Nanobiotix SA (NBTX) 2022 Q1 法說會逐字稿

Thank you, operator. Good afternoon and good morning, and welcome to Nanobiotix conference call to discuss our first-quarter 2022 financial and operational results. Joining me on the call today are Laurent Levy, Co-Founder and Chief Executive Officer; and Bart Van Rhijn, Chief Financial Officer. As a reminder, today's call is being webcast and will be available on our website for replay.

I'd 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 presentations, 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're 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 file with the AMF in France and SEC in the United States, including our most recent URD and 20-F, both of 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 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, I'd like to turn the call over to Laurent. Please go ahead.

Thank you, Kate. I would like to welcome everyone participating via conference call and webcast today. As Kate mentioned, we issued a press release yesterday, not only highlighting the company's first-quarter operating activities, but also identifying some of the key changes taking place at Nanobiotix. Before we open the call for Q&A, I would like to take a moment both to touch on our progress and outline how we plan to move forward to optimize our operational activities to advance the development of NBTXR3 and drive shareholder value in the near and long term.

Our strategy has been focused on three key development priorities: one, securing initial US approval of NBTXR3 as a treatment for locally advanced head and neck cancer; two, developing NBTXR3 in combination with anti-PD-1 therapy as a treatment for advanced cancer and foundation for immunotherapy treatment; and three, leveraging our strategy collaborations to advance and expand the potential profile of NBTXR3 in additional cancer indications, both as a single agent and combination therapy. Our fundamental strategy remains unchanged, and during the first quarter of 2022, we've made significant progress toward this goal.

The most significant milestone was, of course, the randomization of the first patient in our pivotal Phase III trial in head and neck cancer. This achievement reflects the extraordinary commitment, dedication, and hard work of the entire Nanobiotix team and the tremendous support of investigator and patients. While there is a considerable work ahead, we remain driven by our belief in the potential benefit of NBTXR3 and look forward to continuing our efforts to secure approval and fulfill a critical need for patients.

The second truly significant advancement during the first quarter relates to our immune-oncology combination program. This program has been exciting from the start. And the data from the ongoing Study 1100 [on drug] evaluating NBTXR3 in combination with anti-PD-1 therapy has suggested NBTXR3 may be a potent immunostimulant capable, not only of [financing] a response to anti-PD-1 treatment for those that already benefit from treatment, but also overcoming primary and secondary resistance to anti-PD-1 treatment for many more that do not.

The data generated by this program, combined with the potentially transformative benefit for patients, has increased our sense of urgency to identify an appropriate and expedient path to market. In particular, we believe that given the historically low overall response rate to anti-PD-1 treatment and the significant number of patients that demonstrate either a primary or secondary resistance to therapy, pursuing a registration program targeting patients with recurrent or metastatic head and neck cancer who have developed primary or secondary resistance to anti-PD-1 therapy are usually the area of high unmet medical need.

And last year, we initiated a dialogue with FDA regarding a potential registration program in this indication. While we have not yet submitted a full protocol for FDA review, we have received preliminary written comment from the agency suggesting that a single control trial, including a pre-specified comparative analysis on overall response rate, may be suitable to support accelerated approval, with verification of clinical benefit based on overall survival results from the same trial.

Given the consistently [I-O] overall response rate we have seen across our clinical trials, including Study 1100 in which only one patient has experienced progressive disease following administration of our product in combination with pembro or nivo, we are encouraged by the opportunity this could represent to accelerate development of NBTXR3 in combination with I-O and define an attractive path to registration in an area of significant unmet need. Also, the next several months, we will be working to develop a final protocol informed by the data generated from our ongoing study and in line with the guidance received to date. We currently expect to submit this protocol to the FDA for review early next year.

Finally, in addition to this advancement in our single agent and combination program, our partners, MD Anderson, continue to advance their research and reported the first case study on safety and feasibility of NBTXR3 in pancreatic cancer. As we all know, pancreatic cancer continues to be a devastating and incredibly challenging disease to treat. And we are encouraged by the success of this program so far, and we really look forward to the completion of this dose escalation study later this year.

