PDS Biotechnology Corporation (PDSB) Earnings Call Transcript & Summary

Good morning, and welcome to PDS Biotechnology's post 2023 ASCO Conference Call and Webcast. With me today from the company are Dr. Frank Bedu-Addo, Chief Executive Officer; Dr. Lauren V. Wood, Chief Medical Officer; and Matt Hill, Chief Financial Officer. Before we begin, we want to remind everyone that on today's call, the company will be making forward-looking statements regarding regulatory and product candidate development plans, as well as research activities. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in PDS Biotech's most recent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this conference call. Except to the extent required by applicable law or regulation, PDSB undertakes no obligation to update the forward-looking statements included today to reflect subsequent events or circumstances. With that, I would now like to turn the call over to Dr. Frank Bedu-Addo. Frank?

Thanks for joining us today to review the updated interim data from the VERSATILE-002 clinical study in recurrent or metastatic HPV16-positive head and neck cancer. The data was presented at the 2023 ASCO annual meeting yesterday. It should be noted that the data presented yesterday was the same data released by PDS Biotech on May 25, 2023. No new information was presented. Before I start, I would like to remind you that based on all our ongoing Phase 2 PDS0101 trials, we have reported efficacy data from over 90 patients. In addition, we have reported safety data in over 120 patients. The data has been generated at over 30 clinical sites in 4 separate studies, including our Phase I monotherapy study. The antitumor, immunology and safety data continue to be consistent across trials, multiple sites and multiple HPV cancer indications. At PDS Biotech, we are seeking to provide improved treatment options that are tolerable and that extend patients' lives. Here, you see some of the agents that constitute the current state-of-the-art in treating recurrent or metastatic head and neck cancer. I would like to point out that there have been no randomized head-to-head studies comparing the combination of PDS0101 and KEYTRUDA with KEYTRUDA monotherapy or KEYTRUDA plus chemotherapy. We will only provide published data and information as a reference. This slide summarizes the efficacy and safety of the current standards of care against which we are benchmarking the PDS0101 KEYTRUDA combination. In the KEYNOTE-048 published results, KEYTRUDA monotherapy results in an objective response rate of 19% and a 12-month survival rate of 50%. It is also reported in the KEYNOTE-048 published results that KEYTRUDA plus chemotherapy results in an objective response rate of 36% with a 12-month overall survival rate of 55%. The median overall survival for KEYTRUDA and KEYTRUDA plus chemotherapy are 12.3 months and 13.6 months, respectively. Our ultimate goal is not only to improve the objective response rate, but ultimately to extend patients' overall survival. In head and neck cancer, objective response rates to date have not translated to overall survival. It must also be noted that for KEYTRUDA monotherapy, it is published for KEYNOTE-048 that 17% of patients had severe Grade 3 or higher treatment-related adverse events. With KEYTRUDA plus chemotherapy, the Grade 3 or higher severe treatment-related adverse event rate was 72%. As a reminder as to how PDS0101 works. PDS0101 as a monotherapy and in combination with other agents promotes the induction of high levels of the right type of CD8 killer T-cells in the right quantity and with the right tumor-killing potency. This promotion of multifunctional T-cells plus the HPV16 specific memory T-cells, we believe enables PDS0101 to achieve durable clinical responses with prolonged patient survival. It is important to note that achieving prolonged survival with a well-tolerated regimen has been one of the most critical limitations of cancer therapy. Our goal by combining PDS0101 with KEYTRUDA is to increase the percentage of patients who respond to therapy and to enhance the long-term survival of the patients without compounding the toxicity of KEYTRUDA monotherapy. The inclusion criteria for VERSATILE-002 requires patients to be PD-L1 positive with a CPS score of 1 or higher, and all patients must have HPV16-positive cancer. HPV16 positivity represents 60% to 65% of advanced head and neck cancer. The primary endpoint for VERSATILE-002 is best overall response, BOR; of confirmed complete response, CR; or confirmed partial response, PR, per RECIST 1.1. Key secondary endpoints are progression-free survival, PFS, overall survival, OS, and safety and tolerability. We announced this past May that we completed enrollment of the full cohort of 54 immune checkpoint inhibitor naive patients. Patients received KEYTRUDA by IV every 3 weeks for 35 cycles or until disease progression, death or stoppage due to toxicity. PDS0101 is given by subcutaneous injection every 3 weeks during the first 4 cycles only and again at Cycle 12 for a total of 5 doses. Now let's discuss the study's updated interim results. We presented efficacy data on the modified intent-to-treat population of 34 patients. These are the patients who have received at least 1 dose of the combination and who have also had at least 1 imaging scan post treatment. This doubles the patient size compared to the data presented at ASCO in 2022. Let's take a look at the patient disease control and the impact of PDS0101 administering combination with KEYTRUDA on tumor shrinkage and stabilization to date. This waterfall plot shows that the majority of patients, about 68%, experienced tumor shrinkage. To date, 70.6% of the patients have disease stabilization or tumor shrinkage. 