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

Good day, and thank you for standing by. Welcome to the Nanobiotix New Results in patients with Refractory Melanoma conference call. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Joanne Choi. Head of U.S. Investor Relations. Please go ahead.

Thank you, Heidi. Good afternoon, and good morning. Thank you for joining Nanobiotix conference call to discuss new data from the third cohort of our Phase I 1100 study in melanoma presented at the Immunorad conference yesterday in Paris. Joining me on the call today is Laurent Levy, our Co-Founder and Chief Executive Officer. Today's call is being webcast and will be available on our website for replay. Before we begin, I would like to remind you that this call will include forward-looking statements within the meaning of securities laws. These forward-looking statements are based on current information, assumptions and expectations and are subject to significant risks and uncertainties that could cause the company's actual results, including progress and timing of planned research and clinical development to differ materially from our current expectations. We encourage you to 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. 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. Thank you. With that said, I will now turn the call over to Laurent. Please go ahead.

Thank you, Joanne. So good morning, good afternoon, everyone. We are very happy to have you on this call to present the latest data we have generated in our trial 1100. Those data have been presented by Dr. Jason Chan from UCSF. Maybe before jumping right away in those data, I just would like to remind a few basics about our product NBTXR3 or JNJ-1900. We're here to talk about a product that is dedicated for patients receiving radiation therapy, which is the vast majority of cancer patients, around 60%. And those patients, they usually get their radiation therapy right after the diagnosis when they still have a local disease. And that's where the biggest development is about NBTXR3, that's where the biggest market is, that's where the biggest unmet medical need is. Nevertheless, we think we should continue to help patients across the different line of treatment, and that's one of the purpose of this trial, 1100, to go and help patients after they have received several lines of treatment when they fail them to see if we can rescue those patients. So that's the entire purpose of the trial that has 3 cohorts, 2 about head and neck. We'll talk about that later, but not today. Today is about the cohort #3, where a vast majority of melanoma cancer patients have been recruited post-failure of multiple lines of treatment. So that will be a focus for today and the call for now. So we know that melanoma has been very impacted by immune checkpoint inhibitors. Nevertheless, if there is a large number of responders, you can usually see over time that you will have relapse and resistance in around 50% primary and 25% secondary resistance. So there's a large part of patients having melanoma that need further line of treatment post-failure of PD-1 and other line of treatment. Usually, post-failure, you see that those patients, they have a low response rate or low control of disease that goes -- is also a low survival in average for those patients. So this is a trial that is ongoing, and we expect to get more patients in this cohort that will be presented when completed. But for now, we've been able to recruit and treat 21 patients, among which 19 are today evaluable for efficacy, and we are still waiting the two last ones that have been injected to join the '21 cohort as being fully evaluated in terms of efficacy. But as you can see, we've had a majority like around 50-50 of advanced patients, Stage 3 and Stage 4. First of all, safety. We've seen the usual safety about the use of NBTXR3. If you look at the left table, you see the overall safety table and adverse events that have been observed that include radiation therapy as such, PD-1, the injection of NBTXR3 or NBTXR3. On the right table, you see the specific adverse events that have been related to NBTXR3 and for injection. As a first thing, we had no grade 4 or 5 adverse events related to the product or the injection and no serious adverse event. And we don't see any specific adverse events versus what has been observed previously in other trials or in the 1,100 other cohorts, including head and neck patients. So let's go into some of the baseline of those patients. As I mentioned in the intro, those patients received different lines of treatment, and they have all failed PD-1. But when you look at the details of the patients we've been treating, not only they failed PD-1, but for most of them, they fail multiple lines of treatment. You see on this table patient by patient, the line of treatment they got and the fact that they all have progressed under all lines of treatment. So you'll hear in presence of a population that is really at the end of what the therapeutic options today could offer them. So we've been observing when you look at the change from baseline for all target lesions, a good response, as you can see in the waterfall plot, but I think we can directly jump and go into the RECIST evaluation overall for those patients. So what you can see here is a split between the patient having 1 to 4 lesion and 5-plus lesion. And the overall response we've been seeing is 47%, so 9 out of 19 patients got CR or PR. That includes also 4 CR that is important globally across local and systemic treatment. And we've seen a high disease control rate of 78% globally. What you can see if you look at the left of the table is that, obviously, when you have an oligomide patient, you have better response than when you have a patient that have 10, 15 different mets, most likely because the disease being spread into a lot of organ. It may be a bit too late to have those patients. Nevertheless, we still have a DCR with 5-plus lesion of 80% and a decent local control. Now if we look back at what we have been seeing, which is patient by patient, the different line of treatment, I think it's interesting to see that we got a number of responders. And not only in the patients that are primary refractory or only got PD-1, as you can see, for example, there are 4 patients that have received several lines of treatment, including T-VEC, and we got 2 CR and 2 PR out of it. And many patients that got multiple line of treatment got either stabilization of partial response or complete response. So what we can see here is we could help patients regardless of the number of line of treatment they got, meaning that we have a mode of action or do provide something that makes it compatible regardless of the previous treatment they have received. Another interesting finding here, we've been looking at the correlation between injected irradiated lesion and what's happening from a systemic perspective for those patients. So as you can see on this picture, the blue dots are the injected irradiated response and the dark dots are the non-injected non-irradic out of the field response. And you can see there is a tendency showing that the deeper is the response for the primary or injected tumor, the higher is the response for the overall patient, including outside of field response. So clearly, as per our PI comment, this reflects the potential priming of an immune response by NBTXR3 activated by radiation. Thinking that we're still talking here about refractory patient checkpoint inhibitor and most of them have exhausted the primary possibility to have an immune response. So now let's move to what could be the impact. Obviously, it's a bit early. So we're still waiting the OS to mature. But to date, we have 14.6 months median overall survival with an interval confident going from 11.6% to non-bridge. So we're keen to wait and see how it is going to move over time with maturation of this. I would like now to show you one patient. We have different patients, we could, but we choose that one because it's a particular patient that is interesting. So beside the patients that got CR from an overall response or PR from an overall response, as you can see in some of the previous slides, we've seen some patients with stable disease. And I'm going to present you one of those patients. So this is a patient that received multiple treatment and failed multiple treatment. As you can see on the left, you see the PET scan with a very active tumor, and this patient got pembrolizumab, ipilimumab, radiation therapy and also many other treatment. So here, we show you at the time of radiation therapy, this patient has this tumor, did receive radiation therapy, 40 gray in 10 fraction. And as you can see, 6 weeks post radiation therapy, there was no impact on the tumor. So after failure, all of this treatment, this patient joined the trial. And as you can see, the tumor has grown in a much bigger tumor with a very active tumor. And we've been treating this patient after an injection of NBTXR3 with 35 gray in 5 fraction. And what you can see here is a patient with a completely inactive tumor from a metabolic perspective. So this patient then as a stable patient for 19 months now is a patient where you can see that there is an activity after the treatment, showing that the tumor had completely -- a complete metabolic response. And as I mentioned, this patient is now for follow-up and still have stable disease from a systemic perspective after 19 months. Now just before opening the question, I just would like to conclude with what we have seen. First of all, we and our MDs are very happy about the outcome of this trial, showing again in another trial that we could offer option not only frontline, but after several lines of treatment option for patients they don't have today. We've seen that the injection is feasible and safe, and we have reached the maximum dose as per protocol definition. There was no specific adverse events that we can relate on, and we've seen a promising local and systemic control. So overall, 47% response and a DCR of 78%. Even early, the first readout on OS that will mature over time led us to 14.6 months. So we think with our PIs that these results are very interesting and really open the road for NBTXR3 to be tested in a randomized trial for this patient population. So with that, I'm going to open the floor for questions. Thank you.

