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

Good morning, everyone. Very excited to be kicking off the Morgan Stanley Healthcare Conference with the Madrigal team this morning. Thank you guys for joining me. I'm joined by CEO, Bill Sibold; CFO, Mardi Dier; and CMO, Dave Soergel. So thank you guys for joining us early on a Monday. We're very excited to be starting this conference in this way. Before I dive in, I'm going to read a brief disclaimer. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. Okay. So let's get into the latest developments at Madrigal. Bill, let's start with you. The company has had significant progress since the beginning of this year, new IP, and EU approval, a new licensing agreement, you guys have been pretty busy. There's a lot happening. Can you give us the highlights and kind of summarize how this has been impactful for Madrigal?

Yes. Look, it was a fantastic quarter. It's been a fantastic year. As you said, lots going on. We've really created a stronger foundation and given ourselves a really bright future with a long runway. First of all, with our launch, again, we had a great quarter, exceeding expectations. And I think it was -- it just shows just the unmet need that is out there and how great a product Rezdiffra is and also how great a team we have. Big news, of course, with the IP going out to '45, we had EC approval. So Europe is our next destination, so to speak, we'll be starting in Germany. We did the deal, oral GLP-1, and we secured $500 million in financing to help us execute on all of this. So that sounds like it is progress over the course of a year, let alone a quarter. So we're really excited about what's happened so far.

Absolutely. You mentioned the launch of Rezdiffra, which is, of course, front and center for everybody and being the first to market, you're kind of paving the path in MASH. So can you talk a little bit -- I know you just put out your quarter a few weeks ago, how that has gone, what you've learned from that launch experience about the market you're looking to address?

Yes. Look, we had a $213 million quarter. What we do is we track our metrics against other great launches over the last 10 years. And we are meeting or exceeding each of the metrics that we track. It's the most objective way to look at the launch. And we can say without question, this is one of the best specialty launches in the last 10 years. So the metrics that we look at, a key metric is the breadth of prescribing. And we had a target of 14,000 prescribers as we went into the launch and a sub target of about 6,000. And we announced on the call that we had 80% of the 6,000 had written a prescription and 60% of the 14,000 had written a prescription. And that's really important because breadth of prescribing in a launch early on is a great predictor for future performance. You need to -- it's kind of simple in some ways, the math. You need to have enough prescribers prescribing enough product to get you to your ultimate objective. And this is one where we really stand out in metrics versus other launches. The other thing that we have is -- and which is going to the patients, which is why the breadth is so important, over 23,000 patients on drug. Now that in itself is a big number, and we use a very conservative at a point estimate June 30, how many patients are on. So that's net of any discontinuations, et cetera. So on each of the metrics, the launch is going just really, really well. And we think that we're still just at the beginning of a 7% penetration into 315,000 patients. And we described this as multiple paths to victory, so to speak. We know that there's patients that are going to continue to be diagnosed. We know the opportunity is going to get bigger, and we're really just at the beginning.

So you mentioned a lot of the statistics supporting the launch and how great it has been. Anecdotally, what are doctors saying about their experience with Rezdiffra in the real world? How does that support what you've found on paper?

Yes, it does. A lot of times when a product launches, first of all, you never know how it's going to perform in the real world. You have your clinical trial data and then you try to project to say, what's it really going to be like? And in this case, what we're hearing is it's really overdelivering Rezdiffra efficacy. And I think it's part of -- for a number of reasons. First of all, it's a great drug, right? So profile, liver-directed, once-a-day pill, no dose titration, et cetera. And you have to be able to take a medication for it to be able to work. And what we're hearing instead of -- for a clinical trial where you have a regulatory composite endpoint, in the real world, you're looking at the metrics on a quarterly, semiannual, annual basis, liver stiffness, liver fat, lipids, et cetera. And with the broad effect that Rezdiffra has, that allows the physicians to -- and prescribers, I should say, to see the effect across a number of things. Now it's still early. We're just over a year. We're 5 quarters into launch. And so there's just a cohort of patients coming through now that have been on for a year. What's probably the most exciting that we're hearing is that even at the 6-month mark and then at the 12-month mark, physicians are seeing an effect on liver stiffness. And that is a really strong indicator for us. And we've heard of people that have reversed 1 and even 2 steps back in their fibrosis stage. And that's ultimately what we're trying to do. If you can take somebody from an F3 to an F1 or an F2 or hold an F3 and prevent them from going to F4c, that's something which is really, really important. So we're hearing -- and I think what we're hearing is the product has been well tolerated. People find the titration schedule, which there isn't one, makes it really easy. And so I think this is one of those times where the surprise is it's just performing a lot better than what expectations initially were based on, as I told you, a composite endpoint in the clinical trial.

