Again, for joining us at the Citizens JMP Life Sciences Conference. My name is Roy Buchanan on the biotech research team, and we're pleased to have PDS Biotechnology, and we've got founder and CEO Frank Bedu-Addo. He's going to present about the company, and we'll take questions at the end. So thank you, Frank.
Thanks, Roy. Thanks for the invitation to present at your conference this year. And so I will start with the forward-looking statements. There will be some forward-looking statements. Please just make sure you are aware of the risk factors associated with PDS Biotechnology and as filed with the SEC. So PDS Biotechnology is a late clinical stage cancer immunotherapy company. The company is headquartered in New Jersey. And today I'm going to focus mainly on our lead program, which is we're looking to move this into phase three registrational trial later this year, addressing recurrent metastatic head and neck cancer. Now, this is based on our two lead products, which I'll talk about quite a bit today, and also in a robust data package. To date, about over 400 patients treated with our drugs and over 110 patients treated in head and neck cancer specifically.
The company has capital to run into the fourth quarter of 2025, which allows us to evaluate how best to finance this phase three program, including potential partnerships. As I mentioned, the lead program is addressing recurrent metastatic head and neck cancer. Head and neck cancer has been described recently as a silent epidemic. These incidences are growing extremely rapidly, primarily driven by HPV-16. If you see the blue shaded area, this is a recent publication taking into account the current HPV vaccines. The projections are that we're going to see steady increases and significant increases in head and neck cancer, specifically driven by HPV-16, into the mid-2030s. These incidences will remain high for the next couple of decades. Now, why is this the case?
HPV-16 has also recently been found to be highly effective in specifically inhibiting an immunological pathway that the body uses to generate T cells. And therefore, HPV-16-driven cancers are able to exist without the T cells being adequate to prevent or eliminate their existence. We also have recent data showing that the HPV-positive cancers, recurrent metastatic cancers, are much more difficult to treat than the HPV-negative cancers. So very important to remember as we go through the presentation today. Now, to date in the United States, approximately 53,000 new cases of head and neck cancer. The specific type of head and neck cancer we're interested in, the unresectable, recurrent metastatic, approximately anywhere from 13,000-14,000 new incidences per year. That's approximately a $2-$3 billion opportunity in the United States alone. So a significant market and, as I mentioned, quite rapidly growing.
So let's talk about immunotherapy today and the state of immunotherapy today and how PDS's assets actually address some of the limitations of immunotherapy today. Today, immunotherapy hasn't made much progress since the checkpoint inhibitors about 10 years ago. Checkpoint inhibitors have shown durable responses in a small percentage of patients who've been treated with checkpoint inhibitors. We haven't seen significant success with CAR-T in solid tumors. Two key reasons for this: the immunosuppressive environment of solid tumors. These solid tumors in the internal microenvironment are able to suppress the T cell effect or prevent T cells altogether from entering into the tumors. Second critical limitation, the inability to induce the right type of killer T cell in the right quantity and with the right killing potency. Both of these limitations are addressed with PDS's technologies that we'll talk about today.
So here, the first is our PDS01ADC, which is a fused antibody-drug conjugate of IL-12. So you see the cytokine IL-12 conjugated to an antibody that targets necrotic DNA within the tumor microenvironment. So this takes the IL-12 into the tumor, holds the IL-12 in the tumor so it has sustained presence in the tumor, and is able to then minimize or suppress the tumor's ability to inhibit the T cell response. So this overcomes the major limitation, which is inhibition of the T cell response. It also is able to activate the T cells once they get into the tumor microenvironment. And we'll see some of the effects of this antibody-drug conjugate. Our Versamune technology has also shown the ability now to induce, as I referenced, the right type of killer T cell in the right quantity and with the right killing potency.
