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Item 1. Business

2026-02-19 compared with 2025-02-26 · 299 added, 228 removed, 486 unchanged (52% of the section changed)

Executive 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.

MASH was previously known as nonalcoholic steatohepatitis (“NASH”).

In 2023, global liver disease medical societies and patient groups came together to rename the disease, with the goal of establishing an affirmative, non-stigmatizing name and diagnosis.

Food and Drug Administration (the “FDA”) considers the term NASH interchangeable with MASH.

MASH is expected to become the leading cause of liver transplantation in the United States and is already the leading cause of liver transplantation among women in the United States.

Our medication, Rezdiffra (resmetirom), is a once-daily, oral, liver-directed thyroid hormone receptor (“THR-β”) agonist designed to target key underlying causes of MASH.

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.

Rezdiffra is indicated 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).

The FDA's accelerated approval and Rezdiffra's approved prescribing information was 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 (“NAFLD”) activity score.

As part of the post-marketing commitments agreed to with the FDA, MAESTRO-NASH 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, full approval in noncirrhotic MASH could also be based on results from our Phase 3 MAESTRO-NASH OUTCOMES trial.

In this trial, we are assessing progression to liver decompensation events in patients with compensated MASH cirrhosis treated with Rezdiffra versus placebo.

A positive outcome in this trial is also expected to support the full approval of Rezdiffra for noncirrhotic MASH, and expand the eligible patient population for Rezdiffra with an additional indication in patients with compensated MASH cirrhosis.

2024 Highlights

We experienced a transformational year in 2024, highlighted by the following key events:

• In March 2024, we announced that the FDA granted accelerated approval of Rezdiffra 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).

The FDA approved 60 mg, 80 mg and 100 mg doses.

Rezdiffra became commercially available in April 2024 as the first and only approved therapy for MASH.

• In March 2024, we announced that our marketing authorization application (“MA”) for resmetirom for the treatment of MASH with liver fibrosis was validated and is under evaluation with the European Medicines Agency’s (“EMA”) Committee for Medicinal Products for Human Use (“CHMP”).

The CHMP opinion and subsequent decision regarding the Conditional Marketing Authorization by the European Commission (“EC”) in the European Union (“EU”) is expected in mid-2025.

Pending regulatory approval, we expect to launch Rezdiffra in Europe on a country-by-country basis commencing with Germany in the second half of 2025.

• Following FDA approval, we raised $659.9 million in net proceeds from an underwritten public offering.

We intend to use the net proceeds from this offering for our commercial activities in connection with the launch of Rezdiffra in the United States and general corporate purposes, including, without limitation, research and development expenditures, ongoing clinical trial expenditures, manufacture and supply of drug substance and drug products, ex-U.S.

commercialization or potential partnering opportunities, potential acquisitions or licensing of new technologies, capital expenditures and working capital.

• In June 2024, we announced new data from the Phase 3 MAESTRO-NASH trial of Rezdiffra presented at the European Association for the Study of the Liver (the “EASL”) Congress.

During the congress,

the EASL updated their practice guidelines to recommend Rezdiffra as a first-line therapy for MASH, subject to regulatory approval in Europe.

• In September 2024, we announced the publication of health-related quality of life results from the Phase 3 MAESTRO-NASH trial of Rezdiffra.

Patients treated with Rezdiffra experienced clinically meaningful and statistically significant improvements in emotional well-being and health distress.

The results were published in the journal Hepatology .

• In October 2024, the American Association for the Study of Liver Diseases (“AASLD”), a leading organization of scientists and health care professionals committed to preventing and curing liver disease, updated their practice guidance to recommend Rezdiffra as a first-line therapy for MASH and implement recommendations regarding its use for practicing clinicians.

• In October 2024, we announced that we completed enrollment in the MAESTRO-NASH OUTCOMES trial evaluating Rezdiffra for the treatment of 845 patients with compensated MASH cirrhosis.

This event-driven trial is expected to deliver results in 2027.

Positive results from this trial could position Rezdiffra as the only treatment for F2 to F4 MASH and the only therapy with outcomes data this decade.

• In November 2024, we presented 11 Rezdiffra and health economics research abstracts at the AASLD Liver Meeting.

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.

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 therapy approved by the FDA for patients with MASH and was commercially available in the United States beginning in April 2024.

Following receipt of conditional marketing authorization (“CMA”) from the European Commission (“EC”), we launched Rezdiffra in Germany in September 2025.

Rezdiffra was the first medication approved by both the FDA and EC for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis (F2 to F3 fibrosis).

We are also evaluating Rezdiffra in patients with compensated MASH cirrhosis (consistent with F4c fibrosis) in our MAESTRO-NASH OUTCOMES trial, that, if successful, could expand the eligible patient population for Rezdiffra.

In addition, we are advancing a focused pipeline to lead the evolution of MASH treatment for patients for decades to come.

Through our business development efforts, we have acquired rights to MGL-2086, an oral glucagon-like peptide-1 (“GLP-1”) receptor agonist, ervogastat, an oral diacylglycerol O-acyltransferase 2 (“DGAT2”) inhibitor, six small interfering RNA (“siRNA”) programs and additional preclinical MASH candidates.

We plan to evaluate these candidates with the goal of delivering best-in-disease therapies for the treatment of MASH.

As we continue to build our pipeline, we will evaluate mechanisms that fit scientifically, strategically and commercially to enhance our leading position in MASH care.

Key 2025 and Recent Highlights

We experienced tremendous growth in 2025, highlighted by our strong commercial execution.

For the year ended December 31, 2025, we generated $958.4 million in product revenue from sales of Rezdiffra.

In addition, 2025 featured the following key achievements:

• In May 2025, we announced positive two-year results from the open-label compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial of Rezdiffra.

Patients (n=122) achieved significant improvements from baseline in liver stiffness, liver fat, fibrosis biomarkers, liver volume and risk scores for clinically significant portal hypertension (“CSPH”).

The results were presented in a late-breaking oral abstract at the European Association for the Study of the Liver (“EASL”) Congress.

In addition, in November 2025, we announced additional data showing Rezdiffra’s impact in patients with more advanced compensated MASH cirrhosis (those with a platelet count of <100,000/µL at baseline).

In this patient population, Rezdiffra demonstrated improvements from baseline across multiple imaging tests and biomarkers including liver stiffness, liver enzymes and lipids, as well as Baveno risk scores for CSPH.

• In July 2025, we announced that we received a Notice of Allowance from the U.S.

Patent and Trademark Office for a new U.S.

patent covering the FDA-approved use of Rezdiffra.

The patent, which was issued on August 5, 2025, includes claims directed to Rezdiffra’s commercial weight-threshold dosing regimen as prescribed in the FDA-approved label.

patent provides protection to February 2045 and was listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book, in August 2025.

• In July 2025, we entered into a Financing Agreement (as amended, the “Financing Agreement”) with certain funds managed by Blue Owl Capital Corporation as the lenders (the “Lenders”) and LSI Financing LLC as the administrative agent for the Lenders (the “Administrative Agent”).

Under the Financing Agreement, the Lenders committed up to $500.0 million in senior secured credit facilities, consisting of (a) an initial term loan in an aggregate principal amount equal to $350.0 million (the “Initial Term Loan”) and (b) delayed draw term loans in an aggregate principal amount not to exceed $150.0 million (the loans thereunder, if any, the “Delayed Draw Term Loans”).

In addition, the Financing Agreement includes an uncommitted incremental facility in an aggregate principal amount not to exceed $250.0 million (the loans thereunder, if any, the “Incremental Term Loans,” and together with the Initial Term Loan and any Delayed Draw Term Loans, collectively, the “Term Loans”), subject to the satisfaction of certain terms and conditions set forth in the Financing Agreement.

The Initial Term Loan was funded on July 17, 2025.

Delayed Draw Term Loans are available at our election from time to time until December 31, 2027.

Incremental Term Loans are available at our and the Lenders’ mutual consent from time to time.

• In July 2025, we entered into an exclusive global license agreement (the “CSPC License Agreement”) with CSPC Pharmaceutical Group Limited (“CSPC”) for MGL-2086 (formerly SYH2086), an oral GLP-1 receptor agonist.

Pursuant to the CSPC License Agreement, CSPC granted us an exclusive global license to develop, manufacture and commercialize MGL-2086.

We expect to initiate a single ascending dose study of MGL-2086 in the second quarter of 2026.

• In August 2025, we announced that the EC granted a CMA for Rezdiffra for the treatment of MASH with moderate to advanced liver fibrosis.

We launched Rezdiffra in Germany in September 2025.

Rezdiffra was the first medication approved for patients with MASH in the European Union and is included in the European MASH treatment guidelines.

• In January 2026, we announced the expansion of our pipeline with an exclusive global license for ervogastat, a Phase 2 oral DGAT-2 inhibitor.

DGAT-2 inhibitors work by blocking the final step in triglyceride assembly and storage, resulting in lower hepatic triglycerides, reduced lipotoxic fat and decreased inflammation.

In 2026, we plan to conduct a drug-to-drug interaction study with resmetirom and consult with the FDA on the design of a Phase 2 combination trial.

• In February 2026, we announced an exclusive global license agreement (the “Ribocure License Agreement”) with Suzhou Ribo Life Science Co.

and Ribocure Pharmaceuticals AB (together, “Ribocure”) for six novel siRNA programs designed to silence certain genes implicated in MASH disease progression.

By pairing the precision of gene-silencing with Rezdiffra, we are exploring

whether reducing drivers of disease at the genetic level can complement Rezdiffra’s therapeutic effects.

IND-enabling activities in initial candidates are expected to begin in 2026.

The critical components of our business strategy include the following:

Successfully execute on a first-in-disease launch .

Rezdiffra became the first FDA-approved therapy for the treatment of MASH in March 2024 and was commercially available beginning in April 2024.

We have established a full capability commercial organization, including marketing, sales and market access expertise, to support the launch of Rezdiffra in the United States.

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, engaging with payers to increase Rezdiffra coverage and supporting 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.

Deepen our commitment to MASH .

We intend to maximize the value of Rezdiffra by broadening its indication.

We have fully enrolled our Phase 3 MAESTRO-NASH OUTCOMES trial evaluating Rezdiffra in patients with compensated MASH cirrhosis.

A positive outcome from this trial is expected to support the full approval of Rezdiffra for noncirrhotic MASH and an additional indication for Rezdiffra in patients with compensated MASH cirrhosis.

We will continue to evaluate opportunities to expand Rezdiffra's label and generate new data to maintain its leadership position in the MASH treatment landscape.

Drive future growth through geographic expansion .

Rezdiffra is currently under evaluation with the CHMP and has the potential to become the first therapy for patients with MASH with liver fibrosis to receive approval in Europe.

