Madrigal Pharmaceuticals - Earnings Call - Q2 2025

Executive Summary

• Strong quarter driven by Rezdiffra launch momentum: Q2 2025 net sales reached $212.8M, up 55% QoQ and massively higher YoY as adoption broadened; >23,000 patients were on therapy as of June 30, and ~60% of targeted prescribers have written prescriptions.
• Strategic durability and pipeline optionality improved: new U.S. patent extends Rezdiffra protection to Feb. 4, 2045; a global license for an oral GLP‑1 (SYH2086) adds a combination path; and a $500M Blue Owl credit facility strengthens non‑dilutive funding.
• EU expansion nearing: CHMP issued a positive opinion in June; EC decision expected in August with an initial Germany launch approach in 2H25, positioning incremental 2026+ revenue contribution.
• No formal revenue guidance: management reiterated they are not providing revenue guidance near‑term; focus remains on steady patient adds through 2025, with EU monetization more a 2026 story, per call Q&A.

What Went Well and What Went Wrong

What Went Well

• Commercial execution: Net sales grew to $212.8M with 55% QoQ growth; >23,000 active patients; ~80% of top ~6,000 prescribers have written Rezdiffra; ~60% penetration across ~14,000 total targets.
• Strategic moat: New U.S. patent covering weight‑threshold dosing extends protection to 2045, reinforcing exclusivity and label‑aligned dosing regimen.
• Global and lifecycle expansion: Positive CHMP opinion (EU approval anticipated), F4c two‑year data showing broad, sustained efficacy, and a GLP‑1 oral license enabling a once‑daily combo path.
• CEO tone: “We’ve delivered another exceptional quarter driven by continued strong Rezdiffra demand… building a company with the potential to lead in this space for decades”.

What Went Wrong

• Losses persist amid scale‑up: Q2 operating expenses rose to $260.0M (vs. $177.2M YoY) with SG&A at $196.9M to support commercialization; net loss per share was $(1.90) despite strong sales.
• Interest income down on lower cash balances; cash declined to $802.0M from $931.3M at year‑end as operations scale (partially offset by Blue Owl facility).
• Limited visibility on near‑term guidance: Management declined to provide revenue guidance, leaving the buy‑side to extrapolate trajectory from patient adds and prescriber penetration; EU revenue likely more a 2026 story.

Transcript

Speaker 5

Good morning and thank you for standing by. Welcome to Madrigal Pharmaceuticals' second quarter 2025 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question-and-answer session. As a reminder, today's conference call is being recorded. I would now like to introduce Ms. Tina Ventura, Chief Investor Relations Officer. Please go ahead.

Speaker 8

Thank you, Demi. Good morning, everyone, and thank you for joining us to discuss Madrigal Pharmaceuticals' second quarter 2025 earnings. We issued a press release this morning and posted a slide deck that accompanies this webcast on the Investor Relations section of our website. On the call with me today are Bill Sibold, Chief Executive Officer, Dave Soergel, Chief Medical Officer, and Mardi Dier, Chief Financial Officer. They'll provide prepared remarks, and then we'll take your questions. Please note on slide two, we will be making certain forward-looking statements today. We refer you to our SEC filings for a discussion of the risks that may cause actual results to differ from the forward-looking statements. With that, I will now turn the call over to Bill.

Speaker 1

Yeah, thanks, Tina. Good morning and thanks for joining us. We have a lot to cover today. Before we move into this quarter's performance, as you can see on slide three, it's been an incredibly exciting and productive last few months at Madrigal, both driving the launch and building our future. We've accomplished a lot, and each of these milestones reflects the deliberate execution of our long-term strategy to maximize Rezdiffra value and expand our leadership in MASH. In a short time, we've transformed Madrigal into a company with a longer runway, a stronger foundation, and greater flexibility to build for the future. Fundamental to our success is our business in the U.S., which continues to outperform. Rezdiffra's quarterly run rate now exceeds $200 million, well on its way to blockbuster status. We can objectively say it stands among the best specialty launches of the last decade.

Second, we've strengthened the long-term value of Rezdiffra with our new U.S. patent, providing protection to February 2045. This changes how we think about Rezdiffra's growth potential and our investment in the business. It's not about years of opportunity, but decades. Third, we're preparing to expand internationally, beginning with Germany later this year. Geographic expansion adds another potential future growth opportunity for Rezdiffra. Fourth, we're working to expand Rezdiffra with an indication in compensated MASH cirrhosis, or F4C, where our outcomes trial continues to progress. If positive, it could double Rezdiffra's market opportunity. Finally, we're building a pipeline for the next phase of leadership in MASH, with the addition of a promising oral GLP-1 to combine with Rezdiffra. We have the capital in place that will allow us to support and scale all of this.

Each of these pieces adds value to the foundation we are building for long-term leadership in MASH. Let's move into the call with our agenda on slide four. A lot has happened since our last call. I wanted to take the opportunity first to talk about the new U.S. patent that was issued today. We believe it's a significant contributor to our long-term outlook. As we summarize on slide five, the patent covers claims directed to Rezdiffra's commercial weight threshold dosing regimen as prescribed in its FDA-approved label and will be listed in the FDA Orange Book. We recently learned some favorable news. The patent reflects an updated expiration date of February 4, 2045, which is extended from the previously noted date of September 30, 2044.

