PDS Biotechnology Corporation (PDSB) Earnings Call Transcript & Summary

Greetings, and welcome to the PDS Biotech head and neck cancer KOL roundtable. [Operator Instructions] As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Dr. Lauren V. Wood, Chief Medical Officer for PDS Biotech. Dr. Wood, please proceed.

Good morning, everyone, and welcome to PDS Biotech's head and neck cancer KOL roundtable webcast. With me today are Dr. Neil Gross from the University of Texas, MD Anderson Cancer Center; Dr. Katharine Price from the Mayo Clinic Comprehensive Cancer Center; and Dr. Jared Weiss from the UNC Lineberger Cancer Center. I will provide formal introductions in a moment, but before we begin, I would like to caution listeners that comments made during this webcast may include forward-looking statements within the meaning of the federal securities laws, including the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements involve material risks and uncertainties, and the company's actual results may differ materially. For a discussion of these risk factors, please refer to PDS Biotech's SEC filings. Investors, potential investors and other listeners are urged to consider these factors carefully in evaluating the forward-looking statements and are cautioned not to place undue reliance on such forward-looking statements. Please note that the content of this webcast contains time-sensitive information that is accurate only as of the date of the live broadcast, October 26, 2022. Except as required by law, the company undertakes no obligation to revise or update any statement to reflect events or circumstances that take place after the date of this call. It's also important for all attendees to be aware that PDS Biotech is the sponsor of this roundtable and webcast. Each panelist is speaking on behalf of PDS Biotech under the terms of a consulting agreement and all information presented is consistent with FDA guidelines. With me today are a distinguished group of cancer researchers who it is my distinct pleasure to introduce. Again, all of these researchers are consultants for PDS Biotech. Dr. Price has had some challenges connecting with us by video, but she is present for the webcast and is part and will participate by audio. So again, we thank you, Dr. Price for your presence, Dr. Weiss and Dr. Gross. Dr. Neil D. Gross is a dedicated surgeon and scientists with a passion for service, individualized cancer care and cancer research. He completed a head and neck surgery and oncology fellowship at Memorial Sloan Kettering Cancer Center and has since developed an international reputation as a thought leader in head and neck cancer. He has published extensively and has served in many service and leadership roles nationally and internationally. Dr. Gross currently serves as Professor, Director of Clinical Research and Head of the Oropharynx Section in the Department of Head and Neck Surgery at MD Anderson Cancer Center. His clinical and research interest focus on improving functional outcomes using transoral robotic surgery, also known as TORS for HPV-associated oropharyngeal cancer and neoadjuvant approaches to aggressive cutaneous squamous cell carcinomas. Dr. Gross is an expert in the development and execution of surgeon-led clinical trials. Dr. Katharine A.R. Price is a medical oncologist and Associate Professor of Oncology in the Division of Medical Oncology at Mayo Clinic in Rochester, Minnesota. She specializes in the treatment of head and neck cancer and is cochair of the Head and Neck Cancer Disease Group at the Mayo Clinic. A graduate of Harvard University and Mayo Medical School. She completed her internal medicine residency at the Mayo Clinic in Rochester, Minnesota and an oncology fellowship at Memorial Sloan Kettering Cancer Center. She returned to Mayo Clinic Rochester as a head and neck medical oncologist. Her clinical interest include the treatment of head and neck cancer, with a specific focus on HPV-associated cancers and salivary gland cancers. In addition to her work in oncology, she is the diversity and inclusion leader for medical oncology and works with the Mayo Clinic Center for Health Equity to decrease health disparities and increase access to cancer clinical trials for minority and underserved populations. She has a specific interest in promoting education and awareness regarding HPV vaccination and works with local and regional health care providers and community groups in this effort. Finally, Dr. Jared Weiss received his undergraduate degree from Brown University and medical degree from Yale University. He completed his residency at Harvard's Beth Israel Deaconess Medical Center, then a fellowship at the University of Pennsylvania. He is currently a Professor of Medicine at University of North Carolina's Lineberger Comprehensive Cancer Center, where he also serves as the Section Chief of Thoracic and Head and Neck Oncology. Dr. Weiss is proud to volunteer for and serve on the Executive Board of cancerGRACE.org and to advocate with the lung cancer initiative of North Carolina. He has published extensively, including in the New England Journal of Medicine, the Journal of Clinical Oncology and Lancet Oncology. He has frequently presented at international conferences, including the presidential session of the European Society of Medical Oncology also known as ESMO and plenary session of the multidisciplinary head and neck cancer symposium. Dr. Weiss' clinical practice is focused on lung cancer and head and neck cancer and his laboratory research is focused on personalized and adaptive immunotherapy to treat cancer. I want to say to all of our esteemed panelists. Thank you, and welcome for joining us. Over the next hour, we will be discussing the future of treatment of head and neck cancer. Dr. Gross will open our session by reviewing current treatment approaches for head and neck cancer. Dr. Price will then follow and expand on the unmet medical needs in this space. Dr. Weiss will close our session by reviewing the data to date for PDS Biotech's lead asset, PDS0101 in the treatment of head and neck cancer. At the end of the presentation, we will open the discussion for a question-and-answer session. If you have a question and would like to submit a question during the presentation, please feel free to type it into the OpenText field at the bottom of your screen and hit the submit button. For those of you who would like to ask a question directly, please hit star 1 on your keypad. With that, I would now like to turn the meeting over to Dr. Neil Gross. Neil?

