- Phase 2 clinical studies of MGL-3196, a
liver-directed thyroid hormone receptor (THR) beta selective
agonist, are underway in patients with non-alcoholic
steatohepatitis (NASH) and familial hypercholesterolemia (HeFH)
Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) today announced its
first quarter 2017 financial results. During the first
quarter of 2017, Madrigal initiated Phase 2 clinical development of
its lead compound, MGL-3196, a first-in-class, oral, once-daily,
liver-directed, thyroid hormone receptor (THR) β-selective agonist,
in patients with HeFH. The Company had initiated a Phase 2
clinical study of MGL-3196 in patients with NASH in the fourth
quarter of 2016.
“Enrollment is continuing as planned in our two Phase 2
proof-of-concept clinical trials of MGL-3196, for patients with
NASH and HeFH,” said Paul Friedman, M.D., Chief Executive Officer
of Madrigal. “Both indications have serious unmet patient needs
that we believe can be safely and effectively addressed by
MGL-3196. We look forward to data readouts from these studies
which, if positive, should enable us to initiate Phase 3
registration trials in 2018.”
“Because MGL-3196 selectively agonizes THR-β, it has the
potential to safely address key pathological mechanisms responsible
for the progression of liver injury and address the underlying
causes of NASH,” said Rebecca Taub, M.D., CMO and Executive VP,
Research & Development of Madrigal. “Additionally, for the
majority of HeFH patients who do not reach their cholesterol
reduction goals on standard treatment, MGL-3196 has the potential
to provide significant LDL lowering in these patients either as
monotherapy or in combination with existing therapies.”
Clinical Program Summaries for MGL-3196
NASH Non-alcoholic Steatohepatitis (NASH) is a common liver
disease in the United States and worldwide, unrelated to alcohol
use, that is characterized by a build-up of fat in the liver,
inflammation, damage (ballooning) of hepatocytes and increasing
fibrosis. Although people with NASH may feel well and often do not
know they have the disease, NASH can lead to permanent damage,
including cirrhosis and impaired liver function in a high
percentage of NASH patients.
In October 2016, the first patient was treated in Madrigal’s
Phase 2 trial of MGL-3196 for the treatment of NASH. The
randomized, double-blind, placebo-controlled, multi-center study is
expected to enroll up to 117 patients 18 years of age and older
with biopsy-confirmed NASH and more than 10% liver fat as confirmed
by a magnetic resonance imaging-proton density fat fraction
(MRI-PDFF).
In this trial, patients are randomized 2:1 to receive either
MGL-3196 or placebo. The primary endpoint of the trial is the
reduction of liver fat, assessed by MRI-PDFF at 12 weeks. Recent
published data show a high correlation of reduction of liver fat
measured by MRI-PDFF to NASH scoring on liver biopsy.
Efficacy will be confirmed at the end of the trial (36 weeks) by
repeat MRI-PDFF and conventional liver biopsy to examine
histological evidence for the resolution of NASH. Additional
secondary endpoints include changes in clinically relevant
biomarkers at 12 and 36 weeks, improvement in fibrosis by at least
one stage, improvement of NASH, and safety and tolerability.
Top-line results for the primary endpoint of the trial, the
reduction of liver fat, assessed by MRI-PDFF at 12 weeks, are
expected by year-end.
HeFH Heterozygous familial hypercholesterolemia (HeFH) is a
severe genetic dyslipidemia, typically caused by an inactivating
mutation in one copy of the LDL receptor gene that leads to early
onset cardiovascular disease. With conventional therapy, including
statins and ezetimibe, the majority of HeFH and virtually all HoFH
patients fail to reach their cholesterol (LDL-C) reduction goals.
Based on evidence of impressive LDL cholesterol lowering in Phase
1, and data suggesting that MGL-3196 has a mechanism of action that
is different from and complementary to statins, Madrigal initiated
a Phase 2 proof-of-concept trial in HeFH. Top-line results of
this trial are also expected by year-end.
The 12-week, randomized, double-blind, placebo-controlled,
multi-center study will enroll up to 105 patients with HeFH
randomized in a 2:1 ratio to receive either MGL-3196 or placebo, in
addition to their current drug regimen (including high dose statins
and ezetimibe). The primary endpoint of the study is reduction of
LDL cholesterol, with secondary endpoints including reductions in
triglycerides, Lp(a), and ApoB, as well as safety. Lp(a) is a
severely atherogenic lipid particle, commonly elevated in familial
hypercholesterolemia patients and poorly controlled by existing
lipid lowering therapies. THR-β agonism is one of the few
therapeutic approaches that can substantially lower Lp(a). As
previously announced, the first patient in this study was dosed in
February 2017.
