What’s been achieved over the past 12 months?
Happy to, Shaun, and thank you for having us. We're pleased to be here. Nanobiotix is a dual-listed company, headquartered in Paris. It's a phase III company. Oncology is our lead therapeutic area, and we have partnered with J&J. Taking a step back, for us in Nano, it's always been very important to make sure that we're, you know, first in class, that we have high IP barriers, but also can address a very sizable population. Our key asset, NBTXR3, now JNJ- 1900, is a crystalline hafnium oxide product that gets intratumorally injected. When you apply radiation, which is a physical mode of action, you actually create a very profound cancer cell killing effect and create long-term cancer memory. What it essentially is, it's a super X-ray absorber, and therefore creating local control, but also systemic control.
It is a product that fits neatly in the patient flow, and triggers very significant response that we can talk about more. We have two other platforms. Also, those other two platforms, you know, have similar characteristics in the sense that we bring Physics into healthcare and Physics into healthcare as a therapeutic agent. The second platform is a bioavailability and biodistribution platform. We have created a product called Nanoprimer, that is in a preclinical stage. If you were to dose that to a patient and then subsequently IV a therapeutic agent, you have, with this Nanoprimer, transiently occupied the liver clearance pathways. What it does is allowing the therapeutic agent to circulate through the blood flow and reach its intended target with the right level of efficacy and toxicity.
The third platform is nanoparticles that we have created in order to leverage the electrical properties in the neuronal pathways in the brain to help with proper connecting of the electric circuit in the brain that could be helpful in diseases like neuropathic pain, Alzheimer's or Parkinson's.
Brilliant. So lots of applicability there. So you mentioned J&J, who's your partner. So they've assumed cost for pretty much the entire pivotal study. And we believe this signals a sort of great level of commitment from the company. What drives confidence that J&J is best positioned to optimally develop and commercialize NBTXR3?
Excellent question. J&J has established something that they call interventional oncology. It is one of their five priorities. JNJ- 1900 is a lead asset in that interventional oncology drive. Obviously they have strong device capabilities, but also, with their innovative medicine unit, massive drug capabilities. They have a very good holistic overview of the entire treatment paradigm. Obviously they have massive global reach, and one of their key focus areas, and this was stated by their CEO recently, they prioritize oncology and they want it to be a $50 billion therapeutic area by 2030. We believe that they have the right orientation and we hope that JNJ- 1900 plays a big role in that. Maybe, as a testament to that, we have seen them make considerable investments.
They acquired the rights for Greater China from LianBio just after we did the deal with them in 2023. They've been building up manufacturing capabilities. We recently signed an amendment that basically combines the fact that we were transferring the sponsorship with the financial arrangements. They've been very purposeful investing into the asset and its potential.
Brilliant. Could you remind us on the specific economics of the deal with J&J in terms of the combined value, and the royalties and milestones you're entitled to?
Yes, happy to. As it stands today, that is, $2.6 billion. That is post the amendment, in milestones. A significant chunk of that is development milestones. We have royalties in the low- teens to low- twenties. We believe, you know, at the time of the deal, we captured a third of the value. It is a type of product, as I referenced earlier, being tumor agnostic, but also a combination and target agnostic that, you know, if the proof points come in on head and neck or lung, we believe that they can take that much broader and more widely. We believe that we, you know, have a very interesting, you know, future ahead of us. Should those milestones hit, it will turn Nanobiotix into a sustainably financed company.
Okay, understood. So the amended agreement allowed you to free up resources and extend your cash runway to mid 2026, which is now in line with the interim analysis of the NANORAY study just during 1H26. Do you foresee a capital raise ahead of this? And if so, what are the options on the table?
