Good afternoon or good morning, depending on where you are. Thank you very much for attending this webcast of MaaT Pharma, where we will be presenting the data that we presented during the ASH conference. I'll be doing this introduction and opening remarks. Of course, I like to start with the disclaimer. I like to remind you that today this discussion contains forward-looking statement that are subject to various risks and uncertainties. The agenda for today is that I'll be starting with introduction, presenting the company and the providing you with a big picture on where we are and what we are doing.
Professor Mohamad Mohty will be presenting the first presentation that we did during the ASH, which is an oral presentation talking about GvHD and new datasets that we are providing with regards to MaaT013. Professor Florent Malard will be also presenting the first data that we are sharing with the community today on MaaT033, our second product that we have tested as part of a phase I-D study and which was subject to a poster presentation during the ASH. I'll come back with a presentation and the ending remarks, and there will be room for a 15 minutes Q&A session. Just to introduce you to MaaT Pharma. MaaT stands for Microbiome as a Therapy.
We are developing microbiome-based drugs using a platform that we call MET, Microbiome Ecosystem Therapies, to address severe disease in the field of hematological malignancies and oncology. Our pipeline is made of several assets that are late stage and also pre-clinical. We have MaaT013, which is under assessment today as part of the phase III in acute GvHD. Also, we have another program, MaaT033, which will be soon be started as part of potentially another pivotal study in stem cell transplantation patients. That provides investors with news flow, including late stage clinical milestones. Our MET platform is made of two key pillars.
The first one is the data science platform that we call gutPrint, which is about assessing the dialogue between the gut microbiome and the host part of the patient using metagenomics methods mainly. The second part, which is very important because of the biological nature of the product that we are developing, which is the cGMP facility that we run by ourselves. The company is made of 50 people as we speak today. We have raised more than EUR 80 million, and also we have treated more than 200 patients since the inception of the company back in December of 2014. The overall concept of what we are doing is that we want to address the host microbiome interaction.
That's the dialogue between the microbiome and the host part, which is very important regarding the mode of action that we are targeting and which will be presented by Professor Mohty during his presentation. However, the overall concept is really to deal with this blue layer, which is a network of bacteria talking together, but also talking to the immune system. As most of you would know, 80% of the immune cells reside in the gut microbiome. It's understandable that by dealing with the microbiome, you have an opportunity also to modulate the activity of the immune system. There's also now a good evidence is showing that when there's an alteration of the microbiome, there's also hyperinflammation or a dysregulation of the immune system. That's exactly what we will be developing.
We will be developing drugs to address this very important issue of what we call the dysbiosis, which is when the gut microbiome is altered. One very important concept, to go straight to the point, if you want to achieve a good clinical result or benefit for the patient, you need to restore the diversity. All the studies that we have seen so far are showing that one key element in achieving the different primary endpoints in clinical studies is really to restore the diversity. This is evidenced here on the left-hand side, for example, with a publication which is coming from the Sloan Kettering Center. This is not our studies.
They are third-party studies. The first one on the left-hand side is coming from the Sloan Kettering Center, and that's showing that at the time of the engraftment of the neutrophil, when patients are undergoing stem cell transplantation, if you have a high diversity, you increase by 50% your chance of survival at three years. The second graph is basically saying the same. Diversity is very important. Interestingly, we see also the same phenomenon in solid tumors where the rationale is a little bit different here because it's more about cooperation between immune checkpoint inhibitors and the microbiome. Here again, you see the higher the diversity, the most the patient will be responders to immunotherapies, to ICI here in that context.
It's very important to make the anti-cancer drugs efficient to have a good microbiome. To address this important issue of the disequilibrium of the microbiome, we have this MET platform, and that has helped us to generate several candidates. We have a native product that we will be presenting today, and we have MAT13 and MAT33. MAT13 is what we call an enema. This is a present liquid formulation we use for administration as an enema, as a lavage. That's very powerful for patients that are in very severe condition. We have also MAT33, which is a capsule, which you will use when the patient condition is a little bit less severe.
MaaT013 is under evaluation in GvHD, it is also under evaluation in combination with immune checkpoint inhibitors, whereas MaaT033 has been evaluated as part of a phase I-B study. We are hoping to start very soon, potentially pivotal clinical trial to evaluate MaaT033. We have another generation of products which are, which we call the co-culture product, where these products, they are donor-independent. The native product, they come from donations, from healthy donors that we have selected, based on safety criteria. The co-culture product is a different product. We go with master ecosystem bank that we use, to define a specific product, and we are considering using that product in solid tumors, mainly because the size of the market is bigger.