As each of these accomplishments suggest, Nanobiotix has made substantial progress against its fundamental strategic goal and has a clear line of sight to multiple significant potential value driver for the business. However, as each of us knows, the pressure of the biotech sector remains, and prolonged volatility in the financial market appear likely. While the current condition of the capital market do not change our fundamental value proposition, they do require us to apply the same innovative thinking to our corporate finance and development strategy as we have applied to the creation of NBTXR3.

In this regard, we are exploiting the interim flexibility of our pipeline and adapting our current development plans to maintain targeted research effort, focused on the continued execution of our ongoing pivotal Phase III study in locally advanced head and neck cancer, along with the continuation of our I-O combination Study 1100 and the development of the registration path from I-O combination therapy. Having validated the novel physical mechanism of action of NBTXR3 and produced a portfolio of preclinical and clinical evidence supporting the potential safety, feasibility, and efficacy across multiple indication and therapeutic combination, we are well positioned to focus our effort on building an initial franchise focused on the treatment of head and neck cancer, with the confidence that these results achieve will build a solid foundation for future expansion.

In prioritizing late-stage program and strategy collaboration, the company plans to deprioritize direct funding in several areas, including modifying or postponing additional company-sponsored clinical trials that are not required to advance our priority pathway. This includes delaying post-marketing study previously planned to support our CE mark in soft tissue sarcoma as well as modifying the protocol from Study 102 to allow for a reduction in post-treatment follow-up from 24 months to 12 months. Adjustment to Study 102 will meaningfully reduce cost associated with the study without materially impacting the value generated by this program.

As you will recall, Study 102 is fully enrolled, and all the patients have completed treatment. In fact, most of the patients will have reached the 24 months follow-up at the time where we'll stop the trial. Based on this modification, we expect to provide topline data from Study 102 in mid-2023.

And prior to changes, in our clinical program, we'll be reducing ongoing and previously planned preclinical research, including development activities related to the company's subsidiary, Curadigm. In addition to the cost setting afforded by the plan reduction in near-term clinical and preclinical activity, these changes also allow us to make corresponding adjustment to our manufacturing activities and leverage our existing clinical supplies to support our ongoing program and further reduce our near-term expenses.

Finally, two years of operating in a pandemic have changed how all of us do business, and Nanobiotix is no exception. We acted quickly to adjust operational infrastructure to accommodate remote work and promote connectivity across a global footprint. At this time, we can further leverage that efficiency and innovation by reducing satellite office facilities to generate further savings while retaining our primary offices and manufacturing facilities in Paris.

In addition to a planned reduction in our physical footprints and in light of planned adjustment to our development program, we are delaying any expansion of our team until operational needs and circumstance warrant. I would now like to turn the call over to Bart, who will address additional measures we are taking to extend our runway and strengthen our financial flexibility. Bart?

Thank you, Laurent. The initiatives Laurent just detailed have little impact on our long-term strategy that provides significant impact on our ability to execute near-term priorities.

Collectively, these actions are expected to reduce operating costs by approximately EUR12 million to EUR15 million through 2023, adding nearly a quarter to our operating runway. These cost reductions are in addition to the cost efficiency program initiated in the second half of 2021, that will continue to favorably impact operating expenses in 2022 and 2023, resulting in a double-digit reduction in SG&A in 2022 prior to any adjustments to our development programs.

In parallel to our efforts to adjust our cost structure and capital allocation to better insulate us from current market conditions, we have also secured access to approximately EUR25 million in optional capital should we need it. By establishing a flexible equity financing line through Kepler Cheuvreux, we are in a better position to control our exposure to the capital markets.

Fundamentally, this equity line reflects the commitment by Kepler Cheuvreux to purchase incremental equity made available by the company at prices generally in line with the market. So rather than issuing a substantive amount of equity at likely deeply discounted prices, this instrument allows us to access as much or as little capital as maybe required over a two-year period at a discount to market of greater than 5%.

Significantly, we are not committed to sell shares now or at any time in the future, nor are we obligated to do so at any price. Through this restructure, Nanobiotix has the full authority to activate or suspend access to capital through this facility at its sole discretion. However, it does ensure that Nanobiotix has guaranteed access to the capital required to fund operations and control over potential dilution despite any sustained turbulence in the broader market.

