Nanobiotix S.A.

Good day and welcome to the Nanobiotics Business Update and Full Year 2024 Financial Results Conference call. At this time, all participants are in a listen-only mode. After the speakers' presentations, there will be a question and answer session. Please be advised that today's conference is being recorded. At this point, I would turn the call over to Greg West, Senior Vice President of Investor Relations of Nanobiotics.

Please go ahead.

Thank you.

Good afternoon and good morning, and welcome to the Nanobiotics Conference call to discuss our full year 2024 financial and operational results. Joining me on the call today are Laurent Levy, co-founder and chief executive officer, and Bart Van Ryn, chief financial and business officer. As a reminder, today's call is being webcast and will be available on our website for replay. On the next slide, slide two, 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, amongst 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 filed with the AMF in France and SEC in the United States, which are available in the Investor Relations section of our website, along with the press release issued yesterday highlighting our corporate and financial results for the period. 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, Nanobiotics undertakes no obligation to update them to reflect subsequent events or for future circumstances. With that said, I'd like to turn the call over to Laurent. Please go ahead.

Thank you, Craig, and welcome, everyone. Today, we're going to talk about the progress we've been making with NBTXR3 or J&J 1900. And also, we'll give you some financial highlights and operational highlights for 24 and 25. And we will end this call with a Q&A session. We have made very good progress toward our pathway to sustainability and growth. and starting by continuing pushing and developing this collaboration with J&J. In 23, we've been signing this 2.6 biodollar deal plus royalties with J&J and now pushing into different direction and different indication. If you think about just the two first indication in lung cancer and head and neck cancer, those two first only could represent over 100,000 patients addressable in the US and EU5 alone, which could lead to a potential 10 billion market. As you will see, we have many things ongoing, and this collaboration is progressing well. But it's not the only thing that will lead us to sustainability. There is also the new platform we are developing. And this year, we've been launching our new platform, first in class product with Curadigm. We'll talk about that a bit later. But first, let's move to next slide and see how do we tend to address one of the largest untapped markets in oncology? Slide six, you can see our pipeline. And as you will remember, NBT-XR3, our product, is a product that is very versatile, a product that is tumor agnostic, patient agnostic, and target agnostic, which means that we could literally combine that in many indications in oncology, as you can see in our pipeline. So we've been progressing a lot, this pipeline this year, in different indication, including two very important ones. The NanoRay 2E12, which concerns elderly patients in head and neck that are frail and ineligible to cisplatin, but also the Lung Stage 3 program that J&J started this year. Let's move to the key development we've been doing, starting with NanoRAID 312. This is our pivotal phase three study in locally advanced head and neck cancer. It is a global study, 500 patients randomized one-to-one. What we've been doing in 24 is first aligning on the transfer to J&J of this program. And we did that midstream of the development of the NanoRAID 312. Why we did it? Because we thought it was the best thing possible to do with this study Rather than waiting the final data before transferring, which would have caused some delay post-result, we said that it would be much better to do it now in order for J&J to be ready, assuming the data are positive, to push the return and start registration of the product. We expect to complete this transfer around Q3 of this year. So that's for the NanoRay 312, which is progressing and now being transferred to J&J. On the other side, J&J has started a new trial named CONVERGE. It is a randomized phase two study in unresectable stage three lung cancer. And the first patient have been dosed in January this year. And this trial progressed quite well. Moving to next slide. Those are not the two only development or clinical development that have progressed. We also have early stage study that are progressing across solid tumor. Let's start with NNNEC recurrent and recurrent metastatic cancer patients that are eligible to PD-1. So our phase one study, 1100, have been showing last year some positive data showing safety, feasibility, and also very good disease control and tumor response. And we expect to give this year an update on this trial, both on patients that are first line PD-1, but also the refractory PD-1 on the completion of this two cohort. We've been also progressing in pancreatic cancer. That's one of the trials we are doing with MD Anderson Cancer Center. It is about patients that are locally advanced or borderline respectable. We've been completing the phase one and got some really encouraging outcome in terms of safety profile of the product, but also in terms of efficacy. And as we've seen such a good result for the first one, we decided with MDA to expand into a new cohort, which this time will be the same treatment within the standard of care, meaning radiation plus chemo plus nano particle for pancreatic locally advanced cancer patients. This second cohort has started and recruiting well. We should expect also this year to get a result from the escalation part and the expansion part of the trial before the summer. In lung cancer, we recently published some data coming also from MD Anderson Cancer Center. They have completed the dose escalation part of a phase one in non-small cell lung cancer that already received some previous treatment and that are eligible for re-irradiation. So the data were really good in terms of safety and feasibility, again, very consistent versus other trials we've been showing. And we start to see, even early, some very interesting sign of efficacy, meaning local control of the tumor, which is essential for those patients. So as you can see, we have been progressing the pipeline and will continue as we expect many more clinical data coming this year. In parallel to NBT-XR3 or J&J 1900, we've been launched Curadime, our fully-owned next-generation nanotherapeutic platform. This is based on nanoparticles and nanophysics, and again, something that we expect to be useful for many, many patients, millions of patients, but not only for one indication or one therapeutic area. It is something that we expect to be used in many therapeutic areas in combination with many types of products. So as you may remember, those are nanoparticles that are designed to temporarily occupate the liver. And while the liver is busy with those particles, when you inject something else in the patient, then the liver accumulation will be decreased and to a certain extent will completely change the bioavailability of the second product that you inject. So this has a strong potential to increase efficacy or decrease toxicity of existing products. But where we think it could be really, really big is because we can create all new therapy with a unique competitive positioning, something that we work internally to start building our own pipeline. But as I mentioned, this is a technology that could be widely applicable. And therefore, this is an ideal candidate or candidates, I should say, to make potential multiple partnerships. and that's a strong activity we are leading this year, talking to biotech and pharma industry. On the top of progressing our collaboration and platform development, we also have added two new board observer to the nanobiotics board, Margaret and Anat, and we'd like to welcome them for the contribution. Also, they already have brought to the company and the future contribution. We intend to confirm the subserver and make them full member at the next General Assembly. That's it for this party, and I'm now going to give the mic to Bart to give you some operational and financial highlight.

