Nanobiotix - ADR Aktie

Good day, and thank you for standing by. Welcome to the Nanobiotix Full Year 2025 Financial Results Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Joanne Choi, Head of Investor Relations, U.S. Please go ahead.

Thank you, Heidi. Good afternoon, and good morning, and welcome to the Nanobiotix conference call to discuss our full year 2025 financial and operational results. Joining me on the call today are Laurent Levy, Co-Founder and Chief Executive Officer; and Bart Van Rhijn, Chief Financial and Business Officer. Today's call is being webcast and will be available on our website for replay. Before we begin, I would like to remind you that today's discussion will include forward-looking statements within the meaning of applicable securities laws. These statements are based on our current expectations, assumptions and available information and are subject to significant risks and uncertainties that could cause actual results to differ materially.

Such risks include, among others, those related to the timing, progress and outcomes of our research and clinical development programs, regulatory developments and our financial and operational performance. We encourage you to review the full description of risk factors that can be found in the documents we filed with the AMF in France and the SEC in the U.S., which are available on the Investor Relations section of our website. Any forward-looking statements made during this call reflect our views as of today and should not be relied upon as representing our views as of any subsequent date. Thank you. I will now turn the call over to Laurent. Please go ahead.

Thank you, Joanne, and thank you, everyone. Good morning, good afternoon. Really happy to be here with you today to share our 2025 year and to give you a bit of perspective of what's going to happen in the next 12 to 18 months. So today, we're going to go over different aspects of things, how we've been moving the company for the past year and also give some financial highlights and then open for Q&A session. I think we've had a very rich 2025. We've been able to do many things during this year. First of all, start moving forward in a good way in the collaboration we have with Johnson & Johnson and start showing the potential of this first product, along with the potential of this deal in terms of future revenue for Nanobiotix.

While doing so, we've been also pivoting the company towards the new platform, which has been a big effort from the team, and I would like to thank them all for that. While doing those operational things in parallel, we've been able to really improve our cash visibility into 2028. And this is beyond the timing of some of the expected milestones that should come from the collaboration with J&J. So altogether, we've had a rich year, and we are pleased to share that with you. And now we're going to go in some more details to give you a bit of insight. Before getting there, we would just like to remind a few things about the philosophy with which we are developing things at Nanobiotix.

So as you can see here, we mentioned delivering first-in-class directly. But I think definitely, we are doing more than this. We are creating new class of drugs. That's what we have done for the radioenhancer, for the Nanoprimer and also for the last platform OOcuity. And that's really our philosophy. We don't want to do what other biotech are doing, not because it's bad because we think there are enough people working on the same target with the same technology. So we really want to bring something deep and different to help millions of patients. And that's what we're trying to do, and we continue to do.

Our strategy is simple and stay in line with what we told you last year. First of all, is to continue to push and help J&J to address one of the potentially largest untapped market in oncology. And that's through our first product, radioenhancer that has been licensed to Johnson & Johnson. And beyond this product, we're really pushing hard on new platforms, starting with the Curadigm platform, which we think is going to disrupt part of how we think about drug development. And we have been starting making good progress in that regard this year. Obviously, we will come back to that in more detail. But let's focus first on NBTXR3 or JNJ-1900. What do we mean by addressing one of the largest untapped market in oncology? Well, I think for that, we still need to look at patients.

And when patients are diagnosed with cancer, the vast majority of them have a local disease. It's more than 70% of patients having local disease at diagnosis. And our industry, in general, is more focused on late-stage treatment of patients when they get metastatic or have received several lines of treatment. If you think about it, if you want to have a big impact for those patients, it will be much better, if possible, to treat them at the beginning of their disease and try to eradicate the tumor when it's still at the local stage. And that's exactly what we are trying to achieve with NBTXR3. And for that, we're working with radiation therapy, which is one of the largest treatments used in oncology as more than 60% of all cancer patients are getting radiation. And we have a product that we licensed to J&J that fits this existing market with almost no competition.

And as you can see on this slide, we have a very large pipeline linked to this product that have been developing across many tumors. And technically, that's just a few examples of what could be done with this product because there are many, many other patients getting radiation in different oncology indications. But let's try to look at where is the value here, what are the next key point of inflection and how are we going to bring that to next steps. This year, last year, sorry, 2025, we've been publishing additional data in different cancer types. On the top of the already established proof of concept in soft tissue sarcoma, the first data in head and neck cancer, we've been able to continue to show that this product could be widely applicable in oncology.

Through 2025, we've been publishing data on head and neck cancer by talking here about recurrent metastatic patients, also pancreatic cancer, esophageal cancer, melanoma cancer and lung cancer. All those data have been showing not only that you could use safely NBTXR3 in different indications, but also start to show some potential good of efficacy for those different indications. And altogether, some consistency. In the way you administer the product, but more importantly, in the way this product could amplify the radiation therapy and potentially bring new benefits and additional benefit to patients. Let's focus on the 2 key developments. As you know, we've been transferring to Johnson & Johnson last year, the ongoing Phase III in head and neck cancer. That's a very important trial as a Phase III and could lead, if positive, to first approval and first market activity around NBTXR3.

This trial is progressing well. J&J now has the full operation on this and also the financial aspects of this trial are taken care by J&J, and we still expect to get the first readout of this trial the first half of next year. You may have noticed that on the top of this Phase III, J&J has also started a Phase Ib in another population of head and neck, meaning patients getting radiation plus cisplatin. If you think about head and neck cancer, with those 2 trials, you're technically capturing all the patients frontline that have a locally advanced tumor and that received radiation and that cannot go to surgery. So technically, if you -- if you exclude, sorry, the few patients that have metastasis at diagnosis, with those 2 trials, you could capture the vast majority of head and neck cancer patients, first-line treatment with the highest unmet medical need.

So that's a very important pathway and could, if positive, establish NBTXR3 as a key player in whole head and neck cancer treatment. Now there is another trial, which is equally important and potentially even more important. We're talking about here the first lung cancer trial that J&J is running. The name of this trial is CONVERGE. It's a randomized Phase II trial in unresectable Stage III non-small cell lung cancer. This trial is important for many reasons. First of all, as you may have seen, lung cancer is a very important aspect of the strategy of J&J in oncology. And it's also, as you know, a gigantic market, if not the biggest market with breast cancer.

So here, starting with this trial, assuming that the data are positive, what we feel at Nanobiotix is that could be a trigger for Johnson & Johnson to start expanding the development. But if we just stick to lung cancer, that's already a gigantic market per se. Here, we're talking about Stage III, but could expand into some other indication in lung cancer. And maybe as we did not have the occasion to talk about the data that has been generated, the first part of this data, let's have a small focus on that. As I mentioned, we are talking here about patients that have a locally advanced unresectable Stage III lung cancer and the treatment of reference is radiation to chemo followed by consolidation with durvalumab. And as you can see, if you look left and right of this box, many other patients in lung cancer would receive radiation therapy frontline treatment, which could be at some point an expansion of the use of this product, assuming that this trial read positive.