41.2% of patients have a confirmed or an unconfirmed objective response. 44.1% of patients have disease stabilization and 26.5% have progressive disease. Do note that 1 of the 34 patients was not evaluable and is therefore not shown on the plot. However, to ensure that our data is not overstated, 34 is the number used in the denominator to calculate the percent response rates. Let me now explain what we mean by a confirmed or unconfirmed objective response. An objective response occurs when a patient has tumor shrinkage of 30% or more. Patients on the trial received a scan to evaluate their target tumors every 9 weeks. To determine a confirmed response, we adhere to the RECIST 1.1 criteria for best overall response, meaning that if a patient is determined during their scan to have stable disease, partial response or complete response, this result will be confirmed on the subsequent scan 9 weeks later. And at that point, the patient will then be deemed to have a confirmed stable disease, partial response or complete response. If the patient has improved from stable disease to partial response on the subsequent scan, that partial response will again have to be confirmed 9 weeks later on the subsequent scan. The unconfirmed patients are the patients who have seen to have a partial response or complete response but who have not yet received their subsequent scan 9 weeks later. Also important, if a patient had, for example, 90% tumor shrinkage and 9 weeks later, an increase in size of 20% is seen over that 90%, even though the tumor size is still significantly below the 30% threshold, that increase of at least 20% over the best observed results will lead to the patient being characterized as having progressive disease. This is what you see with the 2 patients who are denoted in red, who have tumor shrinkage of about 40% and 70%, respectively. It should be noted that the waterfall plot does not capture the durability of responses, which we will now discuss on the Kaplan-Meier plot for progression-free survival or PFS. The PFS essentially measures the effectiveness of disease control and how long tumor shrinkage or stabilization continues before disease progression occurs. Here, you see the Kaplan-Meier plot showing the calculated median PFS of 10.4 months with PDS0101 administered in combination with KEYTRUDA. As I showed earlier, the PFS published in the KEYNOTE-048 study for KEYTRUDA monotherapy and KEYTRUDA plus chemotherapy are 3.2 months and 5 months, respectively. What we believe is notable about this PFS result is the compelling durability of the anti-tumor response. Now here, you see the Kaplan-Meier plot for overall survival for PDS0101 administered in combination with KEYTRUDA. In this curve, you see here there's a minimal decline towards the X-axis due to the fact that we have only seen 4 deaths to date and approximately 90% of the patients continue to stay alive. As a result of the continued high survival rate of the patients, we have still not reached the median overall survival for the combination. However, we are pleased that the calculated 12-month overall survival rate is 87.1%. As I showed earlier, the 12-month overall survival rate published in the KEYNOTE-048 study for KEYTRUDA monotherapy and KEYTRUDA plus chemotherapy are 50% and 55% respectively. The spider plot shows the patient's anti-tumor response with time and the rates of tumor shrinkage and progression. The key takeaways here are the following: The majority of patients see tumor shrinkage and, therefore, are below the baseline. Also, the majority of patients with tumor shrinkage start to respond quite rapidly within about 60 to 90 days. In our Phase I monotherapy study of PDS0101, we found that high levels of multifunctional HPV16-specific CD8 T-cells were induced within 14 days of PDS0101 subcutaneous injection, and we believe the rapid response rate of tumor shrinkage in VERSATILE-002 is consistent with this observation. This response rate is also consistent with the results in locally advanced cervical cancer. Dr. Ann Clark at MD Anderson reported at SITC in November 2022, that 100% of patients treated with PDS0101 in chemo radiation had an objective response by Day 60, with tumor shrinkage of greater than 60%, and 8 out of 9 patients had a complete response by Day 170. Also, we can see that a number of patients are having a durable response in that the trajectory of their tumor size curves is