UBS Global Healthcare Virtual Conference 2021

May 24, 2021

Good afternoon. Thanks for joining us again at the UBS Global Healthcare Conference. My name is Avin Jacob. I cover Smartcat Biotech and LargeCap Pharma here at UBS. I'm excited to have with me our next session, Madrigal Pharmaceuticals. From Madrigal, we're happy to have with us Paul Friedman, Chief Executive Officer Becky Taub, Chief Medical Officer and President of R and D and the new CFO, Alex Hoard and SVP and Chief Commercial Officer, Remi Isukhaja. So with that, we're going to spend about 15, maybe 20 minutes on a small presentation just to give folks who are not as familiar with Madrigal a chance to learn about the company, after which it will spend about 25 to 30 minutes of Q and A from me to the management team. And if you do have questions, please submit them online. They will be anonymous and I'm happy to read those out to the management team. And without further ado, I will turn it over to Paul for some introductory remarks. Thank you, Paul. Thanks, Navin, and thank you all for tuning in to hear our presentation. I wanted to also do a double welcome to Alex Holworth, our new CFO. And the presentation will be given by Becky and by our Chief Commercial Officer, Remi Sudhicchio. So with that, I'll turn the podium over to Becky. Hi. So for this presentation, we're going to use the slides that you are able to see on your connection. But we will not, in this short time period, not present every single slide. So Paul, why don't you summarize? I'm going to go get a drink of water. Okay, go ahead. Give me the slide, Becky. I apologize. I don't have the slide deck in front of me. Paul, you should be able to see that if you see the tab called slides up top. Oh, yes, yes, yes. So if you click on that, you should be able to see slide number 3, just projecting the future of ResMedoram. So Becky is back now. Okay. Yes. So we're going to just give you a brief overview today. And we have a Phase 3 program that is in development for the treatment of NASH in patients with significant liver NASH and significant liver fibrosis. And we believe that based on our strong Phase 2 data, so this is Slide 3, that both endpoints, NASH resolution and the key secondary endpoints of LDL cholesterol lowering and 1 stage improvement in fibrosis on liver biopsy are highly powered for success in the Phase 3 Maestro NASH study. We have a second Phase 3. So Maestro NASH about 900 patients. Maestro NAFL is a second Phase 3 study, about 1200 patients. Both studies have a very similar design. However, only NASH has serial liver biopsies. Maestro NAFL is a primary safety study. And it provides convincing data to support following the effects of Rismedirom non invasively, also has provided ongoing open label data from 2 arms, a non cirrhotic arm and a cirrhotic arm of the study. Our data and data in the literature have shown that there's a high unmet need for approved NASH drugs based on published literature and supported by our recent market research with physicians and payers that we'll briefly discuss today. The next slide, Slide 4 shows you what I just discussed, which is the overall development path for Rismetaam. The Phase 2, which is published in Lancet and another publication in hepatology communications, Phase 2, MAESTRO NASH, which is coming to completion of enrolling the population of 900 patients that needed to support the approval and that study will read out just over a year from now. And then Maestro NAFL, which has been reading out, as I mentioned, data from the open label arms, that's a fully recruited study, that it where the double blind arms of that study will complete this year and we plan to reveal top line data from the blinded arms of that study. So that's a 52 week study. Maestro NASH is a 52 week study to the liver biopsy endpoint and then also includes a long term outcome to look at clinical benefit over about 4 to 5 years. And if you take all the data from these trials and all the other Phase 1 supportive data, This is a comprehensive data set to support efficacy and safety. It's consistent with regulatory requirement to support accelerated approval of resmetirom for the treatment of NASH in patients with significant liver fibrosis. Now, on the next slide, which is Slide 5, many of you are familiar with NASH that the term that encompasses all forms of non alcoholic fatty liver disease is called NAFLD, simple steatosis, that's fat in the liver, without inflammation is called NAFL. And NASH, it is a progressive form of the disease. It's present in 3% to 10% of the population in the United States, particularly those with metabolic disease, diabetes, obesity, dyslipidemia, hypertension. So the metabolic spectrum predisposes to NASH and the progressive fibrosis, which can lead to cirrhosis. So this is a very high unmet need