Greetings, welcome to Genfit Corporate Pipeline Update Conference Call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Stefanie Magner, Chief Compliance Officer. Please go ahead. Thank you. Good afternoon, everyone, and thank you for joining us for this pipeline and R&D update. We just issued a press release providing details about our pipeline as well as our R&D strategy. This press release can be accessed on our website at ir.genfit.com. During our call, we will be making forward-looking statements as defined under the U.S. Private Securities Litigation Reform Act of 1995 with respect to Genfit, our expected future performance, business prospects, corporate strategy, events, and plans, including our R&D and clinical development programs and financial guidance. These forward-looking statements are based on our management's current assumptions and estimates, which although believed to be reasonable, are subject to numerous known and unknown risks and uncertainties, which could cause actual results to differ materially from those expressed in or implied or projected by the forward-looking statements. For a further discussion of the material risks and other important factors that could affect our business operations and financial results, please refer to those contained in our most recent filings with the SEC and AMF. These forward-looking statements speak only as of the date of this webcast. Other than as required by applicable law, the company does not undertake any obligation to update or revise any forward-looking information or statements, whether as a result of new information, future events, or otherwise. Joining me on the call is Pascal Prigent, CEO, Dean Hum, CSO, and Carol Addy, CMO. Following the prepared remarks, we'll open up the call for questions that will be addressed by Genfit management. Please limit yourself to one initial question to allow time for other questions. I now turn the call over to our CEO, Pascal Prigent. Thank you, Stefanie, and good afternoon, everyone, and thank you for joining this discussion. The purpose of our webcast today is to give you additional details about our R&D strategy, discuss our pipeline and the status of our different programs, and finally, talk about the clinical studies we are about to start and what it means in terms of upcoming milestones. I'll start with a reminder about our corporate strategy and talk about the choices we've made in terms of R&D. Dean will give you more details about our different research programs. Finally, Carol will talk about several new clinical studies that we are planning to initiate later this year, as well as our development plans for the future. Let us first contextualize today's discussion. Exactly a year ago, we announced the disappointing top-line results from our RESOLVE-IT study in NASH. We then took a few months to really analyze the data in depth. In the fall, we announced our new strategy. You will recall that we said we were terminating the development of elafibranor in NASH, as well as a few associated R&D programs that were NASH-related. We announced that we will be focusing on two lead programs, the development of elafibranor in PBC, and the development of our NIS4 NASH diagnostic program. We also indicated that our short-term priorities will be to reorganize the company and eliminate non-essential spend to substantially reduce our cash burn, as well as renegotiate our convertible debt. At that time, we had EUR 180 million convertible debt that was due in October 2022, which was posing a significant threat for the company. Finally, we said that we were going to embark on a critical review of all R&D programs and focus on the most promising ones. We've actually accomplished quite a lot in the last nine months, and I'm pleased to report that we've made good progress on the execution of that strategy. The first patient visit in our phase III PBC registration study, ELATIVE, took place at the end of September last year, and enrollment so far is broadly progressing according to plan. There is no question that it has been a challenging environment and that the COVID pandemic has made things more complicated and slower. That being said, we had planned for this challenging context with our CRO, both in terms of timelines and in terms of implementing mitigating measures. Therefore, considering the fact that vaccination is progressing globally and should improve the situation, we are cautiously optimistic and maintain our guideline of Q1 2023 for high-level results. We will give you an update on the progression of ELATIVE in September this year. We think that in a few more months, we will have more visibility about the evolution of the situation globally and what it means for the conduct of our trial. Regarding our diagnostic program, we just announced the commercial launch of NASHnext by Labcorp. This is a significant milestone, as our NIS4 technology is now going to be widely available for healthcare professionals in the U.S. We are also very pleased to see NIS4 being used by more and more sponsors of NASH clinical trials. This is significant because widespread use in clinical research will allow for further improvement of the product and also lay the groundwork for further future market penetration. As previously indicated, it remains challenging to forecast short-term uptake in a market where no NASH drug is currently approved or commercialized. Now that NASHnext has been launched and commercialized by Labcorp, we expect to start collecting interesting insights. We will discuss NIS4 perspectives during our September corporate update. The third pillar of our strategy was our multi-pronged financial restructuring. We fully implemented our savings plan as well as our reorg, and the rhythm of our cash consumption that was around EUR 110 million per year just before RESOLVE-IT is now less than half that number. We therefore maintain our guidance of a EUR 45 million cash burn in 2022. As already announced, 2021 will be a transition year because we will still incur significant costs related to RESOLVE-IT as well as some restructuring costs. This means that as of today, and based on our projected cash burn, we have approximately two years of visibility. Finally, we successfully restructured our convertible debt at the beginning of the year. The remaining outstanding convertible debt with a partial buyback and the conversions that took place then is now less than EUR 60 million, and the maturity has been pushed back to Q4 2025. The last pillar of our strategy, that fourth box, is the subject