Good afternoon and welcome to Day One of the Jefferies London Healthcare Conference. My name's Lucy Codrington. I'm one of the European Pharma and Biotech Analysts based in London. It's my pleasure to introduce Laurent Lévy, the CEO of Nanobiotix, and then Bart Van Rhijn, the CFO. So we've got some slides, but we're going to do a bit of a hybrid question and presentation session. Why don't we start off with some introductory remarks about the Nanobiotix story?
Thank you, Lucy, and welcome everyone for this first day at the Jefferies Conference. Happy to have you here. Maybe let me start by some of the story of Nanobiotix. What we do at Nano is something a bit different than the pharma and the biotech industry will do, because we decided to bring something different to the patient. When I say something different, I'm talking about nanophysics-based therapeutics. What does it mean? It means that we build some small object, small object that we will send in the body at the cellular level, and this object will trigger a physical effect that will change the fate of the cell, that will modify the cell's life. We can go from oncology treatment to CNS disorder treatment. There is a huge number of possibilities we are developing at Nano.
Out of this concept, for the past 20 years, we've been pioneering nanophysics for healthcare, and I've been building three different platforms. The first one, which is dedicated to oncology. The second one, and I hope we'll have time to talk about that, that is a much broader platform that is supposed to be done to redesign, to rethink the way we look at drugs and we can build drugs. The last one is dedicated to CNS disorder. We'll go to the question and to your question to see how it goes.
Okay, so let's start with NBTXR3, your most advanced program. Here, this is in a phase 3 study for head and neck cancer, and you also have a partnership with J&J. Why don't we start off by you outlining kind of the terms of your deal with J&J? What are the economics there, and who's in charge of running the program at the moment?
Just maybe before getting to the term of the deal, I think that that would be important to understand the size of the opportunity and the potential impact we could have in patients. That will help you to see why those terms look so good. We can start by the patients. When we think about oncology and we look at the time of diagnosis, it's the vast majority of patients that have a local disease. Only a small percentage of them will have metastasis. We see so many trials with metastatic patients. We see so many patients with metastasis. The reason is why? There are so many local treatments that will fail. Whereas the industry will focus on late-stage patients, we decided at Nanobiotix to focus on early stage of cancer.
When I say early stage, it is the first steps of treatment where the disease is still local, because that's where you can have the biggest impact. Believe it or not, that's also where there is the less competition. Now, if we think about how do we treat patients from a local perspective, I think radiation therapy with surgery is the most used tool in oncology. It's more than 60% of all cancer patients that will get radiation, like 87% of breast cancer, 77% of lungs, 74% of head and neck. The vast majority of patients getting radiation, they are getting it when they have a local stage disease. That's where we could do the most for those patients. Nevertheless, radiation has limitations. When you want to irradiate a tumor, you have to cross surrounding healthy tissue.
Therefore, you're limited by the dose you can deliver in the tumor because of the side effect you will provide in surrounding tissue. We have been developing this product, NBTXR3, exactly to answer that question. How can we improve the dose in the tumor without improving the dose in surrounding tissue? This product has a pure physical mode of action, meaning you inject only once this product directly into the tumor. The patient will get radiation, the usual dose he will receive, and those particles, they will absorb the energy of radiation and deliver much more damage into the cell. What's the size of this opportunity? We said 60% of all cancer patients.
If we look at where we stand in terms of development and where the key programs are, J&J now, our partner, is running three different trials, two in head and neck, one in lung cancer. We also have a bench of other trials in different indications that could serve as new indications when J&J is going to move forward with it. The idea here is literally to try to bring this product to as many patients as possible that are getting radiation. If we just think about the three first indications, lung stage three, two indications in head and neck, that's already 160,000 patients for EU5 and US. That's a tremendous opportunity. If you just look at 20% of those patients, that's potential EUR 5 billion-EUR 10 billion that you can imagine with a normal price in oncology.
That's why we've been able to sign this deal with J&J, not only because we think J&J was the right partner, but also that's a partner that is strong enough to develop widely this product and to commercialize broadly this NBTXR3 across the world. Now, about the terms of the deal, maybe Bart, you want to comment on that?
