PDS Biotechnology Corp. Aktie

Good morning, everyone, and welcome to the PDS Biotechnology Virtual KOL event. [Operator Instructions] As a reminder, this [Technical Difficulty] and a replay will be made available on the PDS Biotech website following the conclusion of the event. I'd now like to turn the call over to Frank Bedu-Addo, Chief Executive Officer at PDS Biotechnology. Please go ahead, Frank.

Thank you, Tara. Good morning, and welcome to all attending PDS Biotechnology's key opinion leader event this morning. I'm Frank Bedu-Addo [Tarasi], Chief Executive Officer of PDS Biotechnology. I would also like to offer a warm welcome to Dr. Jonathan Hernandez, who is Chief of the Surgical Oncology Section at the National Cancer Institute and who will be presenting some of the excellent work he has done with his patients and the compelling clinical research that he and his team continue to perform in metastatic colorectal cancer.

Before I start, I will quickly walk through today's agenda. Next slide, please. I will provide a quick introduction to PDS0301, which will be the subject of discussion today. Dr. Kirk Shepard, PDS Biotechnology's Chief Medical Officer, will then address the state of affairs in the treatment of metastatic colorectal cancer, and then he will hand over to Dr. Hernandez, who will discuss his ongoing Phase II study of PDS0301, a second-line and third-line treatment of metastatic colorectal cancer with liver metastasis.

The event will conclude with a summary and question-and-answer session. Please be aware of the company's forward-looking statements and ensure that you are fully aware of the risk factors associated with the company as filed with the SEC.

Next slide, please. Next slide. So let's begin with the introduction to our proprietary immunocytokine, PDS0301. PDS0301 is an antibody conjugated interleukin-12 or IL-12. IL-12 is a broadly studied and naturally occurring immunological protein or cytokine that is well documented to be a potent activator of our T cells and natural killer cells.

IL-12 is also documented to have the ability to promote an effective antitumor immune response. So why then has IL-12 not been successfully commercialized as an anticancer therapy? There are a couple of important reasons. First, IL-12 produces significant inflammatory toxicity when in the circulating blood, therefore necessitating a low dose.

It also has very low presence in the tumors. Now due to these 2 factors, recombinant IL-12, therefore, has a very narrow therapeutic window, which may differ from patient to patient, and these effects have prevented its successful development.

Next slide, please. Now PDS0301 is designed to overcome the specific limitations of IL-12. So with PDS0301, 2 molecules of IL-12 are fused to the antibody called NHS76. This antibody binds to free DNA that is released by dying or damaged cells in the body, which we will find predominantly within the tumors. This construct, therefore, delivers IL-12 into the patient's tumors. And importantly, the binding holds it within the tumor for an extended period of time, as I will show you in the next slide.

Now remember, I also said IL-12 is fused to the antibody. This is a unique but very important feature of PDS0301. So unlike traditional antibody drug conjugates, this fusion is clipping-resistant and, therefore, does not allow for any free or unconjugated IL-12 to exist in the body.

The key takeaway here is that PDS0301 drives IL-12 into the tumors and retains it within the tumors for a prolonged period. In addition, very importantly, any agent that promotes tumor damage or tumor cell death will create ample binding sites for PDS0301, therefore, delivering it even more efficiently into the patient's tumor.

Next slide, please. So here on this slide, we see pictures from a published study that show the unique characteristics of PDS0301. So in this preclinical study, both PDS0301 and traditional recombinant IL-12 had a fluorescent tag attached to them to allow trafficking and quantification of IL-12 in the tumors.

We see the color scale on the right on the right-hand side of the slide, providing a quantitative estimate of the IL-12 in the tumors with time. Now we see that with PDS0301, within 24 hours, there's already a high concentration of PDS0301 in the tumor as we can see by the bright red orange fluorescence in the tumor.

By 48 hours, the fluorescence intensity in the tumor has increased even further with PDS0301. Now notably, recombinant IL-12 levels never get that high and PDS0301 remains present in decent quantities even after 72 hours. So now with this study, the key takeaway is this unique feature, high concentrations of IL-12 in the tumor and the sustained high concentrations within the tumor over a few days.

This sustained presence in this case, provided superior ability to change the tumor's biology or immunology to enable a more effective immune attack on the tumor by the T cells and the natural killer cells.

Next slide, please. So let's quickly review here how we use tumor damage with PDS0301 to promote an antitumor response in the study that we are about to discuss. So chemotherapy, starting with the green and chemotherapy is administered to enhance the initial tumor damage. PDS0301 is then administered by simple subcutaneous injection, just like taking a flu shot.

Next, PDS0301 then targets the tumor and binds to the free DNA/histone complexes within the tumor. IL-12 generates significant local inflammation within the tumor and inhibits immune suppressive cells such as myeloid-derived suppressor cells and regulatory T cells, which are well documented to block or suppress the antitumor immune response, right? So this ability to inhibit the immune suppressive cells within the tumor is an important feature of PDS0301. It also causes T cells and natural killer cells to infiltrate into the tumor where the IL-12 then activates and expands these immune cells.

Now these activated and potent T cells then cause tumor death and expose further binding sites for additional doses of PDS0301. This process continues as tumor shrinkage and patient survival continue.

Next slide, please. So here, we see a slide from a published preclinical study of M38 colon cancer that shows this effect I described very clearly. So in this study, docetaxel is used to induce the tumor damage and to create the binding sites for PDS0301. The bar chart on the left shows high necrosis induced with docetaxel administration and higher necrosis when combined with PDS0301.

Now the tumor regression plot on the right-hand side shows that administration of docetaxel on its own does not induce any tumor shrinkage. You see this from the red line. Recombinant IL-12 does not induce any tumor shrinkage either, as you can see from the gray line.

Now when docetaxel is combined with recombinant IL-12, there is again no antitumor effect as we see with the green line as IL-12 is not designed to recognize the tumor damage. However, when docetaxel is then administered or combined with PDS0301, as we can see from the purple line, all of a sudden, it drives the IL-12 into the tumors and potent antitumor activity is seen.

And as you can see here, actually, PDS0301 is even shown to have some antitumor effect in this model even as a monotherapy, as we can see from the blue line.

Next slide, please. So with this introduction to PDS0301, you may understand why we are so excited about the potential of this investigational therapy to significantly advance the treatment of several solid tumors. We have seen promising results in HPV16-related cancers, in prostate cancer and also in colorectal cancer.

Importantly, as seen on the right, the National Cancer Institute has exposed PDS0301 to almost 400 patients, and it has been well tolerated without the high toxicities traditionally seen with IL-12, which is again, very promising for its advancement. With that said, I will hand over to Kirk.

Thank you, Frank. First slide. So let's look at our lead indication now as far as our project with PDS0301 and the challenges and facts about metastatic colorectal cancer. Colorectal cancer ranks third in incidence. That's 10% of all cancer cases and second in cancer mortality worldwide. That's about 1.9 million new cases and 900,000 deaths in 2022.

And for some unknown reason, the incidence under age 50 is rising in many countries and is now the #1 leading cause of cancer deaths in adults under 50, which is why successful treatment of colorectal cancer beyond localized tumors, that is beyond surgery, is now a large unmet need.

The second point -- about 95% of the metastatic tumors are pMMR and MSS. This is a common description of a molecular biomarker classification used to describe how colorectal cancer tumor handles DNA repair. Our target population will be pMMR or proficient mismatch repair, also referred to as MSS, microsatellite stable, in advanced third-line metastatic colorectal cancer.

This is the most common molecular subtype of colorectal cancer and represents 95% of colorectal cancer, and it does not respond to immunotherapy. Only 5% of colorectal cancers are dMMR, that's deficient mismatch repair or MSI-H microsatellite instable. And these do respond to PD-1 blockade such as pembrolizumab.

The third point, when compared to patients without liver metastasis, the presence of liver metastasis in colorectal cancer is a main driver of morbidity and mortality in these patients. And liver metastasis will occur in approximately 50% of patients with metastatic colorectal cancer.

The fourth point, objective response rates decline with successive treatment lines. Here, you see the 3 columns, first line, second line and third line, and you see that it dramatically decreases as you go through the lines with 53% to 65% in first line, second line, 11% to 20% and then third line, 1% to 6%. So these values illustrate trial benchmarks, not pooled estimates and aren't meant to be direct comparisons above the therapy, but still give you an idea as far as where the treatment is with this disease.

Slide 12. So here, you see a few controlled trials in metastatic colorectal cancer that in third and fourth line. And even though cross-trial comparisons are descriptive, they're not head-to-head comparisons and populations will vary as far as the prior therapy and eligibility, you can see the mean ORR or the objective response rate and the median overall survival are not very encouraging.

The mean ORR in the experimental arms is about 2.5% and the median overall survival is under a year at 7.9 months. Therefore, again, the successful treatment of third-line metastatic colorectal cancer is a large unmet need. And PDS Biotech is fortunate to have an esteemed partner from the NCI to work with us with this challenge.

Next slide. It is now my pleasure to introduce Dr. Jonathan M. Hernandez, Investigator and Chief of Surgical Oncology Section at the NCI and Center for Cancer Research. Dr. Hernandez graduated from medical school with honors from the University of Florida and completed general surgery training at the University of South Florida.

During his residency, Dr. Hernandez spent 2 years at the Moffitt Cancer Center and Research Institute, studying molecular diagnostics for liver metastasis. Following residency, Dr. Hernandez finished a fellowship training in both surgery and oncology and liver and pancreatic surgery at Memorial Sloan Kettering Cancer Center.

The Hernandez lab studies now at the NCI studies hepatic metastasis and has been the home to 20 surgical residents since its establishment at the NIH in 2016. Dr. Hernandez has authored over 175 peer-reviewed publications and contributed book chapters and numerous authoritative surgical texts.

It's now our privilege to have Dr. Hernandez speak to us on the use of hepatic artery infusion to treat liver metastasis and the effect and impact of PDS0301 on clinical outcomes. Welcome, Dr. Hernandez.

