Good afternoon, good morning, good evening, and a Happy New Year to you all. I'm Siân Crouzet, Chief of Staff at 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 3 trial for MaaT Pharma in acute graft-versus-host disease, what it means for patients and for MaaT Pharma from a business perspective. I will be moderating the session today and remind you that the webinar is accessible via a computer or a phone line. Please note the questions may only be asked using the chat box on the computer. After the prepared remarks, we will open up for a Q&A session. Joining me today are Hervé Affagard, CEO and co-founder of MaaT Pharma; Gianfranco Pittari, our Chief Medical Officer; and Eric Soyer, our Chief Financial Officer.
Hervé 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, Hervé, I'll let you take the floor.
Thank you very much, Siân. Am I on the next slide yet? Okay, so Happy New Year to everyone. Let me start with an overview of the company's focus and strategy. So that's the first slide. Since our inception in 2014, we are now a 10-year company. We have been driven by the ambition to demonstrate the transformative potential of microbiome modulation in very severe disease. As a proof of concept, we have been focusing since the early days in graft- versus- host disease, which is one of the most significant threats in today's medicine. So we have decided to show that for the first indication, we are able to deal with inflammation among other things. What we would be providing today is really those outstanding results that we are communicating just yesterday, and we will provide you with a deeper insight on the progress on this development.
To better understand our strategy and our business model, I'd like to highlight three 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 two product ranges. We have our proprietary data science platform that we call gutPrint, 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 sources of funding to support the upcoming milestones of the company.
In the short term, we also will generate revenues through licensing or through different kinds 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 microbiome therapy. So what is microbiome therapy 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 anti-cancer drugs.
This is particularly true in hematology-oncology, where those patients are receiving everything: chemo, antibiotics altogether, then stem cell transplantation. So at the end of the day, not only will it severely damage the microbiome, but it will ultimately 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 two graphics, our products, MET, Microbiome Ecosystem Therapeutics, are capable of restoring the key aspects 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 these dysbiosis. We are reestablishing the essential 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 microbiome therapy, and that MaaT Pharma is very well placed in being a leader on that field. In terms of different products that we are developing, we do produce ourselves the products. As I've said during the introduction, we have two ranges of products that are complementary. The two products that are into the clinics today, they are what we call the MET product, MaaT013 and MaaT033. We do have a next generation product as well that we call MaaT Seeds, not 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.
What sets us apart when looking at other microbiome companies is that we have developed a unique proprietary pooling approach, which helps to make the product standard. We mix together several microbiomes that we get from donors, and we can standardize the product, and 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. That's it for the introduction. 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, Hervé. Again, good morning, good afternoon, and good evening, everybody. Today, the focus is to discuss the ARES data that explore 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. 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 gut. 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 occurs 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 a medical need. And so basically, what happens today is that 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 refractory GVHD. And in 2019, ruxo was approved as a 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% of patients would show a response, and this means that basically approximately 30% of patients, which in absolute terms is as many as 3,000 transplanted patients in Europe and the US, would have a GvHD that is both steroid and ruxolitinib 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 explored this population of third-line acute graft-versus-host disease failing first-line steroids and second-line ruxolitinib.
Patients in the study were to receive three doses of MaaT013, 1, 5, and 10. The primary endpoint of the study was the determination of overall response rate at gastrointestinal level after 28 days, and the secondary endpoint for efficacy was the determination of overall survival at one year. We recruited 66 patients, and today we are all proud to show you the data, which really, as was mentioned earlier by Siân and Hervé, are unprecedented in third-line acute graft-versus-host disease. 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 2, 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 the 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 at 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 ASH24 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 a GVHD extending beyond GI, and these patients also exhibited the response. Because of this reason, the overall response rate at all organ levels 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 deep responses, which is either CR or VGPR. I would say that we are really delighted to see that MaaT013 translates in a remarkable extension of patient survival.
