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 a 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 Hôpital Necker, and a specialist of sickle cell disease. As you know, I'm the CEO of AB Science. I propose that we walk you through a presentation slide by slide, and at the end, as usual, we will open it for your questions. Olivier, up to you to start the presentation.
Let me see, because I don't see very well the slide. Okay, so first 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 two 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 qualitative abnormalities of the beta chain of the globin.
There is a single substitution which change an amino acid, glutamine and valine, 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, the 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 is leading to the precipitation of hemoglobin in red cells, changing the shape of these red cells, and they have the form of sickle. It's for that, we call that sickle cell disease.
We will discuss today of the main form of sickle cell disease, which is a patient with two mutations in the two chains of the beta chains with a S mutation. We call this mutation hemoglobin SS, because the two beta chain have the mutation.
We know also there is a small minor sickle cell disease in which you have different kind of the mutation, but where I will not go into the detail. We know that sickle cell disease affect million of people worldwide, and about 7.7 million patients has sickle cell disease in the world, affecting about 100,000 American people and between 20,000-40,000 in France.
We know the disease 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. It is a major public health challenge because the red cells are fragile, and there 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 these red cells are shaping abnormally, when they get the form of sickle, in the small vessels, they will do what we call vaso-occlusive crisis, because they will lead to thrombosis of the small vessels.
As a result, this vaso-occlusive crisis lead to pain, acute pain, but also chronic pain in these patients. 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 septicemia.
We know also that this crisis, the small vessels in the lung, may lead what we call acute chest syndrome, in which the patient have no more oxygen and they die of acute respiratory distress. It is very important disease because acute chest syndrome is one of the first cause of death of this patient.
In addition, we know the small vessels in the brain, this patient may experience stroke by reducing the flow in the brain, leading to cognitive dysfunction in this patient in about 50%-60% of them with age. So, sickle cell disease is both a life-threatening disease due to vaso-occlusive crisis, acute chest syndrome, stroke, infection.
But in addition, also, it is a disease leading to chronic morbidity in this group of patients, leading to the high social burden in this patient. Next slide. In fact, the pathophysiology of the disease 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 the what we call nitric oxide, nitric oxide depression, leading to activation of endothelial cells, but also mast cells, which is something quite new. And these mast cells, when they get activated, they may release some mediator, which are specific of mast cells, including histamine. And you can see here that at the basal level, histamine is higher in patients with sickle cell disease.
And very interestingly, when they experience some pain, to reduce the pain, these patients take morphine. And we see here that morphine increase further the level of mast cell activation. And we can see here, when the patients have vaso-occlusive crisis and morphine, there are very high level of histamine.
We know that histamine may play a role in these cells, in the whole of system, leading to some chronic complication. In addition, also, it has been shown, and we come back later to that, that mast cell activation may lead to increased level of P substance, which is produced by the mast cells. And P substance interact with the peripheral nerves leading to pain, but also to vessels leading to vasodilation, and probably to the acute chest syndrome.
We came to the idea that blocking mast cells in sickle cell disease may reduce pain and may also reduce complication of a mediator released by mast cells. Next slide. We have demonstrate 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.
Actually, we have demonstrated that in vivo, in patients, for example, in mastocytosis, which is a mast cell disease, where you have a mast cell activation, we are able to block the mast cell activation in this disease. We make the hypothesis that if we treat patients with masitinib, we may block abnormal mast cell activation and may reduce the risk of pain and chronic and acute complication. Next slide. Next slide. So next slide.
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 tissues. When the hemoglobin precipitate, you see the shape of the red cell 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, the abnormal hemoglobin in sickle cell disease, is able to bind to some receptor. One of them is TLR4. And TLR4 induce activation of mast cells and basophil, as you can see here. And if we do block TLR4 receptor, we block this activation .
Next slide. And the consequence of... Next slide, please. The consequence of activation, no, no, before. The consequence of mast cell activation is a 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 infarction, bone infarction, you see leg ulcers, pulmonary hypertension, and so on.
So all of these complications might be due to an abnormal activation of mast cell as a consequence of hemoglobin 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 vessels, leading to, for example, acute chest syndrome. And in addition, we know that substance P may activate the autocrine loop mast cells. So when you stimulate mast cells, you release substance P, which induce pain, which induce abnormal vessel tonicity, and activate also mast cell in the vicious cycle. Next slide.
