A Phase 2, Double-Blind, Multi-Center, Placebo-Controlled Clinical Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of FHL-301 in Adult Patients With Parkinson's Disease

This is a phase 2, double-blind, multi-center, placebo-controlled clinical study to evaluate the safety, tolerability, efficacy, and PK of FHL-301 in adult patients with early-stage PD. Following screening, qualifying patients who meet all inclusion and exclusion criteria will enter the study and be randomized 1:1 to receive FHL-301 or Placebo at a starting dose of 200 mg BID (30 minutes before the morning and evening meals) during the 3-week titration period. To determine the tolerance of each participant for FHL-301, titration will increase by 200 mg BID every week until the maximum dose of 600 mg BID or the highest tolerated dose of 1200 mg daily is reached and maintained for 1 week. Thereafter, patients who complete the dose Titration Phase of the study will enter the Maintenance Phase and remain on the final titrated dose for up to 48 weeks post titration. If at any stage during the titration phase the participant cannot tolerate the increased dose, the dose will be decreased by 100 mg BID weekly until the highest tolerated dose is reached.

Start Date01 Nov 2027

Sponsor / Collaborator-

NCT06809608

/ Active, not recruitingPhase 1

An Open-Label, Fixed Sequence Study to Investigate the Effect of Multiple Oral Doses of Itraconazole, Multiple Oral Doses of Gemfibrozil, and Single Oral Dose of Cyclosporine, on the Pharmacokinetics of a Single Oral Dose of RO7795081 in Healthy Participants

This is a single-center, non-randomized, open-label, cross-over study in healthy male and female participants.
Part 1 of the study has a 2-period (a single fixed sequence) design and will investigate the impact of itraconazole on the pharmacokinetics (PK) of RO7795081 in healthy participants. A maximum of up to 25 participants will be enrolled in Part 1 and sequentially undergo Period 1 (RO7795081 alone) followed by Period 2 (RO7795081 with itraconazole).
Part 2 of the study has an adaptive design with up to 4 periods (a single fixed sequence) and will investigate the impact of gemfibrozil and cyclosporine on the PK of RO7795081 in healthy participants. A maximum of up to 25 participants will be enrolled in Part 2 and sequentially undergo Period 1 (RO7795081 alone) followed by Period 2 (RO7795081 with gemfibrozil), Period 3 (RO7795081 with cyclosporine 200 mg), and finally Period 4 (RO7795081 with cyclosporine ≤600 mg).

Start Date13 Feb 2025

Sponsor / Collaborator-

ChiCTR2400093390

/ SuspendedPhase 1IIT

Evaluation of synergistic effect of temozolomide and gemfibrozil on the patients with glioblastoma

Start Date03 Dec 2024

Sponsor / Collaborator

The First Hospital of Jilin University

100 Clinical Results associated with Gemfibrozil

100 Translational Medicine associated with Gemfibrozil

100 Patents (Medical) associated with Gemfibrozil

7,585

Literatures (Medical) associated with Gemfibrozil

01 Sep 2025·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Integrated network pharmacology and RNA sequencing analysis to reveal the mechanisms of Qici Sanling decoction in the treatment of gemcitabine resistant bladder cancer

Article

Author: Wang, Wanhui ; You, Bosen ; Geng, Bo ; Zhao, Enyang ; Liu, Weiyang ; Li, Xuedong ; Wang, Jinpeng ; Zhang, Wei ; Li, Zhuolun ; Nan, Yunfeng

Bladder cancer (BCa) is the most prevalent cancer of the urinary system in adults; the prognosis is dismal for BCa treated with gemcitabine (GEM) owing to intrinsic or acquired chemoresistance. This study investigated the potential of Qici Sanling decoction (QCSL), an herbal Chinese medicine, to augment the efficacy of GEM in treating GEM-resistant BCa via network pharmacology and RNA sequencing. We screened 103 active components of QCSL and their 226 targets from the TCMSP database and identified 3985 targets of GEM-resistant BCa via transcriptome sequencing. On the basis of the 69 common targets, a proteinprotein interaction (PPI) network was constructed to identify the top 7 targets. Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were conducted to uncover key pathways. CCK-8 assays, Western blotting, flow cytometry, colony formation, and EdU assays were used to assess the apoptosis and proliferation of GEM-resistant T24 and J82 cells treated with QCSL. The BCa gene set was among the top enriched gene sets in the DO analysis; GO analysis revealed enrichment of 2020 terms linked to GEM resistance, and KEGG analysis revealed 161 enriched signalling pathways. Molecular docking indicated that PTGS2 has high affinity for targets of QCSL components. In vitro experiments demonstrated that cells treated with both QCSL and GEM had significantly reduced viability, increased levels of apoptosis, and decreased proliferative capacity. Thus, QCSL enhances the therapeutic effects of GEM in BCa by promoting cell apoptosis and inhibiting cell proliferation. These findings have significant clinical implications, highlighting a potential combined treatment strategy for GEM-resistant BCa to improve patient outcomes.