Hi, Lauren. Thank you so much for having me part of the meeting, and it's a pleasure to be able to share my experience with head and neck cancer and to be part of this really esteemed roundtable discussion. So I've been tasked with just giving an overview of head and neck cancer. And I think the first -- to highlight is that when we talk about head and neck cancer, it's very different than other cancers. So it is a region -- it's based on a region of the body rather than a specific organ. So as opposed to lung cancer or bladder cancer, head and neck cancer typically encompasses a large number of cancer subsites. But for the most part, I'll be focusing on cancers that affect the throat or oropharynx. And the reason for this is because we see a significant number of these cases. This really dominates the patient population in our clinics currently, and it's a ripe opportunity for targeting new treatments. So head and neck squamous cell carcinoma has been around for a long time. This is the 14th (sic) [ 18th ] President of the United States, Ulysses Grant, who died of tonsil cancer. But what's important to know is that he was a chain smoker and an alcoholic and really, I think, highlights the face of head and neck cancer in years past. But what we've noted over the last several decades is a real profound epidemiologic shift. So patients who present now still present with a neck mass, a painless neck mass, that's the most common presenting symptom but different than patients from years before, the etiology for their cancer is HPV-associated disease. So they may have cancers that look very, very similar on scans and on presentation but the cause instead of tobacco-related is from HPV. And this is really the dominant patient population that we see in our clinics today. So what's important to know about HPV-associated head and neck cancer and what we're speaking of here is specifically cancers that affect the tonsils and the base of tongue, you can have HPV-associated squamous cell carcinoma in sites outside of those areas, but those are relatively uncommon. What you can see in the slide here in panel A, that the number of oropharynx cancer cases is rising steadily and has done so for a number of years, but will continue to do so for the decades to come. And it's predominantly in men but we're seeing a similar increase in women, although the absolute numbers are fewer. This highlights that it's predominantly a disease affecting white men and women and what's really very pronounced in the slide here, as you can see the almost asymptotic curves in the increase in incidents in patients whose age is greater than 45. So patients who are in the younger categories are much more likely to be vaccinated. And in the future, the incidence of disease is blunted for that group. But for the next several decades, we'll expect to see a significant increase in the number of these cases coming through our clinic on top of the high number that we already see. And for this reason, HPV-associated head and neck cancer now makes the top 10 list of new -- estimated new cases in the U.S. every year. The database includes or lumps together oral cavity and oral pharynx cancer cases, but you can see here that is approximately 4% of the new cases diagnosed in the U.S. currently in this. This will just continue to kind of jump up this list over the years to come as we see more and more of these oropharynx cancer cases in our clinics. I want to highlight that there's a different biology or different pace of disease for patients who have HPV-associated oropharynx cancer compared to those with tobacco-associated cancers. And this, I think, slide highlights that quite well. So this is a patient who noticed something didn't feel right in the back of his throat and took a selfie of his tonsils, you can see here on the left. That in and of itself highlights the difference in the patient population. They tend to be younger and more technologically savvy. But you can see this was in 2013, and then a year later, he noticed that it was a little bigger and took another picture and continue taking pictures throughout 2014 and then 2015, and then ultimately came to see me in June of 2015. I mean his tonsil was considerably larger. What's very different about this disease then compared to tobacco-related diseases is the protracted course of disease. So tobacco-related cancers progress in a matter of just a few months, whereas HPV-associated cancers can sometimes progress more slowly. And that is important to know that the behavior can be different for this group of patients. So what are the current treatments for head and neck cancer and specifically HPV-associated cancers of the tonsil and basically tonsil? Well, it's really the same treatments that we have for all head and neck cancers. Most patients present with disease that will require multimodality treatment. So the most common treatment approach for patients with this disease is concurrent radiation and chemotherapy of about 7 weeks. There are some patients who are amenable to an upfront surgical approach, and these patients may be dispositioned to adjuvant radiation or adjuvant chemoradiation depending on pathology. And then a smaller number of patients are started with upfront chemotherapy. Those are typically patients who have very aggressive disease. I want to highlight the toxicity of treatment. This is an article that was published by a patient who -- he was a photographer working for the New York Times and published his own experience going through treatment for head and neck cancer. The title of his article was "A Hell I Wasn't Ready For" and I think the article and the pictures that were included really highlight the experience of the patients. It is an intensive treatment. This is a radiation mask that is used for patients. You can see an oral splint. And this is the picture of the patient. Here, you can see radiation damage to the skin, and you can see him holding his head with a cotton ball in his ear because of pain. And I highlight this because patients really have significant morbidity going through treatment. It is intense. And it is not just intense during treatment, but the long-term survivorship issues can also be dramatic. And for this reason, rates of depression and suicide are the highest among patients with head and neck cancer compared to other solid tumors. The reason for this is these cancers are kind of right in the middle of everything. That's where patients eat, it's where they speak, it's where they swallow, it's where they're seen. So the impact on quality of life cannot be underestimated for this disease. Now a lot is said about the improved prognosis of patients who have HPV-associated carcinoma. So we know that these patients fare better than patients who have tobacco-related cancers. And because of the significant impact on quality of life, most of the treatment strategies involve some form of de-escalation. These are two studies that were published back to back in 2019 comparing radiation and cisplatin, which is the current standard of care to radiation and cetuximab. Both were negative trials. These studies showed decreased survival in patients treated with the de-escalated strategy. There is also a study with de-escalated strategies using surgery study out of Mayo that I'm sure Dr. Price is very familiar with, the multicenter trial led through the ECOG 3311 and [indiscernible] trial using reduced dose radiation. So all of the current trial strategies for this disease are some form of de-escalation, although there are risks of undertreatment with de-escalation. So putting this together, we know that there is a baseline instance of disease that is increasing and will continue to increase for decades to come. With that, we'll see treatment failures that can be as high as 20% of patients or higher will fail treatment. And because this disease is more protracted, meaning patients can live longer with recurrent or metastatic disease, that will increase the absolute number of patients that we see. And finally, with the increasing use of circulating tumor DNA, we'll be finding minimal residual disease. We'll be detecting recurrence of disease, metastatic disease earlier in the future than we are now. And you put these together, and it's a large number of patients that we'll see in the future who have recurrent metastatic HPV-associated head and neck cancer. And because of this, I think it's a real opportunity for intervention. And it's one of the reasons I'm excited to be part of this group. So with that, I think I'll turn it over to you again, Dr. Wood and to Dr. Price for her portion of the presentation.