It translates into the go-to-market strategy where we start with a GvHD, 2,000 patients. We go with any patients receiving stem cell transplantation, 22,000 patients. That's for Europe and the U.S. We go with MaaT03X, which is 10 x the size of the stem cell transplantation market, 200,000 patients. We go potentially to any immune-mediated disease. Our objectives, as I said, MaaT013 is evaluated in GvHD with interim analysis for this clinical trial, the phase III, by the first part of the 2023. We will be also proposing this to be in Europe, using MaaT033 in hematological malignancies. MaaT013, sorry, is also under evaluation as part of a phase II clinical trial that's ongoing in France.
MaaT03X, that's under assessment at the preclinical level. Also we are optimizing and scaling up the CMC manufacturing to support the entry into the clinics. Last but not least, we are setting a new GMP facility, which will be based here in France, and that will be of course fully GMP compliant. We'll be presenting the data on MaaT013 and MaaT033, both in hematological malignancies. ASH is a very important conference, and we are happy to share that that's the third year in a row that we've been accepted on oral presentation, and that's the sixth year in a row that we are presenting data. We see that now the microbiome has a strong recognition within the hematological community, and we are very happy with that of course.
I'll introduce the presentation of Professor Mohamad Mohty with regards to MaaT013 in the context of GvHD. The GvHD and MaaT013 data, they are made of two kind of data. On the left-hand side, you have the results from clinical trials. We have achieved a phase II clinical trial, and now we are undergoing phase III in Europe. You're gonna see also the data from the early access program that is accessible within Europe. We already treat patients in several countries in Europe as we speak today. With that, I leave the floor to Professor Mohamad Mohty, who will present to you the data on MaaT013.
Thank you very much, Hervé, for the kind introduction. It is my great pleasure to be with you today to present the data that we have just presented at the American Society of Hematology annual meeting in relation with the pooled microbiota product for refractory gastrointestinal acute Graft-versus-Host Disease. These are the results of the early access program in France. I'm Mohamad Mohty from the Sorbonne University in Saint-Antoine Hospital in Paris. For the sake of introduction, I would like simply to highlight that acute Graft-versus-Host Disease, especially steroid refractory acute Graft-versus-Host Disease, is a huge unmet medical need. Needless to say that allogeneic stem cell transplantation is the only curative treatment for many blood diseases today.
Unfortunately, one key limitation is Graft-versus-Host Disease, especially acute Graft-versus-Host Disease. Beside high-dose corticosteroids, until recently, we had limited option to treat these patients, especially when they become steroid refractory. In terms of pathophysiology, we know very well that actually the chemotherapy we use in these patients as part of the treatment of their malignant blood cancer, the irradiation, the immunosuppressive therapy, but also the broad-spectrum antibiotics are going to generate a significant loss of diversity. This is what we call dysbiosis. This status of dysbiosis is going to initiate, to be a trigger for acute Graft-versus-Host Disease.
When you look into the numbers of transplanted patient every year in Europe and across the globe, you would easily imagine that this is a problem we need to handle, and we need urgently to develop solutions. This is where I think we are already fortunate enough to have this MaaT013 drug or product, which aims to restore the interaction between the gut microbiome and the immune system to treat acute GvHD. Actually, when it comes to the target organs of acute GvHD, we have the skin, we have the liver, but most importantly, the prognosis is related to the gastrointestinal localization. This is why actually the MaaT013 product is able to bring a high richness, high diversity, a Butycore rich product, which would allow to restore, to increase the diversity.
That would help to restore the GI barrier integrity. Through, for instance, some immune regulatory mechanism, we have a complete restoration of immune homeostasis. You can see here the characteristics of the product that we are currently using. We have now a very important experience with this, especially that this is a pooled microbiota product that can include a high richness, high diversity. It's sort of a full ecosystem containing Butycore. If you compare it to a single donor product, I don't need to spot of time highlighting the major differences in favor actually of the pooled MaaT013 product. In terms of administration, we have validated through previous clinical trials, especially the HERACLES Phase II clinical trial, the three doses to be administered.
In general, since we're talking about GI aGvHD, the evaluation is about the overall response, usually at day 28. Here, my focus is gonna be about the early access program in France. This has been authorized by the French regulatory agency. Actually, we have treated, I think more than 100 patient. Here I'm showing you the data from the 81 patient treated between July 2018 and May 2022 in 17 French sites. All of these patients, you can see the characteristics are adult patient with GI acuity grade two- four. The majority, 84% are steroid refractory. A small number, 16% are steroid dependent. When you look to the characteristics of GvHD, you would appreciate that the majority of these patients are the severe patient.