What gives us such high confidence in the strength of this patent is that it's based on the clear and compelling finding that different Rezdiffra doses given to two different cohorts of patients, each with different body weights, optimizes the efficacy and safety of Rezdiffra. This finding is based directly on our clinical team's independent analysis from our phase 3 MAESTRO MASH trial, which was adopted by the FDA for our label. The bottom line, any potential generic competitor will need to adopt the Rezdiffra label and would infringe on our patent. Our confidence in this patent is also supported by precedent U.S. case law. This patent changes the game for us in two ways. First, strategically, it gives us the privilege of time. This extension creates a lot of flexibility for us to pursue our long-term strategy.

We can be very thoughtful and deliberate about how we build our future and shape our pipeline. Second, it adds another potential decade of protected revenue and materially increases our value proposition, creates additional opportunity in MASH, and extends our ability to keep innovating to address unmet patient needs. Now, let's turn to slide six and Rezdiffra's second quarter performance, where we delivered net sales of $213 million, up 55% quarter over quarter. U.S. Rezdiffra net sales are now annualizing at well over $800 million. The significant demand we're generating is driven by strong and consistent execution on two key launch metrics: patients on drug and prescriber penetration. First on patients, as shown on slide seven, we ended the second quarter of 2025 with more than 23,000 patients on Rezdiffra, up from more than 17,000 patients at the end of the first quarter.

As we've noted before, this figure represents patients actively on therapy, accounting for any discontinuations. We are encouraged by Rezdiffra's robust growth, and yet we're still in the early stages of this launch. Only about 7% of the 315,000 diagnosed F2F3 MASH patients under the care of a liver specialist are being treated with Rezdiffra. There is significant opportunity ahead. Moving to slide eight and our progress on physician penetration. As I've said before, building a strong base of prescribers early in a launch is one of the best indicators of long-term success. That's why the pace of adoption has been so encouraging. In fact, in just over a year since approval, we've achieved another key launch goal. 80% of our 6,000 top targets have prescribed Rezdiffra.

This level of penetration exceeds the benchmarks we track and is the direct result of the significant amount of work we've done to wire the system for a first-in-disease launch like Rezdiffra. We're also seeing strong progress as we expand into our broader 14,000 target prescriber base. By the end of the second quarter, 60% or roughly 8,500 healthcare providers had written a prescription for Rezdiffra, up from 50% in the first quarter. Looking ahead, more of our focus will be on depth, which is also tracking in line with best-in-class launches. We believe this is largely due to the positive experience that providers are having with Rezdiffra, and we anticipate that it will continue to drive depth going forward. This positive experience is being driven by Rezdiffra's compelling profile shown on slide nine.

Rezdiffra is the liver-directed medicine with a mechanism of action that improves the critical processes in the liver that drive MASH. It has consistently strong efficacy regardless of patient subtype, including those with type 2 diabetes, who have a higher risk of progression and comprise approximately 60% of the MASH population. Additionally, Rezdiffra works effectively regardless of fibrosis stage, BMI, or genetic makeup. It's very consistent when it comes to treatment effect. It's also easy to prescribe and to take, a once-daily well-tolerated pill with no titration requirements. That simplicity matters to physicians, to patients, and ultimately to adherence. We continue to see strong early signs of adherence consistent with what we see from other well-tolerated oral therapies. As we look ahead to future competition, we believe Rezdiffra's attractive real-world profile gives us a durable advantage.

The next potential entrant in MASH is likely to come from the injectable GLP-1 class. You can see on slide 10, Rezdiffra compares very favorably across key attributes. For example, while semaglutide demonstrated an improvement in fibrosis, it was less pronounced in patients with type 2 diabetes, whereas Rezdiffra works consistently across patient subtypes. Another key difference is adherence in the real world. It's low for semaglutide. Most patients struggle to get to and maintain the 2.4 mg dose. In addition, only approximately 30% of patients with obesity remain on the medicine after one year. This is especially relevant in MASH, where we're talking about a 72-week efficacy endpoint. For a progressive chronic disease like MASH, providers want a medicine that patients will stay on and one that they can administer easily without a titration schedule, and that's where Rezdiffra stands out.

Certainly, a key attribute of a GLP-1 is its impact on weight loss. We also know patients with MASH may benefit from a combination approach. Today, about 25% of patients on Rezdiffra are taking it alongside an injectable GLP-1 to manage their comorbidities. That figure increases to roughly 50% when you include prior GLP-1 users. Combination use is happening in the market today, and we expect it to grow over time. As we look ahead on slide 11 and consider the upcoming GLP-1 launch in MASH, we believe it has the potential to accelerate the growth opportunity for Rezdiffra. Our focus remains squarely on the 315,000 diagnosed patients with moderate to advanced fibrosis. This is our core specialty market. Novo is targeting a much larger population, many multiples of our 315,000. Their efforts will raise awareness and drive broader screening, diagnosis, and treatment.

