RegulationPriority Review (United States), Breakthrough Therapy (United States), Accelerated Approval (United States), Conditional marketing approval (European Union)

Structure/Sequence

Molecular FormulaC17H12Cl2N6O4

InChIKeyFDBYIYFVSAHJLY-UHFFFAOYSA-N

CAS Registry920509-32-6

Clinical Trials associated with Resmetirom

NCT07143968

/ RecruitingPhase 2IIT

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of Resmetirom for the Treatment of Metabolic Dysfunction- Associated Steatotic Liver Disease (MASLD) in People Living With Human Immunodeficiency Virus (HIV)

The purpose of this research study is to test the safety and effectiveness of the study drug, resmetirom, in participants with MASLD and HIV. This is a research study to test a drug that is already on the market with a population that was not included in the original clinical trials. Participants will be people over age 18 with HIV who are on antiretroviral therapy and have been diagnosed with MASLD.
Researchers will compare resmetirom to placebo (a look-alike substance that contains no drug) to see if resmetirom decreases the amount of fat in the liver.
Participants will:
* Complete 3 screening visits to determine eligibility.
* Take resmetirom or placebo every day for 24 weeks if eligible.
* Have 2 MRI scans to measure the amount of fat on the liver. One will be before treatment starts and one will be at the end of 24 weeks of treatment.
* Attend 3 scheduled clinic visits while on treatment for bloodwork and safety assessments.
* Participate in 3 phone calls while on treatment and one phone call 4 weeks after treatment is completed to check for safety and any health changes.

Start Date23 Apr 2026

Sponsor / Collaborator

Indiana University

NCT07541469

/ RecruitingNot Applicable

A Phase 4, Decentralized Observational Registry to Evaluate the Safety in Women With NASH and Their Infants Exposed to REZDIFFRA™ (Resmetirom) During Pregnancy and/or Lactation

To evaluate pregnancy and clinical outcomes in women with NASH and their infants after exposure to Rezdiffra at any time during pregnancy and/or lactation.

Start Date04 Mar 2026

Sponsor / Collaborator

Madrigal Pharmaceuticals, Inc.

NCT07335601

/ RecruitingPhase 2

Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate MGL-3196 (Resmetirom) in Patients With MASH Who Have Undergone Liver Transplant for MASH Cirrhosis or Other Etiologies

A Phase 2 double-blind, randomized, placebo-controlled study to evaluate resmetirom in 2 cohorts of subjects with moderate to advanced fibrosis, consistent with stage F2 and F3 fibrosis, who have undergone liver transplant. Cohort 1 will consist of patients who have undergone liver transplant for MASH cirrhosis who developed recurrent MASH. Cohort 2 will consist of subjects who have undergone liver transplant for indications other than MASH cirrhosis who developed de novo MASH.

Start Date29 Dec 2025

Sponsor / Collaborator

Madrigal Pharmaceuticals, Inc.

100 Clinical Results associated with Resmetirom

100 Translational Medicine associated with Resmetirom

100 Patents (Medical) associated with Resmetirom

338

Literatures (Medical) associated with Resmetirom

01 Aug 2026·PATHOLOGY RESEARCH AND PRACTICE

Nitric oxide pathway: Emerging therapeutic strategies for MASLD

Review

Author: Qi, Fangfang ; Zhang, Yanling ; Zhang, Ying ; Chen, Hongjin

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 30-40% of the global population, making it the most prevalent chronic liver disorder worldwide. Its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), may advance to fibrosis, cirrhosis, and hepatocellular carcinoma, imposing a substantial socioeconomic and clinical burden. The recent FDA approval of Resmetirom for non-cirrhotic MASH has marked a significant therapeutic milestone; however, the multifactorial nature of MASLD continues to necessitate the identification of complementary therapeutic targets. The nitric oxide (NO) pathway has been increasingly recognized as a context-dependent regulator in MASLD pathogenesis, exhibiting dual and sometimes opposing biological effects. Under physiological conditions, low levels of NO derived from endothelial nitric oxide synthase (eNOS) contribute to hepatic microvascular homeostasis and limit lipid accumulation. In contrast, inducible nitric oxide synthase (iNOS) activity is enhanced during chronic metabolic inflammation, leading to excessive NO production, which may promote nitrosative stress through the formation of reactive nitrogen species including peroxynitrite (ONOO⁻). These processes have been associated with mitochondrial dysfunction, eNOS uncoupling, and progressive tissue injury. Accordingly, a more precise understanding of the spatial, temporal and concentration-dependent regulation of NO signaling is required. This review synthesizes current evidence on the dual role of NO in MASLD and critically evaluates emerging therapeutic strategies targeting this pathway, with the aim of informing future translational research.

01 Jul 2026·Journal of Clinical and Experimental Hepatology

Self-Reported Cognitive Function in Metabolic Dysfunction–associated Steatotic Liver Disease and Metabolic Dysfunction–associated Steatohepatitis: A Post-hoc Analysis of the MAESTRO Resmetirom Trials

Article

Author: Nader, Fatema ; Labriola, Dominic ; Taub, Rebecca ; Younossi, Zobair M ; Racila, Andrei ; Stepanova, Maria ; Henry, Linda

Background:

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) may experience cognitive impairment that negatively impacts their health-related quality of life (HRQL).

Aim:

To develop and evaluate a self-reported surrogate measure of cognitive function in MASLD, its associations with baseline clinical characteristics, and changes during treatment with resmetirom.

