MDGL Madrigal Pharmaceuticals Inc.

82.06
-3.08  -4%
Previous Close 85.14
Open 83.38
52 Week Low 74.175
52 Week High 142.6178
Market Cap $1,402,987,205
Shares 17,097,090
Float 11,112,210
Enterprise Value $1,157,399,242
Volume 92,983
Av. Daily Volume 109,403
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Upcoming Catalysts

Drug Stage Catalyst Date
Resmetirom (MGL-3196) - MAESTRO-NASH
Non-alcoholic steatohepatitis (NASH)
Phase 3
Phase 3
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Drug Pipeline

Drug Stage Notes
Resmetirom (MGL-3196) - MAESTRO-NAFLD-1
Non-Alcoholic Fatty Liver Disease
Phase 3
Phase 3
Phase 3 52-week top-line data reported rapid and sustained reduction in liver fat, liver volume, liver fibrosis, and atherogenic lipids. Treatment was safe and well-tolerated at 100 mg per day in patients treated for 52 weeks, noted November 12, 2021.
MGL-3196
Heterozygous familial hypercholesterolemia (HeFH)
Phase 2
Phase 2
Phase 2 top-line data released February 8, 2018 - primary endpoint met.

Latest News

  1. CONSHOHOCKEN, Pa., Nov. 23, 2021 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for cardio-metabolic and fatty liver diseases with high unmet medical need such as non-alcoholic steatohepatitis (NASH), announced today its management team will participate in two upcoming virtual investor conferences:

    Evercore ISI 4th Annual HealthCONx Conference 2021

    Fireside chat at 9:40 AM EST on Tuesday, November 30, 2021

    Piper Sandler 33rd Annual Virtual Healthcare Conference

    Fireside chat at 11:30 AM EST on Thursday, December 2, 2021

    The presentations will be webcast live and archived recordings will be available for replay in the Events & Presentations

    CONSHOHOCKEN, Pa., Nov. 23, 2021 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for cardio-metabolic and fatty liver diseases with high unmet medical need such as non-alcoholic steatohepatitis (NASH), announced today its management team will participate in two upcoming virtual investor conferences:

    Evercore ISI 4th Annual HealthCONx Conference 2021

    Fireside chat at 9:40 AM EST on Tuesday, November 30, 2021

    Piper Sandler 33rd Annual Virtual Healthcare Conference

    Fireside chat at 11:30 AM EST on Thursday, December 2, 2021

    The presentations will be webcast live and archived recordings will be available for replay in the Events & Presentations section of the Madrigal website for 90 days following the live presentations.

    About Madrigal Pharmaceuticals

    Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) is a clinical-stage biopharmaceutical company pursuing novel therapeutics that target a specific thyroid hormone receptor pathway in the liver, which is a key regulatory mechanism common to a spectrum of fatty liver and cardio-metabolic diseases with high unmet medical need. Madrigal's lead candidate, resmetirom, is a first-in-class, orally administered, small-molecule, liver-directed, thyroid hormone receptor (THR)-β selective agonist that is currently in two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO- NAFLD-1, designed to demonstrate multiple benefits in NASH (non-alcoholic steatohepatitis) patients. For more information, visit www.madrigalpharma.com.

    Investor Contact

    Alex Howarth, Madrigal Pharmaceuticals, Inc., om

    Media Contact

    Christopher Frates, Madrigal Pharmaceuticals, Inc.,



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    • This final read-out of the 52-week open-label resmetirom 100 mg treatment study of 171 patients with presumed non-alcoholic steatohepatitis (NASH) and fibrosis, identified using non-invasive tests, demonstrate that resmetirom:
      • provided rapid and sustained reduction in liver fat and liver volume;
      • provided rapid and sustained reductions in liver fibrosis, as measured by biomarkers, magnetic resonance elastography (MRE) and FibroScan;
      • reduced atherogenic lipids, including LDLc and triglycerides, liver enzymes and inflammatory biomarkers;
      • was safe and well-tolerated at 100 mg per day in patients treated for 52 weeks.
    • This "real-life" study supports the potential use of non-invasive assessments to diagnose and manage NASH with fibrosis, including
    • This final read-out of the 52-week open-label resmetirom 100 mg treatment study of 171 patients with presumed non-alcoholic steatohepatitis (NASH) and fibrosis, identified using non-invasive tests, demonstrate that resmetirom:
      • provided rapid and sustained reduction in liver fat and liver volume;
      • provided rapid and sustained reductions in liver fibrosis, as measured by biomarkers, magnetic resonance elastography (MRE) and FibroScan;
      • reduced atherogenic lipids, including LDLc and triglycerides, liver enzymes and inflammatory biomarkers;
      • was safe and well-tolerated at 100 mg per day in patients treated for 52 weeks.
    • This "real-life" study supports the potential use of non-invasive assessments to diagnose and manage NASH with fibrosis, including assessment of individual patient response to resmetirom treatment.

    CONSHOHOCKEN, Pa., Nov. 12, 2021 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), today announced the presentation of positive clinical data from the open-label portion of its ongoing MAESTRO-NAFLD-1 (non-alcoholic fatty liver disease) study of resmetirom at the AASLD The Liver Meeting®, being held virtually November 12th – 15th, 2021. Madrigal will host a webcast and conference call after the meeting on Tuesday, November 16th at 8:00 AM EST to summarize and discuss the data.



    "These new data from MAESTRO-NAFLD-1, our ongoing Phase 3 non-invasive study of resmetirom in patients with presumed NASH, reinforce and deepen our understanding of the therapeutic potential of resmetirom. The positive safety and efficacy findings from the open-label portion of MAESTRO-NAFLD-1 are particularly encouraging as we prepare to report initial topline data from the placebo-controlled double-blind portion of the study by year-end," stated Paul Friedman, M.D., Chief Executive Officer of Madrigal.

    Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal added, "The completed 52-week open-label MAESTRO-NAFLD-1 results being presented at The Liver Meeting 2021 demonstrate resmetirom's ability to potently reduce hepatic fat and liver volume in all subgroups of patients with NASH, including patients stably treated with diabetes medications such as GLP-1 agonists and SGLT2 inhibitors. Liver volume reduction may be explained in part by reduction in liver fat, but is also likely driven by other factors related to resmetirom's mechanism of action, potentially including effects on inflammation. Consistent with previous studies, there was a low discontinuation rate from adverse effects with no changes in central thyroid hormone axis or bone mineral density."



    Stephen Harrison, M.D., Medical Director for Pinnacle Clinical Research, San Antonio, Texas, Visiting Professor of Hepatology, Oxford University, and Principal Investigator of the MAESTRO studies commented, "Patients treated with 100 mg per day of resmetirom for up to 52 weeks achieved rapid and sustained improvements in multiple clinically relevant NASH endpoints and resmetirom continues to be well-tolerated. The MAESTRO-NAFLD-1 study has shown a potential for using non-invasive imaging and biomarkers to diagnose and monitor NASH patients treated with resmetirom without the use of liver biopsies."

    Late-Breaking Poster Presentation (abstract #LP19): Friday, November 12th

    Biomarkers, imaging and safety in resmetirom 52-week non-cirrhotic NASH Phase 3 clinical trial, completed open-label arm of MAESTRO-NAFLD-1. Presenter: Stephen Harrison [click here to view poster]

    MAESTRO-NAFLD-1 is a Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom being conducted in 1,200 patients with NAFLD and presumed NASH. A 171-patient 100 mg open-label arm of the study was completed in July 2021. Patients in the open-label arm demonstrated rapid and sustained reduction in hepatic fat on MRI-PDFF >50% and liver volume >20%, and fibrosis as assessed by biomarkers, magnetic resonance elastography (MRE), and vibration-controlled transient elastography (VCTE) and controlled attenuation parameter (CAP), LDLc and atherogenic lipids, liver enzymes and inflammatory biomarkers. No safety flags were identified; blood pressure (systolic, diastolic) was reduced by ~2mmHg, (p=0.02); bone mineral density was unchanged at 52 weeks.