The CHMP opinion and the subsequent decision regarding the Conditional Marketing Authorization by the EC in the EU are expected in mid-2025.

Pending regulatory approval, we expect to directly launch Rezdiffra in Europe on a country-by-country basis, expected to commence with Germany in the second half of 2025.

In anticipation of a favorable regulatory decision, we have begun establishing commercial capabilities in Europe.

In addition, we may evaluate potential partnership or out-license opportunities to develop and commercialize Rezdiffra in markets outside of the United States and Europe.

Acquire rights to drug development candidates, commercial products and technologies .

We plan to selectively in-license or acquire rights to programs at all stages of development and commercial products to take advantage of our drug development and commercial capabilities.

With a goal of building a well‑balanced and diversified portfolio, we assess a variety of factors for potential product candidates and technologies.

Our criteria for possible acquisition or in-licensing opportunities include the rationale for addressing the targeted disease, likelihood of regulatory approval, commercial viability, intellectual property protection, prospects for favorable pricing and reimbursement and competition.

We intend to be opportunistic in our business development activities to achieve our long-term strategic goals.

Maximize the value of Rezdiffra.

We generated $958.4 million in net product revenue from sales of Rezdiffra in 2025.

With quarterly sales now annualizing at greater than $1.0 billion as of December 31, 2025 and a low market penetration rate, we believe we are well positioned to continue to deliver on this strategic priority.

We have secured broad first-line access across commercial payers through our payer contracting efforts and believe that we will continue to steadily add patients through 2026.

In the United States, we continue to educate healthcare providers and patients on the risks of MASH and the potential clinical benefits and appropriate use of Rezdiffra and believe that the MASH market will continue to grow significantly over time given low MASH diagnosis rates today.

We also launched Rezdiffra in Germany in September 2025 and expect to launch Rezdiffra in other international markets over time.

We continue to believe that 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.

Deliver transformational outcomes data in F4c.

A key component of our strategy is to expand Rezdiffra’s label to treat patients with compensated MASH cirrhosis (F4c), which currently has no approved treatments available.

We have fully enrolled our Phase 3 MAESTRO-NASH OUTCOMES trial evaluating Rezdiffra in patients with compensated MASH cirrhosis, and we expect a data readout from this trial in 2027.

A positive outcome from this trial 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 we believe could double Rezdiffra’s commercial opportunity.

In 2025, we announced positive two-year data from a 122-patient open label cohort from our MAESTRO-NAFLD-1 trial evaluating Rezdiffra in the F4c patient population, reinforcing our confidence in receiving positive results from our OUTCOMES trial.

We plan to continue to evaluate opportunities to expand Rezdiffra’s label and generate new data to maintain our leadership position in the MASH treatment landscape.

Build an industry-leading MASH pipeline.

MASH is a complex and heterogeneous disease, and we expect future treatment will include multiple therapies, combinations and personalized regimens.

Through our business development efforts, we have added several product candidates to our pipeline, including MGL-2086, ervogastat and multiple siRNA programs, and we plan to continue to invest in new mechanisms with complementary biology and combination potential with resmetirom.

We expect to initiate clinical testing of our product candidates with the goal of delivering enhanced efficacy across the MASH spectrum.

By leveraging our research and development capabilities that pioneered MASH treatment, we believe we will be able to design and advance more informative clinical trials and progress the most promising programs to later stage testing in a capital efficient manner.

With patent protection for Rezdiffra expected into 2045, we believe we have a long runway to invest in innovative therapies and build a pipeline that will define the future of MASH care.

Rezdiffra for Patients with MASH

Rezdiffra is our first and only approved product.

Rezdiffra received accelerated approval on March 14, 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).

Rezdiffra 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 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.

Rezdiffra is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of MASH.

Marketing Approval of Rezdiffra

Rezdiffra was granted Breakthrough Therapy designation in April 2023, and we completed the submission of our New Drug Application (“NDA”) to the FDA in July 2023 pursuant to Section 506(c) of the Federal Food, Drug and Cosmetic Act and 21 C.F.R.

Approval of Rezdiffra

In March 2024, the FDA granted accelerated approval for Rezdiffra for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis (F2 to F3 fibrosis) pursuant to section 506(c) of the Federal Food, Drug and Cosmetic Act and 21 C.F.R.

Part 314 Subpart H (Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses) (Subpart H).

Accelerated approval allows drugs that (i) are being developed to treat a serious or life-threatening disease or condition and (ii) provide a meaningful therapeutic benefit over existing treatments to be approved substantially based on an intermediate endpoint or a surrogate endpoint that is reasonably likely to predict clinical benefit, rather than a clinical endpoint such as survival or irreversible morbidity.

The FDA granted our request for priority review of our NDA and assigned a Prescription Drug User Fee Act (“PDUFA”) date of March 14, 2024.

On the PDUFA date, the FDA granted accelerated approval for Rezdiffra.

The FDA's accelerated approval and Rezdiffra's approved prescribing information were supported by results from our Phase 3 MAESTRO-NASH trial and additional safety data from the Phase 3 MAESTRO-NAFLD-1 and MAESTRO-NAFLD-OLE extensions trials, each of which was 52-weeks in duration.

Following 52 weeks of treatment in the MAESTRO-NASH trial, both 100 mg and 80 mg doses of Rezdiffra demonstrated statistically significant improvement compared to placebo on two primary endpoints:

MASH resolution (including a reduction in the NAFLD activity score by ≥ 2 points) with no worsening of fibrosis, and an improvement in fibrosis by at least one stage with no worsening of the NAFLD activity score.

See the section titled “—Clinical Trial Overview” in this Annual Report for additional information on our clinical trials for Rezdiffra.

In connection with the FDA's accelerated approval, we have agreed to certain post-marketing commitments, including completing our MAESTRO-NASH trial to demonstrate a clinical benefit of Rezdiffra on composite endpoints.

In addition, in June 2025, we received a positive opinion from the Committee for Medicinal Products for Human Use (“CHMP”) of the EMA recommending the granting of a CMA of resmetirom for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis (F2 to F3 fibrosis).

The EC issued a decision to grant the CMA for Rezdiffra in August 2025.

The EC decision is valid in all 27 member states of the European Union, as well as in Iceland, Liechtenstein and Norway.

The FDA’s accelerated approval and the EC’s CMA, as well as Rezdiffra’s approved prescribing information, were supported by results from our Phase 3 MAESTRO-NASH trial and additional safety data from the Phase 3 MAESTRO-NAFLD-1 and MAESTRO-NAFLD-OLE extensions trials, each of which was 52 weeks in duration.

Following 52 weeks of treatment in the MAESTRO-NASH trial, both 100 mg and 80 mg doses of

Rezdiffra demonstrated statistically significant improvement compared to placebo on two primary endpoints:

MASH resolution (including a reduction in the non-alcoholic fatty liver disease (“NAFLD”) activity score by ≥ 2 points) with no worsening of fibrosis, and an improvement in fibrosis by at least one stage with no worsening of the NAFLD activity score.

See the section titled “—Clinical Trial Overview” in this Annual Report for additional information on our clinical trials for resmetirom.

In connection with Rezdiffra’s approvals, we have agreed to certain post-marketing commitments, including completing our MAESTRO-NASH trial to demonstrate a clinical benefit of Rezdiffra on composite endpoints.

Patients enrolled in the MAESTRO-NASH trial have continued on therapy after the initial 52-week treatment period for up to 54 months to accrue and measure hepatic clinical outcome events, including progression to cirrhosis on biopsy and hepatic decompensation events, as well as all-cause mortality.

Positive confirmatory outcomes data from this trial is expected to verify a clinical benefit and support the full approval of Rezdiffra in noncirrhotic MASH.

We expect outcomes data from this trial in 2028.

Positive confirmatory outcomes data from this trial is expected to verify a clinical benefit and support the full approval of Rezdiffra in noncirrhotic MASH in the United States.

Separate from our commitment to complete the MAESTRO-NASH trial, we have fully enrolled our Phase 3 MAESTRO-NASH OUTCOMES trial, which is a double-blind, randomized, placebo-controlled trial that noninvasively measures progression to liver decompensation events in patients with compensated MASH cirrhosis.

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We expect results from the OUTCOMES trial in 2027.

Positive data from our MAESTRO-NASH OUTCOMES trial may also support the full approval of Rezdiffra in noncirrhotic MASH and support approval for patients with compensated cirrhosis, expanding the eligible patient population.

Positive data from our MAESTRO-NASH OUTCOMES trial is expected to support the full approval of Rezdiffra in noncirrhotic MASH (F2 to F3 fibrosis) in the United States and support approval for patients with compensated cirrhosis (F4c), expanding the eligible patient population for Rezdiffra.

We have agreed to submit results from these trials to the EMA in support of transitioning the Rezdiffra CMA into a standard marketing authorization in the European Union.

Market Opportunity for Rezdiffra in MASH

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In addition, MASH patients with moderate to advanced fibrosis (consistent with fibrosis stages F2 and F3) have a 10- to 17-times higher risk of liver-related mortality.

MASH is also an independent driver of cardiovascular disease, which is the leading cause of mortality for patients.

In addition to the accumulation of fat in the liver, MASH is characterized by inflammation and cellular damage with or without fibrosis, which may ultimately progress to cirrhosis.

Within MASH cirrhosis, patients can be categorized as being compensated or decompensated.

MASH with compensated cirrhosis is characterized by liver scarring or damage that reduces the ability to process blood supplied to the liver, though patients generally remain asymptomatic with normal liver function.

MASH with compensated cirrhosis (consistent with F4c fibrosis) is characterized by liver scarring or damage that reduces the ability to process blood supplied to the liver, though patients generally remain asymptomatic with normal liver function.

MASH patients with compensated cirrhosis are on the cusp of negative consequences associated with end-stage liver disease including decompensation, esophageal varices, ascites, hepatic encephalopathy, liver cancer and liver failure.

Progression to cirrhosis and other late-stage complications can occur within five to ten years after an initial MASH diagnosis.

MASH patients with type-2 diabetes have a heightened risk of MASH disease progression.

Patients with compensated MASH cirrhosis have a 42-times higher risk of liver-related mortality, underscoring the need to treat MASH before complications of cirrhosis develop.

Progression to cirrhosis generally occurs in approximately 20% of MASH patients with moderate-to-advanced fibrosis and can occur within ten to fifteen years from initial diagnosis.

Further, approximately 20% of patients with advanced fibrosis (stage F3) will progress to cirrhosis in approximately two years.

MASH patients with type-2 diabetes have a heightened risk of MASH disease progression, with an estimated two-to-three times faster rate of progression of fibrosis.

Once the disease advances beyond MASH to such life-threatening conditions as liver cancer or liver failure, liver transplantation is the only treatment alternative.

MASH is the leading cause of liver transplants for women in the United States and is expected to become the leading cause of liver transplants overall.

