Genfit S.A. (GNFT) Earnings Call Transcript & Summary

Good morning, and welcome to the Genfit Virtual KOL event. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be made available on the Genfit website following the conclusion of the event. I'd now like to turn the call over to your host, Pascal Prigent, Chief Executive Officer at Genfit. Please go ahead, Pascal.

Thank you, Sarah, and thank you all for joining for this webcast. So good afternoon for those in the U.S. and good afternoon -- sorry, good morning for those in the U.S. and good afternoon for those in Europe. The purpose of this webcast is to share our view about the MASH diagnostic market and to try and give a little bit more precise guidance about what to expect with specifically all this technology. So maybe let's start with the next slide and talk about Genfit and who we are for those of you who don't know us. So these are the forward-looking statements. And next slide. Yes. So Genfit was founded a little bit more than 25 years ago in France and started with some partnership with big pharma. And that was around specific expertise around PPAR in particular and nuclear receptors in general. And that for about 5 to 6 years, but very early, Genfit started to focus on its own research and specifically the development of Elafibranor and that development was really focused in MASH or MASH as it was called at the time. And that lasted for almost 15 years as Genfit took Elafibranor all the way from drug discovery to end of Phase III. As some of you might know that development did not end well for us because in 2020, the Phase III was not supportive of the marketing approval. The product was safe and was targeted, but the efficacy was not what was needed for marketing approval. So at that time, Genfit had to reinvent itself. Fortunately for us, we had also developed elafibranor in PBC. In PBC, it worked really well. We partnered with Ipsen, eventually launched a product in the U.S. in June '24 in Europe at the end of 2024, and it's been really successful ever since. So today, it's a very different company. We have the Elafibranor business of bringing in some cash. We have a technology, which we're going to talk specifically today. And then we have a pipeline, an R&D pipeline that is focused on CCA and ACLF and that will be the purpose of another call. But the purpose of this quick introduction was really to say that we have been in NASH for a very, very long time. And actually Genfit was among the first company in MASH. We were one of the first company to be in the liver for where we worked with clinician, KOL, but also regulatory agencies and patient association. And we were among those that early on sort of discussed what were the right endpoint and what were the sort of key challenges for this market to develop. And for over 15 years, MASH was our primary focus. Can we move to the next slide. So very early on, we recognized the need for a noninvasive diagnostic solution because obviously, at the time, biopsy was a way to identify those patients and also monitor progress. And it was very clear to us that in order for this market to be or it could be, we had to have a noninvasive scalable solution that was easier to use sample biopsy and more efficient than the tools that existed at the time. And it's one of the situations where it's in everybody's interest to have such a solution. Obviously, for the patient, they need to know that they're sick and they are asymptomatic. So they cannot rely on how they feel. Therefore, they need a tool. Physicians very clearly need a tool to identify their patients. They want to know who to treat and then they want to know whether their patients are getting better or not. The drug makers also need a tool to make sure that their drug is being used correctly, that they're not off label and that they're not missing out on some patients. And then payers obviously are a very strong driving force for the need for diagnostic because they want to make sure that the drug that they pay are being used properly. And they also want to make sure that the money that they spend is money well spent and that the patients actually do get better when the do not get worse. And then, of course, diagnostic manufacturers have an incentive for that market to develop. So everybody wants this to be a success. Next slide. So this technology is actually a decade-long program. We were, as I was saying, one of the first company to start the Phase III in MASH. I think at the time, it was us and Intercept. But what that meant is that we had a very large database of thousands of patients that we followed for 18 months with a biopsy at the beginning and a biopsy at the end and many, many different measures of many different biomarkers in between. So what we did is we started to look at all those variables with the goal of identifying biomarkers that we best replicate what we saw on the biopsy. And we tested hundreds of different variables selected the most predictive one. And then -- I mean -- and we did that by using AI at the time it was called machine learning, but that was essentially what AI is today. And then we selected those most predictive variables, identify a small subset that could best replicate the biopsy and develop a unique algorithm to produce a score. So of course, you can do that on a single cohort, but then you need to make sure on independent cohort that it has some predictive power. And we did that against a series of independent cohorts. Then we optimize the test both from a standpoint of its efficiency, but also thinking about future industrialization and really thinking about IVD, and we'll talk about that data, but really thinking from the beginning that we needed to get that test to a mass market at some point. We published all of that in several scientific journals that will talk about that in more detail. We were also used by several of the pharma manufacturers in a number of clinical trials in Phase II, in Phase III. And that was very important for us because, a, it exposed a number of very important players in this market to our test and they could see it work. But also for us, it give us access to additional data that in turn helped us to further refine the test. Eventually, that test was included in a number of international guidelines in Europe, but also in the U.S. and in Asia. And I think one of the most important thing, it was recognized by independent consortium. We have 2 that are especially significant, one in Europe, one in the U.S. And both of us independent consortium tested all the different diagnostic modalities on the market today and both concluded that this was a very useful tool to identify and monitor patients. The product is now commercially available in the U.S. through LDT through our partner, Labcorp. And then very recently, we got reimbursement by Medicare in the U.S. So if we move to the next slide, -- we believe that we are now at an inflection point because for the longest time, we felt we had a great product, but for a market that did not really exist because obviously, there was no therapy approved for NASH and therefore, little incentive to try and find NASH patients. That has changed with the approval of resmetirom. They've been extremely successful reaching blockbuster stages in the first year, which I think is a testament to the potential of that market. And we think it's just the beginning. Novo is launching. Lilly is not too far behind. And there are also a number of other players starting, I think, very soon with Ida, which is also French. that could potentially get approved. With all those additional molecules in the market, we think this is going to skyrocket and the need for diagnostic is going to become even greater. Physicians are now moving from a position of just watch and wait to we need to identify those patients and treat them. And therefore, we're seeing a shift from a bottleneck that was essentially the availability of drugs to the ability to identify those patients and monitor them. So we believe that now is the right time, and we believe that we have the ideal product to take advantage of this burgeoning opportunity. So with that, I'm going to hand over to Professor Ratziu, which those of you who follow the NASH market under know because that has been an important leader in that space for quite a while now. And he will present a physician view about this and the NASH market.

