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spk05: Good day and thank you for standing by. Welcome to the Nanobiotics First Quarter Operational and Financial Update. 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 1 on your telephone. Please be advised that today's conference is being recorded Thursday 19th May 2022. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Kate McNeil. Please go ahead.
spk07: Thank you, Operator. Good afternoon and good morning, and welcome to Nanobiotics 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 Ryn, 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, your caution 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 20F, 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 on Kansas today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, Nanobiotics undertakes no obligation to update update them to reflect subsequent events or future circumstances. With that said, I'd like to turn the call over to Laurent. Laurent, please go ahead.
spk01: 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 Nanobiotics. 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 NBT-XR3 and drive shareholder value in the near and long term. Our strategy has been focused on three key development priorities. One, securing initial U.S. approval of NBT-XR3 as a treatment for locally advanced head and neck cancer. Developing NBT-XR3 in combination with NTPD1 therapy as a treatment for advanced cancer and foundation for immunotherapy treatment. And three, leveraging our strategic collaborations to advance and expand the potential profile of NBT-XR3 in additional cancer indication, 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 three trial in head and neck cancer. This achievement reflects the extraordinary commitment, dedication, and hard work of the entire naturopathic team and the tremendous support of investigators and patients. While there is a considerable work ahead, we remain driven by our belief in the potential benefit of NBT-XR3 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 evaluating NBT-XR3 in combination with NTPD-1 therapy has suggested NBT-XR3 may be a potent immunostimulant capable not only of enhancing response to NTPD-1 treatment for those that already benefit from treatment, but also overcoming primary and secondary resistance to NTPD-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 NTPD1 treatment and the significant number of patients that demonstrate either 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 addresses the area of highest and net 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 controlled 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 high overall response rate we have seen across our clinical trial, including study 1100, in which only one patient has experienced progressive disease following administration of our product in combination with PEMBRO or NEVO, we are encouraged by the opportunity this could represent to accelerate development of NBT-XR3 in combination with IO and define an attractive path to registration in an area of significant unmet need. Over 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 continued to advance their research and reported the first case study on safety and feasibility of NBTX artery 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 really look forward to the completion of this dose escalation study later this year. As each of these accomplishments suggests, Nanobiotics has made substantial progress against its fundamental strategic goal and has a clear line of sight to multiple significant potential value drivers for the business. However, as each of us knows, the pressure of the biotech sector remains and prolonged volatility in the financial market appears likely. While the current conditions 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 NBT-XR3. In this regard, we are exploiting the inherent 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 higher combination study 1100 and the development of the registration path from IO combination therapy. Having validated the novel physical mechanism of action of NBT-XR3 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 this result achieved will build a solid foundation for future expansion. In prioritizing late-stage programs and strategic collaboration, the company plans to de-prioritize direct funding in several areas, including modifying or postponing additional company-sponsored clinical trials that are not required to advance a priority pathway. This includes delaying post-marketing study previously planned to support or see a 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 costs 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-month follow-up at the time we will stop the trial. Based on this modification, we expect to provide top-line data from Study 102 in mid-2023. In parallel to changes, in our clinical program, we will be reducing ongoing and previously planned preclinical research, including development activities related to the company's subsidiary, Curadagme. In addition to the cost savings afforded by the planned reduction in near-term clinical and preclinical activity, these changes also allow us to make corresponding adjustments 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 has changed how all of us do business, and nanobiotics is no exception. We acted quickly to adjust operational infrastructure to accommodate remote work and promote connectivity across the 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 footprint, 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 runaway and strengthen our financial flexibility. Bart? Thank you, Laurent.
spk03: The initiative Laurent just detailed have little impact on our long-term strategy, but provide significant impact on our ability to execute near-term priorities. Collectively, these actions are expected to reduce operating costs by approximately 12 to 15 million euro 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 insulators from current market conditions, We have also secured access to approximately €25 million in optional capital, should we need it. By establishing a flexible equity financing line through Kepler-Cheveux, we are in a better position to control our exposure to the capital markets. Fundamentally, this equity line reflects a commitment by Kepler-Cheveux 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 may be required over a two-year period at a discount to a market of no 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 structure, Nanobiotics has the full authority to activate or suspend access to capital through this facility at its sole discretion. However, it does ensure that Nanobiotics 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 the 70.6 million euro 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 MBT XR3 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?
spk01: Thank you, Bart. The extended runaway and enhanced flexibility bars as detailed allow us to look forward with excitement, confident in the opportunities we are building to enhance outcome for patients. In the coming months, we look forward to continuing to work with our partner, Lian Bayou, to advance our pivotal phase 3 study in locally advanced head and neck cancer, nanoradiate 312, by expanding our remand to include both U.S. 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 fourth quarter, but taking significant steps of establishing our second registration program in head and neck cancer by finalizing the protocol for a 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 adding depth into our understanding for the potential for combination treatment with immune checkpoint inhibitor. This alliance will continue to be cost efficient an operationally efficient way to characterize the broad potential benefit and future therapeutic profile for NBT-XR3, 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 NBT-XR3 in combination with chemotherapy in head and neck cancer and rectal cancer. As you can see, momentum is building at Nanobiotics and we remain optimistic about the near and long-term opportunities for MBTX artery. I would now like to open the call for questions. Operator?
