MADRIGAL PHARMACEUTICALS, INC.

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

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MADRIGAL PHARMACEUTICALS, INC.

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April 28, 2026

CEO’s Letter

“

With a foundational therapy performing exceptionally well, we have a rare opportunity to build long-term leadership in MASH.”

Dear Fellow Stockholders:

In 2025, Madrigal continued to deliver on one of the most successful specialty launches in recent industry history. We ended our first full year on the market with $958.4 million in net sales, exited the year with quarterly revenue annualizing at over $1 billion and firmly established Rezdiffra as the foundational therapy in MASH. That performance reflects not only strong demand, but disciplined execution and a long-term strategy that is working.

We did not simply launch a product—we built a market. Just a few years ago, MASH was a category where drug development had failed repeatedly. There were no approved therapies, and there was real skepticism that a viable market would emerge. Today, the U.S. F2/F3 MASH population under the care of our target specialists has grown nearly 50%, to 460,000 patients, over the past two years and is continuing to expand at a double-digit pace. Rezdiffra is now the standard of care in this growing specialty market. At year-end, more than 36,250 patients were on Rezdiffra, yet this still represents less than 8% penetration of the currently diagnosed F2/F3 population. That level of penetration, in a rapidly expanding market, underscores the substantial runway ahead. Importantly, we were granted patent protection into 2045, providing a long horizon to build a high-growth franchise.

We believe the next major growth driver for Madrigal is compensated MASH cirrhosis (F4c), where there are currently no approved therapies. We estimate approximately 245,000 patients in this segment in the U.S. alone. If approved, Rezdiffra would be the first therapy indicated for F4c and the only medicine supported by outcomes data. Two-year open-label data in patients with F4c that we presented in 2025 have strengthened our confidence in this strategy and reinforce our belief that Rezdiffra can anchor treatment across F2 through F4c.

With a foundational therapy performing exceptionally well, we have a rare opportunity to build long-term leadership in MASH. Over the past year, we have expanded our pipeline to more than ten programs, including an oral GLP-1, a late-stage DGAT-2 inhibitor (ervogastat) and a portfolio of six siRNA programs. Each was selected for its mechanistic complementarity with Rezdiffra and its potential to enhance efficacy either broadly or within specific patient segments.

MASH is a heterogeneous, chronic disease. Over time, we expect treatment to evolve toward combination regimens resulting in better outcomes for the entire MASH population or patient subpopulations that we expect to emerge—an approach we have seen in other large specialty markets. Our strategy is deliberate: start with a therapy that works broadly across the spectrum and build combinations that can further improve outcomes. We plan to advance programs that demonstrate meaningful benefit and allocate capital with discipline.

Rezdiffra is performing exceptionally well in a market that is still in its early stages. With low current penetration, a growing market and a robust pipeline anchored by a high-growth product, we believe we are uniquely positioned to lead in MASH for years to come. On behalf of our Board and leadership team, thank you for your continued support and confidence. We look forward to updating you on our progress in the year ahead.

Sincerely,

Bill Sibold

Chief Executive Officer

Proxy Statement Table of Contents