Nanobiotix S.A.

Good day, and thank you for standing by. Welcome to the Nanobiotics Business Update and Third Quarter 2023 Conference Call. At this time, all participants are in listen-only mode. After the speakers' presentations, there will be a question-and-answer session. Please be advised that today's conference is being recorded. At this point, I will turn the call over to Craig West, Senior Vice President of Investor Relations of Nanobiotics.

Thank you, Operator. Good afternoon and good morning, and welcome to the Nanobiotics Conference call to discuss our third quarter 2023 financial and operating results and the clinical data presented at this year's ESMO conference. Joining me on the call today are Laurent Levy, co-founder and chief executive officer, and Bart Van Ryn, chief financial officer. As a reminder, today's call is being webcast and will be available on our website for replay. Moving on to slide number two, I would like to remind you that this call will include forward-looking statements, which may include statements regarding the progress, success, and timing of our ongoing and planned clinical trials, collaborations, regulatory filings, dates of presentation, and future research and development efforts, among other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. They are subject to significant risks and uncertainties that could cause the company's actual results to differ materially from our current expectations. Accordingly, you are cautioned not to place undue reliance on forward-looking statements. Please review the full description of risk factors that can be found in the documents we filed with the AMF in France and the SEC in the United States which are available in the investor relations section of our website along with the press release issued yesterday highlighting our corporate and financial results for the period. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, Nanobiotics undertakes no obligation to update them to reflect subsequent events or future circumstances. With that said, I'd like to turn the call over to Laurent.

Please go ahead. Thank you, Craig. I'll propose to start with slide number three. As you may have seen our press release, you could see that we have had a very productive and busy quarter that we think is going to drive nanobiotics into a great future. We've started this quarter by signing this $2.5 billion collaboration with Johnson & Johnson and gave a number of updates, including final data of our head and neck phase 1 trial, plus some exploratory data through ESMO and ASTRO that gave us some strength and some confidence about the potential outcome on the ongoing global phase 3. On the top of that, our partner, Henry Anderson, has been publishing data on pancreatic cancer, showing a good feasibility and safety of this treatment for those specific patients, but also starting to see some strong signal of efficacy. As you will see, our recently completed financing round will really strengthen our financial position, and Bart will give you an update on that. And we will finish this call by a Q&A session. Let's go now to slide four. Just to remind for the new shareholder and the new people in this call, what is our first in-class radio enhancer? Our product, NBT-XR3, is here to combine with radiation therapy. And as a reminder, 60% of all cancer patients we get radiation therapy during the course of their treatment. How this product works, it has been designed to be a one-time injection directly into the tumor in order to maximize the concentration and the efficacy in the tumor and minimize systemic exposure for the patient. And this product is made of crystalline inorganic particle of a very particular material, atrium oxide. HFO2 is, first of all, a very stable inert material, which is good in terms of safety, but also provides a very unique property, being a very strong X-ray absorber, because of the nature of the material and the high atomic number and density of electrons that compose it. But this is not a new product, because we've been able to demonstrate in hundreds of patients safety and first sign of efficacy, including a strong proof of concept in soft tissue sarcoma where in a randomized trial, we've been able to show the superiority of our treatment versus the standard of care. And this product, being a physical universal mode of action, we think that this could be applicable across oncology for many, many patients. That's why if you move to slide five, you'll see the breadth and the size of our pipeline. As a company being focused on head and neck, but also have been showing in many different clinical situations the potential or the feasibility and safety of this product. What we need now to develop that broadly is not only a strong development capability, but also commercial capabilities. As you know, the ongoing phase three in head and neck cancer should have an important readout mid-25. That's why we have been signing recently a partnership, and that's on slide six. with Jensen to make sure that we have enough of muscles, brain, to develop this product potentially in many indications, but also to start and preparing a global commercialization of that. So as I mentioned, it has been an overall deal of $2.5 billion that included some upfront and in-kind support, and a good number of development and regulatory milestones. for the existing program ongoing, and that includes also self-mystone up to 1.8 billion, there are additional regulatory and development milestones for new indication that Jensen may develop over time up to 650 million. And on the other side, for any new indication that nanobiotics will develop and will bring into market, there will be an additional of 220 million per new indication. This is going with also tiered royalties that go to low teens to low 20s. But today, we're here to give you an update on what happened during the quarter, but also what has been published by our partner, MD Anderson, or the final data of the head and neck cancer trial. So going to slide seven and slide eight, as you may have seen, we've