Thanks so much, Kirk. I appreciate that kind introduction. Next slide, please. I just need to say that I'm here in my official capacity as an NIH employee. I am not being paid. I'm not here particularly back any sort of company. I'm here really to share my data.

My sole sort of purpose in all of this is really to move a field forward. And so I'm going to speak about what we've done and the results we've seen so far.

Next slide, please. Okay. So I think it's probably necessary to understand what hepatic artery infusion pump therapy is. It is a way really to get a lot of chemotherapy into the liver. There's only one drug we currently use. That drug is an antimetabolite called floxuridine. The reason this sort of strategy works is because there are 2 different blood flows into the liver. There's the arterial flow, which is derived from the hepatic artery, and there's the portal venous blood flow, which comes from your intestine.

So most of the liver is actually, as it happens, kept alive by the portal venous blood flow. But when the liver has a bunch of tumors in it, it's actually kept alive. Those tumors are fed by the artery. So we're able to take advantage of this difference and put this special catheter into that artery to basically upload chemotherapy straight to these liver tumors.

And so this strategy is not new. It's been around for some time. Again, it uses one drug. And the reason that one drug has sort of remained the sort of cornerstone or backbone of the therapy is because it never leaves the liver. It's got a very high first pass effect. So the patients don't really know when they're getting drug or sort of saline.

And so -- and we're able to give 400x the amount of drug through this pump that we could ever give a person systemically. And so the concept is we're able to give huge mega doses of chemotherapy straight into the liver, and we're able to induce very large responses. What does that do for the patient?

Next slide, please. Before we get to the clinical data surrounding what it does, I want to show you a little bit about what this is. It's about the size of a hockey puck. It works. This pump has 2 sort of mechanisms. I'll draw your attention to the right side. This is -- so it works based on there's gas in the pump and at body temperature, that freon gas expands, pushing medicine slowly and continuously into that hepatic artery.

So the advantage of this sort of system is that you're able to give medicine continuously over a 2-week period of time. That's sort of hard to do in oncology. You basically have to have an oral drug where you have to bring someone in the hospital for 2 weeks at a time that we really don't do that anymore. But this allows us to do this in sort of an outpatient setting.

Next slide. Okay. So what does this sort of strategy putting a lot of chemotherapy into the liver? What does this get us? So the data is really quite older. It's from 2006, Dr. Nancy Kemeny before she retired at Sloan Kettering. So this was a randomized study comparing things that we don't do anymore.

So we don't give hepatic artery infusion pump alone, and we don't use systemic 5-FU alone. So both of these are sort of not really used in the way they are now. But when we compare those 2, what we saw was a very large objective response rate, which I told you expected because we're giving a huge amount of chemotherapy into that liver.

It got us about 4 months of improved overall survival, and this was statistically significant. And for patients with liver metastases, this was, at that time, very good. Now what's changed? We've gotten a lot more systemic drugs. So we've gotten the ability to do a lot more systemically. We really haven't moved hepatic artery infusion pump therapy forward.

Next slide, which brings us to what's happening today. Well, you should be aware that there is a randomized prospective study comparing hepatic artery infusion pump therapy, that pump with that one drug added to modern chemotherapy compared to modern chemotherapy alone in the second line. This is an ECOG study. It's a large randomized study. They want 400 patients.

Friends of mine are running the study. There's been slightly over 100 patients randomized to date, but sort of this is the sort of what's going on nationally with that hepatic artery infusion pump.

Next slide, please. So I sort of said, how should we position this tool? This is a big question for the field. Clearly, we're able to induce these very large responses. I don't think anybody would ever argue that. I think the questions are, does this make people live longer? And if so, how should we position it? Should we put it with first-line chemotherapy?

My feeling is it's probably going to be really hard to get oncologists to insert this into the first line where you get very big responses just with chemotherapy alone. Should we put it in the second line? Clearly, I just showed you that's being evaluated nationally.

My position at the NIH really mandates that I sort of try and do something different, not just position a tool in a different sort of line of therapy. And so the IL-12 drug became very attractive to me because I thought we could utilize the advantages of this pump, which is to induce large amounts of necrosis, giving huge dose of chemotherapy, and we could bring that IL-12 into the tumor microenvironment, potentially changing things.

Next slide. And so our hypothesis was that massive necrosis associated with the hepatic artery infusion pump and delivery of, again, 400x the amount of floxuridine than we could ever give a person systemically will expose those DNA/histone complexes, allow PDS0301 to be delivered into those tumors. Modulating that tumor microenvironment. This is a very suppressive tumor microenvironment, I should say. You think about it, we sort of eat all this -- all the food, all the external environment sort of comes into your GI tract, gets into that portal circulation, gets into that liver.

So your liver can't start acting crazy every time it sees something different. And so that -- there has to be some immunosuppressive environment in order for things to be normal. So the liver is very immunosuppressive. And that allows tumors to grow very well there, unfortunately. And so what we think is that by bringing that IL-12, we could shift the whole sort of immune sort of tolerance and really try and kill tumors, get the immune system to kill tumors. So that was the hypothesis moving forward.

Next slide. And so what I'm going to show you now is some data about 2 studies that -- both of which I ran and I treated every patient on the study. It was all done with our study team. The first was the hepatic artery infusion pump therapy alone patients.

So we ran a trial similar to that going through that I showed you before, where patients were getting this therapy in second or third line. And we did this to establish a program. So this was a number of years ago, but these were sequentially run studies. I should tell you, they are not randomized. So this is not randomized data. It's important that you understand that.

And so when I'm showing you on the left column here, where it says HAIP therapy, there are 20 patients enrolled. And the other -- the other -- the PDS0301 is when we basically took the exact same protocol. We added [PDS0183]. Again, not randomized, but they were run sequentially.

This is some of the data there. Important to show you, and this is -- so we published this with 9 patients. We've now accrued all of the patients on the study. And so what I'm showing you here is the first 9 patients, but a lot of the patients have received oxaliplatin and irinotecan. When we got to the full 22 cohort, most of the patients had already seen irinotecan as well. So this is a very heavily pretreated population of patients.

Next slide. And then so one of the important things is when you're adding a new therapy that's never been done before, you need to understand what toxicity you could be imparting to the patients enrolling on the study. This was very important to us, particularly for one reason. I didn't tell you this before, but that hepatic artery is really important because it is the only blood supply to the bile ducts in the liver, the plumbing system, if you will.

We're very cautious not to damage the plumbing system. And so one worry I had in going forward was would we actually increase damage to the plumbing system, to those bile ducts in the liver. It turned out it's not true. It's actually super well tolerated. The only thing we saw that was significant was some diarrhea, which was, I'll tell you, manageable.

Next slide. So this is how the trial works. This is how it looks. So this is the liver. These patients had these tumors all over the liver. I would take a biopsy at the time I was placing that special pump to deliver floxuridine. Patients would then begin cycle 1 where they had floxuridine and dexamethasone. I'm not going to go into why dexamethasone is used, but basically, it's protective of the plumbing system.

At the end of that time period, these 2 drugs would be taken out. The PDS0301 would be administered subcutaneously, and the patients would get heparinized saline for 2 weeks. And then at the end of cycle 1, they would take -- we would get a biopsy to try and understand what we were doing to that tumor microenvironment.

This slide is a bit older. These cohorts are -- and I'm not going to talk about -- I'm going to focus on the colorectal cohort. Clearly, we've done the 22. We're almost done with the follow-up time. We instituted these other cohorts because of the results we were seeing with the metastatic colorectal cohort. I won't speak about them. These numbers are not accurate, but they are presently accruing.

In cycle 2, the patients get the same sort of thing, but we add in the systemic therapy. Why do we do that? That's done because that's sort of the way this is done as a standard. Whenever anybody does this hepatic artery infusion pump therapy, they do it in a standard way. So we wanted to really mirror really what everybody else does.

So we took what other people are doing. We added PDS01 or PDS0301, and that's sort of what we did. I'm not going to talk about this, but only to say that we didn't compromise, the addition of the study drug did not compromise the amount of floxuridine we're able to give people. That was really important to me because we knew floxuridine really worked, at least inducing that tumor necrosis.

And so if we were compromising on the amount of drug we were giving that we knew had advantages, and that would be problematic. But that was not true. We actually didn't change that at all.

Next slide. And so I think it's important to see what you get. And so this is when we did the original cohort of 20 patients. And the next slide I'm going to show you after this is 22 patients, which is all of the patients accrued to the PDS0301 addition study. But when we ran this study initially, here's what we got. We got what most people show, which is at 3 months, you get great responses. Again, a heavily pretreated population of patients, you're able to induce that tumor necrosis.

The only problem is it doesn't last super long. For some patients, it lasts a long time, but most patients begin to progress and that starts as early as 6 months.

Next slide. But the big difference here is when we added in PDS0301, we saw pretty similar things at 3 months, to be honest with you, I really didn't see any differences at 3 months. But what we started to see at 6 months is patients were not progressing. This is extremely important because this basically says that the responses we were getting were more durable when we added in PDS0301, suggesting we were able to activate the immune system. This is being worked out. I'm not exactly sure why we were getting these better responses yet. I have obviously some ideas about this, but this is ongoing work.

Next slide, please. And so this is -- I apologize for this being slightly blurry. This is the survival data that's already published. It looks very promising, I will say, but we do have updated data. It doesn't look terribly different. This is going to look really -- this is going to look good.

I think next slide, the question for us is why. What we've been able to do so far is looking in people's peripheral blood, we've been able to show natural killer cell signaling. We've been able to show, really crucially, it's really important that you activate both innate and adaptive portions of the immune system that give you durability of response.

When we did this -- I won't go into great detail about how this was done, but this is basically looking at a number of -- a large number of cytokines and immune cells peripherally, not in the tumor, but peripherally, and we've been able to show when you put these sort of analytes through pathway analysis, importantly, we see communication with both innate and adaptive immune cells, which is important.

Next slide. We are actively looking at the tumor tissue biopsies. We have some early data, but we're involved in a large spatial transcriptomics profiling of what exactly we've been able to achieve and why we're seeing these better results. And I think this slide summarizes what -- how I think about this.