Terrific. What else can you share on patient adherence with the drug? And maybe also talk about reauthorizations, how are physicians approaching that for the patients that you've mentioned are reaching 12 months?

Yes. Look, it's still a little bit early, but we're seeing really strong adherence. We would expect this to be like a well-tolerated oral. People ultimately are going to stay on a drug or not for 2 reasons. One, can they tolerate it and were tolerated? And two, is there an effect? And because we're seeing good efficacy in the real world, really strong efficacy and it's so tolerable, we're seeing that adherence rates look really, really strong at this point, which is always, again, reassuring. You're not sure how it's going to perform. Some people have said that it's an asymptomatic disease. So maybe patients won't want to stay on it or they won't know. We're not seeing that at all. I think that we're hearing that patients are incredibly interested in doing something about this very serious disease. Once the prescriber explains to them the serious nature shows them in various liver models and so forth, there seems to be a high interest in taking the product and staying on it. So adherence, we expect to be like a well-tolerated oral. As far as reauthorization, nothing different with Rezdiffra than any other product. Usually, you have to go through a reauthorization at the 12-month mark. And that's not -- hasn't been an issue. They seem to be criteria such as physician attestation or showing improvement on one of the metrics such as stiffness, fat, LFTs, et cetera. So we are seeing that. So we don't consider that to be an issue.

Okay. You mentioned obviously extending the IP for Rezdiffra. Can you talk a little bit about is that -- how significant that is for the franchise?

Yes. Look, as I listed a bunch of things that happened leading up to the quarter. And the single most important accomplishment was the IP. And I would put that above everything else that we've done for the simple reason that, that creates a foundation for us for a very long time frame to build Rezdiffra to really to build Madrigal. And the way we're thinking about now how do we want to do business development. Strategically, what do we add next through business development, we can take a longer view, for instance, even with the oral GLP-1. It's a preclinical asset, but we can afford to be picky and get the product, the asset that we want because we have that long runway with Rezdiffra. And that is -- it's a really, really important patent. And maybe just to spend a minute on it. This is something that was really not obvious. It was an unexpected finding from our Phase III clinical trials. So this is a -- from claims in the label that we have, our commercial threshold dosing regimen. And it was an unexpected finding. Typically -- well, in our Phase II, we had nothing -- no prior art that would suggest that. We had no results that were prior art that would suggest that we would see this result. And in our Phase III protocol as well. So what happened was you had 2 cohorts of patients at different doses that based upon weight, ultimately had a better outcome for safety and for efficacy. And that was really unexpected. And this is for us, as I said, it just creates such a great foundation. And it's a strong patent, and we are really, really proud of the team's work to get this. So again, if you ask me, that is the big piece of news that gives us confidence in the long term of the product and also the foundation for the company.

Congratulations on that.

Thank you.

All right. I'm going to get Dave and Mardi involved. Another high unmet need and value driver for Madrigal is this potential F4 population. Dave, can you talk about the data you presented at EASL recently and your outcomes trial and then kind of how you see Madrigal potentially competing against other, particularly FGF21s that are going to be pursuing that patient subset?

Yes. Happy to. Maybe, Bill, do you want to talk about the population and some of those details first, and then I can go into the data.

Yes, sure. Look, first of all, you say that us competing against FGF21s, I think it's the other way around. We are years ahead. We're going to have tens of thousands of patients that have been on F2, F3. We're really excited about F4c. It's about 245,000 diagnosed patients in the United States. That's sizable, and we would expect that we will be able to be a smaller number of patients than F2, F3, but certainly higher unmet need even. So we would expect higher penetration. So it's an opportunity to potentially double the opportunity for Rezdiffra. So I think that we are in a really strong position based on what Dave will tell you about the data, we're setting up really nicely to really be in this F2 to F4c range.

