Q2 2026 Madrigal Pharmaceuticals Inc Earnings Call

Speaker #1: Good morning, and thank you for standing by. Welcome to MADRIGAL PHARMACEUTICALS, Q2 2026, earnings conference calls. At this time, all participants are in a listen-only mode.

Speaker #1: After the speaker's presentation, there will be a question-and-answer session. To ask a question during the session, you will have to press *11 on your telephone.

Speaker #1: You will then hear an automated message advising that your hand is raised. To withdraw your question, please press *11 again. Please be advised that today's conference call is being recorded.

Speaker #1: I would now like to introduce Ms. Tina Ventura, Chief Investor, Relations Officer. Please go ahead.

Speaker #2: Good morning, everyone, and thank you for joining us to discuss MADRIGAL's Q2 2026 results. We issued a press release this morning and posted a slide deck to accompany this webcast on the investor relations section of our website.

Speaker #2: 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.

Speaker #2: 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.

Speaker #2: With that, I will now turn the call over to Bill on slide 3.

Speaker #3: Thanks, Tina, and thank you all for joining. Before we review our Q2 results, let me remind you why we're so excited about MASH and why we believe MADRIGAL is uniquely positioned to lead this market.

Speaker #3: The market fundamentals are exceptional. MASH is a high-unmet-need disease with the potential for decades of growth given today's low diagnosis and treatment rates and a rapidly expanding patient population.

Speaker #3: We are at the forefront of one of the most attractive growth opportunities in the industry. We also have what we believe is the foundational therapy.

Speaker #3: Resdifra is the first approved medicine for MASH, a liver-directed once-daily oral medication with demonstrated efficacy across each MASH subgroup and an outstanding real-world profile.

Speaker #3: Add to that our commercial execution, our experienced team, and our industry-leading pipeline. We believe MADRIGAL is exceptionally well-positioned to lead in MASH today and define where this market goes over the long term.

Speaker #3: Slide 4 summarizes how we're executing on our two strategic growth priorities: maximizing the value of Resdifra and advancing our pipeline. Resdifra continues to exceed expectations as we steadily add patients quarter over quarter.

Speaker #3: Over the last 12 months, Resdifra has generated nearly $1.3 billion in net sales, reinforcing its mega-blockbuster potential. We're also strengthening the long-term value of the franchise.

Speaker #3: A key pillar of that strategy has been to build a robust patent estate. Last year, we secured our pivotal 2045 F2F3 patent. This month, we build on that foundation with three additional patents.

Speaker #3: Two that reinforce our protection in F2F3, and one supporting our potential F4C indication. As we've done successfully to date, we'll continue pursuing IP that protects the future of Resdifra.

Speaker #3: And because we believe Resdifra is the foundational therapy in what will become a large specialty market, we're investing behind it. In less than a year, we've built what we believe is the industry-leading MASH pipeline, adding more than 10 programs.

Speaker #3: We now have four clinical-stage assets following the initiation of the Phase 1 study of our oral GLP-1 last month. Each of our programs is designed to build on Resdifra's foundation and extend our leadership in MASH for years to come.

Speaker #3: We've accomplished a tremendous amount in a short period of time, but we're just getting started. Our team continues to execute on these priorities to strengthen the leadership position we've established.

Speaker #3: Let's move to our Q2 results, where I'll provide an update on Resdifra. Dave will discuss our pipeline, and Mardi will close with a review of our financials.

Speaker #3: Turning to slide 6 and net sales, we are continuing to see strong demand for Resdifra. Q2 2026 net sales were $364 million, representing year-over-year growth of 71%.

Speaker #3: This performance continues to reinforce that Resdifra is tracking in line with and, in many cases, exceeding the best-in-class specialty launches we compare ourselves to.

Speaker #3: Our strong performance is a result of successful launch execution. It's driving our near-term results and building the foundation for the long-term growth. We have effectively wired the system to build a broad and durable prescriber base.

Speaker #3: And importantly, prescribers continue to tell us that Resdifra is performing even better in the real world, and that experience is translating into action. Today, our target specialists are prescribing Resdifra more often, which is driving greater depth across our prescriber base.

Speaker #3: That growing depth, combined with broad first-line commercial access, Resdifra's differentiated profile and strong patient adherence continues to drive patient growth. That's why we've steadily added patients and, in the Q2, with more than 49,000 active patients on Resdifra.

Speaker #3: More than double a year ago. Importantly, momentum remains strong as we progress through the Q3, where we surpassed the 50,000 patient milestone earlier this month, a significant accomplishment in any launch.

Speaker #3: One of the things we're most excited about is how quickly this market is developing, as shown on slide 8. From year-end 2023 to year-end 2025, the U.S.

Speaker #3: addressable market has grown nearly 50%, from 315,000 diagnosed F2F3 patients at our target specialists to 460,000. That's remarkable growth in just two years. And it's being driven by exactly what you'd expect in a new therapeutic category.

Speaker #3: Greater disease awareness, increasing diagnosis, more patients being referred to specialists, a growing urgency to treat, and increased investment by multiple companies. We have continued to see strong market growth again this year, and expect the MASH market to expand to the double-digit pace for the foreseeable future.

Speaker #3: In fact, we see parallels between MASH and other large chronic disease markets like rheumatoid arthritis, IBD, and psoriasis as shown on slide 9. Each started with one or two therapies and evolved into markets supporting more than a dozen products and more than 20 billion dollars in annual sales.

Speaker #3: We believe that MASH will follow the same path and that Resdifra has a stronger profile than the first products that launched in any of those categories.

Speaker #3: And today, we're only about 10% penetrated in a market with a roughly 10% diagnosis rate. Think about that: 10% of 10%. That's 1% of the total potential market.

Speaker #3: Yet even from that starting point, as shown on slide 11, Resdifra is already generating north of a billion dollars in trailing 12-month net sales.

Speaker #3: That's why we're so excited about the future. We are still at the beginning of what we believe will become one of the largest specialty markets in the industry, where we have a first-to-market medicine with a best-in-disease profile.

Speaker #3: Everything I've discussed so far speaks to the strength and opportunity of Resdifra in F2F3 MASH. But there is another significant unmet need ahead of us in well-compensated MASH cirrhosis, or F4C, as noted on slide 12.

Speaker #3: It's an untapped market with no approved therapies and a much higher urgency to treat. With approximately 245,000 patients under specialist care in the U.S., we believe F4C could double Resdifra's opportunity.

Speaker #3: We have an event-driven outcome trial underway in F4C that, if positive, is expected to support expansion into this indication and support full approval across F2 to F4C.

Speaker #3: And we see the market evolving beyond these initial stages as noted on slide 13. Like other complex chronic diseases, treatment will evolve to include multiple mechanisms, combination regimens, and increasingly personalized approaches.

Speaker #3: That's why we've strategically invested in building the industry-leading MASH pipeline. Resdifra gives us a foundation no one else has, allowing us to thoughtfully add complementary mechanisms that can provide even more efficacy, broaden patient reach, and define the next generation of MASH therapies.

Speaker #3: And one of the reasons we believe Resdifra is foundational is what we've heard consistently from prescribers over the last two years of launch. They not only value its liver-directed efficacy, well-tolerated profile, and once-daily dosing, but appreciate that Resdifra works across each patient subgroup and clinical practice.

Speaker #3: That breadth and consistency across patient subgroups is exactly what you want in a foundational medicine. And it's unique to Resdifra. David will talk more about this in his section and share key data demonstrating Resdifra's broad efficacy.

Speaker #3: So with that, I'll turn it over to David.

Speaker #1: Thanks, Bill. As Bill just mentioned, for a therapy to be truly foundational, it should work effectively across patient subgroups. This is especially true in a heterogeneous disease like MASH.

Speaker #1: The forest plot on slide 14, with data from our phase three MYSTRO MASH clinical trial, demonstrates exactly that. Patients on Resdifra consistently demonstrated improvements across key subgroups, including fibrosis stage, diabetes status, BMI, and genetic background.

Speaker #1: Risk factors that may expedite disease progression. This is another way in which we are differentiating ourselves from the competition and why healthcare providers overwhelmingly prescribe Resdifra when the patient is diagnosed with F2 or F3 MASH.

Speaker #1: But we're not standing still. Leadership means continuing to advance the science and generating evidence that supports Resdifra's clinical benefit well beyond approval. It's an ongoing effort to better understand Resdifra, answer important clinical questions, and continue to raise the bar for what's possible in MASH.

Speaker #1: At ESEL this year, we presented more MASH abstracts than any other company. I'll highlight three presentations that reinforce our belief that Resdifra is the foundational therapy in MASH.

Speaker #1: First is our F4C analysis on slide 15 using the anticipate MASH risk model. Anticipate MASH is a validated model developed specifically for patients with MASH cirrhosis.

Speaker #1: It estimates a patient's likelihood of developing clinically significant portal hypertension or CSPH and future liver-related events. The MASH field is rapidly evolving, and this model is becoming increasingly accepted tool for assessing risk in patients with compensated MASH cirrhosis.

Speaker #1: This is an emerging area of science, and we are an early adopter of this new tool. That's an important part of how we approach leadership at MADRIGAL.

Speaker #1: We're not simply following the evolution of the field, but we're helping pioneer new ways to understand treatment response and disease progression. We applied the anticipate MASH model to the 122 patient two-year open label cohort from our phase three MYSTRO NAFLD1 trial.

Speaker #1: The proportion of patients classified as higher risk for CSPH declined from 75% at baseline to 55% at two years of Resmidarum treatment. Why is this important?

Speaker #1: The development of portal hypertension is the key pathophysiological inflection point in compensated cirrhosis. Once patients progress to CSPH, their risk of decompensation and other serious liver-related events increases by approximately fivefold.

Speaker #1: These findings further strengthen our confidence that Resmidarum has the potential to delay disease progression and improve long-term outcomes in patients with F4C MASH. The second dataset extends our understanding of Resdifra beyond the liver.

Speaker #1: Patients with F2F3 MASH don't just have liver disease. They also carry substantial cardiometabolic risk. In fact, cardiovascular disease remains the leading cause of death in this population, and MASH itself is an independent driver of cardiovascular risk.

Speaker #1: Our secondary analysis from MYSTRO MASH and MYSTRO NAFLD1 showed significant reductions in the ApoB, including Lp(a) and LDL, regardless of baseline statin use. Taken together, these data suggest Resdifra may positively impact both liver disease and cardiovascular risk.

Speaker #1: Slide 17 highlights Resdifra's performance in the real world. Clinical trials establish efficacy, real-world experience builds prescriber confidence. After treating tens of thousands of patients, prescribers continue to tell us Resdifra is performing even better than they expected.

Speaker #1: The data at ESEL support those observations. In one large gastroenterology practice, over a mean follow-up period of approximately nine months, nearly half the patients achieved at least a 25% reduction in liver stiffness, a key measure of treatment response.

Speaker #1: Real-world evidence like this complements what we've already seen in our clinical trials and reinforces Resdifra's best-in-disease profile. To deepen our understanding of Resdifra's full clinical potential, we're broadening our evidence generation efforts across real-world studies, investigator-initiated research, and company-sponsored trials.

Speaker #1: We will continue to pursue the questions that matter most to physicians and patients and work to generate new data that can further inform how MASH is diagnosed, treated, and managed.

Speaker #1: Putting it all together on slide 19, we've translated our leadership into action. In just one year, we've built the industry's leading MASH pipeline with more than 10 programs, including four clinical stage assets, all anchored by Resdifra.

Speaker #1: This momentum will continue into 2027 when we expect to initiate three phase two trials: the first will evaluate MGL2086, our oral GLP-1 in combination with Resmidarum; our goal is to potentiate Resmidarum's anti-fibrotic effect; we began dosing MGL2086 in a phase one single ascending dose study in June; results from this first in human study will inform the phase two trial.

Speaker #1: We also plan to initiate a phase two study of our DGAT2 inhibitor, Avergastat, in combination with Resmidarum; and we'll engage with regulatory authorities on the design of a phase two trial combining Resmidarum with MGL0795, our siRNA-targeting PNPLA3, and license from Arrowhead and MAG.

Speaker #1: We're also progressing one of the six preclinical siRNA assets that we have licensed from Ribocure. We recently nominated the first candidate to move into IND-enabling studies.

Speaker #1: All of this is advancing alongside our two ongoing phase three Resdifra trials. First, our F4C MYSTRO outcome study, which is an event-driven trial that we expect to read out in 2027.

Speaker #1: And second, the F2F3 MYSTRO NASH study, which is primarily histology-driven with data expected in 2028. We've made significant progress in a very short period of time.

Speaker #1: With Resdifra as the foundation and long-term patent production providing the runway to invest and innovate, we have an opportunity to define the future of MASH care and meaningfully improve the lives of patients.

Speaker #1: With that, I'll hand it over to Mardi.

Speaker #2: Thank you, Dave. Turning to slide 20 and the summary of our financial results, we delivered another strong quarter with second quarter 2026 net sales of $364.3 million, representing 71% growth year over year.

Speaker #2: Demand for Resdifra remained strong. We once again steadily added patients, more than doubling patients on Resdifra compared to a year ago. We also continue to effectively manage growth to net and continue to expect our growth to net discount to be in the mid to high 30s for this year.

Speaker #2: Taken together, these fundamentals support our expectation for continued steady patient adds and robust net sales growth. Moving to operating expenses, which included a total of $35.4 million, of non-cash stock-based compensation expense in the quarter compared to $25.2 million in the prior year period.

Speaker #2: Cost of sales for the second quarter of 2026 was $40 million, compared to $9.1 million for the prior year period. Cost of sales was primarily driven by an increase in royalties payable to Roche and a write-down of certain work in process inventory.

Speaker #2: R&D expenses for the second quarter of 2026 were $91.2 million compared to $54.1 million for the prior year period. The increase was primarily due to a one-time upfront business development expense of $25 million related to the in-licensing of MGL0795, a clinical stage siRNA program from Arrowhead.

Speaker #2: SG&A expenses for the second quarter of 2026 were $289.4 million compared to $196.9 million for the prior year period. The increase was primarily due to continued investment in commercial activities for Resdifra, including headcount for the endocrinology field force expansion that occurred in the fourth quarter of 2025, as well as marketing efforts, including our DTC campaign.

Speaker #2: 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.

Speaker #2: We expect a 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 Resdifra and build the foundation for long-term growth.

Speaker #2: Net loss for the second quarter of 2026 was $57.9 million compared to $42.3 million for the prior year period. Net loss for the second quarter was inclusive of a one-time upfront business development expense of $25 million.

Speaker #2: 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 second quarter of 2026 with $838.9 million in cash, cash equivalents, restricted cash, and marketable securities, compared to $988.6 million at year-end 2025.

Speaker #2: With a strong cash position, we continue to be well-resourced to support the ongoing launch of Resdifra, the advancement of multiple pipeline programs, and continued business development.

Speaker #2: So to conclude, on slide 21, we believe MADRIGAL is exceptionally well-positioned for continued value creation. With trailing 12 months net sales, Resdifra is on its way to mega-blockbuster status, and as Bill said, third quarter is off to a great start.

Speaker #2: We've more than doubled the number of patients on therapy over the past year, while the addressable NASH market itself has expanded by nearly 50% in just two years, and we believe it's still in the early stages of what will be decades of growth.

Speaker #2: We're building on Resdifra's foundation with the industry-leading pipeline of more than 10 programs. We look forward to multiple future data readouts, including our phase three F4C trial.

Speaker #2: We're investing from a physician's strength, with an R&D strategy designed to extend our leadership and create long-term value. Taken together, we believe MADRIGAL is exceptionally well-positioned, not only for continued growth in 2026, but for sustained value creation for many years to come.

Speaker #2: I'll now turn the call back over to Tina to begin the Q&A session.

Speaker #3: Thanks, Mardi. Let's move into the Q&A portion of the call. Operator, please go ahead and provide instructions for the Q&A session.

Speaker #4: Thank you very much. At this time, we will conduct the question and answer session. As a reminder, to ask a question, you need to press star 11 on your telephone and wait for your name to be announced.

Speaker #4: To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Prakhar Agarwal, of Canter Fitzgerald.

Speaker #4: Your line is open.

Speaker #5: Hi. Congrats on the quarter, and thank you so much for taking my questions. I had two. Firstly, I wanted to ask about the 3Q trends.

Speaker #5: What are you seeing and expectations for net patient adds for the remainder of the year? Just wanted to get a little bit of better color on what segments are growing to drive further growth here.

Speaker #5: And how do you feel about where the consensus is sitting for 3Q and full year 2026? And second question, you started targeting endocrinologists last year.

Speaker #5: Any initial thoughts on what you are seeing on the uptake among endocrinologists? Could that be a meaningful growth segment, or is it more niche right now?

Speaker #5: Thank you.

Speaker #6: Thanks for the question, Prakhar. It's Bill. Maybe just a comment on where we are year to date here. We had really, I think, an exceptional quarter in Q2.

Speaker #6: That was driven by exceptional execution, exceptional market dynamics, and I think that is really the best indicator of where we're headed for the future.

