We have Laurent Lévy, the CEO, and Bart Van Rhijn, the CFO. We're going to have a kind of hybrid-ish chat today, but we'll get straight into it. So, Laurent, Nanobiotix is more than just NBTXR3. Perhaps you could explain the company's vision before we then get into the details.
Sure. And thank you, Lucy, for having us here. Good afternoon, everyone. Happy to be here to talk about Nanobiotix and to tell you more about what we've been doing for the past years and what's in the front of us. To answer your question about what Nanobiotix is about, maybe we can go back to the fundamental of our company, which is Nanophysics-based therapeutics. Why using physics rather than biology or chemistry? It's because we think that there is much less variability in using physics than biology or chemistry. And therefore, we are bold with that to make a product that could be used in millions of patients with universal mode of action. So that has been our motto for the past decades working on this. And we've been building three platforms out of it.
The first one that is dedicated to oncology, that has now been licensed to J&J. We'll talk about that, I guess. And two other ones, one dedicated to the CNS disorder like Parkinson's, Alzheimer's, and neuropathic pain. And the last one is the one we're going to push in the near future, which is based on defining a new way to design therapeutics. And maybe I will come back if we have time on that at the end of the speech.
Great. Okay. So let's talk about NBTXR3, then your most advanced asset. One of the differentiating factors here about your strategy is perhaps the way you focused quite early on in terms of the locally advanced disease settings. Perhaps you could outline the rationale for this and what the potential implications are for this, both in terms of commercially but also from a competitive standpoint.
Sure. I think there's maybe not a misconception, but at least not the entire way of looking at cancer patients when we think about how investors and Wall Street look at it. I will use one of the slides to illustrate my point. So on this slide, what you see on those dots and the black part are the patients diagnosed with a local disease at the first time of their diagnosis. And as you can see, it's much bigger than the patients that are diagnosed with metastasis. Nevertheless, the pharma and biotech often focus on the late-stage disease, the metastatic patient, where there is a big unmet medical need, but sometimes forgetting that if there are so many metastatic patients, it's because they have failed local treatment.
If we can, with interventional oncology, address those patients when they still have a local disease, that's where we will have the biggest impact in oncology. Talking about this impact, what are the treatments we use for local or to address local issues in cancer? Radiation therapy is necessarily the biggest treatment used in oncology for local issues in patients. It's more than 60% of all cancer patients getting radiation, which is a much bigger treatment than any other. Just to give you an example, if we talk about the PD-1, that's a few hundred thousand patients that will get that. Here, we're talking about millions of patients getting radiation. If you can have a strong impact for those patients when the disease is still local, then you will have a much bigger impact for the life of the patient.
Very clear. And I guess this probably is an opportune moment because we've really covered how it is that NBTXR3 works in terms of incorporating that to kind of take advantage of the use of radiotherapy to treat these patients.
The problem with radiation, what it is, is you have this tumor somewhere in the body, and when you want to irradiate this tumor, you have to cross healthy tissue with the X-ray. Therefore, you also create damage in the surrounding tissue and not only in the tumor. So you're always limited by the dose you can deliver in the tumor because of the side effects. What we have been developing is a unique drug, which is called NBTXR3, which is here to solve this problem for all those patients. And what is R3? It's a drug that you inject directly in the tumor only once. And this drug is designed with a very specific material. We're talking here about nanocrystals of hafnium oxide. Why nano? Because we need small objects that can go in the cell. And why we have been using hafnium oxide crystals, it's for two reasons.
First, it's a very stable material. So in terms of safety, it does offer a good safety profile. And two, hafnium oxide is a super X-ray absorber because of its electron density. It means that when you inject that into the tumor, the product will diffuse, will go into the cancer cell. And when the X-ray will go through, those particles will absorb the energy of radiation and will deliver around them a large quantity of damage, a large quantity of energy. So we're creating into the cell some hotspot of energy deposition that will kill the cell much more efficiently.
And then we can use that in patients to either improve local control, or also what we figured out recently is not only can we kill the tumor and destroy it from a local perspective, but by doing so, we also trigger an immune response that could be useful to destroy this tumor, but also to start taking care of the metastasis the patient will have.
Great. Very clear. And as you mentioned, you've announced you've partnered this program with Janssen, which is a significant endorsement of both NBTXR3, but also your technology. What drives confidence that Janssen is best positioned to commercialize or develop and commercialize this asset?