Thank you so much, Dr. Gross. I appreciate it greatly. Katharine, since you are only on audio connection, you just let me know when to advance your slides and will continue.

Thank you, Dr. Wood and Dr. Gross. Good morning, everyone. It is really a great pleasure to be here this morning and to be part of this discussion. So over the next few minutes, I'll build on some of the themes that were introduced by Dr. Gross and speak to some of the unmet medical needs in head and neck cancer. That's certainly a big topic I will be focusing on, HPV cancers and those patients in the recurrent and metastatic setting. Next slide. Many people on this call are aware of the data that was published in 2010 in the New England Journal of Medicine. We have known since that time, very clearly that survival outcomes for patients with HPV head and neck cancer is significantly improved over those with HPV negative head and neck cancer. This is certainly a very good thing but it's, I think, presents a false picture where sometimes we can be overly optimistic and reassure patients that this is a curable cancer. When the reality is, over time, about 20% to 30% of patients depending on their disease characteristics, develop a recurrence after curative intent treatment. And patients are at risk for different reasons. There's a lot of data and work that has gone into identifying patients who would be at increased risk. Some of the notable risk factors include increased number of involved cervical lymph nodes or advanced T stage tumors. And so I think it's important to balance the improved survival with the reality that we will see increasing numbers of patients with recurrent disease. And we know that unlike head and neck cancer related to alcohol and tobacco, most of the recurrences that we see in this population will be distant metastatic disease. And in the current state of affairs, that is for most patients considered incurable. Next slide. The standard first-line treatment for patients with recurrent and metastatic head and neck cancer is chemoimmunotherapy with pembrolizumab or pembrolizumab alone if the CPS score is greater than or equal to 1. And this was established by the KEYNOTE-048 trial that was published in 2019. What we can see on the left side of the slide are the survival curves for the trial. The control arm in this trial was cetuximab in chemotherapy, which was the standard of care at the time. You can appreciate the survival curves in blue, which are the immunotherapy containing arms compared with red, which is cetuximab and appreciate that over time, the magnitude of benefit of the immunotherapy treatment increases. And this is something that I can say as a clinician, we see play out in practice where patients who are on immunotherapy who stay on immunotherapy stay on immunotherapy. So it is a situation where the benefit can happen, but sometimes that takes time to develop. On the right side of the slide are the survival outcomes for the immunotherapy arm. And we're seeing median overall survivals ranging from 11 to close to 15 months. I think statistics are always difficult and data are always difficult to conceptualize, I think how that translates into practice. And certainly, these numbers are improvement over what the standard of care had been. But one of the things that's important to note, and I talk to patients about this a lot in clinic is that no matter what time -- amount of time somebody has to live there will be a period of time that, that is not usable or good time where they will be too sick, unable to do all of the things that they like to do. So when we look at survival numbers, I think we have to also realize that all of that is not quality time. Certainly, immunotherapy has contributed tremendously and is a major advance, but we need to do better for these patients. Also important to note that KEYNOTE-048 was a trial that enrolled both HPV positive and negative patients. But long-term analyses that I've looked at this have not shown a clear significant difference in response between patients with the HPV positive and negative cancer. So we can still use the data for our HPV population, certainly as a starting point. Next slide. One of the endpoints in KEYNOTE-048 was progression-free survival, which was not met. The survival curves for progression free survival are seen here. And you can appreciate that the curves overlap or sometimes even favor the nonimmunotherapy arm in the