Hello, and welcome to the Virtual Investor Conference Series. On behalf of the Life Science Investor Forum, as well as our co-host, Zach Smallcap Research, we're very pleased you joined us for our next presentation from PDS Biotechnology. Please note you can submit questions for the presenter in the box to the left of the slides. You can also view a company's availability for one-on-one meetings through the Book Meeting tab found on the top toolbar. At this point, I'm very pleased to welcome our next presenter, Frank Bedu-Addo. He's the President and Chief Executive Officer of PDS Biotechnology Corporation, which trades on NASDAQ under the symbol PDSB. Welcome, Frank.
John, thank you very much for the introduction and also for the opportunity to present here today at the Zacks SCR Life Sciences Investor Forum. Next slide, please. Everyone, please be aware of the risk factors associated with PDS Biotechnology and as filed with the SEC. Next slide, please. PDS Biotechnology is a late clinical stage immuno-oncology company developing targeted immunotherapies for cancer. Our lead clinical candidate, Versamune HPV, is a proprietary HPV-16 targeted immunotherapy. The lead indication is recurrent and/or metastatic HPV-16 positive head and neck cancer. This constitutes a $2 billion-$3 billion opportunity in the United States and a $4 billion-$5 billion opportunity in the United States and Europe combined. Now, HPV-16 positive head and neck cancer is on a significant rise, and today, 60%-70% of oral cancers are reported to be HPV-16 positive.
There are currently no FDA-approved drugs for the growing population of HPV-16 positive head and neck cancer, and therefore the treatments are the same across the board, whether or not the patients are HPV-16 positive or negative. Now, our head and neck cancer program has been awarded fast-track designation by the FDA based upon the phase two clinical results, which we'll talk about today. The recently initiated phase three trial is the first-ever registrational trial to be performed in HPV-16 positive, recurrent, and/or metastatic head and neck cancer. FDA fast-track designation, coupled with the ongoing registrational trial, presents strong potential to be first to market, resulting in an opportunity for market leadership. Next slide. Now, here we look at the dramatic rise projected in head and neck cancer incidence over the next 20 or so years.
The increase in incidences of head and neck cancer has been described as a silent epidemic. Here, I show a plot from a 2022 article published in the highly respected Lancet Journal. This article projects a significant increase in head and neck cancer cases, as I mentioned, over the next 20 years or so. What is quite significant is the fact that the projected increase is almost exclusively driven by HPV-16. These incidences take into consideration the current preventive HPV vaccination rates. As I just mentioned, the market potential for Versamune HPV, specifically in recurrent and/or metastatic HPV-16 positive head and neck cancer, is about $2 billion-$3 billion in the United States alone. Next slide, please. Now, let's move on to the limitations of current therapy.
Head and neck cancer is one of the most debilitating cancers, with suicide rates of over three times that of the US general population. Now, this slide highlights the problem that we're seeking to address, specifically the safety and the survival limitations of the current therapies for recurrent and/or metastatic head and neck cancer. Now, as shown here, with any of the three most frequently administered FDA-approved therapies, the median overall survival for these patients is only about 12 months. Now, this means that if a patient is diagnosed with recurrent and/or metastatic head and neck cancer today, on the current therapies, they have a 50/50 chance of living 12 months. That is something to remember as we go along in the presentation: 12 months median overall survival today with the current therapies.
Now, it's also notable, as you can see on the slide on the third column, that even though the EGFR inhibitor plus chemotherapy has a significantly better objective response rate than Keytruda, this did not translate to improved survival. These patients actually had worse survival than the patients on Keytruda. In this population, the objective response rate does not appear to translate to survival. It's also important to note here in the middle column that the addition of chemotherapy to Keytruda provided about one month of additional survival, but more than a fourfold increase in severe adverse events. A significant price to pay for an additional month in survival. This is the state of the art for current therapeutic options in recurrent metastatic head and neck cancer. Next slide. Now, moving on to our study.
