My name is Michael Schmidt, biotech analyst with Guggenheim, and it is my great pleasure to welcome Bart Van Rhijn, the Chief Financial Officer of Nanobiotix. Bart, welcome, and thanks for joining us. Yeah, while I look for my notes, perhaps you could start out by just briefly introducing your company for folks here.
Wonderful. Thank you, Michael. We appreciate you having us. So Nanobiotix is a French-headquartered company. We're dual-listed and have been working hard to bring physics into healthcare. There are three platforms that we have. The first one is NBTXR3, or R3 in short. It really is focused on bringing a significant impact in the oncology space. So what is it? It is a nanoparticle-based product that gets intratumorally injected one time and will work with a physical mode of action because when it's exposed to radiation, it will be very effective at killing cancer cells. So it fits very neatly in the patient flow and drives a lot of local control. The two other platforms, I'll be brief about them. One is Curadigm, which is a platform to essentially transiently occupy the liver clearance pathways.
If you administer a therapeutic agent after the use of what we call our Nanoprimer, you essentially get the right dose of this therapeutic agent to the right spot without triggering toxicity issues or efficacy issues. The last platform, again using physics, is in the CNS space. So we use the electrical properties of the neuronal pathways to up, downregulate, or better connect the electric circuit in the brain.
Okay, super interesting. So Bart, NBTXR3 is obviously your most advanced product candidate right now, which is based on your radio-enhancing technology. So yeah, maybe just remind us again of the mechanism of action of NBTXR3 and perhaps talk about some of its features.
Happy to. So it's essentially hafnium oxide. So it's a heavy metal. And it functions as kind of a dish to absorb the radiation and then reproject it into the tumor to create multiple ways of killing tumor cells. It has a negative surface coating to get into the cells. So it's very small, and it basically stays within the tumor. Again, you need to only inject it once and will be used throughout all of the courses of treatment. It has a great safety and tolerability profile, not unlike radiotherapy.
Right. And so yeah, when we think about this concept, so the product essentially works as a radiotherapy enhancer. Is this something that is evaluated by others in the industry, and are there any peer products in development, perhaps with a similar mechanism of action?
There are radio sensitizers out there, but not really a radio enhancer. So this could be really the first in kind. And I think the beauty of this product is, as it is so effective in killing cancer cells and establishing local control, it's a product that you can apply with the majority of patients that get radiotherapy.
Right. Yeah, maybe then talk a bit more about radiation therapy right now. How is it used in cancer treatment, and what is its outlook longer term? Is it used going up, staying stagnant, and so on? And yeah, where do you see the unmet medical need in this category?
Yeah, that's an excellent question. So when you look at radiotherapy, it's used in 60% of all treatments. So annually, about 20 million people get diagnosed with cancer. So 12 million get radiotherapy. As it is a frontline treatment, I think many patients can benefit. When you think about cancer treatment and diagnosis, diagnosis is going up. Cancer is becoming, unfortunately, more prevalent. So we believe that this could really be the mainstay. And ultimately, the thesis that we're trying to prove with our partner, J&J, is you should be using R3 in combination with radiotherapy because it has such a good benefit-risk ratio and really can move us from where we are today to a curative impact. And where we are today is essentially a standard of care where radiotherapy is limited to what healthy tissue can tolerate. So it's not meant to cure.
With this product, we believe we can get to that next level, which is really a curative potential.
Okay. And yeah, you did mention you have this licensing agreement with J&J. Just remind us of the scope of this deal and how it could potentially maximize the commercial potential of NBTXR3.
This goes back to 2023. We concluded a license deal. It was a co-development commercialization deal. Royalties low teens to low 20s. After J&J acquired the rights for Greater China from LianBio, the milestones now amount to $2.7 billion. Mind you that the majority of those milestones are related to development and regulatory approvals. We believe we have a formidable partner that really can take this product broad and wide. We're in head and neck. They started a late-stage three trial. We believe that this is a partner that not only believes in the technology, but they've been investing commensurately. Yeah, we're excited where this is going.
Sounds good. And then yeah, so maybe then let's talk about some of the ongoing development areas for NBTXR3. And so your most advanced study right now and focus is in head and neck cancers. And so yeah, perhaps just explain to us sort of what drove your decision to focus on that indication initially.
Yeah, no, that's a great question. I think with the head and neck population that we're focused on, so we have a Phase 3 ongoing in cisplatin-ineligible patient population, locally advanced head and neck. The standard of care there is radiotherapy. That's the only thing that these patients can get. They're frail. They're elderly. There's not a big outlook for them, so with a test arm that is radiotherapy plus R3, any benefit that these patients get beyond standard of care will be attributed to R3, so it's a very powerful way to establish the benefit both from a regulatory but also from an economic perspective.
Yeah. And so I know you've generated some phase one data. You have currently a phase three trial enrolling, the NANORAY-312 study. So maybe first remind us of the design of the study, the purpose of this Phase 3 study.
So the design is it's a 500-patient trial. It's randomized one-to-one. Primary endpoint is PFS. It's 65 years and older. It's chemo or cisplatin-ineligible population. Secondary endpoints are OS, quality of life, et cetera. This comes after this phase one study that we ran, study 102, where we showed some very compelling results. The 312 is enrolling. And actually, at this very point in time, we're transferring the sponsorship to J&J. We've completed that already for the FDA, and we're now doing that for the rest of the world.
Okay. And yeah, can you just remind us of the data from the Study 102 and yeah, why that data really gives you confidence and positive outcome potentially of the NANORAY-312 study?
Happy to. The 102 showed an ORR of 82% and complete response of 64%. Really remarkable results. We had a median PFS in the available population of 16.9, and we had median OS in the available population of 23.1 months. When we go back to the study 312, the hurdle that we need to clear is essentially nine months of PFS plus four, so 13 months. Then for OS, it would be 12 months plus four, 16 months. The phase one results brought a lot of confidence for us to do well in this registrational study.
Okay, sounds good. And then yeah, talk a bit about enrollment in the Phase 3. Sort of how has that been tracking relative to your expectations?
We have not disclosed anything publicly on that front. I think from where we sit and looking at the unmet need, it's never fast enough. As I indicated, the sponsorship is now being transferred, which really helps to go through the regulatory pathway, but also commercialization steps in an expedited fashion. So yeah, we're looking forward to sharing an update in H1 2026 when we expect the interim analyses to read out.
Right. And yeah, maybe give a little bit more context around this interim analysis and what exactly is being assessed there.
Interim analysis is a dual trigger. It's an event-driven trial. It's 283 events, and it is last patient in. With that, we should, if the interim analysis is positive, we should have an accelerated pathway towards approval.
Right. And just confirm, this is on PFS as opposed to OS, right? The interim.
Yes, that's correct.
Gotcha. All right, cool. And yeah, let me see. And then yeah, how do you think about the longer-term opportunity beyond this head and neck trial? So what are some of the other activities that are ongoing?
Excellent question. I think maybe first focus on head and neck. There's not a lot of players in first line or front line head and neck, so I think there's more room to play. As I indicated, J&J enrolled and dosed the first patient in the Converge trial, which is a Phase 3 non-small cell lung carcinoma trial in the unresectable population, so there's clear interest from J&J on that front, and just to recap, for those of you who haven't been following us closely, we've treated eight different tumor types and hundreds of patients, so we feel that this solid tumor agnostic, combination agnostic, but very importantly, also target agnostic asset can go really broad and wide.
We're looking forward to getting to interim analyses data on head and neck, or because the non-small cell lung carcinoma trial is an open-label trial, the conviction of J&J so that we can go broader and wider as there's a lot to develop here.
Right. And so my understanding is typically that radiation is used in sort of localized earlier stage cancers as opposed to metastatic. And so, but you do have some data in metastatic head and neck cancer as well. And so yeah, maybe talk a bit about that and if that's an additional opportunity for this type of therapy?
So we have a study ongoing. It's Study 1100 focusing on head and neck metastatic patients, both naive to PD-1 and refractory to PD-1. We've shown results. We had 48% ORR in the naive population, 28% in the refractory population. So we believe that bodes really well. So if you just reflect on refractory, that's three times what you would be able to demonstrate with PD-1 alone if you have a responder. So it, in our view, confirms that not only can we establish local control with R3, but we're basically seeing complete responses in distal lesions that have not been injected nor irradiated. So we believe that there is a lot to do on this front.
Okay. And so J&J, as you mentioned, has committed to this Phase 3 non-small cell lung cancer study. Yeah, just remind us, what are we looking at here? What are they trying to achieve? And what are some of the outcomes that are being assessed in this study?
It is a study that focuses on locally advanced unresectable non-small cell lung carcinoma patients that get a standard of care of chemoradiation followed by consolidation with durvalumab. What we hope to establish is first and foremost ORR, and then we should follow with duration of response, OS, and the like.
Okay, and is that a randomized study?
It is. Yeah. It's a Phase 2 randomized study. So it should, if outcomes are in line with our expectation and J&J's expectation, create a clear pathway for registrational trials.
Right. And then I know you also have some activities ongoing with MD Anderson looking at different studies. And so any learnings from those activities as they might inform additional opportunities for development?
Yeah, we've been extremely pleased with the partnership with MD Anderson. We have five trials ongoing with them. It's been in a variety of indications. We've done pancreatic, esophageal. We've done non-small cell. So it's really an ability for us, together with them, to do signal finding and seeing how it could inform and influence the development roadmap that we share with J&J. So it's cost-effective. I think we have very high engagement of the PIs. So we're pleased with that. And it explains why we have a lot of trials ongoing at this moment.
Right. Right. Yeah. And then just maybe a few logistical questions. So obviously, J&J will lead commercialization globally. Is that correct?
That's correct.
After approval and so yeah, maybe just talk a bit more about logistically how this type of therapy fits into the treatment paradigm relative to traditional systemic drugs or the more localized radiation therapy.
So if you take a step back and think about the journey that a head and neck cancer patient goes through, they have close to 50 visits that they need to do. So the intratumoral injection could take place prior to radiation treatment starting, and that could be combined with one of the visits that patients already do. So it fits neatly into kind of the entire patient flow. You use standard radiation, and you go from there. So logistically, it's entirely doable. It's essentially the reverse of a biopsy. So we expect that that would be something that will find wide acceptance. J&J actually created the INTO group, Interventional Oncology group, with the focus of what else can be done intratumorally. So we believe that this is a great growth area for them and look forward to bringing more news.
Okay, great. So as investors look at the story, so what are some of the key value drivers or data items over the next 12 months or so that people should pay attention to?
Certainly the interim analyses, H1 2026, but this year we have a good number of data updates. We have pancreatic that will be first half. We've got esophageal. Then we have the Study 1100 on the metastatic side with both naive and refractory, as well as the third cohort in that study. Yeah, there's at least five readouts that will be forthcoming.
Okay, great. So looking forward to those. And then the big one, obviously the phase three data in about a year or so.
Yes.
Well, thank you, Bart. Really appreciate it.
Thank you, Michael.