Yes. So thank you, Pascal. Good morning, everyone. I'm Vlad Ratziu, I'm a hepatologist working in academic hospital in Paris, and we have a long-standing interest in this disease, NASH and in all aspects of diagnosis, natural history and drug development. So the next slide, please. So as you might be aware, a significant progress has been done a few years ago, actually in 2023 when an international body of experts decided that it is time to redefine the diagnosis in more positive terms than the negative definition that used to be the one we're using until then, which was Nonalcoholic Steatohepatitis, recognizing that the problem for these patients is not that they don't drink enough, but it is that they have insulin resistance. related to metabolic syndrome. So this whole effort was done first to give the opportunity to define in a positive way this new disease and recognize that the underlying pathophysiological mechanism that drives disease progression is related to lipotoxicity and insulin resistance. The other important achievement of this redefinition of the nosological framework was to exclude the fact that was until then a dog mark, which is that this diagnosis is an exclusionary diagnosis and it can only be retained once we have excluded other causes of liver disease. In reality, many people have more than one cause of liver disease. And in particular, many people who have a metabolic syndrome also drink amounts of alcohol that are at risk for the liver condition. And the previous classification did not allow to label those patients in any specific diagnostic category. And this -- the advantage of the new one is that it recognizes specifically the possibility of the association between metabolic steatosis with another condition. Most of these conditions occur rarely. One that is frequent is alcohol consumption. So as you can see here on this diagram, the MetALD category is precisely the one identifying patients who do have all the MASH requirements for the disease, but who also consume amounts of alcohol that are above the thresholds that have been historically determined to diagnose MASH. And then it also allows to better identify these patients simply by looking at very simple clinical or biological criteria. These are people who have at least 1 of the 5 well-recognized and universally accepted metabolic risk factors, which are based either on BMI, body fat distribution with visceral adiposity or glycoregulation disturbances, lipid disorders. All of these have come actually from the cardiologic and metabolic literature and they have been adapted to serve the purpose here to very easily identify who is at risk. So basically, people who have one or several of these metabolic addictions, metabolic risk factors, if they have steatosis, that triggers investigations procedures that aim to retain a final diagnosis can be either MASLD, MetALD, alcoholic liver disease or more rare conditions. Next one. So enormous simplification that fits to the type of profile of patients we see nowadays. And this is more important than just an academic exercise because I remember 10, 15 years ago, when we started the first trials, industry-sponsored trials for MASH, one of the objections was that the delineation of this diagnostic category, the way we identify and diagnose patients wasn't very clear in everybody's mind. Now I think nobody having a clear name identified clearly a disease and nobody argues about whether this is a disease or not or whether we're able to label patients as such. Now why are we talking about this? Obviously, it's because there is a very high prevalence of metabolic steatosis worldwide. You can see here some estimates. And one of the things that is absolutely striking is that while until now, I mean, at least in the beginning, the way this disease was seen was a disease of affluent countries. And it turns out that it is now very frequent worldwide. And it is particularly frequent in developing countries. And you can see here that surprisingly, people in Latin America or South America have higher prevalence of steatosis than in the U.S. That's a big achievement. But it is the same for North Africa, from the Middle East and of course, not to mention India, where there is a particularly high prevalence of diabetes. So truly a worldwide disease and one of the best examples of how this disease was able to enter the hepatology landscape and change the hierarchy in terms of prevalence of other liver diseases is China. In China, until not so long ago, 15, 20 years, HBV, hepatitis B infection is a major liver disease. Now it has been replaced even in China by metabolic steatosis owing to the way the Chinese society evolved towards Western lifestyle. So truly a very prevalent disease. And please remember that nowadays, exposure to obesity happens earlier in life. So there are many adolescents that are obese, some of them develop diabetes quite early in life. And therefore, we expect that since the disease starts earlier, severe forms of this condition might occur maybe a decade earlier than it is currently. So that's also an important technological shift. Next one. Now the reason why there is such an increase in prevalence is because the underlying conditions that drive the disease, which are obesity and type 2 diabetes, mainly have also increased over the past years. And you can see on the right hand of the slide, the prevalence of diabetes worldwide with some hotspots, again, like India, but it's truly a very prevalent disease with -- particularly in the U.S., many patients -- maybe 29 million patients might have glycoregulation issues and only 8.1 million are being -- are undiagnosed with this disease. So there's a lag between people are exposed and people are being diagnosed. So clearly, the increase in diabetes and the increase in obesity drive the increase in steatohepatitis. There are other factors related to lifestyle, sedentarity related maybe atmospheric pollution, other type of endocrine disruptors that can explain to some extent, the increase in MASLD. So the increase in MASLD, which is shown on the left part of the slide has been documented over the past 3 decades. And of course, part of that increase is also a better recognition of the diagnostic framework, but also a significant part is bona fide real increase in the factors that promote the development of this disease. So clearly, there is an increase, and we have to face that in the future. Next slide. So this funnel here shows you that one of the issues we're facing is that, I would say, exposure to risk factors is very prevalent, but not all people with the risk factors will develop. First, not all will be diagnosed. And second, among those diagnosed, not all will develop a concerning liver disease. And that is the difficulty. When you start with a very large base of people exposed to risk factors and only some of them are at risk of developing the liver disease, you need to find a way to identify more or less precisely those people at risk other than that we will be flooded in investigating too many people that don't have enough of a condition and everybody's efforts will be wasted and also the incentive and enthusiast for these diseases will come down. So we have to take into account the fact that here, it is a difficult situation where we need to very precisely identify people at risk. And why is it difficult? It's because there are no symptoms for this disease. And therefore, we can only rely on laboratory or imaging studies because the patient feels or functions cannot tell us who is at risk. Next one. This is a simple description sort of the natural history of the condition. So it all starts with the healthy liver. Normally, there should be no fat in the liver. But then as the balance of energy intake versus energy expenditure is tilted in favor of energy intake and storage, most of that energy will be stored as triglycerides in different parts of the body. So it should be in the adipose tissue, but it sometimes overflows the adipose tissue, maybe because some people are not able to expand sufficiently the adipose tissue. But the fact is that at some point, this is being overwhelmed and the fat starts going elsewhere in atopic places where it has no place to be. And one of these places is the liver, other places can be the muscle, you get steatosis of the heart. And as far as we're concerned here with the liver, the liver will start stocking, storing energy as triglycerides and then you see a fatty. And the fatty liver by itself is no big deal. It tells you something is wrong in the metabolic homeostasis, but it's no big deal in terms of risk of damaging the liver. The reason being that many patients are able to store the fat in neutral inert deposits of triglycerides, okay? And those do nothing to the hepatocytes. They simply enlarge the hepatocytes, but hepatocytes keep their normal environment around them and have assured all their functions appropriately. Now in some other people, this inert storage is not sufficient and some of the liver fat species, the bioactive lipids will start promoting inflammation lipotoxicity in the liver. And that's when you get on top of steatosis, inflammation and liver cell injury. That's when you cross the thresholds from steatosis to steatohepatitis. The problem with steatohepatitis is that like all long-standing inflammation and liver cell injury, what's going to do to the