Good morning, and thanks for joining us to have a conversation with Laurent Lévy and Bart, CEO and CFO of Nanobiotix. Nanobiotix is developing a radio enhancer, NBTXR3, which is hafnium oxide nanoparticles that can be induced by radiotherapy to enhance radiation, and cause significant tumor cell death in the injected tumor. In 2023, the company forged a global co-development and commercialization agreement with Janssen Pharmaceuticals, part of Johnson & Johnson. So to learn more about the drug, the co-development agreement, and the various clinical studies which are ongoing, I welcome both Laurent and Bart to this fireside chat. Laurent and Bart, thank you very much, and appreciate you accepting our invitation and talking to our audience today. So, Laurent, just when we start thinking about radiation therapy, you know, for a while, it was not in vogue, but now it's coming back, especially as a therapy that can induce immune as a immune therapy as well, you know, in certain cancers. So with that as a backdrop, how do you see Nanobiotix, you know, as a company and also as a major player in radiation therapy? I think first we should go back maybe in history, not too far away, but radiation therapy never has been outside the cancer treatment paradigm. It has been used for more than a century, and more and more over the past few decades. Radiation is one of the key treatment in oncology, always has been, as we treat more than 60% of all cancer patient with radiation. But it's not like any treatment. The radiation therapy, just like surgery, they most of the time, if not all the time, use frontline in the treatment of cancer patient. You have a local problem, and you try to solve it by local treatment. So what we think, and our belief and what we started demonstrating across those years with NBTXR3 in combination with radiation, is that if we take the patient early in their journey of treatment, when they have a local issue, and you have a good control of this problem, then you will have a long-term impact for the patient. And that's also a different way of looking at how we develop product, because you see that most of the pharma and biotech company, they will look for metastatic patient last-line treatment, whereas in radiation, you can go frontline treatment and have a much bigger impact. And it's also the bet that J&J is doing with the creation of this group that they call Interventional Oncology- Mm-hmm ... which this product is part of now. So, NBTXR3, or hafnium oxide, by itself is an inert molecule, but has proven to be a potent radio enhancer. So can you discuss the properties and also what the market potential is for R3? First, we should go back maybe to the primary mode of action. This product is made of an inorganic crystal of hafnium oxide, and we've been choosing this product specifically for two reason. First, hafnium oxide is a very inert material, so it's good for safety of the patient. And two, it's an material, a molecule or nanocrystal that has a lot of electron in it, which is highly dense in electron, and that's what makes it a perfect X-ray absorber. So when you put that in a cell, then X-ray going through the patient and going through the particle, they will absorb much more energy than the cell could do it usually, and will deliver within the cell much more killing effect, much more energy. So when we talk about tumor-agnostic, and the potential of this product could be gigantic, because there's millions of patient getting radiation, and by adding NBTXR3, you could either improve the efficacy of radiation or decrease the toxicity by lowering the dose, still providing the same efficacy. But that, that's the general concept. Now, we have a good experience with this product, as we've been treating hundreds of patient across the world in different indication. We know more about the safety and the feasibility in many indication. We also had a randomized trial showing that if you compare radiation alone versus radiation plus nanoparticle, then you bring benefit to the patient. So yes, we know it's working, and now we're going and expanding into many indication with Johnson & Johnson. Talking about Johnson & Johnson, you know, you received a major validation last in 2023 in the form of a co-development and commercialization transaction. Can you provide us a few details of that transaction, and how it has been, how they have been as a partner for you? We can talk on our side, not for our partner, but I think since we've been signing this collaboration, things are going really well, and we are accelerating the development. We have in front of us a big team, a much bigger than the one we have, obviously. But they are very open and challenging in a good way, and that's reciprocal. So we are building a strong team to develop and this product and bring it to as many patients as possible. So we're really happy about the collaboration. As you may have seen in some of the latest press releases we've made, we see the acceleration through the transfer of the- Mm-hmm ... ongoing phase III to J&J so they can get ready for registration. They're also building another facility to manufacture the product in parallel to ours. So yes, things are moving, accelerating, and getting bigger. Very good. So, before we get to start talking about how they have decided to sponsor the phase III study, what can we go through some of the details of what the phase III study is, which is a NANORAY-312 study? And then also, please, discuss a little bit about the reasoning behind their sponsorship, not only on the conducting of the clinical study, but also on the commercialization. Sure, so maybe to recall what is this phase III, we're talking here about head