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

Good afternoon, everyone, and welcome. I'm Pradyumna from JPMorgan's healthcare team. Thank you for joining us for the call Madrigal Pharmaceuticals presentation today. Madrigal has been one of the most consequential companies in the metabolic and liver disease over the last few years. And today, we're pleased to be joined by Bill Sibold, the Chief Executive Officer; Dr. David Soergel, Chief Medical Officer; and Mardi Dier, the Chief Financial Officer. Bill and David will speak for about 20 minutes, after which we'll move into a live Q&A session. At that point, we'll also be joined by Mardi Dier. With that, Bill, I'll turn it over to you.

Thank you, Prad, and thank you to JPMorgan for having us here. This is always a great way to kick off the year and to provide a progress update for how we're doing. I'll start by saying that this is an exciting time at Madrigal. You've often heard me say that I think this is the best opportunity in the industry. Everything that we've accomplished in the last 12 months, 24 months and looking ahead, I firmly believe that more than I did when I started in this role in September of 2023. On the slide here, leading the fight against MASH, that is our purpose statement. You don't have to look much further than that to understand what we're about. We're about MASH. We're about leadership, and we think we have to bring a little bit of an edge to this to truly fight on behalf of patients. So that's what you can hear about us. We're clearly the leader now with the first ever approved product for MASH after a graveyard of drug development for many, many years. Hopefully, today, you'll be able to see that we have taken steps, and we've positioned ourselves for long-term leadership in the space. Just a reminder here, I'll make some forward-looking statements today. So let's take a look at the impressive progress towards our strategic growth priorities, maximizing the value of Rezdiffra and building our pipeline. We're executing on objectively one of the best launches in the specialty space in the last decade. And with sales annualizing now at over $1 billion, and that is after 6 quarters of launch. Now remember, we're talking about Q3 here through Q3, but really actually quite amazing that we've had that type of trajectory at originally in a market that people wondered, is there even a market and will you be able to have -- is there any unmet need for a product? Well, I think we've shown that clearly, there's a market and that Rezdiffra is quite a special product. The next chapter of growth for Rezdiffra will be F4c indication. That's something that we're expecting data in 2027. And we have an opportunity to double the opportunity for Rezdiffra with the expansion into that indication. And we benefit there actually first-mover advantage and from the product profile that we have. So we're very excited about it. Now the future of Madrigal and where are we headed, and that's building our pipeline. And we have done 2 deals to date. We will hear a little bit more about the DGAT-2, which is something that we announced last week. We're really excited about that. And that's just the start with the 2 deals. We're adding new mechanisms of action. We're really looking at setting the table for us to be the ones that explore looking at combination therapy or stand-alone, but we think really with the wonderful profile that we have with Rezdiffra that it's going to be very amenable to combination therapy to look for additional benefit for either the whole population or for subgroups. So talking a little bit about the progress. And as I say, one of the things I like about JPMorgan is you can look back and see what have you accomplished over the years on an annual basis. And when you look at 2025, it was an extremely, extremely busy year for us. As I said, we have an exceptional launch that's taking place after the sixth quarter. We had new IP, which extends to 2045, which actually that foundation allows us to think about even preclinical stage assets to bring in because we're not in rush of a patent cliff or a pending patent cliff or we have to go fill any holes. We also did the oral GLP-1 deal that I mentioned. Now we're moving into '26 and '26 is going to be a very busy year for us. a good prognosticator for launch success in 2026 is the market access that we have secured. There were some questions about that. I'll spend a minute on that in a few minutes. We'll continue to make progress towards F4c. We'll continue to accelerate Rezdiffra's evidence generation. I think that it's important as you're building a mega blockbuster drug, is that you don't move on from it without asking the questions that the community has and where you can further differentiate and show the value of your product. We also have -- starting off the year strong with our DGAT inhibitor that we and again, you can expect to hear about more BD from us throughout pardon me, throughout the year, it's something that we feel very strongly that we are, as I said, going to set the table with a number of mechanisms of action that allow us to look at a combination strategy with Rezdiffra. So just to recap on the launch that we have going on. And first of all, we've been saying from the beginning that we will -- we have and we will continue to steadily add patients. And on the left panel here, we see the active patients on therapy. And remember, that is net of new adds and any discontinuations. The number of patients that are on Rezdiffra at the final day of the quarter. And at the end of Q3, over 29,500 patients, which is really a very impressive