Welcome to HOOKIPA HB-200 Clinical Trial Update. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would like now to turn the conference over to Michael Kaiser, Head of Investor Relations. Please go ahead.
Thank you for joining HOOKIPA's HB-200 pivotal phase II/II trial update call. Today's call will contain forward-looking statements. These statements are subject to risks and uncertainties which may cause actual results to differ materially. For a description of these risks and uncertainties, please refer to HOOKIPA's annual report on Form 10-K and quarterly reports on Form 10-Q, as updated periodically along with other SEC filings. Contents of this call are based on the current beliefs of HOOKIPA's management team and key opinion leaders as of April 25th, 2024.
The company disclaims any obligation to update any statements to reflect events or circumstances after the date of this call. This call is being recorded, and a replay along with the presentation slides will be available on the Investor Relations section of the company's website later today. I will now turn the call over to Joern Aldag, Chief Executive Officer of HOOKIPA Pharma.
Hi. Thank you all for joining us today. It's a great pleasure to have you on this call. We want to share with you our targeted plan for HB-200 clinical program, which we think is exciting: a seamless, pivotal phase II/III clinical trial for treatment of patients with HPV-16-positive head and neck cancer. You have several distinct speakers with you today. After my introduction, I will hand over to Dr. Alan Ho, a head and neck oncologist at Memorial Sloan Kettering Cancer Center and a trial investigator, and to Dr. Ilian Tchakov, the Head of Clinical Oncology at HOOKIPA.
Both will share with you their perspectives on HPV-positive head and neck cancer, on treatment options and needs of patients, and how we think HB-200 will become a powerful option for treating head and neck cancer. Then you will hear from our new Chief Development Officer, Dr. Mark Winderlich, what our clinical trial plan looks like and how we will execute. Over recent months, we have continued to build our advantage. We have a well-defined and clear path to registration for our lead program, HB-200.
Our phase II data for HB-200, in combination with pembrolizumab, are convincing and show the potential for being best in our field. Our combination with pembrolizumab has doubled the response rates when compared to standard of care alone, pembrolizumab. We achieved this successful combination without adding toxicity, which is important. At ASCO, we will give you a presentation where you will receive an update covering efficacy data for approximately 40 patients, as promised. We have defined a fast path to registration. This entails focus on an initial patient population most in need and, importantly, most likely to make the trial successful. We had very constructive interactions with the regulators.
We have aligned with the FDA on a seamless, pivotal phase II/III trial design and protocol. We plan to have our primary phase II readout in 2026, with subsequent filing for accelerated approval based on objective response rates. Also, the HB-200 program was granted Priority Medicines Designation, or PRIME, by the European Medicines Agency. All of this shows our potential to address a significant unmet need for patients with HPV-16 positive head and neck cancer. In our patient-centric clinical development strategy, HPV-16 positive oropharyngeal cancers are a logical first step for HOOKIPA. There is an increasing incidence of this cancer diagnosis each year.
Currently, there are no targeted therapeutic options for patients with HPV-positive oropharyngeal cancers, despite the uniqueness of HPV-driven disease. And there are ample opportunities to go beyond head and neck cancers with our cancer vaccine. This focused oncology strategy starts with oropharyngeal head and neck cancers. It represents a sequential opportunity for future expansion. We believe we are in the lead position for the first-line treatment in combination with pembrolizumab for oropharyngeal cancers and HPV-positive head and neck cancers.
As you see on the bottom of the slide, the potential addressable market of our upcoming registration or trial is meaningful. We believe this market alone presents an opportunity of more than $500 million worldwide. This addressable market grows rapidly, and it provides additional growth potential. Beyond the first-line setting for OPSCC, it's the abbreviation for oropharyngeal cancers, there is a natural path to expand within the HPV-positive head and neck space for different ranges of PD-L1 CPS, for other head and neck first-line treatments and locally advanced disease, and also for later-line treatment settings. From there, HB-200 can become a tailored treatment option for other HPV-positive cancers in multiple organs beyond head and neck.
It is estimated that each year there are approximately 100,000 new cases globally that could benefit from an HPV-targeted treatment such as HB-200. HPV-positive cancer therapeutics have, in our mind, blockbuster potential. Ultimately, we believe that our RNA virus platform can be applied in different disease areas and for a broad array of antigens. This includes programs such as our KRAS mutated tumor program, for which the FDA cleared the IND just last week. We have large aspirations in clinical oncology. I will now turn the call over to Dr. Alan Ho of Memorial Sloan Kettering Cancer Center and Dr. Ilian Tchakov, HOOKIPA's Head of Clinical Oncology. Dr. Ho.