At one year, the probability of survival is 54%, and this by far exceeds the 15% expected survival at one 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 this 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 non-responders. This is also in line with early access program data, 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 these, I will give the floor back to Hervé, 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 MaaT013 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 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 dynamic in centers, the way our product or how our product will 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 were looking for. And as you can see from the graphic, the demand has been increasing with a fantastic 2024 because we have for the first time exceeded 100 EAP during 2024, and that's the equivalent of two EAP per week, which is really significant. And now we deliver the product in 10 countries. The increase in 2024 was 75%. We deliver in 10 countries. We have expanded the early access program in the U.S. We have treated the first patients in late 2024. Now we have the supply chain, the distribution center.
We have one in the U.S., one in France to cover almost everywhere in the world. So that's really good news. And also, there's 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 number of doses per patient is three doses. So we have been in a position to generate EUR 2.3 million for the first three quarters of 2024, which represents the activity in France. Also, you notice that there's 95% of the early access program, they are GVHD.
But we do also receive 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's 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 want to repeat it because it validates the strategy. The EAP signal that we have seen in the population, which is close to the one from ARES, we had the same signal, 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 Professor Mohamad Mohty, who is a longstanding advisor to the company, to provide us with feedback regarding the relevance of those 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 3 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 patients has driven the relentless pursuit of innovative solutions. Today, we are witnessing the fruits of that determination, a breakthrough that is truly transformative for the field. This new MaaT013 therapy, which we are here to highlight, represents 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 3 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 rate, 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 the mechanism underpinning it. This therapy goes beyond simply suppressing inflammation. It paves the way for precision medicine by aligning with an emerging frontier in healthcare, the modulation of the microbiota. By understanding and harnessing the microbiota's complex role in immune regulation, this treatment offers a new paradigm for managing 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 3 ARES trial is more than just a validation of a drug. It is a beacon of hope and a harbinger for further advancement. It 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're not just advancing medicine, we're also changing lives. Thank you for your attention.
So that was the testimonial 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 regulatory submission in Europe. That's for the next slide, but I want to insist on the central role of MaaT013. And we also have prepared for the next steps of the development of the company, of course.
Notably, we have also started to use 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, phase 2 clinical trial in metastatic melanoma patients where we go together with immune checkpoint inhibitor 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. And as you can see, also we have a triple collaboration with one anti-cancer center here in France and Regeneron, where we will also be assessing the potential of microbiome modulation in lung cancer. And we also prepared to launch into the clinic in 2026 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 are here. Clinical trials are completed. We will continue the early access program in line with our mission to deliver our product to the patients. However, we have marked an important milestone because now we are literally in the phase where we are on the submission process, as illustrated by the fact that we have received already the eligibility letter 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 will submit before the summer.
We will submit the marketing authorization before the summer, which is roughly six months ahead of what we initially thought because once 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 ARES, so we will discuss again. We are discussing again with the FDA 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 ARES 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 expanded access in the U.S. In terms of the initial 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 the 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 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 is because we are targeting a little bit the same kind of partners. Those partners specialize in rare disease or hematology, hospital commercial operation. That's really the initial target for us. And with everything we have developed, not only can we provide licenses for the two first products, but also we can consider co-development because the phenomenon of these dysbiosis is not only restricted to stem cell transplantation. That's also the case for CAR T cell, bispecific in multiple myeloma. There are many opportunities where we could consider co-development. Coming back to the two first products that are phase 2 and phase 3 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 are the fact that we have sufficient space for commercialization of the first two 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 company to the other, which makes it possible to be very accurate in terms of the projections, the forecast, and everything, but also in terms of the control of the cost of goods sold. 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 all of that. Eric, if you want to take the lead on that one.
Absolutely. Thank you. Thank you, Hervé. Bonjour, 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 from MaaT Pharma and summarize our key news flow over the next month, and then mention our financing options going forward. So starting with the news flow, as you have seen from Hervé'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 our advanced developments in the hematology-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 3 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, 2026, 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 3 trial in acute GVHD.
That's the APOLLO trial, unless there is an alternative option, as explained by Hervé 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 3 results in 2027. This is another stream of significant value creation this time in the U.S. And to finish in the hematology space, we have the ongoing phase 2 trial, PHOEBUS, in allogeneic 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 hematology opportunity by adding HSCT to GVHD. Secondly, we also develop the platform in the immuno-oncology space with the development in solid tumors.