    Poster Presentation: (abstract #1922): Friday, November 12th

    Liver volume reduction in resmetirom treated non-cirrhotic and cirrhotic NASH patients. Presenter: Stephen Harrison [click here to view poster]

    Liver enlargement, or hepatomegaly, is a potential cause of pain in patients with NASH and is thought to be driven primarily by high liver fat content. In a 36-week Phase 2 serial MRI-PDFF and liver biopsy study in adults with biopsy-confirmed NASH (NAS≥4, F1-F3) and hepatic fat fraction ≥10%, resmetirom-treated patients showed statistically significant liver fat reduction associated with NASH resolution as assessed by liver biopsy compared to placebo. In a secondary analysis, statistically significant (p<0.0001) reduction in liver volume of ~21% in resmetirom-treated non-cirrhotic NASH patients as compared with placebo was observed. Liver volume reduction was also observed in an open-label resmetirom-treated cohort of well-compensated NASH cirrhotic patients who also had greatly elevated liver volume at baseline. Liver volume reduction was much greater than expected in these patients based on the small reduction in MRI-PDFF; for example, a cohort of NASH cirrhotic patients with normal baseline liver fat (≤5%) experienced an average 15% reduction in liver volume independent of any effect on liver fat. NASH cirrhotics with elevated baseline liver fat >=8% had 30% reduction in liver fat fraction and 18% reduction in liver volume. Liver volume reduction is likely driven by other factors related to resmetirom's mechanism of action in addition to liver fat reduction, potentially including reduced inflammation.

    Oral Presentation (abstract #118): Sunday, November 14th at 4:00 PM EST

    Utilization of the MAST (MRI-PDFF-MRE-AST) score to predict NASH on liver biopsy in MAESTRO-NASH and assess response to resmetirom in MAESTRO-NAFLD-1. Presenter: Mazen Noureddin



    The purpose of this analysis was to investigate the utility of the MAST (MRI-PDFF-MRE-AST) scores for non-invasive identification of patients with NASH with significant fibrosis in the MAESTRO-NASH and MAESTRO-NAFLD-1 Phase 3 studies of resmetirom. The analysis included baseline screening data from more than 1,000 patients who had AST, MRE, MRI-PDFF, fibroscan and liver biopsy assessments. The results show that MAST is predictive of fibrosis stage in NASH and of the level of NASH activity (steatosis, inflammation and ballooning) in the NASH liver. The investigators concluded that in the absence of a liver biopsy, elevated MAST score in the setting of metabolic syndrome may predict NASH with significant liver fibrosis.



    Virtual Product Theatre: Friday, November 12th at 1:00 PM EST

    NASH with Fibrosis: Updates from the Resmetirom Clinical Program

    Manal Abdelmalek, M.D. and Mazen Noureddin, M.D. will discuss NASH disease state, provide an update on the resmetirom development program, review the mechanism of action and summarize new data presented at The Liver Meeting 2021 from the Phase 2 and Phase 3 trials.

    Conference Call and Webcast Information

    Madrigal will hold a conference call and live webcast, Tuesday, November 16, 2021 at 8:00 AM EST to discuss the resmetirom data recently presented at AASLD's The Liver Meeting. To access the conference call, please dial (833) 660-2754 for domestic callers or (409) 350-3497 for international callers and reference conference ID: 2458676. To access the live webcast of the call with slides please visit the Events and Presentations section of Madrigal's website or click here. An archived webcast will be available on the Madrigal website after the event.

    About Madrigal Pharmaceuticals

    Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) is a clinical-stage biopharmaceutical company pursuing novel therapeutics that target a specific thyroid hormone receptor pathway in the liver, which is a key regulatory mechanism common to a spectrum of fatty liver and cardio-metabolic diseases with high unmet medical need. Madrigal's lead candidate, resmetirom, is a first-in-class, orally administered, small-molecule, liver-directed, thyroid hormone receptor (THR)-β selective agonist that is currently in two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO- NAFLD-1, designed to demonstrate multiple benefits in NASH (non-alcoholic steatohepatitis) patients. For more information, visit www.madrigalpharma.com.

    Forward Looking Statements

    This communication contains "forward-looking statements" made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, that are based on our beliefs and assumptions and on information currently available to us but are subject to factors beyond our control. Forward-looking statements include but are not limited to statements or references concerning: our clinical trials, including the anticipated timing of disclosure or presentations of data from our trials; research and development activities; market size estimates for NASH and NAFLD patients; the timing and results associated with the future development of our lead product candidate, MGL-3196 (resmetirom); our primary and secondary study endpoints for resmetirom and the potential for achieving such endpoints and projections; plans, objectives and timing for making a Subpart H (Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses) submission to FDA; optimal dosing levels for resmetirom; projections regarding potential future NASH resolution, safety, fibrosis treatment, cardiovascular effects, lipid treatment or biomarker effects with resmetirom; the efficacy and safety of resmetirom for non-cirrhotic NASH patients and cirrhotic NASH patients; ex-U.S. launch/partnering plans; the predictive power of liver fat reduction measured by non-invasive tests on NASH resolution with fibrosis reduction or improvement; the predictive power of liver fat liver volume changes or MAST scores for NASH and/or NAFLD patients; the effects of resmetirom's mechanism of action; the achievement of enrollment objectives concerning patient number, safety database and/or timing for our studies; the predictive power of NASH resolution and/or liver fibrosis reduction with resmetirom using non-invasive tests, including the use of ELF, FibroScan, MRE and/or MRI-PDFF; the ability to develop clinical evidence demonstrating the utility of non-invasive tools and techniques to screen and diagnose NASH and/or NAFLD patients; the predictive power of non-invasive tests generally, including for purposes of diagnosing NASH, monitoring patient response to resmetirom, or recruiting a NASH clinical trial; potential NASH or NAFLD patient risk profile benefits with resmetirom; the potential for resmetirom to become the best-in-class and/or first-to-market treatment option for patients with NASH; and our possible or assumed future results of operations and expenses, business strategies and plans, capital needs and financing plans, trends, market sizing, competitive position, industry environment and potential growth opportunities, among other things. Forward-looking statements: reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events; include all statements that are not historical facts; and can be identified by terms such as "allow," "anticipates," "be," "believes," "continue," "could," "demonstrates," "design," "estimates," "expects," "forecasts," "future," "goal," "hopeful," "inform," "intends," "may," "might," "planned", "plans," "positions," "potential," "powers," "predicts," "predictive," "projects," "seeks," "should," "will," "will be," "would" or similar expressions and the negatives of those terms. Although management presently believes that the expectations reflected in such forward-looking statements are reasonable, it can give no assurance that such expectations will prove to be correct and you should be aware that actual results could differ materially from those contained in the forward- looking statements.

    Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to: our clinical development of resmetirom; enrollment uncertainties, generally and in relation to COVID-19-related measures that may be continued for an uncertain period of time or implemented; outcomes or trends from competitive studies; future topline data timing or results; the risks of achieving potential benefits in studies that include substantially more patients than our prior studies; limitations associated with early stage, non-placebo controlled study data; the timing and outcomes of clinical studies of resmetirom; and the uncertainties inherent in clinical testing. 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 or furnished with the U.S. Securities and Exchange Commission 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. We specifically discuss these risks and uncertainties in greater detail in the section entitled "Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2020, as well as in our other filings with the SEC.

