PDS Biotech is a late-stage immunotherapy company preparing to initiate a Phase 3 clinical trial evaluating Versamune HPV + pembrolizumab as a potential first-line treatment for recurrent or metastatic HPV16-positive head and neck squamous cell carcinoma (HNSCC). Pulse 2.0 interviewed PDS Biotech President and CEO Frank Bedu-Addo, Ph.D., to learn more about the company.
Frank Bedu-Addo’s Background
Pulse 2.0 (Amit): To start, tell me about yourself and your background.
PDS Biotech (Frank): I am a life science entrepreneur and executive with experience successfully starting and growing biotechnology organizations. In addition to being a Co-founder, I’ve served as Director, President, and CEO of PDS Biotechnology Corporation (PDS Biotech) since its inception in December 2005. My experience includes developing and implementing operational and drug development strategies at several large organizations and emerging biotechnology companies.
I was a founding and senior executive at KBI BioPharma, where I managed all business operations, drug development operations and profit and loss. Before that, I started and oversaw Cardinal Health’s East Coast biotechnology drug development operations. I contributed to the development of numerous drugs in various positions as an Associate Director at Akzo-Nobel, Senior Scientist at Elan (The Liposome Co.), and Principal Scientist at Schering-Plough. I received my M.S. in Chemical Engineering and Ph.D. in Pharmaceutics from the University of Pittsburgh.
Dr. Bedu-Addo on PDS Biotech
Pulse 2.0 (Amit): Can you tell me a little bit about PDS Biotech’s history?
PDS Biotech (Frank): PDS Biotech was established in 2005 with the goal of developing novel immunotherapies that harness the power of T cells to address some of the most devastating illnesses of our time. Prof. Leaf Huang, the scientific founder of PDS Biotech was a Distinguished Professor at the Eshelman School of Pharmacy, University of North Carolina at Chapel Hill.
The first of several patents covering the Versamune technology was acquired by the company in 2006, and drug development operations to develop the very early-stage concept began in 2007. The first of several PDS Biotech-developed patents covering the Versamune platform technology were submitted in 2008. We initially performed R&D and early drug development studies with the National Institutes of Health (NIH) funding and angel investments. That R&D process produced Versamune HPV, a T-cell immunotherapy being developed to treat human papillomavirus (HPV)-positive cancers.
PDS Biotech’s first human clinical trial studied Versamune HPV, the company’s lead product, as a single agent and was successfully completed in late 2016. Between 2018 and 2021, PDS Biotech established Phase 2 clinical collaborations with the National Cancer Institute (NCI), MD Anderson Cancer Center, Mayo Clinic and Merck, USA to study Versamune HPV in combination with standard of care and other immunotherapeutic agents in multiple HPV-positive cancer indications.
Since 2022, Versamune HPV has demonstrated excellent survival results in Phase 2 trials of HPV-positive tumors, such as recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC), locally advanced cervical cancer, and other tumor-agnostic HPV-positive cancers, which have been presented at top clinical oncology conferences. In January of 2023, PDS Biotech acquired exclusive worldwide rights from Merck KGaA, Darmstdat, Germany, to the first tumor-targeting IL-12 immunocytokine now called PDS01ADC.
With this acquisition, PDS Biotech also assumed full rights to multiple ongoing Phase 2 clinical trials of PDS01ADC at the NCI. The combination of Versamune HPV and PDS01ADC in early clinical studies produced objective response and patient survival rates that have generated significant interest and appreciation among members of the medical community who are aware of what has previously been reported to date in any advanced recurrent and/or metastatic HPV-related cancers.
Favorite Memory
Pulse 2.0 (Amit): What has been your favorite memory working for the company so far?
PDS Biotech (Frank): When we founded PDS Biotech, our goal was to develop therapies that could better harness the power of the body’s T-cells to address some of the most devastating cancers of our time. These cancers include advanced HNSCC and locally advanced cervical cancer, both of which are characterized by high mortality rates and short duration of survival. My favorite memories have been seeing the results of our clinical studies that have demonstrated a clear survival benefit in our patients. It motivates me to know that several patients are alive today and spending quality time with their families, in part, because of our investigational therapies.
In the MD Anderson-led cervical cancer trial presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting 2024, the 36-month survival rate in patients who received chemoradiation (CRT) and all 5 doses of Versamune HPV was 100%. The best published 36-month survival rate in these patients with locally advanced cervical cancer is 82.6% with a combination of CRT and Keytruda.
In our study of first-line recurrent and/or metastatic HPV16-positive HNSCC reported at the European Society for Medical Oncology (ESMO) Congress 2024, the median overall survival was 30 months. The best published median overall survival for patients with HNSCC is 17.9 months in the LEAP-010 study.
In our study of a triple combination of Versamune HPV, PDS01ADC and a checkpoint inhibitor in patients with recurrent and/or metastatic HPV-positive cancer whose disease had progressed after checkpoint inhibitor therapy, the median overall survival exceeded 17 months. The published median survival in these patients is only 3.4 months.