Thank you, Laurent. Good morning and good afternoon, everyone. Moving to the next slide. As Laurent mentioned earlier, Nanobiotics has had an extremely productive year, and we've been executing our disciplined financial strategy to move the company towards long-term sustainability and growth. Subsequent to our progress in 2023, in which we signed the license agreement with Johnson & Johnson and completed the follow-on offering, recent activities include the receipt of the first milestone payment in May 2024, when we received the $20 million payment related to NanoRay 312 progress. And continuing this execution, we announced last month the signing of an amendment to the Global Licensing Agreement for MBTXR3. This amendment has several important provisions, including removing the vast majority of the nanobiotics funding obligation for NanoRay 312, releasing J&J from select future potential milestone payments, and safeguarding nanobiotics' path to sustainable cash flow through hundreds of millions in potential milestone payments related to LEED programs expected in the coming years. As a result of these changes to the license agreement, we have extended our cash runway to mid-2026, and not to be missed, these changes should result in a meaningful reduction in cash burn beyond mid-2026, as the full cost of a Phase 3 study will no longer be reflected in our financials. And we're not done. We are continuing to actively explore further financing options, preferably non-dilutive, to extend cash visibility into 2027. This is rooted in the belief that our first platform provides a path for nanobuilders to reach financial stability in the next few years. As we advance to the next slide, we show here the elements of the amended agreement over time. We can share with you what has transpired so far as well as our outlook, should data readouts and regulatory approvals come in positive. The left column represents elements of the agreement that occurred already or are ongoing. This includes the $80 million already received made up of the upfront equity and the first milestone I mentioned previously. There are many elements of the agreement ongoing, such as tech transfer, product supply, J&J investing in duplication of our manufacturing capabilities, and starting the randomized converged study in non-small cell lung cancer. In the middle, you can see that there's 200 million plus of medium-term milestones that we expect in the next two to three years. This should lead to a sustainably financed company with increased commitments from J&J. When we look at the right-hand side of the slide, we can see that we maintain the royalties. We maintain the 220 million per new indication developed by NanoBiotics, which would require funding by NanoBiotics. as well as more than 2.3 billion relating to long-term milestones of the ongoing programs, development and regulatory milestones of potential additional indications, sales milestones that are indication agnostic, as well as the Li-Bio milestones for greater China region. I'll describe these more in a moment. The settlement of these items allows Nano to focus on supporting J&J regarding the operational success of NWA 312 as reflected in the amendments. As we turn to the next slide, I wanted to share a recap of the overall structure post the amendments. We've presented this before, and these are post-amendment numbers. As I already indicated, royalties have not changed, and the $105 million in total has been removed from the first and third buckets from a milestone perspective. The first bucket now reaches up to 1.77 billion, and the third bucket, which was the Li and Bai bucket, now Jensen bucket, reaches up to 165 million versus 205 million prior related to the Greater China region. In total, the agreement and rights assignment represent a potential of 2.6 billion in milestones with potential for additional milestones from indications we may develop and fund and will receive tiered royalties from the low teens to low 20s as percent of sales. Now let's turn our attention to the full year 2024 financial highlights on the next slide. Negative revenue of 7.2 million was recognized in 2024 compared to 36.2 million for the year ended December 31, 2023. Significant revenue was recorded in 2023 in connection with the execution of the license agreement with Jensen, as well as the recognition of the NanoWay 312 development milestone. The negative revenue impact recognized in 2024 results from the transfer of NanoA312 study sponsorship to Jensen signed at the end of 2024, which amounts to a negative €19.3 million revenue impact, which is driven by a one-time recognition of a net liability towards Jensen to reflect this new situation. This net liability is made up of the refund obligation the company has towards Jensen regarding the NanoA312 total remaining costs that will remain with the company, which is offset by residual contract liability and R&D services recognized in 2024. This net liability was recognized at the time of the execution of the amendment and is a result of the application of IFRS 15 revenue recognition accounting treatment, which generates the cumulative negative catch-up. To be clear, this negative revenue amount is a non-cash item and therefore does not impact Nano's cash position. This one-off negative impact is partially offset by other revenues recognized in 2024 that conversely do positively impact our cash position, including sales of clinical products and supplies, for 5.9 million euro, technology transfer services built to Jensen for 1.8 million and research tax credits for 3.3 million. R&D expenses consist primarily of preclinical, clinical and manufacturing expenses related to the development of MBT-XR3 and totaled 40.5 million euros for the 12 month period ended December 31, 2024 as compared to 38.4 million for the 12 months ended December 31, 2023. The 5% increase in net R&D expenses was primarily due to an increase of clinical development activities, driven by the cost related to NanoA312 and the phase one multi-core trial of RT-activated MBTXR3, followed by anti-PD1 checkpoint inhibitors, also known as study 1100, as well as the full year impact of R&D positions that were recruited in 2023. When we turn our attention to selling general and administrative expenses, these were 20.5 million euros for the year ended December 31, 2024, compared to 22 million for the year ended December 31, 2023. The 7% year-over-year decrease is mainly due to one-off fees incurred in 2023 consisting of license agreement execution and equity issuance related legal expenses, next to one-off fees paid to a financial advisor for 1.9 million Euro in total. Net loss attributable to shareholders was Euro 68.1 million, the year-over-year increase of 72%, or one Euro 44 per share for the 12-month period and the December 31, 2024, which is primarily attributable to the one of negative revenue recognition accounting impact, which again was a non-cash item. This compares to a net loss of €39.7 million or €1.08 per share for the year ended December 31, 2023. As we look at cash-in-cash equivalents, as of December 31, 2024, NETObiotics had €49.7 million in cash-in-cash equivalents compared to €75.3 million as of December 31, 2023. Based on the current operating plan and financial projections, Nanobiotics anticipates that the cash-in-cash equivalence of €49.7 million as of December 31, 2024 will fund its operations into mid-2026. To conclude, we have a disciplined capital allocation approach and our recently amended licensing deal arrives at a structure that puts the company on a path towards a sustainably financed company, subject to milestones or regulatory approvals coming in positive. We are very excited regarding the potential of MBTXR3 or J&J 1900 and are focused on bringing this first-in-class radio enhancer to the market together with our partner. And now I will turn the call back to Laurent. Laurent? Thank you, Bart.

