Madrigal Pharmaceuticals Q4 2025 Earnings Report

Madrigal Pharmaceuticals EPS Results

• Actual EPS: -$2.57
• Consensus EPS: $0.04
• Beat/Miss: Missed by -$2.61
• One Year Ago EPS: -$2.71

Madrigal Pharmaceuticals Revenue Results

• Actual Revenue: $321.08 million
• Expected Revenue: $310.36 million
• Beat/Miss: Beat by +$10.73 million
• YoY Revenue Growth: +210.80%

Madrigal Pharmaceuticals Announcement Details

• Quarter: Q4 2025
• Date: 2/19/2026
• Time: Before Market Opens
• Conference Call Date: Thursday, February 19, 2026
• Conference Call Time: 8:00AM ET

Madrigal Pharmaceuticals (NASDAQ:MDGL) is a clinical-stage biopharmaceutical company focused on the development of innovative therapies for cardiovascular, metabolic and liver diseases. The company’s pipeline centers on novel, liver-directed agents designed to address significant unmet medical needs, with an emphasis on nonalcoholic steatohepatitis (NASH) and related metabolic disorders.

The lead product candidate, resmetirom (MGL-3196), is an orally administered, selective thyroid hormone receptor-β agonist in Phase 3 development for the treatment of NASH. Resmetirom has been engineered to target liver tissue in order to reduce hepatic fat accumulation, improve lipid profiles and attenuate fibrosis. The company’s clinical programs include global trials across North America, Europe and Latin America, reflecting its commitment to registering resmetirom in major markets.

In addition to its lead asset, Madrigal is advancing next-generation compounds for lipid disorders and other cardiovascular risk factors. The company engages in strategic collaborations to bolster its research capabilities and expand its therapeutic portfolio. Through a combination of in-house development and partnerships, Madrigal aims to bring multiple first-in-class or best-in-class therapies to patients.

Founded in 2013 and headquartered in Conshohocken, Pennsylvania, Madrigal is led by President and Chief Executive Officer Paul A. Friedman, M.D. The company’s management team comprises experienced biopharmaceutical executives and clinical researchers dedicated to transforming the treatment landscape for metabolic and liver diseases.

Madrigal Pharmaceuticals Q4 2025 Earnings Call Transcript

Key Takeaways

• Positive Sentiment: Madrigal reported a market-leading launch for Rezdiffra with Q4 sales of $321M, ~ $958M in its first full year, and >36,250 patients on therapy as the U.S. MASH market has expanded ~50% since end-2023.
• Positive Sentiment: Management has rapidly expanded the pipeline to more than 10 programs—adding an oral GLP‑1, a late‑stage DGAT2 inhibitor (ervogastat) and six preclinical siRNAs—with a Phase 1 for the oral GLP‑1 expected in Q2 and a DGAT2 combo Phase 2 planned for 2027.
• Positive Sentiment: The company is pursuing indication expansion into compensated cirrhosis (F4c)—a ~245k patient opportunity—backed by 2‑year open‑label data showing 65% of CSPH patients moved to lower risk and an event‑driven outcomes readout targeted in 2027.
• Negative Sentiment: Payer contracting will push gross‑to‑net into the high‑30% range in 2026 (a headwind to net sales) while R&D and SG&A remain elevated after deal upfronts, although the balance sheet holds roughly $989M in cash and marketable securities.

Presentation

[Operator]

Good morning, and thank you for standing by. Welcome to Madrigal Pharmaceuticals' fourth quarter and full year 2025 earnings conference call. At this time, all participants are on 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.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Thank you, Michelle. Good morning, everyone, and thank you for joining us to discuss Madrigal's fourth quarter and full year 2025 earnings. We issued a press release this morning and posted a slide deck to accompany this webcast on the investor relations section of our website. On the call with me today is Bill Sibold, Chief Executive Officer; David Soergel, Chief Medical Officer; and Mardi Dier, Chief Financial Officer. They will provide prepared remarks, followed by Q&A. Please note on slide 2, 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 on slide 3.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Thanks, Tina. Good morning, and thanks for joining us. Today, I'll provide an update on the Rezdiffra launch, where we ended our first full year on the market at nearly $1 billion in net sales and solidified Rezdiffra as the foundational therapy in MASH. We'll discuss the significant growth in the US MASH market, which is up nearly 50% since the end of 2023 and growing at a double-digit pace. And then Dave will provide an update on our R&D strategy, where we now have more than 10 programs in our pipeline. Before turning to our fourth quarter results, I want to reflect on what we accomplished in 2025 and in just the first six weeks of this year.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

In a remarkably short period of time, we've built the leading company in MASH and assembled a pipeline we believe will help define the future of this category. We continue to execute on a fantastic US launch, extended Rezdiffra's patent exclusivity to 2045, and initiated our ex-US rollout beginning in Germany. We're advancing our F4-C trial for Rezdiffra, and we're accelerating evidence generation to further differentiate the product. At the same time, we moved quickly to build a high-quality pipeline around Rezdiffra, completing three transactions in roughly six months, adding an oral GLP-1, a late-stage DGAT-2 inhibitor, and a portfolio of six preclinical siRNA targets, each designed to be studied in combination with Rezdiffra. The reason we're moving with this level of urgency is simple: assets like Rezdiffra don't come along often. We have a high-quality, high-growth, foundational therapy driving strong top-line performance with patent protection into 2045.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

When you have an asset like that, you have an opportunity to build a sustainable and durable franchise for the long term. That's exactly what we're doing. Rezdiffra gives us a unique ability to pursue combinations, to attract high-quality assets, and to shape a market in ways other companies simply can't. As a result, we are fundamentally a different company today than just six months ago, transitioning from a single-asset launch story into a fast-growing biotech with a pipeline designed to extend our leadership for years to come. Let's turn to net sales performance on slide 5. We delivered fourth quarter 2025 net sales of $321 million, more than tripling fourth quarter 2024. For our first full year on the market, net sales totaled $958 million, an exceptional launch by any industry standard.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

That nearly billion-dollar result took a lot of work. We didn't just launch a product, we built a market from scratch. Let's take a second and really think about that. Remember, MASH was long viewed as the graveyard of drug development. No treatments, no market, and skepticism that one would ever exist, particularly with GLP-1s on the horizon. We took a different view. The unmet need was substantial, and demand for an effective therapy was real. We believed in the science and Rezdiffra's ability to become the standard of care. We built the right team, people who have created categories and launched blockbuster brands, and we got to work. We executed with a long-term mindset, wiring the system practice by practice, educating prescribers, establishing care pathways, expanding prescriber breadth and depth, and securing first-line access through disciplined contracting. And we continued to iterate and improve.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