Speaker #6: The fundamentals of the business are terrific. We have great access. 2026 is going to be another great year. As you know, we exceeded Q2 expectations.

Speaker #6: Q3 is off to a great start. We have said and we continue to steadily add patients with 49,000 over 49,000 patients at the end of Q2, more than doubling year-over-year patient numbers.

Speaker #6: And we did announce this 50,000 milestone, which that is a really remarkable number in any launch. I don't care whether you're in a specialty launch, non-specialty launch.

Speaker #6: 50,000 represents great progress. And that's something that we crossed in July. So we continue now looking forward to Q3 and beyond to steadily add patients.

Speaker #6: We've been steadily adding. We're going to continue to steadily add patients through third quarter and through the rest of the year. So I think we're set up really well for '26.

Speaker #6: But Mardi, do you want to talk maybe a little bit about some of the specifics?

Speaker #2: Yes, absolutely. And hi, Prakhar, and good morning, everyone. As Bill said, we're off to a great start in third quarter. And we're going to expect to steadily add patients as he just discussed.

Speaker #2: And with respect to third quarter and fourth quarter, what we'd like to say is that, yep, we're comfortable with a consensus quarterly growth rate.

Speaker #2: For the rest of the year. So that means from going the growth rate, the consensus growth rate from second quarter to third quarter, and then again the consensus growth rate from third quarter to fourth quarter.

Speaker #2: So taken together, just as we've said, robust sales growth for 2026.

Speaker #6: And Prakhar, just to talk about kind of the segments where it's coming from, this continues to be driven by Epson GIs for the most part.

Speaker #6: That's just where the prescriptions have been, where we would expect that they're going to continue. You also asked about endocrinology. Endocrinology was a fourth quarter 2025 focus of ours.

Speaker #6: So we're still really early into that. And you have to remember, endocrinologists, just I'll make two real quick points about them. Number one, they've been using GLP-1s for over a decade, and they still are seeing lots of NASH and want to talk about Resdifra.

Speaker #6: Check that box. Number two, they just got started really in the fourth quarter of last year. So they're in kind of that first year of launch.

Speaker #6: And Epson GIs, they have to take their own time to wire the system, know how they're going to access their NITs, what's the pathway they have for their practice.

Speaker #6: So lots of potential in endocrinology and time, but you have to just know where they are. They're kind of nine months into the launch, really, at this point.

Speaker #6: But certainly, very promising. Thanks.

Speaker #2: Great. Thanks, Prakhar. Corey, next question, please.

Speaker #4: Thank you very much. Our next question comes from the line of Ellie Merlee of Barclays. Your line is open.

Speaker #7: Hey, thanks for taking the question. And congrats on the strong performance. Just in terms of patient growth, it seemed to accelerate versus the first quarter.

Speaker #7: I guess, what are the drivers of this? And your expectations for patient growth from here? And then just in terms of F4C, I guess, how is the event rate tracking in that study?

Speaker #7: And any clarity on when in 2027 you might expect to release the data? I recognize you might not comment, but figured I would try things.

Speaker #6: Thanks, Ellie. Thanks for the question. On the patient growth, now, I just wanted to make sure just to level set. The way we report patient numbers is the number of patients that are on Resdifra on the last day of the quarter.

Speaker #6: And that is the net of patients that are coming in the top of the funnel, and patients that are going out at the bottom of the funnel, right?

Speaker #6: I mean, and you get a bigger and bigger denominator. You have more and more patients exposed to potentially dropping off. Now, the great news this year is that we continue to steadily add patients as I've said.

Speaker #6: And we don't see that slowing down at all. But remember, you really have to do work a lot harder on the top of the funnel as you have a bigger denominator that patients can follow up.

Speaker #6: We're seeing persistency like a well-tolerated oral. A well-tolerated oral at the one-year mark is in that 60 to 70 percent range. No changes there.

Speaker #6: Product's been performing exceptionally well. When we talk to the community, we hear stories of persistence, which are even higher than that. So we have focused our efforts with our internal teams on how do you address persistency to have more patients stay on longer?

Speaker #6: And then how do we work with specialty pharmacies and pharmacies, et cetera, to get that same result? So it's a real focus of ours to drive the top of the funnel, adding new patients, and to keep patients on.

Speaker #6: And then we get to that net number. And we think that we have a really good approach. And that's why we continue to say, well, we expect to steadily add.

Speaker #6: Maybe Dave, I'll turn to you. Epson?

Speaker #3: Yeah, sure. Hi, Ellie. Yeah, quick update. So I mean, clearly, Maestro Outcomes is an important trial for the field, given the unmet medical need.

Speaker #3: And the fact that this is going to be the first outcomes trial in F4C to read out with outcomes, which is a big thing for the field.

Speaker #3: So the good news is we're seeing events accrue in the trial. However, as we said in the past, this isn't like for example, a cardiovascular outcome study where you have a large number of target events.

Speaker #3: So in this case, precision is very difficult. And when we can be more precise where we'll provide you an update at that point. But right now, we're tracking to 2027, as we said.

Speaker #2: Great. Thanks, Ellie. Corey, next question, please.

Speaker #4: much. Our next question comes from the line of Thomas Smith. Thomas, your line is open.

Speaker #5: Hey, guys. Good morning. Congrats on the nice quarter here. And thanks for taking our questions. I was wondering if you could clarify and maybe expand on the comments regarding growth to net and inventory dynamics in the quarter and how you see those evolving.

Speaker #5: Through the balance of '26. And then could you also clarify the contribution of Europe to the worldwide revenues and patient numbers? We saw there was an early access program that launched in France during the quarter.

Speaker #5: And anecdotally, from some KOLs, it sounded like there's been some nice early uptake there. But can you just comment on that program and how you think about Europe contribution for the year?

Speaker #5: Thanks so much.

Speaker #6: Great. Tom, thanks. Marty, do you want to talk about growth to net?

Speaker #2: Yeah, absolutely. So growth to net, as we said last quarter, our growth to net projected for high 30s. And we are right in that zone for Q2.

Speaker #2: And that's what we expect for the rest of the year. And that's really balanced with a mostly with a high demand quarter. With respect to inventory, just as we have with every quarter, no big changes there.

Speaker #2: So overall, everything's going well for the rest of the year in 2026, as we've discussed. What we believe the growth rate is for the rest of the year.

Speaker #2: In Europe, do you want me to?

Speaker #6: Yeah, I'll talk about that. Thanks for the question, Tom. Look, contribution of Europe is negligible in the quarter. And we would expect that to be for the year.

Speaker #6: Now, let me just talk a little bit, just what XUS in general. We've launched in Germany and, as you say, we have the early access program in France.

Speaker #6: And we received approval in the UK. A couple of observations. This is not a US disease. It's a global disease. There's a high unmet need.

Speaker #6: Interest is really high from prescribers and from patients. Reimbursement is a challenge. I remember we're in an MFN context here, where there is still uncertainty about where that all lands.

Speaker #6: And I think we're going to be in a period in the next 12, 18 months where things are still settling down. So systems have not, when I say systems, other countries have not yet adopted what the ask is of the administration in MFM, which is paying US prices.

Speaker #6: So that's something that we're at the table. We're talking with all of the governments there about this. I'm really hopeful for a long-term solution.

Speaker #6: But as I said, in this time where it's just kind of really dynamic, and a lot of uncertainty as to where policy lands and so forth, that's why we say it's going to be negligible.

Speaker #6: But remember, we've only launched in Germany. That's where we've done our build. We've been extremely disciplined about the build and it's been there. So more to come in the following quarters.

Speaker #6: But as I said, it's certainly is there certainly is a high unmet need. It's just we've got to solve the reimbursement piece. And this isn't a Madrigal specific issue.

Speaker #6: This is an industry issue overall.

Speaker #2: Great. Thanks, Tom. Corey, next question, please.

Speaker #4: Thank you very much. Our next question comes from the line of Ritu Burrell of TD Cohen. Your line is open.

Speaker #7: Good morning, guys. Thanks for taking the question. I wanted to drill down a little further on outcomes F4C timing and sort of the drivers there for the data.

Speaker #7: Can you guys confirm that per your design publication, that you're still aiming for that 92 event threshold? Or is there a possibility that you might want to boost powering based on what you're seeing?

Speaker #7: And based on further, just based on our conversations with KOLs, they indicate to us that events in F4 tend to be almost more asymptotic in the sense that they accumulate much, much more rapidly and barely at all in the first part of the trial versus more sort of linear cardiac outcome study event accumulation.

Speaker #7: Can you comment on what the natural history tells you on that that contributes to how you're approaching giving us additional clarity and narrowing of data timing guidance?

Speaker #7: Thanks.

Speaker #6: Great. Thanks, Ritu. I'll pass that over to David.

Speaker #3: Yeah. Thanks, Ritu. How are you doing today? I think the first thing to comment on is we haven't actually confirmed the target number of events.

Speaker #3: So what we've said generally is there's a publication by Harrison that's a few years old that was sort of evaluating an earlier version of the protocol.

Speaker #3: And we've heard other numbers out there. What we said in general is most of these numbers are in the ballpark, but we haven't confirmed the actual number.

Speaker #3: I think to your point about accumulation events, look, I mean, we're pioneering in this space. As we've said many times before, this is really the first well-controlled F4C outcomes trial with a therapeutic agent.

Speaker #3: So what we've heard the same thing from KOLs that the possibility is that events accelerate over time as patients sort of age through the F4C pathophysiology and the development of, for example.

Speaker #3: I think the good news is, like I said, we're seeing events accrue. They're in line with our projected completion date in 2027. So when we can be more precise will provide more precision.

Speaker #3: But I think what you're highlighting is one of the questions that's out there, right? So it's how does the placebo sort of evolve over time within a controlled trial?

Speaker #7: Great. Thanks.

Speaker #2: Thanks, Ritu. Corey, next question. Oh, yeah, go ahead. Corey, next question.

Speaker #4: Thank you very much. Our next question comes from the line of Andy Chen of Wolf Research. Your line is open.

Speaker #5: Hey. Thank you for taking the question. So we noticed that you provided a timeline guidance on the oral GLP-1 and the DGA2. Just curious, can you maybe tell us a bit more about the arrowhead asset?

Speaker #5: When is phase two going to begin? And then with the oral GLP-1, the SAD has initiated. Is it reasonable to maybe predict that maybe we're going to get data next year?

Speaker #5: Thank you.

Speaker #6: Great. Thanks, Andy. Dave?

Speaker #3: Yeah. So well, first of all, thanks for the question, Andy, on the pipeline. I love it. It's one of the main reasons why I came to Madrigal, sort of the opportunity to build a pipeline in the space where there's so much potential and so much need.

Speaker #3: And what I love about our pipeline is that we have a diversity of mechanisms, and yet all of the mechanisms we know a lot about already, right?

Speaker #3: So there's a lot of data on GLP-1. There's a lot of data on DGAT. There's a lot of data on PNPLA3. So specifically with respect to the programs, all of these programs have been chosen because there's a strong scientific rationale for complementarity with thyroid hormone receptor beta agonism, with resmediron.

Speaker #3: So specifically for the oral GLP-1, as you recall, we're developing the oral GLP-1 ultimately in combination with resmediron to dial in a little bit of weight loss to potentiate resmediron's efficacy.

Speaker #3: So as you pointed out, we started our SAD last month. And we'll be running the SAD and the MAD sort of through this year, is our plan.

Speaker #3: And then the data from that trial will then inform the phase two study, which after we talk to health authorities would start in 2027.

Speaker #3: So timing with respect to timing, we haven't given a specific date to expect phase one, but that study will sort of proceed through this year.

Speaker #3: Similar story with DGAT. We've talked about running a pretty straightforward drug-drug interaction study later this year, with resmediron and virgostat. Again, we know a lot about the virgostat because Pfizer took the compound through phase two.

Speaker #3: So we know it provides a lot of PDFF reduction in patients with NASH. And that PDFF reduction could also potentiate resmediron's efficacy. So once we finish that drug-drug interaction study, again, go to health authorities, talk about our phase two plan, and estimate to start that in 2027.

Speaker #3: Same story with PNPLA3. So that SIRNA program that we licensed from Arrowhead, we start with some very good phase one data, where we have a good understanding of dose range, with the molecule as a monotherapy.

Speaker #3: Again, we'd have to go to health authorities, talk about the combination program, and again, estimating a start in 2027. We'll provide more of an update on the specific plans in phase two as we get closer to the initiation.

Speaker #3: But right now, just on based on where the programs are and their life cycle, we'd expect them to start phase two in 2027.

Speaker #6: Yeah. And just maybe just a point on the pipeline, right? We've brought in these assets to be used in combination with resmediron. As Dave pointed out in the presentation, as I said, resmediron is a foundational therapy.

Speaker #6: You see it working across various groups. Within MASH. Consistently. So our objective is to find even more efficacy. Either in a subgroup or in the total MASH population.

Speaker #6: And you think about that in comparison to the rest of the industry. Or those that are participating in MASH. They have single assets that they're hoping still to read out, maybe positive data, and maybe get approved, and then be able to launch.

Speaker #6: They're going to be doing that, and we're going to be already moving forward with our combo strategy, which is going to raise the bar for the entire field.

Speaker #6: But there's only going to be one company that has resmediron. I think that's a point that sometimes just doesn't get quite picked up or understood.

Speaker #6: We are starting from kind of that foundational therapy, which is the building block for MASH. Thanks for the question.

Speaker #2: Great. Thanks, Corey. Next question, please.

Speaker #4: Thank you very much. Our next question comes from the line of Yasmin Rahimi of Piper Sandler. Your line is open.

Speaker #7: Good morning, team. Congrats on a great quarter. And all the color maybe would love to get color as you guys have been and I'm sure you're tracking sort of event rates in the real world in the F2, F3 population, which is the indication.

Speaker #7: But maybe to the extent that you're seeing if there is any off-label use in F4, any observations that being made there, whether it's consistent with the mice to OLE data, which you reminded us of earlier today, just would love to get sort of real-world experience.

Speaker #7: And I know it's limited, and it's probably occurring at a less extent, but appreciate any color around that. And thank you. It seems like probably we could quantify your confidence that the data is in 2027 and the likelihood that it could get pushed out into 2028.

Speaker #7: That could also be really helpful. Sorry for the very long winded. Question.

Speaker #6: Yes. Thanks for the question. I mean, maybe just a comment on kind of the real-world, what we're seeing in F2, F3. It's you never know what's going to happen in the real world, right?

Speaker #6: You have your clinical studies. They read out their well-controlled everything is controlled for patients stay on drug and you do your readout and you create a bar chart and everyone starts preparing against the bar chart.

Speaker #6: Then you get to the real world, and that's really what counts. How does the product perform? And what we're hearing overwhelmingly from patients and prescribers is that resmediron is performing exceptionally well.

Speaker #6: I don't hear stories of resmediron not working. Just and that's in and I speak, as you know, to hundreds of physicians, hundreds of prescribers.

Speaker #6: And I have not heard anyone say, "Bill, it isn't working." What I hear is that this is working better than I even thought it would.

Speaker #6: It is effective. Well tolerated. Safe. Easy to use. Supported by a great patient support program that we have here. So we really take care of patients, take care of prescribers.

Speaker #6: So early feedback, and we're seeing it also in real-world evidence that's being reported, it's product is performing, really, really well. And that's exciting. You never know that.

Speaker #6: So as you think about, as I said, you can compare products on a bar chart, but what really counts is when you move into the real world.

Speaker #6: And you didn't ask questions about SEMA, but SEMA, I think, is on kind of the opposite side of that. Well-controlled clinical trial, looks good in the clinical trial.

Speaker #6: In the real world, though, you have to stay on a drug, get to a high enough dose, and be on it long enough for it to actually work.

Speaker #6: And I think that's a really, really great example. And I think as we look into the future, profiles really matter. And we've got a great profile.

Speaker #6: I like to call it a holy grail profile. Having been in the industry 35 years, this is what the industry has always wanted to have.

Speaker #6: A once-a-day pill that works, right? So maybe that's the place just to give you some context on what we're hearing in the real world.

Speaker #6: Now, regarding off-label use, look, we've been crystal clear from day one. Do not use resmediron. In F4C patients until we have the trial complete and we know that it works.

Speaker #6: And I think that is just the responsible thing to do. And also, look, it makes sense what you don't want to do is have a product used in an area where there could be any kind of adverse event that then carries back to your already indicated population.

Speaker #6: So I think there is some use. We can't quantify it, and there isn't a lot of data to suggest what the experience has been with people.

Speaker #6: So maybe Dave, can I turn it over to you?

Speaker #3: Yeah. Just a quick add. I mean, you made a comment about the open label experience. And so we didn't talk about it this time around, but we have in the past where the event rate in that 122 patient cohort over a two-year period is quite low.

Speaker #3: It's a 2 to 3 percent annualized rate. So that's a even though it's an open label population, it's a well-controlled and well-characterized population with F4C that looks very much like the mice to outcomes phase three population.

Speaker #3: So that low event rate is some of the basis for our confidence that resmediron is could be effective in F4 as well. I think with respect to timing, as we said, when we have more precision on the estimate, we'll provide you with an update.