early months of treatment. So why is this? We all know that immunotherapy can take some time to work; that chemotherapy can work quite quickly, but the effect wears off relatively quickly as well. From a clinical standpoint, this means that many patients will progress before immunotherapy can work or before there can be a measurable benefit in the immunotherapy and then patients are needing to go on to other treatments, which almost certainly are more toxic than what the immunotherapy would be. Sometimes we can treat through a progression early on if there's low-volume disease and patients are asymptomatic, but often, unfortunately, it means a boarding the effort and moving on to more toxic therapy. From a research standpoint, I think this represents a tremendous opportunity to find therapies that will work quicker, immunotherapy-based treatment ideally that will start working quickly to overcome this initial drop off and initial early progression. Next slide. Dr. Gross spoke to this a little bit already that the HPV population is a bit different from the historic head and neck cancer population. These patients tend to be younger, are mostly male and carry with them fewer comorbidities and fewer medical issues from long-term exposure to tobacco and alcohol. So again, trying to take all of this data and what does it mean in real life. Well, it means that these are patients like anybody on this call and patients that are often in the middle of careers and raising families really in the prime of their life, and we truly need to find better treatments that will allow patients to continue living their lives to the fullest. Next slide. One of the really remarkable things about immunotherapy is how well patients tolerate it. And when we think about in medical oncology, how modern antiemetics have really revolutionized the experience with cytotoxic chemotherapy, immunotherapy has truly changed the face of treatment for countless patients. And because of this, we're able to treat patients that previously, we may have referred directly to hospice care if they weren't candidates for chemotherapy. The data shown here is from CheckMate 141. This was one of the early studies that showed benefit of immunotherapy. This was in a platinum-refractory population, so in the second-line setting, where patients were randomized to nivolumab or standard of -- standard therapy investigator's choice chemotherapy. Nivolumab did improve survival outcomes. But if you focus on the bottom part of the graph, the investigators had been measuring quality of life throughout the treatment. And patients who received immunotherapy did not have a significant decline in their functioning and quality of life, whereas those who received chemotherapy did have a quality of life decline. And I really cannot underscore the importance of this and that we should really be building our therapies with this in mind. Next slide. So if we take all of this together, looking at unmet needs in the recurrent metastatic population, well, of course, curative treatments would be fantastic. We're not there yet. That should be the ultimate goal. And hopefully, as our science continues to improve and our immunotherapy improves that perhaps we will be able to cure some patients even in the face of metastatic disease. But in the absence of that goal, we need improved therapies that will allow patients to live longer with their disease while maintaining a good quality of life. And we need better immunotherapy-based treatment that will work quickly in the early months to delay need for cytotoxic chemotherapy, and all of our treatments should be working to preserve quality of life and function well on treatment. Dr. Gross made a very good point, which is worth highlighting again, which is these patients have been through a lot already, typically as part of their definitive initial treatment. And so they're coming to the treatment in the recurrent metastatic setting, also carrying forward a burden of side effects and complications related to their original treatment. So it is critically important to not add to that burden. Next slide. We can't forget that prevention is the best cure of all and that we have a vaccine against this disease. This won't help patients in the immediate years. But as the head and neck community, we should all be good stewards and advocates for HPV vaccination. Next slide. And with that, I will turn it back to Dr. Wood and Dr. Weiss.

