Good morning and good afternoon for the participants to our web conference organized by AB Science about an update of the clinical development of our asset called AB8939. My name is Alain Moussy, I'm the CEO of the company. With me today, we have the presence of Nicolas Short, who is a Professor at the MD Anderson Cancer Center heading the Department of Leukemia, Professor Olivier Hermine, who has co-founded AB Science and is in charge of the Hematology Department at Hôpital Necker and Cochin, and also Chairman of our Scientific Committee and also a member of the French Academy of Sciences. Also, Christian Leclerc, who is an ex-Co-Director of CNRS and IGR and a pharmacologist expert. With me as well, Laurent Guy, Chief Financial Officer, who will at the end of this presentation take your questions so that we can answer. The principle is the same as before. We'll have a presentation which will be rather technical given the content. At the end, you will be able to answer questions and we'll take some of them and try to respond to them. The questions are to be phrased by writing. Today's objective is to update you on this second platform that we call AB8939 because it's our lead drug. As you know, we are in the middle of phase I and we have some news for you. What we are trying to do is to develop this drug in acute myeloid leukemia, which is the most lethal leukemia in humans. There are drugs registered which are here on this slide. 70% of the patients end up anyway dying from this disease. The 30% who survive, they are the ones who can benefit from a stem cell transplantation, which will save them. Most of the patients, they unfortunately cannot benefit from this because it's too toxic or they do it and they relapse. Ultimately, regardless of the treatment that they will take in first line, where most of the drugs are registered, they will relapse and die. It remains a huge and mechanical need in this terrible disease. What we know from the experience is that AML is a heterogeneous disease with outcomes that highly depend on genetic factors. Here we would like to show you a publication which comes from [Donner] and which gives the outcome results in terms of survival on one line of treatment. I show you, I return to the previous slides. You can see here in first line when patients cannot take the high-dose chemotherapy that will lead to stem cell transplantation, they take a combination treatment of azacitidine and venetoclax, which is the standard of care. The next slide, I come back to that, tells you what is the outcome of this treatment depending on the genetics. You can see here in the red circle, the outcome is completely different depending on the different mutations that the patients can have. It's interesting to see which ones can benefit from the treatment, which ones cannot with some survival which are very low, like in average or median five months or 12 months. In fact, the high risk, the one with five months, is essentially made of one mutation called TP53, very well known from the oncologist. The intermediate risk encompasses two mutations called NRAS and KRAS. If you want to memorize one thing from this slide, we know the mutations and that's the problem. We desperately need drugs that could address, in particular, this type of mutations because they lead to very poor prognostic. Now, one more, I would say, genetic which is in fact the worst prognosis in AML is what the oncologists call MECOM. The MECOM is a rearrangement. It's not a mutation, it's a rearrangement of some chromosome, chromosome three. You can see here the blue line that the survival as compared to other kinds of rearrangements. You can see it's the lowest one, which means the lower survival. The survival is very, very low. In fact, on this right-hand side, you can see the outcome depending on whether the patient is in first line untreated here or in relapse already. You can see in relapse, it's terrible because practically all patients die within 12 months. The median is in fact less than 5.5 months. It's even worse than the TP53 that we have seen in the last line. We have already in mind MECOM, TP53, and NRAS KRAS. It looks, you know, names like that, but it's the mutations that are problematic in AML or the rearrangement that are problematic in AML. Now, what can our product do in this disease? We see a problem. The cell lines, the cancer cell lines are very resistant to the treatments. That's the problem number one. We propose the product that we have designed offers a new mechanism of action. It will target microtubules, which you can memorize as being the skeleton of the cell. When the skeleton is destabilized, it does not divide. That is a very well-known mechanism of action because it was used in products very famous like Taxol, Taxotere, vincristine, vinblastine, but never in AML for two reasons. Those drugs are eliminated from the cancer cells by a natural process called multidrug resistance, which consists of the cells producing a protein called PGP to bind to the chemotherapy and evacuate, wash out literally the treatment from the cells. That is how they survive. The other