been publishing the first set of data coming from the pancreatic cancer trial done by MD Anderson. If you go to slide 9, here we're looking at a very specific population of pancreatic cancer. We're looking at locally advanced pancreatic cancer or borderline resectable pancreatic cancer. For those patients that have those big tumor and then cannot go to surgery, radiation therapy with chemo is a very important treatment. in order to try to either control the tumor or hopefully for the borderline respectable pancreatic cancer to get to a surgery. So when you look at the historical outcome for this patient, radiation plus chemo or chemo alone did not provide something big enough to help this patient to get to a potential cure. So in the trial we are talking about here, The first part, that was an escalation part, only included locally advanced pancreatic cancer, so excluding the borderline resectable. So moving to slide 10, you see a summary of the design of this trial. So we've been treating so far 17 patients, where the patient got an induction chemotherapy, and if no systemic progression, got our treatment, which is radiation, plus NBT-XR3. We have a chance here is that at MD Anderson, they have been also treating a number of those patients previously. That's why we've been able to make not a direct control, but an internal historical control done with the same center on 243 patients that received the following treatment, chemo. Then if no systemic progression, they got either radiation plus chemo or chemo alone. So it's important to notice that when you look at the 144 patients, that received the radio plus chemo in the previously treated patient at MD Understand, they got one chemo more than what we have been doing in our trial. Has our patient post-chemo induction just get radiation plus NPT-XR3. Moving to slide 11. So what's the trial status? So as of September, 17 locally advanced patients have been treated with our product and with a median age of 60 years old. RP2D has been established with no DLT related to NBT-XR3 or product, just one level 2 DLT linked to radiation therapy has been observed to the patient. Moving to slide 12. One of the first things that has been observed, which is interesting, that you may know that CA-19 is a biomarker in pancreatic cancer that is interesting because in certain conditions, maybe a surrogate or maybe important to follow a potential response for the patient and a potential outcome in terms of survival. So if you look at the previously treated patients at MD Anderson, you had a number of patients having elevated CA-19 at baseline, and 17% of them have been normalized post all course of treatment. In our trial, what we have been observing is 42% of the patients have been normalized CA-19 post all course of treatment. So more than double what has been observed previously. And let's not forget that we have one less chemo versus most of the patients that have been treated previously. So that's for our first biomarker, which is very interesting, but does not completely reflect the expected outcome for the patient. What is important is looking at slide 13. So at the latest cut-out date, what we have seen on the first 15 subjects evaluated is a median overall survival of 20 months post-diagnosis, which is, if you look at what has been done previously at MD Anderson, slightly better, and we should say even better. If you look at slide 14, you see that patients that previously received a chemoinduction followed by radiation plus chemo got to 19.2 months median overall survival. In our case, with one less chemo, but our product and BTXR3 in combination with radiation, we got to 23 months. which shows a potential improvement for those patients. And obviously, when you remove one chemo in combination with radiation, you should expect or could expect less toxicity and less combined toxicity. So in a nutshell, moving to slide 15, So we've been able to successfully administer this product into patients with a good safety profile. We start getting a good potential signal of efficacy through the 23-month median overall survival. And what we see is when we look at the comparative data that have been previously obtained by MD Anderson, So now, we're going to discuss, obviously, those data with our partner, MD Anderson, Lee & Bio, Johnson & Johnson, to start assessing what could be the next step for pancreatic cancer patients. Let's move now to slide 16. So, as I remind in the introduction, we have an ongoing phase 3 global trial in head and neck locally advanced cancer patients. and those patients being ineligible for cisplatin. I think the two pieces of data that have been lately shown by nanobiotics are very important. There have been two different times, one at ASTRO, followed by the ESMO. First of all, let's go back to the design of this trial. So that's slide 17. Total, the study 102 has been enrolling 75 patients. Part of those patients being in de-escalation and 50 six patients being in the expansion part. The latest data that have been shown, both ASTRO and ESMO, have been extracted from the final data coming from the expansion phase. So in this trial, we take locally advanced head and neck cancer patients that are frail, elderly, and that are not eligible for cisplatin. So the only option, the therapeutic option they have, is radiation alone. And we've been able to add our product Obviously, a big part of this trial was about safety and feasibility, but we also started to look at overall response rate, complete response, PFS, and OS. So, in the conclusion of the ASTRO presentation that you can see in slide 18, first of all, we have seen that this product has been able to be administered safely in all the patients, confirming in the extension phase what we have been already showing in the escalation part. Importantly, on the top of safety, we've been showing a very high response rate, 79% overall response rate. And we've seen a median duration of response which is really high, especially in the tumor that has been treated with our product and irradiated. Two very important