So first, we're -- I think we're likely changing the tumor immune microenvironment, although I need to put data behind that. But I think preliminarily, that's what we're seeing. New cells are being brought into that tumor immune microenvironment. I think critically, when you think about this hepatic artery infusion pump, what it does differently than surgery or ablation is it doesn't just address what one can see.

It addresses all of the cells that are probably spread in that liver that we cannot yet see. And I think we're hitting those cells with drugs, and I think we're probably getting antibody to those places. That is my feeling about why this works so well. I'm not sure about that yet. That's my feeling. The other thing we did see is patients didn't progress as much outside of the liver as well. I think that peripheral immunity part is that I showed you earlier is probably really important.

This is all very exciting for us. We're trying to sort through the exact mechanism about what we are seeing and why we're seeing better results. But I think that's what we are seeing. We are seeing better results. And I think that -- at this point, I'll -- that's about the data that I plan to share with you today. Thanks for your time.

Thank you very much, Dr. Hernandez. And I would again like to thank Dr. Hernandez and his team for the excellent and promising work done in these metastatic colorectal cancer patients who participated in the trial. Again, as you mentioned, very encouraging with the durability.

We're also excited about the translational work you're doing to really understand what types of immune cells are infiltrating into the tumor with PDS0301 that's leading to the durability of these responses. So that will be very, very interesting work as that becomes available.

It's also clear that HAIP is rapidly coming to the forefront in the treatment of colorectal cancer with liver metastasis. As you mentioned, Dr. Hernandez, this is demonstrated with a large ECOG trial currently ongoing at some of the top centers in the country such as Mayo Clinic, Sloan Kettering and so forth.

So the other thing here that's very interesting, I think the audience will appreciate that is how clear it is the elegant approach with the HAIP hepatic artery infusion pump to generating significant tumor damage within the liver that allows PDS0301 to target and bind within the liver, therefore, driving the immune response into the tumors as we saw very clearly in the preclinical models.

This appears to translate really well to the human results, and it will be very exciting, as I mentioned, to really understand the immunology and the types of cells that are infiltrating the tumor. I especially also very highly encouraged by the durability and longevity of the responses seen with PDS0301, where the responses continue to get deeper and deeper with time, right?

We go from no complete responses at 3 months to 3 complete responders at 6 months and the tumor shrinkage continues to get deeper and deeper, which is really encouraging as we develop these therapies to treat these patients with these very difficult-to-treat cancers.

So very encouraging data to date and it's really going to inform how we design our Phase III human clinical trial coming up. Very importantly, the data you presented also correlates with the data presented by the National Cancer Institute at the SITC Conference in December -- in November, rather, suggesting that PDS0301 drives a conversion of T cells to stem-like memory T cells that have the immune memory to continue to drive tumor cell death. So that translational work is all appears to be coming together really nicely, which is very encouraging for the program.

Next slide, please. So colorectal cancer, as Kirk mentioned, unfortunately, has become the leading cause of cancer-related death in young adults and continues to be actually a severe and rapidly growing unmet medical need.

Next slide, please. So PDS0301 presents a unique opportunity for monotherapy and combination strategies across tumor types where we can use treatment-induced tumor damage as an anchor for our antibody fused IL-12. We thank the National Cancer Institute for all the very important clinical research being done with PDS0301 in multiple cancers and the very encouraging results already reported in HPV16 positive cancers, including anal cancer, cervical cancer, head and neck, vaginal and vulvar cancers and also the work being done in prostate cancer and colorectal cancers.

The data in all these studies, which have been progressing over the last 3 years at the National Cancer Institute is beginning to mature. We expect to be able to present these maturing results over the next 6 to 18 months. These results thus far have been highly encouraging, and we look forward to progressing some of these studies into pivotal Phase III studies in due course.

Thank you very much all again, and we will now move to the question-and-answer session. Thank you very much.

[Operator Instructions] So our first question comes from Joe Pantginis at H.C. Wainwright.

Everybody. Can you hear me?

Yes.

Okay. Great. I have a few questions more specific to the study and moving forward. But first, I'd like to ask Dr. Hernandez, if you don't will, if you will. You have some in-process work that's going on here. So I just wanted to ask a little bit of hand waving, if you will. So first, in the current study, you include dexamethasone.

So I'm just curious, any impact you see there from a devil's advocate standpoint regarding immune suppression from dexamethasone, number one. And then number two, you made a comment that there seems to be reduced progression outside of the liver. So I'm just curious as to you and the company's thoughts with regard to the impact of an abscopal immune effect.

Yes. I think excellent question about the dexamethasone. So it is standard that dexamethasone is included in the pump. When you put in floxuridine and that was really based off, I would say, okay data from Nancy Kemeny. I think the year was about -- I don't remember, it's been a long time. But that has become the standard of care.

And so I agree with you that there are some concerns that you would be putting an immunosuppressant into the liver. However, when you do that, when you do it with the floxuridine, that drug's half-life is not that long. And so by the time you give the PDS0301, you have this 2-week window of time where you don't have any dexamethasone.

Do you see any residual effects? I don't know. My feeling is I can't really answer it because we didn't do it in both ways. It's always sort of done this way. I will tell you anecdotally that I will add dexamethasone at sometimes later in that second 2 weeks. Ostensibly, I don't see any differences. I think this works no matter what. Does that really make sense? I don't know.

It seems like it probably would be counterproductive, but I have not observed that. I think it's probably okay to do it as we did. I think I would be a little nervous to take out the dexamethasone because, again, if you damage those -- the plumbing, the biliary tree at all, that creates huge issues for people.

And you must be cognizant that if you do that, you're never going to get any more therapy, not only this or any other, I mean, it creates huge issues. So I think you have to be -- I think erring on the side of protecting the biliary tree is important. My feeling is this works the way we did it. I don't know why. I think it's -- I think your point is well taken, but it seems to be okay.

No, fantastic. I appreciate that. So then maybe looking forward and maybe for all of you and talking about the logistics of the upcoming study. Dr. Hernandez, as you mentioned, obviously, with the much more systemic use of drugs that HAIP maybe hasn't moved forward as much. So just curious, in these patients with HAIP being a great delivery mechanism, how confident are you in the company that you can get adequate sites and patient access now? And then secondly, how does this impact your projections for the time to run the study?

Yes. I think it's a good question. I think I showed that slide with the ongoing phase in the second-line setting. So this is people who only first-line. So obviously, competing with that trial would be problematic. That trial is accruing slowly. The reasons for that trial accruing slowly probably are the fact that they don't allow any crossover and people are being randomized to no surgery, no pump.

Patients generally don't like that. However, when you move this further down the line, I think -- so that takes us away from competing with that trial ongoing. I think if you talk to most oncologists, if you ask me, once you get past oxaliplatin and irinotecan, the options are really not good. No one is really happy about any of those third-line options. It's just -- they just don't work very well. And so I actually think the buy-in will be substantially high once you go past the 2 efficacious lines.

There's always this can you get oncologists to send you these things? Can we do this in a way where the oncologists are agreeable. There's a bit of a fight in the second line. The response rates aren't great with irinotecan up to 20%. But if you look at the data critically, what you'll see is there's some durability to that.

But once you -- again, once you go past that, I really think you're in this no one's happy with this. No one likes giving any of those third-line drugs because they just don't work very well. So I actually think the bar is not going to -- it's the way we've designed this and the way this worked out, it just so happens that a lot of the patients I saw with the PDS0301 had already seen irinotecan and oxaliplatin, which probably tells you a lot there. But I think the way this worked out is I think people will be on board with this because you don't have another good option. So I actually think this is not going to be that big of a deal to accrue.

And I'll add to that, Dr. Hernandez and Joe. And you talked about the extrahepatic responses. So important to remember that IL-12, PDS0301 is given by a subcutaneous injection, and it binds to necrotic sites. And chemotherapy, as Dr. Hernandez mentioned, is also being -- in addition to the HAIP pump, systemic chemotherapy is also being given.

So it's creating those -- it's creating the tumor damage even in those extrahepatic metastatic sites. And so we're getting the IL-12 going not only into the liver, but also to those other extrahepatic metastasis also, right? And so Dr. Hernandez reported in his publication with a minimum follow-up of 13.1 months, the extrahepatic PFS had not yet been reached, which again, is very encouraging to show that not only is it working in the liver, it's also working in those extrahepatic metastasis sites, right? So this was, again, very encouraging, consistent with what we've seen with the other studies. And then coming to the clinical side, I think from what Dr. Hernandez said, which is very important in the way we are looking at this, most of the patients in our study were third line, but it's very important to also recognize the benefit of having this large ECOG study going on in the country.

Because now these sites are being primed to working with HAIP. They're already trained to work with the HAIP. It's well accepted at all these sites that have been -- where the trial is being run. And since that is focused on second line and we are looking at third line, these sites will essentially be generating the population that we need for our study.

So on the bright side, again, it's been broadly -- becoming broadly accepted to treat this kind of cancer liver metastasis, but also the fact that it's becoming more accepted in all these sites actually participating in the clinical trial makes it very important for us as we look where to go and how we get these patients. And again, basically, as the second line these patients going to third line, these sites will ultimately potentially be generating the population that we need to go into our study. So again, look, we think it's -- the timing is right to actually progress rapidly to get the studies going.

That's actually very helpful. I appreciate that. So the study is actually looking to add fuel as patients to the study and could potentially reduce enrollment time lines? Or is that...

Exactly. Exactly.

One more quick question about logistics per se. I guess, is there anything you can comment regarding the cost of the study because it seems pretty focused with regard to the potential powering here. It doesn't seem like it's going to be a massive study. And then number two, manufacturing needs around the asset.

Kirk, do you want to take the clinical study?

Yes, sure. No, it's a great question, Joe. I mean we're fortunate we had communications with the FDA earlier this year about the study itself. And as you said, there's a huge difference as far as the treatment arms. So I don't want to talk about the exact numbers now or the statistics, but we're very encouraged by the fact because of these large targets and the differences between systemic chemotherapy and then adding in the hepatic artery infusion therapy, this will not be a huge study. So we hope to get this started by around the first quarter of 2027.

