Hello and welcome to Beyond Biotech, the weekly podcast from Labiotech. I'm Dylan Cassine and this is episode 211 for the podcast. What if the key to beating cancer wasn't a new drug, but a new way of thinking about matter itself? That's the question Laurent Levy asked when he co-founded Nanobiotix over 20 years ago. And it's a question that is now producing some genuinely compelling answers in the clinic. Nanobiotix is a Paris-based biotech pioneering what they call physics-based nanomedicine. Their lead asset is a radio-enhancer made of hafnium oxide nanoparticles designed to be injected directly into a tumor and amplify the destructive power of radiotherapy from within without ever increasing damage to surrounding healthy tissue. It is currently in phase three trials in head and neck cancer. But that's only half the story. The company's Nanoprimer platform is now emerging as a potential new engine for growth with the promise of making an entirely new class of genetic medicines work better. I hope you enjoy my conversation with Laurent Levy right after this word from our friends at Inside Biotech.
Hi everyone. My name is Karishma Chegani and I'm the co-host of Inside Biotech, the official podcast of Biotech Connection Los Angeles or BCLA. For those who may not know, BCLA is a non-profit organization dedicated to inspiring, educating, and connecting emerging scientists, students, and entrepreneurs to help grow and diversify the biotech ecosystem in Los Angeles. On Inside Biotech, we invite you to get a behind-the-scenes look at one of the fastest-growing biotech hubs in the country. Each month, we sit down with scientists, founders, investors, and industry leaders to talk about the cutting edge science inside their companies and the personal journeys that brought them there. From breakthrough therapeutics and AI in healthcare to career transitions beyond academia, we explore how science, business, and storytelling intersect to shape the future of biotech in SoCal. If you're a student exploring careers in STEM, a young professional navigating the industry, or simply curious about the people driving innovation, this podcast is for you. Search Inside Biotech wherever you get your podcast and give us a listen. We'd love to have you join us.
Laurent, welcome to Beyond Biotech.
Laurent, let's get started. Tell me a little bit about who you are and how you came to find this company Nanobiotix.
Well, maybe we can start with my training. I've been trained as a physicist, mainly. I did some biology, too, but my main stream was physics. And I did my PhD in nanophysics trying to understand what's happening with the laws of physics when you start reducing the size of the material. When you come to nanometers, laws of physics may be tweaked, may change. And that was the basis of my thesis. And later on I did a postdoc. And in between I was wondering what I should do with my life. Should I go to semiconductor industry? Should I do something else? But I always wanted to have an impact for people. So, what better field than trying to improve health of people? That's why I started to think about how can we apply all this new emerging field of nanophysics into doing something to cure people from different disease. And that was the beginning of the whole story.
You know, the tagline on the website there is building new therapies atom by atom. You know, where did this idea come from? What was the original insight? Was it back in that doctoral work?
Well, I mean, technically that's what we do. You know, we do bottom-up approach. Meaning we have to start with atom that we assemble, not one-to-one exactly, but few-to-few in order to build those nanoparticles to have very specific physical properties. If you start from a big material try to reduce the size, you will obtain something very different. So, the ability to build complex object, complex nanomaterial has to come from building almost atom by atom. So, that's technically what we do.
Nanobiotix, it's not a new company. You were founded in 2003. You've got more than two decades now of building something that is genuinely new and really on the cutting edge. How does it feel to be at this point where you've got clinical programs, you've got a major partnership with J&J, you've just closed an 85 million euro raise as well. How does it feel to be 20 years in and hitting these sort of targets?
Well, I mean, 10 years ago I would have tell you who cares. I mean, we still have so much to accomplish. But today, I'm still focused on the goal and I think the whole team is also that we are very keen into helping millions of people and we always look at the future in that way. But I also step back from time to time and say that the team can be proud of what they have achieved over two decades building this very specific knowledge that make us unique in our industry, but also achieving step by step all the key milestone that transform an idea into a product that could be useful to people. So, that's a mix of let's stay focused on the goal and also let's celebrate step by step the journey.
You know, these products that are for people, most people who are working in oncology, they're used to drugs that are working chemically or biologically. They bind to a target, they block a pathway. You're doing something different and I think it's because of this physics here. Can you explain what a physics-based approach to cancer treatment actually means?
Yes, you know, I think that's where we can make the biggest difference. Not that biology and chemistry is not good. I mean, obviously does save billions of people when you look at how important is the field we're working in. But there's something with biology. Biology is hard to scale up. It's very variable. If you think about an individual between two days, it could be different. The biology could be different in the morning, in the afternoon. It could be different when you're baby, when you're an elderly. Also, two individuals are very different. And what we try to target with the biology and chemistry at some point, as you said, is a molecule somewhere that we want to interact with or a biological process. And it's very hard to be certain that you will interact in the right way with these biological pathways. Also, uncertain that if this biological pathway will stay the same over time in one individual. So, biology by essence is complex. Now, if you step back and think about physics, physics has something different. Physics is really reproducible, scalable, and it's the same everywhere. Physics will not be influenced by the biological variability. If you think about gravity as an example, we all feel gravity regardless of our biology. And that's true for every single human. That's also true on every planet. True for every species. So, there is something constant in physics that we can use. Meaning that when we develop a product in a sense that it is a small object that is small enough to go into the body, to go at the cellular level, let's say at the biological level, but this object deliver a physical effect. So, we are sure that in every single patient, it will deliver the exact same physical effect. So, we have a first layer of a mode of action that is universal for every patient. It doesn't mean that the benefit will not be influenced by biology, but at least at the first level, we are not influenced by the biological variability. And we think that's where we can make the whole difference.
