Hello, everyone. Thanks for joining us. My name is Jonathan Chang. I'm part of the Leerink Partners Equity Research team. It's my pleasure to host Hello, everyone. Thanks for joining us. My name is Jonathan Chang. I'm part of the Leerink Partners Equity Research team. It's my pleasure to host Hello, everyone. Thanks for joining us. My name is Jonathan Chang. I'm part of the Leerink Partners Equity Research team. It's my pleasure to host Hello, everyone. Thanks for joining us. My name is Jonathan Chang. I'm part of the Leerink Partners Equity Research team. It's my pleasure to host Hello, everyone. Thanks for joining us. My name is Jonathan Chang. I'm part of the Leerink Partners Equity Research team. It's my pleasure to host the management team of Nanobiotix. We have with us today CEO Laurent Lévy, CFO Bart Van Rhijn. With that, let's get started. Thank you, guys, for joining us. Thank you. Would you like to briefly introduce the company? Sure. Nanobiotix is a company that is developing new treatments for patients at large. The idea here is to try to do what others don't, meaning using new modes of action, new ways of treating patients with one prerequisite: using nanophysics and making products that can literally help millions of patients. We have three different platforms under development. The first one provided the first product named NBTXR3 that is used for oncology, and that has been licensed to J&J. We also have two other platforms, one for redistributing drugs into the body and really rethinking the way we develop drugs, and the last one about CNS disorder. I think for today, we'll focus on the first platform. OK. All right. Thanks for the introduction. Can you discuss the opportunities for radio enhancer in oncology? Sure. I think if we want to step back a little and talk about the patient, when you look at patients in oncology at the time of diagnosis, the vast majority of them, they have a local disease. If we see so many patients with metastatic setting, it's because a lot of local treatments have failed. With J&J, we believe that if we can treat early the patient when they have a local disease, which is the vast majority of patients, then we'll get a big impact in oncology. That's also one of the biggest markets we can imagine in oncology. Why radio enhancer? Because when you think about treating patients early, it's about radiation and surgery. It's more than 60% of all cancer patients that are getting radiation: 87% of breast cancer, 77% of lung cancer, 74% of head and neck cancer patients. Radiation plays a seminal role in the local treatment of patients. Radiation, even though it's widely used, has a strong limitation. When you want to irradiate a tumor in the body, you have to cross surrounding healthy tissue. Therefore, you're limited by the dose you can deliver in the tumor because of the side effects you will provide. There is a huge space for improvement here. The question we should answer is, how do we improve the dose in the tumor without improving the dose in surrounding tissue? That's the spot of radio enhancer. That's the reason why at Nanobiotix, we've been developing this product, NBTXR3, which is a new mode of action, first in class, radio enhancer. The goal here is to inject a product directly into the tumor. This particle will go into the cell. Those products have been designed with a very specific material, which is hafnium oxide. This material is a crystal that has the ability not only to be inert, which is good for safety, but also the ability to absorb X-ray. It's a super X-ray absorber. Imagine a patient going to their usual patient flow for treatment with radiation therapy. Just before the first session, we make a one-time injection of those nanoparticles in the tumor. Those particles will go into the cell. When the patient is receiving radiation, the particle will absorb the energy and will make radiation much more efficient and kill the cancer cell much more efficiently. It's a really universal mode of action based on physics. It's tumor agnostic, patient agnostic, target agnostic. That's why we think and we believe we can use this product in almost all the patients getting radiation and literally help millions of patients. Great. Can you tell us about the J&J partnership for NBTXR3? Sure. Bart, do you want to talk a little about that? Yeah, happy to. Yeah, that is a unique partnership. It's a co-development commercialization deal that we concluded in July of 2023, whereby we have a very good structure that allows both parties to contribute. When you look at the milestones, there is close to $2.7 billion of milestones in total. The majority of that relates to development and regulatory milestones, with royalties in the low teens to low 20s. Once we hit key de-risking points, like interim analyses or regulatory approvals, we're set up to be a sustainably financed company. It's an attractive deal that allows both parties to fully explore the potential of the product, going into multiple tumor types, and try to reach as many patients as possible further toward what Laurent indicated. Got it. Can you discuss where the partnership is today versus when you signed the deal and how things have progressed since? I think we've been progressing a lot in the partnership. I can name a few things. J&J has started a randomized trial in lung Stage III, injecting the first patient at the beginning of this year. They also have duplicated the existing manufacturing line that we have developed at Nanobiotix to make