And also with the logistics, all the drug is -- the Phase III drug is ready and available and ready to go.

Our next question comes from Mayank Mamtani of B. Riley.

I appreciate the level of detail here. I was trying to contextualize, Frank, your docetaxel plus 301 preclinical data with obviously a very impressive HAIP plus 301 data that Dr. Hernandez has shown here. Could you help us understand, obviously, the chemo regimens, systemic chemo are different as they are used in the different settings that Dr. Hernandez pointed to. Like how -- could you explore combinations which are not HAIP only in sort of subsequent work? And then obviously, a big regulatory question on contribution of components, dose response also you're moving from -- instead of doing a Phase IIb, now you're doing a Phase III. So how much of those questions you feel are already addressed? And maybe that's a Dr. Hernandez question. And then I have a follow-up.

Mayank, I'll start and then I'll hand that to Dr. Hernandez. So the first part of the question regarding the translation from the preclinical study to the human clinical studies. So I think -- so let's go back to the basic principle. The basic principle is induction of tumor damage due to tumor cell death, right? So any agent that can induce tumor cell death will promote the driving of -- delivery of PDS0301 into the tumor microenvironment, right?

So for example, in this case, it could be radiation. It could be some kind of immunotherapy. In this case, in this specific study, it's colorect -- it's chemotherapy, as Dr. Hernandez described, the different types of chemotherapy that have been administered. Those will essentially induce the initial tumor cell death that allows the PDS0301 to go into the tumors.

You may recall the presentation earlier this year in January at AACR Prostate by Dr. Ravi Madan and his team in metastatic castration-resistant prostate cancer. In that study, they utilized docetaxel as the chemotherapeutic agent to induce tumor cell death and tumor damage very similar to what we showed in the preclinical study.

Now in the preclinical study, very important, the key basic principle of that preclinical study was docetaxel induced huge significant necrosis, right, that was measured. So you could tell that there was necrosis. Now however, when you deliver regular IL-12, there is no impact, right? The regular IL-12 doesn't bind to the tumors. It doesn't drive the IL-12 into the tumors, and you see absolutely no effect. However, once you add PDS0301 that binds to those tumor -- that site of tumor damage with a free DNA. You then see the IL-12 going into the tumors as we showed in those pictures, you can see significant accumulation of the IL-12 in the patient's tumors sustained for a long time, and that drives the immune infiltration into the tumors and subsequent elimination of the cancer.

Now we don't need chemotherapy to do that. You may recall our triple combination trial in HPV16-positive cancers. We gave PDS0101, which is a highly effective HPV16 targeted immunotherapy. That in its own drives tumor damage. We also gave a checkpoint inhibitor. So between those 2, we got significant tumor damage that allowed the IL-12 to also have significant additional impact in driving that antitumor response.

So again, the principle is you don't necessarily need chemotherapy to do this. Any agent that induces that tumor cell death will create the binding site for PDS0301 to go into those tumors and facilitate that cycle of driving that antitumor immune response and tumor shrinkage.

And hopefully, as we saw in Dr. Hernandez' study, survival of the patients. Mike, I hope that answered the first part of your question.

Yes, it did. Thank you, Frank. And yes, if you could comment on the contribution of components, dose response that you saw so far. So...

Kirk mentioned, we have had some initial feedback from the FDA regarding the trial design. We will include a small third arm that will also measure some of the -- to address the contribution of agents that the FDA would always want to see. But as Kirk mentioned, even with that, we don't expect a really large study, but that will be addressed, and that is part of the consideration as Kirk and his team with Dr. Hernandez work on finalizing the trial design. That is definitely being taken into consideration.

Okay. And the primary endpoint and some of the early signals that you would look to discern activity across maybe different doses or different combinations, would that be a response rate or hepatic PFS? Or like how would you kind of discern that activity?

No, I think the team is working on that. But as you can see, objective response rates are very clear at 6 months. You can see very clear differences between the patients who had PDS0301 over 70% objective response rate versus 35% response rate at 6 months. So we believe that it's a very clear potential endpoint that could be utilized. And we also talked a little bit about the PFS, progression-free survival.

And also you saw the Kaplan-Meier curve that Dr. Hernandez showed with a very clear separation when it comes to survival. So there are a number of endpoints that are being considered, some of which may be primary endpoints and others may be secondary endpoints. But based upon all those criteria that have been studied today in the current study, we have a number of potential endpoints that we could be utilize to get to the study decision pretty quickly. Kirk, anything you'd like to add to that?

No. As I mentioned before, especially with objective response rate, the difference is so great as far as our targets that we probably have an interim analysis very soon within the first year. So we're very encouraged by that. But I think all 3 of the parameters you mentioned with PFS also where we saw also prolongation with extrahepatic disease, which was really delight to see with our PDS0301 that it's not just acting in the liver, but it's going to those lesions around the body that is very important. And of course, the FDA always likes to see survival, which we'll also measure. But I think we could have perhaps even accelerated review or some interim analysis before we get to that point.

Got it. And I guess, finally, the dose reductions that we're seeing in the study, Dr. Hernandez, do you think there was -- there's still like room for exposures to improve for IL-12 like locally as you kind of learn the dosing for this in the kind of immune environment? And also, if you could comment, Dr. Hernandez, your plan for the updated survival data and the immune profiling work that you're doing? Is there a medical conference or something planned or publication?

Yes. So the second question is, yes, we have updated data. It looks good. It will be presented at the Annual Meeting of the Society of Surgical Oncology. And so that will be in March. I believe it's in D.C. this year. So it will be sort of a local-ish meeting, but it's obviously a national meeting, so that will be updated.

We will disclose. We will publish the full results, including all the spatial transcriptomic data and all the really cool scientific endpoints probably shortly thereafter, but it will be not long. We have most of the follow-up data we need.

To address your other question, is there room to go up in the PDS0301 dosing? The answer is yes. We -- so the way I designed this was really a path of least resistance with the FDA. So I took -- we knew the maximum tolerated dose based on studies we've run, single-agent studies we'd run, and I went a dose level below that just to sort of placate the FDA about safety.

And then when we added in the systemic drugs, which had not been used, these specific drugs had not been used. I said we would go down a dose lower. So we start -- the first dose is 12 micrograms per kilogram. The second dose drops down to 8, and then we dose reduce based on sort of criteria that we came up with. But could we go up? I mean, we really didn't see a lot of toxicity.

It's certainly possible. I think that will have to be discussed about what we should do. We haven't given it at higher doses. So this seems to work. And so should we just go with what works? Should we go with the dose-finding study? I think these things will be discussed. But yes.

And you'd attribute the diarrhea a third -- I think it was not a big issue, but like what would -- mechanistically, what would you attribute that diarrhea? I think you had a comment on that.

Yes. You'd say the drug probably only goes where you have some sort of damage. And patients who get irinotecan do get some colitis-type symptoms. It's possible that a small subgroup of those people got exacerbated by the drug. I'm just -- I'm not sure. What I can tell you is it seems to be mostly self-limiting. It wasn't terrible.

We just sort of treated it without too much in the way of difficulty. But it can happen. Again, you're looking at where these drugs cause damage. I mean irinotecan does cause some colitis type, some colon stuff. And so could you exacerbate that? I mean maybe that's what we saw. I'm not entirely sure. I would say I'm pretty happy with the safety profile, though.

Yes. Thanks for the questions, Mayank. So we have time for one more question that came over the webcast. So what interaction has the company had to date with the FDA regarding a Phase III trial for PDS0301 for the treatment of advanced colorectal cancer with liver meta test -- metastasis.

Kirk, do you want to take that? You can start and I can add.

Yes. As I mentioned before, we had great communications with them earlier this year regarding the design of the study as well as our planned endpoints. So there was nothing there to really stop us from moving ahead, which we're doing right now. Of course, also, we got to fill in the details of the protocol, but we plan to have that protocol to the FDA submitted by this quarter so that the FDA will be able to continue communications with them. So that's where it lies right now. Frank?

Yes. Nothing to add to that. That summarizes it.

Great. Thank you both. So Frank, I'll turn it back to you for quick closing remarks.

Thank you very much, Tara. Thank you very much again, Dr. Hernandez. Thank you for all the great work you've done with the patients and also with understanding PDS0301 and how it's working. We really appreciate that. And we strongly believe this is going to significantly advance the treatment of these patients with metastatic colorectal cancer and liver metastasis.

I'd also like to thank all the attendees for the time you've taken today to attend this KOL event. Thank you very much to all, and we wish you a great day today. Thanks a lot.

Thank you.

Greetings, and welcome to the PDS Biotech First Quarter 2026 Earnings Conference Call. [Operator Instructions]

It is now my pleasure to introduce your host, [ Dean Schwartz ]. Thank you. You may begin.

Thank you, operator. Good morning, everyone, and welcome to PDS Biotech's First Quarter 2026 Results and Clinical Programs update call. I'm joined on the call today by the following members of the company's management team: Dr. Frank Bedu-Addo, Chief Executive Officer; Dr. Kirk Shepard, Chief Medical Officer; and Lars Boesgaard, Chief Financial Officer.

Dr. Bedu-Addo and Dr. Shepard will provide an overview of the company's recent highlights in its clinical development program, and Mr. Boesgaard will review the financial results for the quarter ended March 31, 2026. Following management's prepared remarks, we will take questions from covering analysts.

As a reminder, during this call, we will be making forward-looking statements, which are subject to various risks and uncertainties that could cause our actual results to differ materially from these statements. Any such statements should be considered in conjunction with cautionary statements in our press releases and risk factors discussed in our filings with the SEC, including our quarterly reports on Form 10-Q and annual report on Form 10-K and cautionary statements made during this call. We assume no obligation to update any of these forward-looking statements or information.

Now I'd like to turn the call over to Dr. Bedu-Addo. Frank?

Thank you, Dean, and good morning, everyone. It's our pleasure to speak with you again and to provide this brief update on our progress in advancing our clinical programs. This past quarter, our major focus was on advancing our clinical programs and we made significant progress.