MASH is the leading cause of liver transplants for women, the second leading cause of all liver transplantation in the United States, and the fastest-growing indication for liver transplantation in Europe.

With more advanced liver disease as a result of unaddressed MASH with fibrosis, the burden to the healthcare system in terms of healthcare resource utilization and cost increases, driven by hospitalization due to decompensated disease, treatment of hepatocellular carcinoma and liver transplants.

Importantly, due to the limited availability of donor organs and the comorbidities associated with MASH,

patients with MASH who are put on the transplant list are at much lower odds of actually getting transplanted relative to those with liver disease driven by other causes.

Importantly, due to the limited availability of donor organs and the comorbidities associated with MASH, patients with MASH who are put on the transplant list are at much lower odds of actually getting transplanted relative to those with liver disease driven by other causes.

As such, Rezdiffra addresses a significant unmet medical need for patients with MASH.

Commercial Strategy

We launched Rezdiffra in the United States in April 2024.

Prior to receiving FDA approval, we conducted quantitative and qualitative market research studies and secondary data analytics to inform the commercial strategy for Rezdiffra.

We launched Rezdiffra in the United States in April 2024 and in Germany in September 2025.

Prior to receiving approval, we conducted quantitative and qualitative market research studies and secondary data analytics to inform the

commercial strategy for Rezdiffra.

These studies and analytics evaluated the size of the market opportunity for Rezdiffra as well as physician, patient and payer perspectives on unmet needs in MASH patient care and the Rezdiffra product profile.

Based on published epidemiology data and an analysis of medical claims using ICD-10 disease diagnosis codes, we estimate that approximately 1.5 million patients have been diagnosed with MASH in the United States, of which approximately 525,000 have MASH with moderate to advanced fibrosis.

We estimate that approximately 315,000 diagnosed patients with MASH with moderate to advanced fibrosis are under the care of approximately 14,000 specialist prescribers which we are targeting during the commercial launch of Rezdiffra.

Over time, as disease awareness improves and disease prevalence increases, we expect the number of identified MASH patients with moderate to advanced fibrosis eligible for treatment to grow.

Given that Rezdiffra is a first-in-disease launch, we continue to focus our efforts on educating healthcare providers and patients on the risks of MASH and the potential clinical benefits and appropriate use of Rezdiffra.

We also expect to directly commercialize resmetirom in Europe if we receive a positive CHMP opinion and the subsequent grant of Conditional Marketing Authorization by the EC in the EU.

A regulatory decision in the EU is expected in mid-year 2025.

The prevalence rate of MASH in Europe is similar to that of the United States.

In the event of a positive decision, we expect to launch Rezdiffra in Europe on a country-by-country basis, commencing with Germany in the second half of 2025.

To support our planned launch in Europe, we have hired a Head of International and other individuals to serve in a number of other key leadership positions, established our European headquarters in Switzerland and engaged a manufacturer for the primary supply of our commercial product in Europe.

We also intend to employ European sales and marketing personnel on a country-by-country basis.

Based on published epidemiology data and an analysis of medical claims using ICD-10 disease diagnosis codes as of 2023, we estimate that 315,000 patients diagnosed with MASH with moderate to advanced fibrosis (stages F2 to F3) are under the care of specialist prescribers which we are targeting during the launch of Rezdiffra in the U.S.

In addition, we estimate that approximately 370,000 patients with MASH with moderate to advanced fibrosis are currently diagnosed and under the care of specialists across Europe.

We believe the number of patients under specialist care in the U.S.

has grown nearly 50% through 2025, and as disease awareness improves and disease prevalence increases, we expect the number of identified MASH patients with moderate to advanced fibrosis eligible for treatment to grow significantly going forward.

With a growing body of real-world supportive data, we continue to educate healthcare providers and patients on the risks of MASH and the potential clinical benefits and appropriate use of Rezdiffra.

During our first six quarters of launch in the United States, we focused our efforts on hepatologists and gastroenterologists.

Beginning in the fourth quarter of 2025, we expanded our field team to further target select endocrinologists that provide care to MASH patients.

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.

Beyond Germany, we expect to launch Rezdiffra on a country-by-country basis in Europe dependent on multiple factors, including the completion of reimbursement procedures and regulatory approval where required.

In addition, we may enter into distribution agreements with third parties to distribute Rezdiffra in smaller European countries and in other jurisdictions globally.

Clinical Trial Overview

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This trial remains ongoing as part of our post-marketing commitments to the FDA.

The 54-month outcomes portion of the trial is designed to generate confirmatory data that, if positive, is expected to verify a clinical benefit and support the full approval of Rezdiffra in noncirrhotic MASH.

We expect outcomes data from this trial in 2028.

• The MAESTRO-NAFLD-1 (Safety) trial was a 52-week trial that noninvasively evaluated the safety and tolerability of resmetirom and provided a larger safety database to support regulatory benefit-risk assessment.

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MAESTRO-NAFLD-OLE, an open-label active treatment extension of MAESTRO-NAFLD-1, is ongoing to collect additional data in patients with noncirrhotic MASH and patients with compensated MASH cirrhosis.

In 2025, we announced positive two-year data from the open-label compensated MASH cirrhosis (F4c) arm of this trial.

• MAESTRO-NASH OUTCOMES (Compensated Cirrhosis) is ongoing to evaluate progression to liver decompensation events in patients with compensated MASH cirrhosis treated with resmetirom versus placebo.

A positive outcome is expected to support the full approval of Rezdiffra for noncirrhotic MASH and expand the eligible patient population for Rezdiffra with an additional indication in patients with compensated MASH cirrhosis.

A positive outcome is expected to support the full approval of Rezdiffra for noncirrhotic MASH in the United States and expand the eligible patient population for Rezdiffra with an additional indication in patients with compensated MASH cirrhosis.

This event-driven trial is expected to deliver results in 2027.

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The primary efficacy analysis assessed histological response at 52 weeks in 955 patients with biopsy-confirmed MASH with significant fibrosis (modified intent-to-treat (mITT) population) that excluded 11 intent-to-treat patients who had their Week 52 biopsy after Week 60 due to COVID-related reasons per regulatory guidelines.

Patients without a second biopsy due to early trial discontinuation or missing liver biopsy (approximately 17% across treatment arms) were included and considered as non-responders in the primary efficacy analyses (mITT).

Patients without a second biopsy due to early trial discontinuation or missing liver biopsy (approximately 17% across treatment arms) were included and considered as non-

responders in the primary efficacy analyses (mITT).

The compliance to treatment was high and minimally impacted by COVID-19 pandemic restrictions.

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LDL-C lowering (24 weeks)

All biopsies were read independently by two central pathologists.

Each pathologist’s scores showed a similar statistically significant magnitude of response at both doses for both liver biopsy endpoints.

Biopsy endpoints were achieved independent of baseline fibrosis stage or diabetes status, including similar statistical significance and magnitude of effect at both doses in subgroups of F2, F3 and F2/F3 patients.

Other secondary liver biopsy endpoints that were achieved at both doses include ≥2 point reduction in NAS with no worsening of fibrosis, ≥2 point reduction in NAS with ≥1-stage improvement in fibrosis, MASH resolution (with ≥2 point reduction in NAS) with ≥1-stage improvement in fibrosis and a 2-stage reduction in fibrosis without worsening of NAS.

Multiple secondary endpoints were achieved, including statistically significant reduction from baseline in liver enzymes (Alanine aminotransferase (“ALT”), aspartate aminotransferase (“AST”) and gamma-glutamyl transferase (“GGT”)).

Reductions in atherogenic lipids and lipoproteins, fibrosis biomarkers and imaging tests (magnetic resonance imaging proton density fat-fraction (“MRI-PDFF”), controlled attenuation parameter (“CAP”) and liver stiffness measures) were observed in resmetirom treatment arms as compared with placebo.

MAESTRO-NASH included many biomarker and imaging assessments that may be used in real world clinical practice to identify appropriate patients for treatment and monitor response to resmetirom.

Multiple secondary endpoints were achieved, including statistically significant reduction from baseline in liver enzymes.

Reductions in atherogenic lipids and lipoproteins, fibrosis biomarkers and imaging tests were also observed in resmetirom treatment arms as compared with placebo.

The frequency of serious adverse events (SAEs) was similar across treatment arms in the MAESTRO-NASH trial.

11%, 13% and 12% for the 80 mg, 100 mg and placebo groups, respectively.

The rate of trial discontinuation for adverse events over the entire treatment period was low:

2.8%, 7.7% and 3.4 % for the 80 mg, 100 mg and placebo groups, respectively.

SAEs occurred at expected rates based on the patient population.

Consistent with previous Phase 2 and Phase 3 data, the most common adverse events (“AEs”) reported with greater frequency in the resmetirom groups versus placebo were an excess of generally mild and transient diarrhea at the beginning of therapy, in 27%, 33% and 16% of subjects in the 80 mg, 100 mg and placebo groups, respectively, and generally mild nausea that occurred at rates of 22%, 19% and 13% of subjects in the 80 mg, 100 mg and placebo groups, respectively.

Approximately 50% of the diarrhea AEs were described as “worsening of preexisting diarrhea” or “intermittent/loose stool(s)”;

no episodes of severe diarrhea were reported.

The median duration of diarrhea was approximately 15to 20 days, independent of resmetirom dose.

The rate of trial discontinuation for adverse events (“AEs”) over the entire treatment period was low.

Consistent with previous Phase 2 and Phase 3 data, the most common AEs reported with greater frequency in the resmetirom groups versus placebo were an excess of generally mild and transient diarrhea at the beginning of therapy and generally mild nausea.

Trial data indicated resmetirom treatment had no effect on heart rate or body weight and was not associated with arrhythmias.

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Sex hormones were unchanged from baseline.

Independent of thyroxine replacement status, resmetirom treatment reduced prohormone T4, as reflected by free thyroxine (FT4), by approximately 16% to 19% with no effect on thyroid-stimulating hormone (TSH) or the active thyroid hormone, free triiodothyronine (FT3).

Independent of thyroxine replacement status, resmetirom treatment reduced prohormone T4, as reflected by free thyroxine (FT4), with no effect on thyroid-stimulating hormone (TSH) or the active thyroid hormone, free triiodothyronine (FT3).

Relative to placebo, resmetirom-treated patients did not show increases in fractures or fracture risk scores.

MAESTRO-NASH is an ongoing blinded Phase 3 clinical trial, and enrolled patients continue on therapy after the Week 52 liver biopsy for up to a total of 54 months to accrue and measure hepatic clinical outcome events, including progression to cirrhosis on biopsy and hepatic decompensation events, as well as all-cause mortality.

The outcomes portion of the MAESTRO-NASH trial is designed to generate confirmatory data that, if positive, is expected to verify a clinical benefit and support the full approval of Rezdiffra in noncirrhotic MASH.

