Nanobiotix S.A. (NANO) Earnings Call Transcript & Summary

Good morning, good afternoon, everyone. I'm Laurent Levy, CEO of Nanobiotix, and happy to welcome you here to present you our company and what we see for the future in terms of development of new therapeutics to bring that to millions of patients. Before getting into the meat of this meeting, which is about the new platform Nanobiotix is developing, just want to step back and come back to the fundamentals. We've been using to develop our different product and platform in the company. For the past decade, we've been able to develop 3 platforms for different purposes, 1 in oncology, 1 for the CNS disorder and 1 we see multipurpose. All those platforms, they have something in common. They are not purely based on biology or chemistry. They are based on physics and why that? The whole idea of Nanobiotix was to think about the question, can we bring the physics at the sub cellular level to bring new mode of action into patients to help them. And that's what we've been doing with the different platform we are developing today. What's the advantage of this? There's something fundamental with physics, is that the mode of action that you can produce with it will be much less influenced by the viability of biology. And therefore, you can have product or approaches that could be shared by millions or many patients. And that has been the motto for years at NANO to develop only products that are first-in-class, and that can be used in many patients to help all those patients. And today, we're going to talk about Curadigm. But before that, I would like to come back to the priority of the company, which is to bring to life and to bring to market a first-in-class radioenhancer NBTXR3. The idea with this product is really to address one of the largest untapped market in oncology. And we do that with Johnson & Johnson, which is the partner we've been choosing for more than a year now, and we've been licensed our first product to them. So what do we think about when we say oncology. We're thinking at a particular aspect of oncology. And as you can see on this slide, we're looking at interventional oncology, but more precisely at patient at the time of diagnosis. What is clear is the numbers you can see is most of the patients having a cancer at the time of diagnosis, they have a local problem. Only a small part of them have metastasis. As you can see also, most of the pharma and the biotech, they try to tackle this problem of metastatic patient. And there's not much development, not much research down to how can we help this patient when they are still at the early stage of the disease and when they have the local disease because if you can do so, that's where you will have probably the biggest impact in oncology. And that's where we focused our attention. That's where we focus the first development for the company. And talking about global control or talking about local disease, there is one tool that is widely used in oncology, which is radiation therapy. As you can see here, is a patient getting radiation, more than 60% of all cancer patients are getting radiations. All the big cancer like breast cancer, lung cancer, prostate, they all use in the vast majority, radiation therapy. Nevertheless, you have some limitation with this tool. And the limitation is due to the fact that when you try to irradiate tumor, you also have to irradiate surrounding LC tissue. Therefore, you're limited by the dose you can deliver in the tumor versus the side effect you will create. That's what led us to develop a unique drug, which is called NBTXR3 now JNJ-1900, which is a product that has been designed based on crystalline inorganic nanoparticle. So some tiny objects that are small enough to go into the cell. And where they are to the cell, thanks to the specific design of this nano crystal, they are able to absorb the energy of radiation. So after a single injection, those particles will diffuse in the tumor, will penetrate the cell. The patient will get a normal radiation, and the particle will absorb the energy and will create a high quantity of damage around them. So it's a physical mode of action that will lead to the destruction of the cell. The way we want to apply that is the following. For many patients, there is a need of better local control. So we have this injection in the tumor that will irradiate and then we provide better local control to patients. There is a subsequent biological consequences of that, which is the physical destruction of the cell will trigger also a priming for an immune response. That would be useful for the treatment of the primary tumor, but also for sustaining disease. So as you can see here, we have a product based on the physical manufacturing that triggers some biological consequences that could help a lot of patients getting radiation. And here, what you see is the first path to get there. We have a large number of clinical trials ongoing, including 2 late-stage programs, 1 in lung cancer stage 3, 1 in head and neck for a patient inevitable to cisplatin, and we intend to develop this product with our partner J&J for the larger number of patients to reach as many patient as possible. So just in a nutshell, what we intend to do with this first product and this collaboration is really addressing and helping the maximum of patients in oncology. That's why we've been signing in the recent past, a $2.5 billion deal in milestone plus royalties. And when you look at just the 2 first indication, we want to target like lung cancer, Stage 3 and head-and-neck it's around 100,000 patients we could help per year only in U.S. and [ EU 5. ] That's potentially a big market. And associated to that, we also will have a substantial amount of milestone that will lead us to financial sustainability and will allow us to continue to develop. And when I think about continuing developing things, the next big step for us is to develop this new platform, Curadigm. This platform that should lead to many new first-in-class products. And here, what we are doing is really the idea that we can transform the way we design drug and the way we apply them. And this could be applicable for many products that you see every day, like RNA, DNA based product, oncolytic virus and many more. Just to give you a glimpse about what this technology is and what is the potential, I'm going to turn over the mic to Matthieu, our head for the platform, Curadigm, that is going to explain what it is, how it works, and then we will go back together for a panel discussion. Matthieu?