Let's see what's coming in the next 18 months for nanobiotics. As you can see on slide 16, We expect to get a very important milestone next year, and namely the end of recruitment of the ongoing phase three in head and neck. That should lead, assuming the data are positive, to potential registration. There's also the stage three randomized phase two in non-small cell lung cancer that J&J has started that should start reading in the not too distant future. But what's coming for this year is more data. And starting with the head and neck refractory patients that are eligible to PD-1, either as a first-line or second-line or third-line treatment. And we expect to get data on those two cohorts by the end of 25. The non-small cell lung cancer trial coming from FDA have been published just a few days ago. But there will be more coming from the MD Anderson Cancer Center. where we'll have the full data of the pancreatic cancer phase one trial that should be published before mid-year this year. And for second part of the year, we're waiting also the first data coming from the last cohort, coming from the 1100 trial, which are patient that received multiple IO treatment and some others that got refractory. And then we have injected our product plus radiation continuation of PD-1 to see if we can rescue this patient. And most of the patients here have been melanoma patients, and we're really eager to present this data. And finally, coming from MD again, the esophageal phase 1 first data, we will start updating this program by the end of this year. So as you can see, there will be a lot to say from now to the end of the year while waiting some of the key important milestones in locally advanced head and neck cancer, phase 3, or lung stage three randomized phase two run by J&J. In a nutshell for today, what we would like to take away is first of all, we're moving forward with the partnership with J&J. It does evolve and progressing really well. We have continued also to show the potential and opening the potential of NBTX artery in multiple indication. This year, or last year, sorry, has been a good time to introduce our new platform, Curadime. And equally importantly, not only are we growing our different options to develop products to help patients, but we're really moving toward financial sustainability and growth for the company. And last year, we've been clearly strengthening our financial position. And finally, we're coming with the end of the year, where we expect many more clinical readouts and more to come. So with that, I'll conclude the first part and we'll open the session for Q&A.

Thank you. As a reminder to ask a question, please press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. Once again, please press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. We are now going to proceed with our first question. The questions come from the line of Jonathan Chang from LeeWing Partners. Please ask your question.

Hi, good morning. This is Yander Li for Jonathan Chang. Thanks for taking my questions. So I have two questions. So the first one, could you provide more details on the recently initiated phase two converge study by J&J? Specifically, when can we expect to see the initial data? and what factor gives you confidence in the study's potential for success? Thank you.

Thank you. Unfortunately, for now, we can't tell anything more that the trial has started and progressing well, and we'll come to our partners to define when will be the first readout of this trial. Now, concerning the other part of the question about why this population and what should we expect and what do we think NBT-XR3 could make a difference here. I think it's in going to the continuation of having consistently showing very good local control induced by our product when combined with radiation. And in this specific population of locally advanced not small cell lung cancer, so stage 3 patient unresectable, that usually get the Pacific regimen, which is radiation, chemo, and followed by PD-L1, assuming they did not progress in between, they're still low bar in term of local response. And more generally in oncology, when you have good local response for locally advanced cancer patients without MET, then this translate into PFS and OS. What we have seen in head and neck, what we see in other indication, So clearly, the point here is to bring much better local control to those patients. So that's the context of this randomized trial. Now, what we start seeing across different indications, as I mentioned, show already a good local control brought by NBT-XR3, and we think the recent data generated by MDA is also a good sign of what could happen in the CONVERGE study.

Understood. Thank you. Very helpful. And my second question is about the upcoming pancreatic cancer data presentation. We're curious, how will the information presented there be different from the press release last year? And if the results are promising, what would the next step be for MBTXR3 in this indication? Thank you. Thank you.