Speaker #3: At this point, we're still projecting into 2027.

Speaker #2: Great. Okay. Thank you. Next question, please.

Speaker #4: Thank you very much. Our next question comes from the line of Akash Tawari of Jefferies. Your line is open.

Speaker #5: Hey. This is Manoj on for Akash. I just want on the F4C outcomes trial. So given the mean baseline platelet count in open label was around 125K, somewhat higher than the baseline of 150K in the F4C trial, do you view the event rates observed in the OLE as the realistic guide for what we should expect in the F4C?

Speaker #5: And also, other blinded event rates in the outcomes trial, is tracking in line with what we would expect from the OLE data? Just a rough estimate on that point.

Speaker #6: Dave, do you want to?

Speaker #3: Yeah, sure. Yeah. I think with reference to the platelet count, I mean, there's going to be some variability, as you know, in the measure of platelets.

Speaker #3: So in general, we enriched both populations by having a very low exclusion criterion for platelet count. So greater than 70,000 in the study. And the distribution as we've talked about of patients with CSPH is pretty similar when you look at the open label population compared to the mice to outcomes phase three study.

Speaker #3: So if you recall, anticipate NASH scoring and buvino criteria are the combination of liver synthesis measurements by VCTE and platelet count. So when you combine the two, you get a risk of CSPH.

Speaker #3: So I think the fact that we were we've sort of pushed the population towards the CSPH higher CSPH risk is one of the reasons why we're seeing events and maybe in other programs at other sponsor companies are maybe not seeing as robust accrual of events.

Speaker #3: We've we think we've enriched this trial in a particularly effective way, both in terms of CSPH and using other markers like MRE. So I think that's the key point.

Speaker #3: And your second question was?

Speaker #5: Whether the yeah. Thank you in line with the expectation. Yeah.

Speaker #3: Yeah. So as we said, I mean, the events are tracking in a way that would estimate a delivery of the data in 2027. And when we're able to provide more precision on that estimate, we'll give you an update.

Speaker #3: But right now, 2027.

Speaker #2: Great. Thanks, Manoj. Next question, please.

Speaker #4: Thank you very much. Our next question comes from the line of Ash Verma of UBS. Your line is open, Ash.

Speaker #7: Great. Yeah. Thanks for taking a question. Yeah. I got two on F4 also. So just maybe can you talk about what type of relative risk reduction on the composite wood position resmediron as a drug that can have broad adoption based on the feedback that you're getting from physicians?

Speaker #7: Is it heuristic 50% type outcome or can we get even a broad adoption with a lower risk reduction? That's first. And then secondly, yeah, a lot of discussion on just the event rates here.

Speaker #7: Maybe just like if you can help us understand on the placebo events in this study, why would this be any different in this study versus the prior 5 to 10 percent annualized event rate that we've seen?

Speaker #7: And I believe your STAT plans assume the annualized 10%, but if it's more like a 5%, is it still 2027 readout? Thank you.

Speaker #6: All right. Dave.

Speaker #3: Yeah. Well, I mean, I think, look, first of all, what's a clinically relevant reduction and hazard in F4C? The reality is, I think anything that statistically significant and yields an approval would be clinically relevant.

Speaker #3: I mean, this is a disease where there is no treatment, and and these patients are really on the cusp of end-stage liver disease, and either death or a transplant.

Speaker #3: So I think one of the really important things is getting a medicine to these patients and any risk reduction is going to be is going to be a big change in the field for patients.

Speaker #3: With respect to the placebo rate, I mean, we've sort of guided to the 5 to 10 percent range based on the natural history. As you pointed out, in the earlier Harrison paper, which, again, was done sort of drafted using an earlier version of the protocol, the estimate of the placebo rate was about 10%.

Speaker #3: The 10% placebo rate, as you know, determines sort of the duration of the trial. It doesn't really affect trial powering. So the hazard reduction is the key thing that determines trial powering.

Speaker #3: And those two things together, the placebo rate and the drug effect, determine the blinded event event rate is tracking in line with delivery in '27.

Speaker #3: And we have more data. We'll provide you more precision on that estimate.

Speaker #2: Thanks. Thanks, Ash. Corey, next question, please.

Speaker #4: Thank you very much. Our next question comes from the line of Michael DeFiori of Evercore ISI. Michael, your line is open.

Speaker #8: Thank you. Thanks so much for taking my question, guys. Two for me. The first regarding resmediron patient growth and underlying demand. Can you separate two-queue patient growth into new starts versus reactivations following first quarter insurance disruptions versus discontinuations?

Speaker #8: And my second question is, you've already reached over 10,000 prescribers that have indicated that and have indicated that the commercial focus is increasingly shifting towards prescription depth.

Speaker #8: My question is, what percent of two-queue new prescriptions came from existing prescribers versus first-time riders? And how is that mix changing? Thank you.

Speaker #6: Hey, thanks, Mike, for the question. Maybe let me start a little with that. You mentioned the 10,000 prescribers. That is another really, really significant milestone to cross and launch.

Speaker #6: I mean, my experience, you exceed 10,000, and you've really got your base of prescribers that can drive your future into in this case, a megablockbuster.

Speaker #6: And that's something which hasn't stood still in reported on that number in a while, but it continues to grow. We have new prescribers all the time.

Speaker #6: When you think about that mix, you're always going to have more of your scripts on a monthly basis coming from the existing pool of prescribers.

Speaker #6: So think about it. If you add 10 prescribers on the 10,000, just disproportionately, there's so many. That's not the right number adding 10. We're adding more than that, I can assure you.

Speaker #6: So it's always going to be weighted towards the current prescribers. And that's why depth becomes much more important than breadth once you cross that 10,000 threshold.

Speaker #6: And we're continuing to see across all of the prescribers just increase depth of prescriptions. And why is that? Well, because they're having good results.

Speaker #6: Why is that? Because they're diagnosing more patients. And they're learning the product. They're setting up their they're wiring their system. They're setting up their pathways.

Speaker #6: They're making sure they have access to or have their own NITs. So that is what takes time in a launch. And that's why products typically don't go from 0 to 100.

Speaker #6: It takes kind of years to get to full penetration. Because people just get more comfortable and work down through their deck of patients if you will.

Speaker #6: And we're seeing exactly that. And we're tracking exactly like we had hoped and like what we had thought we would. Now, so how does that translate now back to your question about monthly oh, you had said the mix.

Speaker #6: We haven't reported out on the mix of prescribers and so forth. If you think about Pepsin GIs are the predominant riders. GIs outnumber Peps just in the market in the country by about 10 to 1.

Speaker #6: So that's where the volume is going to be. Because they just have more patients and more prescribers, okay? Now, what about patient ads? That net number that we show, we don't break it out into what's coming in the top of the funnel, what's going out the bottom of the funnel, and that.

Speaker #6: And as you can see, that's steadily adding. When you look back over the quarters, that's kind of our definition of steadily adding. And most importantly, we expect to continue to do so going forward.

Speaker #6: Now, we're going to do everything we can to accelerate adding to the top and decelerate leaving from the bottom. That's what we do. That's what that continues to make it a great launch.

Speaker #6: So that's what I'll leave it now, Mike. And we'll update in the future. But we are in really, really great shape on kind of all key metrics and really the one at the end of the day that counts is patients.

Speaker #6: And that's the one that I think that is this 50,000 milestone, that is a big number. Just that's why we kind of pulled that one ahead.

Speaker #6: We didn't want to wait another quarter and say and we knew everyone would be doing the, well, what day of the month was it that it happened?

Speaker #6: Let me assure you, the 50,000 is consistent with the steadily adding patients. It's just it's a big number that the world should know about.

Speaker #6: Thanks.

Speaker #2: Great. Thanks, Corey. Next question.

Speaker #4: Thank you very much. Our next question comes from the line of Jay Olson of Oppenheimer. Jay, your line is open.

Speaker #8: Oh, hey, guys. Congrats on all the progress. And thank you for providing this update. Since you have a number of new patents and multiple levers available to drive resmediron sales growth, including potential combinations, how are you thinking about the peak sales magnitude and timeline to achieve peak sales?

Speaker #8: And what's your vision of how the mass market dynamics may evolve in the next 10 years in terms of patient segmentation, and which genotypes or phenotypes do you suspect might be appropriate to target for a more personalized approach to treating mass with precision medicine?

Speaker #8: Thank you.

Speaker #6: Yeah. Jay, thanks for the question. Let me start with kind of the market dynamics because I think these are this is something which is really so remarkable about mass.

Speaker #6: I'll go back, first of all, to when we communicated what the approachable patient number in F2, F3 was at the end of '23. That was the 315,000.

Speaker #6: And we did that same analysis at the end of '25, and that was 460,000. So almost 50% growth in patients. Now, you would say, well, gee, how sustainable is that?

Speaker #6: Well, here's why it's really sustainable. Because it's about 10% diagnosed today, the disease. And we have about 10% penetration. So we're about 1% into the journey.

Speaker #6: Now, that is a setup where all the demographics, everything that we're looking at is driving towards mass continuing to be a challenge, not just for the next 3, 5, 10 years, but decades.

Speaker #6: So that's the backdrop that we're against. We've got we had almost 50% growth in two years. We expect a double-digit growth for the foreseeable future.

Speaker #6: And you heard me say that Q3 is off to a strong start, but that we are expecting and seeing patient growth in the market in 2026, consistent with what we've communicated before.

Speaker #6: So that growth of the market is where the real opportunity lies. And as great as resmediron is, as I said in my opinion, holy grail profile, we're looking for even more efficacy in either the whole population or segments of the population.

Speaker #6: And a real specific you said, how do you kind of the personalized medicine. This is where the PMP-LA3 deals that we did with Aerohead.

Speaker #6: We're so excited about it. That is a very specific identifiable patient population that could benefit from having a not only a foundational therapy like resmediron, where we work really well in that, if you look at our presentation, but if you add to that this targeted SIRNA, could we get even more efficacy?

Speaker #6: So we look at there's going to be these segments that open up in time, partially driven by the data, partially driven by just natural market evolution.

Speaker #6: So that's why we're not only optimistic about resmediron, but a whole franchise and having a solution for patients that cover really the gamut of mass.

Speaker #6: We haven't commented on peaks, and we're not, but you have heard us say that we think that resmediron has made a blockbuster potential. And that's even before we start to add these next-generation products that we're working on, which again, I'll remind you, as we have combo products, others will be still fighting for their first product in a pathway that we probably already got a combo in.

Speaker #2: Great. Thanks. Thanks, Jay. Corey, next question, please.

Speaker #4: Thank you very much. Our next question comes from the line of Kripa Devarkonda of Truist Securities. Your line is open.

Speaker #7: Hey, guys. Thank you so much for taking my question and congratulations on the quarter. Wanted to ask about the competitive landscape. As we get closer to a competitor phase three data in '40 of this year, I was wondering if you can comment on how you view any potential impact on resmediron if the trial were to be successful and mass patients get another oral option.

Speaker #7: I think it also takes back to the prior question regarding fragmentation because some of our KOL checks have suggested that this drug could target specific subsegments or drugs in general could target different subsegments.

Speaker #7: So would love to hear your comments on that. And also, wanted to just ask about also the recent patents issued for resmediron. You already had previously issued patents extending resmediron till 2045.

Speaker #7: Can you just talk about the impact of the recently issued ones and how that strengthens the profile of the drug? Thank you.

Speaker #6: Look, thank you very much, for the question. There's a lot there. Maybe just starting with IP. Last year, we secured our last July actually, we secured our pivotal F2, F3 patent, which is the weight threshold dosing.

Speaker #6: Which gives us up to 2045. And the reason that patent was so important, it allows us to think about our pipeline and portfolio a little differently.

Speaker #6: We have a lot of time with resmediron, so we can place a bet on earlier stage programs or later stage programs. We don't have a short-term problem.

Speaker #6: So that's really good. The patents that we announced, announced just, I guess, this month, was it? We secured two new F2, F3 patents. And those cover important safety information in our label.

Speaker #6: So generic has to include that type of language in their label. So them trying to do a skinny label really makes it challenging for them.

Speaker #6: And these are both orange booklisted patents. So that's just further reinforcing the 2045 patent that we have. We now have a new F4C patent.

Speaker #6: And I'm really excited about this because this remember, 45 came out of the approved label. And we don't have a label yet in F4C, but we've already secured a use patent which gets us into the 40s as well.

Speaker #6: And that's before a label where there's potentially other opportunities to generate IP. So I feel like we've said all along that we that IP is really important, and we've made it a focus.

Speaker #6: And I think we've made really, really significant progress with our IP strategy. Now, I think you're probably referring to Atlanta Fibrinar. That's what it was, right?

Speaker #6: And look, what we've always said and you've heard me say before, this is going to be a big market. It can support multiple products.

Speaker #6: And the new entrants, we think, help us if there are new entrants. You still have to have a successful product. You have to get it approved and all those minor details build a big commercial organization launch.

Speaker #6: But if you get to market one day eventually, it is can really help to drive growth. And I think we've seen that with Wegovy.

Speaker #6: I think they're being here is really helped us. You heard me say a little bit earlier though, this isn't about comparing bar graphs anymore.

Speaker #6: It's really about the real world. We're over two years on the market, over 50,000 patients. We have high satisfaction by prescribers and patients. And it's just continuing to press.

Speaker #6: So against that backdrop, it's kind of hard to see where Atlanta Fibrinar will fit. It comes down to profiles. If you heard me say many times, and we've got a great profile.

Speaker #6: Atlanta Fibrinar, 1,200 milligram pill. It's a PPAR associated with weight gain. And edema. Now, this is at a time when the world is obsessed with weight loss.

Speaker #6: So we don't see weight gain as a real benefit. Particularly in mass. And we did some market research with prescribers. And 80% of prescribers said they wouldn't use Atlanta Fibrinar because of the weight gain.

Speaker #6: So if they get here, look, mass is a big market. We've got lots of room for more product. That's why we're building our pipeline.

Speaker #6: We think it overall helps. But they got a long way to go. And we wish them luck. I think that's really it.

Speaker #2: Great. Thanks. And actually, we're past the top of the hour, Corey. So I think we'll conclude today's call. And so thank you all for your time and interest.

Speaker #2: This now concludes our call. A replay of the webcast will be available on our website in approximately two hours. Thanks for joining us.

Operator: Good morning, and thank you for standing by. Welcome to Madrigal Pharmaceuticals' Q2 2026 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question and answer session. To ask a question during the session, you will have to press star one one on your telephone. You will hear an automated message advising that your hand is raised. To withdraw your question, please press star one one again. Please be advised today's conference call is being recorded. I would now like to introduce Ms. Tina Ventura, Chief Investor Relations Officer. Please go ahead.

Operator: Good morning, and thank you for standing by. Welcome to Madrigal Pharmaceuticals' Q2 2026 Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. To ask a question during the session, you will have to press star one one on your telephone. You will hear an automated message advising that your hand is raised. To withdraw your question, please press star one one again. Please be advised 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: Good morning, everyone, thank you for joining us to discuss Madrigal's Q2 2026 results. 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.

Tina Ventura: Good morning, everyone, thank you for joining us to discuss Madrigal's Q2 2026 Results. 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 two, we will be making certain forward-looking statements today. We refer you to our SEC filings for a discussion of the risks that may cause actual results to differ from the forward-looking statements. With that, I will now turn the call over to Bill on slide three.

Bill Sibold: Thanks, Tina, thank you all for joining. Before we review our Q2 results, let me remind you why we're so excited about MASH and why we believe Madrigal is uniquely positioned to lead this market. The market fundamentals are exceptional. MASH is a high unmet need disease with the potential for decades of growth, given today's low diagnosis and treatment rates and a rapidly expanding patient population. We are at the forefront of one of the most attractive growth opportunities in the industry. We also have what we believe is the foundational therapy. Rezdiffra is the first approved medicine for MASH, a liver-directed once-daily oral medication with demonstrated efficacy across each MASH subgroup and an outstanding real-world profile. Add to that our commercial execution, our experienced team, and our industry-leading pipeline.

Bill Sibold: Thanks, Tina, thank you all for joining. Before we review our Q2 results, let me remind you why we're so excited about MASH and why we believe Madrigal is uniquely positioned to lead this market. The market fundamentals are exceptional. MASH is a high unmet need disease with the potential for decades of growth, given today's low diagnosis and treatment rates and a rapidly expanding patient population. We are at the forefront of one of the most attractive growth opportunities in the industry. We also have what we believe is the foundational therapy. Rezdiffra is the first approved medicine for MASH, a liver-directed once-daily oral medication with demonstrated efficacy across each MASH subgroup and an outstanding real-world profile. Add to that our commercial execution, our experienced team, and our industry-leading pipeline.

Bill Sibold: We believe Madrigal is exceptionally well-positioned to lead in MASH today and define where this market goes over the long term. Slide 4 summarizes how we're executing on our two strategic growth priorities: maximizing the value of Rezdiffra and advancing our pipeline. Rezdiffra continues to exceed expectations as we steadily add patients quarter-over-quarter. Over the last 12 months, Rezdiffra has generated nearly $1.3 billion in net sales, reinforcing its mega blockbuster potential. We're also strengthening the long-term value of the franchise. A key pillar of that strategy has been to build a robust patent estate. Last year, we secured our pivotal 2045 F2, F3 patent. This month, we build on that foundation with three additional patents. Two that reinforce our protection in F2, F3, and one supporting our potential F4-C indication.