01 Sep 2025·BIOMATERIALS

Bioactive polymers as stimulus-responsive anti-metastatic combination agents to treat pancreatic cancer

Article

Author: Sil, Diptesh ; Gendelman, Howard E ; Panja, Sudipta ; Kapoor, Ekta ; Khan, Rubayat I ; Jogdeo, Chinmay M ; Kumari, Neha ; Singh, Amar B ; Ding, Ling ; Siddhanta, Kasturi ; Oupický, David

The intractable and devastating nature of pancreatic ductal adenocarcinoma (PDAC) necessitates an urgent need for novel therapies. This study presents the development of a novel polymer prodrug system for the combination treatment of PDAC, based on an optimized pharmacologically active anti-metastatic macromolecular carrier, PCQ, conjugated with gemcitabine (GEM). Structure-activity relationship evaluations showed that random PCQ copolymers exhibited superior anti-migratory activity compared to the gradient PCQ analogs. GEM was incorporated into the random PCQ copolymers using disulfide linker to prepare a reduction-responsive prodrug, PCQ(r)6-SS-GEM12. The resultant therapeutic system presents a pharmacologically active delivery strategy that targets both the proliferative and the metastatic phenotype in PDAC. The PCQ(r)6-SS-GEM12 prodrug demonstrated a selective release of GEM under the reductive tumor environment leading to a significant inhibition of tumor growth with pronounced anti-metastatic effect. Collectively, our data show that the combination of anti-metastatic PCQ and cytotoxic GEM-based reduction-responsive prodrug polymer offers an innovative strategy to treat PDAC.

01 Aug 2025·JOURNAL OF HAZARDOUS MATERIALS

A framework to assess pharmaceutical accumulation in crops: from wastewater irrigation to consumption

Article

Author: Trapp, Stefan ; Garduño-Jiménez, Andrea ; Nightingale, John ; Carter, Laura

The reuse of treated wastewater for irrigation can inadvertently introduce a suite of emerging contaminants such as pharmaceuticals into agri-ecosystems. However, current monitoring efforts to characterise exposure usually focus on a limited range of analytes. A modelling framework was developed that employs a sequence of pre-developed models to predict accumulative potential in a model crop, Zea mays (corn), using chemical structure and excretion rate as the only model inputs. Z. mays was selected as the model crop as it is a major food source, stands as one of the highest cultivated crops globally, and is characterised as having a medium uptake potential. The framework was used to predict uptake in Z. mays in three regions characteristic of high wastewater reuse (Australia, the US and the Middle East). Despite regional and plant specific differences, 72.7 % of the calculated concentrations were within a factor of ten of those reported in the literature. Topiramate, furosemide, and gemfibrozil were observed to accumulate to the greatest extent in Z. mays, predicted concentrations ranged between 50.27 and 418.01 ng/g (dw) for the top 10. Acids predominantly accumulated in leaves and fruit whereas a higher proportion of bases were predicted to accumulate in the roots. To the best of our knowledge 56.7 % of the 30 highest-ranked pharmaceuticals have not been previously documented in existing literature or monitoring campaigns. This presented framework demonstrates a method to assess risk posed by pharmaceutical compounds with limited experimental data.

News (Medical) associated with Gemfibrozil

10 May 2025

·ir.madrigalpharma.com

Madrigal Announces New Clinical Data Demonstrating Rezdiffra™ (resmetirom) Significantly Improved Multiple Noninvasive Tests and Portal Hypertension Risk in Patients with Compensated MASH Cirrhosis