    Investor Contact

    Alex Howarth, Madrigal Pharmaceuticals, Inc.,

    Media Contacts

    Christopher Frates, Madrigal Pharmaceuticals, Inc.,



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  2. CONSHOHOCKEN, Pa., Nov. 04, 2021 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) today provides a summary of corporate accomplishments and reports its third quarter 2021 financial results.

    Paul Friedman, M.D., Chief Executive Officer of Madrigal, stated, "Throughout the third quarter, the Madrigal team continued to progress MAESTRO-NASH, the pivotal serial liver biopsy study and a key component of the Phase 3 program for resmetirom for patients with non-alcoholic steatohepatitis, NASH. We remain on track to complete the double-blind portion of our Phase 3 non-invasive imaging and biomarker study, MAESTRO-NAFLD-1, and report topline data by year-end, with additional topline data rollout in early 2022. We will also…

    CONSHOHOCKEN, Pa., Nov. 04, 2021 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) today provides a summary of corporate accomplishments and reports its third quarter 2021 financial results.

    Paul Friedman, M.D., Chief Executive Officer of Madrigal, stated, "Throughout the third quarter, the Madrigal team continued to progress MAESTRO-NASH, the pivotal serial liver biopsy study and a key component of the Phase 3 program for resmetirom for patients with non-alcoholic steatohepatitis, NASH. We remain on track to complete the double-blind portion of our Phase 3 non-invasive imaging and biomarker study, MAESTRO-NAFLD-1, and report topline data by year-end, with additional topline data rollout in early 2022. We will also be presenting additional data from the open-label portion of this study at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting® on November 12-15th."

    Becky Taub, M.D., Chief Medical Officer and President of Research & Development at Madrigal stated, "Data from the recently completed 52 week open-label arm of the MAESTRO-NAFLD-1 study will be presented at AASLD and provides our most informed insights to date regarding the effects of resmetirom in presumed NASH patients, using a variety of non-invasive tests relevant to clinical practice. The double-blinded MAESTRO-NAFLD-1 and MAESTRO NASH studies readouts over the forthcoming months will further inform our understanding of how to identify and monitor NASH patients with significant fibrosis."

    Dr. Taub added, "In October, in recognition of Liver Awareness Month, we announced our alliance with the Fatty Liver Foundation, a leading patient advocacy organization focused on the diagnosis, treatment and support of individuals with non-alcoholic fatty liver disease or NAFLD and NASH. Our alliance with the Foundation is in support of their NAFLD Screening Fund and aligns with our commitment to advance the use of non-invasive techniques to improve the diagnosis and staging of NAFLD and NASH and identify people at risk of NASH earlier in the course of their disease."

    Several abstracts summarizing data from the open-label arms of the MAESTRO-NAFLD-1 study have been accepted for presentation at AASLD's The Liver Meeting® 2021. Madrigal will host a webcast and conference call on Tuesday, November 16th at 8.00 AM ET to summarize and discuss the data that are being presented.

    AASLD Presentations

    • Friday, November 12, 2021: Late-breaker Poster Presentation (abstract #LP21)

      Biomarkers, imaging and safety in resmetirom 52 week non-cirrhotic NASH Phase 3 clinical trial, completed open-label arm of MAESTRO-NAFLD-1
    • Friday November 12, 2021: Poster Presentation (abstract #1922)

      Liver volume reduction in resmetirom treated non-cirrhotic and cirrhotic NASH patients
    • Friday, November 12, 2021 (1:00-2:00pm EST): Virtual Product Theatre

      Live presentation by Manal Abdelmalek, MD, Professor of Medicine, Duke University School of Medicine and Mazen Noureddin, MD, Director, Cedars-Sinai Medical Center, Karsh Division of Gastroenterology and Hepatology entitled: NASH with Fibrosis: Updates from the MAESTRO Phase 3 Clinical Program
    • Sunday, November 14, 2021: Oral Presentation (4:00pm EST) (abstract #118)

      Presentation by Mazen Noureddin, MD, Director, Cedars-Sinai Medical Center, Karsh Division of Gastroenterology and Hepatology entitled: Utilization of the MAST (MRI-PDFF-MRE-AST) score to predict NASH on liver biopsy in MAESTRO-NASH and access response to resmetirom in MAESTRO-NAFLD-1

    Leadership Team Expanded

    Stephen Dodge, PharmD, MBA, has joined Madrigal as Senior Vice President and Global Head of Medical Affairs. Prior to joining Madrigal, Dr. Dodge was Senior Vice President, Cholestasis Program Head at Intercept Pharmaceuticals. Prior to Intercept, he held a number of leadership positions in medical affairs at Merck, Novo Nordisk and Novartis. His experience includes over 20 new product launches in new therapeutic areas, spanning over 20 years, with 10 years in liver and GI diseases. Dr. Dodge received an MBA from Washington University in St. Louis, his PharmD - Doctor of Pharmacy from the University of The Pacific School of Pharmacy and a B.S., Biology from California State University.

    Kia Motesharei, PhD, has joined Madrigal as Senior Vice President Business & Corporate Development. Dr. Motesharei's 20 plus years of industry experience includes over 100 business development transactions and corporate strategy initiatives including therapeutic product licensing and alliances, R&D collaborations, commercial product partnerships, royalty financing and M&A activities with companies in the United States, Europe, Japan, China, Latin America and the Middle East. Prior to joining Madrigal, Dr. Motesharei was Chief Business and Strategy Officer at NeuBase Therapeutics. Since 2004, he has held similar positions with Akcea Therapeutics, EMD Serono (Merck KGaA), Dyax Corporation, Genfit, and Activx Biosciences. Dr. Motesharei completed his Postdoctoral training as a National Institutes of Health fellow at The Scripps Research Institute and received his Doctorate degree from UCLA.

    Financial Results

    As of September 30, 2021, Madrigal had cash, cash equivalents and marketable securities of $299.1 million, compared to $284.1 million at December 31, 2020. The increase in cash and marketable securities was due to net proceeds of $151.2 million from sales of common stock via our at-the-market (ATM) program, partially offset by cash used to support operations of $135.9 million.

    Operating expenses were $63.2 million and $177.9 million for the three and nine month periods ended September 30, 2021, compared to $58.8 million and $147.1 million in the comparable prior year periods.

    Research and development expenses for the three and nine month periods ended September 30, 2021 were $54.9 million and $152.3 million, compared to $53.3 million and $131.4 million in the comparable prior year periods. The increase is attributable primarily to additional activities related to the Phase 3 clinical trials, and an increase in head count.

    General and administrative expenses for the three and nine month periods ended September 30, 2021 were $8.3 million and $25.6 million, compared to $5.5 million and $15.8 million in the comparable prior year periods. The increase is attributable primarily to increases in commercial preparation activities, including an increase in headcount and an increase in non-cash stock compensation.

    Interest income for the three and nine month periods ended September 30, 2021 was $0.1 million and $0.3 million, compared to $0.8 million and $3.9 million in the comparable prior year periods. The decrease in interest income was due primarily to decreased interest rates.