of today's call, and it is our R&D strategy. Following the announcement of our new corporate strategy last year, we conducted a full review of all of our different R&D programs. For each, we assessed the strength of the scientific evidence informing the probability of success of our assets. We carefully looked at the unmet medical need and patient population to determine where we could add the most value. At the end of this exercise, we decided to focus on two areas where the burden of disease is high and where no or little therapeutic options exist today for patients. Those two areas are ACLF, or acute-on-chronic liver disease, and cholestatic diseases. Let's first take a closer look at the rationale for this choice. We considered our strength and experience, both in research for several liver diseases and also in development of novel therapies for liver diseases with no or few therapeutic options. We looked at the data we had, both external but also internally generated, for all various assets in several indications. Our conclusion was that the programs with the greatest potential were actually our programs in acute-on-chronic liver failure, ACLF, a syndrome in patients with chronic liver disease characterized by acute hepatic decompensation resulting in liver failure and one or more extrahepatic organ failures. This condition is associated with an increased risk for mortality within a period of 28 days and up to three months from onset. Unfortunately, there is currently no approved therapy for this patient. Also promising were our programs in cholestatic diseases. As you know, these diseases are characterized by defective bile acid transport from the liver to the intestine, which is caused by primary damage to the biliary epithelium in most cases. As a result, we terminated all of our research programs, except of course, those that are supporting the development of NIS4, and we focused all of our resources in those two fields. Let's first talk about ACLF. First, the unmet medical need is pretty obvious. You have a disease that is life-threatening with a high mortality at 30 days and no approved treatment. There is a strong need for a therapy that will help patients survive ACLF without liver transplantation, which is currently the only option. The market opportunity is substantial with 180,000 patients in the U.S. It's about 10%-30% of cirrhotic patients that are hospitalized in the U.S. The market research estimates this market at roughly EUR 4 billion in the U.S. and about half that number in Europe, $4 billion. The cost to the healthcare system is also important because these patients typically consume lots of healthcare resources, need longer hospital stays, and end up needing transplantation, which, as you know, costs almost $1 million per transplantation. This is an orphan indication, which has obvious implications in terms of exclusivity and regulatory pathway. We have three programs in ACLF. Two are in pre-clinical stage. That's for elafibranor and GFT1575, which is another PPAR. We have also decided to take the third program into clinical development. As far as the two PPAR programs are concerned, we believe there is clear scientific rationale for accelerating those programs. For NTZ, we have already generated strong pre-clinical data, and our KOL advisor was actually really supportive of going into clinical development. We are starting immediately with the phase I. Let's now talk about cholestatic diseases. We are obviously well into the development of elafibranor for the second-line treatment of PBC. We know that although treatment options do exist there is still an unmet medical need. There are, however, other cholestatic diseases for which no treatment option exists and where obviously the unmet medical need is great. PSC is also an orphan disease with currently no approved treatment. The burden of disease is significant. There are slightly fewer patients with PSC than PBC, but the market is significant nevertheless, and we estimate it to be about two-thirds of the PBC market. Finally, there are several pediatric cholestatic diseases for which there is no treatment option to date. Those diseases tend to be genetic diseases, and we started a program to evaluate molecules that could have beneficial effects. With that, I will now turn over to Dean, who is going to provide more granularity about the rationale for focusing on these two franchises and also talk about the different ongoing programs that we have. Dean? Thank you, Pascal, and hello, everybody. As many of you can imagine, this is a very busy time for us at Genfit. However, it's also very exciting and motivating for the teams as we move forward in the execution of our R&D strategy, as described by Pascal, and which I will be providing you with a more detailed overview. Let's start with ACLF. I'd like to describe ACLF, and we can see on this slide, and really this is a program that's exciting for us, and it really builds on our established knowhow in liver disease. In the context of the spectrum of end-stage liver disease, ACLF really is by far the most advanced. It's a syndrome in patients with chronic liver disease and cirrhosis who present with acute hepatic decompensation, along with one or more organ failures. This is associated, as Pascal had mentioned, with a significant increased risk for mortality within a period of 28 to 90 days from onset. This graph here depicts a spectrum of end-stage liver disease, where initially, patients with chronic liver disease have compensated cirrhosis. At this point, patients retain much of their liver function and do not manifest any impairment in other organ systems. However, over time, these patients might undergo an acute decompensation event, which is often associated with a precipitating factor such as bacterial infection, alcohol abuse, or drug-induced liver injury. In general, patients with acute liver decompensation are hospitalized for treatment of the underlying precipitating event. However, about 30% of patients will have further worsening of their condition to include one or more organ failures. At this point, this is referred to as ACLF. These patients often require transfer into an intensive care unit setting for comprehensive care, depending on the organ systems that have failed. These patients are acutely ill, a greater number of organ failures is associated with higher rates of mortality. Here we can see on the right-hand side that the 28-day mortality rate of ACLF patients with one organ failure is 15%. This increases to 32% with two failed organs, if