Methods:

Patients with MASLD or metabolic dysfunction-associated steatohepatitis (MASH) enrolled in resmetirom clinical trials (MAESTRO-NAFLD, MAESTRO-NASH) who had completed HRQL instruments (LDQoL and CLDQ-NAFLD) at baseline, week 24 and week 52 of treatment. Using patients' data from both HRQL instruments, a Cognitive Function Self-Report score was developed.

Results:

There were 2243 patients enrolled in the clinical trials of resmetirom (50% early MASH, 42% F2-F3, 8% MASH cirrhosis). Exploratory factor analysis was performed, and the distribution of factor loadings suggested 5 items for the new Cognitive Function Self-Report score. Younger age, female sex, history of depression, clinically overt fatigue, and higher liver stiffness were independently associated with low Cognitive Function Self-Report scores (all P < 0.05). In turn, the Cognitive Function Self-Report score was strongly associated with the overall HRQL (all P < 0.0001). During treatment with resmetirom, early MASH patients receiving placebo experienced a decrease in Cognitive Function Self-Report score: mean (95% CI) change from baseline to week 24: -3.0 (-4.9 to -1.0), from baseline to week 52-2.7 (-4.7 to -0.6); no similar decrease was observed in patients treated with 80 mg or 100 mg of resmetirom (all P > 0.05). Patients who experienced improvement in their HRQL scores had Cognitive Function Self-Report scores improvement (P < 0.0001).

Conclusions:

The Cognitive Function Self-Report score offers a means of capturing patient-perceived deficits in cognition in both research and clinical care.

Clinical trials number:

MAESTRO-NAFLD-1, NCT04197479.

01 Jun 2026·CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL

Understanding Pharmacokinetic-Drug Interactions With Drugs Approved by the US Food and Drug Administration in 2024 to Better Manage the Risk of Drug Interactions With Concomitant Medications: A Review of Clinical Data From New Drug Applications

Review

Author: Owens, Katie ; Argon, Sophie ; Yu, Jingjing ; Ragueneau-Majlessi, Isabelle ; Wang, Yan

Objective:

This analysis aimed to provide a mechanistic understanding and an evaluation of the clinical relevance of pharmacokinetic drug-drug interactions (DDIs) associated with drugs approved by the Food and Drug Administration in 2024.

Methods:

Drug metabolism, transport, and absorption-based DDI data available in New Drug Applications (NDAs) of small molecular drugs approved (n = 34) was analyzed. The mechanism and clinical outcome of these interactions were characterized based on in vitro, in silico, and clinical data.

Results:

As objects, 11 drugs were identified as clinical substrates. Of these, 7 drugs were substrates of CYP3A, 3 of CYP2C9, one of CYP1A2, and one of CYP2C8, including the sensitive substrates vanzacaftor (CYP3A) and vorasidenib (CYP1A2). As precipitants, 6 drugs (acoramidis, cefepime/enmetazobactam, givinostat, lazertinib, mavorixafor, and resmetirom) were clinical inhibitors of CYP enzymes (2C8, 2C9, 2D6, 2E1, and 3A), with mavorixafor being a CYP2D6 strong inhibitor. Two drugs (elafibranor and tovorafenib) showed weak induction of CYP3A. Regarding transporter data, 3 drugs were substrates of transporters, including seladelpar (BCRP and OAT3), sulopenem (OAT3), and vadadustat (OAT1/3), and 8 drugs (arimoclomol, danicopan, givinostat, lazertinib, mavorixafor, resmetirom, vadadustat, and vazacaftor/tezacaftor/deutivacaftor) were inhibitors of transporters. All clinical DDIs with AUC changes ≥ 2-fold triggered labeling recommendations. Several DDIs with an AUC change <2 also had labeling recommendations, pertaining most often to the concomitant use of drugs with a narrow therapeutic index.

Conclusions:

Mechanistic DDI insights from newly approved therapies can be extrapolated to inform the management of commonly co-administered drugs, supporting a safer and more effective use of new drug products in the context of polypharmacy.

404

News (Medical) associated with Resmetirom

27 May 2026

·www.biospace.com

Madrigal Presents Data Demonstrating Rezdiffra Reduced Markers of Cardiovascular and Liver-Related Risk in Patients with MASH