So what's the design of the trial? There's 2 parts in it. First, a safety leading with very few patients and then what we call a proof of concept with the randomized part of the trial where we compare the standard of care chemo radiation with durvalumab versus the same plus the product with 2 different dose. And this is randomized 1:1:1. Total should have 120 patients. And Johnson & Johnson published that they should expect the readout of the randomized part beginning of 2027. The data that have been presented this week are about the safety leading. So there's a lot of caveat around that. It's a small number of patients, but nevertheless, we can start looking at what we observe here.

So we've been first showing a good safety profile with no serious adverse events linked to the treatment of the procedure and the feasibility of injection in every patient. Then what has been observed is a good first rate of response that we could see as we've seen 5 out of 7 patients responding. And equally importantly, we get 100% disease control, meaning that all those patients will go or went to durvalumab, which is not the case if you look at the details of PACIFIC trial. Many patients have been excluded post radiation and chemo for different reasons, including progression post radiation and chemo, which we did not observe so far in this clinical trial.

But altogether, what we can say it's a first readout encouraging. And we can wait to see the next steps of this safety lead-in or the final data that should come as we mentioned beginning of 2027. So we can say we've been progressing a lot with this collaboration. Also now that we have transferred the Phase III to J&J, they are running most of the operation. We're still running and finishing the 1,100 trial that has completed in terms of recruitment. Now there is some follow-up of patients, and we will continue to deliver some data in that regard. And the collaboration with MD Anderson Cancer Center is still ongoing with many trials that have been completed in terms of recruitment last year, we're going to see data this year, and we may open to new trials with MD Anderson Cancer Center.

But maybe let's take time to talk a little about our new platform, Curadigm. Here, we're still talking about nanophysics. We're still talking about nanoparticle, but with a different perspective with different particle with different potential benefit to the patient. Just as a reminder, for those that are new on the call, as I see many, Curadigm is about trying to help many of the innovations we see in the biotech and the pharma arena. You do notice that most of the new innovation coming out, people are building more and more complex objects. We can talk about oncolytic virus, RNA-based therapy, in vivo CAR-T, cell therapy and all the subjects because being complex, at some point, when you try to inject them IV, the liver will play a role of filter and will capture a big part of them, if not all, in certain cases.

So for many of those innovations, it's very hard to have access to the entire body with a normal IV route. So rather than doing what our industry is usually doing, which is let's try to tweak this subject to make it more efficient and try to escape the liver while delivering at the right place while delivering the payload and get the good transection, for example, so you're building a lot of compromise in one object. With the Curadigm technology, we decided to build what we call a nanoprimer, a second object. This nanoprimer is injected prior to the second product, and this nanoprimer has been specifically designed to transiently getting into the liver and get it occupied for a certain amount of time. So why the liver is busy? When you inject the second product, then it is much less captured by the liver and can have access to many other organ from the body.

So what you could do with this approach is improving pharmacokinetic of a product, allowing when it's not possible to escape the liver, reducing liver toxicity or combination of all this. So there are many, many opportunities and many, many applications we could do with this technology. And now a big part of the team is focused on the development of it. What we've been doing lately is really continuing pushing, meaning filing for 4 new patents applications to continue to build our supremacy with this technology. We also have presented positive new in vivo preclinical combination with different type of combination. And more importantly, we are moving forward towards the IND, and we started the CMC activity with the start of the GMP manufacturing and also preclinical studies allowing to file for an IND.

And while doing that, that the internal program at Nano, we've been expanding a lot our external reach out. We have now more than 20 MTAs that we've been signing with pharma or biotech, where they have taken our product and they are testing it with one of their products to either improving the pharmacokinetic of this product or reducing liver toxicity, and we've done that with many different technologies for different therapeutic areas like oncology, rare disease, CNS disorder. So it's moving quite well. And then we expect in a not-too-distant future to start transforming some of those MTAs into deals. But globally, the way we see the value of this platform and the 3 pillars that we are using to push it is first, continue to build and protect the technology while building an internal pipeline.

We want to have our fully owned product to be developed up to a certain stage. While we are building or piling up deals with different partners, pharma and biotech. And of course, because of all this, we need to prioritize and build the right infrastructure to be able to build to manufacture and to provide this product to many partners and to our internal pipeline. So things are moving well, and we expect to get a bit more update and new data on this platform coming before the end of the summer.

Just of note, last year, we've been entering a new index on the Euronext market, which is the SBF 120, and that's an index that covers 120 largest French listed company by market and cap liquidity. So it does give us a bit more institutional visibility, and we've seen through that some of the new investors coming on the top of specialized biotech investors that have entered our stock last year. And I'm going to take this to give the mic to Bart to talk about the financial part of this presentation.

Thank you, Laurent. Good morning and good afternoon, everyone, and thank you for joining us today. Over the past year, we've materially strengthened the company's financial foundation, positioning us to advance to upcoming value inflection points with greater resilience and strategic flexibility. This progress was supported by 2 strategic initiatives that meaningfully reshaped our capital requirements and hence our long-term operating flexibility. First, we amended our global licensing agreement with Janssen in a way that materially improves our financial profile. Under the revised terms, we have removed the vast majority of our funding obligations for the Phase III NANORAY-312 study while retaining significant upside through milestone payments that could total hundreds of millions of euros over the next 24 to 36 months.

This amendment materially enhances capital efficiency, improves cash flow visibility and better aligns the partnership structure with our long-term strategic priorities. Second, we strengthened our balance sheet to the securing of a nondilutive royalty financing with Healthcare Royalty Partners for up to $71 million. This transaction provides incremental capital while avoiding shareholder dilution extends our projected cash runway into early 2028, excluding potential milestone inflows. Taken together, the strategic initiatives that I just outlined enhance our financial flexibility, reduce near-term funding requirements and position the company to sustainably advance its pipeline while maintaining a disciplined approach to capital allocation and long-term value creation.

Turning to the next slide. Just a brief overview of the deal we announced back in October. We're extremely pleased to have partnered with Healthcare Royalty Partners on this transaction, bringing up to $71 million of nondilutive capital into the company. We selected Healthcare Royalty Partners following a comprehensive evaluation of financing alternatives. And given their deep sector experience and expertise, long-term investment outlook and strong record of supporting innovative biotech companies, we selected to partner with them. We believe that this partnership reflects a high degree of alignment around the long-term potential of JNJ-1900 and our broader strategic objectives.

Critically, this royalty structure ensures that our partners' return is directly linked to the success of our lead program, which aligns incentives while avoiding repayment obligations beyond the nominal value of the bonds. Moreover, this is a construct that is kept from a time and amount perspective and therefore, a capital-efficient way to finance the company beyond anticipated value inflection points to ensure we maximize the value for our shareholders. This financing not only ensures we are funded through those critical inflection points, but validates the commercial potential of JNJ-1900 and supports our continued progress towards long-term sustainability and profitability.

Moving over to our full year financial highlights. For the full year 2025, we recognized positive revenue of EUR 32.6 million compared to negative EUR 7.2 million for the year ended 2024. As a reminder, the negative revenue recorded in 2024 was primarily driven by a onetime recognition of the net liability to Janssen following the transfer of the sponsorship of the NANORAY-312 study. The positive revenue recognized in 2025 reflects a onetime accounting impact of EUR 21.8 million associated with the amendment to a licensing agreement that we executed in March 2025. This amendment, as Laurent alluded to earlier, eliminated the vast majority of the company's development cost obligations related to the NANORAY-312 study. This technical accounting effect related to the transfer of sponsorship and the cancellation of current and future study-related costs resulted in a corresponding impact on our reported top line, which is nonrecurring.