endpoints where median PSS and median OS, because they are the ones that are going to be used for the phase III as primary and co-primary endpoint, So median PFS in the variable population has been 16.9 months, and the median OS 23.1. Just as a reminder, this should be compared, if you want to, versus historical data, where median PFS in similar population, but better, has been nine months, and the median OS has been 12 months. So all those data and final data of this phase 1-2 give us a lot of confidence to the management and to our investigator about the potential success of the ongoing phase 3. Moving to slide 19, those are the latest exploratory data we've been publishing at ESMO and looking a bit more precisely at what's happening in term of correlation. We know here we're looking at locally advanced cancer patients. So what is important is to see, can you get response? Because we know that getting a good response will provide a good PFS, and a good PFS will provide a good OS. So we just wanted to make sure that this is happening, because given the high rate of response we have seen, around 80%, we want to make this correlation. Just as a reminder, in this phase one, we've been having patients that have a primary tumor and a good number of them having surrounding lymph node involved with cancer cell. So both of those will be irradiated with the same dose of radiation, 70 gray. Nevertheless, in the phase one part, we've been injecting only the primary tumor, not the surrounding lymph node. So if you move to slide 20, it is very interesting to see that we find a high correlation between PFS, duration of response, and overall survival. And we find an even stronger correlation when you look at the local, meaning the tumor that have been injected and irradiated with our product, you find a very strong and stronger correlation with PFS and OS. So all this just confirming that our product does provide a good impact in terms of response that induce an improved PFS and a potential improved OS2. Moving to slide 21, it's just a recall of one of the slides that have been shown at ASTRO. Here we see all the response the patient got. As you can see, there is a very large number of complete response. and a large number of response. We get to 81% of response or 79% of response for the overall response rate. Why this is important? If you look at literature, you can look at what radiation plus chemo does in better population that are less frail and you can see what kind of rate of response they obtain and what kind of survival this brings to those patients. Here again, we have just radiation on nanoparticles And that's it. The patient will not get further treatment. So what we did obtain out of the 80% of response is a very big survival. When you move to slide 22, you see the different survival curve. The blue one is the overall survival for all treated population on the left and available population on the right. What is very important is the green curve. Here we have taken patients that got either CR or PR, so the responder. And for those patients, we found a median OS of 42.8 months. And that's very important. Let's remind ourselves that this is a very frail population where radiation therapy is not really curative for a large number of patients. And what we can see usually in head and neck with locally advanced, when you go beyond the 24 months, then you start getting to a good position for the patient, not to be cured yet, but we're getting closer to that point. And the fact that we've been observing this high rate of response, 80% or more, and this is linked to a very strong survival with the median survival of 42.8 months, really let us think that we may be on our way to change the outcome for this patient population. And obviously, that gives us a lot of confidence on what's coming. which is presented on slide 23, and that's the design of the ongoing global phase three, which is made for registration of our product in locally advanced head and neck cancer. So I will not go over the detail here, but what is important to know is this trial is ongoing, as we did mention during our last communications. We expect to have an interim analysis after reaching 283 events on the primary endpoint, which is PFS, and this should occur by mid-25. And that's a very important endpoint and a very important time for the company and this trial, because assuming that this is positive, we should be or could be eligible for an accelerated approval. And therefore, this could be the first indication that our partner, Lianbio and Jensen, may start commercializing across the globe. If you move to slide 24, I think There are a few things that make us really confident in the potential outcome of the phase three. First of all, what we've been observing in the phase one with a good median PFS and a good overall survival when you look at the population we are treating. And in the phase three, there are two differences that we think would be, again, an improvement versus what we have seen in the phase one. First of all, we will have or may have a much broader population than the one in the phase one with overall less comorbidity to make sure that we have time for the product to give some benefit to the patient. And in any case, because we know how comorbidity to this population is important, we've been using ACC-I as a stratification factor. So that should be on the safe side, let's say. On the top of injecting the primary lesion, as we have done in the phase one, in the phase three, we allow not only to inject the primary tumor, but also the lymph node. So that potential will give an additional efficacy versus what we have been seeing in the phase one. But let's be clear. If we just reach the data we've been showing in the phase one, then this trial will be positive. So all these have been very important to us and to our investigator to give us a lot of confidence about what's coming for the phase three. Now, thank you very much for your attention, and I will give the mic to Bart to update you on the cash runaway and the financial update.