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

Ladies and gentlemen, welcome to the AB Science web conference. I would like now to hand over to Alain Moussy and Jean-Pierre Kinet. Gentlemen, please go ahead.

Good evening, and good afternoon for the ones in the United States. Thank you to join us for our web conference, where we're going to discuss this new clinical study, evaluating masitinib combination with isoquercetin in COVID-19. The presentation is going to be structured in 3 parts. With me Jean-Pierre Kinet, who is the Co-President of the Scientific Committee of AB Science, will describe the rationale, the scientific rationale behind this trial, and the combination of masitinib and isoquercetin in COVID-19. And then I will describe the 2 remaining parts of the presentation, the differentiating positioning of masitinib and the design of the study. And after this presentation, there should be less than 30 minutes, we'll open it for your questions as usual. So the call should be less than 1 hour. So quick introduction of each of us, I forgot to give my name. So my name is Alain Moussy. I'm the CEO and Co-founder of AB Sciences. And Jean-Pierre, would you like to briefly introduce yourself?

You just did. Well, I am an MD. I am an immunologist. I have been at Harvard for 30 years. I am a researcher, but I am also clinician. I have founded 2 biotech companies, and I'm happy to be here to hopefully explain the rationale of associating masitinib with isoquercetin in the treatment of COVID-19 and particularly in those patients that are really sick.

Thank you, Jean-Pierre. So we'll start with this -- the section on the scientific rationale, and we can move to Slide 6, which is on the screen of the attorneys.

Okay. So in this slide, I just want to summarize the COVID disease. Not written here, but COVID starts usually with fever in most of the patients and cough and very often headache. And then -- so this is what we would call the viral phase. But the virus then managed to activate the immune system, and this is the -- and provoke, what we call the cytokine storm. So what is the cytokine storm? It is an activation of a number of cells in the immune system that release cytokines and these cytokines themselves call for other sales to come, and there is an inflammatory cascade that really provoke tremendous respiratory distress. So it's particularly severe in the lungs. And that's provoking what's called ARDS, and very often death. And so we will now review of what is really causing the cytokine storm. What can we do to inhibit or to treat these patients. So next slide. Can I get the next slide?

Yes.

