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

Ladies and gentlemen, welcome to the AB Science Conference Call. I will leave the floor to Alain Moussy, CEO of AB Science. Please go ahead.

Thank you, and welcome to everybody from Europe or outside of Europe. We're pleased to hold this conference on new topic, which is sickle cell disease and the development of masitinib in sickle cell disease. With me today to talk about this topic -- I'm with Olivier Hermine, who is Co-Founder of AB Science and also Professor of Hematology at [ Hospital Necker ] and a specialist of sickle cell disease. And as you know, I'm the CEO of AB Science. I propose that we'll walk you through a presentation slide by slide. And at the end, as usual, we will open it for your questions. Olivier, I ask you to start the presentation.

Let me see because I don't see very well the slide. Okay. So slide, please. Okay. So today, we will call about one disease which is called sickle cell disease. So just a reminder for those that do not know, we have what we call hemoglobin which is the main transporter of oxygen in red cells. And there is 2 main genetic disease, very frequent in the world. The first one is beta thalassemia in which one of the chain of hemoglobin, the beta chain is missing, therefore, the patient do not produce enough hemoglobin and they have anemia. The second disease, which is sickle cell disease is due to the [indiscernible] abnormalities of the beta chain of the globin that is a single substitution, we change an amino acid vitamin in [ volume ], leading to the precipitation of hemoglobin in the red cells. And as a result, red cells in the small vessels will aggregate and will induce what we call vaso-occlusion. And this vaso-occlusion, a consequence is ischemia of the tissue and destruction of red cells, leading also to anemia. Next slide. So sickle cell disease is the largest monogenic disease worldwide. And it is an inherited disease of red blood cells. And as I said before, in this case, the mutation leading to the precipitation of hemoglobin in red cells, changing the shape of the red cells, and they have this form of sickle, so that we call that sickle cell disease. And we will discuss today of the main form of sickle cell disease, which is the patients with 2 mutations, with the 2 chains of the beta chains with S mutation. And we call this patient, hemoglobin SS because 2 beta chains have the mutation. And we know also there is a small [indiscernible] sickle cell disease, in which you have different kinds of mutations, but where I will not go into the detail. We know that sickle cell disease affect millions of people worldwide and about 7.7 million patient have sickle cell disease in the world, affecting about 100,000 American people and between 20,000 to 40,000 in France. And we know that this is also quite frequent in Africa, Sub-Saharan region and also in Middle East, including Saudi Arabia, which affect 2.5% of the population. Next slide. So, it is a major public health challenge because the red cells are fragile and that is what we call hemolytic anemia, leading to the destruction of the red cells. And this destruction leads to anemia. So these patients to have a normal hemoglobin level to be able to have a normal function need to receive blood transfusion. And in addition, when the red cells are shaping abnormally when they get the form of sickle, in the small vessels, they will do what we call vaso-occlusive crises because they will lead to thrombosis of the small vessels. And as a result, this vaso-occlusive crisis leads to pain, acute pain, but also chronic pain in these patients. And we know also that this chronic vessels thrombosis may lead to abnormal spleen function because the spleen adds some infection and this abnormal spleen leads to increased risk of infection in this patient, and some of them will die of meningitis, for example, or Septicaemia. We know also that this crises in small vessels in the lung, mainly that we call acute chest syndrome in which this patient have no more oxygen and they die of acute respiratory distress. So it is very important disease because [indiscernible] is one of the first cause of death of the patient. In addition, we know the small vessels in the brain, this patient experience stroke by reducing the flow in the brain leading to a connective dysfunction in this patient in about 75% of them with age. So sickle cell disease is both life threatening disease due to vaso-occlusive crisis, acute chest syndrome, stroke, infection. But in addition also, it is a disease leading to a chronic morbidity in a group of patients leading to the high social burden in this patient. Next slide. In fact, the [indiscernible] of this is more complex that we are thinking for the long period of time. We know that when there is a release of abnormal hemoglobin in the blood, then it lead to what we call nitric oxide depletion leading to activation of [indiscernible] cells, but also mast cells, which is something quite new. And this mast cells, when they get activated, they may release from mediator, which are specific of mast cells, including histamine and you can see here that at basal level, Histamine is higher in patients with sickle cell disease. And very interestingly, when they experience some pain, to reduce the pain this patient take morphine. And we see here that morphine increased further the level of mast cell activation. You can see here when the patients have [indiscernible] and morphine, they are a very high level of histamine, and we know that histamine may play a role in this cells, in all of systems leading to some chronic complication. In addition or so, [indiscernible] that mast cell activation may lead to increase level of P substance, which is produced by the mast cells and P substance interact with a peripheral nerves leading to pain, but also to vessels leading to vasodilatation and probably to the acute chest syndrome. So we came to the idea that blocking mast cell in sickle cell disease, may reduce pain and also reduce complication of mediator release by mast cell. Next slide. So we have demonstrated for the long period of time, that masitinib, which is a KIT inhibitor is able to block mast cell activation, as you can see here. And actually, we have demonstrated that in vivo patients, for example, in mastocytosis, which is a [indiscernible] disease where you have a mast cell activation. We are able to block mast cell activation in this disease, and we make the hypothesis that if we treat patients with masitinib, we block abnormal mast cells activation, and we reduce the risk of pain and chronic and acute complications. Next slide. So to summarize what I said and to be very simple, you see here a normal vessel on the top in which you see red cells, normal red cells go through the vessels to provide oxygen in issues. When the hemoglobin precipitate, you see the shape of the red cells is changing and you have what we call vaso-occlusion leading to ischemia. But in addition, what we have demonstrated in our laboratory is that the hemoglobin S and normal hemoglobin sickle cell disease is able to bind to some receptor. One of them is TLR4. And TLR4 induce activation of mast cells and [indiscernible], as you can see here. And if we do block TLR4 receptor, we block this activation. Next slide. And the consequence of mast cell activation is the release of Substance P as I said, or histamine. And we know and also other markers, which may lead to the complication, as you can see here, in sickle cell disease, which is really a systemic disease actually being stroke, cognitive dysfunction, muscle infection, bone infection, you see [indiscernible] cells, pulmonary dysfunction and so on. So all of this complication might be due to an abnormal activation of mast cell as a consequence of hemoglobins S interaction. Next slide. So to explain the pain in the sickle cell disease, which were not very well known, we have demonstrated that mast cells produce what we call Substance P and Substance P act in some receptor in the peripheral nerve to induce the pain. And in addition, Substance P act on the small vessels leading to vasodilatation of the vessel leading to, for example, acute chest syndrome. And in addition, we know that Substance P may activate the auto [indiscernible] mast cells. So when you stimulate mast cells, you will need Substance P which induce pain, which induce abnormal vessel tonicity, and activate also mast cell vicious circle. Next slide. So we have looked at the mast cell activation in patients with what we call vaso-occlusive crises crisis. The patient came to emergency room with pain, as you can see here on this picture. And we do see that once the experience of vaso-occlusive crises, histamine is increased protecting that when you have pain, your mast cells get activated. In addition, when this patient experience a lot of pain, we add morphine to reduce the sensitivity to the pain. And as you can see here, and we know that morphine increased further mast cell activation, as you can see here. So as a consequence, next slide, we do see a release of P substance. And P substance when is add lead to the acute chest syndrome. We can see here a CT scan of the lung of the patient, and you can see some fluid in the lung, exactly as we do see, for example, in patients with COVID disease. Next slide. So what we have done, we take the substance P and inject the Substance P in mice. And as you can see here, we kill the mice when you inject Substance P in mice with sickle cell disease, because you can see here, it's difficult to see, but