Good afternoon, everyone. Welcome to our second day of our Piper Pharma Healthcare Conference. My name is Yaz Rahimi. I'm a senior biotech analyst at Piper Sandler. Really thrilled to have the team from Madrigal Pharmaceuticals. Bill and Tina, thank you. Oh, Mardi, this is how delirious I am from doing fireside chats. What can I say? What an incredible year you've had, right? Two incredible years from approval to launch to execution. So a great place to would be to give us a brief review of where you are year to date.
Yaz, first of all, thanks for having us. It's a pleasure to be here. Yeah, it has been a remarkable two years as you look back, and, you know, it's been a remarkable 2025 as well, and I think we're really set up for 2026 and beyond. I mean, we, in our last quarter, announced that we were on the billion-dollar run rate, which I think is a huge hurdle for any company in any specialty, in any disease, to meet, reach that milestone, so $287.3 million in sales, over 10,000 prescribers, which is a huge indicator of future uptake as well, and just under 10% penetration, but that's over 29,500 patients on drug, so I look at that, and those are just objectively great outcomes for this stage in a launch. We're only six, six quarters in.
You know, we're making progress on other areas as well, as I said, for 2026. We've secured what appears to be a really great payer contracting for 2026, first-line access, no step-throughs, and where necessary, improved utilization management criteria. And I think that that was one of the questions, how would we come through that in light of a competitor. We've advanced the pipeline. We closed the deal on our oral GLP-1, our F4c trials progressing along. And over this period of time, we also had our Orange Book listed patent for a 2045 patent. So overall, when I look back at this year, I think things have happened as we had certainly wished. And we have put ourselves in this kind of rare category of being a great launch by a company that had not previously launched products before.
No, that's very helpful. A couple of things I want to talk about that happened in November that during the AASLD conference. One was new data that was shared around sort of the off-treatment of worsening of symptoms and NITs in patients who were treated with Rezdiffra. So if you could just kind of talk about the importance of that, how established this is, Rezdiffra is truly a chronic therapy for MASH.
Yeah. So the data showed in F2, F3 population, and in F4c population that when you discontinued the drug, the disease came back, and it came back quickly. And, you know, whenever you launch a new product, especially the first product ever approved in the space, you're going to get questions from the community about, well, you know, how do I use it? Is it chronic? When do I stop? And I think this really emphasized the importance of keeping people on therapy. Now, fortunately, Rezdiffra is a very well-tolerated product, so we think that's something which is amenable to being, having people stay on therapy. But that was important information, and the community really did pick that up and listen to it and is pointing to it. And we think that is, first of all, good for patients. And secondly, good for, Rezdiffra's performance in the future.
And another very important data set was the F4 data set that was shared. Help us understand how does that, even though it was an NIT-based study, how does that de-risk the MAESTRO outcome study, which is reading out in 2027?
Yeah. I mean, look, this is, first of all, it's a really important population. This is F2, F3 patients are sick. F4c patients are very sick and about to decompensate and lead to bad, that leads to really, really bad outcomes for them. And, as you know, we have the 845-patient MAESTRO-NASH outcomes, which is in well-compensated cirrhotics that reads out in 2027. This is a, it's a real benefit. We have this cohort of patients from a study that we had done. And this is an open-label cohort of patients, and we've been following them now for two years. And what we see is a very dramatic reduction in liver stiffness over that time. And what we did at AASLD, we read out on even a sicker population, which are those with platelet counts below 100,000.
We saw a very robust efficacy effect there, a decrease in liver stiffness of over 7 kPa. Really exciting data. Now, why are we excited? Because the baseline characteristics of that cohort are almost identical to the 845-patient phase three program that we're running. You know, while you can't have certainty in any trial readout, you know, that's been in the industry a long time, and, you know, you can de-risk things all you want, but you have to open the envelope, so to speak. This gives us greater confidence, right? We have now a cohort of patients that looks very good. We have mechanistically, we believe that THR-beta is fundamental. You know, we also receive anecdotal feedback from the community and how they've been, the experiences they've had.
So, you know, we feel really good about it, and we don't think that this is something that we've been necessarily given credit for, until recently. So, you know, we'll continue to talk about this study because it is a really important next readout for us.