    About Resmetirom

    Thyroid hormone, through activation of its β-receptor in hepatocytes, plays a central role in liver function impacting a range of health parameters from levels of serum cholesterol and triglycerides to the pathological buildup of fat in the liver. Thyroid hormone receptor (THR)-β action in the liver is key to proper function of the liver, including regulation of mitochondrial activity such as breakdown of liver fat and control of the level of normal, healthy mitochondria. Patients with NASH have reduced levels of thyroid hormone activity in the liver with resultant impaired hepatic function, in part due to the inflamed state of the liver that causes degradation of thyroid hormone.

    To exploit the thyroid hormone receptor (THR)-β pathway for therapeutic purposes in liver and cardio-metabolic diseases, it is important to avoid activity at the THR-α receptor, the predominant systemic receptor for thyroid hormone that is responsible for activity outside the liver including in heart and bone. The lack of selectivity of older thyromimetic compounds, chemically-related toxicities and undesirable distribution in the body led to safety concerns. Madrigal recognized that greater selectivity for thyroid hormone receptor (THR)-β and liver targeting might overcome these challenges and deliver the full therapeutic potential of THR-β agonism. Resmetirom has been shown to be highly selective based on 1) THR-β receptor functional selectivity based on both in vitro and in vivo assays and 2) specific uptake into the liver, its site of action, virtually avoiding any uptake into tissues outside the liver. In short- and long- term human and animal studies, resmetirom has been confirmed to be safe and devoid of activity at the THR-α receptor and without impact on bone or cardiac parameters. Resmetirom does not impact the thyroid axis hormones, including the central thyroid axis. Madrigal believes that resmetirom is the first orally administered, small-molecule, liver-directed, truly β-selective THR agonist.

    About the Phase 3 Registration Program for the Treatment of NASH (Non-alcoholic steatohepatitis)

    Madrigal is currently conducting two Phase 3 Clinical trials, MAESTRO-NASH and MAESTRO-NAFLD-1, to demonstrate the safety and efficacy of resmetirom for the treatment of NASH.

    MAESTRO-NASH is a Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom in patients with liver biopsy confirmed NASH and was initiated in March 2019. The study targets enrollment of 900 patients with biopsy-proven NASH (fibrosis stage 2 or 3, at least 450 fibrosis stage 3), randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, or placebo. After 52 weeks of treatment a second biopsy is performed. The primary surrogate endpoint on biopsy will be NASH resolution, with at least a 2-point reduction in NAS (NASH Activity Score), and with no worsening of fibrosis. Two key secondary endpoints are liver fibrosis reduction of at least one stage, with no worsening of NASH on liver biopsy, and lowering of LDL-cholesterol [ClinicalTrials.gov/NCT03900429]. Madrigal announced achievement of the planned target enrollment on June 30, 2021.

    The first 900 patients in the MAESTRO-NASH study will continue on therapy after the initial 52-week treatment period; and up to another 1,100 patients are to be added using the same randomization plan and the study is expected to continue for up to 54 months to accrue and measure hepatic clinical outcome events including progression to cirrhosis on biopsy (52 weeks and 54 months) and hepatic decompensation events.

    MAESTRO-NAFLD-1 is a 52-week Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom, and was initiated in December 2019 in patients with non-alcoholic fatty liver disease (NAFLD), presumed NASH. The primary endpoint for this study is to evaluate the safety and tolerability of resmetirom. Completion of enrollment of over 1,200 patients into the study was announced in November 2020. Top-line data from the study is targeted by end of year 2021.

    Patients in MAESTRO-NAFLD-1 are randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, or placebo. MAESTRO-NAFLD-1 also includes a 100 mg resmetirom open label arm. 52 week data were presented from the open label arm at The International Liver Congress™ 2021 in June and demonstrated that resmetirom is safe and well-tolerated at 100mg per day [view press release here]. MAESTRO-NAFLD-1 (unlike MAESTRO-NASH), does not include a liver biopsy and represents a "real-life" NASH study. NASH or presumed NASH is documented using historical liver biopsy or non-invasive techniques including FibroScan and magnetic resonance imaging, proton density fat fraction (MRI-PDFF) respectively. Using non-invasive measures, MAESTRO-NAFLD-1 is designed to provide incremental safety information to support the NASH indication as well as provide additional data regarding clinically relevant key secondary efficacy endpoints to better characterize the potential clinical benefits of resmetirom on cardiovascular and liver related endpoints. These key secondary endpoints include LDL-cholesterol, apolipoprotein B and triglyceride (TG) lowering; reduction of liver fat as determined by MRI-PDFF; and reduction of PRO-C3, a NASH fibrosis biomarker. [ClinicalTrials.gov/NCT04197479]. Additional secondary and exploratory endpoints will be assessed including reduction in liver enzymes, FibroScan scores and other fibrosis and inflammatory biomarkers.

    Data from the 52 week portion of MAESTRO-NASH, together with data from MAESTRO-NAFLD-1 and other data, including safety parameters, will form the basis for a potential subpart H submission to FDA for accelerated approval for the treatment of NASH.

    About Madrigal Pharmaceuticals

    Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) is a clinical-stage biopharmaceutical company pursuing novel therapeutics that target a specific thyroid hormone receptor pathway in the liver, which is a key regulatory mechanism common to a spectrum of fatty liver and cardio-metabolic diseases with high unmet medical need. Madrigal's lead candidate, resmetirom, is a first-in-class, orally administered, small-molecule, liver-directed, thyroid hormone receptor (THR)-β selective agonist that is currently in two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO- NAFLD-1, designed to demonstrate multiple benefits in NASH (non-alcoholic steatohepatitis) patients. For more information, visit www.madrigalpharma.com.

    Forward Looking Statements

    This communication contains "forward-looking statements" made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, that are based on our beliefs and assumptions and on information currently available to us but are subject to factors beyond our control. Forward-looking statements include but are not limited to statements or references concerning: our clinical trials, including the anticipated timing of disclosure or presentations of data from our trials; research and development activities; market size estimates for NASH and NAFLD patients; the timing and results associated with the future development of our lead product candidate, MGL-3196 (resmetirom); our primary and secondary study endpoints for resmetirom and the potential for achieving such endpoints and projections; plans, objectives and timing for making a Subpart H (Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses) submission to FDA; optimal dosing levels for resmetirom; projections regarding potential future NASH resolution, safety, fibrosis treatment, cardiovascular effects, lipid treatment or biomarker effects with resmetirom; the efficacy and safety of resmetirom for non-cirrhotic NASH patients and cirrhotic NASH patients; ex-U.S. launch/partnering plans; the predictive power of liver fat reduction measured by non-invasive tests on NASH resolution with fibrosis reduction or improvement; the achievement of enrollment objectives concerning patient number, safety database and/or timing for our studies; the predictive power of NASH resolution and/or liver fibrosis reduction with resmetirom using non-invasive tests, including the use of ELF, FibroScan, MRE and/or MRI-PDFF; the ability to develop clinical evidence demonstrating the utility of non-invasive tools and techniques to screen and diagnose NASH and/or NAFLD patients; the predictive power of non-invasive tests generally, including for purposes of diagnosing NASH, monitoring patient response to resmetirom, or recruiting a NASH clinical trial; potential NASH or NAFLD patient risk profile benefits with resmetirom; the potential for resmetirom to become the best-in-class and/or first-to-market treatment option for patients with NASH; and our possible or assumed future results of operations and expenses, business strategies and plans, capital needs and financing plans, trends, market sizing, competitive position, industry environment and potential growth opportunities, among other things. Forward-looking statements: reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events; include all statements that are not historical facts; and can be identified by terms such as "allow," "anticipates," "be," "believes," "continue," "could," "demonstrates," "design," "estimates," "expects," "forecasts," "future," "goal," "hopeful," "inform," "intends," "may," "might," "planned", "plans," "positions," "potential," "powers," "predicts," "predictive," "projects," "seeks," "should," "will," "will be," "would" or similar expressions and the negatives of those terms. Although management presently believes that the expectations reflected in such forward-looking statements are reasonable, it can give no assurance that such expectations will prove to be correct and you should be aware that actual results could differ materially from those contained in the forward- looking statements.

    Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to: our clinical development of resmetirom; enrollment uncertainties, generally and in relation to COVID-19-related measures that may be continued for an uncertain period of time or implemented; outcomes or trends from competitive studies; future topline data timing or results; the risks of achieving potential benefits in studies that include substantially more patients than our prior studies; limitations associated with early stage, non-placebo controlled study data; the timing and outcomes of clinical studies of resmetirom; and the uncertainties inherent in clinical testing. 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 or furnished with the U.S. Securities and Exchange Commission 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. We specifically discuss these risks and uncertainties in greater detail in the section entitled "Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2020, as well as in our other filings with the SEC.

    Investor Contact

    Alex Howarth, Madrigal Pharmaceuticals, Inc.,

    Media Contacts

    Mike Beyer on behalf of Madrigal Pharmaceuticals

    Phone: 312-961-2502

    Email:

    (Tables Follow) 

    Madrigal Pharmaceuticals, Inc.
    Condensed Consolidated Statements of Operations
    (in thousands, except share and per share amounts)
    (unaudited)
          
          
     Three Months Ended Nine Months Ended
     September 30, September 30,
      2021  2020   2021  2020 
    Revenues:     
    Total revenues$- $-  $- $- 
    Operating expenses:     
    Research and development 54,873  53,292   152,275  131,380 
    General and administrative 8,287  5,494   25,606  15,738 
    Total operating expenses 63,160  58,786   177,881  147,118 
    Loss from operations (63,160) (58,786)  (177,881) (147,118)
        Interest income, net 60  823   311  3,897 
        Other income -  -   273  100 
    Net loss$(63,100)$(57,963) $(177,297)$(143,121)
          
    Basic and diluted net loss per common share$(3.79)$(3.75) $(10.84)$(9.27)
    Basic and diluted weighted average number of common shares outstanding 16,639,776  15,448,425   16,353,428  15,437,018 
          
          
          
    Madrigal Pharmaceuticals, Inc.
    Condensed Consolidated Balance Sheets
    (in thousands)
    (unaudited)
          
          
          
     September 30,December 31,   
      2021  2020    
          
    Assets     
    Cash, cash equivalents and marketable securities$299,144 $284,149    
    Other current assets 3,812  1,014    
    Other non-current assets 1,741  1,832    
    Total assets$304,697 $286,995    
          
    Liabilities and Equity     
    Current liabilities$69,325 $46,557    
    Long-term liabilities 491  468    
    Stockholders' equity 234,881  239,970    
    Total liabilities and stockholders' equity$304,697 $286,995    
          



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  3. CONSHOHOCKEN, Pa., Oct. 04, 2021 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for fatty liver diseases, announces its support of the Fatty Liver Foundation, the leading patient advocacy organization focused on the diagnosis, treatment and support of Americans with non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH). Today, Madrigal and the Fatty Liver Foundation will ring the Nasdaq closing bell to raise awareness of the need for more evidence-based screening and testing to improve diagnosis and staging of NAFLD/NASH.

    NAFLD is estimated to afflict more than 16 million Americans. NASH is the more severe form of NAFLD…

    CONSHOHOCKEN, Pa., Oct. 04, 2021 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for fatty liver diseases, announces its support of the Fatty Liver Foundation, the leading patient advocacy organization focused on the diagnosis, treatment and support of Americans with non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH). Today, Madrigal and the Fatty Liver Foundation will ring the Nasdaq closing bell to raise awareness of the need for more evidence-based screening and testing to improve diagnosis and staging of NAFLD/NASH.

    NAFLD is estimated to afflict more than 16 million Americans. NASH is the more severe form of NAFLD. There are more than 5 million NASH patients with significant fibrosis in the U.S. Once NASH progresses to significant liver fibrosis, the risk of adverse liver outcomes increases dramatically. In fact, NASH is currently the leading cause of liver transplants in the U.S. Additionally, patients with NASH and/or advanced fibrosis, as well as NAFLD patients with concomitant type 2 diabetes, are at high risk for adverse cardiovascular events and increased mortality.

    Paul Friedman, CEO of Madrigal said, "In recognition of Liver Awareness Month, we want to highlight the high unmet need of the millions of Americans who suffer from NAFLD and NASH. NASH is known as a ‘silent disease' because many people don't know they have it until it has progressed to a dangerous stage. By supporting FLF, our objective is to improve the medical and patient community's understanding of the disease, better identify NAFLD/NASH patients, and communicate the growing body of clinical evidence demonstrating the utility of non-invasive tools and techniques to screen and diagnose patients."

    Madrigal is providing an unrestricted grant to support FLF's NAFLD Screening Fund whose primary objective is to scale-up evidence-based screening and testing for NAFLD in a community setting. These efforts would support, and potentially boost, the non-invasive screening needed to identify asymptomatic disease and diagnosing NAFLD/NASH patients at various points of progression.

    Wayne Eskridge, Co-Founder and CEO of FLF, added, "In partnership with industry, advocates and affected communities, we are launching the NAFLD Screening Fund, a public private partnership with the goal of further investigating the findings from our SUNN-1 Study (Screening for Undiagnosed NAFLD and NASH). In this study, we identified a cohort of people who sought to assess their risk of NAFLD and NASH through non-invasive testing, ultimately demonstrating a high incidence of unidentified liver pathology. We are grateful for Madrigal's support, which will contribute to our collective effort to identify and guide patients in need." Eskridge also noted, "The fund will seek collaboration with local patient-focused organizations to facilitate the outreach and education goals of FLF through collective action. We encourage any interested parties to join us in this important outreach."

    Meena Bansal, M.D., Fellow of the American Association for the Study of Liver Diseases (FAASLD) and Professor of Medicine at the Icahn School of Medicine at Mount Sinai noted, "NASH is an asymptomatic disease that increases the risk of hepatic failure and cancer as it progresses. Incorporating non-invasive, evidence-based screening and diagnostic approaches is paramount to catching the disease in patients sufficiently early so that behavior modifications and therapeutic care can help improve their health and clinical outcomes."

    The Nasdaq closing bell ceremony will begin at approximately 3:45 p.m. ET on Monday, October 4, 2021, and can be viewed live at https://livestream.com/accounts/27896496/events/9807812.

    About Madrigal Pharmaceuticals

    Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) is a clinical-stage biopharmaceutical company pursuing novel therapeutics that target a specific thyroid hormone receptor pathway in the liver, which is a key regulatory mechanism common to a spectrum of fatty liver and cardio-metabolic diseases with high unmet medical need. Madrigal's lead candidate, resmetirom, is a first-in-class, orally administered, small-molecule, liver-directed, thyroid hormone receptor (THR)-β selective agonist that is currently in two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO- NAFLD-1, designed to demonstrate multiple benefits in NASH (non-alcoholic steatohepatitis) patients. For more information, visit www.madrigalpharma.com.

    About the Fatty Liver Foundation

    The Fatty Liver Foundation is the only national, non-profit patient organization dedicated to improving the identification, diagnosis, treatment & support of Americans with fatty liver, NAFLD or NASH through awareness, screening, education and patient outreach. FLF's goal is to improve the lives of both asymptomatic and diagnosed patients by raising awareness, developing wellness screening, educating patients and championing the development of a responsive support system for individuals of the growing epidemic of fatty liver disease. For more information, visit www.fattyliverfoundation.org.