Thank you so very much, Dr. Price. We'll now conclude with Dr. Jared Weiss, who will discuss PDS0101 for the potential treatment of HPV16 positive head and neck cancer. Jared?

So we have a question that's actually the perfect transition between these talks. And so if no one objects, I'm going to actually take that first. The question is, how would you describe the overall physician community's ability to keep patients on immunotherapy, both early on and long term, specifically early on, is the community well versed to knowing to keep patients on versus early pseudoprogression and beyond, et cetera? The quick answer is that in contrast to melanoma, pseudoprogression in head and neck cancer is rather rare. The overwhelming majority of perceived perception is real and not pseudo. And this comes to the shape of the PFS curves that Dr. Price shared with you. The inspiration that pembrolizumab and other PD-1 agents offered us is that possibility of durable control. For very good human reasons, we're all obsessed with the tail of the curve. It's what patients want. It's what we want for them. The inconvenient truth about those PFS curves is the left side of them, which is a cliff. Dr. Price showed you PFS and OS data, which is exactly the right thing to do when you have mature data like KEYNOTE-048. But in reflecting on that study, and in transitioning to the data that I'll share with you, the data I'm going to share with you is very early stage data. And so when you're looking at small numbers of patients early on in the experience, you start with response rate. And I want to set the stage in answering this question and setting the stage for what I'll share with you to just remind you what the response rates in KEYNOTE-048 were. So for patients that were CPS positive but low, which is to say 1% to 19%, you had a response rate of 15% in KEYNOTE-048. And for the more enriched population of the CPS that was at least 20%, that rose to 23%, right? So that's our baseline that we are attempting to improve upon. But please do not take that as an intended cross-trial comparison, but this is how you power nonrandomized studies against the null hypothesis from historic baseline. So here's the study design. This is a Phase II study with two patient groups and done in two stages. So the first cohort to open, and therefore, the data I have earlier and to share with you, are from the checkpoint inhibitor naive patients. This is a two-stage design, and I will have data for you on the first stage. Subsequently, an additional cohort was open for checkpoint inhibitory -- checkpoint inhibitor refractory patients, an important question, but for one which we do not yet have available data. As mentioned earlier, the response rate was the primary endpoint of each of these groups. And here's the core outcome that we were able to share at ASCO. I'm sure you're all familiar, but just to make sure this is a waterfall plot. So any growth per RECIST system is expressed as a vertical bar above 0 and any diminution in cancer is demonstrated as a vertical bar going down. And we define response as a 30% reduction in disease by the RECIST system. This waterfall is color coded with the complete responses shown in green, a very rare event with standard of care and partial responses shown in blue. We have an overall response rate of 41% here and a disease control rate of 76.5%. For transparency, I have indicated for you with asterisks, the CPS levels. Those shown with asterisks are the CPS high patients. All other patients are CPS 1 to 19. And I will avoid making cross-trial comparisons that are inappropriate, both because of the small early nature of this data and because Lauren would cut me off for regulatory reasons, but you have full transparency to slice and dice this however you want. And in my opinion, there's no way that you can slice and dice it and make this anything other than a good early signal. And this does -- consistent with that, opinion, this does formally move us on to the second stage. This is favorable data and what toxicity cost, right? Any time you add anything to the standard of care, that's the critical question to ask. And I think to anyone with a clinical background, this profile is rather similar. Most patients treated with pembro alone or pembro plus something else in studies will have some kind of treatment emergent adverse event in the majority of patients. But I note for you here that the majority are low grade. And in my opinion, as a clinician, this is a profile I'm rather familiar with. What I would love to show you but cannot show you for a very happy reason, are curves. This is a small patient number relatively early on. But for a very happy reason, we haven't had enough events. The PFS and OS curves are immature. For transparency, please find what is available at right, which is to say that the absolute PFS rate, so the proportion of patients who have not had a PFS event, either progression of cancer or death over the entirety of the curve is 55.2%, which is why I can't show you a median. It hasn't yet gone under 50%. At a median of 9 months, 89% of patients are alive. And if you look at the totality, 87.2% are alive. Of course, once that data is appropriately mature and medians exist it will be presented somewhere and put into the public realm. And so I would summarize these results as a clinician in saying very early results. very small numbers, but a very, very good and very promising start worthy of additional study. And with that, I will pass this over to Dr. Wood for closing remarks and panel discussion.