MAESTRO-NAFLD-1 Trial

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We reported that resmetirom demonstrated statistical significance for primary and key secondary endpoints summarized below from the double-blind placebo-controlled 969-patient portion of the trial.

These endpoints indicated that resmetirom (1) was well-tolerated at 80 and 100 mg in patients treated for 52 weeks, (2) provided significant and clinically relevant reductions in liver fat as measured by MRI-PDFF and (3) significantly reduced atherogenic lipids, including low-density lipoprotein cholesterol (“LDLc”), apolipoprotein B and triglycerides.

These endpoints indicated that resmetirom (i) was well-tolerated at 80 and 100 mg in patients treated for 52 weeks, (ii) provided significant and clinically relevant reductions in liver fat as measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF) and (iii) significantly reduced atherogenic lipids, including low-density lipoprotein cholesterol (“LDLc”), apolipoprotein B and triglycerides.

A total of 972 patients were randomized in the double-blind arms of the MAESTRO-NAFLD-1 trial:

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The frequency of SAEs was similar across treatment arms and discontinuation for AEs was low.

Consistent with published data, the most common AE reported with greater frequency in the resmetirom groups as compared to the placebo was generally mild diarrhea or increased stool frequency at the beginning of therapy, which occurred in 9% and approximately 17% over the placebo rate in the 80 mg and 100 mg dose groups, respectively.

The following hierarchically-controlled key secondary endpoints were reported for both the 80 mg and 100 mg resmetirom dose groups.

Resmetirom provided significant reductions in liver fat as measured by MRI-PDFF and reduced atherogenic lipids, including LDLc, apolipoprotein B and triglycerides.

Open-label arm data is reported in the far-left column below and double-blind arm data are reported in the remaining columns below.

Although both arms were randomized in MAESTRO-NAFLD-1, lipid reductions were numerically greater in the 100 mg open label treatment arm compared to the 100 mg double-blind arm, and we believe this is due to greater visit and dose interruptions experienced by open-label arm patients during the height of the COVID-19 pandemic, as patients in the open-label active 100 mg treatment arm were less impacted by COVID-related dose interruptions than double-blind patients.

100 mg OL Resmetirom

80 mg p-value Resmetirom 100

mg p-value Placebo

LDLc %CFB (SE) (Week 24) -21 (1.9) -12.7 (2.1) <.0001 -14.4 (2.1) <.0001 -1.7 (2.0)

ApoB %CFB (SE) (Week 24) -22 (1.5) -14.6 (1.5) <.0001 -16.6 (1.6) <.0001 -0.1 (1.5)

MRI-PDFF %CFB (Week 16) -49 % -41 % <.0001 -48 % <.0001 -6 %

Liver volume PDFF correction %CFB -60 %

MRI-PDFF %CFB (Week 52) -53 % -43 % <.0001 -48 % <.0001 -8 %

Liver volume PDFF correction %CFB -61 %

Triglycerides baseline >150 mg/dL, CFB (SE) -65 (8.3) -55.6 (8.6) NA -59 (6.5) NA -6.9 (16.1)

Triglycerides baseline >150 mg/dL (geomean) %CFB (95% CI) -25 (3.1) -19.5 (-27.0 to -11.1) =.0005 -21.5 (-28.0 to -14.3) <.0001 -2.1 (-10.6 to 7.4)

LDLc (low-density lipoprotein cholesterol);

CFB (change from baseline);

SE (standard error);

APoB (Apolipoprotein B);

MRI-PDFF (magnetic resonance imaging proton density fat-fraction);

PDFF (proton density fat-fraction);

CI (confidence interval);

OL (open label non-cirrhotic arm randomized concurrently with double-blind arms)

Compensated MASH Cirrhosis

The MAESTRO-NAFLD-1 trial also included an open label active treatment arm with 180 patients with compensated MASH cirrhosis.

Data following 52 weeks of treatment with 80 or 100 mg of resmetirom daily showed improved liver chemistry tests, a reduction in vibration-controlled transient elastography (“VCTE”) in a responder analysis and a statistically significant reduction in liver volume by an average of approximately 20%.

In addition, following two years of treatment with Rezdiffra, 101 patients from this cohort achieved a mean 6.7 kPa (kilopascals) reduction in liver stiffness, and 51% of patients achieved a ≥25% reduction in liver stiffness, each as measured by VCTE.

In May 2025, we reported two-year data showing that 122 patients in the study achieved significant improvements from baseline in liver stiffness, liver fat, fibrosis biomarkers, liver volume and risk scores for CSPH.

In November 2025, we announced additional positive data from this cohort examining patients with more advanced compensated MASH cirrhosis (those with a platelet count of <100,000/µL at baseline).

In this population, Rezdiffra demonstrated improvements from baseline across multiple imaging tests and biomarkers including liver stiffness, liver enzymes and lipids, as well as Baveno risk scores for CSPH.

These data from this open label active treatment arm continue to support the rationale for our MAESTRO-NASH OUTCOMES trial evaluating Rezdiffra in patients with compensated MASH cirrhosis.

MAESTRO-NASH OUTCOMES Trial

In October 2024, we announced that we completed enrollment of MAESTRO-NASH OUTCOMES, a Phase 3, double-blind, randomized, placebo-controlled trial that will noninvasively measure progression to liver decompensation events in 845 patients with compensated MASH cirrhosis, exceeding our initial enrollment target.

In October 2024, we announced that we completed enrollment of MAESTRO-NASH OUTCOMES, a Phase 3, double-blind, randomized, placebo-controlled trial that is designed to noninvasively measure progression to liver decompensation events in 845 patients with compensated MASH cirrhosis, exceeding our initial enrollment target.

The primary endpoint of MAESTRO-NASH OUTCOMES is the incidence of composite liver-related outcome events, including all-cause mortality, liver transplant, hepatic decompensation (ascites, hepatic encephalopathy, gastroesophageal variceal hemorrhage) and confirmed increase of Model for End-Stage Liver Disease (MELD) score from <12 to ≥15 due to progression of MASH cirrhosis.

Key inclusion criteria are well-compensated MASH cirrhosis (Child-Pugh A) and presence of three metabolic risk factors (metabolic syndrome).

Patients will be randomized 3:1 in a blinded manner to receive 80 mg resmetirom or matching placebo, given orally once daily.

Patients were randomized 3:1 in a blinded manner to receive 80 mg resmetirom or matching placebo, given orally once daily.

We expect results from this event-driven trial in 2027.

A positive outcome is expected to support the full approval of Rezdiffra for noncirrhotic MASH, potentially accelerating the timeline to full approval.

A positive outcome is expected to support the full approval of Rezdiffra for noncirrhotic MASH in the United States, potentially accelerating the timeline to full approval.

In addition, this trial has the potential to support approval of an additional indication for Rezdiffra in patients with compensated MASH cirrhosis.

Our research and development objective is to build the leading pipeline in MASH.

Through our business development efforts, we have added several mechanisms with biology that we believe is complimentary to resmetirom to potentially enhance efficacy across the spectrum of MASH.

Given Rezdiffra’s profile as a liver-directed therapy, we believe it is the best foundation on which to build the future of MASH treatment.

In addition to the following programs, we are evaluating several other candidates that may have the potential to treat MASH either as a monotherapy or as part of a combination.

MGL-2086 (oral GLP-1)

In September 2025, we acquired from CSPC an exclusive global license for MGL-2086 (formerly SYH2086), an oral small molecule GLP-1 receptor agonist.

GLP-1 receptor agonists improve systemic metabolism, insulin sensitivity and weight loss.

Rezdiffra reverses hypothyroidism in the liver, restoring mitochondrial function and increasing fat processing through beta-oxidation.

Based on data from our MAESTRO-NASH trial, Rezdiffra’s efficacy is enhanced by even modest amounts of weight loss.

By combining these complementary mechanisms in an oral combination therapy, we expect to see greater reductions in both liver fat and fibrosis.

An Investigational New Drug application (“IND”) has been accepted and we plan to start a Phase 1 single ascending dose trial of MGL-2086 in the second quarter of 2026.

Ervogastat (oral DGAT-2 inhibitor)

In December 2025, we acquired an exclusive global license for ervogastat, a liver-directed, oral DGAT-2 inhibitor, from Pfizer.

DGAT-2 inhibitors work by blocking the final step in triglyceride assembly and storage, resulting in lower hepatic triglycerides, reduced lipotoxic fat and decreased inflammation.

In a Phase 2b trial conducted by Pfizer, ervogastat demonstrated impressive liver fat reduction as measured by MRI-PDFF, a noninvasive technique to precisely measure the percentage of fat in the liver.

72% of patients treated with ervogastat (150 mg) achieved at least a 30% reduction in liver fat, with 61% experiencing at least a 50% reduction.

Improvements in liver enzymes and liver stiffness as measured by VCTE were also observed, and all active doses studied were well tolerated.

By inhibiting DGAT-2, we believe we can decrease lipid accumulation in the liver and lower inflammation and fibrosis by keeping stellate cells in their inactive state.

Rezdiffra restores mitochondrial function and increases fat processing via beta-oxidation which leads to lower inflammation and a reduction in downstream fibrosis.

In combination, we believe these two mechanisms can be

complementary by addressing both the production and clearance of hepatic fat.

In 2026, we expect to conduct a Phase 1 drug-to-drug interaction study with ervogastat and resmetirom.

In addition, we expect to initiate a Phase 2 combination trial with ervogastat and resmetirom in 2027 following discussions with the FDA.

siRNA programs

In February 2026, we entered into the Ribocure License Agreement pursuant to which we obtained an exclusive global license to six preclinical siRNA programs.

These siRNAs target clinically validated genes implicated in MASH disease progression.

siRNAs may offer a precision approach to gene silencing in MASH by potentially reducing the production of disease-driving proteins.

The siRNAs are N-acetylgalactosamine (“GalNac”) conjugated.

When linked to a GalNac ligand, siRNA molecules are delivered directly into hepatocytes, where they silence genes that have been identified as key risk factors for MASH by breaking down targeted mRNA.

By pairing this precise gene-silencing approach with Rezdiffra, we aim to explore whether reducing drivers of disease at the genetic level can complement Rezdiffra’s therapeutic effects.

IND-enabling activities in initial candidates are expected to begin in 2026.

Collaborations

Roche Agreement

VIA Pharmaceuticals, Inc.

(“VIA”) entered into a research, development and commercialization agreement (the “Roche Agreement”) with Hoffmann-La Roche (“Roche”), on December 18, 2008.

We subsequently assumed all of VIA’s rights in, to and under, and all of VIA’s obligations under, the Roche Agreement pursuant to an asset purchase agreement, dated September 14, 2011.

