MADRIGAL PHARMACEUTICALS, INC.

Madrigal Pharmaceuticals is 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, liver cancer, need for liver transplantation and premature mortality. MASH is the leading cause of liver transplantation in women, the second leading cause of all liver transplantation in the United States and the fastest-growing indication for liver transplantation in Europe.

The development and commercialization of drugs in MASH is highly competitive. Rezdiffra was the first medication approved by both the FDA and EC for the treatment of MASH with moderate to advanced fibrosis. Since then, semaglutide, a GLP-1 agonist developed and commercialized by Novo Nordisk A/S, was approved for the treatment of MASH by the FDA and is pending approval in the EU. There are more than 140 drugs in development for MASH by companies ranging in size from small biotechnology companies to large pharmaceutical organizations. Other companies are conducting Phase 3 trials, including Novo, Inventiva S.A., Roche, Eli Lilly and Boehringer Ingelheim International GmbH. In addition, there are 51 investigational therapies being evaluated in Phase 2 clinical trials in MASH. The company believes that Rezdiffra's product profile and first-to-market advantage provide meaningful points of differentiation in the MASH competitive landscape.

Madrigal generates revenue from the sale of Rezdiffra, its only approved product, which is a once-daily, oral, liver-directed thyroid hormone receptor beta (THR-β) agonist designed to target key underlying causes of MASH. Revenue is recognized at the point in time when the customer obtains control of promised goods or services. Revenue is recorded net of variable consideration, which includes prompt pay discounts, returns, chargebacks, rebates and co-payment assistance. Rezdiffra is distributed in the United States through a network of specialty pharmacy providers that deliver Rezdiffra to patients.

Rezdiffra is the company's first and only approved product. It received accelerated approval from the FDA in March 2024 in conjunction with diet and exercise for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). In August 2025, the EC granted a conditional marketing authorization (CMA) for Rezdiffra, making it the first medication approved by both the FDA and EC for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis. The company is also evaluating Rezdiffra in patients with compensated MASH cirrhosis (consistent with F4c fibrosis) in its MAESTRO-NASH OUTCOMES trial. The company's pipeline includes MGL-2086, an oral GLP-1 receptor agonist; ervogastat, an oral DGAT2 inhibitor; and six siRNA programs. For the year ended December 31, 2025, the company generated $958.4 million ¹ in product revenue from sales of Rezdiffra.

In July 2025, the company entered into a Financing Agreement with certain funds managed by Blue Owl Capital Corporation as the lenders and LSI Financing LLC as the administrative agent, committing up to $500.0 million ² in senior secured credit facilities, consisting of an initial term loan of $350.0 million ³ and delayed draw term loans of up to $150.0 million ⁴. In July 2025, the company entered into an exclusive global license agreement with CSPC Pharmaceutical Group Limited for MGL-2086, an oral GLP-1 receptor agonist. In August 2025, the EC granted a CMA for Rezdiffra, and the company launched Rezdiffra in Germany in September 2025. In December 2025, the company acquired an exclusive global license for ervogastat, a Phase 2 oral DGAT-2 inhibitor, from Pfizer. In February 2026, the company announced an exclusive global license agreement with Suzhou Ribo Life Science Co. Ltd. and Ribocure Pharmaceuticals AB for six novel siRNA programs.

For the year ended December 31, 2025, the company generated $958.4 million ⁵ in product revenue, net, compared to $180.1 million ⁶ in 2024. Net loss was $288.3 million ⁷ for 2025, compared to $465.9 million ⁸ in 2024. As of December 31, 2025, the company had cash, cash equivalents, restricted cash and marketable securities totaling $988.6 million ⁹ compared to $931.3 million ¹⁰ as of December 31, 2024. The accumulated deficit was $2,090.5 million ¹¹ as of December 31, 2025.

A key growth vector is expanding Rezdiffra's label to treat patients with compensated MASH cirrhosis (F4c), which currently has no approved treatments available. The company has fully enrolled its Phase 3 MAESTRO-NASH OUTCOMES trial evaluating Rezdiffra in patients with compensated MASH cirrhosis, and expects a data readout from this trial in 2027. A positive outcome is expected to support the full approval of Rezdiffra in the United States for moderate to advanced liver fibrosis (F2 to F3 fibrosis) and an additional indication for Rezdiffra in patients with F4c, which the company believes could double Rezdiffra's commercial opportunity. The company also expects to launch Rezdiffra in other international markets over time.

