Good day, and thank you for standing by. Welcome to the Nanobiotix full results from completed phase I study of NBTXR3 in pancreatic cancer, ESTRO 2025 conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be the question-and-answer session. To ask a question during the session, you need to press *11 on your telephone keypad. You will then hear an automated message advising you hand is raised. To withdraw a question, please press *11 again. Please be advised that this conference is being recorded. I would now like to hand the conference over to our first speaker today, Ricky Bhajun. Please go ahead.
Thank you, Clarissa. Good morning and good afternoon, and welcome to the Nanobiotix conference call to discuss new data from our phase I study in pancreatic cancer presented at ESTRO this weekend. Joining me on the call today is Laurent Lévy, Co-founder and Chief Executive Officer, and Bart Van Rhijn, Chief Financial and Business Officer. As a reminder, today's call is being webcast and will be available on our website for replay. I would like to remind you that this call will include forward-looking statements, which may include statements regarding the progress, success, timing of ongoing and planned clinical trials, collaborations, regulatory findings, 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 have filed with the AMF in France and SEC in the United States. These documents are available in the investor relations section of our website, along with the press release issued today. In addition, any forward-looking statements represent our view 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, Nanobiotix undertakes no obligation to update them to reflect subsequent events or future circumstances. With that said, Laurent, the floor is yours.
Thank you, Ricky. Good morning, good afternoon, everyone. Really happy to have you here around the table today to discuss our newly released data on pancreatic cancer. This is a trial that has been done at MD Anderson by our PI, Dr. Eugene Koay. Before getting to some of the details, let's maybe reset the scene for pancreatic cancer. As we know, unfortunately, it is still a cancer with limited options for the patient, especially when it comes for patients that are unresectable or borderline resectable. They usually have a poor prognosis, especially for the locally advanced that cannot go for surgery. Radiation therapy is part of the treatment paradigm in pancreatic cancer. Often, when you cannot operate a patient, you will go first for chemoinduction, followed by radiation plus chemotherapy.
It has been seen, as you can see in literature, that giving a high dose of radiation in pancreatic cancer may improve the outcome and improve survival for patients. However, because of the location of this tumor surrounded by sensitive organs, it is very hard to apply that to all patients. Additionally, we see that pancreatic cancer is a very cold tumor where, so far, we have seen poor outcome when it comes to combination with checkpoint inhibitors. To date, there's still a lot to do for this patient, and that's really the intention we have with NBTXR3, first by improving local control and trying to see to which extent we can also impact the systemic disease. We have been completing a phase I/II trial at MD Anderson.
Yeah, we've been completing a phase I/II at MD Anderson, where we've been treating for the escalation and expansion phase 22 patients. Those patients have received induction chemo, and for the patient that did not progress, got a treatment with NBTXR3 plus radiation without any concurrent chemotherapy. On the top of treating patients, we also have been using internal historical reference coming from the same center, MD Anderson, by reviewing historical patient 243 having locally advanced or borderline resectable pancreatic cancer have been getting standard of care, which is induction chemo, and for the one that did not progress, either radiation plus minus concurrent chemotherapy or chemotherapy alone. It is of note that most of the patients receive radiation plus concurrent chemotherapy, which was not the case in our trial, where we just treated the patient with radiation plus NBTXR3.
For the baseline characteristics of the patient, I think the most important part is that most of the patients in this trial have been locally advanced pancreatic cancer patients. Only two out of 22 have been borderline resectable. The first thing we wanted to prove is that we can inject safely the product in such a complex organ, which we have been doing in all patients following an endoscopic ultrasound guidance. One thing that is critical outside the injection of the product is the way we can or cannot deliver radiation therapy per se in those patients. Here we have taken an example where you see the location of the [audio distortion] on the left with the red arrow showing the location of NBTXR3 in the tumor.