In our study, we administer a combination of Versimune HPV and Keytruda. Versimune HPV activates and trains the immune system to recognize, target, and kill cancer cells that are positive for HPV-16. In this trial, the patient receives Keytruda by IV every three weeks until toxicity or death or for up to two years. The patient also receives a total of five subcutaneous injections of Versimune HPV in the upper arm once every three weeks for the first four cycles. The fifth and final dose is received on the 12th cycle. Patients had to be at least 18 years of age, and they had to meet the approved requirements for Keytruda with PD-L1 combined positive score, or CPS, of greater than or equal to one. This study was performed at 31 sites in the United States and Europe. Next slide, please.
Now, this slide shows the demographics of the patients in our study. The majority of the patients, over 90%, were white males with a median age of 64. This is the typical population for recurrent and/or metastatic head and neck cancer. In these patients, Keytruda is shown to perform much better in patients who have a higher PD-L1 expression with the highest CPS status of 20 and above. Do note that in our study, as you can see highlighted, 40% of the patients fall into this category, and 60% of the patients are actually in the lower responding group. Also, 80% of the patients had failed or progressed after prior treatment on other therapies. It is important to note that the patients on our trial are skewed towards the typically lower responders to Keytruda. Next slide, please.
Now, moving on to the results of our study, the VERSATILE-002 study. There are three clinical response characteristics that the next generation of cancer therapies should exhibit. The first is tumor shrinkage. Most chemotherapeutic and cytotoxic drugs, as well as the EGFR antibodies, do this quite well. Versimune HPV plus Keytruda, as we can see, also achieves impressive tumor shrinkage, with over 20% of patients experiencing complete or near complete tumor shrinkage, and almost 80% of patients having tumor shrinkage and/or disease stabilization, which is extremely encouraging. The big limitation facing today's therapies for metastatic cancer is disease recurrence or continued spread after treatment. Disease recurrence is very common once therapy is stopped. Keytruda, for example, as I mentioned, has to be given every three weeks for up to two years. However, the hurdle to administering these drugs with such required frequency is toxicity.
That brings us to characteristic number two, which is durability of the response. Once tumor shrinkage or stable disease is achieved, how durable is that response, or how long can that clinical response be maintained? Your ideal cancer therapy should be able to maintain these responses long-term, and that's exactly what we see in our trial when we add Versimune HPV to Keytruda. Next slide, please. You can see here on the slide that if we look at the patients in green, the complete responders, partial response to tumor shrinkage in blue, or stable disease in yellow, the majority of these patients, whatever their clinical response is, appear to have durable responses with time. Therefore, they maintain that clinical response status over an extended duration of time. This occurs even with just the four to five doses of Versimune HPV.
Now, this is partly due to the induction of what we call a memory immune response, which enables the immune system to continue to combat the disease long-term without the need for continuous treatment. This brings us to characteristic number three, which is patient survival. Next slide, please. Here, if you recall, I mentioned at the start that with the standard of care, the median overall survival today is 12 months. In the VERSATILE-002 study, we report, as seen on the slide, a median overall survival of 30 months. If you were a patient on this trial, you had a 50/50 chance of living for 30 months or two and a half years. Next slide, please.
The combination was well tolerated, with only 9% of patients having a grade 3 or grade 3 toxicity and only one patient having a grade 4 toxicity, which occurred one year after completion of Versimune HPV therapy while the patient was still on Keytruda therapy. Versimune HPV appears to be unique in that by administering it in combination with standard of care such as Keytruda, it does not appear to compound toxicity. Keytruda, as we saw earlier, is reported to have a 17% grade 3 and higher serious adverse event rate when administered alone. The VERSATILE-002 clinical trial has demonstrated an encouraging combination of safety and clinical response. Next slide, please. Can we go to the next slide? Thank you. This slide shows the phase three trial design.