The results speak for themselves. We were first to market, and that matters. Rezdiffra, with its liver-directed and differentiated profile, has established itself as the foundational therapy in MASH. The market is real and only beginning to take shape. GLP-1s are here, and as we expected, we're still steadily adding patients. There is room for competition, which we believe will further expand the market, and we are building a pipeline designed to extend our leadership over time. As a result of the foundation we've built and our large base of prescribers, we continue to steadily add patients quarter over quarter, as seen on slide seven. Remember, the number we report reflects the net of new starts and discontinuations at the end of each quarter.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

We continued to steadily add patients, ending the fourth quarter with more than 36,250 patients on Rezdiffra, up from more than 29,500 at the end of the third quarter. That tells us two things. First, Rezdiffra's profile is exceptional and resonates very well with prescribers and patients. Second, this large and expanding market is capable of supporting multiple therapies... This represents a small fraction of the growing addressable population, and we expect to continue to steadily add patients quarter over quarter going forward. Let me spend a moment on the US MASH market on slide 8. We are still in the early stages of what we expect to become a large specialty market.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

In just the last two years, the F2, F3 target population of 315,000 representative patients seen by our target specialists has expanded nearly 50%, and we expect this market to grow at a double-digit pace for the foreseeable future. Rezdiffra's approval and increased industry investment across the ecosystem has fundamentally changed the market dynamic, driving increased awareness, diagnosis, referrals, specialist involvement, and patients seeking care. This is a category in its very early stages, where Rezdiffra is now established as the standard of care. As the market expands, we expect to benefit from its growth, increased penetration, and ultimately, the introduction of additional therapies from our pipeline. MASH is a rare opportunity in biotech. Few therapeutic areas offer this combination of scale and high growth potential.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

That's why we expect MASH to follow the trajectory of other large specialty markets, as shown on slide 9. Markets that support 10-15+ therapies and have grown over decades to exceed $20 billion in annual sales. We believe MASH will evolve the same way, with one important difference. We are first to market with a product that has an unmatched profile. As an effective liver-directed, safe, and well-tolerated oral medicine, it far surpasses the profile of first-to-market products in those other categories. And we continue to hear from our prescribers that Rezdiffra is performing even better than expected in the real world. This profile positions us well to expand into compensated MASH cirrhosis or F4c, the next phase of our growth strategy outlined on slide 11.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

We believe F4c could double Rezdiffra's opportunity with approximately 245,000 patients, no approved therapies, and a significantly higher urgency to treat. Assuming regulatory approval, we expect to be first to market in F4c. Importantly, our F4c, F4c trial focuses on clinically meaningful outcomes, preventing decompensation rather than relying on biopsy. Rezdiffra would be the only medicine with outcomes data, solidifying it as the standard of care in MASH and supporting full approval across F2 to F4c. Before I turn it over to Dave, I want to briefly outline how we see the MASH market evolving and why Madrigal is uniquely positioned to lead it by building on the pipeline strategy that I described earlier. MASH is a complex, heterogeneous disease.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Over time, we expect distinct patient subpopulations to emerge, each requiring different mechanisms, combinations, and sequencing approaches, all anchored by Rezdiffra. We've seen this evolution before in other diseases, where progress was driven by matching the right combinations to the right patients. That's the model we're pursuing in MASH, and it's why we've moved quickly to add these specific assets to our portfolio. And the reason we can execute on this strategy is our high confidence in the growth potential of Rezdiffra. We're able to build an industry-leading MASH pipeline because we have an outstanding product, one that is performing exceptionally well today and is positioned for continued strong growth. That strong foundation allows us to develop the next generation of MASH therapies for patients. That's exciting, and it's a true differentiator for Madrigal. Dave, I'll turn it over to you to walk through our R&D strategy.

[David Soergel, CMO at Madrigal Pharmaceuticals]

Thanks, Bill. Our objective in R&D at Madrigal is straightforward: build the industry-leading pipeline in MASH to make better therapies for patients. We're doing that through targeted business development and smart clinical execution, leveraging the expertise of an R&D team that pioneered modern MASH drug development. Our strategy has 4 goals. Deliver outcomes, data, and full approval for Rezdiffra from F2 through F4c. Advance complementary mechanisms for combination with Rezdiffra to deliver the best efficacy across the MASH spectrum. Remain modality agnostic, keeping development of the best combination regimens as our strategic aim. Note our recent addition of injectable siRNAs. Leverage our experience to evolve the science. Design smarter, more informative clinical trials enabled by our extensive data and operational experience in MASH. Our aim is to use capital efficiently to take more shots on goal and advance only the most promising programs for patients.

[David Soergel, CMO at Madrigal Pharmaceuticals]

The first pillar of our R&D strategy is delivering outcomes data in F4c. The basis of our high confidence in our outcomes study are the data from our 2-year open-label study. The importance of the 2-year data is better understood in the context of how cirrhosis progresses. Development of clinically significant portal hypertension, or CSPH, is a critical inflection point in the disease. It marks a transition from compensated cirrhosis towards decompensated disease and is when the most serious complications, like variceal bleeding and development of ascites, begin to occur. Crossing the threshold into decompensated cirrhosis predicts poor prognosis, with an average survival time of 2-3 years without a liver transplant. From the literature, it's clear that patients with CSPH have meaningfully higher rates of liver-related events, and reducing CSPH risk lowers liver-related events...

[David Soergel, CMO at Madrigal Pharmaceuticals]

That's why the two-year open label, 122-patient F4C data from our NAFLD-1 trial are so exciting. As shown here on slide 14, 65% of patients with CSPH at baseline moved into lower risk categories by year two. These data support Rezdiffra's potential in F4C and reinforce confidence in our outcomes trial, particularly given that both trials have very similar patient populations. The second pillar of our R&D strategy is advancing combination therapies anchored by Rezdiffra. Slide 15 shows many of the known mechanisms involved in MASH. MASH is driven by excess free fatty acid delivery to the liver, leading to steatosis, inflammation, and fibrosis. While there are many potential points to intervene in the disease, it took decades and more than 20 industry failures before Madrigal cracked the code with Rezdiffra.

