UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, DC 20549



FORM 8-K



CURRENT REPORT
Pursuant to Section 13 or 15(d) of the
Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): January 14, 2021


PDS BIOTECHNOLOGY CORPORATION
(Exact Name of Registrant as Specified in Charter)


Delaware
001-37568
26-4231384
     
(State or Other Jurisdiction of Incorporation)
(Commission File Number)
(I.R.S. Employer Identification No.)

25B Vreeland Road, Florham Park, NJ 07932
(Address of Principal Executive Offices, and Zip Code)

(800) 208-3343
Registrant’s Telephone Number, Including Area Code



(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):


Written communication pursuant to Rule 425 under the Securities Act (17 CFR 230.425)


Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)


Pre-commencement communication pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))


Pre-commencement communication pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class
Trading Symbol(s)
Name of each exchange on which registered
Common Stock, par value $0.00033 per share
PDSB
The Nasdaq Capital Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2 of this chapter).

Emerging growth company ☐
 
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. Yes ☐  No



Item 8.01.
Other Events.

On January 14, 2021, PDS Biotechnology Corporation (the “Company”) issued a press release, a copy of which is filed herewith as Exhibit 99.1 and incorporated herein by reference, announcing the issuance of a white paper regarding the Company’s Versamune® platform technology as a cancer immunotherapy.  A copy of the white paper is filed herewith as Exhibit 99.2 and incorporated herein by reference.

Item 9.01
Financial Statements and Exhibits.

(d) Exhibits.

Exhibit
Number
 
Description

 
 
Press Release, dated January 14, 2021.
99.2  
White paper, dated January 14, 2021.


Signature
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

   
PDS BIOTECHNOLOGY CORPORATION
     
Date: January 14, 2021

By: /s/ Frank Bedu-Addo, Ph.D.
   
Name: Frank Bedu-Addo, Ph.D.
   
Title: President and Chief Executive Officer




Exhibit 99.1

PDS Biotech Releases White Paper Detailing the Potential of the Versamune®
Platform in Overcoming a Major Limitation of Immuno-Oncology

Promotes in-vivo tumor-attacking killer T-cells to facilitate cancer treatment

Florham Park, NJ, January 14, 2021 - PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing novel cancer therapies and infectious disease vaccines based on the Company’s proprietary Versamune® T-cell activating technology, today released a white paper detailing how the Versamune® platform works to treat cancer, and the potential of Versamune® in the treatment of a broad range of cancers.

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. The goal of cancer immunotherapy is tumor eradication and regression or, at least, disease stabilization.  Cancer immunotherapies have significant potential to treat a broad range of cancers, and multiple agents have been approved by the FDA to treat a wide range of cancers at various stages. Though progress has been made in developing new anti-cancer immunotherapeutic technologies and products, significant challenges limiting their clinical effectiveness and safety remain.

There are well recognized hurdles impeding the ability of immunotherapy to harness the body’s immune system most effectively. For example, approved checkpoint inhibitors have resulted in effective, durable responses. Unfortunately, the rates of response reported are only in the range of 15-20% and are most likely to occur in patients with evidence of a pre-existing immune response to their tumor. Furthermore, immune therapies, including checkpoint inhibitors, CAR-Ts and live-vector vaccines, may cause significant systemic toxicities limiting their use either in the early-stage cancer setting or in combination with other approved anti-cancer treatments.

A significant challenge in the development of an effective cancer immunotherapy is creating a simple and easy to administer therapy that can promote the induction of highly potent, targeted, tumor-specific CD8+ killer and CD4+ helper T-cells within patients, that will effectively treat their cancer with minimal side effects.  There is scientific consensus that induction of an adequate number and potency of tumor-recognizing T-cells is necessary for effective immunotherapy. However, suboptimal T-cell activation remains a key limitation of many immunotherapies.

In two recent peer reviewed articles in the Journal of Immunology and the Journal for Immunotherapy of Cancer (available on the company’s website), Versamune®-based immunotherapies were shown to induce superior quantity and quality of tumor-recognizing killer T-cells in-vivo.  This resulted in superior preclinical anti-tumor efficacy.  Versamune®’s ability to be combined with specific proteins found primarily on the tumor cells and its ability to induce an effective anti-tumor immune response specific to the protein and cancer, o-ffers opportunities to treat a variety of cancers. Further, its diverse mechanisms of action and favorable safety profile suggest therapeutic promise when used alone in the single-agent monotherapy setting or when used in combination with standard of care therapies such as checkpoint inhibitors as well as chemo and radiation therapy to enhance the efficacy of treatment.


