MADRIGAL PHARMACEUTICALS INC

Unless otherwise stated, all references to “us,” “our,” “we,” “Madrigal,” the “Company” and similar designations in this Annual Report on Form 10-K refer to Madrigal Pharmaceuticals, Inc. and its consolidated subsidiaries. Madrigal Pharmaceuticals, Rezdiffra™ and associated logos are trademarks of Madrigal Pharmaceuticals, Inc. Other brands, names and trademarks contained in this Annual Report on Form 10-K are the property of their respective owners.

Solely for convenience, the trademarks and trade names in this Annual Report on Form 10-K may be referred to without the ® and ™ symbols, but such references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto.

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CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

This Annual Report on Form 10-K (this “Annual Report”) for the fiscal year ended December 31, 2024 includes “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, that are based on our beliefs and assumptions and on information currently available to us, but are subject to factors beyond our control. Forward-looking statements reflect management’s current knowledge, assumptions, judgment and expectations regarding future performance or events; include all statements that are not historical facts and can be identified by terms such as “accelerate,” “achieve,” “may,” “will,” “should,” “could,” “would,” “expects,” “plans,” “anticipates,” “goal,” “believes,” “estimates,” “positions,” “predictive,” “projects,” “predicts,” “intends,” “potential,” “continue,” “seeks”and similar expressions and the negatives of those terms. In particular, forward-looking statements contained in or incorporated by reference to this Annual Report include statements related to, among other things, the following:

•our ability to successfully commercialize Rezdiffra, our only approved product, in the United States for the treatment of metabolic dysfunction-associated steatohepatitis (“MASH”) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis);

•our ability to obtain and maintain full approval for Rezdiffra from the U.S. Food and Drug Administration (the “FDA”), including our ability to successfully, or in a timely manner, report positive results from either of our outcomes trials, which is required for full approval for Rezdiffra;

•our ability to obtain and maintain regulatory approval to expand Rezdiffra's indication to a broader MASH patient population;

•the degree of market acceptance of Rezdiffra by physicians, patients, third-party payors and others in the healthcare community;

•our ability to obtain and maintain adequate reimbursement from government and third-party payors for Rezdiffra or acceptable prices for Rezdiffra;

•our ability to obtain, at all or in a timely manner, regulatory approvals for Rezdiffra in Europe;

•our ability to effectively scale our operations in Europe to successfully commercialize Rezdiffra, subject to European Commission (“EC”) approval;

•our possible or assumed future business strategies and plans (including potential ex-U.S. commercial or partnering opportunities) and potential growth opportunities;

•competition in the market and our ability to adapt to our highly competitive environment;

•our ability to acquire or in-license new products, product candidates and technologies, or the potential clinical or commercial success of acquired products, product candidates or technology;

•safety or efficacy matters related to Rezdiffra or any other future product candidate;

•anticipated timing of receipt of data from our clinical trials and the public disclosure of such data;

•our potential achievement of primary and key secondary endpoints in our ongoing clinical trials;

•estimates of the number of potential patients with MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) or physicians identified;

•Rezdiffra's potential sector leadership;

•our ability to establish and maintain an effective commercial organization, including sales and marketing representatives;

•our ability to attract and retain qualified personnel or to effectively manage our growth;

•our ability to successfully conduct our current or any future clinical trials necessary for regulatory approval and our ability to enroll or retain sufficient patients to conduct and complete the trials or generate data necessary for regulatory approval;

•the ability of third parties on which we rely to manufacture sufficient quantities of Rezdiffra or any other future product candidate for our commercial or clinical needs and their ability to comply with our agreements or applicable regulations;

•the timely distribution of our product;

•the regulation of the healthcare industry, including potential pricing reform, and our ability to comply with an evolving regulatory landscape;

•anticipated or estimated future results, including our future operating performance and financial position;

•estimates of our expenses and liquidity and our ability to raise additional capital as needed;

•our ability to achieve or maintain profitability;

•our ability to comply with the covenants included in our loan facility;

•our ability to delay certain research activities and related clinical expenses as necessary;

•general economic conditions in the United States, Europe and globally, including inflation, affecting us, our suppliers, third-party service providers and potential partners;

•our ability to adequately protect our intellectual property rights or prevent disclosure of our trade secrets and other proprietary information and costs associated with litigation or other proceedings related to such matters;

•our ability to comply with our obligations under such agreements related to Rezdiffra, including our license agreement with Hoffman-La-Roche (“Roche”); and

•the potential impact of cyber attacks and other security incidents on our operations or business.

We caution you that the foregoing list may not include all of the forward-looking statements made in this Annual Report. Although management presently believes that the expectations reflected in such forward-looking statements are reasonable, management cannot assure that such expectations will prove to be correct and you should be aware that actual results could differ materially from those contained in such forward-looking statements.

You should not place undue reliance on any such forward-looking statements, which speak only as of the date they are made. Any forward-looking statement is based on information current as of the date of this Annual Report on Form 10-K and speaks only as of the date on which such statement is made. Actual events or results may differ materially from the results, plans, intentions or expectations expressed or implied in these forward-looking statements as a result of a variety of factors, many of which are beyond our control. More information on factors that could cause actual results to differ materially from those anticipated is included from time to time in our reports filed with the U.S. Securities and Exchange Commission (“SEC”), including, but not limited to, those described in the section titled “Risk Factors” included in this Annual Report. Moreover, we operate in an evolving environment. New risks and uncertainties emerge from time to time and it is not possible for our management to predict all risks and uncertainties, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual future results to be materially different from those expressed or implied by any forward-looking statements. We disclaim any obligation, except as specifically required by law and the rules of the SEC, to publicly update or revise any such statements to reflect any change in our expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in such forward-looking statements.