organ? Well, it's going to start triggering a fibrogenic response. So if this persists 1 month is not a big deal. If it persists 20 years, it will end up building fibrosis in the liver. And the ultimate stage for fibrosis building, of course, is called cirrhosis. And once you have cirrhosis, the reversibility of this whole process is being in nature and no longer is possible. And the cirrhosis can go on and develop its own complications, which are clinical complications this time, which the patient feels and which can kill the patient if they're not taking care. And one of them is liver cancer, but can be all sorts of complications of cirrhosis, which means what? Which means that the whole challenge here in dealing with these patients is to try to stop the process before they develop cirrhosis. If you do that before cirrhosis, then the whole process can be reversible to a large extent, different but it can be reversible. So what we want is that people don't develop cirrhosis. Now you would say now we have drugs that can help that process delay or slow down fibrogenesis. The problem is that, yes, there are drugs, but you can't give them to everyone. because you could imagine very easily to start giving them on the left part of the site, people already have steatosis. So that will be the safest way you treat everybody at that point and very few people will develop rather than waiting until more advanced stages. Well, that is not possible. first because those drugs are not without side effects; second, because they cost a lot of money. Third, because some people at the steato stage stage or even at steatohepatitis will not run into problems, will not develop fibrogenesis. So you would treat them, I would say, unnecessarily. So then the challenge becomes to identify those people at highest risk of developing cirrhosis. And who are those people at highest risk? Well, it's those that have according to what I said earlier, sufficient disease activity, sufficient inflammation and cell injury, which will trigger a sufficient signal for fibrogenesis. So you have to be able to identify those people who have an active form of the disease, but also who develop enough fibrosis that their fibrolytic process in the liver is being overwhelmed. Because once you start developing fibrosis beyond a certain stage and here it's Stage 2, the risk of that you go even further is higher. So the whole idea here, if you don't want to treat everybody, it would be to select those patients at high risk of progression to cirrhosis. And you can do that by doing a liver biopsy, measuring the 3 cardinal lesions, which are steatosis, inflammation ballooning and also fibrosis separately with a different scale and decide which one has the highest inflammatory activity and which one already crossed the threshold of fibrosis and say, okay, these are the people where I have to concentrate in treating them with pharmacotherapy. So that's fine. You can do that, but they will need a liver biopsy to do that. Or in view of such a large number of patients that are being exposed to the risk, liver biopsy is not a solution. And you've seen that like the the packaging for Resilron or semaglutide do not require a liver biopsy because it would be practical and feasible. So you would have to find something else that biopsy, something that's noninvasive that is able to reliably identify that little right part of the spectrum here where the chances for progression are highest. Next one. So that part of the spectrum is shown on the right-hand side. These people who have sufficient histological activity, so a score of activity at 4 or higher and who already have developed fibrosis, at least Stage 2 fibrosis, so Stages 2, 3 and 4. These are the people who will progress. So the first step, I would say, -- if you're dealing with a large number of patients that have metabolic risk factors, 1, 2, 3 or several of them, is to identify among those people in the red range, the people who have the most concerning forms of active disease. Now this is very different, as I'm trying to explain from the large majority of people who have one or several metabolic risk factors. Most of them will not have steatohepatitis. And among those who have steatohepatitis, not all will have the active form of disease. That's shown on the left side of the slide. So there's a subcategory of people who are exposed to metabolic risk factors, which are a lot in society at large, which would have this profile of disease progression. And the difficulty of diagnosing them without the liver biopsy is remarkably high. And that's a fragment of the population, for instance, the general U.S. population, it has been estimated to be around 4.4%. It doesn't mean all of them will have cirrhosis by the end of the month, but it means that they are at higher risk in the next 10 years, I would say. And that percentage goes higher if you look into people who have more severe disease metabolically like type 2 diabetes because we know that type 2 diabetes is associated with more severe stereotypes. So then the percentage goes up. So the whole challenge is here, try to identify these patients. Next one. That challenge is particularly relevant nowadays. Until now, we have no drugs. So even if you would try to identify those patients, people would object and well, but fine, but then even then what do you do because other than lifestyle and dietary changes, you will not be able to do more, and you can always recommend those without having to do a very fine phenotyping of the patient profile. Now it changed because we do have drugs that are -- that have their own side effects, on price, that they have their own constraints in terms of how you take them, how you inject them. So it is -- it becomes very important to do that identification of the patients. Now as you all know, the way it works is that a drug that is shown to be effective has been -- has done so in a well-conducted Phase III registrational trial. which means what? Which means that these trials identify for inclusion, a particular patient profile, okay? So there's a lot of people are excluded because they don't fit that profile and only patients who fit that profile will be included in the trials. If the trials are positive, you can use the trial data to say, I will treat you with this drug because it has been shown to be. However, it has been shown to be efficient, not in everybody with the disease, but in those who fit the patient profile that served for inclusion in that trial. So then if you want to treat patients, you have to identify people who have the same patient profile. Otherwise, you will be treating either people where the drug might not work as well or those that might not benefit in the same way in terms of tolerance or those that would not progress sufficiently fast to justify for a therapy. So it becomes absolutely crucial to be able to find people that are very similar to those included in pivotal trials, okay? That's the concept. Next one. It turns out that both trials that were positive, whether it's semaglutide or resmetirom have included the same type of patients, patients with active NAS, so NAS score higher than 4 or higher and with sufficient fibrosis Stage I or II that it's called significant fibrosis. So they both included this type of patients. So that's the challenge. You have to identify these type of patients. So how do we do that? We're looking at what the scientific societies have recommended as tools for identifying those patients. So if you look at the most frequent tools like Fibroscan and liver sickness measurements through VCTE, or you look at ELF, which is a blood-based biomarker, these are recommended as a tool to identify those patients. The problem is that these are fibrosis biomarkers almost exclusively. So they are able to identify the fibrotic part of the disease, but not the activity part of the disease. Moreover, if you look at the database from these trials where people had a biopsy were included in the trial because they had this particular aspect of liver injury, with activity and fibrosis. And you look at their VCD baseline values or ELF baseline values, it is very surprising to see that a lot of them did not have a liver se value within the bracket that is now currently recommended for identifying these patients. For instance, 50% of them had a fibroscan value outside the 10 to 15 kilopascals. And actually almost 20% had a very low fibroscan value, which in real world, you would say, okay, these people are not at risk. So you send them back home, less than 8 kilopascals and 1/3 of them had a high positives, false positive, high rate of false positive of fibroscan more than 15 kilopascals. Your ELF is the same, between 21% and 25% of them, depending on whether you're looking at resmetirom semaglutide had a score very low, which by fibrosis standards would identify people with no risk of fibrosis. So if you use those and you look at what the performance would be in a trial where people had a biopsy and was read correctly, you can see that you miss a lot of patients or you miscategorize a lot of that. And these are the figures that come from these AASLD guidance publications that are listed there. So not only do they only identify part of the liver injury spectrum, histologically speaking, but also not sufficiently precisely. So then what do you use, that's where NASH 2 becomes interesting because