All right, so welcome to this next Fireside Chat with Nanobiotix. With me today, I have Laurent Lévy, CEO, and Bart Van Rhijn, CFO. Welcome, and thanks for joining us, and so, Laurent, why don't we start with a general overview of your technology? I know you have different technology platforms that you're leveraging for your pipeline, and yeah, just describe those for us before we dive into more detailed questions.
Sure. Thanks, Michael, and thanks for having us here. So just in a few words, what we are doing is trying to use nanophysics to help patients, and what we try to do with our different technology is to have only first-in-class product based on nanophysics, which allows us to get a widely protected platform with almost no competition. And so far, we've been able to be successful developing those three platforms. I think for today, given the time frame, it will be good to focus on the first one, the one that we dedicate to oncology. But we'll be pleased to talk more about that a bit later.
Great. And then, so yeah, so NBTXR3 is sort of your main product candidate, which is essentially a radio enhancer. And so can you talk about the mechanism of action of this product and how it essentially could potentially be applied to any type of cancer that is treated with radiation?
With pleasure. I would like maybe before that to go back to some of the fundamentals in oncology. When we look at patients at the time of diagnosis, most of them, they have a local disease. Only a small proportion will have metastatic disease. But if we see so many patients in oncology with metastatic disease, it's because they have failed a local treatment. And so that's millions and millions of patients that get diagnosed with a local issue. And when we talk about solving this local issue, radiation therapy is playing a key role. It's more than 60% of all cancer patients that are getting radiation. And radiation is a very powerful technology but has limitations. When you have a tumor in a body, your X-ray, they will have to cross healthy tissue and the tumor.
Therefore, they will cause damage in the surrounding tissue as they will cause damage into the tumor, so you're always limited by the dose you can deliver in the tumor because of those side effects, and we've been developing one drug, one product, which is a single solution for all those patients. The way it's working, it's a drug that you inject one time directly into the tumor, and this drug is made of crystalline inorganic nanoparticles. The goal of those particles is first to be small enough to be able to go into the cell, and when they are in the cell and the patient is receiving the usual radiation therapy, they will absorb the energy of radiation and will deliver ninefold what the radiation can deliver usually around those nanoparticles.
So it does increase a lot the power of killing from radiation, but not only killing more cells and getting better local control, but also triggers an immune response. So that's the basic mode of action.
Yeah. And so the main path to market or the initially prioritized indication now is head and neck cancer. But can you just talk about how you ended up prioritizing that opportunity, perhaps relative to other areas where this could work potentially?
Head and neck is one of those indications, like many others, where radiation is widely used. It's around 74% of all head and neck cancer patients that are getting radiation. And if we have been choosing this indication, it's because not only that's an addressable population that at the time we are alone as a company developing that could address as a small company, but also it is a good surrogate to what can be done in other indications. And more importantly, in head and neck, you have 90%, nine-zero of patients that have a local disease at the time of diagnosis. I think there is some kind of misunderstanding in Wall Street about the head and neck market. We talk about the PD-1 market in head and neck as first-line treatment PD-1 in head and neck.
But those PD-1 treatments in head and neck almost all the time only occur because patients have failed local treatment. So for those 90% of head and neck cancer patients that get radiation or that get local disease, sorry, radiation is almost present for all of them. Either radiation alone, radiation plus chemo, or surgery plus minus radiation and chemo. And we've been choosing the very first population, which is frail elderly patients having radiation as the only treatment.
Okay, great, and so you do have a partnership or collaboration agreement with J&J. Can you just walk us through the details of that deal and how it could potentially help to maximize the potential opportunity for NBTXR3?
Sure. Maybe before going into some of the details and the metrics of the deal that Bart may want to comment, I just want to step back and say why we've been doing this collaboration and licensing out of the product. So it happened a bit more than a year ago where the Phase III in head and neck already started and already had accumulated on this product a large number of proof and feasibility in different indications, so getting closer to market, we thought it was a good timing for us to find a partner, and I think we've been choosing J&J and reciprocally because we share this belief that if we treat patients early in their disease, we'll have a much bigger impact in oncology than just trying to help patients at the end of their treatment, at the end of their disease.
So Bart, maybe you would like to comment on some of the metrics of that deal?
Yeah, happy to. So the total milestones associated with this are $2.5 billion. The first pocket is $1.8 billion that's divided over development, regulatory, and commercial milestones. The second pocket is $650 million, which is related to potential five additional indications. And then if Nano were to develop and bring to regulatory approval an indication that would be remunerated by $220 million, that excludes the rights and obligations that LianBio previously held that have been acquired by J&J at the end of last year. And that goes with royalties. So the J&J ones are low teens to low 20s, and for Greater China is low teens.
Okay. Okay, great. And the other thing that's happening is we talked about you have a Phase III ongoing. We'll come back to that in a second. But so I think you're currently transferring ownership of the IND and the trials that are ongoing to J&J. And maybe talk about what that means specifically in terms of development logistics.