The current PDS Biotech pipeline of Versamune®-based therapies focuses on four key antigens associated with a broad variety of solid tumors that remain challenging to treat.  According to PDS Biotech CEO, Dr. Frank Bedu-Addo, “We are currently pursuing an ambitious development strategy, working with leading oncology experts to assess the potential of Versamune® to bring new and improved treatments to cancer patients.”

Read Versamune®: A New Generation of Cancer Immunotherapies here.

About PDS Biotechnology
 
PDS Biotech is a clinical-stage immunotherapy company with a growing pipeline of cancer immunotherapies and infectious disease vaccines based on the Company’s proprietary Versamune® T-cell activating technology platform. The company’s lead investigational cancer immunotherapy product PDS0101 is currently in Phase 2 clinical studies in multiple indications. Versamune® effectively delivers disease-specific antigens for in vivo uptake and processing, while also activating the critical type 1 interferon immunological pathway, resulting in production of potent disease-specific killer T-cells as well as neutralizing antibodies. PDS Biotech has developed multiple therapies, based on combinations of Versamune® and disease-specific antigens, designed to train the immune system to better recognize diseased cells and effectively attack and destroy them. To learn more, please visit www.pdsbiotech.com or follow us on Twitter at @PDSBiotech.
 
Forward Looking Statements

This communication contains forward-looking statements (including within the meaning of Section 21E of the United States Securities Exchange Act of 1934, as amended, and Section 27A of the United States Securities Act of 1933, as amended) concerning PDS Biotechnology Corporation (the “Company”) and other matters. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current beliefs of the Company’s management, as well as assumptions made by, and information currently available to, management. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” “forecast.” “guidance”, “outlook” and other similar expressions among others. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the Company’s ability to protect its intellectual property rights; the Company’s anticipated capital requirements, including the Company’s anticipated cash runway and the Company’s current expectations regarding its plans for future equity financings; the Company’s dependence on additional financing to fund its operations and complete the development and commercialization of its product candidates, and the risks that raising such additional capital may restrict the Company’s operations or require the Company to relinquish rights to the Company’s technologies or product candidates; the Company’s limited operating history in the Company’s current line of business, which makes it difficult to evaluate the Company’s prospects, the Company’s business plan or the likelihood of the Company’s successful implementation of such business plan; the timing for the Company or its partners to initiate the planned clinical trials for its lead asset PDS0101; the future success of such trials; the successful implementation of the Company’s research and development programs and collaborations, including any collaboration studies concerning PDS0101 and the Company’s interpretation of the results and findings of such programs and collaborations and whether such results are sufficient to support the future success of the Company’s product candidates; the acceptance by the market of the Company’s product candidates, if approved; the timing of and the Company’s ability to obtain and maintain U.S. Food and Drug Administration or other regulatory authority approval of, or other action with respect to, the Company’s product candidates; and other factors, including legislative, regulatory, political and economic developments not within the Company’s control, including unforeseen circumstances or other disruptions to normal business operations arising from or related to COVID-19. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors included in the Company’s annual and periodic reports filed with the SEC. The forward-looking statements are made only as of the date of this press release and, except as required by applicable law, the Company undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise.

Media & Investor Relations Contact:

Deanne Randolph
PDS Biotech
Phone: +1 (908) 517-3613
Email: drandolph@pdsbiotech.com

Jacob Goldberger
CG Capital
Phone: +1 (404) 736-3841
Email: jacob@cg.capital






Exhibit 99.2

 
 Versamune®: A New Generation of Cancer Immunotherapies
 
Despite recent progress in fighting cancer the sad reality is that it remains a leading cause of morbidity and mortality. Some of the most promising new treatments have emerged from the convergence of the oncology and immunology fields. These novel therapies that harness the power of the immune system to fight cancer are called immunotherapies. Cancer immunotherapies have significant potential to treat a broad range of cancers, and several have been approved by the FDA. To date, however, while progress has been made in developing new anti-cancer immunotherapeutic technologies and products, significant challenges limiting their clinical effectiveness remain.
 
On a basic immunological level, considerable hurdles impeding the ability of immunotherapy to harness the body’s immune system most effectively persist. For example, approved checkpoint inhibitors have been demonstrated to be effective and for those patients who respond, the durability of their responses can be significant. Unfortunately, the rates of response reported are only in the range of 15-20%. Importantly, immune therapies, including checkpoint inhibitors, CAR-Ts and live-vector vaccines, remain burdened with significant systemic toxicities limiting their use either in the early-stage cancer setting or in combination with other approved anti-cancer treatments.
 