mechanism of resistance is that those compounds are immediately, in 30 seconds, degraded by an enzyme produced by the disease called myeloperoxidase. That is why they never have been used, or if they had been used, it was a failure. Our product has been designed to avoid that. It does not bind to PGP and it is not metabolized by myeloperoxidase. For the first time, we will be able to use this very effective mechanism of action, microtubule destabilization, in AML. The second problem in this disease is that despite the very toxic chemotherapies used, there are still some cells, which are the very primitive cells called cancer stem cells, that are not killed, destroyed by the treatments because they do not proliferate like the other ones. They are more silent. Those stem cells, even if little remains, will restart the disease immediately. The patients will be, even if there is a partial response. The first problem is no response; here, there is a response, but then there will be a relapse. This is really a problem. We address it through our compound by trying to target the stem cells. We have found a target, which is ALDH, which actually is very relevant to the stem cells. If we inhibit ALDH, which the product does, then we have a chance to kill the stem cells. In fact, this product, our product, proposes two very innovative mechanisms of action that, of course, are of interest for the hematologists. Now, I am going to show you some data that have been already presented just so that you can follow what the product can do in the worst prognosis. The bad mutations, let's call it. What do we have? This is cell lines in vitro, as we say. We have used as a control, there are 100 cell lines here, and we have used it as a control, a standard of care called cytarabine. When this, I would say, the bar is high, it means the product is not effective on the cell line. You can see here all those things are the cytarabine. It's not very effective in 100 cell lines. In fact, AB8939 was much more effective to kill the cell. Here we have 66% of the 100 cell lines that we have tested that could be killed by AB8939 and was not killed by cytarabine. In particular, it included cell lines that were the TP53 mutations, the one we have described before, and even the MECOM. That gives some hope, right? That's another way to look at it. Here you have a selection of cell lines to illustrate, and you have lots of problems here. Mutations, you can see the TP53, you can see a complex karyotype, complex rearrangement of chromosome, for instance. You can see a RAS mutant here, for instance, and you can see MECOM. When there is one, it means it responds. When there is zero, it doesn't respond. You can see here the standard of care, azacitidine and cytarabine, the concentration needed to kill those lines is very high, so it means it's ineffective. AB8939, it's very low, so it means it's effective on all those cell lines that had this complex karyotype or TP53. For instance, here there is a MECOM, and it killed it at that concentration. Here there was another MECOM. Here there was a TP53, and it was effective. It's another way to show that our product is effective in some situations in vitro. Now, we did in vivo in mice, of course. We used cell lines to graft the mice coming from patients who had MECOM, so the terrible rearrangement. We grafted the mice, and we used venetoclax, which is one of the standards of care, or venetoclax in combination with our drug. The first thing here to see is this visual. Here it's the normal cell lines, not the cancer cell lines. You can see venetoclax is not so toxic, and our product is not so toxic. It means it will not destroy the hematopoiesis, so the production of the red blood cells, the white blood cells, by the bone marrow, which is good news. Now, let's go to the cancer cell lines on the right-hand side. Here you can see that venetoclax, which is high here in the blood, in the spleen, in the bone marrow, cannot kill the cells. It cannot kill the MECOM. Our compound, AB8939, can, but with some lack of efficacy still. When we combine them, it's much better. We think, we say through that, that of course there is an additive effect or even a synergistic effect to combine the drug. As you know, the purpose of today is to show you the impact in humans, but this is in mice. We do the same with the same cell lines grafted in the mice, but with another standard of care, which is azacitidine. Here you see azacitidine is toxic on the normal cell lines, hematopoietic cell lines. It's very toxic. In here, our product, single agent, is not. We knew that. We say our product is not as toxic as some other treatments. When we combine the treatments, azacitidine has kind of a similar efficacy of AB8939, but when we combine with the very, very effective drugs, one is toxic. We might not want to use a toxic drug. We might want to use something less toxic, like venetoclax, in combination in humans, or we can do the three together. We will show you. That visual we already presented, I want to show it again. It's to illustrate the capacity of a drug to eradicate stem cells, which is