Madrigal Pharmaceuticals, Inc. Q1 FY2026 Earnings Call

Good morning, and thank you for standing by. Welcome to Madrigal Pharmaceuticals First Quarter 2026 Earnings Conference Call. 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.

Thanks, Brilla. Good morning, everyone, and thank you for joining us to discuss Madrigal's First Quarter 2026 earnings. We issued a press release this morning and put the 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; Dave 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.

Thanks, Tina. Good morning, and thanks for joining us. 2026 is off to a terrific start. We've made impressive progress towards our strategic growth priorities to maximize the value of Rezdiffra and build our pipeline. Rezdiffra has achieved blockbuster status generating more than $1.1 billion in net sales in the last 12 months. That's a $1 billion run rate in a market that's still in its infancy. Penetration is low, the diagnosis rate is low, unmet need is high and the market is expanding at a double-digit pace. When you put those fundamentals together, the future growth opportunity is quite remarkable. Competition has helped grow the market but not at the expense of Rezdiffra. Beyond F2/F3 MASH, we're advancing our F4C outcomes trial, where an indication expansion could double the opportunity for Rezdiffra. And because we believe this is one of the most compelling opportunities in the industry, we've moved quickly to build the leading pipeline in MASH. We added to it yesterday with a new siRNA asset that targets a mutation in the PNPLA3 gene, a genetically validated driver of disease in a meaningful subset of patients. When you step back, it is hard to find another opportunity with this combination of market fundamentals and product strength. We have a first-in-disease approval, a foundational therapy, a rapidly expanding market, and we are building an industry-leading pipeline. We believe Madrigal is exceptionally well positioned to win here and continue to shape the future of MASH. I'll begin with an update on the Rezdiffra launch, hand it to Dave to discuss our pipeline and R&D strategy, and Mardi will wrap up with a review of our financials. Turning to Slide 5 and net sales. First quarter 2026 net sales were $311 million, representing year-over-year growth of 127%. This performance continues to reinforce that Rezdiffra is tracking in line with and, in many cases, exceeding the best-in-class specialty launches we compare ourselves to. Over the last 2 years, we have wired the system to drive Rezdiffra's growth. We built a large and growing prescriber base, secured first-line access with commercial payers and established Rezdiffra as the foundational therapy in MASH. Combined with Rezdiffra's differentiated profile and strong patient adherence, our execution has enabled us to steadily add patients quarter-over-quarter as shown on Slide 6. We ended the first quarter with more than 42,250 active patients on Rezdiffra. On a year-over-year basis, patients on therapy increased by 2.5x compared to the first quarter of 2025. That is a significant achievement by any standard, but especially in a market that didn't exist before Rezdiffra's approval. This momentum reflects strong execution by the team, the clear unmet need in MASH and continued demand from both prescribers and patients. And importantly, we are seeing that momentum carried into the second quarter. Slide 7 shows how quickly the MASH market is expanding. Since launch, we've seen the U.S. addressable market grow nearly 50% from 315,000 patients at the end of 2023 to 460,000 patients at the end of 2025. These are diagnosed F2/F3 patients seen by our target specialists. Rezdiffra's approval, together with increased industry investment has helped transform the market by driving greater awareness, referrals, diagnosis, specialist involvement and more patients seeking care. And yet, this market is still in its earliest stages. The diagnosis rate is just over 10%, and Rezdiffra penetration remains just under 10% of the 460,000 addressable patients. The MASH market has expanded rapidly and the opportunity ahead is substantial. That gives us a clear path to peak sales, and we believe no company is better positioned than Madrigal to capitalize on it. But being first in a large and growing market is only part of the story. We have established this leadership position because Rezdiffra is delivering what the MASH market wants. And that is what Slide 8 highlights. After 2 years on the market, 3 things are clear. First, profile matters. Rezdiffra is the only approved liver-directed therapy in MASH. It has broad proven efficacy across all patient subtypes and is an oral, once-daily, well-tolerated medicine with no titration requirements. In a chronic disease, this profile is a key reason why we continue to see strong persistence and increasing depth of prescribing. Second, real-world performance matters. Pivotal trials get a drug approved, but real-world experience determines a product's success. With tens of thousands of patients treated, we've received overwhelming feedback from the community that Rezdiffra's efficacy continues to exceed expectations in the real world. This includes improvements across liver stiffness, liver fat, liver enzymes, LDL-cholesterol and Lp(a). This is the kind of real-world experience that builds confidence with prescribers and helps establish a true standard of care. And third, we have built not only a leading product but a leading MASH company. We have the right team, the right model and the right start in a market we developed from the ground up. We have executed one of the best launches in the industry where our differentiated specialty model has set a high bar for anyone launching in this space. And we have learned, refined and improved our approach along the way. We were first to market and now have a pipeline with more than 10 programs designed to extend our leadership over time. Our leadership is also reflected in our presence at key hepatology, gastroenterology and endocrinology-focused medical meetings this month where more than 40 Rezdiffra abstracts are being presented. This includes a poster presented at DDW this week where nearly 70% of Rezdiffra prescribers surveyed said Rezdiffra has improved their patient's quality of life and nearly 70% expect to increase their Rezdiffra use over the next 6 months. Later this month at EASL in Barcelona, we will present additional data that reinforce the breadth of Rezdiffra's effect. That includes a secondary analysis from our Maestro NASH and NAFLD-1 trials showing that reduced Lp(a) and LDL-C in patients with MASH supports its potential to reduce cardiovascular risk independent of baseline statin use along with 2 real-world data sets that demonstrate Rezdiffra's benefit in everyday clinical practice. We believe evidence generation is a strategic advantage for Madrigal. The more we can show prescribers and payers about Rezdiffra's performance across clinically relevant endpoints, the more it's solidified as the foundational therapy. Everything we've discussed so far speaks to the strength of Rezdiffra in F2-F3 MASH, but there is another significant opportunity ahead of us in well-compensated MASH cirrhosis, or F4C, as noted on Slide 10. It's an untapped market with no approved therapies and a much higher urgency to treat. We believe F4C could double Rezdiffra's opportunity with approximately 245,000 patients under specialist care in the U.S. We have an event-driven outcomes trial underway in F4C that, if positive, is expected to support expansion into this indication as well as support full approval across F2 to F4C. So before I turn it over to Dave to talk about our pipeline, let me reiterate how rare an opportunity Madrigal has. We were first to launch, we rapidly achieved blockbuster status and we are still at the very beginning of the development of this market. It's hard to find a comparable opportunity in the industry where the fundamentals are this attractive. And from that position of strength, we are now investing in the next wave of innovation to extend our leadership and define the future of MASH. With that, I'll turn it over to Dave.