Yes. So right. So with respect to the data we showed, so at EASL, we shared 122-patient open-label experience from the MAESTRO-NAFLD study, which is one of our earlier Phase II/III studies. And in that population, we showed very important changes in liver stiffness, improvements in liver enzymes and other biomarkers, for example, MRE and other things in the study. And that data set in its totality gives us a lot of confidence in our ongoing Phase III MAESTRO Outcome study. So the trial that will open up that indication for us on the label will be the MAESTRO Outcomes study. So translating that open-label experience to MAESTRO Outcomes is really the critical thing. And there are a couple of things that are important to take away from the open-label experience. First of all, the baseline characteristics of the population that we presented is very similar to the baseline population characteristics from MAESTRO Outcomes. So the data that we saw from that open-label experience gives us a lot of confidence that we should see a beneficial pharmacologic effect in the outcomes trial. The second thing is obviously the data itself, so showing important changes in liver stiffness. For example, we showed a reduction of 6.7 kilopascals in VCTE in this population, which translates to over a 25% improvement compared to baseline. And it's really that 25% improvement that puts patients into a lower risk category in the cirrhosis population. So the other way of looking at those changes is in the F4c population, you actually have a further sub-stratification you can do on the basis of clinically significant portal hypertension. So the risk of having the really bad outcome from cirrhosis, which is developing congestion in the portal system and then having all the bad outcomes related to that. And so the way that's measured typically is using certain criteria to determine whether or not somebody is at high risk for having CSPH. So at baseline, 35% of patients in that open-label experience were predicted to have clinically significant portal hypertension. They already had it. And in those patients, we saw that 2/3 of them were able to improve their status after 2 years of therapy. So they became either low risk or modest risk of having CSPH as opposed to definitely having it. It's really that kind of aggregate look at the data and then comparing it to what we expect coming out of MAESTRO Outcomes that gives us a lot of confidence in that population.

Perfect. So of course, as the first kind of mover in this space, you're right, other people are going to have to compete with you guys. So now we have sema recently approved in MASH. Can you comment on kind of the label thoughts on potential step edits and payer insights you can share on that approval?

Yes. First on the label, no surprises there. That's what we had expected based upon the Phase III data. From a payer perspective, look, it's -- let me first of all, provide the market dynamics and then let me get to the payer. This is a good thing for patients. It's a good thing for the market evolution to have another product there. I mean, as we said, we're 7% penetrated into a population of 315,000. Growth occurs, penetration increases as you have more companies that are out there educating and talking. So talking to prescribers and to the community overall. So we think that what it does is it leads to greater diagnosis, greater treatment and ultimately, an opportunity, we think, for Rezdiffra. So I've seen that in every specialty area as you add more, it just helps. So then it comes down a little bit more to profiles. And as I said before, we've got a once-a-day pill, no dose titration. We work in all subgroups, so type 2 diabetes, et cetera. We were consistent across the board, and we are getting this growing real-world evidence. All those things matter. So you're now going to have a competitor that is out there, as I said, increasing awareness. And I think this is where Rezdiffra will really stand out. Now 2 things. One is we know that the way Novo has talked about this opportunity is millions and millions of patients with F2 and F3 in the United States, and we've been talking about 315,000. So they do need to have that top of the funnel expand dramatically in order to make it an interesting opportunity. Now there's the reality though that tolerability with GLP-1s is a challenge. So as you expand the funnel, if people try a GLP-1 and look, there are, I think, 10 million people on a GLP-1 last year or this year total. And if you have tolerability challenges, you'll be looking for the next product as well. So we feel extremely well positioned as they're driving the top of the funnel, if people start a GLP-1, Novo has reported that about 70%, 7-0 percent of patients discontinue within a year. That leads to a tremendous opportunity, many times greater than the 315,000. Now a couple of other market dynamics here. Right now, about 50%, 5-0 percent of patients that are on Rezdiffra have been on a GLP-1 already. and 25% are with combo therapy. So they are on GLP-1 for another indication. They've had MASH so that Rezdiffra was prescribed. So we think that this dynamic is going to remain now. When you ask about kind of payers and step through, first of all, it's early. We're in discussions with payers now. 2026 gets resolved a little bit later this year. But it's not a simple thing to think about how you would implement a step edit here. So let's say you have a patient on tirzepatide who is -- for diabetes. Are you going to make that patient discontinue, move to Wegovy dose titrate and see how you do or if you have somebody else on Ozempic, et cetera. So I think that -- and with so many people, as I said, that are already on one. So I think we're working closely with the payers. I think we've established good relationships, good partnerships. But we feel that regardless the opportunity gets more significant for us as you have somebody else who's driving this new diagnosis and awareness. Certainly, what we've said is that we're steadily adding patients. We showed that in the Q2 results. And we said that we believe that we will continue to steadily add patients through the launch of Novo this year.

Maybe just one more on this topic, which is just in terms of pricing dynamics and how do you see gross to net evolving with them now -- on market, with sema now on market?

