Good day, and welcome to the Nanobiotix Business Update and Full Year 2024 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speakers’ presentation, 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 Craig West, Senior Vice President of Investor Relations of Nanobiotix. Please go ahead.

Thank you. Good afternoon and good morning, and welcome to Nanobiotix 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 Rhijn, 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 2, 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, an 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 statements represent our views only as of today and should not be relied upon as representing our views out of any subsequent date. While we may elect to update these forward-looking statements at some point in the future. Nanobiotix undertakes no obligation to update them to reflect subsequent events or 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 JNJ-1900, and also will give you some financial highlights and operational highlights for '24 and '25, and we will hand this call with a Q&A session. We have made very good progress towards our pathway to sustainability and growth and starting by continuing pushing and developing this collaboration with JNJ. In '23, we've been signing this $2.6 billion plus royalties with JNJ and now pushing into different directions 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 U.S. 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 would lead us to sustainability. There is also a new platform we are developing. And this year, we've been launching our new platform first-in-class product with Curadigm. We will 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 6, you can see our pipeline. And as you will remember, NBTXR3, our product is a product that is very versatile, a product that is tumor agnostic, patient diagnostic 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 indications, including two very important ones. The NANORAY-312, which concern elderly patient in head and neck that are frail and ineligible to…

Thank you, Laurent. Good morning and good afternoon, everyone. Moving to the next slide. As Laurent mentioned earlier, Nanobiotix 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 NBTXR3. This amendment has several important provisions, including removing the vast majority of the Nanobiotix funding obligation for NANORAY-312, releasing JNJ from select future potential milestone payments and safeguarding Nanobiotix’s path to sustainable cash flow through hundreds of millions in potential milestone payments related to lead 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, preform nondilutive to extend cash visibility into 2027. This is rooted in the belief that our first platform provides a path for Nanobiotix 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…

Thank you, Bart. Let's see what's coming in the next 18 months for Nanobiotix. As you can see on Slide 16, we expect to get a very important milestone next year, namely the end of recruitment of the ongoing Phase 3 in head and neck. That should lead assuming the data are positive to potential registration. There's also the Stage III randomized Phase 2 in non-small cell lung cancer that JNJ has started that should start reading in a 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 have the full data of the pancreatic cancer Phase 1 trial that should be published before 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 patients that receive 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 those patients. And most of the patients here have been melanoma patients, and we're really eager to present those data. And finally, coming from MDA 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 milestone in locally advanced head and neck cancer, Phase 3 or lung Stage III, randomized Phase 2 run by JNJ. In a nutshell, for today, what we'd like to take away is, first of all, we're moving forward with the partnership with JNJ. It does evolve and progressing really well. We have continued also to show the potential in opening the potential of NBTXR3 in multiple indication. This year or last year, sorry, has been a good time to introduce our new platform, Curadigm. And equally importantly, not only we are 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 strengthened our financial position. And finally, we're coming with end of the year where we expect many more clinical readouts and more to come. So, with that, I will conclude the first part, and we'll open the session for Q&A.

[Operator Instructions] The questions come from the line of Jonathan Chang from Leerink Partners. Please ask your question.

This is Yen-Der Li on for Jonathan Chang. Last two questions. First one, could you provide more details on the recently initiated Phase 2 CONVERGE study by JNJ? 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. Unfortunately, for now, we can't tell anything more that the trial has started and progressing well, and we'll come to our partners who 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 MBT3 could make a difference here? I think it's going to the continuation of having consistently showing very good local control in use by our product when combined with radiation. And in this specific population of locally advanced not small cell lung cancer, so Stage III patients unresectable. That usually the PACIFIC regimen, which is radiation, chemo and followed by PD-1 assuming they did not progress in between, there's still a low bar in terms of local response. And more generally, in oncology, when you have good local response for locally advanced cancer patients without meds then this translates into PFS and OS. What we have seen in head and neck, what we see in other indications. 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 NBTXR3, and we think the recent data generated by MDA is also a good sign of what could happen in the CONVERGE study.

Understood. Very helpful. And my second question is about the upcoming pancreatic cancer data presentation. We're curious how will the information presented there a bit different from the press release last year? And if the results are promising, what would the next step be for NBTXR3 indication?

So, end of last year, we announced the completion of the Phase 1 that was including an escalation part and an expansion part 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 is safety, some of the potential biomarkers that have been used so that MDA is working on that asset 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 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 chemo induction, then followed by radiation plus NBTXR3. Now that's not the full standard of care that those patients usually receive as they usually do chemo induction, radiation plus chemo. So, in this expansion part, we have had chemo on the top of radiation plus NBTXR3 and therefore should expect according to the existing nonmanufacturing, a better synergy and even more efficacy than what we have been seeing in the first part of the trial. So, this part of the trial is rusting, and we will tell soon when we should expect data on that.

We’re now going to proceed with our next question. And the questions come from the line of Shan Hama from Jefferies. Please ask your question.

Just on, I guess, what portion of costs are you still liable for NANORAY study? And what are they related to? And how much of it you can disclose? And secondly, I appreciate this might be more JNJ 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 concerns that some programs that we do prioritize or there may be sort of delays in meetings. So, what have you been hearing?