So we have looked at the mast cell activation in patients with what we call vaso-occlusive crisis. The patient came to emergency room with pain, as you can see here on this picture, and we do see that when they experience a vaso-occlusive crisis, histamine is increased, reflecting that when you have pain, your mast cells get activated. In addition, when the 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 increase further mast cell activation, as you can see here. So as a consequence, next slide. We do see a release of substance P, and substance P when it's high lead to the acute chest syndrome.
You 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 patient with a COVID disease. Next slide. So what we have done, we have taken 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 with, difficult to see, but we do see an infiltration 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 do not experience any more acute chest syndrome. Next slide. Next slide.
So to focus on this last experience, you can see here, when you stimulate sickle cell disease mice with a compound like a substance P or other cause of acute chest syndrome, when we add masitinib, we can see the mice are surviving. Next slide. And very interesting, when we cut the lung, we do autopsy of this mice, we can see a normal lung.
A lung of mice with sickle cell disease, in which we see a lot of inflammatory cells, 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 block mast cell activation and mast cell migration in the lung, you see the lung is almost normal, and the mice do not die of acute chest syndrome. Next slide.
Very interesting, for the past 10 years, we are working on masitinib in different disease. As I told you, patients with sickle cell disease may experience stroke, and we know that a stroke may lead to infarction in the brain, as you can see here.
But when we treat mice with masitinib, we reduce the size of the infarction, leading to a better recuperation of the infarct. 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 as you can see here, we can reduce pulmonary hypertension with masitinib in dogs. And also, you can see in experience in, in, in mice, we have shown that cocaine addiction or morphine addiction might be reduced by masitinib.
In the US, for example, we know that patients with sickle cell disease experience morphine addiction, which is a very public health problem in the U.S. And probably if we do block mast cells with masitinib, we may reduce addiction to morphine in this patient.
Finally, we 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 synapse function and the functionality of this mice, which translate in a positive toxicity in human, in which we have shown that masitinib may restore cognitive function.
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. We make the hypothesis that if we do block mast cell activation, as we do see in Alzheimer's, we may restore cognitive function in this patient.
Taken together, we have demonstrated in the last 10 years that mast cells, the key cells, a key factor of acute and chronic complications of sickle cell disease, and if we do block mast cell activation by masitinib, we may improve health care of this patient. Next slide. Currently, in sickle cell disease, next slide, we know there is some treatment.
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 cell activation. One of the problem of red blood cell transfusion is that, transfusion may lead to some infection, may lead to some problem of what we call alloimmunization 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 L-glutamine may induce what we call fetal hemoglobin, which prevent in some way the aggregation of hemoglobin S.
However, this drug is not able, the hydroxyurea, increase fetal hemoglobin, reduce the number of crisis, but not fully, and there is a warning because, hydroxyurea induce some myelosuppression and might be a carcinogenic and induce some, in some patients, transient sterility. So as a consequence, only 27% of the patients use hydroxyurea, but it's still the standard of care. Next slide. So, to cure this patient, the only way to do it is, to perform allo stem cell transplantation. But to do so, we do need to have, what we call a sibling-compatible donor, which appear it's about 50%, 15% of the case.
In addition, we know that stem cell transplantation is an easy procedure, leading to 2%-5% of death because of the bone marrow transplantation, and in 10%-15%, some complications of this patient. It's difficult to be performed in country in which you have a poor health system, and most of these countries have, are the one with higher incidence 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 a CRISPR, in which we edit the genome of stem cells to induce the fetal hemoglobin. To do so, which is quite complicated, we invalidate what we call the enhancer of the suppressor of fetal hemoglobin.
As a result, the ones you set, we increase fetal hemoglobin, reducing the anemia and the sickle cell crisis in this patient. The problem of gene therapy with the 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 associated to some morbidity due to the conditioning of this procedure. Same thing for gene transfer of normal beta globin, which has been tried by bluebird bio company, showing indeed an increase of the normal beta globin in this sickle cell patients.
This one has been approved by the 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 parts of the world. Next slide. Besides these curative procedures, it has been developed iron chelator, which prevent iron overload due to chronic transfusion.
Although it is an efficient treatment which slow down the iron overload, after 20 years of transfusion, this patient have iron overload, leading to some, a lot of complications. We may use also L-glutamine, which is an amino acid, which is very easy to use, which may have some, we call, antioxidant effect, which may, at the end of the day, reduce the number of crises, but has no impact on anemia.