Yes. Mardi, would you like to talk about gross to net?

I would love to talk about.

Over to you.

Thank you, [ Kelly ] and good morning. I mean, for all the reasons that Bill just discussed with sema coming on the market, we believe that everything is going as expected with competition, relationships with payers, et cetera, all flowing into our discussions with gross to net in the future. So it's something we're very focused on. We do look for the long term as well. So we look at competition, we look at time, but we also look at F4c and how we're going to evolve gross to net in the future. But right now, gross to net has been well within our expectations. We look at other specialty launches and where they are at this point in the launch, and we're following that right on top of other specialty launches for this point in our launch. And also from a contracting perspective, which is one component of gross to net, we really started from a position of strength. So for the first year of our launch, we didn't commercially contract with payers, but we spent that time really developing our relationship with payers. And then we've also said that we started contracting this past April in the beginning of the second quarter. So we've just started the commercial contracting, and we'll see more of that in the second half of 2025 as gross to net continues to evolve. But the overarching theme here is it's all within our expectations. It's something that we focus on. And so far, everything is going as planned.

And especially now with the 2045 patent, we have to be thinking in terms of just the long term. And as we entered in market and launched, we -- gross to net was top of mind, right? I think it's really important. That's why we didn't contract initially. We didn't believe that was necessary. Now we've started and which is necessary, and it's something about being -- it's about being a good partner with the payers as well. But we're really looking at things through this lens of the long term -- what's the right thing for the long-term value of the company.

Okay. Thanks for that. Just running down the list of exciting developments, the EU approval came through recently. Maybe, Bill, you want to comment just on how the launch prep is going, anything you see playing out?

Yes. Really exciting. We become a global company. And we had, had a lot of questions initially of EU, why are you doing it? Why don't you find a partner? Well, I think the answer is simple is because we can do it, and we think we can do it better. And also, we want to preserve the value for ourselves. Every decision that we're making at the company, we're looking 3, 5, 10 years ahead. And when it came to a decision about would you commercialize in the EU, a year ago, 2 years ago, when we were focused on just trying to get ready for a U.S. launch, one could say, well, it was -- it's a big decision, and it's a real stretch of management time. And if we had just taken that view, we may have said, well, let's do some kind of deal and just worry about the U.S. But that wasn't the aspiration of the company to build truly what we believe will be the next leading specialty company. So we said, no, let's double down. We will take on that responsibility, hire the right team. And in 3 years' time, we're going to look back and say that was a great decision because we didn't trade away the economics, trade away the value, trade away the control overall the company. So we fortunately have had a great U.S. launch, and we have learned a ton from the U.S. launch. Probably the biggest learning from the U.S. launch is get a great team. And so that's the way we started in Europe. So we put together the right leadership team of the region. We're starting with Germany, obviously, and have put together the leadership team, the whole field team, all the resource, et cetera. So it is a team that is ready to go, that's excited to go that has taken all the learnings from the U.S. and from all of their own backgrounds to be ready to launch in this back half of the year. So we're really, really excited about that. And when you think about Europe, the EU, it's about 370,000 patients that are F2, F3 that are under the care of a specialist. So a pretty sizable opportunity, though you have to go to a country-by-country basis because we're not launching everywhere. We're going to only go to countries where it makes sense. And we have very rigid guidelines. We want to be in a positive contribution position in 2 to 3 years. So we have our criteria. We have a plan on how to get there, et cetera. Now of course, from a pricing perspective, we're very aware of the macro environment and take that into consideration. So as we start finishing off our launch prep here, that's obviously one of the components of it, and we'll report out on that as we get closer to officially launching outside of the U.S. in Germany to expand ourselves.

Okay. Great. I want to spend the last 5 minutes talking a little bit about your BD strategy. You've taken steps already to expand your pipeline. You brought in this oral GLP-1 from CSPC. So maybe, Dave, do you want to talk a little bit about why you decided on this mechanism, maybe some of the key differentiating attributes of this particular compound you went for?