Said differently, as these changes in 2024 and 2025 are considered purchase price adjustments from an accounting point of view, these results flow through the revenue line in our profit and loss account. Let us turn to R&D expenses. These include clinical and manufacturing expenses related to the development of JNJ-1900 and preclinical pipeline activities and totaled EUR 23.1 million for the 12-month period ended December 31, 2025, which compares to EUR 40.5 million for the 12 months ended December 31, 2024. As previously discussed, the significant year-over-year decrease of approximately 43% was primarily driven by the removal of development costs associated with the NANORAY-312 study following the transfer of sponsorship to Janssen. This transition resulted in the elimination of related clinical and operational expenditures previously borne by the company.

More broadly, R&D spending during the period reflects continued prioritization of capital-efficient development across our clinical and preclinical programs, while maintaining investment in key manufacturing and pipeline activities, supporting the long-term advancement of our all platforms that Laurent just spoke to. Selling, general and administrative expense for the 12-month period ended December 31, 2025, were flat to significantly -- sorry, to slightly down year-over-year at EUR 20.4 million compared to EUR 20.5 million, reflecting continued expense control.

Net loss attributable to shareholders was EUR 24 million or EUR 0.50 per share for the 12-month period ended December 31, 2025, reflecting a year-over-year decrease of 65%. The decrease was primarily attributable to the one-off noncash positive revenue recognition accounting impact together with a meaningful decrease in R&D expense resulting from the removal of the funding obligation for the 312 study. This compares to a net loss of EUR 68.1 million or EUR 1.44 per share reported for the same period last year. As we turn to cash and cash equivalents, as of December 31, 2025, that amounted to EUR 52.8 million compared to EUR 49.7 million as of December 31, 2024.

Based on the current operating plan and financial projections, Nanobiotix anticipates that the cash and cash equivalents of EUR 52.8 million as of December 31, 2025, will fund its operations into early 2028, assuming the receipt of the remaining $21 million from Healthcare Royalty Partners expected in Q4 of 2026. To conclude, we remain focused on disciplined execution as we advance through key clinical and strategic milestones. We will continue to prioritize prudent capital allocation, operational efficiency and balance sheet resiliency and believe the foundation we have built positions us well for the periods ahead as we work to deliver long-term value for our stakeholders. Thank you. And now I would like to turn the call back to Laurent.

Thank you, Bart. Just in a nutshell, what's coming for the 12, 18 months in front of us, we will continue to push with our new platform Curadigm and we'll continue to deliver new data and also visibility on how we're going to transform that into business. On the top of that, the NBTXR3 or JNJ-1900 development is still key in our development, as should be the critical next step for value creation as we expect to get the results of the Phase III in first half of '27 and the results of the Phase II in lung cancer in early 2027. Besides this, this year, we're going to deliver 4 different results of clinical trials, which 3 of them have been completed, so you will be able to see the final data for this.

The key takeaway for today, if we think about 2025 and what's coming is the J&J partnership and the development of NBTXR3 is moving in the right direction with amplification of the development through multiple trials. We've continued to show that potential use of NBTXR3 across different indications, which reinforces the potential value of this product. And as mentioned, we've continued the Curadigm development, a new class of drug that we intend to bring to life.

As Bart just mentioned, we're getting in a good financial position as our cash visibility is going into 2028 beyond key milestones in head and neck and lung and potentially other milestones. And as you have just seen, we have multiple near-term data readouts that could continue to show, assuming it's positive, that NBTXR3 could really improve life of millions of patients. Thank you very much for your attention, and now we're going to open the call for questions.

[Operator Instructions] Your first question comes from the line of Tara Bancroft from TD Cowen.

So my question is about the lung data that you guys showed from CONVERGE yesterday that were really interesting even it's only in the first 7 patients. So we were hoping you could give us some context for how you benchmarked that to the 45% to 50% ORR. We ask because PACIFIC seems to be the best comp here where ORR was actually around 30%. So just curious to hear your thoughts on that. And then on follow-up, when were these assessments taken that were in the poster? And how does that length of follow-up so far play into your level of confidence in the data that potentially improving even further in Part 2?

Thank you, Tara. Well, I think there are a few paper or historical control we could look at comparator for that. As a context, we are using the PACIFIC regimen in this trial and patients getting radiation plus chemo and if they do not progress, then they go to durvalumab. If you look at the PACIFIC paper, they start with 983 patients that received radiation plus chemo. And out of that, only 70% will be randomized, 2 patients in the direction of durvalumab, one with placebo. So there is in the evaluation of the response rate in the PACIFIC paper, something telling 40% -- 48% of response, but that excludes the 30% patients that have been not treated after that with durvalumab.

So that's the response rate therefore after radio chemo. And if you look at the response rate post durvalumab, then it's going down, but it's going down slower than the placebo arm. And here, you find the 27% response that you probably mentioned. But again, this 27% response is excluding the patients that have been frontline excluded from the trial before randomization. So altogether, if we take 40%, 50%, that's what we can find in some other paper as what radiation plus chemo is doing for those patients and close to what they find as an optimization in the PACIFIC regimen.

But I think that's just the first part. The most important part is how this evolves over time. Because what we see in PACIFIC, some patients did not get durva, 30%, and then the rate is going down over time. So I think if [R3] can provide a real local control, then we should see something different happening versus what you can observe with durvalumab. But this will be answered a bit later and potentially definitely answered when we will see the results of the Phase II beginning of next year.

Your next question comes from the line of Clemence Thiers from Stifel.

Just to come back to the CONVERGE study. Full data will be in early 2027. Is there any chance you or J&J could file based on that study? Or do you have to run a Phase III afterwards? That's the first question.

Thank you for the question. Well, first of all, we can talk for our partner. J&J now is running the CONVERGE trial and has the license on the product. So that will be their decision. And I think it's a bit early to talk about that. That may be a question we could ask when we see the data coming from the Phase II. But if the data are excellent, everything is open. But again, that will be a J&J's decision to move that direction or to do a proper Phase III after that. But we will hope for the best.

Yes. That was worth the shot. And the second question, in 2026, we'll have all those additional data sets from your IO study and MD Anderson studies. Are those the last ones in the sense that will you be after that at the stage where you again J&J decide whether you move forward with it or not?

Yes. I think some of those trials have been completed like the melanoma cancer trial, the lung re-radiation and the last one, esophageal cancer. Just to know that we are now looking with MD Anderson as opening some potential new trial to explore new avenues, but that's something that will come a bit later. Obviously, out of all those trials, we got a lot of signs of safety, feasibility, potential good efficacy for the product. And now it's within the hands of the J&J, but also discussing with us about potential next step, but nothing that we can say at this stage.