And the improvement, which is observed, is very low, and you can see only 3% of the patients use the drug, which is only registered in FDA but not in EMA because of this small effect. Recently, has been developed a drug, which is crizanlizumab, which is an antibody which prevent the aggregation of abnormal red cells to the endothelial cells, to the small vessel.
But these drugs, although may reduce annual rate of vaso-occlusive crisis, do so very slightly, leading to the EMA revocation of the authorization because of the small effect, and is still registered in FDA. But because of the small effect, only 2% of the patients use the drugs. Recently, Pfizer bought a company which had developed the voxelotor, which is a drugs which prevents the aggregation, the polymerization of the hemoglobin S.
As reduced, it may reduce the sickling and may also increase the level of hemoglobin, which is a case. But one of the problem of the drug, by increasing the affinity of oxygen to the hemoglobin, prevent its release in the tissues...
So taken together, the hypoxia that you do see in this patient is not reduced with these drugs. Also, it may increase the hemoglobin level, but has a very small impact in vaso-occlusive crisis and probably on chronic complications in sickle cell disease. So the use of the drug is quite low at 2.9%. Next slide.
So, by better knowledge of red cell, we have shown it has been shown that some drugs which activate an enzyme, which is pyruvate kinase, which increase the metabolism of the red cell, they prevent, in some way, the sickling and the polymerization of hemoglobin S in a mice model and also, in phases 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 crisis, but probably to some limitation because we don't change, the abnormal hemoglobin. And the phase 2,3 is currently, performed to see if the drugs will improve a little bit the number of pain and increase the hemoglobin, level.
Another company use a similar strategy to activate the pyruvate kinase, which is Agios Pharmaceuticals, and also they are still in phase 2, 3, and we don't know yet the result. Ferroportin inhibitor is used to prevent iron overload due to the transfusion, but has no impact on vaso-occlusive crisis and anemia. Playing with the inflammation, it has been shown that hemoglobin S activate what we call the complement system, which induce aggregation of red cells on the vessels.
This drug, the anti-C5 monoclonal antibody, is currently in phase 2 trial to try if it can reduce the activation of the inflammation and aggregation of red cells to the vessels. We don't know yet the result.
Takeda, using phase one recombinant ADAMTS13 protein, which is a protein which may protect endothelial cells, but currently we have no strong data showing its efficacy in this setting. Next slide. So Alain, for you.
Yes, thank you, Olivier, for this very scientific presentation. Some additional information, more business, I would say, or 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 priced around $130,000.
A nd this looks a price similar to the price of the drugs registered in amyotrophic lateral sclerosis. You know, that AB Science is developing also Masitinib in ALS, so you can see it's as high. And of course, when it comes to a cure or a gene therapy, you can see the extraordinary price of $2.5 million.
And, this is not a mistake or typo from us. It's the real price intended to be favored in the United States. And of course, not everybody will like, will have-- will be able to access, such a drug. This creates a market which is big and, and it 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 pharmaceuticals. So next slide. The next slide is the consequence, of course, of this, market, which is building up, with the new, compounds.
Novartis has started in 2016 by doing the acquisition of Selexys, which led to the registration of crizanlizumab. CSL Behring has followed up with the acquisition of Calimmune, and Novo Nordisk has done the acquisition of Forma Therapeutics, and they are into phase 2, 3 at this time. Pfizer has battled with Johnson & Johnson to acquire Global Blood Therapeutics. Finally, Pfizer has won, and they have approval, et cetera, with this acquisition.
So you can see that those deals have been significant and of course, more are likely to happen because you can see small 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 is 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 scientifically funded. And I will give it back to Olivier to describe the recent news that we press release, which is the-
... the fact that the masitinib program has won a label, a recognition from the French government called SICKMAST. Olivier?
Go next slide. So, in France, there is a Programme d'Investissements d'Avenir, in which we have applied. And the idea of this program is to form basic science, translational medicine, find some new development of a device for diagnosis of, 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 that targeting mast cells in sickle cell disease may be of benefit for the patients. So we applied to this call, which was very selective, and there is a first selection through a jury of 20 members, that designate or, you know, call eligible for an oral hearing in which we have participate.
We have been successfully granted among the 70 selected, and only 19 has been granted. 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 science.
It was very selective with people with a lot of skill and experience in drug development in various diseases. Next slide. This program is divided in two parts. The first part is to try to characterize the patient in which mast cells is the most activated and correlate this activation with acute and chronic complications.
