MaaT Pharma SA (MAAT) Earnings Call Transcript & Summary

Good morning, everyone, and thank you for joining the H.C. Wainwright BioConnect 2022 Conference. My name is Michael Brotherton, and I'm on the Corporate Access team at H.C. Wainwright. While we are virtual this year, we are confident we're going to be able to provide value to you with over 550 companies presenting at this conference, as well as viewer interactions with one-on-one meetings. H.C. Wainwright has a full service of asset bank dedicated to providing corporate finance, strategic advisory, related services to public and private companies across multiple sectors and regions, with a total of 23 publishing senior analysts and over 630 companies covered across all sectors. Please visit hcwco.com for more information. From a logistics standpoint, please make sure to reference your BioConnect virtual conference online portal that provides your individual links for meetings and all presentations. Please join us on corporate presentations and panels available live and streaming on January 10 through 13. With that said, have a productive and enjoyable day. I'd like to introduce our next presenter, I'd like to welcome Herve Affagard, CEO of MaaT Pharma.

Thank you very much, Michael, for the introduction. So I'm Herve Affagard, and I'll be presenting Maat Pharma for you today. So welcome to this eStation and a Happy New Year to all of those who would watch this eStation presentation. So I'm Herve Affagard, Founder and Chief Executive Officer of the company. And MaaT stands for Microbiota as a Therapy, which means that we are developing biological drugs that are made from a microbiome. And the target of, the purpose of the drugs that we are developing is really to modulate the microbiome, so that we can modulate the immune system in the field of oncology. Our vision for the future is really to become the worldwide leader in terms of researching the microbiome of patients using a full ecosystem approach, which means that we are restoring the full ecosystem to patients using our MET platform. MET stands for Microbiome Ecosystem Therapies. And today, we are a clinical research company and also we are penetrating the oncology market in the hematological malignancies and oncology therapeutic area. We have, as we speak today, already completed Phase II in the disease that we call GvHD, and I'll go back to the disease a little bit later into the presentation. As we speak, we are also entering phase III in Europe on that indication. Our pipeline is pretty large already with 2 late-stage assets. The first, the lead candidate, which is entering Phase III; on top of that we have the second candidate, which has the potential to enter in a Phase III pivotal study by the end of '22 as well. Our MET platform is mainly made out of 2 key pillars. The first one is gutPrint, which is used to provide the microbiome as well as profile the immune system, so that we can better understand the impact of the modulation of the microbiome on the host side, on the patient side. And the second pillar is everything related to the GMP platform, the production facility. It's very important for those kind of therapeutic modalities that you master the production component of it. Our MET platform is covered by 13 patent families, and the company is surrounded by strong investors, as we have raised today EUR 75 million. We recently succeeded in an IPO in Euronext Paris, that was back in November. So we are one of the few companies listed in Europe when it comes to microbiome company. So with that, I'll go directly to the concept of what we are doing. What you see here is a cross sectional drawing of an intestine and that represents the different mechanisms within the intestinal microbiome, and in particular, the interaction with the immune system, of which 80% of the immune cells reside. A key element of this overall balance between the immune system and the microbiome is the presence of a diverse and rich bacterial ecology, allowing to modulate the immune system. This phenomenon of good balance is known as symbiosis, which means that both commensal bacteria that reside in our intestine promote the establishment and modulation of innate and adaptative immune defenses on the surface of the mucosa. They are the antibodies, proteins, the macrophages, the T-cells. And they also play a role in preventing outreaching colonization by undesirable microorganisms. However, when a dysbiosis, which is the opposite of the symbiosis when there is a dysregulation of this microbiome, is observed, it represents a danger for the host. And that's typically what's going to happen when patients will receive harsh treatments such as chemotherapy or stem cell transplantation. And also, we see a low efficacy of certain immunotherapy treatments when the microbiome is not fine tuned. So that's exactly what we will be dealing with, to treat that is dysbiosis, this disequilibrium of the guest microbiome. Here we are showing a few data reinforcing the fact that the higher the richness or the diversity of the microbiome, the better the survival. How you can achieve that? You see on the left-hand side, for example, this is patients receiving stem cell transplantation. And you see that at the time of engraftment of neutrophils, when the diversity of the microbiome is high, you like improve by 50% the survival of the patient at 2 years. So that's a very interesting outcome that we have observed. And on the right-hand side, that's a different setting, that's solid tumors, where we see that the higher the richness of the microbiome, the better the response of the immunotherapy treatment, namely the immune checkpoint inhibitors, and therefore the