we do see an [indiscernible] of mast cell in the lung of this mice when we inject Substance P, which is very interesting. And when we treat this mice with masitinib, and we do inject Substance P, you see the mice are surviving and to not experience any more acute chest syndrome. Next slide. The next slide, so to focus on this last experience, you can see here, when you stimulate sickle cell disease mice with a compound like substance P or other cause of acute chest syndrome, when we add masitinib, you can see the mice are surviving. Next slide. And very interesting, when we cut the lung with the autopsy of this mice, you can see a normal lung, a lung of mice with sickle cell disease in which you see a lot of inflammatory sets including mast cells. And you see when this mice experience acute chest syndrome, you see the massive infiltration of mast cells -- but when we do treat this mice with masitinib, because we've blocked mast cell activation and mast cell migration in the lung, you see the lungs is almost normal, and the mice do not die of acute chest syndrome. Next slide. And very interesting for the past 10 years, we are working on masitinib in different diseases. As I told you, patient with sickle cell disease may experience stroke and we know that stroke may lead to infection in the brain, as you can see here. But when you to treat mice with masitinib, reduced the size of the infection, leading to a better recuperation of the infect. In addition, which is very interesting on the right side, we have treated dogs with pulmonary hypertension, which is a complication of sickle cell disease probably because of the mast cell activation. And you can see here, we can reduce pulmonary hypertension with masitinib in dogs. And also, you can see in experience in mice, we have shown that cocaine addiction or morphine addiction might be reduced by masitinib. And in the U.S., for example, we know that patients with sickle cell disease experience morphine addiction, which is a very health public problem in the U.S. And probably, if we do block mast cells with masitinib, we may reduce addiction to morphine in these patients. Finally, you can see here that we have shown and published that masitinib is able to reduce mast cell activation in the brain of patients with Alzheimer's disease, restoring the cognitive function and the functionality of this mice which translate in a positive life case study in human which we have shown masitinib may restore cognitive function. And as I said in the first slide, patients with sickle cell disease because of chronic mast cell activation in the brain, because of release of hemoglobin S, they have cognitive dysfunction in 75% of the case, and we make the hypothesis that if we do block mast cell activation as we do in Alzheimer, we may restore cognitive function in this patient. So taken together, as demonstrated in the last 10 years that mast cells, the key cells, a key factor of acute and chronic complication of sickle cell disease. And if we do block mast cell activation by masitinib, we may approve health care of this patient. Next slide. So currently, in sickle cell disease. Next slide, we know there is some treatment. And today, the main treatment is red blood cell transfusion to reduce anemia in this patient. But transfusion is not able to block fully the complication of sickle cell disease, which is vaso-occlusion and mast cells activation. One of the problem of [indiscernible] transfusion is that transfusion may lead to some inflection, may lead to some problem of what we call alloimmunisation and iron overload. So transfusion, although it improve the health of this patient, is not enough to cure and to relieve all symptoms of sickle cell disease. It has been shown also that for example, some amino acid like [indiscernible] may induce that we call fetal Hemoglobin which present in some way the aggregation of hemoglobin S. However, this drug is not able to [indiscernible] -- to increase fetal hemoglobin, reduce the number of crisis, but not fully. And there is a warning because [indiscernible] and might be carcinogenic and induce in some patients, [ transient stability ]. So as a consequence, is only 27% of the patients use [indiscernible], but is still the standard of care. Next slide. So to cure these patients, the only way to do it is to perform [ a low stem ] cell transplantation. But to do so, we do need to have what we call a sibling compatible donor, which appear it's about 15% of the case. In addition, we know that stem cell transplantation, it's an [ IV ] procedure leading to 2% to 5% of death because of the bone marrow transplantation and in 10% to 13%, some complication of these patients. And it's difficult to be performed in country in which you have a poor health system, and most of this country are the ones with higher incidents of sickle cell disease. Now we know we can use that we call gene therapy and there is 2 strategy of gene therapy, the one developed by Vertex, which is CRISPR in which we edit the genome of stem cells to induce the fetal hemoglobin. To do so, which is quite complicated, we validate what we call an answer of the suppressor of fetal hemoglobin. As a result, the [ obvious ] test result is fetal hemoglobin reducing the anemia and the sickle cell crisis in this patient. The problem of gene therapy with CRISPR, it is a very expensive procedure. We do need also to perform high dose chemotherapy to kill the stem cells of the patient to be able to transfuse and to transplant the edited CD34 cell of this patient. So the cost of this procedure is very high, $2.8 million per patient. And also, it associate to some morbidity due to the conditioning of this procedure. Sensing for gene transfer of normal fetal-globin which has been tried by Bluebird by your company, showing indeed, an increase of the normal beta globin in sickle cell patients. And this one has been approved by FDA and the EMA , but due to this cost and also due to the problem of conditioning regimen, which is high-dose chemotherapy. This procedure is not feasible in most of the parts of the world. Next slide. So besides the corrective procedures, it has been developed iron [indiscernible] which prevent iron overload due to chronic transfusion. But although it is an efficient treatment with slow down the iron overload after 20 years of transfusion, these patients have iron overload, leading to some lot of complication. We may use L-glutamine, which is amino acid, which is very easy to use, which may have some what we call antioxidant effect, which may, at the end of the day reduce the number of IVs, but has no impact on anemia. And this improvement, which is observed is very low. And you can see only 3% of the patients use the drug, which is only register in FDA, but not in EMA because of this small effect. [ Response rate ] has been of this developed drug, which is [ misatinib ], which is an antibody, which prevents the aggregation of abnormal red cells to the -- the [ T cells ] to the small vessels. But these drugs although may reduce annual rate of vaso-occlusive crises, do so very slightly, leading to the EMA revocation of the authorization because of the small effect and still register in FDA. But because of the small effect, only 2% of the patients use the drug. Recently, Pfizer bought a company which has developed the [indiscernible] which is a drug which prevents the aggregation, the polymerization of the hemoglobin S and has reduced, it may reduce [indiscernible] and may also increase the level of hemoglobin, which is the case. But one of the problem of this drug by increasing the affinity of oxygen to the hemoglobin presents [indiscernible] in the tissues. So taken together, the [indiscernible] that you do see in this patient is not reduced with the drugs, also, it may increase hemoglobin level, but has a very small impact in vaso-occlusive crises and probably on chronic complications in sickle cell disease. So the use of the drug is quite low at 2.9%. Next slide. So the better knowledge of [indiscernible], we have shown it has been shown that some drugs, which activate an enzyme, which is pyruvate kinase, which increases the metabolism on the red cells, they present in some way, the sickling and the polymerization of hemoglobin S in mice model and also in Phase 1 and 2 study. We don't know exactly what could be the impact of the drug. It may reduce the hemolytic anemia. It may reduce the frequency of vaso-occlusive crises but probably to some limitation because we don't change the abnormal hemoglobin and the Phase II/III is currently performed. To see is the drug will improve a little bit a number of pain and increase hemoglobin level. Another company use a similar strategy to activate the pyruvate kinase, which is [indiscernible] pharmaceutical. And also, they are still in Phase II, III, and I don't know yet the result [indiscernible] inhibitor is used in event of iron [indiscernible] due to the transfusion, but there's no impact on vaso-occlusive crises and anemia. And pain with inflammation, it has been shown that hemoglobin S activate what we call the complement system which induce aggregation of red cells of vessels and [indiscernible] monoclonal antibody is currently in Phase II trial, to try if we can reduce the activation of the inflammation and aggregation of red cells to the vessels. We don't know yet the result. And Takeda, in Phase I, [indiscernible] and stress protein which is a protein which may protect on the [indiscernible]. But currently, we have no strong data showing the efficacy in this setting. Next slide. So Alain, for you?