This will ultimately benefit patients, and we expect it will also benefit Rezdiffra, both as the foundational therapy in MASH for first-line patients and from the high real-world discontinuation rate of semaglutide. There is clearly a need in this large and underpenetrated market for multiple mechanisms and better combinations to treat this challenging disease. That's why we're excited to study Rezdiffra in combination with our newly in-licensed oral GLP-1, as noted on slide 12. We're taking a differentiated approach focused on MASH. We are looking to develop a chronic therapy for a chronic disease with Rezdiffra as the foundation. We want to optimize the efficacy and tolerability in MASH by balancing the right amount of weight loss from a GLP-1 with the fibrosis and lipid reduction of Rezdiffra in a once-daily well-tolerated pill. Our data has shown that just 5% weight loss can increase Rezdiffra's antifibrotic effect.

As we assessed the oral GLP-1 landscape, we had specific criteria that we were looking for. We wanted an orphaglipron derivative with a favorable stability and pharmacokinetic profile that was amenable to develop as a combination therapy and, of course, an asset that was actionable. We believe SYH2086 from CFPC Pharma is the right oral GLP-1 asset for our program. It gives us the opportunity to develop what we believe could become a best-in-disease, well-tolerated oral combination for MASH. Importantly, we secured this asset with favorable terms. We have exclusive global rights for a $120 million upfront payment and potential future payments based on achievement of development, regulatory, and commercial milestones. We expect the transaction to close in the fourth quarter and expect to enter the clinic in the first half of next year. We will provide additional updates on our clinical development plans on future calls.

Let's briefly move on to two additional growth opportunities, starting with the international expansion of Rezdiffra on slide 13. In June, we received the positive CHMP opinion, a key regulatory milestone that sets the stage for approval across the European Union. We expect a final decision from the European Commission later this month and are preparing to launch in Germany in the second half of this year. As we've discussed, we've made an incredible amount of progress in Germany over the last year. Leadership and our field teams are in place. We understand which providers treat MASH. We're continuing to engage in disease education. We've begun our efforts to wire the system, and importantly, European guidelines already include Rezdiffra as a first-line treatment for MASH, which positions us well.

Like the U.S., we've defined our initial target population as patients already diagnosed with F2F3 MASH and under the care of a liver specialist. Based on our research, we estimate that the population is approximately 370,000 patients across Europe. We believe Rezdiffra can be the first medicine approved for MASH in Europe and the foundational therapy for this population, just as we've established in the U.S. Let's move to slide 14 and the opportunity we see in compensated MASH cirrhosis, or F4C, an important next step in our growth strategy. First, there is a high unmet need with no approved treatments and serious risk of progression. Second, Rezdiffra's liver-directed mechanism targeting fibrosis is well suited for cirrhosis. Third, our two-year open-label data presented at EASL showed sustained efficacy and supports our confidence in the ongoing MAESTRO MASH outcomes trial.

No other product or mechanism in development has shown this level of reduction in liver stiffness with such an attractive product profile. Finally, we have real-world momentum, a clear first-mover advantage with outcomes data expected in 2027 and what we believe will be a best-in-disease profile in F4C. We've learned what it takes to launch in MASH, and we're ready to extend that leadership from F2 to F4C. Slide 15 outlines the opportunity we see in F4C. We've taken a thoughtful approach to understanding the F4C population. Our research shows there are approximately 245,000 patients in the U.S. with compensated MASH cirrhosis who are already diagnosed and under the care of our target liver specialists. These patients are sicker and further along in disease progression, which typically translates to greater and faster adoption. That's why we believe F4C has the potential to effectively double Rezdiffra's market opportunity in the U.S.

With that, I'll hand it over today to walk through the data on slide 16.

Speaker 4

Thanks, Bill. I'll walk through the takeaways now from our two-year open-label extension data in F4C, which we presented at EASL. First, let's look at the liver stiffness data as measured by vibration-controlled transient elastography, or VCTE. Patients experienced a mean reduction of 6.7 kilopascals in liver stiffness at two years, statistically significant versus baseline. Over half achieved at least 25% reduction in liver stiffness. As published in JAMA, that level of improvement is tied to a lower risk of progression to end-stage liver disease. 35% of patients met the criteria for regression from F4 to F3, suggesting potential reversal of cirrhosis. Turning to slide 17, another critical point is Rezdiffra's potential ability to reduce the risk of clinically significant portal hypertension, or CSPH. CSPH is a key driver of the most severe outcomes of cirrhosis, like ascites, variceal bleeding, and hepatic encephalopathy.

It marks the tipping point into decompensated disease. In our open-label study, 65% of patients with CSPH at baseline improved to a lower risk category by year two. That movement away from high-risk CSPH suggests Rezdiffra could help delay or prevent life-threatening complications. Taken together, these data support our confidence in the ongoing phase 3 MAESTRO MASH outcomes trial because the baseline characteristics of the patients in the open-label study align closely with those in our F4C outcomes trial. For us, this means Rezdiffra has the potential to become the first approved treatment for compensated MASH cirrhosis, a very sick segment of the MASH market that currently has no therapeutic options. I'll now turn the call over to Mardi.