(“VIA”) entered into a research, development and commercialization agreement (as amended from time to time, the “Roche Agreement”) with Hoffmann-La Roche (“Roche”), in December 2008.

We subsequently assumed all of VIA’s rights in, to and under, and all of VIA’s obligations under, the Roche Agreement pursuant to an asset purchase agreement in September 2011.

Pursuant to the terms of the Roche Agreement, we, as successor-in-interest to VIA, assumed control of all development and commercialization of resmetirom and hold exclusive worldwide rights for all potential indications.

Under the Roche Agreement, Roche exclusively licensed certain patent rights and know-how relating to resmetirom in exchange for consideration consisting of an upfront payment, milestone payments and single-digit royalty payments based on net sales of Rezdiffra and any derivative products of resmetirom, subject to certain reductions.

Under the Roche Agreement, Roche exclusively licensed certain patent rights and know-how relating to resmetirom in exchange for consideration consisting of an upfront payment, milestone payments and tiered single-digit royalty payments based on net sales of Rezdiffra and any derivative products of resmetirom, subject to certain reductions.

In 2011, we commenced Phase 1 clinical trials and subsequently paid Roche a related milestone payment.

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In March 2024, we received FDA approval of Rezdiffra and subsequently paid Roche a $5.0 million related milestone payment.

The remaining milestone payment obligation under the Roche Agreement is $3.0 million and is tied to regulatory approval in a major market country in Europe for resmetirom or any derivative product.

Pursuant to the Roche Agreement, we must use commercially reasonable efforts to conduct clinical and commercial development programs for products containing resmetirom.

In August 2025, upon receiving a CMA from the EC, a milestone was achieved and we paid $3.0 million to Roche.

Pursuant to the Roche Agreement, we agreed to use commercially reasonable efforts to conduct clinical and commercial development programs for products containing resmetirom.

If we determine not to pursue the development or commercialization of resmetirom in certain jurisdictions, Roche may terminate the license for such territories.

The Roche Agreement will expire, unless earlier terminated pursuant to other provisions of the Roche Agreement, on the last to occur of (i) the expiration of the last valid claim of a licensed patent covering the manufacture, use or sale of products containing resmetirom or (ii) ten years after the first sale of a product containing resmetirom.

The development and commercialization of new drugs in MASH is highly competitive.

We will face competition with respect to all product candidates we have developed or may develop or commercialize in the future from pharmaceutical and biotechnology companies worldwide.

Our obligation to pay royalties based on net sales of resmetirom in a given country will expire, unless earlier terminated pursuant to other provisions of the Roche Agreement, on the last to occur of (i) the expiration of the last valid claim of a licensed patent covering the manufacture, use or sale of products containing resmetirom in a given country, or (ii) ten years after the first sale of a product containing resmetirom in such country.

In January 2026, we entered into an amendment to the Roche Agreement to provide us the full and exclusive right and discretion to control all patent term adjustments and patent term extensions applicable to Rezdiffra, including patents owned by Roche and jointly owned between the parties.

In consideration of the foregoing, the royalty payable to Roche based on net sales of Rezdiffra will not be reduced until the expiration of certain patent term extensions that have been, or could have been, filed.

CSPC License (MGL-2086)

In July 2025, we entered into the CSPC License Agreement with CSPC for MGL-2086 (formerly known as SYH2086), an oral small molecule GLP-1 receptor agonist.

Pursuant to the CSPC License Agreement, CSPC has granted us an exclusive global license to develop, manufacture, and commercialize MGL-2086.

The transaction closed in September 2025.

We paid CSPC an upfront payment of $120.0 million in October 2025.

CSPC is eligible to receive up to $2.0 billion in development, regulatory and commercial milestone payments, as well as royalties on net sales ranging from mid-single digits to low-double digits.

Pfizer License (ervogastat)

In December 2025, we entered into an exclusive global license agreement with Pfizer (the “Pfizer License Agreement”) to develop, manufacture and commercialize ervogastat, a Phase 2 oral DGAT-2 inhibitor, and two additional early-stage MASH assets.

We paid Pfizer an upfront payment of $50.0 million in December 2025.

In addition, Pfizer is eligible to receive up to $70.0 million in development and regulatory milestone payments related to ervogastat and low-

double digit royalties on net sales of ervogastat.

Pfizer is eligible to receive additional development, regulatory and commercial milestone payments and royalty payments on net sales of the two licensed early stage assets.

Ribocure License (siRNA programs)

In February 2026, we entered into the Ribocure License Agreement granting us exclusive global rights to develop, manufacture and commercialize six siRNA programs.

Pursuant to the Ribocure License Agreement, we will pay Ribocure an upfront payment of $60.0 million.

In addition, Ribocure is eligible to receive up to $4.4 billion in development, regulatory and commercial milestone payments across all programs, as well as royalties on net sales ranging from mid-single digits to low-double digits.

The development and commercialization of drugs in MASH is highly competitive.

We will face competition with respect to Rezdiffra and all product candidates we may develop or commercialize in the future from pharmaceutical and biotechnology companies worldwide.

The key factors affecting the success of an approved product will generally be such product’s efficacy, safety profile, drug interactions, method of administration, pricing, reimbursement and level of promotional activity relative to those of competing drugs.

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• attract and retain high-quality research, development and commercial personnel.

While Rezdiffra is currently the only FDA-approved drug for the treatment of MASH, there are more than 150 drugs in development for MASH by companies ranging in size from small biotech companies to large pharma organizations.

Investigational candidates include, among others, thyroid hormone receptor beta agonists, peroxisome proliferator-activated receptor agonists (PPAR) glucagon-like peptide 1 (GLP-1) agonists, dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists, fatty acid synthase (FASN) inhibitors, fibroblast growth factor 21 (FGF-21) stimulators, farnesoid X receptor (FXR) agonists, acetyl-CoA carboxylase (ACC) inhibitors and dual GLP-1/glucagon receptor agonists.

Companies conducting Phase 3 trials include Novo Nordisk A/S, Inventiva S.A., Akero Therapeutics, Inc., 89bio Inc.

and Boehringer Ingelheim International GmbH.

Novo Nordisk plans to submit approval filings for their GLP-1 agonist for the treatment of MASH in the United States and Europe in the first half of 2025.

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 (“Novo”), was approved for the treatment of MASH by the FDA and is pending approval in the EU.

In addition, there are more than 140 drugs in development for MASH by companies ranging in size from small biotechnology companies to large pharmaceutical organizations.

Investigational candidates include, among others, THR-β agonists, peroxisome proliferator-activated receptor agonists (PPAR), GLP-1 agonists, dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists, fatty acid synthase (FASN) inhibitors, fibroblast growth factor 21 (FGF-21) stimulators, farnesoid X receptor (FXR) agonists and dual GLP-1/glucagon receptor agonists.

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.

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See the section titled “Risk Factors—Risks Related to the Commercialization and Continued Approval of Rezdiffra—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.” in this Annual Report for additional discussion of the competitive risks we face.

Research and Development

Since our inception, we have focused significant resources on our research and development activities.

Costs incurred in performing research and development activities include internal costs (including cash compensation and stock-based compensation);

costs for clinical trial consultants, contract research organizations, clinical sites and other external services;

clinical drug manufacturing and supply costs;

milestone payments under licensing agreements;

other costs of conducting trials including the costs of materials and supplies;

the costs associated with seeking regulatory approval and other costs associated with our preclinical and clinical programs.

Please refer to Part II, Item 7, “Management’s Discussion and Analysis of Financial Condition and Results of Operations.” of this Annual Report for a discussion of our research and development expenses incurred during the last three fiscal years.

Manufacturing, Supply and Distribution

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We currently rely, and expect to continue to rely, on third-party contract manufacturers (“CMOs”) for all required starting materials, active pharmaceutical ingredients (“API”) and finished product for the manufacture of any product candidates that we may develop for larger-scale preclinical and clinical testing, as well as for commercial quantities of Rezdiffra and any future drug candidates that may be approved.

In December 2024, we entered into a Resmetirom Commercial Supply Agreement (the “Evonik Supply Agreement”) with Evonik Corporation (“Evonik”).

Pursuant to the Evonik Supply Agreement, Evonik has agreed to manufacture and supply resmetirom, the API in Rezdiffra, in commercial quantities.

We have agreed to provide Evonik with a forecast of our purchases on a rolling basis.

In December 2024, we entered into a Resmetirom Commercial Supply Agreement (the “Evonik Agreement”) with Evonik Corporation (“Evonik”).

Pursuant to the Evonik Agreement, Evonik has agreed to manufacture and supply resmetirom, the API in Rezdiffra, in commercial quantities.

We have agreed to provide Evonik with a forecast of our

purchases on a rolling basis.

Under the Evonik Agreement, our purchase price for supply of resmetirom is based on the volume of material subject to a purchase order.

The initial term of the Evonik Agreement will expire on December 31, 2029 and will be automatically renewed for successive two-year periods, unless terminated in accordance with the terms of the Evonik Agreement.

In addition, in August 2023, we entered into a Commercial Supply Agreement (the “UPM Supply Agreement”) with UPM Pharmaceuticals, Inc.

In addition, in August 2023, we entered into a Commercial Supply Agreement (the “UPM Agreement”) with UPM Pharmaceuticals, Inc.

(“UPM”) for the primary commercial supply of Rezdiffra tablets in the United States.

Pursuant to the UPM Supply Agreement, we must purchase a specified percentage of our annual requirements for Rezdiffra from UPM at volume-driven prices.

Pursuant to the UPM Agreement, we must purchase a specified percentage of our annual requirements for Rezdiffra from UPM at volume-driven prices.

The initial term of the UPM Agreement will expire in April 2032 and will be automatically renewed for two-year periods unless terminated in accordance with the terms of the UPM Agreement.

We have also entered into a supply agreement with a German-based manufacturer for the primary commercial supply of Rezdiffra tablets in Europe, pending EC approval, and to serve as a secondary commercial supplier

We have also entered into a supply agreement (the “Corden Supply Agreement”) with Corden Pharma GmbH (“Corden”), a German-based manufacturer, for the primary commercial supply of Rezdiffra tablets in Europe and to serve as a secondary commercial supplier for the U.S.

Pursuant to the Corden Supply Agreement, we must submit to Corden binding forecasts for our expected delivery of Rezdiffra.

The initial term of the Corden Supply Agreement will expire in 2029 and is expected to renew for successive two-year terms.

All of our CMO partners have extensive technical expertise, GMP experience and experience manufacturing our specific technology.

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Intellectual Property

Our success will depend in part on our ability to obtain and maintain patent and other proprietary protection for Rezdiffra and any current or future product candidates, technology and know-how, our ability to freely operate without infringing on the proprietary rights of others and our ability to establish proprietary rights and prevent others from infringing our proprietary rights.