So as I say, the cytokine storm is driven by a number of cells. And one of the major cell is the mast cells. And mast cells has been known for a long time to be orchestrating inflammatory responses. And the mast cells themselves release a number of cytokines, many of them, but in particularly, IL-6 and IL-1 that are -- have been shown by the Chinese and now by the Italian and other, and the French and the U.S. They have been showing this cytokines, in particular, to be present in the ARDS that we see with COVID-19. So the idea that we had is if we could find an inhibitor of mast cells, so upstream of the cytokine storm that may be very beneficial to the patients. And as you know, AB Science has generated masitinib that is an inhibitor of mast cell. It is a tyrosine kinase inhibitor that inhibits c-Kit. But it also inhibits LYN and FYN, 2,000 kinases that are involved in the activation and the degranulation of mast cell. So we hope that the masitinib would be able to inhibit mast cell and, therefore, preventing the cytokine storm and ARDS and potentially reversing it. Next slide. Another cell that is involved in the cytokine storm is the macrophages, and it just -- you know that masitinib also inhibits macrophages because it inhibits another tyrosine kinase, which is the receptor macrophage colony-stimulating Factor I. And that inhibition of that receptor, inhibit differentiation and activation of the macrophages. And in fact, in the asthma model, we have shown that masitinib was able to inhibit the infiltration of macrophages. Next slide. So masitinib has been also shown to be particularly effective in the lung. And in a preclinical model of lung injury with sickle cell disease, we have shown that masitinib was able to prevent death. And you see the curve on the right, where the mice survive. So this is actually a very severe lung disease. And so this is a remarkable result. And as you know, AB Sciences also finished a Phase III clinical study with 355 patients to show improvement of the severe asthma in the treated patients. So next slide. Then the third cell that is also involved is our neutrophils, and it's -- this is a cell that is inhibited by isoquercetin. So isoquercetin has been shown to inhibit neutrophil degranulation, infiltration of neutrophils within inflammatory cascade. Next slide. So this is a slide I want to spend a bit of time on. When we started to see the patients with the ARDS, remember, there was this note in the press that there were not enough respirators -- that we were lacking respirators, so the patients we are dying in the hospitals. And in fact, it took a while, but we discovered that many of the patients were not improved by respirator. And in fact, in Bergamo, in Italy, they did an autopsy on 50 patients that died. And the 50 patients, when you look at their lungs, all of them had microthrombus in their lungs. And so this microthrombi prevent the flow of blood in the alveola. So there is no way that the oxygen can interact with the red cells. And that -- this microthrombi also explain why the respirator were not necessarily effective in treating the patients. So it's very important to understand now that the death in COVID mostly come from microthrombi. And these microthrombi are generated secondary to the cytokine storm. And also by the interaction -- the direct interaction of the virus with endothelium and the release of an enzyme called protein disulfide isomerase. Now you can read the literature of the -- in China that all of the severe patients, most of them are in 98% of them have an elevation of D-dimer. D-dimer is a biomarker of the thrombotic events of your increased capacity to coagulate, all of the patients that actually have an increase of D-dimer. And that's why we thought about isoquercetin, because isoquercetin has successfully treated cancer patients, in fact, in my hospital, Beth Israel Hospital in Boston, there was a study with late-stage pancreatic cancers. These pancreatic cancer people don't necessarily know that they die not from their cancer, 50% of them died from thrombosis. So this is the third of the patient, I'm saying, late-stage pancreatic cancer die from thrombosis. And isotretinoin has been shown in the Phase II to prevent the thrombosis almost in all patients. So we thought that the association of masitinib with isoquercetin might be very beneficial for the severe patients. Because we already have shown that isoquercetin can decrease D-dimer and prevent thrombosis. Next slide. Now we already have thought about the association of masitinib and isoquercetin in another context. And that's the context of ALS, so amyotrophic lateral sclerosis, that you know that AB Science has done studies in these patients and show clinical efficacy in some of these patients. But this is actually the first time we show this data. We found in preclinical model that the masitinib and isoquercetin had a synergy in killing senescent cells. Senescent cells are very important culprit in driving ALS disease. And so killing them is -- could be very beneficial. So we think that masitinib and isoquercetin have that synergy. With the senescent cells are also digitorus in COVID, and that's known. So we think that by combining masitinib and isoquercetin we have good association that could benefit the patient. So masitinib will work on being upstream of the cytokine storm, on mast cell, macrophages. Isoquercetin will work on neutrophil, on the thrombosis. And together, masitinib and isoquercetin will combine to kill the senescent cells. The next slide. Now masitinib has also been shown to have neurological tropism and to improve neurological symptoms, in particular, in ALS, but also in progressive multiple sclerosis, and that's probably because it inhibits another type of macrophages, which are the microglia that is present in the brain. By virtue of the fact that it inhibits another tyrosine kinase receptor, which is the CSF1 receptor that is expressed by the microglia. So why is that important? Because 1/3 of the patient with COVID present neurological symptoms, confusion, epilepsy, very, very potent headache. And in fact, the mother of one of my best friends died from epilepsy due to COVID here in France. So this is -- these are very severe symptoms. And we think that masitinib could be very helpful on this part of the disease that is probably less well-known than the lung part. Next slide. Now isoquercetin has been known for quite a while to have antiviral activity in vitro. And there are a number of clinical trials being done presently in hepatitis C, in dengue. There is another one that is not written here on Ebola in Congo, and there are a number of studies also done by the Canadian with a number of these viruses. And this is because isoquercetin inhibit 3C-like protease, which is an enzyme that is common in many of these viruses. But it seems also to inhibit the binding of the Spike Protein to the receptor ACE2. Next slide. So the safety profile of masitinib is well known. There has been over 7,500 patients. They've been randomized. We know that drive very well. We think we can provide with risk management plan that will benefit all of the patients. And isoquercetin is well-known also. It has an FDA IND and GRAS dossier, GRAS meaning generally recognized as safe. So it's a very safe molecule. So we think the combination is -- could be a winner. Next slide.