Speaker 5

Yes, thank you, Dave. Second quarter 2025 net sales totaled $212.8 million, up 55% from the first quarter of 2025. This was another strong demand quarter. As we've said, we expected gross-to-net to be somewhat choppy early in launch, and the team has done an outstanding job managing it to date. As we shared last quarter, we've begun contracting with payers. We saw minimal additional impact from contracting in the second quarter, with an expectation for that to increase our gross-to-net discount in the back half of the year. That's fully expected and consistent with what we typically see with specialty medicines at this point in their launches. We have good visibility into the gross-to-net dynamic this year and are confident that gross-to-net will remain within our expected range through 2025.

R&D expenses for the second quarter of 2025 were $54.1 million compared to $71.1 million in the second quarter of 2024. The decrease was primarily due to lower clinical trial cost. SG&A expenses for the second quarter of 2025 were $196.9 million compared to $105.4 million in the second quarter of 2024. The increase was primarily due to increases in commercial launch activities for Rezdiffra. Looking ahead, we expect operating expenses in the third and fourth quarters to be modestly higher than the second quarter. Turning to our balance sheet, we ended the second quarter of 2025 with $802 million in cash equivalents, restricted cash, and marketable securities. As Bill mentioned earlier in July, we also entered into an agreement with Blue Owl Capital for up to $500 million in a senior secured credit facility on favorable terms.

This non-dilutive financing consists of a $350 million initial term loan funded at closing, a portion of which was used to repay all outstanding obligations under the Hercules loan facility, and a $150 million delayed draw term available in multiple draws through 2027. We plan to use these funds to pay the upfront payment for the global license of our oral GLP-1. The Blue Owl agreement also provides a mutual option for an additional uncommitted tranche of up to $250 million to support potential additional strategic business development activities. With a strong cash position, we continue to be well-resourced to support the ongoing launch of Rezdiffra in both the United States and our planned launch in Europe in the second half of this year, as well as for business development opportunities to build our pipeline going forward. Let me briefly recap our second quarter progress on slide 19.

We continue to drive strong momentum in the fifth quarter of our launch with a medicine that's now annualizing at well over $800 million. We have more than 23,000 patients on therapy and expect to continue to steadily add patients going forward. Physician adoption continues to build. We hit a key launch goal with 80% of our 6,000 top targets now prescribing Rezdiffra. We're expanding our leadership in F2 to F4C MASH with our new patent confirming Rezdiffra protection to February 2045, our progress in F4C, our expected expansion into Europe, and our exciting new oral GLP-1 global licensing agreements. Now I'll turn the call back to Tina to open up the Q&A session.

Speaker 8

Thanks, Mardi. Let's move into the Q&A portion of the call. Demi, please go ahead and provide instructions for the Q&A sessions.

Speaker 5

We will now open the lines for questions. To open your line, please press star and you will be added to the queue on the call. Our first question comes from Thomas Smith with Leerink Partners.

Hey, guys. Good morning. Thanks for taking the questions and congrats on the really strong quarter here. I was wondering if you could just expand on the comments regarding gross-to-net and the inventory dynamics in the quarter. I know you guided to there being a little bit of choppiness, but it looks like you may have benefited perhaps from a better net pricing in the quarter versus Q1. If you could just help us kind of frame where you see this going for the rest of the year, and then if you could just comment on inventory stocking in the quarter, that would be really helpful. Thanks so much.

Speaker 4

Hey, Tom. Thanks very much. Mardi, I'm going to turn it over to you to talk about gross-to-net.

Speaker 8

Great. Hi, Tom, and thank you for the question. Let's just start with saying that this was a really strong demand quarter, and the team executed so well once again. Now, with respect to gross-to-net that we addressed in the call, we've been very disciplined and will remain disciplined when it comes to gross-to-net. We've been very consistent with our messages quarter to quarter. We said from the start of launch that gross-to-net will be choppy early in the launch, and we're still just five quarters in. That's the case with what we've seen here in this quarter. We did say last quarter that we began contracting in April, and we also anticipated that we would have minimal additional impact from contracting this quarter and expect to see more of that impact in the second half of the year.

We've explained that we are very focused on gross-to-net, we have very good visibility, and that we plan to stay within the range that we've discussed previously that's very typical for specialty pharma launches at this point in their launch.

Speaker 4

Yeah, thanks, Mardi. Look, and Tom, as you've heard me say, we've been extremely diligent about gross-to-net from the beginning. We don't think about it in terms of a quarter to quarter. We've taken a very long-term view looking over multiple years. We know that Rezdiffra is going to be a big product, and gross-to-net is really important. You want to watch it and work very carefully on it and make sure that you preserve it. Our team's done just an outstanding job on it, and we feel really good about where we're at. As Mardi said, we've got a real strong sense of how it will evolve and where we're going.

Speaker 8

Great. Thanks, Tom. Next question, please.

