Good morning, and thanks for joining us to have a conversation with Laurent Levy, CEO, and Bart Van Rhijn, CFO of Nanobiotix. Nanobiotix is developing a radioenhancer, NBTXR3, which is hafnium oxide nanoparticles that can be induced by radiotherapy to cause significant tumor cell death in the injected tumor. In 2023, the company forged a global co-development and commercialization agreement with Janssen Pharmaceuticals. To learn more about the drug and the development progress to date, I welcome Laurent and Bart to this conversation. Good morning, Laurent and Bart. I'm glad to see you both and appreciate you accepting our invitation to talk to our audience this morning. Laurent, for starters, by talking through your journey with hafnium oxide, which is known as NBTXR3, please explain the nanophysics of this molecule and also what was your vision when you started the company Nanobiotix.
Thanks, Aake, and welcome everyone. I think maybe before talking about hafnium oxide and NBTXR3, we'd just like to reemphasize the fundamentals of what we are doing at Nanobiotix. Maybe even before that, telling how we see the development of biotech or pharma industry in general. You're most of the time developing a molecule or an entity that will target something in the body to have an effect for the patient. What is very hard with this is you never know if the target is going to be really expressed in the patient. You never know also if the target is going to be expressed along the whole course of the disease. It's very hard to predict that your product you inject is going to have the desired outcome for the patient.
There are a lot of uncertainties around biology and the use of a target as a fundamental to treat patients. That's why we have the probability of success we know in the pharma and biotech industry. Not that it's not useful; there are plenty of good drugs that help patients every day. We decided at Nano to do something really different and use nanophysics. Why that? We think when you have a physical mode of action, you're not talking anymore about target or about biology. You just deliver a physical effect somewhere in the cell. Regardless of the patient, regardless of the tumor, regardless of the targets, you will have an effect. The fundamental difference is with our product, and not only the first one, but what we are developing broadly at Nano, we have a product that could fit millions of patients. That makes a big difference.
Also, as a mirror to that, in terms of probability of success, we know the product is working before injecting it into the patient. The only question we have is what's the quantum of benefit we'll bring to the patient?
Perfect. Talking about quantum of benefit, what's the real global opportunity of NBTXR3? Most patients with solid tumors at some point within their treatment journey would see radiotherapy.
Yes, if you look at broadly, it's 12 million or more patients every year receiving radiation therapy. That's 60% of all cancer patients, which is gigantic. When you think about that, those patients, they receive radiation for the vast majority right after the diagnosis because they have a local tumor that you want to treat. That's the positioning of our product. First line of treatment, way before many of the systemic treatments and developments we see in the pharma or biotech industry. It does offer two big opportunities. The first one is if you treat the patient early and you get a good rate of cure, then you have a good chance to have a long-term benefit for the patient.
Also, those patients not only could get direct benefit, but they don't have to handle all the following systemic therapies that you will need if you get a good local control for those patients. That's one. Now, if we go deeper in the product, we were mentioning millions of patients, but if we just look at the two first programs we have, one in head and neck, one in lung cancer, and those are only two subpopulations of head and neck and lung cancer. Between EU 5 and U.S., we are targeting hundreds of thousands of patients. That's very big already and far away from the full potential of the product. When you think about that and you apply the usual pricing for an oncology product that will have a survival benefit and quality of life benefit, then you're already reaching a multi-billion market with just the two first indications.
Before we get into the indications themselves, the NBTXR3 has been tested in multiple clinical trials and there have been multiple physicians who have worked with this. In terms of the feedback that you're getting back from the physicians themselves, what sort of commentary are you hearing from them so that it makes investors believe that radiation therapy is coming back or it has the potential to come back, especially in the last couple of decades when we started seeing targeted and personalized therapies coming on board? It seems like the radiologists keep going down to the basement.
I think that's true. Most of the time, the radiation equipment is in the basement for good reasons and safety reasons. I just want to maybe give or correct something. The radiation therapy is not less used today than it was in the past. It's even more used today than in the past. It is a well-established frontline treatment for a lot of patients in oncology, and the numbers are just growing intrinsically because radiation is getting better and better, but also because the number of patients is growing with the aging population and increasing population. Radiation is here to stay as a frontline treatment for local treatment of cancer. As you said, when you look at the past two decades in radiation oncology, there have been only some incremental progress, making the equipment a little bit better to deliver radiation, a little bit safer.
