Good morning, everyone, and thank you for joining us to discuss Madrigal's second quarter 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; Dave Soergel, Chief Medical Officer; and Mardi Dier, Chief Financial Officer. They will provide prepared remarks, followed by Q&A.

Please note on slide 2, we will be making certain forward-looking statements today. We refer you to our SEC filings for a discussion of the risks that may cause actual results to differ from the forward-looking statements.

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

Thanks, Tina, and thank you all for joining. Before we review our second quarter 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're 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.

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 F4C indication.

As we've done successfully to date, we'll 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'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. 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 Rezdiffra's foundation and extend our leadership in MASH for years to come. 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. Let's move to our Q2 results, where I'll provide an update on Rezdiffra, Dave will discuss our pipeline, and Mardi will close with a review of our financials.

Turning to slide 6 and net sales, we are continuing to see strong demand for Rezdiffra. Second quarter 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'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.

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.

That growing depth, combined with broad first-line commercial access, Rezdiffra's differentiated profile, and strong patient adherence, continues to drive patient growth. That's why we've steadily added patients, ending the second quarter with more than 49,000 active patients on Rezdiffra, more than double a year ago.

Importantly, momentum remains strong as we progress through the third quarter, where we surpassed the 50,000 patient milestone earlier this month, a significant accomplishment in any launch. 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 US addressable market has grown nearly 50% from 315,000 diagnosed F2-F3 patients at our target specialists to 460,000. That's remarkable growth in just two years.

It's being driven by exactly what you'd expect in a new therapeutic category: 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 9. 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'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. Yet even from that starting point as shown on slide 11, Rezdiffra is already generating north of a billion dollars in trailing 12-month net sales.

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.

Everything I've discussed so far speaks to the strength and opportunity of Rezdiffra in F2-F3 MASH, but there is another significant unmet need ahead of us in well-compensated MASH cirrhosis, or F4C, as noted on slide 12. 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 US, we believe F4C could double Rezdiffra's opportunity. We have an event-driven outcomes 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's why we've 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'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 Rezdiffra works across each patient subgroup in clinical practice.

That breadth and consistency across patient subgroups is exactly what you want in a foundational medicine, and it's unique to Rezdiffra. Dave will talk more about this in his section and share key data demonstrating Rezdiffra's broad efficacy.

With that, I'll turn it over to Dave.

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 3 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're not standing still. Leadership means continuing to advance the science and generating evidence that supports Rezdiffra's clinical benefit well beyond approval.

It's an ongoing effort to better understand Rezdiffra, answer important clinical questions, and continue to raise the bar for what's possible in MASH. 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 F4C 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 and this model is becoming an increasingly accepted tool for assessing risk in patients with compensated MASH cirrhosis. 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. 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-NASH model to the 122-patient two-year open-label cohort from our Phase 3 MAESTRO-NAFLD-1 trial. The proportion of patients classified as higher risk for CSPH declined from 75% at baseline to 50% 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 five-fold. These findings further strengthen our confidence that resmetirom has the potential to delay disease progression and improve long-term outcomes in patients with F4C 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.

In fact, cardiovascular disease remains the leading cause of death in this population, and MASH itself is an independent driver of cardiovascular risk. Our secondary analysis from MAESTRO-NASH and MAESTRO-NAFLD-1 showed significant reductions in ApoB, including LP(a) 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.

Real-world evidence like this complements what we've already seen in our clinical trials and 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 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 2 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.

We began dosing MGL-2086 in a Phase 1 single ascending dose study in June. Results from this first-in-human study will inform the Phase 2 trial.

We also plan to initiate a Phase 2 study of our DGAT2 inhibitor, evergestat, in combination with resmetirom, and will engage with regulatory authorities on the design of a Phase 2 trial combining resmetirom with MGL-0795, our siRNA targeting PNPLA3, in-licensed from Arrowhead in May. We're also progressing one of the six preclinical siRNA assets that we in-licensed from RiboCare.

We recently nominated the first candidate to move into IND-enabling studies. All of this is advancing alongside our two ongoing Phase 3 Rezdiffra trials.

First, our F4C MAESTRO-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.

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.

Thank you, Dave. Turning to slide 20 and a 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. 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 discounts 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.

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.

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 MGL-0795, a clinical-stage siRNA program from Arrowhead.

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 Rezdiffra, including head count for the endocrinology field force expansion that occurred in the fourth quarter of 2025, as well as marketing efforts, including our DTC campaign.

Looking ahead, we expect full year 2026 R&D expenses to be roughly the same as 2025, which is inclusive of the one-time upfront payments we've announced for strategic business development investments in both periods. We expect full year 2026 SG&A expenses to increase compared to 2025 with the annualization of the endo sales force as we continue to support the launch of Rezdiffra and build the foundation for long-term growth.