So end of last year, we announced the completion of the phase one that was including an escalation port and an expansion port and just gave the top line overall survival for the patient. So what we should expect as a readout for this is the full data including efficacy, safety, some of the potential biomarker that have been used so that MDA is working on that aspect right now. There's already a next step that has started when we announced that FDA approved an amendment to the protocol that is adding a new cohort. And this new cohort is about giving the full standard of care to patients. Just as a reminder, the first part of the trial was patients that get chemoinduction, then followed by radiation plus NBTX artery. Now, that's not the full standard of care that those patients usually receive, as they usually do chemoinduction, radiation, plus chemo. So in this expansion part, we have added the chemo on the top of radiation plus NBTXR3, and therefore should expect, according to the existing non-model faction, a better synergy and even more efficacy than what we've been seeing in the first part of the trial. So this part of the trial is rotating, and we will tell soon when we should expect data on that.

Thank you. Very helpful. Thank you.

We are now going to proceed with our next question.

And the questions come from the line of Shan Hama from Jefferies. Please ask your question.

Hi there. Thank you for taking my questions. Just on, I guess, what portion of costs are you still liable for for the nanoarray study? And what are they related to? And how much is it if you can disclose? And secondly, I appreciate this might be more of J&J's responsibility. But what's the most recent communication you've had with FDA on the NanoRay program? I think the recent shakeup in the administration and the FDA has caused concerns that some programs might be deprioritized or there may be sort of delays in meetings. What have you been hearing? Thank you.

Thank you. So maybe let me take the second question, then I'll pass the mic to Bart to answer the first one. I mean, we interacted with FDA or other agencies on different matter and J&J is doing the same. As our program already well engaged, we don't have experience, to the best of my knowledge today, any delayed in meetings or interaction. So things looks normal to date.

Thank you, Lauren. Happy to follow on. Thank you, Sean, for the question with regards to the remaining costs with nano buildings. That is relatively immaterial as we've guided the public. The vast majority of the costs are now with J&J that has taken over the obligation to fund further to the exchange of milestones that we announced two weeks ago. That may lead to some payments in 2025, 2026 and 2027 that remain on our end, but they're in the single-digit millions in those respective years and are not impacting the cash runway in a meaningful way. We've guided the cash runway to mid-2026, but the removal of the vast majority of this phase three trial cost will benefit us beyond mid-2026. And that burn rate will come down if one takes a look at our annual R&D expense, of which the majority relates to the NanoRay 312, directly or indirectly, one should expect that we will have a very attractive cost run rate post mid-2026. Thank you.

We are now going to proceed with our next question. And the questions come from the line of Michael Schmidt from Guggenheim Securities. Please ask your question.

Hey, guys. Good morning. I just had a bigger picture question. So now that the NBTRX3 program has essentially transitioned fully to J&J operationally and financially, I guess

As you think about the company longer term, what are some of the R&D initiatives internally at Nanobiotics that you think could create additional value longer term beyond NBT-XR3?

Thanks, Michael, for the question. So maybe first of all, let's say that we're not yet done with NBT-XR3. We still have a lot to do. You're fully right when you say that. GenJ now is taking a good part, a majority, of what is happening with NBT-XR3, with the Converge trial, with the transfer of the 312 and so on. But this transfer is not yet done. As we mentioned, it should be in Q3 this year. And there's still a lot to do around the manufacturing, around preclinical, around preparing everything that should go and will go in the dossier for registration. Outside the 312, which is today a big part of the investment in resources of nanobiotics that NoGenJ is taking, there's still a lot in parallel. And this, we think, will continue for the coming few years. Now, it is true that this shift of the 312 is also opening some doors for us, not only because we are going to spend less money, but also we can free some resources to continue to work on our other platform and mainly the Curadigm platform, which is the platform we want to push after NBT-XR3, which is a very broad applicable platform, not only to potential early deal and partnership, but also to develop our new internal pipeline. But we expect to give more detail on that before the end of this year.

