MaaT Pharma SA (MAAT) Earnings Call Transcript & Summary

Good evening here to you all. I'm Sian Crouzet, Chief of Staff of MaaT Pharma, and it's with great pleasure to have you on the call today. We will be discussing the unprecedented results we published yesterday on the ARES Phase III trial for MaaT013 in acute Graft-versus-Host Disease. What it means for patients and to MaaT Pharma from a business perspective. I will be moderating the session today. I remind you that the webinar is accessible via a computer or a phone line. Please note that questions may only be asked using the chat box on a computer. After the prepared remarks, we will open up for a Q&A session. Joining me today are Herve Affagard, CEO and Co-Founder of MaaT Pharma; Gianfranco Pittari, our Chief Medical Officer; and Eric Soyer, our Chief Financial Officer. Herve will provide an introduction to the company, the strategic implications and opportunity created from these results. Gianfranco will present the key clinical data supported by an expert's view from one of the most renowned hematologists, professor Mohamad Mohty and Eric will conclude the presentation outlining our financing strategy to support our endeavors. So with that, Herve, I will let you take the floor.

Thank you very much, Sian. On the next slide, yes. Okay. So happy new year to everyone. Let me start with an overview of the company's focus and strategy. So that -- that's the first slide. Since our inception in 2014, we are now 10 years company. We have been driven by the ambition to demonstrate the transformative potential of microbiome modulation in a very severe disease. As a proof of concept, we have been producing, since the early days, in Graft-versus-Host Disease, which is one of the most significant threat in today's medicine. So we have decided to show that for the current indication, we are able to deal with inflammation among other things. What we would be providing today is really those outstanding results that we have communicated just yesterday and we will provide you with a deeper insight on the progresses on these developments. To better understand our strategy and our business model, I'd like to highlight 3 key pillars. So the GvHD proof of concept demonstrating the clinical and commercial viability of microbiome-based therapy. The second element is the platform. GvHD is the market entry strategy. We want to go further to do that. We have 2 product ranges. We have our proprietary data sense platform that we call just print, which is supporting all the developments that we are doing within the company. And we have a GMP manufacturing facility. What's unique at MaaT Pharma is that this development platform is fully integrated and run by MaaT Pharma employees, which is an important asset for the company. On the resource side, with a reported cash position of EUR 27 million as of September, we are exploring nowadays different source of funding to support the upcoming milestones of the company. In the short term, we also will generate revenues through licensing or through different kind of deals that we will be performing as we know that we are in a position now to exceed the market opportunity of EUR 750 million when considering the two first products that are close to commercialization. Before I continue the presentation, I'd like to mention the size of the ambition that we are pursuing. Today, what we are doing is that we are creating a new pillar in oncology that we call microbiotherapy. So what is microbiotherapy and how does it work? In oncology, it is common to observe a disruption in the communication between the gut microbiome and the host and especially the immune system, particularly when patients are receiving harsh treatments such as chemotherapy, antibiotics and any other kind of anticonservative drugs. This is particularly true in hematology oncology, where those patients that are receiving like everything, chemo, antibiotics altogether then stem cell transplantation. So at the end of the day, not only it will severely damage the microbiome, but it will internally destroy the microbiome despite the critical role as an ally of the microbiome regarding the immune system. So this is exactly what we want to target. As it is shown on the 2 graphics or products, MET, Microbiome Ecosystem Therapeutics, are capable of restoring the key aspect of the microbiome health, including microbiome diversity, which is on the top part of the slide here, but also the metabolic function. This restoration has the potential to repair [indiscernible]. We are reestablishing the in-central and supportive immune function of the microbiome by doing so. Following the breakthrough of chemotherapy, precision therapy, immunotherapy, we believe the next era in oncology is going to be microbiotherapy and that MaaT Pharma is very well placed in being a leader in that field. In terms of different products that we are developing, we do produce ourselves the product, as I said during the introduction, we have 2 ranges of products that are complementary. The 2 products that are into the clinics today, they are what we call the MaaT end product, MaaT013 and MaaT033. We do have the next-generation product as well that we call MaaT [indiscernible] that's part of the presentation today. And what makes unique also the development platform is the fact that we have this pretty nice manufacturing facility, which is our facility where we can both develop the processes, the bioprocesses and run the GMP production. And what sets us apart when looking at other microbiome companies is that we have developed a unique proprietary pulling approach, which helps to make the product standard, we mix together several microbiome that we get from the owners and we can standardize the product. And also, we can also make sure that we have all the bacteria that are necessary to restore the functional microbiome as expressed on the previous slide. So that's it for the introduction. So I think now it's time to go to the data, and I'll pass it over to Gianfranco, Chief Medical Officer of the company.