Speaker 5

This question comes from Yasmin Rahimi with Piper Sandler.

Good morning, team. Congrats on an outstanding quarter. I guess, team, one of the questions that I think seems to be investors asking us with the entrance of GLP-1 to the market, let's say you maintain your pricing strategy and don't aggressively rebate to the level of matching semaglutide. How do you foresee sort of maintaining the strong growth curve that you have shown so far? I think it's very clear that hepatologists are going to prefer liver-directed therapies, but if there is a sort of a prior authorization of GLP-1, if added needed due to pricing differences, how do you foresee how soon that could play sort of flatten out and not become as important? If you could just talk about that dynamic, we get that question quite a bit, and I'm sure so do you.

Speaker 4

Okay, yeah, there's a lot of questions and nuance in there. Let me just kind of roll through a little bit, provide a little bit of context here. I mean, as we said, we're coming off an outstanding second quarter, which was driven by strong demand. Number one, we've been steadily adding patients since launch, and that doesn't change. We expect this trend will continue through the semi-launch in the second half of the year. In addition to the strong demand, with our in Q2, we also benefited a bit from the Q1 effect. We would expect our quarter-over-quarter growth rates to continue to track right in line with other successful specialty launches with similar dynamics. You heard Mardi talk about gross-to-net that is being choppy quarter to quarter.

We have good visibility and expect for that gross-to-net discount to step up in 2025, but stay within the specialty product range that we've discussed. Everything I've said there is in the context of expecting a semi-approval and launch. You asked a very specific question about step edits and so forth. Right now it's just a little too early to tell. Product hasn't approved yet. We don't know what the label looks like, and those are going to be taken into consideration in the discussions that we have with payers. We've been actively talking with payers. We think that we've established a good partnership and planning with payers, but we're waiting to see ultimately what happens with the label and approval of semaglutide. Either way, we plan for all scenarios.

A step edit here in this space, though, is somewhat complicated, and I think that that's going to be one of the things to take into consideration because these patients have other comorbid conditions such as type 2 diabetes or cardiovascular disease. Think about it. If a patient's well controlled on a different GLP-1, would a payer disrupt their current therapy to put them on semi for MASH? There's a lot of nuance and complications here. We don't have all the data yet, but we have planned for all eventualities, and it doesn't change our excitement for the opportunity that exists.

Speaker 8

Yeah, Bill, I would just add one more thing. Remember, GLP-1s have been on the market for a long time. Our data has been pretty consistent in what we've seen to date that of the patients that we've treated, about 50% are either on or have exposure to GLP-1s already, and probably 25% are on at any given time. There is a lot of familiarity in the market already, and clearly combination use is already established.

Speaker 4

Yeah, it's a really great point, Mardi, because this isn't as though it's a new product that's entering the market that's never been used. I mean, this has been used everywhere. There's nobody who hasn't heard of it or has the ability to get it for some indication now. This is just an extension. You know, that's a very different setup than if you have a brand new mechanism of action entering a market which has more potential to disrupt.

Speaker 8

Great, thanks, yeah.

Speaker 5

Thank you.

Speaker 8

Thank you, Mardi.

Speaker 5

Next question. Next question comes from John Wolloben with Citizens.

Hi, this is Catherine on for John. I just had a quick question about your new GLP-1, oral GLP-1, and how many did you look at, and how did you go about picking it? I know you said that the orphaglipron backbone was a deciding factor, but just to provide a little bit of color on that.

Speaker 4

Yeah, look, thanks for the question. As we've said for a long time, BD is a part of our strategy, and we're looking to add the right assets to our pipeline to extend our leadership in MASH. Oral GLP-1s are something that we've been interested in for a long time. Like with any BD process, you look at a lot of different things before you find the one that's just right. That's what we did. We laid out what we were looking for. We were looking for an orforglipron derivative. We wanted favorable stability and a TK profile that's amenable to combo. We found that in this asset. It was a very systematic approach. We looked at a lot of things before deciding and coming upon the one that we think is just right to create that product, which we think is going to be a next advancement in MASH.

Just the one thing I'll say, there are a lot of oral GLP-1s out there. There are a lot of GLP-1s, triple Gs, et cetera, but there's only one that's going to be combined with Rezdiffra in this form. That's how we differentiate in this market. That's something which is special to Madrigal, and that's something that we see a huge opportunity for.

Speaker 8

Great. All right. Thank you. Thanks. Next question, please.

Speaker 5

Next question comes from Eliana Moo with UBS.

Hey, guys. Congrats on the quarter, and thanks for taking the question. In terms of next year, how are you thinking about sequential quarterly growth once semaglutide is available? Specifically on gross-to-net, can you give us a little bit more color on how you're thinking about how that could trend next year? Lastly, and feel free to just not answer this question, what's your latest thinking around when you might be in a position to issue revenue guidance? Thanks.

Do you want to take the revenue guidance or anything?