Late-breaking results from the open-label compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial presented at the EASL Congress 65% of patients with clinically significant portal hypertension (CSPH) at baseline moved into lower risk categories by year two Patients achieved a mean 6.7 kPa reduction in liver stiffness, which was statistically significant compared to baseline CONSHOHOCKEN, Pa., May 10, 2025 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ: MDGL), a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), today 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) in the study achieved significant improvements from baseline in liver stiffness, liver fat, fibrosis biomarkers, liver volume and risk scores for clinically significant portal hypertension (CSPH). “Rezdiffra demonstrated broad, sustained efficacy across multiple noninvasive parameters at two years of treatment. A high, statistically significant percentage of patients with CSPH or probable CSPH at baseline shifted to lower risk categories,” said Naim Alkhouri, M.D., Chief Academic Officer at Summit Clinical Research and the Director of the Steatotic Liver Disease Program at the Clinical Research Institute of Ohio. “A larger placebo-controlled study will be needed to confirm Rezdiffra’s benefit in F4c, but the totality of data in this high-risk population of patients on the cusp of progressing to liver decompensation is highly encouraging as we await results from the ongoing Phase 3 MAESTRO-NASH OUTCOMES trial of Rezdiffra.” CSPH is a major consequence of cirrhosis and is responsible for its most severe complications, including ascites, variceal bleeding and hepatic encephalopathy. Patients with MASH who progress to cirrhosis face a 42 times higher risk of liver-related mortality. MAESTRO-NAFLD-1 included an open-label active treatment arm of patients with compensated MASH cirrhosis. After one year, patients were given the option to enroll in an open-label extension trial; 122 patients enrolled and 113 completed two years of treatment. At baseline, 35% of patients met Baveno criteria for CSPH, 14% for probable CSPH and 51% for no/low CSPH. The Baveno criteria use a combination of vibration-controlled transient elastography (VCTE) and platelet count to assess CSPH risk. Among patients with CSPH at baseline, 65% moved into lower risk categories by year two (42% to no/low CSPH and 23% to probable CSPH). Among patients with probable CSPH at baseline, 57% moved into the no/low CSPH category as compared to 14% who moved into the CSPH category by year two. Improvement in CSPH risk was statistically significant compared to baseline. Similar shifts to lower risk categories were observed in an analysis using a more stringent modified Baveno criteria that incorporates magnetic resonance elastography (MRE) and the Enhanced Liver Fibrosis (ELF) test as additional evidence for CSPH risk. As previously reported, patients achieved a mean 6.7 kPa reduction in liver stiffness at two years, which was statistically significant compared to baseline. In a responder analysis examining ≥25% improvement or worsening of liver stiffness, 51% of patients achieved improvement. An improvement of this magnitude has been associated with reduced progression to end-stage liver disease.1 Rezdiffra helped 35% of patients achieve liver stiffness measurements consistent with F3 fibrosis, suggesting reversal of cirrhosis. Safety data were consistent with previous studies and Rezdiffra was well-tolerated with a low rate of discontinuation due to adverse events. The most common adverse events were diarrhea, COVID-19 and nausea. There were two deaths unrelated to Rezdiffra. “Lower thyroid-hormone receptor-beta (THR-β) activity in the liver is predictive of hepatic decompensation2 in patients with MASH, so there is a strong mechanistic rationale supporting the potential of Rezdiffra, a THR-β agonist, to improve outcomes in patients with compensated MASH cirrhosis,” said David Soergel, M.D., Chief Medical Officer of Madrigal. “These two-year open-label data from MAESTRO-NAFLD-1 add important clinical evidence that supports our confidence in the ongoing, fully enrolled Phase 3 outcomes trial of Rezdiffra in compensated MASH cirrhosis.” Investor Webcast to Review New F4c Data At 8 a.m. EDT May 13, 2025, Madrigal will host a webcast to review the detailed two-year data from the compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial. To access the webcast, please visit the investor relations section of the Madrigal website or click here to register. About MASH Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), is a serious liver disease that can progress to cirrhosis, liver failure, liver cancer, need for liver transplantation, and premature mortality. MASH is expected to become the leading cause of liver transplantation in the U.S. and is already the leading cause of liver transplantation among women. 