Then it's a new section coming through. Thank you, Jean-Pierre, for this presentation.

Or maybe, we ask whether there are some questions until the vitro.

No. We will finish the presentation and then we move for questions.

Okay.

So we move to the second part of the presentation, which is a sort of summary of where masitinib is in the landscape of all the trials done with other compounds. And so we move to the Slide 17, which is on your screen. There are multiple strategies, but 3 main ones or 2 main ones, I would say. The first one is the antiviral strategy. That applies for mild, moderate and severe cases. So you have heard about remdesivir, which has been registered by FDA recently with one positive study. There is also some negative study coming from China. So it's a debate. But -- and there are others that are tested. And of course, hydroxychloroquine should be classified in this antiviral strategy. There are also some other strategies like stimulation of the immune system through interferon. For instance, plasmapheresis, which is the transfusion of the plasma of the cured patients who have developed the antibodies. And there is this anti-inflammatory or rather immunomodulation, which applies rather except for corticosteroids, for the moderate and severe cases. You have heard about tocilizumab with some positive announcement from the French, Paris and hospitals. It seems that -- and also by the Chinese themselves, who first identified the drug as potentially beneficial for moderate and severe cases. But there are others which are tested throughout the world. And I would say that masitinib plus isoquercetin fits into this box, which is the immunomodulation to try to avoid the moderate and severe patients to go to intensive care unit with the high chance to die. It is not an antiviral, I would say, fitted strategy, but rather to protect against more severe outcome. Next slide. This is the positioning. As I said, we target moderate and severe patients, not the mice. For instance, remdesivir has been granted approval by FDA by reducing by 2 days, the elimination of the virus in the body of the patients, but with no benefit, in terms of survival, for the moderate and severe patients. So it's not -- absolutely not the same objective, absolutely not the same primary endpoint in the clinical study. Here, we'd try to improve actually or save some patients from fatal outcome or severe complication due to COVID. I know, this population, moderate to severe, is not completely homogeneous. And there are some definitions done by the World Health Organization that we are using there. And we are not going to treat the critical patients, the one in intensive care units. Why? Simply because those patients cannot swallow any pill, any tablets, any capsules for isoquercetin that's capsule, so we cannot really treat them. Next slide. As a summary, and I would just repeat what Jean-Pierre has described, we think we have some differentiating factors that are almost unique to this combination. First, it targets the innate immune systems upstream, whereas the other immunomodulation strategy, the target, whether interlukin -- specific interlukin, which are, of course, extremely important in the disease. It can prevent thrombosis. This is something that has not been really researched so far in terms of treatment, I would say. Today, there is no reference trying to read this objective. It can protect against complication, neurological complication that might become reversible with more publications coming on this feature. And maybe the most interesting is the senescent cells because we know the COVID virus kills much more older people than younger people. But really, in a, I would say, logarithmic exponential pattern, which is not explained really by a weaker immune system in the older people. We think it's the importance of the senescent cells, and it makes our strategy rather, I would say, seated for the aged people. And many of the trials exclude the people above 80-year-old for safety reasons. And we have been asked literally by NSM to include those patients, given the rationale, the scientific rationale behind it. And this feature is probably the most specific and interesting, maybe a mechanism of action behind the combination. And only the combination can provide that because, if we go back to the sites presented by Jean-Pierre, none of the product by themselves can keep the senescent cells, only the combination can do. So the importance of testing the combination, in particular, in this age population. Then we move to the last section, which is the study design. So this is a study on Slide 21, called AB20001, it's a Phase II, of course. It's almost a proof-of-concept with extension, so to speak, because we have never treated the patients already. And so it will be a randomized, open-label, multicenter comparative Phase II study. And the main inclusion criteria are, as we said, the moderate and the severe cases. There will be no limitation in terms of age for the reasons that I have mentioned before. And the patient enrollment is 200, 100 per arm in randomized one-to-one. What is important is to understand what is the best supportive care in each of the 2 arms. For the control arm, everything is available at the discretion of the hospital. This is very important. There is no preselection. There is not only -- some of the treatments, everything is