I think we've been choosing us reciprocally, J&J and us. At the time we made that deal, we had different discussions with different partners, and we privileged this deal with J&J. Not only because it's a big company that has the muscles and the brain to go and commercialize this product worldwide, but also capabilities to develop in multiple indications. But more importantly, because we share this belief that going early in the treatment of cancer, that's where the game is. That's where we can help patients. That's where the market is. And that's why we're working with the group inside J&J that is called Interventional Oncology, which is exactly made for what we are doing.
Got it. And so NBTXR3 is currently in a phase III trial, the 312 trial in locally advanced head and neck cancer. Perhaps you could talk us through what the current standard of care is in this setting, and then how NBTXR3 will fit into that treatment paradigm.
Let me use one of the slides, which I think is interesting. Here you see the paradigm of treatment for head and neck cancer. And if we go at the diagnosis time for all the head and neck cancer patients at the time of diagnosis, that's 90% of them that have a local disease. Only 10% have metastasis. And the treatment for local disease in head and neck is radiation. Radiation alone, radiation plus chemo, or surgery plus or minus radiation and chemo. So if we have metastatic patients in head and neck, it's because some of the local treatments are failing. All the existing market of PD-1, as an example, which is here to treat metastatic or relapsed patients in head and neck, only exists or in majority exists because there is failure of local treatment.
Nevertheless, the biggest competition we see in head and neck is for metastatic patients in combination with PD-1. What we want to do primarily with this product is to go upfront, first line of treatment, way before PD-1 occurs. If we are successful here, patients may not need to go to PD-1 treatment after. Believe it or not, but we are one of the only remaining new treatments that are applicable frontline treatment for those patients. That's where we're going. We have the ongoing phase III for frail elderly patients that can only get radiation, no chemo. We also have shown that feasibility and safety in the radiochemo setting. Just those two indications cover the vast majority of head and neck cancer patients' needs. That's where we're going.
Okay. And so perhaps you can talk us through what the 312 trial is hoping to show? You have an interim efficacy analysis upcoming. What are you looking to see in that trial and what would constitute success?
I think maybe some illustration before we go to the design of the trial and see and show you what we want to do and help the patient with. Locally advanced head and neck cancer patients, you have this big mass here that you cannot operate, and you need to destroy it. If you cannot destroy this tumor, then it will continue to grow and will kill the patient from local invasion of the tumor or from mets coming from the primary tumor. So in locally advanced cancer, like in head and neck, but also other types of tumor, having good local control often translates into progression-free survival and survival for the patient and better quality of life. So what we want to achieve with this patient population, it's exactly what you see on the slide. We start with a patient having this big mass.
We make a one-time injection in the tumor, and the patient is going to the usual flow of radiation, trying to achieve better local control. And as you can see here, achieving potentially some complete response that translates into bigger survival for the patient, which is what we have seen in the phase I/II trial, where we've been treating 75 patients, showing not only safety and feasibility of the treatment, but more importantly, a very high rate of response and complete response. We got to 64% of complete response, which is unseen in this patient population. And when you look at the correlation between the response and the survival, it's highly significant. So let's go to the design of the ongoing phase III, maybe. So it is a global phase III that intends to recruit 500 patients, randomized one-to-one.
Control arm will be radiation plus or minus cetuximab as a choice of physician. And the tested arm will be the same plus the product. The PFS is the primary endpoint, and key secondary endpoints are OS and some others. What we expect is to get to the final patient recruited in this trial, H1 2026, and therefore being able to do at the same time the primary analysis on the PFS, which is the primary endpoint. And assuming that this endpoint is positive, then we should be eligible for an accelerated approval, and that will lead J&J to register this product and then start selling the product on the market.
Great. And I perhaps jumped ahead to the 312, but perhaps it would be useful if you recapped what you saw in your 102 trial, just in terms of what has been shown already that drives such confidence that you will be successful in 312.
This phase I/II in head and neck has been used as the premise to define the phase III that is now ongoing and on its way to be transferred to J&J. Here again, we're talking about frail elderly patients, so patients that don't have that many options. The only option they have is radiation therapy. They cannot handle surgery. They cannot handle cisplatin. So it's more like a palliative treatment that you bring to them with radiation. We've been treating 75 patients in the escalation and expansion phase of this trial that is now completed and published. I was mentioning previously what we have seen on top of good safety and feasibility. It's a very high rate of response. Here you get to 82% of overall response rate, including 63%-64% of complete response. That's big.