number. And the 10,000 in the center of the screen here, that is total Rezdiffra prescribers. Really important have enough of a breadth of prescriber and the 10,000 point from my experience is a milestone that sets you up for long-term continued growth. So as we look towards the future, we will be increasing the breadth. But really, the next step is to go deeper into that prescriber pools, have them have more and more patients on therapy. And as you can see, what does this all translate into from a sales perspective, $287 million in the third quarter of 2025. So I think from all measures that we look at from a launch perspective, with every metric, we are objectively at or near the top of all the launches in the last 10 years that we've been looking at. I had mentioned the great access as we set up for 2026. We have first-line access, no step edit requirements and improvement in utilization management criteria at some of the payers as well. This is a question that we have been asked a lot of last year. in the advent of having a competitor, will you be able to maintain your first-line access on the strong access that we've had since launch in 2024. The answer is yes. I think this demonstrates the quality of the product that we have that it shows the value to payers and that you can have multiple products coexisting in a disease and with that, including GLP1s. So we're really excited about the team. We have an extremely experienced team, just like we do in all parts of the organization. Our market access team is outstanding and really did an incredible job for us to get us set for 2026. So let's take a look at the market a little bit here and a couple of things to point out. You've heard me talk about the 315,000 patients the initial target of patients, those are diagnosed patients that are in the prescribers' practices that we are calling on, and that's -- these are diagnosed F2/F3 patients. Only we are -- well, we're 10% penetrated into that 315,000, and the disease is about 10% diagnosed. So think about that for a second. We are 10% of 10%. We are at the very beginning of a market that we see expanding into being a large specialty market with the profile that is a durable profile. We have a great, great asset to build from. So I think this is really exciting for us. And as I say, we expect MASH to follow in the footsteps of some of these other large specialty markets here. Here, we have IBD, RA and psoriasis. And I want to point out is they're all large markets, over $20 billion in sales, almost 30 years after the first products were launched. -- and they support multiple products and multiple mechanisms within those diseases. You go back looking at MASH, where we were in 2024, a $180 million in sales. There's now 2 products on the market. So we see that these dynamics, and I don't think the market really appreciates as much the opportunity that lies ahead of us with Rezdiffra and specifically because of the dynamics of minutes. I've talked about the profile of the product. You've heard me say before, this is a holy grail profile, a once-a-day pill effective, safe, well tolerated. And I think that is something which not only provides us a lot of runway in F2, F3, but as we look at the F4c population, that profile also carries over very well. And when looking at F4c here, it's a sizable opportunity with 245,000 patients. And this is if you were to do a comparison to the 315,000 F2. F3s, the difference being is that these are even higher unmet need patients higher risk of liver-related mortality. So we think that although fewer patients will be a higher urgency to treat and higher penetration. We are going to be the first to market here. And as I said, it's only first to market, but it's first to market with a great profile that will add tens of thousands of patients already on the drug. So familiarity by the prescribers will be extremely high. All of our system will be wired, et cetera, so that we're in a very favorable position just to have somebody -- the physicians begin to move from F2/F3 to F4c as well. We expect to read out from our outcomes trial in 2027, and we're really optimistic about the outcome, and that's partially driven by a cohort of 122 patients from our NAFLD-1 study. where we showed very, very promising results in this F4c population. What gives us further encouragement is that the baseline characteristics of these studies are almost identical. So lots more to come. So how do we see the market shaping for MAS. And look, it's a complex heterogeneous disease. There is a broad spectrum of comorbidities and we think in the future to address the full potential of it and the subpopulations that emerge, you're going to need more than 1 therapy. And we look here showing where MASH is today, where it goes in the future. And really, it's going to be Rezdiffra and Madrigal that drive that transition from treatments only for F2 to F3, to F2 to F 4C will be the leaders there. Combination therapies now. There are some that take place, but it's not very well defined. But we think that we can drive combination therapy and really drive outcomes that way. And as I said, 10% of 10%, we're at the very beginning, and we expect with awareness of the disease, more screening that will go on as there's more of a pipeline of products that are entering the space that's going to bode very well for us. So we are in an exceptionally strong position to drive this disease forward, the treatment of this disease and outcomes for patients. So maybe with that, I will transition to Dave, who can walk us through a little bit how we're going to accomplish that with their pipeline. Dave?