authorized. And in particular, the anti-IL-6, tocilizumab, also, hydroxychloroquine for the ones who prefer hydroxychloroquine and any antiviral strategy, like remdesivir, for instance, are possible in the best supportive care. You know that they are not really a reference treatment, and it depends on the country either. So it's rather complicated, but I would say, in a summary that everything is actually accepted. For the ones who will receive masitinib plus isoquercetin, it's the same. Everything is authorized except hydroxychloroquine or chloroquine for, they are known, I would say, drug-drug interaction that would complicate the safety of the patients. So anything which is excluded is the hydroxychloroquine and chloroquine. But all the rest is possible. So when you read the design of this study, it's rather an add-on design because, of course, now people receive preferred treatment. And so those preferred treatments will be the background treatments, and then we will add masitinib plus IsoQ in one arm and nothing in the other. So it's how we should read the study. Of course, it's going to be extremely important to stratify the use of those compounds, the background treatment. So the background treatments are stratified. Also, the age is stratified, and it's very important when you know we want to treat the population, which is older than 80. The countries if we open more than one country will be stratified, of course and the comorbidities will be stratified as well because you know that the death rate and the outcome is different as far as the comorbidities are concerned. So it's extremely important if you want to interpret the study to stratify all those factors, otherwise, you come with the wrong interpretation. The primary endpoint is the classic clinical status patients. It's either 9 points or a 7 points scale. Here, we'll take the 7-point scale, this is the WHO official scale. And this clinical statutes will evaluate it at day-15, and why day-15 because this is where we -- the patients need to have an improvement. So it's something that should happen very quickly, 7 days, 15 days, sorry, it's quick to get an outcome, but that's what the disease require. And it's going to be the primary endpoints. And so we will compare this clinical status between the 2 arms. Then there are some secondary endpoints that we will also measure. So this is the same clinical status that we will measure at day-7 or at the end of the 28 days treatment. But it's the same measure that we are going to use. And we are going also to measure the time to improvement of 2 categories in this clinical status. We are not -- we are going to calculate it also, but there is no primary endpoint in terms of viral load like remdesivir, for instance, because this is not a strategy to reduce the viral road faster like remdesivir can do. Here. We want to improve the clinical status of the patients at day-15. That's really what we do. Of course, we're going to measure lots of biomarker, inflammatory biomarkers, lots of biomarkers that we need to see if there is any indications of the responders versus the nonresponders and maybe see that some subgroup of patients could benefit more favorably from the treatment like what potentially the age people or some of other categories that we could identify through the biomarkers. We will also do a drug-drug interactions at the beginning for the first 6 patients doing some PK analysis, which is requested because we never tried this combination before for the safety so -- of the patients. Now in terms of timing, first of all, who is the coordinator? The coordinator is Pascal Chanez. It is from the Hospital of Marseille. It's not professor Harvard, it's another hospital. And he will be the coordinator of the study. And many other centers will join in France. And potentially, we might open some additional countries to be able to do the enrollment. As you know, the enrollment is considerably decreased, which is good news for the population. There are still some cases, of course, new cases. The deconfinement might actually recreate some more patient than the hospital, the objective is to see them at a low number, of course, by the government. We can understand that. But we're going to do the enrollment. It's not going to be a super-fast enrollment. It's going to take probably 2 months, maybe 6 months. If we have to do it for 6 months, we will do it for 6 months. We think this COVID will occur again, maybe during winter, maybe the next winter. We don't know when, but it's going -- it's not going to disappear from the planet. And so it will take what it takes, but we're going to do this study. We will do a -- probably the DSMB is going to evaluate the safety and the efficacy on a regular basis. And if they find something like maybe some utility or at the opposite, some available trend, then we might make decisions like stop the study, to not invest on 200 patients for nothing or the opposite to maybe end it a little earlier. So we do not expect any data before at least end of August, September and maybe up to December, this is the reasonable time line that we can expect from this study. We have gone through the highlights of these new opportunities for AB Sciences. And with Jean-Pierre, we are going to open it for your questions. And we are going to answer what you have. You have 2 options, either by phone or by writing. And maybe the...