better the survival. That's basically what we'll be doing, restoring the richness and restoring a network of bacteria that would cooperate with the immune system so that we can improve the survival of patients. We have 2 range of products. The first one is what we call native products. They are native because they come from healthy donors, that's 2 products that we have here, MaaT013, which is the most advanced, entering Phase III. And we have MaaT033, a capsule, for which we are completing a Phase Ib dose escalation study and we hope that we can enter in a pivotal study by the end of '22. The other range of product, which is MaaT03X, will be tailor-made based on the indication that we are targeting and that will be in cooperation with the immune checkpoint inhibitors. This product is a little bit different. It brings the richness as it is for MaaT013 and MaaT033, but also it would set some specific networks within the drug, so that we can improve the compliance with immunotherapies for the patients. For this range of products, we are at a preclinical stage. So now let's go through the data that we have accumulated so far. Before I introduce you to the data, and as I said, we have Phase II data to share with you today, I want to go back to the diseases. So here we are talking about patients with hematological malignancies. They are liquid tumors. So we are talking about leukemia, lymphoma, myeloma patients. And those patients, they will receive stem cell transplantation. This stem cell transplantation procedure is the only way to cure acute myeloid leukemia, for example, today. So this is very interesting for the patient to go to the stem cell transplantation, but this procedure comes with very important complications. One of them is the acute graft-versus-host disease, which is when, I would say, the immune system that has been transferred to the patient is attacking the tissues from the recipient, the patients. This phenomenon appears in some of the patients, but once you are diagnosed with this acute GvHD, your mortality rate is super high with 90% at 1 year. So this is an ultra severe disease and that is what we are addressing with the first project, MaaT013, which is entering Phase III. The other project, MaaT033, will come at the time of the stem cell transplantation. So we have a bigger population for this approach, and that comes with the capsule. So the data now. As I said earlier, those patients, they are very severe. Their survival is only limited. This is usually a one-way ticket. We did a Phase II study in the most severe patients with type 3 and 4, and on this population, we have observed that by treating them with MaaT013 after steroids, which is second line, therefore our product is used in second line; we have seen that we have been able to change the journey of the patient for 38% of them. And you see that from that graphic that when you are getting the primary endpoint, which is the evaluation of the disease at day 28, you see usually correlates with better survival, of course, as it is evidenced here on the red line. So that's on 24 patients, 5 countries in Europe, the Phase II clinical trial. We have also accumulated real life data. We have been granted an early access program in France, and we have treated a lot of patients, actually, and we recently presented during the ASH Conference back in December in San Diego, data from 52 additional patients. So together with the previous set of data, that's 76 patients in GvHD that we have treated. And we see that the primary endpoint is here 58% and you see the survival is really promising. And what is striking to us is the fact that we have treated patients that have received, in average, 4 to 6 lines of treatment, which is usually those patients which are dying. We estimate that the survival of this population would have been 22% after 2 months only, whereas we observe on those data that we have a survival at a year which is close to 60%. So the signal is even stronger. That's coming from the fact that here we have included what we call Grade 2 patients, which are a little bit less severe. But as you can see, 94% of them are still Grade 3 patients. And also, the steroid-dependent patients that have been included into that study are also responding better to the treatment. So altogether, based on the observation that we did, we are now entering the Phase III. This clinical trial is a 75 patients clinical trial running in Europe first. We have received approval from 2 European countries as we speak today and we are starting the study in January this year. So that's all good for Europe. In the U.S., the FDA has not yet validated our IND submission and we have been put on hold, mainly for 2 reasons. The first one is that the FDA is requesting that we justify further the fact that we will be using a single arm study and not on RCT. So we will be coming back to the FDA on that one. And the other one is related to a CMC, I would say, additional data that the FDA is asking to us. So we are in the process of submission for Type A meeting and we are expecting the feedback from the FDA on that part. Moreover, we want also to treat the patients as soon as possible. So we'll be treating the patients at the time of their stem cell transplantation. And by doing that we will multiply by 10 or so the size of the population. And we are in the process to, I would say, we are close to completion with a Phase Ib study, which is a dose escalation study, which will be the basis of the next study, a pivotal study with a big RCT clinical trial. So here we are targeting Leukemia patients. That's the CIMON Study. And this study, in fact, is ongoing. This is a dose limiting toxicity clinical