Good morning. Yes, thank you so much. I'm very happy to be here today. What I'll review is a little bit of the background and the state-of-the-art management of recurrent metastatic head and neck cancers, and also the opportunities that the HB-200 program has for really changing meaningfully the standard of care for our patients. As was depicted on the prior slides, certainly HPV-driven disease is now the most common head and neck cancer that we manage and treat in the clinic, representing more than 70% of all oropharyngeal carcinomas. And by far, HPV-16 is the most predominant serological type that's responsible for HPV-driven head and neck cancers. And indeed, E6 and E7 expression, the viral oncoproteins from that virus, are essential for maintaining malignant transformation and phenotype of these tumors.
And so, because of that, HPV-driven head and neck cancers is really a unique biologic and clinical entity in head and neck disease, distinct from HPV-negative tumors that are really the etiologies of which are really alcohol and tobacco-related. And that extends to unique mechanisms by which the HPV virus helps the cancers evade immune detection, as depicted on the cartoon on the right. Specifically, the two predominant mechanisms that are addressed by the HB-200 program are the ability of the HPV viral oncoproteins to diminish antigen presentation and increase T-cell exhaustion, specifically by increasing PD-L1 expression. So, there's no question that the development of anti-PD-1 therapy with pembrolizumab, which now is the standard first-line option for recurrent metastatic head and neck cancer, irregardless of HPV status, was a paradigm-shifting observation and discovery in the field.
But as this slide depicts, there are also strong limitations to the efficacy of pembrolizumab-based therapies for our patients. So, currently, for patients who have PD-L1 expression that's CPS 1 or higher, pembrolizumab alone or pembrolizumab plus chemotherapy can be used. And for patients, irregardless of their CPS, pembrolizumab plus chemotherapy is also an option. Now, a lot of the benefit of these immunotherapy-based approaches is really rooted in the remarkable duration of response that's achieved with pembrolizumab therapies. You can see this in the pembrolizumab monotherapy arm. So, you can see in the second box here, the median duration of response achieved with pembrolizumab monotherapy is 23.4 months, really a remarkable historic type of duration of response we've seen for therapies in this disease.
But the problem or limitation here is depicted in the table on the left, where you can see whether in the total population or in the population with CPS of 20 or greater or CPS of 1 or greater, that the overall response rate is quite modest, ranging from 19%-23% in the PD-L1 positive tumors. And even more importantly, the rates at which progression was the best response achieved with pembrolizumab was as high as 39% in the CPS 1 or higher, demonstrating that, in fact, the majority of patients are really not garnering any benefit at all to immunotherapy-based approaches in the patients that we treat.
And so, indeed, in the second line, you can see that adding chemotherapy certainly increases the response rate that's comparable to the control arm, which is the third line, chemo plus rituximab, but really at the cost of increased toxicities, as you can see in the third box to the right, where 72% of the patients with pembrolizumab plus chemotherapy had grade three or higher treatment-related adverse events compared to only 17% with pembrolizumab. And additionally, if you go back to the second box with the median duration of response numbers, the median duration of response among the patients who got chemo plus pembrolizumab in that second line is only 6.7 months, again, compared to 23.4 months. And so, what this suggests is that the added responses we're getting with chemotherapy are likely not immune-based.
That's important because it's really the immune-based responses that we predict or hypothesize are really the most impactful for imparting a survival benefit with our immune-based therapies. This really illustrates then that while these are paradigm-shifting observations and really important advances for our patients, there's much room for improvement with immunotherapy-based combinations. Now having seen the nuances of the efficacy data and the safety data seen with pembrolizumab alone or pembrolizumab chemotherapy, you can understand now that the clinical decision-making that we had that it encountered with our patients really has to take into consideration multiple factors, not only PD-L1 status, but also multiple tumor and patient characteristic factors that are kind of depicted on this slide. On the leftmost, of course, is the CPS score, the PD-L1 status, as we've discussed.