it was built in order to identify people with both high level of activity and high level of fibrosis. Next slide. So before, the choice was between a liver biopsy, which can be done in individual cases, tertiary care centers. Problem is that most patients refuse to do it in larger settings, especially in non-tertiary care settings. And even in liver clinics, many people forgot how to do liver biopsy don't have the -- they're not used to perform liver biopsies anymore. So that is a problem. It can be used at a large scale. Then we have imaging. And I've shown you the limitations of FibroScan. Of course, MRI-based imaging techniques are very precise in terms of measuring PDFF, probably better than FibroScan in terms of measuring stiffness but there's a clear issue of availability and cost. And then you have blood-based tests, which were most of them developed for fibrosis and not for a dual activity in fibrotic spectrum of injury. So they're insufficiently performed to identify what we're interested in. So that was the state of affairs before a specific marker was created. And I think Genfit was clearly the first ones that created a biomarker with the precise objective of that particular identification and others followed with the FA score based on FibroScan, but that has their own issues. Next one. So things got a little bit better now that we have -- that GENFIT has developed this biomarker and tested it and started describing its context of use and limits and diagnostic performance. And this is what I'm going to show in the next few slides. Next one. So it all started with a very intensive effort from stored biobank samples from both the Phase II elafibranor trial and the Phase III elafibranor registrational trial and a lot of effort from the team of statisticians at Bioinformatics at Genfit that screened through a very large number of compounds and identified those that are -- have the best correlation with the histological lesions that we were interested in. And it came down to 4 different biomarkers, alpha2 macroglobulin, which is also present in FibroTest, FibroSure, universal marker of fibrosis, YKL-40, also a marker of fibrosis, but also activity. and then HbA1c, which is an indicator of glycodysregulation, given that diabetes plays such an important role in defining this area of the disease. And also they screen more than 2,000 miRNAs and they identify 34A as being one that is particularly related to some transcription factors involved in lipogenesis, but also apoptosis and inflammation. So putting all these together created initially historically the NASH score, which had a very good discriminative ability for at risk NASH. And actually, the association of these 4 biomarkers performed better than each one of them individually, which is what you can see on the right side of the screen. So that's how it all started, and it has been done from a large number of samples from these studies. The advantage being that both the Phase II and the Phase III were read by a central pathologist, which was the same actually in both studies. So the level of variability in pathology, which is never 0, but was reduced because of the central reading. So the data are very solid in terms of the outcome it refers to the histological outcome it refers. Next slide. Now this was the initial NIS4. But then, of course, if you want to move a step closer to optimizing it and to scale it in terms of industry production, you would have to make some adjustments to it. And one of the things that was dropped was HbA1c, although it is an important indicator of the glycemic status, it can change over time. And actually it can change in a few months only if the patient gets optimized antidiabetic therapy. And then, of course, fibrosis doesn't change in a few months. So that would induce a significant bias because of fluctuations of HbA1c. Alpha to microglobulin, it's a little less available. It is possible to do it in clinical practice, but less available, and it will necessitate processing the specimen in a different way. So getting rid of these 2 and only keeping the most performant ones, the miRNA and the YKL-40 with some replacement of the glycolic status by the sex information, meaning the male or female allowed the company to device a simplified version who had the same prognostic value a little better, show you on the next slide, but also who have the advantage of being testable simply on a serum sample and not on a serum and the plasma. So it eliminates the need for a plasma sample, which, of course, makes it much more simpler in practice, small in. This was published after the NIS4 publication and a lot of work has been done to show that. Next slide. that it has a performance that is equal or even a little bit better. You can see on the left side of the direct comparison with NIS4 score than the historical NIS4 score biomarker and much better than what was available at the time before in NAFLD. So it is a quality score going from 0 to 1 has been calibrated that way. And low values are -- indicate low risk of having the aggressive form of the disease, high values indicate high risk of having the aggressive form of the disease. And therefore, 2 thresholds can be devised based on the best sensitivity to identify people without the disease and the best specificity to identify people with the disease in order to, in the first case, reduce as much as possible false negatives. In the second case, to reduce as much as possible false positives. So that creates the 2 thresholds that are shown here. The lower threshold for ruling out has 85% sensitivity, which was -- is a high value for this type of indicators. And the ruling threshold for advanced disease has 85% specificity. So this is how these 2 thresholds were. And of course, in the middle, there's an indeterminate zone where you can't really tell this is true for any biomarker. You will have to repeat that in some time and see how things evolve in order to make decisions based on that. Next one. So once this has been established, an important -- actually a large amount of work was dedicated to understand whether external factors risk to bias the value of NIS2, depending on things that are not necessarily related to actually fibrosis. For instance, age is a very important factor. Most of the biomarkers that are being tested for NASH and actually for fibrosis in NASH are extremely sensitive to changes in age. So there is, in most of them, an increase simply because the patient gets older. So yes, fibrosis increases with age, but a lot of people can get older without having more fibrosis. So it would be good if the biomarker would not be impacted by age. And the same can be said, for instance, about aminotransferases. Any biomarker that has aminotransferases values in it, like FIB-4 could be confounded by situations where enzymes go up or are normalized because you lose some weight or because you stop some other medication. And therefore, part of the information is being lost. As you can see here, this is not the case for NIS2. If you look at the upper hand figure, different categories from blue light to dark blue of age, so less than 45 all the way to 65. And you can see that the diagnostic performance of NIS2 for at risk NASH does not change depending on the age bracket. So age is not a factor that would influence independent of histology, the value of NIS4 whereas it does for for all the others that are shown here, I apologize if it's too small to see, but it is the case for FIB-4 and FS alpha. You can see on the bottom panel that on the left hand, the specificity on the right hand, the sensitivity for each one of the biomarkers is also not changing much with age in for NIS2, but it does so dramatically for the other biomarkers. So yes, so it's clear that it's a much better situation if there's no compounding factors. So this has been done extensively. It has been studied for diabetes, has been studied for BMI in addition to what's shown here. So all this shows the robustness of this biomarker, which depends to the largest extent we can determine to the histological lesions and not the external factors that can bias the calculation. Next slide. Once these studies have been performed and shown and shared with the larger community by the promoter, with help from academics like myself, then independent studies started to use and test on their own the diagnostic performance of this and other biomarkers. And here, we'll have 2 examples. On this slide, a U.S.-based example, and next slide will be a European-based example. On the U.S.