Thank you, Laurent, for the introduction. I'm going to introduce Curadigm platform. And to start this introduction, I would like to mention a fact. If we look at the therapeutic landscape, especially at the innovative therapeutic it's very dispersed in terms of nature of therapeutic agent, ranging from lipid-based polymer-based nanomedicine loaded with small molecule nucleic acid viruses inorganic nanoparticle, recombinant protein and so on. But all this nature of therapeutic shared a common challenge, when you want to deliver by intravenous route of an administration a treatment, they will need to reach their target at a subcellular level, meaning to reduce target, they will have to overcome different barrier. The first one being at the organ level, then one in the right organ. So we need to address a specific cells population and then reach their target at the sub cellular level. At each buyer, you will have off-target loses of your product and degradation of the therapeutic agent. And if we look more specifically at the first buyer, the organ level, an analysis has been performed and shown that for nanoparticle in oncology, the median accumulation of the nanoparticle in the tumor is less than 1%. Of course, it's better than a small molecule injected as such, but still there is some roof for improvement in the field. Why is such a low amount accumulated in the target issue? The first -- the main challenge at this organ level for a therapeutic agent is a liver. The liver is the main organ of the reticuloendothelial system, stem, which is dedicated to the clearance of endogenous west, such as cellular debris, dense cell and so on, but also endogenous materials such as pathogens. Why? How does it work? The liver has a specific structure, allowing to decrease the blood flow within this organ maximizing the interaction with specific cells which are dedicated to recognize and cleared endogenous cellular debris, [ exomapathogen ], but also a large part of therapeutic agents, including the one was mentioning previously. And at the end, if we want to illustrate the impact of the liver, if we take it out and we inject a fluorescent nanoparticle to mimic a therapeutic agent. As you can see on this picture of this mouse, as soon as you inject intravenously the nanoparticle, all the fluorescence is localized within the liver. There is no more fluorescence in the rest of the body of the animal, meaning everything is in the liver and a very tiny portion of the dose will be able to reach the target. Why? What does it come from? The situation is coming from a combination of different physical chemical attributes, size, Sotacharge, RMS and shape and this specific combination of this parameter will drive the recognition by the liver cells involved in the clearance of therapeutics. And all the therapeutic agent I was mentioning at the beginning of the presentation, have this combination of parameters leading to the internalization by the liver. This is why we decided leveraging on this knowledge to design this concept developed by Curadigm, which could be summarized in one sentence. It's really to prime the body to receive the treatment. By priming, I mean we design a nanoparticle, which is called the nanoprimer, which is dedicated to be intravenously administered just before the therapeutic agent. The nanoprimer will reach the liver, and it will occupy transiently the cells involved in the clearance of the therapeutic agent. Meaning that when in a second time, you inject intravenously the therapeutic agent there is less recognition by the liver, you increase systemic viability of the therapeutic agent, allowing a higher accumulation of this therapeutic within the target tissue, which could be a tumor. If we are talking about oncology or another organic tissue, if you are talking about another therapeutic area. So if we come back to our mouse injected with a few recent article, let's take another mouse and we treat this mouse with the nanoprimer first, and then we inject the fluorescent nanoparticle. As you can see, even 1 hour administration of the fluorescent nanoparticle. You can still see the whole body of the animal, which is still fluorescent, meaning that the nanoparticle continue to circulate within the blood and is available for subsequent accumulation in the target tissue to deliver the treatment more efficiently. Of course, this approach has already been tried using different approaches in the past. The first approach, which has been developed was the use of conventional liposome. Commercial liposome mean they use the same liposome that is used to deliver the treatment within a tumor to ensure the pretreatment of the liver. You cannot ensure both aspects. You cannot deliver with the same object, the therapeutic within a tumor, and at the same time, occupies a liver, meaning that the effect is moderate and you will need to use a high dose of the liposome, potentially bringing toxicity. Second approach is the use of lipid emulsion, which is used for parenteral nutrition. The approach is to deliver on the patient body, a high dose of lipid and emulsion of lipid, but obviously, emulsion led to a high polydispersity of the lipid-nanoparticle different composition in fatty acid and so on, meaning that you will also need a very high dose to generate a moderate effect and potentially bringing toxicity. Then finally, the first -- the third approach is to use a small molecule to decrease clearance by the liver. So some this approach us molecules such as clodronate which is toxic for the kupffer cells in the liver, meaning you will kill this Kupffer sales. So there is less clearance by the liver, but you have the toxicity of the small molecule. This is why we really think we've got key differentiating factors within an primer. Why? This nanoprimer is a lipid-based nanoparticle. And the mode of action is related really to the physical chemical parameters of the nanoparticles, the nanoprimer itself. There is no API, no small molecule encapsulated in the nanoprimer. We optimize the physicochemical properties of the nanoprimer to ensure a specific interaction with the sales involved of the clearance -- in the clearance of the therapeutic agent. The effect is transient because the nanoprimer is biodegradable and as soon as a nanoprimer is eliminated by the liver. The liver will come back to it's physical [indiscernible] function trapping again the remaining therapeutic agent. And of course, we checked preliminary safety with the nanoprimer and the first result confirmed that we are safe with our nanoprimer. The beauty of this concept resides also