far from abuse. What did we do? We took some mice and we treated them only for four days by cytarabine, it's called Ara-C, our compound or our combination, but at very low dose, so that at the end it remains some cancer cell lines in the bone marrow, as you can see here. In these remaining cell lines, cancer cells, we don't know if there are some stem cells. To know that, we're going to reimplant what's left in new mice, and we're going to see if the disease is going to restart. If it restarts, it means that the stem cells are there. If it does not restart, it means that the stem cells are not there or they have been considerably reduced. Here, as you can see, with cytarabine, there is a restart of the disease, and it's not the case in AB8939 or the combination. We prove here that our compound really has an impact on the stem cells. As you know, we are in the middle of phase I trial, and we have finished the monotherapy with three days, as we have to do, and then 14 days, which is more interesting. This is finished, and we found the maximum tolerated dose. In AML, all drugs are developed in combination. One of the key questions is what combination, since we have the choice. You have seen in the first slide that there are multiple drugs. It's not so obvious to find the right combinations and also the right population. Right? We have engaged in the most interesting part of the phase I, which is the combination part that we do at 14 days of treatment of AB8939. We are going to do a first combination with venetoclax, and we are going to do then what we call a triplet with venetoclax and azacitidine. That's what we're going to do. In monotherapy, here it's data in monotherapy that you have already seen. In monotherapy, we have already some signal of efficacy in MECOM. We knew it from the in vitro test, as you know. I showed you we had four cell lines and two were responsive. In humans, we have treated four patients and two were responsive, which is very good in MECOM. The survivals were also very good. You remember that all patients died in 12 months' time, and here we have a survival at 18 months, which is good, very good, and 11 months, which is also quite good. There is some signal in MECOM in monotherapy, although we prefer by far to go in combination. The combination therapy is what's new today, really. I will leave it to Professor Olivier Hermine, Hematologist, to describe. Olivier, if you can take over. Olivier, are you there? Maybe you should denude. Can you hear me? It's okay? Yeah. Hello, yeah, okay. Welcome to everybody. As Alain said, you know, in leukemia, there is a chance to have some drugs working in combination. Probably the drugs we have used may synergize with venetoclax, which is an inhibitor of what we call BCL2, which is a survivor gene. We know when we use some combination, we may sensitize the cells to cell death when you add a venetoclax. It was a strong rationale to use the combination of our drugs with BCL2 inhibitors. Can I go to the next slide? We did try to test three patients who were previously heavily treated patients in line three or four of leukemia with what we call high-risk adverse profile with complex karyotypes, mutation in TP53, MECOM rearrangement, and NRAS mutation. We know that these patients have a very, very, very short life expectancy, mostly when they are in the second line or third line or eventually in the fourth line of treatment, as we can see here. We will show you the details on the next slide of this patient. This first patient was an elderly patient, 74 years old, with three lines of prior treatment, including high-dose chemotherapy, azacitidine, and a new compound. He has a very poor prognosis leukemia because he has a lot of cytogenetic abnormalities. In addition, he has a mutation in NRAS. We know that this mutation is associated with a very poor prognosis. Very interestingly, when this patient relapsed with excess of blasts in the bone marrow, 8%, we can see after treatment, after one cycle of treatment, we see a decrease of the blast count to disappearance at day 49, meaning that this patient is in complete response. When you look at the peripheral blood, you see that neutrophil counts increase from 4,000 to 5,000, meaning that the bone marrow starts to work again. The platelet counts remain at a stable level, meaning that we have not too much toxicity in the bone marrow to this patient, which is a great result. It is highly unexpected to see a disappearance of the blasts with a normalization almost of the peripheral blood, except that the platelets remain low. This patient received a lot of treatment before and probably his bone marrow is not very well working. Anyway, with this kind of blood test in the periphery and the reduction and the disappearance of the blasts in the bone marrow, it may have a normal life. The second patient was also an old patient, 73 years old. When I said old, it's old for leukemic patients because we cannot do too much high-dose treatment in this patient and no bone marrow transplantation as well. This patient received in first line azacitidine and then high-dose chemotherapy plus