Yes. Thank you, Olivier, for very scientific presentation. Some additional information more business, I would say, financial is about the price of such drugs. So we have seen that there are an increasing number of drugs registered and they have been priced -- at a high price, as you can see, and the new compounds are on price around $130,000 and this looks a price similar to the price of the drugs registered even for sickle cell for this, that AB Science is developing also masitinib in ILS. So you can see as high. And of course, when it comes to a cure or gene therapy, you can see that extraordinary price of $2.5 million, and this is not a mistake or typo from us, it's the real price intended to be delivered in the United States. And of course, not everybody will have -- will be able to access such a drug. This creates a market which is big and is going to increase. But today -- not today, but in the next 10 years, I would say. The market is going to grow from roughly 3 billion up to 10 billion, attracting, of course, the interest of the bigger pharmaceutical. So next slide. The next slide is the consequence, of course, of this market, which is building up with the new compounds. And Novartis started in 2016 by doing the acquisition of Selexys, which led to registration of crizanlizumab. And CSL Behring has followed up with the acquisition of Calimmune. And Novo Nordisk has done the acquisition of Forma Therapeutics, and they are in 2 Phase II/III at this time. And Pfizer has battled with Johnson & Johnson to acquire Global Blood Therapeutics and finally, Pfizer has won and they are -- and they have approval with this acquisition. So you can see that those deals have been significant and, of course, more unlikely to happen because you can see or medium-sized companies developing new drugs and of course, attracting the interest of a big corporation. What we can say and Olivier has demonstrated through the description of all the drugs registered or into development is that masitinib will -- masitinib completely new now, but will stand out because it is a totally new approach for this disease that does not exist because nobody has thought before of the involvement of mast cells in this disease, which is scientically funded. And I will give it back to Olivier to describe the recent news -- that we press release, which is the fact that the masitinib program has won a label recognition from the French government called SICKMAST, Olivier.