[Operator Instructions] We will take our first question. And the question comes from the line of Jonathan Chang from Leerink Partners.

This is [ Ewan ] on for Jonathan. Congrats on the data. My first question is how should we be thinking about the single-agent activity of NBTXR3 activated by radiation in this melanoma cohort. And a follow-up, if I may, what is your plan for development in this indication given the data we've seen today? And would it be necessary to demonstrate the contribution of components in a registrational trial?

Thank you for the question. So first of all, about the single activity. So that's obviously not the only trial we have with NBTXR3, and there's many ways to look at the single activity of the product, including the randomized trial we have ongoing like in head and neck, but also in lung cancer, where we compare standard of care, including radiation plus the same thing for the tested arm with the product. So here, we can clearly delineate what is the single-agent activity. Now within this trial, particularly, what we can rely on is the local control of this product. So if you remember Slide 10, there is a right column explaining the injected irradiated response. And here, we have 100% of DR -- with no patient that had PD with this. So it does show that when we inject NBTXR3, even with a low dose of radiation, here, we're talking about 35 to 45 gray depending on the organ that is injected, we can have a strong control. So that's step one. And this local control is also what we want to emphasize when we work frontline with patients that receive radiation like in head and neck or lung or prostate or breast cancer and so on. But here, that's a fundamental to have both. First, local control; and two, to have potentially for patients that failed checkpoint kind of a repriming of an immune response, which we start to see. When we look at the link we've been showing between the local response and the systemic response for those patients. So that's, I think, for the single activity. For the contribution of component, that's always a good question and depending on the setting. So if we think about moving forward in a randomized trial in this population, that will open the question of what is the control arm as there is no specific standard of care for those patients. It's best choice of treatment or whatever the physician thinks could be appropriate. When you look at those patients, they have received several lines of treatment. So they pretty much have exhausted for most of them any other possibility. So the real -- in real life for those patients, that will be almost nothing or any palliative care that the doc could give the patient. So in a nutshell, I think between trials, because of the mode of action of the product, we could have cross read in terms of contribution of components. But of course, in any case, this in future trial would have to be discussed with FDA and other regulatory agencies, but we think that could be easily achievable. Now in any case, when we move forward in such indication, a randomized trial could be appropriate to show the benefit overall to the patient because it's a complex population and not always easy to define with a single arm, what is the real outcome for the population.