venetoclax. It's very important because this patient received venetoclax and we know that the chemotherapy may sensitize the cell to venetoclax. Anyway, it remained refractory to this treatment. When you look also at the characteristics of this patient, he has a very complex karyotype with a lot of abnormalities, as we can see here. We know that these complex karyotypes are associated with a very poor prognosis. Interestingly, he has an overexpression of [EVI1 at MECOM], which is associated also with a very poor prognosis. He has also an undifferentiated acute myeloblastic leukemia. You can see here in this patient, after only one cycle of treatment, the number of blasts remains stable and even reduced by 50% from 20% to 8%. You can see also, which is very interesting, a delay in the reduction of blasts, probably because, as Alain said before, we target the leukemic stem cells. Interestingly, you see also in the peripheral blood the disappearance of the blasts, the leukemic cells. Associated to that, we have a stability of the neutrophil count and the platelet count. Despite the reduction of blasts, we still have a normal number of white blood cells and the platelets remain always low in this patient heavily treated. What is also very interesting here is that this patient received before venetoclax. Here, with our drugs, we can resensitize these patients to venetoclax, which is very interesting in terms of proof of concept and mechanistic understanding of our drugs. Next slide. The last patient was a patient of also 75 years old who received high-dose chemotherapy. He was in disease progression after the first line. He received a second line of high-dose chemotherapy and he was primary refractory to this both treatment, meaning that he has a very aggressive leukemia. We used the standard of care, which is a combination of azacitidine and venetoclax, and he was also refractory to this treatment. It is a primary refractory to everything when you look at this patient. Here too, he has complex karyotypes and a mutation of TP53, which is also associated to a very poor prognosis when you have this mutation in patients with leukemia. As you can see, he was totally resistant to all drugs. Here, when we use a combination of our compound plus venetoclax, you can see also a reduction by 50% of the blasts in the bone marrow and the same thing in the peripheral blood. You see the platelets and the neutrophil count remain about the same, which is nice for this patient. Altogether, these patients are very, very aggressive patients with a very poor prognosis leukemia with respect to biological parameters. All patients tolerated quite well the treatment, remaining stable or see a complete response for one patient, which is highly unexpected at this level in combination with venetoclax. To conclude, at this level, we can say that probably this combination with venetoclax may become a potential new standard of care in second line or third line therapy. Eventually, hopefully, in first line therapy, because we know that almost 90% of these patients died within one year after the diagnosis. We expect if you move in first line, they would be better in the future for these patients. Probably we do see here at the mechanistic level a strong synergy between the tubule poisoning and ALDH inhibition and venetoclax addition. Probably to explain this result, we may make the hypothesis that [EVI1 MECOM] and increase the expression of ALDH that we do block with our compound, which may explain why you have sometimes a delay in the response when we kill the stem cells. What are the next steps? First, we have not finished the phase I in combination. We have not even finished the combination with venetoclax. We would like to also try the triplet, even if there is some potential toxicity with azacitidine, but still it's part of the plan. We have to finish this phase I, which is, as you have seen with previous data, encouraging with the combination with venetoclax. What next? Instead of engaging directly to a potential registrational study, we think it's better to do an expansion study of a limited number of patients, which could be 15 AML patients. With the right combination, probably the doublet AB8939 plus venetoclax, given the encouraging, very promising data that you have seen, and at the right dose as well. Suppose this is the best combination from the phase I. We focus on that. We also select carefully the patients that we want to treat. We select them with the same selection factors, I would say, as the ones we would do in a registrational study. We would do a sort of mini trial to see the response rate. If the response rate is as encouraging as what we have seen in the first three patients, the good news is that in hematology, things are quite reputable. It's very objective. There is no questionnaire to be filled in by the patients. It's not a subjective opinion. This is a measure of the blasts in the bone marrow and in the blood and platelets and neutrophils. In fact, it doesn't lie. It's extremely objective. We know the placebo does nothing and cannot reduce spontaneously blasts. That's the