I'm good. 35 questions. I have tough questions for you. All right, so welcome to this fireside chat with Nanobiotix. We've saved the best for last today. With us today, we have Laurent Lévy, CEO. Welcome, Laurent. Thanks for joining us. Maybe, again, stepping back, just could you give us a quick overview of your technology? I know you have three different platforms that you have developed. Maybe describe those to us and how they're contributing to the value creation at Nanobiotix? We started Nanobiotix with the idea that we could use different approaches to treat patients. For that, we've been looking at physics rather than looking at biology and chemistry. Not that we don't like biology and chemistry, it's just that we wanted to bring something different for patients. More than bringing physics, which already exists when you think about surgery, radiation therapy, and many other therapeutic things, we wanted to bring physics inside the cell. That is what led us to develop some tiny objects, some nanoparticles that could carry and hold some physical effect and bring that to patients in many different therapeutic areas. That is what we started to do with three different platforms. I think we'll talk a bit later about all this. All right. Yeah, maybe then let's talk about that. Especially NBTXR3, which is. Hard to pronounce. Exactly. Which is a very interesting mechanism of action that could potentially be useful for any solid tumor therapy. Yeah, maybe remind us of the mechanism of action and the therapeutic approach for that. I think here what we've been looking, first of all, it's about patient in oncology. When you look at patients at diagnosis, most of them have a local disease. It's around 77% of patients getting local disease rather than metastatic disease. If we see so many patients with metastases, it's because some of the local treatments fail. We think that if we can treat patients early at the time of diagnosis, when they have local disease, that's where we'll get the biggest impact in oncology and where is the biggest market also. When you think about those patients, they need local treatment. Radiation therapy is one of the key treatments for those patients. It's around 60% of all cancer patients getting radiation. There is a limitation to this radiation. Very simple. When you look at a tumor, it's surrounded by LC tissue. When you try to irradiate this tumor, you will cross LC tissue and make some damage here. The key question is, if we want to optimize and get a much powerful radiation therapy and bring the cure up for radiation, it's to get a much better dose in the tumor without changing the dose in surrounding tissue. That's what led us to develop our product, NBTXR3, which is a nanoparticle, a drug made of nanoparticles. We inject this product directly into the tumor. Those nanoparticles, they have been made to be inert, but also to be a super X-ray absorber. Therefore, when you inject that only once before the first session of radiation, the patient is getting, following that, different radiation therapy sessions. Those particles in the tumor will absorb the energy of radiation and deliver within the cell a higher quantity of damage. Here we have a product with a physical mode of action that can be used across many solid tumors. I know this is maybe beyond a detail, out of detail beyond this necessary, but you selected hafnium oxide specifically, the material to make the nanoparticles. How complicated is it to manufacture? How did you end up choosing this particular material? We brought physics in the game to choose the material and the benefit-risk ratio for the patient. Those were the two fundamentals when designing the product. We've chosen hafnium oxide over other metallic particles, for example, because hafnium oxide is a stable compound. We minimize the risk of having some part of the product getting around or being disrupted and creating some systemic toxicity, as an example. As hafnium oxide is also a super dense electron product, it does absorb a lot of energy. The ratio is about best efficacy for the best potential safety. That's why it led us to choose HfO2 over gold, for example. Obviously, it makes sense. NBTXR3 is obviously partnered with J &J. Maybe talk about how they're approaching their commercial development strategy for this? I think what I've mentioned initially, that most of the patients have local disease at the time of diagnosis, that's really part of the strategy of J&J. They have been creating some time ago what they call interventional oncology group. It's all about that, trying to treat the patient within the tumor to bring a big benefit. That's where our strategy did align with J&J between our product and their interventional oncology approach. That's one thing. The other one is, when you think about solid tumor or different oncology indications, such a product could anchor any commercial or any pipeline because it can be useful for many patients in different clinical settings. Their initial focus has obviously been on head and neck cancers, right? The first phase III study that's ongoing is in head and neck cancers. I guess what drove, I guess, your decision initially to pursue that indication first over other opportunities? Obviously, when you look at radiation, you could go for prostate, breast, head and neck, lung, many, many solid tumors. We started with head