Your next question comes from the line of Michael Schmidt from Guggenheim.

This is Ruoxi on for Michael. Congrats on the impressive data here. So a couple of bigger -- bigger picture questions for me. So it sounds like for future and next steps, you would primarily be considering kind of developing this for the late-line setting once other options are exhausted. I guess do you also see a place for R3 in an earlier setting for cutaneous melanoma? And then secondly, just thinking about pipeline prioritization and next steps, I guess, would this be something that you would develop yourself? Or would J&J kind of develop this further as part of the collaboration?

Thank you. Well, when it comes to different line of treatment, let's say, for melanoma, obviously, it's a quite different disease than head and neck or lung. But in melanoma precisely, it is sure that if we could have an action at the beginning of the disease and not wait the patient to fail multiple lines, we should potentially get a much better outcome than what we see here. But when you look at the current standard of care, that will also open and require a trial which is much bigger and much longer. So there is the patient need and the regulatory pathway we could, if we want take for this population. But we have observed something in this trial is when you have patients with 15 mets or more and that this is already spread into multiple organ with fast growing, it's a bit late to get an action that could be beneficial for the patient. But this is going too fast. Whereas for patients that have multiple mets, it works unless it's really spread across the whole body. So that's obviously favor to go in earlier line to bring that treatment. Two, your question is about priority and how we could envisage the development more globally across different indications. This one included when we think about J&J's work versus what NANO could do. So maybe broadly, let's go back to the overall strategy. Because this product has a physical mode of action and is not specifically targeting any biological target, we've had a different approach for the development, not going from Phase I to Phase II to Phase III for each indication, but more having 1 or 2 indications going forward with randomized data, which is the ongoing Phase III in head and neck cancer and the ongoing Phase II in lung Stage III, both now run by J&J. And when we get enough data coming from this, we're going to use all the Phase I that have been done showing feasibility, safety and first good sign of efficacy as a potential start for other registration trial. So it doesn't mean that we will move all those indications or J&J will move all those indications into Phase III, but I think we have been establishing a very large base for NBTXR3 to be usable in many indications in oncology. And as there are many discussions with J&J at the moment, we will, in due time, and hopefully not too late from now, tell you more about what could be the next step in the development of NBTXR3.

And the next question comes from the line of Clemence Thiers from Stifel.

Two on my side. First one is, obviously, the lower the number of metastases, the better is the response. First, is there any other factor or baseline characteristics you identified as playing a role in the response? And how would that potentially impact the future pivotal trial? Would you focus on earlier stage of metastatic melanoma. That's the first one. And the second one is, we know that there is some differences in mechanism of primary and secondary resistance to anti-PD-1. Would we expect or did you observe in the trial, any difference in response between the two?

Thank you. Maybe let's start about the primary versus refractory question. So obviously, here, we have a small number of patients, and the trial has not been designed to answer this question. But I think we can also be informed by the other cohort of the 1100, which has much more patients in head and neck. And when we look at the patient being primary or secondary refractory, we don't see differences regardless of being in melanoma or head and neck cancer patients. And I think that's an interesting thing when you mentioned that the mode of action is different and so on. And that's really, I think, one of the key advantage of using NBTXR3 in setting is because regardless of the patient, the lines of treatment, we know we're going to bring high local control. And for a number of patients, we start seeing that we can bring repriming or priming of an immune response that was not existing. So that's a broad applicability. And we don't see right now, to come back to your first question about baseline, is there anything that we could use to select the patient? So far, the HPV status in head and neck or the PD-1 expression or the fact that the patients have received one line or several line of treatment was not influential in the outcome we have observed. But I think that's interesting when you look at one of the slides we've been presenting with all lines of treatment, is that we could expect that the more patients have received treatment, the less they will be willing to respond to a new treatment, what we see usually. But it's not the case here. Even for patients that received 3, 4 or 5 treatment, we get a good number of PR or CR globally for those patients. So for now, but of course, going further in the development, we will refine this question, but that's really a patient agnostic and so far baseline agnostic product.