in the fact that you could, with a nanoprimer answer different need of the therapeutic agent. If we come back to the fact that therapeutic agent is a major part is lose or could bring some toxicity and only a small portion will deliver the efficacy. We can see in different ways. The first one -- sorry, a product could be limited by the lack of efficacy. In this case, when you combine the nanoprimer, you can increase efficacy of the treatment for a same dose administered. But for some of our product, you are not limited by the efficacy, but you are limited by the toxicity of the therapeutic agent. So when you combine the nanoprimer with this product here, you can preserve the same efficacy but for a lower dose administered of the product and a lower toxicity. Also, our nanoprimer is a strong opportunity to be a game changer in the way some treatments are administered to the patient. For this, let's use an example. RNA-based therapeutics. This treatment are very efficient. Everybody is aware of the impact of RNA-based therapeutics COVID infection. There is approved product for liver-related diseases. But when it comes to use this RNA therapeutics by IV route of administration for extrahepatic delivery. It is still a challenge for this nature of therapeutic. And we really think that the nanoprimer could unleash the power of RNA-based therapeutics. And to demonstrate the impact of the nanoprimer on RNA-based therapeutics, we had the opportunity during our collaboration with a longer lab in MIT to evaluate the impact of the nanoprimer on the accumulation and bio ability of small interfering RNA loaded in lipid nanoparticle developed by the longer lab. On this graph, you've got the impact of the nanoprimer on the accumulation of the sRNA in the liver on the mouse model. And what you can see is that when we add a nanoprimer to the treatment, we decreased by 40%, the accumulation of the sRNA within the liver. And it's correlated with an improvement of the blood viability of the sRNA in the systemic circulation of 8x. So clearly, we increase the blood -- the systemic viability of therapeutic agent with the nanoprimer. At the end, what we want to obtain is an improvement of the efficacy of the treatment. For this, during another collaboration we combined the nanoprimer with a sRNA-based therapeutic agent, sRNA-loaded lipid nanoparticle during a tumor grow delay experiment on mice model. We use a triple negative breast cancer model, and we follow the tumor growth during the experiment depending on the treatment administered to the animal. On this graph, the yellow curve correspond to the response obtained with the therapeutic agent alone at a defined dose. You can see we obtain a tumor [ delay ] inhibition of 36%. When we add the nanoprimer, you obtain the pink curve. And this for the same dose of the therapeutic agent administered, we increased the tumor growth inhibition to 80%. So clearly, we significantly increase the efficacy of the treatment when we add the nanoprimer. We also evaluate the impact on the nanoprimer on the efficacy of small molecule loaded nanomedicine. For this, we use irinotecan loaded liposome. We first evaluated the impact of the nanoprimer on the tumor accumulation of the drug loaded in the liposome, CPT11, the prodrug and the active metabolite SN-38. We evaluate the impact of the nanoprimer on colorectal tumor cancer in mice model. And what we obtained is that when we add the nanoprimer, we increased by 3 fold to 4 fold the accumulation of the drug in the tumor. And we make the correlation between the tumor accumulation and the efficacy of the treatment generated with irinotecan loaded liposome. For this we perform a tumor growth delay experiment. And what we obtained is that the red curve corresponds to the response and tumor room with the irinotecan loaded liposome alone at a defined dose. The blue curve corresponds to the same dose of irinotecan loaded liposome, but with the pretreatment of the nanoprimer. As you can see, we significantly increased the efficacy of the treatment with a nanoprimer. And we generate similar efficacy results by combining the nanoprimer with [ rilonivide, ] which is approved in the treatment of pancreatic cancer. Finally, a last example of what we could achieve with nanoprimer by combining it with a recombinant protein asparaginase. Asparaginase is used in the treatment of acute leukemia. The mode of action of asparaginase is localized within the blood. This recombinant protein will degrade asparagine. Asparagine which cannot be synthetized by the tumor cell at the opposite of healthy cells. So by depleting asparagine you will kill the tumor cells. So blood viability of the recombinant protein is very important. But half life of this recombinant protein is also very short. So we perform an experiment to evaluate the impact nanoprimer on the systemic viability of asparaginase on mice model. And what we obtain is that when we add the nanoprimer, we increased by threefold the iron curve, the variability of the asparaginase. This is a great opportunity to improve the duration of the effect of this recombinant protein potentially decreasing the number of injections required for the treatment and potentially decreasing associated toxicity. Now to finish, let's come back to the therapeutic agent. If you look at the therapeutic agent, you will see that you will have to ensure different functions to deliver the treatment in a single nano tech. You will have to take care, of course, of the systemic viability, which is a very big portion to ensure the deliver the treatment. But you will have also to ensure drug loading tissue targeting cell uptake on the Medscape drug release and so on. So a large number of function to be regrouped in a single object. You cannot ensure an optimization of each function. There is a notion of compromise in the design of the therapeutics. And here, the nanoprimer could really be a game changer because we could refine the design of the therapeutics because this nanoprimer will ensure the systemic viability, meaning you will remove the function of viability from the therapeutics to the nanoprimer. So you create a space to improve existing function, such as [indiscernible], for example, or you can create a new function in the therapeutics itself. So clearly, this associated function in 2 independent objects is a strong opportunity to boost other function of the therapeutics and deliver more efficiently the treatment to the patient. And now I'm going to leave the floor to Laurent to give you an overview of the business opportunity associated to this nanoprimer.

