Good day, and welcome to Nanobiotix Study 1100 Data Update conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. Please be advised that today's conference is being recorded. At this point, I will turn the call over to Craig West, Senior Vice President of Investor Relations of Nanobiotix. Thank you. Good afternoon, and good morning, and welcome to the Nanobiotix conference call to discuss new data from our phase 1 IO combination study in head and neck cancer, presented at the ASCO 2024 conference this weekend. Joining me on the call today is Laurent Lévy, Co-founder and Chief Executive Officer. As a reminder, today's call is being webcast and will be available on our website for replay. I would like to remind you that this call will include forward-looking statements, which may include statements regarding the progress, success, and timing of our ongoing and planned clinical trials, collaborations, regulatory filings, dates of presentation, and future research and development efforts, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. They are subject to significant risks and uncertainties that could cause the company's actual results to differ materially from our current expectations. Accordingly, you are cautioned not to place undue reliance on forward-looking statements. Please review the full description of risk factors that can be found in the documents we have filed with the AMF in France and the SEC in the United States, which are available in the Investor Relations section of our website, along with the press release we issued today. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, Nanobiotix undertakes no obligation to update them to reflect subsequent events or future circumstances. With that said, I'd like to turn the call over to Laurent. Please go ahead. Thank you, Craig. Welcome, everyone. As Craig told you, we're very happy to welcome you for this new call, talking about our new data that we've been presenting today at ASCO on our trial 1100, both from head and neck patient being naive to PD-1 and refractory to PD-1. As I see a number of new people, newcomers on this call, I will suggest we start with slide 4, talking about our product and just summarizing what it is. So we're here to talk about a first-in-class radioenhancer named NBTXR3. This product is made to be injected once directly into a lesion and to be activated by radiation. The primary mode of action of this product is a physical mode of action that, when activated by radiation, will physically destroy the cell and destroy the tumor. So the way to use it is to get a better local control in a tumor mass in a patient. So that's the first mode of action. What we found out also, as a subsequent biological mode of action, is when you trigger this physical destruction of the cancer cell, you also prime an immune response. So today, talking about the combination of radiation, NBTXR3, and anti-PD-1, we will see how those two mode of action will play for the patient. So moving to slide 5, we can see here that this is not a new product. We've been doing a lot on this product and start knowing a lot. This is a product that has a potential to be tumor-agnostic, combination-agnostic treatment because of the mode of action, which is universal. This new mode of action have been proven to work in humans, as we've been establishing a proof of concept in humans in a randomized phase III trial in soft tissue sarcoma. We've been also running a number of clinical trials across the world, involving hundreds of clinical sites, treating hundreds of patients, showing feasibility, safety, and sign of efficacy in many tumors. As you can see, moving to slide 6, we have a large pipeline under development that we developed with Johnson & Johnson, which is our partner for development and commercialization of this product. And also, MD Anderson Cancer Center is playing a key role in that. But for today, I think we're gonna focus on the use of this product in combination with PD-1 radiation. Before going to some data, I would just like to reset the scene and give a bit of a context in the head and neck cancer treatment. It is a complex population that could receive different type of treatment depending on the stage of the disease, depending on the previous line of treatment. So before getting into the data, I think it would be useful just to recap some of the key bases for that. So on slide eight, sorry. Here you see, in a summary, how we usually treat head and neck patients. So first of all, the vast majority of head and neck cancer patient are diagnosed with local or local regional disease. That represent roughly 90% of head and neck cancer patient at diagnosis. And for those patients, the first line of treatment is often chemotherapy, radiation, or surgery, or combination of that. Only when this patient will fail this first line of treatment, then they will become eligible to Anti-PD-1 therapy as a second treatment or, or, or later treatment. You can find those patients in some of the reference papers, like KEYNOTE-040 or CheckMate 141, that really treat those kind of patients. On the other hand, you only have 10% of patients at diagnosis that have mets, and that are eligible for Anti-PD-1 treatment as a first line, and those are the patients you find in KEYNOTE-048. So it is important to know some of the parameters that will define the outcome when you treat patients with Anti-PD-1. First of all, the CPS score, for the low CPS score with a poorer outcome than high CPS score for 20 and above. The HPV status, specifically for oropharynx cancer, will play a role, too. Of course, the number of prior line of treatment and exposure to previous systemic