So I will hand the call over to our Chief Medical Officer, Dr. Kirk Shepard, to provide an update. Kirk?

Thank you, Frank. During our first quarter, we adopted an amendment to our VERSATILE-003 trial, revising the design to incorporate progression-free survival as an interim primary endpoint which we believe has the potential to enable a more efficient path to accelerated approval. We also believe this amendment may shorten the trial's duration and reduce the overall costs, all while retaining overall survival as a basis for full approval in accordance with FDA requirements.

Additionally, this approach may also accelerate the availability of this promising treatment to the rapidly growing population of HPV16-positive patients in dire need of effective treatment. For patients living with HPV16-positive head and neck cancer, a disease with significant and growing unmet need, we believe PDS0101 represents a promising treatment option, and we remain focused on advancing it as efficiently as possible.

PDS0101 in combination with KEYTRUDA or pembrolizumab is the only late-stage investigational head and neck squamous cell carcinoma therapy that requires only 5 doses and also the only subcutaneous therapy. These characteristics of PDS0101, together with the tolerability and survival data reported to date, make PDS0101 a potential compelling option for these patients. Key opinion leaders at institutions such as Mayo Clinic, Dana-Farber and Yale Cancer Institute are involved in our trial.

HPV16-positive cancers are rapidly increasing in the U.S. and EU due to poor uptake of the human papillomavirus vaccine and other factors. Along with the unique pathophysiology of HPV16 cancers and the absence of approved targeted therapies, there is a significant unmet need we believe that PDS0101 is uniquely positioned to address.

Elsewhere in our program, we recently reported promising results from ongoing trials for the treatment of prostate and colorectal cancer with PDS01ADC, our novel investigational Interleukin-12 or IL-12 fused antibody drug conjugate that enhances the proliferation, potency and longevity of T cells in tumor microenvironment. In March, the Journal of Clinical Oncology, JCO, Oncology Advances published clinical and immunological biomarker data from Stage 1 of a Phase II trial, evaluating PDS01ADC in colorectal cancer with liver metastasis. We refer you to these press releases issued this morning.

Earlier in our first quarter, we also announced early results from the NCI-led trial investigating PDS01ADC at the AACR special conference on prostate cancer research. In patients with metastatic castration-resistant prostate cancer, the majority of whom received this therapy as a third-line option, the combination of PDS01ADC and docetaxel demonstrated encouraging results included in our press release this morning.

The results from these 2 trials reinforce the potential of PDS01ADC to enhance the efficacy of existing therapies across multiple solid tumor types. We remain focused on advancing PDS01ADC as a key component of our immuno-oncology pipeline.

I will now hand the call back to Frank.

Thank you, Kirk. Finally, during our first quarter, we also strengthened the intellectual property estate for PDS0101 with new patents granted in the United States and Japan. The new U.S. patent, combined with anticipated biologics exclusivity for PDS0101, extends our market protection into the 2040s. The Japanese patent adds broad composition of matter claims to existing protections across major markets.

Now I will turn it over to Lars for a review of our results for the 2026 first quarter. Lars?

Thanks, Frank, and good morning, everyone. We reported a net loss for the quarter ended March 31, 2026 of approximately $7.3 million or $0.13 per basic and diluted share. That compares to a net loss of $8.5 million or $0.21 per basic and diluted share for the quarter ended March 31, 2025.

Research and development expenses for the first quarter were $3.5 million compared to $5.8 million for the prior year period. Decrease was primarily due to lower clinical and manufacturing costs. General and administrative expenses for the first quarter were $3.1 million compared to $3.3 million for the prior year period. The decrease was primarily due to lower professional fees.

Total operating expenses for the first quarter were $6.5 million compared to $9.1 million for the prior year period. Net interest expense for the first quarter were $0.8 million compared to $0.6 million for the prior year period. The company's cash balance, as of March 31, 2026, was $21.7 million.

And with that, operator, we can open the call to questions from analysts.

[Operator Instructions] Our first question comes from the line of Mayank Mamtani with B. Riley Securities.

I appreciate the updates. On the VERSATILE-003 restart enrollment activity, could you remind us what remains sort of pending there? And is there a consideration also maybe of including subcu KEYTRUDA as a combination partner. And I don't, I think, fully follow what would be the procurement of KEYTRUDA considerations that were there last year versus what do you have today for VERSATILE-003. And then I have a follow-up.

Mayank, thanks a lot for your questions. I'll hand over to Kirk. Kirk, why don't you go ahead?

Thank you, Frank. Yes, regarding the enrollment, now that we have alignment with the FDA that we are going through the procedures of amending the protocol and going back to the sites to begin the study in the near future. We're happy to say that the sites all stayed with us during that period of a pause while we did the amendment and discussed it with the FDA. So we're very happy that we still have the momentum with us.

Regarding the possibilities of using the drug with the subcu pembrolizumab in the future, that's something that would be a possibility, but it's certainly not the target now of our research. Our research is with the pembrolizumab given IV in the usual amount that it has been in the past, but that option would remain open in the future for an entirely subcu regimen.

And then on the landscape external to you within HPV16-positive head and neck, it still seems like a relatively open white space or swim lane. Are there any emerging updates you've seen recently or you're expecting particularly from the EGFR bispecific class that you might be watching for? And then I also noticed the colorectal cancer cohort Stage 2 is now fully enrolled and you obviously published data from the Stage 1 cohort. Maybe just remind us when do you expect to have the next data update for Cohort 2. That would be very helpful.

Mayank, I'll start and I'll hand over to Kirk to add anything to it. But in terms of the HPV16 landscape, you're correct, we know that BioNTech is also in the Phase III trial. But both PDS and BioNTech remain the 2 late-stage studies in the space. So you are correct. There are very few potential opportunities for these patients at this present time.

And in terms of the colorectal cancer, yes, you are correct that we have completed enrollment into that colorectal cancer cohort of that study. And we are anticipating that by the end of the year, we should have some additional data on the full population of patients in the colorectal cancer study. Kirk, anything you want to add to that?

No, I would just refer them again to the article that was just published in our press release, but also we're very encouraged by the Stage 1 of the Phase II trial with the NCI. So we're anxious to move it on to the next trial, a controlled trial, with this therapy.

Our next question comes from the line of Joe Pantginis with H.C. Wainwright.

Great to see the recent amendment. So I wanted to actually dive into that a little bit. If you could talk about maybe a little more color on the benefits here. Obviously, Kirk, you mentioned about acceleration of the clinical time lines. I'm hoping you could hit that a little more with regard to attracting patients, anecdotes you may be getting from doctors to be able to quickly get to those reenrolling quicker.

And then next, sort of the second part of that is from Lars' standpoint, what do you believe the financial impact positively for these changes could be? And obviously, would you then look to put -- keep that money towards the filing path or put it towards a pathway sort of the ADC platform?

Yes. Thank you for your question. Regarding the amendments, as far as the protocol, of course, this all started when we did our final data cut back in September of last year. And we were very encouraged by those results. If anything, though, we needed to consider how long the trial will take because the median overall survival, I think you know, increased from around 30 months out to almost 40 months and the trial would take a long time to complete.

At the same time, too, we saw the robustness of our PFS. So we went to the FDA to discuss the possibility of a co-primary, which we have right now, having the PFS as a co-primary along with the median overall survival, which would be needed for full approval, but we'd have a chance for an accelerated review with the PFS. So we're very happy with that as far as the trial design that has come as a result of the latest results as well as discussions with the FDA.

Joe, this is Lars here. So to answer your question about the potential financial impact, the way we expect the amendment to the protocol to affect really the financial requirements for the trial is one, in terms of time and in terms of time to the interim readout in particular, so that we expect that to reduce cost, both external costs, but also our internal operating expenses simply due to that shorter time period.

And another aspect to bear in mind, Joe, is that we did -- as part of the amendment, we changed the randomization and the ratio from 2:1 to 1:1. And so that also allowed us to essentially lower the number of patients from approximately 350 to approximately 250 patients. So that also in and of itself will drive lower external costs associated with completing the trial.

Helpful detail. And then just a quick follow-up question. So look, things are late stage. They're progressing, right, very quickly. Can you talk about your manufacturing needs for Versamune and the pipeline in the near term and then heading beyond potential early commercialization?

Yes, Joe, I can talk a little bit about that. So as you know, we have a pretty straightforward manufacturing process. So in terms of scale-up and commercialization, some scale-up has been done already by the commercialization. Commercial process is already established. And so what we anticipate doing is one in parallel with the Phase III doing the traditional CMC activities, which involve validation of those processes. There may be some additional scale-up required. But since the process is now fixed and established, we would look at the validation process. We need to do a number of those validation budgets heading into the BLA filing.

So those are really the major CMC activities remaining for the program. But in terms of manufacturing itself, the processes are completed and established. So pretty straightforward path to the BLA filing as pertains to the manufacturing specifically.

We have reached the end of the question-and-answer session. I would like to turn the floor back to Frank Bedu-Addo for closing remarks.

Thank you, operator. Combined with early data from our PDS01ADC program and expanded patent protection extending into the 2040s for PDS0101, we believe we have meaningful opportunities ahead as we continue to execute against our priorities for 2026. We look forward to updating you on our progress, and thank you very much again. Have a great day.

Thank you. This concludes today's conference, and you may disconnect your lines at this time. We thank you for your participation.

Greetings, and welcome to the PDS Biotech Fourth Quarter 2025 Earnings Call. [Operator Instructions] As a reminder, this conference is being recorded.

I would now like to turn the conference over to your host, Mike Moyer with LifeSci Advisors. Thank you. You may begin.

Thank you, operator. Good morning, everyone, and welcome to PDS Biotech's Fourth Quarter 2025 Results and Clinical Programs Update Call. I'm joined on the call today by the following members of the company's management team: Dr. Frank Bedu-Addo, Chief Executive Officer; Dr. Kirk Shepard, Chief Medical Officer; and Lars Boesgaard, Chief Financial Officer. Dr. Bedu-Addo will begin with an overview of the company's recent highlights and its clinical development program. Dr. Shepard Will review the data and rationale behind the amendment the company recently adopted to its Phase III VERSATILE-003 trial, and Mr. Boesgaard will review the financial results for the quarter ended December 31, 2025. Following management's prepared remarks, we will open the call to questions from covering analysts.