[Operator Instructions] You may have questions from the webcast platform.

Maybe I'll take your first question that we have received in writing. So the first question is there are some, at least one clinical study reported with the Canadian site clinical study with isoquercetin in China. Do we have results of this study?

I can take this. So this is Professor Michel Chrétien who did press release back in February, I think. And he was putting together a team with the Chinese to start a study with isoquercetin. My understanding is the study has not started yet. So there is no result. There are no results available.

Okay. Thank you. Okay. I will take first question regarding maybe the design of the study, and then I'll go to the biologic and the rationale again. Question received, why an open-label study, I can take it. We so far have an open-label study because we didn't have the placebo, the isoquercetin ready fast enough. Now we're working on it with our partner, and we might -- we'll see if we have it ready fast enough, then we might amount and go blind. Anyway, the first 6 patients have to do PK. So there will be 2 options. Either after the PK, depending on how long it takes to do the PK, placebo is possible, and then we amend and do a blinded study or it's not. And we might not do it because we have to treat the patients. The decision is not made yet. Of course, it's better to do blinded. However, we have a process, procedure to keep the blind, although it's open-label so that we do not access the data. And so the DSMB can recommend it. And we don't see who is taking masitinib and placebo and who is in which arm.

Another question regarding the design of the study, will we have intermediary results?

I take this as well. So as I said, we have a futility test plan with roughly 1/3 of the patients. We think it's necessary to have a minimum of 50 patients before we can see anything, like we stop or we don't stop a little bit like an interactive study. Otherwise, we're not going to have really results intermediary. It's not planned for that. The DSMB can always recommend to stop if they see some safety concerns. To stop for early efficacy with so few patients is very unlikely. They still have the possibility to recommend that. So I would say a futility test is always good, as in the study. Otherwise, it's a likely that we have to wait the 200 patients before knowing the results.

Why would the enrollment take 2 to 6 months?

At 2 to 6 months, I explained already. We don't know how many cases will occur in the next -- in the coming months. Nobody knows. And there are some countries which are more affected by -- are still affected by the COVID, and they have more patients. But United States, it's crowded with clinical studies, crowded. So although they have more patients in there more studies, it's not really the best country to do that. Other countries, which might be more interesting, whether offshore, the clinical studies might be Latin America, as you have seen like me, in the newspaper, we see and we explore possibility to open in such countries, if we face difficulties in France or -- and Europe is also crowded. As you know, discovery, for instance, the discovery 4 arms have not been able to recruit their patients. So Europe is a challenge. U.S.A. is a challenge. And maybe Latin America, we'll see. So 2, 6 months reasonable.

Another question regarding the design of the study. How important is it that patients are randomized, very near to the time of the onset of symptoms, is it to eliminate too late -- those too late, sorry, is it to eliminate those patients too late in the disease?

Jean-Pierre, do you want to answer this question?

But we will not select only the patients that are early in the disease. Do we?

No. No. There is no -- we took -- there is -- no, there is a maximum, but I think this maximum is 10 days or 15 days. So it gives some lots of. We don't take just freshly diagnosed.

So in 15 days, you can have a severe disease or even be dead. So it's not that early. I'm not sure I answered the question, sorry. Is it? Not sure.

Are you measuring IL-6, ferritin and CRP biomarkers?

Yes.

And many others.