This paper provides an overview of cancer immunotherapy, describes some of the challenges to optimizing its potential, and introduces Versamune®, a proprietary T-cell activating platform engineered and developed to overcome some of these challenges in order to improve the treatment outcomes of patients with cancer.


What Is 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. The ultimate goal of cancer immunotherapy is tumor eradication or, at least, regression.
 
The body’s immune system is a complex biological network designed to defend against germs, other microscopic invaders, and cancer cells. Once the immune system recognizes an organism or cell as foreign or dangerous, it begins a series of complex reactions to identify, target and eliminate them. This is called mounting an immune response. Cancer immunotherapy takes advantage of the discovery that most cancer cells express unique proteins, also called tumor antigens, not normally expressed by healthy cells and thus can be recognized as abnormal and dangerous. Because the immune system is precise, it can target these dangerous cancer cells exclusively while sparing healthy cells. However, the challenge remains that cancer cells are often not perceived as dangerous or foreign, so the immune system becomes tolerant to them.
 
An ideal cancer immunotherapy should have the following attributes to maximize the opportunity for clinical effectiveness in patients. It should:
 

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 enemy more visible or susceptible to attack by the immune system
 

Generate immune memory, so if cancer cells return, the immune system is able to recognize and eliminate them
 

Optimize safety and tolerability by limiting systemic inflammation and toxicity
 
As published in the June 2019 issue of The Journal of Immunology, a leading peer-reviewed journal in the field of immunology, Versamune® incorporates each of these attributes, leading to superior anti-tumor responses in pre-clinical studies. (Gandhapudi, et al., 2019). PDS Biotech’s 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.


How Does Cancer Immunotherapy Work?



An important function of the body’s immune system is to scan for antigens not normally expressed in healthy tissue. 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 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.
 
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. 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.
 
An effective cancer immunotherapy must modulate these complex processes, enhancing activation and producing robust expansion of the critically important high-quality, 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.
 
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 suppress the immune system; they camouflage themselves or evade 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.
 
Finally, cancers can be difficult to cure because they may recur even after successful initial treatment due to micro-metastatic (hidden) tumors disease that is not completely eradicated after treatment and that eventually expands. It is yet another task of the immune system to remain ever vigilant for recurrence, a vigilance mediated by memory T-cells which serve as 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.


What Have Been the Challenges of Developing Immunotherapies in Oncology?
 


The inability to generate adequate quantities of unique, high-quality killer 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 daunting challenges confronting the development of effective immunotherapy is the development of a simple and easy to administer therapy that can promote the induction of highly potent, targeted, tumor-specific T-cells that can effectively treat cancer with minimal side effects.
Suboptimal T-cell activation remains a key limitation of immunotherapies. Potential hurdles exist at all 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.
 
Versamune®: Overcoming the Challenges of Cancer Immunotherapy
 
What is Versamune®?
 

Versamune® is a proprietary T-cell activating platform designed to overcome the challenges of current immunotherapy in order to 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. These lipids include the R-enantiomer of 1,2-dioleoyl-e-trimethyl-ammonium-propane (R-DOTAP). 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.


Versamune® Promotes Dendritic Cell Uptake
 
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. 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.


 
In addition, as the surface of Versamune® is positively charged and the body’s cells are negatively charged, Versamune® tends to be quite “sticky” and serves as a depot at the injection site for several days following subcutaneous injection. Large numbers of dendritic cells thus have the opportunity to be recruited and to take up the nanoparticles.

Versamune® Promotes Efficient Antigen Processing and T-cell Presentation
 
When dendritic cells take up Versamune® nanoparticles they become activated, mature and begin recruiting additional dendritic cells. Once inside the dendritic cell, the tumor-associated antigen is released and processed into the requisite small peptides (pieces of protein) in the cell compartment known as the cytoplasm. An important advantage of Versamune® is its ability to fuse with and destabilize endosomes in the cytoplasm, promoting efficient entry of the antigen into the cell compartment where processing can take place. Processed antigen is turned into peptides that then utilize both the MHC class I and class II pathways. The MHC class I pathway is critical to programing 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. 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. Interestingly, Versamune® has been demonstrated to promote presentation of antigens to CD4+ helper cells as well.