As a reminder, during this call, we will be making forward-looking statements, which are subject to various risks and uncertainties that could cause our actual results to differ materially from these statements. Any such statements should be considered in conjunction with cautionary statements in our press releases and risk factors as discussed in our filings with the SEC, including our quarterly reports on Form 10-Q and annual report on Form 10-K and cautionary statements made during this call. We assume no obligation to update any of these forward-looking statements or information.

Now I'd like to turn the call over to Dr. Bedu-Addo. Frank?

Thank you, Mike, and good morning, everyone. It's our pleasure to speak with you again and to provide this brief update on our progress in advancing our clinical programs. The fourth quarter of 2025 capped a period of important progress for PDS Biotech, marked by meaningful advances across our clinical programs, along with financial discipline and expansion of our intellectual property portfolio. Building on the compelling top line data from our VERSATILE-002 Phase II trial, we believe the VERSATILE-003 protocol amendment we've adopted has the potential to create a more efficient path to accelerated approval. shortening the trial's duration, reducing costs and accelerating our time line to regulatory submission, while preserving overall survival as the basis for full approval.

For patients living with HPV16-positive head and neck cancer, a disease with significant and growing unmet need, we believe PDS0101 represents a genuinely promising treatment option, and we remain focused on advancing it as efficiently as possible.

In recent weeks, we also announced early results from the National Cancer Institute-led trial investigating PDS01ADC, our investigational IL-12 tumor-targeted immunocytokine at the American Association for Cancer Research, AACR, Special Conference on Prostate Cancer Research.

In patients with metastatic castration-resistant prostate cancer, the majority of whom had failed at least 2 prior treatments, the combination of PDS01ADC and standard of care docetaxel demonstrated encouraging and durable median progression-free survival or PFS of 9.6 months and a median prostate-specific antigen or PSA decline of 40%. 6 of 16 patients achieved greater than 50% PSA decline. These findings reinforce the potential of PDS01ADC as an immunocytokine that may be used to activate the immune system against multiple solid tumor types. We are encouraged by the progression-free survival and PSA declines observed in this difficult-to-treat population, and we remain focused on advancing PDS01ADC as a key component of our immuno-oncology pipeline.

Since we last spoke with you, we also strengthened the intellectual property estate for PDS0101 with new patents granted in the United States and Japan. The new U.S. patents, combined with anticipated biologics exclusivity for PDS0101 extends our market protection into the 2040s. The Japanese patent adds broad composition of matter claims to existing protections across major markets. To elaborate on progress with our VERSATILE-003 trial, in particular, the data and rationale behind the decision to amend the study protocol, I'll turn the call over to Dr. Kirk Shepard, our Chief Medical Officer. Kirk?

Thanks, Frank, and good morning, everyone. As most of you know, last August, we announced completion of our VERSATILE-002 trial with the final data further supporting the durable clinical benefit of PDS0101 in HPV16-positive recurrent and/or metastatic head and neck cancer. The strength of this final data and of the data in the sub-analysis, we announced in September led to our strategic decision to seek an amendment to our VERSATILE-003 trial to include progression-free survival or PFS as a primary endpoint. As you will recall, the VERSATILE-002 trial evaluated PDS0101 plus KEYTRUDA or pembrolizumab in patients with HPV16-positive head and neck cancer. A total of 53 patients were enrolled. The final data showed median overall survival was 39.3 months in patients with PD-L1 combined positive score or TPS of more than or equal to 1. The lower limit of the 95% confidence interval was 23.9 months and the upper limit was not yet estimable. The VERSATILE-002 trial is the first of patients in recurrent metastatic head and neck cancer population to report a median overall survival of almost 40 months. The PFS and survival results had important implications for the original design of our Phase III VERSATILE-003 trial. In the original trial protocol, as recommended by the FDA, median overall survival was the primary endpoint and progression-free survival was a secondary endpoint. It should be noted that the median overall survival relies on the occurrence of death events and that if a drug works well enough to prevent patient death, it may take a long time to get to the critical data readout. With further increase of the final median overall survival readout from 30 months to 39.3 months in the VERSATILE-002 trial and demonstration of the robustness of the PFS results, we felt we had an opportunity to revise the clinical design to enable a potentially faster readout and opportunity for accelerated approval using PFS as a primary endpoint. To address the potential for an extended trial duration while also abiding with the FDA's recommendation to use median overall survival as a primary endpoint, we approached the FDA to amend the protocol to convert PFS to an earlier interim primary endpoint. Following a productive dialogue with the FDA, we were pleased to announce that following the FDA's standard 30-day wait period since filing, the FDA raised no objections, and we are clear to proceed with the amended protocol. We believe this amendment provides us with an important opportunity to potentially shorten the time to regulatory submission while maintaining median overall survival as the endpoint for full FDA approval. Additionally, we also believe this approach may also accelerate the availability of this promising treatment to the rapidly growing population of HPV16-positive patients in dire need of effective therapy.

For added context, I'll point out that some additional factors that help explain why we and our investigators are so excited about our current path forward. First, PDS0101 is the only subcutaneous injection product currently in late-stage development for recurrent and/or metastatic head and neck squamous cell carcinoma, which is more convenient for the patient. Additionally, PDS0101 in combination with KEYTRUDA is the only late-stage head and neck squamous cell carcinoma therapy that requires only 5 doses. Most therapeutic approaches require over 20 doses. Our approach also presents convenient dosing intervals of 3 weeks and 6 months after the fourth dose. These characteristics of PDS0101, together with the reported tolerability and survival reported to date, make PDS0101 a compelling option for patients. It is, therefore, not surprising that several KOLs and investigators involved in our study and many of the institutions such as the Mayo Clinic, Dana-Farber and Yale Cancer Institute continue to voice their strong support for our approach. HPV16-positive cancers are rapidly increasing in the U.S. and EU due to the poor uptake of the human papillomavirus vaccine and other factors. Along with the unique pathogenesis, physiology of the HPV16-positive cancers and the absence of approved targeted therapies, there is a significant unmet need, we believe that PDS0101 is uniquely positioned to address.

With that, I'll turn the call back over to Frank.

Thank you, Kirk. To Kirk's comments, I would add that as stated by Merck, the subcutaneous version of KEYTRUDA, which was recently approved by the FDA, can be administered by a health care provider in as little as 1 minute. So a potential combination with subcutaneous PDS0101 may shorten administration time and be more convenient for patients. We are excited about the potential of this therapy for head and neck cancer patients. We are, therefore, confident in the potential of our HPV16-tailored approach and the potential of PDS0101 to ultimately provide a well-tolerated treatment without chemotherapy as an option for the growing population of HPV16-positive patients who currently have no effective therapies for this deadly disease and who will soon become the majority of head and neck cancer patients.

Now I will turn it over to Lars for a review of our financial results for the 2025 fiscal year. Lars?

Thanks, Frank, and good morning, everyone. Net loss for the year ended December 31, 2025, was approximately $34.5 million or $0.74 per basic and diluted share, which compares to a net loss of $37.6 million or $1.03 per basic and diluted share for the year ended December 31, 2024.

Research and development expenses for the year ended December 31, 2025, were $19 million compared to $22.6 million for the year ended December 31, 2024. The decrease of $3.6 million was primarily attributable to decreases in manufacturing costs of $2.5 million and personnel costs of $1.8 million. And those decreases were partially offset by an increase in clinical costs of $0.7 million.

General and administrative expenses for the year ended December 31, 2025, were $12.5 million compared to $13.8 million for 2024. The $1.3 million decrease was primarily attributable to a decrease in personnel costs.

Total operating expenses for the year ended December 31, 2025, were $31.5 million compared to $36.3 million for 2024. Net interest expense was $4.1 million for the year ended December 31, 2025, compared to $2.2 million for the year ended December 31, 2024. The change was primarily due to noncash expenses related to extinguishment of debt as well as lower interest income on our cash balances. The company's cash balance as of December 31, 2025, was $26.7 million.

And with that, operator, we can open the call to any questions.

[Operator Instructions] Our first question comes from the line of Joe Pantginis with H.C. Wainwright.

This is Josh on for Joe. So now that you have the amended protocol cleared, could you share what the revised enrollment target is going to look like and how that reduction compares to the original design?

Josh, thanks a lot. I'll hand it over to Kirk to answer your questions.

Yes, certainly. With the revised protocol, and also the increased median survival and robustness of the PFS in 002, we had a meeting with the FDA, which was a very good dialogue. And at that, we were able to shorten the trial to as much as a year as far as getting the final results. And of course, the PFS will be the interim analysis that will first be available most likely in a period of about 1.5 years. That will allow us to get an accelerated review, as you know, to make the drug available to patients. So with the decrease in the end as well as the increased results from the final analysis of the VERSATILE-002, we were able to shorten the duration with this -- a smaller end for the trial.

Great. And so now with this amended protocol, how should we expect R&D to be for 2026? Do you expect that to be a little bit lower than 2025 now with the smaller trial design?

Lars, I'll hand over to you.

Yes. So I think as far as the R&D expenses, we're not providing financial guidance per se. However, of course, once we reinitiate the trial, we do expect cost to pick up. The pickup will be commensurate with the amount of sites that we opened and patient enrollment and so forth. So it's tricky to forecast right now.

Our next question comes from the line of Mayank Mamtani with B. Riley Securities.

Could you touch on your plans to handle patients already enrolled prior to the 003 pause as part of your interim analysis and wonder if you remain blinded to those sort of patients? I assume they're continuing to dose on active drug and placebo.

And then my follow-up question to the prior question was anything you've learned last year from the execution of Phase III that could inform the enrollment pace from here? And sorry if I missed that, did you say what the sample size -- what the new sample size for the Phase III is? And are you willing to share any more details on the 2 -- it looks like you have the 2 PFS interim analysis. So I don't know what they are designed to hit on the first versus the second? If you can give any more details, that would be great.