    About the Fatty Liver Foundation NAFLD Screening Fund

    With recent advancements in the diagnostics and potential treatments for NAFLD, screening and testing are now the critical nexus between identification of disease and effective intervention. To meet this need, the NAFLD Screening Fund's primary objective is to scale-up evidence-based screening and testing for NAFLD. Funded activities would boost the screening practices needed to identify asymptomatic disease and staging of NAFLD/NASH patients.

    The expansion of screening and staging of fatty liver disease is a model of community outreach that has been proven by FLF in medical and non-medical settings. The Fund's impact will be expanded education and awareness of NAFLD, achieved through screening, which has been shown to empower individuals' ownership and participation in their health and healthcare. Through multiple site collaborations, new screening technologies, improved data management systems, and more trained personnel, the Fund will be leveraged to rapidly scale up community screening efforts. The NAFLD Screening fund will be the catalyst for greater patient engagement in research and development, including treatment preparedness as new therapies become available. It is a mechanism through which many streams of financial support, both public and private, can be coordinated and focused on this rapidly growing health threat.

    Forward-Looking Statements

    This communication contains "forward-looking statements" made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, that are based on our beliefs and assumptions and on information currently available to us but are subject to factors beyond our control. Forward-looking statements include but are not limited to statements or references concerning: our clinical trials; research and development activities; market size estimates for NASH and NAFLD patients; the timing and results associated with the future development of our lead product candidate, MGL-3196 (resmetirom); our primary and secondary study endpoints for resmetirom and the potential for achieving such endpoints and projections; plans, objectives and timing for making a Subpart H (Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses) submission to FDA; optimal dosing levels for resmetirom; projections regarding potential future NASH resolution, safety, fibrosis treatment, cardiovascular effects, lipid treatment or biomarker effects with resmetirom; the efficacy and safety of resmetirom for non-cirrhotic NASH patients and cirrhotic NASH patients; the predictive power of liver fat reduction measured by non-invasive tests on NASH resolution with fibrosis reduction or improvement; the achievement of enrollment objectives concerning patient number, safety database and/or timing for our studies; the predictive power of NASH resolution and/or liver fibrosis reduction with resmetirom using non-invasive tests, including the use of ELF, FibroScan, MRE and/or MRI-PDFF; the ability to develop clinical evidence demonstrating the utility of non-invasive tools and techniques to screen and diagnose NASH and/or NAFLD patients; the predictive power of non-invasive tests generally, including for purposes of diagnosing NASH, monitoring patient response to resmetirom, or recruiting a NASH clinical trial; potential NASH or NAFLD patient risk profile benefits with resmetirom; the potential for resmetirom to become the best-in-class and/or first-to-market treatment option for patients with NASH; and our possible or assumed future results of operations and expenses, business strategies and plans, capital needs and financing plans, trends, market sizing, competitive position, industry environment and potential growth opportunities, among other things. Forward-looking statements: reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events; include all statements that are not historical facts; and can be identified by terms such as "allow," "anticipates," "be," "believes," "continue," "could," "demonstrates," "design," "estimates," "expects," "forecasts," "future," "goal," "hopeful," "inform," "intends," "may," "might," "planned", "plans," "positions," "potential," "powers," "predicts," "predictive," "projects," "seeks," "should," "will," "will be," "would" or similar expressions and the negatives of those terms. Although management presently believes that the expectations reflected in such forward-looking statements are reasonable, it can give no assurance that such expectations will prove to be correct and you should be aware that actual results could differ materially from those contained in the forward- looking statements.

    Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to: our clinical development of resmetirom; enrollment uncertainties, generally and in relation to COVID-19-related measures that may be continued for an uncertain period of time or implemented; outcomes or trends from competitive studies; future topline data timing or results; the risks of achieving potential benefits in studies that include substantially more patients than our prior studies; limitations associated with early stage, non-placebo controlled study data; the timing and outcomes of clinical studies of resmetirom; and the uncertainties inherent in clinical testing. 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 filings with the U.S. Securities and Exchange Commission 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. We specifically discuss these risks and uncertainties in greater detail in the section entitled "Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2020, as well as in our other filings with the SEC.

    Media Contacts

    Mike Beyer on behalf of Madrigal Pharmaceuticals

    Phone: 312-961-2502

    Email:

    Henry E. Chang on behalf of Fatty Liver Foundation

    Phone: 917-400-8900

    Email: 



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  4. CONSHOHOCKEN, Pa., Aug. 05, 2021 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) reports today its second quarter 2021 financial results and provides a summary of corporate accomplishments.

    Paul Friedman, M.D., Chief Executive Officer of Madrigal, stated, "The Madrigal team has made great progress on multiple fronts in the first half of 2021. Importantly, we reached our goal of enrollment to support the 52 week liver biopsy accelerated approval portion of MAESTRO-NASH. Top-line results are expected by the third quarter of 2022 for MAESTRO-NASH and by the end of this year for the non-invasive imaging and biomarker study, MAESTRO-NAFLD-1."

    "We made multiple presentations recently at EASL. In particular, data from the open-label…

    CONSHOHOCKEN, Pa., Aug. 05, 2021 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) reports today its second quarter 2021 financial results and provides a summary of corporate accomplishments.

    Paul Friedman, M.D., Chief Executive Officer of Madrigal, stated, "The Madrigal team has made great progress on multiple fronts in the first half of 2021. Importantly, we reached our goal of enrollment to support the 52 week liver biopsy accelerated approval portion of MAESTRO-NASH. Top-line results are expected by the third quarter of 2022 for MAESTRO-NASH and by the end of this year for the non-invasive imaging and biomarker study, MAESTRO-NAFLD-1."

    "We made multiple presentations recently at EASL. In particular, data from the open-label portion of the ongoing MAESTRO-NAFLD-1 Phase 3 clinical trial provide further evidence that treatment with resmetirom for 52 weeks leads to rapid and sustained reductions of liver fat, fibrosis, cell injury and inflammation in non-cirrhotic NASH patients that project favorably on the liver biopsy endpoints in MAESTRO-NASH," stated Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal.

    Dr. Taub added, "Also during the quarter, the Medical Affairs team at Madrigal continued to engage with the NASH physician and patient advocacy communities that recognize NASH with liver fibrosis as a very large unmet need. Our commercial team's product launch planning also supports our objective to demonstrate the value of available non-invasive imaging and biomarkers that better diagnose and allow management of patients with NASH, enabling preparation for the planned launch and commercialization of resmetirom."

    Recent Accomplishments

    1. Clinical and Medical Affairs

    • Positive clinical results presented at the European Association for the Study of the Liver Annual Meeting (EASL), The International Liver Congress™ 2021, further point out the potential therapeutic value of resmetirom in a real-life NASH setting using non-invasive tools (versus serial liver biopsies): [click here to view press release]
      • Oral Plenary Presentation: Reduction in Fibrosis and Steatohepatitis Imaging and Biomarkers in a Phase 3, 52 Week Resmetirom NASH Trial. Presenter: Stephen Harrison [click here to view oral presentation]



      • EASL Poster: Treatment of NASH cirrhotic patients with resmetirom: baseline characteristics and effects on safety, biomarkers and imaging. Presenter: Stephen Harrison [click here to view poster]



      • Madrigal Hosted Symposium: Phase 3 development of resmetirom, a liver-directed thyroid hormone receptor (THR)-β agonist for the treatment of patients with NASH and significant liver fibrosis. Presenters: Vlad Ratziu, Jörn Schattenberg and Stephen Harrison [click here to view slides, click here to view webcast]



    • Analysis of patient reported outcome data from the Phase 2 trial of resmetirom revealed that achieving ≥30% relative reduction in hepatic fat was associated with greater improvements in Quality of Life Scores. Improvements in quality of life scores were also observed in those patients with NASH and fibrosis improvement on liver biopsy. The data has recently been published online in Clinical Gastroenterology and Hepatology: Hepatic Fat Reduction Due to Resmetirom in Patients with Nonalcoholic Steatohepatitis is Associated with Improvement of Quality of Life.