sure we have two different sources for the product. They also have invested widely in getting a lot of people in different countries to be on the ground to make sure we can diffuse the product, be in the different clinical sites. We have initiated also the transfer of the ongoing phase III in head and neck cancer. We anticipate that before the end of the year, this transfer will be completed, and then this trial will be fully run by J&J in order to be ready for the next key milestone and prepare for registration. Understood. Let's start with head and neck cancer. NBTXR3 is being evaluated across different settings of head and neck cancer. Why is head and neck cancer the right indication for this program? I think head and neck, like many others, like breast or lung or prostate, radiation plays a key role. Everywhere radiation plays a key role and there's a need for patients, there's a spot for this product and a good need. Head and neck is one of those indications where we look at numbers. At diagnosis, it's 90% of all head and neck cancer patients that have a local disease. Only 10% have metastasis. When you have met, then you go to immuno-oncology treatment. For the vast majority, it's radiation. Either radiation alone or surgery followed by radiation plus/minus chemo or radiation plus chemo. That shows that for 90% of head and neck cancer patients, the frontline treatment is about local control. We have different trials running here. We have completed a trial in the radio- chemo setting. We have trials also for late-stage metastatic patients in head and neck. One of the most important is the one we are running today, which is a phase III, the one that is being transferred to J&J. This trial is about frail elderly patients being ineligible to cisplatin. They can only get radiation. For those patients, radiation is more like a palliative setting than a curative setting. It is the start. You can imagine that if you go here and you can help those patients that have almost nothing, you can influence and help almost every patient in head and neck that takes radiation. Maybe a quick add to that. I think the beauty of the setting where the phase III is taking place is also that any difference with standard of care, meaning radiation alone, can be and will be attributed to R3. I think it will be a very clear way to establish the medical value, but also the economic value that the product may deliver. Got it. Can you discuss the considerations around treating a patient with NBTXR3? What are the logistics of the administration and who's doing the administration? I think we've been developing this product to be able to minimally change the existing practice. That was a very important thing. That's why it is a one-time injection directly into the tumor. That's the only change into the usual patient flow. Now about the procedure for injection. First of all, we use everything that is in place, like the imaging of the tumor is the one that we're using to determine the dose. It's the imaging you do for radiation therapy. This one-time injection is a new procedure, but usually it is done by the person that will do the biopsy in the indication. Depending on the organ you want to inject, you may have different types of MDs or health care providers that will be involved. For liver cancer, it's echo-guidance and a needle, external injection. For head and neck, that will be either a local injection with a syringe or you'll use an endoscope if you need to go deeper into the head and neck area. For lung, you will go from an endoscope or sometimes from an external perspective. The good point here is there's always someone in this indication that is used to make a biopsy. The way we position the needle to make the injection of this product is the same way that you will position a needle for biopsy. We have a medical practice around that already established. Got it. What has the physician feedback been that you've? Depending on where you go, depending on the physician, depending on the organ, for example, in liver, there are plenty of interventional radiologists. That is their day-to-day work. There is no issue there. In head and neck cancer, when you talk to the surgeon, they used to go there, and they used to do all this. It has never been an issue. In some indications, like pancreatic cancer, it is a bit more tricky because it is a hard way to get to the pancreatic cancer with an endoscope, then pinch a hole into the stomach to get to the pancreatic cancer. That is specialized interventional radiologists that most of the time do that. For the vast majority of cancer, we have people that are used to get to that. Understood. Can you talk about the ongoing phase III NBTXR3 study in locally advanced head and neck cancer? You have already mentioned it, but if you could maybe elaborate on the study and also tell us about the reasons for confidence that you think that study will succeed. OK. This is the ongoing phase III named NANORAY-312. That's the one we are transferring at the moment to J&J, where we expect to get the first readout, H1 of 2026, on the primary endpoint PFS. This trial is about a frail patient that cannot get cisplatin on the top of radiation. It is a randomized one-to-one trial with 500 patients. It's a global trial running across the globe. The idea here is to show benefit through local control, the primary endpoint being PFS and secondary key endpoint being overall survival. There is also a big measurement on quality of life for the patient. Why