Beside the GI localization, there are also other organs being involved. The primary endpoint, of course, for us, is to look into the response rate at day 28, especially that these patients have received and failed a median of two prior lines of treatment. Here you can see the responses in the all population. What is really very important is the high rate of complete remission, but also VGPR and PR. You can appreciate that we are talking about a 49% response rate, 56% when it comes to the GI. I do insist it is the GI which really drive the prognosis of these patients. Here are the overall survival curves and data. Again, although this is not a randomized trial, of course, it's an early access program.
Still, these results, 51% survival at six months, 39% at one year compare favorably to what we know from the literature. What is really amazing is that when you concentrate on those responding patients, this is a blue curve. Almost 70% of the patients are alive at six months, 59%, 60% at one year. This is really, in my opinion, unprecedented and clearly showing that clinical response to MaaT013 would translate to an increased overall survival. Let me dig a little bit deeper into these results. For instance, comparing the steroid-dependent versus the steroid-refractory patient. Obviously, although the numbers are smaller, actually the steroid-dependent patient are doing really very nicely with the MaaT013 administration.
92% GI response rate, whereas in the steroid refractory, as you may guess, because these are the most advanced and most difficult, the hard to treat patient, it's only 49%. What I would like to highlight again is the 69% CR rate in the steroid dependent and 31% CR rate in the steroid refractory patient. Another important feature that I would like to emphasize and insist upon is the response in the ruxolitinib refractory patient. Why we believe that this group of patient is important because ruxolitinib has been recently approved as a treatment for steroid refractory acute GvHD. What does that mean? Well, patient have received and failed ruxolitinib. We are totally in a hopeless and desperate situation. The ruxolitinib refractory patient are really in a very terrible situation.
The good news we can see here is that the MaaT013 administration can also salvage these patients who are ruxolitinib refractory, and you can appreciate the GI. If you use MaaT013 in the third line, which is immediately after the failure of ruxolitinib, you can go up to 65%. Again, 61% of CR. Really amazing results. If you look to the overall survival in this group of patients who are steroid and ruxolitinib refractory, well, 74% are surviving at six months among the responders, and it looks like there is a plateau because we have exactly the same rate at one year. In this population where we have nothing to offer to propose, MaaT013 is leading to some incredible results with an excellent safety profile.
I will not go through all of these details, there's no report of pathogen transmission. We do have only two cases of non-pathogenic commensal bacteria associated with an infectious event, but the procedure is very safe and very well-tolerated. In conclusion, based on this early access program, we could show, and this is a very decent number, 81 patient being analyzed very precisely. MaaT013 is highly effective treatment for steroid refractory or steroid dependent. We're talking about a 56% GI overall response rate at day 28 after administration of the product, 49% overall response rate. These excellent responses are also specifically seen in the ruxolitinib refractory patient, which means when MaaT013 is used as a third line with 65% GI response rate.
All of these responses, as I highlighted, are translating towards an increased overall survival with a very good safety profile. As you can guess, such a very nice, very good results warrant further investigation, and this is why we launched recently the ARES phase III study of MaaT013 as a third line therapy in GI aGvHD. It's a pivotal single arm study. The primary endpoint is a GI response at day 28, and the first patient was included in March 2022. The centers participating are in France, Germany, Spain, Belgium and Austria, and there will be some future expansion to other EU countries. With this, I'd like to thank you all for your attention.
Of course, I'd like to acknowledge all my colleagues who contributed and generated these data, the patient, the caregivers, the healthy donors, which allowed to manufacture the fantastic MaaT013 product. Of course, I'd like to thank the whole MaaT Pharma team for their great efforts and dedication to find solutions for patients who are really desperately in need of a treatment for their GI aGvHD. Thank you very much, and I'll hand it over now to, again, to Mr. Hervé Affagard.
Thank you very much Professor Mohty for this very well-made presentation and very interesting data that you shared with us today. With that, we will be transitioning to MaaT033, which is the next product within the pipeline. MaaT033 will be used in any patients receiving stem cell transplantation. Leveraging on the concept of diversity and based on observations that we have made on our data, but also on data from others, we have seen that the diversity after a stem cell transplantation is very important with regards to the overall survival of the patient at two years. That's exactly what we want to do as part of our next clinical trial.