You don't change fundamentally the issue, which is how can you really increase the dose in the tumor with radiation without increasing the dose in surrounding tissue? That's exactly what our product is made for. To answer the second part of your question about what we heard from physicians, we heard many things because we've been developing this product for a while now. The first thing we heard is, yes, that's good to have a product dedicated for radiation oncologists and for radiation therapy because there's not much product in that arena. Believe it or not, but that's really an untapped medical community by the pharma industry. They really want something to help the patient better than they can do with radiation today. That's why with NBTXR3, we never had a problem to get the attention of medical or radiation oncologists on that matter.
We have had no problem to develop a subtrial and to get the attention of the whole community. That's what we can say in general.
Fantastic. As I said when we started, Janssen Pharmaceuticals signed a large deal, you know, close to $3 billion of a transaction with you back in 2023. What sort of data or what sort of opportunity do you think, do you believe led them to make that transaction?
I think there's two big answers to that question: the data and the strategic fit. Maybe let's start with the strategic fit. We share this belief with Johnson & Johnson that if we treat the patient early in their disease, that's where we'll have the biggest impact. Interventional oncology, which is a unit they have been creating in the recent past, needs to have access to the tumor locally to get a strong impact from a local perspective. That's what our product does. There is already this strong strategic fit. When you think about oncology and solid tumor and all the big cancers we know, NBTXR3 with radiation could be an anchor for any strategy in oncology.
As we cover most of the tumor, you can also have your sales force that are dedicated to prostate or breast cancer or lung cancer, and you still have NBTXR3 as an anchor for all those tumors. That's from a strategic fit perspective. Now, clearly the data that did convince them is the breadth of the opportunity and data we have generated, starting with soft tissue sarcoma. We've done a randomized phase II treatment in soft tissue sarcoma, clearly establishing in humans that this product is working. When we did compare radiation alone versus radiation plus NBTXR3, we've seen superiority in outcome for the patient. Soft tissue sarcoma is a very hard-to-crack disease, resistant to many things. We did crack this disease with this product, at least for part of the patient.
This has been the fundamental thing for the whole development of the company and NBTXR3, including Johnson & Johnson. The other part was head and neck data, where we'll come back to that, I guess, a bit later. When you think for part of the patient, radiation is more like a palliative treatment than a curative treatment. In the phase I, where we've been treating 75 patients, we clearly have seen a gigantic rate of response. If you think about what you can find in literature for those patients, we're talking about a 35% response rate, and we got an 80%+ response rate, including 64% of complete response. That's a strong indicator that our product does impact those patients because with response comes PFS and OS when you have a local disease in oncology. Many other clinical data show them that there's a big potential for this product.
Okay, a question for Bart. There are certain investors who think, you know, it's going to be a royalty play on NBTXR3. Do you think, you know, there is some truth to that statement, or do you expect Nanobiotix to commercialize, you know, indications once Janssen starts commercializing on the initial couple of indications?
Great question. Thank you, Aake. No, we know what we're very good at, which is innovation and development in the early stage. That's what we, you know, will continue to focus on. The transaction that we did with Janssen Pharmaceuticals allows them to commercialize globally. With their expertise, their breadth, their depth that they have, we gladly leave that in their hands. From an investment perspective, yes, there is a royalty arrangement in place with a lot of milestones. There's also an incentive for Nanobiotix to continue to develop and basically spur the clinical development plan to expand the number of indications. It is a very symbiotic relationship that has been established. Beyond NBTXR3, Laurent Levy and the team have been working on other platforms.
We believe that there's a lot more to develop using, you know, the physics into the healthcare theme, whether it is in bioavailability or biodistribution or in CNS.
Perfect. Maybe, Aake, just one more thing, because we heard that from a few investors, not all, because I think there's a part of investors that see the large opportunity we have with NBTXR3. If we look and make some simple math, if we would have been a company developing one product that will target one or two indications to make $2 billion to $3 billion, that's true. Having such a deal would have transformed us into a royalties company and would have maybe capped part of the return. That's not the case with NBTXR3. If you look at the potential of this product going after multiple indications, what we will be able to do with Johnson & Johnson is much bigger than what we could have done as a single and standalone company.
The pie is going to be much, much bigger with Johnson & Johnson than without Johnson & Johnson. When you look at the high rates of royalties that we get, then we, at the end of the day, will get much more revenue with Johnson & Johnson than being a standalone company. It was a no-brainer because of the price of the opportunity of this product to go with a partner such as Johnson & Johnson.
True to that, I know that you've been working with MD Anderson for additional indications beyond what we know of at this point, right? Certainly, we know about sarcoma, where you've already been successful. You've been working with head and neck and also in lung cancer. In terms of additional indications, what should we expect, and what have you seen NBTXR3 to be effective in, in what indications?