And IL-6 receptor, the circulating IL-6 receptor and D-dimers? I mean, yes, absolutely.

And for D-dimers, of course, most relevant given the mechanism of action of combination.

I'll pick another question. You mentioned that the virus invades both the CNS and skeletal muscles. Can you elaborate on the neurological symptoms? And are you including secondary endpoints related to these aspects?

Jean-Pierre, you want to elaborate on neurology symptoms. Hello? We might face technical problem with Jean-Pierre. [Technical Difficulty] Okay. So I will try to answer. So well, we know that the virus infects -- enters into the brain, that's well-known, now and probably stimulates the immune cells present in the brain. We know, of course, microglia and mast cells are very much present in the brain and they probably are activated by the virus, the same way as those 2 cells are activated for different reasons. Of course, in ALS, in MS, also in mastocytosis, where we have lots of data in this disease, and creating so damages, whether those damages are irreversible or not, we don't know yet. It would require some more studies. Anyway, we're going to look at that and some neurological parameters, but it's really exploratory, of course. But it will be interesting to know if patients treated with this combination have fewer neurological symptoms after 1 month and even after.

Sorry, I have been disconnected somehow.

Okay. So I answered for you. But if you want to...

I was saying that in the neurological disease, of course, microthrombi are very important. I don't know when I was disconnected. But I was saying that there had been an MRI of patients showing thrombi in the brain, some of which can lead to epilepsies or even paralysis and confusions, et cetera.

So another question maybe for you, Jean-Pierre. Do you have some thoughts on the use of Gelsolin as inflammation regulator? I don't know if I pronounced it well, G-E-L-S-O-L-I-N.

Gelsolin.

Gelsolin. G-E-L-S-O-L-I-N.

No, I don't.

Or this is a typo, I don't know, in the question.

I've not said anything about that. Is it in the literature somewhere?

No. It's a question, never mind. So another question regarding -- now we have multiple questions regarding the combination of masitinib and isoquercetin in senescent cells. So how was the synergy demonstrated between the 2 molecules?

Can we go to the slide?

Yes.

No. The slides with senescent cells. And there is a little graph.

It's Slide 12. It's on the screen. Jean-Pierre, can you see?

No. I don't. Not yet.

It might be because you have been disconnected because we have the slide.

Okay, I have it too now. So you can see that this shows the viability of the cells, the non-senescent microglia, in the A panel on the left, viability is preserved. Of course, in non-senescent microglia, whether masitinib or isoquercetin, nothing is happening. Okay? Now in the B panel, the senescent microglia, you can see the isoquercetin does very little and masitinib also does very little. And you can see now on the right part of the B panel for the number 6 graph, you can see that when you add isoquercetin with masitinib and you start to have at the higher dose, killing of the senescent microglia, that is the evidence. So this is an in vitro, but I can also tell you that in vivo, we can also see the same thing.

Just one comment on this. This is a new data, as Jean-Pierre explained, this is not published yet. So something we released today. That justify that we explore the combination of masitinib plus isoquercetin. For the ones who are interested by this topic, this is relatively recent, I would say, 4, 5 years. And the targeting of senescent cells is research by others. And there are some combination known with tyrosine kinase inhibitor and quercetin, which, in some publications, interesting to read, tell us that this combination can kill senescent cells and be beneficial, at least, in neurodegenerative disorders, but also in oncology. And it has been described, dasatinib plus quercetin. And we think that masitinib plus isoq is a better combination because masitinib is separate than dasatinib, first; and two, isoquercetin is more bioavailable than quercetin. And if the senescent cell is a good strategy, which we never -- we don't know yet because that's not been tried yet in late-stage study, but if it is a good strategy, then the combination of masitinib plus isoq can do it. It's not the only one, but it can do it. And among all combination, probably is the best available combination. That's why it's interesting to use this one. In COVID, it's interesting because of senescent cells, in particular and also because of the features of the 2 products separately. But this senescent cell is not COVID specific. It's actually many diseases. It's kind of a general new strategy that might be applicable in neurodegenerative disorders first, I would say, and potentially in cancers and potentially in other opportunities or indications like COVID. But this senescent cell, new strategy, new target is relatively recent. And we will try to explore it with the combination isoq, masitinib. That's the message we would like to deliver today on the top of the COVID.