Growing body of clinical and real-world evidence supports the role of Rezdiffra ® (resmetirom) as the foundational therapy for patients with MASH Rezdiffra improved atherogenic lipid profiles associated with cardiovascular risk , including LDL - C, ApoB and Lp(a), in a secondary analysis from the Phase 3 MAESTRO program In patients with well-compensated MASH cirrhosis (F4c), Rezdiffra improved a risk score – ANTICIPATE-NASH – that predicts the probability of experiencing severe liver-related events Multiple real-world analyses evaluating the use of Rezdiffra in routine clinical practice demonstrated early and sustained improvements in cardiometabolic parameters, liver-related biomarkers, and liver stiffness measurements; 49% of patients achieved ≥25% reduction in liver stiffness over a nine-month follow-up period CONSHOHOCKEN, Pa., May 27, 2026 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ: MDGL), a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), today announced new analyses of Phase 3 data and real-world evidence demonstrating Rezdiffra reduced markers of cardiovascular and liver-related risk in patients with MASH. The data are featured across eight poster presentations at the European Association for the Study of the Liver (EASL) Congress 2026, taking place May 27-30 in Barcelona, Spain. “New analyses from the Phase 3 MAESTRO program and a growing body of real-world evidence reinforce Rezdiffra’s position as the foundational therapy for MASH,” said David Soergel, M.D., Chief Medical Officer of Madrigal. “The data we are presenting at the EASL Congress give us new insight into Rezdiffra’s potential to reduce clinically significant portal hypertension risk in patients with well-compensated MASH cirrhosis, a population with no approved therapies. Additionally, we continue to generate evidence supporting the medication’s broad and consistent effects on key biomarkers used to monitor treatment response in everyday clinical practice, as well as markers of cardiovascular risk.” “Cardiovascular disease is the leading cause of death in people with MASH, so the secondary analysis from the Phase 3 MAESTRO program demonstrating that Rezdiffra improved LDL-C, ApoB and Lp(a) is highly relevant for clinicians and patients,” said Meena B. Bansal, M.D., F.A.A.S.L.D., System Chief, Division of Liver Diseases Director, MASH/NASH Center of Excellence, Icahn School of Medicine at Mount Sinai. “Patients achieved key MASH endpoints and significant improvements in multiple atherogenic lipids and lipoproteins regardless of baseline statin use. This is particularly important because statins are not known to meaningfully lower certain lipoproteins such as Lp(a). These results suggest Rezdiffra may provide additional cardiometabolic benefit for patients with MASH, whether or not they are receiving statin therapy. Further research is warranted to evaluate Rezdiffra’s potential to improve cardiovascular outcomes in patients with MASH.” Key Madrigal Data Presentations at the EASL Congress 2026 Poster Presentation: Reducing CV risk in patients with MASH independent of baseline statin use: Lp(a) and LDL lowering by resmetirom [Abstract # ID-FRI-149, Presenter: Meena B. Bansal] Data from a secondary analysis of the Phase 3 MAESTRO-NASH and MAESTRO-NAFLD-1 trials demonstrated that Rezdiffra improved key histologic MASH endpoints and significantly reduced multiple atherogenic lipids and lipoproteins associated with cardiovascular risk, including LDL-C and Lp(a), regardless of baseline statin use. Among statin-treated patients (n=473) receiving Rezdiffra 100mg: 44.4% of patients with baseline LDL-C ≥70mg/dL shifted to <70mg/dL at week 52. 50.0% of patients with baseline LDL-C ≥100mg/dL shifted to <100mg/dL at week 52. Among patients with elevated baseline Lp(a), 36.3% of patients with baseline Lp(a) ≥30mg/dL and 37.5% of patients with baseline Lp(a) ≥50mg/dL shifted below those thresholds. No significant statin-related safety signals were observed. Among patients receiving Rezdiffra 100mg and no statins (n=493): 13.8% of patients with baseline LDL-C ≥70mg/dL shifted to <70mg/dL at week 52. 51.5% of patients with baseline LDL-C ≥100mg/dL shifted to <100mg/dL at week 52. Among patients with elevated baseline Lp(a), 45.4% of patients with baseline Lp(a) ≥30mg/dL and 62.5% of patients with baseline Lp(a) ≥50mg/dL shifted below those thresholds. These findings support the concomitant use of Rezdiffra with statin therapy and suggest the potential for Rezdiffra to address both liver disease and cardiometabolic risk in patients with MASH. EASL Top Poster: Baseline ANTICIPATE score and response predicts liver outcome events in a 180 patient MASH cirrhosis cohort treated with resmetirom [Abstract # ID-TOP-177, Presenter: Naim Alkhouri] In patients with compensated MASH cirrhosis, clinically significant portal hypertension (CSPH) is a key driver of disease progression and severe liver-related complications. While Baveno criteria are used to identify patients likely to have CSPH, ANTICIPATE-NASH is a noninvasive risk stratification model developed for MASH that integrates liver stiffness measurements, platelet count and body mass index (BMI) to estimate future CSPH risk and predict the likelihood of liver-related events over the subsequent three years. The ANTICIPATE-NASH risk model was applied to the open-label extension (OLE) cohort from the MAESTRO-NAFLD-1 trial, which included patients with well-compensated MASH cirrhosis (F4c) treated with Rezdiffra for up to two years. Results demonstrated progressive improvements in ANTICIPATE-NASH risk scores over time: The proportion of patients classified as high risk for CSPH decreased from 75% at baseline to 60.3% at Year 1 and 54.5% at Year 2. Mean ANTICIPATE-NASH scores declined by up to 