this includes three or more organ failures, the mortality rate actually goes up to 80%. The organ systems involved in ACLF are the liver, the kidney, the circulation, heart, brain, and the lung. Some patients may ultimately require liver transplantation in order to improve survival. Taken together, it is easy to see the drivers for increased healthcare costs that is required to optimally care for these critically ill patients. It is known that ACLF patients who survive an event are at risk of having subsequent events. It's important to note that less liver function is retained after each event, the risk of mortality is further increased. The objective of therapy includes the treatment of patients who present with an acute event to prevent the short-term mortality, to halt the progression to additional organ failures, to prevent subsequent decompensation events, and ultimately, to reverse organ failure. Following with this brief description of ACLF, let's now try to understand why and how PPARs and NTZ may benefit ACLF patients based on the mechanisms of action. The etiology of ACLF is heterogeneous, this has to be taken into consideration that different chronic liver diseases lead to ACLF, such as viral hepatitis, the alcoholic liver, cholestasis, and NASH. However, there are pathways and biological systems which are commonly involved regardless of the associated liver disease. One major element in ACLF is the intense systemic inflammation leading to organ failure, which is driven by damage-associated molecular patterns, which are also known as DAMPs, as you see here on the right-hand side of the slide, as well as pathogen-associated molecular patterns, known as PAMPs. DAMPs are molecules released from stressed and dying cells, where several forms of liver damage has been shown to release DAMPs into the circulation, which go on to activate the innate immune system, and to production of pro-inflammatory cytokines leading to the so-called cytokine storm, as you see depicted here. This is actually leading to subsequent organ damage. PAMPs, on the other hand, are microbe-derived molecules which are released into circulation, leading to overactivation of systemic inflammation and organ damage and failure. For example, a well-known paradigm of this mechanism is the engagement of the Toll-like receptor 4 by lipopolysaccharides, or LPS, which many of you have heard of. An LPS is a DAMP, is a PAMP, sorry, it's a PAMP derived from the cell wall of Gram-negative bacteria. Another important aspect, however, of the innate immune system is the impact it has on metabolism in different organ systems. As an example, in ACLF, the increased systemic inflammation down-regulates PPAR alpha target genes involved in mitochondrial beta-oxidation, with the consequence of decreasing energy supply from fatty acid oxidation. As well, the accumulation of these non-oxidized fatty acids and the stimulation of mitochondrial ROS, or reactive oxygen species, production by inflammation may also occur in ACLF and cause mitochondrial damage. Taken together, the mitochondrial dysfunction and a decreased energy supply can contribute to the development of organ failures. Therefore, based on the pathophysiology of ACLF, it's apparent that there are multiple contributory pathways in the process which may be impacted by drug intervention. If we consider what is known about the antibacterial and anti-inflammatory activities of NTZ activity, it would be expected to impact the microbial dysbiosis in the gut, and as a consequence, lead to the decreased production of PAMPs. As well, NTZ should impact beneficially on the intestinal barrier, and through this mechanism, also decrease the risk of bacterial infection. NTZ also has direct effects on inflammatory pathways. Taken together through these multiple mechanisms of action, it is hypothesized that NTZ might significantly decrease systemic inflammation and prevent organ dysfunction and organ failure in ACLF, and potentially decrease the high rate of mortality in these patients. The other drug candidates which we will move forward with in ACLF are the proprietary PPAR agonists, which we have in our portfolio of molecules. The three PPARs, Alpha, Delta, and Gamma, are each regulators of metabolism, and they each have anti-inflammatory activities. Therefore, it is hypothesized that the activity of PPARs could impact beneficially on different steps in the pathophysiology to decrease systemic inflammation. PPARs can also potentially alleviate the metabolic stress in organ systems to prevent organ dysfunction and failure. Now that I've briefly described this and we have an understanding of the mechanisms of both PPARs and NTZ, let's see what the literature tells us about their potential in ACLF. As you know, we have repositioned NTZ in liver diseases based on properties we have identified in pre-clinical models with this compound. Through its antibacterial activity on anaerobic gram-negative bacteria, it is hypothesized that NTZ could address dysbiosis in the gut to decrease production of PAMPs, such as LPS, and help retain function of the intestinal barrier to prevent infections and dampen systemic inflammation. In terms of mechanism, NTZ was shown to inhibit several steps in the NF-kappa B inflammatory pathway and the phosphorylation of components in the MAP kinase pathway. Therefore, it is apparent that the anti-inflammatory activity of NTZ involves both the NF-kappa B and MAP kinase pathways. Now, in our own experiments performed at Genfit, we have also shown that NTZ has anti-inflammatory activities in macrophages where it addresses LPS-stimulated cytokine production. If we think about PPARs, for PPARs, there is ample evidence of their anti-inflammatory activities demonstrated both in in vitro and in vivo models, as well as in the clinic. It is equally important for the hypothesized efficacy of PPAR agonists in ACLF is their role in maintaining metabolic equilibrium. Of PPAR activities which should be beneficial in avoiding organ dysfunction in ACLF includes increasing and maintaining mitochondrial beta-oxidation and use of fatty acids as energy source, decrease of oxidative stress, and maintenance of mitochondrial function. Beyond what is known in the literature, at Genfit, we have been profiling NTZ, as mentioned by Pascal, in different in vitro models, and we have generated results on inflammation and cell survival, which are indicative of a hypothesized benefit of NTZ in ACLF. We have also profiled NTZ in in vivo models. If we think about the clinical situation for