Thanks a lot, Bill. Our objective in R&D is straightforward: deliver the industry-leading pipeline in MASH to make better therapies for patients with Rezdiffra as the foundation. As shown on Slide 11, 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 four goals: first, deliver outcomes data and full approval for Rezdiffra from F2 through F4C. Second, advance complementary mechanisms for combination with Rezdiffra to deliver the best efficacy across the MASH spectrum. Third, remain modality-agnostic with development of the best combination regimens as our strategic gain. The recent addition of siRNA assets to our pipeline underscores that approach. And fourth, leverage our experience to design smarter, more informative clinical trials and use capital efficiently, taking more shots on goal and advancing only programs that serve patients' needs more effectively. The first pillar of this strategy is delivering outcomes data in F4C. Our confidence in the MAESTRO MASH outcomes trial is informed by the 2-year open-label experience in 122 F4C patients from our MAESTRO NAFLD-1 trial. Those data are best understood in the context of how MASH progresses to cirrhosis. The critical inflection point in this process is the development of clinically significant portal hypertension, or CSPH. It marks the transition from well-compensated disease towards decompensation when the most serious complications begin to occur. The literature is clear that patients with CSPH have meaningfully higher rates of liver-related events, and reducing CSPH risk lowers those event rates. That's why the 2-year data are so important. Sixty-five percent of patients with CSPH at baseline shifted into lower-risk categories by year 2. We also saw a favorable movement in other biomarkers, including liver stiffness and fibrosis-related measures. Taken together, these results support Rezdiffra's potential in F4C and reinforce confidence in our event-driven outcomes trial. The second pillar of our R&D strategy is advancing combination therapies anchored by Rezdiffra, which we know works broadly across patient subtypes. Slide 13 highlights our newest addition, ARO-PNPLA3, a clinical-stage siRNA that we recently in-licensed from Arrowhead. We're especially excited about this asset for a couple of reasons. One, PNPLA3 is a well-understood and known target for MASH based on extensive epidemiological and genome-wide association studies. Two, this is a clinical-stage asset that has completed Phase I studies. And three, we know Rezdiffra works well across all patient subtypes, including PNPLA3 carriers. So a combo including Rezdiffra and this asset has the potential for improved efficacy in a subset of patients that are especially vulnerable due to their genetics. The PNPLA3 mutation is particularly prevalent among Hispanic patients. Compared to those with wild-type PNPLA3, patients homozygous for the I148M mutation of PNPLA3 have a twofold higher risk of liver-related events. Approximately 30% of F2-F3 MASH patients are homozygous carriers of the PNPLA3 mutation making it a meaningful target for our development efforts. This asset completed Phase I studies and demonstrated two important things. First, it's selectively effective in the genetically defined population of PNPLA3 homozygotes. Second, after a single dose, it reduced liver fat by up to 46% at 12 weeks at the highest dose. We know from MAESTRO NASH that greater reductions in MRI-PDFF are associated with better fibrosis reductions with resmetirom. So the goal here is straightforward: combine a foundational therapy, Rezdiffra, that works broadly with a targeted agent that may move more patients into a high-response category and potentially improve antifibrotic efficacy with a genetically tailored approach. Stepping back on Slide 14, our pipeline now includes more than 10 programs. Rezdiffra continues in two Phase III outcomes-based trials. First, our F4C study, which is an event-driven trial that we expect to read out in 2027, and second, the F2/F3 study, which is primarily histology-driven with data expected in 2028. These trials would make Rezdiffra the first fully approved drug with outcomes data, well ahead of other competitors. Moving down the pipeline for the DGAT2 inhibitor, the drug-drug interaction study with resmetirom remains on track to begin in the fourth quarter of this year, and we expect to initiate a Phase II combination study in 2027 following regulatory discussions. For MGL-2086, our oral GLP-1, the Phase I single ascending dose study remains on track to initiate later this quarter. For ARO-PNPLA3, our next step will be to engage with regulatory authorities on the Phase II combination trial. And our six siRNA targets are progressing at various stages of preclinical development. Our approach is consistent. We're building around a foundational therapy and prioritizing mechanisms that we believe are complementary, mechanistically sound and capable of improving outcomes either broadly across the population or in important patient subgroups. Our goal is to ensure Madrigal is engaging with the community and driving the science, so we are delivering meaningful advances for patients. With Rezdiffra's long-term patent protection, we have the runway to invest, innovate and define the future of MASH care. With that, I'll hand it over to Mardi.