That's a big question, but more precisely, I mean, we have started this collaboration some time ago, and we logically ask ourselves, when's the best moment to transfer this ongoing Phase III? Is it after the interim readout or before the interim readout, so logically, we thought that if our partner wants to be ready in time when the data are coming to register the product and do all the activity needed for pre-marketing, then it will be better to transfer it before than after the data, so that's what led us to take this decision before the summer break, and we are on our way to execute that, but it will take some time because from a logistical point of view, that requires a good number of steps and interaction, and imagine this is a global trial.
So we have centers across the world, and we need to transfer every and any single contract and interaction with all our partners in that regard.
As part of this collaboration with J&J, what role will Nanobiotix play in the continued development of the product?
So we obviously had a good role to play for a very basic reason at the beginning, which is this product is new. So it's not like a monoclonal antibody or a small molecule. It does require some knowledge, and we have been developing this knowledge over the past decade. So it takes time to transfer. And also, as Bart mentioned, in this licensing agreement, there is a specific part of it saying that for Nano, for any new indication we will develop and bring to market, there will be additional milestones that we will be eligible for on the top of the $2.5 billion. But outside this, we are continuing the program we've been developing, like the trial 1100, where we combine radiation, nano, and PD-1 in different populations. We keep running the collaboration we have with MD Anderson.
And so far, we are the only source of the product because we manufacture this product in our own premises, which also start to be transferred to J&J, where we'll have two different sources for the product. So there's still a lot to do for us to maximize the value of this collaboration and to bring this product to market.
Okay, great. And so we mentioned a few times now, so you're enrolling a Phase III study right now in head and neck cancer. Just remind us of the design of the study and sort of what outcomes you're hoping to achieve.
So maybe before just a few words about the data that have led us to get to this Phase III, if you're okay with that, Michael.
Sure.
We're talking here about a very specific population in head and neck. Those are the frail elderly patients that are ineligible to cisplatin, meaning the only treatment they have is radiation, and radiation alone as a definitive treatment. If you look at literature, you'll find that for those patients, it's more a palliative treatment than a curative treatment. Reference will give you around 12 months median overall survival and a short PFS and a response rate around 40%, which is very low in head and neck. We've been running Phase I and II of 75 patients, having an escalation and expansion phase. What we have been seeing here on top of a good safety for this product, we've been seeing a very high rate of response, like 82% response rate, including 63% complete response, which is big.
In such population, getting to 63% complete response transfers into improvement of quality of life because you have been killing this big tumor growing in the head and neck area. Looking then on the transfer of this complete response into survival, we've been seeing in the evaluable population a median overall survival of 23.1 months, which is almost double compared to what you can find in literature usually. If you look and step back, you have a frail population with a palliative treatment, and we've been able to give a new treatment to this population, showing good safety and having a high rate of response, unprecedented, 82%, translating into a potential long-term survival. These are the bases that we've been using to design the Phase III, which is ongoing and on its way to be transferred to J&J.
And the design of this Phase III is 500 patients randomized one-to-one, where the control arm will be radiation plus minus cetuximab. That will be the choice of physician versus the same plus our product. And the primary endpoint we've been choosing is the PFS. And that's what we expect to read out in H1'26, the PFS. And assuming it's positive, that should lead us to a potential filing for approval.
Great. And what is the size of the commercial opportunity in this particular setting?
So that's a subset of head and neck. If we think about just U.S. and EU5, we're talking about 20,000 patients, something like this.
Okay. And then let's see. Talk about, so this is one-time administered, and I think we talked offline, but just to set the reference about pricing and how we should think about sort of TAM assumptions, perhaps.
It's always hard to talk about pricing, what we can say. And at the end, that will be our partner to decide and to negotiate that with payers. But first of all, we've been talking in the past with payers across Europe and US. And what they like about this product is it is a one-time injection. So they know how much they're going to give to every patient. And also, there's no compliance problem because of that. And the pricing we obtain is something that you can imagine for an oncology product providing all these benefits. And you can apply the usual price that you will think in the US as a reference.
Okay. And then you had some additional data earlier this year at ASCO as well in more advanced head and neck cancer patients and metastatic patients. And yeah, can you just talk about how you think about potential opportunities in that sort of market area?
Sure, so again, as I was mentioning, in head and neck, 90% local disease, and this patient getting PD-1, most of them only getting PD-1 because local treatment failed. And that's the population we are talking about here, the locally recurrent patient or metastatic patient coming mainly from local failure. And the treatment reference here is PD-1. And you can take KEYNOTE 48 or 41 as a 40, sorry, as a reference or CheckMate 141. What you see here is usually with PD-1, a poor rate of response, around 15%, and a survival that could go from eight to 12 months, depending on the setting.
What we've been able to show here is a much higher rate of response in patients being naive to PD-1 by just having a one-time injection in one of the lesions of the patient, plus a few fractions of radiation, not only to control locally the tumor, but to trigger an immune response based on that, so the data we've been showing, they were early. Nevertheless, this high rate of response is very encouraging, and we're starting to see also a potential impact on overall survival for that, and we've been also treating not only the naive patient, but another cohort was dedicated to refractory patients to PD-1, where we also have seen some very good initial data, but stay tuned as we're going to continue to mature the data and show it a bit later.