Very importantly, we'll see the impact of these drugs as we go through the data. So first, our VERSATILE-002 trial, phase 2 trial, addressing recurrent metastatic HPV-16 positive head and neck cancer. This is a trial combining our Versamune HPV with Keytruda, which is the standard of care for recurrent metastatic, first-line recurrent metastatic head and neck cancer. So here, PDS0101 is dosed with Keytruda. Keytruda is taken once every three weeks for up to two years if the patient continues to survive and have a response to Keytruda. PDS0101 is given in five doses, the first four cycles given with Keytruda every three weeks. And then six months later, the patient will get the fifth dose of Versamune HPV.
Now, it's important here, the reason why we only given 4 doses of Versamune HPV is the fact that in our single-agent monotherapy studies, what we have demonstrated clearly is the ability to induce what we call a memory T cell response. So we don't have to give too many doses of the drug because it's able to train the immune system and train the T cells to continue to recognize that specific HPV-16 agent and continue to generate the T cells to fight the cancer. Okay, so let's look at the data here. So here, very importantly, the demographics. If you look at the CPS scores on the bottom, very importantly, with Keytruda, what has been shown with the checkpoint inhibitors is that they work much better at the higher CPS scores greater than 20. They're less effective at the lower CPS scores.
What we show here is that the majority of our patients fall into the lower CPS score. 60% of the patients are in the lower CPS score who don't traditionally respond very well to checkpoint inhibitors. So the data is skewed actually against good, strong responses. Also, very importantly, this is mature data. The median number of doses that the patients have taken, over 75% of the patients have had their 4 doses of PDS0101. And remember, there's a 6-month gap between dose number 4 and dose number 5. And 38% of the patients have had all 5 doses of PDS0101. So quite mature data. Median number of Keytruda doses to date, 8, and over 43% have received more than 10 doses of Keytruda today. So this slide summarizes the results, looking at both CPS score greater than one. So the CPS score greater than one is the inclusion criteria.
Anybody with a CPS score greater than one is eligible to enroll in this trial. The confirmed objective response rate. So very importantly here, this trial has met its primary objective, which is best objective response rate. We show for CPS greater than one, 34% response rate, with Keytruda as a standard of care and published results, say, 19%. And for CPS greater than 20, we see a 48% response. And the published results for CPS greater than 20 with Keytruda is 23%. Median PFS, 6.3 and 14.1. However, what's very interesting here, if you look at the median overall survival, we see 30 months median overall survival, which is the longest median overall survival reported to date in recurrent metastatic head and neck cancer. And you can compare this with the published results for Keytruda in the KEYNOTE-048 study of 12.3 months and 14.9.
Very importantly, we don't see a difference in survival between CPS greater than 1 and CPS greater than 20. Also, very well tolerated, grade 3 to grade 5 adverse events, only 13% of patients compared to published for Keytruda monotherapy, 17%. And so what's of note here is, despite the significant improvements we've seen in clinical benefit, we don't see any added toxicity to date by the addition of PDS0101, 13% grade 3 and higher response rates, 1 grade 4, no grade 5 toxicities to date. Now, why is this working? Why do we see this level of survival? Here is a plot looking at the tumor sizes, tumor growth on top, at the top of the X-axis, and then tumor shrinkage below the X-axis.
We see the vast majority of patients having either stabilization of disease or shrinkage of the tumors, 87% of patients having tumor shrinkage or stabilization of the disease, which is very, very important. If you look at the spider plot, what we see is durable responses. These patients who have seen tumor shrinkage or stable disease see that long term. We do not see significant tumor growth once the response has occurred. This also leads to our Kaplan-Meier plot over here. There has been quite a bit of confusion and misinformation regarding this Kaplan-Meier plot. This is the standard Kaplan-Meier plot. On the Y-axis, we have the survival fraction. 100% at the top, 1.0. Every step down we see here is a patient's death. The dots we see on there are patients who have been confirmed to be alive today.