and neck cancer patient, not any head and neck cancer patient, and before getting into some of the detail, just would like to remember the audience that head and neck cancer patient, when you're diagnosed with that, it's 90%, nine- zero, of the patient that have a local disease. Only 10% of them will have a metastatic disease, so the primary cure that you try to give to this patient is a local treatment, and that's where radiation plays a key role, because 75% of all head and neck cancer patients are getting radiation, and that's where our product is playing. And if you look at competition or people trying to help head and neck cancer patient, there's almost nothing outside us in local treatment of head and neck cancer, I mean, in term of new treatment. So here we're talking about a specific head and neck cancer population, which is frail, elderly patient that are ineligible to cisplatin, and the only treatment they have is radiation. So we've been showing excellent data in our phase I, II in the past, and have been starting for a few years this new ongoing phase III global. There's 500 patient that will be treated for that, randomized one-to-one. And there is the control arm, which is radiation ± cetuximab, that would be the choice of physician. And in the tested arm, you have the same plus our product. The primary endpoint here is PFS, and key secondary is OS. The rationale behind- The transfer, yes. Yes. So obviously, to commercialize the product in head and neck, at some point, J&J needs to be the sponsor of the trial for registration and for all the pre-market activities, and so on. So we had two choices. Either we would wait the interim readout, which is expected now, H1 2026, and then transfer the trial to J&J, or transfer it before and lose some time now, but winning time after. Because what we want is, at the time of the data are available, that we can go as fast as possible to registration and to market, assuming that the data will be positive. So that's really what led us to do the transition now rather than later, to be ready on time and full speed for the commercialization. Very good. So let's see, and then on NANORAY-312, so which is a phase III study, you developed the design based on some of the data that you have been seeing from Study 102. So what's the data that we have seen so far in Study 102 that has given you this confidence? And also, is there any additional data that we should expect, you know, in terms of long-term following from Study 102? The 102 study was a trial that has been done in the equivalent population that recruited 75 patients within the escalation and expansion phase. What made us confident in it is really first the safety. In a very frail population with a lot of comorbidity, being able to add a treatment without causing too many toxicity, that's a very good achievement already. More than this, we've seen very high rate of response, like 82% roughly overall response rate, including 63% of complete response. For those patient, having this big tumor in the head and neck area, getting to a complete response is a very big achievement already, because then you can reinstall some of the basic function. Then what we have seen is the strong correlation with response, PFS, and survival. If we look, for example, at the 81.8% of the patient that responded, they had a median survival of 42 months, which is gigantic for this patient population. Very good. And then, J&J has also taken up on conducting a phase II study in stage three lung cancer. So what's the status of that program? And, you know, when should we expect any data from that? As you may recall, FDA gave the go-ahead to start this trial, which is a randomized trial in stage three lung cancer. We should expect news soon now about the design, about the first patient getting in the trial and so on, but we'll keep the market updated on that, of course. As soon as the design is getting public, then we will be able to talk a bit more about what we should expect and when we could expect something on this trial. In the head and neck cancer space, you know, outside of the locally advanced disease, you're also conducting a study in the metastatic disease with Study 1100, especially that you're combining with the anti-PD-1 nivolumab or pembrolizumab. We have seen some data at the ASCO in early June. Can you highlight the data from there, and do you think J&J will be interested in, you know, looking at that indication as well? So what we've been showing in this population, and again, now we're not talking about any more than 90% of local head and neck cancer patients, but when they have failed the local treatment, or for the ones that have metastatic diagnosis, then the PD-1 is becoming a big option for them. Nevertheless, even if it's working, there's like 20% of real patients that we could provide benefit. When you look at the patients when they get the PD-1, roughly there's 2/3 of those patients that have a local disease plus mets, or just a local recurrence. And for those patients, treating locally the cancer is as important, and sometimes even more important, than the metastatic disease because it's the hardest part to control. So what we have seen in this overall population of PD-1 naive or PD-1 resistant is when we had our product with few fraction of subtherapeutic dose of radiation, then we can have an overall response that is getting really interesting. What we have seen in the naive patient population is 48% overall response as per RECIST, and we start seeing, but still immature, a potential for overall survival too. We think that with six, nine, 12 more months of follow-up for those patients, we'll get a better understanding of not only about the