a minute where patients present with acute decompensated liver function, it is, or it will be important for the therapeutic approach to have a rapid activity on inflammation. To address this in one model in wild-type rats, we can see on the left-hand side here that the administration of LPS leads to a rapid increase in systemic inflammation and pro-inflammatory cytokines in the circulation observed only after three hours. If we administer NTZ, we can see that it has an immediate effect to inhibit the increase in cytokines, and similar results were obtained when we looked at liver enzymes such as ALT, AST, and gamma GT. Which when taken together, is indicative that NTZ has a rapid action to impact on inflammation and potentially have an impact on organ function. We also profiled NTZ in the gold standard model of ACLF, where liver fibrosis and cirrhosis are first established by CCl4 treatment. This is on the right-hand side. LPS is administered to induce acute decompensation, where we have observed rapid improvement in liver markers and markers on renal function. The totality of the data has been presented to several of our scientific advisors, who are KOLs in ACLF, and the feedback has been unanimous that the results are very compelling and in particular, the data from in vivo disease models, which when taken together, are very supportive of proceeding with the clinical evaluation of NTZ, which Carol will be outlining for us later on in this webcast. Let's transition from our focus on ACLF to our focus on cholestatic diseases. As highlighted by Pascal, considerable unmet needs remain for patients with cholestatic liver diseases, some of whom would benefit from optimization of approved treatment options, and some of whom are currently lacking any approved treatment options. With this in mind, let's consider the underlying pathophysiology of cholestatic diseases. Although these diseases are heterogeneous in terms of patient population and underlying mechanisms, they do have a common denominator, and that is defective bile acid transport from the liver to the intestine. Simplistically, bile acids are toxic and impaired flow of bile acids results in damage to the liver and to cholangiocytes, which are cells that line the bile ducts. This toxicity results in either damage to the liver and/or damage to the bile ducts, which over time may result in inflammation, fibrosis, cirrhosis, and if left unchecked, may result in end-stage liver disease, increased risk for malignancy, and the need for liver transplant. Of course, there is not one specific pathway that is ultimately responsible for cholestatic disease. We currently understand, however, that there are multiple contributing pathways that result in the development of and the progression of cholestatic diseases, including those pathways responsible for bile acid synthesis and output, bile acid toxicity, and the resulting inflammatory pathways. Mechanistically, there is considerable evidence of the potential for PPAR agonists to impact these pathways. Considering that PPARs are nuclear receptors which can regulate different genes involved in biological pathways, the anti-cholestatic activity of PPAR agonism can be explained, at least in part, by different mechanisms, which include the ability to regulate the synthesis of bile acids through the inhibition of genes like CYP7A, which catalyzes the conversion of cholesterol to bile acids. However, PPARs can also regulate the elimination of bile acids by increasing their glucuronidation and sulfation. As well, PPARs regulate the expression of transporters which are involved in the transport of bile acids from hepatocytes to the bile duct. PPARs can also regulate the transporters of cholesterol and phospholipids into the bile ducts to form mixed micelles, which engulf and detoxify bile acids. Last but not least, the three PPARs have anti-inflammatory activities, where inflammation, of course, is a key component of many, if not all, cholestatic diseases. These mechanisms explain, at least in part, the anti-cholestatic activity of PPAR agonists like elafibranor, as has been shown in the phase II trial. There are several examples of PPARs having established clinical proof of concept in cholestatic disease. We know this from the elafibranor phase II trial in PBC, in which we observed reductions in a panel of relevant markers, which include gamma GT, 5'-nucleotidase, IgM, CRP, and serum alkaline phosphatase, which is a major marker of cholestasis. We see this along with reductions in bile acid precursors and a trend for improvement in pruritus, which is a major symptom for patients with PBC. As well, elafibranor was well-tolerated without safety issues in the phase II trial in patients with PBC. Furthermore, a study was recently conducted with a pan-PPAR agonist, which is summarized on this slide. The FITCH study evaluated patients with cholestatic disease, including PBC, PSC, and secondary sclerosing cholangitis with moderate to severe pruritus. Following 21 days of treatment, the use of the fibrate was associated with significant improvement of pruritus and clinically meaningful reductions in alkaline phosphatase compared to placebo. This molecule was generally safe and well-tolerated. The published data on various PPAR agonists are supportive of clinical proof of concept in cholestatic disease. Clinical data, as I had just highlighted, demonstrate a clear correlation of PPAR agonism and anti-cholestatic activity, including the reduction in serum alkaline phosphatase, which we understand to be well associated with long-term clinical outcomes in PBC, and which in part would serve as the basis for an application for approval in this disease under the accelerated pathway. The correlation of alkaline phosphatase reduction with clinical outcome. In other cholestatic diseases, such as PSC, it is less clear, although there are some studies that support this correlation, as is highlighted on the right-hand side of this slide. For this reason, and in contrast to PBC, it is likely the alkaline phosphatase reduction will not be a standalone endpoint for initial registration in PBC. This would require active discussion with regulatory authorities. Having walked you through the scientific rationale for our programs moving forward in ACLF and cholestatic diseases, let me provide you with an overview of our R&D programs on the next slide. Here, just let me conclude with the overview summarizing our research programs in both franchises. In cholestatic disease, we will be considering rare pediatric cholestatic