Okay. And, team, another topic that we get is, I think on the third quarter earnings call, you guys have shared that you want to expand your focus of going from specialty GI and hepatologists to endocrinologists. You've also made us aware of your core calling group, which is 6,000 prescribers. So maybe tell us, help us understand, like, what do you envision this mix going to look like by adding and what that proportion of endos are going to be, because I think we do know that semaglutide is maybe more positioned or advertised to endocrinologists.
Yeah. So, look, when we launched, we had three specialties that we were targeting: hepatologists, gastroenterologists, and some endocrinologists. And that was a prescriber base of about 14,000 prescribers. Now, 6,000 of that 14,000 are your highest targets, and that's where you'd expect the majority of the business to come from. Just when you look at the numbers, it's about a 10 to 1 ratio of GI to hepatologists. Just by number in the country, there's less than 1,000 hepatologists. What we found in the last, you know, six quarters is we've been getting increasing reach out by endocrinologists asking us to please come talk to us about Rezdiffra. And these were people that weren't originally on our target list. So we spoke to them, we did an assessment, and we decided to put a dedicated effort towards endocrinology.
And to give you a sense, it's about 2,000 high targets that we're looking at now. These are, it's really interesting, you know, because there's this, there's this myth out there that GLP-1s alone are going to prevent MASH and take care of any MASH that there is. Yet you have the most, the highest utilizers of GLP-1s that are calling us proactively saying, despite being on GLP-1s, these patients still have MASH, and we'd like Rezdiffra. So that in itself, you know, gave us some interesting market insight for how this could unfold in the future. But we've put this dedicated effort towards it. And, when I say it's dedicated, they're not focused on the other targets. They're exclusively endocrinology, so not to create any disruption with the rest of the commercial effort.
What is the profile of these endocrinologists who have reached out and really wanted to have, you know, education and availability to prescribe Rezdiffra? How do they differ from?
I mean, they’re interested, first of all, in MASH. You know, a lot of times it’s just a matter as you learn about a disease. When I say a new disease, it’s not a new disease, but a disease that’s become a little bit more in focus, and you start to look, you see. I think that is that’s probably the biggest insight. Now, these tend to be, you know, metabolism-interested physicians. They’re very interested in the mechanism of action of Rezdiffra. They understand metabolism, and, you know, they are expressing this interest to treat these patients rather than, you know, necessarily pass them on or even worse, just ignore them.
Yeah. No, that's, well, that's helpful, and another great opportunity to bring Rezdiffra to.
And maybe.
When will this start?
Yeah, so fourth quarter it started.
Fourth quarter. Okay.
You know, these, they are starting just like where the hepatology and gastroenterology community started in March of 2024. They've got to wire their own system, so to speak. They have to learn about the product, how they're going to diagnose, access to NITs, etc. They're going to have to go through that learning curve. A lot of them, they don't necessarily have NITs in their practice. That's another step that they have to go through. We would expect that adoption is going to take a little time, but clearly the patients are there and the interest is there.
Yep. And, team, another big win this year was, I think there was definitely a significant fear that once semaglutide becomes available, that there would be very aggressive rebating going on. So, Mardi, you did a great job on highlighting all the great work that you guys have done with payers. So if you could just help us understand, like, how do you envision contracting, you know, in 2026 and beyond?
Yeah. I'd be happy to. So, gross-to-net, we talk a lot about gross-to-net. It's very important to the company. We're very disciplined around gross-to-net. We have a great team that focuses on this, our market access team, to help us tiptoe through the minefield, so to speak, of contracting with payers. But just reel the tape back a little bit. When we launched Rezdiffra, we were the first product into a MASH space that had nothing and no competition. So we took a step, maybe a rather bold step, but didn't actually contract with payers, basically for the first five to six quarters of launch and had great access for our patients, really good access. So, we wanted to continue that going forward and particularly subsequent to the Wegovy launch. We are in a position now where we're contracting.
So you're going to see a little bit of the contracting with the big payers that'll cover over 80% of our lives, start in the fourth quarter and then go into 2026 as well. And that switch will flip on January 1 in terms of the full impact of that commercial contracting and gross-to-net. I should say the reason we're doing this is to maintain our excellent access. So we will continue with our first line access for Rezdiffra on parity with any other programs. Right now it's just Wegovy, no step through, and improved utilization management criteria. So that remains the same great access. Now, in terms of specifics, the details, so we had talked and had guided to gross-to-net discount. Remember, gross-to-net has many components of which contractual commercial contracting is just one of 20%-30% for 2025.