Collectively, these efforts reflect measures within our immediate control -- actions we can take that can be calibrated at our discretion to ensure we're optimizing investment in our priority pathways and ensuring future value for our patients and shareholders. Combined with this EUR70.6 million in cash, cash equivalents, and investments available as of March 31, 2022, we can be confident in funding our planned operations well into at least the fourth quarter of 2023. This extended runway also affords us the flexibility to pursue additional measures that could materially impact our capital allocation and significantly reduce the need for future dilutive capital.

Specifically, we have initiated discussions related to the potential restructuring of our debt obligations. Our goal is to realign the repayment schedule with our anticipated commercial timelines and defer the majority of our principal payments due in 2022 and 2023. This would allow us, instead, to redirect the capital towards our R&D programs.

The efforts reflect our commitment to safeguarding the disciplined development of NBTXR3 for our patients and our shareholders. As we continue to progress our programs, we will continue to assess the efficiency with which we are deploying our capital and seek to optimize our spend to drive near- and long-term value.

And now, I'll turn the call back to Laurent. Laurent?

Thank you, Bart. The extended runway and flexibility Bart has detailed allow us to look forward with excitement, confident in the opportunities we are building to an end outcome for patients.

In the coming months, we look forward to continuing to work with our partner, LianBio, to advance our pivotal Phase III study in locally advanced head and neck cancer, NANORAY-312, by expanding enrollment to include both US and Asia. We look forward to continued progress in our I-O program, not only reporting updated data from the ongoing Study 1100 in the first quarter, but taking significant step of establishing our second registration program in head and neck cancer by finalizing the protocol for our pivotal study for recurrent and metastatic head and neck cancer.

As we focus our internal development effort on two registration programs in head and neck cancer, we welcome the continued contribution from our partner at MD Anderson. This comprehensive collaboration is expected to provide new data in pancreatic cancer this year, esophageal cancer early next year, and continue to explore indication like non-small cell lung cancer while having depth into our understanding for the potential for combination treatment with immune checkpoint inhibitor.

This alliance will continue to be cost efficient and operationally efficient way to characterize the broad potential benefit and future therapeutic profile for NBTXR3, complementing the rich data set already generated by the company and its partner, including data that will be presented at ASCO in June, highlighting the safety and feasibility of NBTXR3 in combination with chemotherapy in head and neck cancer and rectal cancer. As you can see, momentum is building at Nanobiotix, and we'll remain optimistic about the near- and long-term opportunities for NBTXR3.

I would now like to open the call for question. Operator?

(Operator Instructions)

Thank you, operator.

Apologies.

No, that's okay. I think we actually received a number of questions from shareholders prior to the start of the call. And I think we'll address a couple of those before we jump to the queued questions online.

So Bart and Laurent, as you know, we did receive some questions prior to the call. They relate to four general topics, and I thought we might start with one or two.

Specifically, the first series of questions relate to our registration program in head and neck and largely focus on Study 312. And the questions include -- questions related to the status of patient recruitment and site activation for Study 312; expectations around the timing of the planned futility analysis and how many patients we would expect to inform that analysis; and what, if any, milestone payments from LianBio are triggered by the start of the Phase III study in head and neck?

Thank you, Kate. So as you know, this Phase III registration trial is the priority of the company, and we've been tremendously worked in the past years to put that into place. And as you have seen, beginning of January, we have initiated the recruitment of the patients in this Phase III. So things are moving according to plan.

We're still, as you know, in early stage of this trial. And many sites have been opened and activated, especially across Europe. Now, we anticipate in H2 to start opening site in Asia, but also in United States.

In regard to the potential milestone of LianBio linked to a first patient, this contract has many milestones in it, but not linked to the first patient recruited in the Phase III in head and neck. So in the next months, years, we will continue to give you an update on where we are with this trial and how we move forward. As for now, things are moving as we anticipated. As per the futility analysis readout and the interim readout, we're still in the timelines that have been provided to the market.

Operator, I think we can jump to some questions that are queued on the line.

Lucy Codrington, Jefferies.

Hi there. Thanks for taking my questions -- just a few. So starting with the planned Phase III in combination with PD-1, just -- if you can give us a bit more of an idea of what needs to be done between now and the first quarter of 2023, and just whether your discussions with FDA have been influenced by recent events surrounding the PI3K kinase inhibitors and Project Optimus. And is there any possibility that actually that Phase III could have initial data before your head and neck Phase III reads out?