spk05: Thank you. As a reminder, if you do wish to ask a question, please press star 1 on your telephone. To withdraw your question, please press the hash key. Please stand by while we compile the Q&A roster. This will take a few moments. Thank you, operator. Apologies.
spk07: 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 Q questions online. So, Bart and Laurent, as you know, we did receive some questions prior to the call. They relate to sort of four general topics. And I thought we might start with one or two. Specifically, the first series of questions relate to our registration program and 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 Lean and Bio are triggered by the start of the Phase 3 study in head and neck.
spk01: Thank you, Kate. So, as you know, this Phase 3 registration trial is the priority of the company, and we've been tremendously working in the past years to put that into place. And as you have seen, beginning of January, we have initiated the recruitment of the patient in this phase three. 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 sites in Asia, but also in the United States. In regard to the potential milestone of Young Bio linked to a first patient, this contract has many milestones in it, but not linked to the first patient recruited in the phase three 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.
spk07: Operator, I think we can jump to some questions that are queued on the line.
spk05: Of course. Your first question comes from the line of Lucy Codrington from Jefferies. Please ask your question.
spk08: Hi there. Thanks for taking my questions. Just a few. So starting with the planned phase three in combination with PD1, just if you 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 three could have initial data before your head and neck phase three reads out? Secondly, just with regards for the protocol amendment for 102, I may have misheard, did you say that most patients have completed 12 months or 24 months already? You mentioned that it would reduce costs but not affect the study readout, but what was the original decision to follow up for 24 months and why didn't you go for 12 months originally? 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 manufacturing, does that have any implications for your ongoing trials? And then finally, just the data coming at ASCO this year, should we be doing that more as incremental updates with the more material update being the 1100 update by the end of the year? Thank you.
spk01: Okay, thank you, Lucie. 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 IO trial we are planning. So as we mentioned, we are at the early stage of developing a protocol based on the feedback we've 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 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 three. 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, U.S. will be part of it, but we're 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 abandoned patients is important, especially for the ones that are ineligible to cisplatin, is because that's where you see if you could, from a theoretical perspective, have 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 patients have been recruited way later, the final numbers of patients. It means that when we will stop the follow-up of the patients at 12 months, there will be only a 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 cut it 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 three in the IO setting. And obviously, as needed, we can reengage and continue to produce new batches on demand with our facility. Now, there was a question about STS, Lucie. I'm not sure I got it completely. Would you be able to restate it?
spk08: Yeah, sure. It was just in terms of the implications of postponing those post-marketing studies. Given, I guess, the priority is head and neck, is that immaterial, not conducting those now? Can you just conduct them later?
spk01: Yes, that's the reason why we have postponed the study, is that we don't see any material impact on our way forward. Now, 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, ASCLAN. 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 course in the rectum cancer, where patients 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 and many other indications and will help us to establish Artery, not only as a single agent, like we do in soft tissue sarcoma or head and neck cancer factory trial, but also in combination with chemo and in combination with IO. That's the way we move forward to try to establish franchise in head and neck first, then to expand it into other indications. So I hope you see I did cover your questions.
spk08: Yeah, very helpful. Thank you.
spk01: Thank you.
spk05: Thank you. Your next question comes from the line of Michael Diffel from Evercore. Please ask your question.
spk02: Hi, guys. Thanks so much for taking my question. I guess the biggest issue for, I guess, investors and the question where we're standing is whether or not you guys will have runway to do the interim analysis for the phase three 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 to $15 million of OPEX. Will all of these measures plus the equity line of credit, will that get you into 4Q23 runway? Or will tapping the equity line of credit provide an additional runway beyond that such that the interim analysis could possibly take place? Will the equity line, the debt restructuring, and all the current efforts to save money, is that it? Will that only get you to the fourth quarter of 23? Thank you.
spk03: 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 23. That provides us the necessary flexibility to continue to drive value and use other 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 answers your question.
spk02: Yeah, and I guess as a follow-up to that, that very bridgeable gap, could that be satisfied by the possible debt restructuring?
spk03: Not in its entirety, but it's a good step in the way.
spk02: Also, just as an add-on too, you mentioned manufacturing changes that will be taking place, and just recognizing that a lot of these companies 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?
spk01: Thank you, Mike. As the manufacturing is concerned, nanobiotics itself in its own facility is manufacturing the API. So the vast majority of it is controlled by us. So if any penalty is 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 final steps of manufacturing, but they are not representing the vast majority of the cost of the product manufacturing.