If you turn your attention to the gray column on the left that lists all the different other patient and tumor factors that we have to consider. So, clinical presentation and tumor burden. So, what this really references is that patients who have tumors in really high-risk areas in the neck, for instance, encasing the carotid or ulcerating or protruding through the skin or is rapidly progressive or causing tremendous pain, the low response rate with pembrolizumab alone really does not make that a viable treatment option for those patients. We have to, in those cases, turn to the chemotherapy plus pembrolizumab option to really ensure that we're going to get a response rate and decrease the rate at which progression is best response in those patients. In the third box, you see there's treatment toxicity and other comorbidities.
So, again, even in those patients where we have really advanced and fast-paced tumors and we want to use chemotherapy, in some patients, that's just not possible, where their performance status is not high enough to really tolerate the grade three toxicities we see with chemotherapy. And lastly, and even more importantly, is patient preference. There's a huge movement in the field, both among patients and physicians, to really find chemo-free options for the treatment of our patients, to impart greater immunotherapy benefit to more of our patients that is devoid of the toxicities we see with chemotherapy.
And so, as you can see with KEYNOTE-048 data, the efficacy and toxicity data, we have to go through all these different tumor and patient factors when deciding what's the optimal treatment for our patients. But listed among them is not HPV status. So, currently, despite the fact that it's well recognized that HPV-driven head and neck cancers is a distinct and unique biologic and clinical entity, HPV status currently does not enter into our decision-making for which immunotherapy approach should be utilized.
And so, there's real biologic and clinical opportunity here to develop more effective treatments for these HPV-driven head and neck cancers that are safe and effective. So, that brings me to the current HB-200 study. We've been really fortunate at Memorial to have been involved in the early development of this program and really been happy. And really, it's really been profoundly satisfying to be a part of this. So, this includes the first phase I monotherapy evaluation of HB-200, where the primary endpoint was really identifying the recommended phase II dose of the 2-vector therapy.
The secondary endpoints were the safety and preliminary anti-tumor activity and, of course, immunogenicity and other immune-based biomarkers were evaluated in the exploratory objective. So, in this phase I, which was done in previously treated HPV-16 positive head and neck cancer patients, we were really satisfied to see that there was really good anti-tumor activity and tumor regressions and even surprisingly promising survival outcomes in these patients just treated with the viral vaccine alone. This then led to the current phase II trial that's now accruing, where we're combining HB-200 with pembrolizumab in patients with PD-L1 positive head and neck cancers, looking at a primary endpoint of overall response by RECIST and secondary endpoints of safety, duration of response by RECIST, and then the exploratory objectives endpoints of immunogenicity and biomarkers.
And this is the data that will be shared in just a few minutes. Now, with regards to the safety profile observed in the phase I and phase II trial thus far, these are all listed here. Suffice it to say that the viral vaccine alone in combination with pembrolizumab has been extraordinarily well tolerated. Really, the predominant adverse event that we've observed in clinic is quite manageable flu-like symptoms that occur within a day of the administration of the first dose of the viral vaccine that's well managed with antipyretics and supportive care. Interestingly, the severity of those events do not recur with subsequent viral vaccine administrations. It seems to be the most severe with the first dose.
Upon subsequent doses, either it doesn't occur at all or occurs at a very low grade. It also goes without saying that we haven't seen any enhancement of other immune-related adverse events in combination with pembrolizumab. So, indeed, this combination certainly reaches the bar of being a safe immunotherapeutic approach that really avoids the chemotherapy grade three adverse events we saw with chemotherapy. With that, I'll just hand it over to Ilian.
Thank you, Dr. Ho. I would like to start with a brief summary of the T cell data in these patients. Our engineered RNA virus platform is designed specifically to drive targeted anti-tumor responses. Efficient induction of tumor-specific T cells has been a longstanding goal of immunotherapy, and our mechanism has consistently demonstrated best-in-class, safe, powerful, and specific T cell activation against target antigens. On the left-hand side here, we see the percent increase of antigen-specific T cells in the blood for patients. The data show unprecedented tumor-specific CD8+ T cell induction in this sense. On the right, you see the increase is very quick and continuous in high-level, durable, non-exhausted tumor-specific T cells that also increase functionality over time. All of this is the basis of our clinical activity. These are the data that we reported at last ASCO.