Consistently bringing forth this quality of data in diverse indications in multiple studies gives us confidence that our Versamune research and immunotherapeutic approaches are contributing to significant advancements in the treatment of debilitating cancers.
Platform Differentiation
Pulse 2.0 (Amit): Can you describe your platforms and what makes them different?
PDS Biotech (Frank): The core component of PDS Biotech’s oncology platform is Versamune, our proprietary technology designed to harness the power of the immune system to successfully recruit, train and arm T-cells to execute a precise attack on cancer.
Versamune has been shown to induce a significantly higher quantity and quality of highly potent (multifunctional) killer T-cells, a specific sub-type of killer T-cell that is more powerful at attacking cancer. By promoting the induction of the right type of killer T-cell, with strong potency and in the right quantity, Versamune has demonstrated impressive activity in trials to date.
PDS Biotech is also developing a potentially potent combination of Versamune with PDS01ADC, our proprietary antibody-drug conjugate (ADC), which is designed to target the tumor’s inner core. PDS01ADC works synergistically with Versamune-based immunotherapies to promote a targeted T-cell attack against cancers by specifically targeting and infiltrating the tumor to make it more susceptible to killing by the Versamune-induced T cells. Clinical data suggest the addition of PDS01ADC to Versamune-based immunotherapies may enhance disease control by more effectively shrinking tumors and/or prolonging survival in recurrent and/or metastatic cancer patients who have poor survival prognosis.
Challenges Faced
Pulse 2.0 (Amit): What challenges have Bedu-Addo and the team faced in building the company?
PDS Biotech (Frank): I think all clinical-stage biotechnology companies face similar hurdles in developing and commercializing their products and technologies. Clinical trials tend to be long and expensive, particularly in the later stages where you’re seeking to confirm safety and efficacy. The financial constraints of drug development also often limit product development to one asset/technology and indication until the product is approved or validated, and the company can generate sales and licensing revenues.
We have successful ongoing collaborations with top oncology researchers to independently study our product in different indications, leading to three investigator-initiated Phase 2 clinical trials of Versamune HPV.
We also acquired exclusive rights to PDS01ADC, which had been developed by Merck KGaA and tested in human clinical trials to evaluate safety and clinical responses. By acquiring this asset, PDS Biotech also established a pipeline of clinical trials studying PDS01ADC as a monotherapy or in combination with standard of care in prostate cancer, gall bladder cancer, liver cancer, Kaposi sarcoma, and other solid tumors.
By taking this approach, PDS Biotech has been successful with relatively low capital burn in establishing a deep clinical pipeline of products based on Versamune + the standard of care, PDS01ADC + the standard of care and Versamune + PDS01ADC + the standard of care.
The company has also been able to attain independent expert validation of the potential efficacy of our therapies in development. We believe this approach has put the company in a strong position for clinical and commercial success.
Evolution Of PDS Biotech’s Technology
Pulse 2.0 (Amit): How has PDS Biotech’s pipeline evolved since launching?
PDS Biotech (Frank): The company’s initial focus was to develop Versamune HPV as a monotherapy to treat cervical intraepithelial neoplasia (CIN), a precancerous condition that occurs when abnormal cells grow on the surface of the cervix.
By the time we concluded our Phase 1 study of Versamune HPV in CIN, we had achieved a much better understanding of Versamune HPV’s mechanism of action. We also understood the limitations of current immunotherapy and the fact that cancer is most effectively treated by activating multiple anti-tumor pathways. We therefore concluded that Versamune HPV had great potential to promote strong anti-tumor responses and therefore, patient survival when combined with other promising immunotherapies and standards of care. The pipeline was then transitioned to examine Versamune HPV in advanced HPV-positive solid tumors through clinical studies.
The Versamune platform technology has also been applied to MUC1-positive cancers, and we anticipate that the product will enter human clinical trials to treat cancers such as colon, non-small cell lung cancer (NSCLC) and ovarian cancer. Our acquisition of PDS01ADC has allowed us to expand our pipeline into various cancers, including prostate cancer, liver, gallbladder and Kaposi sarcoma.
In October 2024, we announced the design of and rationale for a clinical trial led by the NCI of PDS01ADC + Xtandi (a nonsteroidal antiandrogen medication approved by the U.S. Food and Drug Administration in the treatment of prostate cancer) vs. Xtandi alone in biochemically recurrent prostate cancer.
Significant Milestones
Pulse 2.0 (Amit): What have been some of the company’s most significant milestones?
PDS Biotech (Frank): Meeting our primary endpoints in our VERSATILE-002 study evaluating Versamune HPV + KEYTRUDA (pembrolizumab) in patients with HPV16-positive HNSCC. Phase 2 for any company usually represents the first time a drug is tested in actual patients for its efficacy in treating the disease, and failures can be common, because previously unknown toxic side effects may occur, or the trial may show insufficient efficacy. So, to have met our primary endpoint decisively was a major accomplishment. We have been following the patients from that trial and recently published updated data, which was presented at ESMO 2024 and continues to be exciting and impressive in light of other published data:
- Median Overall Survival (mOS) was 30 months with a lower 95% confidence interval of 19.7 months; Published mOS for pembrolizumab is 12-18 months
- Objective Response Rate (ORR) of 36%; published ORR for pembrolizumab is 19-25%Disease Control Rate (DCR) is 77%
— 21% of patients had complete or near complete tumor shrinkage of 90-100% - 9% of patients had a complete response with no evidence of the cancer
Based on these study results, Versamune HPV was given a Fast Track designation by the FDA, and PDS is now aligned with the FDA regarding the Phase 3 pivotal trial.