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.

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. 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, the third quarter is off to a great start. We've more than doubled the number of patients on therapy over the past year, while the addressable MASH 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.

We're building on Rezdiffra's foundation with the industry-leading pipeline of more than 10 programs. We look forward to multiple future data readouts, including our Phase 3 F4C 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.

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.

Hi, congrats on the quarter, and thank you so much for taking my questions. I had two.

Firstly, wanted to ask about the 3Q trends, what are you seeing and expectations for net patient adds for remainder of the year? Just wanted to get a little bit of better color on what segments are growing to drive for the growth here, and how do you feel about where the consensus is sitting for 3Q and full year 2026?

Second question, we have 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.

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 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 we exceeded Q2 expectations.

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.

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, 50,000 represents great progress.

That's something that we crossed 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 third quarter and through the rest of the year.

I think we're set up really well for '26. Mardi, do you want to talk maybe a little bit about some of the specifics?

Yes, absolutely. 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. With respect to third quarter and fourth quarter, what we'd like to say is that, yes, we're comfortable with the consensus quarterly growth rates for the rest of the year.

That means the consensus growth rate from second quarter to third quarter, and then again, the consensus growth rate from third quarter to fourth quarter. Taken together, just as we've said, robust sales growth for 2026.

Prakhar, just to talk about kind of the segments where it's coming from. This continues to be driven by heps 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 fourth quarter 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 fourth quarter of last year, they're in kind of that first year of launch.

Heps and 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. Lots of potential in endocrinology in time, but you have to just know where they are.

They're kind of nine months into the launch really at this point. Certainly very promising.

Thanks.

Great. Thanks, Prakhar.

Cory, next question, please?

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.

I guess, what are the drivers of this and your expectations for patient growth from here? Then just in terms of F4C, I guess, how is the event rate tracking in that study?

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.

Thanks, Ellie. Thanks for the question.

On the patient growth, now I just want to make sure just a 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 work a lot harder on the top of the funnel as you have a bigger denominator that patients can fall out of.

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 pharmacy and pharmacies, etc., 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 we expect to steadily add.

Maybe, Dave, I'll just turn to you on F4C.

Sure. Yeah.

Hi, Ellie. A quick update.

Clearly MAESTRO-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 F4C to read out with outcomes, which is a big thing for the field. 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 outcomes 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.

Great. Thanks, Ellie.

Cory, next question, please?

Hey, guys. Good morning.

Congrats on the nice quarter here, and thanks for taking our questions. 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 '26.

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, and 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.

Great, Tom. Thanks.

Mardi, do you want to talk about gross-to-net?

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

Overall, everything is 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?

I'll

talk about Europe.

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 challenging.

You have to remember we're in an MFN context here, where there's 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.

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, and this isn't a Madrigal-specific issue.

This is an industry issue overall.

Great. Thanks, Tom.

Cory, next question, please?

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. 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?

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?

Thanks.

Great. Thanks, Ritu.

I'll pass that over to Dave.

Yeah. Thanks, Ritu.

How you doing today? 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. We've said in general is most of these numbers are in the ballpark, but we haven't confirmed the actual number.

I think to your point about accumulation of events, look, we're pioneering in this space. This as we've said many times before, this is really the first well-controlled F4C 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 F4C pathophysiology and the development of portal hypertension, for example. 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. 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? How does the placebo sort of evolve over time within a controlled trial.

Great, thanks.

Thanks, Ritu.

next question. Oh yeah, go ahead, Cory.

Next question.

Hey, thank you for taking the question. We noticed that you provided 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 2 going to begin? 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? Thank you.

Great. Thanks, Andy.

Dave?

Yeah. 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. 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. Then the data from that trial will then inform the Phase 2 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 1, 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 evergestat. Again, we know a lot about evergestat because Pfizer took the compound through Phase 2.

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 2 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 1 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, 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 2 as we get closer to the initiation, but right now just based on where the programs are in their lifecycle, we'd expect them to start Phase 2 in 2027.

Yeah. Maybe just a point on the pipeline.

Right, we've brought in these assets to be used in combination with Rezdiffra. Dave pointed out in the presentations, as I said, Rezdiffra 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 follow the 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. There's only going to be one company that has Rezdiffra.

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 blocks for MASH.

Thanks for the question.

Great. Thanks, Cory.

Next question, please?

Good morning, team. Congrats on a great quarter and all the color.

Maybe would love to get color, and I'm sure you're tracking sort of event rates in the real world in the F2-F3 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 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. Sorry for the very long-winded question.