I have one mention to do, is to maybe take a particular look at the MD Anderson cancer trial about lung reraadiation. This trial, the recruitment has been completed last year, and we'll see the final data this year on more patients with more follow-up. I think this trial is very important because it's not like the same population that is treated in CONVERGE, but to a certain extent, could be seen as a surrogate of what we could observe in CONVERGE. So we will pay particular attention to this trial, but also we'll bring that to your attention.

Your next question comes from the line of Jonathan Chang from Leerink Partners.

This is Albert Agustinus, on for Jonathan Chang. Congrats on all the progress. So my question also reflects on the CONVERGE data, is how do we extrapolate these results to your other ongoing trials and potential indications? And secondly, if I may, how do you foresee JNJ-1900 will be positioned within the landscape of non-small cell lung cancer treatment paradigm?

Well, I think lung stage III cancer, like locally advanced head and neck cancer and other tumor are different because they are coming and they are in different organ, but they all share something is that if you can improve the local control and have a strong rate of response and CR, then you can deeply change the PFS and overall survival. And what our product does is improving the absorption of energy, killing more cells. And we know when you have a local disease, killing more cells may lead to more control. So that's the basic thesis that led us to start developing NBTXR3 and going into frontline treatment when patients have a local disease. And that's also what J&J is going after if we think about the 2 trials in head and neck and this trial in lung cancer.

For us, it does establish the strong power of having local control transforming into benefit for patients. And starting from this point, then we could anticipate or imagine the diffusion of this product across different populations that are also getting radiation. But it's always pure to demonstrate that this work when local control plays the key role in the survival and quality of life of patients. So that's how we will extrapolate the results of CONVERGE, but also that's what we started to do with the randomized data coming from soft tissue sarcoma, which was a similar situation, even though this is really different.

And that's a good start to any tumor type. And if we think about how to extrapolate to other indications, that could be a path. Now for lung cancer, there are many patients receiving radiation beyond lung Stage III. It is around 77% of lung cancer patients getting radiation. And not to mention that small cell lung cancer is also another indication where radiation is key. So we could imagine, but again, that will be J&J's decision to spread this product across different lung subpopulation.

We will take our next question. And the question comes from the line of Swayampakula Ramakanth from H.C. Wainwright.

This is RK from H.C. Wainwright. I also have a couple of quick questions on CONVERGE. So in your mind, do you see J&J when they're spending time on both NANORAY-312 and CONVERGE, do you see them sourcing equal time for both of these projects? And additionally, does -- do you have any data from your partner regarding abscopal effect in the lung? Because injecting into lung lesions are potentially technically challenging. So how do we -- how do you and your partners see this being a successful therapeutic modality in the lung?

Well, first of all, about the bandwidth or the investment in lung versus head and neck. I think a Phase III is always bigger than the Phase II. And in that case, that's a very big Phase III versus the CONVERGE trial. So there's much more people working on one than the other, which is normal given the size of things. But the attention is equally important from our perspective and what we can observe. And obviously, as I mentioned previously, the lung is a very important trial for J&J and also for us because if it does work, that's really opening a big market for JNJ-1900 or NBTXR3. But let's say that what we observe is they're pushing all front to make sure that all this could happen. Now on the abscopal effect, I think that's a big question. That's an effect we already observed that in melanoma patients, head and neck patients, some of the lung patients, when they have met with or without primary tumor, when we do inject one lesion and irradiate that lesion, we see a distant effect in the non-irradiated non-injected lesion.

So that's something we start observing in many different clinical situations. That will be very useful to understand and to investigate when we think about metastatic patients. But for the vast majority of patients getting radiation, they have no met. They have a local or local regional disease. And here, local control is much more important than any potential immune response. And if we can provide it through local injection of the particle plus the radiation, that could be a win. And in the case of local regional when some of the lymph node could be involved, then we've seen in different trials now that we are able to inject lymph node on the top of the primary tumor, which could add also an additional immune response.

But RK, if we just step back a minute, I think this abscopal effect or the possibility to trigger an immune response is really critical for met, as I mentioned. But also if you think about local regional disease where radiation plays a role, usually the local regional area is irradiated, which is not in favor of having an immune response because the X-ray, as we know and have seen, could kill some of the activity of the immune system. So here, the local control brought by physical treatment like radiation with the addition of JNJ-1900 is where we should play and where we should try to win.

One quick question on Curadigm. You did present some preclinical data previously. Now thinking -- going forward, since you also have collab MTAs with multiple parties. Are you planning to initiate an IND from the internal pipeline? Or do you expect some of these external collaboration partners to file first? How should we think about that program going forward?

We are pushing both because we think building our internal pipeline will go through have a first proof of concept of this product into human, and that's what the team is working on, not only by manufacturing the product and starting pre-IND studies, but also designing the first proof of concept we want to bring to life. And if we think about it, as soon as we have established the safety and feasibility of this product into human, that's also opening many more combination possibilities with other products that are already into clinical development. So that will not only push forward our pipeline, but also will open many other opportunities for collaboration and licensing out.

We will take our next question. Your question comes from the line of Kiara Montoni from Van Lanschot Kempen.

This is [indiscernible] on for Kiara. So for the J&J driven Phase II trial in lung, do you expect that J&J will report an interim before the readout in early 2027? And if they do, what do you think they will most likely disclose the ORR or the post durvalumab from Part 1?

Thank you for the question. So yes, that's true. There are multiple readouts in this trial, different rate of response depending on timing, PD-L1 and also potential measurement as exploratory for other more systemic endpoints like PFS and OS. Now we can't talk for J&J. What we can say is what has been said publicly, which is the readout of the Phase II beginning of '27. But in between, who knows.

Okay. And on the MD Anderson lung reirradiation trial, you said you expected to read out in 2027. Is there any possibility you can narrow down on the timing?

We filed for different abstracts. If first one accepted, that should be around the summer.

We will take our next question, and the question comes from the line of David Dai from UBS.

Congrats on the progress. So a couple of questions from me as well. So just on the CONVERGE trial, so just thinking about the JNJ-1900, how do you think this early post-CCRT response we saw from the Part 1 could translate into durable load control and PFS benefit in Part 2? And I have a follow-up after that.

Well, I mean, that's depending on how durable will be the response. But generally what we have observed in other clinical trials with different disease, when you start getting radiation, you usually get the optimal efficacy of radiation a few months after the end of the last session. Here, patients are going directly, I mean, rapidly into durvalumab. The good point is that, first of all, all of them went to durvalumab, which is not the case when you look at the overall population. And now we need to wait the next set of data to conclude on that. But if we believe of what we have seen previously in other trials, we should expect a much greater local control. And now we'll see how this potentially impacts a more systemic aspect of things for the patient.

Got it. Okay. And then just on -- for next follow up, just on the Part 1 study here, will we expect another follow-up of this data from the Part 1? And also for the Part 2, which we're expecting to have some data in early 2027. Could you just help us understand a little bit more around what's the sort of expected data readout? Would it be OR? Or should we look at PFS as well?

I don't know. What we know is that all this that you mentioned are endpoint of the trials, but we don't know what J&J is going to communicate yet.

Your next question comes from the line of Michael Schmidt from Guggenheim.