Thank you very much, Harve. And again, good morning, good afternoon and good evening, everybody. And today, the focus is to discuss the IRS data that is for MaaT013 in refractory acute Graft-versus-Host disease. This is a condition as shown in this slide, that arises when donor immune cells do not recognize the recipient's tissues and mistakenly attack these tissues as foreign. And it is a condition that typically manifests within the first 100 days post transplant. It can affect various anatomical locations, including the skin, the liver and the guts. And among these locations, the gut really stands out as a critical site due to its association with high morbidity and mortality rates. GvHD is certainly among the most, if not the most significant complication of allogeneic hematopoietic stem cell transplantation. Firstly, due to its frequency as it, of course, in about 50% of transplant recipients, but its clinical significance critically depends on its prognosis especially in those cases where it becomes refractory to treatment. And unfortunately, refractory GvHD can often lead today to lethal outcomes. So refractory GvHD, as I was alluding to in the previous slide, still represents an area of unmet medical need. And so basically, what happens today is the patients with severe GvHD receive a standard first-line treatment of high-dose steroids. Only approximately 50% of patients have a lasting complete response with systemic steroids and for the remaining patients, ruxolitinib a second line of treatment is required given the high mortality rate of steroid retrofactory GvHD. And in 2019, ruxo was approved as second line option in steroid refractory GvHD patients in the U.S. and then in 2022 in Europe. However, even after ruxolitinib, only approximately 50% patients would show a response. And this means that basically, approximately 30% patients, which in absolute terms, is as many as 3,000 transplanted patients in Europe and the U.S. would have a GVHD that is both steroid and ruxo refractory. And this patient population really is characterized by a truly dismal prognosis with a median follow-up of only 28 days and a long-term survival of 10%, 15% and no available standard of care. So again, the median survival is only 28 days in these patients. And so of course, these patients urgently necessitate new and effective therapeutic options. And so based on these considerations, with ARES, we exactly explore this population of third-line acute Graft-versus-Host Disease, failing first-line steroids and second-line ruxolitinib. And patients in the study were to receive three doses of MaaT013, the 1, 5 and 10. The primary point of the study was the termination of overall response rate of gastrointestinal level after 28 days, and the secondary end point for efficacy was the determination of overall survival at 1 year. So we recruited 66 patients. And today, we are all proud to show you the data, which really, as was mentioned earlier by Sian and Herve are unprecedented in third-line acute Graft-versus-Host Disease. So I wanted to spend a few words on the patient characteristics. I'd like to highlight the fact that even if the study allowed inclusion of patients with lower grade acute Graft-versus-Host Disease basically grade II and also patients intolerant but not refractory to ruxolitinib. The study eventually basically exclusively enrolled patients with severe G3 and G4, acute Graft-versus-Host Disease, almost exclusively, we're talking about 91% patients and only patients with refractoriness to ruxolitinib. So therefore, we can say that ARES cohort represents the classically hard-to-treat refractory acute Graft-versus-Host Disease population. In terms of responses, so responses to MaaT013 were truly outstanding. So day 28, the overall response was 62%, and it was consistent and even numerically superior, I would say, to the ARES like population in our Early Access Program. As a reminder, the GI-ORR in the EAP based on the latest ASH'24 data was 59% at day 28. So it's pretty consistent. And again, numerically slightly higher. Responses were typically deep with the vast majority of them being either complete or very good partial response. Importantly, we had a proportion of patients with aGvHD extending beyond GI and these patients also exhibited the response. And because of this reason, the overall response rate at organ level keeps high and it is actually 64%. Again, also in terms of overall response rate for all organs, a significant proportion of such patients has [indiscernible] responses, which is either CR or VGPR. And I would say that we are really delighted to see that MaaT013 translates in a remarkable extension of patients on [indiscernible]. So 1 year, the probability of survival is 54%. And this, by far, exceeds the 15% expected survival at 1 year in patients receiving non-microbiome Best Available Therapy for third-line acute Graft-versus-Host Disease. I think it is important to note that these unprecedented survival is driven by response. So patients showing GI response at day 28 have a probability of survival of 67% as opposed to 28% in nonresponders. This is also in line with early access program beta, where responders similarly exhibited a remarkable survival advantage. So in essence, ARES demonstrates that MaaT013 is really a powerful asset. It is able to significantly extend survival in severe refractory acute Graft-versus-Host Disease. And with this, I will give the floor back to Herve, and thank you very much for listening to these important updates. Thank you.

