Okay, and thank you for standing by. Welcome to the Nanobiotix new results in patients with refractory melanoma conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star one, one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one, one again. 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 US Investor Relations. Please go ahead.
Thank you, Heidi. Good afternoon and good morning. Thank you for joining the 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 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 your 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. 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 into the data, I just would like to remind a few basics about our product NBTXR3, or KMJ 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%. Those patients usually get their radiation therapy right after they're diagnosed when they still have a local disease. 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 lines of treatment.
That's one of the purposes of this trial 1100, to go and help patients after they have received several lines of treatment when they failed them, to see if we can rescue those patients. That's the entire purpose of the trial that has three cohorts, two about head and neck. We'll talk about that later, but not today. Today is about the cohort number three, where a vast majority of melanoma cancer patients have been recruited post failure of multiple lines of treatment. That will be the focus for today and the call for now. 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.
There's a large crowd of patients having melanoma that need further lines of treatment post failure of PD-1 and other lines of treatment. Usually, post failure, you see that those patients have a low response rate or low control of disease that goes with also a low survival in average for those patients. This is a trial that is ongoing, and we expect to get more patients in this cohort that will be presented when completed. For now, we've been able to recruit and treat 21 patients, among which 19 are today evaluable for efficacy, and we're still waiting on the two last ones that have been injected to join the 21 cohorts as being fully evaluated in terms of efficacy. As you can see, we've had a majority, like around 50-50 of advanced patients, stage III and stage IV. 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/or injection. As a first thing, we had no grade four or five adverse events related to the product or the injection and no serious adverse events. We don't see any specific adverse events versus what has been observed previously in other trials or in the 1100 other cohorts, including head and neck patients. Let's go into some of the baselines of those patients. As I mentioned in the intro, those patients receive different lines of treatment, and they have all failed PD-1.
When you look at the details of the patients we've been treating, not only have they failed PD-1, but for most of them, they failed 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. You're here in the presence of a population that is really at the end of what the therapeutic options today could offer them. 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. I think we can directly jump and go into the resistance evaluation overall for those patients. What you can see here is a split between the patient having one to four lesions and five plus lesions. The overall response we've been seeing is 47%.
Nine out of 19 patients got CR or PR. That includes also four CR, that is important globally across local and systemic treatment. 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 oligomet patient, you have a better response than when you have a patient that has 10, 15 different mets, most likely because the disease has been spread into a lot of organs. It may be a bit too late to have those patients. Nevertheless, we still have a DCR with five plus lesions of 80% and a decent local control. If we look back at what we have been seeing, which is patient by patient, the different lines of treatment, I think it's interesting to see that we got a number of responders.
Not only the patients that are primary refractory or only got PD-1, as you can see, for example, there are four patients that have received several lines of treatment, including TBEC, and we got two CR and two PR out of it. Many patients that got multiple lines of treatment got either stabilization or partial response or complete response. What we can see here is we could help patients regardless of the number of lines 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 lesions and what's happening from a systemic perspective for those patients.
As you can see on this picture, the blue dots are the injected irradiated response, and the dark dots are the non-injected, non-irradiated out-of-the-field response. 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. Clearly, as per our PI comments, this reflects the potential priming of an immune response by NBTXR3 activated by radiation. Thinking that we are still talking here about refractory patients with checkpoint inhibitors, and most of them have exhausted the primary possibility to have an immune response. Now let's move to what could be the impact. Obviously, it's a bit early, so we're still waiting for the OS to mature. To date, we have 14.6 months median overall survival with a confidence interval going from 11.6 to non-reach.
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. Besides the patient 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. I'm going to present you one of those patients. This is a patient that received multiple treatments and failed multiple treatments. As you can see on the left, you see the PET scan with the very active tumor. This patient got pembrolizumab, ipilimumab, radiation therapy, and also anemia, many other treatments. Here we show you at the time of radiation therapy, this patient has this tumor.
The patient did receive radiation therapy, 40 Gy in 10 fractions. As you can see, six weeks post-radiation therapy, there was no impact on the tumor. After failure of all of this treatment, this patient joined the trial. As you can see, the tumor has grown into a much bigger tumor with a very active tumor. We've been treating this patient after an injection of NBTXR3 with 35 Gy in 5 fractions. What you can see here is a patient with a completely inactive tumor from a metabolic perspective. This patient then had 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 a complete metabolic response. As I mentioned, this patient is now for follow-up and still has stable disease from a systemic perspective after 19 months.