Is this something you've been working on, like we said, for more than two decades now. Were there moments early on where people push back against this idea of using physics in drugs and drug discovery? People said it wasn't going to work or nanotech was something separate to healthcare?
Well, the story of my life. I mean, not anymore, obviously, but when we started, clearly there was some question around. I mean, that's science fiction. Why it should work. I mean, and why no one has done it before. That kind of things. But the more you progress, the more you show data, the more you get into what people are used to see, like clinical data or different in vitro in vivo experiment that you can show and fit into an existing framework, then the more believer you get. And at the end of the day, the clinical benefit that you can measure into patient is the goal. And that's where you can make a difference, and that's where people start to see that it's working. I remember that the first data of the phase two three randomized trial in soft tissue sarcoma has been the first time for this new class of product we were showing it does work in patient. When comparing the radiation alone versus radiation plus the product, we did meet all primary and secondary endpoint. And this trial has been a critical step in our development. Not only to convince the medical community, but also to get more and more investor on board. So, even if you develop something really different, at the end getting to some of the usual framework does help.
But just out of interest, who are you hiring to work on these projects? And are you drawing in physicists? Are you taking biologists and teaching them something new? Who are the people who are actually doing the work?
It's a mix of people. We have different chemists, biologists, engineer, physicist, physical chemist. And all together, we've been building for the past 20 year this very specific knowledge. Because you have the basic science that you need to handle, but also the interfaces of the science together. And that's where the innovation occur, that's where the discovery occur. That's also where we can file very broad and large patents to literally patent new fields of applications for health care.
Let's talk a little bit about your lead program. This is NBTXR3. It's now partnered with J&J as JNJ-1900. It's a radio enhancer made of hafnium oxide nanoparticles. Walk me through. What does it mean? How does it work? What happens when these particles are injected into a tumor?
Maybe we should start by the goal of this product and why we've been developing this product. And I think we can again start with the patient. At diagnosis, cancer patient, for most of them they have a local disease. They don't yet have metastases, is around 75% plus of the patient diagnosed with cancer that have a local tumor. And for those patients, if you want to bring a large level of cure, you need to kill this primary tumor before it's getting to a more spread disease. Nevertheless, when you look at our industry, most of the time, people will start like last line of treatment post every known treatment try to make a difference here then come back into the earlier line of treatment. But again, if you want to bring a large rate of cure, going early in treatment where the cancer is local, that's where you can have the biggest impact for cancer. And that's our target. Talking about local control or local treatment of cancer, surgery, radiation therapy are two of the big treatment, sometimes combined with chemo, with some other biological approaches, but literally radiation and surgery are really two key pillar of treatment. And if you think about radiation, it's more than 60% of all cancer patient that are receiving radiation during their treatment. And most of the time when you have a local disease. So, that's our target. If we can improve radiation and make it much more efficient, then we could potentially improve the rate of cure for patient. So, how can we improve radiation? For that, maybe we need to step back and to look at what is radiation. Technically, you send ionizing radiation, but when you want to irradiate a tumor, it's surrounded by healthy tissue. Therefore, sending ionizing radiation will create damage in the tumor, obviously, but also in surrounding tissue. And then, you're always limited by the dose you can bring into the tumor because of those damage you're creating in the surrounding tissue. Regardless of the technology you're using, regardless of how fancy is the equipment, you don't change the fact that you have to cross healthy tissue. So, there is an intrinsic limitation of the dose you can deliver in the tumor and therefore the efficacy of radiation. So, the question we ask ourselves is how can we improve the dose in the tumor without changing the dose in surrounding tissue? That's what led us to develop this drug, NBTXR3 or hafnium oxide, which is a small particle that is made of a crystal, hafnium oxide, that we inject directly into the tumor only one time before the first session of radiation. And when this crystal they float into the cell, the patient is getting the usual radiation therapy, but the radiation will be highly absorbed by those particles that will deliver a high quantity of damage around them and kill more cells. So, that's the basic principle of what we are developing.
The question for me then becomes if it's putting all of this extra energy into the tumor, it's killing the tumor cells at a much higher rate, why doesn't the energy spill over into the healthy tissue? Is that just a function of the physics?
Yes. When the particle absorb the energy, they will deliver their damage in a very short range. You can go more than one or two cells. So, technically the particle will provide additional efficacy versus radiation where they are.
And there's also this other component, the immune component. In the data it says you can also prime the immune system against the tumor cells beyond that primary site. Honestly, it's one of those things that sounds almost too good to be true. Can you explain what's going on there?
Sure. Well, first of all, the primary mode of action, absorbing energy, killing more cells, that's what brings a good local control. You literally kill more cells. But by killing cells, you also make visible part of the cells that are usually not visible, that help the immune system to start recognizing the tumor, getting equipped against it, and having a potential impact not only for the primary tumor, but for some metastasis that are distant from the treatment. So, that's something we've been showing in different clinical setting like head and neck metastatic patient or melanoma patient that are resistant to multiple line of treatment including immunotherapy, where we clearly see the injection and irradiation in one lesion not only have an impact on this lesion, but has an impact on distant lesion that haven't been treated.
So, this head and neck cancer, I think you're also looking at lung cancer. These are areas where the patients can be elderly, they can be more frail, they're not going to tolerate really aggressive treatments including things like chemo. You know, did you start there because you can have that really big impact right there in the tumor?