So that leads to another question that we have. Do you plan or to make other studies with masitinib plus isoquercetin combination?

That's the ideal transition to what I just said, Jean-Pierre...

In fact, we had the ID before COVID. We have the ID of associating masitinib with isoquercetin well before we knew COVID based on this data. There are other data, but we just show you this data. This is sort of the most striking data. And based on this data, yes, we had envisioned to do a clinical trial in ALS, in particular of the association. And then when came COVID, we already have thought about the association. So we had done all the literature on isoquercetin, interact with this other company, et cetera. And so we thought that because of the composites, in particular, and antiviral capacity of isoquercetin that combining the two to also kill the senescent cells, because it would be a winning combination. But historically, the association was not sought because of COVID.

So it's a new opportunity for masitinib and isoquercetin. Because isoquercetin has its own development in cancers and thrombosis. But it's a new opportunity for the 2 compounds to do a synergistic development like one plus one is equal to three. With senescent cells, it's even more spectacular. It's zero plus zero is equal to something, one maybe, if it works, if it works, nobody knows. But if it works, it can be remarkable. It needs to be evaluated properly in clinical studies.

Can you describe your intellectual property on the proposed therapy to treat COVID-19 indication?

We can only say that before launching any new development, we make sure that we have filed, at minimum, some patents, which is the case, of course, both for isoq and masitinib. And so in case there is something it will be protected.

You would agree that it's not obvious.

What else. The combination was not -- well, what I would like to say, just maybe the question has not been raised, but ideally, we should have done 4 arms like masitinib alone, isoq alone, the combination and the control. That would be the ideal, I would say, factorial design except that it's extremely complicated, given that we are at the end of the curve of the COVID, it might -- we might get another one. But now it's getting complicated. So we prefer to do the combination versus the control to give the maximum chance to the patients. And how to interpret the combo versus the product separated, it's going to be difficult, of course. Isoquercetin is exploring -- and there are some studies with isoquercetin alone, and we might have an indirect comparison using those studies. But it's one question, metallurgically, that will be asked, if there is anything positive, of course. Okay. So it was a good set of questions, Laurent. Is it -- we had covered most of it. So it's exploratory at this stage. 200 patients is not a lot, as you can imagine, and COVID is not the key priority for AB Sciences. Masitinib is exported in late-stage in, as you know, mastocytosis, dialysis, multiple sclerosis and severe asthma. However, it creates a new opportunity with a strong scientific rationale. And on the top of that, the combined -- this is the beginning of the exploration of a combination with isoquercetin, and as Jean-Pierre has told you, it's not going to be the only one. And we're going to further explore other indications because we think it makes sense, these senescent cells, which should play a critical role, at least, in neurodegenerative disorders, potentially in this COVID situation, because what's striking in this disease is the high mortality rate among all people. It's very, very striking. So there might be a reason. And who -- and the senescent cell looks like one of the most possible reason why there are so much deaths, the age, the immune system, the comorbidities in the aged patients. And also I would say, arguments that can explain this high mortality rate, but it might not be enough. And so we do this trial potentially to answer this question. But if this is true, then it can change dramatically the fate of the aged patients. And today, this is the problem. They are the population at risk, and no strategy today target this population. The opposite, it avoids them. So this is why I think it's necessary to try the combo today in COVID. That would be my conclusion. Thank you, everybody. Thank you, Jean-Pierre, to drive our scientific strategy and inspire us, give us good ideas. And I hope to have the pleasure to have other calls on the same topic and on other topics. Thank you for your participation.

Thank you, too bye-bye.

Thank you, gentlemen. Ladies and gentlemen, this concludes today's web conference. Thank you all for your participation. You may now disconnect.