I had a couple more on the CONVERGE data from yesterday. Obviously, very interesting. Could you confirm whether Part 2 of that study is enrolling? Or are still patients being added to Part 1, sort of the safety lead-in component of the trial?

Yes. Part 1 has been completed and the Phase II part, randomized part is enrolling since last year.

Okay. That makes sense. And then, yes, so just -- so you did note the sort of next update in early 2027. Is your impression that this is sufficient for your partner to potentially make a Phase III go decision? Or do you think more follow-up may be needed to look at things like DFS or maybe even OS to make that move into a large Phase III trial?

That's a very good question, Michael. I think overall, first of all, a response in those patient population, if you find a high rate of response, then you should get an impact and a correlation with PFS and OS. I think the number of CR globally also could be a surrogate of that as PACIFIC did show very little rate of CR, less than 1.7% in the post [indiscernible] treatment. But globally, patients, if you look at the dynamic of the curve, they're relapsing quite fast in [indiscernible] arm and versus radio plus chemo. So I think comparing all those data, we can say if you beat that bar, then you move to Phase III directly, you don't need PFS, you don't need OS.

I think that should be a mix of results linked to number of patients getting to [indiscernible] because usually 30% are not, number of patients getting response, number of patients getting complete response and then you can start following PFS and OS to see. But a combination of all these or just a few of them, depending on the magnitude could be enough. But at the end, that's J&J's decision to look at this and to take the path moving forward.

Okay. Makes sense. And then another one, I know this may be, again, difficult to answer, but what is your sense how J&J may prioritize other indications beyond head and neck and lung. For example, breast cancer is obviously a very big opportunity in prostate as well. And to what degree do you think they're incorporating data that's sort of coming out of the ISTs that have been ongoing?

Well, that's a tricky question. We can't answer. What we can say is you can see the priorities of J&J in terms of indications like lung, bladder, head and neck and so on. So as you mentioned, breast cancer is not part of those priorities. Also, we have all the trials we've been running or are still running with MD Anderson that could serve as a base for expansion. But even though we have a lot of discussion with J&J's team about optionality, there's nothing we can say at this moment.

So we'll keep our eyes out for any other updates.

[Operator Instructions] We will take our next question, and the question comes from the line of Shan Hama from Jefferies.

Just 2 from me, please. Actually, just on potential indication expansion on J&J's part. I know there's obviously not much you can comment on their behalf. But the indications that NDA is working on, is there scope for J&J to actually expand the [R3] program into those indications, so pancreatic, esophageal, et cetera? That's my first question. And then I can ask a follow-up after.

I'm sorry, I'm not sure I got. The question was can they or will they?

As in, can they?, are they able to?

Yes, of course, they are able to. And obviously, all the clinical trial we've been running serve really as a base for discussion with them, and they can.

Okay. That's clear. And then just actually on cash burn. So obviously, R&D has come down pretty sharply post the transfer to J&J. So what's the sort of steady-state annual cash burn we should assume through to 2027?

Thank you for the question. We don't provide specific forward-looking guidance to the individual years, and we refer to the cash runway that is in early 2028. But we have a very disciplined approach to how we allocate capital. So what you've been used to in the past few years, you should expect to continue to see from us. Maybe one high-level comment is that as the 312 costs have been transferred to our partner, Janssen, we should expect to see development cost on the new platforms that Laurent talked to.

Your next question comes from the line of Clement Bassat from Portzamparc BNP Paribas.

I have 2. First, I was wondering how much R&D you spent in oncology in H2? And how much was allocated to Curadigm just in order to assess the shift? And secondly, regarding the mechanism of Curadigm, my understanding is that with the Nanoprimer, we will reduce the effective dose level, but at the same time, we may also reduce the dose. So could you please provide some insight into the relationship between these 2 dose, if the relationship is linear or not? And if this could lead to narrowing the trend between these 2 dose due to the suspension of the liver clearance?

Let me try to address the question on the R&D spend and how that is proportion between our 3 new platforms. What I can share is that at this time, and this is relating to full year 2025, the spend on Curadigm has been ramping and should be in the low single-digit millions. Again, as we start to pivot and have pivoted meanwhile to these new platforms, that spend will obviously increase. But for the past year, it was a smaller amount compared to the total R&D spend.

So to your second question about Curadigm, I think the answer is yes, there is a correlation, but will depend also on the need of the product. Let me try to get to that. So what the Nanoprimer does is by occupying transiently the liver, it will allow a second product to circulate more freely. So if this product had a strong accumulation in liver, but not much toxicity, what you're going to play on is the ability for the second product to circulate more freely and to reach other targets that will not be able to reach normally. But if this product has a high liver toxicity, would prevent him to be used at the right dose, then you will play more on the liver toxicity by preventing the accumulation while allowing some circulation of a therapeutic dose.

But there's always a correlation between the dose of the Nanoprimer and the quantity that you will avoid to be captured in the liver and the quantity that will be allowed to circulate. And there is a link to that but different products will request different outcome, and that's where we're going to play A or B, meaning more efficacy or less safety issue. In some cases, we can play on both.

This concludes today's question-and-answer session. I'll now hand back for closing remarks.

Everyone, thank you very much. It was a pleasure, as usual, to talk to all of you. And I think that you are numerous today assisting to the call. It's a very good thing and hope to see you all in a short for more news about Nanobiotix. Thank you very much. I wish you a great day. Thank you.

Thank you all.

This concludes today's conference call. Thank you for participating. You may now disconnect.

Good day, and thank you for standing by. Welcome to the Nanobiotix New Results in patients with Refractory Melanoma conference call. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to hand the conference over to your speaker today, Joanne Choi. Head of U.S. Investor Relations. Please go ahead.

Thank you, Heidi. Good afternoon, and good morning. Thank you for joining Nanobiotix conference call to discuss new data from the third cohort of our Phase I 1100 study in melanoma presented at the Immunorad conference yesterday in Paris.

Joining me on the call today is Laurent Levy, our Co-Founder and Chief Executive Officer. Today's call is being webcast and will be available on our website for replay. Before we begin, I would like to remind you that this call will include forward-looking statements within the meaning of securities laws. These forward-looking statements are based on current information, assumptions and expectations and are subject to significant risks and uncertainties that could cause the company's actual results, including progress and timing of planned research and clinical development to differ materially from our current expectations.

We encourage you to review the full description of risk factors that can be found in the documents we filed with the AMF in France and the SEC in the United States, which are available in the Investor Relations section of our website.

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. Thank you.

With that said, I will now turn the call over to Laurent. Please go ahead.

Thank you, Joanne. So good morning, good afternoon, everyone. We are very happy to have you on this call to present the latest data we have generated in our trial 1100. Those data have been presented by Dr. Jason Chan from UCSF. Maybe before jumping right away in those data, I just would like to remind a few basics about our product NBTXR3 or JNJ-1900. We're here to talk about a product that is dedicated for patients receiving radiation therapy, which is the vast majority of cancer patients, around 60%.

And those patients, they usually get their radiation therapy right after the diagnosis when they still have a local disease. And that's where the biggest development is about NBTXR3, that's where the biggest market is, that's where the biggest unmet medical need is.