treatment will define some of the outcome of the patient. The more line of treatment and the more systemic exposure you had to treatment previously, the harder it will be for you to respond in a new line of treatment. So that's for the different line of treatment you can find in head and neck cancer. Now, as we know, anti-PD-1 does not help all the patients in head and neck, and many of them will fail. And today, post anti-PD-1 failure, there's no established standard of care to treat those patients in third line or further line. Let's move to slide 10, just to remind some of the outcome that have been observed for head and neck cancer patients treated with anti-PD-1. So here, just as a reference, we've been just highlighting some of the key findings that have been done in KEYNOTE-048, KEYNOTE-040, and CheckMate 141. So what we can see here is for most of the patients, they will not respond to PD-1. You see a short median PFS of around 2 months, regardless of the trials that have been done, and a response rate that goes usually from 13% to 16.9%. But in any case, looking at the shape of the curve of the PFS, as you can see here, there are many patients that will fail the treatment within the first months. And at the end of the day, only a small proportion of those patients will really benefit from anti-PD-1. If we move to slide 11, you also see that some previous attempts have been done to try to help the PD-1 to get better by combining with radiation therapy. So this is one of the trials that has been done at the MSK, where they were comparing Nivo versus Nivo plus radiation therapy. And there have been no significant improvement by adding radiation therapy on the top of anti-PD-1. So it shows that it is a very hard-to-treat patient population, and there's a need to do more. That's where we think our product comes. If you move to slide 13, the idea here is to try to provide local control and priming an immune response with our product in combination with radiation. In doing so, we would like to improve the response and deepness of immune response for patients naive to anti-PD-1. And 2, to reverse the resistance to anti-PD-1 for refractory patients. So that's what we try to accomplish in this trial, and that's why we've been designing this trial the following way. So on slide 14, you see that today, we're gonna talk about the expansion part of our 1100 trial that has been designed with 3 different cohorts. And today, we're gonna talk about the 2 first cohorts. The first one is about anti-PD-1 naive patients that will receive anti-PD-1 as a treatment in combination with radiation plus nanoparticle. The other cohort for head and neck is the one that are anti-PD-1 resistant, receiving PD-1, failing PD-1, and therefore, after receiving radiation, nano, and continuation of PD-1. As you can see here, there is a third cohort in this trial that take multiple primary tumor leading to resistance to PD-1, but that's not for today. We'll talk about that next year. Let's move now to the baseline of the patient that you can find on slide 16. We have been showing here in 68 patients treated in head and neck, both naive and resistant patients, the following characteristic. I will not go over all the slide, but just highlight few of the thing. First of all, as you can see in the previous line of treatment, we have patients that have been treated a lot before getting into this trial. And as we mentioned previously, that's very important in term of potential outcome for those patients. Then you get the tumor burden. You see that our patients got a good number of lesions at the time they entered the trial, and that's also some of the prognostic factors. The higher the burden, the harder it is to treat those patients. And finally, the CPS score. As you can see, the vast majority of our patients got a low CPS score of less than 20. So we'll come back to this baseline when we talk about first line of efficacy, we can see. But let's first talk about the safety. As you know, we've been publishing already the data coming from the escalation part of this trial, and we found an appropriate safety and tolerability of the product as well as the feasibility of the treatment. So what we've been showing in safety for this trial is consistent with what has been seen in the first part of the trial, but also consistent to what has been seen in other trial with this product. On slide 18, you see a summary of the safety findings for this treatment. Altogether, we've been observing for the product and the injection procedure around 3% and respectively 6% of adverse event for this product. Altogether, when you look at the serious adverse event, there is around 8.8% linked to radiation therapy, injection, anti-PD-1, or NBTXR3, or a combination of that. In a nutshell, what we see is a single injection of NBTXR3, followed by radiation therapy, has been shown safe and feasible for this patient population, with less than 10% of grade 3 related to our product, injection procedure, radiotherapy, or anti-PD-1. There's no unexpected side effect that we've been seeing here compared to what you can find in literature or what we have been observing before. There's no specific side effect emerging as a new side effect in this clinical trial. Let's move now to the efficacy and start looking at the patient naive to anti-PD-1. I will suggest we move to slide 20, where we see some of the baseline of those patients. Total, there have been 33 patients treated, evaluable for safety. 