Thank you, Matthieu. As you have seen, this is a new concept that will bring many opportunities, many potential product development. And we're starting at Nanobiotix to think about how can we use that not only for our own internal development, but also to help the industry out there. When you look at the first approach we could go for, you have many approved products that could benefit from this. By improving the benefit risk ratio, they exhibit in some indication to get to label expansion or improvement of safety of those products. You have so many other products under development that could be benefiting for this new approach, making it more efficient or it could be for a late-stage product but for preclinical product too. And if you think about the industry, about the number of products that have failed, not because of lack of efficacy, but because some hepatotoxicity. So that's also here a big area where this product can revive some of the product and make them use for the benefit of patients. When you look at those 3 first pockets, we already have many things to do. And that's probably where we're going to start looking at partners are looking at licensing of this technology to help the industry to get better or a larger number of product. What we're going to do also is developing our own platform that will provide product for Nanobiotix to develop. And here, we're going to focus on what Curadigm platform can bring that you cannot do without. It's very important. Matthieu was mentioning RNA-based delivery product. If you have this Curadigm or nanoprimer into the game, then you'll be able to deliver RNA IV. And that's opening a new field for this type of product. It's true for RNA but it's true for many other approaches and the history of medicine is full of products that could not be developed because of this barrier. With Curadigm, the possibility to overcome this barrier allow the nano to be able to develop many products for its home benefit based on this platform. But we will have time later to talk about that. And what I would like to do now is to introduce some of our colleagues and discuss about this technology and open the panel for discussion. For this panel, I would like to welcome 2 members. I will first introduce Dr. Margaret Liu, which is a seasoned scientific and entrepreneur that is starting now working with us at Nanobiotix as a new center of the supervisory board and soon to come fully board member. And we've been -- have a long discussion with Margaret about this technology and how this could help patients and how this could help industry. That's the reason why I invited her to participate in this panel for her to be able to share thinking and how they should see what we try to develop with Curadigm. On the other side of the screen, you can see Dr. Jeff Bockman, which we've been working with for quite a long time now on different projects, trying to help to share this industry with new product. And Jeff has also helped us to animate many panels in oncology in different set up for different technology. And we thought that it's always good to have an external view on what we do and some challenge that Jeff always bring into the game. So thank you for being here. And Jeff, if you want to start shooting question and asking things and challenges, free to go.