Another growth vector is building an industry-leading MASH pipeline through business development. The company has added several product candidates, including MGL-2086, ervogastat and multiple siRNA programs. The company expects to initiate a single ascending dose study of MGL-2086 in the second quarter of 2026. In 2026, the company expects to conduct a drug-to-drug interaction study with ervogastat and resmetirom, and expects to initiate a Phase 2 combination trial with ervogastat and resmetirom in 2027 following discussions with the FDA. IND-enabling activities in initial siRNA candidates are expected to begin in 2026.

The filing does not contain specific margin or cost outlook figures.

The company does not own or operate, and currently has no plans to establish, any manufacturing facilities. It currently relies on third-party contract manufacturers for all required starting materials, active pharmaceutical ingredients and finished product. In December 2024, the company entered into a Resmetirom Commercial Supply Agreement with Evonik Corporation, with an initial term expiring on December 31, 2029 ¹² and automatically renewed for successive two-year periods. In August 2023, the company entered into a Commercial Supply Agreement with UPM Pharmaceuticals, Inc. for the primary commercial supply of Rezdiffra tablets in the United States, with an initial term expiring in April 2032 ¹³. The company has also entered into a supply agreement with Corden Pharma GmbH for the primary commercial supply of Rezdiffra tablets in Europe, with an initial term expiring in 2029 ¹⁴.

Research and development expenses were $388.5 million ¹⁵ for the year ended December 31, 2025. The company did not report specific capital expenditure plans. As of December 31, 2025, $300.0 million ¹⁶ remained available for sale under the Sales Agreement and its related prospectus supplement. The company has not paid any cash dividends on its common stock and does not anticipate paying any cash dividends in the foreseeable future.

The company faces headwinds including the highly competitive environment for MASH treatments, with over 140 drugs in development. The company also faces risks related to obtaining and maintaining adequate coverage and reimbursement from government and third-party payors, as well as the impact of healthcare reform legislation such as the Inflation Reduction Act of 2022, which includes provisions that may impact the business, including a $2,000 ¹⁷ out-of-pocket cap for Medicare Part D beneficiaries and the imposition of new manufacturer financial liability on most drugs in Medicare Part D.

The company faces constraints related to its dependence on a limited number of specialty pharmacies for distribution of Rezdiffra in the United States, which account for substantially all of its revenue in the U.S. The company also faces risks associated with operations outside of the United States, including multiple, conflicting and changing laws and regulations, difficulties in staffing and managing operations in diverse countries, and complexities associated with managing government payor systems.

The company is highly dependent on the success of its only approved product, Rezdiffra, which was approved under the accelerated approval pathway in the U.S. and conditional marketing authorization in the EU. Full approvals are contingent on completing trials to successfully confirm clinical benefit, and failure to meet post-marketing commitments could result in withdrawal of approvals. The company operates in a highly competitive environment with over 140 drugs in development for MASH. The company has a history of operating losses, with an accumulated deficit of $2,090.5 million ¹⁸ as of December 31, 2025, and expects to continue incurring operating losses. The company's Financing Agreement requires maintenance of a minimum unrestricted cash balance of $100.0 million ¹⁹ at all times, and contains restrictive covenants that may limit operating flexibility. The company's rights to develop and commercialize resmetirom are subject to the terms of the Roche Agreement, and any uncured material breach could result in loss of exclusive rights.

Management's message emphasizes the company's tremendous growth in 2025, highlighted by strong commercial execution. For the year ended December 31, 2025, the company generated $958.4 million ²⁰ in product revenue from sales of Rezdiffra. Management states that with quarterly sales now annualizing at greater than $1.0 billion ²¹ as of December 31, 2025 and a low market penetration rate, the company believes it is well positioned to continue to deliver on this strategic priority. The strategic priorities emphasized for the period ahead are: maximizing the value of Rezdiffra, delivering transformational outcomes data in F4c, and building an industry-leading MASH pipeline.