trial. We evaluated 5 cohorts in total. We are reviewing the data as we speak and we are hoping to communicate soon on some interim review, and we are on track to complete the study before the end of H1 '22, which means that we are also on track to start in H2 '22 the pivotal study for all patients receiving stem cell transplantation, where we will be dealing with complications of stem cell transplantation being GvHD, but also infections and also other kind of benefits for the patients. So that's it for the hematological segment. Now we are going to solid tumors. Here in solid tumors, the rationale is, I would say, basically the same when it comes to restoring the richness and the diversity of the patients. But moreover, we want to set a specific, I would say, network of bacteria. We see from the literature that interesting studies showed that by transferring the microbiome of responders to nonresponder ICI patients, you can turn back the response. And in 6 out of 15 on the first study -- on 6 out of 15 patients, we have been able to turn back the response and the sensitivity to ICI, whereas on the other one, that was 3 on 10. So for those patients which are refractory to ICI, that's super-promising signal as well that the microbiome is important for the efficacy of the treatment itself. So the way we will be addressing that, first, we will do a first proof of concept using MaaT013, which is the same product as the one for GvHD, because we know that within our mix of bacteria that are within MaaT013, we have, as I said, the good bacteria that are usually seen in responder to ICI patients. They are, for example, Faecalibacterium, Akkermansia, Bifidobacterium and other drugs. So we know that by recarpeting the microbiome of the patients with this rich ecosystem and those good bacteria, we have a chance to improve the response to the treatment, to the ICI. This clinical trial that we'll be doing is a randomized control trial, Phase II, 60 patients against placebo. We got the authorization and we are about to start this clinical trial here in France. Moreover, we go further using our co-fermentation platform, and I won't go too much into the details, but focusing on the graphic which is on the top, you see that using our gutPrint platform, we have been able to, I would say, evaluate within a cohort of 300 patients what is the ecosystem that you need to be a responder. They are the blue boxes, and what is the ecosystem of a nonresponder and they are the red boxes. And from that, in fact, with our technology, we are able to build a biological drug, which is an ecosystem and which is a mirror of those patients responding to ICI. So that's the principle. And with that and with the data that we will be accumulating with the first clinical trial that I've presented before, we will leverage on our platform to generate MaaT03X candidates. And that will be each candidate, MaaT03X, the first one; the second one will be specific to the indication. It could be any solid tumors as long as you use immune checkpoint inhibitors. So this is a pretty versatile platform that will allow us to generate as many candidates as needed when it comes to addressing the dysbiosis of the patient on that setting. The milestones, that's the summary. I've already disclosed the different key milestones during the presentation, but I want to focus for the next 12, 18 months, where we know that we are expecting 2 first patients in soon, that's on the Phase III with ARES, the GvHD trial, and also the other one in immuno-oncology with PICASSO. So we are expecting the first patient in here. We will be also completing, before the end of H1 '22, the MaaT033, the capsule, program in time as per plan. One important milestone also is that we are expecting an intermediate review on half of the patients in the Phase III program as early as mid '23, which will be a significant inflection point for the company. Because we know that when you have achieved the primary endpoint, as I've showed before, those patients achieving the primary endpoint, they are the survivors. So we will have a good sign here on the benefit of the drug that we are developing. So that will be a very important milestone. To conclude, I'd like to stop on that slide. The takeaways from MaaT Pharma is that we are mastering the full ecosystem approach from any form, the native project, the co-fermented project. We have a manufacturing platform which is pretty versatile, connected to gutPrint, so that we can generate many candidates based on signatures that we have identified in cohort of patients that we have access to. We have a strong focus in oncology. When you use the 2 key worlds, microbiome and oncology, MaaT Pharma is the most advanced company in the microbiome industry in terms of clinical development. And the most important, I think, is that we have a proof of concept with this both Phase II data that modulating the microbiome influences the activity of the immune system. And in the context of GvHD, by modulating the microbiome, you can reduce the inflammation in the gut of the patient. So this proof of concept is very important. With that, I will leave it here. And I know there is a potential for Q&A, and I'll be very happy to take any questions you may have.

Okay. Thank you, Herve. I want to thank all of our presenters taking part in what has been a very productive and informative series of presentations. We appreciate the time and effort that went into preparing them. Hopefully, our next conference would be the one that we can hold in person rather than virtually. But in the meantime, we're very grateful for your flexibility and your presence online this year. Thank you again from the H.C. Wainwright team.