diseases, where we plan to conduct early-stage drug discovery to identify innovative hit compounds and drug candidates. This can also include the profiling of existing proprietary Genfit drug candidates in specific disease models to identify those with a high probability of success to advance into development. In ACLF, we will proceed with the profiling of elafibranor and GFT1575 in disease models. We are particularly excited on the prospect of targeting PPARs and addressing the role of immunometabolism in ACLF in this emerging area of high unmet need. I would like to note that we have robust IP for all these programs. We have patents covering the use of elafibranor in both cholestatic diseases, PBC and PSC, which do not expire until 2037, and that excludes any patent term extension. In ACLF, IP protection does not expire until 2040 with NTZ, again, excluding any patent term extension. With that said, I will now hand things over to Carol, who will walk us through the development programs. Carol, the floor is yours. Great. Thank you, Dean. Over the last few minutes, Dean has provided you with an overview of the mechanisms of action and the scientific literature that are supportive of NTZ as it pertains to ACLF, and as well for Genfit PPAR agonist development candidates for both ACLF and cholestatic diseases. In addition, as Dean has mentioned, we've also taken the opportunity to engage with KOLs and thought leaders so that we may review these disease states, the scientific rationale for the mechanisms of action of our development candidates, our available preclinical and clinical data, all of which will help us to better understand the probability of success for moving these programs forward into clinical development. As for ACLF, there's been general consensus from KOLs with whom we've engaged, including Jonel Trebicka from the University of Frankfurt, and just generally supported in terms of the NTZ preclinical data that Dean shared with you, all of which are quite supportive of advancing into a phase I study in patients with hepatic impairment. I'll provide you with an overview of that study in a moment. We've engaged with highly regarded leaders in the field of cholestatic diseases, including Dr. Christopher Bowlus at the Liver Institute Northwest in Seattle, Washington, all of whom are very supportive of further exploration of PPAR agonists, and in this case, specifically elafibranor in other cholestatic disease indications such as PSC. On this slide, on the development side of things, we're of course, currently concentrating most of our efforts on ELATIVE, our ongoing phase III pivotal trial in PBC. We're also planning to explore the activity of elafibranor on a number of parameters in treatment-naive patients with PBC. I'll tell you more about that in a moment. As well, we'll be moving forward with our elafibranor program in PSC with a phase II proof of concept study. As it pertains to ACLF, we plan to initiate a phase I PK/PD study with NTZ in patients with impaired liver function based upon the rationale and the mechanisms that Dean has described earlier. With all of that as a backdrop, why don't we advance to the next slide, and I'll provide you with an overview of our upcoming development plans. Go on. Firstly, let me provide you with an overview of our cholestatic disease programs at the top of the slide. As you're aware, our elafibranor phase III ELATIVE trial is underway, and we're well on track for top-line data readout in the first quarter of 2023, which, if favorable, of course, will be supportive of NDA submission under the accelerated approval pathway based upon week 52 biochemical markers. We're also very excited about the initiation of an exploratory study to be initiated later this year to broaden our experience with elafibranor in patients with PBC, this time specifically to evaluate treatment-naive patients. To remind, these are patients who are not currently eligible to participate in the ELATIVE trial and who were not previously evaluated in the phase II study in PBC. At the same time, we're also keenly aware of the significant unmet needs that remain for patients with PBC as it pertains to quality of life. This study is also going to give us an opportunity to do a deeper dive in terms of quality of life assessments and patient-reported outcomes. As you know, fatigue and sleep disturbance are particularly troublesome for patients with PBC, and we're planning to utilize a novel sleep tracking device in this study, which we hope will provide us with some valuable insights related to sleep quality in patients with PBC, and which may, in fact, provide us data that could serve as hypothesis generation, potentially serving as the basis for longer-term and more definitive assessment of sleep and quality of life in the future. Our current projections for that study in terms of data availability, targeting toward the end of 2022. Moving on to PSC, given the solid scientific rationale that Dean has described in terms of PPAR agonism in cholestatic disease, we're planning to initiate an elafibranor proof-of-concept study in patients with PSC also by the end of this calendar year. This is currently in the concept stage, but initially, we're looking at this as a six-week study that will be aimed to evaluate serum alkaline phosphatase, which of course, we well understand to be a prototypic marker of cholestasis, and as Dean pointed out, the reduction of which, at least in some studies that we've shared with you, has been associated with improved outcomes. We also are giving consideration to including a longer-term open label extension in this study, which will not only afford us with opportunity for longer-term assessment of durability of effect, but as well an evaluation of hepatic fibrosis, which we know, of course, is an important element in the progression of disease in these patients. Lastly, but certainly not least, the opportunity to have a longer-term evaluation of safety in this new treatment population. Right now, we're anticipating data for this study to read out toward the end of 2022. Let's change gears and move on to ACLF toward the bottom of the slide. As mentioned, we will be initiating a phase I study to evaluate NTZ in patients with varying levels of hepatic impairment. This study also planned to initiate toward the end of this year, initially evaluating a single dose so that we may have an initial assessment of PK and safety in this patient population, which will better inform dose selection for multiple dose administration that will follow. Of