37.6% over two years of treatment. Liver-related events were infrequent and occurred exclusively in patients with baseline ANTICIPATE-NASH scores associated with elevated CSPH risk. These findings support the potential use of ANTICIPATE-NASH as a risk stratification tool to identify patients with a high-risk of disease progression, informing prognosis and clinical decision-making. Additional Poster Presentations (Real-World Data): Early real-world effectiveness of resmetirom in adults with metabolic dysfunction associated steatohepatitis and moderate-to-advanced- fibrosis [Abstract #ID-FRI-141, Presenter: Naim Alkhouri] Twelve-month changes in liver function enzymes and lipids in patients receiving resmetirom [Abstract # ID-FRI-186, Presenter: Anthony Martinez] Non-invasive test-driven modeling of patient eligibility for resmetirom therapy in MASLD: Data from the German SLD-Registry [Abstract #ID-WED-155, Presenter: Maurice Michel] Multiple real-world studies evaluating patients treated with Rezdiffra for up to 12 months in routine clinical practice are also being presented at EASL. Collectively, these studies demonstrated that patients achieved clinically meaningful improvements in biomarkers of liver disease and cardiometabolic risk. Improvements were observed as early as approximately six months following treatment initiation and sustained through approximately 12 months. Rezdiffra was generally well tolerated, with low rates of treatment-related adverse events and discontinuations reported in routine clinical practice. Abstract #ID-FRI-141: In an analysis of data from a large gastroenterology practice, Rezdiffra use was associated with clinically meaningful improvements in laboratory and non-invasive clinical measures. Over a mean follow-up period of approximately nine months, 48.6% of patients achieved ≥25% reduction in liver stiffness, a key measure of treatment response. Rezdiffra was well tolerated in this analysis, and discontinuation due to treatment-related adverse events was <1%. Abstract # ID-FRI-186: In another electronic health record analysis of 728 patients treated with Rezdiffra over 12 months, statistically significant reductions in ALT and AST were observed; these reductions in liver enzymes were consistent across all subgroups, irrespective of baseline type 2 diabetes status, obesity, GLP-1 and statin use. LDL-C levels also decreased significantly in the overall cohort and showed directional reductions across all subgroups. Abstract #ID-WED-155: A prospective registry study (Germany Steatotic Liver Disease [SLD]) aimed to characterize patients eligible for Rezdiffra treatment based on noninvasive tests (NITs) in a real-world cohort in Germany. Of the 1,308 patients analyzed, approximately one in five met the criteria for treatment. The treatment-eligible cohort showed a higher distribution of three or more metabolic comorbidities simultaneously. Identification of such patients using NITs such as liver stiffness may support risk stratification and inform treatment strategies in routine clinical practice. About Rezdiffra Rezdiffra (resmetirom) is a once-daily, oral, liver-directed thyroid hormone receptor (THR)-β agonist designed to address key underlying causes of MASH. It was the first medication approved for the treatment of MASH in the U.S. and Europe. In the pivotal Phase 3 MAESTRO-NASH biopsy trial, Rezdiffra achieved both fibrosis improvement and MASH resolution primary endpoints. Rezdiffra also reduced liver stiffness, liver fat, liver enzymes and atherogenic lipids in the MAESTRO-NASH trial and improved health-related quality of life. At one year, 91% of patients treated with Rezdiffra 100mg achieved improvement or stabilization of liver stiffness. 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). Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials. Rezdiffra is not approved in any geography for the treatment of patients with cirrhosis. About MASH Metabolic dysfunction-associated steatohepatitis (MASH) is a serious liver disease that can progress to cirrhosis, liver failure, liver cancer, the need for liver transplantation and premature mortality. MASH is the leading cause of liver transplantation in women and the second leading cause of all liver transplantation in the U.S., and the fastest-growing indication for liver transplantation in Europe. Once patients progress to MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), the risk of adverse liver outcomes increases dramatically: these patients have a 10 to 17 times higher risk of liver-related mortality as compared to patients without fibrosis. Patients with MASH who progress to cirrhosis face a 42 times higher risk of liver-related mortality, underscoring the need to treat MASH before complications of cirrhosis develop. MASH is also an independent driver of cardiovascular disease, the leading cause of mortality for patients. As disease awareness improves and disease prevalence increases, the number of diagnosed patients with F2 to F4c MASH is growing. What is Rezdiffra? Rezdiffra is a prescribed medicine used along with diet and exercise to treat adults with metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver. This indication is approved based on improvement of MASH and liver scarring (fibrosis). There are ongoing studies to confirm the clinical benefit of Rezdiffra. Before you take Rezdiffra, tell your healthcare provider about all of your medical conditions, including if you: have any liver problems other than MASH. have gallbladder problems or have been told you have gallbladder problems, including gallstones. are pregnant or plan to become pregnant. It is not known if Rezdiffra will harm your unborn baby. A pregnancy safety study for women who take Rezdiffra during pregnancy collects information about the health of you and your baby. You or your healthcare provider can report your pregnancy by visiting or calling 1-800-905-0324. are breastfeeding or plan to breastfeed. It is not known if Rezdiffra passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Rezdiffra. Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins and herbal supplements. Rezdiffra and other medicines may affect each other, causing side effects. Rezdiffra may affect the way other medicines work, and other medicines may affect how Rezdiffra works. Especially tell your healthcare provider if you take medicines that contain gemfibrozil to help lower your triglycerides, because Rezdiffra is not recommended in patients taking these medicines. Tell your healthcare provider if you are taking medicines such as clopidogrel to thin your blood or statin medicines to help lower your cholesterol. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. What are the possible side effects of Rezdiffra? Rezdiffra may cause serious side effects, including: liver injury (hepatotoxicity). Stop taking Rezdiffra and call your healthcare provider right away if you develop the following signs or symptoms of hepatotoxicity: tiredness, nausea, vomiting, fever, rash, your skin or the white part of your eyes turns yellow (jaundice) or stomach pain/tenderness. gallbladder problems. Gallbladder problems such as gallstones, or inflammation of the gallbladder, or inflammation of the pancreas from gallstones can occur with MASH and may occur if you take Rezdiffra. Call your healthcare provider right away if you develop any signs or symptoms of these conditions including nausea, vomiting, fever, or pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen to your back and the pain may happen with or without vomiting. The most common side effects of Rezdiffra include: diarrhea, nausea, itching, stomach pain, vomiting, dizziness and constipation. These are not all the possible side effects of Rezdiffra. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or You may also report side effects to Madrigal at 1-800-905-0324. Please see the full Prescribing Information, including Patient Information, for Rezdiffra. About Madrigal Madrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), a liver disease with high unmet medical need. Madrigal’s medication, Rezdiffra (resmetirom), is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of MASH. Rezdiffra was the first medication approved by both the FDA and European Commission for the treatment of MASH with moderate to advanced fibrosis (F2 to F3). An ongoing Phase 3 outcomes trial is evaluating Rezdiffra for the treatment of compensated MASH cirrhosis (F4c). For more information, visit and follow us on LinkedIn . Forward-Looking Statements This press release includes “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended, including statements related to Rezdiffra’s ability to potentially improve cardiovascular outcomes in patients with MASH and the potential benefit of Rezdiffra in patients with compensated MASH cirrhosis. Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to: the assumptions underlying the forward-looking statements; our ability to successfully commercialize Rezdiffra in the U.S. and Europe; risks related to obtaining and maintaining regulatory approvals, including, but not limited to, potential regulatory delays or rejections; our history of operating losses and the possibility that we may never achieve or maintain profitability; risks associated with meeting the objectives of our clinical trials, including, but not limited to our ability to achieve enrollment objectives concerning patient numbers (including an adequate safety database), outcomes objectives and/or timing objectives for our trials; any delays or failures in enrollment, and the occurrence of adverse safety events; risks related to the effects of Rezdiffra’s (resmetirom’s) mechanism of action or of any other product candidate; market demand for and acceptance of Rezdiffra; our ability to service indebtedness and otherwise comply with debt covenants; outcomes or trends from competitors; future topline data timing or results; our ability to prevent and/or mitigate cyber-attacks; our ability to protect our intellectual property rights; the uncertainties inherent in clinical testing; uncertainties concerning analyses or assessments outside of a controlled clinical trial; and changes in laws and regulations applicable to our business and our ability to comply with such laws and regulations. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made. Madrigal undertakes no obligation to update any forward-looking statements to reflect new information, events, or circumstances after the date they are made, or to reflect the occurrence of unanticipated events. Please refer to Madrigal’s submissions filed with the U.S. Securities and Exchange Commission (SEC) for more detailed information regarding these risks and uncertainties and other factors that may cause actual results to differ materially from those expressed or implied. Madrigal specifically discusses these risks and uncertainties in greater detail in the sections appearing in Part 1A of its Annual Report on Form 10-K for the year ended December 31, 2025, and as updated from time to time by Madrigal’s other filings with the SEC. Madrigal may use its website to comply with its disclosure obligations under Regulation FD. Therefore, investors should monitor Madrigal’s website in addition to following its press releases, filings with the SEC, public conference calls, and webcasts. Madrigal Pharmaceuticals, Rezdiffra® and associated logos are trademarks of Madrigal Pharmaceuticals, Inc. Investor Contact Tina Ventura, IR@madrigalpharma.com Media Contact Christopher Frates, media@madrigalpharma.com

