 1%;

beginning on July 1, 2022, the payment was adjusted downwards by 2%.

In addition, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap,

currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.

Further, the American Taxpayer Relief Act of 2012, among other things, reduced CMS payments to

several providers, including hospitals, and increased the statute of limitations period for the government to recover Medicare overpayments to providers from three to five years.

These legislative changes may result in additional reductions in

Medicare and other healthcare funding and otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used.

Recently, the cost of prescription pharmaceuticals has been the subject of considerable discussion in the United States.

Congress considered and passed legislation, and the former

Trump administration pursued several regulatory reforms to further increase transparency around prices and price increases, lower out-of-pocket costs for consumers, and decrease spending on prescription drugs by government programs.

Congress also

continued to conduct inquiries into the prescription drug industry’s pricing practices.

While several proposed reform measures will require Congress to pass legislation to become effective, Congress and the Biden administration have each

indicated that it will continue to seek new legislative and/or administrative measures to address prescription drug costs.

The Biden administration has taken several recent executive actions that signal changes in policy from the prior

administration.

For example, on July 9, 2021, President Biden signed an executive order to promote competition in the US economy that included several initiatives addressing prescription drugs.

Among other provisions, the executive order directed

the Secretary of HHS to issue a report to the White House within 45 days that includes a plan to, among other things, reduce prices for prescription drugs, including prices paid by the federal government for such drugs.

In response to the

Executive Order, on September 9, 2021, HHS issued a Comprehensive Plan for Addressing High Drug Prices that identified potential legislative policies and administrative tools that Congress and the agency can pursue in order to make drug prices

more affordable and equitable, improve and promote competition throughout the prescription drug industry, and foster scientific innovation.

Additionally, on February 2, 2022, the Biden Administration signaled its continued commitment to the

Cancer Moonshot initiative, which was initially launched in 2016.

In its recent announcement, the administration noted that its new goals under the initiative include addressing inequities in order to ensure broader access to cutting-edge cancer

therapeutics and investing in a robust pipeline for new treatments.

At the state level, legislatures are increasingly passing legislation and states are implementing regulations designed to control spending on and patient out-of-pocket costs for

drug products.

Implementation of cost containment measures or other healthcare reforms that affect the pricing and/or availability of drug products may impact our ability to generate revenue, attain or maintain profitability, or commercialize

products for which we may receive regulatory approval in the future.

Congress considered and passed legislation, and the

former Trump administration pursued several regulatory reforms to further increase transparency around prices and price increases, lower out-of-pocket costs for consumers, and decrease spending on prescription drugs by government programs.

Congress also continued to conduct inquiries into the prescription drug industry’s pricing practices.

While several proposed reform measures will require Congress to pass legislation to become effective, Congress and the Biden administration

have each indicated that it will continue to seek new legislative and/or administrative measures to address prescription drug costs.

The Biden administration has taken several recent executive actions that signal changes in policy from the

prior administration.

For example, on July 9, 2021, President Biden signed an executive order to promote competition in the U.S.

economy that included several initiatives addressing prescription drugs.

Among other provisions, the executive

order directed the Secretary of HHS to issue a report to the White House within 45 days that includes a plan to, among other things, reduce prices for prescription drugs, including prices paid by the federal government for such drugs.

response to the Executive Order, on September 9, 2021, HHS issued a Comprehensive Plan for Addressing High Drug Prices that identified potential legislative policies and administrative tools that Congress and the agency can pursue in order to

make drug prices more affordable and equitable, improve and promote competition throughout the prescription drug industry, and foster scientific innovation.

Additionally, on February 2, 2022, the Biden Administration signaled its continued

commitment to the Cancer Moonshot initiative, which was initially launched in 2016.

In its recent announcement, the administration noted that its new goals under the initiative include addressing inequities in order to ensure broader access to

cutting-edge cancer therapeutics and investing in a robust pipeline for new treatments.

At the state level, legislatures are increasingly passing legislation and states are implementing regulations designed to control spending and patient

out-of-pocket costs for drug products.

Implementation of cost containment measures or other healthcare reforms that affect the pricing and/or availability of drug products may impact our ability to generate revenue, attain or maintain

profitability, or commercialize products for which we may receive regulatory approval in the future.

Most recently, on August 16, 2022 the Inflation Reduction Act of 2022, or IRA was signed into law.