disease with no approved therapies. Now, our 2 studies shown on Slide 6, Maestro NASH is focused on the more advanced patients, particularly the fibrosis stages 2 and 3, which are right before F4, which is cirrhosis. MysoreNAFL has a spectrum that does overlap with Maestro NASH, but also includes some earlier patients. And just to note that in addition to providing benefit in the liver and treatment of NASH, Resmediram also has is very active against cardiovascular risk factors, particularly dyslipidemia. And most NASH patients have very high cardiovascular risk and die of heart disease more than liver disease. So this is an important feature of resmetirom. The target itself is a thyroid hormone receptor beta agonist. We've shown that this is a critical pathway in the liver. It's a liver selective drug and target. And thyroid hormone receptor beta is responsible for the metabolic effects of thyroid hormone in the liver, which is deficient in patients with NASH. We have a very large safety database with resmetirom already. It's been shown to be safe and effective, well tolerated and has pleiotropic actions in the treatment of NASH and treats all components of NASH, which I'll show you, reduces liver fat through the breakdown of fatty acids and normalizes mitochondrial and liver function. Now on Slide 8, you see without going into detail, this is summary of data from the Phase 2 study where we showed that the dose related reduction in liver fat was associated with improvement of NASH on liver biopsy and correlated with the resolution of NASH. So patients who had a very robust reduction of liver fat also had a higher incidence of reduction of NASH and NASH resolution. And what you see on Slide 9 is looking at patients who had at least a 30% reduction in liver fat as measured by a PDFF, an MRI that measures liver fat very accurately. If patients had a response in the Phase 2 study, such that they had at least 30% reduction in liver fat, they had improvement on liver biopsy at week 36 of multiple components of NASH, not just fat in the liver, but inflammation, ballooning, which is a marker of liver damage and fibrosis. So a greater reduction in all aspects of NASH due to the effect of resmetirom. So at the doses used in Phase 3, this is Slide 10, what we've shown is that a high percentage of patients have 50% fat reduction, as well as 30% fat reduction. And both of these reductions predict a high rate of both NASH resolution and fibrosis reduction. I'm going to show you 1 slide from the open label arm of MaestroNAFL. This is a 100 milligram dose arm. And this study, as I mentioned, is a 52 week study. This is primary safety study, but we've been monitoring the effects on rosmetirom on a variety of imaging and biomarkers. And I'm only going to show you 1 slide from this, which is slide 12. And what you see here is that at week 12, patients treated with 100 milligrams of resmetirom had on average at week 16 of the 52 weeks when they had an MRI of 53% liver fat reduction. If they had higher exposure to rasmetirom, they had a 62% fat reduction. And they also had a reduction in MRE, which is another type of MRI. MRE is a lastography. It's highly specific and sensitive for liver fibrosis and predicts the liver fibrosis stage. And at week 16, they already had a reduction in MRE. And this magnitude of this reduction correlates with almost a full stage fibrosis reduction. And this is based on published data in hundreds of patients who have had MREs. So at this point, I want to just simply move to Slide 14, which is the design of Maestro NASH, which is a serial liver biopsy study, just to remind you that we're using, this is a 3 arm study, placebo 180 milligrams blinded study, reads out a serial second liver biopsy at week 52. We are on target to complete the enrollment of the patients needed to support accelerated approval for the treatment of NASH within this study. And finally, on Slide 15, what you see here is that Madrigal has been among the leading companies in showing how NASH patients can be identified without using a liver biopsy, based on metabolic risk factors, noninvasive imaging techniques and laboratory tests. And when we use this series of tests in our Phase 3 studies and then perform the liver biopsy, more than 80% of the patients using the screening paradigm have definitive NASH with significant liver fibrosis on liver biopsy. So at this point, I would like to hand over to Remi. He's going to talk about the commercial application of and the analyses and market research that we've done. And this will be beginning on Slide 17. Yes. Thank you, Becky. A quick introduction to me, been part of the team for about a year. Before Madrigal, I have about 25 years in our industry, all commercial. I worked in companies like Pfizer and GSK in commercial roles, big biotech like Biogen and