We seek to protect our proprietary position by, among other methods, filing United States and foreign patent applications related to our proprietary technology, and maintaining the confidentiality of inventions and improvements that are material to the development of our business.

We also rely on trade secrets, know-how, continuing technological innovation and licensing opportunities to develop and maintain our competitive position.

We will be able to protect our technology and products from unauthorized use by third parties only to the extent we are covered by valid and enforceable patents or such knowledge is effectively maintained as trade secrets.

Patents and other proprietary rights are thus an essential element of our business.

We also rely on trade secrets, know-how, continuing technological innovation and licensing opportunities to develop and maintain our competitive position.

Our success will depend in part on our ability to obtain and maintain patent and other proprietary protection for our current product and future product candidates, technology and know-how, our ability to freely operate without infringing on the proprietary rights of others and our ability to establish proprietary rights and prevent others from infringing our proprietary rights.

As of December 31, 2024, we own or co-own eight United States issued patents and 103 foreign issued patents, 16 United States pending patent applications and 98 foreign pending patent applications and one international patent application filed under the Patent Cooperation Treaty.

Each of these patents and patent applications is directed to resmetirom, including composition-of-matter, certain polymorph forms, methods of making resmetirom, the use of resmetirom in the treatment of key disease indications or other THR-β analogs and uses thereof.

We monitor for activities that may infringe our proprietary rights, as well as the progression of third-party patent applications that may have the potential to interfere with the development of our business.

As of December 31, 2025, we owned or co-owned nine United States issued patents and 107 foreign issued patents, 24 United States pending patent applications and 97 foreign pending patent applications and three international patent application filed under the Patent Cooperation Treaty.

Issued patents directed to resmetirom have statutory expiration dates between 2026 and 2045, excluding any patent term extensions or equivalents thereof that might be available following the grant of marketing authorizations.

Each of these patents and patent applications is directed to resmetirom, including composition-of-matter, certain polymorph forms, Rezdiffra’s commercial weight-threshold dosing regimen as prescribed in the FDA-approved label, methods of making resmetirom, the use of resmetirom in the treatment of key disease indications or other THR-β analogs and uses thereof.

Our current patent portfolio covers the United States and certain other jurisdictions worldwide.

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The Roche Agreement imposes various diligence, milestone payment, royalty payment, insurance, indemnification, and other obligations on us.

Issued patents directed to resmetirom have statutory expiration dates between 2026 and 2038, excluding any patent term extensions or equivalents thereof that might be available following the grant of marketing authorizations.

We have pending patent applications directed to resmetirom that, if issued, would be expected to expire in the United States and in countries outside of the United States in 2044, excluding any patent term adjustment that might be available following the grant of the patent.

We have a pending patent application for other THR-β analogs that, if issued, would be expected to expire in the United States and in countries outside of the United States in 2043, excluding any patent term adjustment that might be available following the grant of such patent.

In addition, pursuant to the Roche Agreement, we have the exclusive right to control all patent term adjustments and patent term extensions applicable to Rezdiffra patents, including patents owned by Roche and jointly owned between the parties.

Of the patents and applications related to Rezdiffra, there are six U.S.-issued patents listed in the FDA Orange Book.

These patents and their expiration dates, excluding any patent term extensions, are as follows:

7,452,882 (expires September 12, 2026)

9,266,861 (expires September 17, 2033)

10,376,517 (expires September 17, 2033)

11,564,926 (expires September 17, 2033)

11,986,481 (expires September 17, 2033)

12,377,104 (expires February 4, 2045)

In addition, we have licensed several patents and patent applications related to our pipeline candidates, and have filed several patent applications directed toward our product candidates in combination with resmetirom.

Our trademarks are protected under the common law or by registration in the United States and other countries.

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A new drug must be approved by the FDA through the new drug application (“NDA”) process before it may be legally marketed in the United States and must be approved by foreign regulatory authorities via various analogous procedures before it can be marketed in the applicable country.

The animal and

other non-clinical data and the results of human clinical trials performed under an Investigational New Drug application (“IND”) and under similar foreign applications will become part of the NDA.

The animal and other non-clinical data and the results of human clinical trials performed under an IND and under similar foreign applications will become part of the NDA.

Even after obtaining initial marketing approval, a product and its manufacturer remain subject to extensive, continuing regulatory requirements, including with respect to manufacturing, quality control, adverse event reporting, advertising and promotion and periodic inspections by regulatory authorities.

United States Drug Development Process

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Failure to comply with the applicable United States requirements at any time during the product development process, approval process or after approval, may subject an applicant to administrative or judicial sanctions.

These sanctions could include, among other things, the FDA’s refusal to approve pending applications, withdrawal of an approval, a clinical hold, warning letters and other types of enforcement-related letters, requesting product recalls, product seizures, changes to the conditions surrounding marketing approval such as labeling changes or changes to a Risk Evaluation and Mitigations Strategies (“REMS”) program, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, debarment, restitution, disgorgement of profits or civil or criminal investigations and penalties.

These sanctions could include, among other things, the FDA’s refusal to approve pending applications, withdrawal of an approval, a clinical hold, FDA Form 483, untitled letters, warning letters and other types of enforcement-related letters, requesting product recalls, product seizures, changes to the conditions surrounding marketing approval such as labeling changes or changes to a Risk Evaluation and Mitigations Strategies (“REMS”) program, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, debarment, restitution, disgorgement of profits or civil or criminal investigations and penalties.

Any agency or judicial enforcement action could have a material adverse effect on us.

The FDA may also prevent the import or export of products manufactured in non-compliant facilities or under non-compliant conditions.

The process required by the FDA before a drug may be marketed in the United States generally involves the following:

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• approval by an institutional review board (“IRB”) before each clinical trial may be initiated at each clinical site;

• performance of adequate and well-controlled human clinical trials under protocols submitted to the FDA and reviewed and approved by each IRB, conducted in accordance with federal regulations and according to Good Clinical Practices (“GCP”) to establish the safety and efficacy of the proposed drug for its intended use;

• performance of adequate and well-controlled human clinical trials under protocols submitted to the FDA and reviewed and approved by each IRB, conducted in accordance with federal regulations and according to GCP to establish the safety and efficacy of the proposed drug for its intended use;

• preparation and submission to the FDA of an NDA (and the FDA’s acceptance for filing of the NDA);

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An IND sponsor must submit the results of the preclinical tests, together with manufacturing information and analytical data, to the FDA as part of the IND.

The sponsor will also include a protocol detailing, among other things, the objectives of the clinical trial, the parameters to be

used in monitoring safety and the effectiveness criteria to be evaluated, if the trial lends itself to an efficacy evaluation.

The sponsor will also include a protocol detailing, among other things, the objectives of the clinical trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated, if the trial lends itself to an efficacy evaluation.

Some preclinical testing may continue even after the IND is submitted.

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If during this 30-day period the FDA does not raise any concerns or issues that must be addressed prior to the commencement of clinical trials or does not impose a clinical hold, the IND becomes effective 30 days following the FDA’s receipt of the IND and the clinical trial proposed in the IND may begin.

Clinical holds also may be imposed by the FDA at any time before or during clinical trials due to safety concerns or non-compliance, or other reasons.

Clinical holds also may be imposed by the FDA at any time before or during clinical trials due to safety concerns, non-compliance or other reasons.

All clinical trials must be conducted under the supervision of one or more qualified investigators in accordance with GCP.

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Foreign trials conducted under an IND must meet the same requirements that apply to trials being conducted in the United States.

The FDA may inspect foreign clinical sites to ensure data integrity and compliance with GCP.

Data from a foreign trial not conducted under an IND may be submitted in support of an NDA if the trial was conducted in accordance with GCP and the FDA is able to validate the data.

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These trials are intended to establish the overall risk-benefit ratio of the product candidate and provide, if appropriate, an adequate basis for product approval and product labeling.

In most cases, the FDA requires two adequate and well controlled Phase 3 clinical trials to demonstrate the efficacy of the product candidate, although a single Phase 3 clinical trial with other confirmatory evidence may be sufficient in certain instances.

Generally, the FDA requires two adequate

and well controlled Phase 3 clinical trials to demonstrate the efficacy of the product candidate, although a single Phase 3 clinical trial with other confirmatory evidence may be sufficient in certain instances.

The FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk.

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Competitors and others may use this publicly-available information to gain knowledge regarding the design and progress of our development programs.

Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and more frequently if SAEs occur.

Written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected adverse events, findings from other studies or animal or in vitro testing that suggest a significant risk for human subjects and any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

The sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting.

The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction within seven calendar days after the sponsor’s initial receipt of the information.

During the development of a new drug, sponsors are given opportunities to meet with the FDA at certain points.

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The targeted action date can also be shortened to within 6 months of the 60-day filing date for products that are granted priority review designation because they are intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs.

The FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s identity, strength, quality and purity.

The FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended

use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s identity, strength, quality and purity.

Before approving an NDA, the FDA will inspect the facility or facilities where the product is manufactured.

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In clinical trials, a surrogate endpoint is a measurement of laboratory or clinical signs of a disease or condition that is thought to predict clinical benefit, such as how a patient feels, functions, or survives, but is not itself a measure of clinical benefit.

Surrogate endpoints can often be measured more easily

or more rapidly than clinical endpoints.

Surrogate endpoints can often be measured more easily or more rapidly than clinical endpoints.

As a condition of accelerated approval, the FDA requires that a sponsor of a drug receiving accelerated approval perform confirmatory adequate and well-controlled post-marketing clinical trials.

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Under PREA, such original NDAs and supplements thereto must contain a pediatric assessment unless the sponsor has received a deferral or waiver.

The required assessment must assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product has been assessed to be safe and effective.

The required assessment must assess the safety

and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product has been assessed to be safe and effective.

The sponsor or FDA may request a deferral of pediatric studies for some or all of the pediatric subpopulations.

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In that instance, the exclusivity period does not preclude filing or review of an ANDA or 505(b)(2) application;

rather, the FDA is precluded from granting final approval to the ANDA or 505(b)(2)

application until three years after approval of the RLD.

rather, the FDA is precluded from granting final approval to the ANDA or 505(b)(2) application until three years after approval of the RLD.

Additionally, the exclusivity applies only to the conditions of approval that required submission of the clinical data.

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The FDA maintains several programs to facilitate and expedite the development and review of drug applications that are intended for the treatment of a serious or life-threatening disease or condition that meet certain other criteria, including Fast Track Designation, Breakthrough Designation, Priority Review (discussed above in United States Review and Approval Processes), and the Accelerated Approval pathway (discussed above in United States Review and Approval Processes).

Under the Fast Track Designation program, the sponsor of a new drug candidate may request that the FDA designate the drug candidate for a specific indication as a fast track drug concurrent with, or after, the filing of the IND for the drug candidate.