If you go on the picture below, you can see how the dose is distributed in the tumor, but also in the surrounding organ of the body. Looking at the right part of the slide, you can imagine how hard it is, given the number of organs at risk, like the small bowel or the liver or the kidneys that are surrounding the pancreas, to deliver such a high dose of radiation. That is why, as a main standard of care for this patient, it is preferred to deliver 45 Gy in 15 fractions, which we have done in our clinical trial. Now let's see first the safety. In the escalation part of the trial, we had no single DLT and have been defining recommended phase II dose as the maximum dose defined per protocol, which was 42% of the GTV.
When we combine escalation and expansion phase, we have seen three grade 3 adverse events, transiently adverse events that have been observed in three patients, one that has been related to NBTXR3 and two related to other treatments. Altogether, given the condition of this patient, we have observed a very good safety for this patient population. Now, when we move to the first hint we got on overall survival, we're quite happy with what we have seen because we got a 23-month median overall survival from diagnosis for the patient we have been treating. If we compare that to historical control coming from MD Anderson Cancer Center, we got to 19.2 months. Of note, most of those patients at MD Anderson in standard of care have received chemotherapy on the top of radiation.
We start to see a nice delta appearing that could be very important for those patients. Another important thing that we've been looking at is the CA19, which is a biomarker that usually is a good surrogate for survival in pancreatic cancer. When you get patients with high CA19 and you get to a normalization of this post-treatment, usually it's going with higher survival, which we have been showing here in our trial where you look at the left part with the OS curve where a patient having CA19 normalization having a longer survival than the patient having not normalized CA19. Importantly, if you look at the historical control coming from MDA, you usually find 17% of patients having normalization of CA19, and in our trial, we got 59% of patients, which is a nice and good delta.
In summary, before going into the next step, if we look at what we've been showing in this trial, first of all, it's a potential for improvement of survival for the patient getting radiation plus NBTXR3 of 23 months that should be compared to the 19 months for the standard of care coming from MDA. In terms of CA19, as we just saw, we got 59% of the patients getting to normalization versus what you could find around 17%, again, coming from the same center. We think altogether we have here a good potential to improve outcomes for patients when we combine R3 to radiation therapy in this patient population. On the top of that, we started exploring some additional biomarkers, like circulating tumor mutational burden. What we have observed, interestingly, is the patients that have an increase of cTMB also have a longer local PFS.
We also have observed the same for overall survival. The proportion of this patient is quite high because 40% of the patients had an increase of cTMB. It is not yet a biomarker that is widely recognized, but very interesting, especially in the context of pancreatic cancer. If you think about cTMB in general, when you look at literature, you'll find that the increase of cTMB could be sometimes associated with improved survival and often linked to an immune response. In pancreatic cancer, we are here in the presence of a very cold tumor, and when you look at TMB at baseline, it is very low. It is a very cold tumor. In our trial, we've seen those 40% of patients having this increase of cTMB post-treatment, which could be an interesting finding.
We're going to continue to study that, continue to look at this biomarker and see how we can use it also in further development, and why not maybe reopening the potential use of ICI in pancreatic cancer thanks to that. In a nutshell, what we have seen in this clinical trial, and we hope to publish those data soon, is the possibility and the feasibility of using NBTXR3 with radiation therapy, and this being proven to be safe and feasible. We also observed a median overall survival of 23 months and an association of CA19 and cTMB with survival of local PFS. Overall, we think the oncologic outcomes are really encouraging, and this really warrants further investigation in a randomized trial.
In parallel, we've been starting a new cohort at MD Anderson, where this time, not only will we continue to do this chemoinduction, but when it comes to radiotherapy, we're going to have a concurrent chemo on the top of NBTXR3. We expect to end the recruitment within the next 12 months, and first patients already have been injected and treated in this trial. In parallel, because of such good results, we're starting exploring potential next steps in pancreatic cancer, and especially in a randomized fashion. Thank you for your attention. Now I'm going to open the floor for question operator.
Thank you so much, dear participants. As a reminder, if you wish to ask a question, please press star 11 on your telephone keypad and wait for your name to be announced. To withdraw a question, please press star 11 again. Please then bow or compile the Q&A roll, so this will take a few moments. Now we're going to take our first question for today. It comes from line of Jonathan Chang from Leerink Partners. Your line is open. Please ask your question.