even VC backed startup. So all to say that bringing a whole host of experiences and I'm really excited to be here at Madrigal. So over the last year, we've done quite a bit of commercial planning any other company would be in our position. And I think everybody understands there is going to be a large therapeutic category for NASH. What you have in front of you are U. S. Figures on Slide 17. What may not be so widely known is that there is a NASH market today. So, physicians are treating patients, are actively identifying these patients using non invasive techniques and treating them in whatever they can off label. There is such high unmet need. And when I say physicians, I'm talking about hep's GIs, but also endocrinologists. So the need is there for the patients to be identified and treated with whatever tools physicians have. NASH category will grow over time. And at a high level, I can say that the treatment of NASH and the unmet needs are not just present in the U. S, but also ex U. S, European markets, Japan based on our market research. Going over to the next slide, Slide 18 kind of shares with you some of our primary market research done with again what we consider to be the physicians that more than likely will be the first ones to prescribe NASH drugs once they get approved. So these are HEPs, GIs and Endo's that see maybe 20, 30 NASH patients per month today. So these are going to be the target sort of treaters for us. And in our research, they have told us that, you know, the 3 out of 4 have said, so 76% have said that the unmet need for FDA approved drugs to treat NASH versus fibrosis patients is extremely high. And these physicians understand the mechanism of the disease, they value NASH resolution, they value fibrosis improvement. So, the knowledge base in this physician population around the disease is significant and positive. That's positive for drugs to come. I've had a chance to launch 10, 12 drugs so far in my professional career and what I have never seen is that when we put Resimiter on product profile, the expected product profile in front of them. So, depth of liver efficacy, once a day dosing, very sort of favorable safety profile, 91% of them highlight that the clinical utility is extremely high. So, lots still to see as far as the product profile as it emerges through Phase 3. But if Phase 3 data yields what we're expecting, this could be a very attractive option for physicians that are managing patients today. Last slide that I will share with you is Slide 19, which is kind of give you a flavor of where we are. Like I said, I've been here about a year. We have done commercial planning, not just in the U. S, but also EU5 and Japan. We're looking at what the payers are going to require. So all the things that we should be exploring now. Under Becky's team, we have a team of MSLs out there having scientific engagements. With payers, our engagements both with U. S. Strategic payers and also some of the health technology assessment organizations ex U. S. Are going to start second half of the year. And we have started our work is primarily for XUS, the health economics outcomes research that we need to do, which is going to be required for getting the right sort of pricing reimbursement ex U. S. We started building the infrastructure mindfully. My leadership team is in place. We will think about hiring the Head of Sales, maybe closer to data readout, but medical affairs, market access, data analytics, those capabilities are being built. This is going to be a drug that has application for a wide variety of patients and it's going to be important for us to make sure that we educate physicians on who are the right patients to treat and it's very positive that the clinical trials that the product is going to get approved on has such a robustness of non invasive data. So we think that's very positive. We expect the U. S. Launch will be around targeted at 15, 000 to 20, 000 physicians, so specialty care sort of launch. That's where payers would like to see the initial drug use. They don't feel comfortable for primary care physicians to be using these drugs at this point. And with current timelines, I mean, you have the potential to be first to market. For ex U. S, like I said, we've done the start of the commercial planning, but we made it clear that we expect to commercialize ex U. S. Via a partner or partners. And then under our new CFO, those discussions are starting. And of course, we are not going to be signing anything as partnerships until we have Phase 3 data readout, but these things take time. So that's where we are with commercial planning. I'll turn it back to Becky, close out. Yes. So just I did want to just take the last slide and remind everyone of what our timelines are. I mentioned these in the quick overview we just gave. We're expecting to