Thank you, Dave. Turning to Slide 15 and a summary of our financials. First quarter 2026 net sales totaled $311.3 million, up 127% year-over-year. We're off to a strong start in 2026. As we discussed on the last call, our results reflect the typical Q1 effect due to benefit plan changes in insurance reverifications plus a step-up in gross-to-net related to our commercial contracting efforts for first-line access. The team did an excellent job managing all the moving parts in the quarter. We were able to steadily add patients and our gross-to-net came in better than we anticipated. We now expect our gross-to-net discount to be in the mid- to high 30s for the rest of 2026. Looking ahead, the fundamentals of the business are strong. And as Bill discussed, Q2 is off to a great start. For the rest of 2026, we expect to steadily add patients and generate robust net sales growth. Moving to operating expenses, which include a total of $34 million of noncash stock-based compensation expense in the quarter. Cost of sales for the first quarter of 2026 was $26.8 million compared to $4.5 million in the prior year period. Cost of sales at this point primarily reflects royalties owed to Roche. R&D expenses for the first quarter of 2026 were $108.7 million compared to $44.2 million in the prior year period. The increase was primarily due to one-time upfront business development expenses of $54.3 million. As a reminder, the $25 million upfront payment and related expenses for ARO-PNPLA3 will be recorded in the second quarter. SG&A expenses for the first quarter of 2026 were $268.5 million compared to $167.9 million in the prior year period. The increase was primarily due to continued investment in commercial activities for Rezdiffra, including head count for the endocrinology field force expansion that occurred in the fourth quarter of 2025, as well as marketing efforts, including our DTC campaign. Looking ahead, we expect full year 2026 R&D expenses to be roughly the same as 2025 which is inclusive of the one-time upfront payments we've announced for strategic business development investments in both periods. We expect full year 2026 SG&A expenses to increase compared to 2025 with the annualization of the Endo sales force as we continue to support the launch of Rezdiffra and build the foundation for our expected long-term growth. This includes some choppiness with higher Q2 SG&A expenses in 2026 due to timing of certain marketing expenses, including DTC, then steadier for the rest of the year. Net loss for the first quarter of 2026 was $94.4 million compared to $73.2 million for the prior year period. Net loss for the first quarter was inclusive of one-time upfront business development expenses of $54.3 million. While our focus remains on supporting our top-line growth and building our pipeline, we are also preparing for profitability. Turning to our balance sheet. We ended the first quarter of 2026 with $817.9 million in cash, cash equivalents, restricted cash and marketable securities compared to $988.6 million at the end of 2025. The balance reflects several quarter-specific uses of cash, including one-time upfront business development payments and timing of API purchases to support future Rezdiffra manufacturing. 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 16 captures what we've discussed this morning. Rezdiffra continues to deliver incredible commercial performance with a trailing 12-month net sales now exceeding $1.1 billion, and demand remained strong with patient growth more than doubling since Q1 2025. We are leading in a market that is still in the early stages of development, but has already expanded nearly 50% in the last 2 years. This reinforces both the scale and the opportunity and the runway that remains ahead of us. We also see significant upside beyond F2-F3 with F4C representing an important next phase of growth in an indication where there are currently no approved therapies. And importantly, we're not standing still. We're investing in our pipeline of more than 10 programs designed to build on Rezdiffra's foundation and extend our leadership across the full spectrum of MASH. Taken together, this is a company built for sustainable value creation. We believe Madrigal is exceptionally well positioned in 2026 and beyond. I'll now turn the call back over to Tina and open the Q&A session.

