Hey, everyone, and welcome to our next Fireside Chat. Again, my name is James Molloy, biotech and specialty pharmaceutical analyst here at AGP. In this chat, we're talking with another of our coverage companies, PDS Biotechnology, which we have as BioRated with a $4.50 price target. PDS Biotechnology is developing Versamune, their lead T-cell activating technology. It's currently being studied in a phase III VERSATILE-003 trial in HPV-16 positive head and neck cancers. With us today from PDS Biotechnology is CEO Frank Bedu-Addo. Thank you for joining us here today, Frank. Thank you very much for the introduction and for having me participate in AGP's healthcare company showcase. I was hoping we were going to start with a brief overview of PDS Biotechnology for our listeners. I'll be happy to do that. PDS Biotechnology is a New Jersey-based late clinical stage biotech company developing targeted immunotherapies for cancer. Our lead investigational product, Versamune HPV, is currently in a phase III clinical trial for recurrent or metastatic HPV-16 positive head and neck cancer and is being developed to treat various HPV-16 positive cancers. Now, Jim, something that many of our listeners may not know is that because of the rapidly increasing incidence of head and neck cancer, head and neck cancer has been described as a silent epidemic. Some publications even project that by 2030, the incidences will be increasing at a rate of about 30% per year. What's interesting is that it's also reported that these increases in incidence are driven almost exclusively by one specific type of aggressive head and neck cancer, HPV-16 positive head and neck cancer. Right? These are cancers of the head and neck area caused by infection with the most carcinogenic type of HPV, which is called HPV-16. Right? Head and neck cancers that have been traditionally related to alcohol and tobacco consumption. Today, the experts project that by the 2030s, the majority of head and neck cancers in the United States and Europe will be HPV-16 positive. Today, this market represents about a $4 billion-$5 billion opportunity in the United States and Europe for PDS Biotechnology. It has also been published that these patients with advanced HPV-16 positive head and neck cancers may have the worst survival prognosis compared to the HPV-negative head and neck cancers, as well as other head and neck cancers caused by other types of HPV. This registrational trial is the first-ever registrational trial to be performed in HPV-16 positive head and neck cancer. Versamune HPV has been granted fast-track designation by the FDA based on our phase II VERSATILE-002 data. Now, I'm sure a lot of listeners heard about the immunotherapies, the PD-1s, PD-L1s, and all these things. Obviously, everyone knows chemo. How does the immunotherapy like Versamune, how does that have the advantage in targeting cancer, obviously HPV-16 focus? How does that play a role within the treatment paradigm? Should it be approved? Jim, that's an interesting question. To be able to put my response in context, I'll first of all provide some of the limitations of the current approaches to cancer treatment, such as chemotherapy, cytotoxic drugs, and even the EGFR inhibitors. These approaches have been effective in rapidly shrinking tumors. However, they are not as effective in treating the underlying cause of many cancers, nor do they appear to be effective in promoting the long-term and sustained clinical benefit. Therefore, with advanced cancers, the survival times are still short on the current therapeutic approaches. Now, in recurrent metastatic head and neck cancer, specifically, even with the combination of chemotherapy and the EGFR inhibitor, cetuximab, or also known as Erbitux, the median overall survival is only about 10 months, right? Meaning that you have a 50% chance of living for about 10 months on this therapy. Now, how does an immunotherapy such as Versamune HPV differ? I'll say first, let's consider the fact that what typically kills the cancer patient is not the primary tumor, but rather the micro-metastatic cancer cells that spread and grow very aggressively. Now let's assume that we can develop a therapy that trains the immune system to target a specific marker that's present in all these cancer cells and that we can activate and deploy the immune system to invade the body, seek out, infiltrate, and kill these cancer cells, including the micro-metastatic tumors. What I just described is Versamune HPV, and the target markers are called the E6 and E7 proteins of HPV-16, right? Jim, to provide a little bit more color to this question and the answer, in the February issue of Clinical Cancer Research, Dr. Ann Klopp and her team at MD Anderson Cancer Center published a study of Versamune HPV in locally advanced cervical cancer patients. Now, in this study, they measured the quantity of cancer cells, including the micro-metastatic