Madrigal Pharmaceuticals Reports 2021 Second Quarter Financial Results and Provides Corporate Update

Madrigal Pharmaceuticals Reports 2021 Second Quarter Financial Results and Provides Corporate Update

Conshohocken, PA., August 5, 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

2. Launch and Commercial Preparation

3. Leadership Team Expanded

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.

Thyroid hormone, through activation of its -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)- 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)- pathway for therapeutic purposes in cardio-metabolic

and liver diseases, it is important to avoid activity at the THR- 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)- and

liver targeting might overcome these challenges and deliver the full therapeutic potential of THR- agonism. Resmetirom has been shown to be highly selective based on 1)

THR- 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- 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 -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.

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. 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

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)- 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.

Alex Howarth, Madrigal Pharmaceuticals, Inc., IR@madrigalpharma.com

Laura Morgan, Sam Brown Inc.,

lauramorgan@sambrown.com, tel +1-951-333-9110

Bob Conrad, Sam Brown Inc., bobconrad@sambrown.com, tel

Madrigal Pharmaceuticals, Inc.

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