Your next question comes from the line of Swayampakula Ramakanth from HCW.

Congratulations, Laurent and team. I think this is pretty good data for these advanced melanoma patients. So just to understand a little bit more about the CR and PR, can you -- is there any trend among the patients that achieved a CR versus a PR? And the other question is, how should we think about metastatic tumors in other organs, who are also in that cohort 3? How should we think about -- or what should be our expectations regarding data in those additional tumors?

Thanks. So for the second question first, this trial initially, the Cohort 3 has been designed to take any primary tumor that will be resistant to PD-1 to start exploring other organ other tumor. But rapidly, there have been a good number of melanoma patients and seeing the first results, the PI of the trials are really focused on melanoma cancer patients. So the remaining patients for this trial will be mainly melanoma patients, and we'll have only a few having other type of tumor. So of course, they will be included in all the safety and feasibility assessment. But given the small number we will have in other tumor, I don't think we could extrapolate anything from it. But that may be the occasion to look at other type of cancer that have metastases that we could help. RK, I'm not sure I got your first question. about the response and the CR. What do you want to know exactly?

Is there any trend among patients who achieved a CR versus a PR?

Okay. Like anything differentiate them or in terms of baseline or outcome and long-term outcome? No, not at this stage. We'll be looking at the detail. But again, that's still a small number of patients. And the trial has not been designed with TAT. So we could look at different type of baseline for patients. But so far, in this trial, like in head and neck 1100 trial, we don't see really anything from baseline that could help us to differentiate patients either predict CR or PR or influencing the outcome of the response.

One additional question is on the study that MD Anderson is doing, again, in metastatic melanoma who have progressed beyond anti-PD-1. So how about -- what could be the read-through for that study? And do you know when they could -- that data would come out?

The NDA is not working on melanoma per se. They have trials where they have effectively refractory patients to PD-1 was a different population than melanoma.

Your next question comes from the line of Lucy Codrington from Jefferies.

Only a few left. Just a clarification to begin with the overall survival of 14.6 months. I think on the slide, the confidence intervals are slightly different to that on the press release, and it seems like it wasn't reached on the slides, but I think it said 16.7 months at the upper end on the press release. So just to clarify that. And then I appreciate it might not be possible, but is there any way to contextualize that overall survival compared to what you might expect in this population? May not be probable, but it would be helpful. Thank you.

Thank you. And we'll look at it about the table. But it's correct number 11-point something up to non-rich. That's the interval confidence. So again, for patients that have received multiple line of treatment, there's no specific definition of how you could look at OS and PFS or response, but there are a few references that show, for example, that after failure of PD-1 when patients take EP or a mix of EP plus nivo or BRAF or MEK, they have an overall median survival of 6.8 months. We also have some oncolytic virus that could provide additional benefit post-failure, where the survival could go up to 14 or 13-point-something months with a response rate around 30%. But again, having direct comparison with last-line patient treatment, it's very complicated. But when you look, for example, of the PATRINAVY and our trial, where they have been trying many things like EP plus nivo or BRAF plus MEK, there is almost no CR for those patients. So again, if you want to have a potential of really improving the life for those patients, getting through CR is an important thing and getting to long duration of response is an important one. And when you look at the median survival in this paper, we have 6.8 months.

Got it. And then just one follow-up on the safety. So the episode of hypertension and fluidic pain, that was a Grade 3 event. I'm just quite confused by the Grade 3 plus. So I know you said nothing to do with the injection for Grade 3, 4 or 5, but just to confirm that it was a grade 3 event.

Yes, that's a great 3. There was no grade 4, 5 linked to the product or the injection procedure.

Your next question comes from the line of Chiara Montironi from Van Lanschot Kempen.

This is Chiara Montironi from Kempen. Congratulations with the data. So just going back to NBTXR3 clinical development. I was wondering how will this data inform the next step for the development, maybe a combo development? Is this all in the end of J&J or which factors do you think will be determining the choice of further developing in this indication? Could this expand the case beyond head and neck?