Bill Sibold: We believe Madrigal is exceptionally well-positioned to lead in MASH today and define where this market goes over the long term. Slide four summarizes how we're executing on our two strategic growth priorities: maximizing the value of Rezdiffra and advancing our pipeline. Rezdiffra continues to exceed expectations as we steadily add patients quarter-over-quarter. Over the last 12 months, Rezdiffra has generated nearly $1.3 billion in net sales, reinforcing its mega blockbuster potential. We're also strengthening the long-term value of the franchise. A key pillar of that strategy has been to build a robust patent estate. Last year, we secured our pivotal 2045 F2, F3 patent. This month, we build on that foundation with three additional patents. Two that reinforce our protection in F2, F3, and one supporting our potential F4-C indication.

Bill Sibold: As we have done successfully to date, we will continue pursuing IP that protects the future of Rezdiffra. Because we believe Rezdiffra is the foundational therapy in what will become a large specialty market, we are investing behind it. In less than a year, we have built what we believe is the industry-leading MASH pipeline, adding more than 10 programs. We now have 4 clinical stage assets following the initiation of the phase I study of our oral GLP-1 last month. Each of our programs is designed to build on Rezdiffra's foundation and extend our leadership in MASH for years to come. We have accomplished a tremendous amount in a short period of time, but we are just getting started. Our team continues to execute on these priorities to strengthen the leadership position we have established. Let us move to our Q2 results, where I will provide an update on Rezdiffra.

Bill Sibold: As we have done successfully to date, we will continue pursuing IP that protects the future of Rezdiffra. Because we believe Rezdiffra is the foundational therapy in what will become a large specialty market, we are investing behind it. In less than a year, we have built what we believe is the industry-leading MASH pipeline, adding more than 10 programs. We now have four clinical stage assets following the initiation of the phase I study of our oral GLP-1 last month. Each of our programs is designed to build on Rezdiffra's foundation and extend our leadership in MASH for years to come. We have accomplished a tremendous amount in a short period of time, but we are just getting started. Our team continues to execute on these priorities to strengthen the leadership position we have established.

Bill Sibold: Let us move to our Q2 results, where I will provide an update on Rezdiffra. Dave will discuss our pipeline, and Mardi will close with a review of our financials. Turning to slide six and net sales, we are continuing to see strong demand for Rezdiffra. Q2 2026 net sales were $364 million, representing year-over-year growth of 71%. 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. Our strong performance is a result of successful launch execution.

Bill Sibold: Dave will discuss our pipeline, and Mardi will close with a review of our financials. Turning to slide six and net sales, we are continuing to see strong demand for Rezdiffra. Q2 2026 net sales were $364 million, representing year-over-year growth of 71%. 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. Our strong performance is a result of successful launch execution. It is driving our near-term results and building the foundation for the long-term growth. We have effectively wired the system to build a broad and durable prescriber base. Importantly, prescribers continue to tell us that Rezdiffra is performing even better in the real world, and that experience is translating into action. Today, our target specialists are prescribing Rezdiffra more often, which is driving greater depth across our prescriber base.

Bill Sibold: It is driving our near-term results and building the foundation for the long-term growth. We have effectively wired the system to build a broad and durable prescriber base. Importantly, prescribers continue to tell us that Rezdiffra is performing even better in the real world, and that experience is translating into action. Today, our target specialists are prescribing Rezdiffra more often, which is driving greater depth across our prescriber base.

Bill Sibold: That growing depth, combined with broad first-line commercial access, Rezdiffra's differentiated profile, and strong patient adherence, continues to drive patient growth. That is why we have steadily added patients, ending the Q2 with more than 49,000 active patients on Rezdiffra, more than double a year ago. Importantly, momentum remains strong as we progress through the Q3, where we surpassed the 50,000-patient milestone earlier this month, a significant accomplishment in any launch. One of the things we are most excited about is how quickly this market is developing, as shown on slide eight. From year-end 2023 to year-end 2025, the US addressable market has grown nearly 50%, from 315,000 diagnosed F2, F3 patients at our target specialists to 460,000. That is remarkable growth in just two years, and it is being driven by exactly what you would expect in a new therapeutic category.

Bill Sibold: That growing depth, combined with broad first-line commercial access, Rezdiffra's differentiated profile, and strong patient adherence, continues to drive patient growth. That is why we have steadily added patients, ending the Q2 with more than 49,000 active patients on Rezdiffra, more than double a year ago. Importantly, momentum remains strong as we progress through the Q3, where we surpassed the 50,000-patient milestone earlier this month, a significant accomplishment in any launch. One of the things we are most excited about is how quickly this market is developing, as shown on slide eight. From year-end 2023 to year-end 2025, the US addressable market has grown nearly 50%, from 315,000 diagnosed F2, F3 patients at our target specialists to 460,000. That is remarkable growth in just two years, and it is being driven by exactly what you would expect in a new therapeutic category.

Bill Sibold: Greater disease awareness, increasing diagnosis, more patients being referred to specialists, a growing urgency to treat, and increased investment by multiple companies. We have continued to see strong market growth again this year and expect the MASH market to expand at a double-digit pace for the foreseeable future. In fact, we see parallels between MASH and other large chronic disease markets like rheumatoid arthritis, IBD, and psoriasis, as shown on slide nine. Each started with one or two therapies and evolved into markets supporting more than a dozen products and more than $20 billion in annual sales. We believe that MASH will follow the same path, and that Rezdiffra has a stronger profile than the first products that launched in any of those categories. Today, we are only about 10% penetrated in a market with a roughly 10% diagnosis rate. Think about that.

Bill Sibold: Greater disease awareness, increasing diagnosis, more patients being referred to specialists, a growing urgency to treat, and increased investment by multiple companies. We have continued to see strong market growth again this year and expect the MASH market to expand at a double-digit pace for the foreseeable future. In fact, we see parallels between MASH and other large chronic disease markets like rheumatoid arthritis, IBD, and psoriasis, as shown on slide nine. Each started with one or two therapies and evolved into markets supporting more than a dozen products and more than $20 billion in annual sales. We believe that MASH will follow the same path, and that Rezdiffra has a stronger profile than the first products that launched in any of those categories. Today, we are only about 10% penetrated in a market with a roughly 10% diagnosis rate. Think about that.

Bill Sibold: Even from that starting point, as shown on slide 11, Rezdiffra is already generating north of $1 billion in trailing 12-month net sales. That is why we are so excited about the future. We are still at the beginning of what we believe will become one of the largest specialty markets in the industry, where we have a first-to-market medicine with a best-in-disease profile. Everything I have discussed so far speaks to the strength and opportunity of Rezdiffra in F2, F3 MASH. There is another significant unmet need ahead of us in well-compensated MASH cirrhosis, or F4C, as noted on slide 12. It is an untapped market with no approved therapies and a much higher urgency to treat. With approximately 245,000 patients under specialist care in the US, we believe F4C could double Rezdiffra's opportunity.

Bill Sibold: Even from that starting point, as shown on slide 11, Rezdiffra is already generating north of $1 billion in trailing 12-month net sales. That is why we are so excited about the future. We are still at the beginning of what we believe will become one of the largest specialty markets in the industry, where we have a first-to-market medicine with a best-in-disease profile. Everything I have discussed so far speaks to the strength and opportunity of Rezdiffra in F2, F3 MASH. There is another significant unmet need ahead of us in well-compensated MASH cirrhosis, or F4C, as noted on slide 12. It is an untapped market with no approved therapies and a much higher urgency to treat. With approximately 245,000 patients under specialist care in the US, we believe F4C could double Rezdiffra's opportunity.

Bill Sibold: We have an event-driven outcome trial underway in F4C that, if positive, is expected to support expansion into this indication and support full approval across F2 to F4C. We see the market evolving beyond these initial stages, as noted on slide 13. Like other complex chronic diseases, treatment will evolve to include multiple mechanisms, combination regimens, and increasingly personalized approaches. That is why we have strategically invested in building the industry-leading MASH pipeline. Rezdiffra gives us a foundation no one else has, allowing us to thoughtfully add complementary mechanisms that can provide even more efficacy, broaden patient reach, and define the next generation of MASH therapies. One of the reasons we believe Rezdiffra is foundational is what we have heard consistently from prescribers over the last two years of launch.

Bill Sibold: We have an event-driven outcome trial underway in F4C that, if positive, is expected to support expansion into this indication and support full approval across F2 to F4C. We see the market evolving beyond these initial stages, as noted on slide 13. Like other complex chronic diseases, treatment will evolve to include multiple mechanisms, combination regimens, and increasingly personalized approaches. That is why we have strategically invested in building the industry-leading MASH pipeline. Rezdiffra gives us a foundation no one else has, allowing us to thoughtfully add complementary mechanisms that can provide even more efficacy, broaden patient reach, and define the next generation of MASH therapies. One of the reasons we believe Rezdiffra is foundational is what we have heard consistently from prescribers over the last two years of launch.

Bill Sibold: They not only value its liver-directed efficacy, well-tolerated profile, and once-daily dosing, appreciate that Rezdiffra works across each patient subgroup and clinical practice. That breadth and consistency across patient subgroups is exactly what you want in a foundational medicine, and it is unique to Rezdiffra. Dave will talk more about this in his section and share key data demonstrating Rezdiffra's broad efficacy. With that, I will turn it over to Dave.

Bill Sibold: They not only value its liver-directed efficacy, well-tolerated profile, and once-daily dosing, appreciate that Rezdiffra works across each patient subgroup and clinical practice. That breadth and consistency across patient subgroups is exactly what you want in a foundational medicine, and it is unique to Rezdiffra. Dave will talk more about this in his section and share key data demonstrating Rezdiffra's broad efficacy. With that, I will turn it over to Dave.

David Soergel: Thanks, Bill. As Bill just mentioned, for a therapy to be truly foundational, it should work effectively across patient subgroups. This is especially true in a heterogeneous disease like MASH. The forest plot on slide 14 with data from our Phase III MAESTRO-NASH clinical trial demonstrates exactly that. Patients on Rezdiffra consistently demonstrated improvements across key subgroups, including fibrosis stage, diabetes status, BMI, and genetic background, risk factors that may expedite disease progression. This is another way in which we are differentiating ourselves from the competition and why healthcare providers overwhelmingly prescribe Rezdiffra when a patient is diagnosed with F2 or F3 MASH. We are not standing still. Leadership means continuing to advance the science and generating evidence that supports Rezdiffra's clinical benefit well beyond approval. It is an ongoing effort to better understand Rezdiffra, answer important clinical questions, and continue to raise the bar for what is possible in MASH.

Dave Soergel: Thanks, Bill. As Bill just mentioned, for a therapy to be truly foundational, it should work effectively across patient subgroups. This is especially true in a heterogeneous disease like MASH. The forest plot on slide 14 with data from our Phase III MAESTRO-NASH clinical trial demonstrates exactly that. Patients on Rezdiffra consistently demonstrated improvements across key subgroups, including fibrosis stage, diabetes status, BMI, and genetic background, risk factors that may expedite disease progression. This is another way in which we are differentiating ourselves from the competition and why healthcare providers overwhelmingly prescribe Rezdiffra when a patient is diagnosed with F2 or F3 MASH. We are not standing still. Leadership means continuing to advance the science and generating evidence that supports Rezdiffra's clinical benefit well beyond approval. It is an ongoing effort to better understand Rezdiffra, answer important clinical questions, and continue to raise the bar for what is possible in MASH.

David Soergel: At EASL this year, we presented more MASH abstracts than any other company. I'll highlight three presentations that reinforce our belief that Rezdiffra is the foundational therapy in MASH. First is our F4-C analysis on slide 15 using the ANTICIPATE-NASH risk model. ANTICIPATE-NASH is a validated model developed specifically for patients with MASH cirrhosis. It estimates a patient's likelihood of developing clinically significant portal hypertension, or CSPH, and future liver-related events. The MASH field is rapidly evolving, this model has become an increasingly accepted tool for assessing risk in patients with compensated MASH cirrhosis. This is an emerging area of science, we are an early adopter of this new tool. That's an important part of how we approach leadership at Madrigal. We're not simply following the evolution of the field, we're helping pioneer new ways to understand treatment response and disease progression.

Dave Soergel: At EASL this year, we presented more MASH abstracts than any other company. I'll highlight three presentations that reinforce our belief that Rezdiffra is the foundational therapy in MASH. First is our F4-C analysis on slide 15 using the ANTICIPATE-NASH risk model. ANTICIPATE-NASH is a validated model developed specifically for patients with MASH cirrhosis. It estimates a patient's likelihood of developing clinically significant portal hypertension, or CSPH, and future liver-related events. The MASH field is rapidly evolving, this model has become an increasingly accepted tool for assessing risk in patients with compensated MASH cirrhosis. This is an emerging area of science, we are an early adopter of this new tool. That's an important part of how we approach leadership at Madrigal. We're not simply following the evolution of the field, we're helping pioneer new ways to understand treatment response and disease progression.

David Soergel: We applied the ANTICIPATE-NASH model to the 122 patient, two-year open label cohort from our phase III MAESTRO-NAFLD-1 trial. The proportion of patients classified as higher risk for CSPH declined from 75% at baseline to 55% at two years of resmetirom treatment. Why is this important? The development of portal hypertension is the key pathophysiological inflection point in compensated cirrhosis. Once patients progress to CSPH, their risk of decompensation and other serious liver-related events increases by approximately fivefold. These findings further strengthen our confidence that resmetirom has the potential to delay disease progression and improve long-term outcomes in patients with F4-C MASH. The second data set extends our understanding of Rezdiffra beyond the liver. Patients with F2, F3 MASH don't just have liver disease, they also carry substantial cardiometabolic risk.

Dave Soergel: We applied the ANTICIPATE-NASH model to the 122 patient, two-year open label cohort from our phase III MAESTRO-NAFLD-1 trial. The proportion of patients classified as higher risk for CSPH declined from 75% at baseline to 55% at two years of resmetirom treatment. Why is this important? The development of portal hypertension is the key pathophysiological inflection point in compensated cirrhosis. Once patients progress to CSPH, their risk of decompensation and other serious liver-related events increases by approximately fivefold. These findings further strengthen our confidence that resmetirom has the potential to delay disease progression and improve long-term outcomes in patients with F4-C MASH. The second data set extends our understanding of Rezdiffra beyond the liver. Patients with F2, F3 MASH don't just have liver disease, they also carry substantial cardiometabolic risk.

David Soergel: In fact, cardiovascular disease remains the leading cause of death in this population, MASH itself is an independent driver of cardiovascular risk. Our secondary analysis from MAESTRO-NASH and MAESTRO-NAFLD-1 showed significant reductions in the ApoB, including Lp and LDL, regardless of baseline statin use. Taken together, these data suggest Rezdiffra may positively impact both liver disease and cardiovascular risk. Slide 17 highlights Rezdiffra's performance in the real world. Clinical trials establish efficacy, real-world experience builds prescriber confidence. After treating tens of thousands of patients, prescribers continue to tell us Rezdiffra is performing even better than they expected. The data at EASL support those observations. In one large gastroenterology practice, over a mean follow-up period of approximately nine months, nearly half the patients achieved at least a 25% reduction in liver stiffness, a key measure of treatment response.

Dave Soergel: In fact, cardiovascular disease remains the leading cause of death in this population, MASH itself is an independent driver of cardiovascular risk. Our secondary analysis from MAESTRO-NASH and MAESTRO-NAFLD-1 showed significant reductions in the ApoB, including Lp and LDL, regardless of baseline statin use. Taken together, these data suggest Rezdiffra may positively impact both liver disease and cardiovascular risk. Slide 17 highlights Rezdiffra's performance in the real world. Clinical trials establish efficacy, real-world experience builds prescriber confidence. After treating tens of thousands of patients, prescribers continue to tell us Rezdiffra is performing even better than they expected. The data at EASL support those observations. In one large gastroenterology practice, over a mean follow-up period of approximately nine months, nearly half the patients achieved at least a 25% reduction in liver stiffness, a key measure of treatment response.

David Soergel: Real-world evidence like this complements what we've already seen in our clinical trials, reinforces Rezdiffra's best-in-disease profile. To deepen our understanding of Rezdiffra's full clinical potential, we're broadening our evidence generation efforts across real-world studies, investigator-initiated research, and company-sponsored trials. We will continue to pursue the questions that matter most to physicians and patients and work to generate new data that can further inform how MASH is diagnosed, treated, and managed. Putting it all together on slide 19, we've translated our leadership into action. In just one year, we've built the industry's leading MASH pipeline with more than 10 programs, including four clinical stage assets, all anchored by Rezdiffra. This momentum will continue into 2027 when we expect to initiate three phase II trials. The first will evaluate MGL-2086, our oral GLP-1 in combination with resmetirom. Our goal is to potentiate resmetirom's anti-fibrotic effect.