present both our cirrhotic and non cirrhotic open label arms, upcoming EASL at the end of June, in both abstract and company presentations. We are completing the enrollment of the Phase 3 population for accelerated approval by the end of this quarter. I mean, it's essentially now in the next month. That's Maestro NASH for readout of in 52 weeks from the last patient. And then by year end of this year, we expect top line data from the blinded arms of Maestro NAFL. And we're finished with our presentation and happy to answer questions. Okay, perfect. Thanks everyone for that nice intro and to magical for folks who haven't who don't know the name, but obviously many of you do. And so with that, we'll jump straight into questions. Maybe 1 actually for Alex, I'll throw him a softball because he's new. But Alex, congrats on your new job, but just wanted to get your thoughts on some of the learnings from Akcea that you can break to the table. Madrigal, Remi alluded to you potentially starting some conversations about ex USI would love to get your thoughts. Sure. So I'm not familiar with this game if you refer to a softball. Is that cricket or not? Yes. Baseball. And I'm joking. But anyway, so no, I mean, clearly, sort of a core priority right now as we anticipate the Phase 3 data readout is, as Remi has mentioned, is the planning and preparation for commercialization. So the transition from a development stage company to a commercialization and development stage company is not an insignificant activity. And I've got a lot of experience here, not just from Akcea, frankly, but also prior companies with commercialization that we've built out. And I think 1 of the key sort of things for me is that in addition to having a very clear strategic plan, it's critically important that we have a long range financial plan that dovetails with that strategic plan. That enables us to evaluate different scenarios, different options, understand the trade offs between those equally, help us understand what key investment decisions are further down the road and how we may be able to gate those against derisking events. So that's an area that definitely, based on my prior experience, is something that I really want to be able to make sure we've got, as I say, dovetailing with the strategic plan. And then building on sort of your last point, as you say, sort of from a partnering perspective, as Remi mentioned, our intention is that we do have an ex U. S. Partner or partners, but preference is to have a single partner ex U. S. That we will execute on the back of the Phase 3 data next year. But again, all prior experience tells me that those discussions don't start next year, they start now, particularly in an area where this is clearly a phenomenal opportunity, but it's a new market and sort of understanding how we approach that new market, making sure we have a meeting of minds with our potential partners, all of that can be done ahead of time so that when we do turn the cards on the data, we can be very effective and expeditious in closing that partnership. So that's something that, yes, I'm sort of eager to be working with the team and then obviously potential partners between now and next year. Okay, great. And then a couple for Paul or Becky or both. And then we'll also I'd like to bring in Remi, whom many folks have not had a chance to speak to. But Paul and Becky, obviously this morning started off with some NASH news. We saw the discontinuation of NGM's FGF19 and F2, 3 NASH patients. They showed actually a NASH resolution benefit in a statistically significant manner with a decent amount of MRI PDFF fat reduction, but did not show fibrosis improvement. Wondering if at all these data set apply in any way to resverum understanding obviously it's a different mechanism of action. But what are the learnings from the little bit that we know, understanding again still early days? Yes. So I had the opportunity to see review their slides and also their webcast, which was consistent with what I know about how they were positioning this drug for non cirrhotic NASH. So really, before we get to study design, just simply say that this is a daily injectable that requires a statin to control LDL. And so they were really looking for a very large effect on fibrosis to make that sort of therapeutic viable or potentially viable. And they were even thinking about it being a short term therapy, like an induction therapy, like a 6 month therapy. And so it's very different than a well tolerated once a day oral medication that lowers LDL cholesterol to a level that is very significant and to the level that could easily support development for dyslipidemia, which rizmetirom is. So that's 1 like really, really big differentiator. In terms of study design and what they saw with this study, if you look back at their data, their