Okay. And what is your sense? You or your partner to advance that, is that something that's under consideration into a registration study?
There's plenty of things under consideration with our partner, but that will come a bit later.
Okay, great. And then I know J&J is also conducting a Phase II, a randomized study, I believe, in non-small cell lung cancer. Yeah. Can you just talk about what the plan is in that setting?
So I think that when the design will be published, we will be able to talk a bit more. But what we know is about the population. We've seen the PACIFIC trial, where we have locally advanced lung cancer patients that receive radiochemo then PD-1. So that's the setting of Stage III lung cancer patients. And when you think about it, PD-1 does bring a lot to those patients, but it's still an underserved population, as around 30% only get response. And after a few years, you have more than half of the patients that have relapsed. So there's a lot to do for those patients. And it's all about local control here, making sure that we can destroy and kill this big tumor that will either grow if you cannot control it or will generate metastasis for the patient.
So again, let's stay tuned, and we'll get soon more about that.
Okay. So you have the head and neck Phase III ongoing data in the first half of 2026. You have J&J ramping up the Phase III lung cancer study, and then perhaps a decision in the metastatic head and neck cancer setting coming up at some point. And so I know there's other studies going on. And so help us understand sort of some of the other opportunities and some of the more near-term data disclosures that investors should be looking forward to.
So, I think the good point is we've been treating hundreds of patients with this product across the world in different indications. Just rapidly, and to name a few, we've been treating patients in pancreatic cancer, rectal cancer, soft tissue sarcoma, esophageal cancer, hepatocellular cancer, head and neck, and some others. So far, we've been able to show that it is feasible and safe to inject this product in many clinical situations. And as I mentioned at the beginning, 60% of all cancer patients getting radiation, that offers a gigantic opportunity. Now, as I said, also, there's many discussions with our partner to see what could be the next steps and how we could grow this opportunity. But definitely, when you look at all the big tumors like prostate, breast cancer, lung, there's plenty of patients in need where radiation could do a lot with our product.
Yeah, so I know your Study 1100, which included the metastatic head and neck cancer patients. There's another cohort that's been enrolling where I think you've guided to presenting some data from in the coming months. Can you just talk about that and what you've been doing there?
So that's the last cohort of three in this clinical trial where we try to help patients that have met with radiation, nano, and checkpoint inhibitor, and here more precisely pembrolizumab or nivolumab. In the third cohort is all patients except head and neck. But what we have seen is a big recruitment into the melanoma setting. So that probably will be some of the cool and key insight that we may give in the near future.
Okay. And then you mentioned you have that collaboration with MD Anderson, and I know there's been a few studies that have been enrolling as well. And anything we could learn there in the near term about the profile of the drug?
Yeah. At MD Anderson, the goal here really is pushing the boundaries of medicine with this product and trying to explore new usage of radiation with this or to reinforce where radiation is not big enough. And there's two trials, for example, that are very important where we should get some data really soon. One is pancreatic cancer, where we all know that it's very hard to treat cancer with not a good outcome so far. And radiation is playing a key role in trying to control the tumor, especially for locally advanced or borderline resectable patients. Here, the goal again is to kill the tumor to make it operable if possible and to prevent this cancer to make mets. So we've seen some very encouraging first data on that, and we should get an update on the program before the end of this year. That's for panc.
There is also a lung cancer trial that is running at MD Anderson, which is a different population from the Phase II in Stage III cancer that J&J is running, is patients that have failed local control and that have a local relapse. So, potentially, patients that got radiation or radiation plus chemo or radiation plus chemo plus PD-1. And then we go back with those patients with an injection of our product and a small dose of radiation to try to see if we can catch those patients back and help them and kill the tumor. So again, should get an update on the program by the end of this year.
Okay, great, so looking forward to that, and then I have one more for Bart. I know the company's been running on a very lean operating structure, but can you just comment on your sort of cash balance and runway and potential financing needs?
Yeah, happy to, Michael, sure . Cash runway is into Q4 of 2025. Maybe for context, we had an interim analysis that was planned for mid-2025. We were financed through that. So this got pushed out to H1 2026. That interim analysis is an important value inflection point for the company. So there might be some milestones associated with that. The interim analysis is now a dual trigger event, both event-driven as well as last patient in. So there's no possibility to bias any of the recruitment arms. With that, there's also de-risking of the study itself. So we're in discussions with our partner to see how we should solve that. But I think more broadly, we're not beholden to dilution, but we're certainly sensitive to it. So we're looking to finalize an outcome that is in the interest of our existing shareholders, but also resulting in an effective cost of capital.
Great. Okay, super. I think with that, it's time to wrap up, and I really appreciate Laurent Lévy for joining us at the healthcare conferences here.
Thank you, Michael.
Thank you.
Thank you.
Thanks for having us.