staying flat below the baseline and extending beyond 500 days. This result of the observed durability of the clinical response appears to translate to prolonged overall survival. As we look at the swimmer plot, it shows the survival of each patient over time. Most notable in this plot is that several patients are approaching 2 years of survival, and we have seen very few deaths to date with almost 90% of the patients still alive. As I mentioned at the start, we have not compared the combination of PDS0101 and KEYTRUDA head-to-head with any agents in a controlled study. This slide is simply to put the results generated to date in perspective based upon the published results for the state-of-the-art in recurrent metastatic head and neck cancer. So how are we doing when it comes to tolerability of the combination. With safety, we have evaluated the full intent-to-treat population of 48 patients. Many patients see mild to moderate injection site reactions and fatigue as their main side effects. Only 4 patients out of the 48 have had treatment-related Grade 3 side effects. There have been no Grade 4 or 5 treatment-related adverse events. This is highly encouraging and in agreement with the feedback we have received from several investigators regarding the quality of life experienced by their patients on the combination and the tolerability of the treatment. To date, no patients have left the trial due to treatment-related adverse events, which is very encouraging. To date, PDS0101 does not appear to compound the known toxicity of KEYTRUDA. To understand how the clinical results and outcomes are evolving as we enroll more patients, we compared key outcomes that were reported at ASCO 2022 for the first 17 patients with the results presented at ASCO 2023 in 34 patients. The analysis shows that the results have remained practically identical and have stayed consistent as more patients have been enrolled. The promising combination of prolonged overall survival and tolerability of the combination, we believe warrants a rapid progression to a controlled registrational trial. As we announced recently, we plan to initiate VERSATILE-003 in the fourth quarter of this year. As mentioned previously, we have successfully transferred our manufacturing of PDS0101 from our clinical manufacturer to our commercial manufacturer and the Phase III clinical product has been successfully made and released for use. We expect to file the amended IND in the third quarter of this year, start qualifying sites with a goal of activating 90 to 100 worldwide sites. We plan to initiate the trial in the fourth quarter of this year. Again, this will be a randomized control trial and is being powered for overall survival and progression-free survival as the primary endpoints. We anticipate having 2 interim analysis, which may provide the opportunity for early discussions with the FDA regarding possible accelerated approval pending on the results. To conclude the ASCO presentation overview, PDS0101 continues to provide strong proof of concept for the Versamune platform across multiple Phase II studies. We have efficacy data from over 90 patients to date. Importantly, the antitumor biomarker and immunology data have shown strong consistency and correlation across all types of HPV cancer and at all study stages of the disease. There has been a strong agreement between preclinical and human results, which we believe is primarily due to the technologies mechanism of action leading to clear translation between preclinical and human clinical results. We look forward to continuing to update you on our progress, not only on VERSATILE-002 and VERSATILE-003 but also on our other PDS0101 clinical programs. Additionally, our antibody conjugated and tumor-targeted IL-12, PDS0301 Phase II pipeline is being studied with standards of care in various solid tumors. In closing, I would like to take a moment to address a situation that occurred yesterday, mainly in social media, where certain data from the poster presentation were mischaracterized and untrue assertions were directed at our company. Rather than going into a point-by-point discussion of what was posted or the correction and apology that were later issued, I want to use this opportunity to assure all of our stakeholders that PDS Biotech is an ethical company that takes great care in communicating data from our clinical trials. We strive to present information accurately, objectively and in great detail in order to minimize the chance for misunderstanding, and because it is the right thing to do considering we are in the business of developing medications that one day will hopefully benefit people who are in the direst of circumstances. What's happened yesterday was unfortunate on several levels. But thankfully, I believe the impact will be short-lived. These data as presented yesterday and discussed this morning are quite promising, and we are highly optimistic about the opportunity to initiate the VERSATILE-003 trial later this year. At this time, I will hand the call over to the operator for the question-and-answer session.

