Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage
biopharmaceutical company pursuing novel therapeutics for
non-alcoholic steatohepatitis (NASH), today announced acceptance of
four abstracts for oral presentation at the European Association
for the Study of the Liver’s (EASL) International Liver Congress,
including a late-breaker presentation of data from the Phase 3
MAESTRO-NAFLD-1 trial, as well as other resmetirom clinical
development program updates. The Company also reported financial
results for the first quarter of 2022, including the completion of
a $250 million term loan facility to support resmetirom clinical
and commercial development objectives and position Madrigal for a
potential first-to-market launch in NASH. The company drew $50
million from the facility at closing and has the ability to draw a
further $200 million under the agreement.
Paul Friedman, M.D., Chief Executive Officer of Madrigal,
stated, “The MAESTRO-NAFLD-1 data as described below have
reinforced our confidence in the safety and potential efficacy of
resmetirom in treating non-cirrhotic NASH with significant
fibrosis. We look forward to sharing detailed MAESTRO-NAFLD-1
results in a late-breaking presentation at EASL followed by topline
results from the MAESTRO-NASH biopsy study in Q4. Based on the
totality of efficacy data generated thus far in our clinical
development program, we believe resmetirom can both address the
underlying drivers of NASH in the liver and also reduce the level
of fibrosis that is associated with progression to more advanced
disease.”
Dr. Friedman added, “The term loan facility we are announcing
today strengthens Madrigal’s balance sheet, providing an additional
source of funding that can be drawn at the appropriate times to
meet our operational needs and support our strategic priorities,
including a new MAESTRO study and the ramp-up for the potential
launch of resmetirom in the U.S.”
Becky Taub, M.D., Chief Medical Officer and President of
Research & Development of Madrigal, stated, "We are planning to
expand our NASH development program by initiating a second study in
the next few months to complement the clinical outcomes portion of
MAESTRO-NASH; this second study, MAESTRO-NASH Outcomes, will
non-invasively examine liver-related outcomes (decompensation
events) in patients with early NASH cirrhosis. In contrast,
MAESTRO-NASH relies primarily on serial liver biopsy to measure
progression to cirrhosis. Resmetirom has been studied in over 180
patients with well-compensated NASH cirrhosis in an open-label arm
of MAESTRO-NAFLD-1. The safety and efficacy results that will be
presented at EASL are supportive of a potential for benefit in this
population. A positive outcome in this study, in a group of
patients with the highest unmet need, has the potential to
significantly broaden the label for resmetirom and increase the
commercial opportunity. Furthermore, it is expected to accelerate
the path to full approval and enhance the statistical power to
assess benefit in patients with non-cirrhotic NASH. The addition of
MAESTRO-NASH Outcomes does not alter our timeline for the subpart H
NDA submission in non-cirrhotic NASH that is based on the results
of the liver biopsy portion of MAESTRO-NASH.”
Dr. Taub added, "As we have continued to gain confidence that we
will achieve both the NASH resolution as well as the fibrosis
improvement endpoints in the MAESTRO-NASH biopsy study we are
moving one point fibrosis reduction up the hierarchy to a primary
endpoint along with NASH resolution. While we expect to achieve
both endpoints, dual primaries allow for a successful outcome of
the study that can be filed for subpart H approval if either the
NASH resolution or one point fibrosis reduction liver biopsy
endpoint is met.”
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, “There is an urgent need for NASH treatments
that can prevent progression to hepatic decompensation in patients
at the early stages of NASH cirrhosis, but few late-stage
development programs have focused on this population. The
MAESTRO-NASH Outcomes study will help us determine if resmetirom
can benefit patients with more advanced disease and achieve the
endpoints that are valued most by healthcare providers, regulators,
payers and, most importantly, patients.”
Clinical Program Updates
Late-Breaking Presentation and Multiple Oral Presentations at
EASLMultiple resmetirom abstracts have been accepted at EASL’s
International Liver Congress taking place June 22-26 in London:
- Late-breaking presentation: “Primary data analyses of
MAESTRO-NAFLD-1, a 52 week double-blind placebo-controlled phase 3
clinical trial of resmetirom in patients with NAFLD” [Saturday,
June 25 at 3:00 PM. Presenter: Stephen Harrison]
- Oral presentation: “Impact of resmetirom-mediated reductions in
liver volume and steatosis compared with placebo on the
quantification of fibrosis using second harmonic generation in a
serial liver biopsy study” [Thursday, June 23 at 4:00 PM.