Yeah, happy to hear, Laurent. We signed a deal in July of 2023 that contained EUR 2.6 million at a time. It is now EUR 2.6 billion of milestones and royalties in the low teens to low twenties %. On the basis of the vast patient population we believe we can address, that will turn into significant economics over time.
Got it. Okay. And then I guess if we're going back to basics, you mentioned about how many patients are treated with radiotherapy. How will R3 fit into the current treatment protocols? Is this going to be something that is cumbersome to incorporate or fairly easy to incorporate? Who does the injecting? Who does the prescribing?
We have designed this product to fit into the existing practice. Imagine all the patients getting radiation. There is a well-established protocol per indication, a patient flow from the diagnosis to the first imaging session, to the dosimetry, to the radiation therapy. In head and neck, for example, that is around 50 visits that the patient will do in the hospital from the diagnosis to the end of radiation therapy. We wanted this product to be used as easily as possible. That is why we have designed the product to be administered only once in the patient. It is a one-time injection that you can do before the first session of radiation. Technically, you can do that the day before, a week before, because what we have seen is this product stays in the tumor from the day you inject it to the end of radiation.
You have here a lot of flexibility. As far as the injection is concerned, the person that is going to inject this product will depend on the indication. Usually, that's the doc that is making the biopsy that will do the injection. It could be the interventional radiologist or it could be the surgeon, depending on the indication. What is important to know is in those different indications, there is already an access to this tumor. Every time you do a biopsy, you need to position a needle in the tumor. To inject this product, you use the exact same pathway you will use to do a biopsy. Instead of removing a piece of tissue, you just inject the product.
Got it. I guess related to that then, are there any radiotherapy-treated cancers for which R3 can't be used?
Technically, we did not treat every patient that received radiation, but we do not see potential limitation to use this product. We need to think about two ways of using it. The first one is for the patients that get radiation that do not get a rate of cure that is satisfying. Here, you just apply the standard dose of radiation and try to improve the outcome by adding NBTXR3. The other part of patients that could benefit from it are the ones that are getting a cure out of radiation. As you know, there is also a lot of side effects linked to it. Here, that is for a more long-term purpose. It will be about injecting this product, reducing the dose of radiation, still providing the same curative power, but with less side effects.
To date, we did not find except extreme cases where we could not inject or treat patients with this product.
Got it. And then head and neck cancer is the most advanced indication for the moment. What was the rationale in pursuing this particularly with R3 then?
I think head and neck is a very interesting and important indication. First of all, there is a huge unmet medical need for those patients. Radiation, just like in prostate or breast or lung cancer, is widely used. If you look at the picture global for head and neck patients, at the time of diagnosis, it's 90% of all cancer patients that have a local disease. Only 10% have mets. For those patients, they directly go to PD-1 treatment or to some other treatment. For the patients that have local disease, if you want to have a chance of cure, you need to get rid of the primary tumor. You need to kill the primary tumor. Either you can go for surgery for a small proportion of them. If you can't, radiation is the only option to kill the primary tumor.
Unfortunately, for patients that are getting radiation alone or radiation plus cisplatin, only a small proportion of them will get a cure out of it. The strong positioning of our product here is to go frontline treatment with radiation alone or radiation plus chemo and to try to improve the rate of cure by killing this tumor more efficiently.
Okay. You have got this phase three ongoing, and that builds on your phase one study 102. Perhaps you could recap the data we've seen so far and what the read across from that data is to the ongoing phase three.
Sure. We have been treating 75 patients in this phase one two. There was an escalation part to define the dose and then an expansion part of this trial. What was important here, because we are talking about a very frail elderly population, is first of all to show safety and feasibility for those patients, which we did. The second very important thing we have seen is a very high rate of response. We are talking here about 81% overall response rate, including 63% of complete response. Remember what I said, if you want to cure those patients, you need to get to a complete response for those patients. What we have been showing here is a very high rate of complete response for those patients, 63%, which is big.
More than the overall response rate we've been observing, we have seen a strong statistical link between the response, the PFS, and the overall survival for the patient. When it comes to overall survival, we got 23 months median overall survival in the evaluable population, which is almost the double of what you may find in similar populations that get radiation alone. Those data served as base to design the ongoing phase three that now J&J is running.
Okay. You talked about the population being based on study 102. Are there any differences in the trial 312, the phase three, compared to 102 that we should consider when we're thinking about the outcome?