Thank you very much, Gianfranco. One key element of our business model is also our strategy regarding Early Access Program. You'll notice that Early Access Program has started at MaaT Pharma in 2019, a little bit at the same time when ruxolitinib was first approved. And the intention was really to deliver the product because we knew that the product will be -- is -- was promising. So we wanted to deliver it to the patients. That was the initial rationale. Interestingly, because also it was at the same time at the advent of ruxolitinib, we have been also in a position to get real world evidence and we have better understand the dynamics in centers, the way our products or how our product going to be efficient in different contexts, including for those who are refractory to ruxolitinib, so that has been a fantastic tool to position the product and make sure that we have the maximum clinical value from the product. For the first indication, we wanted to make it right, right in terms of the positioning for the right population of patients and right in terms of getting the clinical benefit we are looking for and as you can see from the graphic, the demand has been increasing with a fantastic '24 year because we have, for the first time, exceeded 100 EAP during '24. And that's the equivalent of 2 EAP per week, so which is already significant. And now we deliver the product in 10 countries. The increase in '24 was 75%. We delivered in 10 countries. We have expanded the Early Access Program in the U.S., we have treated the first patient in late '24. Now we have the supply chain, the distribution center. We have 1 in the U.S., 1 in France to cover almost everywhere in the world. So that's really a good news. And also, there is a specific aspect in France, where you can invoice for the Early Access Program, and we have been today in a position to invoice EUR 26,000 per MaaT013 and the average dose -- average number of dose per patient is 3 dose. So we have been in a position to generate EUR 2.3 million for the first 3 quarters of '24, which represents the activity in France. Also, you notice that there is 95% of the Early Access Program are GVHD. But we do also request -- received requests for other indications and we are also analyzing this demand in terms of positioning also the rest of the development of the company because if there is a demand it's interesting to engage with the physicians to better understand why they think the microbiome could help, and that's exactly what we are doing, especially in the field of immuno-oncology. And last but not least, as already said, but I won't repeat it, because it validates the strategy. EAP signal that we have been on the population, which is close to the one from ARES. We had sensible 62% against 59%. So that's the first part of the presentation, we think it's also interesting to get the point of view of the physician and we have requested a professor, Mohamad Mohty, who is a long-standing advisor to the company to provide us with feedback regarding the relevance of both data. So that's a registration and we'll be back once it's completed.

Hi, everyone. It is with immense pride and excitement that I stand before you today to celebrate a groundbreaking milestone in our field, the remarkable success of the ARES Phase III clinical trial, introducing a new innovative therapy, namely MaaT013 for steroid refractory severe acute Graft-versus-Host Disease particularly in the gut. Steroid-refractory acute GvHD has long represented one of the most formidable challenges in transplant medicine. For decades, it has been a condition with limited effective options and its devastating impact on patient has driven the relentless pursuit of innovative solutions. Today, we are witnessing the fruits of that determination, a breakthrough that is truly transformative with the field. This new MaaT013 therapy, which we are here to highlight represent a major leap forward, by targeting GvHD in the gut, a region notoriously difficult to manage. It addresses one of the most severe and life-threatening complications of this disease. The results from the ARES Phase III trial have demonstrated not only the safety and efficacy of microbiota modulation, but also its potential to dramatically improve outcome for patients. For many, this therapy with its high response rates unprecedented and a very impressive overall survival will mark the difference between life and death, between suffering and recovery. What makes this innovation even more extraordinary is a mechanism undermining it. This therapy goes beyond simply suppressing inflammation, it paves the way for precision medicine by aligning with an emerging frontier in healthcare, a modulation of the microbiota. By understanding and harnessing the microbiota complex role in immune regulation, this treatment offers a new paradigm for managing a Graft-versus-Host disease and potentially other transplant-related complications. It signifies a shift from reactive care to proactive targeted interventions. The success of this Phase III ARES trial is more than just a validation of a drug. It is a beacon of hope and a harbinger for further advancement. It's set a precedent for the potential of microbiota targeted therapies and opens the door to a broader exploration of how we can modulate the immune system safely and effectively. This success will undoubtedly inspire ongoing research and innovation, pushing the boundaries of what is possible in transplant medicine and beyond. In summary, let us celebrate this achievement as a testament to the power of innovation, collaboration and commitment to improving patient care. Together, we are not just advancing medicine. We're also changing lives. Thank you for your attention.