Secondly, just with regards to the protocol amendment for 102 -- I may have misheard -- did you say that most patients have completed 12 months or 24 months already? And just what -- you mentioned that it would reduce costs, but not affect the study kind of readout. But what was the original decision to follow up for 24 months, and why didn't you go for 12 months, originally?

And in line with that, how important were the post-marketing studies for soft tissue sarcoma? What are the implications of delaying those? And similarly, with the manufacturing reductions or changes to your manufacturing, does that have any implications for your ongoing trials?

And then finally, just the data coming at ASCO this year, is -- should we be viewing that more incremental updates with the more material update being the 1100 update by the end of the year? Thank you.

Okay. Thank you, Lucy. So that's a lot of questions. So let's try to remind all of them.

Maybe I can start with the PD-1 pathway and the I-O trial we are planning. So as we mentioned, we are at the early stage of developing a protocol based on the feedback we just received from FDA. So what is interesting here is, when we look at the 1100 study we have, which encompass a number of head and neck patients having metastasis and being refractory to PD-1, we can start looking at what could be a potential outcome for those patients, both from a response rate perspective, but also from a survival perspective.

Now, the next steps that are in the front of us is obviously designing and refining a protocol based on the feedback, but also enriching this protocol based on the data we are seeing in this first step, 1100 trial. We plan to submit this to FDA beginning of next year. But in between, we'll have an update on this 1100 trial that should occur H2 this year, where we'll get more patients and could lack -- and we'll see what the results could be in this Phase III.

So that's where we're moving at the moment. There is also feasibility to be done to see how many countries are going to be involved. Obviously, US will be part of it, but we are also looking at Europe and other potential countries there.

Now in terms of the 102 amendment. So why the 24-month follow-up for head and neck locally advanced patient is important, especially for the ones that are ineligible to cisplatin, is because that's where you see, if you could, from [ontological] perspective, has transformed the treatment into some curative pathway.

After two years of follow-up, if you have no relapse -- for the patient -- then you have a good chance to go to the five years that could be considered at some point as a cure. That's why we have defined 24 months in this trial initially.

Now, when the COVID hit, there have been a gap in recruitment in this trial, as you know. And the very last patient had been recruited way later the final numbers of patients. It means that when we will stop the follow-up of the patient at 12 months, there will be only few patients that will have only 12 months follow-up versus the vast majority of other patients having 24 months or more follow-up. So that's why we thought -- rather than continuing spending money on this trial to make an amendment to [carry] after 12 months follow-up for the last patient, in order to save money and do not degrade what results could come from this trial.

Now for the manufacturing, what we have in place now is everything that is needed to cover every ongoing clinical trial, including a potential registration Phase III in the I-O setting. And obviously, as needed, we can re-engage and continue to produce new batches on demand with our facility.

Now, there was a question about STS, Lucy. I'm not sure I got it completely. Would you be able to restate it?

Yeah, sure. It's just in terms of the implications of postponing those post-marketing studies, just given the -- I guess, the priority is head and neck. Is that immaterial -- not conducting those now? Can you just conduct them later?

Yes, that's the reason why we have postponed this study, is that we don't see any material impact on our way forward. Now, there -- I think there was a question about ASCO. I did mention just a minute ago that the 1100 trial will be updated later this year, not at ASCO, but H2 as planned.

At ASCO, what we are waiting are the results of two trials that have been done by our former Asian partner, PharmaEngine, which means the expansion cohort in the rectum cancer were patients who have received radiation, chemo, plus nanoparticles. And the other one will be in head and neck cancer for patients that have received radiation, chemo, and nano. So those are different settings of patients that have been treated previously.

And for us, what is important here is to look at the possibility of combining our product with radiation and chemotherapy. Because, as we know, this is a standard of care in many other indications and will help us to establish our treatment, not only as a single agent like we do in soft tissue sarcoma or head and neck cancer Phase III trial, but also in combination with chemo and in combination with I-O. That's the way we move forward to try to establish -- franchising head and neck first, then to expand it into other indications. So I hope, Lucy, I did cover your questions.

Yeah, very helpful. Thank you.

Thank you.

Michael DiFiore, Evercore.

Hi guys. Thanks so much for taking my question. I guess, the biggest issue for, I guess, investors and the question we're receiving is whether or not you guys will have runway to do the interim analysis for the Phase III NANORAY study.