[David Soergel, CMO at Madrigal Pharmaceuticals]

To date, only two mechanisms have crossed the finish line: THR-β agonism, addressing MASH at its source in the liver, and indirect-acting GLP-1 agonism. But MASH is a heterogeneous chronic disease, and therefore, we expect treatment to evolve toward combinations. Rezdiffra gives us a unique, solid foundation on which to build combinations to achieve better efficacy overall or in certain patient subpopulations. Our combination strategy is simple: prioritize validated, mechanistically complementary approaches that enhance efficacy while preserving Rezdiffra's strong safety and tolerability profile. In orange, you see where we've already acted, an oral GLP-1, a late-stage DGAT-2 inhibitor, and multiple targets using siRNA. Let's discuss why we're excited about these new mechanisms, starting with siRNA on Slide 16. First, siRNAs target validated genes that drive MASH progression. Using precise mRNA knockdown, we can either enhance efficacy broadly or develop more tailored approaches for defined patient subpopulations. Second, the modality.

[David Soergel, CMO at Madrigal Pharmaceuticals]

GalNAc conjugated siRNA is well established and highly liver-targeted. The clinical safety of the platform is supported by multiple marketed products. We acquired six preclinical siRNA assets that are highly complementary to resmetirom, positioning us for next generation, more personalized combination regimens. Slide 17 covers our DGAT2 inhibitor, which we're excited about for a number of reasons. First, DGAT2 inhibition is a complementary mechanism to THR beta agonism. Ervogastat prevents free fatty acids from being incorporated into triglycerides, and resmetirom restores mitochondrial function to allow those free fatty acids to be turned into energy through beta oxidation. The two mechanisms together, therefore, address both the production and clearance of excess hepatic fat. Second, we know a lot about ervogastat. It's already completed a Phase 2B trial in MASH, demonstrating a robust MRI-PDFF reductions and clean safety.

[David Soergel, CMO at Madrigal Pharmaceuticals]

In the MYRNA study, 72% of patients at the 150 mg dose achieved at least a 30% reduction in PDFF, and 61% achieved a 50% reduction, what many experts now consider a super response, predicting a greater likelihood of a reversal of fibrosis. The combination of these two mechanisms has the potential to move more patients into that super responder category and drive better antifibrotic efficacy and better outcomes. We plan to initiate a drug-drug interaction study this year and expect to begin a phase 2 combination program in 2027 following FDA discussions. Next, our oral GLP-1 on Slide 18. Let's start by acknowledging that there's strong real-world enthusiasm for combining GLP-1s with resmetirom, with an understanding of the mechanistic complementarity of GLP-1 and resmetirom.

[David Soergel, CMO at Madrigal Pharmaceuticals]

GLP-1s act outside the liver by improving systemic metabolism and reducing free fatty acid delivery to the liver. This complements resmetirom's liver-directed mechanism of action. Importantly, our focus for this program is on developing a better treatment for MASH, not maximal weight loss, and therefore, our goal is to balance the right amount of weight loss to potentiate resmetirom's antifibrotic effect. So what is the right amount of weight loss to achieve better efficacy in MASH? In MAESTRO-NASH, we saw that as little as 5% weight loss meaningfully potentiated Rezdiffra's fibrosis benefit. So our aim is a once-daily, well-tolerated, oral fixed-dose combination that optimizes efficacy while maintaining good tolerability. A phase 1 single-ascending dose study of MGL-2086 is expected to start in the second quarter.

[David Soergel, CMO at Madrigal Pharmaceuticals]

Putting it all together on Slide 19, we are translating our leadership into action with one goal in mind: build the leading MASH pipeline. This is really just the beginning of an exciting journey. With Rezdiffra protected into 2045, we have a long runway to invest and innovate, building a pipeline that will define the future of MASH care. With that, I'll hand it over to Mardi.

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

Thanks, Dave, and good morning. Turning to Slide 20 and a summary of our financials. Fourth quarter 2025 net sales totaled $321.1 million, reflecting another quarter of strong demand and bringing full year 2025 net sales to $958.4 million. As we've discussed, we've made excellent progress contracting for first-line access in 2026, with some contracts taking effect in the fourth quarter of last year, as anticipated. As a result, our Gross to net impact increased from the third quarter to the fourth quarter. As a reminder, Gross to net includes several components: commercial rebates, government rebates, co-pay assistance, and channel distribution costs.

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

The team did an exceptional job managing these dynamics, resulting in a full year average at the low end of the 20%-30% range we previously outlined, an excellent outcome for 2025. We're off to a strong start this year and continue to steadily add patients. As indicated last year, last quarter, we expect our payer agreements to bring our full year 2026 gross to net impact into the high 30% range, consistent with specialty medicine analogs. Looking ahead, we expect robust net sales growth in 2026, despite the step-up in gross to net from contracting that begins in Q1, plus the typical first quarter dynamics related to benefit plan changes and insurance re-verifications. The fundamentals of the business are strong, and we're looking forward to another outstanding year of performance.

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

Moving briefly to operating expenses, R&D expenses for the fourth quarter and full year 2025 were $116.3 million and $388.5 million, respectively. The increase over the prior year periods was primarily due to business development. In the third quarter, this included a $120 million upfront payment for our oral GLP-1, and in the fourth quarter, a $50 million upfront payment for Ervogastat and our two additional early-stage MASH pipeline assets. Of note, the upfront payment of $60 million for our siRNA targets will be paid and included as an R&D expense in the first quarter of 2026. SG&A expenses for the fourth quarter and full year 2025 were $240 million and $813.8 million, respectively.

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

The increase over the prior periods was expected to support the Rezdiffra launch. Looking ahead, we expect 2026 R&D expenses to be roughly the same as 2025, as we build our organization and begin to invest in our pipeline programs. We anticipate SG&A expenses to increase next year as we continue to support the launch of Rezdiffra and build the foundation for exceptional long-term growth. Turning to our balance sheet, we ended the fourth quarter of 2025 with $988.6 million in cash, cash equivalents, restricted cash, and marketable securities. With this strong cash position, we continue to be well resourced to support the ongoing launch of Rezdiffra and the advancement of multiple pipeline programs and continued business development. So to close, slide 21 captures why we're so confident about where Madrigal is headed.