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 10-17 times higher risk of liver-related mortality as compared to patients without fibrosis. Those 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. An estimated 1.5 million patients have been diagnosed with MASH in the U.S., and Madrigal is focused on reaching approximately 315,000 patients with moderate to advanced fibrosis who are under the care of liver specialists. As MASH disease awareness improves and disease prevalence increases, the number of diagnosed patients with MASH with moderate to advanced fibrosis is expected to grow. About Rezdiffra Rezdiffra is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of MASH. It is the first approved medication for the treatment of MASH in the U.S. In the pivotal Phase 3 MAESTRO-NASH biopsy trial, Rezdiffra achieved both fibrosis improvement and MASH resolution primary endpoints, and 91% of patients treated with Rezdiffra 100 mg experienced improvement or stabilization of liver stiffness. In the U.S., 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 Europe for the treatment of patients with MASH with moderate to advanced liver fibrosis and not approved in any geography for the treatment of patients with cirrhosis. The ongoing, fully enrolled MAESTRO-NASH OUTCOMES trial is evaluating progression to liver decompensation events in patients with compensated NASH cirrhosis treated with Rezdiffra 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. What is Rezdiffra? Rezdiffra is a prescribed medicine used along with diet and exercise to treat adults with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver. It is not known if Rezdiffra is safe and effective in children (under 18 years old). This indication is approved based on improvement of NASH 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 NASH. 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. 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, or cyclosporine to suppress your immune system, 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), pain or tenderness in the upper middle or upper right area of your stomach (abdomen). gallbladder problems. Gallbladder problems such as gallstones, inflammation of the gallbladder, or inflammation of the pancreas from gallstones can occur with NASH 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 (abdominal) pain, vomiting, dizziness, 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 www.fda.gov/medwatch. 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 is the first and only medication approved by the FDA for the treatment of MASH with moderate to advanced fibrosis (consistent with stages F2 to F3). An ongoing Phase 3 outcomes trial is evaluating Rezdiffra for the treatment of compensated MASH cirrhosis (consistent with stage F4c). For more information, visit www.madrigalpharma.com. 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 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; risks of obtaining and maintaining regulatory approvals, including, but not limited to, potential regulatory delays or rejections; the challenges with the commercial launch of a new product, particularly for a company that did not have commercial experience prior to 2024; our history of operating losses and the possibility that we may never achieve or maintain profitability; risks associated with meeting the objectives of Madrigal’s clinical trials, including, but not limited to Madrigal’s ability to achieve enrollment objectives concerning patient numbers (including an adequate safety database), outcomes objectives and/or timing objectives for Madrigal’s 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; market demand for and acceptance of Rezdiffra; the potential inability to raise sufficient capital to fund ongoing operations as currently planned or to obtain financing on acceptable terms; our ability to service indebtedness and otherwise comply with debt covenants; outcomes or trends from competitive trials; future topline data timing or results; our ability to prevent and/or mitigate cyber-attacks; 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 I, Item 1A of its Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on February 26, 2025, and as updated from time to time by Madrigal’s other filings with the SEC. 1. Lin H, Lee HW, Yip TC, et al. Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease. JAMA. 2024;331(15):1287–1297. 2. Kendall TJ, Jimenez-Ramos M, Turner F, et al. An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease. Nat Med. 2023 Nov;29(11):2939-2953. Investor Contact Tina Ventura, IR@madrigalpharma.com Media Contact Christopher Frates, media@madrigalpharma.com Source: Madrigal Pharmaceuticals, Inc.