Dave Soergel: Real-world evidence like this complements what we've already seen in our clinical trials, reinforces Rezdiffra's best-in-disease profile. To deepen our understanding of Rezdiffra's full clinical potential, we're broadening our evidence generation efforts across real-world studies, investigator-initiated research, and company-sponsored trials. We will continue to pursue the questions that matter most to physicians and patients and work to generate new data that can further inform how MASH is diagnosed, treated, and managed. Putting it all together on slide 19, we've translated our leadership into action. In just one year, we've built the industry's leading MASH pipeline with more than 10 programs, including four clinical stage assets, all anchored by Rezdiffra. This momentum will continue into 2027 when we expect to initiate three phase II trials. The first will evaluate MGL-2086, our oral GLP-1 in combination with resmetirom. Our goal is to potentiate resmetirom's anti-fibrotic effect.

David Soergel: We began dosing MGL-2086 in a phase I single ascending dose study in June. Results from this first-in-human study will inform the phase II trial. We also plan to initiate a phase II study of our DGAT-2 inhibitor, ervogastat, in combination with resmetirom and will engage with regulatory authorities on the design of a phase II trial combining resmetirom with MGL0795, our siRNA targeting PNPLA3 in-licensed from Arrowhead and MEG. We're also progressing one of the six preclinical siRNA assets that we in-licensed from Ribocure. We recently nominated the first candidate to move into IND-enabling studies. All of this is advancing alongside our two ongoing phase III Rezdiffra trials. First, our F4-C MAESTRO-NASH OUTCOMES study, which is an event-driven trial that we expect to read out in 2027. Second, the F2/F3 MAESTRO-NASH study, which is primarily histology-driven with data expected in 2028.

Dave Soergel: We began dosing MGL-2086 in a phase I single ascending dose study in June. Results from this first-in-human study will inform the phase II trial. We also plan to initiate a phase II study of our DGAT-2 inhibitor, ervogastat, in combination with resmetirom and will engage with regulatory authorities on the design of a phase II trial combining resmetirom with MGL0795, our siRNA targeting PNPLA3 in-licensed from Arrowhead and MEG. We're also progressing one of the six preclinical siRNA assets that we in-licensed from Ribocure. We recently nominated the first candidate to move into IND-enabling studies. All of this is advancing alongside our two ongoing phase III Rezdiffra trials. First, our F4-C MAESTRO-NASH OUTCOMES study, which is an event-driven trial that we expect to read out in 2027. Second, the F2/F3 MAESTRO-NASH study, which is primarily histology-driven with data expected in 2028.

David Soergel: We've made significant progress in a very short period of time. With Rezdiffra as the foundation and long-term patent protection providing the runway to invest and innovate, we have an opportunity to define the future of MASH care and meaningfully improve the lives of patients. With that, I'll hand it over to Mardi.

Dave Soergel: We've made significant progress in a very short period of time. With Rezdiffra as the foundation and long-term patent protection providing the runway to invest and innovate, we have an opportunity to define the future of MASH care and meaningfully improve the lives of patients. With that, I'll hand it over to Mardi.

Mardi Dier: Thank you, Dave. Turning to slide 20 and a summary of our financial results. We delivered another strong quarter, with Q2 2026 net sales of $364.3 million, representing 71% growth year-over-year. Demand for Rezdiffra remains strong. We once again steadily added patients, more than doubling patients on Rezdiffra compared to a year ago. We also continue to effectively manage gross to net and continue to expect our gross to net discount to be in the mid to high 30s for this year. Taken together, these fundamentals support our expectation for continued steady patient adds and robust net sales growth. Moving to operating expenses, which included a total of $35.4 million of non-cash stock-based compensation expense in the quarter, compared to $25.2 million in the prior year period.

Mardi Dier: Thank you, Dave. Turning to slide 20 and a summary of our financial results. We delivered another strong quarter, with Q2 2026 net sales of $364.3 million, representing 71% growth year-over-year. Demand for Rezdiffra remains strong. We once again steadily added patients, more than doubling patients on Rezdiffra compared to a year ago. We also continue to effectively manage gross to net and continue to expect our gross to net discount to be in the mid to high 30s for this year. Taken together, these fundamentals support our expectation for continued steady patient adds and robust net sales growth. Moving to operating expenses, which included a total of $35.4 million of non-cash stock-based compensation expense in the quarter, compared to $25.2 million in the prior year period.

Mardi Dier: Cost of sales for Q2 2026 was $40 million compared to $9.1 million for the prior year period. Cost of sales was primarily driven by an increase in royalties payable to Roche and a write-down of certain work-in-process inventory. R&D expenses for Q2 2026 were $91.2 million, compared to $54.1 million for the prior year period. The increase was primarily due to a one-time upfront business development expense of $25 million related to the in-licensing of MGL0795, a clinical stage siRNA program from Arrowhead. SG&A expenses for Q2 2026 were $289.4 million, compared to $196.9 million for the prior year period. The increase was primarily due to continued investment in commercial activities for Rezdiffra, including headcount for the endocrinology field force expansion that occurred in Q4 2025, as well as marketing efforts, including our DTC campaign.

Mardi Dier: Cost of sales for Q2 2026 was $40 million compared to $9.1 million for the prior year period. Cost of sales was primarily driven by an increase in royalties payable to Roche and a write-down of certain work-in-process inventory. R&D expenses for Q2 2026 were $91.2 million, compared to $54.1 million for the prior year period. The increase was primarily due to a one-time upfront business development expense of $25 million related to the in-licensing of MGL0795, a clinical stage siRNA program from Arrowhead. SG&A expenses for Q2 2026 were $289.4 million, compared to $196.9 million for the prior year period. The increase was primarily due to continued investment in commercial activities for Rezdiffra, including headcount for the endocrinology field force expansion that occurred in Q4 2025, as well as marketing efforts, including our DTC campaign.

Mardi Dier: 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 payment we've announced for strategic business development investments in both periods. We expect a 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 long-term growth. Net loss for Q2 2026 was $57.9 million compared to $42.3 million for the prior year period. Net loss for Q2 was inclusive of a one-time upfront business development expense of $25 million. While our focus remains on supporting our top-line growth and building our pipeline, we are also preparing for profitability.

Mardi Dier: 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 payment we've announced for strategic business development investments in both periods. We expect a 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 long-term growth. Net loss for Q2 2026 was $57.9 million compared to $42.3 million for the prior year period. Net loss for Q2 was inclusive of a one-time upfront business development expense of $25 million. While our focus remains on supporting our top-line growth and building our pipeline, we are also preparing for profitability.

Mardi Dier: Turning to our balance sheet, we ended Q2 2026 with $838.9 million in cash equivalents, restricted cash, and marketable securities, compared to $988.6 million at year-end 2025. With a strong cash position, we continue to be well-resourced to support the ongoing launch of Rezdiffra, the advancement of multiple pipeline programs, and continued business development. To conclude, on slide 21, we believe Madrigal is exceptionally well-positioned for continued value creation. With nearly $1.3 billion in trailing 12-month net sales, Rezdiffra is on its way to mega blockbuster status. As Bill said, Q3 is off to a great start. We've more than doubled the number of patients on therapy over the past year, while the addressable NASH market itself has expanded by nearly 50% in just two years, we believe it's still in the early stages of what will be decades of growth.

Mardi Dier: Turning to our balance sheet, we ended Q2 2026 with $838.9 million in cash equivalents, restricted cash, and marketable securities, compared to $988.6 million at year-end 2025. With a strong cash position, we continue to be well-resourced to support the ongoing launch of Rezdiffra, the advancement of multiple pipeline programs, and continued business development. To conclude, on slide 21, we believe Madrigal is exceptionally well-positioned for continued value creation. With nearly $1.3 billion in trailing 12-month net sales, Rezdiffra is on its way to mega blockbuster status. As Bill said, Q3 is off to a great start. We've more than doubled the number of patients on therapy over the past year, while the addressable NASH market itself has expanded by nearly 50% in just two years, we believe it's still in the early stages of what will be decades of growth.

Mardi Dier: We're building on Rezdiffra's foundation with an industry-leading pipeline of more than 10 programs. We look forward to multiple future data readouts, including our Phase III F4-C trial. We're investing from a position of strength with an R&D strategy designed to extend our leadership and create long-term value. Taken together, we believe Madrigal is exceptionally well-positioned, not only for continued growth in 2026, but for sustained value creation for many years to come. I'll now turn the call back over to Tina to begin the Q&A session.

Mardi Dier: We're building on Rezdiffra's foundation with an industry-leading pipeline of more than 10 programs. We look forward to multiple future data readouts, including our Phase III F4-C trial. We're investing from a position of strength with an R&D strategy designed to extend our leadership and create long-term value. Taken together, we believe Madrigal is exceptionally well-positioned, not only for continued growth in 2026, but for sustained value creation for many years to come. I'll now turn the call back over to Tina to begin the Q&A session.

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

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

Operator: Thank you very much. At this time, we will conduct a question and answer session. As a reminder, to ask a question, you need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Prakhar Agrawal of Cantor Fitzgerald. Your line is open.

Operator: Thank you very much. At this time, we will conduct a question-and-answer session. As a reminder, to ask a question, you need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Prakhar Agrawal of Cantor Fitzgerald. Your line is open.

Prakhar Agrawal: Hi. Congrats on the quarter and thank you so much for taking my questions. I had two. Firstly, wanted to ask about the Q3 trends. What are you seeing in expectations for net patient adds for remainder of the year? Just wanted to get a little bit of a better color on what segments are going to drive further growth here, and how do you feel about where the consensus is sitting for Q3 and full year 2026? Second question, you started targeting endocrinologists last year. Any initial thoughts on what you are seeing on the uptake among endocrinologists? Could that be a meaningful growth segment, or is it more niche right now? Thank you.

Prakhar Agrawal: Hi. Congrats on the quarter and thank you so much for taking my questions. I had two. Firstly, wanted to ask about the Q3 trends. What are you seeing in expectations for net patient adds for remainder of the year? Just wanted to get a little bit of a better color on what segments are going to drive further growth here, and how do you feel about where the consensus is sitting for Q3 and full year 2026? Second question, you started targeting endocrinologists last year. Any initial thoughts on what you are seeing on the uptake among endocrinologists? Could that be a meaningful growth segment, or is it more niche right now? Thank you.

Bill Sibold: Thanks for the questions, Prakhar. It's Bill. Maybe just a comment on where we are year to date here. We had really, I think, an exceptional quarter in Q2 that was driven by exceptional execution, exceptional market dynamics, and I think that is really the best indicator of where we're headed for the future. The fundamentals of the business are terrific. We have great access. 2026 is going to be another great year. As you know, we exceeded Q2 expectations. Q3 is off to a great start. We have said, we continue to steadily add patients with over 49,000 patients at the end of Q2, more than doubling year-over-year patient numbers. We did announce this 50,000 milestone, which that is a really remarkable number in any launch.

Bill Sibold: Thanks for the questions, Prakhar. It's Bill. Maybe just a comment on where we are year to date here. We had really, I think, an exceptional quarter in Q2 that was driven by exceptional execution, exceptional market dynamics, and I think that is really the best indicator of where we're headed for the future. The fundamentals of the business are terrific. We have great access. 2026 is going to be another great year. As you know, we exceeded Q2 expectations. Q3 is off to a great start. We have said, we continue to steadily add patients with over 49,000 patients at the end of Q2, more than doubling year-over-year patient numbers. We did announce this 50,000 milestone, which that is a really remarkable number in any launch.

Bill Sibold: I don't care whether you're in a specialty launch, non-specialty launch, 50,000 represents great progress, and that's something that we got across that in July. We continue now looking forward to Q3 and beyond, to steadily add patients. We've been steadily adding. We're going to continue to steadily add patients through Q3 and through the rest of the year. I think we're set up really well for 2026. Mardi, do you want to talk maybe a little bit about some of the specifics?

Bill Sibold: I don't care whether you're in a specialty launch, non-specialty launch, 50,000 represents great progress, and that's something that we got across that in July. We continue now looking forward to Q3 and beyond, to steadily add patients. We've been steadily adding. We're going to continue to steadily add patients through Q3 and through the rest of the year. I think we're set up really well for 2026. Mardi, do you want to talk maybe a little bit about some of the specifics?

Mardi Dier: Yes, absolutely. Hi, Prakhar. Good morning, everyone. As Bill said, we're off to a great start in Q3. We're going to expect to steadily add patients as he just discussed. With respect to Q3 and Q4, what we'd like to say is that, yes, we're comfortable with the consensus quarterly growth rate for the rest of the year. Would that mean from going the growth rate, the consensus growth rate from Q2 to Q3, and then again, the consensus growth rate from Q3 to Q4. Taken together, just as we've said, robust sales growth for 2026.

Mardi Dier: Yes, absolutely. Hi, Prakhar. Good morning, everyone. As Bill said, we're off to a great start in Q3. We're going to expect to steadily add patients as he just discussed. With respect to Q3 and Q4, what we'd like to say is that, yes, we're comfortable with the consensus quarterly growth rate for the rest of the year. Would that mean from going the growth rate, the consensus growth rate from Q2 to Q3, and then again, the consensus growth rate from Q3 to Q4. Taken together, just as we've said, robust sales growth for 2026.

Bill Sibold: Prakhar, just to talk about kind of the segments where it's coming from. This continues to be driven by hep and GIs for the most part. That's just where the prescriptions happen, where we would expect that they're going to continue. You also asked about endocrinology. Endocrinology was a Q4 2025 focus of ours. We're still really early into that. You have to remember, endocrinologists, just I'll make two real quick points about them. Number one, they've been using GLP-1s for over a decade, and they still are seeing lots of MASH and want to talk about Rezdiffra. Check that box. Number two, they just got started really in the Q4 of last year.

Bill Sibold: Prakhar, just to talk about kind of the segments where it's coming from. This continues to be driven by hep and GIs for the most part. That's just where the prescriptions happen, where we would expect that they're going to continue. You also asked about endocrinology. Endocrinology was a Q4 2025 focus of ours. We're still really early into that. You have to remember, endocrinologists, just I'll make two real quick points about them. Number one, they've been using GLP-1s for over a decade, and they still are seeing lots of MASH and want to talk about Rezdiffra. Check that box. Number two, they just got started really in the Q4 of last year.

Bill Sibold: They're in that first year of launch and hep and GI, they have to take their own time to wire the system, know how they're going to access their NITs, what's the pathway they have for their practice. Lots of potential in endocrinology and time, but you have to just know where they are. They're 9 months into the launch really at this point. Certainly very promising. Thanks.

Bill Sibold: They're in that first year of launch and hep and GI, they have to take their own time to wire the system, know how they're going to access their NITs, what's the pathway they have for their practice. Lots of potential in endocrinology and time, but you have to just know where they are. They're 9 months into the launch really at this point. Certainly very promising. Thanks.

Mardi Dier: Great. Thanks, Prakhar. Corey, next question, please.

Mardi Dier: Great. Thanks, Prakhar. Corey, next question, please.

Operator: Thank you very much. Our next question comes from the line of Eliana Merle of Barclays. Your line is open.

Operator: Thank you very much. Our next question comes from the line of Eliana Merle of Barclays. Your line is open.

Eliana Merle: Hey. Congrats on the strong performance. Thanks for taking the question. Just in terms of patient growth, it seemed to accelerate versus Q1. I guess, what are the drivers of this and your expectations for patient growth from here? Then just in terms of F4-C, I guess, how is the event rate tracking in that study and any clarity on when in 2027 you might expect to release the data? I recognize you might not comment, but figured I would try. Thanks.

Eliana Merle: Hey. Congrats on the strong performance. Thanks for taking the question. Just in terms of patient growth, it seemed to accelerate versus Q1. I guess, what are the drivers of this and your expectations for patient growth from here? Then just in terms of F4-C, I guess, how is the event rate tracking in that study and any clarity on when in 2027 you might expect to release the data? I recognize you might not comment, but figured I would try. Thanks.

Bill Sibold: Thanks, Eliav. Thanks for the question. On the patient growth, now I just want to make sure, just to level set. The way we report patient numbers is the number of patients that are on Rezdiffra on the last day of the quarter. That is the net of patients that are coming in the top of the funnel and patients that are going out the bottom of the funnel, right? As you get a bigger and bigger denominator, you have more and more patients exposed to potentially dropping off. Now, the great news this year is that we continue to steadily add patients, as I've said, and we don't see that slowing down at all. Remember, you really have to do work a lot harder on the top of the funnel as you have a bigger denominator that patients can fall out of.

Bill Sibold: Thanks, Eliav. Thanks for the question. On the patient growth, now I just want to make sure, just to level set. The way we report patient numbers is the number of patients that are on Rezdiffra on the last day of the quarter. That is the net of patients that are coming in the top of the funnel and patients that are going out the bottom of the funnel, right? As you get a bigger and bigger denominator, you have more and more patients exposed to potentially dropping off. Now, the great news this year is that we continue to steadily add patients, as I've said, and we don't see that slowing down at all. Remember, you really have to do work a lot harder on the top of the funnel as you have a bigger denominator that patients can fall out of.