And we've been hovering at that low end of that range. But you will see some of that commercial contracting take hold in the fourth quarter. So we'll exit the year in the midpoint of that range. Now, with that switch flipping that I talked about with the full commercial contracting starting in 2026, you see gross-to-net step up a bit to the high 30 percentile for 2026. And that really is every quarter throughout 2026. There is some variability because of all the other components. There's some estimates in there, but really in that high 30% range. Now, just to finish, it's a long explanation, but like I said, we spend a lot of time here in gross-to-net. In 2027 and beyond, this is sort of the last piece of the gross-to-net impact that we'll feel is on the Medicare contracting, right?
You have commercial and you have government. Our business mix is 50%-55% commercial, that's commercial contracting, 30%-35% Medicare. You do, we will see that number, that high 30 percentile number does include some of the Medicare contracting, but we'll see the rest of that in 2027. There'll be less of an impact, but still an impact in 2027 on gross-to-net. Then it stabilizes. As Bill likes to say, it only goes one direction, gross-to-net discount, but, you know, it stabilizes and then kind of trickles down versus more of a step, step function.
And then, team, obviously you guys have had an incredible launch. How should we think about fourth quarter and 1Q 2026?
For Rezdiffra?
Yeah.
Yeah. So, we talked about this on our third quarter. We did. We have had an excellent launch and we had an exceptional third quarter as well. So, big consensus pretty handily coming in with a big base into the fourth quarter. So as we look at the fourth quarter, remember, the primary objective to the health of our business is our patient adds. And we have messaged pretty strongly that fourth quarter in 2026, we're going to see steadily adding patients, you know, and continue that, you know, into the foreseeable future. But there are components like fourth quarter has fewer selling days. It just does, you know. That's a fact. And then we just talked about the gross-to-net impact in the fourth quarter. So what we've said is high single digit growth rate, quarter over quarter from third quarter to fourth quarter.
And then going into the first quarter, typical, you'll see the step up of the gross-to-net, right? But you also have the Q1 effect as patients get back on drug and get things going for the new year. So you have a little bit of a magnified effect. So we think net revenues, we've talked about this, will be flat to down, typical, very, very typical for most pharma companies selling into the first quarter. But I think it's important to say that we anticipate robust sales growth for 2026. It's just more the phasing of the quarters. You have a little bit of that impact in Q1, Q1 effect, and then you'll see the quarter over quarter growth continue through 2026.
Mardi, if we look at the consensus and we look at 2026, I think 2026 is sort of projected to be like $1.45 billion. So it represents sort of 50% year over year growth versus 2025. Do you think this is like, and I know you guys have your internal comps, right, on against other specialty launches?
We do.
Do you think that expectation right now by the street is sort of in line with your own expectations?
Yeah, so we just talked about the first quarter, and we also think I've also said robust growth into 2026, so I think that what you've said, where consensus is, plays right into that explanation, but while we're talking about consensus, you know, we have the top line, but we also have OpEx, so R&D and SG&A, and it's really important for us as we expand into the endos, as we make sure patients have the best access they can to the drug and going and supporting this launch for peak, that we continue to invest in SG&A, then of course we're developing our pipeline, our ongoing phase three, so there'll be an increase in R&D expense as well, so I would say from a consensus standpoint, OpEx should be a little higher, but again we expect that robust net sales for the next year.
Then, many investors have asked us. I was wondering, with a competitor conference in January, if you plan on providing guidance for 2026 or early this year.
No guidance.
Maybe why? What's the rationale for not giving it?
I think we do a really good job of looking at each quarter and then looking ahead at the next quarter. If we need to, you know, if there's just like we did with the third to fourth quarter, you know, so I think we've done a very good job of helping the street and helping investors understand the growth of our business. From that perspective, we're not planning to give guidance. I should also say we're not planning to pre-announce fourth quarter at JP Morgan either. We did that last year, mainly because it was our third quarter of launch and we needed to help, you know, make sure people were on the right track, but we don't feel like we need to this year. We think we've said enough going into the new year.
And Bill, you guys have done a very good job at each quarter to provide as much color, right, around the sales bridge, the outreach, the payer mix. Like, is there anything that we haven't gotten in 2025 that you hope to provide more color on in 2026?