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

Our first question comes from the line of Prakhar Agrawal with Cantor Fitzgerald.

Congrats on the quarter. Maybe just on Rezdiffra. What are you seeing on the 2Q trends so far and the expectations for patient adds for the rest of the year? And as a follow-up, now that GLP-1s have been on the market for MASH for a few quarters, what are you seeing on the impact to Rezdiffra in the market, if any?

Thanks for the question, Prakhar. As we take a look at the Q2 trends, they're great. We exited Q1 with over 42,250 patients on drug, 2.5x growth over last year at this time. We are at the very beginning of a market. We fully expect this is going to be a mega blockbuster; $1.1 billion in the last 4 quarters shows we're in a really strong position. So to put in perspective how things are going in the second quarter: we're off to a strong start and carrying that momentum. We're steadily adding patients. Regarding Wegovy and GLP-1s that you mentioned, they're being used, but certainly not to the detriment of Rezdiffra. We continue to steadily add patients. GLP-1s are becoming background therapy. In fact, most of the doctors we talk to say patients are already on a GLP-1 when they come into the office with F2-F3 MASH. So our profile looks really strong in that context. We're seeing GLP-1s in the patient background, but not any real negative impact to our launch. As a proof point, we had our best MBRx week in the last quarter, and as we exit April, it's been our best NBRx month since launch. So we're really excited about the rest of the year. We'll be steadily adding patients, just as we've said.

The next question comes from the line of Ashwani Verma with UBS.

Congrats on the quarter. So maybe can you talk about the breadth of prescribing right now? And how do you think that would evolve? Is it fair to assume that bulk of the prescribing right now is coming from gastroenterologists? When do you start to get traction from hepatology, which is a smaller patient audience, and then endocrinology — when does that become a big source? And then on the Q1 new patient dynamic: it seems like of the ~36,000 new patients that you added, which is lower than some of the recent quarters, we saw this dynamic in the first quarter of last year as well when you had 5,000 and then kind of doubled from there. So is it primarily the New Year insurance deductible reset that's driving that? And how does the rest of the year shake out on new patient dynamics?