-based example, this is a nimble consortia for testing biomarkers for MAB. And this has been done so independent of English cooperation. And it does confirm the same diagnostic value in terms of area of the drug curve. You can see here for steatohepatitis or at-risk steatohepatitis, it performs better than any of the other ones that are being tested with values that are pretty much in line with the initial publications for -- and the current studies performed with this biomarker confirm that the performance is entirely acceptable for the identification of these people and particularly for the soft spot of this category of patients, which are the ones with early fibrosis -- early significant fibrosis Stage 2, which are the most difficult to diagnose. Of course, the more fibrosis you have the easiest -- more perform all these biomarkers are, but for Stage 2, it's partly difficult. And this one achieves good discrimination even for early stages of significant fibrosis. Next one. And this was confirmed, in fact, done at the same time in the European consortium, the consortium who tested head-to-head in the same patients who had all these biomarkers that are performed at the same time, including imaging biomarkers. And you can see here the results. The only one that was in terms of area under above 0.8 for at-risk steatohepatitis was indeed NIS2 plus, ranking highest among all those that are being tested and thus confirming the initial results provided by Genfit and also corroborating the data from the American consortium. So both large consortiums found the same thing. And what I'm showing here on this slide is a prospective study, not a retrospective study. It's a prospective study with centrally read biopsies. -- by the whole panel of pathologists. So that doesn't eliminate variability in pathological really, but it reduces that variability to a reasonable extent. Next one. And I'd like to show this slide because it is -- in my view, it confirms the reality of what this test is truly indicating. What we try to do here is to understand whether the 3 category of patients based on these 2, people at low risk, people have middle risk and people at high risk correspond to a patient profile that could be corroborated with other -- with other diagnostic markers. In other words, Yes, the NIS score is different. Yes, those are existing categories. But do they really reflect a different level of injury, a different severity of liver injury or a different severity of metabolic dysfunction. And the answer is yes. Because if you look at the table, and it is very interesting to see that the percentage of people with high liver stiffness measured either by FibroScan or by MRE, which are slightly different techniques, but entirely different from a blood-based biomarker. It shows that with increasing values of NIS4, there is an increasing in the same direction of liver stiffness. So the 3 categories identified by using this threshold with NIS2 clearly are categories of patients that have more fibrosis and as measured by ASM and also more steatosis is measured by CAP. Not only that, but if you look at indicators, surrogate markers of insulin resistance like a HOMA IR level, here, again, the percentage of people with high HOMA, so very insulin resistant, goes from 35% in those with a low score to 82% in those with a high score. So this composite index of YKL, MIR5 and adjusted on sex identifies people who have a bona 5 more severe liver disease. However, else you measure it with other totally independent metrics and more severe metabolic dysfunction. So it clearly separates people with different levels of liver injury. And this is very reassuring because otherwise, it would be just an arithmetical concern. So that gives a lot of credibility, I think, to the fact that biologically speaking, this biomarker, although it has nothing to do with stiffness, it has nothing to do with resistance directly, identifies people with more severe. Next one. And finally, it is a quantitative score. So there are thresholds, you have these categories, but you can also use the quantitative measurement of this score because it goes from 0 to 100. And that allows you to monitor patients during their course of therapy or else otherwise. And this has been very nicely shown here in this study, where people, I believe those were -- yes, a result Phase III trials of elafibranor. So basically, this was a negative trial in the sense that there was improvement with elafibranor, but not significantly -- it was numerically higher than placebo, not significantly. Nonetheless, some people did improve histologically. And when that was the case, these values went down. And that's true for the activity part, and that's true also for fibrosis part. You see on the left-hand side, the graph there, you see the lines dropping or the pink lines dropping. Those are people who improved the activity level histologically or the fibrosis level. Their the values went down, whereas those where there is no histological improvement stayed more or less the same, which means that this could be used for monitoring purposes on therapy as the score is indeed used in people who get better. And in those who don't get better, while the score doesn't change. So this could be very helpful in identifying responders versus nonresponders when you start treating everyday. Next one. Well, since -- no, -- since all these data have accumulated both from the sponsor and independently, of course, in the end, it has to permeate and to be integrated into clinical practice guidelines. And it didn't take long before the major societies recognize that there is a clear place for this type of biomarker for identifying patients at risk of disease progression. And this is why they are now listed as options in this clinical patient management in everyday clinical practice. That's the left part of the slide. And consequently, therapeutic trials, industry-sponsored ones started integrating among other biomarkers, NIS2 as well. And it's very fortunate that now we have data coming -- independent data coming specifically from the AKIRO, fuxafarin trial from tirzepatide from Lilly, also from AstraZeneca, a GLP glucagon agonist retatutide. And all of them have been tested in these trials and all of them have shown that the levels go down in patients who respond to the drug. And you can see that -- although it's very small, you can see the details here in terms of the level of change with increasing doses of tirzepatide versus placebo. So minus 002 in placebo, almost no change versus minus 0.34, which is significant on a scale from 0 to 1 in people who had the high dose of tirzepatide who induced the highest antifibrotic effect. So independently tested in clinical trials, clear dependence on the score of the value within histological improvement. Next one. And speaking of trials, using a tool that would better identify people who should undergo liver biopsy in order to be selected for the trial would be a big advantage for the sponsors because by using this tool rather than just based on fibroscan values, age, ALT, AST values, which is why we use routinely would help identify better the patients who should not have the biopsy because you won't find enough lesions and those conversely who -- where biopsy should be done because there's a much higher probability of finding active fibrotic NASH. And this is clearly the case. You can see here in red, the proportion of patients that express increasing with increasing values of NIS2 and the proportion of patients with non enough physiological injury in blue, decreasing with increasing values of NIS2. Well, if you fix the thresholds here, you could very easily help clinical trial recruitment by better targeting people who should have a biopsy. And that has not only clinical consequences for patients who don't have to go necessarily to a biopsy, but also has cost consequences because that would help you reduce the number of biopsies to find the same number of patients to be included. So that was calculated that the biopsies could be reduced by 30%, and there could be a 16% reduction in overall cost only for selecting patients for the trial. So this should be used in trials, and that's probably why most of these trials have started implementing it so far. Next one. So in this final slide, I'd like to reiterate again 2 important concepts. So the first one is that among the very large number of patients at large with metabolic risk factors, we need to identify those that are at risk of having severe liver injury and that need to be referred to a specialist in order to confirm that or not, sometimes okay? So we need something for better referral to the specialists because the specialists cannot take care of and it's not all these patients at. We've seen how many there are in the society at large. The second point is that now that these drugs are available, we need to be able to find once these people reach the specialist care, those that are at higher -- those that fit to the clinical profile that was included in the Phase III registration trials so that you use the drug in the context of use where it was designed to work best. And those 2 things can be achieved to a various degree with existing biomarkers, but you see that many of them do not -- are not performing enough for these 2 purposes, whereas these 2 was with the current body of data, the most performant one for fulfilling these objectives, these dual objectives. And I would like to say that the patient profile to be treated with these drugs is, of course, derived from -- again, from the clinical trials, Phase III registration trials. It's not something we invented. And the Phase III registration trials are dictated by the FDA. So fundamentally, the FDA agreed upon a patient profile that is amenable to be treated with drugs if they work. And that patient profile is exactly the one I've shown. And you can see the reference here, official reference by the FDA saying that these are the patients we need to -- that could benefit from pharmacotherapy. And that's why it's important to have this active fibrotic NASH in mind and have a good tool to identify these patients. I think this is the last slide as far as my presentation. Thank you so much.