course, that multiple dose administration will be very important for us as we initially explore the pharmacodynamic effects of NTZ in this population, and specifically looking at those markers that Dean described to you in preclinical studies, including liver, renal, and importantly, inflammatory markers. Based on current projections here, we anticipate that the totality of data from this study will be available in 2023 to inform a go, no go decision for our moving forward into a more definitive proof-of-concept study to be conducted in more acutely ill patients with acute decompensation and early ACLF. Dean mentioned as well, we've got some preclinical work ongoing in ACLF models, both with elafibranor and our GFT1575 development candidate. Of course, depending on the results of these preclinical studies, we may be positioned to move forward as early as the end of 2022 to a proof-of-concept study with elafibranor and potentially sometime in 2023 with a phase I study with our 1575 candidate. All of this taken together, this is an extremely exciting time for us as we move forward with these clinical programs, and in particular, strongly supported by the scientific rationale and the encouragement that we have received from the thought leaders with whom we have engaged. With that, Pascal, I'm going to hand it back to you for our Q&A session of this webcast. Thank you, Carol. We will now open this for Q&A. Thank you. If you would like to ask a question, please press star one on your touch-tone telephone. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Once again, if you would like to ask a question, please press star one on your telephone keypad. Our first question today is from Thomas Smith of SVB Leerink. Please proceed with your question. Hey, guys. Good afternoon. Thanks for taking the questions. I have a few. Just to start on NTZ, I know there's been a fair amount of data generated for this compound historically. Can you provide a little more color on the data that's been generated in NASH-induced fibrosis? I guess, how does this help inform your development plans here, and are there plans to present those data? Tom, this is Carol. I can address that question, and I'll invite Pascal and Dean to add in. As you're well aware, the NTZ study to evaluate NASH-induced fibrosis is an investigator-initiated study. In fact, that study did recently complete, and we've just, in fact, received the data and we're in the process of reviewing it. I think the important thing for us moving forward, acknowledging the different pathways contributing to fibrosis are not entirely the same pathways that we're giving consideration to for ACLF, so not necessarily an apples to apples comparison. I think the real critical thing is that the safety data from that study, at least the extent to which we've reviewed at a very high level, are very supportive of our now moving forward from a patient population, NASH with fibrosis, now moving into patients with hepatic impairment, as I described, that we'll be evaluating in our phase I study. Okay. Thanks, Carol. Appreciate that color. I guess, given the heterogeneity of ACLF, can you maybe provide some color or talk to the types of ACLF patients you ultimately intend to target in a clinical program? Is there any regulatory guidance here, or are there any precedent clinical programs that you can look to as a guide? Yeah. I'd have to say that this kind of harkens back to Genfit being a pioneer with NASH. I think we're finding ourselves in a similar situation with ACLF as the science is really emerging. As Dean highlighted, the multiple contributory pathways where we feel that we can reasonably have impact with our development candidates. That's even part of the story as we continue to learn more and similarly learning more about the clinical aspects of the disease. We know, to your point, this is a very heterogeneous population in terms of the basis for the underlying liver disease, whether it be due to viral infection, alcohol, NASH. As Dean pointed out, we also know that precipitating events can be variable, whether that be acute alcoholic hepatitis, drug-induced liver injury, infection typically being one of the more common. What we are going to be doing in our program, as we work with KOLs to optimize the design of our program, and ultimately we'll be discussing with regulatory authorities, how can we identify the common denominator that's really going to be critical and undermine the pathophysiology regardless of the patient type. I think one of the big challenges, as we've been working with KOLs, is how to identify the subset of patients who are admitted with acute decompensation, who ultimately do progress to ACLF with one or more organ system failures. I think that's going to be really critical, as we will be looking at our very early phase I data to help us have some insights in terms of where we stand the best opportunities with NTZ moving forward. I think the only thing I would add to that, Tom, thank you for the question, is that the initial approaches that we're moving forward with, if we take NTZ to start with, I think what's important is that when you think about ACLF, the one important aspect, of course, is the systemic inflammation. When we think about NTZ, irrespective of the source or the underlying cause of the acute decompensation or the underlying cause of the ACLF, it's expected that NTZ should have or is hypothesized to have an impact or a major impact on systemic inflammation. That's coming through the different mechanisms which I tried to convey, which is the different activities NTZ can have on the level of microbiota on the gut, but also direct effects on the different pathways of inflammation or the inflammatory pathways. Same thing for PPAR. We're excited to move forward with the PPAR approach. That's because of our understanding that in these patients, there is an interplay between the immune system as well as the metabolic system. The PPARs, not only will they impact directly on inflammation, but of course, this interplay between inflammation and metabolic pathways is something that's defective in these patients. Part of it's due to the systemic inflammation. Part of it is the inflammatory pathway reacting to a dysregulated metabolic pathway. I think PPARs really play a cross role in this, having both activities on inflammation, of course, as well on the metabolic pathways. Dean, maybe I'll just add one more thing there. When we give consideration to NTZ, I think one of the data findings that you presented that I think are