We will share some further insight. Here, we're seeing a consistent and meaningful overall response rate improvement over standards of care therapy. The historical RR observed in patients treated with pembrolizumab alone ranges from 19%-24% and a disease control rate of 40%-47%, as observed and reported in KEYNOTE-12 and the KEYNOTE-048 studies. In 20 patients, 19 were evaluable, defined as having at least two or more scans. Responses were all confirmed and assessed by RECIST 1.1, which was, in fact, the primary endpoint of this part of the study. And for the overall ITT population, the confirmed objective response rate was 40%, while for the evaluable, this was 42% here. The disease control rate was 74%.
Now, if you take a closer look at the subset of patients who had a PD-L1 CPS score of 20 or greater, the overall response rate improved to approximately 60%, including one CR and five partial responses. Please note, in this group, we have a disease control rate of 100%. And from a medical perspective, being able to provide such positive outcomes with an immunotherapy combination for more than 50% of patients in this treatment setting would represent a significant step forward and a compelling treatment option. This is the basis of our patient selection decision for phase II/III pivotal study. And as our initial data matures, it continues to be very consistent. For these ESMO patients, we now have a significant extension of the observation period by seven months to March 2024, which we show here.
Now, on this spider plot, we have marked the individual patients by CPS, with CPS 1-19 shown in red and CPS 20 or greater in blue. We can see that not only are the responses and control of disease more pronounced and deeper in patients with higher CPS scores, but we also continue to see that they are much faster. This is very important for patients and for the control of their disease. And our data suggests that this is an immunogenic tumor death. And as Dr. Ho indicated, this is important for the durability of responses and for expecting longer survival outcomes. Now, with regards to overall survival, data are still maturing. The median follow-up time for this group is 14 months at the moment. And 18 out of the 20 patients are still alive, which is very promising.
These 20 patients, as well as the totality of our data, in fact, provide the strong support to move forward with phase II/III trial, focused specifically on these patients with higher PD-L1 CPS ≥20. On with the safety. Dr. Ho already took you through the overall safety profile for the study population and his clinical perspective. So here, I would like to summarize the safety data specifically for first-line patients treated with HB-200 and pembrolizumab. The most common treatment-related reported adverse events are flu-like symptoms, mostly through the first treatment cycle, which is consistent with what you would expect for this vaccine-like mechanism.
There were very few severe treatment-related adverse events, with only one treatment-related adverse event leading to discontinuation, which was a grade three pembrolizumab-related pneumonitis. And we will have additional safety data at ASCO. But we're already looking at a consistent and favorable safety and tolerability profile with no apparent other toxicity to pembrolizumab alone. With this, I would like to pass back to Dr. Ho, who will show you an example with one of his patients treated with HB-200 and pembrolizumab.
Yeah. I just want to share with you one of the cases that was treated at Memorial Sloan Kettering on the clinical trial that's reflective of the safety and efficacy profile that we've been observing. So this was a 66-year-old man, white, nonsmoker. He had an oropharyngeal carcinoma that was stage two when it was first initially diagnosed and got standard chemoradiation but quickly had multiple neck relapses that were addressed with surgical resection and one course of reirradiation and finally did develop lung metastases almost two years more than two years later after his initial diagnosis.
Now, his tumor had a PD-L1 CPS of 30, and he had a very good performance status, ECOG of 0. So he started treated on HB-200 plus pembrolizumab. As you can see on this graph here, very quickly after six weeks of therapy, he achieved a partial response. I believe it was a 44% regression in the target lesions. Then on the subsequent scan at 12 weeks, he already achieved a complete response that remains sustained to this day. So total time on treatment now has been 299 days with a complete response, and it's ongoing.
And he's tolerating it quite well. Almost all of his AEs have only been grade one. And you can see here the structural responses seen on the scans in these mediastinal lymph nodes that have now returned to normal size. So really kind of illustrated with the fact that in this patient with difficult and aggressive disease, that the combination has been well tolerated and quite effective. So really, in conclusion, we at Memorial have been quite impressed by the results so far with HB-200 plus pembrolizumab in the first-line setting.
We really believe that there is an opportunity here to make a significant change in the standard of care for our patients as the first targeted HPV-16 positive immunotherapy combination, given the fact that we've seen really encouraging response rates and response durability, illustrating that these indeed, of course, as you might hypothesize, are immune-based or immunogenic tumor cell death-related responses. Overall, the tolerability of the combination has been extraordinarily promising. It illustrated above really this unmet need in the field and the excitement in the field to develop HPV-directed immunotherapy-based combinations was we were happy to receive the notification that the abstract detailing the HB-200 plus pembrolizumab data has been selected for an oral presentation at ASCO, which we really look forward to.