Hi guys. Thanks for taking the questions. First question, what's the latest status of the ongoing cohort of NBTXR3 plus standard of care chemoradiation in this locally advanced or borderline resectable pancreatic cancer? When might we see data from this combination? Second question, how are you guys thinking about next development steps for NBTXR3 in pancreatic cancer? Thank you.
Thank you, Jonathan. Just as a small recap, this new cohort has been open. The first patient has been treated, and we hope to complete this part within the next 12 months. It does not prevent us in the meantime from starting to look at next steps. Obviously, until things are settled, we can't tell you more about what may come as a subsequent step for pancreatic cancer. I think we have different options here we can directly talk about, starting with either locally advanced cancer patients or borderline resectable or resectable patients. I think there's no efficient situation in pancreatic cancer or treatment that will allow a good outcome for patients.
Now, it's about what kind of design could help NBTXR3 to prove not only that it's working in a randomized fashion in the pancreatic cancer, but also provide significant benefit for the patient for a good demonstration. Definitely, when you think about locally advanced or borderline resectable, those are two populations where we think we could have a good impact for the patient. Promise in due time, we will keep you informed on potential next steps for that. As you may guess, we are running this new cohort, including capecitabine or 5-FU, because that will be a good hint of safety prior to moving to next steps.
Understood. Thank you.
Thank you.
Thank you. Now we're going to take our next question. The question comes to line of Michael Schmidt from Guggenheim Securities. Line, is it open, please ask your question?
Hey, good morning, guys. This is Rosianne for Michael . Two questions for me. I guess, can you help us contextualize the 23-month median OS relative to modern benchmarks such as FOLFIRINOX plus chemoradiation? Secondly, I saw on the poster that two patients had undergone R0 resections. I guess I'm wondering if R3 meaningfully enhances the resectability for the locally advanced patients, or is that result more likely for the borderline resectable cases? Thank you.
Thank you. Let's maybe start with the second question. The patient that got R0 resection, they were unresectable patients, so coming from the locally advanced cancer patients, which is not an usual event to be able to move from unresectable to resectable, especially with such a high rate of pCR or near to complete pathological response, sorry. For the question one, I think in pancreatic cancer, it is important to not only look at the baseline, but also at the dose of radiation that is given. If you look at different papers, you can see that patients that have been able to receive or when we have been able to deliver around 60 Gy or a bit more, then we get better outcome for the patient versus the 50 Gy or 45 Gy.
If we want to compare carefully, the dose given to patients is an important thing. That's also the entire purpose of using NBTXR3 in this population, because as we have seen in the slide where you see the location of the pancreatic cancer with all the surrounding organ, it's very hard to deliver safely such a high dose of radiation. The purpose here is R3, as we know, increase the efficacy combined with radiation. With a safe dose of radiation, we intend to have a good local control. I think the only efficient comparator we could have for this specific trial is the one coming from MD Anderson, because that's the same patient, same standard of care, and treated with the same [audio distortion] most of the time.
The only difference we have in the slide we presented is in the standard of care, most of the patients receive concurrent chemo, which probably had something in terms of efficacy to the patient versus all cohorts that have been only radiation plus NBTXR3.
Thank you so much.
Thank you.
Thank you. Now we're going to take our next question. The question comes to line of David Dai from UBS. Your line is open. Please ask your question.
Great. Thanks for taking my questions. I have two questions as well. Laurent, maybe just talk a little bit more about that, the one DLT related to R3. Can you just help us understand what are the grade 3 DLTs associated with the patient?
Thanks, David. Here, when we talk about the [audio distortion] adverse event, we've seen they haven't been disclosed fully in the poster presented by MD Anderson, but those are the ones we've been showing in the past when we presented the trial. Two were not related to NBTXR3. One could have been related to NBTXR3, but was a transient adverse event. As we always do in every trial, when it's absolute that this cannot be linked to R3, it is not related. When it could be, regardless of the causality, then that's attributed generally as potentially being part of NBTXR3. If you want, David, we can send you offline some details about this specific safety event.