Bill Sibold: We're seeing persistency like a well-tolerated oral. A well-tolerated oral at the one-year mark is in that 60% to 70% range. No changes there. Product's been performing exceptionally well. When we talk to the community, we hear stories of persistence, which are even higher than that. We have focused our efforts with our internal teams on how do you address persistency to have more patients stay on longer, and then how do we work with specialty pharmacies, et cetera, to get that same result. It's a real focus of ours to drive the top of the funnel, adding new patients, and to keep patients on, and then we get to that net number. We think that we have a really good approach, and that's why we continue to say, Well, we expect to steadily add. Maybe Dave, I'll turn to you on F4-C.

Bill Sibold: We're seeing persistency like a well-tolerated oral. A well-tolerated oral at the one-year mark is in that 60% to 70% range. No changes there. Product's been performing exceptionally well. When we talk to the community, we hear stories of persistence, which are even higher than that. We have focused our efforts with our internal teams on how do you address persistency to have more patients stay on longer, and then how do we work with specialty pharmacies, et cetera, to get that same result. It's a real focus of ours to drive the top of the funnel, adding new patients, and to keep patients on, and then we get to that net number. We think that we have a really good approach, and that's why we continue to say, Well, we expect to steadily add. Maybe Dave, I'll turn to you on F4-C.

David Soergel: Yeah, sure. Hi, Eliav. Yeah, a quick update. Clearly MYSTIQ Outcomes is an important trial for the field, given the unmet medical need and the fact that this is going to be the first outcomes trial in F4-C to read out with outcomes, which is a big thing for the field.

Dave Soergel: Yeah, sure. Hi, Eliav. Yeah, a quick update. Clearly MYSTIQ Outcomes is an important trial for the field, given the unmet medical need and the fact that this is going to be the first outcomes trial in F4-C to read out with outcomes, which is a big thing for the field.

David Soergel: The good news is we're seeing events accrue in the trial. However, as we've said in the past, this isn't, for example, a cardiovascular outcome study where you have a large number of target events. In this case, precision is very difficult. When we can be more precise, we'll provide you an update at that point. Right now, we're tracking to 2027, as we've said.

Dave Soergel: The good news is we're seeing events accrue in the trial. However, as we've said in the past, this isn't, for example, a cardiovascular outcome study where you have a large number of target events. In this case, precision is very difficult. When we can be more precise, we'll provide you an update at that point. Right now, we're tracking to 2027, as we've said.

Mardi Dier: Great. Thanks, Eliav. Corey, next question, please.

Mardi Dier: Great. Thanks, Eliav. Corey, next question, please.

Operator: Thank you very much. Our next question comes from the line of Thomas Smith. Thomas, your line is open.

Operator: Thank you very much. Our next question comes from the line of Thomas Smith. Thomas, your line is open.

Thomas Smith: Hey, guys. Good morning. Congrats on the nice quarter here, thanks for taking our questions. I was wondering if you could clarify and maybe expand on the comments regarding gross to net and inventory dynamics in the quarter and how you see those evolving through the balance of 2026. Could you also clarify the contribution of Europe to the worldwide revenues and patient numbers? We saw there was an early access program that launched in France during the quarter. Anecdotally from some KOLs, it sounded like there's been some nice early uptake there. Can you just comment on that program and how you think about Europe contribution for the year? Thanks so much.

Thomas Smith: Hey, guys. Good morning. Congrats on the nice quarter here, thanks for taking our questions. I was wondering if you could clarify and maybe expand on the comments regarding gross to net and inventory dynamics in the quarter and how you see those evolving through the balance of 2026. Could you also clarify the contribution of Europe to the worldwide revenues and patient numbers? We saw there was an early access program that launched in France during the quarter. Anecdotally from some KOLs, it sounded like there's been some nice early uptake there. Can you just comment on that program and how you think about Europe contribution for the year? Thanks so much.

Bill Sibold: Great, Tom. Thanks. Mardi, do you want to talk about gross to net?

Bill Sibold: Great, Tom. Thanks. Mardi, do you want to talk about gross to net?

Mardi Dier: Yeah, absolutely. Gross to net, as we said last quarter, our gross to net projected for 2026 is in the mid to high 30s. We are right in that zone for Q2, that's what we expect for the rest of the year. That's really balanced with a high-demand quarter with respect to inventory, just as we have with every quarter. No big changes there. Overall, everything's going well for the rest of the year in 2026 as we've discussed what we believe the growth rate is for the rest of the year. In Europe, do you want me to-

Mardi Dier: Yeah, absolutely. Gross to net, as we said last quarter, our gross to net projected for 2026 is in the mid to high 30s. We are right in that zone for Q2, that's what we expect for the rest of the year. That's really balanced with a high-demand quarter with respect to inventory, just as we have with every quarter. No big changes there. Overall, everything's going well for the rest of the year in 2026 as we've discussed what we believe the growth rate is for the rest of the year. In Europe, do you want me to-

Bill Sibold: Yeah, I'll talk about Europe

Bill Sibold: Yeah, I'll talk about Europe

Mardi Dier: Go ahead. Why don't you talk about Europe?

Mardi Dier: Go ahead. Why don't you talk about Europe?

Bill Sibold: Thanks for the question, Tom. Look, contribution of Europe is negligible in the quarter, and we would expect that to be for the year. Now, let me just talk a little bit just with ex-US in general. We've launched in Germany, and as you say, we have the early access program in France, and we received approval in the UK. A couple observations. This is not a US disease. It's a global disease. There's a high unmet need. Interest is really high from prescribers and from patients. Reimbursement is a challenge. You have to remember, we're in an MFN context here where there is still uncertainty about where that all lands. I think we're going to be in a period in the next 12, 18 months where things are still settling down.

Bill Sibold: Thanks for the question, Tom. Look, contribution of Europe is negligible in the quarter, and we would expect that to be for the year. Now, let me just talk a little bit just with ex-US in general. We've launched in Germany, and as you say, we have the early access program in France, and we received approval in the UK. A couple observations. This is not a US disease. It's a global disease. There's a high unmet need. Interest is really high from prescribers and from patients. Reimbursement is a challenge. You have to remember, we're in an MFN context here where there is still uncertainty about where that all lands. I think we're going to be in a period in the next 12, 18 months where things are still settling down.

Bill Sibold: Systems have not, when I say systems, other countries have not yet adopted what the ask is of the administration in MFN, which is paying US prices. That's something that we're at the table. We're talking with all of the governments there about this. I'm really hopeful for a long-term solution. As I said, in this time where it's just kind of really dynamic and a lot of uncertainty as to where policy lands and so forth, that's why we say it's going to be negligible. Remember, we've only launched in Germany. That's where we've done our build. We've been extremely disciplined about the build and the spend there. More to come in the following quarters. As I said, there certainly is a high unmet need. It's just we've got to solve the reimbursement piece. This isn't a Madrigal specific issue.

Bill Sibold: Systems have not, when I say systems, other countries have not yet adopted what the ask is of the administration in MFN, which is paying US prices. That's something that we're at the table. We're talking with all of the governments there about this. I'm really hopeful for a long-term solution. As I said, in this time where it's just kind of really dynamic and a lot of uncertainty as to where policy lands and so forth, that's why we say it's going to be negligible. Remember, we've only launched in Germany. That's where we've done our build. We've been extremely disciplined about the build and the spend there. More to come in the following quarters. As I said, there certainly is a high unmet need. It's just we've got to solve the reimbursement piece. This isn't a Madrigal specific issue.

Bill Sibold: This is an industry issue overall.

Bill Sibold: This is an industry issue overall.

Mardi Dier: Great. Thanks, Tom. Corey, next question, please.

Mardi Dier: Great. Thanks, Tom. Corey, next question, please.

Operator: Thank you very much. Our next question comes from the line of Ritu Baral of TD Cowen. Your line is open.

Operator: Thank you very much. Our next question comes from the line of Ritu Baral of TD Cowen. Your line is open.

Ritu Baral: Good morning, guys. Thanks for taking the question. I wanted to drill down a little further on OUTCOMES F4-C timing and sort of the drivers there for the data. Can you guys confirm that per your design publication that you're still aiming for that 92-event threshold? Or is there a possibility that you might want to boost powering based on what you're seeing? Further, just based on our conversations with KOLs, they indicate to us that events in F4 tend to be almost more asymptotic in the sense that they accumulate much, much more rapidly and barely at all in the first part of the trial versus more sort of linear cardiac outcome study event accumulation. Can you comment on what the natural history tells you on that event accumulation curve and how that contributes to how you're approaching giving us additional clarity and narrowing of data timing guidance?

Ritu Baral: Good morning, guys. Thanks for taking the question. I wanted to drill down a little further on OUTCOMES F4-C timing and sort of the drivers there for the data. Can you guys confirm that per your design publication that you're still aiming for that 92-event threshold? Or is there a possibility that you might want to boost powering based on what you're seeing? Further, just based on our conversations with KOLs, they indicate to us that events in F4 tend to be almost more asymptotic in the sense that they accumulate much, much more rapidly and barely at all in the first part of the trial versus more sort of linear cardiac outcome study event accumulation. Can you comment on what the natural history tells you on that event accumulation curve and how that contributes to how you're approaching giving us additional clarity and narrowing of data timing guidance?

Ritu Baral: Thanks.

Ritu Baral: Thanks.

Bill Sibold: Great. Thanks, Ritu. I'll pass that over to David. Yeah. Thanks, Ritu. How are you doing today?

Bill Sibold: Great. Thanks, Ritu. I'll pass that over to David. Yeah. Thanks, Ritu. How are you doing today?

Ritu Baral: Hey.

Ritu Baral: Hey.

Bill Sibold: I think the first thing to comment on is we haven't actually confirmed the target number of events. What we've said generally is there's a publication by Harrison that's a few years old that was sort of evaluating an earlier version of the protocol, and we've heard other numbers out there. What we said in general is that most of these numbers are in the ballpark, but we haven't confirmed the actual number. I think to your point about accumulation events, look, we're pioneering in this space. As we've said many times before, this is really the first well-controlled F4-C outcomes trial with a therapeutic agent. We've heard the same thing from KOLs that the possibility is that events accelerate over time as patients sort of age through the F4-C pathophysiology and the development of, for example.

Bill Sibold: I think the first thing to comment on is we haven't actually confirmed the target number of events. What we've said generally is there's a publication by Harrison that's a few years old that was sort of evaluating an earlier version of the protocol, and we've heard other numbers out there. What we said in general is that most of these numbers are in the ballpark, but we haven't confirmed the actual number. I think to your point about accumulation events, look, we're pioneering in this space. As we've said many times before, this is really the first well-controlled F4-C outcomes trial with a therapeutic agent. We've heard the same thing from KOLs that the possibility is that events accelerate over time as patients sort of age through the F4-C pathophysiology and the development of, for example.

Bill Sibold: I think the good news is, like I said, we're seeing events accrue. They're in line with our projected

Bill Sibold: I think the good news is, like I said, we're seeing events accrue. They're in line with our projected

David Soergel: completion date in 2027. When we can be more precise, we'll provide more precision. I think what you're highlighting is one of the questions that's out there, right? It's how does the placebo sort of evolve over time within a controlled trial?

Dave Soergel: completion date in 2027. When we can be more precise, we'll provide more precision. I think what you're highlighting is one of the questions that's out there, right? It's how does the placebo sort of evolve over time within a controlled trial?

Ritu Baral: Great. Thanks.

Ritu Baral: Great. Thanks.

Tina Ventura: Thanks, Ritu.

Tina Ventura: Thanks, Ritu.

Operator: Thank you very much.

Operator: Thank you very much.

Tina Ventura: Corey, next question. Oh yeah, go ahead. Corey, next question.

Tina Ventura: Corey, next question. Oh yeah, go ahead. Corey, next question.

Operator: Thank you very much. Our next question comes from the line of Andy Chen of Wolfe Research. Your line is open.

Operator: Thank you very much. Our next question comes from the line of Andy Chen of Wolfe Research. Your line is open.

Andy Chen: Thank you for taking the question. We noticed that you provided a timeline guidance on the oral GLP-1 and the DGAT2. Just curious, can you maybe tell us a bit more about the Arrowhead asset? When is phase II going to begin? With the oral GLP-1, the SAD has initiated. Is it reasonable to maybe predict that maybe we're going to get data next year? Thank you.

Andy Chen: Thank you for taking the question. We noticed that you provided a timeline guidance on the oral GLP-1 and the DGAT2. Just curious, can you maybe tell us a bit more about the Arrowhead asset? When is phase II going to begin? With the oral GLP-1, the SAD has initiated. Is it reasonable to maybe predict that maybe we're going to get data next year? Thank you.

Bill Sibold: Great. Thanks, Andy. Dave?

Bill Sibold: Great. Thanks, Andy. Dave?

David Soergel: Yeah. Well, first of all, thanks for the question, Andy, on the pipeline. I love it. It's one of the main reasons why I came to Madrigal, sort of the opportunity to build a pipeline in a space where there's so much potential and so much need. What I love about our pipeline is that we have a diversity of mechanisms, and yet all the mechanisms we know a lot about already, right? There's a lot of data on GLP-1, there's a lot of data on DGAT, there's a lot of data on PNPLA3. Specifically with respect to the programs, all of these programs have been chosen because there's a strong scientific rationale for complementarity with thyroid hormone receptor beta agonism with resmetirom.

Dave Soergel: Yeah. Well, first of all, thanks for the question, Andy, on the pipeline. I love it. It's one of the main reasons why I came to Madrigal, sort of the opportunity to build a pipeline in a space where there's so much potential and so much need. What I love about our pipeline is that we have a diversity of mechanisms, and yet all the mechanisms we know a lot about already, right? There's a lot of data on GLP-1, there's a lot of data on DGAT, there's a lot of data on PNPLA3. Specifically with respect to the programs, all of these programs have been chosen because there's a strong scientific rationale for complementarity with thyroid hormone receptor beta agonism with resmetirom.

David Soergel: Specifically for the oral GLP-1, as you'll recall, we're developing the oral GLP-1 ultimately in combination with resmetirom to dial in a little bit of weight loss to potentiate resmetirom's efficacy. As you pointed out, we started our SAD last month, and we'll be running the SAD and the MAD sort of through this year, is our plan. The data from that trial will then inform the phase II study, which, after we talk to health authorities, would start in 2027. With respect to timing, we haven't given a specific date to expect phase I, but that study will sort of proceed through this year. Similar story with DGAT. We've talked about running a pretty straightforward drug-drug interaction study later this year with resmetirom and ibrutinib. Again, we know a lot about ibrutinib because Pfizer took the compound through phase II.

Dave Soergel: Specifically for the oral GLP-1, as you'll recall, we're developing the oral GLP-1 ultimately in combination with resmetirom to dial in a little bit of weight loss to potentiate resmetirom's efficacy. As you pointed out, we started our SAD last month, and we'll be running the SAD and the MAD sort of through this year, is our plan. The data from that trial will then inform the phase II study, which, after we talk to health authorities, would start in 2027. With respect to timing, we haven't given a specific date to expect phase I, but that study will sort of proceed through this year. Similar story with DGAT. We've talked about running a pretty straightforward drug-drug interaction study later this year with resmetirom and ibrutinib. Again, we know a lot about ibrutinib because Pfizer took the compound through phase II.

David Soergel: We know it provides a lot of PDFF reduction in patients with MASH, and that PDFF reduction could also potentiate resmetirom's efficacy. Once we finish that drug-drug interaction study, again, go to health authorities, talk about our phase II plan, and estimate to start that in 2027. Same story with PNPLA3. That siRNA program that we licensed from Arrowhead, we start with some very good phase I data where we have a good understanding of dose range with the molecule as a monotherapy. Again, we'd have to go to health authorities to talk about the combination program, and again, estimating a start in 2027. We'll provide more of an update on the specific plans in phase II as we get closer to the initiation. Right now, just based on where the programs are in their life cycle, we'd expect them to start phase II in 2027.

Dave Soergel: We know it provides a lot of PDFF reduction in patients with MASH, and that PDFF reduction could also potentiate resmetirom's efficacy. Once we finish that drug-drug interaction study, again, go to health authorities, talk about our phase II plan, and estimate to start that in 2027. Same story with PNPLA3. That siRNA program that we licensed from Arrowhead, we start with some very good phase I data where we have a good understanding of dose range with the molecule as a monotherapy. Again, we'd have to go to health authorities to talk about the combination program, and again, estimating a start in 2027. We'll provide more of an update on the specific plans in phase II as we get closer to the initiation. Right now, just based on where the programs are in their life cycle, we'd expect them to start phase II in 2027.

Bill Sibold: Yeah. Just maybe just a point on the pipeline, right? We've brought in these assets to be used in combination with Rezdiff. As Dave pointed out in the presentation, as I said, Rezdiff is a foundational therapy. You see it working across various groups within MASH consistently. Our objective is to find even more efficacy, either in a subgroup or in the total MASH population. You think about that in comparison to the rest of the industry or those that are participating in MASH. They have single assets that they're hoping still to read out maybe positive data and maybe get approved and then be able to launch. They're going to be doing that, and we're going to be already moving forward with our combo strategy, which is going to raise the bar for the entire field.