So that was the testimony from Professor Mohamad Mohty. So that's very important for us to get guidelines from physicians as we are developing our strategy. And I would say also when we look at the market, it's important also to explain the way we see it. The MaaT013 has been central on everything we have done. We have been focusing on MaaT013 a lot. So now we are at a stage where we are the first ever microbiome company to have communicated data on a pivotal study. And those data, they are super positive. So we are very happy with that, and we do consider a regulatory submission in Europe. That's for the next slide, but I want to insist on the central role of MaaT013. And we also are prepared for the next steps of the development of the company, of course. Notably, we have also started 2 use also MaaT013 because it's safe and we have seen characteristics within MaaT013 that were of interest also in the field of immuno-oncology. And we have completed a clinical trial -- a Phase II clinical trial in metastatic melanoma patients where we go together with immune checkpoint and anti-PD-1 and anti-CTLA-4. And so that's another milestone which is going to be coming soon. And with the second presentation of the product, MaaT033, we also do have started a large clinical trial in any patients receiving stem cell transplantation. As you can see also, we have a triple collaboration with 1 anti-cancer center here in France and [indiscernible] where we will also be assessing the potential of microbiome modulation in lung cancer. And we also prepared for -- to launch into the clinic in '26, the next gen product. With that, it's also important, focusing back on MaaT013. I would say in a nutshell in Europe for the regulatory path, we are now on track, data here. Clinical trial are completed. We will continue the Early Access Program in line with our mission to deliver product to the patients. However, we have marked an important milestone because now we are literally in a phase where we are on the submission process as illustrated by the fact that we have received already the eligibility from the EMA, which means we are eligible to the centralized procedure. So with the different steps that's going to be taking place, we do -- we will submit before the summer. We will submit the marketing authorization before the summer, which is roughly 6 months ahead of what we initially thought because once we have get -- we have accessed the data, we formed the conviction that those data are sufficient to submit the marketing authorization. In the U.S., and of course, that's a different situation because in the U.S., we have an IND, which is open but now we have the data from IRS. So we will discuss again -- we are discussing again with the FDA to -- as part of the readiness phase of what we want to do in the U.S. And of course, we want to have something which is going to be optimized on that sense that we need also to have a look to the IRS data in Europe so that we can make sure everything we do in the U.S. will be optimized and expedited as fast as we can. In parallel, of course, we do continue also the program for extended access in the U.S. In terms of the inshore market for MaaT013, so that's GvHD, 3,000 patients, EUR 380 million total available market. We do consider a market penetration of 65% in line with the level of clinical benefit that we are bringing to the patient. And with that, we do consider EUR 250 million. Based on the EAP data, we see also that physicians, they are using the product in second line. That's a little bit less than 10% of the patients that are used in second line. So assuming we can also go in second line, that will be another additional 1,400 patients that we can accumulate to the previous market size. We have a strategy where we will be preferably look for a partner to distribute the products, and it would make sense to us to have the two first products together. The reason why it's because we are targeting a little bit the same kind of partners that those partners specializing rare disease or hematology, hospital, commercial operation, that's really the initial target for us. And with everything we have developed, not only we can provide licenses for the two first products, but also we can consider co-development because the phenomenon of this disease is not only restricted to stem cell transplantation. That's also the case for CAR-T cell, bispecific in multiple myeloma. There is many opportunities where we could consider co-development. Coming back to the two first products that are Phase II and Phase III completed. That's a total market of EUR 750 million. The manufacturing, I think we have already spent a bit of time on that. Maybe the key takeaways on that slide is the fact that we have sufficient space for commercialization of the first 2 products. So the market of EUR 750 million. We do have everything we need to access this market. There's no problem. The manufacturing facility is also the pharmaceutical license of this center is also okay for commercial products. So this is an integrated platform. Interestingly, I want to focus a little bit on the yield like for any biological product, it's important to have a consistent yield. And for us, that's exactly the case. We have less than 10% variation between one compound to the other, which makes it to be -- which makes it possible to be very accurate in terms of the projection, the forecast and everything, but also in terms of the control of the cost of [indiscernible]. Those data that I'm reporting now in terms of the variability and all the rest, that's based on processes that have been authorized and informed by FDA and EMA in Europe. I'll now go in another direction, it's just to do a wrap up in terms of the milestones and how we're going to be financing out of that, Eric, if you want to take the lead on that one.