tumors, using a technique that measured what is called the circulating tumor DNA. In one arm of the study, they had patients who received Versamune HPV with the standard of care chemotherapy and radiation. In another arm of the study, they had patients who received only the standard of care chemotherapy and radiation. Among the HPV-16 positive patients who were evaluated in the Versamune HPV arm, there was a 100% elimination of the circulating tumor HPV-16 DNA at three to four months after start of treatment. In the patients who only received the chemotherapy and radiation, there was only a 50% reduction in the circulating tumor DNA. What they also reported was that in the patients who had no detectable circulating tumor DNA, their two-year recurrence-free survival was 92%. However, if there was any detectable circulating tumor DNA, their two-year recurrence-free survival rate dropped drastically to only 30%, right? What I just described is the advantage of an effective T-cell immunotherapy such as Versamune HPV in promoting patient survival. Now, if you look at the EGFR inhibitors, for example, there are several publications reporting much weaker efficacy in HPV-positive head and neck cancer versus HPV-negative head and neck cancer. A key reason for this is because they do not target the underlying HPV integration into the host genome, right? That is where an effective T-cell targeted immunotherapy differs from your standard approach to treating cancer and the potential advantages. You've got some numbers to back it up. The phase II VERSATILE-002 trial that read out mid-last year, it had some excellent median overall survival, what, 30 months versus 12-18 months for historical controls. Could you walk sort of listeners through the 002 data and how that informs the ongoing 003 trial? Yes, so that's a very good question, Jim. With the VERSATILE-002 trial, as you mentioned, we've had some very encouraging survival data. Today, with the historical published results, if you look at the standard of care, which is Keytruda or Keytruda plus chemotherapy, typically the median overall survival ranges between about 12-13 months, which means that if you go on those therapies today, you have approximately a 50% chance of living 12-13 months on average. However, if you went on to the VERSATILE-002 trial, with the median overall survival being 30 months, you had about a 50% chance of living 30 months or more, a significant improvement over what the standard of care is. Today, that's actually the 30-month median overall survival, to the best of our knowledge, is by far the most extensive survival reported in recurrent or metastatic head and neck cancer to date. As we've also discussed in the past, the primary endpoint for our phase III VERSATILE-003 trial is median overall survival. With the maturity of our phase II data to date, it gives us significant encouragement and confidence going into this phase III clinical trial based upon the really durable responses that we have seen in the VERSATILE-002 trial. Also, very important, not even just the survival, which is important here, but also the tolerability of the combination of Versamune HPV with Keytruda or pembrolizumab, and also the tumor shrinkage levels that we have seen. We also reported that over 20% of the patients in the trial had complete or almost complete 90-100% tumor shrinkage. So, again, demonstrating that Versamune HPV appears to be highly effective in generating the right type of killer T-cells in the right quantity to promote a pretty potent anti-tumor immune response. So, very encouraging data moving into our phase III clinical trial. Walk through the 003 trial, PDS0101 with Keytruda, first line, very similar to the phase II trial that had good results. Sort of walk through the key differences and similarities between the two trials, if you would, please. What is the next interim look or next catalyst we should be looking for, please? Yes, so, Jim, those two trials, our VERSATILE-002 phase II trial and our VERSATILE-003 phase III trial, are practically identical, except for the fact that in the phase III trial, we are including a control arm, which in this case would be Keytruda. This trial is designed to have a two-to-one randomization, meaning that for every two patients who enroll and get onto the treatment arm, one patient will be enrolled onto the control arm. In this trial, also, slightly different from the initial, the initial objective response rate was the primary endpoint, whereas survival was a secondary endpoint. In this case, based upon discussions with the FDA, the FDA highly encouraged that we utilize median overall survival as the primary endpoint for the VERSATILE-003 phase III trial. What we have also done with the phase III trial is to build into that trial design two interim data readouts. These would give us the opportunity to have early discussions with the FDA pending what the results turn