Thank you to your presentation because we have seen how large is the unmet medical need and the amazing amount of data supporting MYST2+. But I'm sure we will all agree the validation is only one part of the story. And the next part of the presentation will focus on the commercial value. And we will see that to create the commercial value, we need to have a technology that would address huge bottleneck in the current Medicare journey for the MASH patients. And that's exactly what we will address right now, especially because we have seen due to the availability now of the treatment for sure, the bottleneck is more than ever the opportunity to identify diagnosed and then start monitoring later on patients. So it's all about the diagnostic journey. And that's exactly the question we asked to IQVIA. And you can see here that now the next part we focus on insight coming from the market research we did with IQVIA, asking them how large is this new diagnostic opportunity and what is the role that MYST2+ could play to unlock this new diagnostic opportunity in MASH. Next slide, please. So this market research has been performed by IQVIA on a quantitative aspect where they made -- they had interviewed 50 physicians from some GPs, endocrinologists, hepatologists and gastroenterologists. And they made also qualitative part for this market research with the interview of 5 key opinion leaders. The main purpose was not only to understand or to get data on the awareness and the understanding about the value of MYST2+. We wanted really to better understand what is the current patient journey for the MASH, in this MASH field and what are the main bottlenecks, bottlenecks that for now, despite the availability of the drug does not create a huge market opportunity yet for the pharma companies. That's what we will address. Next slide, please. The first insight and then I will share later on more details coming out from IQVIA is quite clear. since the successful launch of resmetirom 1 year ago, more than 1 year ago, this has already totally changed and has entered in a new phase. And in this new phase, again, back to what we discussed previously, because the drug are already -- one drug has been already commercialized. The second one has been now approved, the availability of the drug is not anymore this bottleneck the bottleneck. All is about patient and monitoring of patients. So next slide, please. So I will not go back to the patient flow that has been already shared, but I will only focus on the 90 million of patients, the ones that have elevated hepatic enzyme and at least one risk factor because as it has been described by Vlad, definitively those patients, those 90 million they should be considered as being suspected of MASH. And then the key question is how we can reduce this already a huge existing gap that we can see here, meaning despite the fact the prevalence is telling us between 5 million to 7 million of patients are at risk NASH patients, it means the ones that are fully aligned with the approval that has been made for [indiscernible] and Silverturaxac, we can see that only 50,000 patients have been treated after 1 year with [indiscernible]. So it means we have a huge gap between this large addressable patient population and the less than 1% of patients that have been already treated. So that's the first insight, how we can -- the key question will be how we can somehow change this gap, change the momentum. in our recommendation coming out from this market research, if we do succeed to consider those 90 million of patients suspected of Match to be systematically screened by PCPs or later on potentially also by hepatologists or gastroenterologists, it will give really an opportunity to identify and then diagnose those patients later on as at-risk mat patients. So that's really the first insight we should all of us, the pharma company and of course, the diagnostic companies with the physicians see how we can compensate this huge first gap. Next slide, please. So we have seen a huge gap between the large population and the second huge gap is the one that we can see here. Despite the fact that still only 50,000 patients have been treated, so less than 1%. On top of that, you can see on the right side of the slide, then 50% of the 50,000 treated patients have been, either because they were F0 or F1 patients, so meaning patients without enough fibrosis to be considered as being MASH patients with risk or already F4 patients, meaning already cirrhotic patients. In both cases, so meaning for the 50% of patients, the lack of stratification, the lack of awareness to really and the lack of access to a relevant test, diagnostic test to stratify the population is the reason why we have this. So very few patients treated. And when those patients are treated, 50% of them are off label if we do consider the approval by. Next slide, please. What we try to do with IQVIA was to better understand what are the main bottlenecks that could explain why so few patients are treated despite this large eligible population. So more from a qualitative aspect. And you will see on the next 2 slides, this one and the following one, then 6 bottlenecks have been clearly identified that may justify more than 80% of the gaps. The first important message because we don't go into the details of this presentation, this part of the presentation of the bottlenecks are diagnostic issues related to diagnostic technologies. It means, and that's the first confirmation, the important confirmation because the drugs are now available, definitively, the main bottleneck as it could have been the case in the past, is not anymore the lack of availability of the drug, but definitively the capability of the market of physicians to really diagnose and monitor those patients. So I would just list the main bottleneck starting first with, of course, up to today, and that's something we can easily understand based on the presentation made by up today and before will be available later on in the market via I will come back to this topic. The market is missing a really relevant way to identify at-risk patients at scale. That's the first bottleneck today. The second one, I will not come back to the topic and the presentation made on the liver biopsy. But of course, we are well aware following the presentation about all the issues related to liver biopsy. But the fact is up to today, liver biopsy remains the d gold standard. So we are seeing it's not suitable. Definitively, it's expensive. It's associated with risk for patients, but still the gold standard. The third bottleneck is about the limited physician confidence in the current first-line blood test and the one that is more used being -- and the main reason for that, and again, it has been part of the data shared by this type of current first-line blood tests have not been developed to really address diagnose and monitor the at-risk NASH patients. A concrete example, F4 is not able to measure the disease activity. So at the end, you get data or you get a stratification of your patient with a very limited ability to detect the disease activity what is definitively key for the at-risk NASH patients. Next slide. So the next bottleneck is for now the test, the diagnostic test that is the most being FibroScan. And here 2 main comments came out from this market research. The first one, FibroScan is impacted negatively by a limited accessibility. And of course, it's easily understandable because fibroscan can be performed by specialists. So if we link with the 90 million patients that are suspected of at NASH, of course, the bottleneck, the quantitative bottleneck is easily understand. But of course, on top of that, we have also in terms of performance with FibroScan. And again, because this diagnostic test has not been developed with a specific focus on at-risk NASH, it can deliver specific data on fibrosis level. NASH disease activity data will come out from any fibroscan that will be performed. So at the end, again, we don't have a fit between the use of fibroscan and what we are looking the specific at-kAS population. The second bottleneck maybe somehow linked with the last one, meaning the lack of awareness. This lack of awareness is still a fact not only at physician level but also at the patient level. It means majority of the MASH, at-risk MASH patients, they are not aware. In some cases, they are sick because they don't have so early symptoms. And without symptoms, without an early diagnostic tool, relevant diagnostic tool, at the end, you don't know that you're sick. And because you don't know that you're at sick, your physicians will not take care of this potential risk. And that's a very negative circle where this limited awareness of MASH leads to a miss or at least a delayed recognition of the disease and a delayed start of the management of the MASH patients. That's one of the key learning for -- so on the last one, again, that's the link between the lack of awareness or the low awareness and up to last year, the lack of drug. And this somehow the fact that no drug were available in the market was not supportive of a high motivation by physicians with no incentive to actively identify and start managing patients. So at the end, the clinical and the economic value of a broad screening was really difficult to demonstrate without available therapy, what has been changed again with the launch of the drug. What is clear and the summary of those bottlenecks for the market, for physicians, the next breakthrough in NASH is not another drug, even if many of them will be in the market, that's what is expected. But the next breakthrough in NASH is definite identify patients at scale thanks to diagnostic tool and thanks we hope so to [indiscernible]. Next slide, please. In this part, the key message coming out from the IQVIA market research is the collaboration, the partnership and the huge investment that will come from the pharma companies in terms of market building. And it's quite obvious and it has been well qualified in this market research, pharma companies will be the primary driver of the m market development. Why? Because by launching new therapies, they want to increase the awareness and the education from physicians. And the more they will increase the education of physicians, the more physicians will start diagnosing and prescribing treatment to the eligible patient