MADRIGAL PHARMACEUTICALS INC

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.

2024 Annual Meeting of Stockholders

Voting Items and Board Recommendations

Business Highlights

2023 was a transformational year for Madrigal. The Company successfully achieved its clinical, regulatory, operational, and financial objectives, setting the stage for the landmark approval and launch of Rezdiffra™ (resmetirom) in March 2024.

Advanced Our Leadership Position in NASH Drug Development: Madrigal has established the most advanced and comprehensive clinical development program in noncirrhoticnon-alcoholic steatohepatitis (“NASH”). Our Phase 3

study results were featured in plenary presentations at the major liver disease medical conferences throughout the year and key Rezdiffra data were published in leading journals, including the MAESTRO-NAFLD-1 safety study in Nature Medicineand the pivotal MAESTRO-NASH biopsy study in the New England Journal of Medicine. We announced full enrollment of the 54-month clinical outcomes portion of MAESTRO-NASH in April 2023 and continued to enroll patients with compensated NASH cirrhosis in our MAESTRO-NASH OUTCOMES study. Successful completion of these studies carries the potential to secure 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 NASH competitive landscape.

Pioneered the NASH Regulatory Pathway: The positive efficacy and safety data from the MAESTRO studies put Madrigal in a strong position to navigate the FDA’s review of our new drug application (NDA) seeking accelerated approval of Rezdiffra. The medication received Breakthrough Therapy designation and the NDA was granted Priority Review without an Advisory Committee meeting. On March 14, 2024, Rezdiffra was approved for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). Madrigal’s NDA resulted in a “best-case” label for Rezdiffra: the prescribing information includes no biopsy requirement for diagnosis, reflects the intended patient population for the medication, and provides physicians with patient management guidance that is consistent with current clinical practice.

Built Our Team for Launch and Beyond: As clinical and regulatory execution accelerated, Madrigal built new commercial launch capabilities and expanded its leadership team for the next phase of the Company’s growth. Bill Sibold joined Madrigal as Chief Executive Officer in September, succeeding Dr. Paul Friedman, who continues to serve on the Board of Directors. Madrigal announced a series of new leaders with strong biopharma specialty launch experience, including Mardi C. Dier as Chief Financial Officer and Carole Huntsman as Chief Commercial Officer. Madrigal has grown from approximately 100 employees at the beginning of 2023 to more than 400 as of today. In September 2023 and March and April of 2024 Madrigal executed successful financing events that together generated more than $1 billion in proceeds to support our commercial, R&D, and business development objectives. As the Rezdiffra launch progresses, Madrigal is in a strong financial position to capitalize on its leadership position in NASH.

Proposal 1 Election of Class II Directors (Page 52)

Our Board of Directors has nine members divided into three classes, six of whom are independent. Three Class II Directors, Bill Sibold, Rebecca Taub, M.D. and Fred B. Craves, Ph.D., are standing forre-election at the 2024 Annual Meeting of Stockholders.

Our Board of Directors is responsible for overseeing the affairs and performance of Madrigal and acting in the best interests of stockholders. The Board selects senior management and has oversight responsibility over senior management and the conduct of Madrigal’s business operations. The experience of our Board members is summarized below and described in greater detail beginning on page 8.

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.

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Board Skills Matrix

Our Board possesses a broad range of qualifications and skills that facilitate strong oversight of the Company’s management and strategy. The following table provides a summary of our directors’ key skills and core competencies*:

Board Diversity Matrix

The following table illustrates the composition of our directors by self-identified diversity statistics. Each of the categories listed in the below table has the meaning used in Nasdaq Listing Rule 5605(f).

Proposal 2 Ratification of Auditors (Page 53)

We are requesting stockholders ratify the appointment of PricewaterhouseCoopers LLP as our independent registered public accounting firm for our fiscal year ending December 31, 2024.

Proposal 3 Say-On-Pay Advisory Vote (Page 56)

In 2023, stockholders continued their historically strong support for our executive compensation program with 94% of the votes cast voting in favor of approvingthe say-on-pay proposal. We have received 94% or higher support for the last four years. Our Compensation Committee believes that the objectives of our executive compensation program, as it relates to our named executive officers, 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 named executive officers, achieves an appropriate balance between fixed compensation and variable incentive compensation, pays for performance and promotes an alignment between the interests of our named executive officers and our stockholders.

Proposal 4 Approval of Amendment to Madrigal Pharmaceuticals, Inc. 2015 Amended Stock Plan (Page 57).

We are seeking stockholder approval of an amendment to the Madrigal Pharmaceuticals, Inc. 2015 Amended Stock Plan to increase the shares authorized for issuance under the Plan by 750,000 shares and to extend the expiration date of the Plan by 10 years through April 23, 2035.

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PROXY STATEMENT

We prepared this proxy statement under the direction of our Board of Directors to solicit your proxy for use at our 2024 Annual Meeting of Stockholders to be held via internet webcast on Tuesday, June 25, 2024, at 9:00 a.m. Eastern Time. As used in this proxy statement, the terms “Madrigal,” “Public Madrigal,” the “Company,” “we,” “our” and “us” refer to Madrigal Pharmaceuticals, Inc., a Delaware corporation that has been publicly traded since July 22, 2016.