Madrigal Pharmaceuticals, Inc. Q4 FY2025 earnings call

William J. Sibold provided update on Rezdiffra launch, noting it ended first full year on market with nearly $1B in net sales and solidified as foundational therapy in NASH. Discussed significant growth in U.S. NASH market. Dave Soergel gave update on R&D strategy with more than 10 programs in pipeline. Mardi C. Dier discussed financials, including fourth quarter and full year 2025 net sales, operating expenses, and balance sheet. Company built leading MASH company, assembled pipeline, executed U.S. launch, extended Rezdiffra’s patent exclusivity to 2045, initiated ex-U.S. rollout in Germany, advanced F4C trial, and completed three transactions to build pipeline around Rezdiffra

Fourth quarter 2025 net sales were $321,000,000, more than tripling fourth quarter 2024. Full year 2025 net sales totaled $958,000,000. Rezdiffra ended its first full year on the market at nearly $1,000,000,000 in net sales and solidified as foundational therapy in NASH. Fourth quarter ended with more than 36,250 patients on Rezdiffra up from more than 29,500 at the end of the third quarter. U.S. NASH market up nearly 50% since 2023 and growing at double-digit pace. F4C could double Rezdiffra’s opportunity with approximately 245,000 patients, no approved therapies, and higher urgency to treat

Expect robust net sales growth in 2026 despite step up in gross-to-net from contracting beginning in Q1 plus typical first quarter dynamics. 2026 R&D expenses expected to be roughly same as 2025. SG&A expenses anticipated to increase next year as continue to support Rezdiffra launch and build foundation for long-term growth. Payer agreements expected to bring full year 2026 gross-to-net impact into high 30% range

Q: You are seeing meaningful growth in the number of diagnosed patients. Can you elaborate on the drivers here and talk about your expectations for category growth in 2026? And then second, you are also seeing an acceleration in patient starts despite the launch of Wegovy. Can you elaborate on the types of patients you are seeing starting on Rezdiffra now versus say, in the past and any trends you are seeing across the types of different prescribers.

A: William J. Sibold responded on drivers of diagnosed patient growth, mentioning awareness increase and market growth, and on patient starts, noting steady patient adds, even mix between F2 and F3 patients, and prescriptions mostly in hep GI space.

Q: Hey, guys. Good morning. Maybe just one quick clarification question on I just wanted to ask about the contribution of the Germany launch to the worldwide revenues and patient numbers, and maybe if you could expand a little bit on expectations for 2026. And then on the pipeline combo programs, I know you are starting to look and you have guided today to a phase 2 study with Evogastat next year. Could you just elaborate on how you are thinking about sort of mid-stage phase 2 studies from here? Do you think these studies will need to evaluate liver histology via biopsy before you progress into, pivotal studies is there potential for a more accelerated path that perhaps leverages NITs?

A: William J. Sibold and Mardi C. Dier responded on Germany launch contribution, stating negligible in 2025 and not much in 2026, and on phase 2 studies, noting need to go to FDA, phase 2 expectation of NITs playing major role.

Q: Firstly, it is maybe help us understand for MAESTRO-NASH outcomes in F4C, how are you tracking blinded event rates? Like and how is this, like, tracking for on-time data? At what point in this year might you tighten guidance in that regard? And is there any additional cirrhosis open-label NAFLD data follow-up that we could get to further strengthen conviction in the test?

A: Mardi C. Dier responded on MAESTRO-NASH outcomes, stating events track in expected range, data to be delivered in 2027, and open-label data already shown with positive effects.

Q: Maybe firstly on gross-to-net, you could comment on gross-to-net for 4Q and cadence for the rest of 2026. And would you still expect broad first line access without step edits for Rezdiffra in 2026. Now that we are seeing no contract. And maybe just another follow-up, if you can comment on compliance persistence and discontinuation rates that you are seeing especially since Wegovy’s launch in the market.

A: William J. Sibold and Mardi C. Dier responded on gross-to-net, stating 4Q ended in midpoint of 20%-30% range, 2026 gross-to-net impact in high 30s, broad first line access with no step edits, and compliance persistence in 60%-70% range.

Q: You mentioned about, like, 60% to 70% persistence rate. When we looked at the AASLD data, there was, like, some presentation showing more than 90% adherence rate in the real world. How important is to keep the adherence rate to that 90 is to maintain the current patient adds and the revenue growth. And also, do you expect any acceleration in patient adds going forward now with all the contracts in place, or should we think about, probably around 6,000 to 7,000 patients net patient adds every quarter?

A: William J. Sibold responded on persistence rate, stating efforts to improve persistence, and on patient adds, stating steadily adding patients and expecting to continue.

Q: Over the past several months, you have added multiple combination assets around Rezdiffra, including DGAT2 and GLP-1 and siRNA programs. My question is how do you avoid diminishing return from putting too many synergistic mechanisms into the pipeline? And what is your go, no-go criteria for advancing a second agent both clinically and commercially? And then my second question is briefly has there been any change in expected timing of MAESTRO-NASH outcomes now that the FDA has approved AI-supported pathology rates?

A: William J. Sibold and Mardi C. Dier responded on avoiding diminishing return, stating mechanism and patient benefit focus, and on MAESTRO-NASH outcomes timing, stating no change as study is event-driven.

Q: Since you have two all oral combos, where do you envision the siRNA modality to fit into the future treatment landscape of NASH? And is there any color you can share with us on the targets of those six siRNA programs, and when should we expect the timing of clinical development?

A: William J. Sibold and Mardi C. Dier responded on siRNA modality fit, stating combination potential, and on siRNA targets, stating competitive reasons for not disclosing now but to stay tuned.

Q: Wondering how should we think about you know, five years from here, the F2-F3 target population, growing? And then also, should we expect, you know, further growth of the F4 population as well with patients still advancing?

A: William J. Sibold responded on F2-F3 target population growth, expecting double-digit growth for foreseeable future, and on F4 population growth, stating expected growth as market evolves.

Q: I am just wondering about the extensive script growth needed over the fiscal year 2026 to grow revenue off of the increased for the gross-to-net. And just a quick second question, what do you think companion diagnostics predisposition would need to be developed to show any genetic to for NASH if you are going to eventually move forward with the siRNAs if data is positive.

A: William J. Sibold and Mardi C. Dier responded on revenue growth, stating robust growth expected, and on companion diagnostics, stating early to comment, genetic screening becoming more common.

Q: Just sort of sticking with what you were just talking about, Bill, in terms of the market increase from 315,000 to 460,000. Just curious if you or know, if you see that correlated with the increase of patient prescriber interest and potentially we should think about that as reading through to sort of new patient adds. Is this more of a longer term, just more runway in terms of patients? Or is this actually feeding increased new patient additions. And then I have a follow-up. In reference to your GLP-1 and your DGAT, it looks like GLP-1 might be, initiation starting for your for phase 1. It looks like it might be pushed back slightly from first quarter to second quarter. In terms of both those programs, just curious what remaining gating activities still need to be completed.

A: William J. Sibold responded on market increase correlation, stating wiring of system successful, and on GLP-1 and DGAT programs, stating refined to second quarter with no delay.

Q: Now that we are seeing more and more patients on for longer time periods, we want to know, have you seen any challenges in the reimbursement process to keep patients on drug for the extended time periods? We can imagine that for many patients with Rezdiffra, that their fibrosis scores could improve, and they might technically be outside of the label requirement.

A: William J. Sibold responded on reimbursement process, stating reauthorizations routine, belief Rezdiffra is chronic therapy