Great. Let me start there. The Q1 adds fall into our steadily adding patients narrative, and it is largely a Q1 effect. When you think about the Q1 effect, it applies broadly to patients on therapy. Remember, what we present is the number of patients on drug on the last day of the quarter, so you have patients who come on and those who cycle off in verification processes. That's the Q1 effect since everyone is exposed to it. So as I said earlier, we expect to steadily add patients throughout the rest of the year. Q2 is off to a strong start. On breadth of prescribers: we have over 10,000 prescribers now, which is plenty of breadth for us, and we continue to add new prescribers every day. Gastroenterologists outnumber hepatologists roughly 10:1, so the majority of prescriptions flow through gastroenterology. Hepatologists were out of the gates a little faster; they've treated the disease longer and were better prepared. Endocrinology is just coming on board; we started efforts there in the fourth quarter of 2025. Think of endocrinologists as where gastroenterologists were about 2.5 years ago. They've been seeing patients on GLP-1s, but they haven't really focused on MASH historically. Now they're starting to look more actively and we're wiring the system for each of those endocrinologists as well. We see endocrinology as a future productive specialty for us. Regarding the F2/F3 split, we still see about a 50-50 split. Some might expect prescribers to treat F3s first, but if a patient is one to two steps away from cirrhosis, physicians are unlikely to wait. They will make a clinical decision on that patient's risk factors and initiate therapy. That pattern has been consistent since launch.

The next question comes from the line of Kripadwar Kunda with Truist Securities.

I have a question about patient mix. I think you just mentioned that GLP-1s are likely going to be backbone therapy. But you had also previously talked about how 25% of referred patients are on a combo. Can you talk about how that has evolved over the last few quarters? Also, some of the KOL tracks say that they prefer treating F2 patients differently; it would be helpful to understand the F2/F3 split that you are seeing in the real world?

Thanks for the question. We continue to see 25-plus percent of patients on Rezdiffra also on a GLP-1 and over 50% have been previously exposed. We expect that trend to continue; most patients coming in will likely have had experience with a GLP-1. Those dynamics are in place. On the F2/F3 split: it's still roughly 50-50. Some thought prescribers would want to treat F3s first, but as I said, when a patient is close to cirrhosis, physicians often initiate therapy rather than waiting.

50-50 still.

The next question comes from the line of Ritu Baral with TD Cowen.

I have a more high-level question on diagnostic growth as you see it through the rest of the year and next year. Do you think it would be worthwhile to spend more on disease awareness now that some competitive diagnostic awareness programs may be slowing with the maturity of the GLP-1 launches in MASH? How do you think about stepping up SG&A to support top-line growth versus clinical development and your approach to profitability? And do you have any color on estimates for the full year given the change in gross-to-net?

Thanks, Ritu. On diagnostic growth: the proof is in the market sizing. In just two years, the market grew almost 50% from 315,000 addressable patients to 460,000. Diagnosis went from 1.5 million to 1.9 million and more patients are being diagnosed and getting into specialist offices. Our efforts, and the fact that other companies have entered the space, have helped grow awareness. We're also seeing more practices purchasing noninvasive tests and doing point-of-care diagnosis, which should continue to facilitate staging, treatment and longitudinal follow-up. I'll turn the rest of your questions over to Mardi.

Yes. Thanks, Ritu. I'll pick through the embedded questions. Starting with SG&A: we want to support what we believe is going to be a mega-blockbuster brand through our sales force and commercial efforts, including marketing and DTC. You will see an increase in Q2 and then steadier SG&A for the rest of the year. We want to be in front of the growth and support the brand. Regarding gross-to-net, we now have better clarity after completing Q1. This is a new brand and we get more clarity each quarter; the team did an excellent job managing gross-to-net for the quarter and set us up for the rest of the year. We believe we'll be in the mid- to high-30s for the rest of the year. For the full year, we are comfortable with consensus estimates you mentioned; we're on track. On profitability: we believe profitability is inevitable and we're preparing for it. For 2026 specifically, we will not be profitable in 2026, and specifically in Q2, with the PNPLA3 acquisition-related expenses, we will not be profitable in Q2. There could be other quarters where we tip into profitability, but it will depend on one-time spend. Beyond 2026, profitability is inevitable and we're planning for that.

The next question comes from the line of Yasmeen Rahimi with Piper Sandler.

Congrats on a strong quarter and also really great news on hearing gross-to-net go down. We transition to MAESTRO outcomes: we're almost halfway through the year; at what point do you get visibility on how events are tracking and fine-tune guidance? You've been consistent saying they're tracking — could you add color on what we could learn between now and year-end that would give insight on this important pipeline expansion opportunity?