Clinical ResultPhase 3Drug Approval

27 May 2026

·www.biospace.com

Hepta’s Blood Test Outperforms FIB-4, ELF, and FibroScan in Identifying Treatment-Eligible MASH Patients

Validation on an independent cohort confirms superior accuracy in detecting MASH with F2/F3 fibrosis, the stages where therapy is now approved FOSTER CITY, Calif.--(BUSINESS WIRE)--Hepta, a liquid biopsy company developing blood tests for chronic disease, today announced clinical data showing its blood test more accurately identifies metabolic dysfunction-associated steatohepatitis (MASH) patients eligible for treatment than the three non-invasive tests recommended by current clinical guidelines: FIB-4, ELF, and FibroScan. The 528-patient, multi-cohort study will be presented at the European Association for the Study of the Liver (EASL) 2026 Congress in Barcelona on May 30. The data will be presented by Jörn Schattenberg, M.D., Director of the Department of Gastroenterology, Hepatology, Endocrinology and Nutritional Medicine at Saarland University Medical Center in Germany, at EASL 2026 as Abstract OS-099. The work was selected for oral presentation and chosen for Best of EASL 2026, which highlights the most clinically and scientifically impactful data, including late-breaking results, presented at the annual Congress. Rezdiffra and Wegovy are now approved for MASH with moderate-to-advanced fibrosis, stages F2 and F3, but identifying these patients at scale has remained challenging. MASH, a progressive form of fatty liver disease characterized by liver inflammation and damage linked to obesity and metabolic dysfunction, typically produces no symptoms until liver damage is advanced. Liver biopsy, the gold standard, is invasive, resource-intensive, and impractical for routine clinical use. The non-invasive blood tests commonly used today were built to identify F3 and F4 fibrosis, the more advanced stages, and miss nearly one-third of the patients now eligible for therapy. Imaging-based testing further depends on specialized equipment and trained operators, putting it out of reach for the population scale this disease requires. These gaps point to the need for an accurate, scalable, blood-based test that can identify treatment-eligible patients in routine clinical practice. The study included 528 biopsy-confirmed MASLD patients across three independent cohorts: Duke University, the University Medical Center Mainz, and the screening population of Akero Therapeutics' SYNCHRONY, a contemporary Phase 3 program in MASH. The dataset is one of the largest multi-cohort cell-free DNA (cfDNA) methylation studies in MASH to date. Hepta's test analyzes methylation patterns, epigenetic marks on DNA fragments shed from the liver and other organs into the bloodstream, giving clinicians a molecular readout of disease biology from a standard blood draw. Hepta's LiquidTransformer platform, a large AI model with more than 100 million parameters designed for cfDNA methylation data, was trained on samples from Duke and Mainz cohorts (n = 349) and validated on the SYNCHRONY cohort (n = 179). In head-to-head comparisons on the hold-out validation set, the platform outperformed FIB-4, ELF, and FibroScan in detecting significant fibrosis (F2+) with an AUC of 0.83. It also outperformed all three tests in separating treatment-eligible F2/F3 patients from earlier-stage and cirrhotic disease, using a Pareto frontiers comparison method. A separate meta-analysis showed the Hepta score outperformed published performance benchmarks for a wide range of non-invasive tests, including all three in clinical guidelines. The hold-out validation cohort was collected across more than 50 sites and is completely independent of the training cohort. By design, this rules out overfitting to the training data, a central concern for clinical machine-learning diagnostics, and supports confident generalization of the results to new patients and populations. “Existing non-invasive tests for MASH predate effective therapies and were never optimized for treatment selection,” said Hamed Amini, Ph.D., CEO and co-founder of Hepta. “ We built a classifier for the clinically actionable question of identifying treatment-eligible patients. On hold-out validation, head-to-head on the same samples, it outperforms FIB-4, ELF, and FibroScan. Our test identifies adults with noncirrhotic MASH with moderate to advanced liver fibrosis, that is F2-F3, the patient population for whom Rezdiffra and Wegovy are now approved." The findings extend a growing body of evidence for Hepta’s LiquidTransformer, its purpose-built AI platform that captures tissue biology from cfDNA to enable application of liquid biopsy in chronic disease. At Digestive Disease Week 2026, the company presented data showing the same cfDNA methylation approach can identify semaglutide weight-loss responders before treatment begins and track drug-induced biological changes over time, extending its capabilities from disease characterization to treatment response. Data presented at AASLD 2025 demonstrated that the platform reads disease biology at the pathway level, establishing the foundational science for both diagnostic and monitoring applications. “The ultimate blood test for MASH needs to do three things: detect treatment-eligible disease, guide therapy selection, and monitor patient response over time to signal whether a therapy is working,” said Soheil Damangir, Ph.D., CTO and co-founder of Hepta. “This data establishes that we can identify the patients who should be on therapy more accurately than the tests in current guidelines. Our recent DDW data demonstrated the second and third: predicting treatment response before therapy begins and tracking MOA-specific drug effects from blood. Together, this is a platform built to serve the continuum of biomarker needs in MASH.” About Hepta Hepta is building a blood-based epigenetic measurement platform for chronic disease, starting with MASH. Founded by former Illumina, GRAIL, and Google scientists, the company is backed by Felicis Ventures, Illumina Ventures, SeaX Ventures, Alumni Ventures, and AME Cloud Ventures. Hepta's liquid biopsy-native AI platform, LiquidTransformer, decodes cfDNA methylation data from a standard blood draw, enabling tissue-level biological insight without the need for a biopsy. For more information, visit hepta.bio . Contacts Media Contact Patrick Schmidt hepta@consortpartners.com

27 May 2026

·www.biospace.com

Sagimet Biosciences Presents Two Posters at EASL 2026 on Denifanstat/Resmetirom Combination in MASH