No, look, I think that we've been, you know, pretty clear, as you said, about what are some of the key metrics. And, you know, I think more and more this becomes a revenue story in time and some of the metrics aren't as necessary. For instance, you know, we're giving a payer metric early on in launch, but, you know, we achieved this 80% commercial coverage in about six months' time. So it's kind of like check the box, move on. We've now talked about the penetration to the 6,000 top prescribers and the 14,000. We've kind of hit the, kind of the sweet spot. So probably not so relevant. And I think as we go through each metric, we'll look and see at the time what's relevant, what's important, and we'll make decisions at that point.
Okay. Team, another question that comes up often is how do you think about BD development, and acquisition in 2026 and beyond to continue to establish Madrigal as the leader in the space?
Yeah, we think about it a lot. We've thought about it a lot and we've already started to take action with it with our GLP-1. That was our first BD transaction. We think it was a smart one, a great one, that asset will go into the clinic in the first half of 2026 into a phase I, and then we'll look at it in combination. You said it well, we're the leaders today. The objective is long-term leadership. Now, a big event of 2025 has been securing IP to 2045 for Rezdiffra. And with that foundation of Rezdiffra, it helps us think very strategically about how we're going to do BD. And that's why we could do a preclinical asset with the oral GLP-1, because we're not in a rush to try to fill a hole that's going to exist anytime soon.
Now, it's a matter of how do you set the rest of the table and we're looking at next best mechanisms of action in MASH or combination therapy with Rezdiffra and that allows us to think about as well not just how a product works or in combination but what would be a regimen as well that's the ultimate regimen. An important piece of this is that I said MASH. The initial focus is going to be to build this long-term leadership in a disease that is just at the beginning of treatment and you know we think that we are better placed than anyone to do this so you know stand by stay tuned. It's activities we've had in place for a long time. We're looking at everything in the MASH space from very early to late stage.
And as you make and evaluate all opportunities for BD, how important is the potential regulatory clearance to move away from histological endpoints and open it up to an NIT base because that will be a big hurdle that will be removed and expedite the drug development path for therapy? So does that, does that take an alternative consideration as you're thinking about to enrich the pipeline? Because then you could think about adding multiple, multiple, assets.
Yeah, sure. I mean, look, I think that it is a consideration, but it's not a determination, if you will. It could make it perhaps easier, but you know, still, these are not going to be just because you take biopsy away, doesn't mean that it becomes an inexpensive, easy trial to do, right? That's just one piece of it. So it's a consideration. It ultimately would help us, I suppose, in the long run because you know, it may cut some of the expense down, but you know, it's not like a magic bullet, and we're really happy to see the FDA considering this because then it matches with clinical practice. There hasn't been. Biopsies just aren't used. We don't hear of any physicians for the MASH diagnosis using a biopsy.
If they're really confused about what the patient may have, then they may go to a biopsy, but it's neither required by payers, label nor desired by prescribers.
Okay. And maybe like, obviously Madrigal, since the patent extension that was announced in August, it's been an incredible trajectory, right? And I have a lot of clients who feel like they missed it and they're like, how did I miss it so quickly? I kept saying to them, don't worry, it's not too late, you know? So I guess the question to you is really a strong year. Where do you think it can go from here?
Up.
Yeah. No, that could have to be more than that.
I think that if you take a look where we are, I think what people are sometimes forgetting is we're at the very beginning of a long story. This is the first product to get approved in an incredibly high unmet need disease. People die from this disease. They have liver transplants from this disease. If we can prevent that and help people, that is huge value add. Two products approved now. When you look at other large categories, they support 15+ products and they're over $20 billion. So we have what we think is the winning profile. We see nothing behind us in the pipeline that looks any better. Lots of runway with Rezdiffra. We're reading out an F4c , which is almost an opportunity to double the opportunity for us because the unmet need is that much higher, maybe some fewer patients, but higher penetration.
And then we've got the pipeline, which is going to take us well into the future, all capped by the 2045 IP. So we have a huge market opportunity. We've got a great asset. We've got a pipeline that's going to develop, and we've got a team that can pull it off. And I put us up against any opportunity in this industry for what lies ahead. So do we have room to grow? Absolutely.
Wonderful. Well, we have to stop at this high note, right? Because anything else that we're going to say is just going to not top this, which is great. So just want to say a big thank you. It's been incredible to watch this journey. I think many of you guys know Madrigal was my first covered stock as an analyst, and this is the type of things that has made me really proud of being my journey of from the early stage to development to a successful launch and more to come. So thank you again. Keep doing what you're doing. We're so proud to be covering you and working with you. So let's give a big applause.
Thank you.