Great, Yasmeen. Thank you for the question. This is a huge opportunity for us. It's a really high unmet need study. Dave, could you address the specifics on event tracking?

Sure. It's a critical study and we're seeing events track in the range of our expectations. We continue to project the trial to deliver in 2027. With smaller-sized event-driven trials, precision is sometimes difficult, and when we have better precision we'll provide an update. For now, the events are tracking and we're on target for a 2027 readout.

The next question comes from the line of Eliana Merle with Barclays.

Bill, you alluded to this with patients coming in already on GLP-1, but can you elaborate on what you're seeing in terms of combination use with GLP-1 specifically, maybe the latest in terms of the proportion of patients on concomitant therapy? And what does payer coverage for combination look like since GLP-1s got the formal label for MASH?

Thanks, Eliana. We're still seeing around 25% of patients concomitantly on GLP-1 with Rezdiffra, and we think that's going to increase. There's a large number of patients on GLP-1s. Regarding access, we have had very good access since day one of launch. As we moved into 2026 with contracting, we maintained that access. Payers typically allow a GLP-1 to be used for another indicated condition and Rezdiffra for MASH. We haven't seen widespread coverage for two MASH-specific prescriptions simultaneously; payers generally wouldn't allow that. What we are seeing from prescribers is that the combination makes clinical sense in many cases. We believe combining Rezdiffra with an agent that provides weight loss, like a GLP-1, could enhance antifibrotic effects. We plan to explore that: our oral GLP-1 Phase I study is expected to initiate in the coming weeks.

The next question comes from the line of Thomas Smith with Leerink Partners.

Congrats on the quarter. Your pipeline has expanded substantially over the last 12 months with multiple programs. Can you provide updated thoughts on the clinical strategy and positioning across doublet or triplet combos, the criteria you'll use to advance programs beyond proof of concept, and comment on your appetite for additional business-development deals following recent transactions?

Thanks, Tom. Let me provide context for how we're thinking about the pipeline and then I'll turn it to Dave. We're at the front end of treating a disease with high unmet need and we have a foundational therapy that is already a blockbuster. That creates a long-term opportunity to lead. We've targeted mechanisms that are complementary to Rezdiffra. Some mechanisms may not be sufficient as monotherapies but could add meaningful efficacy in combination with Rezdiffra. We're focusing on combinations that could be fixed-dose oral combinations or regimens mixing frequent and infrequent dosing modalities like siRNA. We've assembled this pipeline very capital-efficiently — under $300 million to build a leading pipeline — and we've been disciplined. Going forward, we'll continue to evaluate opportunities in MASH that fit our mechanistic rationale and are transactable. Dave, I'll hand it over to you for more specifics.

Thanks, Bill. Our approach is to use Rezdiffra as the foundation and look for combination partners with validated targets and complementary biology. We're modality-agnostic: small molecules, siRNAs, etc. Rezdiffra sets a high bar because it works well across subpopulations, so any combination partner must demonstrate meaningful benefit. In early clinical development, we will focus on biomarkers like MRI-PDFF and other blood and imaging biomarkers to make go/no-go decisions for Phase III. For example, PNPLA3 targets a genetically defined population where we saw up to a 46% reduction in liver fat in Phase I; combined with Rezdiffra, if we can increase the number of super-responders, we would advance. Decisions will be data-driven and programs that show meaningful clinical signal will be advanced rapidly; those that do not will be stopped.

Right. To put a finer point on it: if the data show a benefit, we will move forward fast; if they don't, we will stop them quickly. We're not beholden to any single pipeline asset to define the company's future; we can be disciplined and ruthless in advancing or terminating programs based on data. Rezdiffra is the enabler of our combination strategy.

The next question comes from the line of Akash Tewari with Jefferies.

This is Manoj on for Akash. One on MAESTRO outcomes: baseline mean platelet count in the population is around 150,000 in MAESTRO. That seems lower than the ~180,000 in the Symmetry Phase II but higher than some F4C data where it was around 120,000. Given this baseline platelet count difference, do you expect to see any difference in the event rate based on this platelet count difference?

Great question. Dave, I'll pass it to you.