advantage. With 15 patients, we can really have some comfort. Those 15 patients will be very certainly predictive of a registrational study. If we do that, and we can do it relatively quickly next year, we have the data that will tell us whether we have a high chance to register. This is to generate a hypothesis, a strong, robust hypothesis that makes us comfortable at a reasonable price. I think this expansion phase, a study, could be strategic, I would say, in the development plan. If we move to a further next step, what could we do to register the drug in a registrational study? We have started to discuss that with FDA and EMA, although it's very preliminary at that stage, but still. We have several opportunities there. The first one is to go in line one. To go in line one in the patients who are aged and who cannot take the high-dose chemotherapy that would lead them, hopefully, to a graft. Here we would not do all patients, but we would do only the adverse genetic, which we have seen includes TP53 mutations, NRAS KRAS mutations, complex karyotype, what we call Monosomy [5 7]. It's abnormal, I would say, abnormal rearrangement on 5 and 7, on Chromosome 5 and 7, and the famous and terrible MECOM. That group of adverse genetics we know defeats the standard of care, which is the combination venetoclax plus vidaza. The combination to beat is, or the standard of care is, venetoclax plus vidaza. You have seen the data, the previous data, venetoclax plus AB8939. The difference is vidaza will be replaced by AB8939. What is interesting is that we have two patients who took venetoclax and even one who took venetoclax plus vidaza and failed. We know that because they responded to the treatment and they had MECOM and they have TP53 and complex karyotype. It means that where the doublet, the standard of care, venetoclax plus vidaza is not so good or very poor, our combination could be much better and can become the standard of care. That is the strategy we would like to pursue with an expansion phase to limit the risk of 15 patients and then a registration study. I hope I have been clear to explain to you the strategy going forward. Clearly, this option one makes sense and will be so previously we will have this expansion phase before. The second option is also to combine AB8939 plus venetoclax, but not in line one, later in line two or three. That is possible. We can take again only the adverse genetics, so those ones you will see after how much of the market it represents, or all patients. That we can do also because there is a high unmet clinical need in what we call line two, line three refractory relapse because if they relapse, then they die. Right? We could do that as well, but those patients are more fragile, more complex. Maybe in line one, in fact, it's better if we focus on those negative or adverse genetics. We have another strategy, and they are not mutually exclusive, those three. We can do all of them if we have the money, but we can focus on the small MECOM. It's a small group of patients, however, with terrible prognoses. You have seen that our compound has even activity in monotherapy. Can we combine with venetoclax as well? Not so obvious. We have to discuss with the agencies, but still we could at least do monotherapy. This is what we are discussing with the authority. Progressively, with the data that we're going to generate, it's going to be clearer and clearer. We'll engage in one registrational study, which doesn't mean we're not going to do another one because you see we can position the product in different lines of treatments. I would like to leave the opportunity to our experts to comment on what we have, the science and the clinical data. We'll ask Christian Auclair to give whatever opinion he wants to give on the data that we have generated so far. Christian, are you there? I am there. Okay. Hello everyone. I am very pleased to participate in the webinar. I would like to share the feeling of a veteran pharmacologist. In fact, we have been involved in the first historical experiment that led to the selections of the molecules for the treatment of a refractory acute leukemia. Some experiments were conducted in collaboration with the Institut Gustave Roussy, which is the largest anti-tumor hospital in Europe. We have also been every time in collaboration with a specialist, including those of Institut Pasteur for the tubulin experiment. What struck us was the following three points. First of all, it's an exceptional ability to disrupt tubulin. The people of Institut Pasteur, who are very familiar with such molecules, are very surprised by the very efficiency in the disruptions of the tubulin, which result, of course, in apoptosis and the killing of tumor cells. The second point is the strong anti-proliferative actions on blasts coming from patients having AML. Usually, these blasts, which are characterized by the many mutations and also complex karyotypes, are resistant to many anti-tumor agents. We have observed very surprisingly that this molecule was very efficient, including in the blasts having, as an example, some critical mutations of Monosomy 