Absolutely. Thank you. Thank you, Herve. [Foreign Language], good morning, good afternoon, and good evening, everyone. It's my true pleasure to be with you all today and share the relief, the pleasure and the pride of this unprecedented data. Before we conclude the presentation and open the call for questions, I would like to take a few minutes to wrap up what's next for MaaT Pharma and summarize our key news flow over the next month and then mention all financing options going forward. So starting with the news flow. As you have seen from Herve's and Gianfranco's presentations, we have an ambitious program ahead and a dense related news flow in the next couple of years with several major value inflection points, some already in the near term. I will not go into the details of this busy slide, but the key highlights are to start with for advanced developments in the hemato-oncology space. This is, of course, the GvHD opportunity with our product MaaT013. We just achieved the first milestone with the release of the Phase III data, strongly positive again and they are positioning us for the submission of a marketing application in Europe in the middle of this year. We expect additional data on overall survival later this year and expect a European approval next year '26, which is the next major value milestone on this program. That's on the European side. In the U.S. we are also in the readiness phase, which at this stage, includes the preparation of a U.S. phase trial in acute GvHD. That's the APOLLO trial, unless there is an alternative option, as explained by Herve on the regulatory plan. The goal is to launch the trial before the end of this year, subject, of course, to appropriate funding in view of Phase III results in 2027. This is another stream of significant value creation this time in the U.S. And to finish in the heme oncology space, we have the ongoing Phase II trial, Phoebus in neurogenic hematopoietic stem cell transplantation, there has been and will be regular DSMB meetings on safety and mortality over the next month and final results are set for the second half of 2027. That would open the full heme-oncology opportunity by adding HSCT to GvHD. Secondly, we also developed the platform in the immuno-oncology space with the development in solid tumors. That's the PICASSO IST trial in adenoma, which is fully recruited and the immuno life IST trial, which is to be started in lung cancer. This development in solid tumors could well be the next additional chapter of the company's history. And that goes also with the development of the larger-scale coculture and donor independent product called MaaT034, which was covered earlier by Herve for further developments of immuno-oncology strategies in solid tumors. So I'm moving now to the next slide on financing consideration. Thank you, Sian. The company reported a cash position at the end of Q3 last year of EUR 27 million, which we believe will cover the operating needs and programs of the company into Q2 this year. So not surprisingly, we are currently exploring several funding opportunities, both with dilutive and nondilutive options to fund our ambition and programs. We plan to do that in a stepwise fashion, building on the progressing value of the company and as we continue to develop and derisk our platform. The first step for investors and our partners will be to seize the immediate value opportunity of bringing our GvHD therapy to the European markets based on the positive and strong Phase III results from the ARES trial. We intend to fund the company for at least the next 2 years, i.e., past the potential marketing approval for MaaT013 in Europe expected in the second half of '26. This will likely be a blend of several options, an equity market financing is an obvious option, but we also expect to have a number of partnership discussions starting with our GvHD asset, which is getting close to the market and these discussions will also likely include a financing dimension. I want also to mention that expanding in the United States is the next logical step for MaaT Pharma with the launch of a dedicated U.S. Phase III trial in acute GvHD. In this context of crossing over to the U.S., the company has decided to prepare a plan for a U.S. NASDAQ listing within the next 18 to 24 months with the intent of maximizing the ability to fund the company as well as gaining a better valuation and liquidity. So again, a number of options to further fund the company as we enter in our next phase of development and also a new era for MaaT Pharma. With that, I would like to thank you all already for your attention, and I will hand the mic over to Herve for concluding remarks before we open the call for a Q&A session. Thank you.