HoFH Homozygous familial hypercholesterolemia (HoFH) is a much
rarer form of severe genetic dyslipidemia, which results from
inactivating mutations in both copies of the LDL receptor gene, and
can produce cardiovascular disease before age 20. The protocol for
a Phase 2, open-label study of MGL-3196 in HoFH is in development.
The 12-week trial will have endpoints similar to the HeFH study and
is expected to begin enrolling patients by the end of 2017.
Financial Results for the Three Months Ended March 31,
2017
As of March 31, 2017, Madrigal had cash, cash equivalents and
marketable securities of $40.1 million.
Operating expenses were $6.1 million for the three month period
ended March 31, 2017, compared to $0.7 million in the comparable
prior year period.
Research and development expenses for the three month period
ended March 31, 2017 increased to approximately $4.4 million, as
compared to $0.5 million in the first quarter of 2016. The
increases are primarily attributable to higher expenses for
personnel, particularly non-cash stock based compensation, and
increased expenses for our preclinical and clinical development
programs for MGL-3196.
General and administrative expenses for the three month period
ended March 31, 2017 increased to approximately $1.7 million, as
compared to $0.2 million in the first quarter of 2016. The
increase is primarily attributable to higher expenses for
personnel, particularly non-cash stock based compensation, and
professional services related to Madrigal becoming a public company
in mid-2016.
Interest income (expense), net, for the three month period ended
March 31, 2017 was $76 thousand, as compared to $(975) thousand for
the comparable period in 2016. The decrease in interest expense in
2017 was due to the conversion of convertible debt to shares of
common stock in connection with the Company’s merger, which closed
on July 22, 2016.
About Madrigal Pharmaceuticals
Madrigal Pharmaceuticals, Inc. (Nasdaq:MGDL) 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. The
company’s lead candidate, MGL-3196, is a first-in- class, orally
administered, small-molecule, liver-directed, thyroid hormone
receptor (THR) ß- selective agonist that is currently in Phase 2
development for NASH and HeFH. 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. Forward-looking
statements reflect management's current knowledge, assumptions,
judgment and expectations regarding future performance or events.
Although management believes that the expectations reflected in
such statements are reasonable, they 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, the company's clinical development of MGL-3196, the timing and
outcomes of clinical studies of MGL-3196, 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.
(Tables Follow)
Madrigal Pharmaceuticals, Inc. |
Condensed Consolidated Statements of
Operations |
(in thousands, except share and per share
amounts) |
(unaudited) |
|
|
|
|
|
Three Months Ended |
|
|
March 31, |
|
|
|
2017 |
|
|
2016 |
|
|
Revenues: |
|
|
|
Total
revenues |
$ |
- |
|
$ |
- |
|
|
Operating
expenses: |
|
|
|
Research
and development |
|
4,380 |
|
|
516 |
|
|
General
and administrative |
|
1,695 |
|
|
222 |
|
|
Total
operating expenses |
|
6,075 |
|
|
738 |
|
|
Loss from
operations |
|
(6,075) |
|
|
(738) |
|
|
Interest
income (expense), net |
|
76 |
|
|
(975) |
|
|
Net
loss |
$ |
(5,999) |
|
$ |
(1,713) |
|
|
|
|
|
|
Basic and
diluted net loss per common share |
$ |
(0.50) |
|
$ |
(9.72) |
|
|
Basic and
diluted weighted average number of common shares outstanding |
|
11,955,739 |
|
|
176,158 |
|
|
|
|
|
|
Madrigal Pharmaceuticals, Inc. |
Condensed Consolidated Balance
Sheets |
(in thousands) |
(unaudited) |
|
|
|
|
|
March 31, |
|
December 31, |
|
|
2017 |
|
2016 |
|
|
|
|
|
Assets |
|
|
|
Cash, cash equivalents
and marketable securities |
$ |
40,127 |
|
$ |
40,499 |
|
Other current
assets |
|
225 |
|
|
708 |
|
Other non-current
assets |
|
5 |
|
|
3 |
|
Total
assets |
$ |
40,357 |
|
$ |
41,210 |
|
|
|
|
|
Liabilities and
Equity |
|
|
|
Current
liabilities |
$ |
5,906 |
|
$ |
4,800 |
|
Long-term
liabilities |
|
- |
|
|
- |
|
Stockholders’
equity |
|
34,451 |
|
|
36,410 |
|
Total
liabilities and stockholders’ equity |
$ |
40,357 |
|
$ |
41,210 |
|
|
|
|
|
|
|
|
Investor Contact:
Marc Schneebaum, Madrigal Pharmaceuticals, Inc.
IR@madrigalpharma.com
Media Contact:
Mike Beyer, Sam Brown Inc.
mikebeyer@sambrown.com
312-961-2502
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