Thank you, Dr. Ho. Thank you, Ilian. It's my pleasure now to introduce our new Chief Development Officer, Mark Winderlich, to you. Mark brings tremendous experience across the drug development cycle from early preclinical development through to regulatory approval in both the U.S. and in Europe. He's managed several programs, starting in discovery through to commercialization. We're fortunate to have added him to our team. Now I will let Mark introduce himself and talk you through the great design of our clinical trial.
Thank you, Joern. It's a pleasure to introduce myself to you today. As Joern said, I'm new to the HOOKIPA team, and many reasons actually attracted me to HOOKIPA. First, it's the science behind the HOOKIPA platform. I think it's the best-in-class cancer vaccination technology and has the potential to be the backbone for many therapies in the future. Second, as you just have heard, the clinical results of HB200 are very compelling and show that it has a high potential to become an approved drug, which makes a true difference for patients. I'm now very excited to share with you our HB200 registration strategy and how we envision to execute our strategy. I have been deeply involved in the trial design process with the team since December of last year.
We just had a Type C meeting with the FDA and are happy to share that the design and the protocol were aligned with the FDA. This alignment includes the path for potential accelerated approval. We have designed a seamless and adaptive double-blinded phase II/III trial for the first-line treatment of patients with oropharyngeal squamous cell carcinoma. Key eligibility criteria are recurrent or metastatic disease, HPV positivity, and a PD-L1 expression with a combined positive score of 20 or higher, which gives us the highest probability of trial success. In total, 250 patients will be randomized 1:1 to either HB-200 plus pembrolizumab or placebo plus pembrolizumab.
Overall response rate is the primary endpoint of the phase II part with approximately 50% of the study participants and the attempt of submission for potential accelerated approval. The anticipated analysis time point is 2026. The primary endpoint of the phase III part of the trial is overall survival, and the anticipated analysis time point here is 2028 for a subsequent submission and potential for full approval. We are just now actively qualifying clinical trial sites, and we are on track to enroll our first patient in the fourth quarter of this year.
So in summary, you have heard from Dr. Ho and members of our management team today. HB-200 is a novel, first-in-class cancer vaccine for HPV positive malignancies. We start with head and neck cancer, where a high significant unmet need for a disease-specific therapeutic exists. HB-200 has the potential to deliver just that. The data you have seen today and what you will see at ASCO just in a couple of weeks show that we have a drug candidate that shows a meaningful improvement over standard of care pembrolizumab monotherapy.
Our phase II/III clinical trial and the selected patient population gives us the highest probability of success and a fast way of getting HB-200 to patients in need. Importantly, the design and the protocol is aligned with our regulators, so we have a clear path through registration that includes the potential for the accelerated approval. We are just at the beginning. Our arenavirus cancer vaccination platform can serve as a backbone for future oncology indications, and we want to unlock the full potential of it. We are excited for the year ahead. I'm personally looking forward to leading our great clinical development team here at HOOKIPA.
Our next significant readout will be the combination data update presented at ASCO by Dr. Ho, as said, on approximately 40 patients. The date and time details of the presentation, you can see it here on the screen, but you can also look it up in our press release that was issued earlier today. With that, I will turn the call over to the operator for Q&A. Thanks a lot.
Thanks, Mark.
Thank you. As a reminder to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from Nevin Wergies with RBC Capital Markets. Your line is open.
Hi, everyone. Thanks for taking my question. This is Nevin with Brian Abrahams team at RBC Capital. Just had a quick question on why you all decided to pursue oropharyngeal as a subset of cancers that you were looking at within head and neck. Is that a subset that you saw more efficacy from within the initial subgroup or within the head and neck trials that we'll see updated data for at ASCO? And if so, what did that efficacy look like within that subgroup? And then additionally, what are your thoughts about whether you're going to pursue some of these pivotal trials on your own or perhaps partnering for this effort? Thank you.
Ilian?
Hi. Thank you for the question. This is Ilian Tchakov. Why oropharyngeal cancer first, and then maybe for the second part, I can hand over to Joern Aldag. We have recruited the majority of our patients, in fact, more than 95% of oropharyngeal cancer. In addition, we know that this histological, this anatomical subtype of head and neck cancer is pathogenetically linked to HPV disease as a driver. And in discussions also with the regulatory authorities and our design, this was their recommendation as well, which we have, for both these reasons, taken into phase II/III trial.