spk02: Okay. Thank you very much.
spk01: You're welcome.
spk05: Thank you. Your next question comes from the line of Clement Bassett from Portons and Park. Please ask your question.
spk00: Hello, thank you for the presentation. I have just two questions following the cost reduction started in 2021. Just would like to know if you have further steps to improve more the cash runways, such as delaying other site studies in collaboration with MD Anderson, for example, which are in preclinical phases. And the other question concerns the number of patients. I would like to know how many are already enrolled for a nanoway. And how many do you expect for the next NIO? And the last question, do you expect also some milestones from LionBuild this year? Thank you.
spk01: So in regard 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 on costs 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 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 nanobiotics. Now, sorry, what was the last question about, please? Lianbio. And what you...
spk00: My question was about LionVio, if you have some milestones expected in the upcoming years?
spk01: Yes, there are milestones expected in this contract, not to the first patient injected in AGI countries, but many more milestones coming up from different steps of development and also commercial steps in this collaboration.
spk00: Okay, thank you.
spk01: You're welcome.
spk05: Thank you. Your next question comes from the line of R.K. Surajan Pakula from H.C. Wainwright. Please ask your question.
spk06: Thank you. Good morning or good afternoon, Lauren. Most of my questions have been asked, but I just want to touch base on a couple of 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, I just want to understand, you know, 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, you know, would you not be interested right away or you need to show up funds before you get back to them? I'm just trying to understand, you know, how you could expand on that patient population.
spk01: Okay. Okay. 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 one that has 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 patient that will have 12 months versus 24 months follow-up will be a very small number of patients because of the timing for equipment 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.
spk06: 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 year and a half 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 in terms of relationships with outside collaborators?
spk01: Thank you. That's a 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 control 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 expansion part. And I think that's a very interesting trial because we start with patients that are truly unoperable, that have usually a very short life expectancy, and a 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 expansion phase that will go to borderline respectable patients, where there is a huge need for them to get to surgery because if you get that then do you limit the chances of the patient to get at a later stage some metastasis and at least improving survival currently for this patient. 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 patient, 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 for 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... Thank you, Laurent. Sorry, 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 IO, 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.
spk06: Thanks. Thanks, Lauren. Thanks for taking the questions. You're welcome.
spk05: Your next question comes from the line of Frederick Gomez from Shamiem Securities. Please ask your question.
spk04: Thanks, Laurent, for taking my questions. A few on street trials now that 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 EOS And also the PFS, should we understand maybe that the PFS is overpowered if you have a decent power for the OS? And just also maybe to check what are the assumptions in terms of gain on PFS versus the Kimo arm, the Compa arm. When you look at the literature, the gain is C2 plus 30 is 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 of 102. Can you maybe confirm that this study will be supported when you will fight with the US FDA? And I got your explanation on the rationale for the amendment. But are you sure that these amendments will have absolutely no impact when you will file for approval with FDA? Thanks.
spk01: Thank you, Fred. So did I have any questions around the 312? Just a general 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, 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're looking at. And I think you'll find all your answer 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 would 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 patient 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 re-precise 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 patient will receive either radiation alone or radiation plus ceftuximab. And in one of the two arms, we will have the nanoparticle or products. So here there is a stratification in the trial with the use or not of ceftuximab. And the choice of putting ceftuximab 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 patient versus radiation alone, but if you look at the frail elderly patient, 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 PI 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 Frédéric, I will be happy to extend this discussion and to go in deeper detail as you need.
spk05: As there are no further questions from the audio, I would now like to hand the conference back to Kate McNeil for submitted questions.
spk07: Yes, thank you, Operator. Bart and Lauren, as you know, we did receive several additional questions in 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 IO 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-irradiation-IO combination study in head and neck. Second to that, there is... questions related to the availability of the products 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 Curadime and specifically the ongoing development with Sanofi.
spk01: 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 have been registered in Europe. Now, as you know, our product is a medical device in Europe and a drug in the U.S., And unlike drugs, the medical device does not offer a predefined pathway to give access to the patient, the product, until it is reimbursed in a country. So that's why we're 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 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 IO trial that are running there and how do we handle that versus other trial. 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 trials in IO 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 trials with them and we'll see that later, but we're also refining our current strategy about what are the IO trials running and internally, the one we are sponsoring, or the one that MD Anderson sponsors. 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 Curadam. As we did mention in the call and in the press release, for now, internal work at Curadam is on hold until we have different financial perspectives. But externally, our partners continue to work with the technology and making progress. So that's where we are today with the CuraDyn program.
spk05: Thank you. This concludes today's question and answer session. I would now like to hand back to the speaker for any closing remarks.
spk01: So I just would like to thank you. 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 do not have time to ask your question, please feel free to reach us and to send us any questions 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.
spk05: This concludes today's conference call. Thank you for participating. You may now disconnect.
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