Good afternoon. I'm Carolina Ibanez-Ventoso , and I'm joined here with Bart van Rhijn, Chief Financial and Business Officer of Nanobiotix, which is covered by our biotech analyst in Europe, Clement Serres, who could not be here today, so I will be moderating the session. Bart, to start things off, could you please give us an overview of Nanobiotix, your technology, and at a high level, what are you trying to accomplish?
Wonderful. Thank you, Carolina, for having us at the conference. We're pleased to be here. Nanobiotix is a French-headquartered company. Our lead asset is in oncology, and we have two other platforms, one in bioavailability and biodistribution, and the last one is in the CNS space, but as Nanobiotix, we look for challenges that have some common characteristics. One, high unmet need. Secondly, first in kind. And thirdly, high walls of IP that we can build around these platforms and assets, and when we look at the first asset, that is NBTXR3, or R3 in short, in oncology, that and the other two are really centered around bringing nanophysics into healthcare, and that's a unique proposition that hasn't been done a lot, but when you think about it, it is a product that is tumor agnostic. It's combination agnostic, and it is target agnostic.
So we're not following a specific cell mutation. So it has a very wide applicability. And with that, I think there's a lot for us to accomplish. The first indication is in head and neck. That is in phase III stage. So that's more or less.
Excellent. For your lead product candidate, the R3, you said that this Nanophysics-based asset. Can you tell us a little bit more about the mechanism of action?
Yes. Yeah. So radiotherapy is really physics. If you think about oncology, it's about 60% of all oncology treatments that feature radiotherapy. And what is common among all of those is that you try to bring local control. And local control really evident is because when you use these physics-based approaches, you get a very high response rate, which translates to not only PFS, but also OS, and much more so than in a metastatic setting. So it's really a universal mode of action that we apply. So in that way, you can see this first asset, R3, as a pipeline in a single product.
So it's tumor agnostic. It has broad application. But realistically, are there any limits of what you can address with the product candidate?
Yeah, that's an excellent question. We believe not, because anything that can be biopsied can be intratumorally injected. And we've done this in eight different tumor types, to name a few: head and neck, soft tissue sarcoma, in which we, by the way, have a randomized approval, lung, PDAC, esophageal, rectal, prostate, and so on. So we've been able to demonstrate that in many situations. And if you think about it, also from a population perspective, the number of patients that we can reach is really large. And what is unique because of this physics-based approach is that you typically get in front line. Oftentimes, in oncology, you start in a metastatic setting and try to work your way towards first line or front line. We actually go in the other direction. And because local control is such an important aspect in triggering the response in patients with cancerous tumors.
Therefore, you also start at the top of the funnel from the number of patients.
So you are developing this R3 in collaboration with J&J in certain indications, while you are also pursuing other indications on your own and in collaboration with MD Anderson. Strategically, how do you think of the clinical development of R3?
Yeah, excellent question. So yeah, maybe a few words on the J&J collaboration first. So we struck a co-development commercialization deal with them last July. Originally, they were very focused on lung, but the more they looked at the asset, the more they liked what they saw. And as for in head and neck, that is now a strategic asset to them because we're in a phase III on our way to commercialization. But as a testament to their focus on lung, they received a Study may proceed letter from the FDA earlier this year with regards to a stage three lung study. That is a phase II randomized study that they'll be conducting. So first focus, again, head and neck, that is in process, and then they focus on lung. And with MD Anderson, we've really focused on very hard to crack challenges.
We have done lung, head and neck, pancreatic, esophageal. So we're really trying to move science one step. So I think these two combined provide for a very rich opportunity to build out this tumor agnostic, combination agnostic, and target agnostic asset.
Can you speak a bit more about the structure of the J&J deal?
Yes. Yeah, happy to. So, there's a lot of biobucks associated with it, $2.5 billion. The royalties are low teens to low twenties, and at the time of the deal, we believe we secured about a third of the value and two thirds for J&J. The numbers that I just quoted exclude the Greater China rights that were owned by LianBio. Those rights and obligations were acquired by J&J at the end of last year, so with the value inflection points upcoming, we believe it will have hundreds of millions coming as cash inflow into the company, and that will be linked to key de-risking events that will materialize. We're very happy with J&J. As a matter of fact, I don't think we could have had a better partner. They take innovation very, very seriously. This is a new mode of action.
It's been taking a while to get to this point, but they embrace it. And we believe that together we can go far.
You're currently in the process of transferring the phase III study to J&J. So what are the timelines and the logistics involved there?
Yeah, a little bit of context. So we had an interim analysis planned for mid 2025 that was a single trigger-based interim analysis because it was just event-driven. After J&J took a good look at the phase I study that we did prior, which is the study 102, they basically came to the conclusion that we don't need a futility analysis, and they didn't want to bias any of the recruitment in either arm. So they said, well, why don't we make it a dual trigger? So it's last patient in and event-based, which pushed that interim analysis out to H1 2026. So we're moving forward with that. And yeah, I think that is a very, very involved process because they do it essentially during the phase III study that's ongoing. So it means that they need to go out to each and every country to get approval.
It's a very involved process, anywhere between nine to 12 months. But it helps them to complete the study based on the regulatory standards that they want to apply, and it shortens the path to commercialization. So although it is a delay on the interim analysis, we believe it's a very palpable sign of J&J's interest in this asset and where they want to take it because we believe that, FDA willing, we should qualify for an accelerated approval post the interim analysis.
Excellent. And once the transfer of the study is complete, will J&J fully manufacture the product, or you will continue supplying it?
So at this time, they're duplicating the manufacturing capabilities. So more likely than not, they will take the commercial manufacturing on board. But already at this time, we're in a position to serve tens of thousands of patients. And I think it's a testament of their interest in this asset by duplicating these manufacturing capabilities. So there's a lot of investment made.
Moving on to your specific studies, your pivotal phase III trial of the R3 in head and neck cancer, the Nanobiotix 312. First, can you outline the design of the study? And then second, share the rationale for targeting elderly patients first that are platinum-based, that are not eligible for platinum-based chemotherapy?
Yes, yes. So maybe I'll share a little bit about phase 1 to make that jump to the registrational trial. So in the Study 102, we saw some very tangible results. We had a PFS of 16.9 months. We had an OS, median OS of 23.1 months in the available population. So combined with a complete response of 63% and an overall response rate of 82% for those very frail and elderly patients, that was a very remarkable outcome. When we look at the phase III study, the bar that we need to, the hurdle that we need to get over, if you will, is for PFS, it's 9 plus 4. And for OS, it is 12 plus 4. And based on those results in the phase 1 study, we believe that we will meet that and go beyond.
There's two important differences between the phase I and the phase III. In the phase I, one couldn't inject the lymph node. What we've seen is that a lot of the relapse that's happening with patients is coming from the lymph node. There was kind of a change in the pattern of failure, if you will. The other difference is the phase I had a very high concentration of patients with high comorbidities, so 67%. The patients in the phase III are a little less frail. In the phase III, we can also inject the lymph node. Management is very confident about the results of that study. I think looking at the statistical power of the study, which is very, very high, we cannot wait to get there.
Great. At ASCO, we also saw some encouraging data with R3, followed by checkpoint inhibitors in anti-PD-1 naive and refractory patients with head and neck cancer. How does this update inform the next steps? And also, how do you weigh the opportunity in the anti-PD-1 naive versus refractory patients in light of the results?
Yes. So in general, we've seen that this cancer cell killing effect is very good of R3. It's kind of a super X-ray absorber that's very effective at killing cancer cells. But what we've also seen is that R3 has been able to trigger an immune system response. And that is because we believe the cancer cell effect, killing effect, is such that it is so vast and deep that it triggers that immune system response. So in our Study 1100, where we have cohorts in naive, but also in resistant, we've seen very, very compelling results, whereby the objective reduction of the lesion has been demonstrated in 71% of the patients. So there clearly is something happening that not only demonstrates local control, but also systemic control. So we believe that there is a pathway forward on the metastatic setting.
To that effect, we've had discussions with the FDA a little over a year ago that informed us about a potential design of the study. That said, with J&J at the helm in a joint strategy committee, ultimately, they'll be making the decision together with us, but they ultimately have the vote. We'll see where that goes.
Okay. So these were from recurrent, this data were from recurrent or metastatic head and neck cancer patients. But we are also waiting to see data from a third cohort with liver-lung metastasis from inoperable primary tumors. What are the expectations for this third cohort?
Yeah, we're looking forward to bringing data on that cohort. But because it is a universal mode of action, we believe that we will be showing some very good responses, not unlike what we've seen in the first two cohorts with the naive and the resistant patients. And I think that's the beauty of physics, right? There is a certain expectation of what it will bring, irrespective of tumor type or target or prior RT history.
What are the timelines for this?
So we haven't specifically announced it, but next year during the medical congress, we'll be bringing more data. And we're looking forward to bringing that data.
Okay. Good. Also, we mentioned that you have clinical studies ongoing with MD Anderson for challenging indications. Can you elaborate that they are a little bit more? And what kind of results will make you excited and wanting to move forward the clinical studies?
Yes. So as I briefly referenced, we have about five ongoing now. We brought some very compelling data with regards to PDAC last year. We'll have a PDAC update before the end of this year. We'll have esophageal next year. And I think if one were to characterize the type of studies that we do with them, it's kind of signal finding. But we have some brilliant investigators at MD Anderson that we're working with. And all what we've seen to date has been very compelling. For instance, the median overall survival in PDAC that we shared last year was 23 months. And it's not easy to get to those numbers. And we're equally optimistic about bringing more data in PDAC or esophageal going forward.
This update, PDAC is going to be at a medical conference or will be more of a corporate update?
That will likely be done prior to this year-end and may not be at a medical conference. Again, maybe to highlight, I think there's a couple of unique aspects about this product, and oftentimes, it goes unrecognized, but when you start with frontline, where radiotherapy is used so much, you can really address so many patients, right, so if you think about just the first two indications alone, you can get to 100,000 patients because the local setting is so important, but not only that, I think these studies with MD Anderson show that there's so much more potential beyond that first beachhead.
Beyond R3, you are also exploring other facets of nanoparticles completely outside the oncology setting. Can you share a little bit more of the work that you are doing there? And how should we think about the cadence of advancing these programs in the clinic?
Yeah, that's an excellent question. So maybe the first one, the Curadigm platform is a bioavailability and biodistribution platform. I'll say it in layman's terms as I'm not a scientist, but essentially, we keep the liver occupied. So when you were to administer a therapeutic agent via IV, you really upregulate the efficacy thereof because typically, the liver would, once the therapeutic agent, it would go one time through the blood circulation and get trapped by the liver, creating tox issues or efficacy issues. If you use this Nanoprimer that is part of this Curadigm platform, you basically start occupying the liver. So when you administer the therapeutic agent, it can circulate through the bloodstream and get it to its intended target and have its intended effect. That is in a preclinical stage. And then the last product in CNS is essentially looking at the brain as an electric circuit.
So when you think about Alzheimer's or Parkinson's, it's misfiring of the electric circuit. So the neurons are not getting connected because the electric circuit is not functioning well. It's either not connected. It needs to be upregulated or downregulated. And Laurent Lévy, our founder and CEO with the team, essentially created a library of nanoparticles that can help to create a better conduction. That is in a discovery stage. But the priority for the company is to, after, or well, I should say, while making R3 a success, to stand up this Curadigm platform more. We'll bring more information to the market before year-end while we continue to move Oocuity out of a discovery stage more towards a preclinical setting. So it's still 85% focused on R3, but we hope to be in the clinic with Curadigm in a few years, but not much longer.
That's fascinating. Any questions from the audience?
Relating to your Johnson & Johnson collaboration, there was an equity investment. Was that separate or was it pooled into the total?
That was.
Stayed separate?
It was separate. So we had $60 million that was a combination of an upfront and an in-kind, and then $30 million that was an equity component. And we did a raise last year in November when that $30 million, but that's separate from the $2.5 billion. And maybe $2.5 billion is a big number, but let me break it down a little bit because more than half of that number is linked to regulatory and development milestones. $1.8 billion is both lung and head and neck, the first two indications, as well as tumor-agnostic commercial milestones. And then there is a pocket of $650 million that relates to up to five additional indications and regulatory approvals there. If Nano were to do something, there would be $220 million if and when successfully commercialized globally. But that's separate from the $2.5 billion.
And maybe too obvious or not, but I think it was a clear focus of Nanobiotix to make sure that there is a long tail value that we create because this tumor-agnostic profile of the asset.
In the last few minutes that we have, after the radiation, my understanding is that the R3 product still remains in the body. What kind of long-term safety data you think that regulators will need to see?
That's an excellent question. Yes, it is an inert product. It stays in the tumor. We do CT scans of patients after treatment. You can see that visualized. The safety and tolerability profile has followed the standard radiation profile. Obviously, you also take a good look at what happens when you intratumorally inject, if there's anything related to the injection. That gets concerning if you need to do massive tumors where you have very, very large quantities that you need to inject, but that's not the case. That would be very much atypical. So far, I don't think we have received any specific questions on long-term safety. We look at that. For instance, even if there might be leakage into the bloodstream of the product, but that, to our knowledge, has not occurred in very minor single percentage points in a few patients.
So looking good.
Yeah. Very interesting. And how should we think also about the pricing of R3?
So you should think of a typical oncology pricing. It's a drug in the U.S. And it brings very distinct overall survival, quality of life. So you would need to use that as a proxy for the pricing of this product.
Okay. And just like one final question for me, what's your current cash runway?
The current cash runway is into Q4 of 2025. That's a little short of the H1 2026 interim analysis readout. Maybe just some color around it. I mentioned that the interim milestone has been moved to a later point in time because it became a dual trigger versus a single trigger interim analysis. There might be some discussions with our partner on that front, but we look forward to addressing this with confidence given the small delta there is and us wanting and needing to be a good partner to J&J given the plans that they have with this product and the potential it has. Because if you were to apply tens of thousands of patients with the oncology pricing, then you can imagine what the size of the product could be.
So there are no additional questions. So that would conclude the session. Thank you very much.