You can go and see in the literature, you won't find such a big rate of response for radiation alone in any patient population. More importantly, is that this response really translates into survival for the patient? In the overall patient population that receives radiation alone in head and neck, what you should expect is 12 months median overall survival. And what we've been observing in the available population in this trial is 23 months, almost double. So with this gap of almost 12 months in the OS, whereas the phase III should be positive if we get four months delta, we have a lot of room to play and to be successful, especially because we also have added in the phase III some potential to get even more efficient than in this phase I.
Would you care to expand on what that is?
I knew you would ask. Okay. In the first part, the phase I /II, what we've been doing is patients have a loco regional disease. Local tumor, some lymph node involved with cancer. The standard of care is to deliver radiation both to the primary and the surrounding lymph node. They both receive 70 gray. In the phase I, we've been injecting only the primary, but giving 70 gray to both primary and lymph node as the standard of care is requiring it. What we have seen is most of the patients that relapse in this trial, the relapse did not come from the primary injected tumor, but from the lymph node that did receive radiation, but did not respond as well as the primary tumor, which is unusual because usually that's the opposite.
So it tells us that not only our product is efficient, but also in the phase III, if we could inject the lymph node on the top of the primary, then we'll be potentially even more efficient, which we have a lot.
Great. And you recently made the decision to transfer the sponsorship of the trial to Janssen. What was the reasoning for that decision? And what is your continued involvement in the trial as a result?
So that's a tricky question because it's never simple. That's a big trial, global trial. And at some point, we knew we would have to transfer that to J&J for them to be able to register and start marketing the product. So we had two choices. Either to do it before the results or after the results. So in order to be efficient and for them to be ready to push the button at the time of the results, there was no other choice than transferring that before, which may slow down a little versus what was initially planned, but will accelerate the time to market. And we'll get a much shorter time to market with that than what we could expect before. So that's why we started now. And we officially launched this transfer starting with U.S.
We're going to expand in other countries little by little to make sure that within the next quarter, we can fully transfer this trial to J&J so they can get ready for H1 2026.
Great. And Janssen also is prioritizing lung cancer as the kind of next most advanced opportunity for R3. And I appreciate it's their trial and their rationale, but perhaps you could talk us through the setting that they're looking at and why you think R3 will fit in with that well in the treatment of that setting.
Just like in head and neck, in lung cancer, radiation is playing a major role. It's treating more than 70% of the patients, and there's two big populations that we can think about. The first one is locally advanced inoperable patients, so lung stage three cancer, but also the metastatic or oligometastatic patients in lung stage four, so those are two gigantic populations that still do not have an efficient standard of care, and the first population J&J is going after is the lung stage three patients, so for those patients, the standard of care is you have this big tumor, you get radiation plus chemo. If you do not progress, then you get to PD-1 treatment, and that's the population they are targeting in a randomized trial. The trial just has been published on clinicaltrials.gov and is open for recruitment.
There will be a three-arm trial with two different doses of R3 and a third arm that will be the control arm with radiation and chemo alone and PD-1. When you look at the data that you can find in the PACIFIC trial, you see that the hurdle is not high. The bar to bring some benefit to patients is not that high, especially if you start before the radiation. So we expect here, again, just like in head and neck, to have a much better local control and therefore impact the survival for the patient.
Okay, and look, I appreciate that this requires an element of forward thinking, and we haven't got final data for lung or head and neck cancer yet, and also how this might be priced, but if we were to think about this on a kind of average pricing level for a new therapeutic in cancer, and if we see a replication, I guess, of the 102 data in your 312 trial, how should we be thinking about the potential commercial opportunity for R3 provided it's successful and it gets to market?
So we can't talk for our partner in terms of pricing and reimbursement, but we can still look at what is standard in the U.S., for example, as a pricing in drug. What you can see in the past years, the average pricing of a drug per year per patient is around $190K per patient. So I'm not saying that's the target price. What I'm saying is for an innovative product in oncology that should show some benefit in overall survival, we should expect an innovative type pricing for this product. And beyond the pricing, there's something very important, and maybe I can use one of the slides to illustrate that. That's the size of the market itself. We're not talking here about a product that is targeting a specific mutation in a patient, in a subpopulation, in one indication.
