Madrigal Pharmaceuticals, Inc.

Good day, and thank you for standing by. Welcome to Madrigal Pharmaceuticals' fourth quarter and full year 2024 earnings conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. As a reminder, today's conference call is being recorded. I would now like to introduce Ms. Tina Ventura, Chief Investor Relations Officer. Please go ahead.

Thank you, Marvin. Good morning, everyone, and thank you for joining us to discuss Madrigal's fourth quarter and full year 2024 earnings. We're also sharing this morning new two-year data from the Active Treatment Open Label Compensated MASH cirrhosis, or F4C arm, of the Phase III Maestro NAFLD trial. We issued a press release this morning and have a slide deck that accompanies this webcast, which we'll post on the Investor Relations section of our website right after the call. On the call with me today is Bill Sibyl, Chief Executive Officer, and Marty Deer, Chief Financial Officer. They'll provide prepared remarks, and then we'll take your questions. Dr. Michael Charlton, our Head of Clinical Development, will join us for the Q&A portion of the call. Dr. Charlton has more than 30 years of experience in MASH as a leading hepatologist, head of the Mayo Clinic Hepatology Group, and a treating physician. We plan to keep today's call to about 45 minutes. 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. And with that, I will now turn the call over to Bill on slide three.

Well, thanks, Tina. Good morning, and thanks for joining. Today, I'll provide an update on the significant momentum we're building with the U.S. launch of ResDifera. We ended 2024 strong, and we're pleased with how we've started the year in 2025. I'll also share an update on new two-year data from an open-label study for F4C patients, as Tina mentioned. The results are very promising and support Red Differ's potential to benefit this high-risk patient population, if approved. But before we look ahead, I want to take a moment to reflect on 2024, a year of remarkable transformation and achievement for the company. I've been in the industry a long time, and I've launched a lot of successful medicines. I'll be the first to attest to the tremendous amount of work required for any successful launch, let alone a first in disease therapy. And the launch of ResDifera is no exception. We worked to meet or exceed our high expectations last year and started to lay the foundation for ResDifera to potentially become a blockbuster therapy. I'm incredibly proud of our team's accomplishments, highlighted on slide four. These are the things that we said that we would do, and we did them. We built a world-class team to drive the launch of resdifera and support Madrigal's long-term aspirations. Our groundbreaking resdifera phase three trial data were published in the New England Journal of Medicine. On March 14th, we achieved the milestone for the MASH field, the landmark approval of resdifera, the first ever treatment approved for this disease. This achievement was further validated by two top-tier liver societies in Europe and the U.S., both updating their guidelines to include ResDifera as first-line therapy for MASH. And we made significant progress expanding ResDifera's reach both geographically and clinically, submitting ResDifera for approval in Europe and completing enrollment in our Maestro NASH outcomes trial. Importantly, these accomplishments are translating into thousands of patients now benefiting from ResDifera, and building a strong foundation for Madrigal's future as the leader in MASH. Let's move to the U.S. ResDiffer launch update on slide five. As we detailed in our earnings release this morning and first previewed at JPMorgan in January, we generated $103 million in net sales in the fourth quarter of 2024, reflecting 66% quarter-over-quarter growth. This was another strong demand quarter with inventory well within our expected two to four week range. For the full year 2024, we generated $180 million in net sales, a remarkable achievement considering we launched in April and these figures represent just three quarters of performance. Our launch trajectory continues to track in line with some of the most successful specialty medicine launches in the past decade. This confirms the urgent need Resgifra is addressing in the MASH community, its excellent product profile, and the exceptional execution of our team. These strong financial results are driven by the key performance indicators critical to any successful drug launch, patients on therapy, prescribers, and access. In the third quarter of 2024, on our payer metric, we reached a key milestone one quarter ahead of schedule. achieving greater than 80% commercial coverage for ResDifera. Since then, we've continued to make great progress on the other two launch metrics. First on patients, as noted on slide six, we ended the fourth quarter with more than 11,800 patients on ResDifera, an incredible accomplishment in just nine months. Crossing the 10,000 patient threshold, is a significant milestone, and we continue to steadily add patients at a rate that's consistent with other top-tier specialty medicine launches. Importantly, this figure represents patients actively on therapy, meaning it accounts for any discontinuations, making it the most rigorous and meaningful metric to track sustained treatment adoption. Yet, we're still in the early days. we have penetrated only a fraction of the market with resgifera, less than 4% of the 315,000 diagnosed patients with F2, F3, MASH. We remain focused on the 315,000 diagnosed patients, which represents a highly attractive specialty market. Looking ahead, the stated efforts of the next entrant are focused on expanding the market to many multiples of 315,000. We believe that the strength of resgifera's profile positions it for leadership in either scenario, creating multiple paths to success for ResDifera in the years ahead. Our ability to steadily add ResDifera patients quarter over quarter is directly tied to increased penetration of our prescriber base. From day one, we've talked about wiring the system, how we have been laying the foundation to support the patient volume we expect in the years ahead. And we're seeing real progress as we've engaged providers driven change in clinical practice, and helped build the infrastructure necessary for sustained prescription growth. On slide seven, the bar graph on the left illustrates this progress. As a reminder, our field team is focused on a total of 14,000 target prescribers, primarily hepatologists and gastroenterologists, with a concentrated effort on the top 6,000 prescribers. In the fourth quarter, approximately 60% of our top 6,000 targets prescribed ResDifera. up from 40% in the third quarter. We are steadily adding new prescribers, and we are seeing increased depth of prescribing from current writers. Both metrics are tracking exceptionally well with other successful Blockbuster launches. As expected, our top target prescribers have driven more than 75% of our prescriptions. Just as we've