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

Rezdiffra is the foundational therapy in F2, F3 MASH, and it's just getting started. F4c represents another meaningful growth driver that could double our commercial opportunity. Our pipeline, now more than 10 programs deep, positions us to extend our leadership position as a durable, category-leading franchise. Taken together, this is a company built for sustained value creation across our launch, indication expansion, and pipeline. We believe we're exceptionally well positioned to lead in MASH in 2026 and beyond. I'll now turn the call back to Tina to open the Q&A session.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Thanks, Mardi. Let's move into the Q&A part of the call. Michelle, please go ahead and provide instructions for the Q&A session.

[Operator]

We will now open the lines for questions. To open your line, please press star one, one, and you will be added to the queue. Our first question is going to come from Ellie Merle with Barclays. Your line is open.

[Ellie Merle, Senior Biotech Equity Research Analyst at Barclays]

Hey, guys. Thanks for taking the question. So you're seeing meaningful growth in the number of diagnosed patients. Can you elaborate on the drivers here and talk about your expectations for category growth in 2026? And then second, you're also seeing an acceleration in patient starts despite the launch of Wegovy. Can you elaborate on the types of patients you're seeing starting on Rezdiffra now, versus, say, in the past, and any trends you're seeing across the types of different prescribers? Thanks.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Great. Ellie, thanks for the question. Yeah, we are seeing really strong growth. As you saw on the slides, which say a lot, almost 50% growth over a two-year period. And this, you know, we had talked about the market is in a position to grow, right? The 315,000 diagnosed patients was diagnosed sitting in the offices of the target specialists that we were calling on. And what we're seeing is our efforts are really paying off on a couple of fronts. Number one, as awareness goes up, there's gonna be more people that are diagnosed. I think that having another company in the mix, Novo, who's really trying to drive, I would say, broad awareness and uptake in the primary care offices, et cetera, is leading to more diagnosis.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Our focus has always been the $315, as we see a path to peak, essentially, through what's already available. Now, inevitably, though, as you bring products to market, you see higher growth in that space, and that's where we've seen the 50% and double-digit growth we're expecting into the foreseeable future. So, we're really quite excited about it, and it gives us not only a clearer path to peak, but also perhaps it gives us a greater opportunity than we had even anticipated and planned around. So, growth you see in all these markets, you're going to see patient growth for really years and years. And, you know, I'll leave that there.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

The question on patient adds, you know, we've been staying, and we continue to steadily add patients, and we've seen really no difference in the type of patients that is being prescribed Rezdiffra. They tend to be a pretty even mix between F2 and F3 and as it relates to, I think you mentioned a little bit about endocrinology, or how our efforts are just in general with growing. You know, we're seeing prescriptions mostly in the hep GI space. That is the predominant number of physicians, obviously more gastroenterologists than endocrinologists.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

They've just gone deeper into the deck, I would say. You know, we've said that we've established really great breadth of prescribing, and now it's a matter of going deeper into their patient population. And I think what we're seeing is proof points that this is becoming the standard of care. Patients are being put on Rezdiffra, having great experiences, staying on the drug, and you see that reflected in the patient adds.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Great. Thanks, Ellie. Next question, please.

[Operator]

Our next question will come from Thomas Smith with Leerink Partners. Your line is open.

[Thomas Smith, Senior Research Analyst at Leerink Partners]

Hey, guys. Good morning. Congrats on the quarter, and thanks for taking our questions. Hey, just one quick clarification question on, I just wanted to ask about the contribution of the Germany launch to the worldwide revenues and patient numbers, and maybe if you could expand a little bit on expectations for 2026. And then, on the pipeline combo programs, I know you're starting to look, and you've guided today to a phase 2 study with Ervogastat next year. Could you just elaborate on how you're thinking about sort of mid-stage phase 2 studies from here? Do you think these studies will need to evaluate liver histology via biopsy before you progress into pivotal studies, or is there potential for a more accelerated path that perhaps leverages NITs? Thanks so much.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Tom, thanks for the question. I'll start off with answering Germany. Germany contribution in 2025 was negligible, and we don't see actually a lot in 2026 as well. You know, really, part of the driver of that is as we're launching into an MFN world, it is still uncertain how ex-US is going to evolve. And that's not a Madrigal issue, that's for the whole industry. So, negligible in 2025. We're just getting started really in 2026. Don't expect a lot of contribution from Germany or ex-US in 2026. This is, US is the base business. US is, has exceptionally strong dynamics to it, as you've seen, not only from a performance perspective, but from an outlook perspective.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

We're very, very comfortable being able to have robust growth in 2026, the way 2026 is unfolding from an international market perspective.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Maybe I'll just put on a finer point-

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Yeah.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

about our 2026, Tom. We really do expect robust growth, and where consensus is coming out for 2026 already, we feel really good about that, which reflects very good growth from where we ended up with the $958 for 2025.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Dave, do you want to-

[David Soergel, CMO at Madrigal Pharmaceuticals]

Yeah, sure. For the, for the combination... Thanks, thanks for the question, Tom. So, you know, it's a bit early to be definitive about our program in phase two at this point, because, you know, we do need to go to the FDA and have a conversation about their expectations for the phase two B program, you know, then leading into the phase three program. However, what I'll say with respect to NITs is that, you know, clinical care has moved well past biopsy. You know, biopsy is not used in clinical care anymore, and FDA has shown more and more interest in qualifying non-invasive tests for use in drug development. I'd say in phase two, our expectation is that NITs will play a major role in our assessment.

[David Soergel, CMO at Madrigal Pharmaceuticals]

As you know, as we show in the slides, we have a strong understanding of the relationship between PDFF reduction and a potential improvement in fibrosis. So, as you can see, we're anchoring a lot of how we're looking at the program around evaluation of NITs in phase two.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Great. Thanks, Dave. Michelle, next question, please.

[Operator]

The next question will come from Yasmin Rahimi with Piper Sandler. Your line is open.

[Yasmeen Rahimi, 5-star analyst and Md at Piper Sandler]

Yeah, good morning. This is Emma on for Yas. Thanks for taking our questions. Firstly, maybe help us understand for MAESTRO-NASH outcomes in F4C, how are you tracking blinded event rates, and how is this like tracking for on-time data? At what point in this year might you tighten guidance in that regard? And is there any additional cirrhosis, open label, NAFLD data follow-up that we could get to further strengthen conviction and success? Thank you.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Great, thanks for the question. Dave, I'll turn that over to you.