All right. Great. Well, it's an honor to be participating, moderating once again. Yes, it's been a long time by Laurent going back to early days of Nanobiotix and excited to hear Dr. Liu's comments very, very honored and esteemed guests. So let's just start off at the highest level here, given the slides that have just been presented kind of giving an overview of Curadigm and this platform. So this nanoprimer approach. How would you say it's differentiated from other approaches in the industry that are designed to improve bioavailability, whether bioavailability of small molecules, large molecules, et cetera. I poise that to you first, Laurent.

Well, I think what Matthieu did present at the end of this presentation is the key thing. Most of the product we are developing in our industry, we're thinking about one object, one object that will be everything. And when we start doing so, it's a very -- it's the science of compromise. And you do those compromises even before injecting this product into a patient. And we know how important bioavailability is, but also efficacy and many parameters that are embedded in one check. So as soon as you start releasing one of the constraints, that's where you're opening many doors and many opportunities. So I think that's the beginning of a new story for our industry to start developing new type of treatment that are not only based on one thing, doing everything, but maybe different approaches to fulfill different function that is needed by the patients.

Great. So I think one thing I'm curious about is that clearly, there are various approaches that address some of these various elements that have been talked about that can compromise, let's say, the therapeutic window for drugs, right? There's use of ritonavir, for example, to block liver metabolism and increase the drug levels in certain cases. And of course, there are all sorts of delivery platforms which are designed to address some of these issues of increasing accessibility. Maybe you can just talk a little about either you, Laurent or Matthieu, about kind of how the nanoprimer is either an alternative to those or may actually be useful in combination with some of those other approaches, whether those are physical approaches like a pump or a subcutaneous device or something or some of the currently used kind of drug approaches to modulate activity.

I could start if you want to add. I think we could identify synergies between nanoprimer and some of our approaches delivered to optimize the delivery of therapeutic agent because the nanoprimer will lead with liver viability, lever by increasing the liver clearance. But after this, biodistribution typically remain related to the physical chemical property of the therapeutic agent, there is a lot of different approaches designed to optimize the therapeutic agent to enhance the delivery within a target in specific tissue organs. So really, there is synergies between these approaches to deliver more efficiencies of treatment. And after it come back to what Laurent was mentioning really to rethink the design of the therapeutics when you add a nanoprimer to this treatment. So I can see it really as a synergy, especially in the nanomedicine field to have a better every different cargo small molecule nucleic accidents, so definitely.

Margaret, did you have any comments at this point?

No, I think that those are really the key things. But I did want to add something slightly different, that's complementary to what you're mentioning, which is that using the nanoprimer means that one can still add on other targeting moieties to whatever you're delivering. So it is good in that it helps to get rid of the nonspecificity of the uptake in the liver. But at the same time, it doesn't preclude anyone from developing other rationales, other parts of the molecules for targeting, whether it's targeting a receptor on a tumor cell, for example. So it's a very synergistic approach that can really help to augment then whatever additional approaches people are using for designing targeting specifically. And I think that, that's 1 of the advantages. It's a little different issue than what you mentioned, but I think it's important to point out that you can still then have the synergy of using additional targeting rather than this just being the 1 thing that you do, which is to decrease the hepato delivery, hepatic delivery.

Yes. Curious about kind of the residency or half-life or how long that Nano primer kind of remains in the body. And then I do have a related question to that, which has been touched on in the slides, but I'd like to probe a little bit more in terms of kind of the effects on the therapeutic window. But maybe you can just take the first point first.

Yes. Sure. This is a very important question. It's related to the duration of the effect of the nanoprimer also the residency of this nanoprimer in somebody. Clearly, if we go step by step. I mean, as soon as you inject the nanoprimer accumulation within the liver is very short. I mean, it's very quickly accumulated in the liver due to the physical chemical properties of this plan of primer. And now right after accumulation, you will have an interaction with specific receptors on macrophages, on total cell then the nanoprimer will be internalized in the endosomal lysosomal pathway. And it will -- since this is a lipid based on protect, it will be metabolized by the phospholipase in this lysosome and it's related to the duration of the effect of the nanoprimer because the time for the sale to ensure the metabolization of the nanoprimer will slow down the rate of internalization of the therapeutic agent within this pathway. And as soon as the nanoprimer is fully metabolized, the effect is more present and the liver will come back with physiological function. The duration of the effect is about 24 hour the time for the sentences metabolization, so this is the time of residency of nanoprimer within the body.