    • Well over 2,000 patients enrolled in MAESTRO trials that will help support the required safety database for NDA approval. Recent highlights:
      • Enrolled sufficient patients in the Phase 3 clinical trial MAESTRO-NASH to support the planned Subpart H (Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses) submission to the US Food and Drug Administration (FDA). Madrigal will continue to enroll additional patients beyond those required for accelerated approval to provide for the clinical outcomes portion of the MAESTRO-NASH Phase 3 clinical trial.



      • First patients enrolled in Phase 3 MAESTRO-NAFLD Open Label Extension Study (OLE). Patients who complete the first 52-week randomized portion of the study can receive 52 weeks of active treatment with resmetirom. The study is expected to provide both additional long-term safety and tolerability data as well as further efficacy measures documenting reduction of NASH using non-invasive scans and blood chemistries.



    • Medical Affairs Outreach:
      • Scientific engagements are occurring at NASH-focused meetings including: EASL, the American Association of Clinical Endocrinology (AACE), the American Association for the Study of Liver Diseases (AASLD), NASH-TAG, Paris-NASH, the GI Alliance and the Chronic Liver Disease Foundation (CLDF). These activities are intended to build awareness of the evolving clinical data supporting the therapeutic value of resmetirom, improve the medical community's understanding of NASH, identify the unmet needs of NASH patients, and communicate the growing body of clinical evidence regarding the utility of non-invasive tools and techniques to diagnose and monitor NASH patients.

    2. Launch and Commercial Preparation

    • In preparation for the planned U.S. launch of resmetirom, Madrigal is building its commercial resources and infrastructure, as well as developing a comprehensive product launch plan to position resmetirom for success. To date, our market research projects have involved over 1,000 hepatologists, gastroenterologists and endocrinologists as well as payers who together provide prescription coverage for the vast majority of the patients in the U.S. Results from these efforts confirm that (i) NASH patients with significant liver fibrosis (F2/F3) are already being non-invasively identified by physicians, but given the lack of approved treatment options they are looking for effective new medications to manage the disease; and, (ii) the majority of these physicians believe an ideal therapy for NASH patients with significant fibrosis which addresses the underlying pathophysiology of the disease in the liver will slow, halt and/or reverse disease progression.

    3. Leadership Team Expanded

    • Alex Howarth, appointed Chief Financial Officer of Madrigal, adds important skills to Madrigal's executive team and is responsible for the development of financial and corporate strategy, long-range planning, business development and implementation of financial and operational systems to support Madrigal's continued growth and its transition to a commercial company.



    • Robert Waltermire, newly appointed as Chief Pharmaceutical Development Officer of Madrigal within Research and Development with responsibility for all aspects of chemistry, manufacturing and controls (CMC) and commercial product supply.

    Financial Results

    As of June 30, 2021, Madrigal had cash, cash equivalents and marketable securities of $323.8 million, compared to $284.1 million at December 31, 2020. The increase in cash and marketable securities was due to net proceeds of $130.2 million from sales of common stock via our at-the-market (ATM) program, partially offset by cash used to support operations of $90.3 million.

    Operating expenses were $61.7 million and $114.7 million for the three and six month periods ended June 30, 2021, compared to $50.3 million and $88.3 million in the comparable prior year periods.

    Research and development expenses for the three and six month periods ended June 30, 2021 were $51.6 million and $97.4 million, compared to $44.7 million and $78.1 million in the comparable prior year periods. The increase is attributable primarily to additional activities related to the Phase 3 clinical trials, and an increase in head count.

    General and administrative expenses for the three and six month periods ended June 30, 2021 were $10.1 million and $17.3 million, compared to $5.6 million and $10.2 million in the comparable prior year periods. The increase is attributable primarily to increases in commercial preparation activities, including an increase in headcount, and an increase in non-cash stock compensation.

    Interest income for the three and six month periods ended June 30, 2021 was $0.1 million and $0.3 million, compared to $1.2 million and $3.1 million in the comparable prior year periods. The decrease in interest income was due primarily to decreased interest rates.

    About Resmetirom

    Thyroid hormone, through activation of its β-receptor in hepatocytes, plays a central role in liver function impacting a range of health parameters from levels of serum cholesterol and triglycerides to the pathological buildup of fat in the liver. Thyroid hormone receptor (THR)-β action in the liver is key to proper function of the liver, including regulation of mitochondrial activity such as breakdown of liver fat and control of the level of normal, healthy mitochondria. Patients with NASH have reduced levels of thyroid hormone activity in the liver with resultant impaired hepatic function, in part due to the inflamed state of the liver that causes degradation of thyroid hormone.

    To exploit the thyroid hormone receptor (THR)-β pathway for therapeutic purposes in cardio-metabolic and liver diseases, it is important to avoid activity at the THR-α receptor, the predominant systemic receptor for thyroid hormone that is responsible for activity outside the liver including in heart and bone. The lack of selectivity of older thyromimetic compounds, chemically-related toxicities and undesirable distribution in the body led to safety concerns. Madrigal recognized that greater selectivity for thyroid hormone receptor (THR)-β and liver targeting might overcome these challenges and deliver the full therapeutic potential of THR-β agonism. Resmetirom has been shown to be highly selective based on 1) THR-β receptor functional selectivity based on both in vitro and in vivo assays and 2) specific uptake into the liver, its site of action, virtually avoiding any uptake into tissues outside the liver. In short and long term human and animal studies, resmetirom has been confirmed to be safe and devoid of activity at the THR-α receptor and without impact on bone or cardiac parameters. Resmetirom does not impact the thyroid axis hormones, including the central thyroid axis. Madrigal believes that resmetirom is the first orally administered, small-molecule, liver-directed, truly β-selective THR agonist.

    About the Phase 3 Registration Program for the Treatment of NASH (Non-alcoholic steatohepatitis)

    Madrigal is currently conducting two Phase 3 Clinical trials, MAESTRO-NASH and MAESTRO-NAFLD-1, to demonstrate the safety and efficacy of resmetirom for the treatment of NASH.

    MAESTRO-NASH is a Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom in patients with liver biopsy confirmed NASH and was initiated in March 2019. The study targets enrollment of 900 patients with biopsy-proven NASH (fibrosis stage 2 or 3, at least 450 fibrosis stage 3), randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, or placebo. After 52 weeks of treatment a second biopsy is performed. The primary surrogate endpoint on biopsy will be NASH resolution, with at least a 2-point reduction in NAS (NASH Activity Score), and with no worsening of fibrosis. Two key secondary endpoints are liver fibrosis reduction of at least one stage, with no worsening of NASH on liver biopsy, and lowering of LDL-cholesterol [ClinicalTrials.gov/NCT03900429]. Madrigal announced achievement of the planned target enrollment on June 30, 2021.

    The first 900 patients in the MAESTRO-NASH study will continue on therapy after the initial 52-week treatment period; and up to another 1,100 patients are to be added using the same randomization plan and the study is expected to continue for up to 54 months to accrue and measure hepatic clinical outcome events including progression to cirrhosis on biopsy (52 weeks and 54 months) and hepatic decompensation events.