Presenter: Dean Tai]
- Oral presentation: “Utility of FIB-4 thresholds to identify
patients with at-risk F2-F3 NASH based on screening data from a
2000 patient biopsy confirmed cohort of resmetirom Phase 3 clinical
trial, MAESTRO-NASH” [Saturday, June 25 at 9:15 AM. Presenter: Jörn
Schattenberg]
- Oral presentation: “Biomarkers, imaging and safety in a
well-compensated NASH cirrhotic cohort treated with resmetirom, a
thyroid hormone receptor beta agonist, for 52 weeks” [Saturday,
June 25 at 5:45 PM. Presenter: Stephen Harrison]
- Poster: “A higher Fibrosis-4 (FIB-4) score is associated with
higher healthcare costs and hospitalizations in patients with
nonalcoholic steatohepatitis” [Presenter: Elliot Tapper]
- Poster: “Retrospective AI-based measurement of NASH histology
(AIM-NASH) analysis of biopsies from Phase 2 study of Resmetirom
confirms significant treatment-induced changes in histologic
features of non-alcoholic steatohepatitis” [Presenter: Janani
Iyer]
Additional Phase 3 MAESTRO-NAFLD-1 DataIn January, Madrigal
announced that primary and key secondary endpoints from the
double-blind, placebo-controlled, 969-patient MAESTRO-NAFLD-1
safety study were achieved; resmetirom was safe and well-tolerated
and provided significant reductions in liver fat, LDL-c and other
atherogenic lipids vs. placebo.
Similar to what has been reported for the 100 mg open-label arm,
patients in the resmetirom 80 mg and 100 mg double-blind arms
achieved reductions in ALT (p=0.002; <0.0001) relative to
placebo. ALT increases ≥3 times the upper limit of normal occurred
in 0.61% in the resmetirom 80 mg group, 0.31% in the 100 mg group
and 1.6% of patients in the placebo group.
Treatment-emergent adverse events ≥ grade 3 in severity occurred
in 7.6% of patients in the resmetirom 80 mg group, 9.0% in the 100
mg group and 9.1% in the placebo group. Withdrawals due to adverse
events were 2.4% in the 80 mg group, 2.8% in the 100 mg group and
1.3% in the placebo group. GI-related adverse events (diarrhea,
nausea) were increased relative to placebo at the initiation of
therapy but not after the first few weeks.
FibroScan CAP (controlled attenuation parameter) scores
reflective of hepatic fat were statistically significantly
(p<0.0001) reduced in resmetirom arms as compared with placebo.
FibroScan liver stiffness reductions were similar in the 100 mg
open-label and double-blind arms. Responder analyses of FibroScan
vibration-controlled transient elastography (VCTE) reduction and %
reduction from baseline comparing resmetirom 100 mg open-label and
double-blind arms with placebo showed a significant increase in
responders in resmetirom treatment arms (~44% averaged across the
arms) compared with placebo (25%); magnetic resonance elastography
(MRE) responders as measured by kPa reduction were significantly
greater in resmetirom-treated groups compared with placebo. Mean
reduction in FibroScan VCTE in resmetirom double-blind patients was
greater than placebo but not statistically significant.
Detailed results of MAESTRO-NAFLD-1 are under embargo until the
late-breaking presentation at EASL.
MAESTRO-NASH Outcomes Study In the next few months, Madrigal
plans to initiate a second NASH outcomes study, MAESTRO-NASH
Outcomes, a randomized double-blind placebo-controlled study in
approximately 700 patients with early NASH cirrhosis to allow for
non-invasive monitoring of progression to liver decompensation
events. Several biomarker and imaging techniques will also be
employed to assess correlates with disease progression. Ongoing
open-label studies of more than 180 patients with well-compensated
NASH cirrhosis (MAESTRO-NAFLD-1 open-label arm) support the
potential of resmetirom in this patient population.