That's the PICASSO IST trial in melanoma, which is fully recruited, and the ImmunoLife 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 co-cultured and donor-independent product called MaaT034, which was covered earlier by Hervé for further developments of immuno-oncology strategies in solid tumors. I'm moving now to the next slide on financing consideration. Thank you, Siân. 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 non-dilutive 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 de-risk our platform. The first step for investors and/or partners will be to seize the immediate value opportunity of bringing our GVHD therapy to the European market based on the positive and strong phase 3 results from the ARES trial. We intend to fund the company for at least the next two years, i.e., past the potential marketing approval for MaaT013 in Europe expected in the second half of 2026. 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 3 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 18-24 months with the intent of maximizing the ability to fund the company as well as gaining 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 Hervé for concluding remarks before we open the call for Q&A session. Thank you.
Thank you very much, Eric, and thank you to the entire team for this presentation, so Siân 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 two geographies. Also, we have a pipeline with several additional products. The MaaT033 product is already highly de-risked as well. It has been used in HSCT, but also in two other clinical trials, so we have already information at least on the safety profile. We have treated 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 JP Morgan. The full team will be there. We are welcoming meetings with partners and investors, of course, and with everybody actually, but we are mainly focusing on those kinds 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 Siân 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 Clémence Stifel. The non-responders' survival rate is almost twice what has been observed in historical data. Is there any reason that could explain this?
Thank you for this question, Clémence, and thank you, Siân. I think this is a very interesting question, and indeed a difference was noted. There is an increase as compared to what we observed in the EAP of non-responders in ARES. But first of all, I'd like to highlight two 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 non-responders also in ARES. So the difference actually is present, but the survival, the probability of survival between responders and non-responders is really remarkable also in ARES. And also, very importantly, that the survival remains low for non-responders. And even if a little bit higher, it is pretty much in line with what one could expect for this specific population.
Of course, at this point in time, we are in the realm of speculations because these data are very recent. It is only possible to make hypotheses, and the analysis of these elements 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, the dose density of MaaT013. We 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 add another element to the already exciting data that we are observing.
Thanks. I have a question here from Pierre Deschelot. I suggest Gianfranco, if you can take this one. How different is the post-treatment microbiome profile of very good responders versus low responders?
That's a very important question too. The data are not yet available, of course, but the microbiome analysis will be conducted. Of course, we may assess its potential as biomarker of clinical benefit. We are all very excited to see the data. Just stay tuned.
Thanks. Moving on, I've 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 comments. And thank you for the comments on the impressive efficacy data. Question is, any initial assessment of the safety on this cohort?
Of course, there is an ongoing monitoring of the data. We already had a DSMB in the recent past that assessed approximately half patients where a confirmation of the safety of this treatment, which comes, of course, on top with the EAP that 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 body of data coming from both the EAP and ARES 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 from Suzanne at Kempen. For you, Hervé, can you clarify with MaaT013 now close to the market, you're looking to partner, is launch subject to partnering, or would you consider going it yourself? And if no partner is found by the time you get to EU approval?
So bottom line, the preferred option is to go with a partner. Today, we do not have 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 an innovation company. We want to be very strong on what we do, and we want to license or co-develop with pharmaceutical partners. That's really what we are targeting. That being said, if we were in a position to commercialize by ourselves, the HSCT market is highly centralized. 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, yeah.
Thanks. And a question here on the regulatory, I think asking just for a little bit more clarity. And from Suzanne, can you just remind us of the input you've had so far for the EMA? And what sort of filing procedure do we anticipate? Any special designation?
We are funded with designation. Then we have not been looking for any kind of specific pathway, and now it's really way too late. We are changing, and now we are discussing with the CHMP, so we are on track. In a year from now, we will know already where we stand, so there's no need for any breakthrough on that end.
Okay, thanks. 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% at one 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 you give the confidence for the data as we read out at the end of the year?