Among other things, the IRA requires manufacturers of certain drugs to engage in

price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap;

Among other things, the IRA requires manufacturers of certain drugs to

engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap;

imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in

replaces the Part D coverage gap discount program with a new discounting program (beginning in 2025).

The IRA permits the Secretary of the Department of Health and Human Services (HHS) to implement many of these provisions through guidance, as

opposed to regulation, for the initial years.

and replaces the Part D coverage gap discount program with a new discounting program (beginning in 2025).

The IRA permits the Secretary of the Department of Health and Human Services (HHS) to implement many of these provisions through

guidance, as opposed to regulation, for the initial years.

For that and other reasons, it is currently unclear how the IRA will be effectuated, and the impact of the IRA on the pharmaceutical industry cannot yet be fully determined.

We expect that these and other healthcare reform measures that may be adopted in the future may result in more rigorous coverage criteria and/or new payment methodologies, and

place additional downward pressure on the price that we receive for any approved product and/or the level of reimbursement physicians and other healthcare providers receive for administering any approved product we might bring to market.

We expect that these and other healthcare reform measures that may be adopted in the future may result in more rigorous coverage criteria and/or new payment methodologies,

and place additional downward pressure on the price that we receive for any approved product and/or the level of reimbursement physicians and other healthcare providers receive for administering any approved product we might bring to market.

Reductions in reimbursement levels and imposition of more rigorous coverage criteria or new payment methodologies may negatively impact the prices we receive or the frequency with which our products are prescribed or administered.

Any coverage or

reimbursement policies instituted by Medicare or other federal health care programs may result in similar policies from private payors.

The implementation of cost containment measures or other healthcare reforms may affect our ability to generate

revenue, attain or maintain profitability, or commercialize our drug candidates.

We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state

governments will pay for healthcare products and services, which could result in reduced demand for our drug candidates or additional pricing pressures.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price

or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

addition, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other health care programs.

or reimbursement policies instituted by Medicare or other federal health care programs may result in similar policies from private payors.

The implementation of cost containment measures or other healthcare reforms may affect our ability to

generate revenue, attain or maintain profitability, or commercialize our drug candidates.

We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal

and state governments will pay for healthcare products and services, which could result in reduced demand for our drug candidates or additional pricing pressures.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including

price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

In addition, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other health care

These measures could reduce the ultimate demand for our products or put pressure on our product pricing.

We expect that additional state healthcare reform measures will be adopted in the future, which could limit the amounts that state governments

will pay for healthcare products and services and result in additional pricing pressures.

The boom in state laws targeting drug pricing is unprecedented and the requirements are not uniform from state to state, creating additional compliance and

commercialization challenges for manufacturers.

If PDS is able to obtain marketing approval for one or more of our products, our revenue and future profitability could be negatively affected if these or other inquiries were to result in legislative

or regulatory proposals that limit our ability to increase the prices of any products for which we obtain marketing approval.

We expect that additional state healthcare reform measures will be adopted in the future, which could limit the amounts that state

governments will pay for healthcare products and services and result in additional pricing pressures.

The boom in state laws targeting drug pricing is unprecedented and the requirements are not uniform from state to state, creating additional

compliance and commercialization challenges for manufacturers.

If PDS Biotech is able to obtain marketing approval for one or more of our products, our revenue and future profitability could be negatively affected if these or other inquiries were

to result in legislative or regulatory proposals that limit our ability to increase the prices of any products for which we obtain marketing approval.

Foreign Regulation

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regarding quality, safety and efficacy and governing, among other things, clinical studies, marketing authorization, commercial sales and distribution of its products.

Whether or not PDS obtains FDA approval for a product, it would need to obtain

the necessary approvals by the comparable foreign regulatory authorities before it can commence clinical studies or marketing of the product in foreign countries and jurisdictions.

Although many of the issues discussed above with respect to the

United States apply similarly in the context of the European Union, the approval process varies between countries and jurisdictions and can involve additional product testing and additional administrative review periods.

The time required to

obtain approval in other countries and jurisdictions might differ from and be longer than that required to obtain FDA approval.

Regulatory approval in one country or jurisdiction does not ensure regulatory approval in another, but a failure or

delay in obtaining regulatory approval in one country or jurisdiction may negatively impact the regulatory process in others.

