MADRIGAL PHARMACEUTICALS INC

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PROXY STATEMENT SUMMARY

This summary highlights information contained elsewhere in this proxy statement and does not contain all of the information that you should consider. You should read the entire proxy statement carefully before voting.

As used in this proxy statement, the terms “Madrigal,” the “Company,” “we,” “our” and “us” refer to Madrigal Pharmaceuticals, Inc., a Delaware corporation.

This proxy statement is first being made available to our stockholders on or about April 29, 2025.

2025 Annual Meeting of Stockholders

Voting Items and Board Recommendations

Company Overview

We are a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (“MASH”), a serious liver disease with high unmet medical need that can lead to cirrhosis, liver failure and premature mortality. Our medication, Rezdiffra (resmetirom), is a once-daily, oral, liver-directed thyroid hormone receptor-beta (“THR-β”) agonist designed to target key underlying causes of MASH. In March 2024, Rezdiffra became the first and only therapy approved by the U.S. Food and Drug Administration (the “FDA”) for patients with MASH.

2024 Business Highlights

2024 was a tremendous year for Madrigal. We received the landmark approval of Rezdiffra™ (resmetirom) in March 2024 and have successfully executed a first-in-disease launch. We believe we are well positioned for 2025 and beyond.

Established Madrigal as the Leader in MASH: In February 2024, Rezdiffra Phase 3 MAESTRO-NASH trial 52-week results were published in The New England Journal of Medicine (“NEJM”) and were subsequently chosen as one of NEJM’s 14 notable scientific research articles of 2024. In March 2024, Rezdiffra became the first and only therapy approved by the FDA for patients with MASH and was commercially available in the United States beginning in April 2024. The FDA’s accelerated approval and Rezdiffra’s approved prescribing information were supported by 52-week data from our Phase 3 MAESTRO-NASH trial in which both 100 mg and 80 mg doses of Rezdiffra demonstrated statistically significant improvement compared to placebo on (i) MASH resolution with no worsening of fibrosis and (ii) an improvement in fibrosis by at least one stage with no worsening of the nonalcoholic fatty liver disease activity score. Our MAESTRO-NASH trial remains ongoing as an outcomes trial where we are generating confirmatory outcomes data to 54-months that, if positive, is expected to verify a clinical benefit and support the full approval of Rezdiffra in noncirrhotic MASH. In addition, we completed enrollment of our Phase 3 MAESTRO-NASH OUTCOMES trial where we are evaluating progression to liver decompensation events in patients with compensated MASH cirrhosis treated with Rezdiffra versus placebo. Successful completion of this trial is expected to support full approval of Rezdiffra, expand the eligible population for Rezdiffra to include patients with more advanced disease, and reinforce Madrigal’s long-term leadership position in the MASH competitive landscape.

Executed a First-in-Disease Launch with Exceptional Results: Rezdiffra became the first FDA-approved therapy for the treatment of MASH in March 2024 and was commercially available in the United States beginning in April 2024. We established a full-capability commercial organization, including marketing, sales and market access expertise, to support the launch of Rezdiffra in the United States. For the year ended December 31, 2024, we generated $180.1 million of net revenue from sales of Rezdiffra. We continue to execute our launch strategy by educating healthcare providers and patients on the risks of MASH and the potential clinical benefits and appropriate use of Rezdiffra. We are also supporting the creation of care pathways for patients at physician offices, driving breadth and depth of Rezdiffra prescribers and engaging with payers to support patient access to therapy. We believe Rezdiffra’s product profile as a liver-directed, once-daily, generally well-tolerated oral therapy, as well as its first-to-market position, provide meaningful points of differentiation in the MASH competitive landscape.