Phase 1 clinical data poster selected as a Best of EASL 2026 presentation Combination of denifanstat and resmetirom was generally well-tolerated in Phase 1 clinical trial Phase 1 data show rapid reductions in cholesterol levels, suggesting the potential for a cardiovascular benefit SAN MATEO, Calif., May 27, 2026 (GLOBE NEWSWIRE) -- Sagimet Biosciences Inc. (Nasdaq: SGMT), a clinical-stage biopharmaceutical company developing novel therapeutics targeting dysfunctional metabolic and fibrotic pathways, today announced the presentation of two posters at the European Association for the Study of the Liver (EASL) Annual Congress 2026, being held in Barcelona, Spain on May 27-30, 2026. The Late-Breaking denifanstat/resmetirom poster, covering Phase 1 clinical data on the combination of Sagimet's oral once-daily fatty acid synthase (FASN) inhibitor, denifanstat, and resmetirom, a thyroid hormone receptor beta (THR-β) agonist, was selected as a Best of EASL 2026 presentation. A second poster presents preclinical data on the combination's mechanism of action. EASL Poster Presentation Details: Selected for Best of EASL 2026 : Denifanstat and resmetirom combination therapy rapidly decreased atherogenic lipids in healthy adults in Phase 1 open-label trial Presenter: Mary E. Rinella, MD, University of Chicago Session: LBP-032 Date: Wednesday to Saturday, May 27-30, 2026 Author attending: Friday, May 29 th 12:45 to 1:45 PM CEST Location: Fira Barcelona, Spain Poster Highlights: This Phase 1 trial built on preclinical data showing that the combination of a FASN inhibitor and resmetirom improved liver histology versus monotherapy through complementary mechanisms of liver fat reduction and denifanstat’s direct anti-fibrotic effect. The Phase 1 open label clinical trial evaluated the safety, pharmacodynamics, and pharmacokinetics of the denifanstat/resmetirom combination in 40 healthy adults with a mean BMI of 30-32 kg/m 2 . Two cohorts assessed different dosing sequences: subjects received 7 days of monotherapy followed by 7 days of combination therapy. Cohort 1 initiated monotherapy with denifanstat and Cohort 2 with resmetirom. Denifanstat was dosed at 50 mg and resmetirom utilized weight-based dosing (80 or 100 mg). Topline safety data reported in December 2025 showed that the combination of denifanstat and resmetirom was generally well-tolerated over the duration of the study, with no safety signals. Clinical data reported for the first time at EASL 2026 show rapid reduction in total and LDL cholesterol levels (p<0.001) after two weeks of treatment, suggesting a potential cardiovascular benefit: Cohort 1 (denifanstat followed by denifanstat/resmetirom): total cholesterol -23mg/dl, LDL cholesterol -17mg/dl Cohort 2 (resmetirom followed by denifanstat/resmetirom): total cholesterol -16mg/dl, LDL cholesterol -14mg/dl Target engagement was demonstrated for both agents, with key pharmacodynamic biomarkers confirming the mechanism of action for each agent. Together with prior clinical evidence of fibrosis improvement with each monotherapy, these results support the potential benefit of a denifanstat and resmetirom combination for MASH and liver fibrosis. Poster Title: Transcriptomic analysis revealed distinct mechanisms underlying the synergistic effect of a fatty acid synthase (FASN) inhibitor and resmetirom combination in LDL receptor knockout MASH mice Presenter: Wen-Wei Tsai, PhD, Senior Director R&D, Translational Sciences, Sagimet Biosciences Session: SAT-227 Date: Saturday, May 30, 2026 Author attending: Saturday, May 30 th 11:45 to 12:45 PM CEST Location: Fira Barcelona, Spain Poster Highlights: The combination of a FASN inhibitor and resmetirom showed greater improvements in liver histology and lipid lowering compared to monotherapy in mouse model of diet-induced MASH. Transcriptomic analysis further characterized the molecular mechanisms driving these effects, showing enhanced anti-inflammatory and anti-fibrotic activity and improved metabolic regulation including lipid and cholesterol synthesis. About Sagimet Biosciences Sagimet is a clinical-stage biopharmaceutical company developing novel FASN inhibitors designed to target dysfunctional metabolic and fibrotic pathways in conditions resulting from the overproduction of the fatty acid, palmitate. FASN is a regulator of lipid synthesis, and a key pathway implicated in multiple diseases, such as acne, MASH and certain FASN-dependent tumor types. For additional information about Sagimet, please visit . About MASH MASH is a progressive and severe liver disease which is estimated to impact more than 265 million people worldwide 1 . MASH is characterized by the build-up of fat in the liver and various degrees of inflammation and fibrosis along with systemic metabolic changes including dyslipidemia (increased fat levels in blood) and insulin resistance. Patients with moderate to severe disease who have advanced fibrosis (F3) or cirrhosis (F4) have the highest risk of liver-related outcomes such as decompensation, hepatocellular carcinoma, and liver transplantation. There are few approved treatments for non-cirrhotic MASH (stages F1, F2 and F3 fibrosis) and no approved treatments for MASH cirrhosis (F4). 1. Younossi ZM, et al. Hepatology . 2023;77(4): 1335-1347. Forward-Looking Statements This press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, The Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical facts or statements that relate to present facts or current conditions, including but not limited to, statements regarding the expected timing of the presentation of data from ongoing clinical trials, Sagimet’s clinical development plans and related timelines and anticipated development milestones, are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause Sagimet’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, these statements can be identified by terms such as “may,” “might,” “will,” “should,” “expect,” “plan,” “aim,” “seek,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “forecast,” “potential” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this press release are only predictions. Sagimet has based these forward-looking statements largely on its current expectations and projections about future events and financial trends that Sagimet believes may affect its business, financial condition and results of operations. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, some of which cannot be predicted or quantified and some of which are beyond Sagimet’s control, including, among others: the clinical development and therapeutic potential of denifanstat, TVB-3567 or any other drug candidates or combination therapies developed by Sagimet; Sagimet’s ability to advance drug candidates into and successfully complete clinical trials within anticipated timelines; Sagimet’s relationship with Ascletis, and the success of its development efforts for denifanstat; the accuracy of Sagimet’s estimates regarding its capital requirements and Sagimet’s ability to maintain and successfully enforce adequate intellectual property protection. These and other risks and uncertainties are described more fully in the “Risk Factors” section of Sagimet’s most recent filings with the Securities and Exchange Commission and available at . You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in these forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Moreover, Sagimet operates in a dynamic industry and economy. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that Sagimet may face. Except as required by applicable law, Sagimet does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Investor Contact: Joyce Allaire LifeSci Advisors JAllaire@LifeSciAdvisors.com Media Contact: Maggie Whitney LifeSci Communications mwhitney@lifescicomms.com

Clinical ResultPhase 1

100 Deals associated with Resmetirom

External Link

KEGG	Wiki	ATC	Drug Bank
D11602	-	-	DB12914

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Fibrosis, Liver	United States	Madrigal Ltd.	14 Mar 2024
Fibrosis, Liver	United States	Madrigal Pharmaceuticals, Inc.	14 Mar 2024
Metabolic Dysfunction Associated Steatohepatitis	United States	Madrigal Ltd.	14 Mar 2024
Metabolic Dysfunction Associated Steatohepatitis	United States	Madrigal Pharmaceuticals, Inc.	14 Mar 2024

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Liver Cirrhosis	Phase 3	United States	Madrigal Pharmaceuticals, Inc.	26 Aug 2022
Liver Cirrhosis	Phase 3	Belgium	Madrigal Pharmaceuticals, Inc.	26 Aug 2022
Liver Cirrhosis	Phase 3	Canada	Madrigal Pharmaceuticals, Inc.	26 Aug 2022
Liver Cirrhosis	Phase 3	France	Madrigal Pharmaceuticals, Inc.	26 Aug 2022
Liver Cirrhosis	Phase 3	Germany	Madrigal Pharmaceuticals, Inc.	26 Aug 2022
Liver Cirrhosis	Phase 3	Italy	Madrigal Pharmaceuticals, Inc.	26 Aug 2022
Liver Cirrhosis	Phase 3	Spain	Madrigal Pharmaceuticals, Inc.	26 Aug 2022
Liver Cirrhosis	Phase 3	United Kingdom	Madrigal Pharmaceuticals, Inc.	26 Aug 2022
Metabolic dysfunction-associated steatotic liver disease	Phase 3	United States	Madrigal Pharmaceuticals, Inc.	16 Dec 2019
Fibrosis	Phase 3	United States	Madrigal Pharmaceuticals, Inc.	28 Mar 2019