response, which is one thing, but not everything, and what could be OS for such a patient population. But we're really interested to complete this trial and look at it, and now is our partner interested to move forward in this indication for Nanobiotix? That will be a subsequent discussion. Okay. So in terms of the regulatory pathway itself, do you foresee yourself doing a phase II and a phase III, or would it be, like, a combination study? How could this go forward? There's many way to look at the development in general, and for this product too. Now, it's a very underserved population that die quite quickly when the PD-1 does not work. So there's option to get an appropriate trial that could lead to registration with not a big number of patient, as long as you demonstrate something strong enough. But again, I think that would be for subsequent discussion. Okay. So, before J&J came on board, you know, you had and continue to have a big collaboration with MD Anderson Cancer Center. They have been conducting few studies to evaluate the drug in different indications, you know, such as pancreatic cancer, non-small cell lung cancer, and esophageal cancer. Each one of them can be huge indications. We have seen some data from the pancreatic cancer, but not. At least I have not seen any of the data from other two indications. What's the status of all these three studies, and what the data that we have seen from pancreatic cancer, can you highlight that? And do you think either you or partner would like to take it in-house and move them forward? Yeah, I think this collaboration with MD Anderson is a very key one. I mean, they have been pushing, helping, developing this product for with us for quite some time now. They're really trying to push the boundaries of medicine, trying to find something better, new, for patient. That always has been their philosophy, and I think they do that quite well with our product. So we have a number of trial ongoing. They are designing new ones, too, that will be hopefully public soon. The three you have mentioned, pancreatic, esophageal, and lung, are tricky indication. That's also the versatility of the usage of our product. What we should expect in the coming weeks, months, is really having a strong update on the pancreatic cancer and what could be some of the next step with that. The lung cancer is also now almost completed, so we should expect to get that in a conference as soon as a scientific or medical conference will be available for that, and esophageal is getting near completion, where we could start getting some data, but clearly, this collaboration is moving in the right direction with a group of motivated and really good people. So in terms of, clinical or developmental milestones that, you know, we as investors should be on the lookout for, what should we expect over this, say, let's say, next twelve months? There will be, obviously, as I just mentioned, a good number of update and potential next step coming from MD Anderson. We will have also from the 1100 trial that we're running in head and neck cancer patient, but also in other type of patient; we should expect a big update here. More maturity for head and neck cancer patient and see what could be the impact on survival, but we also have a cohort 3 in this trial that treat different type of patient than head and neck cancer patient, including some melanoma patient. We'll be really keen on seeing what's going to happen here. So, as a last question, Laurent, I've known you for eight or nine years, and how you've gone through a lot, especially there have been times where financially you've been in a difficult place. But J&J came along, they've kind of really changed, you know, changed the way that you could think about Nanobiotix from here onwards. So a few words about the collaboration itself on the financial terms, and also how has that helped you to think beyond R3? So maybe, Bart, you want to comment later? Yeah, happy to. Thank you, RK, for the question, and thank you for having us. Yes, the collaboration has been really pivotal for the technology and for the company. As we all know, the, you know, financial markets haven't been the most conducive over the past couple of years, but, you know, at your conference and having had many engagements with investors, we can really feel the momentum turning. I think the breakdown of the deal with J&J is a very attractive one for Nanobiotix. With a product that is tumor-agnostic and combination-agnostic, further to the versatility that Laurent indicated, there's many directions that this can be taken forward. There's a significant amount of clinical development, but also regulatory and sales milestones, with a very healthy royalty rate of low teens to low twenties. So we look forward to bringing a lot of value to patients in close collaboration with J&J. And financially, the last guidance that we've given publicly is the cash runway into Q3 2025. We'll be updating that shortly, as we'll be announcing our mid-year results mid to late next week. And we've always been very disciplined in our capital allocation. So from a cost perspective, it's well controlled for those that have followed us for a long time, so we will continue to see that. So it's fair to say that runway will be, you know, towards the end of 2025. More to come. Laurent, on the strategy side beyond R3? Yeah, I think this collaboration brought us some validation, but also, you know, helping us to see beyond this product. That's where we have two new platform we're working on. But stay tuned for that. We will talk about it a bit later. Okay. Thank you. Thanks for joining us this morning, and talk to you soon. Thank you, RK. Thank you. Thank you.