And I just want to clarify certain things. Will -- after all of these measures have taken place in order to save the incremental $12 million to $15 million (sic - see Press Release, "EUR12 million to EUR15 million") of OpEx, will all of these measures -- plus the equity line of credit, will that get you into 4Q 2023 runway?

Or will the -- will tapping the equity line of credit provide an additional runway beyond that such that the interim analysis could possibly take place? Or will the equity line, the debt restructuring, and all the current efforts to save money -- is that it? Will that be -- will that only get you to the fourth quarter of 2023? Thank you.

Thank you, Michael. We appreciate the question. I'm happy to respond.

As our press release and comments on our call indicate, we're highly disciplined to preserve the long-term value. We've taken steps that are in our control to extend our runway. And that includes both the actions that we've taken as well as the equity line that will get us to Q4 of 2023. That provides us the necessary flexibility to continue to drive value and use all the opportunities in order to bridge the gap.

And these additional measures could materially impact our capital allocation. As we've indicated in the press release, the restructuring of the debt is one of them. We believe that there still is a smaller gap to get us to interim analysis, but it's now a very bridgeable gap. I hope that that answers your question.

Yeah. And I guess, as a follow-up to that, that very bridgeable gap, could that be satisfied by the possible debt restructuring?

Not in its entirety, but it's a good step in the way.

Also, just as an add-on, too, you mentioned manufacturing changes that will be taking place. And just recognizing that a lot of these manufacturing plans are done well in advance, and making changes are often very costly, has that been taken into consideration? And will there be any penalties that may cause an unexpected shortfall in funds?

Thank you, Mike. So as the manufacturing is concerned, Nanobiotix itself is, its own facility, is manufacturing the API. So the vast majority of it is controlled by us. So if any penalty, it's on us, not externally.

So that's why we can control easily the spending in the manufacturing without incurring penalties or other issues linked to that. So we are in full control of that. Nevertheless, we still have external partners to help us to work on the final steps of manufacturing. But they are not representing the vast majority of the cost of the product manufacturing.

Okay. Thank you very much.

You're welcome.

Clément Bassat, Portzamparc.

Hello. Thank you for the presentation. I have just two questions. [Following] that the cost reduction started in 2021, just like to know if you have further step to improve more the cash runway, such as delaying other site studies in collaboration with MD Anderson, for example, which are in preclinical phases.

And other question concerns the number of patients. I would like to know how many are already enrolled for NANORAY, and how many do you expect for the next -- in I-O? And the last question, do you expect also some milestones from LianBio this year? Thank you.

Okay. So in regards to the 312, I think I have covered this part in the first question, and I can't go far beyond that.

For the MD Anderson collaboration, so just -- in the structure of this collaboration with MD Anderson, there is a very small amount of money that is involved in it, as MD Anderson is taking the vast majority of cost on them. The preclinical work we are doing with them is coming to an end, at least, for this phase. So there is no need to re-engage on that matter in the short term. So the only cost that is linked to MD Anderson is really linked to the ongoing clinical trial, which has -- which are already covered in the contract we signed with them.

So we'll continue to work there, as the engaged cost is very low for Nanobiotix. Now -- sorry, what was the last question about, please?

LianBio.

LianBio. And what are you --

My question was about LianBio, if you have some milestones expected in the upcoming years.

Yes, there are milestones expected in this contract, not to the first patient injected in Asian countries, but many more milestones coming out from different step of development and also commercial step in this collaboration.

Okay. Thank you.

You're welcome.

RK Swayampakula, H.C. Wainwright.

Thank you. Good morning or good afternoon, Laurent. Most of my questions have been asked, but just want to touch base on a couple things.

On the Study 102, where you're amending the protocol to decrease the follow-up period to 12 months from 24 months, on that trial, just want to understand how the follow-up would go on. So once the follow-up is done and, let's say, the data is positive and it looks mighty interesting, does that mean your interest in that particular patient population, which is the cisplatin ineligible head and neck cancer population, in terms of developing the next phase of studies, would you not be doing them? Would you not be interested right away, or you need to sure up funds before you get back to them? I'm just trying to understand how you could expand on that patient population.