Next slide. So in French, there is a Programme d'investissements d'avenir in which we have applied. And the idea of this program is to -- from basic science, transactional medicine, find some new development of device for diagnosis or for treatment of disease with unmet medical need. So what we did, we presented a program in this call to try to demonstrate that mast cells may play a role in sickle cell disease and the targeting mast cells in sickle cell disease may be of benefit for the patients. So we apply to this call, which was very selective, and there is a first selection through a jury of 20 members that design or goal eligible for an oral hearing in which we have participated, and we have been successfully counted among the 70 selected grant and only 19 has been granted. So it's very important to see that the jury is composed of people from the pharma, from the investment, from the scientific world, from almost everywhere in the ecosystem of drug development and so on. It is very selective with people with a lot of skill and experience in drug development in various disease. Next slide. So this program is divided in 2 parts. The first part is to try to characterize the patients in which mast cells is the most activated and correlate this activation with acute and chronic computation. And the second part of the disease is to select the group of patients with higher level of mast cell activation in which we do think that masitinib might be the most efficient when you compare to the first. So the idea here is to be more fall and select the patient in which mast cell activation is the most show and which mast cell activation is leading to the most complication and then taking this patient to validate the concept of mast cell might be efficient. So here, we increased the change to have a successful Phase II in this study. Next slide. So the program seems complicated here, but I tried to explain to you very rapidly. So first, what we will do first, we will try to analyze in the blood of patients, deterrent kind of a biomarker, as I show you, already, we know that Histamine and P Substance correlates very well with the Vaso Occlusive Crises complication and also to acute chest syndrome, but we know they may also correlate to stroke or to preliminary functions and so on. So we try to make a correlation between mast cell activation biomarker and acute and complication of sickle cell disease. What we will do from that, we will develop test to be sure that mast cell is indeed activated and to see which marker is the most correlated to acute and/or chronic complication of sickle cell disease to use this marker to patient in protocol. The second thing we will do we call with a collaboration with another company, which is Codoc. We try to define clinical symptoms from the history of the patient, which may predict mast cell activation in sickle cell disease patient. So here at the end of this first part, we'll be able to select the best patient is a complication which are due to mast cell activation. And if we do block mast cell activation in these patients, we expect to see an improvement of their syndrome. And then we will do Phase I and meanwhile Phase IIb study in which we will try to include patients with this complication and to see if we do see an improvement, as I showed you before, which correlate to the improvement of the biomarker. Next slide. So to do this program, we are working in the Paris hospital. And we can see around 3,000 patients in 4 hospitals to Adult Center of Pediatrics Hospital in Paris. And already, we have included 700 patients in which we have already done some biomarker and will extend in this patient, a full set of biomarkers to try to show what is the best showing the mast cell activation. And we'll correlate marker with acute complication, acute in Vaso Occlusive Crises, acute chest syndrome and also chronic complication that will be chronic pain, addiction to opioids and chronic organ failure in the lung, in the kidney, in the liver and so on and will extend this cohort of patients to 1,500 patients. So here, we'll be able to have a strong correlation between the biomarker and the chronic and acute complication. And among these patients, we'll be able to select the 1 with the most mast cell activation, with the most complication to see if masitinib is able to decrease the biomarker and also the chronic and acute complications. Next slide. So in the clinical trial, first, we will use 2 dose of masitinib to assess its safety in the population, but we have no -- that it will be set in this population. But what we will do, we will use a set of a small number of patients that take Hydroxyurea, which is a standard of care today to see if we do see a synergistic effect with Hydroxyurea because we don't act the same level in the physiopathology of the disease, and we'll be sure that the combination of the 2 drugs is faced in this patient. And then the effect is sure, the small number of patients, we will use a Phase II study in which we compare the efficacy of masitinib in patients with acute or chronic complication. And at first, we will use the worst patient, meaning patients were experiencing at least 3 Vaso Occlusive Crises per year, which required hospitalization of this patient and patients who experienced acute chest syndrome. And in this patient, we will assess also the chronic complication and low cognitive dysfunction, for example, pulmonary hypertension because we know that in this population, masitinib may help to improve the symptom of the disease. And meanwhile, during this study, we will have set and will monitor all relevant markers to see if we do see a decrease of mast cell activation upon masitinib and we try to make correlation between this marker their decrease value as the helpful amount of clinical symptom in this patient. Next slide. So -- is that all right?