We're contemplating non-dilutive financing. You know, just on the back of what I shared, there's a lot of value that is spent up should the data read out positive. We want to make sure that we bring that into a safe harbor. Whether that is head and neck and/or lung, I think that is a priority, because we would like the shareholders to reap the long-term benefits of what we have developed. Secondly, we have these other two platforms, the Curadigm Nanoprimer Platform in the bioavailability and biodistribution, as well as on the CNS side that we want to further along. It would help us to extend that runway so we can accelerate some of that development now while having secured JNJ- 1900.
Brilliant. Thank you. What role will Nanobiotix continue to play in the development of NBTXR3, and how will indications beyond head and neck cancer be decided with J&J?
Yeah, that's a great question. It's a co-development commercialization agreement. Maybe to illustrate the co piece in co-development, both parties have milestones, or an incentive to drive this development forward. Whenever J&J develops, we're entitled to $130 million of milestones should there be regulatory approval in the various geographies. That, times five, is $650 million. If we develop something, then we're eligible for milestones as well. There's an incentive for both parties to generate more and help address unmet needs. J&J will take care of global commercialization.
Great. Let's dive a bit more into head and neck cancer. Your phase III trial is ongoing, as we know. Could you talk us through the current standard of care in the head and neck cancer setting and how NBTXR3 will fit in this treatment paradigm?
Yes. Maybe just a final piece on your prior question that I failed to complete. In terms of decision making, there is a joint strategy committee. Both parties have a voice, but, as you would imagine, ultimately J&J has a voice. We will see that clinical development plan evolving. As soon as, you know, more can be set, we will be happy to share that. With regards to head and neck, we are focused on locally advanced head and neck. It is a very frail and elderly population. The standard of care is radiotherapy. This phase III trial, the study 312, as you referenced, is a perfect opportunity for us to illustrate the benefit clinically, but also value-wise that JNJ- 1900 will bring over the standard of care because you have, you know, two arms, RT versus RT plus R3.
and, you know, it's been, a palliative setting and it's frontline. I think that is something that, you know, we really want the audience to grasp because we establish local control first and foremost. it's the patients that come in at the top of the funnel, right? Imagine the patient is an inverse pyramid. They come in at the top and that's where most patients are. unlike most oncology development, we start frontline and move to later lines while the rest starts, you know, last line moving front, line. The size of the opportunity that, JNJ- 1900 can address is very significant.
I see. So the NANORAY trial builds on top of the study 102, which was a phase I study evaluating the safety and sort of early signs of efficacy. How does the results you saw there compare to other head and neck cancer studies? What are the implications of this data on the ongoing phase III trial?
Yeah, so we had this study 102 showing 83% complete response. So very, very significant in a population that was, you know, even frailer than the 312 study, which gave us a lot of confidence to go into the 312. To translate that to, you know, what is the bar for success in 312, that would be nine months of PFS plus four. For OS, that would be 12 plus four, which is 16. We've shown in the study 102 that we meaningfully beat both of those endpoints. You know, we have high conviction. We have, you know, great ratios on PFS and OS. So 96%. We feel that, you know, things will validate what we've seen in the study 102. The difference between those two studies is in the 312, we can also inject lymph nodes.
We've seen that a lot of relapse happens from, you know, lymph nodes. We believe we should, you know, have a very good opportunity to demonstrate success.
Brilliant. That's exciting. So could you tell us how recruitment is progressing for the 312 trial? And are you confident that the trial will be fully recruited by 1H 2026?
Yeah, we have guided to H1 2026. No updates there. Yeah, we're looking forward to,
Fantastic. Can we just move on to lung cancer now? There are two ongoing studies in non-small cell lung cancer, one headed by J&J, the other one by the MD Anderson Cancer Center. We saw first data in 12 patients, from which the latter demonstrated a 12-month local progression-free survival of 64% and a 12-month overall survival of 83%. Could we use this data to give us an idea of what to expect in the J&J Converged study in lung cancer?