Sure. Thanks for the question. So first of all, we can't talk for our partner. But as I mentioned sooner in the call, there are many discussions to see how to move forward in the development beyond what is known by the market today, and we will inform you in due time as soon as we can. But more broadly, I think there are indications that J&J would or could take to move forward as Nanobiotix could also because in the contract we've been signing with them, there is a specific section and specific reward to that if Nanobiotix will do some trial beyond what J&J wants to do. But that's a part. I think we should go back to fundamentals. I think going frontline treatment for patients, when radiation therapy is used for local control, which is the vast majority of the millions of patients getting radiation, here, the clear goal is to get much better local control. Like if you think about head and neck, frontline treatment, the majority is about local control, 90%. And here, radiation is playing a key role. But 60% of those patients will fail over time and eventually, we'll go to PD-1 and other treatment. So here doesn't need to get better control. And in head and neck, if you want to cure a patient, you need to get to a strong local control, possibly including CR. If not, the patient will eventually die from local invasion or development, and it's very hard to treat such a patient as we can see in head and neck. So frontline will be NBTXR3 as such. Now when we move to further line, that's a different thing, and that really depends on the population of patients and what is available for them. We can see in melanoma that you could use some oncolytic virus, for example, that could be interesting to have the patient but the oncolytic virus will work from another angle that NBTXR3. So we could combine and get a much bigger outcome for the patient or use that as a single agent. If you think about head and neck metastatic patient, even the last line of treatment, again, you see some bispecifics and some new treatment that could help the patient, but they are not enough to cure the patient. And for head and neck, there's always a need to have local control regardless of the systemic control you can provide. So again, you could either choose to have this modality to any other systemic treatment and combine better outcome. And because of the local aspect of this product, we should not expect to have large combined toxicity because we're really combining a local agent with a potential systemic agent. So we see that as a product that could be used in many situations offering first local treatment, then in some patients, offering a potential to prime or reprime an immune response. So that offer multiple possibilities and multiple potential combo.

[Operator Instructions] Your next question comes from the line of David Dai from UBS.

I also want to congrats on the data here. So a couple of questions from me. So Laurent, I know you didn't present the progression-free survival data in this data set. I'm just curious, can you share some preliminary analysis on progression-free survival aspect of the data analysis? So that's the first question. And second question just around how should we think about this data be able to read through to the NALORAE-312 trial in the locally advanced head and neck cancer. I understand that the data should be expecting in first half next year. So any kind of read-through from this data set into that data set here?

Okay. Thanks, David, for the question. We did not present the PFS just because of the size, but we have to date a 6.3 months median PFS for this trial. And of course, as the OS, it has to matter, but it's quite consistent with what we see between PFS response and OS. Now about the question about read-through, I think it's really 2 different populations. So it's very hard to look at what happened in melanoma and try to expand into head and neck, neither from a local perspective in head and neck or metastatic perspective in head and neck. What we can say is in this indication, like we have seen in others, there is a very strong close to 100% local control. So the only thing we could read is we have a strong local control when we inject NBTXR3 and use radiation to activate it. And that's what the 312 is about, having a strong local control. But besides, I don't think there's much to read through. Now from a metastatic perspective, I think as we know that there is different tumor mutational burden or hotness of the tumor depending of the characteristic of the tumor and the nature of the disease. If we want to get in order, we can think that melanoma is the hottest tumor than lung, then head and neck and some others. So here, it's about what the capability potentially of the product to prime an immune response when there is no immune response at baseline or to reprime an immune response. But that's a complex question, that will require further study to look at it. Because if we look across studies where we've been treating metastatic patients, or patients like with pancreatic cancer, we see clearly some activation of the immune system, one way or the other. But it's hard to see because this is a new modality to link that to any specificity of the tumor. But I think when we have enough patients, we will be able to explore that point and see if the priming of an immune response could be better or less better in some patients, depending on their characteristics. But I think that's for later. And again, when we look at where the patient need is, front-line treatment, follow co-treatment, that's where the millions of patients need radiation therapy and where we could have the biggest impact.

Got it. That's really helpful. And then just maybe another question on the timing for development for this in the melanoma setting, the randomized trial. Any thoughts around when should we -- when are you planning to start the randomized trial? Any kind of preliminary thoughts around the development time line would be helpful.

So for now, as I mentioned, we can't say anything about further trial, even though we're discussing that with our partner and we'll inform the market as soon as possible. Nevertheless, this trial is still ongoing, right? So we need to finish our equipment, which we expect to complete within the next few months to get more patient and also to have broader readout with this larger number of patients. And based on that, then if we want to move forward or J&J wants to move forward, we could design more efficiently a trial to get to next step in melanoma.

There are no further questions. I would like to hand back for closing remarks.

Well, thank you, everyone. Thank you for the very active discussion. And again, we're really happy to have brought that to you this new data. And let's keep posted. We have much more to come in the not-too-distant future. Thank you very much. I wish you a lovely day and talk to you soon.

This concludes today's conference call. Thank you for participating. You may now disconnect.