Speaker 8

Any part of it? Yeah, thanks, Ellie. Thanks for the question. Revenue guidance is easy. We haven't discussed that publicly, and we have no plans in the near term to give guidance. In terms of growth, you're asking about 2026 already, but we're in Q2 of 2025. We're focused on the rest of the year of 2025. We discussed on the call, and we'll say it again now, that we believe that we'll be steadily adding patients through the rest of the year and continue our growth trend. As you know, we follow a basket of analogs of specialty medicines that have launched successfully over the last 10 years, and we are tracking right along that growth rate of those top analogs in this basket. We feel very good about the growth in the rest of the year.

Gross-to-net, I think we made those comments in 2025, and we feel good and have good predictability. As the year goes on, we'll start focusing on 2026 and discussing that more. Great. Thanks, Ellie. Next question, please.

Speaker 5

Next question comes from Andrea Newberg with Goldman Sachs.

Good morning. Thanks for taking the question, and congratulations on the quarter. Bill, if you think to a potential EU approval next month, just curious how you're thinking about the shape of a potential launch curve there versus what you've seen in the U.S., and when might you expect to recognize first revenue?

Speaker 4

Thanks, Andrea. I think we've got a very good view on what curves can look like having just gone through the U.S. launch. It all starts with how do you wire the system? How do you prepare? How do you educate? How do you create pathways for patients there? The benefit in Europe is they've had more time to prepare for this launch than the U.S. did. Because remember, in the U.S., since we were the first product ever approved in MASH, the community had been met with disappointment over 20 times. There are the guidelines in Europe that exist already, and with the U.S. getting approved, Europe's had a little bit longer to prepare. Like any other launch, and especially when it's a first-in-disease, it takes time. We have some really good first-hand experience with that in the U.S., and we're taking essentially all the learnings from the U.S.

and transferring them to the really outstanding team that we've hired in Europe and specifically Germany. I just want to put a fine point on that. It's Germany that we're launching in first. We're not going everywhere all at once. We put extremely rigid guidelines in place for what we need to see in a market for it to launch. More to come. When will we start recognizing revenue? I would say it's really not much of a, there's not much happening in 2025. We're going to be starting in the second half of the year in order to get the teams deployed, et cetera. It takes a little time. Really, it's more of a 2026 and on story.

Speaker 8

Great. Thanks, Andrea. Next question, please.

Speaker 5

Next question comes from Andy Chen with Wolfe Research.

Thank you for taking the question. Mardi, you talked about this basket of specialty drugs. Can you give some numbers around what this gross-to-net range is in that basket that you're analyzing? This 20 to 30% that the gross-to-net that you're guiding to, is that an educated guess and prediction, or is that already a largely known fact given your existing contracting negotiations and you know that it's going to end up in the 20 to 30% range? Thank you.

Speaker 4

Hey, Andy, thanks for that. I'll turn it over to Mardi in a second. Just to be clear on that, we are very, very clear on the 20 to 30%. That is based on decades of experience and knowledge and how our conversations have gone with the payer community. Like everything else that we've talked about in this launch, we've been very accurate in our comments that we make to all of you. Maybe I'll turn it over to Mardi for any other comment that you have, Mardi. We don't say things just to say things. We say things because we're confident in them.

Speaker 8

Right. Yeah, just to reiterate that, Andy, we have good visibility for the rest of the year. We've talked about this range since, I think, our first launch quarter. We feel very strong that we're tracking along with typical specialty medicines and that the gross-to-net for 2025 falls within that range. There are a lot of components to gross-to-net, many components, of which contracting is just one. We did say we started contracting in April and that you'd see more of that in the second half. That's just the natural dynamics in this marketplace, launching in the U.S., all very predictable for 2025 as we move forward. We feel good about that. Just to reiterate a point that Ellie asked too, we haven't commented on 2026, but we see this drug as continued growth and robust growth as we move forward and as we steadily add patients. Good. Thanks, Andy.

Next question, please.

Speaker 5

Next question comes from Ritu Baral with TD Cowen.

Hi, guys. Thanks for taking the question. I wanted to ask about some of your underlying plans, Bill, as far as continuing this growth momentum into the potential Wegovy label expansion. You hit your target of 80% prescribers in that top tier. What's the next target, and how does that overlap with your understanding of Novo's potential detailing target for that label expansion? As part of that answer, could you address the sort of growing awareness of MASH in the diabetic population and amongst endocrinologists? Are they part of that next tier? Thanks.

Speaker 4

Thanks, Ritu. Look, we don't have a next target that we're going to talk about. Really, what happens now is it's a focus on depth. I mean, we have the breadth of prescribing that we're seeing is, as we said, it's leading the other products that we're looking at, the analogs. We have done just an outstanding job there. It really becomes a depth story now. We're seeing all the signs that we're tracking right with those analogs as well. The next, the first leading indicator is really the breadth. Now you go to depth, and we're seeing more of that. Why do people use more? Because they see the results. The real-world experience that we're seeing is actually very impressive. We have physicians, every physician I speak with talks about just how what they're seeing in the real world is impressive and exceeding expectations.