Maybe we can go back to the fundamental I was describing a bit earlier about the physical mode of action. We know that for all solid tumors, when you combine radiation plus NBTXR3, you will kill more cells in the tumor. You will have a better killing power of the radiation. We did not adopt a usual strategy. What we've been choosing to do is going for one or two indications toward the market. That's what Johnson & Johnson is leading with the phase III in head and neck cancer and the phase II randomized trial in lung cancer. That's a clear pathway toward the market. In parallel, we've been running in the past and we continue to expand with MD Anderson Cancer Center and multiple phase I to establish the feasibility and the safety.
We believe that when the first indication hits it, then it will be easier to jump directly into phase III in any of those indications where we have established safety and feasibility. I will pick any of the tumors we've been treating so far. There are multiple clinical trials already showing this. The natural expansion will be to expand in head and neck and expand in lung cancer because there are multiple populations that could benefit from this product.
Very good. In terms of catalysts, what are the major catalysts that we should expect on the clinical side, you know, not only in this second half of 2025, but also in 2026?
I think let's talk first about this year. We should expect in the not-too-distant future at least three different readouts in terms of clinical data. There is one about the head and neck late-stage cancer patients that are receiving PD-1 or other kinds of treatments, being naive to PD-1 or refractory to PD-1. There is also the melanoma, where we're going to present the first data, and esophageal cancer. That's one trial that Nanobiotix is running and the two others coming from MD Anderson Cancer Center. That's part of what's going to be shown for this year. Next year, obviously, we are awaiting one of the key milestones for Nanobiotix, which is the interim readout of the phase III. In the not-too-distant future, but we can't precise that yet, we should also expect to get the first outcome of the converged trial that Janssen Pharmaceuticals is running.
In those two clinical studies where, you know, whether it's interim data that we're going to see from the phase III, ongoing phase III, or the other study that Janssen Pharmaceuticals is running, what sort of data do you think is meaningful or, you know, would indicate that it bodes well for the final results?
First, let's restage the head and neck disease. 90% of head and neck cancer patients at diagnosis have a local disease. They are not going to get PD-1 as a primary treatment, except a few that got surgery. For those patients, they have a tumor in place and you need to kill this tumor if you want to get any chance of cure. That's the realm of radiotherapy, either alone, which is the ongoing phase III we have, or in combination with cisplatin. That's also another trial we've been running in the past. That's where the biggest opportunity is in head and neck because that's where you can cure patients. When they're going to fail this line of treatment, they're going to be eligible for PD-1 and other systemic treatments like bispecifics and so on. Here, the chance of curing patients is getting really low.
Across different lines of head and neck, including the last line of treatment with PD-1 treatment and others, you always need to get to the primary tumor because as long as you can cure this primary tumor, you'll always have local relapse or systemic relapse. There is a spot for Nanobiotix, which is, first of all, first-line treatment when the disease is local, and that's where we put our effort. Across the different lines of treatment, everywhere the patient needs a local treatment, that's where we could also play. We've also seen that this product, on top of having a local action, can prime also an immune response, and that could help the PD-1 and other treatments. Really happy that soon we're going to be able to present more data of this completed trial.
There is another study, NanoRay 312, right? That data is, I believe, expected in the 2026 timeframe. What should we be expecting in that data set?
The phase III, by design, has a target in terms of primary endpoint linked to PFS. We should hit that target for sure. With what we have seen in the phase I treating 75 patients, we think we have a good chance to get there. That is not the only thing we hope to see in this trial. What is really important for those patients is, as I mentioned previously, how much of a cure you can bring. This, you don't see in the primary measure of PFS and OS, which is a median. You will look at it from the tail of the efficacy. That is what we really count on, that we could transform for part of those patients palliative treatment into a curative treatment. What we have seen again in the phase I gives us a lot of confidence that we are going to get there.
As you stated, or as Bart Van Rhijn stated, NBTXR3 is not the only part of the story. There's additional things, especially you have been developing, you know, the Curiline and Oocuity. What can you tell us about molecules from there? When should we expect any of them to get into the clinic?
Given the fact that we have zero seconds remaining for our rating, I'm going to try to be short. Yes, we are developing two new platforms that lead to different products. We think the two new platforms we are developing are even bigger than the first one. The Curiline platform is a multiple indication purpose platform that will help us to create business development opportunities, multiple ones. We are also developing our own pipeline of products based on that. You should get an update before the end of the year about where we're going with this and new data coming from it. For the last platform, being about CNS, here again, we have multiple products that we expect to extract from this platform to tackle some of the major diseases like Alzheimer's, Parkinson's, dementia, and so on, all based on nanophysics.
Very good. Last question. In terms of your balance sheet, what's your current cash position and what sort of a runway can we get?
The last reported cash balance, which is the end of 2024, was close to €50 million. That will take us into mid-2026. The company's hard.