are we confident here? It's because we've been showing in 75 patients in the previous trial a very interesting finding. First of all, in a frail patient population that cannot usually take many drugs, we've been able to inject safely this product and have a good feasibility of the injection. That was one. Two, we found a very high rate of response. We got to 82% response of radiation plus nanoparticle. If you want to compare this 82%, you can look at the literature. You see, usually, when it's shown, something around 30%, 35%. It is more than doubling what you can find in literature. More importantly, the 82% of responder includes 64% of complete response. You can imagine that when you have this big tumor getting to complete response, it has and will have an impact on quality of life. More importantly, there is a strong statistical correlation between response, PFS, and OS for the patient. That is what we have shown in our trial. When you look at the 82% of patients that responded, we got a median overall survival of 42 months, which is huge. Usually, those patients getting radiation alone, the overall population, get to 12 months in average. There is a good potential for efficacy with this product and radiation. That is why we are confident, plus some other minor detail for the phase III. Got it. What are the timelines for the study? How should we be thinking about disclosures for readouts? That's what we've announced to the market. It's interim readout based on end-of-recruitment of the trial and 283 event. We should expect that for H1 next year. As I mentioned, now J&J, before the end of the year, will fully run this trial while we are transferring it at the moment. Got it. Does that affect the transfer of any of the timelines? I mean, transferring is big work. You're running a global trial across the world. There's hundreds of contracts everywhere. There's plenty of interaction. It does take time to transfer that. What we are trying with J&J is to really push the recruitment while transferring. That's extra work on both sides. I think with the spirit of this collaboration and the good people on both sides that are working on it, we're getting there. Understood. What's the latest status of J&J's plans and efforts for NBTXR3 in lung cancer? As I did mention briefly, they have started a trial in lung Stage III. That is typically the PACIFIC regimen, patients getting radiation plus chemo. If they do not progress, they get the anti-PD-L1 as a secondary treatment. When you look at this overall population, there is still a large unmet medical need because a majority of the patients over time will either relapse or do not respond to the treatment at baseline. Getting a much better control with radiation, chemo, and nano before the PD-L1 will be instrumental in bringing more or better outcome for the patient. That is what this trial is about, comparing the standard, the PACIFIC regimen, versus the same plus our product. When you look at the bar, I think there is a good room to be successful here. In that regard, I think there are some trials that could be interesting. We could look at the trial that is run today by MD Anderson about reirradiation of patients that have failed local treatment, including the PACIFIC regimen. Looking at those patients, if we can rescue them, could be also a good surrogate to see what could be the impact frontline of the treatment. There are many things that are going to happen in the next few months, as we said it in our news flow, that could help us to start not reading because it's a different population, but start envisaging a potential surrogate for the concurrent trial. Understood. What are the expansion opportunities for NBTXR3 beyond head and neck and lung cancer? It is clear that given the mode of action, as we described at the beginning of the chat, there is a huge potential of this product. If we, for example, just look at the two first indications, head and neck, frail patient, and lung cancer stage III, just in EU5 and U.S., we're talking about 100,000 patients and more than 500,000 if you look at the overall world. There are plenty of other indications where we already have shown some safety, feasibility, and good sign of efficacy. There is a huge potential to move forward in other indications. We did not yet disclose and talk about all the internal discussion we have with J&J, but there is a potential to go much beyond what has been disclosed. That is some of the things we are discussing at the moment. We will say it in due time. Yeah, maybe to build on that, Jonathan, we have either completed or have ongoing 13 trials, eight different tumor types. We've seen very consistent safety and tolerability. The same for efficacy, although some of these trials are phase I, phase II. There is a tremendous opportunity that we'd like to move forward. We've brought data on, for instance, pancreatic, esophageal, and the like. The tumor agnostic, combination agnostic, but also target agnostic profile lends itself well to be a highly versatile asset. Got it. What are the NBTXR3 data readouts that investors should be looking forward to this year? I think there's two key for next year, but that's something we've been talking about. For this year, we have six different readouts that we may expect, one in the lung cancer trial that is done by MD Anderson Cancer Center, another one in esophageal cancer, one also two in head and neck metastatic patient, either frontline PD-1 or after failure of PD-1. We also have