Bill Sibold: Yeah. Just maybe just a point on the pipeline, right? We've brought in these assets to be used in combination with Rezdiff. As Dave pointed out in the presentation, as I said, Rezdiff is a foundational therapy. You see it working across various groups within MASH consistently. Our objective is to find even more efficacy, either in a subgroup or in the total MASH population. You think about that in comparison to the rest of the industry or those that are participating in MASH. They have single assets that they're hoping still to read out maybe positive data and maybe get approved and then be able to launch. They're going to be doing that, and we're going to be already moving forward with our combo strategy, which is going to raise the bar for the entire field.

Bill Sibold: There's only going to be one company that has Rezdiff. I think that's a point that sometimes just doesn't get quite picked up or understood. We are starting from kind of that foundational therapy, which is the building block for MASH. Thanks for the question.

Bill Sibold: There's only going to be one company that has Rezdiff. I think that's a point that sometimes just doesn't get quite picked up or understood. We are starting from kind of that foundational therapy, which is the building block for MASH. Thanks for the question.

Tina Ventura: Great. Thanks, Corey. Next question, please.

Tina Ventura: Great. Thanks, Corey. Next question, please.

Operator: Thank you very much. Our next question comes from the line of Yasmeen Rahimi of Piper Sandler. Your line is open.

Operator: Thank you very much. Our next question comes from the line of Yasmeen Rahimi of Piper Sandler. Your line is open.

Yasmeen Rahimi: Good morning, team. Congrats on a great quarter and all the color. Maybe would love to get color as you guys have been, and I'm sure you're tracking sort of event rates in the real world in the F2/3 population, which is the indication. Maybe to the extent that you're seeing if there is any off-label use in F4s, any observations that are being made there, whether it's consistent with the MAESTRO OLE data, which you reminded us of earlier today. Just would love to get sort of real-world experience, and I know it's limited and it's probably occurring at a less extent, but appreciate any color around that. Thank you. It seems like probably if you could quantify your confidence that the data is in 2027 and the likelihood that it could get pushed out into 2028, that could also be really helpful.

Yasmeen Rahimi: Good morning, team. Congrats on a great quarter and all the color. Maybe would love to get color as you guys have been, and I'm sure you're tracking sort of event rates in the real world in the F2/3 population, which is the indication. Maybe to the extent that you're seeing if there is any off-label use in F4s, any observations that are being made there, whether it's consistent with the MAESTRO OLE data, which you reminded us of earlier today. Just would love to get sort of real-world experience, and I know it's limited and it's probably occurring at a less extent, but appreciate any color around that. Thank you. It seems like probably if you could quantify your confidence that the data is in 2027 and the likelihood that it could get pushed out into 2028, that could also be really helpful.

Yasmeen Rahimi: Sorry for the very long-winded question.

Yasmeen Rahimi: Sorry for the very long-winded question.

Bill Sibold: Yes. Thanks for the question. Maybe just a comment on Kind of the real world, what we're seeing in F2, F3. You never know what's going to happen in the real world, right? You have your clinical studies. They read out. They're well-controlled. Everything is controlled for. Patients stay on drug, and you do your readout, and you create a bar chart, and everyone starts comparing against the bar chart. You get to the real world, and that's really what counts. How does the product perform? What we're hearing overwhelmingly from patients and prescribers is that Rezdiffra is performing exceptionally well. I don't hear stories of Rezdiffra not working. I speak as you know to hundreds of physicians, hundreds of prescribers, and I have not heard anyone say, Bill, it isn't working. What I hear is that, This is working better than I even thought it would.

Bill Sibold: Yes. Thanks for the question. Maybe just a comment on Kind of the real world, what we're seeing in F2, F3. You never know what's going to happen in the real world, right? You have your clinical studies. They read out. They're well-controlled. Everything is controlled for. Patients stay on drug, and you do your readout, and you create a bar chart, and everyone starts comparing against the bar chart. You get to the real world, and that's really what counts. How does the product perform? What we're hearing overwhelmingly from patients and prescribers is that Rezdiffra is performing exceptionally well. I don't hear stories of Rezdiffra not working. I speak as you know to hundreds of physicians, hundreds of prescribers, and I have not heard anyone say, Bill, it isn't working. What I hear is that, This is working better than I even thought it would.

Bill Sibold: It is effective, well-tolerated, safe, easy to use, supported by a great patient support program that we have here. We really take care of patients, take care of prescribers. Early feedback, and we're seeing it also in real-world evidence that's being reported, the product is performing really, really well. That's exciting. You never know that. As you think about, as I said, you can compare products on a bar chart, but what really counts is when you move into the real world. You didn't ask the question about semaglutide, but semaglutide, I think is on kind of the opposite side of that. Well-controlled clinical trial looks good in a clinical trial. In the real world, though, you have to stay on a drug, get to a high enough dose, and be on it long enough for it to actually work.

Bill Sibold: It is effective, well-tolerated, safe, easy to use, supported by a great patient support program that we have here. We really take care of patients, take care of prescribers. Early feedback, and we're seeing it also in real-world evidence that's being reported, the product is performing really, really well. That's exciting. You never know that. As you think about, as I said, you can compare products on a bar chart, but what really counts is when you move into the real world. You didn't ask the question about semaglutide, but semaglutide, I think is on kind of the opposite side of that. Well-controlled clinical trial looks good in a clinical trial. In the real world, though, you have to stay on a drug, get to a high enough dose, and be on it long enough for it to actually work.

Bill Sibold: I think that's a really, really great example, and I think that as we look into the future, profiles really matter, and we've got a great profile. I like to call it a holy grail profile. Having been in the industry 35 years, this is what the industry's always wanted to have, but once they've told that it works, right? Maybe that's the place just to give you some context on what we're hearing in the real world. Now, regarding off-label use, look, we've been crystal clear from day one, do not use Rezdiffra in F4C patients until we have the trial complete and we know that it works. I think that is just the responsible thing to do, and also, look, it makes sense.

Bill Sibold: I think that's a really, really great example, and I think that as we look into the future, profiles really matter, and we've got a great profile. I like to call it a holy grail profile. Having been in the industry 35 years, this is what the industry's always wanted to have, but once they've told that it works, right? Maybe that's the place just to give you some context on what we're hearing in the real world. Now, regarding off-label use, look, we've been crystal clear from day one, do not use Rezdiffra in F4C patients until we have the trial complete and we know that it works. I think that is just the responsible thing to do, and also, look, it makes sense.

Bill Sibold: What you don't want to do is have a product used in an area where there could be any kind of adverse event that then carries back to your already indicated population. I think there is some use. We can't quantify it, and there isn't a lot of data to suggest what the experience has been with people. Maybe, Dave, can I turn it over to you?

Bill Sibold: What you don't want to do is have a product used in an area where there could be any kind of adverse event that then carries back to your already indicated population. I think there is some use. We can't quantify it, and there isn't a lot of data to suggest what the experience has been with people. Maybe, Dave, can I turn it over to you?

David Soergel: Yeah, just a quick add. You made a comment about the open-label experience, we didn't talk about it this time around, but we have in the past where the event rate in that 122-patient cohort over a two-year period is quite low. It's a 2% to 3% annualized rate. Even though it's an open label population, it's a well-controlled and well-characterized population with F4C that looks very much like the MAESTRO-NASH OUTCOMES phase III population. That low event rate is some of the basis for our confidence that resmetirom could be effective in F4 as well. I think with respect to timing, as we said, when we have more precision on the estimate, we'll provide you with an update. At this point, we're still projecting into 2027.

Dave Soergel: Yeah, just a quick add. You made a comment about the open-label experience, we didn't talk about it this time around, but we have in the past where the event rate in that 122-patient cohort over a two-year period is quite low. It's a 2% to 3% annualized rate. Even though it's an open label population, it's a well-controlled and well-characterized population with F4C that looks very much like the MAESTRO-NASH OUTCOMES phase III population. That low event rate is some of the basis for our confidence that resmetirom could be effective in F4 as well. I think with respect to timing, as we said, when we have more precision on the estimate, we'll provide you with an update. At this point, we're still projecting into 2027.

Tina Ventura: Great. Okay. Thanks.

Tina Ventura: Great. Okay. Thanks.

Bill Sibold: Great.

Bill Sibold: Great.

Tina Ventura: Next question, please.

Tina Ventura: Next question, please.

Operator: Thank you very much. Our next question comes from the line of Akash Tewari of Jefferies. Your line is open.

Operator: Thank you very much. Our next question comes from the line of Akash Tewari of Jefferies. Your line is open.

[Analyst] (Jefferies): Hey, this is Manoj on for Akash. Just one on the F4-C OUTCOMES trial. Given the mean baseline platelet count in open-label was around 125,000, somewhat higher than the baseline of 150,000 in the F4-C trial, do you view the event rates observed in the OLE as the realistic guide for what we should expect in the F4-C? Are the blinded event rates in the OUTCOMES trial is tracking in line with what we would expect from the OLE data? Just a rough estimate on that point.

[Analyst] (Jefferies): Hey, this is Manoj on for Akash. Just one on the F4-C OUTCOMES trial. Given the mean baseline platelet count in open-label was around 125,000, somewhat higher than the baseline of 150,000 in the F4-C trial, do you view the event rates observed in the OLE as the realistic guide for what we should expect in the F4-C? Are the blinded event rates in the OUTCOMES trial is tracking in line with what we would expect from the OLE data? Just a rough estimate on that point.

Bill Sibold: Dave, do you want to?

Bill Sibold: Dave, do you want to?

David Soergel: Sure. I think with reference to the platelet count, there's going to be some variability, as you know, in the measure of platelets. In general, we enriched both populations by having a very low exclusion criterion for platelet count, greater than 70,000 in the study. The distribution, as we've talked about, of patients with CSPH is pretty similar when you look at the open-label population compared to the MAESTRO-NASH OUTCOMES phase III study. If you recall, ANTICIPATE-NASH scoring and the Baveno criteria are the combination of liver symptoms measurements by VCTE and platelet count. When you combine the two, you get a risk of CSPH.

Dave Soergel: Sure. I think with reference to the platelet count, there's going to be some variability, as you know, in the measure of platelets. In general, we enriched both populations by having a very low exclusion criterion for platelet count, greater than 70,000 in the study. The distribution, as we've talked about, of patients with CSPH is pretty similar when you look at the open-label population compared to the MAESTRO-NASH OUTCOMES phase III study. If you recall, ANTICIPATE-NASH scoring and the Baveno criteria are the combination of liver symptoms measurements by VCTE and platelet count. When you combine the two, you get a risk of CSPH.

David Soergel: I think the fact that we've sort of pushed the population towards the CSPH, higher CSPH risk is one of the reasons why we're seeing events in other programs at other sponsor companies are maybe not seeing as robust accrual of events. We think we've enriched this trial in a particularly effective way, both in terms of CSPH and using other markers like MRE. I think that's the key point. Your second question was?

Dave Soergel: I think the fact that we've sort of pushed the population towards the CSPH, higher CSPH risk is one of the reasons why we're seeing events in other programs at other sponsor companies are maybe not seeing as robust accrual of events. We think we've enriched this trial in a particularly effective way, both in terms of CSPH and using other markers like MRE. I think that's the key point. Your second question was?

[Analyst] (Jefferies): Whether the.

[Analyst] (Jefferies): Whether the.

David Soergel: Oh, 100%.

Dave Soergel: Oh, 100%.

[Analyst] (Jefferies): Yeah. If it is tracking in line with the expectation. Yeah.

[Analyst] (Jefferies): Yeah. If it is tracking in line with the expectation. Yeah.

David Soergel: Yeah. As we've said, the events are tracking in a way that would estimate a delivery of the data in 2027. When we're able to provide more precision on that estimate, we'll give you an update. Right now, 2027.

Dave Soergel: Yeah. As we've said, the events are tracking in a way that would estimate a delivery of the data in 2027. When we're able to provide more precision on that estimate, we'll give you an update. Right now, 2027.

Tina Ventura: Great.

Tina Ventura: Great.

Bill Sibold: Okay.

Bill Sibold: Okay.

Tina Ventura: Thanks, Anish. Next question, please.

Tina Ventura: Thanks, Anish. Next question, please.

Operator: Thank you very much. Our next question comes from the line of Ash Verma of UBS. Your line is open, Ash.

Operator: Thank you very much. Our next question comes from the line of Ash Verma of UBS. Your line is open, Ash.

Ash Verma: Great. Thanks for taking our question. Two on F4 also. Just maybe, can you talk about what type of relative risk reduction on the composite would position Rezdiffra as a drug that can have broad adoption based on the feedback that you are getting from physicians? Is it realistic 50% type outcome or can we get even a broader adoption with a lower risk reduction? That is first. Secondly, a lot of discussion on just the event rates here. Maybe just if you can help us understand on the placebo events in this study, why would this be any different in this study versus the prior 5% to 10% annualized event rate that you have seen? I believe your stat plans assume to annualize 10%, but if it is more like a 5%, is it still 2027 readout? Thank you.

Ash Verma: Great. Thanks for taking our question. Two on F4 also. Just maybe, can you talk about what type of relative risk reduction on the composite would position Rezdiffra as a drug that can have broad adoption based on the feedback that you are getting from physicians? Is it realistic 50% type outcome or can we get even a broader adoption with a lower risk reduction? That is first. Secondly, a lot of discussion on just the event rates here. Maybe just if you can help us understand on the placebo events in this study, why would this be any different in this study versus the prior 5% to 10% annualized event rate that you have seen? I believe your stat plans assume to annualize 10%, but if it is more like a 5%, is it still 2027 readout? Thank you.

Bill Sibold: All right, Dave.

Bill Sibold: All right, Dave.

David Soergel: Well, I think, look, first of all, what is a clinically relevant reduction in hazard in F4-C? The reality is, I think anything that is statistically significant and yields an approval would be clinically relevant. This is a disease where there is no treatment, and these patients were really on the cusp of end-stage liver disease and either death or a transplant. I think one of the really important things is getting a medicine to these patients and any risk reduction is going to be a big change in the field for patients. With respect to the placebo rate, we have sort of guided to the 5% to 10% range based on the natural history. As you pointed out, in the earlier Harrison paper, which again was done sort of drafted using an earlier version of the protocol, the estimate of the placebo rate was about 10%.

Dave Soergel: Well, I think, look, first of all, what is a clinically relevant reduction in hazard in F4-C? The reality is, I think anything that is statistically significant and yields an approval would be clinically relevant. This is a disease where there is no treatment, and these patients were really on the cusp of end-stage liver disease and either death or a transplant. I think one of the really important things is getting a medicine to these patients and any risk reduction is going to be a big change in the field for patients. With respect to the placebo rate, we have sort of guided to the 5% to 10% range based on the natural history. As you pointed out, in the earlier Harrison paper, which again was done sort of drafted using an earlier version of the protocol, the estimate of the placebo rate was about 10%.

David Soergel: The 10% placebo rate, as you know, determines sort of the duration of the trial. It doesn't really affect trial powering. The hazard reduction is the key thing that determines trial powering. Those two things together, the placebo rate and the drug effect, determine the blinded event rate. As we've said, the blinded event rate is tracking in line with delivery in 2027. When we have more data, we'll provide you more precision on that estimate.

Dave Soergel: The 10% placebo rate, as you know, determines sort of the duration of the trial. It doesn't really affect trial powering. The hazard reduction is the key thing that determines trial powering. Those two things together, the placebo rate and the drug effect, determine the blinded event rate. As we've said, the blinded event rate is tracking in line with delivery in 2027. When we have more data, we'll provide you more precision on that estimate.

Tina Ventura: Thanks. Thanks, Ash. Corey, next question, please.

Tina Ventura: Thanks. Thanks, Ash. Corey, next question, please.

Operator: Thank you very much. Our next question comes from the line of Michael DiFiore of Evercore ISI. Michael, your line is open.

Operator: Thank you very much. Our next question comes from the line of Michael DiFiore of Evercore ISI. Michael, your line is open.

Michael DiFiore: Thank you. Thanks so much for taking my question, guys. Two for me. The first regarding Rezdiffra patient growth and underlying demand. Can you separate Q2 patient growth into new starts versus reactivations following Q1 insurance disruptions versus discontinuations? My second question is, you've already reached over 10,000 prescribers and have indicated that the commercial focus is increasingly shifting towards prescription depth. My question is, what % of Q2 new prescriptions came from existing prescribers versus first-time writers, and how is that mix changing? Thank you.

Michael DiFiore: Thank you. Thanks so much for taking my question, guys. Two for me. The first regarding Rezdiffra patient growth and underlying demand. Can you separate Q2 patient growth into new starts versus reactivations following Q1 insurance disruptions versus discontinuations? My second question is, you've already reached over 10,000 prescribers and have indicated that the commercial focus is increasingly shifting towards prescription depth. My question is, what % of Q2 new prescriptions came from existing prescribers versus first-time writers, and how is that mix changing? Thank you.