Clinical ResultPhase 3Drug ApprovalAccelerated Approval

29 Apr 2025

·ir.madrigalpharma.com

Madrigal to Present Late-Breaking Resmetirom Data in Patients with Compensated MASH Cirrhosis at the EASL Congress

CONSHOHOCKEN, Pa., April 29, 2025 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ: MDGL), a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), today announced six presentations at the upcoming European Association for the Study of the Liver (EASL) Congress, taking place from May 7-10, 2025, in Amsterdam, the Netherlands. Madrigal will share detailed two-year data from the open-label compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial in a late-breaking oral presentation titled, “Treatment with resmetirom for up to two years led to improvement in liver stiffness, fibrosis biomarkers, fibrosis scores and portal hypertension risk in 122 patients with compensated MASH cirrhosis.” “Patients with compensated MASH cirrhosis who develop clinically significant portal hypertension are at greatly elevated risk of experiencing life-threatening complications of late-stage liver disease so there is an urgent need to advance new treatment strategies for this vulnerable population,” said Bill Sibold, Chief Executive Officer of Madrigal. “The late-breaking data we will be presenting at EASL suggest that resmetirom may help halt or reverse disease progression in patients with compensated MASH cirrhosis, and we look forward to sharing important new findings examining the medication’s impact on portal hypertension risk. These data reinforce our conviction in resmetirom’s potential to become the foundational therapy across F2 to F4c MASH.” “This EASL Congress comes at an ideal time for our growing team in Europe,” added Neil Archer, Executive Vice President and Head of International for Madrigal. “As we prepare for a European Commission decision on our marketing authorization application for resmetirom, EASL will provide a valuable opportunity to listen, learn and engage with healthcare providers, patient advocates and other stakeholders who are working to improve care for this serious disease.” Resmetirom is a once-daily, oral, liver-directed thyroid hormone receptor (THR)-β agonist designed to target key underlying causes of MASH. It is the first approved medication for the treatment of MASH in the U.S. In the pivotal Phase 3 MAESTRO-NASH biopsy trial, resmetirom achieved both fibrosis improvement and MASH resolution primary endpoints, and 91% of patients treated with resmetirom 100 mg experienced improvement or stabilization of liver stiffness. In the U.S., resmetirom 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. Resmetirom is not approved in Europe for the treatment of patients with MASH with moderate to advanced liver fibrosis and not approved in any geography for the treatment of patients with cirrhosis. A marketing authorization application (MAA) for resmetirom is under evaluation with the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). The CHMP opinion and subsequent European Union (EU) decision are expected in mid-2025. Madrigal expects to launch resmetirom in Europe on a country-by-country basis commencing with Germany in the second half of 2025, pending European Commission approval. Madrigal Data Presentations at the EASL Congress 2025 Late-Breaking Oral Presentation: “Treatment with resmetirom for up to two years led to improvement in liver stiffness, fibrosis biomarkers, fibrosis scores and portal hypertension risk in 122 patients with compensated MASH cirrhosis” [Saturday, May 10, at 13:15 CEST. Presenter: Naim Alkhouri] Poster: “Baseline characteristics in well-compensated NASH cirrhosis patients diagnosed with or without a liver biopsy in MAESTRO-NASH-OUTCOMES, a clinical outcome phase 3 study assessing the effect of resmetirom in well compensated NASH cirrhosis” [Presenter: Jörn M. Schattenberg] Poster: “Use of noninvasive tests (NITs) to diagnose and follow non-alcoholic steatohepatitis (NASH) with liver fibrosis patients treated with resmetirom” [Presenter: Jörn M. Schattenberg] Poster: “Metabolic dysfunction-associated steatohepatitis (MASH) prevalence in Germany – results from a claims analysis” [Presenter: Thomas Ramezani] Poster: “Metabolic dysfunction-associated steatohepatitis as a risk factor for hepatocellular carcinoma mortality” [Presenter: Robert G. Gish] Poster: “Use of the LiverRisk score for prediction of moderate to advanced liver fibrosis in United States adults” [Presenter: Mary E. Rinella] Investor Webcast to Review New F4c Data At 8 a.m. EDT May 13, 2025, Madrigal will host a webcast to review the detailed two-year data from the compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial. To access the webcast, please visit the investor relations section of the Madrigal website or click here to register. About MASH Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), is a serious liver disease that can progress to cirrhosis, liver failure, liver cancer, need for liver transplantation, and premature mortality. MASH is expected to become the leading cause of liver transplantation in the U.S. and is already the leading cause of liver transplantation among women. 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 10-17 times higher risk of liver-related mortality as compared to patients without fibrosis. Those 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. An estimated 1.5 million patients have been diagnosed with MASH in the U.S., and Madrigal is focused on reaching approximately 315,000 patients with moderate to advanced fibrosis who are under the care of liver specialists. As MASH disease awareness improves and disease prevalence increases, the number of diagnosed patients with MASH with moderate to advanced fibrosis is expected to grow. About Rezdiffra What is Rezdiffra? Rezdiffra is a prescribed medicine used along with diet and exercise to treat adults with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver. It is not known if Rezdiffra is safe and effective in children (under 18 years old). This indication is approved based on improvement of NASH 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 NASH. 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. 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, or cyclosporine to suppress your immune system, 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), pain or tenderness in the upper middle or upper right area of your stomach (abdomen). gallbladder problems. Gallbladder problems such as gallstones, inflammation of the gallbladder, or inflammation of the pancreas from gallstones can occur with NASH 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 (abdominal) pain, vomiting, dizziness, 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 www.fda.gov/medwatch. 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 is the first and only medication approved by the FDA for the treatment of MASH with moderate to advanced fibrosis (consistent with stages F2 to F3). An ongoing Phase 3 outcomes trial is evaluating Rezdiffra for the treatment of compensated MASH cirrhosis (consistent with stage F4c). For more information, visit www.madrigalpharma.com. 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 role as a foundational therapy, the potential benefit of Rezdiffra in patients with compensated MASH cirrhosis and timing for an expected regulatory decision regarding resmetirom in Europe and the expected commencement of commercialization in Germany. Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to: the assumptions underlying the forward-looking statements; risks of obtaining and maintaining regulatory approvals, including, but not limited to, potential regulatory delays or rejections; the challenges with the commercial launch of a new product, particularly for a company that did not have commercial experience prior to 2024; our history of operating losses and the possibility that we may never achieve or maintain profitability; risks associated with meeting the objectives of Madrigal’s clinical trials, including, but not limited to Madrigal’s ability to achieve enrollment objectives concerning patient numbers (including an adequate safety database), outcomes objectives and/or timing objectives for Madrigal’s 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; market demand for and acceptance of Rezdiffra; the potential inability to raise sufficient capital to fund ongoing operations as currently planned or to obtain financing on acceptable terms; our ability to service indebtedness and otherwise comply with debt covenants; outcomes or trends from competitive trials; future topline data timing or results; our ability to prevent and/or mitigate cyber-attacks; 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 I, Item 1A of its Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on February 26, 2025, and as updated from time to time by Madrigal’s other filings with the SEC. Investor Contact Tina Ventura, IR@madrigalpharma.com Media Contact Christopher Frates, media@madrigalpharma.com Source: Madrigal Pharmaceuticals, Inc.