Olivier, I can take over. So this -- the program called RHU the government program, I would say, finance program is a significant investment from the government EUR 10 million, difficult to get and is really a recognition of the validity of the centric approach reviewed by intentional experts people from the academic work but also people from the industry. And we are glad to report that masitinib program has been selected. And the other advantage is that it signs completely the Phase II and another advantage is that it will give, we hope, markers, biomarkers, clinical markers so that we can optimize the chance of registration. This is good. And you have noted that the sponsor will be APHP so the group of hospitals in Paris and the region of Paris. So what about AB Science in fact, AB Science is going to, of course, participate to all of those activities. But at the end of the Phase II, AB Science will be free and that the message of the Slide 34 will be free continue to use the data, of course, including the biomarkers and to continue the program up to registration. So that's why we wanted to make the clear here. And of course, we will have to pay some royalties to the partners, which is absolutely normal. And we'll do so, of course, as I would say, spirit of partnership with the academic people. And of course, as you have seen, different strategies are possible, including partnering with big pharma since the interest is high this disease. Next slide. And this needs to be protected somehow with patents and that what we have done and we have filed a patent for the use of masitinib in sickle cell disease. And this patent should -- could protect masitinib commercialization up to 2040, throughout the world. It's not -- it's filed, it's not guaranteed yet. And on the top of that, we still have the possibility to reinforce the protection by trying to get orphan drug status in the regions where it's possible like the U.S.A. and Europe, of course, and this is precisely what we're going to do in the near future. So that closes the presentation and the messages that we wanted to deliver. So it's a new program for masitinib, which is entirely financed for the coming years and which could open new avenues of growth for the product. So we think, of course, Olivier with the origin of that and has carried that through and has convinced the reviewers to finance heavily this program that now we are going to execute in the coming years. This closes the presentation, and we can now respond to your questions.