particularly exciting is the speed with which NTZ can quiet down that inflammatory response following LPS administration in that rodent model. When you think about the patient population, these are acutely ill patients, and there's a very narrow window of opportunity to get whatever precipitating events may have caused their hospitalization, but just to get everything under control in order to prevent that progression to organ dysfunction. I think that's one of the really exciting elements that we've seen with NTZ that I think will be very exciting to evaluate in the clinic. Got it. Okay. Yeah, appreciate the color. Maybe just one last question, then I'll hop back in the queue. Just, I guess provide a little more detail or color on GFT1575 and how the profile of this compound compares versus elafibranor. Yeah, Tom. Thank you again for that question, a very important question. I think first it's important to realize where 1575 is coming from. Both elafibranor and GFT1575 are coming from our own internal medicinal chemistry efforts. Over the years, we've generated several thousands of different PPAR compounds, and we've also now shortlisted several of them who are getting really close to be drug candidates, and this includes 1575. These different PPAR agonists, they have different potencies, different maximal activities. Some of them may have SPPARM activities. Sorry, SPPARM is Selective PPAR Modulation activity. Also they have different valencies, meaning they have different activities on the three PPARs, whether they are Alpha, Gamma, and Delta. This is where 1575 is coming from. As of today, I cannot provide more detail about 1575. We are moving forward aggressively with this molecule, and there are different intellectual property considerations to be taken account. We will be guiding further as we move forward and we go through different steps of IP protection. Okay. Dean, when can we expect to learn more about the profile of that compound? Well, I think we're going to need some time to get the IP stuff figured out. I would say reasonable to think later on this year. Okay. Thanks for the color, guys. I appreciate you taking the questions. Thanks, Tom. The next question is from Ed Arce of H.C. Wainwright. Please proceed with your question. Great. Thanks for taking my questions. Thank you very much for this overview on your expanded pipeline. A few questions for me. Firstly, on ACLF. Very intriguing. As you know, this is a very difficult-to-treat condition. As you described, it often precipitates ultimately to multi-organ failure and has a heterogeneous nature, both the disease and the patient profiles. I'm curious, as you discuss the potential for NTZ with its rapid systemic anti-inflammatory properties and potential PPARs, and the interplay between those two PPARs with their role in maintaining metabolic equilibrium, as you mentioned. Ultimately, do you believe that what's needed to really address this disease state meaningfully is a study of a combination treatment regimen? Just in general, how would you view the prospects of either one of those as a monotherapy in this disease? Thank you, Ed. Dean, if you want to go ahead and I can add some clinical color perhaps. Sure. Ed, thank you for that question. Moving forward, Ed, our vision is that we are hopeful and the hypothesis and the expectation is that both of these molecules should provide benefit to the patients and provide clinically relevant impact to be able to read out. At this point, we're not thinking necessarily about combination therapy. The reason for that, Ed, is, again, I'll just use PPARs as an example. It's the same for NTZ. Because NTZ and PPARs have activities on different aspects of ACLF. Okay? We expect it to have a major impact on the pathophysiology processes and different pathways. PPARs, for example, we all know they have different anti-inflammatory activities, and if you think about Tom's question on what do we know about 1575? Different PPARs have different anti-inflammatory activities. Having said that, let's come back to this question of immunometabolic pathways. What we know, for example, is that very high systemic inflammation actually impacts on metabolic pathways. I spoke at a high level about this, where increased systemic inflammation actually decreases and inhibits mitochondrial function and inhibits oxidative phosphorylation. This leads to less energy use, but this also leads to increased oxidative stress and defective, and then decreased mitochondrial function. You know that different PPARs can act on that. For example, we know that PPAR delta has a good activity to increase mitochondrial function, whereas PPAR alpha can actually increase beta-oxidation. Another interesting aspect is that systemic inflammation actually leads to the decrease of PPAR alpha activity, or PPAR alpha downstream pathways. Inhibition of those pathways. I think one way to address that is with a PPAR alpha agonist. On the flip side, what we also know when you think about immunometabolic pathways is that the immune system, the activity of the immune system is impacted by defective metabolic pathways. For example, in systemic inflammation, you have an increased use of glucose. What's happening is that when the inflammatory system uses up all that glucose, it actually gives you an energy deficit at the other organ systems. Could that be part of the decrease or loss of organ function? That could be the case, I think one way to address this is, again, because PPARs are major regulators of metabolic pathways, that you can address the defective or lacking metabolic system in the immune system itself. Okay? Address it that way as well. The short of your question, Ed, is really we are thinking that both NTZ and the PPARs should independently provide clinical benefit in these patients. Okay. Thank you, Dean, for that. The other question I had, well, actually the second question is around the phase II study that you plan to initiate with elafibranor in PSC. I think it was briefly mentioned, but if you could go over again the biomarkers that you intend to evaluate for putative activity in PSC patients, kind of the measures that you're looking for that will also help you inform next steps for that program. Sure, Ed. I'd be happy to address that question. Right now, our concept and vision is for a proof of concept study where we will administer elafibranor or a placebo for six weeks duration for assessment of serum alkaline phosphatase. Of course, that being kind of the prototypical cholestatic marker. Now, we know that alkaline