that should be identified. And the more they will diagnose, prescribe the more you will need treatment monitoring. So it's a very positive virtuous circle where this huge investment that I will share more details in the next slide will coming out from the pharma action plan will support increasing the education in the awareness, more patients will be treated and it will require more monitoring. Next slide. Here in a little bit more detailed view why the pharma companies they will need scalable diagnostic tool in their marketing action plan. Again, innovation has been already and is already in the market coming out from the therapeutic launches. That's already done. The primary bottleneck again, as it has been seen is definitively the lack of relevant and very well-documented selection of patients that are currently eligible but are not well identified. And that's the first primary bottleneck. So it means if we stop here for a few seconds, if you try as a pharma company to build your market building action plan, the first lever will be definitively to invest in a huge implementation of a diagnostic tool that will help to identify and diagnose and later on stratify the risk of your patients. So that's definitely the first activity they will do in terms of marketing. They cannot expect to have a huge acceleration in the commercialization of the drug without having access to a better and earlier identification of the eligible patients that should be treated. So that's why a diagnostic solution will be essential, and that's also the reason why we started many decisions in terms of potential partnership with pharma companies, and I will come back later on to this type of value also for the pharma company, and it's also in this slide is how differentiated is NIS2+ with regard of the current blood test or imaging tests that are available. And the good news for us from a qualitative view, we can see for the specialist, but also for PCs and ENDOs, all of them following a quick presentation of NIS2+, they see huge differentiation compared to the current tests that are available and especially if we compare with the other blood-based panels. You can see here the 3 main value that have been identified by the physicians. First, NIS2+ will give accessibility at any point of care. So it means definitively, and of course, it will be also linked to the development and the commercialization of the IVD kit, it will become easier for patients and physicians to go to the point of care to get your blood-based outcome, the NIS2+ outcome. The second big added value that is seen by physicians is this dual sensitivity for, on one hand, the inflammation and on the other hand, the fibrosis staging. And again, to the presentation made by Vlad, I'm sure we are all aware now it's critical because for selecting the right at-risk MASH patients, you need both data, meaning inflammation and fibrosis safety. The third added value by commercializing NIS2+ will come from the workflow simplicity also for PCPs and ENDOs. And again, back to what has been said earlier, if we are trying to change the current mat journey for the patients, starting first with an important screening activity at PCPs better refer or to refer more selective patients to the specialist, this workflow simplicity will be key for the future success of NIS2+. I will not come back to the competitive landscape. I think we shared already many data, but the summary offerenti the opportunity to identify new value proposition and clearly identified by PCPs and ENDOs and as referral efficiency by using a test that will give you both disease activity and fibrosis. So it's a huge plus in terms of screening referral tool and activity that we would like to implement later on. Next slide, please. Only one comment because on the previous slide, it was a differentiation seen from a qualitative perspective in this IQVIA market research. It's not often that you can link a qualitative market research with real data. And this slide has been already shared and presented by Vlad. But if you link both, you can see view the differentiation view shared just in the previous slide. And the differentiated data coming out from the litmus data, but also the nimble active work that has been done, at the end, we have one clear message. If you combine the plus that NIS2+ will bring to the market, so inflammation data and fibrosis strategy, that's exactly the mechanism of action of all the drugs that have been already commercialized or that are currently in Phase III clinical studies. So it means we have a perfect fit because the differentiation -- the positive differentiation NIS2+ will bring to the market is exactly what will be needed for the pharma company first to select the right patients and then later on to monitor the efficacy of their mechanism of action, the efficacy of their therapies. So it's a perfect fit between our design, the data that we have been sharing and definitely the positive perception by the market. Next slide, please. So if we go a little bit further in terms of data, again, we are seeing the medical need. If we focus now from the diagnostic side, maybe the first important message on this slide, of course, the first activity with NIS2+ will be to diagnose new patients that potentially can be treated. And here, you can see in terms of volume, if we look at picture 2033, it should -- we should get 1.7 million in volume coming out of the diagnosis testing. part of the base case, it's also a huge volume will come out from the monitoring activities and the monitoring testing with NIS2+. So the split will be more or less 75% coming out from monitoring, 25% of the volume coming out from the diagnosis. And the total picture will be 7.4 million NIS2+ volume, combining the LDT testing and the IVD testing. And you can see on the right the value that this monitoring aspect, key in terms of volume, in terms of the size of the opportunity will bring value on one hand of the pharma company because they will need to get access to monitoring data to engage with payers to confirm the efficacy of the drug with real-world data. And for GENFIT, of course, then we switch from the business with only one test to a recurring testing revenue via the monitoring aspect. So it's a totally game changer with this focus on the monitoring development. The next slide, please. One comment on the split between the LDT market and the IVD. First of all, at Genfit, we don't see at all any competition between the LDT and the IVD market. We started many years ago to develop and working with our partner, it's public information with LabCorp because it gave us the opportunity to access earlier to the market to generate many additional data to give access to the pharma company to somehow already a test that has been industrialized. We have been able to perform thousands of NIS2+ tests already. So this access, this early access to the market via the LDT has been quite important in our journey at Genfit. Starting a few months ago and with a targeted completion date in 2028, we have started already our activity to develop the IVD kit. And of course, then in the future, we will combine both an LDT business and an IVD business. And that's the combination of the 2 that will optimize the access to the market, the opportunity to partner with pharma companies and thanks also to the LDT that gave us already access to the reimbursement. And again, we'll come back to that just in the next slide. Thanks to this work, LabCorp has been able to get the reimbursement by Medicare. And as you can imagine, the big part of the dossier that has been evaluated and granted by Medicare will support all the future direction also for the IVD kit developer. And the same in terms of technical all the work that has been done with LabCorp will be more or less 70% of the IVD dossier that will be needed for the approval of the in the future. So that's why we are first, definitively, we see both as a complementary business model, and we are really confident, thanks to the work already done, that we will be successful to launch the IVD kit in 2028. Next slide, please. So now we will give you a little bit more precise data to support our guidance and to better understand what are the assumptions behind our guidance. So to the next slide, please. Again, a few words, but just to explain and not to come back to the 10 years of development, but as it has been said by Pascal as an introduction, this diagnostic journey started more than 10 years ago. Coming back to where we are today and what are the key activities that make us quite confident in the future success. First of all, it has been said that the recognition by independent consortia like NUSS and LIBER. We have already been able to deploy in large-scale clinical trials, more than in Phase II or Phase III used NIS2+ and NIS4 also. On top, it means definitively with LabCorp, we have been able to perform thousands of tests already. So terms of industrialization, we have a huge expertise and we know exactly how to be with the good quality approach in terms of execution of this test. outcomes, we have already many scientific publication, and it's also important because to get an IVD approval, you need to bring in dossier many clinical data. And often the challenging part of the discussion with the FDA or EMA is based on the lack of relevant data, based on the sent publication based on the clinical trials, based on the evaluation made by Medicare for the reimbursement, the evaluation that has been made with our partner to deliver the IVD kit makes us very confident in our opportunity to get this approval quite soon, meaning early 2028. If we move to what will happen between started already in 2026 and up to the end of 2028 on the commercial aspect. I hope at the end of this presentation, the question for all of you will not be anymore do we have a test that will bring value to patients, to physicians to the market. The only question should be how fast will be the commercial success. And because we started already to meet some of the goals to achieve some of the goals that we have identified in terms of commercialization, the first one, our test is already available in the U.S. market via LabCorp. So we are already commercial stage. The second one, always key, you may have a good test, a relevant test. If you don't get it reimbursed, it becomes very difficult in terms