RISK FACTORS SUMMARY

The following is a summary of the principal risk factors that make an investment in our common stock speculative or risky. Before you invest in our securities, you should read the following summary together with the more detailed description of material risks described in the section titled “Risk Factors” in Part I, Item 1A of this Annual Report and the other information contained in this Annual Report.

•We are highly dependent on the success of our only approved product, Rezdiffra. If we are unable to successfully commercialize or maintain approval for Rezdiffra, our business, financial condition, results of operations, prospects and the value of our common stock will be materially adversely affected.

•We obtained regulatory approval of Rezdiffra in the United States through an accelerated approval process, and we are subject to certain post-marketing commitments.

•The commercial success of Rezdiffra will depend on market acceptance by physicians, patients, third-party payors and others in the healthcare community.

•If we are unable to successfully further develop and maintain internal commercialization capabilities, future sales of Rezdiffra may be negatively impacted.

•We may become subject to unfavorable pricing regulations or third-party coverage and reimbursement policies, which would harm our business.

•The pricing of pharmaceutical products has come under increasing scrutiny as part of a global trend toward healthcare cost containment. Resulting changes in healthcare law and policy, including recently enacted changes to Medicare, could have a material adverse effect on our business and financial condition.

•Rezdiffra remains subject to ongoing regulatory review, and if we fail to comply with continuing regulations, we could lose our approval and the sale of Rezdiffra could be suspended.

•Rezdiffra could develop unexpected safety or efficacy concerns, which would likely have a material adverse effect on us.

•We operate in a highly competitive and changing environment, and if we are unable to adapt to our environment, we may be unable to compete successfully.

•We may never obtain approval or commercialize Rezdiffra outside of the United States, which would limit our ability to realize its full market potential.

•Governments outside of the United States tend to impose strict price controls, which may adversely affect our revenues, if any.

•If the FDA or other applicable regulatory authorities approve generic products that compete with Rezdiffra, the sales of Rezdiffra would be adversely affected.

•We currently rely on a limited number of specialty pharmacies for distribution of Rezdiffra in the United States, and the loss of one or more of these specialty pharmacies or their failure to effectively distribute Rezdiffra would materially harm our business.

•If estimates of the size of the potential market for Rezdiffra is overstated or data we have used to identify physicians is inaccurate, our ability to earn revenue could be materially adversely affected.

•Product liability lawsuits brought against us could cause us to incur substantial liabilities and could limit commercialization of Rezdiffra or any future product candidates that we may develop.

•Pharmaceutical research and development is very expensive, time-consuming and difficult to design and implement and involves uncertain outcomes. Furthermore, the results of preclinical studies and earlier clinical trials are not always predictive of future results. Any product candidate that we advance into clinical trials may not have favorable results in later clinical trials or receive regulatory approval.

•If we fail to develop and commercialize other product candidates, we may be unable to grow our business.

•Interim, topline and preliminary data from our clinical trials that we announce or publish from time to time may change as more data become available, may be interpreted differently if additional data are disclosed and are subject to audit and verification procedures that could result in material changes in the final data.

•If clinical trials or regulatory approval processes are prolonged, delayed or suspended, we may be unable to advance the development of or commercialize our product candidates on a timely basis, which would require us to incur additional costs and delay our receipt of any revenue from potential product sales.

•If we fail to comply with foreign regulatory requirements governing human clinical trials and marketing approval for drugs, we could be prevented from selling our drug candidates in foreign markets.

•We depend on enrollment of patients in our clinical trials. If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected.

•We are dependent on retaining and attracting key personnel, the loss of whose services could materially adversely affect our business, financial condition, results of operations, prospects and the value of our common stock.

•We expect to continue to expand our development and commercialization capabilities, and as a result, we may encounter challenges in managing our growth, which could disrupt our operations.

•Any strategic transactions we enter into may not be clinically or commercially successful and may require financing or a significant amount of cash, which could adversely affect our business.

•A failure of our information technology infrastructure and cybersecurity threats may adversely affect our business and operations.

•If the third parties on which we rely for the conduct of our clinical trials and results do not perform our clinical trial activities in accordance with good clinical practices and related regulatory requirements, we may be unable to obtain regulatory approval for or commercialize our product candidates.

•Adverse consequences to our business could result if our manufacturing partners fail to comply with applicable regulations or our agreements or fail to maintain required approvals.

•We have a history of operating losses, expect to incur operating losses in the future and may never achieve or maintain profitability.

•We may need to raise additional capital to fund our operations, but we may not be able to access capital.

•Our Loan and Security Agreement with Hercules Capital, Inc. contains restrictive and financial covenants that may limit our operating flexibility.

•Government healthcare reform could materially increase our costs, which could materially adversely affect our business, financial condition, results of operations, prospects and the value of our common stock.

•If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate program or other governmental pricing programs, we could be subject to additional rebate requirements, penalties or other sanctions.

•If we are found to be in violation of federal or state “fraud and abuse” laws, we may be required to pay a penalty or may be suspended from participation in federal or state healthcare programs.

•Our rights to develop and commercialize our product candidates are subject in part to the terms and conditions of a license to resmetirom granted to us by Roche.

•Our success depends on our ability to protect our intellectual property and our proprietary technologies.

•The price of our common stock has been, and may continue to be, volatile.