phosphatase as a sole readout in the setting of PSC is challenging. We know that alkaline phosphatase is far more variable in patients with PSC, and we also know that fibrosis is an important pathophysiology underlying the progression of disease. Whereas our short-term readout of alk phos, we also will be implementing assessment non-invasively, assessment of fibrosis in the open label expansion, which will afford us opportunity to evaluate what we would anticipate being lack of progression in fibrosis. Hopefully, that helps. Current thinking is, although there's no clear regulatory roadmap for registration in PSC, current thinking as we understand it from the International PSC Study Group and regulatory authorities, including FDA, is that registration for accelerated approval would be based upon alkaline phosphatase and some assessment of fibrosis. Then not dissimilar to PBC, that full approval would be based in part on clinical outcomes, long-term clinical outcomes. Okay. That's very helpful. Thank you, Carol. You're welcome, Ed. Thank you. One, I guess final question then is just to make sure I understand the timelines now, given that you have an expanded pipeline here of programs at different stages. I'm just going to lay these out, and please correct me at the end if any of these were stated incorrectly. I believe your ongoing phase III ELATIVE is expected to have a readout in first quarter of 2023, or perhaps first half of 2023. The PSC study, the phase II, would have data at the end of next year, 2022. The ACLF study, the phase I study, would have data in the second quarter of 2023. I guess a related question to that final one is, as a phase I study, looks like the full duration from initiation to data would be about 18 months. I'm just curious as to why that would take that long for a phase I. Obviously, these are extremely severe patients, and so perhaps just recruitment is a big part of that. Yeah. That's a great question. Firstly, you're right on target in terms of the timelines, in terms of PBC phase III, first quarter 2023. Same thing for the phase II proof of concept in PSC, that being toward the end of 2022. Good observation with regard to the phase I study with NTZ. What we need to do first is to do a single-dose PK assessment in varying levels of hepatic impairment. This is critical because we need to ensure that the dose we select for NTZ moving forward in acutely ill patients is going to be a safely administered dose. The first part of this study is just that. It's a relatively routine phase I hepatic impairment PK study so that we will match Child-Pugh A, B, and C patients with healthy volunteers, looking at the PK profile and safety in order to inform that decision on dose, which then will move forward into the multiple-dose section that I made mention of, that will help guide and give us a better understanding of pharmacodynamic effects of NTZ. Again, looking specifically at liver, renal, and inflammatory markers to inform decision-making to move forward. Does that help? Yes. That's fantastic. Thank you, Carol. You're welcome. Appreciate the perspectives. Of course. As a reminder, if you would like to ask a question, please press star one on your telephone keypad. Our next question is from Geoff Meacham of Bank of America. Please proceed with your question. Hey, guys. It's Aspen on for Geoff. Just two questions from us. Thanks for taking them. First off, just want to confirm what I think you said on one of the prior questions on PSC. There's been no real development with the FDA in terms of the appropriate development pathway for that asset, right? They haven't specifically indicated what an approvable endpoint would look like? There's been no formal guidelines issued, but certainly through their publication, their contributions to publications. For example, Lara Dimick-Santos, who's one of the major reviewers at FDA for this reviewing division, has contributed to a paper sharing current thinking of regulatory authorities, at least here in the U.S. As mentioned, looking at kind of a co-primary endpoint, alkaline phosphatase plus some assessment of fibrosis. We can get a sense of this as we look at the Gilead study that's ongoing with cilofexor, where they're doing just that. I think that will serve as a benchmark. Clearly, as we complete our proof of concept study, we, of course, will seek to engage with regulatory authorities so that we may have a better understanding of that pathway to registration. Got it. Okay. That's very helpful. Appreciate that. Sure. My second one is, maybe you can just walk us through how you're thinking about the cost-benefit analysis of elafibranor in that newly diagnosed patient population. Essentially given the availability of UDCA. Thanks. This is truly going to be an exploratory study. As mentioned, we're really seeking, number one, to broaden our experience with elafibranor. This will be a very small study, not definitive by any stretch of the imagination. Really do want to take the opportunity to look at this segment of the patient population who is truly naive to therapy. Of course, we'll be looking at biochemical markers. I think one of the real exciting things for us here is, as I said, the deeper dive that we want to take in doing some of the quality of life assessments, and in particular, the sleep quality assessment, which we're particularly excited about. We know that healthcare technology is emerging, and to be able to utilize such technology in a study such as this, I think really is, in some ways, going to just really open things up in terms of where this field may move as we give consideration to patients and the unmet needs that they have. Okay, great. Thanks for the feedback. Sure. There are no additional questions at this time. I'd like to turn the call back to Pascal Prigent for closing remarks. Thank you. Well, I find these R&D calls to be very relaxing, with very few questions coming my way. Our R&D strategy was really the last piece of our new corporate strategy. We carefully reviewed the programs we had, and we decided to focus on those two franchise, ACLF and cholestatic diseases. The unmet need is high, with a significant burden of disease, and usually no or few therapeutic options. We are very excited about the prospect we see for our programs to eventually, potentially help patients with those diseases. We are now committed to execute this R&D program, and we will keep you posted about the development of these programs. Thank you very much. This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.