earlier studies were not statistically significant or powered effectively. I think this study suffered from the same issue. Each arm had a very small number of patients. This is a Type 2 error. If you look at our Phase 3, we have 10 times more patients in each arm. And our study is powered to show a fibrosis statistically significant fibrosis benefit if we got numbers like this. I mean, 30% reduction in fibrosis is not a bad result. And they'll go back and they'll look and see whether any of it makes sense in terms of subgroups and things like that. And the NASH resolution rate was reasonable. So there is always a variability in fibrosis. We expect about a 20% response in placebo, not because the placebos are responding, but because the measurement is not accurate any more than down to about 20% who apparently get better, but really it's just the fact that their liver is heterogeneous. So that's kind of how we look at it. We don't think it impacts us in any way. We believe that our linkage with PDFF and the endpoints, which are NASH reduction and fibrosis reduction are that it's very solid data. And that we're dosing at levels at drug levels in Phase 3 where we will achieve NASH resolution and which is the primary endpoint and also fibrosis reduction, the secondary endpoint. So if I could just add a couple of things to that. So we believe that their 3 milligram dose was active, but that the N is too small and the study is not powered to show STATSTIG unless they had a remarkable result. That's 1 thing. Secondly, what NASH is, it is hepatitis, just like viral hepatitis, all induced hepatitis and the final common pathway pathologically is the same for all these things with some distinguishing characteristics. Basically, tissue could only respond many ways. In all of those cases, in alcohol and in viral hepatitis, when you remove the offending agent, you get an improvement in what the liver is doing and what the hepatocytes look like and how much inflammatory cells are present and what lags and comes after is fibrosis improvement. So we know from our Phase II data and now from the MRE data that Becky referred to in the 100 milligram open label NAFLD arm that all the parameters that we're seeing indicate that we're going to see an effect in fibrosis. And if you simply took that 19% 30% that they had at the 3 milligram arm and took it to a 900 patient study, you'd have very high statistical significance. So we're quite confident that we're going to make the primary endpoint in both of the key secondary. And 1 other comment I just wanted to make that I forgot to make is that they only had about 35% of patients in each arm, so 10 to 15 patients per arm that had F3 fibrosis. Now our Phase 3 is focused on F3 fibrosis because that's where we saw the biggest differentiation between placebo in the Phase 2, you don't get as much of a kind of a variability once a patient has gotten to the level of F3. So I think also that hurt a drug that has a potential for an anti fibrotic effect, just having so few patients with significant fibrosis in that study. Sure. And Vicki, you started the answer talking about the overall risk benefit profile of the drug and which is as critical as the agencies is looking at all of these NASH products, particularly in the context of what we saw with 1 of your what used to be the leading NASH product in the form of Ocaliva. At the time, Intercept had been suggesting that there was some changing goalposts at the agency, but perhaps the reality was it was the overall profile of the drug, which makes sense in the context of what you're saying about this particular product. But just to be clear, understanding there have been some updated guidelines and commentary from the agency. Have you in any way seen any change from the agency with regards to standards for moving a drug or submitting a drug for NASH? We don't believe that there's been any change. They're still focused on accelerated approval pathway. We designed our development program based on the view that this is a chronic therapy and that we needed numbers of patients treated at the approvable doses that would be commensurate with a chronic therapy. And so that's why we have such a large Phase 3 program with 2 Phase 3 studies. I think what came out of FDA was exactly that. So in other words, they simply reemphasize what was already known that when you are developing a drug for a chronic therapy like this, just like diabetes or lipids or whatever, you need a larger safety database. And I think that INTERCEPT fell a little short on that, even though they had been approved and they had a lot of patients at lower doses of 5 10 milligrams in the PBC population. They didn't have such high numbers in 25 mg. So I don't think there was any change of the goalposts at all. I think it was just kind of not fully understanding