out to be. As you mentioned, this trial has actually started. We anticipate that there will be some key enrollment and site activation milestones as we go along. Also, for our VERSATILE-002 phase II trial, we will continue to give other milestones as the trial gets to completion, right? We should hopefully have quite a bit of updates on these two trials in the next few months. In just a couple of weeks, you'll have some three abstracts at ASCO. Care to tease a little bit what we'll be seeing there at ASCO? Yes, so I think for ASCO, we are very pleased to have three abstracts accepted. For the first abstract, we'll deal with our VERSATILE-002 phase II trial, as we've said. This trial is a mature trial at this stage, and we'll be providing an update on the survival data for this trial. For the VERSATILE-003 trial, as you mentioned, we will be presenting a trial in progress. As I mentioned, this is the first ever registrational trial to be performed in recurrent metastatic first-line HPV-16 positive head and neck cancer. We will be happy to provide more details on the trial design. For the third poster, Dr. Rautmann at Mayo Clinic will be presenting some exciting data on the neoadjuvant treatment of HPV-16 positive, locally advanced oropharyngeal cancer with Versamune HPV and Versamune HPV plus Keytruda. Some interesting data from Versamune HPV. Beyond the HPV, you've got a MUC1 program with Versamune. Would you care walking our listeners through the PDS0101, ADC, and Versamune combination, please? Jim, are you talking about the MUC1 program? Yeah, MUC1. The MUC1 program, okay. MUC1 combination with the antibody drug conjugate. Yes, I'll be happy to do that. A lot of the early preclinical work on this program was actually done by and at the National Cancer Institute. The National Cancer Institute developed and patented the novel modified, or what we call the agonist peptide sequences of MUC1 that we are using with our Versamune platform. The initial work that was done focused on confirming that these novel MUC1 sequences were highly immunogenic in these cancer patients and that the derived T-cells would recognize, target, and kill human cancer cells in vitro, right, including colon cancer, breast cancer, ovarian cancer, and pancreatic cancer, right? This work was done with those types of cancer cells in an in vitro fashion. This work is published, by the way. These novel sequences were then formulated with our Versamune and demonstrated to promote enhanced MUC1 specific CD8 killer T-cells that targeted and killed MUC1 targets in vivo. That enhanced potency was also demonstrated with the combination of Versamune MUC1 and PDS01ADC. This trial is a typical phase I to II trial design. The details of the trial are not yet public as we are waiting for the timelines from the National Cancer Institute, who will be running this trial under our collaborative research and development agreement with the National Cancer Institute. We anticipate that the trial will be made public on clinicaltrials.gov in due course. The IND was just recently approved, right? That is correct. Is the timing, any word on the timing on the start or anything like that? Is that still to be determined? It's still to be determined. As you know, there's a lot going on within the government agencies at the moment. All those things are currently being worked out to get some clarity on the timing. Anything else on the pipeline you want to touch on as we're getting towards about three minutes to go? I think I'll say we have made some really significant progress over the last 12 months with our Versamune HPV program. We're extremely excited about the potential to have the first FDA-approved therapy for HPV-16 positive head and neck cancer. We are also extremely encouraged with the market potential of Versamune HPV, not only in the first target indication, which is recurrent metastatic HPV-16 positive head and neck cancer, a huge potential market opportunity, but for the same product in HPV-16 positive locally advanced head and neck cancer, as well as other indications like cervical cancer, anal cancer, penile, vaginal, vulva cancers, which could eventually lead to over a $10 billion opportunity in the United States and Europe for this product. As we discussed, we look forward to providing an overview of the accepted ASCO abstracts and also to update the markets on our continued progress as we continue to focus our efforts and resources on execution of the VERSATILE-003 program. With that, I would like to thank you again for the opportunity to discuss the potential impact and market and potential market and clinical impact of our program. Thank you very much again. Our pleasure. Thank you, Frank, very much for taking the time out and walking our listeners through this afternoon and for all of you listening as well. This ends our PDS Bee Chat. Please stay tuned for the next Fireside Chat coming up right after this.