25 patients have been evaluable for efficacy and response, and for those patients, what we see in the 33 patients, is we have a heavy tumor burden. We see patients that have been pretreated with other treatment before getting to the PD-1. We have 75% of the patients that have a CPS score low, lower than 20. Concerning the HPV status, out of the 33 patients, we have 10 patients with oropharynx, and HPV positive status. So what you can see here is that there is no specific selection of patients, and in terms of CPS score, pretreatment, tumor burden, and HPV positive status, we are on the poor prognosis side more than the good prognosis side. So if you want to compare, not directly, obviously, this population to what you can find in literature, we, we could assume that this population is similar to the population you will find in KEYNOTE-040 or CheckMate 141. Now let's look at the response. Slide 21. What we've been showing, first of all, and what you can see in the waterfall plot, is a good number of response for those patients, including a good number of complete response. When we did measure as per RECIST 1.1, the response observed in this patient, we got to an overall response rate of 48%, including 12% of complete response, and a disease control rate of 76%. It is interesting to see that here in this trial, we inject 1 lesion, irradiate 1 lesion, and those patients have several lesions. So the combination of radiation, nano, and PD-1 in this patient population looks to give a systemic control that could be greater than what you observe with PD-1 alone. We also have been starting to measuring PFS and OS, but those data are preliminary as the data are maturing and will mature over time. But as a first hint of what we start seeing in PFS and OS, you can go to slide 22. So we've seen so far, median PFS of 7.3 months and median OS of 26.2 months. I think what is interesting here, because the data are early, is to look at the boundaries and at the interval, the confidence interval. What you can see is for the median of PFS, the lower bar is 2.2 months, which is close to the median PFS that you could find with the PD-1 alone. But when we see that, we think there is a good room for an improvement and for a maturation of those data that will lead to a good PFS and OS. But let's wait over time to see how this is building. In any case, when you look at these numbers, they are big and they are important, and may lead to big outcomes for the patient. So going to slide 23, not as a direct comparator, more as an illustration. I think when you look at the response we obtain in naive patients with an ORR as per RECIST of 48%, we are good, and we are in a good path versus what you can find in the KEYNOTE-040 and the CheckMate-141, and same for PFS and OS. Now, as we said, we need to wait the maturation of the data specifically for PFS and OS to get some established number. In any case, we think the data we've been showing here are great and may lead to a good outcome for the patient. Let's now move to the other population. So the other cohort we've been treating, namely the patient resistant to anti-PD-1. And for that, I will invite you to move to slide 25. Just to set the scene here, what we've been doing is getting patients that received previous line of treatment, then got to PD-1, then failed PD-1, then entered our trial. We thought it was important to look at when they entered the trial, post failure of PD-1, to see if there was no bias in selection of patients. So we've been looking at this graph that you can see on slide 26, which gives you the number of patients that entered the trial after how many months before failure of PD-1. So what you can see here is that the majority of patients we've been receiving in our trial, they came for early failure of anti-PD-1 treatment. Only few got long-term response before failing with anti-PD-1, which is the population you want to help the more, because when you look at the drop of the PFS, it's within the first six months that you see this giant drop, and that's the patient you want to help the most, and that's the patient we got the most in our trial. Now, moving to slide 27. Let's look at the baseline of the patient we've been treating here. So we had 35 patients treated, evaluable for safety, including 25 evaluable for response. So 83% of those patients, they entered the trial in progression, meaning they had multiple lesions in progression when getting into our trial. The 17 patients remaining doesn't mean that they did not have progression, it's just that those data are not yet recorded in the eCRFs, as this trial is ongoing. Also, we've seen patients with a high tumor burden, and of course, patients that have been heavily pretreated before getting into the trial. The majority of the patients got a CPS score below 20. In terms of HPV status, we have 12 patients with oropharynx and HPV status, HPV positive status, which make a fair and balanced population. So in a nutshell, this patient is heavily pretreated, have low CPS score for the majority of them, and almost all the patients enter the trial having a progression. When you move to slide 28, you see the response of this patient. So being able to move from progressive patients with a good number of line of pretreatment and getting to this rate of disease control, 68%, it's good. It means that you can potentially reverse the course of the disease and reverse the resistance to the PD-1. And if we just look at the overall response rate we've been measuring using RECIST 1.1, we get 28% of response, which is very big, for refractory patients in head and neck, especially when you have progressor in this population. So now let's move to PFS and OS. As for the naive patient population, it's still maturing, so those are preliminary data and should wait, the completion of this trial to get to the