- MGL-3196 is a first-in-class, oral, once-daily,
liver-directed, thyroid hormone receptor (THR) β -selective
agonist that is being developed for patients with non-alcoholic
steatohepatitis (NASH) and heterozygous familial
hypercholesterolemia (HeFH) -
Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) today announced
its fourth quarter and year-end 2017 financial
results, highlighting a substantial cash position and
significant progress for MGL-3196, its lead compound being
developed as a treatment for non-alcoholic steatohepatitis (NASH)
and heterozygous familial hypercholesterolemia (HeFH).
“Madrigal had a very productive 2017 and 2018 looks to be
equally transforming. During the year, we intend to report
for the NASH study with MGL-3196, both the full 12-week Phase 2
results as well as the top-line 36-week data, including liver
biopsy results. In addition, we expect to report the full Phase 2
results from the HeFH study later in the year. We also intend to
meet with representatives from the FDA to discuss our plans for
Phase 3,” stated Paul Friedman, M.D., President and Chief Executive
Officer of Madrigal. “Importantly, we are well funded to
expeditiously advance MGL-3196 forward in NASH and HeFH, and
possibly in other dyslipidemic indications.”
Key Accomplishments
- Successfully recruited two double-blind, placebo-controlled
Phase 2 clinical trials evaluating MGL-3196 as a treatment for
patients with NASH and HeFH.
- Reported that MGL-3196 demonstrated highly statistically
significant results for the primary endpoints in both Phase 2
trials.
- Achieved acceptance of an MGL-3196 NASH abstract for a main
plenary presentation at the Annual Meeting of the European
Association for the Study of the Liver (EASL) during The
International Liver CongressTM 2018.
- Raised net proceeds of more than $170 million through
well-supported public offerings of Madrigal stock.
Becky Taub, M.D., CMO and Executive VP, Research &
Development of Madrigal stated, “Achieving these highly
statistically significant results for the primary endpoints in the
ongoing NASH Phase 2 trial and the completed Phase 2 trial in HeFH
is very encouraging. Anticipating continued positive data,
we’re moving ahead with preparations for Phase 3 studies.”
Clinical Program Summaries for
MGL-3196NASHNon-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 patients.
In October 2016, the first patient was treated in the
ongoing Phase 2 trial of MGL-3196 for the treatment of NASH. The
randomized, double-blind, placebo-controlled, multi-center Phase 2
study enrolled 125 patients 18 years of age and older with liver
biopsy-confirmed NASH and included approximately 25 clinical sites
in the United States.
Patients were randomized to receive either MGL-3196 or placebo
in a 2:1 ratio.
The primary endpoint of the study, the reduction of liver fat at
12 weeks compared with baseline (relative change), assessed by
magnetic resonance imaging-estimated proton density fat fraction
(MRI-PDFF), was achieved. Liver fat was reduced by 36.3% in all
MGL-3196 treated patients (78) and 42.0% in a pre-specified group
of high exposure MGL-3196 treated patients (44/78), as compared
with 9.6% median reduction in liver fat in 38 placebo treated
patients. These results were statistically significant
(p<0.0001) for both MGL-3196 treatment groups. MGL-3196 was well
tolerated with few serious adverse events noted during the 12-week
portion of the study, none of which was related to MGL- 3196.
The study is ongoing and remains blinded. Additional efficacy
endpoints are being assessed at the end of the 36-week treatment
period by repeat MRI-PDFF and conventional liver biopsy to examine
histologic evidence for the resolution of and improvement in
NASH.
Results of the 36-week endpoints are expected in the second
quarter of 2018. In addition, based on liver enzyme inclusion
criteria, some patients (blinded as to whether they were on placebo
or MGL-3196 in the main 36-week portion of the study) are receiving
extended treatment beyond 36 weeks for up to 36 additional weeks.
All patients in the extension study will receive MGL-3196 and only
non-invasive assessments will be made, including serial MRI-PDFF,
safety labs, and circulating biomarkers. Additional information
about the study [NCT02912260] can be obtained at
www.ClinicalTrials.gov.
HeFH Heterozygous familial hypercholesterolemia (HeFH),
and a much rarer form called homozygous familial
hypercholesterolemia (HoFH), are severe genetic dyslipidemias
typically caused by inactivating mutations in the LDL receptor.
