Full Press Release Details
Madrigal Pharmaceuticals Provides an Overview of Upcoming Resmetirom Data
Presentations and Reports 2022 Third Quarter Financial Results
CONSHOHOCKEN, PA, November 3, 2022 Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage
biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), today provides an overview of upcoming resmetirom Phase 3 data presentations and reports third quarter 2022 financial results.
Paul Friedman, M.D., Chief Executive Officer of Madrigal, stated, The Madrigal team is focused on delivering topline data from the pivotal MAESTRO-NASH
biopsy study in Q4 2022. Positive results from the study would allow us to finalize our new drug application for resmetirom, with the goal of filing for Subpart H accelerated approval in the first half of 2023. The efficacy and safety data we are
generating across four Phase 3 MAESTRO studies put Madrigal in a strong position to navigate this accelerated approval pathway and potentially address the unmet needs of patients who currently have no approved therapy to treat NASH with significant
Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, stated, The MAESTRO program
continues to generate data that reinforce our conviction in the potential of resmetirom to become a foundational therapy for patients with NASH. At the upcoming American Association for the Study of Liver Diseases (AASLD) Liver Meeting, we ll
be presenting results from the compensated NASH cirrhosis cohort studied in MAESTRO-NAFLD-1. The safety and efficacy data in this more advanced patient population helped support our decision to initiate the
Phase 3 MAESTRO-NASH Outcomes study, a noninvasive clinical endpoint study that assesses the rate of progression from early well-compensated NASH cirrhosis to decompensated NASH cirrhosis.
Dr. Taub continued, A second oral presentation at AASLD will examine the ability of several noninvasive strategies to identify NASH patients with
significant liver fibrosis using screening data from the MAESTRO-NASH biopsy study. Given the comprehensive diagnostic strategies included in MAESTRO studies, Madrigal has a unique opportunity to define noninvasive measures to diagnose and manage
patients with NASH in real world clinical practice.
Presentations at the AASLD Liver Meeting
The following abstracts have been accepted for presentation at the AASLD Liver Meeting, taking place November 4-8 in
Oral Presentation (abstract 100): Sunday, November 6th
A 52-week Phase 3 clinical trial of resmetirom in 180 patients with well-compensated NASH cirrhosis. Presenter:
In patients with well-compensated cirrhosis included in an open-label active resmetirom treatment arm of the Phase 3 MAESTRO-NAFLD-1 safety study, resmetirom lowered markers of cardiovascular risk and NASH fibrosis. Following 52 weeks of treatment with resmetirom, patients achieved reductions in magnetic resonance imaging proton
density fat fraction (MRI-PDFF), FibroScan controlled attenuation parameter (CAP), FibroScan vibration-controlled transient elastography (VCTE), magnetic resonance elastography (MRE), liver and spleen volume,
ALT, AST, GGT, LDL-C, triglycerides, ApoB, and lipoprotein (a). Resmetirom appeared safe and was well-tolerated during 52 weeks of treatment.
Oral Presentation (abstract 102): Sunday, November 6th
Utility of FIB-4, MRE, MRI and FibroScan to identify patients with at-risk F2-F3 NASH based on screening data from a 2000 patient biopsy confirmed cohort of the resmetirom Phase 3 clinical trial, MAESTRO-NASH. Presenter: Rohit Loomba
FIB-4 of 1.3 is frequently used to identify potential at-risk patients
with NASH, but an analysis of screening data from the MAESTRO-NASH biopsy study found this threshold lacked the sensitivity to accurately identify patients with NASH with significant fibrosis (F2-F3). The
authors concluded the influence of age on FIB-4 may require an age adjustment to ensure younger patients are not removed from consideration for therapy. MRE, MAST
(MRI-AST) and FAST (FibroScan-AST) showed reasonable accuracy for identifying patients with NASH with significant fibrosis.
Financial Results for the Nine Months Ended September 30, 2022
As of September 30, 2022, Madrigal had cash, cash equivalents and marketable securities of $153.2 million, compared to $270.3 million at
December 31, 2021. This decrease in cash and marketable securities resulted primarily from cash used in operations for the nine months ended September 30, 2022 of $166.3 million, partially offset by the net proceeds ($49 million) from
the Loan Facility ( Loan Facility ) with Hercules Capital, Inc. ( Hercules ).
Operating expenses were $80.4 million and
$208.3 million for the three month and nine month periods ended September 30, 2022, compared to $63.2 million and $177.9 million in the comparable prior year periods.