Yes. We've been changing a few things in the phase 3 in order to first enlarge a little the population, but also have made some modifications to hope to get also more efficacy versus what we've been observing. In this phase 1, in those data that you're seeing here on the screen, what we have seen is most of the patients that have relapsed, they did not relapse from the primary tumor, but did relapse from the surrounding lymph node that received radiation but no product, which is an unusual pattern. Usually, that's the primary tumor that will relapse, not the surrounding lymph node. What we did allow in the design of the phase 3 is not only you can inject and irradiate the primary tumor, but also inject and irradiate the surrounding lymph node.
We could hope again for even more efficacy than what we have been observing in the phase one. Those were the main changes.
Got it. What about the fact that the phase three allows for the investigator to decide whether to use cetuximab in addition? Are there any implications of that?
Cetuximab is part of the standard of care for those patients or in general, the patients that are not eligible to cisplatin, they can receive in the top of radiation some cetuximab. If you refer to the Bonner paper, you see that for elderly patients, cetuximab may not bring benefit. Nevertheless, it's still in the standard of care or in the guidelines. We allow the physician to use cetuximab on the top of radiation plus our product if they want to. In order to make sure the trial will be balanced, we've made that a stratification factor. The number of patients receiving cetuximab will be the same in both arms.
Got it. The trial's ongoing. Perhaps you could update us on how the trial is progressing, when we might expect first data, and what the regulatory path could be with this trial.
We started the trial at Nanobiotix. Then we signed the deal with J&J. Around a year ago and a bit more, we started the transfer of this phase 3 to J&J in order for them to be ready when the data are out to push the button and go for registration. Also allowing them during all this period to do all the pre-market activities that are necessary to prepare a good launch of the product. We just completed the transfer, started 12 months ago, finished it end of September. Now J&J is fully running and taking all the costs of the trial. The expected data will come H1 2027, sorry. That is the interim readout on primary endpoint PFS that is expected by that time.
Got it. What are you expecting to see and what would be considered success in this trial to enable potential filing on the PFS endpoint?
The trial has been designed to be successful if we go from nine months to 13 months for the PFS between the control arm and the tested arm. During the discussion we had with FDA and interaction, assuming the data are positive at the interim readout, that should be used as registration data for US.
Got it. Okay. J&J has also recently initiated a phase 1 study in cisplatin-eligible head and neck cancer patients. How does this opportunity compare to the ongoing phase 3 population? Are they able to leverage your existing data to potentially move quickly into a pivotal trial?
I think we can talk for our partner, but it would seem logical if you start treating patients that are not eligible for cisplatin and get radiation alone to also move into this population, radiation plus cisplatin. Because those two patients together, those two populations represent where is the biggest frontline unmet medical need for the patient. Moving into phase one while the phase three is still ongoing shows also confidence from our partner to start expanding into another indication, which is adjacent to the first one that is ongoing.
Okay. All right. Let's move on to lung cancer then. When you did the deal with J&J, you had your ongoing collaboration with the MD Anderson Cancer Center where you've looked at R3 across a number of indications. When you did the deal, J&J opted lung cancer to be the first indication that they pursued. Perhaps without speaking for them, you could talk to why they might have thought lung cancer was such an attractive opportunity and how you think R3 can be positioned here.
First of all, when you look at J&J's pipeline, they are big in lung. They said that should be one of the strong therapeutic areas where they are going in oncology. Radiation therapy is widely used in lung cancer, more than 70%. It makes sense to think NBTXR3 could play a seminal role in this indication. Starting with lung stage three, when you have this big local tumor that you cannot remove surgically, it's a very good way to start developing in lung cancer. Here, you're thinking about the patient that gets the radiation, the chemo, and if they do not relapse, they get the durvalumab. This population has a new treatment, the durvalumab, and it's quite good, but it's quite good only for a small number of patients.
Having a stronger local control here, just like in head and neck, could play a very important role. That's why they started this phase 2 randomized trial in lung stage 3 to see how much more local control we can bring with NBTXR3 and how this will influence the survival for the patient.
Okay. You have reported some data in lung yourself through your MD Anderson collaboration. Perhaps you could talk us through what we saw in that trial and is there any read across to the ongoing trial?