Thanks a lot, Bill. Yes, I mean, so great setup. So we have a very straightforward goal in R&D at Madrigal, build the leading pipeline in MASH in the industry. And the way we're going to do that is essentially through targeted business development and then utilizing our internal expertise and capabilities for internal innovations and be able to deliver new therapies more efficiently and more effectively than anybody else in the industry can do. The team in R&D pioneered the development of MASH drugs. They developed the first effective and safe therapy for these patients who had no hope. And so we have a specific opportunity to leverage that expertise. So the 4 pillars that we're working in right now, ensuring that we deliver transformation outcomes data. As Bill referenced, we have the MAESTRO OUTCOMES trial and F4c reading out in 2027, and we have the ongoing MAESTRO NASH study that will deliver data in F2, F3 in 2028. And that will allow us to secure full approval in F2 through F4c. MASH. Second, as Bill alluded to, the field is going to move towards combination therapies, every complex heterogeneous disease does that. And so we're looking for mechanisms of action that are complementary to Rezdiffra can deliver better efficacy to patients with MASH and still deliver a great tolerability profile for these patients. Third, look for new modalities where we can broaden patient reach and deliver efficacy to different patient subpopulations and individuals with risk sets. So we're looking across the spectrum, not just oral small molecules, but we're looking for injectables or really anything that can drive efficacy in these patients. And then last, as I alluded to, execute disciplined capital efficient clinical development trials to get to go/no-go decisions effectively and efficiently. So as we've talked about, MASH is a complex disease, and this is a complex slide. describing all of the potential pathways or many of the potential pathways that are involved in MASH. So the key -- the fundamental issue in MASH is over-delivery of free fatty acids to the liver where they then converted into lipid droplets that are abnormally stored in the hepatocyte. And that causes inflammation and fibrosis ultimately and leads to progression of disease -- the second issue with MASH is hypothyroidism in the liver, which leads to mitochondrial dysfunction, which makes it so the liver can't properly clear those fatty acids. And so of course, THR-ß agonism addresses that liver hyperthyroidism. So this is where we see the opportunity for combination products where if you can intervene at multiple pathways within this disease process, you'll be able to deliver better efficacy for these patients ultimately. So we already have a solid foundation for combination therapy in Rezdiffra. And so we're looking for mechanisms now that can be added on to Rezdiffra and deliver better efficacy. And we've already acted in 2 areas. First, GLP-1, as Bill mentioned, we in-licensed an oral GLP-1 molecule last year, and we'll talk a little bit more about that. And then most recently, we in-licensed a DGAT-2 inhibitor, which targets a distinct pathway within hepatocyte that's linked to MASH pathophysiology as well. And so in our hands, we believe that these combination products can deliver better efficacy and ultimately better outcomes for patients with NASH. So let's talk a little bit more about Ervogastat, the DGAT-2 inhibitor we just in-licensed. So a couple of things we found particularly attractive about this molecule. The first is that it's clinically validated. So there was a Phase IIb study conducted with Ervogastat that gave us data to show us that there's reassuring pharmacology with this medicine that we believe can work mechanistically in a complementary way with resmetirom. And so that's the second key characteristic, having a scientific rationale for why combining THR-ß with another mechanism would make sense. In this case, we'll go through why that does make sense. Of course, it's an oral molecule, which has an opportunity to develop a fixed-dose combination is particularly attractive to us. Mechanistically, the way this -- the way DGAT2 inhibition works is it inhibits the final step of de novo lipogenesis in the hepatocyte. So it prevents the addition of the final free fatty acid to the triglyceride droplet and therefore, prevent the inhibition of that enzyme prevents accumulation of hepatic fat. And what we've seen from the Phase IIb data is that, indeed, that's what this molecule does. It reduces hepatic fat. And we predict when you combine it with resmetirom, it will reduce fibrosis even more effectively, and we'll get into that in a second. So our next steps for the program are our drug-drug interaction study with resmetirom and Ervogastat in 2026 with consultations with the FDA to discuss combination rule development and then ultimately, a Phase II program in 2027. So we'll go a little bit deeper into the data with Ervogastat. So what we show you on the left-hand panel of the slide is the MRI-PDFF effects of Ervogastat. MRI-PDFF is a way of quantifying hepatic fat and a 30% reduction in MRI-PDFF has been strongly linked to improvement in fibrosis in patients with MASH. A 50% reduction in MRI-PDFF is being called a super responder level, which is even more likely to result in better fibrosis resolution in patients with MASH. And as you can see on the far left, Ervogastat at 150 milligrams reduces MRI-PDFF by 30% in 72% of patients. and 50% reduction in 61% of patients. So this is a very profound effect on liver fat that we think could be compelling when you add it to the resmetirom mechanism of action. What we show you on the right-hand panel of the slide is a really strong connection between reduction of hepatic fat on the X-axis and improvement in fibrosis on the Y-axis in patients treated with resmetirom. So this is an example of some of the data that we have that helps us identify targets that would be useful combinations for resmetirom. So we believe that if you can get more patients into that super responder category with the combination product, we'll be able to get better antifibrotic efficacy in patients with NASH. So the way these 2 mechanisms work in a complementary manner, so DGAT-2, as I mentioned, inhibits that final step of de novo lipogenesis, the free fatty acid that's not incorporated into the triglyceride because the DGAT inhibitor is inhibiting that from happening. Normally, the question would be what would happen to that free fatty acid. In a patient who has MASH, as I said, typically, the mitochondria don't function properly. And resmetirom, we know, can reverse that mitochondrial suppression and therefore, allow that free fatty acid now that's free floating in the cytoplasm to be burned up into energy by the mitochondria. So we see that these 2 mechanisms by correcting both the mitochondrial dysfunction and by inhibiting the lipid production, we're going to be able to get even more fat reduction, less lipotoxicity, less inflammation and less fibrosis. So now we'll turn the page and take a look at the oral GLP-1 program that we in-licensed last July. So what we noticed from the MAESTRO NASH study is that in patients treated with Rezdiffra, only a small amount of weight loss, 5% weight loss potentiates resmetirom antifibrotic efficacy. So that led us to the conclusion that if we could drive more patients into that modest weight loss category with a pharmacologic agent, i.e., a GLP-1 inhibitor agonist, we could get better antifibrotic efficacy with a combination product, while still maintaining a great tolerability profile. So with this program, we're not tolerating 10, 15 weight loss, we're targeting modest weight loss and introducing it gradually in order to potentiate the antifibrotic effects of resmetirom. So the next step for this program is to start a Phase I study, first in human, single-ascending, multiple-ascending dose in the second quarter of this year and then conduct some additional drug-drug interaction work, FDA consultations and combination development next year in 2027. So we're really excited about this because we think that the combination of both GLP-1 and resmetirom and DGAT2 and resmetirom offer 2 complementary combination approaches that could deliver even better efficacy to patients living with MAS. So the way GLP-1 works, as everybody knows, is that you eat less food. So when you deliver fewer calories to your body, fewer free fatty acids to deliver, you improve insulin sensitivity and also on that basis, reduce free fatty acid delivery to the liver. And again, THR beta regulation will allow that fat to be cleared more effectively and more rapidly and provide a much more effective antifibrotic effect. So at the end of the day, you clear the hepatic fat, you improve lipotoxicity, inflammation and fibrosis. So it's an exciting time. We have a growing pipeline. We're bringing our strategy into action, and we're going to have multiple products in development now patients living with mash and be able to address the growing unmet need in this population and hopefully make a big difference. I'll pass it back to Bill.