and neck because, like some other tumor, 90% of head and neck cancer patients at diagnosis have a local disease. If you want to get a cure in head and neck, you need to kill this primary tumor. Until you can kill it efficiently, you will not bring a cure to patients. Here, the importance of local control is important for the benefit of the patient, like in lung cancer stage III, for example, and some others. That is what drove us to choose head and neck as a first indication. Also, there is not much competition for applying treatment in head and neck. Those two things made us choose that to start with. When you look now at what Johnson & Johnson is doing, not only are they running now this phase III, but they also have their phase II in lung stage III, have started a new trial in cisplatin-eligible patients in head and neck. Potentially, in the future, they will start also more indications. Makes sense. Yeah, maybe then still in head and neck. What is the magnitude of that opportunity that the Nanoray 312 study is pursuing, the size of the opportunity? When you look at the potential number of patients we could help between EU-5 and North America, we think about 30,000 patients for this indication alone. If you add up the lung stage III or add up the cisplatin-eligible population, in those two geographies, we're talking about 160,000 patients. That's already making a bigger and bigger number of patients we could help. Before we talk about Nanoray 312 in more detail, how does this cisplatin-eligible patient population fit in the treatment paradigm in head and neck compared to the Nanoray 312 patient population? At diagnosis, it's 90%, nine, zero, head and neck cancer patients that have a local disease. Only 10% have met at diagnosis. Those 10%, they go to immunotherapies and some other treatment. For the vast majority, nine, zero, it's local treatment. There is the small proportion that could get to surgery. Those are the patients with the best prognosis because you have removed the primary tumor and the source of potential metastasis. The vast majority of patients have a locally advanced tumor. They will either get radiation alone if they are not eligible to chemo or radiation + chemo. By getting to radiation + chemo with NBTXR3, you can expand the use for every patient that has a need of local control at diagnosis in head and neck. Gotcha. So the Nanoray 312 study is for chemo ineligible, right? And then this new study, phase II, sounds like initially is capturing the rest of the opportunity? Yes. All right. Makes sense. Yeah, there's been some movement recently in head and neck cancer. We saw a positive study for pembrolizumab in a locally advanced setting. Does that impact the landscape in any way, in your opinion? Yeah, I mean, that's the locally advanced setting getting to surgery, which is the other fringe of the population I've been describing. Here, it's expected that getting some immunotherapy will bring benefit to patients because you have removed the primary tumor. You get the benefit of a systemic treatment of PD-1 combined with radiation, combined with chemo, which is, at the end, maybe the same benefit you will get if you treat the same patient after failure. The previous attempt to go for locally advanced head and neck cancer patients when the tumor is in place and you cannot remove by surgery has been a failure so far. Gotcha. So it's a different part of the market. Correct. All right. J&J licensed the program now fully. You recently transferred sponsorship of the Nanoray 312 study over to J&J. I guess, what does that mean in terms of the R3 development logistics? What role will Nanobiotix actually play in the continued development of the product? First of all, transferring an ongoing phase III is a tremendous effort. So kudos to both teams that have done that because it was not an easy task. What it means now is that we're transferring this trial. We started 12 months ago also. It took almost one year to transfer. We started with the U.S., then moving into different areas of the world. And now J&J has almost full operation in all countries for this trial. But the team and our experts specifically continue to work with them on this aspect. OK. I think you recently announced that the PFS interim analysis will now be in 2027 rather than 2026, as anticipated previously. What drove that shift? As I was just mentioning previously, we've been transferring for the past 12 months this trial. J & J has taken country by country in their operation. At the end of this transfer, we got the latest hypothesis coming from that. That is what led us to reassess potential readout. We've been giving H127 as a conservative readout for the timing. OK. Yeah, remind us, what gives you confidence in the positive outcome of the study, actually, at the end of the day? I think that's the data we've been showing in the previous trial, where we see for a very frail population that has radiotherapy as the only treatment, which is usually more a palliative treatment than a curative treatment, we've been able to show a very high response rate, like 81% overall response, including 63% of complete response. That level of complete response is quite unusual in this population. The good thing is, if you get to CR, to complete response for this patient population, then you impact PFS, then you impact OS for the patient. Makes