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 people. So the idea here is to demonstrate fully and select the patient in which mast cell activation is the most shown, and which mast cell activation is leading to the most complication, and then taking this patient to validate the concept of what mast cell might be efficient. So here we increase the chance to have a successful phase two in this study. Next slide. So the program seems complicated here, but I'll try to explain to you very rapidly.
So first, what we will do first, we will try to analyze in the blood of patients different kind of biomarker. As I show you, already we know that histamine and substance P correlate very well with the vaso-occlusive crisis complication, and also to acute chest syndrome.
But we know they may also correlate to stroke or to pulmonary hypertension and infection and so on. So we try to make a correlation between mast cell activation biomarker and acute and chronic complication of sickle cell disease. What we will do from that, we will develop tests 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 entry patient in protocol.
The second thing we will do is we collaborate with a collaboration with another company, which is Predilife. We try to define clinical symptoms from the history of the patient, which may predict mast cell activation in sickle cell disease in this patient.
So here, at the end of this first part, we will be able to select the best patient with the complications which are due to mast cell activation. And if we develop mast cell activation in this patient, we expect to see an improvement of their symptom. And then we will do a phase 1 and the phase 2B study, in which we will try to include patient with this complication and to see if we do see an improvement, as I showed you before, and which correlate with the improvement of the biomarker. Next slide.
So, to do this program, we are working in the Paris Hospital, and we will see around 3,000 patients in 4 hospitals, 2 adults and 2 pediatrics hospitals in Paris. And already we have included 700 patients, in which we have already done some biomarker, and we extend in this patient a full set of biomarker to try to show what is the best showing the mast cell activation.
And we will correlate marker with acute complication, including vaso-occlusive crisis, acute chest syndrome, and also chronic complication, that will be chronic pain, addiction to opioid, and chronic organ failure in the lung, in the kidney, in the liver, and so on. And we 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 one 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 complication. Next slide. So in the clinical trial, first, we will use two dose of masitinib to assess its safety in this population, but we have no doubt that it will, it will be safe in this population.
But what we will do, we will use a set of a small number of patients that take hydroxyurea, which is the standard of care, today, to see if we do see a synergistic effect with hydroxyurea, because we don't act at the same level in the physiopathology of the disease.
And we'll be sure that the combination of the two drug is safe in this, patient. And then, if the safety is sure, the small number of patients, we will use a phase two study, in which we'll compare, the efficacy of masitinib in patient with acute or chronic complication. And at first, we'll use the worst patient, meaning patient who are experiencing at least three vaso-occlusive crisis per year, which required hospitalization of this patient and patient who experience acute chest, syndrome.
And in this patient, we will assess also the chronic complication, including neurocognitive dysfunction, for example, pulmonary hypertension. Because we know that in this population, masitinib may help to improve the symptom of this disease.
And meanwhile, during this study, we will assess and we'll 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 decreased value, and the improvement of clinical symptom in this patient. Next slide. So, Olivier?
I can take over. So this, the program, called RHU or RHU, the government program, I would say, finance program, is a, is a significant investment, from, from the government, EUR 10 million. Difficult to get, and is really a recognition of, the validity of the scientific approach. Reviewed by, international experts, people from the academic world, but also people from the industry. And we are glad to report that, masitinib program has been, has been selected. And the other advantage is that it finances completely the phase two. 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 AP-HP, so the group of hospital 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 2, AB Science will be free, and that's the message of the slide 34, will be free to continue to use the data, of course, including the biomarkers, and to continue the program up to registration. So that's what I wanted to make very clear here. And of course, we will have to pay some royalties to the partners, which is absolutely normal.
We'll do so, of course, in a spirit of partnership with the academic people. Of course, as you have seen, different strategies are possible, including partnering with Big Pharma, since the interest is high in this disease. Next slide. This needs to be protected somehow with patents, and that's exactly what we have done. We have filed a patent for the use of masitinib in sickle cell disease. This patent could protect masitinib commercialization up to 2040 throughout the world. It's not—It's fine. It's not granted yet.
On 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 are 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 thank, of course, Olivier, who is at 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.
First question, relates to the biomarkers. How do you select your patients during SICKMAST phase 1 and phase 2, and, is there a biomarker-based test to do so?
Okay, so it's an excellent question. What we have shown already, and I'll show you first that, for example, histamine and substance P are two biomarker which are elevated in acute complication, and maybe they may correlate also on the basal state to the chronic complication that we are looking for, currently.
So during this first period, when we will perform the phase one, actually we can see, for example, 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 in the phase two, probably we will include patients with a higher level of histamine or substance P at the basal level, and to see if it correlates with some complication.