Thank you so much Dr. Weiss and again, to doctors Price and Dr. Gross. As we kick off our panel discussion, I'd like to ask a couple of questions before we take additional questions from our listeners.

It really is important, I think, for our listeners to understand how knowing that a head and neck cancer is associated with HPV. How that HPV status affects your initial treatment approach for those patients as well as your approaches in the recurrent metastatic setting. So if you all could just speak and weigh in regarding that, I think that would be very informative.

So I'm hearing crickets, so I'll start. If you look at guidelines, there is absolutely no role in standard of care for HPV to play into therapeutic [indiscernible]. I think we all expect that to evolve over time. There is now a rather, I think, high-quality and growing body of evidence that in the definitive setting, we can reduce the intensity of treatment for our curative stage patients with the idea of rendering our patients not only cured but preserving their quality of life for the rest of their life. There are many efforts that have been done and many efforts that are ongoing. In my opinion, the most successful thus far is the decreased escalation of radiotherapy dose that's gone a bit better than the attempt to de-escalate chemotherapy. And I think it's like, what's the party game where you try to get under the bar without hitting over? I think the question is how low can you go? My institution and others have shown that it's quite safe to go down to 60 gray. Our colleagues in New York with the use of hypoxia imaging have made some provocative data that I hope is confirmed that maybe you can go as low as 30 gray. And this makes a really big difference because certainly, between 50 and 70 gray, you have a steep relationship between dose and toxicity. And of course, it's at least linear below that. So getting this dose lower and lower is of high value. Others have done valuable work looking at the combination of induction therapy and transoral surgeries. But in the definitive setting, nothing per standard of care, but a rapid evolution towards decreasing the intensity of therapy, particularly radiation therapy. And I would note, I'm not a surgeon, but looking at the outcomes of transoral surgeries, transoral robotic, transoral laser, while we don't use the words de-escalation in reference to these surgeries, they are -- they have blood loss on par with a blood draw. They have no -- at least the primary reception has no cosmetic deficit, recovery is rapid. These are, in a way, de-escalated surgery. So as a consumer of radiation and surgery, I don't do either. I'm rather impressed with both my surgical colleagues and my radiation colleagues in how they've de-escalated therapy to the benefit of our patients and that's going to rapidly become standard of care. Now in the metastatic setting, there's heterogeneity in study results looking at PD-1 efficacy by HPV, and you can get a brawl going at a conference on this subject. I'll leave it aside that level of detail for the moment and say that HPV does not play into standard of care decision-making when deciding on the use of our standard agents like pembrolizumab, cetuximab, cytotoxic, chemotherapy. Where I think it gets fascinating is exactly what we're here to discuss. So I spend a lot of my research time working on personalized immunotherapy approaches, in particular, bioinformatics-driven vaccines, right? And that's very hard work. With HPV, we have a luxury that does not exist in HPV-negative cancers, which is that we have preserved neoantigens. And our hope is of all of us at company and investigators who are putting efforts in this is that we can exploit these biologic differences of HPV, these preserved neoantigens with a vaccine approach and improve outcomes in that way. That's what we're all here to talk about. But just to summarize and make sure I actually answered your question because in academia, we're not allowed to do that directly, but that failed joke aside, in standard of care, HPV does not play into decision-making. It plays into counseling for prognosis. It plays into expectations. But for strict standard of care, it does not change what we are doing yet.

