Madrigal Pharmaceuticals, Inc. (MDGL) Earnings Call Transcript & Summary

Good afternoon. Thanks for joining us again at the UBS Global Healthcare Conference. My name is Navin Jacob. I cover smid-cap biotech and large-cap 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&D; and the new CFO, Alex Howarth; and SVP and Chief Commercial Officer, Remy Sukhija. 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 we will spend about 25 to 30 minutes of Q&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 Howarth, our new CFO. And the presentation will be given by Becky and by our Chief Commercial Officer, Remy Sukhija. So with that, I'll turn the podium over to Becky.

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 deck, Becky. I apologize. I don't have the slide deck in front of me.

Paul, you should be able to see there, 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 #3, just projecting the future of resmetirom.

Okay. So Becky is back now. Okay.

Yes. So we're going to just give you a brief overview today. And we have a Phase III 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 II data -- so this is Slide 3, that both end points, NASH resolution and the key secondary end points of LDL cholesterol lowering and one-stage improvement in fibrosis on liver biopsy are highly powered for success in the Phase III MAESTRO-NASH study. We have a second Phase III. So MAESTRO-NASH is about 900 patients. MAESTRO-NAFLD is a second Phase III study, about 1,200 patients. Both studies have a very similar design. However, only MAESTRO-NASH has serial liver biopsies. MAESTRO-NAFLD is a primary safety study. And it provides convincing data to support following the effects of resmetirom 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 resmetirom, the Phase II, which is published in Lancet and another publication in Hepatology Communications, Phase II MAESTRO-NASH, which is coming to completion of enrolling the population of 900 patients that's needed to support the approval. And that study will read out just over a year from now. And then MAESTRO-NAFLD, which has been reading out, as I mentioned, data from the open-label arm, so that's a fully recruited study that -- 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 end point 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 I supportive data, this is a comprehensive data to support -- 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. The term that encompasses all forms of nonalcoholic fatty liver disease is called NAFLD. Simple steatosis, that's fat in the liver without inflammation, is called NAFL. And NASH is a progressive form of the disease. It's present in of 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 are 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. MAESTRO-NAFLD 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, resmetirom 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. Now the target itself is a thyroid hormone receptor beta agonist. We've shown that this is -- has -- 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 can see -- without going into detail, this is a summary of data from the Phase II 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 this Phase II 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 III -- this is Slide 10, what we've shown is that a high percentage of patients have 50% of 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 one slide from the open-label arm of MAESTRO-NAFLD. This is a 100-milligram dose arm. And this study, as I mentioned, is a 52-week study. This is a primary safety study, but we've been monitoring the effects of resmetirom on a variety of imaging and biomarkers. And I'm only going to show you one 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, a 53% liver fat reduction. If they had higher exposure to resmetirom, they had a 62% fat reduction. And they also had a reduction in MRE, which is another type of MRI. MRE is elastography. 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, 100 and 80 milligrams blinded study, reads out a serial second liver biopsy at week 52. We're 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, non-invasive imaging techniques and laboratory tests. And when we use the series of tests in our Phase III 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 Remy. 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. I've been part of the team for about a year. Before Madrigal, I have about 25 years in our industry, all commercial, have worked in companies like Pfizer and GSK in commercial roles, big biotech like Biogen and even VC-backed start-up. 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 as 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 with whatever they can off-label. There is such high unmet need. And when I say physicians, I'm talking about HEPs, 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 endos 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 the -- 3 out of 4 have said -- so 76% have said that the unmet need for FDA-approved drugs to treat NASH 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 resmetirom 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 a lot still to see as far as the product profile as it emerges through Phase III. But if Phase III 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 to 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 EU-5 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 -- it's primarily for ex U.S., 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 a 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 the primary care physicians to be using these drugs at this point. And with current time lines, I mean we have the potential to be first to market. For ex U.S., like I said, we've done the -- started 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 III data readout. But these things take time. So that's where we are with commercial planning. I'll turn it back to Becky to close this out.

Yes. So just -- I did want to just take the last slide and remind everyone of what our time lines are. I mentioned these in the quick overview we just gave. We're expecting to present our -- both our cirrhotic and non-cirrhotic open-label arms at upcoming EASL at the end of June in both abstract and company presentations. We're completing the enrollment of the Phase III population for accelerated approval at the end -- by the end of this quarter. I mean it's essentially now in the next month. That's MAESTRO-NASH for readout 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-NAFLD. And we'll -- we're finished with our presentation and happy to answer questions.

Okay. Perfect. Thanks, everyone, for that nice intro into Madrigal for folks who haven't -- who don't know the name, but obviously, many of you do. And so with that, let's jump straight into questions. Maybe one actually for Alex. I'll throw him a softball because he's new. But Alex, congrats on your new job, but I just wanted to get your thoughts on some of the learnings from Akcea that you can bring to the table for Madrigal. Remy alluded to you potentially starting some conversations about ex U.S. I would love to get your thoughts.

Sure. Sorry, I'm not familiar with this game you refer to as softball. Is that [ like cricket ] or not?