Thanks, Dave. So here just shows you how we see some of the -- how we Rezdiffra cutting across F2 to F4c. Obviously, F4c is dependent on our outcomes trial that we'll read out in '27 and then resmetirom and our Madrigal MOAs that we're adding, also will bridge across this as well. So we're in a very strong position to lead the market, not only now but in the decades ahead. So maybe in conclusion, just to summarize where we're at here, we are in an outstanding position. I just don't think you can find a better setup of market dynamics. We'll actually go back to disease, high unmet need disease, great market dynamics where you get to enter the market as the first product with an exceptional profile with an ability to add to it, we believe, to make it perhaps even better for at least some patients. We're off to a great start annualizing at over $1 billion in just the sixth quarter of launch, steadily adding patients, optimistic about '26 and beyond robust growth. We have our indication expansion opportunity, as I mentioned, with outcomes, which is essentially a doubling of the opportunity and just an exciting chance to help more patients that are even in more need. Pipeline. We're well on the way to building. We have 1 new Phase II. We have 2 ongoing Phase III trials, and we have 3 clinical stage assets. We are becoming a company that has a present short-term future and a long-term future as well, and we're really excited about it. And as I say, we're leading the fight against MASH and take that very seriously. So thank you for coming. We'll now turn it over to some Q&A.