Research and development expenses for the three and nine month periods ended September 30, 2022 were $68.3 million and $174.7 million, compared
to $54.9 million and $152.3 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, 2022 were
$12.1 million and $33.6 million, compared to $8.3 million and $25.6 million in the comparable prior year periods. The increase is due 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, 2022 was $0.7 million and $1.1 million, compared to $0.1 million and $0.3 million in the comparable prior year periods. These increases in interest income were due primarily to higher average interest rates in
Interest expense for the three and nine month periods ended September 30, 2022 was $1.5 million and $2.3 million, compared to
$0 million and $0 million in the comparable prior year periods. The increase in interest expense was as a result of the Loan Facility with Hercules, which we closed in May of 2022.
About the Resmetirom Phase 3 Registration Program for the Treatment of NASH
Madrigal is currently conducting four Phase 3 clinical trials to demonstrate the safety and efficacy of resmetirom for the treatment of NASH: MAESTRO-NASH, MAESTRO-NAFLD-1, MAESTRO-NAFLD-OLE, and MAESTRO-NASH Outcomes.
a multicenter, randomized, double-blind, placebo-controlled Phase 3 study of resmetirom in patients with liver biopsy-confirmed NASH and was initiated in March 2019. The study enrolled more than 1,000 patients with biopsy-proven NASH (at least half
with F3 (advanced) fibrosis, the remainder F2 or F1B (moderate fibrosis, with a few earlier F1 patients), randomized 1:1:1 to receive once-daily resmetirom 80 mg, resmetirom 100 mg, or placebo. After 52 weeks of treatment, a second biopsy is
performed. The dual primary surrogate endpoints on biopsy are NASH resolution with 2-point reduction in NAS (NAFLD Activity Score), and with no worsening of fibrosis OR a
1-point decrease in fibrosis with no worsening of NASH. Achievement of either primary endpoint is considered a successful trial outcome. A key secondary endpoint is lowering of
LDL-C. The planned target enrollment was announced as completed on June 30, 2021.
All patients enrolled in
the MAESTRO-NASH study (up to 2,000 in total) continue on therapy after the initial 52-week treatment period for up to 54 months to accrue and measure hepatic clinical outcome events including progression to
cirrhosis on biopsy (52 weeks and 54 months) and hepatic decompensation events.
MAESTRO-NAFLD-1 was initiated in
December 2019 and the 52-week multicenter, randomized, placebo-controlled Phase 3 study of resmetirom in over 1,200 patients with NAFLD, presumed
NASH, has completed the double-blind arms and an open-label 100 mg arm. An additional open-label active treatment arm in patients with early (well-compensated) NASH cirrhosis is ongoing. The
primary endpoint was to evaluate the safety and tolerability of resmetirom. A separate 52-week Phase 3 clinical trial, an open-label extension study of MAESTRO-NAFLD-1 (MAESTRO-NAFLD-OLE) is ongoing.
Patients in the 52-week Phase 3 MAESTRO-NAFLD-1 study were randomized 1:1:1:1 to receive once-daily resmetirom 80 mg, resmetirom 100 mg, placebo in double-blind arms, or resmetirom 100 mg in an open-label arm.
MAESTRO-NAFLD-1 (unlike MAESTRO-NASH) did not include a liver biopsy and represents a real-life NASH study. Patients with 3 metabolic risk factors were documented with NASH or NAFLD by historical
liver biopsy or noninvasive techniques. Using noninvasive measures, MAESTRO-NAFLD-1 was 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. The primary safety endpoint and several key secondary endpoints were
met, including LDL-C, apolipoprotein B, and triglyceride lowering and reduction of liver fat as determined by MRI-PDFF. Additional secondary and exploratory endpoints
were assessed, including reduction in liver enzymes, FibroScan, and MRE scores, and other NASH biomarkers.
52-week first 1,000 patient 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 of resmetirom for treatment of NASH.
In August 2022, Madrigal initiated MAESTRO-NASH
Outcomes, a randomized double-blind placebo-controlled study in approximately 700 patients with early NASH cirrhosis to allow for noninvasive monitoring of progression to liver decompensation events. A positive outcome is expected to support the
full approval of resmetirom for noncirrhotic NASH, potentially accelerating the timeline to full approval. In addition, this study has the potential to support an additional indication for resmetirom in patients with well-compensated NASH cirrhosis.