Okay. Thanks, RK. So the 102 trial has been the premises to define what the 312 trial will be, which is now ongoing. And as you know, the 312 trial will take part of the population, will be the ones that have been treated in the 102. If we have stopped this trial or, at least, changed the final follow-up for the very few patients remaining in terms of follow-up, then it's because we extracted, we think, everything we could from this trial.

And what we extracted in the past helped us to design the 312, which is now moving forward. As I did mention previously, the patients that will have 12 months versus 24 months follow-up will be a very small number of patients because of the timing for recruitment of different patients. Now, the population in the 312 will get this population plus a broader population in order to enlarge the market we can target with our product in locally advanced head and neck patients that are eligible for cisplatin.

Thank you for that. And then the various studies that MD Anderson is doing in different indications, I'm just trying to see if within the next year or 1.5 years that you have the current runway for, would there be any data updates from any of those studies? The reason I'm asking is -- would that be a subject for soft money by -- in terms of relationships with like outside collaborators?

Thank you. That's good question. We like the collaboration with MD Anderson because -- not only MD Anderson but, also, because of the cost-efficient collaboration we have with them. And they're running a number of clinical trials, and we expect later this year to have the first potential readout on the pancreatic cancer trial, which is a devastating disease, as we know.

Here, we intend to define what would be the RP2D dose, and then to move into the extension part. And I think that's a very interesting trial because we start with patients that are truly inoperable, that have usually a very short life expectancy and high risk of having a metastatic setting following the locally advanced tumor.

So here, if we could control those patients, that will allow us to move into the extension phase that will go to borderline resectable patients, where there is a huge need for them to get to surgery. Because if you get that, then you eliminate the chances of the patients to get at a later-stage [some] metastasis and, at least, improving survival currently for these patients.

So we are eager to look at what the data will be on that and if we can move to the expansion part of this trial. Obviously, this will happen H2 this year, so very soon.

Now the second trial that should give us the data in MD Anderson will be the one with esophageal cancer. Again, that's a setting where you have radiation, chemo, plus nano. And here, the goal is to get to a good response for the patients, so you can either avoid surgery or to get to a surgery that will not be detrimental to keep the function of the organ. And we're waiting these results for next year from MD Anderson.

Along the way, we will also inform you about other trials that are running and when we should expect some clinical data coming from it. And I think (multiple speakers) --

Thank you, Laurent.

Sorry, RK. To go back to the other part of your question about how this will be seen from a partnership perspective, I think the more we show that our product can be combined with chemo, can be combined with I-O, and can be used in so many settings in oncology, the broader is the option for us to go to find a partner out there.

Thanks. Thanks, Laurent. Thanks for taking my questions.

You're welcome.

Frédéric Gomez, Pharmium Securities.

Yes. Thanks, Laurent, for taking my questions -- two on 312. Now, the study is ongoing. On the design itself, can you tell us -- maybe can you share with us more colors on the statistical power of the study? Is it 85%, 90%?

And I would like maybe to get a better understanding around this statistical power between the OS and also the PFS. Should we understand maybe that the PFS is overpowered if you have a decent power of the OS?

And just also maybe to check, what are the assumptions in terms of gain on PFS versus the chemo arm, the [control] arm, when you look at the gain (inaudible) close to seven months? You mentioned in the past that you were looking for a gain of three months. So should we still use this number of three to four months gain in PFS between the two arms?

And my last question is on the amendment on the Study 102. Can you maybe confirm that this study will be supportive when you will file with US FDA? And I got your explanation on the rationale for the amendments, but are you sure that these amendments will have absolutely no impact when you will file for approval with FDA? Thanks.

Thank you, Fréd. So these are many questions around the 312.

Just additional statement on how the trial has been designed. You're right; that's a trial that's been designed with PFS as a primary endpoint but, nevertheless, being able to demonstrate an OS benefit. So it makes that the PFS power is -- the PFS is overpowered versus the OS, and the interim readout is planned to be done on the PFS.

For the sake of time, I will send you the details that are publicly available on the design of the trial and the different powers or the different endpoints we are looking at. And I think you'll find all your answers there.

Now, on the question of the 102. The population being included in the 312, I don't think we can directly use what is the overall outcome of the 102 to the 312. That will be supportive in terms of understanding what the potential impact of the product for a frail population. And what we have at 24 months is something which could be good enough in terms of supportive data.