Thank you so much, Dr. Weiss. We've got a question that actually is a great segue that relates to standard of care that I wanted to pose to the panel. And that is when we think about differentiating activity of new interventions, what is the best measure of efficacy that we would like to see to differentiate newer treatments against the standard of care? What kind of outcomes would be differentiating over the standard of care in this disease?

So this is Katharine. I can start with this one. I mean on a very high level, of course, we're looking for prolonging life and prolonging good quality of life and keeping people from getting into trouble from cancer-related side effects and morbidity. But I think it's more difficult than that. And I -- and Dr. Weiss highlighted the response rates of immunotherapy. And I think one of the things we struggle as -- in clinical practice is there's a discrepancy between the response rates that we're measuring and then what can happen with survival with some of these patients. And so it's really -- response rate is a very poor marker and we need to be thinking of other ways to move away from it. Certainly, any studies need to have robust quality of life and function endpoints as well as survival. But I think what's really exciting is some of the emerging technologies with circulating DNA and adding a level of sophistication to our ability to know for something happening underneath the surface. And also to be able to know, okay, are these patients that we can keep treating through because there is something happening. So it's really exciting. I think the technology that will allow us to look at efficacy while patients are on treatment. And one of the other areas that's just critically important is trying to be able to better predict who are the patients that will have those amazing benefits from immunotherapy. Right now, that's one of the biggest clinical challenges.

Yes. As an immunologist, I am very excited about the opportunity to investigate biomarkers that may reflect antitumor activity as patients are receiving treatment. Dr. Gross, do you have any comments on outcomes that you would like to see in terms of differentiating improvements over the standard of care?

Yes. No. Great discussion. I really appreciate the points made by Doctors Price and Weiss. The -- I think progression-free survival is still really, really important. Ultimately, the FDA and patients, everybody wants survival part of it. But I guess I would echo what was said before in that a biomarker of response is really going to be helpful. And I think there's a lot of enthusiasm for circulating tumor DNA and how that could be incorporated and it's particularly useful for HPV-associated disease. And so I think that that's very promising. But it does I think we'll be seeing -- these patients are really, really savvy. They are aware of -- many of these patients, they're not the type of patients who come in and say, okay, doc, whatever you want. They oftentimes come in aware of options for treatment. And as I've kind of highlighted before, we'll be seeing more and more patients who have minimal disease, minimal detectable disease. And there -- so there's going to be a lot of anxiety and concern around that and being able to offer treatments that don't hurt patients but do offer probe survival is going to be key.

Great. Well, we've actually been able to address one of the other questions that have been posed and that is actually the adoption of circulating tumor DNA in the head and neck cancer space. I don't know if any of our panelists might want to just quickly comment on recent presentations at the Multidisciplinary Head and Neck Cancer symposium that was held earlier this year regarding the use of ctDNA in terms of detection before tumor recurrence on imaging studies, if anybody would like to comment on that briefly?

I can comment on that a little bit. I think it's -- the ability of the circulating DNA to detect potential recurrence and the positive predictive values are very exciting. So I think that is potentially a very useful tool, and there's both ongoing studies looking at this and also, we're seeing this increasingly used in clinical practice through commercially available tools. I think the challenge that we're in is what do you do with the information, and we're going to find ourselves increasingly in a situation similar to ovarian cancer where you have a blood marker that says that there's probably something developing and imaging studies that are negative and that creates a whole other opportunity for research investigations looking at what do you do with those patients. Is early introduction of immunotherapy or other therapies potentially able to basically stave off a recurrence. So I think it's really exciting this technology. It's going to create a lot of questions. We don't quite know what to do with all that data just yet. But I think that's a good position to be in.