[Operator Instructions] Our first questions come from the line of Louise Chen with Cantor Fitzgerald.

Congratulations on the data at ASCO. So I have 3 for you. First, where do you think this VERSATILE-002 median overall survival will shake out? And why do you think that? Secondly, how is the reception at ASCO to the presentation of your data? And then last one is just on your VERSATILE-003, what would you consider a win in overall survival and progression-free survival in that study? And then will there be any differences in terms of the patient population you enroll? And how quickly do you think this trial will enroll?

Thanks, Louise, for your questions. So I will start with question number 1. I'll hand over to Lauren for the second question regarding the feedback at ASCO yesterday and then -- so I'll address questions 1 and 3 and then hand over to Lauren. So for VERSATILE-002, where do we think median overall survival will shake out? Well, the data we have today is extremely encouraging in terms of the fact that patients continue to live and have a sustained survival. It is difficult to predict how long the patients are going to live. I think one of the key reasons why we -- there was a gap of duration between when we had our meeting with the FDA regarding moving into Phase III and designing the Phase III clinical trial is that we had really no visibility to what our PFS was or what our overall survival is going to be, right? So currently, based upon the fact that we have the 12 months -- 12-month overall survival rate versus what we are comparing -- what we will be comparing PDS01 against, we're able to understand what the potential hazard ratios may be. And therefore, we gained some level of comfort in designing those statistical endpoints. But I think all I can say at this point is we are extremely encouraged by the high rate of survival we are seeing, which we believe translates very well based upon what we saw in our preclinical studies and what we are seeing in other studies, for example, the triple combination that was run by the National Cancer Institute. Again, we've seen very strong durability of responses there. And very similarly, with -- with this data that was presented by MD Anderson at SITC. So this prolonged survival is consistent among the trials that we're running with PDS0101. So we will continue to follow these patients and continue to update the markets as we gain more visibility to how long those patients are continuing to survive. In terms of PFS and OS, what do we consider would be a win? I think based upon the data that we have generated today with the PFS, for example, I think you would agree that the 10 months is significantly higher than what we would have to meet for this product to be approved. And so very similarly, with the overall survival, as I mentioned, we don't have our median overall survival yet. But based upon the 12-month overall survival rates, we can identify what an appropriate hazard ratio should lead us to. And so as we've designed the Phase III clinical trials, we've made sure to ensure that we are not being overly aggressive with those endpoints. We also -- as we design these, we also take into consideration the fact that our control arm may do better than has been reported in KEYNOTE-048, for example. And so all these are taken into consideration as we design those endpoints to make sure that we are not being overly aggressive in what we consider those endpoints to be, especially considering the fact that we don't believe we have to meet -- the goals we've achieved today with PFS and potential overall survival to have this product approved. Lauren, I'll hand over to you to address the feedback we received at the ASCO conference yesterday.

Great. Thanks, Frank, and for your question, Louise. There was a lot of enthusiasm and interest from ASCO attendees during the head and neck poster session. In her discussing review, Dr. Erminia Massarelli of the City of Hope Comprehensive Cancer Center in Los Angeles noted PDS0101's novel mechanism of action, favorable toxicity profile and impressive 12-month overall survival rate. We're absolutely in agreement with her opinion that a prospective comparative trial is needed to confirm the long-term outcomes in a larger sample size with further examination of biomarkers as we're planning to do in VERSATILE-003. As the data matures from VERSATILE-002, we'll also continue to examine the durability of the consistent trends that Frank has previously noted and highlighted in the clinical and safety efficacy outcomes that we've observed to date.