Yes, baseball.

All right. And I'm joking. But anyway. So no, I mean, clearly, sort of the core priority right now is we anticipate the Phase III data readout is -- as Remy 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 one 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-off 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 Remy 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 III 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 Remy, who many folks have not had a chance to speak to. But Paul and Becky, the -- obviously this morning started off with some NASH news. We saw the discontinuation of NGM's FGF19 in 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 did these datasets apply in any way to resmetirom understanding. Obviously, it's a different mechanism of action. But what are the learnings from the little bit that we know, understanding, again, it's 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 resmetirom is. So that's one, 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. The -- each arm had a very small number of patients. This is a type 2 error. If you look at our Phase III, we have 10x 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's 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 is 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 end points, which are NASH reduction and fibrosis reduction, are -- that is very solid data and that we're dosing at levels at drug levels in Phase III, where we will achieve NASH resolution and -- which is the primary end point, and also fibrosis reduction, the secondary end point.

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 end is too small and the study is not powered to show stat sig unless they had a remarkable result. That's one. Secondly, what NASH is it is hepatitis, just like viral hepatitis, alcohol-induced hepatitis. And the final common pathway pathologically is the same for all these things with some distinguishing characteristics. Basically, the tissue can only respond in so many ways. In all of those cases, in alcohol and in viral hepatitis, when you remove the offending agent, you get an improvement in the -- 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% and 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 end point and both of the key secondaries.

Yes. And one other comment I just wanted to make that I forgot to make. It's that they only had about 35% of patients in each arm, so 10 or -- 10 to 15 patients per arm that had F3 fibrosis. Now our Phase III is focused on F3 fibrosis because that's where we saw the biggest differentiation between placebo in the Phase II. 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 Becky, you started the answer talking about the overall risk-benefit profile of the drug and -- which is critical as the agencies is looking at all of these NASH products particularly in the context of what we saw with one of your -- what used to be the leading NASH product in the form of Ocaliva. At the time, Intercept had been suggesting that there were 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 approvable doses that would be commensurate with a chronic therapy. And so that's why we have such a large Phase III program with 2 Phase III studies. I think what came out of FDA was exactly that. So in other words, they simply reemphasized 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 and 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 in the goalpost 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 Remy. Folks haven't had -- including myself, have not really had a chance to interact with him as much. So I would love to get -- especially as you get closer to a potential readout next year. You have to start thinking about the commercialization of resmetirom. Remy, 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 resmetirom 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 GIs. They are select endos. They're 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 one it is, by specialists. And the way they define specialist 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, are payers willing to -- even if the physicians are willing to "diagnose" 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 million lives together, right? So a 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 reimbursed non-invasive. They do that right now. So they will be looking to the clinical data and advice from experts, KOLs, on what are the sort of non-invasive algorithms or tools to use in any particular product, including resmetirom. And I said -- as I said before, I mean if there's one program that is creating just the intense amount of data around non-invasive use with a compound, it's resmetirom. So that's how we see the world forming. And we look forward to playing our part in that.

One more question for you before I switch back to Becky and Paul is, what pricing analogs do you see as sort of realistic for resmetirom? I mean we could look at GLP-1s. We could look at PCSK9s. 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 III 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, I think about GLPs, some of the novel ones, which are around $10,000, $12,000 or something like that or continuing with the price increases, or think about obesity drugs like Saxenda, $15,000, $16,000. They are aware of OCA and ICER sort of noise when that was relevant, around $15,000, $20,000. 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 resmetirom. We will really base that on Phase III data and assuring that we have broad access for the patients that are right based on our Phase III data.

Got it. And Becky, I do want to confirm with you that -- 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. No. We were on track prior to COVID with -- for enrollment by last year, by December of 2020. And we had 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. 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 -- one of the dynamics that perhaps people are not fully appreciative of or understand is what the learnings you can get from the MAESTRO-NAFLD 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 am 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 MAESTRO-NAFLD 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 resmetirom is such a -- has such an -- is so active that we have ways of following resmetirom 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-NAFLD 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 we -- it's like we can pick and choose which are these -- which are the -- 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 MAESTRO-NAFLD data for the 52-week data at EASL that we have MRE, 52 weeks. We have fiber scan, 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 resmetirom is particularly interesting in the context of being an oral pill that looks very safe. You've -- over the last 2 years, you've seen several companies that are in the CV metabolic space, attracts 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 in triglycerides alone could result in a unique CV benefit, which is not one that's been shown very often, right? I mean there's only one 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 one 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 end points into our drug label for NASH. And that's why they're key secondary end points in both MAESTRO-NASH and MAESTRO-NAFLD. So they're very -- these CV end points are very important, the lipid end points, 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. It 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 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 the last question from me is the open-label arms from MAESTRO-NAFLD that you're going to be starting at EASL. What end points and time points will you be sharing there?

So we -- 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, 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 resmetirom. 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 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 Remy for joining us today. Thank you, everyone. And everyone, have a great day.

Thank you.

Thank you, Navin.

Thank you very much.

Thanks a lot.

Bye-Bye.