Got it. That's helpful. The second question is related to part one and part two median overall survival. Can you break down the overall survival between part one and part two or provide additional color around that?
Part one and part two were essentially escalation versus expansion, right? There have been only a few patients treated at the lower dose, and most of the patients have been treated at the higher dose of 42% GTV . I mean, it hasn't been presented, but we don't see a significant difference. Or more precisely, there's not enough patients in both parts to see a difference in terms of the few patients that have received low dose versus the ones that have received or the majority that have received higher dose.
Thank you so much.
Thank you. Dear participants, as a reminder, if you wish to ask a question, please press star 11 on your telephone keypad and wait for your name to be announced. Now we are going to take our next question. The question comes to line of Sean Lee from H.C. Wainwright. Your line is open. Please ask your question.
Hey, good morning, guys. Thanks for taking my question. I was just wondering, how was the radiation treatment of 45 Gy over 15 fractions chosen? Considering that you did not reach any DLTs, would you be considering increasing that in the future? Thanks.
Thanks, Sean. It's a good question. I think we've chosen 45 Gy because that's the standard of care given by MD Anderson, and we wanted to be able to stay within this framework. The entire purpose here is if we can deliver a safe dose of radiation with NBTXR3 and produce some benefit, then I think we'll stick to that. Now, there's always a possibility to go for higher dose, again, providing benefit with subtoxic dose of radiation could be more beneficial for those patients. For now, this is not settled yet for potential first step.
Great. Thanks for that.
Thank you. Now we're going to take our next question. The question comes from the line of Clémence Thiers from Stifel. Your line is open. Please ask your question.
Hi. Thanks for taking my question. The first one is on biomarkers. For the first moment, we're looking at them after treatment. Would there be any way to target patients that are more likely to have high cTMB or normalized CA19-9 before we see the end of the treatment? The second one, sorry, if it's redundant. You mentioned exploring next step while the new cohort is ongoing. Why not wait for the end of this cohort before moving on to phase II? Logically, it should be more efficient, and there are not much safety concerns with NBTXR3. Why not wait, basically? Thanks.
Thanks, Clémence. To answer your first question, when we measure the CA19 or cTMB or other biomarker, obviously, we take the baseline and then measure it after treatment. That's how we determine the increase or the decrease. So far, we did not find a biomarker at baseline that could be a predictor of patients that will respond or not. When you look at the spread of CA19, it goes all over the place, and patients are normalized with no specific indication at baseline of who could respond. Same for cTMB. We continue to investigate. We have tissue samples, and MDA has an extensive biomarker work in general and specifically for this trial. That is something we continue to dig in. Obviously, we'll continue to do in the ongoing cohort.
Now, to my comment about we don't need necessarily to wait the end of this new cohort. There's twofold in that. First, this new cohort is ongoing and should finish in a not too distant future. If we want to design something, potential trial as a next step, we'll have time to see what's happening for those patients before moving into any potential further steps. It's more sequence than not waiting for data.
Okay. If I can have one last question, I don't know if you can answer, but could the next trial be pivotal, the phase II, or would you have to go for a phase III afterward?
Nothing we can answer at that time.
Okay. Thank you.
Right, Clémence. Thank you.
Thank you. Dear participants, as a reminder, if you wish to ask a question, please press star 11 on your telephone keypad and wait for your name to be announced. Dear speakers, we'll just give a moment to our analysts. Once again, if you would like to ask a question, please press star 11. There are no further questions for today. I would now like to hand the conference over to the management team for any closing remarks.
Thank you very much. Thank you, everyone, for being here today. Stay tuned for our next piece of information. Always happy to talk and interact with you. Feel free to reach us offline if you need more precision or anything you would like to discuss with us. Thank you very much, and I wish you a very good day and end of the week.
This concludes today's conference call. Thank you for participating. You may now disconnect. Have a nice day.