Hi. This is Joern. You're also asking for partnering. And would we do this alone or partner the program? At this point in time, it's very clear that there is interest in the community looking at the data that we've shown to actually get their hands on HB-200 as a product for this specific group. We would obviously start this trial off on our own. And we've done all the preparations necessary to be able to execute on this trial without a partnership.
Having said that, you're probably also asking fundability. We're well funded, including all the steps that we need to do for HB-200 and getting it through the next couple of years. And therefore, there is no imminent need for us. Would we partner? In case that we get very, very, very good terms from someone, we would consider it. But as I said, we're prepared to go it alone.
Okay. Thank you so much.
One moment for the next question. The next question comes from Andrew Berens with Leerink. Your line is now open.
Hi. Thanks. And thank you for doing this presentation. A couple of questions for me, maybe one for the company or maybe the doctor. Wondering what you think about potentially exploring combination efforts that include any of the EGFR MABs or bispecifics. They tend to obviously respond well in HPV-negative patients but not as well in HPV-positive groups. And then maybe one for Dr. Ho. It seems like there's very little data for KEYTRUDA monotherapy activity in HPV-positive patients. Wondering if you could share any anecdotal experiences or point us to data in that regard. Do these patients that are HPV-positive, do they do better or worse on KEYTRUDA monotherapy, and how much?
I would like to turn the answer to this question over to Dr. Ho.
Yeah. So for the second question, absolutely that there aren't clear prospective comparisons in terms of outcomes with KEYTRUDA monotherapy in HPV-positive versus negative. But if you take an aggregate, what has been reported in some of the smaller prospective studies, institutional data, including our own, my impression is, in fact, the HPV-positive patients do slightly better with pembrolizumab monotherapy compared to negative, but in a modest incremental way. And in fact, probably the KEYNOTE-12 data that separates out p16-positive versus p16-negative patient outcomes is probably most illustrative, where the response rate to pembrolizumab alone in that patient population, HPV-positive patients, was only about 25%. So my impression is it probably is a little bit there is probably a little higher efficacy in the HPV-positive patient population, but in an incremental, modest way.
And then with regards to the EGFR targeting, it's an interesting idea. I'm actually not sure because indeed, when you look across all different EGFR-targeted antibody approaches, including the more recent bispecific data, absolutely correct that much of the clinical benefit is enriched in HPV-negative patient population. The mechanisms by which, honestly, I'm not really clear on. So even though we've seen these patterns and the fact that they're less effective in the HPV-positive patients, and that's clear now with cetuximab and the other EGFR bispecifics, whether or not a combination with the viral vaccine is actually mechanistically rational, I'd have to go back and look. But there may be an opportunity where combining EGFR with other agents may overcome that disparity in efficacy between the groups.
Okay. And if maybe, could I squeeze one more? And I got disconnected. With the trial design, I'm assuming that eventually, you'll have to show a survival benefit in the earlier line, the front line. We've seen some trials recently, like the LEAP-010 trial, where response rates didn't translate into survival benefits. Just wondering about your thoughts there. Is it that KEYTRUDA monotherapy doesn't get formal responses in more than one out of five patients, but a large portion of patients get stable disease, and that contributes to survival? Or is there something else going on there? How difficult do you think it is to be KEYTRUDA in a survival head-to-head?
Yeah. I think the LEAP-010 data is very important and instructive for developing in this setting, specifically because it's not only about response, but what is the mechanistic basis of that response, I think, is important. So this is all highly speculative. But this is why I'm more excited about the data we just presented because we know that those are immune-based responses. So it's only about the response, but the durability of those responses. And those really are rooted typically in immune-based or immunogenic cell death. So here, we've got a total immunotherapy-based approach giving us these higher response rates and impressive duration of responses.
And so when we see the higher response rates or even the PFS benefits with different combinations, when one of the agents may not be working through immune-based mechanisms, you're left to kind of tease out how much of that is immune-based and how much of that is going to really translate to survival. That's one thing. And the second issue is toxicity. I mean, so having worked with that combination in a variety of different clinical trials that were not in the head and neck squamous setting, toxicity is a very important factor here. These are patients that quickly get quite toxed out and struggle with performance status. Excuse me. Sorry. So their ability to make it through toxic therapy is more limited and then also influences their ability to really tolerate second-line and beyond treatments.