We want to restore the diversity within the gut of the patient to improve the survival of the patient. The way we're gonna be improving the survival, it's really by dealing with the reduction of the prevalence of GvHD, with the infections. We believe there will be less infection in patients that have been treated regarding their microbiome. This is what we'll be presenting today. This is really the first step in terms of the clinical development. If we look at who is receiving stem cell transplantation, there are many leukemia patients. You see here that half of the patient, they are acute myeloid leukemia patients, and that's where we have done our first clinical trial, because the conditioning is very similar to the conditioning that is received for stem cell transplantation patients.
Also, we have a longer history in terms of clinical trial in the field of acute myeloid leukemia, where we can compare data that we have obtained in the past, being on the same setting. Those data are very interesting, and Professor Florent Malard will be presenting the poster that we have presented during the ASH. With that introduction, I'll leave the floor to Florent Malard.
Thank you, Hervé, for this introduction. Now I will have the pleasure to present you the result of MaaT033 for a gut microbiota diversity restoration in patient with acute myeloid leukemia. This is a result of the phase I-B CIMON trials. MaaT033, what is MaaT033? This is an optimized oral capsule that restores and maintain an healthy gut microbiome in patients with severe dysbiosis. Here are the characteristic of the product. This is so an oral pool fecal microbiota that is produced through a strict screening process from healthy donors with high richness, high diversity, full ecosystems with, this is very important, an ileocecal delivery on with more than 10 to the nine viable bacteria per capsules.
This is oral and lyophilized capsule. This is very important because patients can have the capsule at home. This is very easy for the administrations. As indications develop so far, this is to improve the survival in patients that are planned to receive allogeneic stem cell transplantations. As I just said, this is intended to be an adjunctive on maintenance therapy for patients with hematological malignancies and in particular, for patients that receive allogeneic stem cell transplantation.
Why we want to focus at the moment in those patients, because there is some very strong data, in particular this analysis published in The New England Journal of Medicine that included more than 1,000 patients that demonstrate that patients with the lower diversity after a graft month have a lower overall survival compared to patients that have a higher microbiome diversity. It seems very important to restore microbiome diversity to improve the outcome. Why these patients have a decreased diversity? They receive chemotherapy and very large spectrums antibiotics. This will induce dysbiosis that is associated with complications such as infectious complications, obviously, but also Acute Graft-versus-Host Disease, that is a life-threatening complications of allogeneic stem cell transplantations. How do we expect MaaT013 to work?
We expect that MaaT013 will allow immune homeostasis restorations, in particular induced regulatory T cells. It will of course induce, increase the diversity of the microbiome. It will inhibit pathogen growth and production of metabolite. That will produce some beneficial bacteria that will produce a butyrate, short-chain fatty acid, induce on immunoregulation that will allow this immune homeostasis restorations. It will also have a direct effect on the barrier integrity of the gut epithelium. It will restore this higher integrity and prevent infections, and it will allow the prevention or the remissions of symptoms, in particular of Graft-versus-Host Disease. So far, this MaaT033 capsule was evaluated in the SIMON Phase I-B open-label dose-finding study that including 21 patients. Patients were included in six different hospital in France. It was a dose escalations design with five cohorts.
In the first cohort, we give the capsules only once a week, so they receive two capsules of MaaT033. Cohort II, six patients included, it was planned to give once a day for one week. Cohort III, six patients included also, it was three capsules a day for one week. Cohort IV, it was three capsules a day for two weeks. The Cohort V, what not perform because we have already enough data from previous cohort. Our patients were receiving induction chemotherapy for acute myeloid leukemia. After a neutrophil recovery, they were included in this clinical trial. They received one-two weeks of treatments, and we assess microbiome diversity at baseline after one week, after two weeks, before the consolidation chemotherapy. Again, after patient received this additional chemotherapy, we assess the outcome on the microbiome diversity.
Here are the results regarding gut microbiota diversity and the engraftment of the MaaT033 product. We have different colors. It corresponds to the different cohort I just presented you. As you can see here in the first cohort, we already have a good engraftment in the patients, but with around 40% of engraftment of the MaaT033 product as early as W2, as W3, and very importantly, at W4. That means that also when patient receives some additional chemotherapy and of course, antibiotics, we maintain this good engraftment of the product. When we look at the further cohort, we again improve the MaaT033 engraftment because it reached 60% of engraftment. Also it was maintained up to visit four, after the consolidation chemotherapy.