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04197479 (MAESTRO-NAFLD-1, Pubmed \| J Clin Exp Hepatol)	Phase 2/3	Metabolic Dysfunction Associated Steatohepatitis \| Metabolic dysfunction-associated steatotic liver disease	2,243	Resmetirom 80 mg	olldbtviij(miovjapxwb) = vwoumopniv glahakptzi (rnaetkjdai, -4.9 to -1.0) View more	Positive	01 Jul 2026
				Resmetirom 100 mg	olldbtviij(miovjapxwb) = dsaslfxwas glahakptzi (rnaetkjdai, -4.7 to -0.6)
NCT02912260 (MAESTRO \| MGL-3196-05, CTgov)	Phase 2	Metabolic Dysfunction Associated Steatohepatitis	125	MGL-3196 (MGL-3196)	nqensrrjqs(uizshpkevv) = vfiyhxzmmn uzmqmbyfog (zsuazjmepr, 3.0) View more	-	23 Dec 2025
				Placebo (Placebo)	nqensrrjqs(uizshpkevv) = pvnmjxhonb uzmqmbyfog (zsuazjmepr, 4.3) View more
NCT03038022 (CTgov)	Phase 2	Heterozygous familial hypercholesterolemia	116	MGL-3196 (resmetirom) (MGL-3196)	yziebmtbkt(lgplqqjumt) = hmkhaezeie zuhxbgqqwq (lpbkffheoi, 2.59) View more	-	23 Dec 2025
				Placebo (Placebo)	yziebmtbkt(lgplqqjumt) = aretczggjg zuhxbgqqwq (lpbkffheoi, 3.71) View more
NCT04951219 \| NCT04197479 (MAETRO-NAFLD-1, AASLD2025) Manual	Phase 3	Metabolic Dysfunction Associated Steatohepatitis	122	Resmetirom (80 mg)	skhdrdkjxc(wlfusotbgk) = yflvvableu lkxqlrzqvy (zfjjpmlztb ) View more	Positive	07 Nov 2025
				Resmetirom (80 mg) (Platelet <100 K)	skhdrdkjxc(wlfusotbgk) = srbwqrfwiv lkxqlrzqvy (zfjjpmlztb ) View more
NCT03900429 (MAESTRO-NASH, Pubmed \| Aliment Pharmacol Ther)	Phase 3	Metabolic Dysfunction Associated Steatohepatitis	165	Resmetirom 80 mg	gutexxznxg(kmjwbyabdo) = ugexheffjx jptlzuytjc (umiqwbdqqs ) View more	Positive	23 Oct 2025
				Resmetirom 100 mg	gutexxznxg(kmjwbyabdo) = obybbxvlos jptlzuytjc (umiqwbdqqs ) View more
NCT04197479 (MAESTRO-NAFLD-1, Company_Website) Manual	Phase 3	Metabolic Dysfunction Associated Steatohepatitis	113	Rezdiffra	djtchxseia(nnktjuuiuz) = gyrxsgalhe kdgoiambdg (uxwrgpvckk ) View more	Positive	10 May 2025
NCT04197479 (MAESTRO-NAFLD-1, Pubmed \| Gastro Hep Adv)	Phase 3	Metabolic Dysfunction Associated Steatohepatitis	32	Resmetirom (MASH-related Child-Pugh A cirrhosis)	wnzvqdmqyy(cqxeqdptho) = diixdzwsdv wmylqnbfjs (rwluigzwwj ) View more	Positive	01 Jan 2025
NCT03900429 (MAESTRO-NASH, UEGW2024)	Phase 3	Metabolic Dysfunction Associated Steatohepatitis	966	Resmetirom 80 mg	vkcykvrinx(kngrvyuvsa) = xnosbwgybf xmixkstmrl (csdznfeyqe ) View more	Positive	13 Oct 2024
				Resmetirom 100 mg	vkcykvrinx(kngrvyuvsa) = utdfvhlvvr xmixkstmrl (csdznfeyqe ) View more
NCT03900429 (MAESTRO-NASH, UEGW2024)	Phase 3	Metabolic Dysfunction Associated Steatohepatitis Carbohydrate Deficient Transferrin (CDT) \| PEth test	966	Resmetirom 80 mg	ywvzlosvmf(bwyzzgjbdc) = hithwaqksq uzbheqymny (khnkdjlebv ) View more	Positive	13 Oct 2024
				Resmetirom 100 mg	ywvzlosvmf(bwyzzgjbdc) = btvqplnbbe uzbheqymny (khnkdjlebv ) View more
UEGW2024	Not Applicable	Metabolic Dysfunction Associated Steatohepatitis	-	Resmetirom 80 mg	gjabvdmuvz(nogtduaffi) = bwjkycmtfh qhdgtiglkm (vuymwxnhaf, 4.61)	-	13 Oct 2024
				Resmetirom 100 mg	gjabvdmuvz(nogtduaffi) = ryvrdjqwwj qhdgtiglkm (vuymwxnhaf, 4.76)

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis