Madrigal Pharmaceuticals, Inc.

Good day, and thank you for standing by. Welcome to Magical Pharmaceuticals' first quarter 2025 earnings conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. As a reminder, today's conference call is being recorded. I would now like to introduce Ms. Tina Ventura, Chief Investor Relations Officer.

Please go ahead. Thank you, Tawana. Good morning, everyone, and thank you for joining us to discuss Madrigal's first quarter 2025 earnings. We issued a press release this morning, and I 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. 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. With that, I will now turn the call over to Bill on slide three.

Thanks, Tina. Good morning, and thanks for joining. Today, I'll provide an update on the significant momentum we continue to build with the U.S. launch of RISDFRA. I'll briefly recap the impressive two-year F4C data we shared on our last earnings call, which has since been selected as a late-breaking oral presentation at the EASL Congress in Amsterdam next week. We plan to review this data in an investor webcast following EASL on Tuesday, May 13th. And I'll close with a review of our strategy to expand our leadership position in MASH. But before we move to the quarter, I want to take a moment to recognize Becky Taub, Madrigal's founder and a driving force behind the development and ultimate approval of ResDifera. As we announced in April, Becky is taking on the new role of Senior Scientific and Medical Advisor, and she will continue to serve on our Board of Directors. And we are very pleased that Dave Sorgel joined us on April 21st as our new Chief Medical Officer, succeeding Becky. Becky's vision, pioneering work, and relentless drive led to the development and approval of the first ever FDA-approved medicine for MASH. This is a landmark achievement in our industry and one that has already changed the lives of thousands of patients. It's also changed Madrigal. We've transformed from an R&D-focused company to a fully integrated commercial stage organization. Dave brings more than 20 years of leadership experience in metabolic, and cardiovascular disease drug development, spanning both biotech and large pharma. He was most recently the EVP and global head of cardiovascular, renal, and metabolism development at Novartis, where he was overseeing 10 late-stage clinical development programs. We believe Dave is the right leader to take the reins at this critical juncture and build on the foundation Becky created. Along those lines, I'd also like to highlight the recent addition to our board of directors, Jackie Faust. Jackie brings a depth of experience from her leadership roles at several successful biotechs, including Agios and Celgene. I look forward to working with her as we continue to grow the company. Now, let's turn to slide four and ResDifera's first quarter 2025 performance. We're a little more than 12 months into the launch of ResDifera, and what a difference a year makes. We've gone from zero approved mass treatments and no market infrastructure to securing FDA approval in March 2024, launching with a best case label and a world-class team, achieving over 80% commercial payer coverage, helping lay the foundation practice by practice to build the infrastructure required for patient treatment, treating more than 17,000 patients who previously had no options, and generating $317 million in net sales in our first 12 months on the market. By any measure, this is an exceptional launch. And we know that because we're benchmarking ourselves against some of the most successful specialty medicine launches in the past decade. Whether it's patient growth, depth and breadth of prescribing, payer coverage, or net sales, we're performing at or near the top. But the most exciting part? We're just getting started. As we enter year two, we're bringing the same intensity and focus on execution that got us here, and we believe the best is still ahead. This momentum carried us into another impressive quarter, with first quarter 2025 net sales of $137 million, up 33% quarter over quarter, despite the typical headwinds we see in Q1 across the industry. Our patient support and field teams did a great job navigating those dynamics to keep patients on therapy. And we're continuing to generate strong demand and steadily add patients into the second quarter, driven by the urgent need res differ addresses, its compelling product profile, and the exceptional execution of our team. In addition to net sales, we continue to make great progress on key performance indicators that are driving our launch. First on patients, as shown on slide five. We ended the first quarter of 2025 with more than 17,000 patients on resdifera, up from 11,800 patients at the end of the fourth quarter of 2024. This figure represents patients actively on therapy, accounting for any discontinuations, making it the most rigorous and meaningful metric to track sustained treatment adoption. And when we compare it to other top-tier specialty launches, We're adding patients at a rate that's consistent with those benchmarks. And yet, we're still in the very early innings of this launch. Only about 5% of the 315,000 diagnosed F2, F3, MASH patients who are currently under the care of our target prescribers are being treated with Red Zebra. We also see that awareness is driving action. Our disease and product education efforts are preparing patients to have better conversations with their MASH specialists about their care. We remain focused on those 315,000 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 our initial target market. We believe that the strength of RIS differs efficacy, An attractive real-world profile positions it for leadership in either scenario, creating multiple paths to success for RISDFRA in the years ahead. Moving to slide six in our progress on physician penetration. Across the many launches I've led, one thing is clear. Building a strong base of prescribers early in a launch is one of the best indicators of long-term success. That's why the pace at which we've added new prescribers has been so encouraging. In just a year since approval, 70% of our 6,000 top targets have prescribed ResDifera. This level of penetration puts us at the high end of the benchmarks we track and shows we've built a strong foundation of healthcare providers who believe in ResDifera and are seeing the benefits. Achieving this type of uptake this quickly is the result of the work we've been doing since day one. Wiring the system for a first in disease launch like ResDifera is no small feat. We built and deployed a world-class team. We educated physicians on a disease that had no approved therapies. We partnered with payers to secure broad access and worked hand-in-hand with practices to help create the infrastructure needed to support sustained prescribing. As a result, more and more practices are integrating ResDifera into their standard of care. We're driving the same momentum as we establish a strong base within our 14,000 total targets to support the significant peak sales potential we expect. At the end of the first quarter of 2025, approximately 50% of the 14,000 target prescribers had prescribed risdifera, up from 40% at the end of the fourth quarter of 2024, reflecting a growing and durable foundation. Our in-office support and cross-functional field engagement are not only driving breadth, they're also driving depth. We are steadily turning new writers into repeat prescribers and seeing more prescriptions written per provider. That has consistently increased quarter over quarter as well. ResDipper's broad uptake is being driven by its attractive real-world profile. A medicine's profile often diminishes once it enters real-world. With resdifera, we hear the opposite. Physicians and patients continue to highlight meaningful improvements they see on the efficacy measures that matter most to patients, such as liver stiffness, liver fat, liver enzymes, LDL, and triglycerides. And our Phase III data demonstrate that resdifera halts or improves liver stiffness in 91% of patients. As a once-daily, well-tolerated pill with simple dosing, it's also easy to take. We're seeing strong early signs of adherence with rates that are comparable to other well-tolerated oral therapies. We believe ResDiffra's liver-directed mechanism, strong efficacy, and attractive real-world profile will translate well from F2, F3 MASH patients to those with F4C or compensated MASH cirrhosis, as noted on slide 8. As MASH progresses, it can lead to cirrhosis. marked by significant liver damage, loss of liver function, liver cancer, and death. Many F4C patients also experience clinically significant portal hypertension, or CSPH, a major consequence of cirrhosis that's responsible for its most severe complications such as ascites, variceal bleeding, and hepatic encephalopathy. The risk of progression is striking. F2-F3 patients face a 10- to 17-fold increase in liver-related mortality compared to patients without fibrosis. For F4, that number jumps to a 42-fold increase. That's why we are evaluating RESDIFRA in 845 F4C patients in maestro NASH outcomes, a large Phase III double-blind placebo-controlled trial evaluating progression to liver decompensation. We expect data from this trial in 2027. Last quarter, we shared two-year data from the open-label active treatment arm of our Maestro NAFLD-1 trial in F4C patients. These results demonstrated Red's difference ability to reduce liver stiffness, a key predictor of adverse liver-related events. Turning to slide nine, let me quickly recap the two primary efficacy findings. Patients saw a mean reduction of 6.7 kilopascals in liver stiffness at two years, which was statistically significant as compared to baseline. For context, physicians used the Bovino Rule of Five to stratify risk in MASH cirrhosis. So a 6.7 kPa reduction suggests that many patients are moving into a lower risk category. 51% of patients achieved a greater than or equal to 25% reduction in liver stiffness. As published in JAMA, this level of reduction is associated with a lower risk of progression to end-stage liver disease, essentially a reversal of cirrhosis. These results and additional insights will be presented at the upcoming EASL Congress on May 10th by Dr. Naeem Al-Khoury, Chief Academic Officer at Summit Clinical Research and the Director of the Steotic Liver Disease Program at the Clinical Research Institute of Ohio. This abstract was accepted as a late-breaking oral presentation, and one of the most important findings we'll highlight is resdipra's impact to reduce liver stiffness measures and other biomarkers that are linked to a reduction in risk of CSPH. Importantly, CSPH is the cause of many adverse liver-related outcomes that mark the progression from compensated to decompensated cirrhosis. Preventing these devastating outcomes is the central goal of treating liver disease. As I mentioned earlier, we'll also be hosting a brief investor webcast on May 13th to review the data and discuss the evolving MASH cirrhosis landscape. Dr. Elkori will join us for that discussion, and we hope many of you will tune in. The expansion to treatment of F4C is a key pillar of our long-term MASH leadership strategy, as shown on slide 10. While we continue to execute a successful U.S. launch in F2, F3, we're advancing efforts to expand res differs indication to F4C. Our phase three maestro NASH outcomes trial is in alignment with FDA guidance for clinical trial design in cirrhosis patients. We expect to have data years ahead of the competition and first mover advantage in this segment of the market as well. If approved, this could potentially double res differs market opportunity. We're also preparing to bring ResDifera to patients outside the U.S. We remain on track for a mid-year regulatory decision in Europe, and if we receive a positive outcome, we plan to launch in Germany in the second half of the year. Beyond Europe, we're evaluating additional high-priority global markets. At the same time, we're focused on building the right pipeline beyond ResDifera. We're in the enviable position of delivering a first in disease medicine to patients today. And now we're looking to extend that leadership with a portfolio of differentiated assets. We're actively evaluating opportunities across multiple mechanisms and stages of development. And as I mentioned earlier, we're excited to have Dave Sorgel on board as our new chief medical officer to help lead our pipeline development efforts. With that, let me briefly recap our first quarter progress on slide 11. We're off to a great start in year two of our launch. We generated $317 million in net sales over the last 12 months and are seeing continued momentum into the second quarter. Physician adoption continues to build with 70% of our 6,000 top targets now prescribing ResDifera. We're expanding our leadership in MASH with compelling two-year F4C data, two pivotal outcome trials underway, and a potential EMA approval on the horizon. We believe ResDifera is well on its way to becoming the foundational therapy across F2 to F4C period. With that, I'd like to turn it over to Marty.