Our next questions come from the line of Kalpit Patel with B. Riley.

Maybe first on the data set, from those 9 confirmed responses that you have for the doublet, do we know what the CPS range was for those patients, specifically, how many of those patients had high CPS maybe greater than 20 in that update?

Kalpit, thanks for your question. So in the demographics, and we've noted that 50% of the patients had CPS score greater than 20, and the other 50% in the MITT population had CPS score between 1 and 19. And this is very similar for the -- for what was supported in KEYNOTE-048, where I believe about 51% to 52% of patients had CPS greater than 20. As we've analyzed our data, there is no statistically significant impact of CPS score on the results that we've seen today with PDS0101 plus KEYTRUDA, which is what you would hope to see because PDS0101's immune response is independent of PD-L1 expression. And that appears to be what we're seeing with these patients where we are not seeing a significant impact of CPS score on the efficacy results.

Okay. Great. And then for the Kaplan-Meier curve for the overall survival, can you talk a little bit about the censoring in that study? It looks like only 4 patients died and the rest were censored. So were most of these patients lost to follow-up? Or is it just an immature data set that sort of yielded these results? Any additional color would be useful here.

Yes. I think the censored may be creating a little bit of confusion. But essentially all the patients were -- all the patients were evaluated. If you look at that overall survival plot, the early -- the patients involves the full ITT population, right, of 48 patients. And we have the earlier patients, the first 14 patients who do not constitute that MITT, but a part of the ITT are the patients, as I described earlier, who have had 1 dose but who have not yet had their first scan. And so when you look at these patients over here, the way this 12-month overall survival rate is calculated, much -- the statistical waiting gives much more weight to the patients who have stayed longer on the trial and who have survived longer. And so there's much less impact from the patients who have not stayed very long on the trial. So for example, if we take out those 14 patients and just concentrate on the MITT, the 12-month overall survival rate goes to 86.5%. So really not much impact of those early -- the earlier 14 patients. So it's a pretty robust calculation based upon the statistics that I used to evaluate these patients. But all of these patients have gone through studies. And as I mentioned, we've only had 4 deaths on the trial. And if you look at the swimmers plot, it identifies specifically which patients have left the trial and which ones are still on the trial.

Okay. That's helpful. And then one last question just to be crystal clear on the unconfirmed responses. You had 5 unconfirmed responses, but you said 2 of those 5 have progressed and will not be confirmed as responses. Is that correct?

That is correct. So the 2 patients who have had the red in -- about 70% and 40% tumor shrinkage, those 2 patients due to the fact that the tumor sizes have increased by more than 20% over the best identified response at the previous scan, based upon that, those 2 patients will not be confirmed, will not have a confirmed PR or CR. One of them, for example, had a complication and had to come off the trial. And so once the patient comes off the trial and miss their treatment, which one of those patients did, that patient then saw progression and had to leave the trial. But we still have to document that the patients who came on the trial have seen progression of their disease. And so we capture it on that plot just to make sure that everything is accurately captured. So the patient who had the 70% tumor shrinkage, for example, that patient took the dose, had to come off the trial because they couldn't take the subsequent dosing, but we still captured that in our plots. The other 3 patients are still on the trial and just haven't gone through their subsequent complementary scan yet. I hope that... Go ahead.

Yes. That's helpful, Frank. And could we see the data for the other 3 patients in second half this year?

Our anticipation is that in -- probably in the second half of this year, but in the second -- by the second quarter of next year, based upon the fact that we have enrolled all the patients at this time, we anticipate that the full data package of the results for the full cohort, the final results will potentially be presented at ASCO next year.

Our next questions come from the line of Leland Gershell with Oppenheimer.