the kinds of things that would be required for approval in an indication like this. I could keep going with you, Paul and Becky, but I do want to bring in actually also Remi folks have been adding, including myself, have not really had a chance to interact with them as much. So we'd love to get especially as you get closer to a potential readout next year. You have to start thinking about the commercialization of resmederemi. What type of beyond hepatologists and gastros, I saw that in your slide, I mean, what is the ideal target for NASH and NAFLD? I mean, is primary care ever a target for NASH or NAFLD? Yes. So I think the first thing to realize is, we expect that the indication for resimiterom will be for the treatment of patients with significant fibrosis, which is F2, F3, roughly speaking on biopsy. So then the next question we have to ask is, okay, who are the right physicians that are ready to treat these patients currently see those patients and those are the specialists. So they are hepatologists, they are GI, they are select endos, they are the ones that are managing these patients. PCPs are playing some role in identifying NAFLD patients that should be referred over. Quite honestly, that's a bit slow and it's not where we want it to be. I think it will improve over time. And then you also have to have a lens of what the payers are going to first allow and they do want the prescribing of NASH drugs, regardless of which 1 it is, by specialists. The way they define specialists is anybody that is not a PCP sort of a thing. So to answer your question, yes, I mean, the initial sort of focus is going to be on those 3 specialties. You mentioned payers, are payers willing to pay for a NASH drug if there's no biopsy done to confirm fibrosis staging. You've alluded to a potential algorithm to find NASH patients. But if biopsies are not done, our payers willing to even if the physicians are willing to diagnose a NASH patients, are the payers willing to do that? Yes, very good question. So the way to think about this is that in our research and we've done research with 40 to 50 U. S. Payers, medical directors, pharmacy directors, they roughly cover 300, 000, 000 lives together, right, so pretty substantive sort of piece of work here. They are not in favor of having biopsy as the way to identify patients for their own reasons. So they are very willing to use non invasives or reimburse non invasives. They do that right now. So they will be looking to the clinical data and advice from experts, AOLs, on what are the sort of non invasive algorithms or tools to use in any particular product, including ResMedirom. And as I said before, I mean, if there's 1 program that is creating just the intense amount of data around non invasive use with a compound, it's resmitterum. So that's how we see the world forming and we look forward to playing our part in that. 1 more question for you before I switch back to Becky and Paul is, what pricing analogs do you see is sort of realistic for rismidarum? I mean, we could look at GLP-1s, we could look at PCSK-9s. There are a whole lot of comps, but what are some of the comps that you guys look at? So listen, I think it would not be appropriate for me to signal anything on pricing right now because we have to look at Phase 3 data and pricing is such a big decision that's taken when you know what the label is going to be, things of that sort. Nevertheless, to pay respect to your question, based on our research, I can share with you how payers think about, generally speaking, NASH drugs. So yes, I mean, in that context, to think about GLPs, some of the novel ones, which are around 10, 12 ks or something like that or continue with the price increases. I think about obesity drugs like Saxenda, 15 ks, 16 ks. They are aware of OCA and ICER sort of noise when that was relevant around 15, 20 ks. So that's how they're sort of processing it, but it's way too early for us to think how we're going to price resimiteram. We will really base that on Phase 3 data and assuring that we have broad access for the patients that are right based on our Phase 3 data. Got it. And Becky, I do want to confirm with you and you mentioned this a couple of times, but I just I do want to confirm because there have been some delays now with the full enrollment of Maestro NASH, but that you will be completing enrollment June of in just about a month here. Yes. We were on track prior to COVID with for enrollment by last year, by December of 2020. And we have a few months delay and to really cover it, we extended to the this quarter. So we're enrollment is going really well and has been for several months now, but it was definitely slow, especially ex U. S. And in the middle of last year. And ex U. S. Has been was more impacted, as you're well aware compared to the U. S. Where the