7, which is disappearance of Chromosome 7. It was also very surprising. The third point is a complex insensibility to the multidrug resistant phenotype. Alain previously mentioned this point. The phenotype resistance is very common in leukemia, especially in this kind of leukemia and in leukemia stem cells. This multidrug resistance is very efficace to efflux, to release the drug inside the cells. It's the result of a strong resistance either at the beginning of the treatment or maybe for the acquired resistance. That is to say the increase of the phenotype increases during the time course of the treatment. Honestly, we have never seen such properties combined with single molecules. You know, in pharmacology, you have molecules which have a very strong activity in such a mechanism of actions of [noscapine]. The characteristic of these molecules is that they combine a lot of characteristics, which is very efficient in terms of anti-leukemic activity. The last point, and a strongly important point, is that the effect on leukemic stem cells. The point is for the treatment of so-called residual disease. Residual disease, it's a fact that when after maybe a complete remission or partial remission, the people in maybe one month or six months start a new development of the disease. This point comes from the fact that it remains in the bone marrow, some leukemic stem cells. Unexpectedly, also, the molecules target one enzyme which is involved in the metabolism of the stem cells. The stem cells have a special metabolism, and it's designed to survive in difficult conditions. The high LDH, LDH dehydrogenase, provides some components which allow the stem cell to survive. The molecules, our molecule, is able to selectively inhibit this enzyme and kill the stem cells. That is a very critical point. When we can summarize the situations, we have a molecule which is very efficient in the inhibitions of the blast and the cells which are proliferative cells. It's also very efficient in the inhibitions of leukemic stem cells. Of course, it's a very, very, very important point. Thank you. All this point has led us to propose to develop this molecule for the treatment of a refractory leukemia. Clearly, the first clinical result proves us right. Thank you. Thank you, Christian, for this detailed opinion. Our question has been at the origin of this discovery of this drug in his lab. We're pleased to see the progress. Now we are going to leave, Nicolas Short. Professor Short, are you there? Yes, I am. Yeah. It's a pleasure to welcome you here. I know it's very early because you're in Houston and very early for you. Thank you very much to be there. Nicolas has been, you know, he followed the development of the drug since the beginning. He has been advising us. It's a honor to have you on board. Please, Nicolas, tell whatever you want about our program. Thank you very much. Thank you. Yeah, thank you for the invitation. As mentioned, yeah, I'm a Clinical Investigator at MD Anderson in our Leukemia Department. I focus mostly on acute leukemias, and I also run our phase I group within our department. As mentioned, I've been working with AB Science for quite a while, advising on this drug. Just as background, I know this was already stated, but just from a clinical perspective, I would really, really reinforce what Alain said earlier, which is that the TP53 mutated and the MECOM rearranged AML really are absolutely the worst subtypes of AML. This is like the lowest hanging fruit to find a drug. If you can just find some clinical activity, the standard of care is so poor in these that you can, you know, that I think this is really ripe for development of a drug if it is active in either of these subsets or both. The median survival of these patients newly diagnosed is six months. I would argue there's no standard of care because even though AZA- VEN is the quote unquote standard for older patients with these diseases, if you look at the subgroup, if you look at the trial that led to azacitidine venetoclax being approved, AZA versus AZA- VEN, there's no benefit to adding to the combination compared to the standard in these subtypes. We really don't have any good outcomes. Even young patients who are treated with intensive chemotherapy, their median survival, if they have a MECOM or high-burden TP53, can still be six to nine months. It's extremely poor outcomes. We have no good salvage, certainly no good salvage therapies, no frontline therapies. As far as the KRAS and NRAS, this is not as bad as the TP53 and MECOM, but this is particularly a poor prognostic molecular profile for patients treated with AZA- venetoclax, for example. Older patients, these patients do not do as well, and the median survival is only about a year. We definitely need, and separately, these are mutations that we also see emerge with some of our therapies, like venetoclax-based therapies, FLT3-based therapies. There's a lot of NRAS, KRAS driving resistance across AML. That's just some background on why I think these subtypes are so important that we have targeted therapy for them. As has been shown, the single agent activity, I think that obviously it's only four patients, but in MECOM rearranged AML to have two out of four responses is very significant. Again, I would, we've shown and we've published that the response to maybe salvage therapy in these patients is like at best 10%. 10%, 15% at most. Two out of four is impressive in this particular group. I think when we think about what would lead to an approval of a drug in this space, this is, yes, it's a very rare subtype of AML, but it is such a poor risk subtype that if we look for reference from other recent approvals in AML, for example, menin inhibitors for KMT2A rearranged leukemias, those got an FDA approval with a response rate of 20%. Now, [CR, CRh], right? A very specific type of response, but a response rate of only 20% was what was basically submitted to the FDA in a single arm study and led to approval in those diseases. Now these drugs, even though they're only approved in that specific subtype, are being used all the time off-label because they're in NCCN guidelines for NPM-1 because there's also activity there. They're being used in the frontline setting. Obviously, there's a lot of clinical trials developing that, but once you get a drug approved, even in a very narrow space, there's a lot of use of it, at least in the U.S., where we can use drugs off-label. I think that if this was recapitulated, like you could get anywhere near a 50% response rate in a larger study of MECOM, even really 25%, 30% based on the historical expectations, this could be adequate for kind of an FDA approval based on a single arm study. I think ultimately our goal with any of these drugs that are showing activity as single agents is to do combinations, to do either the AB8939 plus venetoclax, which has already been studied, or do the triplet combination, the AZA-VEN, AB8939. I think what we've seen at least with the doublet, with this AB8939 plus venetoclax is significant blast reductions in what I would call ultra high-risk AML. If you look at stratification, there's adverse risk, but within adverse risk AML, the really, really high risk are the TP53 and the MECOM. I think the activity that's been seen so far is very encouraging, but obviously we want to see this with larger studies. What I would say is that the early data that we've seen so far really suggests significant activity in the highest risk subtypes of acute myeloid leukemia (AML). These are the subtypes that actually other companies don't want to, you know, their drugs are not working in these subtypes. They're trying to develop their drugs in the subtypes that are not as high risk. These are the types of trials that would enroll extremely well and very quickly in these high-risk patients because these are what comprise the vast majority of our relapsed population. The bar is so low, I think, to show a benefit in these particular subtypes. I would just say that if these response rates, again, are shown in a larger trial, expansion, I think that there's really well positioned to have this drug developed in both the salvage setting, which is where most of these adverse risk patients are, but also in the frontline where our standard of care is so poor with what we currently have. Thank you. Nicolas, thank you very much for this very clear, I would say, summary of the key points. We are following your direction, in fact, to develop this drug. Now, no more science, just some business consideration. We, of course, are interested to understand what's the market. Given the incidence, given the estimation of the percentage of patients which would be in the high-risk profile, this high-risk is defined as this group of patients who are at ultra high risk or high risk, given the data. We don't here differentiate between line one, line two, line three. It's all the ones who are high risk, I would say. We see that the market could be $1 billion in the U.S. and a little bit less in Europe, but with the rest of the world, we top $2 billion. It's an extremely large market for a small company like us, despite the fact that they are treated only, you know, by hematology. The number of hospitals is limited to visit. It's a sort of indication which we can actually deliver throughout the value chain. Now, let's have a look at the IP. We have two patents there. We have a first patent, which is we have different lines of protection. We have orphan drug status, which we have received both from FDA and EMA. We have the composition of matter. The composition of matter has an extension of five years. We need to add it at the end. Our patent would protect the component in 2036, but with the five years, 2041. We have another patent for the adverse genetics. You have seen that our drug could make a strong difference on these adverse genetics. That's another patent that would protect until 2044. You should probably memorize 41, 44, which gives us plenty of time to do the development and try to register. That is the end of this presentation. Thank you for listening. It's not completely finished because we're going to take a few questions, not a lot, because we would like to limit the call to one