Nevertheless, we think we should continue to help patients across the different line of treatment, and that's one of the purpose of this trial, 1100, to go and help patients after they have received several lines of treatment when they fail them to see if we can rescue those patients. So that's the entire purpose of the trial that has 3 cohorts, 2 about head and neck. We'll talk about that later, but not today.

Today is about the cohort #3, where a vast majority of melanoma cancer patients have been recruited post-failure of multiple lines of treatment. So that will be a focus for today and the call for now. So we know that melanoma has been very impacted by immune checkpoint inhibitors.

Nevertheless, if there is a large number of responders, you can usually see over time that you will have relapse and resistance in around 50% primary and 25% secondary resistance. So there's a large part of patients having melanoma that need further line of treatment post-failure of PD-1 and other line of treatment.

Usually, post-failure, you see that those patients, they have a low response rate or low control of disease that goes -- is also a low survival in average for those patients. So this is a trial that is ongoing, and we expect to get more patients in this cohort that will be presented when completed.

But for now, we've been able to recruit and treat 21 patients, among which 19 are today evaluable for efficacy, and we are still waiting the two last ones that have been injected to join the '21 cohort as being fully evaluated in terms of efficacy.

But as you can see, we've had a majority like around 50-50 of advanced patients, Stage 3 and Stage 4. First of all, safety. We've seen the usual safety about the use of NBTXR3. If you look at the left table, you see the overall safety table and adverse events that have been observed that include radiation therapy as such, PD-1, the injection of NBTXR3 or NBTXR3.

On the right table, you see the specific adverse events that have been related to NBTXR3 and for injection. As a first thing, we had no grade 4 or 5 adverse events related to the product or the injection and no serious adverse event. And we don't see any specific adverse events versus what has been observed previously in other trials or in the 1,100 other cohorts, including head and neck patients.

So let's go into some of the baseline of those patients. As I mentioned in the intro, those patients received different lines of treatment, and they have all failed PD-1. But when you look at the details of the patients we've been treating, not only they failed PD-1, but for most of them, they fail multiple lines of treatment.

You see on this table patient by patient, the line of treatment they got and the fact that they all have progressed under all lines of treatment. So you'll hear in presence of a population that is really at the end of what the therapeutic options today could offer them. So we've been observing when you look at the change from baseline for all target lesions, a good response, as you can see in the waterfall plot, but I think we can directly jump and go into the RECIST evaluation overall for those patients.

So what you can see here is a split between the patient having 1 to 4 lesion and 5-plus lesion. And the overall response we've been seeing is 47%, so 9 out of 19 patients got CR or PR.

That includes also 4 CR that is important globally across local and systemic treatment. And we've seen a high disease control rate of 78% globally. What you can see if you look at the left of the table is that, obviously, when you have an oligomide patient, you have better response than when you have a patient that have 10, 15 different mets, most likely because the disease being spread into a lot of organ. It may be a bit too late to have those patients. Nevertheless, we still have a DCR with 5-plus lesion of 80% and a decent local control.

Now if we look back at what we have been seeing, which is patient by patient, the different line of treatment, I think it's interesting to see that we got a number of responders. And not only in the patients that are primary refractory or only got PD-1, as you can see, for example, there are 4 patients that have received several lines of treatment, including T-VEC, and we got 2 CR and 2 PR out of it. And many patients that got multiple line of treatment got either stabilization of partial response or complete response.

So what we can see here is we could help patients regardless of the number of line of treatment they got, meaning that we have a mode of action or do provide something that makes it compatible regardless of the previous treatment they have received. Another interesting finding here, we've been looking at the correlation between injected irradiated lesion and what's happening from a systemic perspective for those patients.

So as you can see on this picture, the blue dots are the injected irradiated response and the dark dots are the non-injected non-irradic out of the field response. And you can see there is a tendency showing that the deeper is the response for the primary or injected tumor, the higher is the response for the overall patient, including outside of field response. So clearly, as per our PI comment, this reflects the potential priming of an immune response by NBTXR3 activated by radiation. Thinking that we're still talking here about refractory patient checkpoint inhibitor and most of them have exhausted the primary possibility to have an immune response.

So now let's move to what could be the impact. Obviously, it's a bit early. So we're still waiting the OS to mature. But to date, we have 14.6 months median overall survival with an interval confident going from 11.6% to non-bridge. So we're keen to wait and see how it is going to move over time with maturation of this.

I would like now to show you one patient. We have different patients, we could, but we choose that one because it's a particular patient that is interesting. So beside the patients that got CR from an overall response or PR from an overall response, as you can see in some of the previous slides, we've seen some patients with stable disease.

And I'm going to present you one of those patients. So this is a patient that received multiple treatment and failed multiple treatment. As you can see on the left, you see the PET scan with a very active tumor, and this patient got pembrolizumab, ipilimumab, radiation therapy and also many other treatment.

So here, we show you at the time of radiation therapy, this patient has this tumor, did receive radiation therapy, 40 gray in 10 fraction. And as you can see, 6 weeks post radiation therapy, there was no impact on the tumor. So after failure, all of this treatment, this patient joined the trial.

And as you can see, the tumor has grown in a much bigger tumor with a very active tumor. And we've been treating this patient after an injection of NBTXR3 with 35 gray in 5 fraction. And what you can see here is a patient with a completely inactive tumor from a metabolic perspective. So this patient then as a stable patient for 19 months now is a patient where you can see that there is an activity after the treatment, showing that the tumor had completely -- a complete metabolic response. And as I mentioned, this patient is now for follow-up and still have stable disease from a systemic perspective after 19 months.

Now just before opening the question, I just would like to conclude with what we have seen. First of all, we and our MDs are very happy about the outcome of this trial, showing again in another trial that we could offer option not only frontline, but after several lines of treatment option for patients they don't have today.

We've seen that the injection is feasible and safe, and we have reached the maximum dose as per protocol definition. There was no specific adverse events that we can relate on, and we've seen a promising local and systemic control.

So overall, 47% response and a DCR of 78%. Even early, the first readout on OS that will mature over time led us to 14.6 months. So we think with our PIs that these results are very interesting and really open the road for NBTXR3 to be tested in a randomized trial for this patient population. So with that, I'm going to open the floor for questions. Thank you.

[Operator Instructions] We will take our first question. And the question comes from the line of Jonathan Chang from Leerink Partners.

This is [ Ewan ] on for Jonathan. Congrats on the data. My first question is how should we be thinking about the single-agent activity of NBTXR3 activated by radiation in this melanoma cohort. And a follow-up, if I may, what is your plan for development in this indication given the data we've seen today? And would it be necessary to demonstrate the contribution of components in a registrational trial?

Thank you for the question. So first of all, about the single activity. So that's obviously not the only trial we have with NBTXR3, and there's many ways to look at the single activity of the product, including the randomized trial we have ongoing like in head and neck, but also in lung cancer, where we compare standard of care, including radiation plus the same thing for the tested arm with the product.

So here, we can clearly delineate what is the single-agent activity. Now within this trial, particularly, what we can rely on is the local control of this product. So if you remember Slide 10, there is a right column explaining the injected irradiated response. And here, we have 100% of DR -- with no patient that had PD with this.