So if you're compromising a patient's performance stats with toxic combinations upfront, that may be another opportunity where the survival benefit where the response rate and the PFS benefit may not translate into survival benefit, given the fact that they aren't able to tolerate the combination and/or influences their ability to get subsequent treatments. So when you see those disparities, those are kind of some of the hypotheses that are kind of rambling around.
So that's why I think really important when we develop these phase II signals into phase II, phase III trials, that we try our best to really develop the ones that are immune-based responses and those that are tolerable for the patients. And so we've achieved both, I think, both of those things through this program, which is why I think it's promising. But yes, LEAP10 is very instructive in that way.
Great. Thank you for all the detail. Very helpful. Appreciate it. And congrats again, guys.
Yeah. And if I may add to this, so all what Dr. Ho said was the basis, obviously, for our trial design, plus, of course, our own data we have observed so far with the overall response rate, disease control rate, durability of response, and the overall survival. So this was the basis for the trial design. Plus, as I said, it's an adaptive trial.
So when we are at the phase II primary readout and go for accelerated approval, we have already preliminary overall survival, but also the element of an adaptive module, which allows us to increase the sample size for the phase III confirmatory part if required. But as all information we have as of now and the data makes us feel very confident that we are sufficiently powered with the size of the trial as it is.
Okay. Great. Thanks.
One moment for the next question. The next question comes from Roy Buchanan with Citizens JMP. Your line is open.
Hey, great. Thanks for taking the questions. I guess to follow up on the last point, I think that was Mark, about the trial design. Can you just tell us a bit more about what you need to hit in the phase II as far as the response rate delta to be able to file? Just what's the powering and end design around that? Thanks.
Yeah. The basis for the power is obviously what we expect for the control arm. And there, there are many historical trials of pembrolizumab monotherapy in HPV-positive subgroup and CPS20 subgroup. Dr. Ho said KEYNOTE-048, KEYNOTE-012 gives us a good understanding of what this basis is. And then our own data, we observe in our phase II, what we presented to you today and what we will present at ASCO to you is what we assume for the target overall response rate. Of course, with a, so to say, statistical buffer, let's say, that we can have a statistical significance for the clinically meaningful effect and overall response rate. Plus, of course, it will be the totality of evidence. We will also submit the other endpoints, which we also endpoint data, which we also feel very comfortable about.
Okay. Great. And then it sounds like the CPS above 20 cutoff was your suggestion, I guess, and the FDA accepted it. Is that correct? And you have a couple of patients that actually have pretty durable responses with a CPS of 1 in the phase I/II . I guess, is there going to be any option for those patients? Are you going to keep the phase I/II going?
Yeah. You're correct. We're seeing some good responses also in the CPS 1-19. We wanted to make sure with this trial that we get the highest probability of success and the fastest path forward. And the data that we're seeing suggests that the CPS larger 20 will give us all that. Having said that, we also really clearly see that there are some responses in the one to 19, which means that we will be developing a path forward at some point in time for that patient population as well. But to get to a result, a positive result fast, this design is the best we could find.
Okay. Great. And then last one for me, the ASCO presentation about 40 frontline patients. How many do you expect to have circulating T cell and/or tumor DNA data for? Thanks.
This is Ilian. Thank you. We expect to continue to collect those data from this current set where we have for the most patients. So we expect that we will also have T cell data at ASCO as well.
Okay. Great. About how many patients can we expect? Half, or?
We guided to around 40.
40 patients in total, and approximately half of them with selected biomarker data we would like to present.
Okay. Great. Thank you.
One moment for the next question. The next question comes from Arthur He with H.C. Wainwright. Your line is open.
Hey. Good morning, everyone. Thanks for hosting this. Just a quick question regarding the updated HB-200 data. Could you tell us, within the first 20 patients enrolled, how many patients still remain under treatment?
This is Mark speaking. The majority of our responders in this set of the first 20 patients are ongoing, so have a durable response, which is really exciting. Exact numbers, we would like then to report and publish at ASCO for the new data cutoff.
Thanks, Mark. My second question is, we were thinking about beyond the first line of the head and neck. Do you have any plan, or what's the broadest development strategy for that setting?