of commercial opportunity. We got already this reimbursement of [indiscernible] grated by Medicare for patients meeting eligibility criteria in this quarter. goals, critical in terms of commercial, that has been already started. I mean we need to be successful in terms of strategic partnership with the major diagnostic players, but all those discussions have been already started. Many activities have been already partnered with pharma companies. It's, of course, I'm considering the clinical studies, I'm considering all the meetings to be included in guidelines. So even if we did not disclose yet any partnership, activities have been -- discussions have been started and some activities have been already achieved. And in terms of deployment and development of the, again, I told you already quite confident because the plan has been started a few months ago. And part of this dossier will be mainly based on what has been already performed for the LDT development. So again, 2028 will be a key year for us. If we go to the next slide. Next slide, please. So we can go directly to the next one because this is just a summary in terms of volume that we have set, the next slide. So if we combine, again, the scale of the opportunity, the clinical evidence and the market need from a physician perspective and how differentiated we are, we will be and we are already here, you can see we plan for a peak sales annual laboratory market opportunity around $1.5 billion in 2033. And with an uptake, we plan to be above $1 billion in 2031. So it means definitively, we can see and here, we are really talking about this related revenue to the partner lab, meaning the LDT partner or the IVD partner, not the private labs. And of course, the royalties that we do expect at Genfit will be based on this peak annual laboratory market opportunity. Again, the big number, $1.5 billion. If we go to the next slide, the first message, and we try to summarize the main assumptions that we have used to build this forecast. And I would like just to make sure that at the end, you will understand then our approach has been to be as much as example, of course, it's the prevalence, it's quite easy because all the data in terms of numbers that we have figures that we have in terms of prevalence. But we have now and we took a conservative approach when it's about the differentiation because we have seen the majority of the prescribers where they get a presentation, an introduction of NIS2+, they see clearly the differentiation and the value created by NIS2+. Nevertheless, we took only 35% of frontline testing will be done via NIS2+ at peak sales. So it's a conservative approach in terms of differentiation. In terms of market access, we took again a conservative approach. I mean in terms of payer coverage, we took -- we take 60% after 4 years. And we know and especially in the U.S. as soon as you get the Medicare coverage normally in the next, the following 2 years, you should reach, you should at least target 80% of coverage. So taking 60% of reimbursement coverage at year 4 is definitively for us a conservative approach in terms of market access. We included the monitoring aspect in the forecast, and we explained why. And 2028, sorry, will be definitely a year -- the critical year for the commercialization of the IVD kit. So they are the main assumptions here. The last comment, maybe you have seen at the start of the forecast, meaning '26 and '27 we have low and slow start. And the main reason for that being we need to be successful via the action plan that we have just shared through the partnership with pharma companies, with IVD players to transform this market. And to do so, we will focus mainly on qualitative objectives in 2026 and 2027. And nevertheless, we do expect to get $10 million laboratory revenues in 2027 and then based on the commercial, a huge acceleration starting in 2028. Next slide, please. So thank you so much for your time and your attention. We are at the end of the presentation and more than welcome your questions.

Great. A big thank you to our speakers. [Operator Instructions] We're a bit over, but he have about 10 minutes left for questions. So our first question comes from Thomas Smith at Leerink. Thomas Smith says, hi team, congrats on the progress, and thanks for putting together this event. For Dr. Ratziu and the Genfit team, can you elaborate a bit on the history of NIS4, the level of adoption of this blood-based test in the U.S. and some of the learnings from this experience? And what gives you the confidence that NIS2+ adoption will be better in comparison?

So I can start. The issue, I think, as was alluded to by Pascal and Ratziu is that we had a great product on the market that did not exist because at the time of the invention of NIS4, if you want, there was no drug in the market. And with no drug in the market, there was little incentive to find those patients, especially those at-risk match patients because what would you do with that information, except say, you need to sort of watch your diet and exercise it a bit more, which was what you would have said to all patients anyway. So very little incentive. Nevertheless, where LabCorp was very successful is in talking to the only folks that had a very strong interest in finding those patients and Vlad actually alluded to that group, and that's the pharma companies because those pharma companies were actually conducting trial and they had to identify those patients for inclusion in their studies. And because those were biopsy studies, they had to do biopsy to a large number of people just to identify those that could be randomized. And of course, we know and we've lived that in our own study, sometimes you had a fail rate in excess of 70% to 75%, which means you were doing a lot of unnecessary biopsies. And of course, it's an invasive procedure. So it's not good for a patient. And it was also a waste of money because biopsies are quite expensive, especially in the context of a clinical trial. So what LabCorp did was position as a prescreening tool. And because the data was very clear and quite frankly, the evidence was overwhelming, we had a very large proportion, actually, almost all of them that started to use NIS4 as a prescreening mechanism just to avoid unnecessary biopsy and save money and sort of negative for patients in the process. So I would not say that those years with NIS4 were not important for us because what it did, it was not the cash generated, obviously, but it was the fact that all of those pharma companies got exposed to the technology could see for themselves that it works. And of course, now that they are being approved or on the verge of being approved, they can, of course, take that learning into their market building efforts. But we may have to the success story during this period, quite quickly, we took the decision, and that's something we discussed with Labcorp to focus a lot of the activities on the payer aspect -- and it's a huge achievement to get this -- when they got this Medicare reimbursement, sharing not only the NIS+ data, but also a big part of the NIS2+ because the discussion has been also started with medical NIS2+, and it's a big plus to why we are confident for the future because it's always a long journey and sometimes a difficult journey. So now the baseline for the future commercial success based on this medical reimbursement of the NIS technology is for us a huge commercial achievement and now we have to translate in a successful sales with NIS2+. And the last thing I would say is, for me, it all boils down to do you believe in the success of this market therapy-wise. And if you do, you've got to believe that pharma companies will be successful in their market building efforts -- and there's just -- I mean, I just don't see how you could build that market without leveraging heavily a diagnostic tool because at the end of the day, I think most speakers said it, you have to identify those patients and the only sort of practical way to do it is to do it through those blood-based tests. So therefore, it comes down to -- I don't think there's any question that, that market is going to be huge unless you don't believe that the MASH market itself will be big. But if you do believe it will be big, then the diagnostic/monitoring market has got to be big. And then the question becomes which test is going to be used as the reason why we feel that pharma companies are going to push our solution is not because they like us. But it's more that this is the test that will allow them to get to the large mass of the market, which is the F2 patients because obviously, you have more -- a lot more F2s than F3s in the approved indication. And if you are looking for patients with low fibrosis, those tests that were developed to look for fibrosis very clearly are not going to work as well. And hence, the test that will look also at that inflammation part, which is why those patients are in the approved indication in the first place is going to be the preferred approach.

Great. So our next question also from Tom Smith at Leerink. For the Genfit team, can you clarify the royalty rate that you received from Labcorp and your expectations for revenue from the NIS2+ test to Genefit?

Yes. So I mean, we understand the question. I mean, obviously, from a modeling perspective. So we've not disclosed the exact amount, and we will not disclose the exact amount with IVD either because as you can imagine, those are business development activities. So usually, our partner doesn't really want us to discuss those numbers because otherwise, I have a disadvantage in future negotiation with other potential partners. And likewise for us, for example, IVD, we might decide to work with several several payers and hence, we don't want to give the exact terms. However, what I can say is that it's going to be within industry benchmarks. So industry benchmark typically for IBD are between 7% and 15%. It's not that different for LDT. So that's where we are and also where we will be.

Great. So our next question comes from Sushila Hernandez at Kempen. Could you share color on the initial rollout via the Labcorp offering? How many tests have been sold? What income did it generate for Genfit? Is Labcorp working on getting reimbursement in other geographies? And what efforts are they putting in to get private payers to pay for the rest?