Thanks, Mayank. Kirk, do you want to start?

Yes. Certainly, I'll [ do ]. There were many questions asked there. Well, we -- first, the patients who were started on the trial, they will all continue their treatment as indicated by the protocol. It was discussed with the FDA, and they said it was up to us as far as whether to include or not include these patients in the trial. They just wanted to be stated ahead of the protocol restart. But these patients will be on the trial as the treatment indicated. They will most likely be put in a special subset of the data that will be included for safety in the intent-to-treat data trial. So they will continue to receive their therapy. Let's see the other parts of the study. Sorry, could you repeat something else what Frank [indiscernible].

Yes. enrollment pace based on what you saw last year, and I believe there's no competitive trial now enrolling given the other trials that were accepting HPV16-positive are fully enrolled maybe.

And then if you can share with us the sample size of the new -- of the study and the interim analysis, PFS analysis that -- what are the underlying assumptions of separation between the 2 arms?

Yes. So the enrollment pace was very good and will continue to be good because we've had a very positive response from the sites that we've gone to, to run the study. As you've mentioned now, there's less competition than was when we first began the trial. so that we have a robust recruitment of sites. And we're happy to say, too, even with the pause we had while talking to the FDA, we didn't lose 1 site. They're all excited by this therapy and ready to begin again. So we're very happy about that. Also the fact that we figured out our time lines by looking at the VERSATILE-002 study, which was done at a certain rate. And now we expect even increased rate because most of the sites came back so that the VERSATILE-002 sites are now going to be involved in the 003 study, which is good because they know the workings of the protocol and the product, and we expect to have pretty brisk recruitment of the patients.

Got it. Mayank, I hope that answered your questions.

I -- sorry to push you, if you can share with us the powering assumptions for the interim PFS and the new sample size for the Phase III.

No. So we haven't made the sample size public yet, but the PFS, again, powered it high power to detect changes in -- statistically significant changes in PFS, 1 at completion of recruitment and the other about 6 months later. So both provide high power to detect statistically significant differences between the 2 arms.

Ladies and gentlemen, that will conclude our question-and-answer session. I'll turn the floor back to Dr. Bedu-Addo for any final comments.

Thank you, operator. Combined with early data from our PDS01ADC program and expanded patient protections extending into the 2040s, we believe we have meaningful opportunities ahead as we continue to execute against our priorities in 2026. We look forward to updating you on our progress. Thank you very much.

Thank you. This concludes today's conference call. You may disconnect your lines at this time. Thank you for your participation.

Greetings. Welcome to the PDS Biotech's Third Quarter 2025 Earnings Conference Call. [Operator Instructions] Please note that this conference is being recorded.

At this time, I'll turn the conference over to Tom Johnson with LifeSci Advisors. Tom, you may now begin.

Thank you, operator. Good morning, everyone, and welcome to PDS Biotech's Third Quarter 2025 Results and Clinical Program Update Call. I'm joined on the call today by the following members of the company's management team Dr. Frank Bedu-Addo, Chief Executive Officer; Dr. Kirk Shepard, Chief Medical Officer; and Lars Boesgaard, Chief Financial Officer. Dr. Bedu-Addo will begin with an overview of the company's recent progress and its clinical development program. Mr. Boesgaard will review the financial results for the quarter ended September 30, 2025, and Dr. Shepard will then join the call to help address questions from covering analysts.

As a reminder, during this call, we will make forward-looking statements, which are subject to various risks and uncertainties that could cause our actual results to differ materially from these statements. Any statements should be considered in conjunction with the cautionary statements in our press release and risk factors as discussed in our filings with the SEC, including our quarterly reports on Form 10-Q and our annual report on Form 10-K and cautionary statements made during this call. We assume no obligation to update any of these forward-looking statements or information.

Now I'd like to turn the call over to Dr. Bedu-Addo. Frank?

Thank you, Tom, and good morning, everyone. It's our pleasure to speak with you again and to provide this brief update on our progress in advancing our clinical programs. During our third quarter of 2025 and recent weeks, we continued to advance PDS0101 or Versamune HPV in HPV16-positive recurrent and/or metastatic head and neck cancer. In August, we announced completion of our VERSATILE-002 trial with the final data further supporting the durable clinical benefit of PDS0101 in this patient population. The strength of this final data and of the data in sub-analysis we announced in September led to our strategic decision to seek an amendment to our VERSATILE-003 trial to include progression-free survival as a primary endpoint in addition to median overall survival. Our rationale for taking this step will be the focus of today's call.

Let's begin. Last August, we announced final top line survival data from the VERSATILE-002 Phase II clinical trial. As you will recall, the VERSATILE-002 trial evaluated PDS0101 plus KEYTRUDA or pembrolizumab in patients with HPV16-positive head in neck cancer. The final data showed median overall survival was 39.3 months, in patients with combined positive score or CPS of greater than or equal to 1. The lower limit of the 95% confidence interval was 23.9 months, and the upper limit was not yet estimable.

Importantly, the progression-free survival was 6.3 months among patients with CPS greater than or equal to 1. This PFS result is notable considering the fact that over 62% of patients in the VERSATILE-002 study had low CPS of 1 to 19. These patients have historically had significantly lower PFS results. A total of 53 patients were enrolled in the VERSATILE-002 trial. Unlike the VERSATILE-003 Phase III trial, the primary endpoint for the VERSATILE-002 trial was objective response rate or ORR. The VERSATILE-002 study included 9 censored patients who discontinued the study after the primary endpoint of ORR was reached and were, therefore, lost to follow up. To understand the potential impact of these 9 patients on PFS and MOS, a sensitivity analysis was performed in the second quarter of 2025 prior to our presentation at ASCO.

Our statistical experts obtained the survival records and disease progression status for these 9 patients. The resulting censoring analysis showed no negative impact on either PFS or MOS. The VERSATILE-002 trial is the first of patients in the recurrent and/or metastatic head and neck cancer population to report a median overall survival of almost 14 months. The PFS and survival results also have important implications for the current design of our Phase III VERSATILE-003 trial.

In the current trial protocol, median overall survival is the primary end point and progression-free survival is a secondary endpoint. However, even before our final readout of VERSATILE-002 a key concern external to PDS Biotech was the fact that MOS relies on the occurrence of death events. The concern being that if a drug works well enough to prevent patient death, it may take a long time to get to the critical data readout. With the further increased final MOS readout from VERSATILE-002 this concern was further exacerbated. To hopefully address the potential for an extended trial duration, while also abiding by the FDA's recommendation, to use MOS median overall survival as the primary endpoint, we have amended the protocol to convert PFS to a surrogate primary endpoint.

As announced, we have requested a meeting with the FDA to discuss the described amendment to the current trial protocol to include PFS as a surrogate primary endpoint independent of median overall survival, which will continue to remain as the primary endpoint for full approval. Our request to meet with the FDA to propose an amendment to VERSATILE-003 is based on careful consideration of the final data from VERSATILE-002. We believe the robust PFS data now presents us with an important opportunity to potentially shorten the time to regulatory submission while maintaining median overall survival as the endpoint for full FDA approval.

Importantly, we believe this approach may also accelerate the availability of this promising treatment to the rapidly growing population of HPV16-positive patients in dire need of effective treatment. Treatment with PDS0101 for currently enrolled patients in our VERSATILE-003 Phase III trial will continue during the temporary pause of the trial. We believe that the industry is waking up to the realization that HPV positive head and neck cancer is rapidly becoming a real problem, and several industry publications just in the last few months have reported on this developing situation.

Some of you might be familiar with independent market research published by DelveInsight on the oropharyngeal cancer market published this month. The article states that they performed interviews with KOLs at leading cancer research centers. And based on a quote from the publication with declining rates of head and neck cancers related to alcohol and tobacco, HPV has become the principal etiologic factor in oropharyngeal cancer, redefining prognostic outlooks and informing the development of tailored therapeutic approaches.

Based on established research, over 90% of HPV-positive oropharyngeal cancers, or HPV16-positive. We are, therefore, confident in the potential of our HPV16 tailored approach and the potential of PDS0101 to ultimately provide a well-tolerated treatment without chemotherapy as an option for the growing population of HPV16-positive patients who currently have no effective therapies for this daily disease, and who will soon become the majority of head and neck cancer patients. Elsewhere in our pipeline, we announced that the National Cancer Institute or NCI, presented new clinical data at the 2025 Society for Immunotherapy of Cancer SITC annual meeting. The NCI presented 3 abstracts highlighting emerging clinical and translational findings from PDS Biotechnologies novel investigational immunotherapy platforms, including PDS0101, our lead Phase III clinical stage HPV targeted immunotherapy and our tumor targeting IL-12 used antibody drug conjugate PDS01ADC.

The presented translational biomarker studies demonstrated the unique immunological properties of PDS0101 and PDS01ADC leading to antitumor immune responses and the predictability of clinical responses. PDS0101 combination immunotherapy was observed to induce broad immune activation and quantitative measurements of various blood analytes predicted clinical benefit with good accuracy. PDS01ADC monotherapy in patients with advanced solid malignancies was observed to increase blood frequencies of stem-like memory and effector CD8 and CD4 T cells that had self-renewing properties. We believe the data presented at SITC further validate the scientific underpinnings of our immunotherapy platforms and confirm that our development approach is achieving the intended immunological and clinical effects.

These findings provide a deeper understanding of how our immunotherapies are generating such promising results in advanced cancers. Earlier in the quarter, we announced that the colorectal cancer cohort of the Phase II clinical trial with PDS01ADC, met the criteria for expansion to Stage 2, following positive Stage 1 results. This trial is also being led by the National Cancer Institute. Our Phase II clinical collaborations with a National Cancer Institute, MD Anderson Cancer Center, the Mayo Clinic as well as our preclinical collaboration with NIAID allow us to focus our resources on our VERSATILE-003 Phase III clinical trial, while progressing development of our pipeline via these investigator-led studies.

Now I will turn it over to Lars for a review of our results for the third quarter of 2025. Lars?