So it does show that when we inject NBTXR3, even with a low dose of radiation, here, we're talking about 35 to 45 gray depending on the organ that is injected, we can have a strong control. So that's step one. And this local control is also what we want to emphasize when we work frontline with patients that receive radiation like in head and neck or lung or prostate or breast cancer and so on.

But here, that's a fundamental to have both. First, local control; and two, to have potentially for patients that failed checkpoint kind of a repriming of an immune response, which we start to see. When we look at the link we've been showing between the local response and the systemic response for those patients.

So that's, I think, for the single activity. For the contribution of component, that's always a good question and depending on the setting. So if we think about moving forward in a randomized trial in this population, that will open the question of what is the control arm as there is no specific standard of care for those patients. It's best choice of treatment or whatever the physician thinks could be appropriate. When you look at those patients, they have received several lines of treatment.

So they pretty much have exhausted for most of them any other possibility. So the real -- in real life for those patients, that will be almost nothing or any palliative care that the doc could give the patient. So in a nutshell, I think between trials, because of the mode of action of the product, we could have cross read in terms of contribution of components.

But of course, in any case, this in future trial would have to be discussed with FDA and other regulatory agencies, but we think that could be easily achievable. Now in any case, when we move forward in such indication, a randomized trial could be appropriate to show the benefit overall to the patient because it's a complex population and not always easy to define with a single arm, what is the real outcome for the population.

Your next question comes from the line of Michael Schmidt from Guggenheim.

This is Ruoxi on for Michael. Congrats on the impressive data here. So a couple of bigger -- bigger picture questions for me. So it sounds like for future and next steps, you would primarily be considering kind of developing this for the late-line setting once other options are exhausted. I guess do you also see a place for R3 in an earlier setting for cutaneous melanoma? And then secondly, just thinking about pipeline prioritization and next steps, I guess, would this be something that you would develop yourself? Or would J&J kind of develop this further as part of the collaboration?

Thank you. Well, when it comes to different line of treatment, let's say, for melanoma, obviously, it's a quite different disease than head and neck or lung. But in melanoma precisely, it is sure that if we could have an action at the beginning of the disease and not wait the patient to fail multiple lines, we should potentially get a much better outcome than what we see here.

But when you look at the current standard of care, that will also open and require a trial which is much bigger and much longer. So there is the patient need and the regulatory pathway we could, if we want take for this population. But we have observed something in this trial is when you have patients with 15 mets or more and that this is already spread into multiple organ with fast growing, it's a bit late to get an action that could be beneficial for the patient. But this is going too fast.

Whereas for patients that have multiple mets, it works unless it's really spread across the whole body. So that's obviously favor to go in earlier line to bring that treatment. Two, your question is about priority and how we could envisage the development more globally across different indications. This one included when we think about J&J's work versus what NANO could do.

So maybe broadly, let's go back to the overall strategy. Because this product has a physical mode of action and is not specifically targeting any biological target, we've had a different approach for the development, not going from Phase I to Phase II to Phase III for each indication, but more having 1 or 2 indications going forward with randomized data, which is the ongoing Phase III in head and neck cancer and the ongoing Phase II in lung Stage III, both now run by J&J.

And when we get enough data coming from this, we're going to use all the Phase I that have been done showing feasibility, safety and first good sign of efficacy as a potential start for other registration trial. So it doesn't mean that we will move all those indications or J&J will move all those indications into Phase III, but I think we have been establishing a very large base for NBTXR3 to be usable in many indications in oncology.

And as there are many discussions with J&J at the moment, we will, in due time, and hopefully not too late from now, tell you more about what could be the next step in the development of NBTXR3.

And the next question comes from the line of Clemence Thiers from Stifel.

Two on my side. First one is, obviously, the lower the number of metastases, the better is the response. First, is there any other factor or baseline characteristics you identified as playing a role in the response? And how would that potentially impact the future pivotal trial? Would you focus on earlier stage of metastatic melanoma. That's the first one. And the second one is, we know that there is some differences in mechanism of primary and secondary resistance to anti-PD-1. Would we expect or did you observe in the trial, any difference in response between the two?

Thank you. Maybe let's start about the primary versus refractory question. So obviously, here, we have a small number of patients, and the trial has not been designed to answer this question. But I think we can also be informed by the other cohort of the 1100, which has much more patients in head and neck.

And when we look at the patient being primary or secondary refractory, we don't see differences regardless of being in melanoma or head and neck cancer patients. And I think that's an interesting thing when you mentioned that the mode of action is different and so on.

And that's really, I think, one of the key advantage of using NBTXR3 in setting is because regardless of the patient, the lines of treatment, we know we're going to bring high local control. And for a number of patients, we start seeing that we can bring repriming or priming of an immune response that was not existing. So that's a broad applicability. And we don't see right now, to come back to your first question about baseline, is there anything that we could use to select the patient?

So far, the HPV status in head and neck or the PD-1 expression or the fact that the patients have received one line or several line of treatment was not influential in the outcome we have observed. But I think that's interesting when you look at one of the slides we've been presenting with all lines of treatment, is that we could expect that the more patients have received treatment, the less they will be willing to respond to a new treatment, what we see usually.

But it's not the case here. Even for patients that received 3, 4 or 5 treatment, we get a good number of PR or CR globally for those patients. So for now, but of course, going further in the development, we will refine this question, but that's really a patient agnostic and so far baseline agnostic product.

Your next question comes from the line of Swayampakula Ramakanth from HCW.

Congratulations, Laurent and team. I think this is pretty good data for these advanced melanoma patients. So just to understand a little bit more about the CR and PR, can you -- is there any trend among the patients that achieved a CR versus a PR? And the other question is, how should we think about metastatic tumors in other organs, who are also in that cohort 3? How should we think about -- or what should be our expectations regarding data in those additional tumors?

Thanks. So for the second question first, this trial initially, the Cohort 3 has been designed to take any primary tumor that will be resistant to PD-1 to start exploring other organ other tumor. But rapidly, there have been a good number of melanoma patients and seeing the first results, the PI of the trials are really focused on melanoma cancer patients. So the remaining patients for this trial will be mainly melanoma patients, and we'll have only a few having other type of tumor.

So of course, they will be included in all the safety and feasibility assessment. But given the small number we will have in other tumor, I don't think we could extrapolate anything from it. But that may be the occasion to look at other type of cancer that have metastases that we could help. RK, I'm not sure I got your first question. about the response and the CR. What do you want to know exactly?

Is there any trend among patients who achieved a CR versus a PR?

Okay. Like anything differentiate them or in terms of baseline or outcome and long-term outcome? No, not at this stage. We'll be looking at the detail. But again, that's still a small number of patients. And the trial has not been designed with TAT. So we could look at different type of baseline for patients. But so far, in this trial, like in head and neck 1100 trial, we don't see really anything from baseline that could help us to differentiate patients either predict CR or PR or influencing the outcome of the response.

One additional question is on the study that MD Anderson is doing, again, in metastatic melanoma who have progressed beyond anti-PD-1. So how about -- what could be the read-through for that study? And do you know when they could -- that data would come out?

The NDA is not working on melanoma per se. They have trials where they have effectively refractory patients to PD-1 was a different population than melanoma.