And we will see if upon masitinib, we can reduce this biomarker and also, reduce the complication of, sickle cell disease. To be in line with, what we call, the guideline of FDA and EMA, we will include first, obviously, the patient who, who has the worst prognosis, meaning the patients which are doing at least three vaso-occlusive crises per year or one acute chest syndrome.
And already we know, that this patient has a higher level of mast cell activation, assessed by the histamine level and substance P. So here we can see, we may include this patient with a higher level of substance P and histamine, which is a reduction of vaso-occlusive crisis, which is the main endpoint used by FDA and EMA for registration.
Probably if we take the patient with a higher level of this biomarker, we have a greater chance of success when you compare to the placebo. But-
Thank you, Pierre. A question for Alain, maybe. How long would the phase 2 trial last?
Well, it's for Olivier, as well. Olivier,
Yeah, I think what we... There is two things. The first thing is that we will start quite rapidly the phase one 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 the Paris network hospital.
So we can go very fast in term of recruitment of patients and in term 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, assessed either by the clinical symptom or by a biomarker.
It may take probably from now, 1 year, or maybe even less, to start to see which patient we will include. After, you know, the time to deposit the dossier to health authorities and to perform the study, it may take 18 months more, or something like that.
But, of course, as you have seen, we have 2 steps. The biomarker and the clinical markers, I would say, slows down, but is a smart way to optimize the rest of the program. Because if we can, and that's the idea for this year, find 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 1 year or less, but it's key. Then we take you to phase 2, which is usually take less than 10 years, 2 years, sorry, to get the results, depending on how many patients we invest there.
But we will try to compact that and have it, of course, as soon as possible, not to spend time and can then go through phase three. There is also another possibility, which is to do phase two, three together. There are some programs which can do that, where you save, so to speak, the time to finish with phase two and then to start a phase three, where you have to file a new study and sign the contract, et cetera.
So that is possible and can save 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 the IP. So how masitinib is protected against competitors with similar mechanism or masitinib analogies for this disease?
I would say, first of all, there is no analog for masitinib with similar, or even drugs, not analog of masitinib with similar mechanism of action. We gave you the list of the strategy. So the strategy are the usual ones to increase the 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% of whole sickle cell disease, right? We're not talking about the marginal part of the business case. And those people, they have to live with the disease for their entire life, and it's life threatening. It's explaining why the price of a drug is high.
What we are trying to do is to minimize, to reduce, the crisis and then the complications. And maybe to have an impact on survival. It's not going to be the endpoint of a study. So in fact, the endpoint is the vaso-occlusive crisis, the typical in a study. And we will try to succeed on this primary criteria.
Another question for you, Alain. AB Science, will AB Science have enough resources to manage this new study on top of all the other ongoing studies?
Alain, resources can be split it in two: human resources and then financial resources. So as you've seen, the nice thing in this program is that we just won this SICKMAST, SICKMAST won the recognition through RHU labeling, and it's financed.
So financial 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, which we have, to the program, to just implement it as it should be.
Another question on the 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 pathophysiology of 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 abnormal activation of mast cells.
And in AB Science, for the last 20 years, we have demonstrated that mast cells may play a role, not only in allergy and asthma, but also in some disease like Alzheimer disease. And we know that patients with sickle cell disease have some symptoms which looks like Alzheimer disease, not because activation of mast cells, because of the amyloid position.
But here, because hemoglobin S itself, as it might activate mast cells leading to cognitive dysfunction. Here I think we are very unique, really unique drugs, which may improve this cognitive dysfunction of this patient, which is a high social burden for them.
The second thing is, that by blocking mast cells, we may reduce 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, like substance P or histamine release, we may reduce aggregation of hemoglobin to endothelial cells, reducing the risk of vaso-occlusion.
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. We have shown nicely in mouse models, 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. Probably in the future, maybe there will be some synergistic effect between drugs which are developed currently, only focusing on the red cells, on the red cells itself. 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 thing beyond science, which is the striking incidence and prevalence in some countries. As you have explained, Olivier, this disease, it 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, have, you know, 2.6% of the population which suffer from this genetic disease. Imagine if it was in France, 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 ALS, for instance. But yeah, 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 governments.
And the answer is probably yes, because, first of all, we attracted the attention 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, we'll try to seize 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 AB Science and networks, 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 ideas. And we close the session. Okay, no more questions, so from the audience, so thank you to everybody.
Thank you very much.