Well, thank you, team. We'll move into the Q&A portion. We've had a number of questions come in. So I'll start us off and then time permitting, we can also open it to the floor here. So the first question is for you, Bill, around the pipeline strategy. As you laid out in your presentation, you're focused on building an industry-leading pipeline in math. Just philosophically, can you discuss that in more detail, i.e., are you only looking at mash? Are you looking at oral medicines or later-stage assets and then a decade from now, based on your strategy and the pipeline you want to build, what does Madrigal look like?

Great. Thanks for the question. Look, -- it's very rare when you are at the beginning of something that is such a big opportunity. It's even rare that you have a great asset to start to tackle that with. I mean I've been in the industry over 30 years now, and the setup for this is better than anything that I've seen. I've seen what some companies have done is they kind of squander an opportunity to extend leadership in a disease or an indication and try to diversify into something else prematurely. That's not what we're doing. Before the table is set by somebody else, we want to be the 1 who sets the table to have not only Rezdiffra as a fantastic asset, but then what can we do enhance it and enhance our leadership in the space. So that's why, as Dave said, very clearly, we're looking at all mechanisms, all modalities, et cetera. If it's going to help patients, it's something that we're really interested in. There's a really good example of somebody who has taken a combo approach, and that's Vertex. Vertex is the unmitigated leader in CF. We see no reason why we can't be the unmitigated leader in MASH. And I think you've seen how that's worked out for them. So the focus is MASH. Let's win here. We will be driven by the science, if there's an adjacency we want to move into or if there's an opportunity down the road. But remember, this industry is driven by great assets, first and foremost. We have a great asset today. We think that we can extend within MASH. And we will be on the look for great assets in other areas in time, but we don't want to move prematurely from really setting ourselves up for success in helping a lot of patients in this disease first.

Next one is for Dave. It's about the DGAT-2 deal. You said you announced last week and spoke about that you got to inhibitor you in-licensed. Can you tell us more why you're excited about that compound? What are you looking to see in the drug-drug interaction study? How do you expect the DGAT-2 and resmetirom to work together to achieve efficacy, more importantly, how do you see the gap fitting in with your oral GLP-1 that you also in-license?

Yes, great questions. Yes. I think -- well, when we think about the mechanisms of action, as I pointed out, there are a variety of places where you can intervene in this complex disease. And the goal has to be to identify mechanisms that are complementary and don't overlap too much. So the reason why we liked DGAT is because it's in a completely different aspect -- it occurs the enzyme is in a completely different part of the disease process, the de novo lipogenesis process. We like the molecule itself. Pfizer did a very -- we did a great job. They did a big pharma job developing the drug and have a lot of great data for us to evaluate during the diligence. And when you think about the efficacy and tolerability profile, if you think about other targets in de novo lipogenesis like ACC inhibitors where you have triglyceride elevation that could be difficult to manage or fashion where if there's systemic exposure, you can have hair loss and other issues, DGAT really seem to be a standout kind of enzyme to target. And then as I said, the idea of intervening de novo lipogenesis and at the same time, sort of opening the plug on the sink to allow the free fatty acids to flow out through the mitochondrial beta oxidation process was very attractive. So from the -- with respect to the drug-drug interaction study, we're at a minimum, what we want to do is make sure the 2 drugs don't have a pharmacokinetic interaction. So that's 1 key outcome. We're still in the process of deciding exactly how we'll run the trial. There's a possibility we could enroll patients in the study, for example. And maybe you got some early measures, but we haven't made that decision yet.