It's a different population, but you can see that as a surrogate of what could be seen in this phase two randomized trial that J&J is running. Because in the MD Anderson trial, what they have done is basically taking the patient that have failed either the radiochemo or the radiochemo plus the PD-L1. The patient that would have failed the frontline treatment. By re-radiating those patients with a much smaller dose of radiation plus NBTXR3, they have been able to show a high rate of control and a potential impact on the survival for those patients. You can imagine that if you can rescue the patient after they have received all the frontline treatment and get good results, if you go back frontline with a much higher dose of radiation plus the product, then you may have a much bigger impact.
That's why everyone got really excited about this trial and what we could do to help the patient.
Okay. You have talked about why R3 is best positioned in the kind of frontline settings and the kind of commercial opportunity and competitive positioning there. You also have shown some very interesting data in combination with immune checkpoint inhibitors in later line patients. Let's start, I guess, with what's the rationale for combining R3 with immune checkpoint inhibitors and what have you seen so far?
If you think about NBTXR3, obviously the biggest unmet medical need we could solve are for the patient frontline when they have a local disease. That's where the radiation is applied. That's where we think we will have the biggest impact. It does not mean that we cannot help patients at later stage. If we think about head and neck patients that have failed the local treatment, for most of them, like around two-thirds, they still have a local problem because they had a local recurrence of their disease. As long as you do not kill this local recurrence, then there is no chance of cure. The interesting thing we have been seeing in this trial, treating around 100 patients, both for patients that are naive to PD-1 or refractory to PD-1, is first of all, we get a very strong local control.
Strong local control of the primary tumor, which is needed for most of those patients. Let's say as a cherry on the cake, we also saw that we can start priming an immune response out of this local control and this local destruction of the tumor. Meaning that by destroying physically this tumor, you allow the immune system to recognize the tumor and to get equipped against the tumor and potentially the systemic disease. We see some nice tendency showing that when you have deep response in the primary tumor that you have treated, you also see some systemic response.
What are the next steps here? We've seen initial data in the head and neck cancer patients. You've shown some promising data in melanoma. How do you go about evaluating R3 in this combination approach in such a broad? There's a broad range of ways in which you can evaluate it. What are your priorities here? What are J&J's thoughts?
Again, we want to, sorry, we want to talk for our partner, but it is clear that if this product works as we think it's going to work, it should be broadly used in oncology. Now there is a predefined process within the collaboration we have with J&J and where we evaluate opportunities. At some point, we bring that to a joint steering committee to decide where to go. At the end, that's J&J's product now. They have the final say to move forward in different indications. I will invite you to look at previous collaborations that J&J has done with the biotech. When they have a product that works, that could be widely applicable, usually they try to optimize the patient reach with it.
Okay. J&J are now in charge of the phase 3 program. They've got the lung program underway. What are Nanobiotix's priorities right now? Specifically, you have your two other platforms, Curadigm and Acuity. Perhaps you could talk us through those in the last couple of minutes that we've got left.
First of all, I think the way we see the future of Nano is now we have enough cash to go to the beginning of 2028. During this timeframe, we should start receiving hundreds of millions coming from the J&J deal, first of all, through milestone payment. Within a short timeframe also, start getting this product into commercialization and having some recurrent revenue linked to royalties. Let's say that's one pathway. We do not want to stop here. We think that the Nanophysics-based approach we have been developing for the past 20 years could be widely applicable way beyond oncology. That is why we are super excited about this new technology, Curadigm. If you may allow, I can just take one minute to explain it. Thinking about many innovations in healthcare, there are many products like cellular therapy, like RNA-based therapy, or oncolytic virus, and many others.
When you try to inject them IV in the blood, they will be captured by the liver. To a certain extent, for some of those technologies, that will render almost impossible to escape the liver. We have been looking at this problem slightly differently and thought about developing what we call a nanoprimer. It is a particle that you will inject in the blood that will go in the liver. For a predefined amount of time, we keep the liver busy, two hours, a few days, depending on the design. While the liver is busy, if you inject another product, then it will go through being much less captured by the liver. What you are doing is just reopening the entire body for distribution of this product. Simple concept, but hard to design product and to manufacture.
Based on that, we think we can not only develop new products for Nanobiotix to develop being fully owned, but as a huge business development opportunity, which we have started as long as the GMP process to bring this product to.