Just one question for me. With respect to the PFS, I know it's early estimated based on the K-M analysis of 10.4 months. Obviously, a pretty strong number. At the same time, there's a wide confidence interval there. If you could put sort of into context based perhaps on other studies, how that may narrow and how PFS may -- median PFS may come down, even though I know you are presuming that there will be less of a value down the road as you plan your Phase III, but how we should think about kind of the trajectory of median PFS and the spread as data continue to mature.

Thanks, Leland. So I think what I would be very hesitant to do is to project what we are going to see based upon what other people have seen in other studies. Because as you know, our mechanism of action is very different, and we are seeing very differentiating data in this trial. So I think, I would be very hesitant to say we're going to see X, Y, Z because somebody else has seen X, Y, Z with a different technology in another study. I think what's very encouraging to us, as you look at the waterfall plot and the spider plots is how long these patients are continuing to have ongoing responses. We see very few people -- patients who, if you look at the spider plot, start to have increase in their tumor size. And so based upon that data today in terms of some of those patients who have even approached 600 days, I think we are very encouraged by what we're seeing over there. And I think with a trial that's continuing to enroll, we are taking data at certain -- we've taken a snapshot of the data at a specific time. And so I think once -- we've now enrolled all these patients, let's give it some time, let's get the data accumulated from all the patients. And at that point, we can report what the final PFS and overall survival rates are. But just based upon what we've seen, we can see that this appears to be differentiating from what has been reported in other trials. So we are highly encouraged and we are very optimistic, but just waiting to see what those final numbers will be, so we can -- we'll have those final numbers as we -- and that should come in parallel once we've started the Phase III clinical trial, as I mentioned, by sometime in the first half of next year.

Our next questions come from the line of Joe Pantginis with H.C. Wainwright.

So Frank, obviously, the -- we think the picture speak volumes. And I'd like to link the spider plot with some of your earlier comments that you touched upon with regard to mechanism of action and maybe get a little more emphasis on it as well. So this -- the way we view it is that this spider plot really box against the conventional thinking of I/O that would need to see responses evolve over much longer time periods. But the fact that you're seeing these T-cells come in within 14 days and see such rapid responses, just hoping you could link that a little more to the mechanism of action versus typical I/O thinking?

Joe, thanks a lot for the question. Yes, I think that's something that we have really -- we've analyzed and seen. So based upon the mechanism of action, one of the key things that our technology is able to do, as we've discussed before, is really recruit a large number of T-cells pretty rapidly by effectively presenting these tumor-specific antigens into the right presentation and processing compartments of the immune system, but simultaneously activate the Type 1 interferon signaling pathway, which is a critical immune activating pathway for CD8 and CD4 T-cells. By being able to perform this function pretty rapidly, we see that we're able to generate a pretty rapid antitumor response. And actually, when we met with the FDA, Dr. Katharine Price from Mayo Clinic, she was at us at that meeting with the FDA. And one of the things she mentioned was that when she puts patients on other treatments like checkpoint inhibitors, for example, it takes quite a while for her to even be able to determine whether or not that patient is going to be a responder. However, with the combination of PDS0101 and KEYTRUDA, she sees those responses occur pretty rapidly and what's also very interesting or encouraging to hear was also the tolerability of the combination and that the patients really like getting on this combination. And so based upon that mechanism of action, the 2 key things. One of the reasons why we give just 4 doses and don't have to continuously dose the patients multiple times is because of this rapid induction of the immune response. And also very importantly, the mechanism of action leads to a memory T-cell response. And so by generating that memory T-cell response with the PDS0101 monotherapy study, we saw that memory T-cell response to be generated after the -- by the third dose, right? And so we give a subsequent fourth dose. But again, we don't have to continuously dose the patient and the fifth dose on Cycle 12 is really given to re-boost that memory response, just in case that memory response is waning in some patients, we could then boost that response. So if you look at the spider plot, that rapid T-cell induction. If T-cells are being generated and T-cells are actively infiltrating the patient's tumors as we saw at SITC last year, we would expect that if those T-cells are active, we should start to see rapid shrinkage of those tumors. And that's exactly what we've seen. The other thing that we seem to be able to achieve here is even after inducing tumor shrinkage, we are able to induce a durable response, and we believe that's due to the fact that the patients are generating or developing a memory T-cell response. So the body's immune system continues to recognize that foreign agents and continues to fight against that foreign agent, therefore, prolonging not only the durability, but also the survival of the patient. So we believe this is directly linked to the mechanism by which PDS0101 is acting. And also what's very encouraging is the fact that we're seeing this across multiple trials, right, very consistent with the cervical cancer trial, where they show those T-cells actually very rapidly infiltrating the patient's tumors. And also the National Cancer Institute study, where they show that even terminally ill patients who have failed all treatment options were generating large quantities of these multifunctional HPV-specific T-cells. It's again, very consistent across the trials we're running today, which is also very important on investigational immunotherapy.