This is a controlled study of Versimune HPV plus Keytruda versus Keytruda alone in a two-to-one randomization, meaning that for every two patients who get onto the combination, one will receive Keytruda standard of care alone. This was highly recommended by the key opinion leaders to maximize the number of patients who actually get the combination. The patient size is 351 patients, and the trial has an 85% statistical power to detect a 10-month difference in survival between the two arms. The trial's primary endpoint is designed based upon death events to be for median overall survival as guided by the FDA. Secondary endpoints include objective response rate, disease control rate, duration of response, and progression-free survival.
What I'm going to do is, on the next few slides, I'll briefly discuss corroborating biomarker and clinical results from our phase two IMMUNOSERVE trial and the National Cancer Institute-led trial that support the encouraging results seen with Versimune HPV. On this slide, we see a study that was independently run by MD Anderson Cancer Center, the IMMUNOSERVE study. Here, the investigators studied two critical parameters. First, quantification of the tumor accumulating HPV-16 specific killer T cells. Now, the inability to effectively achieve the induction of adequate numbers of tumor accumulating killer T cells has been a major deficiency of immunotherapy. Here, in this study, we see highly effective accumulation, which are the green bars, of active HPV-16 specific killer CD8 T cells in the tumors over a 24-week period.
Now, secondly, it's well established that what kills the patients isn't usually the primary tumor, but rather the micro metastatic cancer cells that remain and grow aggressively. Now, these tumor cells can be quantified using a technique to measure the DNA of the circulating tumor cells in the blood, what we call the circulating tumor DNA. Here, if you look at the green line here, the study shows that as the T cells accumulate in the tumors, the circulating tumor DNA falls to zero. In the February 2025 issue of Clinical Cancer Research, the MD Anderson investigators report that in the study of Versimune HPV plus standard of care chemoradiotherapy, or CRT, in the next slide, next slide, please. This was a study of Versimune HPV plus chemoradiotherapy versus chemoradiotherapy standard of care alone.
What they report in this publication is that in the HPV-16 positive cancer patients, at three to four months, circulating tumor DNA was not detectable in 100% of the tested HPV-16 positive cancer patients. However, on standard of care CRT alone, ctDNA was detectable in 50% of the patients. Now, importantly, ctDNA was also shown in this study to be a predictive biomarker. What they reported here, look in the second table below, was that in the patients who had no detectable ctDNA, their two-year recurrence-free survival was 93%. However, in patients who had detectable ctDNA, recurrence-free survival dropped significantly down to 30%. The ability of Versimune HPV to clear this HPV-16 positive circulating tumor DNA appears to be largely responsible for the strong clinical responses and patient survival that we're seeing in these phase two clinical trials. Next slide, please.
Now, a third study was also published in the highly respected JAMA Oncology Journal in February of this year by the National Cancer Institute. Now, in the study, they enrolled 37 HPV-16 positive recurrent and/or metastatic cancer patients. They also enrolled 17 patients whose tumors were HPV-16 negative. Now, the difference in clinical responses between the two groups of patients was quite dramatic. As we see here on the slide, when we look at the objective response rate, the HPV-16 positive patients had a 75% response rate versus 0% in the patients whose cancer were not HPV-16 positive. Now, the progression-free survival in the HPV-16 positive cancer patients was 11.3 months. In the combined group of HPV-16 positive and HPV-16 negative patients, the PFS was only 2.9 months.
This study appears to confirm that Versimune HPV may be a highly effective HPV-16 targeted immunotherapy as it was designed to be. With these corroborating results, we are highly optimistic about the registrational trial in HPV-16 positive recurrent and/or metastatic head and neck cancer, and we look forward to reporting the results in the future. Next slide, please. Meanwhile, as we run the phase three study, there are a number of milestones and catalysts that we anticipate over the next three to 18 months. In late Q2 or early Q3 of this year, we anticipate announcing the final results from the VERSATILE-002 study in recurrent and/or metastatic HPV-16 positive head and neck cancer, the exact same patient population that we are studying in our registrational trial. We also expect preliminary results from the neoadjuvant study of Versimune HPV and Keytruda in early stage oral cancer.