sense. Yeah. You did mention J&J is also doing the randomized phase II study now in stage III non-small cell lung cancer. What can you tell us about the study, perhaps, and opportunity? I think lung cancer stage III is different, but similar spirit than head and neck. You have a local disease. And you need to treat this local disease if you want to prevent relapse or prevent metastasis to occur. There is today the Pacific regimen, which is radiation + chemo followed by PD-L1 if you did not progress after radiation + chemo. But when you look at the outcome of lung cancer patients, after a while they are in Pacific regimen, there's still a lot of unmet medical need. The idea here is, by having a much more powerful radio chemo with NBTXR3, is to improve the rate of response. That should also improve the PFS and the OS for the patient. That's what this trial is about. Makes sense. Do you have a sense of what sort of the goalposts are for the next steps? Is there a certain effect size they're looking for to demonstrate in terms of the randomized aspect of the phase II? Oh, sure. There is a precise design with the idea to demonstrate a higher response rate that should be linked to tendency for PFS and OS. Gotcha. Do you have a sense of how the study's been progressing? Is it up and running? When do you think J&J will disclose some data from that at some point? I'm sure they will disclose some data at some point. Even if we know cancer exactly when. Gotcha. Is it up and running, though? Yeah, sure. Yeah, for sure. OK, great. Yeah, this was a bad question, but you did recently announce royalty financing, actually, for $71 million, bringing in some capital. Maybe just walk us through the economics of this transaction and how it extends your runway? Assuming we pull out the entire $71 million, this will bring us into 2028, which gives us a lot of time. Maybe before going into the metrics, we've been doing this deal to make sure we have sufficient runway to not only accelerating or continuing developing our other asset and platform, but also to get enough time to ensure that some of the milestones coming from the collaboration with J&J we have could occur within this time frame. If everything's going well, this should put us in a very positive financial position. Right. Now about the metrics. Against $71 million, we will reimburse depending on timing for reimbursement around 2030. Is there 1.75 times this or 2.5 that amount, depending on if we are able to reimburse before 2030 or after 2030? That is for the capped amount. Then, depending on the level of revenue that we will make later, there is also a tail, but that is limited on the first tranche of royalties that we will have. Gotcha. Maybe just, sorry, going back to R3, to what degree is J&J leveraging data from their studies that are you doing in-house or some of the phase I and phase II studies and the investigator-sponsored studies that you're sponsoring, essentially, at MD Anderson and elsewhere? We can't talk for our partner. What is sure is twofold, that everything that we are generating in parallel coming from Nanobiotix or IMDA could serve as options and potential for new indications. As soon as you can show safety, feasibility in a population, and you can start also seeing some quantum of efficacy, that will help to go to some more pivotal trial. I think in due time, J&J will communicate on that. Right. I know you disclosed some additional data earlier this year in some other indications, melanoma, I think GEJ as well. How supportive were these data just to providing general additional evidence around R3's opportunity in general as a cancer therapy? I think, first of all, it does continue to build up all the body of evidence we have with this product, not only on safety and feasibility. Every time you go for a hard-to-crack disease and you can show some potential level of benefit for the patient, that contributes to the hypothesis that it will be a universal mode of action that could be applicable across many, if not all, solid tumors that get radiation. I think the data we've been showing in esophageal cancer, in head and neck metastatic patients, in melanoma, really continue to add to many other trials we've been looking at. OK, great. Maybe lastly, sort of investment community, sort of what are there any sort of particular events or data disclosures that investors should be paying attention to over the next 12 or 18 months or so? Sure. Already before the end of the year, we plan to give an update on our second platform to explain to the market how we move forward to create value with this. Now, within the next 18 months, obviously, there is this important milestone in H127 about the interim readout of the phase III. We should also wait, even though we don't have clear guidance on that, the data or the first potential outcome from the CONVERT trial, which is the trial in lung stage III. We will have next year also a good number of data coming from MD Anderson. There is the completion of pancreatic cancer trial, the one in lung reirradiation, some update on esophageal cancer. From a Nanobiotix side, we will also complete our melanoma trial somewhere next year. There should be a continuous flow of things coming from NBTXR3. Perfect. All right. Thank you, Laurent. That's all I had. So appreciate the time. Thank you. Yeah, we'll talk to you soon. Thank you. Thank you.