Just before opening the question, I'd 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 options not only frontline, but after several lines of treatment, options 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 of the physician. There was no specific adverse event that we can relate on. We've seen a promising local and systemic control. 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.
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. With that, I'm going to open the floor for questions. Thank you.
Thank you. As a reminder, to ask a question, you will need to press star one, one on your telephone and wait for your name to be announced. To withdraw your question, please press star one, one again. We will take our first question. The question comes from the line of Jonathan Chang from Lierinc Partners. Please go ahead. Your line is open.
Hey, this is Ewan Allen for Jonathan. Thanks so much for taking our questions and 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? A follow-up, if I may, which is, what is your plan for future development in this indication given the data we've seen today? Would it be necessary to demonstrate the contribution of components in a registrational trial? Thank you.
Thank you for the question. First of all, about the single activity. That's obviously not the only trial we have with NBTXR3. There are 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. Here we can clearly delineate what is the single-agent activity. Within this trial particularly, what we can rely on is the local control of this product. If you remember slide 10, there is a right column explaining the injected irradiated response. Here we have 100% of disease control rate with no patient that had PD with this.
It does show that when we inject NBTXR3, even with a low dose of radiation, here we're talking about 35 to 45 Gy, depending on the organ that is injected, we can have a strong local control. That's step one. 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. Here, that's fundamental to have both. First, local control, and two, to have potentially for patients that fail 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. That's, I think, for the single activity. For the contribution of components, that's always a good question.
Depending on the setting, 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 the 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. They pretty much have exhausted for most of them any other possibility. In real life, for those patients, that would be almost nothing or any palliative care that the doc could give the patient. 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. Of course, in any case, this in future trial would have to be discussed with FDA and other regulatory agencies.
We think that could be easily achievable. 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.
Got it. Very helpful. Thank you.
Thank you. We will take our next question. Your next question comes from the line of Michael Schmidt from Guggenheim. Please go ahead. Your line is open.
Hey, good morning, guys. This is Rose Dionne from Jefferies. Thanks for the question. Congrats on the impressive data here. A couple of bigger picture questions from me. It sounds like for future next steps, you would primarily be considering kind of developing this for the late line setting once other options are exhausted. Do you also see a place for NBTXR3 in an earlier setting for cutaneous melanoma? Secondly, just thinking about pipeline prioritization and next steps, would this be something that you would develop yourself or would Janssen kind of develop this further as part of your collaboration?
Thank you. When it comes to different lines of treatment, let's say for melanoma, obviously, it's a quite different disease than head and neck or lung. In melanoma precisely, it is sure that if we could have an action at the beginning of the disease and not wait for the patient to fail multiple lines, we should potentially get a much better outcome than what we see here. When you look at the current standard of care, that will also open and require a trial which is much bigger and much longer. There is the patient need and the regulatory pathway we could, if we want, take for this population.
We have observed something in this trial: when you have patients with 15 mets or more, and the disease has already spread into multiple organs with fast growing, it's a bit late to get an action that could be beneficial for the patient. The disease is going too fast. For patients that have multiple mets, it works unless it's really spread across the whole body. That's obviously favorable to go in earlier line to bring that treatment. Your question is about priority and how we could envisage the development more globally across different indications, this one included, when we think about Janssen's work versus what Nanobiotix could do. 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 targets, we've had a small different approach for the development, not going from phase one to phase two to phase three for each indication, but more having one or two indications going forward with randomized data, which is the ongoing phase three in head and neck cancer and the ongoing phase two in lung stage III, both now run by Janssen. When we get enough data coming from this, we're going to use all the phase one that have been done showing feasibility, safety, and first good sign of efficacy as a potential spot for other registration trials.
It doesn't mean that we will move all those indications or Janssen will move all those indications into phase three, but I think we've been establishing a very large base for NBTXR3 to be usable in many indications in oncology. As there are many discussions with Janssen 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.
Great, thanks so much.
Thank you.