Thank you very much, Eric, and thank you to the entire team for this presentation. So Sian is pressing me because she's saying to me that there are many questions. So I'll be very short. In a nutshell, we have generated efficacy data on GvHD which have never been seen before with any kind of drugs. So that's really unprecedented. This is a very powerful asset that we will continue to develop in the 2 geographies. Also, we are -- we have a pipeline with several additional products. The MaaT033 product is already highly derisked as well. It has been used in HSCT but also into other clinical trials. So we have already information at least on the safety profile. We are treating more around 150 patients already with MaaT033. So that's already a significant database that we have. We believe that we are really paving the way when it comes to providing microbiotherapy in oncology, which is a new area, why not like the area of immunotherapy like 20 years ago when it started. So that's where we see us today, and that gives a sense of the projection that we could consider. Many questions, we will start to respond today. We'll be at JPMorgan, the full team will be there. We are welcoming meetings with partners and investors of course, and with everybody actually, but we are mainly producing those kind of meetings. And we will be happy to meet with you and go deeper based on your interest. So thank you very much. We are now transitioning to the Q&A, and I'll leave it to Sian to organize this part.

Sure. Thanks, everyone, and thank you all on the call today for all the questions. I'll start off on a few medical clinical questions for Gianfranco. The first from Clemence, Stifel. The nonresponder survival rate is almost price what has been observed in historical data. Is there any reason that could explain this?

Thank you for this question, Clemence, and thank you, Sian. I think this is a very interesting question. And indeed, the difference was noted there is an increase as compared to what we observed in the EAP of nonresponders in ARES. But first of all, I'd like to highlight 2 important elements. So the first one is that we both have a trend, which is significant. It's not just a trend. It's a significant difference between responders and nonresponders also in ARES. So difference actually is present, but the survival, the probability of survival between responders and nonresponders to really remarkable also in ARES. And also, very importantly, that the survival remains low for nonresponders. And even if a little bit higher, it is pretty much in line with what one would expect for this specific population. Of course, at this point in time, we are in the realm of speculation because these data have better reasons. It is only possible to make hypothesis and the analysis of this element, specifically will require individual patient analysis, which I would anticipate will extend to both clinical and microbiota parameters. There could be potentially an impact of the use of vancomycin and dose density of MaaT013 will have to see that potentially. But I think it is tempting to think that MaaT013 may actually impact survival in ways that are not only dependent on GvHD response. And I think this will have another element to the already exciting data that we are observing.

Thanks, I have a question here from [indiscernible]. I suggest, Gianfranco, if you can take this one, "how different is the post-treatment microbiome profile of very good responders versus late responders?"

That's a very important question too. The data not yet available, of course, but the microbiome analysis will be conducted. And of course, we may assess its potential as by marker of clinical benefit. We are all very excited to see the data. So just stay tuned.

Thanks. Moving on, I got a question on safety here. Again, Gianfranco, coming back to you, obviously, the excitement of the data is bringing a lot of questions for you and comment -- thank you for the comments on the impressive efficacy data. Question is any initial assessment of the safety on this cohort?

So of course, there is an ongoing monitoring of the data we already had a DSMB in the recent past that assess approximately half patients were a confirmation of the safety of this treatment which comes, of course, on top with the EAP data has been given. So we know already that this treatment is outstanding, not only in terms of efficacy, but also in terms of safety. Of course, we're going to continue monitoring and we will keep you updated as soon as an additional assessment would become available. But again, we are very confident based on the cumulative volume of data coming from both the EAP and RS that MaaT013 is an outstanding treatment also in terms of safety.

Slightly different theme to change directions. I know there's some more clinical-related questions, but this one is from Suzanne, both [indiscernible] or you Herve, can you clarify with MaaT013 now post the market, you're looking to partner. Is launch subject to partnering? Or would you consider doing it yourself? And if no partner is found by the time you get to approval?

So bottom line, the preferred option is to with the partner. Today, we do not have a reason to think it will not fly because we have many different discussions. So that's really the preferred option by far because we want to remain on the innovation company. We want to be very strong on what we do, and we want to license our codevelop with pharmaceutical partners. That's really what we are targeting. That being said, if we were like in a position to commercialize by ourselves, the HSP market is highest in July. Just France, for example, with 25 centers, you are covering the entire territory. So it's not a big deal to create our own sales force. It's more a strategic decision that we want to remain what we are an innovation company and use any kind of resources of the company to continue to innovate and let the pharmaceutical partners do what they know to do very well. And that's really the option, yes.