Built to Support Continued Growth: Madrigal has grown from approximately 100 employees at the beginning of 2023 to more than 500 employees as of the end of 2024. In addition, in anticipation of a regulatory decision regarding resmetirom in Europe, we have hired individuals to serve in a number of key leadership positions in Europe, established our European headquarters in Switzerland and engaged a manufacturer for the primary supply of our commercial product in Europe, if approved. We also raised approximately $660 million of net proceeds from an equity financing in 2024, strengthening our balance sheet to support the launch of Rezdiffra and other key corporate initiatives. A successful 2024 has created strong momentum for 2025 and beyond where we are focused on executing on the following growth objectives:

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continuing our successful execution of a first-in-disease launch of Rezdiffra;

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deepening our commitment to the MASH community by seeking full approval of Rezdiffra for the treatment of MASH with moderate to advanced liver fibrosis (consistent with stages F2 and F3 fibrosis) and expanding the eligible patient population for Rezdiffra with an additional indication in patients with compensated MASH cirrhosis (consistent with F4c), subject to positive results from our MAESTRO NASH OUTCOMES trial and FDA approval;

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driving future growth through geographic expansion in Europe on a country-by-country basis, including our planned launch in Germany in the second half of 2025, subject to regulatory approval; and

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expanding our pipeline by selectively acquiring or in-licensing programs at all stages of development to take advantage of our drug development and commercial capabilities.

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Summary of Proposals and Board Recommendations

Proposal 1: Election of Class III Directors

Our Board of Directors (the “Board”) has ten members divided into three classes, seven of whom are independent. Four Class III Directors, Julian C. Baker, Raymond Cheong, Ph.D., M.D., Jacqualyn A. Fouse, Ph.D., and Richard S. Levy, M.D., are standing for re-election at the Annual Meeting.

Our Board is responsible for overseeing our affairs and performance and acting in the best interests of our stockholders. The Board provides independent oversight of senior management and the conduct of our business operations. For additional information on the experience of our Board members, see the section titled “Management and Corporate Governance—The Board of Directors” on page 17 of this proxy statement.

We are committed to a Board composition that reflects an optimal mix of skills and experience necessary to carry out critical oversight of operations, clinical and commercial objectives and overall strategy. We believe our current Board membership effectively oversees our business strategy and operations, contributes to the long-term, forward-looking strategy and performance objectives of the Company and complements senior management’s objectives and efforts to create and sustain value associated with the long-term interests of the Company’s stockholders.

We are requesting stockholders to elect each of the four Class III director nominees standing for re-election to serve on the Board, each for a three-year term expiring at the Annual Meeting of Stockholders to be held in 2028, or until their successors are duly elected and qualified. For additional information, see “Proposal 1: Election of Directors” on page 66 of this proxy statement.

Proposal 2: Ratification of Auditors

We are requesting stockholders ratify the appointment of PricewaterhouseCoopers LLP (“PwC”) as our independent registered public accounting firm for our fiscal year ending December 31, 2025. For additional information, see “Proposal 2: Ratification of Appointment of Independent Registered Public accounting Firm” on page 67 of this proxy statement.

Proposal 3: Non-Binding, Advisory Say-On-Pay Vote

In 2024, stockholders continued their historically strong support for our executive compensation program with 95% of the votes cast voting in favor of approving the say-on-pay proposal. We have received 94% or higher support for each of the last five years. The Compensation Committee of our Board (the “Compensation

Committee”) believes that the objectives of our executive compensation program, as it relates to our named executive officers (“NEOs”), are appropriate for a company of our size and stage of development and that our compensation policies and practices help meet those objectives. In addition, our Compensation Committee believes that our executive compensation program, as it relates to our NEOs, achieves an appropriate balance between fixed compensation and variable incentive compensation, pays for performance and promotes an alignment between the interests of our NEOs and our stockholders. In addition to holding an annual advisory vote on executive compensation, we conduct engagement with our stockholders on executive compensation and corporate governance matters. We have in the past modified our compensation practices based on constructive feedback from stockholders.

We are requesting stockholders to approve, on a non-binding advisory basis, the 2024 compensation paid to our NEOs. For additional information, see “Proposal 3: Non-Binding, Advisory Vote on Executive Compensation” on page 71 of this proxy statement.

Recent Say-on-Pay Results

Proposal 4: Non-Binding, Advisory Say-On-Frequency Vote

We are requesting stockholders vote, on a non-binding, advisory basis, for the “1 Year” option for the frequency of future non-binding, advisory votes on the compensation of our NEOs. For additional information, see “Proposal 4: Non-Binding, Advisory Vote on the Frequency of Future Advisory Votes to Approve the Compensation of Our Named Executive Officers” on page 72 of this proxy statement.