Thank you. We will take our next question. The next question comes from the line of Clemens Diaz from Stifel. Please go ahead. Your line is open.
Hi. Thank you for taking my question and congrats on the results. 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 characteristic you identify as playing a role in the response, and how would that potentially impact a future pivotal trial? Would you focus on earlier stage of metastatic melanoma? That's the first one. The second one is, we know that there are some differences in the 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.
Thank you, Clemens. Maybe let's start about the primary versus refractory question. Obviously, here we have a small number of patients, and the trial has not been designed to answer this question. I think we can also be informed by the other cohort of the Phase I 1100 study, which has much more patients in head and neck. 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. I think that's an interesting thing when you mentioned that the mode of action is different and so on. That's really, I think, one of the key advantages of using NBTXR3 in such a setting because regardless of the patient, the lines of treatment, we know we're going to bring high local control.
For a number of patients, we start seeing that we can bring a repriming or priming of an immune response that was not existing. That's a broad applicability. 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 lines of treatment was not influential in the outcome we have observed. I think that that's interesting when you look at one of the slides we've been presenting with all lines of treatment, that we could expect that the more patients have received treatment, the less they will be willing to respond to a new treatment, which is what we see usually. It's not the case here.
Even for patients that receive three, four, or five treatments, we get a good number of PR or CR globally for those patients. For now, going further in the development, we'll refine this question. Actually, a patient agnostic and so far baseline agnostic product.
Okay. Perfect. I'll ask the question again when we have more data, then. Thank you so much.
Thank you, Clemens.
Thank you. We will take our next question. Your next question comes from the line of Swayam Pakula from H.C. Wainwright. Please go ahead. Your line is open.
Thank you. Congratulations, Laurent, and team. I think this is pretty good data for these advanced melanoma patients. Just to understand a little bit more about the CR and PR, is there any trend among the patients that achieved a CR versus a PR? The other question is, how should we think about the metastatic tumors in other organs who are also in that cohort three? How should we think about, or what should be our expectations regarding data in those additional tumors?
Exactly. For the second question first, this trial initially, the cohort three has been designed to take any primary tumor that will be resistant to PD-1 to start exploring other organs, other tumors. 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. The remaining patients for this trial will be mainly melanoma patients and will have only a few having other types of tumors. They will be included in all the safety and feasibility assessments. Given the small number we will have in other tumors, I don't think we could extrapolate anything from it. That may be the occasion to look at other types of cancers that have metastases that we could help. AK, 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 achieve a CR versus a PR?
Okay. Anything different with them in terms of baseline or outcome and long-term outcome?
Yeah.
No, not at this stage. We've been looking at the detail. That's still a small number of patients, and the trial has not been designed with stratification, so we could look at different types of baselines for patients. So far, in this trial, like in the head and neck Phase I 1100 study, we don't see really anything from baseline that could help us to differentiate patients, either predict complete response or partial response, or influencing the outcome of the response.
Thanks for that. One additional question is on the study that MD Anderson is doing, again, in metastatic melanoma who are progressed beyond anti-PD-1. What could be the read-through for that study? Do you know when that data could come out?
The NDA is not working on melanoma per se. They have trials where they have effectively refractory patients to PD-1, but it's a different population than melanoma.
Okay. Thank you.
Thank you, AKAID.
Thank you. We will take our next question. Your next question comes from the line of Lucy Codrington from Jefferies. Please go ahead. Your line is open.
Hi. Thank you for taking my questions. Any of you left? Just a clarification to begin with. The overall survival of 14.6 months. I think on the slides, the confidence intervals are slightly different to that on the press release. 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. Just to clarify that. 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? It may not be possible, but it'd be helpful. Thank you.
Thank you. We'll look at it about the table. It's a correct number, 11 point something up to non-rich. That's the confidence interval. For patients that have received multiple lines of treatment, there's no specific definition of how you could look at OS and TFS or response. 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 MEC, they have a median overall 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%. Having direct comparison with last-line patient treatment is very, very complicated.
When you look, for example, at the patronage and our trial, where they have been tried in many things like EP plus Nivo or BRAF plus MEC, there is almost no complete response for those patients. If you want to have the potential of really improving the life for those patients, getting to complete response is an important thing, and getting to a long duration of response is an important one. When you look at the median survival in this paper, we have 6.8 months.