pancreatic and melanoma cancer patient that will be disclosed this year. A total of six readouts, including four new data presented in new population of patients. Understood. Let me just check with the audience, see if we have any questions on NBTXR3. All right. Maybe beyond that program, how are you thinking about the next chapters for the company? Yeah, first of all, this program is not yet done because we have a lot to do. The vast majority of the company is involved in this collaboration and work hand in hand with J&J to move forward this product in different indications and beyond clinical development. We should expect that for the next 18 months-24 months, there will still be a large proportion of our investment attention toward this program. Now, we are still preparing the future. As I briefly mentioned, we have two other platforms, one dedicated to CNS disorder and another one that we think could be a very good investment at that time with not too long return on invest for Nanobiotix and our shareholder. Maybe I can describe briefly this platform. When you think about some of the most innovative products, like RNA-based therapy, cell therapy, oncolytic virus, and many others, when you inject them IV in a body, the liver will act as a filter and will capture the vast majority of this product. Therefore, the quantity that is available to go to the target is very small and sometimes is equal to zero. We have looked at this problem and developed what we call Nanoprimers. Those Nanoprimers, they are nanoparticles, completely different from the first one we have been developing. Nanoparticles that you can inject IV, they will stick into the liver and will, let's say, keep the liver busy for a certain period of time. It could be hours, it could be days, depending on the design. While the liver is busy with those particles, when you inject other products, they could go through the liver and minimize the capture of the liver. Therefore, you're reopening the entire access to the body with this product. We have been establishing proof of concept with different biotechs, some pharma, to show that this is widely applicable. Our intention here is really to start making deals, licensing out of the technology, and start building a pipeline with external partners. We have also started internally to develop our own pipeline based on this technology. We think there is space for many, many products and many, many return on invest short term and medium and long term also. That would be a good lever for growth after NBTXR3. Got it. How should we think about timelines for those efforts? We're already in. We're working on that. As I said, it's not the vast majority, far from it, of our investment as it is toward NBTXR3. I think this year we'll get more news about the data we have been generating and continue to generate. We think in not too distant future, we can start establishing partnerships with pharma or biotech. Got it. Maybe you can expand on how you're thinking about business development opportunities across your platforms and programs. I think that the first product is licensed to J&J. This one is done. We want to find at Nanobiotix the right balance between what we develop and what we license out. If I think about this second platform, about the liver, I think here we can think about products that are under development, let's say RNA-based products, for example. It's very hard with those products to escape the liver when you do an IV. There is a place here where we could use our product in combination with such approach to make them better and to make them available to the rest of the body. We can imagine preclinical co-development or licensing out to the RNA companies and giving them a very special positioning versus the rest of the RNA companies. That's one. We could also imagine products that are on the market that are not efficient enough in some indication that we could render more efficient. Here, again, there is space for BD in this aspect. There is a full continuum and spectrum of opportunity with this product or products. Got it. How should we be thinking about your cash position and runway relative to your clinical milestones? Maybe how BD may interplay with your plans? Excellent question. Thank you, Jonathan. We have a cash runway into Q4 of 2025. That is short of the interim analyses in H1 2026 that was referenced. We are working hard to solve for that in a non-dilutive fashion. We are making great strides and hope to be able to update the markets in the not too distant future that that is addressed, at least partially addressed. With regards to BD and how that could interplay, we do not see that as an immediate driver for our cash evolution. Over time, that will. I think first priority will be to get external validation and get things moving such that we can have first-in-patient data and signal the value of the platform to other market and industry participants. Over time, I think that will bode itself well for higher upfront, better economics. First priority is establishing the validation. Yeah, I just want to make clear and rebound on what Bart has said. I mean, given the current market, there's no intention to go and raise equity. We're really focusing on trying to bridge that gap with non-dilutive financing because we think that's what will be more efficient for the company and for the shareholders. Understood. Thank you guys for joining us and for taking the time. Thank you, Jonathan. Thank you. Thank you for having us.