Previously reported data from the patients with NASH cirrhosis
in the open-label arm of MAESTRO-NAFLD-1 demonstrated that
resmetirom reduced hepatic fat, liver volume, liver enzymes,
fibrosis markers and atherogenic lipids. Madrigal will be
presenting additional results from the MAESTRO-NAFLD-1 cirrhosis
population in an oral presentation at EASL.
Term Loan Facility to Support Expansion of Clinical
Development Program and Resmetirom Launch
Madrigal has secured a $250 million term loan facility with
Hercules Capital, Inc. (NYSE: HTGC), a leader in customized
specialty financing for life sciences companies. The committed
capital strengthens Madrigal’s balance sheet, providing an
additional source of funding both to support the expanded clinical
program and ramp-up for a potential launch of resmetirom in the
U.S.
Under the terms of the loan agreement, $50 million was drawn at
closing. Madrigal may also draw an additional $125 million in two
separate tranches upon achievement of resmetirom clinical and
regulatory milestones. An additional $75 million may be drawn by
Madrigal, subject to the approval of Hercules Capital. The loan
facility has a floor rate of 7.45% and adjusts with future changes
in the prime rate, subject to the floor rate. The loan bears
initial interest at a rate of 7.95%. Madrigal will pay
interest-only for a period of 30 months, which may be extended to
60 months upon the achievement of certain milestones. The loan
matures in May 2026 and may be extended an additional year upon the
achievement of certain milestones.
R. Bryan Jadot, Senior Managing Director and Life Sciences Group
Head at Hercules Capital stated, “Hercules is pleased to provide
both upfront funding and future potential funding capacity to help
Madrigal deliver on its important mission to address a large unmet
medical need and improve the lives of people suffering from NASH
and liver disease.”
Additional details of the loan agreement will be filed with the
Securities and Exchange Commission on a Current Report on Form
8-K.
Financial Results for the Three Months Ended March 31,
2022
As of March 31, 2022, Madrigal had cash, cash equivalents and
marketable securities of $220.0 million, compared to $270.3 million
at December 31, 2021. The decrease in cash and marketable
securities resulted primarily from cash used in operations of $49.9
million.
Operating expenses were $57.6 million for the three month period
ended March 31, 2022, compared to $53.0 million in the comparable
prior year period.
Research and development expenses for the three month period
ended March 31, 2022 were $47.9 million, compared to $45.8 million
in the comparable prior year period. 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 month period
ended March 31, 2022 were $9.7 million, compared to $7.2 million in
the comparable prior year period. The increase in general and
administrative expenses for the latest three month period is due
primarily to increases in commercial preparation activities,
including an increase in headcount.
Interest income for the three month period ended March 31, 2022
was $0.1 million, compared to $0.2 million in the comparable prior
year period. The decrease in interest income was due primarily to a
lower average principal balance in our investment account in
2022.
Conference Call at 8:00 am EST
Madrigal will hold a conference call and webcast at 8:00 am EST.
To access the conference call, please dial (833) 660-2754 for
domestic callers or (409) 350-3497 for international callers and
reference conference ID: 9765409. To access the live webcast of the
call with slides please visit the Investors section of Madrigal’s
website or click here. An archived webcast will be available on the
Madrigal website after the event.
About the Resmetirom Phase 3 Registration Program for
the Treatment of NASH
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 targeted 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 dual primary surrogate
endpoints on biopsy are NASH resolution, with at least a
2-point reduction in NAS (NASH Activity Score), and with no
worsening of fibrosis OR a one point decrease in fibrosis with no
worsening of NASH. Either primary endpoint can be achieved for a
successful trial outcome. A key secondary endpoint is lowering of
LDL-cholesterol. The planned target enrollment was announced as
completed on June 30, 2021.