Our operator have that individual be able to pose their question to the panel and then we can also return to some additional questions that are still on the chat box. Thank you.

Certainly. Our next question is coming from Kalpit Patel from B. Riley.

Great presentation. Dr. Price mentioned that the outcomes for HPV-associated head and neck cancer patients are significantly improved compared to those patients with HPV negative disease. I guess we know that PDS0101 is being advanced in HPV-positive patients only. So what would be the bar in the KOL's opinion for those patients? I know we can make comparisons to the KEYNOTE-048 trial, but how much better do you responses and maybe PFS -- data fair for the HPV positive patients or HPV negative patients?

So I would -- I'm not going to dive too deeply into cross-trial comparisons because to really answer your question, you're in the supplementary appendix of the KEYNOTE-048 presentation. But I would say if you so dive, you see no hint of HPV-positive patients doing better in the metastatic setting with pembro. If anything, they're doing worse. And so I would say that the benchmarks that I shared with you are conservative ones for this population.

Any other comments? We have time for just a couple of more questions. There has been a question about how much interest there has been in the community, specifically physicians, but maybe Doctors Weiss and Dr. Price can comment on not only physician interest, but in patient interest in terms of PDS0101 and the investigational combination that we're pursuing in VERSATILE-002.

I can say there's a ton of -- sorry, go ahead, Jared.

Go ahead.

I can say there's a ton of interest. This is not a hard sell, just like patients have really sought out in the curative setting looking for de-escalation strategies because they want something different. Patients come and they want a strategy that is not chemotherapy-based. So it has been extremely well received and as I said, an easy sell for patients.

Absolutely.

Wonderful. Okay. There is a question that has just come in. There is published data that supports the concept that PD-L1 expression correlates with greater benefit with KEYTRUDA, and that indeed was highlighted by Dr. Weiss' presentation, as well as Dr. Price's presentation. What is the panelists outlook on the role PDS0101 could have in patients who may be less responsive to KEYTRUDA or CPI refractory patients? That will be our final question.

So I view agents like KEYTRUDA, not as the match that lights the fire of immunotherapy, but rather as gasoline that amplifies an existing immune response. So if you have a small fire and you pour gasoline on it, you get a bonfire rather quickly. If you have an unlit log and you pour gasoline on it, all you get is a wet smelly log. And I think that, that's what happens often with immunotherapy. I would point you to a neoadjuvant lung paper by New England Journal by Patrick Forde and Jamie Chaft to justify the idea of PD-1 as amplifier of immune response. And so I think that as a researcher and as a clinician seeing an unmet need, I'm highly interested in mechanisms that can light that fire. And I think this is a very exciting idea on how to do so.

Great. Do any of our panelists have any other comments in addition to Dr. Weiss?

I mean I would just add that it's clear that a combination therapy is needed. And everybody is sort of that's the goal is what can be added to what is already an improvement, but an incremental improvement in outcome of these patients. But there's a lot more room for improvement. And as Dr. Price mentioned, there is a strong appetite for something better than what we're doing now.

Wonderful. Do you have any concluding remarks, Dr. Price?

Yes. The one thing I would say, I agree with everything that's been said and the future is going to lie in combination therapies. And I think the complexity of the immune system is both its allure and the challenge. I think for me, I'd love to also see incorporation of strategies including drug therapy and how can we use other strategies to augment drug therapy. I'm thinking specifically about diet and the activity and other things that we know impact the immune system as well. And so I think there's space in this for looking at it really holistically and maximizing what we can do with our drug really light that fire under the immune system, but also really harnessing all of the tools that could be out there. I think that's really compelling.

Well, I'm going to conclude our program for today. But once again, I would like to thank our very esteemed panelists for their insights today. PDS Biotech is committed to advancing the study of PDS0101 in head and neck cancer to ensure that we can provide this access to this potentially more effective and safer treatment option to physicians and patients as quickly as possible. An audio recording of today's session will be available on the PDS Biotech website for 90 days. You can access that recording at www.pdsbiotech.com. Again, thank you very much to all of our panelists and to all of our participants for your interest and participation in today's session. Thank you very much.

Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.