Phase 3Clinical ResultDrug Approval

28 Apr 2025

·www.relmada.com

Relmada Therapeutics Presents Positive Initial Phase 2 NDV-01 Data at AUA2025

90% of patients achieved high grade disease-free status at any time point with NDV-01, demonstrating strong proof-of-concept for sustained-release “GEM/DOCE” formulation* NDV-01 showed promising clinical activity in BCG-naïve and BCG-unresponsive patients, with favorable overall tolerability Data to be reviewed at Investor Event on April 28, 2025 at 4:30 PM ET CORAL GABLES, Fla., April 28, 2025 (GLOBE NEWSWIRE) -- Relmada Therapeutics, Inc. (Nasdaq: RLMD, “Relmada”, “the Company”), a clinical-stage biotechnology company, today announced that positive initial data from the Phase 2 study of NDV-01 showed that 90% of patients achieved high-grade disease-free status at any time point following treatment, demonstrating strong clinical activity and supporting further development of NDV-01 for the treatment of non-muscle invasive bladder cancer (NMIBC). The data were presented today at the American Urology Association 2025 (AUA2025) Annual Meeting with a data cutoff date of April 20, 2025. To register for the virtual Investor Event, click here. Highlights of Phase 2 data presented at AUA2025: Efficacy Data: 3-month Assessment: Overall Response Rate (ORR): 85% (17/20 patients at 3 months) High-Grade Recurrence-Free Survival (HGRFS) in papillary disease: 83.3% (15/18 patients) Complete Response (CR) in CIS patients: 100% (2/2 patients) At any time point: ORR: 90% (18/20 patients) HGRFS in papillary disease: 88.8% (16/18 patients) CR in CIS patients: 100% (2/2 patients) Disease status at 6 months: 100% (n=7) of evaluable patients (1 CIS, 6 Ta/T1) achieved disease free status. One of these patients was re-treated at 3 months. “I am impressed by these promising NDV-01 data reported at AUA2025. Gemcitabine and docetaxel (GEM/DOCE) have long shown clinical utility in NMIBC, but the complexity of administration has limited their broader use,” said Yair Lotan, MD, Professor of Urology and Chief of Urologic Oncology at UT Southwestern Medical Center. “A formulation like NDV-01, which is designed to increase exposure to drug and simplify delivery and accessibility, has the potential to significantly change how we manage patients with NMIBC in routine practice.” “We believe NDV-01 has the potential to become the class-leading therapy for NMIBC across a wide spectrum of patients,” said Sergio Traversa, CEO of Relmada. “The data presented at AUA2025 provide compelling proof-of-concept for NDV-01 as a bladder-sparing therapy. With its strong responses and tolerability combined with an administration time of less than 10 minutes, NDV-01 represents a potentially significant advance in outpatient bladder cancer treatment. We are enthusiastic about advancing this differentiated, ready-to-use GEM/DOCE formulation to improve patient outcomes and expand treatment options in NMIBC.” Overall: The treatment effect of NDV-01 was consistent across all patient groups, demonstrating robust activity, regardless of prior BCG exposure (BCG-naïve and BCG-unresponsive) or disease pathology (including CIS or Ta/T1 papillary). Safety: NDV-01 was well tolerated, with no treatment related adverse events greater than Grade 1. The most common treatment emergent adverse events (TEAEs) were urinary urgency, flank pain, and dysuria, all of which were mild and transient, resolving in 24-28 hours. No patients discontinued treatment due to adverse events. Study Overview: Open-label, single-arm, single-center Phase 2 study evaluating NDV-01 in patients with HG-NMIBC (including BCG-naïve (n=8) and BCG-unresponsive (n=12)) AUA 2025 data based on 20 enrolled patients with HG-NMIBC, including 2 patients with carcinoma in situ (CIS) and 18 patients with papillary disease (Ta/T1) The study continues to actively enroll patients. As of the latest cut-off, a total of 26 patients have been enrolled: 20 patients have reached the 3-month assessment. Seven patients have reached 6-month assessment * The primary efficacy endpoints are safety and complete response rate (CRR at 12 months), and secondary efficacy endpoints are duration of response (DOR) and event free survival (EFS). About NDV-01 NDV-01 is an innovative, investigational sustained-release formulation of two complementary chemotherapy agents, gemcitabine and docetaxel (GEM/DOCE). Designed for intravesical administration, NDV-01 forms a soft matrix within the bladder, gradually releasing drug over 10 days without requiring anesthesia or special equipment. NDV-01 is intended to simplify outpatient NMIBC treatment while maximizing local exposure, minimizing systemic toxicity, and improving patient convenience. NDV-01 is protected by patents that