So kind of curious about the kind of what you can say about the translation of the preclinical results, which mostly you've shown are in cancer models, how you anticipate or what evidence or clues you have about that translatability into humans as you anticipate going into kind of some type of a first in-human study.

Well, I think, as you know, there's a big difference between animal model and human especially when we look at some targeted molecule, we designed the model to respond to a molecule and the model works, and it's different when it's in human. Here, I think there is a different level of correlation we can think about because every member have a system with a lever. Of course, they are different. There's different volumes, different synergies and things, but still the concept the same. At some point, that the liver will capture some of the subjects. And we know from the literature and all the clinical trials that have been done, that some of the objects that Matthieu has mentioned in the presentation, they are captured by the liver in human. So if we can just go to the first step of this process, which is to bring an object that will mimic the object you want to avoid to be captured by the liver we think, translation between an animal and UN is very high. Now of course, we'll have to adjust a number of parameters, like concentration, et cetera, et cetera. but the concept itself should be highly transferable to a human being.

And I want to ask a follow-on question and maybe to both of you, but also be curious for Margaret perhaps to weigh in. So I think when you just think about this in the presentation, the first thing you say is, wow, it's very cool, can increase the activity. You certainly talked about the ability to conceivably address the safety tolerability by reason of increased activity for the same dose or maybe even able to lower the dose. But certainly, there are on-target off-tissue toxicities that one might presume with just greater circulation time could still result in problems. I'm thinking really through a cancer lens at the moment, can you comment on that at all? And to what degree you think that is or is not relevant?

Yes, I can answer this question. Of course, yes, off-target toxicity is very important since with the nanoprimer will modulate systemic viability, we'll have to ensure that we preserve the biodistribution. We had the opportunity to evaluate on some of the products we combine with nanoprimer especially on liposome. What was the impact of the nanoprimer on the biodistribution profile of the therapeutics. And what we obtain is that Typically, we increased the accumulation within the tumor by three to fourfold due to the enhanced permabit retention effect in this issue. And for the healthy organs, I mean, the [indiscernible] distribution remain quite similar compared to the one without the nanoprimer. There's still a small portion in some secondary organ of the reticuloendothelial system, which contain macrophages and so on. So we are focused with nanoprimer on the liver, but the increase is quite small, if I may say, it's 1.5 fold compared to the therapeutics alone. So it doesn't really change the biodistribution profile and of target toxicity of the therapeutics. And if I may jump also on a very important aspect regarding the safety, there is the safety of the nanoprimer itself also, which is very important because we cannot have any sign of toxicity due to the nanoprimer. I mean you -- since we are not a therapeutic agent as itself. And we have the opportunity to or preliminary safety with a nanoprimer performing in vitro and in vivo experiment and 1 in vitro, we didn't observe any sign of toxicity cellular. Toxicity even with maximized dose in nanoprimer. No immunological toxicity. I mean there is no activation of the complement, no modification of the cytochemical kine expression profile on human blood. So typically, the first results are very good, and they have been confirmed by evaluation performed by the NCL, Nanotechnology Characterization Lab in U.S., which is an organization dedicated to promote the medicine development, and they generated the same result, confirming the safety of the Nanoprimer. And in vivo and rodent model, we didn't observe any variation in terms in hepatic enzyme such as AST/ALT, hematobiological parameters and so on, no sign of toxicity envisage. Of course, we'll move on in deeper exploration of the preclinical safety package. But first results are very encouraging from cytotoxic.

Yes. And this may be something that you'll be doing down the road and certainly would need to be thinking about. And that is since certainly oncology, we're mostly talking about combination therapies. You would need to be thinking in a more holistic way about the impact on the regimen of the multiple agents. There might be some small molecule cytotoxic, there might be a biologic antibody, something else and all of those are conceivably going to be affected depending on the timing and the regimen and when the Nanoprimer gets used.

Yes. But the good point also we see here is that the Nanoprimer is really focused on reticuloendothelial system, Kupffer and liver sinusoidal endothelial cell. So If you have a cotreatment involving a small molecule injective as such. The metabolic pathway is going to be through the cytochrome within the hepatocytes. And the nanoprimer is not dedicated to interact to metabolization pathway. So it won't impact the metabolization of the small molecule. It's very dissociated. So this is a good point also for multi-therapy treatment.

Yes. Yes. That's a good point of clarification for everyone, I think. Thank you Margaret, any comments, thoughts?