Bill Sibold: Hey, thanks, Mike, for the question. Maybe let me start a little with that. You mentioned the 10,000 prescribers. That is another really significant milestone to cross in a launch. My experience, you exceed 10,000 and you've really got your base of prescribers that can drive your future into, in this case, a mega blockbuster. That's something which hasn't sit still. We haven't reported on that number in a while, but it continues to grow. We have new prescribers all the time. When you think about that mix, you're always going to have more of your scripts on a monthly basis coming from the existing pool of prescribers. Think about it. If you add 10 prescribers on the 10,000, disproportionately, there's so many. That's not the right number, adding 10. We're adding more than that, I can assure you.

Bill Sibold: Hey, thanks, Mike, for the question. Maybe let me start a little with that. You mentioned the 10,000 prescribers. That is another really significant milestone to cross in a launch. My experience, you exceed 10,000 and you've really got your base of prescribers that can drive your future into, in this case, a mega blockbuster. That's something which hasn't sit still. We haven't reported on that number in a while, but it continues to grow. We have new prescribers all the time. When you think about that mix, you're always going to have more of your scripts on a monthly basis coming from the existing pool of prescribers. Think about it. If you add 10 prescribers on the 10,000, disproportionately, there's so many. That's not the right number, adding 10. We're adding more than that, I can assure you.

Bill Sibold: It's always going to be weighted towards the current prescribers, and that's why depth becomes much more important than breadth once you cross that 10,000 threshold. We're continuing to see across all of the prescribers just increased depth of prescriptions. Why is that? Well, because they're having good results. Why is that? Because they're diagnosing more patients and they're learning the product. They're wiring their system. They're setting up their pathways. They're making sure they have access to or have their own NIT. That is what takes time in a launch, and that's why products typically don't go from zero to 100. It takes kind of years to get to full penetration because people just get more comfortable and work down through their deck of patients if you will.

Bill Sibold: It's always going to be weighted towards the current prescribers, and that's why depth becomes much more important than breadth once you cross that 10,000 threshold. We're continuing to see across all of the prescribers just increased depth of prescriptions. Why is that? Well, because they're having good results. Why is that? Because they're diagnosing more patients and they're learning the product. They're wiring their system. They're setting up their pathways. They're making sure they have access to or have their own NIT. That is what takes time in a launch, and that's why products typically don't go from zero to 100. It takes kind of years to get to full penetration because people just get more comfortable and work down through their deck of patients if you will.

Bill Sibold: We're seeing exactly that, and we're tracking exactly like we had hoped and like what we had thought we would. Now, how does that translate now back to your question about monthly adds? Oh, you had said the mix. We haven't reported out on the mix of prescribers and so forth. If you think about HEPs and GIs are the predominant writers. GIs outnumber HEPs just in the market in the country by about 10 to one. That's where the volume is going to be because they just have more patients and more prescribers Okay. Now what about patient adds? That net number that we show, we don't break it out into what's coming in the top of the funnel, what's going out the bottom of the funnel and net.

Bill Sibold: We're seeing exactly that, and we're tracking exactly like we had hoped and like what we had thought we would. Now, how does that translate now back to your question about monthly adds? Oh, you had said the mix. We haven't reported out on the mix of prescribers and so forth. If you think about HEPs and GIs are the predominant writers. GIs outnumber HEPs just in the market in the country by about 10 to one. That's where the volume is going to be because they just have more patients and more prescribers Okay. Now what about patient adds? That net number that we show, we don't break it out into what's coming in the top of the funnel, what's going out the bottom of the funnel and net.

Bill Sibold: As you can see, that steadily adding, when you look back over the quarters, that's kind of our definition of steadily adding. Most importantly, we expect to continue to do so going forward. Now, we're going to do everything we can to accelerate adding to the top and decelerate leaving from the bottom. That's what we do. That continues to make it a great launch. That's what I'll leave it now, Mike, and we'll update in the future. We are in really, really great shape on all key metrics and really the one at the end of the day that counts is patients. That's the one that I think that is this 50,000 milestone. That is a big number. Gee, that's why we kind of pulled that one ahead.

Bill Sibold: As you can see, that steadily adding, when you look back over the quarters, that's kind of our definition of steadily adding. Most importantly, we expect to continue to do so going forward. Now, we're going to do everything we can to accelerate adding to the top and decelerate leaving from the bottom. That's what we do. That continues to make it a great launch. That's what I'll leave it now, Mike, and we'll update in the future. We are in really, really great shape on all key metrics and really the one at the end of the day that counts is patients. That's the one that I think that is this 50,000 milestone. That is a big number. Gee, that's why we kind of pulled that one ahead.

Bill Sibold: We didn't want to wait another quarter and say, we knew everyone would be doing, Well, what day of the month was it that it happened? Let me assure you that 50,000 is consistent with the steadily adding patients. It's just it's a big number that the world should know about. Thanks.

Bill Sibold: We didn't want to wait another quarter and say, we knew everyone would be doing, Well, what day of the month was it that it happened? Let me assure you that 50,000 is consistent with the steadily adding patients. It's just it's a big number that the world should know about. Thanks.

Tina Ventura: Great. Thanks, Corey.

Tina Ventura: Great. Thanks, Corey.

Bill Sibold: Thank you.

Bill Sibold: Thank you.

Tina Ventura: Next question, please.

Tina Ventura: Next question, please.

Operator: Thank you very much. Our next question comes from the line of Jay Olson of Oppenheimer. Jay, your line is open.

Operator: Thank you very much. Our next question comes from the line of Jay Olson of Oppenheimer. Jay, your line is open.

Jay Olson: Oh, hey, guys. Congrats on all the progress, thank you for providing this update. Since you have a number of new patents and multiple levers available to drive Rezdiffra sales growth, including potential combinations, how are you thinking about the peak sales magnitude and timeline to achieve peak sales? What's your vision of how the MASH market dynamics may evolve in the next 10 years in terms of patient segmentation, and which genotypes or phenotypes do you suspect might be appropriate to target for a more personalized approach to treating MASH with precision medicine? Thank you.

Jay Olson: Oh, hey, guys. Congrats on all the progress, thank you for providing this update. Since you have a number of new patents and multiple levers available to drive Rezdiffra sales growth, including potential combinations, how are you thinking about the peak sales magnitude and timeline to achieve peak sales? What's your vision of how the MASH market dynamics may evolve in the next 10 years in terms of patient segmentation, and which genotypes or phenotypes do you suspect might be appropriate to target for a more personalized approach to treating MASH with precision medicine? Thank you.

Bill Sibold: Yeah. Jay, thanks for the question. Let me start with kind of the market dynamics, because I think this is something which is really so remarkable about MASH. I'll go back, first of all, to when we communicated what the approachable patient number in F2, F3 was at the end of 2023. That was the 315,000. We did that same analysis at the end of 2025, and that was 460,000. Almost 50% growth in patients. Now, you would say, "Well, gee, how sustainable is that?" Well, here's why it's really sustainable, because it's about 10% diagnosed today, the disease, and we have about 10% penetration. We're about 1% into the journey. Now, that is a setup where all the demographics, everything that we're looking at is driving towards MASH continuing to be a challenge, not just for the next three, five, 10 years, but decades.

Bill Sibold: Yeah. Jay, thanks for the question. Let me start with kind of the market dynamics, because I think this is something which is really so remarkable about MASH. I'll go back, first of all, to when we communicated what the approachable patient number in F2, F3 was at the end of 2023. That was the 315,000. We did that same analysis at the end of 2025, and that was 460,000. Almost 50% growth in patients. Now, you would say, "Well, gee, how sustainable is that?" Well, here's why it's really sustainable, because it's about 10% diagnosed today, the disease, and we have about 10% penetration. We're about 1% into the journey. Now, that is a setup where all the demographics, everything that we're looking at is driving towards MASH continuing to be a challenge, not just for the next three, five, 10 years, but decades.

Bill Sibold: That's the backdrop that we're against. We had almost 50% growth in two years. We expect double-digit growth for the foreseeable future. You heard me say that Q3 is off to a strong start, but that we are expecting and seeing patient growth in the market in 2026, consistent with what we've communicated before. That growth of the market is where the real opportunity lies. As great as Rezdiffra is, as I said, in my opinion, holy grail profile, we're looking for even more efficacy in either the whole population or segments of the population. A real specific, you said, having kind of the personalized medicine. This is where the PNPLA3 deal that we did with Arrowhead, we are so excited about.

Bill Sibold: That's the backdrop that we're against. We had almost 50% growth in two years. We expect double-digit growth for the foreseeable future. You heard me say that Q3 is off to a strong start, but that we are expecting and seeing patient growth in the market in 2026, consistent with what we've communicated before. That growth of the market is where the real opportunity lies. As great as Rezdiffra is, as I said, in my opinion, holy grail profile, we're looking for even more efficacy in either the whole population or segments of the population. A real specific, you said, having kind of the personalized medicine. This is where the PNPLA3 deal that we did with Arrowhead, we are so excited about.

Bill Sibold: That is a very specific, identifiable patient population that could benefit from having not only a foundational therapy like Rezdiffra, where we work really well in that if you look at our presentation, but if you add to that this targeted siRNA could we get even more efficacy. We look at there's going to be these segments that open up in time, partially driven by the data, partially driven by just natural market evolution. That's why we're not only optimistic about Rezdiffra, but a whole franchise and having a solution for patients that cover really the gamut of MASH.

Bill Sibold: That is a very specific, identifiable patient population that could benefit from having not only a foundational therapy like Rezdiffra, where we work really well in that if you look at our presentation, but if you add to that this targeted siRNA could we get even more efficacy. We look at there's going to be these segments that open up in time, partially driven by the data, partially driven by just natural market evolution. That's why we're not only optimistic about Rezdiffra, but a whole franchise and having a solution for patients that cover really the gamut of MASH.

Bill Sibold: We haven't commented on peak, and we're not, but you have heard us say that we think that Rezdiffra has mega blockbuster potential, and that's even before we start to add these next generation products that we're working on, which again, I'll remind you, as we have combo products, others will be still fighting for their first product in a pathway that we probably already got a combo in.

Bill Sibold: We haven't commented on peak, and we're not, but you have heard us say that we think that Rezdiffra has mega blockbuster potential, and that's even before we start to add these next generation products that we're working on, which again, I'll remind you, as we have combo products, others will be still fighting for their first product in a pathway that we probably already got a combo in.

Tina Ventura: Great. Thanks. Thanks, Jay. Corey, next question, please.

Tina Ventura: Great. Thanks. Thanks, Jay. Corey, next question, please.

Operator: Thank you very much. Our next question comes from the line of Srikripa Devarakonda of Truist Securities. Your line is open.

Operator: Thank you very much. Our next question comes from the line of Srikripa Devarakonda of Truist Securities. Your line is open.

Srikripa Devarakonda: Hey, guys. Thank you so much for taking my question, and congratulations on the quarter. Wanted to ask about the competitive landscape. As we get closer to a competitor phase III data in Q4 of this year, I was wondering if you can comment on how you view any potential impact on Rezdiffra if the trial were to be successful and MASH patients get another oral option. I think it also takes back to the prior question regarding fragmentation because some of our KOL checks have suggested that this drug could target specific subsegments or drugs in general could target different subsegments. Would love to hear your comments on that. Wanted to just ask about also the recent patents issued for resmetirom. I know you already had a previously issued patent extending resmetirom till 2045.

Srikripa Devarakonda: Hey, guys. Thank you so much for taking my question, and congratulations on the quarter. Wanted to ask about the competitive landscape. As we get closer to a competitor phase III data in Q4 of this year, I was wondering if you can comment on how you view any potential impact on Rezdiffra if the trial were to be successful and MASH patients get another oral option. I think it also takes back to the prior question regarding fragmentation because some of our KOL checks have suggested that this drug could target specific subsegments or drugs in general could target different subsegments. Would love to hear your comments on that. Wanted to just ask about also the recent patents issued for resmetirom. I know you already had a previously issued patent extending resmetirom till 2045.

Srikripa Devarakonda: Can you just talk about the impact of the recently issued ones and how that strengthens the profile of the drug? Thank you.

Srikripa Devarakonda: Can you just talk about the impact of the recently issued ones and how that strengthens the profile of the drug? Thank you.

Bill Sibold: Look, thank you very much for the question. There's a lot there. Maybe just starting with IP. Last July actually, we secured our pivotal F2, F3 patent, which is the weight threshold dosing, which gives us out to 2045. The reason that patent was so important, it allows us to think about our pipeline and portfolio a little differently. We have a lot of time with Rezdiffra so we can place a bet on earlier stage programs or later stage programs. We don't have a short-term problem. That's really good. The patents that we announced just, I guess this month, was it? We secured two new F2, F3 patents. Those cover important safety information in our label. Generics have to include that type of language in their label. Them trying to do a skinny label really makes it challenging for them.

Bill Sibold: Look, thank you very much for the question. There's a lot there. Maybe just starting with IP. Last July actually, we secured our pivotal F2, F3 patent, which is the weight threshold dosing, which gives us out to 2045. The reason that patent was so important, it allows us to think about our pipeline and portfolio a little differently. We have a lot of time with Rezdiffra so we can place a bet on earlier stage programs or later stage programs. We don't have a short-term problem. That's really good. The patents that we announced just, I guess this month, was it? We secured two new F2, F3 patents. Those cover important safety information in our label. Generics have to include that type of language in their label. Them trying to do a skinny label really makes it challenging for them.

Bill Sibold: These are both Orange Book listed patents. That's just further reinforcing the 2045 patent that we have. We now have a new F4-C patent and I'm really excited about this because remember, '45 came out of the approved label. We don't have a label yet in F4-C, but we've already secured a use patent, which gets us into the '40s as well. That's before a label where there's potentially other opportunities to generate out of peak. I feel like we've said all along that IP's really important and we've made it a focus, and I think we've made really significant progress with our IP strategy. Now, I think you were probably referring to the lanifibranor. That's what it was, right? Look, what we've always said, and you've heard me say before, this is going to be a big market. It can support multiple products.

Bill Sibold: These are both Orange Book listed patents. That's just further reinforcing the 2045 patent that we have. We now have a new F4-C patent and I'm really excited about this because remember, '45 came out of the approved label. We don't have a label yet in F4-C, but we've already secured a use patent, which gets us into the '40s as well. That's before a label where there's potentially other opportunities to generate out of peak. I feel like we've said all along that IP's really important and we've made it a focus, and I think we've made really significant progress with our IP strategy. Now, I think you were probably referring to the lanifibranor. That's what it was, right? Look, what we've always said, and you've heard me say before, this is going to be a big market. It can support multiple products.

Bill Sibold: The new entrants we think help us if there are new entrants. Still have to have a successful product. Have to get it approved and all those minor details, build a big commercial organization launch. If you get to market one day eventually, it can really help to drive growth. I think we've seen that with Wegovy. I think their being there has really helped us. You heard me say a little bit earlier, though, this isn't about comparing bar graphs anymore. It's really about the real world. We're over two years on the market, over 50,000 patients. We have high satisfaction by prescribers and patients, and it's just continuing to crest. Against that backdrop, it's kind of hard to see where lanifibranor will fit. It comes down to profiles, if you heard me say many times, and we've got a great profile.

Bill Sibold: The new entrants we think help us if there are new entrants. Still have to have a successful product. Have to get it approved and all those minor details, build a big commercial organization launch. If you get to market one day eventually, it can really help to drive growth. I think we've seen that with Wegovy. I think their being there has really helped us. You heard me say a little bit earlier, though, this isn't about comparing bar graphs anymore. It's really about the real world. We're over two years on the market, over 50,000 patients. We have high satisfaction by prescribers and patients, and it's just continuing to crest. Against that backdrop, it's kind of hard to see where lanifibranor will fit. It comes down to profiles, if you heard me say many times, and we've got a great profile.

Bill Sibold: lanifibranor, 1,200 milligram pill. It's a PPAR associated with weight gain and edema. This is at a time when the world is obsessed with weight loss. We don't see weight gain as a real benefit, particularly in MASH. We did some market research with prescribers, and 80% of prescribers said they wouldn't use lanifibranor because of the weight gain. If they get here, look, MASH is a big market. We've got lots of room for more product. That's why we're building our pipeline. We think it overall helps, but they got a long way to go and we wish them luck. I think that's where I'll leave it.

Bill Sibold: lanifibranor, 1,200 milligram pill. It's a PPAR associated with weight gain and edema. This is at a time when the world is obsessed with weight loss. We don't see weight gain as a real benefit, particularly in MASH. We did some market research with prescribers, and 80% of prescribers said they wouldn't use lanifibranor because of the weight gain. If they get here, look, MASH is a big market. We've got lots of room for more product. That's why we're building our pipeline. We think it overall helps, but they got a long way to go and we wish them luck. I think that's where I'll leave it.

Tina Ventura: Great. Thanks. We're past the top of the hour, Corey, I think we'll conclude today's call. Thank you all for your time and interest. This now concludes our call. A replay of the webcast will be available on our website in approximately two hours. Thanks for joining us.

Tina Ventura: Great. Thanks. We're past the top of the hour, Corey, I think we'll conclude today's call. Thank you all for your time and interest. This now concludes our call. A replay of the webcast will be available on our website in approximately two hours. Thanks for joining us.

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

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