extend to 2038. About the Phase 2 Study The Phase 2 study (NCT06663137) is an open-label, single-arm, single-center study evaluating the safety and efficacy of NDV-01 in patients with HG-NMIBC. Patients are treated with NDV-01 in a biweekly induction phase, follow by monthly maintenance for up to one year, with regular assessments via cystoscopy, cytology, and biopsy, as indicated. The primary efficacy endpoints are safety and complete response rate (CRR at 12 months), and secondary efficacy endpoints are duration of response (DOR) and event free survival (EFS). About NMIBC More than 90% of the approximately 83,000 new U.S. cases of urothelial cancer are estimated to be bladder cancer. For the overall bladder cancer population, 5-year survival ranges from 70 to 96% of patients, moving to 6% for patients with advanced disease. Roughly 75% of bladder cancer cases are classified as non-muscle invasive (NMIBC) and approximately 50% of cases are classified as high-grade disease, considered to have increased risk of progression and recurrence. Sources indicate that NMIBC has a 50-75% recurrence rate (over seven years) and that the U.S. prevalence of NMIBC is approximately 600,000 patients. The U.S. NMIBC market is estimated to be a multi-billion-dollar opportunity. Global numbers are higher, in line with projections for significant growth due to the increasing incidence of bladder cancer and the demand for effective, minimally invasive potential therapies like NDV-01. Approved treatment options remain limited (mainly the immunotherapy, BCG, which has been supply constrained for some time), with high recurrence rates leading to frequent re-treatment and progression. Other emerging programs include immunotherapy combinations, single agent chemotherapy formulations and targeted therapies. NDV-01 stands out based on the large body of published data that support the efficacy of treatment with gemcitabine and docetaxel, its ease of administration and potential for durability of action. Expansion beyond first-line treatment into use as a salvage treatment or in other subgroups of NMIBC, including naïve patients, could further increase the opportunity for NDV-01. About Relmada Therapeutics, Inc. Relmada Therapeutics is a clinical-stage biotechnology company committed to advancing innovative breakthrough therapies that have the potential to bring meaningful clinical benefits to targeted patient populations. Lead investigational program, NDV-01, for High-Grade Non-Muscle Invasive Bladder Cancer, is being evaluated in a Phase 2 study. In addition, preparations are underway to advance sepranolone, a Phase 2b-ready investigational program for compulsion-related disorders including Tourette’s Syndrome and Prader-Willi Syndrome, into further studies. For more information, visit www.relmada.com. Forward-Looking Statements: The Private Securities Litigation Reform Act of 1995 provides a safe harbor for forward-looking statements made by us or on our behalf. This press release contains statements which constitute “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Any statement that is not historical in nature is a forward-looking statement and may be identified by the use of words and phrases such as “if”, “may”, “expects”, “anticipates”, “believes”, “will”, “will likely result”, “will continue”, “plans to”, “potential”, “promising”, and similar expressions. These statements are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements, including potential for Phase 2 NDV-01 data to continue to deliver positive results supporting further development, potential for clinical trials to deliver statistically and/or clinically significant evidence of efficacy and/or safety, failure of top-line results to accurately reflect the complete results of a trial, failure of planned or ongoing preclinical and clinical studies to demonstrate expected results, potential failure to secure FDA agreement on the regulatory path for sepranolone, and NDV-01, or that future sepranolone, or NDV-01 clinical results will be acceptable to the FDA, failure to secure adequate sepranolone, or NDV-01 drug supply, and the other risk factors described under the heading “Risk Factors” set forth in the Company’s reports filed with the SEC from time to time. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Relmada undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Readers are cautioned that it is not possible to predict or identify all the risks, uncertainties and other factors that may affect future results and that the risks described herein should not be a complete list. Investor Contact: Brian Ritchie LifeSci Advisors britchie@lifesciadvisors.com Media Inquiries: Corporate Communications media@relmada.com Released April 28, 2025