You talked about kind of where do we go from here from an endocrinology perspective. Yep, endocrinology, there's some, it's not all of endocrinology, but some endocrinologists are very excited about Rezdiffra. We've started spending a little bit more time with those physicians and will continue to do so. As I said, the key focus is hepatologists and gastroenterologists. We also talked about endocrinologists, but we'll continue to pursue additional endocrinologists that have an interest. You know, interesting, endocrinologists are super interested in mechanism of action. This being a THR beta, their eyes light up saying, look, this is in our alley to be talking about something with a cool mechanism like this, albeit very specific to the liver in our case. Yeah, we have those targets that will increase as well. Anything else, Ritu, with that, or does that answer it for you?

Speaker 8

That covers it. Thank you so much.

Speaker 4

Great. Okay, thanks.

Speaker 8

Thanks, Ritu. Next question, please.

Speaker 5

Next question comes from Akash Tewari with Jefferies.

Hi, this is Cathy on for Akash. To follow on the gross-to-net question from before, I know you said you'll see more of the contracting happen in the second half of the year, but based on our math, it looks like the gross-to-net for this quarter roughly returned to Q4 levels. We also anticipated a potentially higher Part D impact from this quarter versus last quarter. What are the biggest drivers behind this price improvement for the quarter? Can you give us some color on the Part D redesign impact this quarter, as well as the stocking contribution and the driving factors behind that increase? Thank you.

Speaker 4

Thanks for the question. There was a lot, a couple thrown in at the end there I'm not sure we can get to, but Mardi, what are your comments?

Speaker 8

Let's start on the easy one on stocking, which was not part of gross-to-net, as you know, but let's reiterate what we said in the script as well. It was a strong demand quarter, and so inventory is not, you know, we don't need to discuss that anymore, strong demand quarter. With respect to gross-to-net, a lot of focus here. Let's reiterate. Again, the range that has been brought up on this call already for typical specialty medicines at this point in the launch for this year is 20% to 30%. What we said is that contracting, which is one component of many components in gross-to-net, will see a bigger start in April, normal part of our business, and will continue to widen that through the end of the year. That's all predictable in that 20% to 30% range and expected.

In Part D, I thought we kind of put this to bed, but the Part D impact was, we discussed this on the fourth quarter, and I believe the first quarter call was just incremental to what we saw in the fourth quarter. That's because we had rebates in the fourth quarter given the timing of our launch. The new IRA Part D impact was pretty minimal going into 2025, given the base from which we started in the fourth quarter of 2024. All in all, you know, gross-to-net again falls within the range and will continue to do so through the rest of 2025.

Speaker 4

Yeah, look, I mean, we were clear on our first approval call that we would have choppy gross-to-net for a period of time. That's just what happens in a launch. You know, just to reiterate again, there are a number of components of gross-to-net, including copay assistance. I mean, we have a $0 copay assistance program as well, which is getting greater and greater utilization. It's really important. We want patients on copay assistance because that just makes it more affordable, which leads to better persistency and leads to better outcomes for patients. Next question.

Speaker 8

Good. Thanks. Next question, please.

Speaker 5

Next question comes from Mayank Mamtani with Canaccord Genuity.

Yes, good morning, team. Thanks for taking your questions and congrats on a very strong quarter. Could you give us a little bit more detail on the claims of this newly issued patent with 2045 expiry? I guess it's related to the method of treating MASH, where those findings work in humans was a non-obvious finding. I was curious if there's plan to further build on this with the F4C outcomes data emerging. I have a quick follow-up.

Speaker 4

Sorry, what was the F4C question? I missed that.

Yeah, if there's additional patent work you may do as the F4C and the outcomes data still kind of emerging there.

Yeah, great. That's something, look, you know, we don't have the trial outcome yet. We don't have approval yet. Certainly, we will look for opportunities with the F4C indication, we hope, in the future. I think the patent you saw this morning, or you are, it's available now. As we said, it's based on clear and compelling evidence that different Rezdiffra doses given to two different cohorts of patients, each comprising different body weights, optimizes the efficacy and safety of Rezdiffra. That's the headline for it. We think this is a very strong patent. This is something that has become our base case now as we think about all of our planning in the company and how we're thinking about our plans for everything from BD to just the investment, et cetera. 2045 is our base case.

I think I'm going to let you all spend a little bit more time reading it and so forth, but we think all the facts are very clear. We think that there's good precedent as well in case law, and you know, we're really excited about this. This is a really, really, really important development for us as a company.

Speaker 8

Great. Thanks, Mayank. Next question, please, Demi.

Speaker 5

Next question comes from Jay Olson with Oppenheimer.

Oh, hey, congrats on the quarter and all the impressive progress, especially with lifecycle planning. In your due diligence process, can you talk about any preclinical or clinical work done to support a fixed dose combination of SYH2086 with Rezdiffra? Now that you have an oral GLP-1, what other mechanisms are you considering and how are you thinking about future business development deals in terms of timing and priority? Thank you.