Versamune® Demonstrates Effective
Antigen Presentation to Both CD8+ Killer and CD4+ Helper T-cells


Versamune® Promotes Efficient Activation and Robust Expansion of High Quality Polyfunctional CD8+ Killer T-cells in Lymph Nodes
 
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 immunological activity pertaining to the priming and expansion of T-cells takes place.
 
In the lymph nodes the dendritic cells present the tumor antigens to T-cells resulting in activation or priming of the T-cells to recognize the particular antigen expressed by the cancer. Importantly, Versamune® also upregulates type 1 interferon genes (type I IFN), which are responsible for critical immunological processes. This induces an important immunological protein called CD69 that facilitates interactions between the dendritic cell and T-cells in the lymph nodes. Upregulation of type I IFN signaling also induces multiple immune messengers called cytokines and chemokines that further signal T-cells to infiltrate into the lymph nodes. Powerful activators of CD8+ killer T-cells, such as CCL2 and CXCL10 are documented to be induced by Versamune® as well. As the Versamune®-induced production of chemokines appears to be restricted to the lymph nodes, the site of T-cell activation, it provides for both superior activation and expansion of CD8+ killer T-cells. Localization of these immune messengers within the lymph nodes and their limited presence in the blood circulation enhances the safety of the Versamune®-based immunotherapies. Thus, through the versality of its mechanisms of action, Versamune® safely promotes 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® Promotes Activation and Robust Expansion of Both Antigen-specific CD8+ Killer and CD4+ Helper T-cells

 
Versamune® Overcomes 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. In cancer however, they are utilized by the cancer cells to evade immune detection. Versamune® results in significant alteration of the tumor microenvironment to reduce dramatically the Treg to killer CD8+ T-cell ratio 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.


Versamune® Makes Tumors More Susceptible to Destruction by Activated CD8+ Killer T-cells


Overcoming 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.
 
Versamune® Induces 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. Preliminary studies demonstrated that Versamune® protected mice who 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 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 has also been demonstrated in a phase 1 clinical trial in humans.


Enhancing tumor-specific memory responses to monitor for and eradicate cancer cells well after initial treatment provides potential for significant clinical benefit by possibly reducing the incidence of tumor recurrence.

When cured mice are re-exposed to the same tumor, they remain free of cancer, confirming the presence of immune memory that recognizes the tumor when it reappears.

Versamune® Safety
 
Today, many cancer immunotherapies produce serious systemic autoimmune effects as well as inflammatory toxicities due to the increased presence and spikes of cytokines in the blood circulation. The mechanism of action of Versamune® as well as its design both 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 expectation is that Versamune®-based therapies will exhibit an improved and favorable safety profile compared to currently available treatments.
 
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. 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, thus mitigating the potential for short- or long-term accumulation of the nanoparticles. These pre-clinical 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 systemic toxicity at all doses tested. In a phase 1 clinical study 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. No dose-limiting toxicities or long-term safety concerns were observed.


In choosing and designing a Versamune®-based therapy, 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.
 
Versamune® Potential as an Immunotherapy
 

Cancer Immunotherapy
 
The unique ability of Versamune® to modulate and enhance numerous critical steps required for an effective immune response and to be combined with targeted specific antigens found on tumor cells, offers several exciting opportunities to treat a variety of cancers. 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 checkpoint inhibitors as well as in the single-agent monotherapy setting.
 
The current PDS Biotech pipeline of Versamune®-based therapies focuses on four key antigens associated with a broad variety of solid tumors that remain challenging to treat:


Human Papillomavirus (HPV)-Related Cancers
 
Despite the successful introduction of HPV preventive vaccines, HPV-related cancers remain a significant component of the global cancer burden. HPV infection occurs in both men and women and is associated with head and neck (oropharyngeal), cervical, anal, vaginal, vulvar and penile cancers.
 

PDS0101 is PDS Biotech’s lead Versamune®-based immunotherapy. 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. These data prompted 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 34th 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.

PDS0102: T-cell receptor gamma Alternate Reading frame Protein (TARP)-Related Cancers
 
The TARP antigen is strongly associated with prostate and breast cancers. In the U.S. 450,000 patients are projected to be diagnosed with prostate or breast cancer this year. Approximately 90% of prostate cancers and 50% of breast cancers overexpress the TARP tumor antigen. In a human clinical study, the National Cancer Institute 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 PDS-designed TARP antigens were combined with Versamune®. Preclinical development is ongoing.