Phase 2Clinical ResultImmunotherapy

100 Deals associated with Gemfibrozil

External Link

KEGG	Wiki	ATC	Drug Bank
D00334	Gemfibrozil	C10AB04	DB01241

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hyperlipoproteinemias	China	Hunan Qianjin Xiangjiang Pharmaceutical Co., Ltd.	01 Jan 1991
Coronary Artery Disease	United States	Pfizer Inc.	21 Dec 1981
Hyperlipidemias	United States	Pfizer Inc.	21 Dec 1981

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Coronary Disease	Phase 3	United States	Parke-Davis & Co. Ltd.	01 Jun 1991
Neuronal Ceroid-Lipofuscinoses	Preclinical	European Union	Premier Research Group Ltd.	21 Mar 2018

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03539432 (CTgov)	Phase 2	Alcohol Use Disorder	3	Gemfibrozil 600 MG (Gemfibrozil)	scfntbwgne(nhpdmmkokp) = zyiluvvciz fiwcvkzmnw (hwsczjghmu, ofixszuarl - djtwbdtzkm) View more	-	18 Oct 2021
				Placebo oral capsule (Placebo)	scfntbwgne(nhpdmmkokp) = yzluhmfyyl fiwcvkzmnw (hwsczjghmu, vissqtjwfd - pxlvoilnbe) View more
NJLCG1302 (WCLC2019)	Not Applicable	squamous cell lung carcinoma	71	Cisplatin plus gemcitabine	bexvtiiurb(kplbvtasfz) = vuxqolltqu omronsazgp (kkxgqqjtwn, 27.3 - 58.5) View more	-	08 Sep 2019
				Carboplatin plus weekly nab-PTX	bexvtiiurb(kplbvtasfz) = jplqipsfxy omronsazgp (kkxgqqjtwn, 31.7 - 62.7) View more
ISN WCN2019	Not Applicable	Chronic Kidney Diseases	82	Low-dose Fenofibrate 100 mg	xsloqeenws(loqiqdgkxw) = Three patients died (2 in fenofibrate group and 1 in gemfibrozil group) from causes determined not to relate with fibrate therapy wamvqqieof (ocvrhdciwg ) View more	Positive	01 Jul 2019
				Gemfibrozil 600 mg
NCT02638597 (GEMNIC, CTgov)	Phase 2	Smoking Cessation	16	smoking cessation counseling+Gemfibrozil (Gemfibrozil)	wkdwkhqxtv(dsdhhmmfyc) = aumitmmokf tuwstkciot (agppgnbmyd, 12.63) View more	-	01 Feb 2019
				smoking cessation counseling (Waitlist)	wkdwkhqxtv(dsdhhmmfyc) = owpjzqtqmz tuwstkciot (agppgnbmyd, 22.04) View more
NCT01876810 (CTgov)	Phase 2	Nicotine Dependence	28	Gemfibrozil	aqhpjybfcp(fwxaanuwhm) = jwslzoxzzm eiyfcklogf (vvwfnnonvo, 0.1) View more	-	20 Apr 2017
ESC2016	Not Applicable	-	-	Gemfibrozil	hebgbtrpfy(lzqhmcacbt) = ioxwdljnub qtpwofcatm (zlislylteb ) View more	-	28 Aug 2016
				Vehicle	hebgbtrpfy(lzqhmcacbt) = ufuszrksga qtpwofcatm (zlislylteb ) View more
WCLC2013	Not Applicable	Non-Small Cell Lung Cancer Adjuvant	8	CBDCA+GEM	eewajivlyk(sgxlvgtnqm) = ijndlarwyx ftpcqhmtwj (tejnznbtdy )	-	30 Oct 2013
IAS2004	Not Applicable	Hyperlipidemias	8	Gemfibrozid	xuncaldxan(aapeoduxsg) = jlhvuuzpbx lzuisqxhxn (ndsrluzryc )	-	01 Jan 2004
				Omega 3 unsaturated fatty acids	xuncaldxan(aapeoduxsg) = libxrijsyo lzuisqxhxn (ndsrluzryc )
NCT04681924 \| NCT00283335 (Pubmed \| N Engl J Med)	Phase 3	Coronary Disease	2,531	Gemfibrozil	axctjogaxl(gkusevqwkn) = oagwwieevz froutlrxjt (afjpulowus ) View more	Positive	05 Aug 1999
				Placebo	givpkanbge(rpoptyjgxx) = jbaojnklst ocvnitnduu (akgygxbrlu )

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