Thanks. And a question here on the regulatory, I've been asking just a little bit more clarity, perhaps [indiscernible]. Can you just remind us of the input you've had so far for the MA and what sort of filing procedure do we anticipate, any special designation?

We are [indiscernible] designation, then we have not been looking for any kind of specific pathway and it's really way too late and we are changing and how we are issuing with [indiscernible]. So we are on track in a year from now, we will know already where we stand. So there is no any need for any breakthrough on that end.

So Gianfranco coming back to you now on a couple of questions, I think, both from Suzanne and from Jacob, on the line. For the initial survival of 54% of 1 year, we understand this is a subset of data. The number of patients has not been disclosed. Can you just give a little bit of color for the audience of how robust this is so that it gives the confidence for the -- as we read out at the end of the year?

That's a very important question, too. Thank you for asking. So the follow-up of RS is now ongoing since quite some time. And we're actually very confident that the probability of survival is really based today on a substantial number of evaluable patients. I would also like to remind the audience that these data are remarkably consistent with the Early Access Program. Just as a quick reminder, in the RS like population, responders of day 28 had survival at 1 year of 75%. This is pretty much identical to the probability of survival that we today see in ARES. And so in summary, based on these 2 considerations, I do believe that these data are strongly representative or what we are going to observe in the longer run.

Okay. A few questions around our intentions in the U.S. here. First, [indiscernible] looking up, what might -- the question, I think I'll put it to Herve or Gianfranco, what might the design of the U.S. followed the Phase III trial?

I will let Gianfranco comment on the details about top line. There are the same patients treated a little bit the same, same approach, same ruxolitinib. So I would say it's very similar. The question is more on how we can leverage on what we have done in Europe to optimize the plan in the U.S., but the design could be maybe, I don't put a figure but very close to what we have done in Europe, but maybe with a different parameters in terms of the sizing in few elements.

Absolutely, this is exactly how the design looks like. It's a pretty similar. It's not -- basically superposable to what we have in ARES, so if the intent of the question is also to explore whether we would be expecting different results in the U.S.-based population, third-line aGvHD. At this point in time, I would [indiscernible] if that was okay. I think we're going to see very similar data there.

Thanks. Question around the competitive landscape, specifically in terms of third line aGvHD. Maybe you can talk to add a little bit Gianfranco, what is the competitive landscape for third line GvHD?

So I would say, to begin with, that, of course, there are a number of potential treatments for third-line acute Graft-versus-Host Disease. But actually, there are several limitations to that. First of all, we observed that many of these agents show some inconsistent responses and also that are treatment-related toxicities. I, perhaps also in the interest of time, going down into those individual agents and discuss the reasons why the path to have approval in refractory Graft-versus-Host Disease is actually complex. It's not really appropriate at this point in time, but I'd just like perhaps to highlight a couple of points that really discriminate and differentiate actually MaaT013 as compared to other approaches. Basically, one important consideration is that we address like several other agents, BGI in particular. And we have, I think, highlighted in this presentation how this has been a particularly problematic anatomical side. And the success that we are observing through this innovative approach, I think it relies on the immune modulation through microbiome, and this is actually resulting from a complex interplay of a variety of different mechanisms. And I think this is very different from other potential approaches, most of them actually that rely on the identification and modulation of individual mechanism. I would like to also highlight the fact that unlike immunosuppressive treatments that have been tested to date, our safety doesn't seem to really pose, actually does not post issues in terms of safety for the onset of opportunistic infections and actually by providing a more competitive niche for the growth and potentially [indiscernible] biomes, we might potentially observe some level of protection at this level, which is very important. I think another important difference is that the effects are very, very rapid. We often see responses before day 28 with a treatment that only lasts for 10 days from day 1 to the day 10 and only three administrations. So if you put together the difficulties in aGvHD and they have been observed and the outstanding characteristics coupled with the responses. I would have to say that I'm quite confident that competition is going to be better limited.