[David Soergel, CMO at Madrigal Pharmaceuticals]

Yeah, sure. I guess for... Thanks for the question. I think on the, let's start with the last part. Is there gonna be any additional open label data? I mean, I think we've shown quite a bit already. So we've gotten quite a lot of information out of those 122 patients in the open label, NAFLD-1 study. And I think what you can see from that, that experience is that, even patients with the most severe disease, so individuals with clinically significant portal hypertension, we see what look like positive effects of Rezdiffra in that population. You can move people into lower risk categories of CSPH over a 2-year timeframe. So we've already gotten a lot out of this, out of this open label experience.

[David Soergel, CMO at Madrigal Pharmaceuticals]

With respect to the progress of MAESTRO outcomes, we are seeing events track in the range that were expected. So, as, as we've talked about, historically, if you look at natural history data, you see about a 5%-10% annual event accrual in patients with cirrhosis. We estimate in the placebo group somewhere in that range, and we are seeing events track with expectation to deliver data in 2027. With respect to guidance, we, we need to get a little bit further along to get more precise on our, on our timing.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Great. Thanks, Dave. Michelle, next question, please.

[Operator]

... The next question will come from Prakar Agrawal with Cantor Fitzgerald. Your line's open.

[Prakhar Agrawal, Senior Biotech Analyst at Cantor Fitzgerald]

Hi, good morning, and thank you for taking my questions, and, congrats on another strong quarter. Maybe firstly, on gross to net, if you could comment on gross to net for Q1 and cadence for the rest of 2026. Will you still expect broad first line access without step edits for Rezdiffra in 2026, now that we're seeing no contract? Maybe just another follow-up, if you can comment on compliance, persistence, and discontinuation rates that you're seeing, especially since Wegovy's launch in the market. Thank you.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Great. So, maybe I'll start a little bit with just the payer contracts. They're complete. They were in place January first or earlier, and as we previously said, we were contracting for broad first line access, no step edits, and improved utilization criteria where where it's possible. So that holds true. We are in a really great place for contracting. I think this, when I think about kind of the accomplishments, the way we've managed contracting and gross to net is absolutely best in industry that I've seen, certainly any launch I've been a part of. Remember, we came out of the gates, we didn't contract. It's now only entering into the eighth quarter of launch that you're going to be having broad contracting.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

So the focus really has been preservation of gross to net, and I think we've done a great job at it, and we've set ourselves up exceptionally well for 2026. Before turning it over to Marty for gross to net, let me finish the compliance and persistence questions. Same as what we've said, well-tolerated oral. You know, a well-tolerated oral at the one-year mark is in this 60%-70% range. Certainly, we're continuing to see that strong performance and, you know, really encouraged. As I said, we've seen some institutions have been able to have persistence up in the 90% range. We're doing everything we can to learn from kind of the best performance and how to apply that to the broader population.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

We've got an outstanding patient services team that is all over this. We work closely with specialty pharmacy and providers and patients to work on that. You asked the question about Wegovy, and you know, what's the, what's the impact that we're seeing there? Well, you know, look, Wegovy's being used, but certainly not to the detriment of Rezdiffra. In fact, we just had our best NBRX week since launch, which says to me that just as we had said, you can have multiple products in the space, but that Rezdiffra really is the winning profile. So maybe with that one, why don't I turn it over to Marty to talk about gross to net evolution?

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

Yeah. Great. Thanks, Bill. Yeah, let's break down gross to net a little bit. Prakar, thanks for the question, and maybe a little comment on Q1 as well. So nothing's really changed from what we discussed last quarter with respect to gross to net. So we ended the fourth quarter exactly where we thought we'd be, which was the midpoint of our 20%-30% range. And that was a bit of an increase from third quarter, as anticipated, as some of the commercial contracting, which remember, is one component of gross to net, took hold in the fourth quarter. But so again, ending fourth quarter in that midpoint of the 20%-30% range, as expected. Now, going into 2026, none of our messages have changed here either.

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

With the basically zero to contracting that we've been discussing, as we put those commercial contracts into effect as of 1/1/2026, that moves our gross to net discount, our overall gross net discount, with all the components into the high thirties, for 2026. And we've broken that down really by quarter. It really stays in that high thirties for each of the quarters for 2026. There's always interquarter variability because there's so many components, but generally in the high thirties, for gross to net, all as expected. And remember, as Bill just said, we get that excellent first line access, no step edits, et cetera. So, we are in very good shape and have always taken our gross to net, our diligence around gross to net very seriously. But you know, for...

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

As we discuss about Q1, looking at Q1 and what our expectations are for Q1, not much has changed there either. So we have to take into effect, which is different than most companies, that we have this zero to contracting impact to gross to net for Q1, in addition to just the normal Q1 effect. So if we look at our analogs, all the specialty medicine analogs that we refer to frequently and have since launch, if we look at what the typical first quarter impact is, it's a decline in net sales of, you know, mid- to high-single digits. And that takes into effect the reverifications of the insurance plans and sort of the typical Q1 effect. And that's really reflective of where we believe our first quarter will be as well.

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

But you have to consider not only do we have the Q1 effect, we're never immune to that, but we also have this in this quarter, the zero to contracting impact on gross to net that we just discussed. So we feel that that's pretty impressive, considering that we've been able to steadily add patients and still have a strong Q1 with the typical Q1 effect and zero to contracting. So we think we're gonna be in good shape overall for 2026, and as I already mentioned, we'll have robust sales growth in 2026.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Great. Thanks, Marty. Next question, please, Michelle.

[Operator]

The next question comes from Akash Tewari with Jefferies. Your line's open.