When we look at the richness, this is even more interesting because in addition to the engraftment, use of this MaaT033 capsule allow a good increase of the richness of patients' microbiome as early as V2. It was even increased at V3, and we see a small decrease at V4, but it still remained significantly higher compared to baseline. This is after induction chemotherapy, and this is after consolidation chemotherapy. We don't have the same detrimental effect of the consolidation chemotherapy of the microbiome diversity when patients receive our MaaT033 capsules before the consolidation chemotherapy. MaaT033 induced an increased microbiota richness at the OTU levels. MaaT033 display a strong and persistent bacterial engraftment with higher in cohort III and cohort IV.
That was a cohort with three capsules per day for two weeks, compared to cohort I and II with only one capsule per week and one capsule per day. On MaaT033 bacterial engraftment in inversely correlated with patients' baseline microbiota richness. We have some preliminary results regarding the host parameters analysis. This is some PCR analysis, so it can be a bit complex to just understand. Just to clarify, we were able, in the same statistical analysis, to look at the production of short-chain fatty acids. This is some products that are produced by the microbiome, add some chemokine, also add some inflammatory parameters such as a pro-inflammatory cytokine such as IL-18, TNF-α, C-reactive protein. We see three different patterns depending on the visit of the patient.
V1, this is at baseline, right after the induction chemotherapy and before we give MaaT033 to the patients. We find that the patient has some very pro-inflammatory parameters with some increase into the inflammatory, so CRP, IL-6, IL-18, TNF-α. At V2 and V3, this is at the seven day and 14 day after the MaaT033 administrations. We see that patients are less inflammatory, and in the contrary, we find some increase into the short-chain fatty acids, so produced by an LC microbiomes. At V4 we have a small shift to baseline with more inflammatory parameters, but still we maintain some protective short-chain fatty acid production. Overall, we find that MaaT033 engraftments correlates with anti-inflammatory markers, levels, and inversely correlated with inflammatory markers such as IL-2 and neopterin.
MaaT033 treatment was always also safe with a good tolerance. We had only four adverse event reported in four patients. Only one was considered as possibly related by the investigators. We have only one severe neutropenia in cohort II, none in the cohort III or IV, with more capsule given. One neutropenic colitis in cohort III, and one diarrhea, infectious, and 1one hyperkalemia, but that have some difficulty to directly related to the product given. The next step now is to go to a randomized clinical trial to evaluate MaaT033 to prevent infections and complications of allogeneic stem cell transplantation, including Graft-versus-Host Disease. We plan to include this 389 patients. It's a randomized double-blind placebo-controlled studies. The primary endpoint will be the efficacy of MaaT033 to improve overall survival at 12 months, very ambitious primary endpoint.
We'll also evaluate safety and tolerability before and after allogeneic stem cell transplantation. We'll of course evaluate engraftment of MaaT033 on activity to prevent complications of infections and Graft-versus-Host Disease. We'll give a pre-phase, so before the start of the conditioning regimen, with one-two weeks of MaaT033. After we stop, of course, because it will be the neutropenic phase. Around day 15 - day 21, we will start again to give the MaaT033 daily up to three months. We'll at the end evaluate overall survival at one year. To conclude, MaaT033 appear to be safe and effective for gut microbiota restoration in acute myeloid leukemia patient that receive induction chemotherapy and antibiotics. We have a good tolerance with the maximal minimal toxicity after treatment and post neutropenia.
We think that three MaaT033 capsule per day for one week is enough to induce and increase this microbiota richness on an effective and persistent multiliter bacterial engraftment in acute myeloid leukemia that was maintained after further chemotherapy and use of antibiotics. Now we plan to evaluate in this phase II-B trial as an adjunctive on maintenance treatment in patients with hematological malignancy that receive allogeneic hematopoietic stem cell transplantations. I would like to thank you, and after I will give the now again to Hervé for the next step of the meeting. Thank you.
Thank you very much, Professor Malard for the presentation of the data. Now time has come to go to the back to the company and the ending remarks. I'll be sharing with you the key takeaways as well as the next milestones and provide you with an update on where we are with the manufacturing facility. The key takeaway message here, we have showed once again, we have treated more than 300 patients, and that's ongoing. We are continuing to recruit pretty well in our clinical trial that are ongoing. MaaT013 has a significant data set now coming from the EAP program, but also from our clinical trials.
It has showed to have a good overall safety and a high effective therapy in steroid refractory mainly, but also steroid-dependent, GI predominant acute GvHD patients. To us, it's very promising. This, I would say phase III is really results from these studies very expected soon. Further investigation in steroid refractory and steroid-dependent GvHD is ongoing with the phase III. We will go through the milestones on the next slide. The next product, MaaT033, has also showed to be safe in leukemia patients where their immune status is pretty bad because when they get the TMO, they are immunocompromised, they receive antibiotics. The status of their immune system and also their microbiome is pretty bad.