successfully driven adoption among our top target prescribers, We plan to continue shaping clinical practice and expanding access across our full prescriber base as we build ResDifera towards its peak sales potential. We're already making meaningful progress. By year end, approximately 40% of the 14,000 had prescribed ResDifera, reflecting a strong and growing foundation of support. ResDifera's broad-based uptake is being driven by its attractive profiles. It's a liver-directed therapy that halts or improves liver stiffness, a proxy for liver fibrosis, in 91% of patients out to three years. It's also a once-daily, well-tolerated pill with simple dosing. And with a chronic and serious liver disease like MASH, this favorable profile supports long-term adherence, with early data continuing to indicate persistency rates comparable to other well-tolerated oral therapies. We're also hearing overwhelmingly positive feedback on resdifera from both physicians and patients. They continue to highlight the benefits of the medicine, including improvements in liver function tests and lipid levels, reduced fatigue, increased physical activity, and improvement in fibrosis. And these real-world outcomes really matter. We recently heard from one resdifera patient diagnosed with F2 MASH, she said, Quote, living with MASH felt like having a time bomb in my body. ResDifera gave me hope and my life back, end quote. Our goal is to be the leader in MASH and help patients for many years to come. As noted on slide nine, our long-term strategy builds on the success of ResDifera's U.S. launch. First, we are expanding geographically and remain on track for a mid-year regulatory decision for ResDifera in Europe. Assuming a positive outcome, we plan to take a targeted country-by-country approach to commercialization, beginning with Germany in the second half of the year. Beyond Europe, we are also assessing opportunities to bring ResDiffer to patients in additional attractive geographies. Second, we're advancing ResDiffer for patients with compensated MASH cirrhosis. Approval in F4C would represent a major step forward for the MASH field and for patients, significantly expanding the treatment landscape and effectively doubling ResDiffer's market opportunity. I'll spend some more time on the data we shared this morning in a moment. And third, we are committed to building a strong pipeline beyond ResDifera. We're in the enviable position of providing a highly meaningful medicine to the MASH community today, and we are now focused on building the right pipeline behind it. We are evaluating assets at different stages of development across multiple mechanisms of action, all with the goal of strengthening and extending our leadership position in MASH. Moving to slide 10 and the unmet need in compensated MASH cirrhosis. It's a chronic progressive liver disease characterized by significant liver damage, loss of liver function, liver cancer, and death. A substantial portion of compensated MASH cirrhosis patients also suffer from portal hypertension, which often leads to life-threatening complications such as hepatic encephalopathy, ascites, and variceal bleeding. While patients with F2, F3 fibrosis face a 10 to 17 times higher risk of liver-related mortality, F4 patients are at a staggering 42 times increased risk. In this very sick F4 patient population, preventing progression to adverse clinical outcomes is the central treatment goal. This is reflected in FDA guidance, which recommends that clinical trials in compensated MASH cirrhosis use outcomes as an endpoint. as opposed to biopsy-based surrogate endpoints. This guidance, along with data from our open-label F4C cohort, informed the design of our ongoing maestro NASH outcomes trial. We believe that resdiferous liver-directed mechanism of action should deliver a benefit not only in F2F3 MASH patients, but in F4C MASH patients as well. Therefore, as shown on slide 11, we included a separate open-label active treatment arm of patients with compensated MASH cirrhosis in our Maestro-NAPLD-1 trial to begin evaluating res difference safety and efficacy in F4C. As a reminder, Maestro-NAPLD-1 was a double-blind, randomized, placebo-controlled phase three safety trial to support regulatory approval. We previously presented positive one-year data from the F4C cohort of this trial and are highlighting new two-year VCTE data in 101 patients on slide 12. VCT, or vibration-controlled transient elastography, is a widely used non-invasive test conducted with a FibroScan that measures liver stiffness as a proxy for fibrosis. It's also a strong predictor of clinical outcomes. The two-year results show that patients achieved a mean 6.7 kPa or kilopascal reduction in liver stiffness at two years, which represents the largest mean kPa reduction reported in an F4C MASH patient population to date. While this was a single-arm open-label trial, this reduction was highly statistically significant versus baseline. Physicians used the Babino rule of 5 kPa to stratify risk of liver-related events in patients with MASH, so a 6.7 reduction suggests that many patients are moving into a lower risk category. 51% of patients achieved a 25% or greater decrease in liver stiffness as measured by VCTE. This level of reduction in liver stiffness has been associated with reduced progression to end-stage liver disease, moving patients further away from the risks of cirrhosis and its complications. And ResDifera's safety profile was consistent with other ResDifera clinical trials with a low rate of discontinuations due to adverse events. We look forward to sharing more details from this two-year cohort at a future medical meeting. These data add to the growing body of evidence supporting ResDifera's potential benefit in this high-risk patient population and support continued confidence in our fully enrolled cirrhosis outcomes trial. As noted on slide 13, Maestro Nash Outcomes is a large phase three double-blind placebo-controlled trial evaluating progression to liver decompensation events in 845 patients with compensated MASH cirrhosis. We expect to announce data from this trial in 2027. So, looking ahead to the opportunity in F4C and assuming today's results translate to Maestro Nash Outcomes and ResDifera obtains regulatory approval. we believe resdifera is and will be the leading therapy in F2 to F4C period. Before I hand it over to Marty, let me briefly summarize our progress on slide 14. 2024 was a transformational year for Madrigal. We secured FDA approval for resdifera and are executing on a highly successful launch. We see significant runway for growth with less than 4% of the US target market penetrated and an attractive real world Profile Red's differ is well positioned for continued strong momentum in 2025 and beyond. We are preparing for global expansion. We see a significant opportunity in F4C and believe we will be first to market. And we continue to build for the future as we actively explore opportunities to expand our pipeline. With that, I'll turn it over to Marty.