[Manoj Garg, Analyst at Jefferies]

Hey, this is Manoj on for Agas. Thanks for taking our question. Just one from our end. So you mentioned about like 60%-70% persistence rate. When we looked at the AASLD data, there were, like, some presentations showing more than 90% adherence rate in the real world. How important is to keep the adherence rate to that 90% to maintain the current patient adds and the revenue growth? And also, do you expect any acceleration in patient adds going forward now with all the contracts in place, or should we think about like probably around 6,000-7,000 patients net patient adds every quarter? Just to trying to understand that point. Thanks.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Great. So thanks for the question. Let me start with the patients. Look, we've said that we have been steadily adding patients, and we expect to steadily add patients going forward. And I think that is, and it's certainly an important measure as we show you this quarter, how we did, in light of having a another product on the market. So you know, the fundamentals are really, really great, and we would expect in this environment to continue to steadily add. The contracting... Remember, we've had great access from the beginning. The contracting doesn't really accelerate anything, because, if there was no policy in place, if you had a medical exception, those were flowing through very quickly.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

But in this next phase of launch, you know, we've partnered with the payers. I think we've had some really great discussions. I think they've understood the value of Rezdiffra. They see the cost of these patients in their systems, and, you know, I think we've landed in a really good place for the future with them, and, you know, we do appreciate the partnership that we have. Now, regarding persistence, you know, we are in that well-tolerated oral range, as I said, the 60%-70%. And yes, as you point out, there are some institutions that have reported rates all the way up to 90%. Now, what we will always try to do is look for ways to, you know, help appropriate patients stay on product as long as they need it.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

I think that sense of urgency has increased coming out of AASLD, where we presented data from both the F2, F3 population and the F4C population. If you discontinue therapy, disease comes back, and it comes back quickly. So, you know, we do believe this is a chronic therapy and that it's in patients' best interest, obviously prescribers' best interest, and overall for the system best interest, that they stay on therapy. So we have a lot of initiatives underway that we're doing with our own patient services group, partnering with specialty pharmacy and institutions, and working with patients as well directly to try to help that persistence rate improve to a level which is even higher than the well-tolerated oral range. But that takes a lot of work, and, you know, there's just...

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

You know, people, look, they regardless of whether it's for, regardless of the type of indication, people tend to drop off of drugs in time. But we're gonna do everything we can to educate, to keep people on appropriately.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Great. Thanks so much. Next, next question, please.

[Operator]

The next question will come from Michael Dufour with Evercore. Your line's open.

[Michael DiFiore, Equity Research Analyst at Evercore]

Hi, guys. Thanks so much for taking my questions, and congrats on the continued progress. Two for me. The first, over the past several months, you've added multiple combination assets around Rezdiffra, including DGAT2, GLP-1, and siRNA programs. My question is: How do you avoid diminishing return from putting too many synergistic mechanisms into the pipeline? And what is your go, no-go criteria for advancing a second agent, both clinically and commercially? And then my second question is briefly: Has there been any change in expected timing of MAESTRO-NASH outcomes now that the FDA has approved AI-supported pathology reads? Thank you.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Okay, Dave, I'm gonna pass over to you in a second, but just, you know, let's just take a step back, what we're trying to do here, Mike, and thanks for the question because I think this is really important. So with Rezdiffra, we have what has become standard of care and is truly a foundational therapy. And that's just not from use. Looking at the clinical data, one of the things that is really striking is that across all subgroups, you have essentially a consistent effect. So in other words, it tends to be that, you know, all these F2, F3 patients do well. It's not as though one group does, you know, like a super responder group. Now, that is a great therapy, and, you know, rarely do you see something that has that type of results.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Now, if we can, through the addition of new mechanisms of action, find a way to have the whole population or a subpopulation do better, then that really provides an opportunity for better patient outcomes. And that's how we're thinking about this. So when we're going out and looking at any of the, any of the mechanisms we're bringing in, it starts with, we believe that there's a strong mechanistic rationale that in combination, we could see a better effect for all or some patients. Now, we have to test that theory, and that's why we're gonna do these trials to quickly determine whether if there's a there, there, and we will kill or move forward quickly. The goal is not to have a lot of straggling things in the pipeline that never do anything except for suck up resource. We're not doing that.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

We're gonna try to only take forward what is meaningful for patients. Now... We also see the market evolving, though, where various subpopulations, or, or let's call them segments, may emerge. And we're well-positioned not only with Rezdiffra, but now as we make these combo programs, to provide a better product for those segments. So this is extremely, when I say well thought out, it's well thought out. It's, it's deliberate. It is based on, mechanism, what we like, and it all starts with the fact that Rezdiffra is a foundational therapy that is really one which is amenable to either fixed those combinations or, combinations, for instance, with siRNA, where you may have a pill and an injectable, but in a very favorable regimen. So that's just to give you the thinking of it. Dave, maybe-

[David Soergel, CMO at Madrigal Pharmaceuticals]

Yeah.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Just over to you for a little bit more color around it.

[David Soergel, CMO at Madrigal Pharmaceuticals]

Yeah, yeah. I think, I think the only thing I would add there is that when you start with a solid foundation that works in everybody, that's not necessarily true of every combination partner you add, right? So it could be that a particular combination partner, for example, DGAT or the GLP-1 or one of the siRNAs, does better for certain patient subtypes, whether they're a genetic predilection to disease progression, or they have some comorbidity that sort of the combination partner happens to target more effectively. So there... The other thing I think that's really important about our strategy is that it's adaptable, right? It's adaptable to the science.

[David Soergel, CMO at Madrigal Pharmaceuticals]

So as we run our phase 2 studies, we'll be able to determine whether or not, you know, the drug is kind of gonna be broadly applicable in the population and broadly does something, you know, that's gonna be meaningful for patients with MASH, or a subsegment within that, the MASH population is gonna be a better target for that combination treatment. So, I would just add the adaptability part for how we're thinking about pursuing these agents.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Yeah.

[David Soergel, CMO at Madrigal Pharmaceuticals]

Then I think your second question was about MAESTRO Outcomes and AI path reading. So it's great, you know, that the agency, again, is sort of evolving their perspective on MASH drug development. MAESTRO Outcomes is an event-driven trial, so it doesn't, it's not a histology-driven study. So, you know, AI path reading would really wouldn't be relevant there. For MAESTRO-NASH, our F3 study, that is a biopsy-driven trial, but it's a landmark study. So in other words, everybody gets a biopsy at month 54, which is then, you know, compared to baseline. So, we would certainly consider using AI path reading as part of our analysis, but it's not the primary assessment we would do. Thanks for the question, Mike.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Thanks. Next question, please.

[Michael DiFiore, Equity Research Analyst at Evercore]

Thank you.

[Operator]

Next question comes from Jay Olson with Oppenheimer. Your line is open.