Yes. And just to comment on DGAT-2 as well, we were at MASH-TAG, which was -- which is a MASH-focused meeting with KOLs in the space. We just came from there yesterday. And there was a lot of discussion about DGAT-2 and I can say a lot of enthusiasm. I think people had perhaps underappreciated it, but they're very happy to see it in the hands of a company that is dedicated towards MASH.

Did you want to address me to GLP-1 -- yes. So the GLP-1. I mean, look -- so GLP-1 acts at a completely different part of the MASH process. So -- as Bill alluded to earlier, we want to take multiple shots on goal, and that's one of the reasons why we need to stay capital efficient in our development programs and in our expertise and capabilities and sort of the history of our R&D team, We think we can do that. So we'll have multiple opportunities. We can evaluate which programs look the best and maybe even do more complex combinations in the future. more than 2 products, for example.

Just to double click on your GLP-1 combination strategy. So if you've pointed out to analyses suggesting that a greater than 5% weight loss may amplify reflects on resmetirom. What weight loss sweet spot would you be aiming for in the MASH with an oral GLP-1 approach? And what are you looking for in a single ascending dose trial that you expect to start next quarter?

Yes. So maybe I'll start with the second question first. So from the Phase I single ascending multiple ascending dose study is sort of the meat and potatoes of drug development. So it's a new chemical entity. So healthy volunteer trial, pharmacokinetics. The good news about GLP-1 as a target is that we can measure pharmacodynamics in a multiple ascending dose. So we can see some weight loss and get an idea of the efficacious dose range multiple ascending those studies. So that helps us. The partner -- our partner companies, CFTC did a very nice job for clinically developing this molecule, and they did a lot of the preclinical experiments directly compared to orforglipron and MGL2a6 is a derivative for orforglipron. So we have a pretty good sense already of where we need to head in terms of dose. So that's the idea for the early trial.

Super. Thank you. The next one is on the F4c. You referred to the market opportunity. You position it as potentially doubling Rezdiffra's opportunity outcomes data expected in '27. Commercially, how are you thinking about uptake dynamics about Fc4? And Dave, how does the 2-year open-label experience inform confidence in the '27 do you have?

Go ahead, Dave. Why don't you start?

Yes, sure. So Bill alluded to this earlier in his presentation, but -- so we have 122 patient cohort from one of our earlier trials called MAESTRO NAFLD-1 where these individuals have been -- have gotten resmetirom now for 2 years, and we recently showed those 2-year data. So these patients at baseline have stiff livers, they have cirrhosis, they are kind of right on the cusp of having decompensation. And what we're able to show is that over that 2-year treatment period, we can have patients liver stiffness decline substantially. -- to levels that you would predict they would be at lower risk now of progressing to clinically significant portal hypertension, which is really kind of the end stage of liver disease. So that gives us a lot of confidence just in terms of the response to the drug. So that's liver stiffness. There were a variety of other biomarkers in the study as well that gave us even more confidence. And as Bill mentioned, the patient population in that open-label cohort mirrors the patient population we enrolled in MAESTRO outcomes. So those who pieces of information, both what we're seeing in terms of the efficacy measures, but also the fact that the patient populations are similar gives us a lot of confidence.

And then commercially, the setup is great, right? Because it's a really, really sick population that's in need of medicine. And we believe that uptake quite rapid, more rapid than an F2, F3, and you're going to have a prescriber base that is several years into prescribing Rezdiffra they're extremely familiar with it, how to get it, et cetera. So it's a very simple transition we believe.

Perfect. Thank you. Mardi, moving on to you. This is about spend and profitability. So how are you thinking about expenses in the near term and the longer term based on the SG&A spend on launch as well as spend you're planning with the new pipeline programs? And when do you expect to reach profitability?

Yes. Great questions. Thank you, Brad. So we're very much, as Bill has said and David said, very focused on our top line growth and then our pipeline development. So that's our focus. Profitability is really not a matter of if but when. So again, we're doing what we can with SG&A to support our top growth with Rezdiffra and of course, with Dave, with the R&D spend, that will take some time to ramp up because it will take a little while to get to the Phase I and then into the Phase II. So you won't see a big change in R&D in the short term. But really, in terms of spend paradigm going forward. And in the near term, there may be a quarter or 2 where we dip our toe into profitability, but it's not our focus for the near term. But eventually, you'll see the growth rate at the top line is going to diverge from how much we can spend and we will be in a profitable position. But again, right now, we're just focused on moving the business forward as best we can.