That's great, Frank. Appreciate all the color. I think it's really important and looking forward to the start of VERSATILE-003.

[Operator Instructions] Our next questions come from the line of Robert LeBoyer with Noble Capital Markets.

Congratulations on the data. My question has to do with the pattern and the response that you see and whether the tumor shrinkage followed by return of growth of the tumor is something that's common that would result in a sawtooth pattern or whether it's more of a steady decline and just what the tumor is actually doing over the course of the therapy?

Well, thanks, Robert, for the question. I will attempt to answer that, and I'll also let Lauren add if there's anything I missed that she would like to add. Every patient is different. Some patients are going to generate stronger immune responses than others and other patients' tumors are probably going to find ways to eventually start to evade immune attack. That's just the way cancer behaves. Some patients may be a lot sicker, may have much weaker immune responses than others, right? So we see significant differences in the way these patients respond to treatment. However, what's notable here is as we compare to the KEYNOTE-048 studies is the number of patients who are seeing tumor shrinkage, almost 70% of patients seeing tumor shrinkage, which suggests that a really large percentage of these patients are having clinical responses to the combination. But in addition to that, not only the percentage of patients who are responding, but how long these patients are continuing to have these clinical responses, right? And so that's something also very notable that we've seen here that we believe is differentiating. But in terms of one of the key things we've noted also is that a patient just having progressive disease hasn't necessarily translated to the patient not surviving. If you look at our swimmers plot, there are many patients who have been identified with progressive disease, but who continue to thrive and continue to do very well. Now one of the things that we have seen in our preclinical studies is what we call pseudoprogression, right? And so as T-cells infiltrate tumors, the tumors may swell initially, but then we see a rapid decline, right? That's something that's very difficult to prove in humans, right? But the fact that patients who may see some disease progression continue to thrive and do really well tells us that the combination is actually changing the immunology of the tumors and how the tumors behave. And therefore, even if the tumor is progressing, it appears to be progressing at a much slower rate, right? And therefore, the patients continue to live much longer. And so all these lead us to be highly encouraged about the ultimate goal that we're trying to achieve here, which is keep the patients alive, have the patients live a high-quality life and also make it -- a therapy that is very well at least well tolerated within the standards of oncology treatment, right? That's our ultimate goal. Today, everybody thinks about improved efficacy in cancer has to come with increased toxicity. What we are showing here is that we have the potential to improve therapy and survival with a combination of therapy that is actually quite well tolerated and on which the patients can live high-quality lives. I think that's what we're seeing with the results that we've presented to date. Lauren, is there anything on your end that you think I might have missed, that you'd like to add?