Speaker 4

Great, thanks, Jay. Maybe I'll start with just the last bit and then I'll turn it over to Dave. Look, BD is still very much part of our strategy. Now, we think this is a great first step, but we will continue to look at next best mechanisms of action that are going to add potential value to MASH patients, either as a standalone or in combination with Rezdiffra. Now, you know, we really believe that the market is going to move towards combination therapy and that Rezdiffra is going to be the foundational therapy. It already is. It's the standard of care today. What you see in a lot of different diseases is that you add to that standard of care, whether it be for a different effect you're looking for, a subpopulation, et cetera.

Remember, we are at the absolute very beginning, 7% penetrated into this 315,000 population with decades, I would say, of growth in this marketplace ahead of us. It's going to support multiple mechanisms of action, multiple products, and as the leader with the foundational product, looking for those next white spaces or areas of opportunity is something that we are going to be a part of, and more than that, we are going to drive. Dave, maybe do you want to talk a little bit about this asset?

Yeah, sure. I think first of all, let's touch on two things. First of all, the scientific rationale for combining a GLP-1 with resmetirom, and then second, we can talk about this molecule in particular. We already know, based on our experience in MAESTRO MASH, that as little as 5% weight loss will enhance the efficacy of resmetirom in MASH. We see better biopsy results in patients who achieve as little as 5% weight loss. As we talked about, we can achieve that more effectively and in more patients, that level of weight loss by adding a GLP-1 mechanism drug to Rezdiffra. The scientific rationale, I think, is very, very strong for combining the mechanisms. Second, with respect to this molecule in particular, Bill touched on some of the properties that we were looking for. We were looking for chemical properties like the structure.

We wanted to make sure that it came with a de-risked structure like an orforglipron backbone. We wanted to make sure that the pharmacokinetics and sort of initial pharmacology were consistent with what we were seeing with other molecules in this class. That gave us that assessment. I think it's important to mention that this is still a preclinical asset and there's still work to be done before we get into the clinic. From what we've seen, we're very excited about combining 2086 with Rezdiffra.

Maybe just one final point on that, Jay. Fixed dose combo would be great, but it's not completely necessary, right? I think this, you have to go back to when you've got the runway that we've got to 2045, right? We have the time to do things in a very thoughtful, precise way. Ideally, it's a fixed dose combo, but it doesn't have to be. It would just be more convenient for patients. We like the properties that would make that a good probability.

Speaker 8

Great, thanks so much, Jay. Demi, it looks like we have time for one more question, please.

Speaker 5

Next question comes from Cavalier Pullman with Clear Street.

Hi, good morning. Congrats on the progress and thanks for taking my question. I just want to kind of understand a little bit about the competitive landscape, you know, and your rationale for choosing GLP-1 over there are a lot of dual and triple agonists going on and how you are thinking about whether, you know, with increase in weight loss, if you can see more benefit to MASH patients and you expect any kind of off-label use there as this space grows, as well as, you know, with the combination specifically for the oral drug you have, any concerns related to kind of overlapping toxicities and based on that, how you are thinking about developing it, whether you plan to, when you like test different doses and scheduling of both drugs or GLP-1 will be adjusted according to the approved regimen for Rezdiffra.

Speaker 4

Thank you. I appreciate the question. There's a lot there. Let me just take a couple of things really quickly. First of all, we like oral GLP-1 for the reasons Dave mentioned and that we mentioned in the call. With as little as a 5% weight loss in combination with Rezdiffra, we see a better effect on fibrosis from Rezdiffra. That makes it better. Now, you're talking about a whole group of products, triple Gs, et cetera, where their fundamental approach is the battle of who can show the greatest weight loss. There are comparisons of a %, 2% in the teens and beyond, and that becomes a competitive set. That's not the game we're playing. We need an oral GLP-1 that gets us past that 5%, but it's well tolerated.

It's something that people can stay on so that the overall profile of the new product with Rezdiffra remains what it is, which is really as good as it gets in a profile of a drug. It's a holy grail profile. Once-a-day pill, it's something we've been looking for in my whole career, are products like this. We have a very different approach on how we're thinking about this. The primary objective isn't for massive weight loss. The primary objective is to get to this threshold weight loss that makes Rezdiffra perhaps an even better drug. That's a different frame, and I think people got to get their head around that because that's how we very thoughtfully approach this. As it relates to what's the impact on the product profile, as I said, we're trying to make it a well-tolerated profile and not give up anything on it.

That's how we hope to satisfy that with dosing, et cetera, but it's premature to talk about our development plan. We're going to come back at a later time. As I said as well, BD remains part of our strategy, and it's something that we'll continue to be very thoughtful about how we might extend our leadership in MASH. Dave.

Yeah, just add one thing with respect to the diligence on the molecule. Of course, one of the things that we were looking at was the preclinical profile and ensuring that this molecule would be, at least from a preclinical standpoint, you know, compatible with resmetirom. We were reassured by our diligence process, so we're very excited to have this and to test it in the clinic.

Speaker 8

Great. Thanks, Dave. Thanks, everyone. Thanks, Demi. Thank you all for your time and interest today. This now concludes our call. A replay of this webcast will be available on our website in about two hours. Thank you for joining us.

Speaker 5

and gentlemen, thank you for your participation in today's conference. You may now disconnect. Have a wonderful day.