And first question relates to the bulk biomarkers. How do you select your patients during SICKMAST Phase I and Phase II? And is there a biomarker based test to do so?

Okay. So one question. What we have shown already, and as for you first that for example, Histamine and Substance P are two biomarkers, which are elevated in acute complication. And maybe they may correlate also on the basophil state to the chronic complication that we are looking for currently. So during this first period when we will perform the Phase I, actually, we can see for Histamine and Substance P as a biomarker of mast cell activation. If we do see a reduction of the biomarker, it means that we can reduce the mast cell activation. And then Phase II, probably we will include patients with a higher level of Histamine or Substance P as basophil and to see if it's correlated with some complication, and we will see if upon masitinib can reduce this biomarker and also reduce the complication of sickle cell disease. And to be in line with what we call the guideline of FDA and EMA, we will answer first, obviously, the patient who has the worst prognosis, meaning the patients which are doing at least 3 Vaso Occlusive Crises per year or 1 like acute chest syndrome. And already, we know that this patient has higher level of mast cell activation assessed by Histamine and Substance P. So here, we can see we may include this patient with a higher level of P Substance and Histamine, is a reduction of Vaso Occlusive Crises, which is the main end point used by FDA and EMA for registration. And probably if we take the patient, the higher level of this biomarker we have a greater sense of success when you compare to the placebo.

Question for Alain. How long would the Phase II trial last.

Well, it's led as well. Olivier...

Yes, I think what we -- there are 2 things. The first thing is that we will start quite rapidly the Phase I study. And meanwhile, we will confirm very rapidly what population of patients we can include in this study that we know because we will have 1,500 patients, if not 1,000 patients in this Paris network hospitals, so we can go very fast in terms of recruitment of patients and in terms of time of inclusion. The problem is, it's not a problem, but we would like to optimize this study to be sure to include the patient with the most mast cell activation as either by the clinical symptom or by biomarker. So it may take probably from now 1 year or maybe even less to start to see which patients we will include. And after the time to deposit the dossier to health authorities to perform this may take 18 months more or something like that.

But of course, as you have seen, we have steps. The biomarker and the clinical markers, I would say, slowed down but is a smart way to optimize the rest of the program because if we can and at the idea of Olivier, fine and then select the patients who are more responsive to masitinib. We completely maximize the chance of registration. So we think it's completely key, hopefully, it will take a year or less, but it's key. Then we execute a Phase I which is usually take less than 10 years -- 2 years, sorry, to get the result depending on how many patients we invest there. But we will try to compact that and have it, of course, as soon as possible and not to spend time and can then go through Phase III. There is also another possibility, which is to do Phase II/III together. There are some programs which can do that, where you save, so to speak, the time to finish the Phase II and then to start where you have to file a new study and sign the contract extra. So that is possible and can spend time. But we are flexible and we're going to work on that, trying to optimize time, but not minimizing this very important point of the biomarker.