Got it. Just one follow-up on the safety. The episode of hypertension and pleuritic pain, that was a grade three event. I'm just slightly confused by the grade three plus. I know you said nothing to do with the injection for grade three, four, or five, but just to confirm that it was a grade three event.
Yes, that's a grade 3. There was no grade 4 or 5 linked to the product or the injection procedure.
Perfect. Thank you.
Thank you.
Thank you. We will take our next question. Your next question comes from the line of Chiara Monteroni from Van Lanschot Kempen. Please go ahead. Your line is open.
Hello, team. This is Chiara Monteroni from Kempen. Thanks for taking my question and congratulations with the data. 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 Johnson & Johnson, or which factors do you think will be determining the choice of further developing in this indication? Could this expand the case beyond the head and neck?
Sure. Thanks for the question. First of all, we can't talk for our partner. 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. We'll inform you in due time as soon as we can. More broadly, I think there are indications that Janssen 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 trials beyond what Janssen wants to do. That's a part. I think we should go back to two fundamentals.
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. If you think about head and neck, frontline treatment, the majority is about local control, 90%. Here, radiation is playing a key role. 60% of those patients will fail over time and eventually will go to PD-1 and other treatments. There's a need to get better local control. In head and neck, if you want to cure patients, you need to get to a strong local control, possibly including complete response. If not, the patient will eventually die from local invasion or will develop mets, and it's very hard to treat such a patient, as we can see in head and neck. Frontline will be NBTXR3 as such.
When we move to further line, that's a different thing. 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 help the patient. The oncolytic virus will work from another angle than NBTXR3. 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 patients, even the last line of treatment, again, you see some bi-specific and some new treatments that could help the patient, but they are not enough to cure the patient. For head and neck, there's always a need to have local control regardless of the systemic control you can provide. You could either choose to have this modality to any other systemic treatment and combine better outcomes.
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. 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. That offers multiple possibilities and multiple potential combos.
Clear and very helpful. Thank you.
Thank you.
Thank you. Once again, if you wish to ask a question, please press star one, one on your telephone. We will take our next question. Your next question comes from the line of David from UBS. Please go ahead. Your line is open.
Great. Thanks for taking my questions. I also want to congrats on the data here. I see a couple of questions from me. Laurent, I know you didn't present the progression-free survival data in this data set. I'm just curious, you know, can you share some preliminary analysis on the progression-free survival aspect of the data analysis? That's the first question. A second question just around how should we think about this data being able to read through to the NanoRay 312 trial in the locally advanced head and neck cancer? I understand that the data should be expected to be in the first half next year. Any kind of read-through from this data set into that data set here?
Great. Thanks, David, for the question. We did not present the PFS just because of the size, but we have to date 6.3 months median PFS for this trial. Of course, as the OS, it has to matter. 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 two different populations. 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 a 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. The only thing we could read is we have a strong local control when we inject NBTXR3 and use radiation to activate it.
That's what the treat well is about, having a strong local control. Besides this, I don't think there's much to read through. From a metastatic perspective, I think as we know that there is different tumor mutational burden or oddness of the tumor depending on the characteristics of the tumor and the nature of the disease. If we want to get in order, we can think that melanoma is the oddest tumor, then lung, then head and neck, and some others. 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. That's a complex question that will require further study to look at it.
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. It's hard to see because this is a new modality to link that to any specificity of the tumor. I think when we will have enough patients, we'll 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. I think that's for later. Again, when we look at where the patient's need is, frontline treatment or local 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. Just maybe another question on the timing for development for this in the melanoma setting with randomized trial. Any thoughts around when are you planning to start the randomized trial? Any kind of preliminary thoughts around the development timeline would be helpful.
As I mentioned, we can't say anything about further trials, 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? We need to finish our recruitment, which we expect to complete within the next few months to get more patients and also to have a broader readout with this larger number of patients. Based on that, if we want to move forward or Janssen wants to move forward, we could design more efficiently a trial to get to the next step in melanoma.
All right, thank you so much.
Thank you, David.
Thank you. There are no further questions. I would like to hand back for closing remarks.
Thank you, everyone. Thank you for the very active discussion. Again, we're really happy to have brought that to you, this new data. 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.