Whether or not PDS Biotech obtains FDA approval for a product, it would need

to obtain the necessary approvals by the comparable foreign regulatory authorities before it can commence clinical studies or marketing of the product in foreign countries and jurisdictions.

Although many of the issues discussed above with

respect to the United States apply similarly in the context of the European Union, the approval process varies between countries and jurisdictions and can involve additional product testing and additional administrative review periods.

required to obtain approval in other countries and jurisdictions might differ from and be longer than that required to obtain FDA approval.

Regulatory approval in one country or jurisdiction does not ensure regulatory approval in another, but a

failure or delay in obtaining regulatory approval in one country or jurisdiction may negatively impact the regulatory process in others.

European Union member states and other foreign jurisdictions, including Switzerland, have adopted data protection laws and regulations which impose significant compliance

Moreover, the collection and use of personal health data in the European Union, which was formerly governed by the provisions of the European Union Data Protection Directive, was replaced with the European Union General Data Protection

Regulation, or the GDPR, in May 2018.

The GDPR, which is wide-ranging in scope, imposes several requirements relating to the consent of the individuals to whom the personal data relates, the information provided to the individuals, the security and

confidentiality of the personal data, data breach notification and the use of third-party processors in connection with the processing of personal data.

The GDPR also imposes strict rules on the transfer of personal data out of the European Union

to the United States, provides an enforcement authority and imposes large penalties for noncompliance, including the potential for fines of up to €20 million or 4% of the annual global revenues of the noncompliant company, whichever is greater.

recent implementation of the GDPR has increased our responsibility and liability in relation to personal data that we process, including in clinical trials, and we may in the future be required to put in place additional mechanisms to ensure

compliance with the GDPR, which could divert management’s attention and increase our cost of doing business.

In addition, new regulation or legislative actions regarding data privacy and security (together with applicable industry standards) may

increase our costs of doing business.

In this regard, we expect that there will continue to be new proposed laws, regulations and industry standards relating to privacy and data protection in the United States, the European Union and other

jurisdictions, and we cannot determine the impact such future laws, regulations and standards may have on our business.

Protection Regulation, or the GDPR, in May 2018.

The GDPR, which is wide-ranging in scope, imposes several requirements relating to the consent of the individuals to whom the personal data relates, the information provided to the individuals, the

security and confidentiality of the personal data, data breach notification and the use of third-party processors in connection with the processing of personal data.

The GDPR also imposes strict rules on the transfer of personal data out of the

European Union to the United States, provides an enforcement authority and imposes large penalties for noncompliance, including the potential for fines of up to €20 million or 4% of the annual global revenues of the noncompliant company,

whichever is greater.

The recent implementation of the GDPR has increased our responsibility and liability in relation to personal data that we process, including in clinical trials, and we may in the future be required to put in place additional

mechanisms to ensure compliance with the GDPR, which could divert management’s attention and increase our cost of doing business.

In addition, new regulation or legislative actions regarding data privacy and security (together with applicable

industry standards) may increase our costs of doing business.

In this regard, we expect that there will continue to be new proposed laws, regulations and industry standards relating to privacy and data protection in the United States, the

European Union and other jurisdictions, and we cannot determine the impact such future laws, regulations and standards may have on our business.

Employees and Human Capital Management

Our management team possesses considerable experience in drug development research, manufacturing, clinical development and regulatory matters.

PDS’ virtual operating

strategy of collaborating with scientific and clinical experts in cancer immunology, tumor immunology and gynecological oncology provides additional considerable experience in immunotherapy development, clinical design and execution.

collective bargaining agreements with our employees and we have not experienced any work stoppages.

As of December 31, 2022, we had 26 employees, all of which were full time employees.

PDS Biotech’s virtual

operating strategy of collaborating with scientific and clinical experts in cancer immunology, tumor immunology and gynecological oncology provides additional considerable experience in immunotherapy development, clinical design and execution.

We have no collective bargaining agreements with our employees, and we have not experienced any work stoppages.

As of December 31, 2023, we had 25 employees, all of whom were full time employees.

Our employees are highly skilled, and many hold advanced degrees.

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We believe we are compliant in all material respects with applicable environmental laws.

Presently, we do not anticipate such compliance will have a material effect on capital

expenditures, earnings, or our competitive position with respect to any of our operations.

Presently, we do not anticipate such compliance will have a material effect on

capital expenditures, earnings, or our competitive position with respect to any of our operations.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business