Yas, 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. Then 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 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.

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 been reported, 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 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.

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. I think that's a really, really great example.

I think 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 has always wanted to have, a once-a-day pill that 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.

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.

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?

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-Outcomes Phase 3 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've 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.

Great. Okay.

Thanks, Yas. Our next question, please?

Hey, this is Manoj on for Akash. Just one on the F4C outcomes trial.

Given the main 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? Also, are the blinded event rates in the outcome trial is tracking in line with what we would expect from the OLE data, just rough estimate on that point?

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-Outcomes Phase 3 study.

If you recall, ANTICIPATE-NASH scoring and Baveno criteria are the combination of liver stiffness measurements by VCTE and platelet count. When you combine the two, you get a risk of CSPH.

I think the fact that we've sort of pushed the population towards the 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. 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?

Whether the tracking in line with expectation, yeah.

Yeah. As we've said, the events are tracking in a way that would estimated delivery of the data in 2027.

When we're able to provide more precision on that estimate, we'll give you an update, but right now 2027.

Great. Thanks, Manoj.

Next question, please?

Great. Thanks for taking our question.

I got 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're getting from physicians?

Is it statistically 50% type outcome, or can we get even a broad adoption with a lower risk reduction? That's first.

Then secondly, yeah, a lot of discussion on just the event rates here. Maybe just if you can help us understand on the placebo events in the study, why would this be any different in this study versus the prior 5% to 10% annualized event rate that we've seen?

I believe your stat plans assume so annualized 10%, but if it's more like a 5%, is it still a 2027 readout? Thank you.

Yeah.

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

This is a disease where there is no treatment, and these patients are 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've sort of guided to the 5% to 10% range based on the natural history. As you pointed out, in the earlier Harrison paper, which was again sort of drafted using an earlier version of the protocol, the estimate of the placebo rate was about 10%.

The 10% placebo rate, as determines sort of the duration of the trial. It doesn't really affect trial powering.

The hazard reduction is the key thing that determines a 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 '27. When we have more data, we'll provide you more precision on that estimate.

Thanks, Ash. Cory, next question, please?

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 2Q patient growth into new starts versus reactivations following first quarter 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 percent of 2Q new prescriptions came from existing prescribers versus first-time writers, and how is that mix changing?

Thank you.

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 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. Since 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 onto 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 of that.

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? 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 NITs. That is what takes time in a launch.

That's why products typically don't go from 0 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.

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 1. 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.

As you can see, that 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. 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 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 kind of all key metrics.

Really the one at the end of the day that counts is patients, and that's the one that I think this 50,000 milestone, that is a big number. That's why we kind of pulled that one ahead.

We didn't want to wait another quarter, and we knew everyone would be doing, well, what day of the month was it that it happened. Let me assure you the 50,000 is consistent with the steadily adding patients.

It's just a big number that the world should know about. Thanks.

Thanks, Cory. Next question, please?

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 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.

Yeah. 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 '23, that was the 315,000.

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

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. That's the backdrop that we're against.

We had almost 50% growth in two years. We expect a 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 kind of the personalized medicine.

This is where the PNPLA3 deal that we did with Arrowhead we're so excited about. 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 presentations, 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.

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.

Great. Thanks, Jay.

Cory, next question, please?

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 3 data in 4Q 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.

Also, wanted just to ask about the recent patents issued for resmetirom. You already had a previously issued patent extending resmetirom till 2045.

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

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, 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, we can place a bet on earlier-stage programs or later-stage programs.

Like we're not we don't have a a a short-term problem. 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.

Generics have to include that type of language in their label, them trying to do a skinny label really makes it challenging for them. These are both Orange Book-listed patents.

That's just, further further reinforcing the 2045 patent that we have. We now have a new F4C patent, and, 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.

That's before a label, where there's potentially other opportunities to generate IP. I feel like, we've said all along that we that IP is really important, and we've made it a focus, and I think we've made really, really significant progress with our IP strategy.

Now, I think you're probably referring to 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.

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.

If you get to market one day eventually, it is can really help to drive growth. I think we've seen that with Wegovy.

I think they're being here 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 continuing to press. Against that backdrop, it's kind of hard to see where lanifibranor will fit.

It comes down to profiles. You've heard me say many times, and we've got a great profile.

Lanifibranor, 1200 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, we don't see weight gain as a real asset, 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 products, that's why we're building our pipeline. We think it overall helps, but, they got a long way to go, and, we we wish them luck.

I think I think that's really it.

Great. Thanks.

Actually, we're past the top of the hour, Cory, 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.