So every dot on this plot is a surviving patient. So what's really notable about this plot is the fact that extremely few patients, no patients left the trial due to treatment-related adverse events. All patients stayed on the trial. To date, two patients have been lost to follow-up. And when these two patients are censored, what is done on this Kaplan-Meier plot is those two patients are documented as being dead as of the last date on which their survival was confirmed. So two patients lost to follow-up today, and those two patients are confirmed in this plot to be dead or taken to be dead at the date at which they were last confirmed to be alive. So only two patients lost to follow-up to date. All those dots are surviving patients.
The way the standard Kaplan-Meier plot statistics are done, the longer the patient lives, the greater they are weighted in the statistical analysis. Based upon this Kaplan-Meier analysis, the standard statistical analysis, the median overall survival is 30 months. Now, going back, so now we can see that with Versamune HPV alone, so with this, what we've walked through today, we're looking at the T cell induction. Now, if we go back to our waterfall plot, we can see here that there are still some patients who are not seeing a strong response, and some patients have a stable disease. So there is more room for improvement. By adding our PDS01ADC, that can actually go into the tumor microenvironment and mitigate the tumor's ability to block the T cell response, can we see improved responses here?
And so let's go to PDS01ADC included in the so here we're showing the mechanism of action of the three-agent combination. Agent number one is our PDS01ADC, the antibody-conjugated IL-12. So that targets tumor necrosis in the tumor. So you see that infiltrates the tumor and is able to induce inflammation within the tumor. It has a sustained presence in the tumor. It's able to suppress or mitigate the tumor's ability to inhibit the T cell response. That's the inside attack. Versamune induces the T cells, which can now infiltrate the tumor much more effectively and are further activated by the IL-12 in the tumor microenvironment. And of course, the checkpoint inhibitor restores pre-existing T cell responses. And so this study was done by the National Cancer Institute. And this looks at the inclusion criteria.
Again, the primary goal here was to look at the best overall response and also look at survival as an exploratory outcome. So what we see over here is very interesting. So the published results with pembrolizumab to date, as I mentioned on the earlier slide, 12.3 months median overall survival. There has been a recent study, the LEAP-010 study, which showed a median overall survival of 17.9 months. When we add Versamune to pembrolizumab, as I showed earlier, we see a median overall survival of about 30 months. And then with our triple combination now, by adding in the PDS01ADC to be able to suppress the tumor's ability to hide from T cells, we see a further one-year increase to about 42.3 months median overall survival.
So again, very dramatic improvement in survival patients utilizing these assets, both of which are able to perform a very effective and very specific task, T cell activation and also suppression of the tumor's ability to mitigate the immune response. So the conclusions from the triple combination study, we see the best objective response of 63% by RECIST 1.1. And by iRECIST, we've seen a 75% best objective response. Now, iRECIST takes into consideration what we call pseudoprogression. In many patients who are treated with immunotherapy, very often you'll see a T cell response that leads the tumors to swell. That swelling can look like a progression. And then you see the subsequent decline in the tumor size and sustained regression of those tumors. And one patient had that response, a pseudoprogression. That patient included in the iRECIST, given us a 75% best objective response rate.
Again, extremely impressive for, as I mentioned, HPV-16 positive tumors, which have been shown to be potentially a lot more difficult to treat. Median ORS of 42 months. And we also looked at what we call a higher bar, a stress test in second-line patients who have actually failed checkpoint inhibitor therapy. These are the patients who, when treated with a checkpoint inhibitor, have a reported published median overall survival of only 3-4 months, 3.4 months to be specific. In these patients, the National Cancer Institute reports median overall survival of 19-20 months, so more than a sixfold improvement in the survival of these patients. Again, quite significant impact in clinical response rates. The triple combination appears to be well tolerated.