We have showed here again to be safe and effective in terms of restoring the microbiome as they are happy with that. Now we are considering going to the next step, which is about having a significant phase II-B clinical trial, which has the potential to be pivotal, assuming the results are good enough. The objective is clearly the objective you are looking for in oncology, that's to improve the survival of the patient receiving stem cell transplantation. We have generated, and we continue to generate promising clinical data to improve patient survival, which is at the heart of the DNA of the company.
In terms of the more precise milestones, within the next 12 months, MaaT013 expected interim results in half of the patients by the first semester of 2023. We are on track. We do not report any delay here. We will continue the early access program in France and in Europe. For MaaT033, the capsule, we are planning to start early 2023 a significant randomized controlled trial in any patients receiving stem cell transplantation. MaaT013, which is through a partnership with the Hospital of Paris, AP-HP, and Institut Gustave Roussy, the largest anticancer center in Europe. We have a partnership with them. We are evaluating MaaT013 in combination with immune checkpoint inhibitors.
Here also, we're gonna have internal data read out in the first semester of 2023, and that will be very important. Those data, they will be very important to inform us regarding next stage of development in melanoma. Regarding solid tumors and the 3X product, which is just to remind the culture product, we are expecting to enter into the clinics in 2023 with this very disruptive technology. All of this is possible because we master the GMP, the GMP manufacturing of full ecosystem microbiome, which is a pretty complex biological process. Since 2016 now, we are dealing with the production by ourself of those products.
We have reached a point where we need to expand, so we will leave the manufacturing location where we are today, and we will go in more larger facility, which will be also more convenient to support our R&D activity because the MaaT03X product is even more demanding regarding the complexity. We need to expand to have enough space to continue the development of the company. The first step of this manufacturing location, which will be up and running in 2023 as well, would be to produce, of course, native product, but also we will be able to work on the design of the bioprocess for the 03X program. That will be ready by 2023.
The way we are dealing with this new facility is that we are establish a partnership with an existing CDMO, which is named Skyepharma. They're our partner. We are working with them since three years to establish, I would say the setup of what it is we want to do together. At the end of the day, they will be taking care about everything related to the facility itself, the GMP and quality system. That will be with them. Whereas we will be taking care about buying or sell the equipment. That will be our staff, our people. We will continue to control everything which is related to the development of the bioprocesses and also the execution of the process when it comes to the GMP production. That's the way we have set the deal.
You know, because of that deal, which I believe is really, really modern, each of us will be able to concentrate on where we are good at, and we will not be defocusing on stuff where we are not good at. That's I think a very well-balanced deal that we have established with Skyepharma. In summary, the four key partners of the company, we are a full ecosystem company. We are not focusing in one strain or several strains. We have taken the challenge to restore the diversity that has proven to be efficient and safe. We will continue with that. We are focusing in oncology. We have established a proof of concept in a very complex disease, GvHD.
The Phase II, as by dealing with the microbiome, you can deal with the immune system and the data that we are accumulating are still confirming that Phase II study. The concept is established. Also we continue to master the field of the biomanufacturing with both the R&D activity and the GMP facility. To the best of my knowledge or facility when it will be up and running, it will be the biggest facility in Europe to deal with full ecosystem products. We have the capacity to go even further to support our development and potentially additional developments. I want to thank you for this first part of the presentation, and now it's time to go through the Q&A.
Feel free to ask any question you might have, and we'll be happy to answer all those questions. Thank you very much. Okay. Now that we have been through the different data that we have presented during the ASH meeting, that's gonna be the opportunity to answer your questions. In terms of the organization, I'm together with my team, and Shan here will be asking the question that we have received. There's already several questions that are on the list. Let's start, Shan.
Hi. The first question, can you comment on the recent REBYOTA approval?
Yeah, good question. Recently, REBYOTA, which is a product developed in another indication that in Clostridioides difficile, has been approved by the FDA. That was November 3rd year. It's the first ever FDA-approved microbiome product. What is important is the fact that this product is a fecal microbiota transfer product. This approval is very important because one of the challenge of this nascent industry of the microbiome is really to make sure, especially for investor and for pharmaceutical company, it is important to show that we have a clear regulatory path. This approval is establishing like a building block. Based on what we have learned from this approval, we have a very good understanding now on what you need to do in terms of donor selection, in terms of duration of follow-up of the patient.