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

Thank you, Laurent. Happy to follow on. Thank you, Shan, for the question. With regards to the remaining costs with Nanobiotix. That is relatively immaterial as we've guided the public. The vast majority of the costs are now worth JNJ 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 there 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 3 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.

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

I just had a bigger picture question. So now that the NBTXR3 program has essentially transitioned fully to JNJ operationally and financially. I guess, as you think about the Company longer term, what are some of the R&D initiatives internally at Nanobiotix that you think could create additional value longer term beyond NBTXR3.

Thanks, Michael, for the question. So maybe -- sorry, maybe first of all, let's say that we're not yet done with NBTXR3. We still have a lot to do. You're fully right when you say that JNJ now is taking a good part, the majority of what is happening with NBTXR3 with the CONVERGE trial with the transfer of the 312 and so on, but this transfer is not yet done, as we mentioned, should 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 registration. So, outside the 312, which is today a big part of the investment in resources of Nanobiotix that no JNJ 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 happening 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 NBTXR3, 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, but how much additional R&D spend in 2025 and 2026 will be on NBTXR3 versus other programs?

Bart, do you want to take that one?

Yes, I was on muting. So, what will remain essentially is the 1100 study, MD Anderson preclinical and discovery work as well as cured. Each of those are single-digit millions. So, the burn will come down quite significantly on the R&D side with the [indiscernible] study, making up the majority of the R&D spend. So that is millions per quarter less. The beauty of the Curadigm 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 filled. 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 3 liability be significantly less on a net basis going forward.

We’re now going to proceed with our next question. The questions come from the line of Swayampakula Ramakanth from HCW. Please ask your question.

This is Art He from H.C. Wainwright. So, a couple of quick questions here. So, this is for Bart. You were talking about the runway, which currently stands to mid-2026 and you were also saying there are potential ways for you to extend it into '27. So, what could be the potential nondilutive way? And also, how much of a gap is there for you to fill so that you can take it up to 2027 or into 2027 from where it stands currently?

Thank you, RK. So, we feel that the enterprise value significantly disconnected with the market cap. Therefore, dilutive options are not our preference. We have EIB debt in our cap structure. And adding more that, we believe, is not the ideal way to go about things. But other nondilutive financing options, such as royalty financing, we believe, hold good promise for the Company given the type of asset this is 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 investments by our partner, JNJ, we expect 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 would be low teens to get into 2027. It just moves 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 is 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 these assets and bring it, hopefully, in many indications should data readouts be positive.

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

Thank you 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 it always a risk getting some first randomized data. So, as a risk until you have them not having a partner to market the product or to make sure we develop broadly, would that 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. So, I will say that we are in a very derisked situation right now. Now, there's never 100% guarantee in any of the things. So, think what we should just do is wait is not too much time to wait now to get to next big inflection point and to, on our side, help JNJ to move as fast as they can and to bring this product to market.

And then the last question from me is also on the Curadigm asset. Probably, I've asked this question in the past. What's the gating event that needs to get done so that you can initiate a clinical program. Is it resources? Or is the time in the sense getting all the material together to start a program?

Well, I think it's essentially timing. We have enough results to push this program. As Bart mentioned, at this stage of development, it is. It doesn't cost enough money, but also as we want to reemphasize the partnership activity on that, and 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 number of MTS already signed on their way. So, things are moving, and we hope I will give much more inflow by the end of this year.

[Operator Instructions] We’re now going to proceed with our next question. The questions come from the line of Eric Musonza from UBS. Please ask your question.

Actually, this is David Dai from UBS. So yes, just actually two things for me as well. So, regarding the NANORAY-312 trial, so you're planting roll patients with and without cetuximab. These patients who receive cetuximab would likely have survival. Could you just 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 are -- who have the cetuximab background?

Thanks, David. So, cetuximab is not the biggest used drug in head and neck when it comes to fell 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 cetuximab. The reason why this drug has been added is because they are in the guidelines. 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 biased, 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 bone paper, what you see is that for elderly people, the cetuximab use is detrimental versus radiation and all. 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 plus a little plus. But if there is some small benefit, we should assume that benefit will be at the minimum equal in the arm with NBTXR3 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 cool. And then just another question on the upcoming data readout. There are many updates in 2025 including the Phase 1 data from the relapse metastatic head 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 serve better systemic benefit for those metastatic patients?

Sure. First of all, before getting to the benefit of systemic activity of NBTXR3, just want to remind that for patient getting PD-1, the first time they will get PD-1. There are usually 1/3 of those patients that are only locally relapsed, 1/3 that will have local relapse plus met and certainly 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 NBTXR3, we should just remind that those patients get in 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 relapse plus met is good, but usually does not translate into direct linked to PFS and overall survival. There's always this need and an important need to control the local tumor. And that's where we know NBTXR3 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 system, we've been proven in multiple study with MD Anderson that when we combine our three to radiation versus radiation alone, we can trigger a much deeper systemic immune response with different mechanisms, and this has been fully extended studied in clinical 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 1100 is really those two things, local control and systemic control. And we clearly see that it's -- 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.

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

Thank you. Listen, thank you, everyone. It was another fruitful conversation. We'll 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 we wish you a very good day. And let's talk soon.

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