In the first half of 2026, we expect readouts from two exciting ongoing studies at the National Cancer Institute with our PDS-0180C investigational immunocytokine in colorectal cancer and gallbladder cancer, as well as a second trial in biochemically recurrent prostate cancer. The latter is a controlled study of PDS-0101 plus Astellas Xtandi versus Xtandi alone. As I mentioned, the next 12-18 months could be quite exciting for the company. Next slide, please. To conclude, I will reiterate the fact that our primary focus today is our VERSATILE-003 registrational trial in HPV-16 positive recurrent and/or metastatic head and neck cancer, the first registrational trial in this rapidly growing population. The data to date strongly supports Versimune HPV as an effective HPV-16 targeted immunotherapy. With the FDA Fast Track designation, we are in strong position for potential market leadership.
Thank you very much for your attention, and I will be pleased to answer any questions at this time. Thank you very much.
Thank you very much, Frank. It seems like we have a couple of questions from the audience submitted here to us. I will just go through a couple of them, Frank. The first question says, "Your results for VERSATILE-003 are very encouraging. Are you talking to Merck about partnering for VERSATILE-003 and receiving drug?"
Thank you, Lars, for the questions. To answer the question you just asked, Merck was part of our joint development committee for the VERSATILE-002 phase two trial, so we do remain engaged with Merck. However, as has been widely reported, Keytruda does come off patents in a couple of years. As many of you may be aware, Merck has not really been anxious to do phase three Keytruda supply deals. For now, we do not anticipate a drug supply deal, and we are proceeding accordingly.
Thanks, Frank. The next question is, "You recently raised $11 million and potentially $22 million. What is your cash burn with the phase three being started, and how are you funding the trial?"
Thanks a lot for this question. That is correct. We raised $11 million recently, and this has provided us with enough capital to get the trial started. We are pleased with the financing in a very challenging environment for biotech companies like PDS, but what we raised is not going to take us through completion of the trial. We plan to raise the necessary capital in a stepwise manner as we make progress with the VERSATILE-003 trial.
Thanks, Frank. There's another question here. Since you've started the trial, how long will it take you to get to your interim data readout?"
The interim data readout timeline is, as some of you may be aware, dependent on the recruitment rates, which also depend on recruitment by the sites and the total number of sites that we have on the trial. We have most of the phase two sites participating. They know our therapy quite well, but there are also several new sites coming online. It will take us a few months to better understand what to expect from the recruitment rates and the timing of events, and we will update the markets as that becomes clearer.
Thanks, Frank. I think we have time for one more question here. The question is, "What are you doing with your triple combination? The data is very impressive." It goes on to ask, "You have a reasonably deep pipeline, and you just raised $11 million to fund your phase three. How do you plan to develop your pipeline?"
Okay. Just to make sure I'm clear on it, what are we doing with the triple combination, and how do we plan to develop the timeline? Yeah. The pipeline. The pipeline. Our current plan with the triple combination is to follow the simplest regulatory strategy, which will also feed into our product lifecycle management strategy. The goal is to get Versimune HPV plus Keytruda, what we're running in our VERSATILE-003 program, get that combination approved, and then add PDS-0180C to the approved combination to develop the second-generation product that may address both checkpoint inhibitor naive as well as checkpoint inhibitor resistant patients.
However, today, our focus is on VERSATILE-003 and getting that dual combination approved. That is what the capital that's been, that's what our capital is being applied to. We have been successful in partnering with the National Cancer Institute and top-tier academic institutions who have been willing to independently progress these trials with our Versimune HPV as well as PDS-0180C. That allows us to utilize our funds for our lead program, which again is the Versimune HPV in recurrent metastatic head and neck cancer, as we have discussed today. You are correct. It is unlikely that we will be able to develop our full pipeline without any partnerships. Getting studies through phase two via academic collaborations and ready for registrational trials provides us with significant non-dilutive benefit and value.
That's really the big picture in terms of working with our partners and non-academic institutions, get through phase two and prepare some of these programs for phase three, where we may be able to bring in some partnerships in the future to get these to the finish line.
Thanks, Frank. I believe that's all we have time for today in terms of questions.