About Madrigal Pharmaceuticals
Pharmaceuticals, Inc. (Nasdaq: MDGL) is a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver disease with high unmet medical need. Madrigal s lead candidate, resmetirom, is a
once daily, oral, thyroid hormone receptor (THR)- selective agonist designed to target key underlying causes of NASH in the liver. For more information, visit www.madrigalpharma.com.
Forward Looking Statements
This communication includes 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:
anticipated or estimated future results, including the risks and uncertainties associated with our future operating performance and financial position; our possible or assumed future results of operations and expenses, business strategies and plan
(including ex-US. Launch/partnering plans), including incurrence of indebtedness and compliance with debt covenants under the Loan and Security Agreement with Hercules Capital, Inc., as agent and lender,
market trends, market sizing, competitive position, industry environment and potential growth opportunities, among other things; our ability to delay certain research activities and related clinical expenses as necessary; our clinical trials,
including the anticipated timing of disclosure, presentations of data from, or outcomes from our trials; research and development activities, and the timing and results associated with the future development of our lead product candidate, resmetirom
(formerly known as MGL-3196), including projected market size, sector leadership, and patient treatment estimates for NASH and NAFLD patients; the timing and completion of projected future clinical milestone
events, including enrollment, additional studies, top-line data and open label projections; plans, objectives and timing for making a Subpart H (Accelerated Approval of New Drugs for Serious or
Life-Threatening Illnesses) submission to FDA; projections or objectives for obtaining accelerated or full approval for resmetirom for noncirrhotic NASH patients with compensated cirrhosis; our primary and key secondary study endpoints for
resmetirom and the potential for achieving such endpoints and projections, including NASH resolution, safety, fibrosis treatment, cardiovascular effects, and lipid treatment with resmetirom; our ability to address the unmet needs of patients
suffering from NASH with significant fibrosis; optimal dosing levels for resmetirom and projections regarding potential NASH or NAFLD and potential patient benefits with resmetirom, including future NASH resolution, safety, fibrosis treatment,
cardiovascular effects, lipid treatment, and/or biomarker effects with resmetirom; the potential efficacy and safety of resmetirom for noncirrhotic NASH patients and cirrhotic NASH patients; the potential for resmetirom to become the best-in-class and/or first-to-market treatment option for patients with NASH and liver
fibrosis; anticipated or estimated future results of operations and expenses as we expand our resmetirom clinical development program and our commercial development program; ex-U.S. launch/partnering plans;
the ability to develop clinical evidence demonstrating the utility of noninvasive tools and techniques to screen and diagnose NASH and/or NAFLD patients; the predictive power of liver fat reduction with resmetirom, as measured by noninvasive tests,
on NASH resolution and/or fibrosis reduction or improvement, and potential NASH or NAFLD patient risk profile benefits with resmetirom; the predictive power of liver fat, liver volume changes or MAST scores for NASH and/or NAFLD patients; the
predictive power of NASH resolution and/or liver fibrosis reduction or improvement with resmetirom using noninvasive tests, including the use of ELF, FibroScan, MRE and/or MRI-PDFF; the predictive power of
noninvasive tests generally, including for purposes of diagnosing NASH, monitoring patient response to resmetirom, or recruiting and conducting a NASH clinical trial; market demand for and acceptance of our products; research, development and
commercialization of new products; obtaining and maintaining regulatory approvals, including, but not limited to, potential regulatory delays or rejections; risks associated with meeting the objectives of our clinical studies, including, but not
limited to our ability to achieve enrollment objectives concerning patient numbers (including an adequate safety database), outcomes objectives and/or timing objectives for our studies, any delays or failures in enrollment, the occurrence of adverse
and the risks of successfully conducting trials that are substantially larger, and have patients with different disease states, than our past trials; risks related to the effects of
resmetirom s mechanism of action and our ability to accomplish our business and business development objectives and realize the anticipated benefit of any such transactions; the achievement of enrollment objectives concerning patient number,
safety database and/or timing for our studies; and assumptions underlying any of the foregoing.
Forward-looking statements reflect
management s current knowledge, assumptions, judgment and expectations regarding forward-looking statements, future performance or events; include all statements that are not historical facts; and can be identified by terms such as
accelerate, achieve, allow, anticipates, appear, be, believes, can, continue, could, demonstrates,
design, estimates, expectation, expects, forecasts, future, goal, help, hopeful, inform, informed, intended,
intends, may, might, on track, planned, planning, plans, positions, potential, powers, predicts,
predictive, projects, seeks, should, will, will achieve, will be, would or similar expressions and the negatives of those terms.
Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to: our clinical and commercial development of