That's a very important question too, and thank you for asking. The follow-up of ARES is now ongoing since quite some time. We're actually pretty confident that the probability of survival is really based today on a substantial number of valuable 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 ARES-like population, responders at day 28 had survival of one year of 75%. It is pretty much identical to the probability of survival that we today see in ARES. In summary, based on these two considerations, I do believe that these data are strongly representative of what we are going to observe in the long run.
Okay, thanks. A few questions around our intentions in the U.S. here. First, Jacob. What might the question, I think I'll put it to Hervé and Gianfranco. What might the design of the US follow-on phase 3 trial be?
I will let Gianfranco comment on the details. But top line, they are the same patients, treated a little bit the same, same approach, same role to retain. 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 US. 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 different parameters in terms of the sizing and fueling.
Absolutely, Hervé. This is exactly how the design looks like. It's a scribble of similar, if 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 US-based population, third-line aGvHD, at this point in time, I would be very surprised if that was the case. I think we're going to see very similar data there.
Thanks. Question around the competitive landscape, specifically in terms of third-line GvHD. Maybe you can talk to that a little bit, Gianfranco. What is the competitive landscape for third-line GvHD?
Sure. 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 there 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, is 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, unlike several other agents, the GI in particular.
We have, I think, highlighted in this presentation how this has been a particularly problematic anatomical site. The success that we are observing through this innovative approach, I think it relies on the immune modulation through microbiome. This is actually resulting from a complex interplay of a variety of different mechanisms. 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 pose, issues in terms of safety or the onset of opportunistic infections.
And actually, by providing a more competitive niche for the growth and potentially aggressive blast rate of pathobionts, 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 one to day 10 and only three administrations. So if you put together the difficulties in aGvHD and that 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 very limited.
Thanks. I'm just conscious of time here. I've got just one question. We're looking at the data again compared to the phase two. Response rates are a lot higher than observed in the phase two. 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 two study was enrolled in 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 comes 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 that there could be some kind of heterogeneity that may be explained by the numbers that we were having there, and the other important element is that, like for many other real-world 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 could be due to a combination of these factors, but I think at this point in time, we can confidently interpret those differences based on one or more points that I've raised here.
I'd like to add also the fact that the phase 3 conforms with the feedback from authorities and conforms in terms of the population with the precedent, both in the U.S. and Europe. If you look at Ruxolitinib, they would have the same kind of population as compared to the phase 3, whereas the population we had on phase 2, they were different, way more severe on the phase 2 on our side. But I just can confirm that the phase 3 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, if there's any read-through between MaaT013 and MaaT033, taking into account the underlying biology of microbiome modulation, could there be any read-through from MaaT013 to MaaT033?
Yeah, I think so. Let me just read the question, taking into account the underlying biology. Yeah, 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 now doing is to explore MaaT013 and MaaT033 in a different context. But I believe that those different settings would be conducive to certainly the correction of these dysbioses. And these 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 efficacy with MaaT033 too.
Okay, thanks. I think it's time for a couple more questions, more on the product itself using pooled microbiota. Is it appropriate to treat people with their gut microbiota composition? Obviously, the pooled microbiota provides microbial diversity. And then how appropriate is it to treat people, whatever their gut microbiota composition? And is it the way ahead for precision medicine?
Yeah. 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. I see it's a question from a scientist. Sometimes you do not have even DNA to extract to do the sequencing because there's 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 MaaT0 13. With MaaT0 33, 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 graft.
When it goes to the next generation MaaT00 3, that's exactly what we're going to be doing. We will be looking for more functional dysbioses 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 we do in terms of refining the product so that we can also target more functional dysbioses. But to make it clear, the HSCT business, that's really very strong dysbioses, so it's not that relevant on that context. But for the rest of the development, of course, we are taking that into consideration.
Okay, thanks. I think we've gone through all the questions and a multitude of them, and we're out of time now. So if we didn't get to your question, as we mentioned, the team will be at JP Morgan next week. Happy to meet people if you're there and obviously available, contact us via our website. A few questions about whether there will be the replay. The replay will be online. So feel free to connect on to our website. Thank you all very much for the 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, Siân.
Thank you, Siân .
Thank you all. Bye-bye.
Thank you all.
All right.
Bye-bye.