Thanks. Just conscious of time here. I've got one -- just one question when looking at the data again compared to the Phase II, response rates are a lot higher than observed in the Phase II, so what do you think contributed to this improvement?

So that's another very important question. And it is important to, I believe, highlight a number of different elements here. So first of all, the Phase II study was enrolling patients with really high risk. And by this, I mean that not only these were patients that were exclusively G3 and G4 in terms of Graft-versus-Host Disease, but they were all refractory to corticosteroids. So we didn't have the proportion of patients that were dependent on steroids meaning that there is some control of GvHD, but the moment you try to taper steroids, then the disease come back. And we know that there is some better response in that specific category of patients. And this might also explain the difference. I think the other consideration is the fact that, of course, that study was quite limited, and there could be some kind that originated that may be explained by the numbers that we were having there. And the other important element is that like for many other realms of clinical practice, it is possible that the experience of the clinical management of these patients has grown over time, which has led to different and improved ways of identifying the best point in time and identifying patients that would have some different or differential chances of responding to the treatment. Of course, this would be due to a combination of these factors. But I think at this point in time, we can confidently interpret those difference based on one or more of the points that I've raised here.

I'd like to add also the fact that the Phase III conforms with the feedback from authorities and conforms in terms of the population with the precedence both in the U.S. and Europe, if you look at [indiscernible]. They would have the same kind of population as compared to the Phase III, whereas the population we had on Phase II, they were different, way more severe on the Phase II on our side. But I just can't confirm that the Phase III conforms to what you would expect in terms of the recommendation from the agencies.

Okay. Thanks. A few minutes left here. Another question just around how -- is there any read-through between MaaT013 and MaaT033, taking into account the underlying biology, microbiome modulation, could there be any read-through from that MaaT013 to MaaT033.

Yes, I think -- so let me just reiterate the question, taking into account the underlying biology. Well, yes, I believe that what we are observing with MaaT033 may constitute a solid rationale to anticipate what we might be observing with also MaaT033. Of course, here, what we are -- what we are now doing is to explore MaaT013 and MaaT033 in a different context. But I believe that the different -- those different settings, that settings would be conducive to certainly the correction of these biosis. And this may result in clinical benefits through a variety of different mechanisms that could be disease specific. And what we are observing with GvHD may very strongly predict the efficacy with MaaT033 too.

Thanks. I think this -- a question on, I think, time for a couple of more questions. More on the product itself using [indiscernible], is it appropriate to treat people with gut microbiota composition. Obviously, the pooled microbiota provides microbiome diversity and then what -- in which what appropriate is it to treat people whatever [indiscernible] composition. And is it the way ahead for precision medicine?

No, no, that's a very good question. And from a scientific point of view, this question makes a lot of sense. And that's an opportunity to explain how different are the products, but also the positioning. In GvHD and in hematology oncology in general or those going through stem cell transplantation. Sometimes, you do not have a microbiome anymore. Not -- I see it's a question from a scientist. Sometimes you do not have even DNA to extract to do the sequencing because there is nothing remaining. So here, we are more considering the situation of the patient and the situation of the gut. And we believe there's an urgency to restore the microbiome. So that's MaaT013. With MaaT033, it's also the same, but we go with patients where the environment is a little bit less aggressive, so that the product has time to engraft. When it goes to the next generation [indiscernible], that's exactly what we're going to be doing. We will be looking for more like functional dysbiosis where we will be fine-tuning and if you look on the corporate presentation, in a certain slide, we have published already in vitro, in vivo data showing what to do in terms of refining the product. so that we can also target more functional dysbiosis. But to make it clear, the HSCT business that's really very strong dysbiosis. So it's not that relevant in that context. But for the rest of the development, of course, we are taking that into consideration.

Okay. I think yes, we've been gone through all the questions and the multitude of them, and we are out of time now. So if we didn't get to your question, as we mentioned, the team will be at JPMorgan next week. Happy to meet people, if you're there, and obviously available contact us via our website. A good question of whether there will be the replay. The repay will be online. So feel free to connect on to our website. Thank you all very much for your interest in the call today. We very much enjoyed sharing the data with you. And if you have further follow-up questions, feel free to reach out and wish you a good evening, a good day, and thank you for your interest in MaaT Pharma.

Thank you, Sian.

Thank you, Sian.

Thank you all. Bye-bye.

Thank you all. Bye-bye.