Perfect. Just adding on that also on gross to net. You've talked about the step-up to high 30%. GTN in '26 is commercial contracting begins. Can you talk more about the components of the gross to net and why the significant change?

Sure. Well, we've gone from commercial contracting, which is 1 component, of course, of our gross to net. And first, you have to look at business mix, we have 50% to 55% of our business is 30% to 35% Medicare, and the rest is Medicaid and other. And we were very fortunate that we launched almost 2 years with no commercial contracting. So as time goes on, will be coming on the market in August, just the way our business -- our general industry business is set up to start contracting with the commercial and Medicare PBMs. And so we're going from this point from 0, where we have great access to contracting with all the major PBMs. Again, preserve our great access. So first-line therapy, no step-throughs and in some cases, improved utilization. So we're in a very good position. But that will step up into 2026. Those contracts start 12. Of course, there's some domino effect of the downstream plans coming on board as well, but you'll see our gross to net for commercial payers go into the high 30s as we said, the impact. I would say, though, that our growth is continuing to be strong. So we're going to steadily add patients to 2026. And despite the changes in gross to net, we expect robust net revenue growth for 2026.

And just to confirm, the high 30s is all the components of gross to net put in, right, co-pay assistance, et cetera.

Super. Just continuing on that, on the growth, what is the nature? What's driving that growth the breadth of prescribing that depth of prescribing, our endo expansion, payer access? And how does that ramp over the course of the year?

Yes. The answer is yes. All these things are driving it again because we are at the -- we're at the very beginning here, 10% so there's lots of room to grow. Where is it going to come from mostly though, it's going to be more depth driven than breadth with over 10,000 prescribers, breadth is not really objective though we have new prescribers every day. It's going deeper. And just moving people along that distribution curve where they move from a few to many to of patients. And what we're hearing from every prescriber is nobody is maxed out yet, and there's plenty of patients that are still in their practices that could benefit potentially from risk difference. So tons of room to growth. What we've done is we removed the barriers that could have come into place in 2026 and that being one of the access. So we've lined up extremely well as we move into this year, and we think that carries through not only '26, but into the future.

Another interesting -- at the end of last year, and you mentioned it, but an old version of semaglutide was approved. How do you see it having an impact on the MASH landscape?

Yes. Well, look, this is high-dose Rybelsus, right? This has been a product that has been approved -- so this is not a new product, those -- some of the press may speak a little bit differently about that. It's a GLP-1, and we know that what we're seeing with real-world data is that a, hard to keep somebody loading somebody to a therapeutic dose and b, to keep somebody on any GLP-1. Now this GLP-1, as I said, has been on the market. It just has -- since 2019, it has a higher dose, and it's not for MASH. So what -- hopefully, if it leads to a little bit more awareness and people using the product, ultimately, we believe that would just set up a lot more people to be potential candidates for Rezdiffra use. But I think it falls in pretty much the same message as with the other GLP-1s oral or injectable. It's just really hard to get to that target dose and stay on long enough effect on this disease.

Perfect. We're just coming up on time. So I will add one last question [proceeds]. This is about your launch strategy. So you've launched in Germany last year. How should people think about that as a contributor to your net sales in '26? And more broadly, longer term, how do you expand beyond how do you see the ex U.S. opportunity.

Yes. Look, I think that there's still a significant opportunity outside of the U.S. It's just going to take a little bit of time. Don't look for much contribution in 26. It's something that scales over time. Germany is the only country that we're launched in at the moment. There's other countries that we're looking at. For instance, countries in the Middle East, we think that, a, there's a high unmet need there and reimbursement is actually quite favorable. So it's going to take a little bit of time. We're living in an MFN world. We are very aware of that, and we are following the principle of that. We launched in Germany at the U.S. government price. So parity the U.S. government in a something that we'll see how things unfold as we get more clarity with MFN along the way and so forth. But we're going to be very pragmatic about it. The U.S. is market that is the biggest, it is the most important, and we're not going to sacrifice the U.S. market in any way.

Thank you very much. With that, I would just like to extend a thank to all the Madrigal team here and to all of you for being here with us today that would bring us to the end of this presentation. Thank you.

Great. Thank you for having us.