And so I think you mentioned earlier about how much additional R&D spend in 2025 and 2026 will be on NBT XR3 versus other programs.

But do you want to take that one?

Yep. It was unmuting. So what will remain essentially is the 1100 study MD Anderson preclinical and discovery work as well as Curadime. Each of those are single digit millions. So the burn will come down quite significantly on the R&D side with the 312 study making up the majority of the R&D spent. So that is millions per quarter less. The beauty of the Curadine program is that, as explained to the market, It's a platform that can be partnered, whether it's with existing new drugs or drugs that have failed. So we expect that the burn will be very efficient in that regard. It will go up versus what it is now. but it will on a net basis with the removal of the phase three liability be significantly less on a net basis going forward.

Thank you.

Thank you, Michael.

We are now going to proceed with our next question. The questions come from the line of Saiyam Pakula Ramakant from HCW. Please ask your question.

Thank you. This is RK from HCW. Good afternoon, Rohan and Bart. So a couple of quick questions here. So this is for Bart. You know, you were talking about the runway. which currently stands still mid 2026. And, and you were also saying, you know, there are potential ways for you to extend it into 27. So what, what could be the, you know, the potential non dilutive ways, and also, you know, how much of a gap is there, you know, for you to fill, so that you can take it up to 2027, or into 2027? from where it stands currently.

Thank you, RK. We feel that the enterprise value is significantly disconnected with the market cap, therefore dilutive options are not our preference. We have EIB debt in our cap structure and adding more debt, we believe, is not the ideal way to go about things. But other non-dilutive financing options, such as royalty financing, we believe hold good promise for the company, given the type of asset this is. Just to remind, it's a very versatile asset. Laurent mentioned it in the call, it's tumor agnostic, combination agnostic, target agnostic. We see significant engagement and investment by our partner, J&J. We expect that to continue, so it is a very interesting asset for many of providers in that space. As our burn will come down quite significantly, we don't need a lot of money, it would be low teens, to get into 2027. It just behooves us at this point in time to remove the finance overhang and get into a safe harbor because there's tremendous value in this asset that needs to result in value creation for our shareholders. And we want to make sure that we do that so that there's no finance overhang and people can just appreciate the technology, the versatility of it, that is partnered with a partner that we believe is an ideal partner for this asset and bring it hopefully in many indications should data readouts be positive.

Thank you for that, Bart. And then, Lorraine, just thinking about R3 for a second, you know, having seen the data that we have seen so far, you know, both on the safety side and on the efficacy side. To me, there doesn't seem a real reason why this should not get into the market. Granted, it may take a little bit of time, but there's no reason to think that it should not get to the market. However, what could be potentially the reasons why it cannot get to the market? You know, I was just thinking about it because based on what we know about the molecule, I feel quite confident, but other than the timing part of it, are there any other things that, you know, I'm being blindsided?

Well, thank you, RK, for the question, the $10 billion question. Well, I think we could have had a different answer to this question depending on timing you would ask for it. In the past, we would have indicated manufacturing is always a risk. Getting some first randomized data is always a risk until you have them. Not having a partner to market the product or to make sure we can develop broadly would have been a risk. and many other things, but I think where we stand now, I think all those usual big impactful risks that the biotech is facing is behind us. I will say that we are in a very de-risked situation right now. There's never 100% guarantee in any of the things. I think what we should just do is wait. There's not too much time to wait now to get to the next big inflection point and to, on our side, help GenJ to move as fast as they can and to bring this product to market.

Thank you for that. And then the last question from me is also on the curidime asset. Probably I've asked this question in the past. What's the gating event that needs to get done so that you know you can initiate a you know a clinical program um is it uh is it resources or is it time time in the sense getting all the material together you know to start a program well i i think it's essentially timing we have enough resources to push uh this uh this program um as about mentioned at the stage of development it is it does not

cost a lot of money, but also as we want to re-emphasize the partnership activity on that, then there probably will be a big part of it that will be done on other times. So we're working on our internal pipeline and also have been starting interacting with many biotech and pharma. We have a good number of MTAs already signed on their way. So things are moving, and we hope I will give much more info by the end of this year.