final number. Even though what we see here is a median PFS of 4.2 months and a median OS of 7.8 months. Again, let's wait this to mature, but when you look at the usual PFS and OS of patients being refractory to PD-1 post-failure, this is already a good sign that we see here. Now, let's move to slide 30. It is hard to see what is the real outcome of a patient that failed PD-1 and then gets subsequent treatment. This is a highly fragmented population with many treatments under development, but there's no standard of care. Nevertheless, we've been able to look at some of the references, and I think there is one which is interesting among others, is the CheckMate 141 trial, where they have been following patients beyond progression, and they have been continuing treating those patients with PD-1. So those patients, they entered the CheckMate 141 trial. Some of them, some of the patients that did not respond, have been followed after the trial and have been receiving PD-1 as a continuation treatment, even though they were under progression with that. So what you can see here is a low response for those patients, but still one or two respond post-failure. And what is interesting is that they have been measuring what they call the OS2. So they've been measuring the overall survival of those patients, but starting from the first treatment of PD-1, to see if continuation of PD-1 for some of the patients will give a better outcome than just giving nothing. And what they observe here is a 12.7 months median overall survival in that category of patients. So we've been doing the same to try to understand what does it mean for the patient if after failure, they receive NBTXR3 plus radiation and continuation of PD-1, and how do we compare that to a patient that would just have received the PD-1? So what we've been observing here is 31.8 months median overall survival when we measure the OS2. And of course, this is starting at the first treatment of PD-1. If we compare that on slide 32 with what we just see in the follow-up of CheckMate 141, I think we show here something which is interesting. First of all, we see a good number of response, even in PD-1 failure patients. But when we look at the OS 2, and I will invite you to look at the lowest bar, which is 16.7 months, which is higher than the highest bar of the median of OS 2 that we see in the first CheckMate 141 follow-up. So what we see here is interesting, and from our perspective, it does say a few things. First of all, that we've been taking patients after failure of PD-1 or naive patients, and being able to potentially improve response and also give a broader overall survival to be confirmed with maturation of the data, said to us that we could use NBTXR3 and radiation therapy, regardless of the timing for this patient. Is it naive or after a different timing of failure, and we could still provide some benefit for those patients. Overall, if we just look at the number, I think we have a good thing here. As a conclusion, I will invite you to go to slide 34. In a nutshell, the safety of NBTXR3 single intratumoral injection has been good. Treatment has been shown feasible and safe, even with this pre-treated population. We have seen no specific or unexpected adverse event emerging. Specifically for the ICI-naive patient, we've been observing 48% of overall response rate and a disease control around 76%. The preliminary median PFS was 7.3 months, and the median OS was 26.2. In ICI-resistant patient, we got 28% of overall response and a disease control rate of 68%. The preliminary PFS in this population has been observed around 4.2 months, and the median OS was 7.8. So what we see here is a high response rate with metastatic patients, naive or refractory, and that suggests a strong systemic control of our product. And overall, these results were on further exploration in randomized trial for both ICI-naive and resistant head and neck cancer patients. So thank you for listening, and, now we're gonna open the call for question. Operator? Thank you. If you wish to ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. If you wish to cancel your request, please press star one and one again. Please stand by while we compile the Q&A roster. We will take our first question. Your first question comes from the line of Jonathan Chang from Leerink Partners. Please go ahead. Your line is open. Hi, guys. Thanks for taking my questions. First question: how do these results shape your thinking on how NBTXR3 may resensitize patients to anti-PD-1? And how could that translate into future development opportunities, for NBTXR3 in head and neck cancer and other tumor types? Thanks, Jonathan. So that's, that's a, that's a good question. I think maybe we should go back to the initiation of the work we've been doing in combination with PD-1, or more broadly, on the notion of priming an immune response with this product. So we've been doing extensive preclinical program to try to understand what happen when we combine NBTXR3 with radiation versus radiation alone, and notably in term of priming an immune response. What has been clear with all this work that have been done internally, but also at MD Anderson Cancer Center and some other establishment, that there is a fundamental difference when we add R3 to the radiation. Radiation itself has been shown as a potential immunoprimer. We've seen that in the specific population, in combination with anti-PD-L1, and so on, but there is something different when we add our product. And in a nutshell, what we found adding R3 to radiation is that there is a priming of a much deeper and broader immune response. And we've been able to crack most of the model, all the models, sorry. We've been testing, model resistant to PD-1, to anti-CTLA-4, to LAG-3, to TIGIT. All this showing that if you have a strong priming of an immune response, then all the subsequent treatment you will use in term of immunomodulation could be improved. So that was all the basis we've been working on from a preclinical perspective, and now showing that into a, into patient really open, a new pathway for, for the product. Nevertheless, when you look at how radiation is used in oncology, the vast majority of patients, the 60% of patients getting radiation during their treatment, they get radiation frontline treatment. So that's where the biggest impact could be done for the patient in general, in oncology. But on the other hand, if we can help also the metastatic patient, last line of treatment, I think that could be a very good opportunity for the product and, of course, for the patients. So now we're looking more broadly about NBTXR3, and as you know, we have this big partnership with Johnson & Johnson. And, of course, this will be part of the thinking about what could be the next indication and how do we position the product overall, in oncology. But if we just think about head and neck, what it shows here is we can go almost for any population in head and neck cancer patient. If we put on the side a surgery alone, which can bring a good notion of cure, you have all the trial that are ongoing, the phase III, in frail, elderly patient being ineligible to Cisplatin, and that's one population. We already have shown the feasibility and combination with radiation plus chemo, which is another. And now we are going last line, showing that even when you failed all this, then there is a chance to catch up the patient and to offer them a possibility by adding R3 and radiation therapy on top of PD-1. So for us, it's just showing that what we do with head and neck here could be something that could be replicated in other tumor types. Got it. Thank you. Second question: Can you discuss the role of re-irradiation in this head and neck cancer setting? And what does that achieve in terms of clinical activity? Sure. If I understand correctly the question, Jonathan, you're mentioning that in this trial, there is a part of the patient that already received radiation in the primary tumor and then need to receive another radiation, right? Or just generally in the treatment landscape, what role does that play and what kind of outcomes can be expected from that? ... So in general, when you look at head and neck patient, what we try to achieve with radiation is a curative dose, and you give the maximum tolerated dose, which is 70 gray. And when you have achieved that, if there is a relapse within the previous, previously radiated lesion, then it's very hard to give another curative dose. When I say hard, it's impossible. So you need to go for lower dose, what we did in this trial as an example. And the fact that we got a good response, including in the injected irradiated tumor, shows that you can go back in a pre-irradiated lesion with R3, giving a sub-toxic dose of radiation and still provide local control and systemic control. So again, that's opening the possibility more broadly of going back in a pre-irradiated lesion, not only in head and neck, but in other cancer also. For example, that's one of the trial that is ongoing at MD Anderson, where we go back into lung cancer patient that receive already, an irradiation with the maximum, dose, and then going back to them with a lower dose on the top of R3 to try to control even a tumor that have been resistant to radiation. Got it. Thanks for taking my questions. Thanks, Jonathan. Thank you. We will take our next question. Your next question comes from the line of Swayampakula Ramakanth from HCW. Please go ahead. Your line is open. Hi. Thank you very much. Good morning or good afternoon, Laurent. Couple of quick questions. One, just following up with the previous question. In terms of the way you talked about the mechanism by which R3 is kind of not only stimulating immunity, but also deepening it up. So have you thought about, you know, dispensing R3 and either anti-PD-1 or PD-L1? How do you think that will help at the earliest stage of the early line of trial? Okay, it's very hard to hear you. I guess you're still at ASCO. Yes. Let me rephrase the question to make sure I understood. So, your question is about how the priming or the modification of NBTXR3 could be used or help not only the patient in combination with PD-1, but more broadly in different line of treatment? Correct. Correct. Okay. Yeah, because if the sequence it change the sequence of events, in the sense you first do it with R3 and then come back and later it with anti-PD-L1. Okay, I'm gonna try to make a systemic answer to that. So I think first of all, priming an immune response is or could be always interesting, with or without PD-1. I think when we look at some of the findings we've been having in the earlier line of treatment without any PD-1, we've been observing some of the patient very... With some of the patients, some very interesting feature. So here it was about the head and neck, frail, elderly patient, that just got radiation plus NBTXR3, with no subsequent treatment and no PD-1, zero. We've been observing in some of the patient, very late response and very late complete response. To be clear, those patients, they receive radiation for a few months on the top of NBTXR3, and then there is no further treatment. What we have been observing for a number of patients is that they got complete response, months and months after the end of radiation, including some of them that got a pseudo progression before getting to complete response. So when you get to such a response, late response, with no intervention on any immunomodulator, we could assume that there have been some involvement of the immune system that have been triggered by the initial treatment. But now to demonstrate that, we will need a trial specifically to answer that question. But that's something we've been observing in different clinical setting, head and neck, but also in hepatocellular cancer and so on. So for us, that may reshape at some point, but that's a much bigger question, how we try to treat patient. I'm just launching an hypothesis here. That could be always interesting, regardless of the setting in which the patient are treated, to try to prime an immune response. And as long as you will have a tumor somewhere that can receive an injection and irradiation, regardless of the potential further line of treatment, that could be interesting to make a one-time injection of NBTXR3, a sub-toxic dose of radiation, and then to let the patient go to a other line of treatment, that will also potentially include PD-1. So that's a long-term question, but I think with everything that's happening in oncology in general, and how radiation is regaining and playing more role than it has been in the past, I think there is space to reshape part of the oncology here. Okay. Okay. And then in terms of the resistant population data that you showed. And the comparison that you're doing with the CheckMate 141 trial, where they followed the patients beyond failure of PD-1, what sort of therapies were they being treated with? You know, because you're comparing this, your population versus them, and I'm just trying to figure out what are we comparing against, you know, in terms of what they are being treated for after they've failed or after they became resistant to anti-PD-1? Sure. So, first of all, it's very hard to compare directly those population, right? Because even in the KEYNOTE, in the CheckMate 141, it's not all the non-responder they have been taken. So they have been taken part of the non-responders that could still be followed in term of survival and could still get additional treatment. So those patients, they continued under PD-1, and they may have had further treatment after. So I think that the interesting part here was just to see, okay, what's the right sequence? Or can we bring NBTXR3 and radiation at any time, from naive to refractory? So that's why we've been looking at this, at this picture. And also to see when a patient fail PD-1, continue to get PD-1, he does have a certain overall survival. That's the 12 months or so we have seen in this example. But when we did the same with our trial, and as not having a subselection of interesting patient, we've taken all comers, as you can see in the baseline, and here we got to 31 months of median overall survival. So for us, it does show that you have a lot of room to win with NBTXR3 in refractory patient population. Now, it's all about how do you define the primary population that you will enter in a randomized trial to ensure the success of such a trial? Yes. Very good. So one last quick question. So the data that you're currently showing is all for patients who have been treated with PD-1, anti-PD-1. Do you... If you take patients who are resistant to anti-PD-L1 or any other immune therapy, should we just assume we'll get the same sort of data? Or is it something to do with what the CPS score is of the PD-1 in these patients? Or is there any other nuances that we should also worry about? Well, I think to answer this question, we should do the test, right? We should do the trial. But from a theoretical perspective, or at least from a mode of action perspective, what we do is priming a deeper and bigger immune response in a larger number of patients. So we should assume, as a hypothesis, that any subsequent immunomodulator will benefit from that. And that's what we have seen in all animal model we've been testing. I mean, when we've been doing experiment with TIGIT, LAG-3, CTLA-4, PD-1, all this have been working, when we have added NBTXR3 in the game. So that's yes. The answer in short would be yes, but to confirm that, we need to prove it in a clinical trial. Okay. So actually I think more, more studies from you guys. Fantastic. Thank you very much. Appreciate, taking all my time. Thank you, R.K. Thank you. We will take our next question. Your next question comes from the line of Clémence Thiers from Stifel. Please go ahead. Your line is open. Hi, thanks for taking my question. I had two. First, what's the plan for the subsequent phase III trial? 'Cause you had good results in the two population. Is it gonna be one trial with the two population? Do you need two, two separate for each one? And, secondly, a short one. Did you see any subgroup that were driving up the results, especially in the resistant cohort, where characteristics were more distributed within the subgroup, be it the HPV status or CPS status? Thank you. Thank you, Clémence. Maybe I start with question number two. So it's a small number of patients. It's 68 patient total. Nevertheless, we've been exploring those subgroup based on HPV status for pharynx or CPS. So we did not see any specific parameter driving the efficacy in this. And overall, when you look at how the criteria are distributed, we have majority of patient having a low CPS score, just a small number, I mean, a third of the patient getting a HPV positive, and that could be influencing the outcome. So we... No, we did not see any parameters driving that. That's really also consistent, as I was mentioning, the mode of action is, if you prime an immune response from a physical perspective, destroying the cell, then you should be much less influenced by the biological parameter linked to the tumor. So that's for the question number two. Now, question number one about, okay, how do we think about the future and what could be the future in that? I think we could remember some of the previous discussion we have had with FDA concerning the refractory patient population, where the discussion has led to a potential randomized trial to get to approval based on overall response rate as a primary endpoint and a confirmatory endpoint linked to overall survival. So I think with this data getting better and better, that should still be the case as a context. Now, as you also know, we've been signing this collaboration with J&J, and during one of the two of the last call we've been doing all together, we've been mentioning that for now, we're moving in head and neck, the phase III we have, plus the lung, and there is a much broader discussion ongoing about what could be, will be the next kind of indication. So when this will be settled, then we will be able to to tell the market what are the, the future plan, potentially including head and neck, PD, PD-1 refractory or naive patient. But I think altogether, to see, it should be wise to make two different trial than, rather than, than one for such, for such approach. Very clear. Thank you very much. Thank you, Clarence. Thank you. Once again, if you wish to ask a question, please press star one and one on your telephone. We will take our next question, and the question comes from the line of Suzanne van Voorthuizen from Van Lanschot Kempen. Please go ahead. Your line is open. Hi, this is Chiara Montironi. I'm on behalf of Suzanne. Thanks a lot for taking my question. First of all, I wanted to congratulate with the data, and then I was wondering a couple of stuff. So the first one, to pick up the previous answer, how will this data feed into making decision for expansion of development and the J&J collaboration? If you can comment on that. And then I have a second question, because I think here at ASCO, we saw many programs on head and neck cancer, and looks like there are finally many options being developed for these patients. So I was wondering if you could comment for me on how you believe you stand against competition. Thank you. Sure. Well, thank you for the question. So concerning the first question, I think at this stage, we can't say more about what could be the future plan in head and neck patient getting a PD-1 treatment, and I think we should wait the collaboration with J&J also to mature. Even though we're heavily working on many, many options, then that's something we're not able to communicate at the time to the market. But to the second question about the evolving environment around head and neck patient. First, I think it's a very good, very good news. When you look at the previous standard or the current standard of care of head and neck patients, refractory to PD-1 or even naive to PD-1, there's no satisfactory outcome for those patients. So having many companies working with different approaches is a good thing. And we start seeing some emerging results that are very interesting. Now, to compare those results from one to the other, it's kind of hard because we always need to look at the baseline of the patient population. I think some of the data have been published on some bispecific, showing some very good data in terms of response, but this has been, I think, on the first-line treatment patient. So there have been also some results shown on HPV-positive patient, which is also a favorable prognosis factor. Now, it's all about, okay, how do we try to help a maximum of patients? So we think that the vast majority of patients getting the PD-1 treatment today, the one that are first receiving previous line of treatment, failing the previous line, then getting to a stage, where they need something else and where PD-1 is entering. And here, for all new systemic treatment that will be given to this patient, that will be, potential harder task, to get there. That's why when you, you look at some of the data, there either subselect a population that are responder, like the HPV positive, or going for patient that did not receive some previous line of systemic therapy, which give a new line of systemic therapy better chance to respond. So in a nutshell, at the end, there will be speed and result of randomized trial that will define what's the next standard of care for those patients. But I think there, there's a lot of space. When you look at the baseline of 15% of patients really responding as a long-term responder, there's a lot to do here. And as long as you have product that could be combined with acceptable toxicity as a single agent, but also in combination, I think little by little, we're gonna see more combination in head and neck and see potentially a rate of cure emerging for those kind of patients. So I will see that more as opportunities than competition, but of course, the first to establish the next standard of care will win part of the market in that. Got it. Thank you very much. Thank you. Thank you. There are no further questions. I will now turn the call over to Dr. Lévy for his closing remarks. Thank you, and thank you all, for being so numerous on a Sunday, to listen to this call and asking the question. We'll be happy to have further discussion with some of you after this call, to go deeper into some details. And on that note, I'm gonna wish you an excellent Sunday and talk to you very soon. Have a great day. Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect.