AB Science S.A. (AB.PA) Earnings Call Transcript & Summary

Ladies and gentlemen, welcome to the AB Science Webcast. I would like now to hand over the call to Alain Moussy, CEO of AB Science. Sir, the floor is yours.

Thank you. Good evening, and good afternoon for the participants in the United States. Thank you to join our web conference that will give a development update on the key topics of AB Science. With me for this presentation, there is Laurent Guy, the Financial Director; and Oliver Hermine who is the President of the AB Scientific Committee. Disclaimer as usual. Next slide. So the first [indiscernible] the structure of the presentation is, as usual, which means that we will deliver 30-minute presentation and then we will leave it to your questions where we see already lots of questions, so we'll try to address them in due time. And thank you who have sent us questions by writing even before this call. So first [indiscernible] which is the [indiscernible] masitinib in ALS with [indiscernible] EMA and Health Canada. Next slide. All right. So EMA, we press release already. What I'm going to say is clarification, a repetition of what has been said. But we try to make it extremely clear for the audience. So for EMA, the application was filed in 2022. And then in January this year 2024, we were invited to present our responses to pending concerns [indiscernible] whole explanation. And, secondly, focus to AB Science a couple of days before the date instead of going to [indiscernible] explanation to submit a return response to the list of issues pending, which is very -- as usual, which we said in the press release and we, of course, accepted this procedure which gives more time for the sponsor and more time for the agency to look at the responses. So now why [indiscernible] has decided to switch from [ overall ] explanation to a return response to new cycle, so to speak, [ isn't now ]. But if the responses of AB Science are satisfactory, there is -- there might be no need to go to [ overall explanation ] anymore. That's the important point. So it adds literally one cycle within this phase of review. The decision, of course, is delayed and now is expected by the end of Q2 2024. Health Canada, as you know, we are also into a conditional approval process with Health Canada and we press released that we have received recently a notice of noncompliance withdrawal as the formal letter saying that they still have concerns, and we also press released that we intend to submit a request for reconsideration. What does it mean? In fact, in the process of an approval by Health Canada, there is this possibility to ask for a reconsideration. It means that the process is not over. This reconsideration process is different from the 2 cycle. Why? Because the assessors, the team of assessors change or had in the second cycle that we've just finished, it was the same team. So now we are going to have a new assessor team. The second modification is that for the very first time, it gets the possibility to have an opinion of the panel of experts, which was not possible in the previous cycles. And we hope that this panel of experts will be used by Health Canada, but this is the decision of Health Canada for diseases [ as serviced as ] ALS, we hope it will be granted. Of course, the decision is delayed and we have been informed that the process might take up to 6 months, which means that it might end now in end of Q3 or even Q4 2024. Next slide. So we press released in details what we think are the key major clinical objections, but also the intended arguments, I would say, a possible answers from us. And we thought it was important because we wanted to leave to the public a good understanding of why we go to reconsideration. The reconsideration is done because we think that we have logical credible answers to the concerns that we could not provide before. I know that some of you [indiscernible] by writing why we have not communicated those answers before because we cannot. And why we cannot, because the Canada process is working differently from the EMA or the FDA. There is a submission. And then sometimes, you receive some [indiscernible] which is a clarification email. But if you do not receive any [indiscernible], then you cannot answer to any possible concerns that the agency has and you [ discover the objection ] at the end, well, for instance, EMA [indiscernible] intermediary cycles, when you receive the concerns and so you have an opportunity to respond to them. So that's why actually it might come at the end and then you have to engage into a new cycle, if you want to respond to those concerns. Anyway, we have 2 cycles, and we resolve some concerns, but still there are some concerns left, and we think that reconsideration to a new cycle is useful to try to answer those concerns. So let's go into the details. The first key major clinical objection is on the [ amendment ]. So there is no surprise that there has been an [ amendment ] with [indiscernible] we have solved, I would say, some very critical aspects of that concern. For instance, Health Canada agreed with us that for a disease, which is a [indiscernible]. It's not unusual to move from a Phase II to a Phase III, which was not of use at the beginning. Health Canada also agreed that multiple [ amendments ] is not unusual. Health Canada agreed that the [ amendments ] are not data-driven, which is very important, of course. And Health Canada also agreed, we said it in the press release and the number of [ amendments ] we did, which is, in fact, 3 amendments when we concern with residual Phase II to Phase III is not unusual since the average of the number of amendments for [ clinical ] studies, in fact, [ 3.3% ] according to the publications. Health Canada also agreed that the [indiscernible] study were very broad. And so there was a need to lead [indiscernible]. And also Health Canada agreed that in one [indiscernible], we define, we distinguished [ fact ] progressor for normal progressor and we use [indiscernible] that, in fact, may be relevant. So all that is important, of course, in the context of trying to solve this issue. However, it remains one point and the point is that Health Canada considers that the timing of this amendment was maybe late and maybe still not sufficiently justified. So what are the possible answers to those -- to such objections. First, we think the amendment was not too late. Why? Because it was 2.5 years prior to the [ completions ], but also it was not too late in sense of that actual because only 12% of the enrolled patients today, which the time point of the primary analysis meaning that 88% of the data need to -- remain to be acquired. And when we remove the first 12%, the study is still a success statistically, which means that the first 12% will not be as differently than the remaining of the study, the 88% and also since the key amendment was to distinguish normal from [ fast ] progression, it's important to know how many fast progression they were at the time of the amendment, only 8 spread across 3 arms, which means that, of course, you cannot [ release ] nothing with only 8 fast progressors. And also another point is that at the interim analysis, the study was positive in the population normal plus fast. And it's only because the EMA asked us to continue that we continue, there was no amendment [ after ]. We think that the amendment was justified because in distinguishing normal from fast progressor and removing the fast progressor from the primary analysis because it was expected that fast progressor could not meet the week 48 time point for a large part of them. That was the recommendation from the principal investigators. And in fact, it's exactly what happened. And you know that the guideline we commenced minimize [indiscernible] that at week 48. So that was -- that expectation that was the primary driver of the amendment. And in fact, exactly what happened in the study since no more progressor in average would reach at 25%, 30% at week 48, but fast progressor discontinued for more than 50%. And when you have more than 50% of missing data, it becomes extremely complicated to interpret this missing data. So these are the arguments that we would like to share with Health Canada for reconsideration. Next slide. The next slide is technical. That's why we are doing this call is to try to explain very technical arguments that most of you might not understand through the form of the press release. And I will try to be as clear as possible so that you can share, I would say, the logic of the argument. So Health Canada said that the primary analysis was based on what they call [indiscernible] which potentially creates a [ bias ], let me explain. Last observation [indiscernible] discontinuation -- the last data before discontinuation. If you consider that data before discontinuation and you say that's the one I'm going to use at week 48, it's going to create a bias because we're talking about the neurodegenerative disease. And so we expect the score -- symptomatic score to decline and not to say the same as the time of discontinuation, okay? So that's why it might be a bias unless there is the same percentage of discontinuation of the set timing between the [ 2 ] arms, which was more or less the case by the way for our study, but still methodologically lots of [indiscernible] carryforward is not the base methodology to treat the data. And what -- how do we respond to that? First, they have criticized, let's say, what we call a very technical again, the linearity of the distribution of the data point of [indiscernible], what does it mean? It means that because there is some [ death] before week 48, It is not linear. You can see that the score [indiscernible] can be 20, 30, 48 to 48, right? But when there is a death, the score becomes 0, and that creates a big distortion in the distribution, calling nonlinear, now it becomes very technical. When the distribution is linear, you can use some form of calculation, which is called [indiscernible]. And when it's nonlinear, then you cannot, that's not recommended by statisticians and we have to use another form of calculation, which is called [indiscernible], right? Now although our distribution is nonlinear again, they have accepted one of our arguments, which is very technical called [indiscernible] I'm not going to detail that, which makes the nonlinearity acceptable, so to speak. It's important because it means that we'll not criticize a nonlinearity for the ones who know very well in this industry, you will see that, for instance, and this was criticized on that as well by FDA in its registration process. So [ we've solved ] one of the key arguments which is very technical. Now, we are left with LOCF, okay? So we use LOCF and of course, Health Canada does not recognize LOCF, but we never actually stressed LOCF. We stressed and we want to provide this information again to Health Canada. We actually said that beyond LOCF in the study, there was some prespecified non-LOCF analysis, sensitivity analysis that are successful like, for instance, [indiscernible] for most of you, it will not be anything, but it really is non-LOCF and it's positive that [ effect is significant ]. Then there are some additional analysis, which are even more conservative like what we call a [ jump to reference ]. It means the penalty in case of discontinuation for masitinib, where we treat the missing data as placebo [ interesting ] not only the decline of the placebo, but even that as the placebo at the time of the discontinuation, which is a massive penalty and we did another sensitivity analysis, which is [indiscernible] methodology, which are super technical, are recognized by the agencies in the world as being very conservative and robust is successful, which is the case. And the [ CAFS ], which is a recognized methodology of calculation by Canada and by India as well as a trend, okay? And this trend is P value 00.7 and it's not a win, but the study was not designed to be a win on the [ CAFS ] because it requires more patients, right? However, that is a good sign of the efficacy of masitinib and Health Canada told us that the [ CAFS ] cannot be actually considered because it encompasses LOCF [ tons of ] calculation, which, in fact, is not the case. No [ CAFS ] can be calculated using [indiscernible]. So we don't understand, by the way, why they said that, but we're going to provide this correction -- I would say a clarification in the reconsideration. So all that is very technical, and we understand that most of you could not understand the technicity and technicality behind statistical calculation with missing data. But process the missing data treatment is paramount in the registration in any neuro generative disease, and we think that the sensitivity analysis that we have are robust enough to convince agencies that the [indiscernible] and the bronchitis. So if I cough, I would [ constitute -- your apologies ]. Next slide. So the next slide is on the third objection, which again is technical. What is it? It is the application of a guideline on the [ subgroup ]. Most of you know that our study is positive, but in some subgroups, it's even more positive or even very strong. So we are using a guideline from EMA, which is called a guideline of subgroups where we try -- where we apply this guideline strictly and we try to convince agencies that the product can have a reuse claim on these subset of patients, but with, I would say, stronger benefit and even better safety. So the point is to say if we can apply the guideline, yes or no. And at that stage, Health Canada consider the guidelines, of course, good. It's an EMA guideline, but could not apply to our case. And the argument they use is that they consider that that guideline of the subgroup is applicable only to subgroups that are prespecified, which means it's already written somewhere in the protocol. And in fact, the guidelines says something opposite, and we actually have literally stated what the guidelines said and it says it might be of interest [indiscernible] group, but it has not been [indiscernible]. So in fact, the argument of Health Canada is contradicted by the guidelines itself. So that's the point we would like to bring for reconsideration. And of course, once we have done that, which is to a methodology, we have to look at what is this subgroup. In fact, the subgroup is all patients, except the one where who have already lost functions, which means [ motoneuron ] and we know medicine cannot generate muscle. So this subgroup makes sense. And in this group, we have exceptionally strong data. The [ CAFS ] specifically significant, the most preferred calculation of [indiscernible], but the survival is significant. And you know that in the extension phase, some placebo switch to masitinib and because masitinib is effective on survival apparently. The fact that placebo switch to masitinib creates a penalty on masitinib. So there is a methodology, which considers to sensor the data at the time of the switch. And that actually is a classic. So when we sensor the data at the time of the switch to try to neutralize the penalty that way because the placebo switched to masitinib. In fact, we observed that the additional survival is 22 months, almost 2 years, which is considerable in this disease. So we think those arguments are very important and should be brought to the agency for reconsideration. So I hope that those [ 3 sites ], although very technical help you to understand better why we engage into reconsideration. It's because we think it's worth doing it and we have 6 months to talk to them a new asset search team and possibly a panel of independent experts. Next slide. Now we go to operational program, starting with masitinib platform with 2 platforms, masitinib and microtubulin destabilizing agents. Let's talk about masitinib first. So masitinib has, in fact, 8 programs active, 3 in neurodegenerative disease, 2 [indiscernible] cell disease, 1 in hematological orders, sickle-cell one in [indiscernible] and one in oncology, which is prostate cancer eligible [ dyslexia ] and we'll go very shortly to tell you where we stand in each of the car. Next slide. ILS, which is the key program among the program. What can we see recently? First, we're not alone. So we have served what's happening for the other projects from other companies with other mechanism of actions. We have seen -- for instance, the analytics, which drug which has been approved by FDA, has been rejected by [indiscernible] Europe, [ you don't observe the 2] and we know that an unique confirmatory study, which will end -- will be done on offer, which is designed on 48 weeks, where as the first study was in 24 weeks, and you have seen the impact of missing data, which is increasing with time because there is more and more discontinuation and debt, which is not accessible to confirm the data as we can [indiscernible] 48, we would see what will be the confirmatory data from this program. [indiscernible] there are 2 drugs, in fact. The first one coming to [indiscernible], which has been registered at the FDA but not in Europe, they've been refused. And there has been other formulation of [indiscernible] population. The second one, developed by Spanish company [indiscernible] on a Phase III for discussion in Europe because I would say the Japanese Mitsubishi [ cannot ] stopped the investigation there. But their study held with the primary endpoint at week 48. Then more recently, there has been a competitive program led by [ Sanofi ] based on the [indiscernible], which is a kinase as well, which also targets microglial like masitinib and this program held its primary endpoint, which has been at least recently. [indiscernible] is the product from Biogen is an [indiscernible] which target the [indiscernible] mutation of the disease, it's in [indiscernible] officials. This one is fairly studied in terms of improving [indiscernible] which is a biomarker. [indiscernible] PET study, but the agencies they think that the reduction of neurofilament is enough despite the fact that there is no clinical benefit. So [indiscernible] like in Alzheimer, where there is a reduction of the [indiscernible] but there is no benefit in some studies. And by the way, [indiscernible] like that in the United States. Here, it's a little bit the same, no clinical benefit [indiscernible] but the success on the biomarker, which was a secondary endpoint, [ that registered and this ] concern only 5% of the patients. So what we can see is that besides [indiscernible] is very peculiar, [indiscernible] But there is no per-winner in this NPI -- I would say, breakthrough in ILS unfortunately, which remains an [indiscernible]. Now where do we stand with our [indiscernible] program? Our confirmatory [indiscernible] and the study enrollment is slow and slower than the previous study, anytime [indiscernible]. We received many questions on that. So it went slow. And why it is low because it is slowed down by its design, in fact, in the design, which was actually, we follow the recommendation of [indiscernible]. They recommended to do a 3-month running period. What does it mean? that for 3 months, the patients will take [indiscernible] before being able to have their treatment, which is masitinib or placebo. The patients on [indiscernible] they want to continue immediately with the [ drive ] and not with 3 months in a disease where the median survival is only 18 months. So that is, of course, this came onto the recruitment. Then we chose moderate in severity patients because you have seen that and you know that the benefit is higher for those moderate. Of course, [indiscernible]. Also, EMA recommended not too low, not to make eligible, the alternative work registered in the United States, [indiscernible] And of course, it does not facilitate the recruitment at least in the United States 4-point is the extension is blinded or had if you want to make it more friendly for the patients to be open level, but because EMA wants to punch within 10 points, branding extension was necessary to try to get -- let's say, trend at least in either survival or [indiscernible] survival. So you see it's technical, but that slowed down the recruitment. But that has been the choice initial. Next slide. Multiple sclerosis, progressive forms. What is happening above the landscape. First, there is only one drug which is approved, which is [indiscernible] in part of the progressive form, which is the progressive forms coasters. There is a second form, which is called inactive [indiscernible]. Then what? There is -- there were 3 drugs, which are in Phase III. You have [ 2 drugs alone ] inhibitors. The first 2 are called BTK inhibitors, [indiscernible] BTK inhibitors and the 2 drugs tolebrutinib, which is developed by Sanofi and [ tolebrutinib ], which is developed by Roche. If not in this program, but they have been put on hold by FDA, a big information due to liver in June, which means that BTK inhibitors and at least 1 toxicity sits. And another word called evobrutinib, which is developed by Merck Serono. Merck Germany, which went so reveal no, as announced, it seller in a Phase III, Marinopoulos, which does not give a good signal of efficacy of this Bruton Tyrosine Kinase inhibitors. And met is a challenger. So some analysts said the situation potentially can't go away from a strategy to emerge a standard for Alcon. We can is business journalist. And we think that that there is scarcity of potential drugs in public forms and masitinib as its own net and not the problem that we see for BTK inhibitors. We call that positive with growth. So we, of course, focused on our development, but we are also observing the development of others. And when the programs alternatives do not match their expectation, it might be positive for us. So where do we stand with the masitinib platform? As you know, the Phase IIb was positive and published. Conference is authorized by FDA and key European agencies. And we expect initiation of this program in 2024. And I will tell you how with partnerships, of course, it's public. We announced the strategy, and I will come back to the partnership later. Next slide. So the next slide is on Alzheimer. What needs to be -- is that massive [indiscernible] because it's positioned in a product of Alzheimer, where there is nothing, which is the man and especially they mode of response of Alzheimer. In fact, you have 3 forms of Alzheimer, which are classified by their, I would say, advance in the disease. The first 1 is called early Alzheimer, the second 1 mild and the third is modeled and there is even a fourth one we call severe, but nobody is going there with any drug. And that is measured by a scale called [ MMSO ], okay? So what do we have? We have 2 drugs, which have been approved by FDA and -- on antibodies, one belonging to Biogen Eisai, the other one to [indiscernible] and they are in early Alzheimer. And the part of [ mild ], but not all of [ mild ]. And these are the winners. But there are others, lots of others, with the same mechanism of action itself. And recently, one called [indiscernible] In fact, 2 drugs from Roche failed recently in Alzheimer in this position. You have different strategies. You have the antibodies, again, the beta [indiscernible] That's the one I just described. And some are [ too ], but not all of them, of course, because they said. There is another strategy targeting the 2 protein. You know that there is also [ a way of ] 2 protein. We don't have data yet. Hopefully, next, next week. And then there is a third avenue, which is our avenue, which is to target the environment of the neuron and to target the immune response and impact the [indiscernible] in early Alzheimer and mild, but not in moderate. And then there is our drug, which is in mild and moderate. So that's the picture. When you look at that, who is in moderate, primarily [indiscernible] Who is in mild? Lots of people, but not exactly the same positioning of the mild. So imagine it [indiscernible] as a purposeful drug for moderate Alzheimer and also full mild. Where do we stay in our program? The Phase IIb was positive and published. The confirmatory space we have been discussed, we [indiscernible] for MS and has been authorized both by [ AB ] into European countries, and we expect initiation in 2024 with the same strategy of partnership that we make there. Next slide. Next slide is on mastocytosis. Mastocytosis is a long, well-known indications for us. There has been some novelty here. In fact, there are 2 companies. One is called [ Brooklyn ], the other one is called Cogent, and they are developing KIT existing inhibitors because an aspect of this, with this mutation, which is the driver of the activation of mast cells. And [indiscernible] in this mutation target other kinases, but with efficacy as well. So those compounds are different mechanisms of actions. And it seems they have benefit of different symptoms of mastocytosis, specific in [indiscernible] which is a spot there on the skin, and GI symptoms. And [indiscernible] is more of the [ skin ] on neurological symptoms with [indiscernible] so to some extent, they might be complementary. In terms of efficacy, you can see a difference between the response, the response [indiscernible] 50% for the competitors, 75% for us, published and the difference between the treatment and the control is 15% for [indiscernible] which looks above the same. It's not the same end point though. And the long-term safety is well-known for masitinib, less well known for the other ones. And it's technical, but when you press on the mutation, the [ key P16 ], there is a risk to emerge [ pools ] since we do not press on [ key P16 ], there is no emergence of [indiscernible] possible with masitinib. For the other programs, we don't know yet. To be monitored. Where do we stand? What is in there? We're doing the ongoing study, okay? If we take more time, of course, [indiscernible] And we have a Phase II in [ NCAP ], which is another subset of [ masitinib ] where there is no mutation, where we're doing a Phase II. And if the Phase II is effective, we would continue for. So that mast cell diseases continue and the appearance of competitors makes it more challenging. But still, the pushing of masitinib is differentiating from the other one. Next slide. The next slide is on sickle cell disease called in France, in French, drépanocytose. Drépanocytose is a hematological disorders with some mutation of the hemoglobin gene, which leads to problems that can go -- the patient does not produce enough hemoglobin and can die from that in severe forms. And the last time, there is 1/3 of the patients, the severe forms, and these severe forms, they die before [indiscernible] they die around 50. So they shorten the lifespan considerably. It's the broadest, I think, genetic disorder in the world. Now what's happening in the landscape? You have 2 companies which gives you the [ lesser ] technology called CRISPR that you have certainly heard of. And they have come with a products, 2 products, which are very effective and cure patients, which is beautiful in the field of the industry. Still, there were some problems. The problems, the unique [ runners ]. The second problem is that sometimes toxic because of side effects. And the very key problem is that the prices, at a price of $2 million or $3 million because it's a cure. Based on that, analysts estimate that the number of patients insured enough to pay that will be 5%, probably even less in Europe, which is a progress, of course, but doesn't solve the issue for other patients. You have new drugs which have been registered, and we have given there some. And all of them are used but not massively, like less than 5%. And I do not get into the details of each of them, so [ this room ] for some. And our cofounder and key scientist, Olivier Hermine, Prof. Olivier Hermine, was at the call here. He had discovered something that we patented within showing the involvement of mast cells in what is the main problem of disease, which is the battle [indiscernible] that can kill, ultimately, the patients. And that is new. Completely new. And the only product that targets mast cells in the [ SCD straw cell ] would be masitinib. It's the first one of its kind. Now based on that discovery, we submitted with Olivier -- Olivier submitted with us rather, a request for financing from the government or [indiscernible] and there has been hundreds of projects. And our project has been one of the winners and has been awarded by grant of EUR 10 million, which will go to [ EPC ], the Parisian Hospital, would be the academic leaders of the program, would receive a part of that budget. But the sponsor will be [ EPC ], so they will implement the Phase II with their team with our product, okay? And there will be 2 parts. The first part is a research of a biomarker to detect the signature of the mast cells because [ mix ] not all patients will have mast cells involved. This would need to [indiscernible] and then we'll do a part 2, which will be the Phase II by itself. And biomarker increase the chance of winning and being registered, ultimately, the [ 2 case ] of products from Biogen called [indiscernible] and ILS. The good news is that one is Phase II finished. AB Science, we [ need ] to continue the development. Of course, there will be licensing with this [ PHP ] with that on part of the job, but we can continue, and this is [ refining ]. So that's the message for [indiscernible] Next slide. The next slide is the oncology. So we did a lot in oncology to explore [ validity ] but in the end of the day, we selected drug. The data show that the most promising is metastatic prostate cancer, eligible to [indiscernible]. And in that landing, there is an unmet medical need because there is only docetaxel and no drugs could combine with docetaxel to improve survival or progression-free survival in metastatic prostate cancer. There are lots of [ words ], but there are positions before those [ effects ] in what we call prostate cancer metastasis indicative of a [indiscernible] therapy but not advanced enough to be eligible to chemotherapy. When it comes to chemotherapy, only docetaxel and masitinib stand out because we succeeded in the Phase III. That's not enough to register. We need to do [indiscernible] now what we did is that we are [indiscernible] advice [ through any FDA ]. We receive it and we validated the primary endpoint. But most important, we received the information that we don't need in the confirmatory study to prove benefit of survival. That is important point because if we had, then we need to recruit, then it's more risky. And we need to recruit more patients, and the study will take more time. And for all [indiscernible] before docetaxel, you need to provide evidence of benefits on both the PFS and the survival, which is challenging. Here, you just have to do [indiscernible] PFS. Knowing that, we think the confirmatory study has a chance of success, which is higher, so we wanted to do it. Now where do we stand in this program? We plan a submission for authorization in the coming months. And so we expect with authorization in 2024 and to be able to start this program in 2024. Next slide. Next slide is COVID. So as you know, we have received a grant from the European Bank of Investment to develop one study in COVID, which is the first one, which is patients suffering from COVID and being hospitalized in need of oxygen, having moderate or severe COVID. In fact, we did 2. We did this one, and we did a second study for patients who are infected, and we use masitinib as an antiviral, but the patients are not necessarily hospitalized. They are in ambulatory status or they are hospitalized but not in need of oxygen. But all of them have a comorbidity, which is a risk to develop severe symptoms. So we did 2 instead of one. And as you know, it's much more difficult to recruit [ a fact ]. It would -- there were a lot of [ TDs ] and no -- if it can by [ weight ], so it's very difficult to recruit patients. However, we are going to finish those 2 studies, late, of course, but we will [ finish ] those studies, and we're going to read them in 2024. And we have to thank the European Bank for Investments. People might think that it's over. I would disagree respectfully with this statement because it might come back. It might come back not as COVID. It might come back as another disease, but a viral disease. And as you know, masitinib is published as a [ more than ] the antiviral activity. So even if it's not hot anymore, or I thought that it used to be, it might can come back, and it's important to have antiviral in your portfolio that in case viral infection come back might be useful for the next disease to come, and there will be next disease to come. So even if it is late, not late for potential new disease that can strike on the planet anytime. Next slide. Key, of course, is masitinib partnership. And next slide, as you can understand, this is something which is very sensitive and covered by confidentiality that we want with everybody. So I cannot tell you a lot, but I can share with you some information. The first information is that we want some discussions and the discussions are ongoing. The second information I can share, which is very important, is that we expect the process to be completed by 2024, which was the objective. We started in 2023. We said it would take 12 to 18 months, and we hope to complete this process by the end of 2024. Now very important. Those discussions that we have today are with companies, which do not condition the signature of a binding offer to a positive opinion from the EU and Canada on the conditional approval of ALS. That's important to say because we have, of course, validated with them, then they do not invest for an opportunistic conditioner pool that might take 2 years or less. And we need something like a lower oncology, okay? So we carefully watch that with them and we can tell you that we are serious -- and they are serious about that. And it's -- the risk is low for us. Now let's talk about the license, which has been one of your questions I read that you have. It's not only on your journey, but it's mainly on that, okay? And among those disease, it's on our head, including, we said in the strategy that we expect of ALS, we want to focus on ALS and we expect partners to do bigger diseases like MMSE and Alzheimer, true. But the partners are interested by us, and it's very logical because it's the most advanced one. So we need to report here that the license is likely to be on MDE and likely to include. Is it a problem. No, it's not a problem. It's just the way it is, okay? So you know that, that's the only thing we can share with you, but it's already a lot because we have not communicated a lot because we have this continental agreement. The rest will come in due time when it comes to be the first one and everybody will notice that. Next slide. Next slide is important for the partnership and for the future of masitinib. We want to develop a new formulation of masitinib, which is a liquid formulation of masitinib for 2 reasons. The first reason is because after some time, patients could not -- cannot swallow the tablet anymore. And it's a problem in our clinical study because they cannot rely on it, right? And so for the patient because they would like to continue and they cannot. So a liquid formulation will solve this problem. The second benefit is that we have different possibilities of success. And the price will be different, like we know the price of masitinib, $140,000 in the USA, while the price for microtubule destabilizer in the USA $3,000 and the price for Aduhelm is different. We know that because the products -- some of the products are registered. How to manage that with the same combination is very difficult. But if we have 2 different formulations, on 1 specific formulation, which would be the liquid formulation, then we can maybe -- we can certainly maintain high price, okay? And not that to reduce the price because target will be for ALS. That is logical, and that is important for the partnership. To do that, we need to do a biothermal study and develop the liquid formation. So it's an effort that will take years. Next slide. Then we'll go to the second platform, the Microtubule-destabilizing agent called NDA to be to use an acronym that will simplify the communication. Next slide. Various drugs in this second platform. One is an injectable and is developing hematology in particular Myeloid Leukemia. And the other one is a novel formulation that is developed and will be developed in sarcoma. Next slide. The important thing to understand is that we have full invaluable differentiation through this program on 3 things, which are technical, but I try to make it clear. The first one is that the new contributing variation. And we have, it already exists. The existing, developing, et cetera, those drugs are metabolized by an enzyme produced by the disease, excuse me, in leukemia, which is called megakaryoblastic, and because of that, the drugs have reduced efficacy or no efficacy at all. Now we report the 8939, the microtubule, which by the way, is a code name of 12319. Those works are not metabolized by this enzyme, making it possible for the first time to use a new contributing destabilizing agent in AML. It has not been tried effectively so far. So that's a key advantage. Second advantage. You have heard of a terminology called multi-dose resistance. What is multi-dose resistance? It's the ability of an oncogenic cell to washout the drug from the cell, okay, because nature have had millions of years to indent some ways of supply. And how does it do that? It does that with protein called Pgp. And so this Pgp is produced -- this protein is produced by the stem cell, and the more you put the chemotherapy, the more the cell produce Pgp, the chemotherapy will bind to the Pgp, and the chemotherapy will exceed the cell will be wash out reducing the efficacy of the chemotherapy. Now we report that our drugs do not bind to Pgp, and they can avoid proliferation. What does it mean? It means that we can treat with our drugs refractory reluctant patients, which are the ones. We have the utmost maintaining in the ABs. And the third differentiating advantage is a synergy between our drug and another drug registered called Vidaza or azacitidine. That are the spots that you can see on the graph below. And the red is -- the black is no treatment, so you see a lot of oncogenic cells. The red is our drug. The green is the Vidaza and the green (sic) [ blue ] on the right-hand side is, in fact, a comparison. You can see there is no more bad cells. It kills all cells. This is super synergistic effect. And Vidaza is registered. It is registered for patients who cannot -- are not eligible to high-dose chemotherapy to almost 50% of the patients. And so we expect our drug to be developed, maybe, I think with the information with Vidaza. There is 1 drug which is at called venetoclax, completely different mechanism of actions from our brand, and they've been very successful. Next slide. Next slide is where do we stand? So we're on Phase I, and there are 4 steps, as you can see. The first step is a treatment of [indiscernible]. The objective of the Phase I is to reach what we call Microtubule destabilizer to produce any efficacy, just to see what the maximum dose states that can be used in patients. There are 4 steps. The first step is the treatment of [ Radicava ]. Radicava cannot be effective. It's twofold. Still, we take minimum risk, and we treat patients with Radicava and we try to reach the MTD. Then once we reach the MTD, we actually reduced even the dose, but we go to step 2, where we treat patients 14 days. Then once we reach MTD in 14 days, we go to step 3, which is the combo as we have seen because of the synergistic effect, and we do also 28 days clinical-direct so around 4 steps. Now the news is what -- we finish that one. And in fact, with -- in move to our protocol because we plan some doses based on the animal that were too low, and the product was not the peak enough, I would say, to reach the MTD. And so we had to find new dose and took more time than expected, but we have finished the step 1, and as I stated earlier, they get -- we like to go to stage 2. Now we're going to start Phase II, that's where we stand. And we expect to finish the Phase I by the end of 2024. And then -- we do not expect efficacy from that, maybe some kinds of activities, but not efficacy demonstrations. Once we finish that, we'll see if we prefer to go combination with others in a single agent or both, then we will engage into Phase II. And in Phase II, we try to design the Phase II to be compliance with a possibility of [indiscernible] that FDA offers. Now the 2 additional information I'd like to share with you is what our product, which is a cytotoxic chemotherapy, we observed that the neutrophil or key white cells are not reduced by our compound. So it's not so cytotoxic. And in fact, neutrophil counts are stabilized or even increased afterwards -- after a few days and even at day 28. What does it mean? It means that, first, we don't observe high toxicity hematologic for our product. But it means that we could use our product maybe in a chronic fashion, not in an acute, I would say, 2 weeks and then we cannot go on, but chronic. And if we can go chronic, we can treat another disease which is close to ML, which is called high risk myelodysplastic syndrome, which gives another opportunity for this drug. So that's important. And we have also observed a response in MECOM rearrangement. What you have to know is that the very negative prognosis where people die very quickly and have here with an unexpected response which is always a good sign, of course, in [indiscernible] development. Next slide. Next slide is intellectual property. It's important because we know [ masitinib ] product now and -- but it has been rejuvenated by use of patents strategy. And this use patent strategy give us a lot of time to develop our indications. It has been by the way granted in ALS, not even pending, it has been granted in most of the countries, and ALS is protected worldwide until 2037. MS will be protected until 2041; Alzheimer '41; mastocytosis '36; sickle cell, we patented as well, 2040; and prostate metastatic, 2042. Plenty of time to develop the drug and sign partnerships because they look at that, of course. Plus, we have orphan drug status in ALS, but also in mastocytosis and possibly in sickle cell. Next slide. And the patent for the second platform is 2036, but we took patents for MECOM and other rearrangement that could protect in 2044. I think we finish there. Yes. So it has been known, but I think it was necessary, you have a probably better picture than before, and it's global. You can see what's on the highlights. I just would like to summarize in one same things. The milestone expected in 2024 are the conditional approvals both EMA and Canada, which will come end of first semester for EMA and end of the year, I would tell, [ Q2 -- Q4 ], end of Q3 for Canada. And we are doing everything to get registered. And we know it's difficult, and we know it's technical, but it's the way it is. And the second milestone is a partnership that we're working very actively. The rest continues. And with the partnership, we'll continue all programs that we described in this presentation. Thank you for your listening, and I know you have lots of questions. So you might have to stay another 30 minutes. Laurent is going to take hopefully, most of the questions. I would like to know if Olivier is there in case there is question for you, Olivier. Olivier, are you there?

Yes. I'm here.

Okay, excellent. Everybody knows Olivier. Thank you, Olivier, for your presence. I know you're very busy. So Laurent?

First question. I take them in the order received. Is masitinib ready for industrial production? I mean how long will it take after granting of marketing authorization?

It's an important question for partnership. Yes, we're ready for production from [indiscernible] in case of registration ALS. However, you have seen we have a liquid formulation in mind, which will take 2 years. So we're not ready for liquid formulation, but more ready for the other formulation.

You had supply issues with Masivet in 2022. Is this resolved? And is there a risk of occurrence of such problem with the potential marketing authorization?

Okay. So we have not talked about of the situation in [ vet ] or continuing to commercialize in [ vet ] not the key, of course, but are doing it in mast cell tumor. So yes, we have the shortage because of an unexpected problem with our supplier. However, that was purely on the vet. The question [indiscernible] and of course, we were looking to avoid any shortage in the -- with a partner. Now the question, I'd like to make one precedence. Are we going to license the production of masitinib? The answer is no. In case of partnership, we'll keep the production even if we are sorted, and we sell it, which is a stream of revenues. So we'll better be good in production, as the question said. It was a good question. Next. Is the risk related to nitrosamine fully under control? Okay. So nitrosamine, we publicly shared this risk that it was put up. It's a guideline coming from EMA, which is -- it's not a problem on medicine. It's a guideline. So they have to answer the question. It took us time to answer the question because it took us new research studies to do. Whether it's satisfactory or not, I cannot tell you because we have to wait for the end of the process. But from our perspective, yes, we have the answers to the questions.

Last year or recently, you downsized the staff at AB Science and then reducing head counts. Have you completed this process?

Yes, it has been completed. We also publicly informed our change of strategy by saying that we go for licensing and that we will concentrate with our own money on ALS program and the [ second ] platform. And then given that strategy, we would restructure the company to try to be more lean, which we did. It was tough to do, but we did it, and it was implemented at the end -- midyear last year, which had a benefit, which is the reduction of the caliber.

You have financing until end '24. With what financing will you carry out the development in 2025?

It's a financial question. So Laurent, you're -- it's your predilection. You might want to answer that question. For the second part of the question, we are looking for partnership as you know. So partnership can bring money, of course. And this is how we intend to continue. We can also [ want ] money, but the partnership is there in 2024 to solve this problem now. Now how much -- how much money do you -- do we have, Laurent, if you want to respond to the question? I think we met some on this last year.

Well, last figures we provided were when we released the accounts. And so as of June '23, we had EUR 14.8 million in cash. And we expect to receive research tax credit. The outstanding amount prior to 2022 with EUR 11.1 million. And the estimated amount for '23 to be received in '24 is EUR 2 million. And as we have indicated in the past, we have reduced our cash burn. And so we approximately spend EUR 1 million per month.

All right. So we can refer you to the previous communication we did on this topic, and you can work out the numbers easily to make sure your projections.

Next question. Next question regarding the approval process with Health Canada. So Health Canada is rejecting the application currently based on information, which are known since the beginning of the application. So why did it took you so long to clarify those points?

It's a good question. In fact, in the 2 cycles that we had, we solved problems. It's not visible, but I tried to explain in the first 2 slides. For instance, in the amendment, there were 600 questions. At the end, there are still 2 remaining, but they were more at the beginning, the 2 remaining problems still holds, but we did it in the previous cycles. So that's what we did, plus some other questions that were solved, of course. But typically, you receive lots of questions, you reduce them. And it's only when [ at the end ] there is no major objections that you are given and granted conditional or an approval. That's how it works. So let's try to take an analogy. Where we stand now if there are 3 possible steps, and there were 3. Okay. We are at the end of the step 2. It's 2/3 of the process which has elapsed. Now we're engaging you the third one, right? So it's not over. Remember [indiscernible] at the end of a process of the FDA and totally unexpectedly in the next 10 [indiscernible] where they finally got it from the FDA. So you see ALS difficult to register, we know that. If you take another [ cytotoxin in that cycle ] that's enough cycle. All right. And we will go through this other cycle.

Excluding rare diseases, why not create a clinical partnership for one disease and commercial partnership for all the others to keep the most value?

in the past, we mostly said that one partner is likely because difficult for pricing reasons. The information we delivered tonight that we are going to have 2 formulations now make it easier to have potentially different partners. So that's one point. We can also have partners by regions, which are different, of course. So yes, it is possible that ultimately, we might have possible partner -- more than 1 partner.

Could you clarify again the position from Health Canada on the distinction between normal and fast progressors?

Can you repeat the question, sorry?

Could you clarify again what is the position from Health Canada regarding the distinction between normal and fast progressors?

Health Canada told us that now they more or less agree with the fact that [indiscernible]. They are trying to distinguish and sequence the analysis on the basis of fast progressor versus normal progressor, which, at the beginning, was not so clear for them, okay? So there is an interest to what they call decustomize, but sequence -- and we move the fast progressor from the final analysis because they said it's heterogeneous. And being heterogeneous is one thing, same with the fast is a logical or accessible population too is another thing, but now they agree, okay, on the basis of the data that we provided them. And then we had to -- cap of that because there was no clear consensus on how to define a fast They agree now. Before it was not so good, but during the cycles, we had opportunities to defend this position. So it's no more that. It's only -- it's too late. But you have noticed, it's too late, but it's not data-driven, which is kind of company story. If it is not that data-driven, why late is a problem, okay? I don't know, but we will see by responding to these points into a reconsideration process.

Next question. Health Canada has refused the statistical analysis for the clinical data. Will EMA take a different position on this technical issue?

First, we have not shared with you with the same precision. We have not shared at all with you the objections of EMA. Why? Because we're into the process. So we don't have even these objections, but we have to respond and then we'll see. So let's wait, okay? We're not at the same level of the process between EMA and Canada. Now your question is, would in theory EMA would have the same argument technically on how to fit missing data [indiscernible] the answer is no. I already explained. Canada, is very much like FDA. hey first look at the distribution of the [indiscernible] does that effect. If it is nonlinear or nonparametric, which is the case, they would say, I'm going to look at [indiscernible]. Here, we have more facility because according to them the seniority has not been violated. I try to make it clear. I'm not so sure I was -- that I was clear enough. But -- so it means that they are, in our case, they're not going to like only on [ caps ]. That's what it means, which is good for us this way. And then I have not done as of yet but we have not -- we have many other measures. Yes, that's Canada. Then what is the practice for EMA? They don't care about [indiscernible] they don't own caps. They don't care, they know how it works. They ask for experiencing continuation for your product. That's what want. So it's the [indiscernible] portfolio products. And get their guidelines. So definitely, yes, we had discussion with EMA on that point. Definitely. That's the only thing I can share with you.

We have a question regarding AB8939. First signs of activity were detected and promising with some results promised by end of '23. And now we understand that you do not wait any more for efficacy on step 2, but step 3 in 2025.

Okay. We should not over expect from the Phase I. Phase I design is not to deliver any efficacy Signs of activity, but not efficacy. It's not a design to demonstrate any efficacy concerns. If some patients respond, we are happy, but we cannot say the product is effective at all, okay? That's only a Phase II or Phase III that can say that. But still encouraging, of course. And we are always happy to have some signs of efficacy. So -- and we have done in the MECOM, as you've seen, which led us to say it happened. Now we have those signs. It's encouraging. Let's be modest. Now when do we finish Phase I? Yes, it's not in 2023, in 2024. Why? Because we took more time since the product was not, as I said, to kick it off. And no -- and not with the MTD, okay, so we had to. We also have to know that if we go very slowly almost one by one in terms of the patients because we don't -- we minimize risk for the patient. It's Phase I. It's a cytotoxic. It's not stereotactic. So it takes what it takes, so far so good. We have finished step 1. Now it's going to take a little bit -- now there was some measures of the maximum therapeutic dose. Now we are just going to add a number of days of treatment at [indiscernible] the same dose and combined with masitinib, which is another, okay? But all in all, Phase I should be finished by the end of the year.

I think we are reaching the end of the questions. Are you waiting for a response from EMA and Canada to sign a license?

That's the question I already answered in the presentation. We anticipated it. No, the answer is no. And a license, if it is MS and Alzheimer disease, but if it is ALS, is not impacted by the decisions, positive or negative, from both Canada and Europe. And that's good news because we are clear about the strategy. Any other questions, Laurent?

I think we covered all topics.

All right. I hope that this presentation has responded to -- has given you first a more integrated vision of the company. We have 10 programs, and some are late stage. That's where we stand. We have 2 innovations, which can be very beneficial to the patients. We treat [indiscernible] innovation. The other companies and some very big have spent billions, and they have not been able to find a cure or even made significant progress in the disease that we try to treat. So masitinib remains competitive even if it is slow because, one, strategy is good and it is now better. In Alzheimer's, in MS, in ALS, we're not seeing breakthrough emerging that would [indiscernible] completely medicine. We are not seeing that, none of the indications that we are pursuing. And the new platform is totally innovative as I try to convince you. So we are going to continue to those 10 programs. They're extremely valuable. We cannot continue alone. That was a clear strategy change that we enforced last year. We are executing this change of strategy take time, okay? We expect this change in practice to be implemented and finish by the end of the year. We are into volatility because of 2 conditional pools that are everything but obvious. But if you have not tried it, most of you today [indiscernible] report to us that we have lack of [ coverage ], strong data and [indiscernible] at least keep something in mind. This is due to the patients. If we're not tried, it would have been really detrimental for the patients. I hope it would be a win at the end of the effort, okay? We're doing the job very seriously. The data runs good. It's difficult, true. We have not chosen the easiest indications in the world. I take volatility, but we will finish the job. Now I would like to -- I know Olivier -- Olivier, are you still there?

Yes. I'm still here.

Thank you to have stayed so far. Do you want to conclude?

No, I think it's very important to know that what we are doing is based on very strong and robust tie-ons. And as you know, clinical development is not very -- and always very easy, but the clinical results are also in line on what we are doing in the preclinical and [indiscernible]. So I'm very confident that this drug and all of the mechanisms that we have discovered are very new and very difficult to be acceptable, [indiscernible] could go forward to the science, and -- but I'm very confident that we will succeed, hopefully soon.

Thank you, Olivier. You have been -- you have inspired us from the very beginning, and we just follow you, okay. Thank you for the audience who have stayed extended time. Hope this helped you.

Thank you.

Thank you.