This approval was very important in terms of the go-to-market strategy and also for us at MaaT Pharma and other competitors. It is also very important because we have learned a lot on what the FDA is expecting. It is pretty positive for the field, and we hope there will be several additional approval soon.
Thanks.
Next question.
Yeah. Question for Emilie in terms of the MaaT013 results, from an investor. How were MaaT013 responders versus non-responders defined?
Good question. Thank you. Indeed, responder to MaaT013 were defined as patients who achieved a complete response or a good partial response or a partial response of the GI, at day 28 after first administration of MaaT013. Other patients, non-responder, were patients with stable disease progression or death before day 28.
Thanks, Emilie. Mohamad, a question for you. What are the differences between GI ORR and overall ORR? Why are overall ORR rates generally lower? Do you see an impact of MaaT013 on liver and skin?
Yeah, very good question indeed. Well, obviously, as it is suggested by the question, acute GvHD can have three major target organs, GI, liver, and skin. The most life-threatening and serious one is about GI. Obviously, if you're assessing the response at the GI level exclusively, then this is usually different from the overall assessment when you consider all organs. Given the mechanism of action of the microbiota modulation, of course, it's important to consider the response of the GI first. However, the good news, what we have seen in the MaaT013 data is that the other organs usually also respond when they are involved.
Thanks. Just coming back and looking at the early access program results and the ongoing phase III trial, a few questions from Jacob, from Kempen. How does the EAP data set compare to the phase III trial of MaaT013? What sort of responses could we expect to see in the phase III trial on MaaT013? Can the EAP program be... the data set be seen as a benchmark? Emilie, can you comment on those comments on those questions?
Yes, sure. The early access program, as you know, include a more heterogeneous population. Indeed, the high number of patients we include, we have now 31 patients corresponding to the exact population of the ARES trial, which is patients who are refractory to corticosteroids and ruxolitinib, and MaaT013 is now a third-line therapy. We have 31 patients in this setting, and we have very good results in terms of ORR, of course, but also in terms of survival and which is more important. We expect to have comparable results in the ARES trial because we are, I mean, this is the same population.
I would like to add to this that 31 patients, actually for this population, is really a significant and meaningful number of patients. That would give us quite a good confidence that in the ARIS ongoing prospective trial, the results are likely to be as good. To make it short, is it a good benchmark? I think it is a good benchmark. Emilie emphasized also that in addition to the response rate, what is really amazing is the high survival rate in the responder, 74%. Never seen this in my practice in the last 25 years.
Thanks. Just a further question, Mohamad, from Thomas Vranken from KBC. Is there any expected impact of EMA's recent class review of JAK inhibitors for the use of ruxolitinib in aGvHD in Europe?
I guess the question relates to the fact that ruxolitinib has been recently approved for steroid-refractory acute and also chronic GvHD. I believe this is rather good news for the field. As a transplanter, I'm not gonna complain about it. The other good news is that the development of MaaT013 and the ARES trial is exactly targeting the population of patients who have failed, actually, ruxolitinib. Unfortunately, despite the enthusiasm we have all for ruxolitinib, we know very well that there is a significant proportion of patients who will not respond or cannot receive ruxolitinib or even will lose their response to ruxolitinib. The post-ruxolitinib, I would say, population is a truly huge unmet medical need, and this is why new options like MaaT013 are eagerly needed.
Thanks, Mohamad and Emilie. Moving on to MaaT033. Florent, I've got a few questions for you. Firstly, again from Thomas, the decrease in the OTU between visit three and four related to consolidation chemotherapy, or does the treatment effect always fade slightly?
Thank you. This is indeed a very good question, and this is a very important point. In fact, during the consolidation chemotherapy, patient receive, again, high-dose chemotherapy and a large spectrum antibiotics. We expect a very important impact of the, on the microbiota, an important decrease into the number of OTU. In fact, the small decrease we observe is a very important result since it highlight that with the MaaT033 treatment, we have a long-term effect, and we preserve the microbiome during the further chemotherapy and despite the use of antibiotics. We expect this small decrease, but in fact, this small decrease just highlight that we have a long-term effect of the treatment.
Thanks, Florent. Just another follow-up question, again from Thomas. What is your current hypothesis on the origin or source of the EPEC bacteria leading to the SAE?
Yeah, this is a good point to raise this issue of this adverse event. In fact, we're able to look very closely into the MaaT033 product, and we don't find the effect within the product. We are able to quickly rule out that it was transmitted by MaaT033. In fact, in this kind of patients that have acute myeloid leukemia, receive chemotherapy, this kind of side effect is very frequent. We have very frequently this kind of infectious complication, so we can suppose that it was a bacteria that was present within the patients and it was clearly not related to MaaT033.