Well, I just wanted to add that I think that when 1 thinks about it, fortunately, there are tools to determine what the impact is. So you do your normal pharmacokinetics, for example, during the administration of a drug. And what may happen is the effects will be distinguished both by longer presence of your drug potentially because you don't have all of this absorption in the liver. And that may differ then as well depending on what the entity is. So for example, mRNA molecules need to be formulated and lipid nanoparticle precisely because they're so easily degradable. And so besides the issue of being able now not to get stuck in the liver, you have is you have more in the regulation but the persistence then may differ between a molecule like that or a virus, which may target other cell types, for example, if you're delivering some kind of virus as your vector for killing cells. So the issue is that you can measure the impact depending on what the entity is that you're delivering because you'll have this primary effect of not being trapped by the liver. But then each entity that you're looking at has its own particular targeting in pharmacokinetics and other ways of finding that may take it to the tumor or to other cells, et cetera, but these are all things that get evaluated anyway for each product. And so the tools exist in order to determine exactly what the impact is -- that might affect dosing or even regimens.

Great. Thank you, Margaret. [indiscernible].

During the talk with Margaret, it was -- remind me a bell. There is also an important aspect of the Nanoprimer mechanism is transient as we were discussing. And clearly, I think this is an advantage regarding the safety aspect also. If you look at nanomedicine, I mean, everybody is using PEGylation to extend the systemic viability of therapeutic agent. But at the end, let's take an example, Doxil. Doxil has been generated to decrease the cardiotoxicity of doxorubicin, encapsulating the drug within the pegylated liposome. The PEGylation means that you will keep your therapeutic agent in the blood for something like a week and at the end, you will have a modification of the biodistribution in other tissue, I mean, in the extremities, the feet and in the hand, bringing a new to limiting toxicity. So you replace toxicity by another one. With the Nanoprimer, the improvement of the systemic viability is transient. I was mentioning approximately 24 hours. That's enough to accumulate our therapeutic agent in a tumor typically, but that's short enough also to prevent accumulation in other tissue due to a very extended circulation time. So I think we have an advantage from this side also.

Great. Great. And then actually -- we'll come back on that shortly, I think. But Laurent, just to kind of pull us a little bit out of the weeds for a moment. How is the company thinking of developing Curadigm? I mean, from a kind of a corporate development BD standpoint, bringing it forward on your own, doing partnership partnerships plural, and that may tie back to the issue of different applications of even the Nanoprimer let alone any follow-on Nanoprimers, but Laurent?

I think with this concept, what we do is 2 things. First, we could solve some of the problem of our industry today, problem that people have developing some of the drugs. So we think here, there is a big opportunity to develop partnerships with different type of partner for different type of application with different type of product. That will be definitely part of the drug we're going to do. We already have a good number of MTAs that have been signed and product being tested in many combinations. That's part of the job. The other part is really building in-house our own platform and products so we can have the ownership of a full product, the Nanoprimer plus the other to develop that and to bring that to human and as far as in our development up to market. So that will be the mixed business model we are going to use. And this is needed because there's a lot of applications. So we can do everything, that's for sure. And so finding partners, validating the technology, developing with us increasing the use of this product for patient will be the right path.

So in fact, you've just kind of alluded to it as although the presentation does focus on oncology, clearly, the applications are beyond that. Can you speak a bit to that Laurent or Matthieu?

Well, I think the application are not necessarily linked to a therapeutic area, obviously, but more to the type of subject we develop. So if you just take hiring, as example, it can be used in many indications, if you delivery system, that's the same. There are many products that exhibit that kind of physical chemical [ property ] that we can help. So yes, it's going to way beyond oncology. Nevertheless, the company has already developed knowledge oncology, and that should be logical for us to continue in this field at least for a while.

So this has all the appearances of being quite transformative. I'm just curious kind of what type of reaction you've had from anyone externally that you might have spoken with, whether early partners or financial folks or others in terms of kind of how they're viewing this?

Well, I think we have had different type of things. What I share is because, as I said, it does solve some of the well-known problem of our industry, there is a natural, okay, it's it has value. That's the first thing. And it's interesting. And after it's different. So how does this work? How you sell that? How do you reimburse this. How do you develop it? Is it a combo? Is it 2 different product? So the natural question when you develop something new. But we have an answer for all that. And I think in a broad view, we found mainly, if not only people that think there is a big opportunity here. But it's the beginning, so we need to push and to make that happen.