Under the Fast Track Designation program, the sponsor of a new drug candidate may request that the FDA

designate the drug candidate for a specific indication as a fast track drug concurrent with, or after, the filing of the IND for the drug candidate.

The FDA must determine if the drug candidate qualifies for fast track designation within 60 days of receipt of the sponsor’s request.

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Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance.

We rely, and expect to continue to rely, on third parties for the production of

clinical and commercial quantities of our product candidates.

We rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of our product candidates.

Future inspections by the FDA and other regulatory agencies may identify compliance issues at the facilities of our contract manufacturers that may disrupt production or distribution, or require substantial resources to correct.

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Whether or not we obtain FDA approval for a product, we must obtain approval by the comparable regulatory authorities of foreign countries or economic areas, such as the EU, before we may commence clinical trials or market products in those countries or areas.

The approval process and requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from place to place, and the time may be longer or shorter than that required for FDA approval.

Under the EU regulatory systems, a company may submit an MAA either under the centralized procedure or one of the national procedures, depending on the type of product.

The centralized procedure provides for the grant of a single marketing authorization by the EC that is valid throughout the EU and in the additional countries of the European Economic Area (Iceland, Lichtenstein and Norway) (“EEA”).

The approval process and

requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from place to place, and the time may be longer or shorter than that required for FDA approval.

Under the EU regulatory systems, a company may submit a marketing authorization application (“MAA”) either under the centralized procedure or one of the national procedures, depending on the type of product.

The centralized procedure is compulsory for medicinal products produced by certain biotechnological processes;

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exposure of an insufficient number of patients to the medicinal product concerned), to mandate one additional five-year renewal.

In specific circumstances, applicants may obtain a CMA prior to having the full clinical data normally required for a standard marketing authorization where (i) the benefit-risk balance of the product is positive, (ii) it is likely that the applicant will be able to provide comprehensive clinical data, (iii) the product addresses an unmet medical need and (iv) the benefit to public health of the immediate availability of the medicinal product on the market outweighs the risk inherent in the fact that additional data are still required.

A CMA may contain specific obligations to be fulfilled by the marketing authorization holder following grant of the marketing authorization, including obligations with respect to the completion of ongoing or new studies, and with respect to the collection of pharmacovigilance data.

CMAs are valid for one year, and may be renewed annually, if the risk-benefit balance remains positive, and after an assessment of the need for additional or modified conditions and/or specific obligations.

The timelines for the centralized procedure described above also apply with respect to the review by the CHMP of applications for a CMA.

There are also two other possible routes to authorize products for therapeutic indications in several countries in the EU, which are available for products that fall outside the scope of the centralized procedure:

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• Mutual recognition procedure—In the mutual recognition procedure, a medicine is first authorized in one EU Member State, in accordance with the national procedures of that country.

Following this,

additional marketing authorizations can be sought from other EU Member States in a procedure whereby the countries concerned recognize the validity of the original, national marketing authorization.

Following this, additional marketing authorizations can be sought from other EU Member States in a procedure whereby the countries concerned recognize the validity of the original, national marketing authorization.

In both cases, as with the centralized procedure, the competent authorities of the EU Member States assess the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy before granting the marketing authorization.

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The EU CTR replaced the previous EU Clinical Trials Directive and aims to simplify and streamline the approval of clinical trials in the EU.

For example, the EU CTR implements a coordinated procedure for authorization of clinical trials (through a centralized EU portal known as the Clinical Trials Information System) that is similar to the mutual recognition procedure for marketing authorization of medicinal products, and includes obligations on sponsors to publish clinical trial results.

For example, the EU CTR

implements a coordinated procedure for authorization of clinical trials (through a centralized EU portal known as the Clinical Trials Information System) that is similar to the mutual recognition procedure for marketing authorization of medicinal products, and includes obligations on sponsors to publish clinical trial results.

As in the United States, it may be possible in foreign countries to obtain a period of market and/or data exclusivity that would have the effect of postponing the entry into the marketplace of a competitor’s generic or biosimilar product.

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• The manufacturing of authorized medicinal products, for which a separate manufacturer’s license is mandatory, must also be conducted in strict compliance with the applicable EU laws, regulations and guidance, including Directive 2001/83/EC, Directive (EU) 2017/1572, Regulation (EC) No 726/2004 and the European Commission Guidelines for Good Manufacturing Practice.

These requirements include compliance with EU cGMP standards when manufacturing medicinal products and active pharmaceutical ingredients, including the manufacture of active pharmaceutical ingredients outside of the EU with the intention to import the active pharmaceutical ingredients into the EU.

These requirements include compliance with EU GMP standards when manufacturing medicinal products and active pharmaceutical ingredients, including the manufacture of active pharmaceutical ingredients outside of the EU with the intention to import the active pharmaceutical ingredients into the EU.

• The marketing and promotion of authorized products, including industry-sponsored continuing medical education and advertising directed toward the prescribers of products and/or the general public, are strictly regulated in the EU.

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The EC introduced legislative proposals in April 2023 that, if implemented, will replace the current regulatory framework in the EU for all medicines (including those for rare diseases and for children).

The EC has provided the legislative proposals to the European Parliament and the European Council for their review and approval, and, in April 2024, the European Parliament proposed amendments to the legislative proposals.

Once the EC’s legislative proposals are approved (with or without amendment), they will be adopted into EU law.

In April 2024, the European Parliament adopted its position on the legislative proposals and, in June 2025, the Council of the European Union adopted

its position.

A common position on the text has been agreed upon on December 11, 2025, in the context of subsequent inter-institutional trilogue negotiations.

The proposed revisions remain to be adopted, and are not expected to become applicable before 2028.

The UK formally left the EU on January 31, 2020.

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In particular, the Medicines and Healthcare products Regulatory Agency (the “MHRA”) is now responsible for approving all medicinal products destined for the UK market (i.e., Great Britain and Northern Ireland), and the EMA no longer has any role in approving medicinal products destined for Northern Ireland under the EU centralized procedure.

A single UK-wide marketing authorization will be granted by the MHRA for all novel medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorization throughout the UK.

A single UK-wide marketing authorization is granted by the MHRA for all novel medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorization throughout the UK.

In addition, the new arrangements require all medicines placed on the UK market to be labelled “UK only,” indicating they are not for sale in the EU.

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Our drug candidates may not be considered medically necessary or cost-effective.

If third-party payors do not consider a product to

be cost-effective compared to other available therapies, they may not cover the product after approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow a company to sell its products at a profit.

If third-party payors do not consider a product to be cost-effective compared to other available therapies, they may not cover the product after approval as a benefit under their plans or, if they do, the level of payment may not be sufficient to allow a company to sell its products at a profit.

A decision by a third-party payor not to cover a product could reduce physician ordering and patient demand for the product.

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For example, the EU provides options for its Member States to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.

A member state may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market.

An EU Member State may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market.

There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products.

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Further, under the IRA, orphan drugs are exempted from the Medicare drug price negotiation program, but only if they have one orphan designation and for which the only approved indication is for that disease or condition.

If a product receives multiple orphan designations or has multiple approved indications, it may not qualify for the orphan drug exemption.

The implementation of the IRA is currently subject to ongoing litigation challenging the

constitutionality of the IRA’s Medicare drug price negotiation program.

The effects of the IRA on our business and the healthcare industry in general is not yet known.

Under the One Big Beautiful Bill Act of 2025, this restriction was eliminated;

and effective for the 2028 initial price applicability year, all orphan drugs, regardless of the number of orphan drug designations or indications, are exempt from the Medicare drug price negotiation program.

The implementation of the IRA is currently subject to ongoing litigation challenging the constitutionality of the IRA’s Medicare drug price negotiation program.

The effect of the IRA on our business and the healthcare industry in general continues to evolve and we may discover adverse impacts on our company or our industry.

The IRA is anticipated to have significant effects on the pharmaceutical industry and may reduce the prices we can charge and reimbursement we can receive for our product, among other effects.

On December 2, 2020, the HHS published a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through PBMs, unless the price reduction is required by law.

The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a safe harbor for certain fixed fee arrangements between PBMs and manufacturers.

Implementation of this change and new safe harbors for point-of-sale reductions in price for prescription pharmaceutical products and PBM service fees are currently under review by the current United States presidential administration and may be amended or repealed.

Implementation of this change and new safe

harbors for point-of-sale reductions in price for prescription pharmaceutical products and PBM service fees are currently under review by the current United States presidential administration and may be amended or repealed.

Further, on December 31, 2020, the Centers for Medicare & Medicaid Services (“CMS”) published a new rule, effective January 1, 2023, requiring manufacturers to ensure the full value of co-pay assistance is passed on to the patient or these dollars will count toward the Average Manufacturer Price and Best Price calculation of the drug (“Accumulator Rule”).

On May 17, 2022, the U.S.

District Court for the District of Columbia granted the Pharmaceutical Research and Manufacturers of America's (PhRMA) motion for summary judgement invalidating the Accumulator Rule.

District Court for the District of Columbia granted the Pharmaceutical Research and Manufacturers of America’s (PhRMA) motion for summary judgment invalidating the Accumulator Rule.

We cannot predict how the implementation of and any further changes to this rule will affect our business.

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Both the current United States presidential administration and Congress have indicated that they will continue to seek new legislative measures to control drug costs.

On April 15, 2025, the Trump Administration published Executive Order 14273, “Lowering Drug Prices by Once Again Putting Americans First,” which generally directs the federal government to take measures to reduce drug prices, including eliminating the so-called “pill penalty” under the IRA that creates a distinction between small molecule and large molecule products for purposes of determining when a drug may be eligible for drug price negotiation.

On May 12, 2025, the Trump Administration published Executive Order 14297, “Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients” which generally, among other things, directs the federal government to establish and communicate most-favored-nation price targets to pharmaceutical manufacturers to bring prices for American patients in line with comparably developed nations.

Further, the Executive Order directs the federal government to support regulatory paths to allow direct-to-patient sales for companies that meet these targets.

It also states that the Administration will take additional aggressive action (for example, examining whether marketing approvals should be modified or rescinded or opening the door for individual drug importation waivers) should manufacturers fail to offer American consumers the most-favored-nation lowest price.

It also directs the Secretary of Commerce and the U.S.

Trade Representative to “take all necessary and appropriate action to ensure foreign countries are not engaged in any act, policy, or practice that may be unreasonable or discriminatory or that may impair United States national security .

including by suppressing the price of pharmaceutical products below fair market value in foreign countries.” Notably, a similar “Most Favored Nation” pricing rule enacted under the first Trump Administration was subject to an injunction resulting from judicial challenges to the rule, which was formally rescinded by the former Biden Administration in August 2021.

On November 6, 2025, CMS announced a new drug payment model designed to make Most Favored Nation (MFN)-level prices available to state Medicaid programs via manufacturer rebates.