[Jay Olson, Managing Director and Senior Biotechnology Analyst at Oppenheimer]

It's always... Oh, hey, congrats on the impressive progress, and thanks for taking our question. Just to follow up on the previous question, since you have two all-oral combos, where do you envision the siRNA modality to fit into the future treatment landscape of MASH? And is there any color that you can share with us on the targets of those six siRNA programs, and when should we expect the timing of clinical development? Thank you.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Thanks, Jay. Look, first of all, on the siRNA targets, for competitive reasons, we're not gonna disclose the targets at this point, but stay tuned as we move along, we'll certainly be sharing that with you. Look, where does it fit? So first of all, you know, we thought any of the targets that we're looking at, we believe there's a rationale for MASH and potentially making a better product. As I said, it starts with mechanism and the rationale to make a better drug. I'm gonna let Dave kind of walk through our whole siRNA strategy, but you know, we really think it's a nice combo when you think about it. A every 3-6 month injection and a daily pill. Pretty easy.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

You know, if you get a better effect from that, that is not a... That's a pretty strong value proposition. What makes it an even stronger value proposition is it's all within the same company. So this isn't going to be a, it's not a battle for somebody having to optimize a single product. It is us being able to look holistically across the disease and say, "What's the right solution for that patient or segment of patients?" And we can provide that in an efficient manner. And so it'll always be about what's the right therapy rather than having to sell a therapy. So Dave, maybe I'll pass it over to you.

[David Soergel, CMO at Madrigal Pharmaceuticals]

Yeah, I mean, I, I think, just to add on, I mean, from a scientific standpoint, you know, as, as Bill mentioned, siRNA technology has really, you know, had a breakthrough over the last 10 years or so, and we can develop now, highly targeted, well-tolerated therapies that last 3-6 months, as, as Bill said, or even up to 12 months. You know, the, the latest technology can even get you that, that much farther. So we're, you know, we're very fortunate to be working with Ribo Life Science, you know, a leader in siRNA technology, to, to be, developing these, these drugs.

[David Soergel, CMO at Madrigal Pharmaceuticals]

And, you know, I think the key is that that sort of combination regimen, that sort of approach will make sense for either all patients or some patients. Again, we look for drugs that either have preclinical, clinical, or genetic validation, and all of these targets kind of fit within those categories. And so we think that, you know, with Rezdiffra, that solid foundation to add on these long-acting therapies, this could be a real advantage for patients with MASH.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Good. Thanks, Dave. Thanks, Jay, for the question. Next question, please, Michelle.

[Operator]

Next question will come from Jon Wolleben with Citizens. Your line's open.

[Jon Wolleben, Managing Director at Citizens]

Hey, thanks for taking the question, and congrats. You guys have talked about this growth of the market. This is the first time you guys have put some numbers to it, and it doesn't seem like any of these dynamics you're attributing it to are going to go away anytime soon. So wondering, how should we think about, you know, five years from here, the F two, F three target population growing? And then also, should we expect, you know, further growth of the F four population as well, with patients still advancing? Just trying to get a bigger picture about the road ahead. Thanks.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Jon, thanks for the question. Yeah, I mean, look, what we said is that we'd expect double-digit growth for the foreseeable future. That's certainly for the five-year period, so you know, pretty robust growth. I think now, again, you've got a therapy that works. People are talking about the disease and, you know, as I said, we're benefiting from having a competitor that's out there talking a lot about it. And as we know, they need, you know, really lots of patients in order to make MASH a meaningful indication for them. So we think that it's for years of growth. And your other question was?

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

F four.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Oh, F4. Look, yes, we would expect to see similar... Not similar growth, but growth there. We're still working through the details of what that F4c population looks like. But I think you can assume that there will be growth. As we get a little bit further into our analysis of the market and we're getting closer to our launch, we'll provide updates as to where that's going. But overall, you know, as MASH grows, F4c will grow as well.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Great. Thanks, Jon. Next question, please, Michelle.

[Operator]

Next question is from Ritu Baral with TD Cowen. Your line's open.

[Ritu Baral, Equity Research Analyst at TD Cowen]

Hi, everyone. This is Nicole on the line for Ritu. I'm just wondering about the extent of script growth needed over the fiscal year 2026 to grow revenue off of the increase for the gross to net. Just a quick second question, what do you think companion diagnostics would need to be developed to show any genetic predisposition for MASH if you are going to eventually move forward with the siRNAs, if data is positive? Thanks.

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

Hey, Nicole, can you just clarify your first question? It was a little-

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

We missed a word.

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

Yeah.

[Ritu Baral, Equity Research Analyst at TD Cowen]

Sure. Yeah, absolutely. The extent of script growth or patient adds needed over fiscal year 2026 to see a growth in revenue to offset the increase in gross to net.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Well, okay, so let me, let me start, but let me be clear. There's... We're growing. The fundamentals of the business are exceptional. We're steadily adding patients. We are going to see robust growth in 2026 and into the future. So I mean, let me just be crystal clear. When we talk about Q1, Q1 has two Q1 things going on. First of all, the Q1 effect that every single product in the industry experiences, reauthorizations, et cetera. On top of that, though, we have this zero to contracting. So instead of contracting for the two years previously and having a steady increase in gross to net, we held off contracting until the seventh quarter of launch and, or eighth quarter of launch, I guess. And so you have this zero to contracting effect.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

So we are still, despite that, in the range of the comps that we look at, which is kind of really remarkable. It says how strong the underlying business is. So expect to see growth. Our, you know, look, we're not going to do the model is the number of patient adds, et cetera, but robust growth now and in the future. Mardi, do you have any other comment on that?

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

Yeah, exactly. We talked about it, Nicole, for 2026. From a consensus standpoint, we feel really good where the street is right now for 2026, which reflects robust growth from where we ended in 2025. So we feel like we're in good shape. We already talked about the Q1 effect and growth net, but steadily adding patients. And I'll just reiterate what Bill said, last week was our best NBRX week ever. So the underlying business is in really good shape, and we anticipate that growth through 2026 and beyond, quite frankly.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Yeah. And yeah, that's right. Go ahead, Dave.

[David Soergel, CMO at Madrigal Pharmaceuticals]

Yeah, so companion diagnostic, real interesting question. I mean, you know, it's early to sort of comment on that because, you know, to consider a companion diagnostic, you've got to be looking for a particular, for example, genetic or biomarker-type target, to tie your therapy to. So, as Bill mentioned, Rezdiffra, of course, doesn't need that because it works very well across all patient subpopulations. We'll see, you know, as the combination products move forward, you know, if there is a need to develop a companion diagnostic, but as of right now, we don't foresee that with these programs.

[Mardi Dier, CFO at Madrigal Pharmaceuticals]

Great.

[Ritu Baral, Equity Research Analyst at TD Cowen]

Just really quickly to follow up, are genetic screenings common in the clinic already?