reopening was a lot quicker. The 1 of the dynamics that perhaps people are not fully appreciative or understand is what the learnings you can get from the Maestro Nafo D study could be and how those learnings could be applied to once the NASH study is read out. I mean, in terms of diagnosing patients or what is that overarching and perhaps a question for Paul or Becky, what is that overarching strategy of how you want to take both those data sets to utilize for commercialization in both those populations. Yes. No. So I would say, I mean, we have probably, I'm sure, the biggest data set of any company in the world relative to NASH because of the numbers of patients that we've enrolled in MaestroNAFL and Maestro NASH. And because Madrigal has been a leader in non invasive technology and using imaging, state of the art, all the biomarkers that are being in the process of being validated for NASH. And this comes up all the time. And we have a huge amount of data. We're interacting with many NASH experts who are very interested in our data, whatever. And so we have a handle on use of non invasive methods to diagnose NASH and also in part because ResMedirom is such a has such a is so active that we have ways of following our resimiterom response that are really convincing and will be convincing to the payers. So I think those 2 things will come out of both of our studies, not just Maestro NAFL, but also Maestro NASH, because we'll get the liver biopsy results and we'll have all these other data. We'll have MR serial MRE, serial MRI, serial fibrosis biomarkers, and then all the cheap tests, like AST and ALT and everything else. So it's like we can pick and choose which are these whatever is the most is needed as part of our commercial plan and what's accessible. It might not be the same in every location. And you'll see with the MaestroNAFL data for the 52 week data at EASL that we have MRE 52 weeks, we have FibroScan 52 weeks, we have fibrosis biomarkers. And so you'll see how we're going to use those data to show that the patient improvement. The lipid profile of rismidarum is particularly interesting in the context of being an oral pill that looks very safe. Over the last 2 years, you've seen several companies that are in the CV metabolic space attract significant valuations. Paul, Becky, perhaps even Alex, is there a way to monetize that profile sort of separate from NASH? Why not run a separate CV outcomes trial? I mean, the benefit that you're showing alone could result in a unique CV benefit, which is not 1 that's been shown very often, right. I mean, there's only 1 drug that's effectively done that in a robust clinical trial. And that company's the company that had that drug had a pretty sizable valuation at 1 point before running into some IP issues. Just wondering your thoughts about that. I was just going to say, Paul can answer as well, but it just becomes a question of timing and how long these things take. But we do expect to get these CV endpoints into our drug label for NASH. And that's why there are key secondary endpoints in both Maestro NASH and Maestro NAFL. So they're very these CV endpoints are very important lipid endpoints to our program. I don't really have much to add to that except we have talked about a CV outcome study and we just haven't pulled the trigger on it yet, could happen. But just having those parameters in the label will help physicians to want to prescribe the drug both for the cardiovascular potential cardiovascular benefits, I think obvious, but we won't have a claim of in the patient population that dies more frequently and have more morbidity from cardiovascular issues than they do from progression of the liver disease. So it will help commercially in the NASH population and we have considered at some point initiating a CV outcome study. And last question for me is the open label arms from Maestro, NAFLD that you're going to be showing at EASL, what endpoints and time points will you be sharing there? So what we focus on was some of the patients in that arm, and it's a significant number. About half of the study have completed 52 weeks. So we want to focus on those 52 week readouts, as I mentioned, to show the durability of the effect and look at some of the interesting readouts that are things that physicians can follow when they're treating patients with Rismetirom. So that will be the focus of the non cirrhotic. And then the cirrhotic, we're earlier with that arm. And so we'll show some very interesting and so we'll show some very interesting baseline data and some about week 16 data in the cirrhotic NASH cohort. Fantastic. And with that, we are a little bit over time. I want to sincerely thank Becky and Paul and Alex and Remi for joining us today. Thank you everyone and everyone have a great day. Thank you, Liam. Thank you very much.