Following patients longer will not bring that much value versus what we have today. Now in regards to the pure registration strategy and what data will be submitted to the FDA at the time of registration, we did not communicate that yet to the market. And that will, obviously, include the 312, but also the 102 as supportive data and every other trial as addition.

I think there was another question about the potential control arm, radiation plus cetuximab. Just to [represent] the design of the clinical trial we are running, so this is a two-arm trial with 500 patients, randomized one to one. So in each arm, the patients will receive either radiation alone or radiation plus cetuximab. And in one of the two arms, we will have the nanoparticle of products.

So here, there is a stratification in the trial with the use of cetuximab. And the choice of putting cetuximab in the trial was linked to the fact that cetuximab is still standard of care in some of the population we want to treat. Nevertheless, when you look at literature, it is true that in the general population, cetuximab on the top of radiation bring benefit to patients versus radiation alone. But if you look at the frail elderly patients, it does not.

If you look at the Bonner paper, it will tell you that for elderly patients, cetuximab is even detrimental versus radiation alone. And in the past, one of our PIs has published, during one of the head and neck conference, some real-world evidence data showing that the PFS for elderly patients being treated either with radiation or radiation plus cetuximab is quite similar. I think there's less than a month difference between the two.

So that's why we think, when we look at what could be the comparator -- what the comparator could look like, in literature, it's really important that we really look at what population we are talking about. But Fréd, I will be happy to extend this discussion and to go in deeper detail, as you need.

As there are no further questions from the audio, I would now like to hand the conference back to Kate McNeil for submitted questions.

Yes. Thank you, operator. Bart and Laurent, as you know, we did receive several additional questions. And going through the Q&A and prepared remarks, so far, I believe we've actually covered a majority of the questions related to potential financing strategies and our I-O development program. However, we do have three remaining questions, which I'd like to present for you to address before we close out the call.

The first series of questions relate to anticipated data from our MD Anderson studies and, specifically, include questions about when we expect to see results from any of these studies and a request to clarify the status of the re-radiation I-O combination study in head and neck. Second to that, there is -- questions related to the availability of the product in soft tissue sarcoma in the European market and if there are any patients that currently have access to that product. And the final question relates to the status update on Curadigm and, specifically, the ongoing development with Sanofi?

Thank you, Kate. So let's start maybe with the access to patients for -- soft tissue sarcoma patients to the product. So as we've seen, head and neck is our priority. And the company will start looking at soft tissue sarcoma commercialization after head and neck had been registered in Europe.

Now, as you know, our product is a medical device in Europe and a drug in US. And unlike drugs, the medical device does not offer a pretty fine pathway to give access to the patients -- the product -- until it is reimbursed in a country. So that's why we are eager to move forward as fast as we can -- our head and neck trial -- not only to bring this product to head and neck patients, but also to soft tissue sarcoma patients.

Now in the second question about MD Anderson, I think for the deadline to next data point, we've covered this point in the previous question. But there's still a remaining question about the I-O trial that are running there and how do we handle that versus other trials.

So I think, especially, with the latest feedback coming from FDA about a potential pathway forward, along with the amendment of our protocol in order to redefine the expansion cohort, we are reviewing with MD Anderson the different trial in I-O in order to optimize the resources that are developed there and to prevent any potential redundancy with the different population we are treating.

So not only we are discussing new trial with them -- and we will see that later -- but we're also refining our current strategy about what are the I-O trials running internally: the one we are sponsoring or the one that MD Anderson sponsor. But we'll, obviously, give an update as we do regularly on the overall portfolio of trials we are running.

I think that the last question concerns Curadigm. As we did mention in the call and in the press release, for now, internal work at Curadigm is on hold until we have different financial perspective. But externally, our partners continue to work with the technology and making progress. So that's where we are today with the Curadigm program.

Thank you. This concludes today's question-and-answer session. I would now like to hand back to the speaker for any closing remarks.

So I just would like to thank you, everyone, for participating in the call today. We really appreciate your time and look forward to seeing you and many of you in the coming weeks as we attend the UBS, the HCW, and the Jefferies conferences. And also, we'll have our general assembly in June where we hope to see you there.

If you don't have -- if you do not have time to ask your question, please feel free to reach us and to send us any question that haven't been answered during that call. I just would like to thank you again and wish you a great day. Thank you, everyone.

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