Yes. You're highlighting an important point: F4C is heterogeneous. Patients who have just transitioned from F3 to F4 may take longer to progress to decompensation, whereas patients with clinically significant portal hypertension (CSPH) are much closer to decompensation and more likely to drive near-term events. We enrich trials to enroll the right F4C population by using criteria including platelet counts and liver stiffness with Baveno criteria. In our studies we've allowed enrollment for platelet counts greater than or equal to 70,000, so there are patients with quite low platelet counts. Inclusion criteria in different Phase III protocols vary, but our outcomes trial is enriched appropriately using multiple criteria to ensure we observe events while having the potential to demonstrate benefit by moving patients to lower-risk states. When you compare our open-label extension and MAESTRO outcomes, the populations are broadly comparable and the inclusion criteria are similar. While sample sizes differ, the data give us confidence in the event rates we're seeing.

The next question comes from Michael DiFiore with Evercore ISI.

Congrats on all the progress. On PNPLA3: that program was previously partnered and later returned to Arrowhead. Without asking you to speak for the prior partner, can you walk us through what Madrigal saw in the asset that made it attractive today? What diligence gave you confidence in the program?

Great. I'll make a general statement and turn to Dave for specifics. Many large companies have opted out of MASH for various reasons, but with Rezdiffra we see an opportunity to build combinations. Dave, please expand on why this asset is attractive.

Yes. PNPLA3 fits our strategy: it's a validated genetic target linked to more rapid disease progression and liver-related events in homozygous carriers. siRNA is a proven modality with favorable tolerability and infrequent dosing, and this asset had Phase I clinical data showing reductions in liver fat. Given Rezdiffra's efficacy, combining these mechanisms is complementary. The Phase I data showing up to a 46% reduction in liver fat at 12 weeks at the highest dose provided proof of concept. That combination of validated target, modality suitability and clinical proof of concept made it attractive to in-license.

Yes. A 46% reduction in liver fat is impressive, and it's exciting to see what the combination with Rezdiffra could do. It's an acceleration of our siRNA efforts and complements our broader pipeline.

The next question comes from Andy Chan with Wolfe Research.

We're curious to know if you can rank order the different NASH combos that you have — which one are you most excited about clinically?

That's like asking to pick amongst our children. We brought each asset in because of complementary biology or population relevance. The decision on which combinations to advance will depend on Phase II combination data. We have mechanisms that could provide benefit either across the broader population or in genetically defined subgroups like PNPLA3 homozygotes. We'll use biomarkers such as MRI-PDFF and fibrosis biomarkers to make data-driven decisions. If a program shows meaningful improvements, we'll move it forward; if not, we'll stop it.

The next question comes from Jon Wolleben with Citizens.

Congrats on the progress. Bill, you made a comment about a path to peak sales. Can you talk a little bit about what that path looks like in terms of timing, how long to get there and how big you think Rezdiffra could be down the road?

Thanks, Jon. We believe this will be a mega-blockbuster. The path to peak sales is straightforward: continue to increase diagnosis rates, add more patients, expand prescriber adoption and maintain momentum. The market is underpenetrated with low diagnosis rates and significant runway for expansion over years. As more companies come into the space, it helps expand the market further and creates more opportunities for Rezdiffra. We remain focused on execution, steady patient growth and evidence generation to capture that long-term opportunity.

Great. Thanks, Jon. Operator, we have time for one more question, please.

And the next question comes from William Wood with B. Riley Securities.

Congrats on a very nice quarter. Thinking about the pipeline: you have about 10 pipeline assets now. Should we expect any more add-ons to your pipeline? If so, what might you be looking for — more oral options, more siRNAs, or something else? And in terms of go/no-go decisions, have any projects you've brought on or developed internally already hit that threshold where you've called a decision? Any changes in focus based on what you've seen?

William, thanks. We have assembled what we believe is the leading pipeline in NASH for less than $300 million. We are still looking at opportunities that fit our mechanistic rationale and that are transactable. There are a couple of mechanisms that still look interesting; the question is finding a partner and deal that make sense. Expect there may be additional add-ons as we round out the pipeline, but our efforts now are focused on getting these programs into the clinic, generating data and making decisions. In less than a year we've evolved from a single-asset company to one with a diversified pipeline built around a blockbuster foundational drug, and we're focused on executing the next steps.

Great. Thanks, Bill. And thank you, Brilla, and 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 2 hours. Thanks for joining us.

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