PDS0103: Mucin-1 (MUC1)-Related Cancers
 
MUC1 is highly expressed in multiple solid tumor types and has been shown to be associated with drug resistance and poor disease prognosis. PDS Biotech is developing PDS0103, a 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, similarly to PDS0102, a dramatically enhanced MUC1-specific killer T-cell response was observed when the novel antigens were combined with Versamune®. Preclinical development is ongoing.

PDS0104: Melanoma-Specific Antigens
 
The rates of melanoma have been rising rapidly over the past few decades and approximately 96,480 new melanomas will be diagnosed this year alone. More than 7,000 of these will prove fatal. PDS0104 combines Versamune® with various melanoma antigens including the Tyrosinase-related protein 2 (TRP2) which is highly expressed in melanoma. PDS0104 has been demonstrated in pre-clinical animal models of aggressive melanoma to have unique and significant anti-tumor activity as a monotherapy and has also demonstrated strong anti-tumor synergy in combination with checkpoint inhibitors. Preclinical development is ongoing.
 
Versamune® has demonstrated immunological compatibility with a wide array of tumor and pathogenic antigens. While PDS Biotech’s current pipeline pairs Versamune® with four different tumor antigens, to address over 10 cancer types, more than 75 tumor antigens have been identified. The versatility of the platform suggests that Versamune® could work well with a wide range of identified tumor antigens and neoantigens. PDS Biotech is exploring the expansion of its Versamune®-based pipeline by pairing the technology with multiple tumor antigens to develop additional product candidates.


Versamune®: A Next Generation Cancer Immunotherapy with Exciting Promise


 
The field of cancer immunotherapy continues to make significant strides in the battle against cancer. Versamune® platform-derived products have several important potential immunotherapeutic advantages that may overcome many of the shortcomings of current immunotherapies and lead to new cancer treatments with strong efficacy and a highly favorable safety profile.
 
Versamune® appears to be unique in its ability to activate each of the critical steps required for effective immunotherapy. Most importantly Versamune®’s demonstrated ability to activate the critical immunological steps outlined below provide strong potential for superior efficacy in the treatment of several cancers:
 

Induces an antigen-specific CD8+ killer and CD4+ helper T-cells response within the body
 

-
Promotes the uptake and processing of tumor antigens by dendritic cells

-
Promotes cross-presentation of these processed tumor antigens by the MHC class I and class II pathways to effectively stimulate both tumor-specific CD8+ killer and CD4+ helper T-cells, respectively

-
Triggers type I interferons within the lymph nodes associated with the ‘foreign’ and ‘danger’ signals of the immune system
 

Activates, arms and expands large numbers of T-cells that recognize the tumor
 

Alters the tumor microenvironment (TME) to “de-camouflage the tumor” to make the cancer more susceptible to attack by the primed T-cells
 

Generates powerful immune memory, so if cancer cells return, the immune system is able to recognize and eliminate them
 

Optimizes safety and tolerability by limiting systemic inflammation and toxicity
 
The above results in powerful anti-tumor CD8+ killer T-cell responses. Alteration of the tumor microenvironment allows for effective killing of the tumor by the active killer T-cells. Activation of Type I interferon signaling also promotes the induction of T-cell memory. Versamune®’s simple engineering, its ease of subcutaneous administration when admixed with proprietary antigens tailored to individual cancer types, its robust immunological activity and its favorable safety profile that avoids off-target systemic toxicities, make it an ideal platform to study in combination with other agents, where it may prove to be synergistic, and also as a monotherapy treatment.
 
In conclusion, the immunological mechanisms of action of the Versamune® platform result in a unique combination of potency and safety. Versamune®-based therapies offer tremendous promise for producing new treatments targeting a broad range of cancers. To this end, PDS Biotech looks forward to advancing the science of Versamune® to bring new and improved treatments to cancer patients.


 
References
          Gandhapudi, S., Ward, M., Bush, J., Bedu-Addo, F., Conn, G., & Woodward, J. (2019). Antigen priming with enantiospecific cationic lipid nanoparticles induces potent antitumor CTL responses through novel induction of a Type I IFN response. J Immunol, 202 (12): 3524-3536
          Wood, L., Edwards, L., Ferris, D., Nevadunsky, N., Isani, S., Conn, G., . . . Einstein, M. (2019, November 8). A Novel Enantio-Specific Cationic Lipid R-DOTAP + HPV16 E6 & E7 Antigens Induces Potent
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