The immunological and clinical data we've generated to date in both the doublets combinations as well as the triple combination suggests that PDS01ADC may be highly effective in targeting the tumor to overcome the tumor's immunosuppressive mechanisms. How do we go into our phase 3 clinical trial, and how do we decide what our phase 3 clinical design is going to look like? In first-line recurrent metastatic disease, as I mentioned, we've shown with the VERSATILE-002, Versamune HPV, and Keytruda pembrolizumab, 53 patients, median overall survival calculated and projected as 30 months. With the National Cancer Institute triple study, not only in head and neck cancer, but all types of HPV-positive cancers, they've shown a median overall survival of 42 months.
Now, when we look at what we call the stress test in the even much more difficult-to-treat patients, in 29 patients, we've seen a median overall survival of 19-20 months versus what's been published of 3.4 months. Therefore, taking all that information into consideration, our phase 3 pivotal trial is going to be Versamune HPV plus PDS01ADC plus pembrolizumab, so the triple combination moving with the primary endpoint being median overall survival as requested and suggested by the FDA. This is what the phase 3 pivotal trial design looks like. Our initial VERSATILE-003 study was going to be comparing Versamune HPV and pembrolizumab against pembrolizumab. This protocol design was okayed by the FDA.
Based upon the more recent information, with the understanding of how PDS01ADC is working, we are actually requesting the FDA that we add another arm, which would be the triple combination arm. So we have pembrolizumab as a control arm and two active arms, Versamune HPV plus pembro, where we've seen the 30-month median overall survival, and Versamune HPV plus pembro plus PDS01ADC, where the data projects approximately a 42-month median overall survival. Now, this is going to be a 1-to-1-to-1 randomization. And very importantly, this is powered for success with the doublet arm, Versamune plus pembrolizumab. Therefore, as I sometimes describe, overpowered for the triple combination. So we're very optimistic about getting this trial up and running based on all the data that has been generated today. We continue to validate our pipelines. We're hopeful that we'll have some more updates as the year goes on.
We'll update our Versamune plus HPV chemotherapy, the IMMUNOCERV trial that's being run by MD Anderson. We're hoping to have an update later this year. We have not had any updates yet from our trial being run by Mayo Clinic looking at Versamune alone or Versamune plus pembrolizumab as a neoadjuvant treatment in earliest stage oral cancer. And of course, we have our non-HPV program, Versamune MUC1, that we anticipate filing an IND for later this year. So quite significant progress being made. And so what gives us confidence going into our phase three human clinical trials today? Consistency in our results across multiple clinical trials. We are one of the few companies and one of the few among our peers today who have strategically been able to have independent studies performed to evaluate Versamune HPV.
The results are all coming in very consistently in agreement with each other. So as you see over here, when we look at the median overall survival, when we look at the VERSATILE-002 trial, Versamune HPV plus a checkpoint inhibitor, we see 30 months median overall survival, 34 months objective response rate. When we add PDS01ADC on top of that, completely independent trial, 42 months median overall survival, 75% objective response rate, we see the consistent building up now that we're adding that additional agent. When we look at the MD Anderson results they reported at SITC a couple of years ago, 100% survival at 1 year, 100% objective response rate with Versamune HPV plus chemoradiotherapy, the IMMUNOCERV trial. So again, very strong consistency in the survival results reported from independent trials. What also makes us very confident are the biomarker studies.
So in addition to this, we have biomarker studies done independently by each of these expert institutions in addition to our multi-site, multi-country VERSATILE-002 trial. IMMUNOCERV trials shown by MD Anderson, very important in the activation of the right type of CD8 killer T cells that are not just circulating in the blood but actually accumulating in the patient's tumors. So again, very important to characterize these T cells and show that they are actually accumulating in the patient's tumors. What they also showed was 92% reduction in circulating HPV-positive tumor DNA at five weeks compared to without Versamune HPV. They only see a 53% reduction at five weeks. With the VERSATILE-002 multi-country, multi-site trial, we've shown a Th1 that was presented at ESMO, Th1-type immune response induced and also active CD4 and CD8 T cell, specific T cell induction in the VERSATILE-002 trial.