Recently announced updated results from the IMMUNOCERV study led by Dr. Ann Klopp, M.D., Ph.D., at MD Anderson Cancer Center in locally advanced cervical cancer were another major milestone for the company. The study evaluated the combination of Versamune HPV and chemoradiation (CRT) on patient safety and treatment efficacy. HPV causes 99.9% of cervical cancers. In these patients, which included 70.6% Stage III and Stage IV patients, it is the first time that complete responses with no evidence of the cancer were reported in as many as 88% of such patients. It is the first time, to the best of our knowledge, that any subset of these patients has had a reported 100% survival rate and 100% disease progression-free survival rate at 36 months, based on treatment sufficiency (received all five doses of Versamune HPV). In patients who received two or more doses of Versamune HPV, the 36-month survival rate was 84.4%. The best-published result to date is in CRT + KEYTRUDA of 82.6%.
The study also reported on levels of HPV-positive circulating tumor DNA (ctDNA) in patients’ blood and reported that 5 weeks after start of treatment, patients who received Versamune HPV had 92% decline in ctDNA versus 53% in patients who received CRT alone. This study provided strong clinical and biomarker evidence of the clinical activity of Versamune HPV.
Total Addressable Market
Pulse 2.0 (Amit): What total addressable market (TAM) size is the company pursuing?
PDS Biotech (Frank): Versamune HPV is being developed to address HPV-positive cancers, including anal, cervical, HNSCC, penile, vaginal and vulvar cancers. Versamune HPV has a potential market of $2-3B for its lead indication of HPV16-positive HNSCC in the United States. The current annual incidence of HPV16-positive HNSCC is 18,000 (about 35-40% of all HNSCC). The incidence of locally advanced, unresectable recurrent and/or metastatic HPV16-positive HNSCC is about 13,600. In the EU, the trends for HNSCC are similar. The total addressable market for Versamune HPV across all HPV-positive cancers exceeds $6B in the United States alone.
The addressable market for the pipeline products currently in development exceeds $80 billion.
Differentiation From The Competition
Pulse 2.0 (Amit): What differentiates PDS Biotech from its competition?
PDS Biotech (Frank): We consider our competition to be clinical-stage companies developing T-cell immunotherapies for cancer.
PDS Biotech is very different from the competition in several areas: technology/science, clinical development strategy, pipeline development and operational/financial efficiency.
The Versamune technology is the first of its kind and is based on a single, biodegradable and immunologically active synthetic lipid. The lipid forms virus-like nanoparticles and is uniquely effective in activating the correct immunological pathways to promote a powerful long-acting anti-tumor response. Versamune is protected by several patents in the US and internationally.
The Versamune HPV formulation combines the Versamune nanoparticles with a proprietary mixture of short proteins from the HPV16 virus and is designed to promote T-cells that specifically recognize and target tumors expressing HPV16. Versamune HPV has attracted the interest of various clinical oncologists wanting to collaborate on investigator-initiated clinical studies of Versamune HPV in various indications and perform important biomarker studies. These studies, alongside the VERSATILE-002 trial, have provided strong validation of the potential of Versamune HPV due to the consistent and promising tolerability and clinical responses across all trials.
The compelling results across multiple indications to date provide strong evidence of the product’s potential, a solid proof of concept and also present opportunities to progress Versamune HPV into multiple late-stage registrational trials. Our approach of independently developing our Versamune technology platform from a preclinical concept while simultaneously identifying and acquiring a competitive cutting-edge and complimentary clinical stage asset in PDS01ADC has allowed us to position PDS Biotech as a potential leader in the field of cancer immunotherapy. The company has 12 Phase 2 clinical trials in progress (with two recently completed) while maintaining a quarterly cash burn of $7 million.
Future Company Goals
Pulse 2.0 (Amit): What are some of the company’s future company goals?
PDS Biotech (Frank): The company’s mission has always been to bring a pipeline of safer, more effective Versamune-based therapies to market in cancers where a clear unmet need exists.
Additional Thoughts
Pulse 2.0 (Amit): Any other topics you would like to discuss?
PDS Biotech (Frank): Head and neck cancer has been described as a silent epidemic. As reported in The Lancet, based on the current preventive vaccination rates in the US and EU, HNSCC incidences will continue to increase steeply into the mid-2030s and stay elevated for another few decades. This increase in incidence is being driven almost exclusively by HPV16. By the mid-2030s, the majority of HNSCC cases in US and EU are projected to be HPV16-driven.
Our immediate goal is to help this growing population of patients by targeting the underlying cause of the cancer to shrink the tumors and extend patient life with a well-tolerated treatment.