No, Frank, I think you've covered it all. We really have not seen any [Technical Difficulty] had a kind of sawtooth progression, increase in -- shrinkage of tumor, increasing tumor, shrinkage of tumor. You've highlighted the fact that, yes, there are -- is a great deal of variability in terms of the connects of tumor shrinkage among individuals based on their ability to mount an immune response. But we are seeing this consistent tumor shrinkage that then is prolonged. And that is contributing, I believe, strongly to the overall survival trends that we're seeing. Importantly, we do want to try and get at the issue of pseudoprogression. We know that that it rarely occurs in head and neck cancer. We have had an investigator report to us one case of pseudoprogression to date. So we're continuing to monitor for that. We're also trying to explore tumor growth rate kinetics that may help us understand tumor growth rates and impacts of PDS0101 and KEYTRUDA combination therapy on the tumor growth rates because if there's not only tumor shrinkage, but also slowing of the ability of tumors to grow based on the tumor-specific responses that are induced by the combination, that again would lead to prolonged and more sustained and durable responses. I thought the question might come up regarding the median duration of response. And for those individuals who have been responded in this data set, the median duration of response is actually not estimable with a lower 95% confidence down of 9.5 months in the upper confidence interval not [Technical Difficulty]. I think the data is consistent in what we're observing in terms of PFS and overall survival and tumor shrinkage. And just to throw back to Joe's comment about the mechanism of action, we have preliminarily confirmed in VERSATILE-002 subjects that we see induction of HPV16 specific CD8 and CD4 T-cell responses that are multifunctional and hope to be able to present at a scientific meeting later this year any potential correlation of those multifunctional responses with clinical outcomes.

Okay. Great. You just answered my follow-up question. So the other thing I was going to ask is whether there are any updates on the triple therapy trial design since the last -- just the last mention of it?

Frank?

Sorry, Robert. For some reason I thought Lauren was taking that. So no, there are no updates to our triple combination study design at this time.

Our next questions come from the line of Kalpit Patel with B. Riley.

One more question on that waterfall plot. On that footnote, it says 4 patients experienced unconfirmed tumor shrinkage and subsequently experienced PD. Can you point out in the plot which 4 patients those are?

Yes. So Kalpit, you'll notice that there are 4 patients below the baseline who are colored in red. Only 2 of them had an objective response. So they are 2 who had tumor shrinkage, but not an objective response. So those other 2 are not even in the discussion for confirmed or unconfirmed objective responses. They just had some tumor shrinkage and then subsequently saw some increase in their tumors again, right? So you'll see that 2 are below the 30% tumor shrinkage line and 2 are above the 30% shrinkage line. Those above the 30% shrinkage line are considered stable disease and not PR. So those would not be involved in either a confirmed or unconfirmed objective response.

So the 4 red bars that are pointing downwards that you're referring to, correct?

The 4 red bars that are pointing downwards exactly. Those are the 4 who had tumor shrinkage and then became a PD after they showed some increase in their tumor size. So remember, Kalpit, as I explained earlier, so long as you have a 20% increase over your best response, you'll be considered PD in using our approach even if your tumor size is significantly lower than the 30% shrinkage. But we also have to -- there's -- also have to distinguish between those who have tumor shrinkage and are stable disease versus those who have tumor shrinkage and have an objective response, which is greater than 30%, right? So there's a key distinction between those 2 populations.

Okay. I just -- maybe we can take it offline, but I don't see the purpose of why you would include those 2 patients and sort of highlight them that didn't reach 30%, but any more clarity there would be useful.

I think we're just trying to be very transparent with everyone, right? Yes, we want to make people understand this. Yes, they're still stable disease or the other 2 still have -- are still stable disease and the other 2 have tumor shrinkage greater than 30%. However, according to RECIST 1.1 for the best objective response that we are following, we will characterize anybody who has a tumor size increase of greater than 20% as progressive disease. And we're just trying to be extremely transparent as to how we are characterizing these patients and how they are responding.

There are no further questions at this time. I would now like to hand the call back over to management for any closing comments.

Thank you very much. So to all who attended our call today, we appreciate you joining today's conference call. We are extremely pleased with the response to our data presented at ASCO this year and also our continued progress. We continue to be excited about our upcoming milestones, and we look forward to continuing to update you on our progress. I wish you all a great week, and thank you very much.

Thank you. This does conclude today's teleconference. We appreciate your participation. You may disconnect your lines at this time. Enjoy the rest of your day.