The first 900 patients in the MAESTRO-NASH study will
continue on therapy after the initial 52-week treatment period; up
to another 1,100 patients are to be added using the same
randomization plan. 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 was initiated in December 2019 and the 52-week
Phase 3 multi-center, double-blind, randomized, placebo-controlled
study of resmetirom in over 1,200 patients with non-alcoholic fatty
liver disease (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
is to evaluate the safety and tolerability of resmetirom. An
open-label extension study, MAESTRO-NAFLD-OLE is ongoing.
Patients in the 52-week blinded phase of MAESTRO-NAFLD-1 were
randomized 1:1:1:1 to receive resmetirom 80 mg once a day, 100 mg
once a day, placebo or a 100 mg resmetirom 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 non-invasive techniques. Using non-invasive 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. These key secondary endpoints included LDL-cholesterol,
apolipoprotein B and triglyceride (TG) 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.
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 for non-alcoholic steatohepatitis (NASH), a liver
disease with high unmet medical need. Madrigal’s lead candidate,
resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β
selective agonist that is designed to target key underlying causes
of NASH in the liver. Resmetirom is currently being evaluated in
two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO-NAFLD-1,
designed to demonstrate multiple benefits in patients with NASH.
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, presentations of data from, or outcomes from our
trials; research and development activities; market size and
patient treatment 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 and/or biomarker effects with resmetirom; the
potential 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, as 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 or improvement 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 liver fibrosis; 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 “accelerate,” “achieve,” “allow,” “anticipates,”
“be,” “believes,” “can,” “continue,” “could,” “demonstrate,”
”design,” “estimates,” “expectation,” “expects,” “forecasts,”
“future,” “goal,” “hopeful,” ”inform,” “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. 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, and patients with different disease
states, than our prior studies; limitations associated with early
stage or 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, 2021, our Quarterly
Report on form 10-Q for the Quarter ended March 31, 2022, and in
our other filings with the SEC.
Investor Contact Alex Howarth, Madrigal
Pharmaceuticals, Inc., IR@madrigalpharma.com
Media ContactsChristopher Frates, Madrigal
Pharmaceuticals, Inc., media@madrigalpharma.com
(Tables follow)
Madrigal Pharmaceuticals, Inc. |
Condensed Consolidated Statements of
Operations |
(in thousands, except share and per share
amounts) |
(unaudited) |
|
|
|
|
|
|
|
Three Months Ended |
|
March 31, |
|
2022 |
2021 |
Revenues: |
|
|
Total revenues |
$ |
- |
|
$ |
- |
|
Operating expenses: |
|
|
Research and development |
|
47,929 |
|
|
45,770 |
|
General and administrative |
|
9,658 |
|
|
7,209 |
|
Total operating expenses |
|
57,587 |
|
|
52,979 |
|
Loss from operations |
|
(57,587) |
|
|
(52,979) |
|
Interest income, net |
|
69 |
|
|
160 |
|
Other income |
|
- |
|
|
273 |
|
Net loss |
$ |
(57,518) |
|
$ |
(52,546) |
|
|
|
|
Basic and diluted net loss per common share |
$ |
(3.36) |
|
$ |
(3.32) |
|
Basic and diluted weighted average number of common shares
outstanding |
|
17,103,395 |
|
|
15,840,401 |
|
|
|
|
|
|
|
|
|
|
Madrigal Pharmaceuticals, Inc. |
Condensed Consolidated Balance Sheets |
(in thousands) |
(unaudited) |
|
|
|
|
|
|
|
|
|
|
March 31, |
December 31, |
|
2022 |
2021 |
|
|
|
Assets |
|
|
Cash, cash equivalents and
marketable securities |
$ |
219,953 |
|
$ |
270,346 |
|
Other current assets |
|
1,217 |
|
|
1,338 |
|
Other non-current assets |
|
1,492 |
|
|
1,648 |
|
Total assets |
$ |
222,662 |
|
$ |
273,332 |
|
|
|
|
Liabilities and
Equity |
|
|
Current liabilities |
$ |
76,635 |
|
$ |
76,838 |
|
Long-term liabilities |
|
283 |
|
|
387 |
|
Stockholders’ equity |
|
145,744 |
|
|
196,107 |
|
Total liabilities and stockholders’ equity |
$ |
222,662 |
|
$ |
273,332 |
|
|
|
|
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