[David Soergel, CMO at Madrigal Pharmaceuticals]

They're becoming, I think, generally speaking, I can't speak in MASH in particular, necessarily, but across general clinical care, genetic screening is becoming more common, yes. But, you know, I think producing a genetic or another biomarker companion diagnostic, you know, takes an additional lift for sure.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Yeah, and just remember, we're let's just put a fine point on this. We are 7 quarters into the launch of an entirely new category. There are decades of growth and evolution in front of us. The decisions that we're making today with the pipeline aren't 2026 decisions. They're not even 2027 decisions. These are helping to form treatment, which will include diagnosis, any kind of tests that obviously will be done to segment patients, et cetera, that will evolve in time. So we are very much on the forming side of this. And remember, we're less than 12% penetrated into the 315. It's less than 8% into the 460 that we talked about. This is at the beginning of a very significant specialty market.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

We are the company at the front end of it that can drive it, not only for the coming years, but for, we believe, decades in advance.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Great, thanks. Next question, please, Michelle.

[Operator]

Next question is from William Wood with B. Riley Securities. Your line's open.

[William Wood, Biotech Equity Research Analyst at B. Riley Securities]

Thank you so much for taking our questions, and congrats on a very nice quarter. Just sort of sticking with what you were just talking about, Bill, in terms of the market increase from 315 to 460,000, I'm just curious if you or, you know, if you see that correlated with the increase of, of patient prescriber interest and potentially how we should think about that as reading through, just sort of new patient adds. Is this more of a longer term, just more runway in terms of patients, or is this actually feeding increased, new patient additions? And then I have a follow-up.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Yes, thanks. Look, so I think one of the real important pieces of this, of the update is if you look and see where that real growth is taking place, is in the target specialists that we are calling on. And I think that's really important. What it's saying is that our efforts really are working, and that patients that are diagnosed are making their way to the specialists that treat MASH. And, you know, we've been clear from the beginning, we think this is a specialist disease. That's why we're focused on hepatology, gastroenterology, and now some endocrinology as well. That's where the patients are. Those are the experts that should be treating it, and that's where we're seeing the biggest growth taking place, which is indicative of our wiring of the system being extremely successful.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

So I think what you're gonna see is, remember, we're still at a very low penetration rate in the already diagnosed. And so we still have a lot of patients to get through just in that initial 315. And then as more and more come in and this becomes standard of care, that's when you see just treatment rates get higher as well as diagnosis rates gets higher. So, you know, that just gives you a little bit of flavor around it. And you said you had a quick follow-up, maybe, if it's just real quick, because we've got to move on.

[William Wood, Biotech Equity Research Analyst at B. Riley Securities]

Yeah, thanks. In reference to your GLP-1 and your DGAT, it looks like GLP-1 might be initiation starting for your phase one. It looks like it might be pushed back slightly from first quarter to second quarter. In terms of both those programs, just curious what remaining gating activities still need to be completed.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Yeah, so I think we got it initially to first half, and then we've refined it to second quarter. So, there's been no delay. No change, no delay. Okay, thanks.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Okay, thanks. Michelle, we have time for one more question, please.

[Operator]

Okay, the last question will come from Kripa Devarakonda with Truist. Your line's open.

[Alex Xenakis, Research Associate at Truist Securities]

Hi, this is Alex calling for Kripa. Thanks for taking our question. Congrats for the progress. Now that we are seeing more and more patients on Rezdiffra for longer time periods, we want to know, have you seen any challenges in the reimbursement process to keep patients on drug for the extended time periods? We can imagine that for many patients with Rezdiffra, that their fibrosis scores could improve, and they might technically be outside of the label requirement. That's that. Thanks.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Okay. Thank you very much for the question. So, you know, first of all, the reauthorizations we said are very routine. Oftentimes it's physician attestation or showing some kind of stabilization or improvement in one of the NITs that has been used initially. I think, you know, look, we're again, we're really early into the treatment of the disease. I think what is very compelling for the community is, I'll go back to the AASLD data, which showed that discontinuation of Rezdiffra led to a return of disease in both F2 and F3 and also F4c patients.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

So I think that, you know, more and more, the belief is that this is a chronic disease, and, you know, you just can't stop the medicine even if you have a response, because you will have done all that hard work, and then you're just gonna have disease come back. So, we think that's how it's going to evolve in the future. Again, though, you know, look, it's early, but our belief is that this is a chronic therapy. That's the way the community tends to be using it. So we feel really, you know, quite confident that'll be the case.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Great.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

So.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

All right.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Yeah. Maybe we'll, maybe we'll end it there. Maybe... Look, just, just, maybe I'll finish off just with, with a remark of just kind of what's the state of the union, if you will. Rezdiffra is performing exceptionally well. This is truly a best launch I've ever been associated with, and I can tell you that is from a... That's a factual perspective. Nothing's done as well as this. And it's poised for substantial long-term growth in a rapidly growing market. It's because of those two things that we can build a pipeline now to establish long-term leadership.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Most companies have a pipeline looking for a great product. We have a great product that is performing exceptionally, is poised to perform exceptionally for the future. Now we have a chance to build long-term leadership. It doesn't happen often. This is an opportunity.We are not gonna waste the opportunity. With that, we'll close the call.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Perfect.

[Bill Sibold, CEO at Madrigal Pharmaceuticals]

Thanks.

[Tina Ventura, Chief Investor Relations Officer at Madrigal Pharmaceuticals]

Thanks, Bill. 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.

[Operator]

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

Participants

Executives

• Bill Sibold, CEO
• David Soergel, CMO
• Mardi Dier, CFO
• Tina Ventura, Chief Investor Relations Officer

Analysts

• Alex Xenakis, Research Associate at Truist Securities
• Ellie Merle, Senior Biotech Equity Research Analyst at Barclays
• Jay Olson, Managing Director and Senior Biotechnology Analyst at Oppenheimer
• Jon Wolleben, Managing Director at Citizens
• Manoj Garg, Analyst at Jefferies
• Michael DiFiore, Equity Research Analyst at Evercore
• Prakhar Agrawal, Senior Biotech Analyst at Cantor Fitzgerald
• Ritu Baral, Equity Research Analyst at TD Cowen
• Thomas Smith, Senior Research Analyst at Leerink Partners
• William Wood, Biotech Equity Research Analyst at B. Riley Securities
• Yasmeen Rahimi, 5-star analyst and Md at Piper Sandler