hour. Laurent. We have a first question regarding the next steps. Do you plan in the coming 12 months to initiate new clinical studies with AB8939? Okay, new studies as compared in AML or outside of AML, according to the question? In AML and outside AML. Okay, so outside of AML, no. Although I'm sure Nicolas and Olivier will say why not high-risk myelodysplasia, which is another indication close to the AML. No, so far. Maybe later. For the AML, yes, we plan to finish the phase I, so it's not a new study, and start the extension phase. In the next 12 months, the strategy would be one, to finish the phase I, and two, to implement the expansion study that would secure the whole development, and then to engage in the phase II. Okay, any other questions? No more questions for this time. Okay, I don't know if any of you, Olivier, Nicolas, Christian, you want to add anything? Can you hear me, Olivier, on the phone? Olivier, vas-y. Yes, I think it's a very important trial because, as Nicolas Short said before, it is a real unmet medical need. We have a lot of patients in which we, you know, we cannot, we don't know what to do to this patient. Mostly the elderly one because we cannot perform bone marrow transplantation. Even in younger patients, bone marrow transplantation usually is associated to the failure because this patient relapses even after bone marrow transplantation. We do need something here. As we have been saying before, nobody wants to engage in this unmet medical need population of patients which are highly resistant to chemotherapy and standard of care with AZA and venetoclax. Here, maybe because we have this unique mechanism of action, which is a tubule poisoning and ALDH inhibition and sensitization to venetoclax, we may expect to see something here very interesting for this population. Although I hope that we do see will last very long, as we said before, the life expectancy today is only six months, which is very short. To reach like nine months of survival, or even one year, would be a great advance in this disease. Hopefully, we may cure some patients also. In addition, I would like to say also, because we do not see too much toxicity, and we see quite a stabilization of the peripheral blood and particularly the neutrophils, which allows the patient, even if they are not in complete response, to have almost a normal life outside the hospital because they are not at high risk of infection because of the neutrophil count. If the platelets remain at around 30,000 or 40,000, it's also good for this patient. Also, you know, with chemotherapy, usually we see some toxicity and we cannot prolong the treatment. Here it seems that the treatment is quite well tolerated, which is quite good news also for this patient. We have a question in the program, whether we have enough money to carry out the next phase. Okay, so for phase I, yes, of course. For the registrational study, that would entail 200 patients, except MECOM, probably 80 patients, no, we would need to raise the money. For the expansion phase, it would be probably nice to, we'll see what we do on that. I would say it's a question that is on our table at this time. Another question? Okay, as a conclusion, I think the conclusion could be the slide 21. For the slide, first of all, the combination with venetoclax, which has been highly recommended by our R&D team and the discussions we had with the different hematologists, seems to be really the right one. There was, it's the combination of three mechanisms of actions. Venetoclax inhibits a BCL2 pathway that blocks the apoptosis of the chemotherapy. We bring with AB8939 destabilization of the skeleton, so microtubule, plus the targeting of the stem cells that we hope to be able to remove. The three together, the two together give three mechanisms of actions, which add up and at the end are probably synergic. That looks the right one, plus, as Olivier said, safe, because you have seen venetoclax is relatively safe as compared to others, and our product also. The two together are relatively safe. There is no such high toxicity in any of those two compounds. The choice of the chemo was very smart. When we have the three first patients, which is the important readout, it's very, very preliminary, but so important for us, that's why we have a web call today. It's three out of three with a response, not complete response in all the cases, but still a response in what Nicolas calls ultra high-risk situation in line three, in line four. We wanted to share that with you. It's highly preliminary, but it gives a lot of credit to the mechanism of actions, to the choice of the doublette, and of course, encourages us to continue because we see something like the light into darkness, and we want now to follow it up to the end. We're going to go step by step. Of course, we'll be very pleased to organize more web calls for you to give you the outcome. Thank you for your listening, and hope it has been clear enough. Otherwise, you can still write us. We'll try to respond to your questions. Thank you to all of you, and in particular to Nicolas, who in Houston. Thank you. Goodbye now.