And with the triple combination done by the National Cancer Institute, again, active HPV-16 positive CD8 T cell induction in those patients, including in the checkpoint-resistant patient population. So again, very strong consistency across all the trials done to date, very strong consistency in the response data as well as in the survival data, very important for us as we move into the phase 3 clinical trials. So I will end here. Thank you very much for your time, and I'll be happy to answer any questions you may have at this time.
All right. Thank you, Frank. A few minutes. Any questions, audience? Anybody? No? Okay. I had a few. I guess so you gave us that. I guess any sense of so this dose-finding portion on the VERSATILE-003 plus, just any sense on when the timing, when that might complete? And can you give us any details on the interim? I know you need to talk to FDA and work all this stuff out, but I guess what are you proposing to them for this interim analysis?
So we have 2 interim analyses. The first one will be coming after the dose optimization study. With the dose optimization study, the goal there is with the National Cancer Institute study, they looked at 16.8, which is the maximum tolerated dose. They also looked at a much lower dose, 8 microgram dose, where they showed much less clinical responses at the 8 microgram dose. But they've also done the dose-finding study, which is now published, where they showed that they saw strong immune responses at the 12 microgram dose. So our proposal to the FDA is to do a small study first, evaluating the 12 microgram dose versus the 16.8 microgram dose. If the 12 microgram dose is just as active, there's no point in moving forward with the 16.8 microgram dose. So really, that's what the first part is looking at. We know it's biologically active.
Even with the 8 microgram dose, we still saw the same median overall survival. So we saw prolonged survival rates, but the objective response rates were significantly lower with the 8 microgram dose. So really, that's what the goal is there, to make sure that we are not dosing the patients with more than we actually have to dose them. So there'll be a readout there. We'll report the results there, and then we'll move into the randomized phase of the study. With the randomized phase of the study, we'll also have an interim data readout. That interim data readout is where, pending what the data looks like, we would have the potential to talk to the FDA about an accelerated approval, if possible, at that point. And we have the 3 arms. So the goal here is we look at the way the study is designed.
We first of all look at the triple combination arm. And then based upon the responses in the triple combination, we either keep going or we open it up to review the results of the doublet arm also. And so we've given ourselves a really strong opportunity for potential accelerated approval at that second interim data readout.
Okay. It sounds like a response rate.
For the first one.
Okay.
Then survival for the second.
I didn't see in the slides, but are you thinking about any specific CPS cutoff? Like KEYNOTE-048 initially over 20 to get to fast-to-market? Are you guys thinking of doing something similar? Are you going to take everything above 1?
The advantage we've shown with our T cell activation is we don't have to go to the highest CPS scores. As you saw with the survival, we've seen very similar survival, CPS greater than 1 and CPS greater than 20. We believe that's because of the power of the T cells. Plus, we have this additional, the third component, which is the PDS01ADC. So with our trials, the advantage we have really is that we're going for CPS score 1 greater than 1, 1 or greater. We are not restricted to CPS greater than 20 because we've seen really strong responses even within the lower CPS score 1-19 range.
Okay. Great. Maybe squeeze in a couple more if I can. The 002 trial, when do you think you'll update us next on the overall survival?
We may have another update later this year. I can't confirm that. That's something that the clinical team would have to evaluate. We have not projected any other additional readouts this year for that trial. We will be presenting some data from that trial potentially later in the year, in the Q4, potentially.
Okay. All right. And then last one, the MUC1. Is that included in your cash runway guidance? And what's the plan there? Are you going to partner that, keep it internally?
Currently, that program is actually under our collaborative research involvement agreement with the National Cancer Institute. And so we're evaluating what the opportunities there are for us in terms of whether we do it as an IIT with the National Cancer Institute or whether we partner with another industrial partner to move that forward. So those are all options that we are currently looking at.
Okay. All right. Great. Thank you very much, Frank.
Very welcome. Thanks for.