Yes. So given the diverse applicability across therapeutic areas, specific diseases, different types of therapies. How are you thinking of prioritizing? And you mentioned oncology, obviously, as kind of leveraging the resident knowledge from Nanobiotix work. But how are you thinking about kind of diversifying or derisking or increasing the optionality given that this can be applied to areas that are kind of well validated that involve, as you said, kind of RNA or nanoparticles like some of the gene therapy or related areas, or vaccines that are in nanoparticles and others that are, let's say, not so well validated, including still sadly, as a lapsed virologist oncolytic viruses and other places. So how are you kind of weighing that? And I'm sure Margaret would like to kind of comment as well, but I'll start with you, Laurent.

So in terms of priorities in the company, we have a well-defined pathway to develop our own product and platform. So that's something we will disclose later next year. But we have a clear pathway moving forward. On the other side, from the BD perspective, that will be more based on the partners need. As I mentioned, we have different MTAs ongoing. We test with this product. It's a lot in oncology, but not only. So we will see how these things move forward and we'll go step by step.

Right. Any comments there, Margaret?

I think that oncology is an obvious place to start a there has been so much focus on how do you take treatments from intratumoral injection to intravenous injection because of the issues of not all tumors are accessible or the challenge. And so having something that could be given intravenously for oncology, whether it's a drug or whether it is a virus that can kill the tumor cells is a very obvious and I think, a big opportunity as a first step. What I think is really important though is that other arenas, let's say, gene therapy for inherited disorders, where right now, the viral vectors that are used for delivery have to be given in huge numbers. The thing about that is this to me seems like an area that really is right for exploring. But what it will take is it will take people in those areas to recognize that instead of just focusing on how do you make a vector, what's the payload, how do we manufacture enough of this to say, Oh, this is actually the same issue that confronts oncologist every day. And so that it's important then to get people in other arenas to recognize that this same type of technology is really addressing a similar problem, which is if you're losing a lot of your vector to some place like the liver, you have less vector that's going to the intended targets to make your therapeutic product regardless of what that therapeutic product is, whether it's for treating cancer or whether it's treating an inherited disorder. So I think that 1 of the keys is actually just to get people who are in these other fields to think outside of the box that they've been working in, which has been payload and maybe stabilization of the vector or manufacturing, which is, of course, can be a challenge when people are manufacturing viral vectors and some people have accomplished the numbers, but I think that, that's the issue is having people understand the value for other arenas as well as for cancer.

Absolutely. And I think, of course, just a personal experience, having started in the dark side of industry at a biotech, working on delivery of ribozymes and other agents and working with nanoparticles and 30 years on, people still trying to optimize lipid nanoparticles or related LNPs that will avoid the liver for delivering the active 2 places other than the liver where you want to go. Still does remain a challenge, and this does look like a very transformative approach that at least to some degree and maybe to a significant degree, might obviate some of those limitations. So I'm curious then, Laurent, what's next for Curadigm?

Well, I think we have a lot to do when you see the potential of this as I said, is a big part for us now. The team is focusing on developing our own product based on this platform. That's something we'll be able to talk about second half of next year. And for the first part of next year, we'll be able to show some new data coming out from this Nanoprimers and how we could apply that in terms of the situation that could be very beneficial to patients. But we'll make an update to the rest of the world and the market soon to explain how we're going to develop that and more importantly, what's coming in terms of news flow about this technology.

Absolutely. And of course, there still R3, which was kind of started the story many years ago with Nanobiotix.

Right. And there's a lot to do here, too. There's a big collaboration with our partner, J&J, and we need to make sure that this is a success, and we can bring this product to market.

Great. Any further comments from any of you? I think we've covered a lot of ground today. So Laurent. We've had a great discussion. Clearly a tremendously interesting and quite potentially broadly utilizable transformative, if we may say and we've used that platform technology that you have here in Curadigm. So how would you kind of summarize kind of the benefits, the potential kind of the so what, if you will, for Nanoprimer?

So for us, it's like the continuation of Nanobiotix story. We've been always looking at how a physics could help patients and preferably millions of patients. So that's a good step for us. This technology offers many opportunities that we're going to explore step-by-step, having daily activities but also having an internal activities developing our own products, and we're going to start delivering that to the patients. So there's a lot to do, but we think we have a unique opportunity to change the face of the industry with this, so that's where we're going to go.

Great. I want to thank, everyone, for the time today. Thank you for those overviews. Matthieu and Laurent. Thank you for your comments, Margaret. Thanks, everyone.

Thank you, everyone.

Thanks, everyone.