Both forms of FH lead to early onset cardiovascular disease. HeFH,
the most common dominantly inherited disease, is present in up to 1
in 200 people; the disease is found in higher frequencies in
certain more genetically homogenous populations. Treatments exist
for both HeFH and HoFH but many patients (as many as 40 percent of
HeFH patients) are not able to reach their cholesterol (LDL-C)
reduction goals on these therapies, reflecting the lifetime burden
of cholesterol buildup in their bodies. 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 in February 2017 and enrolled
116 patients.
In this Phase 2 HeFH trial, patients who were not at their LDL-C
goal were randomized in a 2:1 ratio to receive either MGL-3196 or
placebo, in addition to their current cholesterol lowering regimen,
which included approximately 75% taking high intensity statins
(20/40 mg rosuvastatin or 80 mg atorvastatin), and about 2/3 of
patients also taking ezetimibe. MGL-3196 treated patients (placebo
corrected) achieved highly significant (p< 0.0001) LDL-C
lowering of 18.8%, and 21% LDL-C lowering in those on an optimal
dose of MGL-3196. LDL-C lowering was 28.5% in MGL-3196 treated
compared to placebo in a prespecified group of patients who did not
tolerate high intensity statin doses. Highly significant reductions
(p<0.0001) relative to placebo were also observed with ApoB,
triglycerides (TG) (25-31%), apolipoprotein CIII (Apo CIII) and
Lp(a) (25-40%) in all MGL-3196 treated patients and prespecified
subgroups, irrespective of statin treatment.
MGL-3196 was well-tolerated with primarily mild and some
moderate AEs, the numbers of which were balanced between placebo
and drug-treatment groups.
Financial Results for the Three Months and Twelve Months
Ended December 31, 2017
Operating expenses were $8.9 million and $32.1 million for the
three month and twelve month periods ended December 31, 2017,
respectively, compared to $7.8 million and $25.2 million in the
comparable prior year periods.
Research and development expenses for the three month and twelve
month periods ended December 31, 2017 increased to approximately
$6.5 million and $24.4 million in 2017, as compared to $5.5 million
and $15.9 million, respectively, in 2016. The increases are
primarily attributable to higher expenses for our clinical and
preclinical development programs for MGL-3196, and increased
personnel costs, in both the three and twelve month periods ended
December 31, 2017, as compared to the same periods in 2016.
General and administrative expenses for the three month period
ended December 31, 2017 increased to approximately $2.4 million
from approximately $2.2 million in the comparable period in 2016,
due primarily to higher compensation expenses. General and
administrative expenses for the twelve month period ended December
31, 2017 decreased to approximately $7.7 million from $9.3 million
in the comparable period in 2016, due primarily to expenses
incurred in 2016 associated with the Company’s merger.
Interest income (expense), net, for the three month and twelve
month periods ended December 31, 2017 was $216 thousand and $558
thousand, respectively, as compared to $6 thousand and $(1.2)
million, respectively, for the same periods in 2016. The change in
interest income (expense) was due primarily to the conversion of
all outstanding promissory notes to equity upon the consummation of
the merger in 2016, and a higher average principal balance in our
investment account in 2017.
About MGL-3196 Among its many functions in the
human body, thyroid hormone, through activation of its beta
receptor, plays a central role in controlling lipid metabolism,
impacting a range of health parameters from levels of serum
cholesterol and triglycerides to the pathological buildup of fat in
the liver. Attempts to exploit this pathway for therapeutic
purposes in cardio-metabolic and liver diseases have been hampered
by the lack of selectivity of older compounds for the thyroid
hormone receptor (THR)-β, chemically-related toxicities and
undesirable distribution in the body.