Thanks, Frank, and good morning, everyone. We reported a net loss of $9 million or $0.19 per basic and diluted share for the 3 months ended September 30, 2025, that compared to $10.7 million or $0.29 per basic share in the prior year's quarter. Decrease in net loss was primarily due to lower operating expenses. Research and development expenses were $4.6 million for the 3 months ended September 30, 2025 compared to $6.8 million for the prior year period. The decrease was primarily due to lower manufacturing and clinical expenses and personnel costs.

General and administrative expenses were $3.6 million for the 3 months ended September 30, 2025, compared to $3.4 million for the prior year period. The increase was primarily due to higher professional fees, which were partially offset by lower personnel costs. Total operating expenses were $8.1 million for the 3 months ended September 30, 2025, compared to $10.2 million for the prior year period. Net interest expense was $0.9 million for the 3 months ended September 30, 2025, compared to $0.5 million for the prior year period. The increase was primarily due to lower interest income from our cash deposits. Our cash balance as of September 30, 2025, was $26.2 million, which compared to $41.7 million as of the beginning of the year. Yesterday, we completed the sale of $5.8 million of our common stock or prefunded warrants as well as $5.8 million company warrants for gross proceeds of approximately $5.3 million.

And with that, operator, we can open up the call for any questions.

[Operator Instructions] And our first question is from the line of Mayank Mamtani with B.Riley Securities.

I appreciate the update. So on the VERSATILE-003 protocol pause, can you touch on how you plan to handle the patients that are already enrolled and assume that they will make it to the -- this new PFS analysis that now you're going to propose to the agency? See if you could just give us an update logistically how patients enrolled will be included there? And then also, what's the new sample size, I believe you might be having some awareness of what the new protocol size would look like? And I was also curious what the net cost savings would be for you as a result of that?

Well, Mayank, thanks a lot for your question. So I think as we mentioned in the -- in the -- in the script that we just read through, we are going to continue to treat those patients who have already been enrolled on the trial -- on the study trial. In terms of incorporating them into the trial as a whole, these are not significant amendments, but these are part of the discussions that we will be having with the FDA. In terms of the new size, we have not disclosed that publicly yet. We don't want to do any of that until we have actually sat down with the FDA. We've made certain proposals to the FDA by the anticipation and the whole tier is that we will address some of those concerns by getting to those clinical trial readouts earlier than the currently designed trial will allow us to get there, right?

But I will -- I'll hand over to Kirk and see if he has anything to add to that.

No. Nothing to add, Frank. You said these discussions will take place soon. We think there are very reasonable amendments that we're asking for. We're also very happy that in reviewing these amendments and strategy for the study that the steering committee that we have as well as our investigators are with the program. They believe very much in what we're doing. And the emphasis here, as Frank said, is that these patients will be continued to receive drug on the protocol during the pause.

And are you able to share any information on what the expected PFS would be under control KEYTRUDA. It's obviously much lower than what we see relative to the OS, as you said, but just was curious what you're seeing in studies that have recently published on PFS control arm. And obviously, that feeds into your analysis for what you would power the Phase III study for?

My answer, I think I'll just reiterate something that Kirk just mentioned. These amendments and the work that's going into what we have suggested to the FDA is something that has been thoroughly discussed with the experts and principal investigators, and is very strongly supported by those experts in the field and also what we're proposing is nothing unusual in terms of clinical trial design. So we -- the goal here is to make sure that not only is it very well supported by investigators and experts in the field, but also that it is nothing unusual regarding the FDA regulations, everything we're suggesting should be -- should abide by the regulatory guidelines, right?

So we're making sure we stick with that. And in terms of the VERSATILE-003 trial, Mayank, just to make sure I address exactly what you asked, could you just repeat the last part of that section -- last part of your question?

The PFS for the control arm that you have incorporated and if that has changed relative to your prior assumption when you initially started the study?

Correct. So the PFS, as you know, in the KEYNOTE-048 study as well as the LEAP-010 study, it was 3.2 months for CPS greater than 1 in the KEYNOTE-048 study, and it was 2.8 months. in the LEAP-010 study. Now these studies were predominantly -- we assume the LEAP-010 study was predominantly HPV negative, that hasn't been published yet, but we know that the KEYNOTE-048 study was predominantly in HPV negative patients. We know that there are 2 studies that have been published that actually compared HPV-16 positive patients with HPV negative and other types of HPV infected head and neck cancer patients.

And so we know from those studies that the prognosis, if you have HPV-16 positive head and neck cancer appears to be worse than if you have HPV negative or other types of HPV positive head and neck cancer, right? And so at this point, we are conservatively assuming that the PFS in the control arm is going to be around the 3-month range, which has been reported for KEYNOTE-048 and also in the LEAP-010 study, which was 2.8 months.

That's a big delta. So Lastly, there's been a lot of strategic interest in the head and neck cancer space. A lot obviously -- on the bispecific or ADC side of things and including at ESMO, any thoughts on how you're looking at the broader landscape, especially on the HPV positive side where there's or HPV-16 positive side there is not a whole lot going on.

Right. Mayank, as you mentioned, there is quite a bit of work going on also with ADCs and so forth in head and neck cancer. But as you may know, those are really primarily targeted to HPV-negative patients. As I just mentioned, it appears that there is becoming that realization now in the industry that HPV positive head and the cancer is becoming a really serious medical problem, right? Just in the last few months, we've had several publications report on the growing incidents of HPV positive head and cancer, and this independent market research report I mentioned, specifically stated that HPV negative or the traditional head and neck cancers caused by tobacco and alcohol are on the decline and the new phase of head and neck cancer is HPV positive head and neck cancer, right. As I mentioned, we are very confident in the approach we've taken to focus on HPV-16 positive head and neck cancer, which again in oropharyngeal cancer, for example, over 90% of these HPV-positive oropharyngeal cancer are HPV-16 positive, right?

We've shown on our slide, the growing projection from some of the top medical journals such as Lancet, showing the significant increase in the prevalence of HPV-16 positive head and neck cancer. And so we are very encouraged with the results we've seen today. And we are also very encouraged that this growing population of patients will hopefully have a therapy that specifically addresses this growing type of head and neck cancer, which it appears from the expert reports could potentially be the dominant type of HPV of head and neck cancer in the next decade, right? So we continue to be pleased with the approach we've taken to really target and focus on HPV-16 positive head and neck cancer. But the majority of -- the majority of studies and the products are being developed in head and neck cancer are not focused on HPV positive head and neck cancer.

Our next question is from the line of Joe Pantginis with H.C. Wainright.

So 2 questions, if you don't mind. On 002, can you remind us or inform us on what have you, patients that have been such long-term survival, have they seen any additional therapeutic interventions? I don't believe they have? And then second, on 003, since you're looking at PFS, can you tell us about the conduct of that study with regard to physician training and awareness and to obviously have a lot more sites than 002 with regard to being able to adapt to and not make calls early based on potential pseudo progression of the tumors from the center immunotherapy.

Joe, I'll start and then I'll hand over to Kirk. Now in terms of what patients may go on after they come off the VERSATILE-002 trial, it is important to remember that at that stage, the patients are checkpoint inhibitor resistance. And in HPV-positive disease, this is published. The median overall survival is only 3 to 4 months, right? So we have to bear that in mind in this discussion, once you become checkpoint inhibitor resistance in HPV positive disease, your median overall survival is 3 to 4 months. And therefore, if you come off PDS0101 and go on to some other therapy, and all of a sudden, you see prolonged survival, then very likely, it's only reasonable to resume that, that prolonged survival came from was a result of the therapy, PDS0101 therapy, right?

Because it is very well established that if you're a checkpoint resistant, you are not going to have long survival. Right now, when patients come off the VERSATILE-002 trial, there is no FDA-approved therapy for checkpoint resistant patients. And so they will very likely go into any investigator choice chemotherapy. And that's the most likely therapy that anybody who comes of PDS0101 will go on to, right. In terms of the VERSATILE-003 design and investigators been trained in how they look at things like pseudo progression, that's something that's very important with an immunotherapy and some of the discussions that have been had with our steering committee.

So I'll hand over to Kirk to address that question.

Yes. Thank you, Frank. First of all, just a comment on the answer as far as the subsequent treatment after the protocol, you're correct. I mean there's really nothing, it's tragic that for those who are ICI resistant, that really, there's been nothing really to show that they have any survival benefit or even a high response rate. So unfortunately, we're comfortable with the fact that after the protocol, most likely any effects would be from our drug, PDS0101.

Regarding the PFS, that's a good question because it's very important as we look at these patients that the investigators are trained as far as the response. And also, this will be reviewed, as you know, by a central review from experts who will be reading the scans, et cetera. Where we've discussed this a lot, so people are sensitive to the fact that there may be pseudo progression. And so that with patients who are still clinically well and yet not determined yet as far as a response, we will continue to follow them. So this is very important and different than the 002 because now 002, remember the primary was ORR as far as response rate.

And after the patients had a response, some of them were not followed any further. We will be following these patients all along, not only for the response, but also for safety. So we're comfortable now with the training we've had and the discussions we've had with the steering committee that we will be able to properly judge these patients as far as PFS.

And also, we're very fortunate that with the current site accruals that we have, a lot of the sites are returning who were on VERSATILE-002. So they've been trained before. They are also familiar with the drug and we're very happy to know that a number of them want to be a part of now the VERSATILE-003. So we have a good core of sites that have had experience with the drug as well as judging these responses. Thanks for your question.

I appreciate all the feedback. Thanks a lot.

Thank you. At this time, I'll hand the floor back to management for further remarks.

Thank you, operator. So thank you to all for your time today. We are excited based on the strong VERSATILE-002 results and our fast-track designation about the potential for PDS0101 in head and neck cancer. Our engagement with multiple leading clinical investigators and oncology institutions has validated our approach and the long-term opportunity that we believe our HPV-16 targeted immunotherapy represents in the HPV-16 positive head and neck cancer indication. We look forward to keeping you updated on our progress, and thank you very much again.

Thank you. Ladies and gentlemen, thank you for your participation. This does conclude today's teleconference. You may now disconnect your lines, and have a wonderful day.