Thank you. Thanks for taking all my questions.

Thanks, RK.

Thank you. As a reminder, to ask a question, please press star 1 and 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 and 1 again. We are now going to proceed with our next question. The questions come from the line of Eric Musunza from UBS.

Please ask your question. Hello, Eric. Your line is open. You may ask your question.

Actually, this is David from UBS. Can you hear me?

Yes, David.

Yes, great. So, yeah, just actually two questions from me as well. So, regarding the NANA RAID 312 file, So you're planning to enroll patients with and without cetuximab. These patients who receive cetuximab will likely have a longer survival. Could you help us understand what percentage of patients are going to be enrolled with cetuximab and what percentage will not have cetuximab? And just curious if there's going to be a cap in terms of patients who have the cetuximab background.

Thanks, David. Citriximab is not the biggest used drug in head and neck when it comes to frail and elderly patients. Nevertheless, that's something that is in the standard of care guideline. But when you look at it, not many people are using Citriximab. The reason why this drug has been added is because they are in the guideline. So we need to leave the choice open for physicians to use it or not. So that's one. And in order to make sure that the trial is balanced and there is no bias, we've made cetuximab use as a stratification factor. So we should assume a balanced number of patients getting it in both arms. Now, why cetuximab is not used that much in those patients is because when you look at the detail of the Bonner paper, what you see is that for elderly people, the cetuximab use is detrimental. versus radiation alone. So of course, looking at the overall data, you see a benefit for cetuximab, but this benefit is exclusively driven by younger patients. So at the end of the day, we think that cetuximab in this trial will have either a neutral effect, we should not expect more efficacy coming from it, or a plus, a little plus. But if there is some small benefit, we should assume that this benefit will be at the minimum equal in the arm with NBT-XR3 or better if we anticipate synergies. So that's why we don't think cetuximab in this trial will play a key role.

That's really helpful. And then there's another question on the upcoming data readout. There are many updates in 2025, including the placement data from the relapsed metastatic and neck cancer in combination with PD-1. Can you just share with us mechanistically how do you think R3 will be additive to PD-1 to exert better systemic benefits for those metastatic patients?

Sure. First of all, before getting to the benefit of systemic activity of NBT-XR3, I just want to remind that for all patients getting PD-1, the first time they will get PD-1, they're usually one-third of those patients that are only locally relapsed, one-third that will have local relapse plus MET, and a third only will have MET only. And most of the patients, the 60% I mentioned previously and beyond, they're coming from the failure of previous lines of treatment. So before getting into any systemic activity of NBT-XR3, we should just remind that Those patients getting PD-1, they also need and primarily need a local control. That's what our PIs are mentioning quite repeatedly when we talk to them, that systemic control in head and neck metastatic patients or locally relapsed plus met is good, but usually does not translate into direct link to PFS and overall survival. There's always this need, an important need to control the local tumor. And that's where we know MBTXR3 could play a key role first. So even if we don't look at the systemic effect, we have a strong potential to improve outcome for patients just based on local control. Now when it comes to systemic, we've been proven in multiple studies with MD Anderson that when we combine R3 to radiation versus radiation alone, we can trigger a much deeper systemic immune response With different mechanism and this has been fully extended studied in preclinical model by James Welsh So what we start seeing and that's part of what we would like to show in the next set of data we will Explore to for the 1100 is really those two things local control and systemic control and we clearly see that it's a The magnitude of effect we see cannot just be linked to local control, not to what extent we have the systemic control.

That's something we are exploring. That's really helpful. Thank you so much. Congrats on the progress. Thanks, David.

There are no further questions at this time. I would like to turn the call over to Dr. Levy for his closing remarks.

Thank you. Listen, thank you, everyone. It was another fruitful conversation. We have plenty of news to deliver this year, so we're going to go back to work and prepare that for you. Thank you for your attention, and I will wish you a very good day. And let's talk soon.

Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect your lines. Thank you, and have a great day.