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. Madrigal believes that MGL-3196 is the first orally
administered, small-molecule, liver- directed, truly β-selective
THR agonist. MGL- 3196 has demonstrated the potential for a broad
array of therapeutically beneficial effects, improving components
of both metabolic syndrome, such as insulin resistance and
dyslipidemia, and fatty liver disease, including lipotoxicity and
inflammation. These pleiotropic actions, coupled with an excellent
safety profile, suggest that MGL-3196 could be the preferred
treatment option for 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, MGL-3196, is a first-in- class, orally
administered, small-molecule, liver-directed, thyroid hormone
receptor (THR) β- 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. Such statements contain words such as “expect,” “could,”
“may,” “will,” “believe,” “estimate,” "continue," "future,” or the
negative thereof or comparable terminology and the use of future
dates. 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.
Investor Contact: Marc Schneebaum, Madrigal
Pharmaceuticals, Inc. IR@madrigalpharma.com
Media Contact: Mike Beyer, Sam Brown Inc.
mikebeyer@sambrown.com 312 961 2502
|
|
Madrigal Pharmaceuticals, Inc. |
|
Condensed Consolidated Statements of
Operations |
|
(in thousands, except share and per share
amounts) |
|
(unaudited) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended |
|
Twelve Months Ended |
|
|
December 31, |
|
December 31, |
|
|
|
2017 |
|
|
2016 |
|
|
|
2017 |
|
|
2016 |
|
|
Revenues: |
|
|
|
|
|
|
Total
revenues |
$ |
- |
|
$ |
- |
|
|
$ |
- |
|
$ |
- |
|
|
Operating
expenses: |
|
|
|
|
|
|
Research
and development |
|
6,512 |
|
|
5,523 |
|
|
|
24,390 |
|
|
15,933 |
|
|
General
and administrative |
|
2,399 |
|
|
2,232 |
|
|
|
7,672 |
|
|
9,290 |
|
|
Total operating expenses |
|
8,911 |
|
|
7,755 |
|
|
|
32,062 |
|
|
25,223 |
|
|
Loss from operations |
|
(8,911 |
) |
|
(7,755 |
) |
|
|
(32,062 |
) |
|
(25,223 |
) |
|
Interest income (expense), net |
|
216 |
|
|
6 |
|
|
|
558 |
|
|
(1,165 |
) |
|
Other income |
|
250 |
|
|
- |
|
|
|
350 |
|
|
- |
|
|
Net
loss |
$ |
(8,445 |
) |
$ |
(7,749 |
) |
|
$ |
(31,154 |
) |
$ |
(26,388 |
) |
|
|
|
|
|
|
|
|
Basic and
diluted net loss per common share |
$ |
(0.67 |
) |
$ |
(0.67 |
) |
|
$ |
(2.54 |
) |
$ |
(5.07 |
) |
|
Basic and
diluted weighted average number of common shares outstanding |
|
12,597,864 |
|
|
11,509,791 |
|
|
|
12,244,939 |
|
|
5,204,644 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Madrigal Pharmaceuticals, Inc. |
|
Condensed Consolidated Balance
Sheets |
|
(in thousands) |
|
(unaudited) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
December 31, |
December 31, |
|
|
|
|
|
|
2017 |
|
|
2016 |
|
|
|
|
|
|
|
|
|
|
|
|
Assets |
|
|
|
|
|
|
Cash, cash equivalents
and marketable securities |
$ |
191,527 |
|
$ |
40,500 |
|
|
|
|
|
Other current
assets |
|
485 |
|
|
707 |
|
|
|
|
|
Other non-current
assets |
|
301 |
|
|
3 |
|
|
|
|
|
Total
assets |
$ |
192,313 |
|
$ |
41,210 |
|
|
|
|
|
|
|
|
|
|
|
|
Liabilities and
Equity |
|
|
|
|
|
|
Current
liabilities |
$ |
10,054 |
|
$ |
4,800 |
|
|
|
|
|
Long-term
liabilities |
|
- |
|
|
- |
|
|
|
|
|
Stockholders’
equity |
|
182,259 |
|
|
36,410 |
|
|
|
|
|
Total
liabilities and stockholders’ equity |
$ |
192,313 |
|
$ |
41,210 |
|
|
|
|
|
|
|
|
|
|
|
|
Madrigal Pharmaceuticals (NASDAQ:MDGL)
Historical Stock Chart
From Aug 2024 to Sep 2024
Madrigal Pharmaceuticals (NASDAQ:MDGL)
Historical Stock Chart
From Sep 2023 to Sep 2024