    MAESTRO-NAFLD-1 is a 52-week Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom, and was initiated in December 2019 in patients with non-alcoholic fatty liver disease (NAFLD), presumed NASH. The primary endpoint for this study is to evaluate the safety and tolerability of resmetirom. Completion of enrollment of over 1,200 patients into the study was announced in November 2020. Top-line data from the study is targeted by end of year 2021.

    Patients in MAESTRO-NAFLD-1 are randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, or placebo. MAESTRO-NAFLD-1 also includes a 100 mg resmetirom open label arm. 52 week data were presented from the open label arm at The International Liver Congress™ 2021 in June and demonstrated that resmetirom is safe and well-tolerated at 100mg per day [view press release here]. MAESTRO-NAFLD-1 (unlike MAESTRO-NASH), does not include a liver biopsy and represents a "real-life" NASH study. NASH or presumed NASH is documented using historical liver biopsy or non-invasive techniques including FibroScan and MRI-PDFF. Using non-invasive measures, MAESTRO-NAFLD-1 is designed to provide incremental safety information to support the NASH indication as well as provide additional data regarding clinically relevant key secondary efficacy endpoints to better characterize the potential clinical benefits of resmetirom on cardiovascular and liver related endpoints. These key secondary endpoints include LDL-cholesterol, apolipoprotein B and triglyceride (TG) lowering; reduction of liver fat as determined by magnetic resonance imaging, proton density fat fraction (MRI-PDFF); and reduction of PRO-C3, a NASH fibrosis biomarker. [ClinicalTrials.gov/NCT04197479]. Additional secondary and exploratory endpoints will be assessed including reduction in liver enzymes, FibroScan scores and other fibrosis and inflammatory biomarkers.

    Data from the 52 week portion of MAESTRO-NASH, together with data from MAESTRO-NAFLD-1 and other data, including safety parameters, will form the basis for a potential subpart H submission to FDA for accelerated approval for the treatment of NASH

    About Madrigal Pharmaceuticals

    Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) is a clinical-stage biopharmaceutical company pursuing novel therapeutics that target a specific thyroid hormone receptor pathway in the liver, which is a key regulatory mechanism common to a spectrum of cardio-metabolic and fatty liver diseases with high unmet medical need. Madrigal's lead candidate, resmetirom, is a first-in-class, orally administered, small-molecule, liver-directed, thyroid hormone receptor (THR)-β selective agonist that is in currently in two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO- NAFLD-1, designed to demonstrate multiple benefits across a broad spectrum of NASH (non-alcoholic steatohepatitis) and NAFLD (non-alcoholic fatty liver disease) patients. For more information, visit www.madrigalpharma.com

    Forward-Looking Statements

    This communication contains "forward-looking statements" made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, that are based on our beliefs and assumptions and on information currently available to us but are subject to factors beyond our control. Forward-looking statements include but are not limited to statements or references concerning: our clinical trials; research and development activities; the timing and results associated with the future development of our lead product candidate, MGL-3196 (resmetirom); our primary and secondary study endpoints for resmetirom and the potential for achieving such endpoints and projections; plans, objectives and timing for making a Subpart H (Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses) submission to FDA; optimal dosing levels for resmetirom; projections regarding potential future NASH resolution, safety, fibrosis treatment, cardiovascular effects, lipid treatment or biomarker effects with resmetirom; the efficacy and safety of resmetirom for non-cirrhotic NASH patients and cirrhotic NASH patients; the predictive power of liver fat reduction measured by non-invasive tests on NASH resolution with fibrosis reduction or improvement; the achievement of enrollment objectives concerning patient number, safety database and/or timing for our studies; the predictive power of NASH resolution and/or liver fibrosis reduction with resmetirom using non-invasive tests, including the use of ELF, FibroScan, MRE and/or MRI-PDFF; the predictive power of non-invasive tests generally, including for purposes of diagnosing NASH, monitoring patient response to resmetirom, or recruiting a NASH clinical trial; potential NASH or NAFLD patient risk profile benefits with resmetirom; the potential for resmetirom to become the best-in-class and/or first-to-market treatment option for patients with NASH; and our possible or assumed future results of operations and expenses, business strategies and plans, capital needs and financing plans, trends, market sizing, competitive position, industry environment and potential growth opportunities, among other things. Forward-looking statements: reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events; include all statements that are not historical facts; and can be identified by terms such as "allow," "anticipates," "be," "believes," "continue," "could," "demonstrates," "design," "estimates," "expects," "forecasts," "future," "goal," "hopeful," "inform," "intends," "may," "might," "planned", "plans," "positions," "potential," "powers," "predicts," "predictive," "projects," "seeks," "should," "will," "will be," "would" or similar expressions and the negatives of those terms. Although management presently believes that the expectations reflected in such forward-looking statements are reasonable, it can give no assurance that such expectations will prove to be correct and you should be aware that actual results could differ materially from those contained in the forward-looking statements.

    Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to: our clinical development of resmetirom; enrollment uncertainties, generally and in relation to COVID-19-related measures that may be continued for an uncertain period of time or implemented; outcomes or trends from competitive studies; future topline data timing or results; the risks of achieving potential benefits in studies that include substantially more patients than our prior studies; limitations associated with early stage, non-placebo controlled study data; the timing and outcomes of clinical studies of resmetirom; and the uncertainties inherent in clinical testing. 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 filings with the U.S. Securities and Exchange Commission 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. We specifically discuss these risks and uncertainties in greater detail in the section entitled "Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2020, as well as in our other filings with the SEC.

    Investor Contact:

    Alex Howarth, Madrigal Pharmaceuticals, Inc.,

    Media Contact:

    Laura Morgan, Sam Brown Inc., , tel +1-951-333-9110

    Bob Conrad, Sam Brown Inc., , tel +1-703-980-0997



    (Tables Follow)



    Madrigal Pharmaceuticals, Inc.
    Condensed Consolidated Statements of Operations
    (in thousands, except share and per share amounts)
    (unaudited)
          
          
     Three Months Ended Six Months Ended
     June 30, June 30,
     20212020 20212020
    Revenues:     
    Total revenues$- $-  $- $- 
    Operating expenses:     
    Research and development 51,632  44,688   97,402  78,088 
    General and administrative 10,110  5,639   17,319  10,244 
    Total operating expenses 61,742  50,327   114,721  88,332 
    Loss from operations (61,742) (50,327)  (114,721) (88,332)
    Interest income, net 91  1,204   251  3,074 
    Other income -  100   273  100 
    Net loss$(61,651)$(49,023) $(114,197)$(85,158)
          
    Basic and diluted net loss per common share$(3.72)$(3.18) $(7.05)$(5.52)
    Basic and diluted weighted average number of common shares outstanding 16,571,322  15,433,348   16,207,880  15,431,251 
          
          
          
    Madrigal Pharmaceuticals, Inc.
    Condensed Consolidated Balance Sheets
    (in thousands)
    (unaudited)
          
          
          
     June 30,December 31,   
     2021

    2020

       
          
    Assets     
    Cash, cash equivalents and marketable securities$323,846 $284,149    
    Other current assets 2,221  1,014    
    Other non-current assets 1,888  1,832    
    Total assets$327,955 $286,995    
          
    Liabilities and Equity     
    Current liabilities$56,710 $46,557    
    Long-term liabilities 594  468    
    Stockholders' equity 270,651  239,970    
    Total liabilities and stockholders' equity$327,955 $286,995    
          


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