Your next question comes from the line of Lucy Codrington from Jefferies.

Only a few left. Just a clarification to begin with the overall survival of 14.6 months. I think on the slide, the confidence intervals are slightly different to that on the press release, and it seems like it wasn't reached on the slides, but I think it said 16.7 months at the upper end on the press release. So just to clarify that.

And then I appreciate it might not be possible, but is there any way to contextualize that overall survival compared to what you might expect in this population? May not be probable, but it would be helpful. Thank you.

Thank you. And we'll look at it about the table. But it's correct number 11-point something up to non-rich. That's the interval confidence. So again, for patients that have received multiple line of treatment, there's no specific definition of how you could look at OS and PFS or response, but there are a few references that show, for example, that after failure of PD-1 when patients take EP or a mix of EP plus nivo or BRAF or MEK, they have an overall median survival of 6.8 months.

We also have some oncolytic virus that could provide additional benefit post-failure, where the survival could go up to 14 or 13-point-something months with a response rate around 30%. But again, having direct comparison with last-line patient treatment, it's very complicated.

But when you look, for example, of the PATRINAVY and our trial, where they have been trying many things like EP plus nivo or BRAF plus MEK, there is almost no CR for those patients. So again, if you want to have a potential of really improving the life for those patients, getting through CR is an important thing and getting to long duration of response is an important one. And when you look at the median survival in this paper, we have 6.8 months.

Got it. And then just one follow-up on the safety. So the episode of hypertension and fluidic pain, that was a Grade 3 event. I'm just quite confused by the Grade 3 plus. So I know you said nothing to do with the injection for Grade 3, 4 or 5, but just to confirm that it was a grade 3 event.

Yes, that's a great 3. There was no grade 4, 5 linked to the product or the injection procedure.

Your next question comes from the line of Chiara Montironi from Van Lanschot Kempen.

This is Chiara Montironi from Kempen. Congratulations with the data. So just going back to NBTXR3 clinical development. I was wondering how will this data inform the next step for the development, maybe a combo development? Is this all in the end of J&J or which factors do you think will be determining the choice of further developing in this indication? Could this expand the case beyond head and neck?

Sure. Thanks for the question. So first of all, we can't talk for our partner. But as I mentioned sooner in the call, there are many discussions to see how to move forward in the development beyond what is known by the market today, and we will inform you in due time as soon as we can. But more broadly, I think there are indications that J&J would or could take to move forward as Nanobiotix could also because in the contract we've been signing with them, there is a specific section and specific reward to that if Nanobiotix will do some trial beyond what J&J wants to do.

But that's a part. I think we should go back to fundamentals. I think going frontline treatment for patients, when radiation therapy is used for local control, which is the vast majority of the millions of patients getting radiation, here, the clear goal is to get much better local control.

Like if you think about head and neck, frontline treatment, the majority is about local control, 90%. And here, radiation is playing a key role. But 60% of those patients will fail over time and eventually, we'll go to PD-1 and other treatment. So here doesn't need to get better control. And in head and neck, if you want to cure a patient, you need to get to a strong local control, possibly including CR.

If not, the patient will eventually die from local invasion or development, and it's very hard to treat such a patient as we can see in head and neck. So frontline will be NBTXR3 as such. Now when we move to further line, that's a different thing, and that really depends on the population of patients and what is available for them.

We can see in melanoma that you could use some oncolytic virus, for example, that could be interesting to have the patient but the oncolytic virus will work from another angle that NBTXR3. So we could combine and get a much bigger outcome for the patient or use that as a single agent. If you think about head and neck metastatic patient, even the last line of treatment, again, you see some bispecifics and some new treatment that could help the patient, but they are not enough to cure the patient.

And for head and neck, there's always a need to have local control regardless of the systemic control you can provide. So again, you could either choose to have this modality to any other systemic treatment and combine better outcome. And because of the local aspect of this product, we should not expect to have large combined toxicity because we're really combining a local agent with a potential systemic agent.

So we see that as a product that could be used in many situations offering first local treatment, then in some patients, offering a potential to prime or reprime an immune response. So that offer multiple possibilities and multiple potential combo.

[Operator Instructions] Your next question comes from the line of David Dai from UBS.

I also want to congrats on the data here. So a couple of questions from me. So Laurent, I know you didn't present the progression-free survival data in this data set. I'm just curious, can you share some preliminary analysis on progression-free survival aspect of the data analysis? So that's the first question. And second question just around how should we think about this data be able to read through to the NALORAE-312 trial in the locally advanced head and neck cancer. I understand that the data should be expecting in first half next year. So any kind of read-through from this data set into that data set here?

Okay. Thanks, David, for the question. We did not present the PFS just because of the size, but we have to date a 6.3 months median PFS for this trial. And of course, as the OS, it has to matter, but it's quite consistent with what we see between PFS response and OS.

Now about the question about read-through, I think it's really 2 different populations. So it's very hard to look at what happened in melanoma and try to expand into head and neck, neither from a local perspective in head and neck or metastatic perspective in head and neck. What we can say is in this indication, like we have seen in others, there is a very strong close to 100% local control. So the only thing we could read is we have a strong local control when we inject NBTXR3 and use radiation to activate it. And that's what the 312 is about, having a strong local control. But besides, I don't think there's much to read through.

Now from a metastatic perspective, I think as we know that there is different tumor mutational burden or hotness of the tumor depending of the characteristic of the tumor and the nature of the disease. If we want to get in order, we can think that melanoma is the hottest tumor than lung, then head and neck and some others.

So here, it's about what the capability potentially of the product to prime an immune response when there is no immune response at baseline or to reprime an immune response. But that's a complex question, that will require further study to look at it. Because if we look across studies where we've been treating metastatic patients, or patients like with pancreatic cancer, we see clearly some activation of the immune system, one way or the other.

But it's hard to see because this is a new modality to link that to any specificity of the tumor. But I think when we have enough patients, we will be able to explore that point and see if the priming of an immune response could be better or less better in some patients, depending on their characteristics.

But I think that's for later. And again, when we look at where the patient need is, front-line treatment, follow co-treatment, that's where the millions of patients need radiation therapy and where we could have the biggest impact.

Got it. That's really helpful. And then just maybe another question on the timing for development for this in the melanoma setting, the randomized trial. Any thoughts around when should we -- when are you planning to start the randomized trial? Any kind of preliminary thoughts around the development time line would be helpful.

So for now, as I mentioned, we can't say anything about further trial, even though we're discussing that with our partner and we'll inform the market as soon as possible. Nevertheless, this trial is still ongoing, right? So we need to finish our equipment, which we expect to complete within the next few months to get more patient and also to have broader readout with this larger number of patients. And based on that, then if we want to move forward or J&J wants to move forward, we could design more efficiently a trial to get to next step in melanoma.

There are no further questions. I would like to hand back for closing remarks.

Well, thank you, everyone. Thank you for the very active discussion. And again, we're really happy to have brought that to you this new data. And let's keep posted. We have much more to come in the not-too-distant future. Thank you very much. I wish you a lovely day and talk to you soon.

This concludes today's conference call. Thank you for participating. You may now disconnect.