We believe we can. Just to put it in perspective, the 83% compares to what you normally would see being closer to 30%. Clearly, the beauty of that study with MD Anderson is one where we provide a sub-therapeutic dose. With a sub-therapeutic dose, we create a very clear and powerful response. If we can do that there, then when you think about the Converged trial, the primary endpoint of that randomized trial is ORR. If we can do it in one, we believe that, you know, there's good translatability across to the Converged trial. That is an open label trial. You know, we're curious to see what will transpire and hope that, you know, as soon as there's clear signals that our partner will, you know, take subsequent decisions.
Brilliant. When could we first see data from Converged?
Unfortunately, I'll need to leave that in their hands. But, you know, they started enrollment early this year. They have a very, you know, good network and ecosystem in lung. So, we hope sooner, rather than later, but TBD.
Of course. Obviously whilst final data for 312 and, and eventual pricing is still unknown, could you perhaps give us an idea of what the potential commercial opportunity could be in head and neck and then actually also by extension in lung cancer?
Yeah, that's an important question because I think we can illustrate the value of the product. When you think about head and neck, the 312 study population, that's about 22,000 patients across North America and EU5. If you look at non-small cell lung cancer, stage three, that's more than 80,000. You have an addressable population in these first two indications that, you know, exceed 100,000 patients. That's massive for oncology. Actually, that nicely lines up with, you know, the mission of the company, right? To bring, to address unmet need in millions of patients. If you think about pricing, it's an oncology drug, so it would get priced like an oncology drug given the overall survival that we bring and quality of life. Average pricing in the U.S. of an oncology drug is $200,000. That's actually an annual number.
This is, however, a one-time intratumoral administration. So it needlessly gets absorbed in the typical patient flow. So, you know, that can be a very large drug if you multiply, right? It would be an addressable market of billions.
Understood. Just to clarify, is that $200,000 net or gross price?
I believe that is a net price. If you were to say, well, you know, it's not an annual recurring cost for the healthcare system. It's actually a very, you know, interesting product for the healthcare system at large because it's a one-time administration. We're happy to partner with J&J because they'll look at this very carefully to make sure the right decision gets made from both a value as well as a healthcare benefit perspective.
Understood. Are there likely to be any barriers with incorporating NBTXR3 into the treatment protocols? And what type of physician would administer the therapy?
Very good question. In essence, it's the inverse of a biopsy, which is done all the time. Depending on the indication, it may be an interventional, interventional or, you know, a Med Onc or a Rado nc. It's different by tumor type. We don't foresee that an issue. We have now experience with literally hundreds of patients that have been dosed and randomized across the world. Our phase III, 312 study is done in well over 100 centers. It's a fairly straightforward intratumoral injection. The beauty is with J&J focusing on intratumoral with their Into initiative and drive, we feel very good about that.
Great. Now let's move on to sort of looking at combination. So more broadly, what's the rationale for combining R3 with Anti-PD-L1 immuno and Anti-PD-L1 drug?
Yeah, we've seen that PD-1 doesn't always provide benefit, right? 15%, or thereabouts, depending on, you know, the tumor type and the situation at hand. And oncology known for combining therapies in order to get to the desired result. We've seen with the study 1100 that we run, it has three cohorts, head and neck naive, head and neck resistance, as well as metastases from primary tumors being lung, liver, and soft tissue sarcoma, that we've been able to generate very powerful responses. We know that we can do massively better than PD-1 alone. It speaks to the type of product it is because the cancer cell killing effect is so profound. It triggers this systemic effect. We've seen situations where distal lesions that weren't injected and not irradiated were completely gone.
and we, you know, see that on the PET scans that we do. And we have some of our KOLs talking about that. Yes, there's certainly an opportunity to build on the current standard of care and improving it.
Understood. Now let's look at sort of your other collaboration. So you have a collaboration with the MD Anderson Cancer Center and you reported results recently from the phase I pancreatic cancer study. Could you talk us through the findings and what the next steps are here?
Yeah, so we had a median overall survival of 23 months, which compares to 19.2 months. This is a study run by MD Anderson. It's compared to the patients that they typically see, but with one less chemo administration. We believe that's very interesting, as it's, you know, such a, you know, impactful disease and there's so little available for patients. At the same time, we also saw some very interesting biomarker activity, for instance, CA 19-9 normalizing in 59% of the patients. We've picked up signals that require us to do more. There's been a protocol amendment in order to start, you know, catering to getting more visibility to what we can do in pancreatic together with our principal investigator at MD Anderson. We're very happy with them being on board.
They're really enthused and driving this forward to really, you know, understand, you know, the boundaries of where we can go. Encouraging also on the biomarker front.
Of course. What other readouts can we expect from, from MDACC over the next year?
We have esophageal later this year. We haven't really guided beyond this year, but we have that plus readouts on the 1100 cohort. That will be three different data sets. One of them will be melanoma. That's a new cancer type that we haven't reported on previously. We believe that we'll have some, you know, intriguing data for people to take note of. I think, you know, not jumping to any conclusions, but we've shown data in eight tumor types, the physical mode of action has been getting very clear responses. We expect no different for melanoma. We look forward to that. Then the other two cohorts, so naive. We had a 48% response rate, compared that to about 15%. We had 26.2 months median overall survival, which you should compare to something around 12.
and then on the resistant patient side, we had 7.8 median overall survival and a response rate of 28%. There's not enough literature to compare to, because, after that, there's not a lot that happens unfortunately for, for patients, but these are indicators for us to continue to explore.
Understood. Let's focus something on more of a technicality. So if we think about NBTXR3, how complex is the manufacturing? and are the nanoparticles consistently reproduced in, to the correct size?
Yes, it has taken us a while to get there. There is kind of a big moat around it. You cannot just, you know, go out and start producing these nanoparticles. A good component of the intellectual property is embedded in it, so that is all in place. We have built it up from the ground. We have got our manufacturing. J&J, as I mentioned earlier, is duplicating that, so that is in place. You know, it has all kinds of sizes and numbers. It is billions of nanoparticles in a vial. Size-wise, they will not be exactly the same. With guidance from the FDA on how to genericize nanoparticles, that is another barrier because you need to reproduce something if you were to come in from not only a process perspective, but also from an outcome perspective.
That's nearly impossible.
Understood. And so we know that NBTXR3 has been described as a radio enhancer. So do you think regulators would sort of view this as a device or as a drug?
It's been a medical device in Europe and some other countries and a drug in the U.S. and most other countries. More to come on that front, but, you know, we believe it is, you know, ultimately, a drug, with the benefits that we just discussed.
Understood. And just looking at the bigger picture. So now that NBTXR3 has been transferred to J&J, what are Nanobiotix's next priorities?
We're still in the midst of the transition, although that's getting closer to the end of the transition. We keep supporting them, also on the co-development side. It will be starting to, you know, make sure that we land JNJ- 1900. Its full potential can be reached as a product. Meanwhile, we've started to build out the bioavailability and biodistribution. We'll start to take steps later on, on the CNS side.
Brilliant. Is there anything else you wanna speak on today that we haven't touched on?
I think if we take a step back, innovation happens where land meets the sea, right? It's not doing more of the same. I think this is a very different approach. It, you know, addresses a massive immediate need. It starts with local control. It leverages radiotherapy, which is, you know, 60% of all Cancer Treatment Protocols. To be able to leverage such a standard and actually turn it into a curative potential, we believe is massive. You know, if you think about radiotherapy today, it is not designed to cure. It can only, you know, be as much as healthy tissue can withstand. We're driving, you know, innovation here that could be quite palpable. We believe we, you know, have a lot to bring to the markets to appreciate.
We hope that the markets will recognize its full value in the not too distant future.
Hopefully they will. Thank you very much, Bart.
Thank you.
Thank you.
Appreciate it.