We're talking about a product that is combined with radiation, and that could literally help millions of patients. If we just look at the two first indications, not thinking about all the others we already have started developed. So let's just take lung stage three and locally advanced head and neck in frail elderly patients. Just in U.S. and EU5, it's already 100,000 patients, not taking the rest of the world. If you look at other indications, then you add hundreds of thousands of patients. But let's just focus on the two first indications, EU5 and U.S., and finding the usual price of oncology drug. That's a multi-billion market already.
Okay. Very clear. And speaking of money, so obviously a key catalyst then is going to be that recruitment of the 312 trial and that interim readout in first half 2026. Your current cash runway is 4Q25. So maybe, Bart, you'd like to talk us through kind of how we should be thinking about that small bridge.
Happy to, Lucy. I think when we take a step back, we had an interim analysis that was mid-25 that moved to H1 2026 because after careful review by J&J, they looked at the design of the 312 and deemed that the futility analysis would be futile, so the interim analysis is now based on not only events, but also last patient, and so that moved the value inflection point to a later point in time, so there are some discussions around that. It's a small bridge, as you indicate. We have numerous options, and we're going to choose an option that is best for existing shareholders, but we're confident that we're going to bridge that.
Great. And I guess something that could help trigger that is potential other readouts for R3. So what catalysts are we looking for in the meantime over the next 12 months or so?
So we have a different program with the same product, some that are led by J&J, like the lung cancer trial, but also the head and neck now that is being transferred to them. And Nanobiotix is still running some other trials, like the one we have in immuno-oncology, where we combine radiation, nano, and PD-1 in different patients. So that's a trial with three different cohorts. And we expect to give data on this trial on the three cohorts next year. That's part of the news flow. We should expect before the end of this year, some news coming from MD Anderson, which is also part of this big collaboration. And there's a trial in lung cancer, another one in pancreatic cancer, where we should get some news from the program before the end of this year. And there's five trials ongoing with them and more to come.
So that should start recruiting also next year. So we have a lot to show in the coming months and in the next 18 months too.
Great. And then you mentioned at the start, Nanobiotix is more than just R3. So maybe you could give us an overview of the other opportunities that you're looking for now with Janssen on board for R3. What else is taking up your focus at the moment?
First of all, we still have a lot to do with NBTXR3. And our priority in the company is to make sure this collaboration is a success. So even transferring the trial to J&J requires a lot of effort from the company. And we should not expect to have less than 80% of our effort on NBTXR3 during the next few years. It's still a big push that we are doing with our partner to make sure that we extract all the value of this collaboration and help as many patients as possible. Nevertheless, we are preparing next steps. And the next steps are about the new technology, the two new technologies we have, and more precisely, the one we're going to disclose a bit more by the end of this year.
The idea is to bring to market knowledge about what it is, how it works, why we've been developing that, what are the data that have been generated, what's the plan moving forward, what are the expected milestones in the coming years coming with this technology. But in a nutshell, the next technology that we call Curadigm, when you look at many of the innovative products we see today that are in development on the market, candidates like the RNA-based therapy or cell therapies or some protein-based therapies, you see that those subjects, they are not native. So most of the time, they are seen as the body as a non-self. So if you try to inject the subject IV, they will go in the liver. They will be captured by the liver, which most of the time prevents a large good pharmacokinetic of those products.
Like a limited amount of product, less than 1% will go in the body, whereas the rest will be captured in the liver and sometimes even make it impossible. That's why you see for most of the RNA therapies, all the companies, they are working either on liver disease or using a local injection because they cannot go IV because of the liver. So we've been developing different nanoprimers, which are nanoparticles that we inject IV. Those particles, they will go in the liver and will sort of keep the liver busy from a few hours to a few days, depending on the design we choose. And so while the liver is busy and you, for example, injecting those RNA-based particles, they will go through and they will have access to the rest of the body, which is impossible without.
So it's true for the RNA particles, true for the oncolytic virus from the cell therapy, from many, many, many options. So it's not one product. It's a platform that will lead to many options and many products, some that we will keep for us to develop internally and some that we will license and develop in collaboration.
Okay. Sounds very exciting. And with that, we've run down the clock. So I'd like to take this opportunity to thank Laurent and Bart for their time and to.