Referred to as the “GENErating cost Reductions fOr U.S.

Medicaid Model” (“GENEROUS”), the initiative is designed to run from 2026 through 2030 and is voluntary for both manufacturers and state Medicaid programs.

Under the model, participating states will be able to access MFN-level prices for participating manufacturers’ drugs through CMS-negotiated supplemental rebates tied to an MFN net price benchmark.

On December 19, 2025, CMS proposed a mandatory Center for Medicare and Medicaid Innovation (“CMMI”) drug payment model to test whether alternative methods for calculating Medicare rebates, based on international pricing metrics rather than inflation-based metrics, reduce costs for Medicare fee-for-service (“FFS”) beneficiaries and the Medicare program while preserving quality of care.

The Guarding U.S.

Medicare Against Rising Drug Costs (“GUARD”) Model, would test an alternative approach to calculating rebates for certain Medicare Part D products using international pricing benchmarks.

The GUARD Model would begin on January 1, 2027, and run through December 31, 2033.

Public comments on the Proposed Payment Models are due by February 23, 2026.

Federal and state legislatures and health agencies may continue to focus on additional health care reform measures in the future that will impose additional constraints on prices and reimbursements for our marketed products.

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Individual states in the United States have also increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including by requiring pharmaceutical manufacturers to report to state agencies when they introduce new drugs to market with prices over a certain threshold, or when they increase the price of a drug over a certain threshold.

If healthcare policies or reforms intended to curb healthcare costs are adopted, the prices that we charge for any approved product may be limited, our commercial opportunity may be limited and/or our revenues from sales of our product and any future products, if approved, may be negatively impacted.

If healthcare policies or reforms intended to curb healthcare costs are

adopted, the prices that we charge for any approved product may be limited, our commercial opportunity may be limited and/or our revenues from sales of our product and any future products, if approved, may be negatively impacted.

It is possible that the above-mentioned measures, as currently enacted or may be amended in the future, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, and new payment methodologies and additional downward pressure on coverage and payment and the price that we receive for any approved product.

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In the United States, these laws include, without limitation, state and federal anti-kickback, false claims, physician transparency and patient data privacy and security laws and regulations, including but not limited to those described below.

certain rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward or in return for, either the referral of an individual for, or the purchase order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid.

• The federal Anti-Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, paying, receiving or providing any remuneration (including any kickback, bride or certain rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward or in return for, either the referral of an individual for, or the purchase order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid.

A person or entity need not have actual knowledge of the federal Anti-Kickback Statute or specific intent to violate it in order to have committed a violation.

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The government may also assert that a claim including items or services resulting from a violation of the federal Anti-Kickback statute constitutes a false or fraudulent claim under federal civil monetary penalties laws;

• The Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) imposes criminal and civil liability for knowingly and willfully executing a scheme or attempting to execute a scheme, to defraud any healthcare benefit program, including private payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense or falsifying, concealing or covering up a material fact or making any materially false statements in connection with the delivery of or payment for healthcare benefits, items or services.

payment for healthcare benefits, items or services.

Similar to the federal Anti-Kickback Statute, a person or entity need not have actual knowledge of the statute or specific intent to violate it in order to have committed a violation;

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state and foreign laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers;

state and foreign laws that require drug manufacturers to report information related to drug pricing and payments and other transfers of value

to physicians and other healthcare providers and restrict marketing practices or require disclosure of marketing expenditures and pricing information;

state and foreign laws that require drug manufacturers to report information related to drug pricing and payments and other transfers of value to physicians and other healthcare providers and restrict marketing practices or require disclosure of marketing expenditures and pricing information;

state and local laws that require the registration of pharmaceutical sales representatives;

state and foreign laws that govern the privacy and security of health information in some circumstances.

In addition, some states have passed laws that require pharmaceutical companies to comply with the April 2003 Office of Inspector General Compliance Program Guidance for Pharmaceutical Manufacturers and/or the Pharmaceutical Research and Manufacturers of America’s Code on Interactions with Healthcare Professionals.

In addition, some states have passed laws that require pharmaceutical companies to comply with the April 2003 Office of Inspector General Compliance Program Guidance for Pharmaceutical Manufacturers and/or the PhRMA Code on Interactions with Healthcare Professionals.

These data privacy and security laws may differ from each other in significant ways and often are not pre-empted by HIPAA, which may complicate compliance efforts.

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Our co-pay coupon programs could become the target of similar insurer actions.

In addition, in November 2013, the CMS issued guidance to the issuers of qualified health plans sold through the ACA’s marketplaces encouraging such plans to reject patient cost-sharing support from third parties and indicating that the CMS intends to monitor the provision of such support and may take regulatory action to limit it in the future.

The CMS subsequently issued a rule requiring individual market qualified health plans to accept third-party premium and cost-sharing payments from certain government-related entities.

In addition, in November 2013, CMS issued guidance to the issuers of qualified health plans sold through the ACA’s marketplaces encouraging such plans to reject patient cost-sharing support from third parties and indicating that CMS intends to monitor the provision of such support and may take regulatory action to limit it in the future.

CMS subsequently issued a rule requiring individual market qualified health plans to accept third-party premium and cost-sharing payments from certain government-related entities.

In September 2014, the Office of Inspector General (the “OIG”) of the HHS issued a Special Advisory Bulletin warning manufacturers that they may be subject to sanctions under the federal anti-kickback statute and/or civil monetary penalty laws if they do not take appropriate steps to exclude Part D beneficiaries from using co-pay coupons.

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It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations.

we become subject to a corporate integrity agreement or similar settlement to resolve allegations of non-compliance with these laws and the curtailment or restructuring of our operations.

If our operations are found to be in violation of any of these laws or any other related governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, disgorgement, exclusion from government funded healthcare programs, such as Medicare and Medicaid, reputational harm, additional oversight and reporting obligations if we become subject to a corporate integrity agreement or similar settlement to resolve allegations of non-compliance with these laws and the curtailment or restructuring of our operations.

If any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to similar actions, penalties and sanctions.

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It also makes several changes to the Medicare Part D benefit, including the creation of a new manufacturer discount program in place of the current coverage gap discount program (beginning in 2025).

Finally, in order to be eligible to have its products paid for with federal funds under the Medicaid and Medicare Part B programs and purchased by the Department of Veterans Affairs (“VA”), Department of Defense (“DoD”), Public Health Service, and Coast Guard (the “Big Four agencies”) and certain federal grantees, a manufacturer is required to participate in the VA Federal Supply Schedule (“FSS”) pricing program, established under Section 603 of the Veterans Health Care Act of 1992.

In order to be eligible to have its products paid for with federal funds under the Medicaid and Medicare Part B programs and purchased by the Department of Veterans Affairs (“VA”), Department of Defense (“DoD”), Public Health Service, and Coast Guard (the “Big Four Agencies”) and certain federal grantees, a manufacturer is required to participate in the VA Federal Supply Schedule (“FSS”) pricing program, established under Section 603 of the Veterans Health Care Act of 1992.

Under this program, the manufacturer is obligated to make its covered drugs available for procurement on an FSS contract and charge a price to the Big Four Agencies that is no higher than the Federal Ceiling Price (“FCP”), which is a price calculated pursuant to a statutory formula.

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The rebates are calculated as the difference between the annual Non-FAMP and FCP for the calendar year that the product was dispensed.

In addition, at the state level, legislatures have increasingly passed legislation and implemented regulations similar to those under consideration at the federal level, as well as laws designed to control pharmaceutical and biotherapeutic product pricing, including restrictions on pricing or reimbursement at the state government level, limitations on discounts to patients, marketing cost disclosure and transparency measures, restrictions or other limitations on patient assistance, and, in some cases, policies to encourage importation from other countries (subject to federal approval) and bulk purchasing.

Certain states are also pursuing cost containment efforts through Prescription Drug Affordability Boards (“PDABs”) and similar entities.

While many PDABs have been granted authority to promote drug price transparency and reporting, some states have granted PDABs more expansive authority, including to set Upper Payment Limits (“UPLs”) on select, high price drugs.

The adoption and implementation of UPLs may put downward pressure on drug prices and impact our company’s future revenues.

Human Capital

As of December 31, 2025, we had 915 full-time employees, including 258 engaged in research, development and medical affairs, 526 in commercial activities and 131 in general and administrative functions.

In 2025, we added a significant number of employees to support our commercial operations in both the United States and Europe.

In addition, we have added employees in research and development as we continue to expand our pipeline activities.

None of our employees are covered by collective bargaining agreements and we consider relations with our employees to be good.

We expect our headcount to increase in 2025 in anticipation of continuing our U.S.

infrastructure growth and expanding our commercial activities in Europe, pending approval of Rezdiffra by the EC.

We also retain consultants on an as-needed basis.

We believe that our future success will be shaped by our continued ability to attract and retain highly skilled employees.

provide our employees with a competitive total rewards package inclusive of salaries, bonuses and equity ownership.

We provide our employees with a competitive total rewards package inclusive of salaries, bonuses and equity ownership.

We also provide robust benefits designed to promote well-being across all aspects of their lives, including health care, disability, retirement investment options and paid time off.

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No portion of our website is incorporated by reference into this Annual Report.

We advise you to read this Annual Report in conjunction with other reports and documents that we file from time to time with the U.S.

Securities and Exchange Commission (“SEC”).

In particular, please read our definitive proxy statement, which will be filed with the SEC in connection with our 2025 annual meeting of stockholders, our quarterly reports on Form 10-Q and any current reports on Form 8-K that we may file from time to time.

We advise you to read this Annual Report in conjunction with other reports and documents that we file from time to time with the SEC.

In particular, please read our definitive proxy statement, which will be filed with the SEC in connection with our 2026 annual meeting of stockholders, our quarterly reports on Form 10-Q and any current reports on

Form 8-K that we may file from time to time.

You may obtain copies of these reports after the date of this Annual Report directly from us or from the SEC at its website at www.sec.gov.

We make our periodic and current reports available on our internet website, free of charge, as soon as reasonably practicable after such material is electronically filed with, or furnished to, the SEC.

We have adopted a Corporate Code of Conduct and Ethics and written charters for our Audit Committee, Compensation Committee and Nominating and Corporate Governance Committee.

We have adopted a Corporate Code of Conduct and Ethics, Corporate Governance Guidelines and written charters for our Audit Committee, Compensation Committee, Nominating and Corporate Governance Committee and Science and Technology Committee.

Each of the foregoing is available on our website at www.madrigalpharma.com under “Investors & Media—Corporate Governance.” In accordance with SEC rules, we intend to disclose any amendment (other than any technical, administrative or other non-substantive amendment) to the above code, or any waiver of any provision thereof with respect to any of our executive officers, on our website within four business days following such amendment or waiver.

2 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business