Thanks. Again, sort of following up on the MaaT, MaaT033. I've got a question. For Halby now, what do you believe the greatest challenge to be in the development of MaaT033?
I believe the difference between what we are doing since years with the 13 and 33 is really the volume. Here we are considering a larger clinical trial, especially with the next clinical trial, for all patients receiving stem cell transplantation. One challenge was the supply chain, because we needed to scale up the supply chain to make sure we have enough volumes for the production. Today we did not report any issues on that one. We have had to scale a little bit the supply chain process for the upstream supply chain process to get enough donors.
Thanks. Just generally talking about the timing of the phase II-B trial of MaaT033, can you comment on the timing?
Yeah, that's true that we have announced initially that we will be starting the clinical trial in Q4 2022, so we only have 18 days now. It's important to say that we are on track to start very soon, and we confirm that we will be starting soon. However, we have taken a little bit more time to discuss with certain stakeholders, including regulatory bodies, but also potential partners, just to make sure that what we are doing is appropriate for the next step. Little bit of delay, but nothing significant at the end of the day.
Thanks. Sort of looking about, broadening the pipeline, I guess, this is question, on the landscape, how do you see the promising data that came out on the EO2401 from Enterome in glioblastoma?
Yeah. They are competing indeed. Here we are, we can't really compare with them because this modality is very different. That's proteins that are generated by bacteria, and then they are developed as a small molecule, which has nothing to do with us as a biological. Neither in terms of the therapeutic area nor the modality, it's comparable. Probably I will skip any comments on that one because for us, it's not something we should be comparing to.
Okay, thanks. I guess the sort of, coming wrapping up, there's a few questions, wanting an update on the status with the FDA, from both analysts and investors, a status on the clinical hold, but equally how the REBYOTA approval has or doesn't influence, in your opinion, the hold for MaaT Pharma.
The hold, we have made significant progress on responding to the FDA. Just would like also to remind that the microbiome product, they are hosted by the Office of Vaccine OVRR in the U.S. We feel there was a deprioritization process in place at the FDA to put priority on vaccines and not on other products. Today we believe there is more traction with the FDA. We have submitted our answers to the FDA. We are waiting feedback from them. I can't comment that much both in terms of the process, the timing of the process and the results of the process, of course. We have made good progress in terms of the interaction and submitted additional data to the FDA.
Let's follow the situation. Regarding the approval of REBYOTA, of course, that has helped us because even if they have been approved in November of the 30th, there was already in September the advisory committee, and we have learned from that has helped us to refine the proposal that we have made. For example, we know that the quarantine that has been proposed by REBYOTA, just to make sure there is no new pathogen emerging during the all of a sudden, you will put the product in quarantine. We have been able to compare what we are doing with what they are doing. We have a very good understanding of what is reasonable for the FDA in terms to get an approval.
We have been able to bench our process against that and sometimes improve our process. That was very useful to have this transparent process starting in September and ending in November with the approval of REBYOTA. That has helped a lot in terms of the way we have responded to the FDA. Yes.
Thanks. I don't believe we have any questions, so do you want to wrap up?
No. Yeah. Thank you very much. You. That was many of you today participating to this conference. Thank you very much for your interest to the company. Thank you for the new participants as compared to the previous presentations. Thank you again to all of those who are present at each conference. Thank you very much for that. The 22 has been very intense with a lot of programs starting with the ARES study phase III, the PICASSO study phase I-A, and also the conclusion of the MaaT033 SIMON product. That was very important. We have accumulated a lot of data.
We're gonna have additional data soon for the first part of 2023 with the interim analysis of MaaT013 in GvHD. We're gonna have also a biological readout in the PICASSO advanced melanoma patients. With MaaT013 again, we'll be starting MaaT033 in all patients receiving stem cell transplantation. We're gonna have also the new factory, the new manufacturing location that we are starting. We do not report any delay today, it's also on time. We continue to establish the foundation for the company. We are getting close to the end of the first phase III for the company. We are pretty happy with the progress that we are doing today.
We want to thank all the investors that are supporting the company up to where we are today. We hope that we can continue together to develop the company.
Yeah. I'd like to add that we are here live from ASH 2022 in New Orleans with Emilie, and I can assure you the excitement about the microbiome modulation and the MaaT Pharma work is amazing. It's incredibly exciting.