So focus strategy means we're focusing on what will get us the highest probability of success in the shortest period of time. And that's what we're doing. At this point in time, we're very clear that we're looking at the CPS ≥ 20 and that we're trying to get to a result. Having said that, we full well know that there are opportunities beyond that group that we're looking at initially. And those include first-line settings, second-line, also earlier-line settings, neoadjuvant and adjuvant, where you could think that even alone, a vaccine like ours could have potential. And then you can also look at other organs that are HPV-positive infected and expand in that direction as well. So at this point in time, focus. And regarding the development plans, Mark will add.
Yeah. And we are very happy that we, as we go already collecting data in the adjuvant and neoadjuvant setting for local regional head and neck cancer, you may have seen that we have a presentation with the University of Chicago investigator-initiated trial at ASCO as well. And this exactly goes into this direction and will inform the further development path.
Great. Thanks for taking my question.
One moment for the next question. Our next question comes from Asthika Goonewardene with Truist. Your line is open.
Hey. Good morning, guys. And thanks for taking my questions. I got a couple for Dr. Ho, if I may. Dr. Ho, we talked about the patients that you treat who maybe have a CPS above 1% but who may be intolerant to chemotherapy or have a preference not to have chemotherapy. Can you quantify that for us, please? About what proportion of those patients would be ineligible due to performance status or personal preference for chemotherapy?
And then when you think about Pembro monotherapy in kind of like the in this first-line setting, if you look at the KEYNOTE-048 data, 23-something% response rate for the monotherapy and about 15 months of overall survival. But this is a broader head and neck population. About 40% of the patients on KEYNOTE-048 were oropharyngeal. So in your clinical experience, does the oropharyngeal patients represent the data for Pembro monotherapy? Does that look like the rest of the overall rate? Thanks.
Yeah. So for that last question first, kind of as I talked about before, I think some of the limitations of the therapy still is reflected in our HPV-positive patients, despite the fact that even in our own retrospective data, as I mentioned, I do believe that pembrolizumab monotherapy has slightly greater efficacy in the HPV-positive patient population versus the HPV-negative, though I think the differences are probably more modest. And then to your first question, really hard to quantify. I mean, you might say that outright can't get any chemotherapy might be in that 10%-20% range.
But what's even more predominant there is patient preferences. I mean, we have so many patients that come to clinic that just outright refuse chemo because they really don't want to go through the grade three or higher adverse events that are seen. So even more so than the appetite in the field to develop these therapies, this is really coming from the patients where there really is a desire to avoid chemo. So the more common situation even is just them outright refusing it.
Dr. Ho, can you please quantify that first about what proportion just outright prefer not to, even though they might be?
Well, I think if you ask patients 100% would prefer not to have chemo. But there are situations where they outright refuse it despite the fact that it's recommended. That's probably a little bit higher than what I quoted in terms of not qualifying it, probably more in the 20%-30% range.
Great. Thank you very much.
One moment for the next question. Our next question comes from Chiara Montironi with Van Lanschot [crosstalk] .
Hello. Hello. Thanks for taking my question. I was wondering if you could remind us what to expect about the ASCO data, if it's going to be new data cuts? And then I was also wondering, what should we think about the cost of this trial? How is it going to ramp up in the next years?
Yeah. Sorry. Mark speaking. So ASCO data will be around 40 patients with a new data cutoff. Yes, exactly. So not only more patients, but also longer follow-up for duration of response and overall survival. And I think your second question was about the enrollment. So we have done a thorough feasibility, and we will enroll globally. So it will be a global study. And we will be on track to enroll or complete the enrollment to have for the phase II primary readout, which would be the basis for accelerated approval, in 2026. Did I understand this second part correctly?
In short, I was wondering more if you thought about the cost, if you can disclose anything?
Yeah. So roughly, we're expecting for the entire program, phase II/ III, to registration, about $100 million.
Okay. Thank you.
Welcome.
One moment for the next question. The final question comes from Roy Buchanan with Citizens JMP. Your line is now open.
Hey. Thanks for taking that really quick follow-up. Just the targeted HPV presentation at ASCO, do you know how many patients are going to be featured and if that's going to have intratumoral T cell data? Thanks.
This is Ilian. It will be around 20 patients. Yes, there will be T cell data.
Thank you.
Thank you.
I show no further questions at this time. I would now like to turn the call back to management for closing remarks.
Yeah. Thanks a lot for taking the time to participate in our call today. We're excited here for the prospects we have for the start of our pivotal clinical trial. We're obviously looking forward to great results to benefit our patients. Thanks a lot.
This concludes today's conference call. Thank you for your participation. You may now disconnect.