Another question regarding IP. So how many of them are protected against competitors with similar mechanisms from masitinib and analog from [ diseases ].

I would say, first of all, there is no analog for masitinib with similar or even drugs not analog, I think with similar mechanism of action. We gave you the list of the strategy. So the strategy are the usual ones to increase hemoglobin or to do gene therapy, which is completely different. It's not what we are doing. What we are doing is we are taking the most severe population, still 65% full sickle cell disease, we're not talking about the marginal part of the business case and we are -- and those people they have to live with the disease for their entire life, and it's life threatening explaining why the price of the drug is high. And what we are trying to do is to minimize, to reduce the price and then the complications. And maybe to have an impact on survival. It's not going to be the endpoint of the study. So in fact, the endpoint is the Vaso Occular Crises typically in a study. And we will try to succeed on this primary criteria.

Another question for you, Alain is AB Science. Will AB Science have enough resources to manage this new study on top of all the other ongoing studies.

And our resources can be split it into human resources and then financial resources. So you have seen the nice thing in this program is that we just won this SICKMAST one, the recognition through RHU labeling and it's financed. So finance resource is not a problem anymore, which is important, especially at that time. And then, of course, we're going to allocate human resource, which we have to the program to just implement it as it should be.

Another question on sickle cell.

All right. Olivier, would you like to add something like give some perspective or...

I think this program will shed light on the physiopathology of mast -- sickle cell disease which were not very well known before because everybody was focusing on red cells itself, but we have demonstrated for the last 10 years that -- in fact, sickle cell disease is more an inflammatory disease due to the normal activation of mast cells. And in AB Science, for the last 20 years, we have demonstrated that mast cells may not only in allergy and asthma but also in some disease like Alzheimer disease. And we know that patient with sickle cell disease have some samples, which looks like Alzheimer's disease, not because activation of mast cells because of specific time and the position. But here, because hemoglobin itself as an acute mast cells leading to connective dysfunction. And here, I think we are very unique, really unique drugs, which may improve this connective dysfunction of this patient, which is a high social burden for them. The second thing is that the blocking mast cells may reduce the risk and the risk of stroke, for example, and the risk of complication of stroke, which is a big problem in this patient. And also by reducing inflammation due to mast cell activation, Substance P or Histamine release, we may reduce aggregation of hemoglobin to acute chest reducing the risk of vaso occlusion. And one of the problems in this patient because of their chronic pain, they use morphine and then they get dependent to morphine because of the pain, but because also of the mast cell activation. And we have shown nicely in mice model so that blocking mast cells may induce an improvement of morphine dependency. So I think with this disease, first, we will provide a strong improvement of the patient. We have a unique view of treating sickle cell disease, not in competition with other drugs. And probably in the future, maybe there will be some synergistic effect between drugs, which are developed currently only focusing on the red cells itself. And also this study may provide a strong scientific and new development for AB Science in the future. I think it's a very important study.

All right. Thank you, Olivier. I would add one 1 thing beyond science, which is the striking incidence and prevalence in some countries. As you have explained, Olivier, this disease as strikes essentially the population with some origin from Africa. And so in particular, the black population, which has migrated to Europe to the United States and in the Gulf and some countries in the Gulf, Saudi Arabia and others and 2.6% of the population, which suffer from this genetic disease. Imagine if it was in more than 2% of the population would be more than 1 million people suffering from this disease. In France, it's 30,000, which is more than ILS for instance. But yes, 2% in some countries. It's a national priority. So one question is whether because of that, this kind of program could attract the attention of some government. And the answer is probably yes because, first of all, we attracted the assumption of the French government, and it's already a problem in France, but it's even more a problem in some countries, which, by the way, have money and are keen to welcome some research programs. So it creates opportunities that, of course, will try to size in the coming years. But we are very happy to report the start of a new program, which is secured for the coming years and with a sound science and network, the message that we're pleased to convey today. We'll put the presentation on our site, of course, and we'll keep you updated when we have more data on this program. Thank you, Olivier, for your time.

Thank you very much.

And your IDs. And we close the session. Okay. No more questions from the audience. So thank you to everybody.

Thank you very much.