Yes, yes, sure. Well, I mean, first of all, we've kind of scoured the landscape in MASH, kind of modality agnostic, target agnostic and really are looking for the best additions to our pipeline. And this molecule, which is currently SYH2086 from CSPC, kind of rose to the top in a couple of ways. The first is it's derisked from a target standpoint. So I already talked about GLP-1s. Obviously, GLP-1s have an effect on metabolism and can possibly affect the pathophysiology of MASH. So from a target standpoint, it was straightforward. From a chemical standpoint, it's an orforglipron backbone compound. So we already know that orforglipron has been in thousands of patients already. It's had a very good tolerability and safety profile thus far. And so from those 2 -- and then it was available and there was an interest in doing a partnership. So from those perspectives, it kind of rose to the top. Now from a scientific standpoint, the great thing about resmetirom is that you only need a little bit of additional weight loss to really boost its efficacy. So what we showed from MAESTRO-NASH is that patients who lost about 5% greater than or equal to 5% of their body weight had an enhanced effect of resmetirom. Now interestingly -- so then you say yourself, okay, well, the GLP-1 that we have in our portfolio is then going to be differentiated on the basis of its combination with resmetirom, right? So you don't need to get to 15% weight loss, 20% weight loss, which is where the current battle, the titans is happening in weight loss therapy. You only need to get 5% weight loss. So if we can get instead of 20% of people to 20% weight loss -- to 5% weight loss, instead we can get 80% or 90% of people to 5% weight loss, we can enhance resmetirom's efficacy. So that's the approach there. And we continue to look for new opportunities for the pipeline.

Yes. I mean, look, I think that we've got this opportunity in front of us where we are at the very beginning of what we think is a very significant specialty market. And we're in a leadership position. Our goal is to maintain that leadership position. Now we've got -- again, we've got a long runway for Rezdiffra now out to 2045. So we have this opportunity to really thoughtfully build. So we're looking at next best mechanisms of action or something that could enhance in combination with Rezdiffra, the product profile, et cetera. So we're looking at everything. Anything that is MASH related, we're looking at it. And it's a matter of finding something that we think is just right and is something that we can get done as well. So expect more from us, but it's going to be something which is going to make sense in the context of everything else that we've said. And we have the financing runway. Mardi, maybe you want to comment on that to help us execute on the strategy.

That's right. So BD is very much a main pillar of our strategy moving forward, and we did complete an up to $500 million senior debt security this quarter as well with excellent business terms. And we did it from a position of strength. So it gave us ultimate flexibility to do more BD in the future. And what Dave and Bill just said, not only are we looking and actively looking, but also we can be very thoughtful since our IP runs to 2045 now. We can take our time that we find the right opportunity, we're in a great position to move forward and from a position of strength from a cash standpoint.

And what are the next steps on the GLP-1 Dave in terms of clinical plans? And do you need to do more preclinical work?

Yes. it's a preclinical asset. So we have a really great pharmacology package. So we know that the drug in preclinical species is an effective GLP-1 agonist. We're still waiting on the completion of some of the IND-enabling work and then expect to be in the first-in-human study first half of next year.

Okay. We'll stay tuned then.

Yes. Look, that's -- it's a really exciting program for us. We were really thoughtful about what we were looking for. And as Dave said, if we can just get that little bit of weight loss. So it allows us to kind of reframe the whole oral GLP-1, GLP-1, GGG, et cetera, race that's on. People are racing towards who can get that extra percent of weight loss and differentiate themselves and companies move kind of wildly based on that move. We're not interested in that. Our focus is how do we make a better MASH product. And therefore, when we went through the whole diligence process, it was something that, first of all, we made the decision pretty early on. We wanted an orforglipron derivative, which leads you down one path. It had to have the ability to be amenable to a fixed-dose combination. That's the objective. So we are very, very thoughtful about it, and that's what we plan to do with the rest of the pipeline to expand it. So we feel like by being the leader with a foundational therapy like [indiscernible] we can think about things differently because we are in a white space, which is yet to be defined and the company defining it is Madrigal with Rezdiffra at the front of it. So it just allows us to really think towards leadership differently than anyone else in the space.

Well, congratulations on all the progress. There's a ton of great execution behind you. Maybe we'll just finish with a comment from Bill. What excites you sitting here today? What excites you the most looking forward for Madrigal?

I mean, look, the opportunity is just so exciting. 7% penetration. We're just getting started. We have a long runway out to 2045. We have a pipeline now. We have performance, which just indicates that we know how to launch. We have -- we've done, I think, an outstanding job. This is an objectively outstanding launch when we look at metrics from other product launches over the last 10 years. I mean we are well on our way to having a long-term leadership position in MASH. We are well on our way to building a mega blockbuster. We are well on our way to building a specialty company that is durable and I think really can compete with the best specialty companies in the industry over time.

Terrific. Thank you to the Madrigal team for joining us. Enjoy the rest of your conference.

Thank you very much.

Thank you