Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL) today announced its
second quarter 2018 financial results and described recent clinical
and corporate accomplishments including:
- Positive Phase 2 Clinical Results - MGL-3196 demonstrated
highly statistically significant results for the key 36-week
endpoints in its Phase 2 clinical trial in non-alcoholic
steatohepatitis (NASH), including statistically significant
reductions of liver fat and resolution of NASH
- Madrigal’s abstract "In a Placebo-Controlled 36-Week Phase 2
Trial, Treatment with MGL-3196 Compared to Placebo Results in
Significant Reductions in Hepatic Fat (MRI-PDFF), Liver Enzymes,
Fibrosis Biomarkers, Atherogenic Lipids, and Improvement in NASH on
Serial Liver Biopsy" has been selected for oral presentation at The
Liver Meeting® 2018 in San Francisco. The presentation will
take place on Monday, November 12, 2018, at 8:15 AM during the
Presidential Plenary – Clinical Science
- Increased Capital Position – Madrigal completed an underwritten
registered public offering in which the gross proceeds to Madrigal
from the offering, before deducting the underwriting discounts and
commissions and other estimated offering expenses, were
approximately $329 million
- Progress in out-licensed legacy oncology programs – Madrigal’s
licensee for its Hsp90 inhibitor program, Aldeyra Therapeutics,
Inc., recently announced that, ADX-1612, its lead Hsp90 compound,
is being advanced in multiple indications: mesothelioma, ovarian
cancer and lymphoproliferative immune disease
“We believe the 36-week data from our recently completed Phase 2
clinical study of MGL-3196 in patients with NASH suggest a high
likelihood of success in a similarly designed Phase 3 study, for
which we are actively preparing, pending regulatory agreement,”
stated Paul Friedman, M.D., Chief Executive Officer of
Madrigal. “With our financial raise completed, which provided
more than $300 million of additional capital, we are in a strong
position to expedite the MGL-3196 development program in NASH and
dyslipidemias.”
Becky Taub, M.D., CMO and Executive VP, Research &
Development of Madrigal added, “We believe the totality of data
from our clinical and preclinical studies to date, including the
consistency of the various parameters related to clinical benefits
and safety, demonstrate the potential of MGL-3196 to resolve NASH
and improve multiple atherogenic lipids. We are pleased our
abstract was selected by AASLD as an oral presentation in the
presidential plenary clinical session and look forward to
presenting these encouraging clinical outcomes in November at The
Liver Meeting® 2018.”
Financial Results for the Three Months and Six Months
Ended June 30, 2018
As of June 30, 2018, Madrigal had cash, cash equivalents and
marketable securities of $490.3 million, compared to $191.5 million
at December 31, 2017. The increase in cash and marketable
securities resulted primarily from the net proceeds of $311.8
million from Madrigal’s public offering of common stock in June
2018, partially offset by cash used in operations of $14.0
million.
Operating expenses were $7.8 million and $14.9 million,
respectively, for the three month and six month periods ended June
30, 2018, compared to $8.4 million and $14.5 million in the
comparable prior year periods.
Research and development expenses for the three month and six
month periods ended June 30, 2018 were $5.1 million and $10.3
million, respectively, as compared to $6.8 million and $11.2
million in the comparable prior year periods. The decreases are
primarily attributable to completion of treatment in our Phase 2
clinical studies in 2018.
General and administrative expenses for the three month and six
month periods ended June 30, 2018 were $2.7 million and $4.6
million, respectively, as compared to $1.6 million and $3.3 million
in the comparable prior year periods. The increases are due
primarily to higher non-cash stock compensation expense from stock
option awards.
Interest income for the three month and six month periods ended
June 30, 2018 was $1.2 million and $1.9 million, respectively, as
compared to $92 thousand and $168 thousand in the comparable prior
year periods. The change in interest income was due primarily to a
higher average principal balance in our investment account in
2018.
Out-Licensed Legacy Oncology Programs
Madrigal’s licensee for its Hsp90 inhibitor program, Aldeyra
Therapeutics, Inc., provided a pipeline update during its June 2018
Research Day. ADX-1612 is a novel Hsp90 inhibitor in
development for the treatment of post-transplant
lymphoproliferative disorder and cancer. Hsp90 is a protein
that facilitates cell replication, which is excessive and
uncontrolled in certain inflammatory diseases and cancer.
ADX-1612 is currently being studied in investigator-sponsored
trials for mesothelioma, with clinical results expected in the
second half of 2018, and ovarian cancer, with Phase 2 clinical
trial initiation expected in the second half of 2018. Aldeyra
is further developing ADX-1612 for the treatment of
lymphoproliferative immune disease, with Phase 2 clinical testing
expected to start in 2019.
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
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 was the reduction of liver fat
at 12 weeks compared with baseline (relative change), assessed by
MRI-PDFF. Key secondary endpoints at 36 weeks included:
reduction in liver fat compared with baseline (relative change),
also assessed by MRI-PDFF; a two-point reduction in NAS (NALFD
activity score) on biopsy; resolution of NASH on biopsy; and,
safety and tolerability based on adverse events and changes in
laboratory values.
The primary endpoint of the study at 12 weeks 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. Further, 75% of the high-exposure MGL-3196 treated patients
showed liver fat reductions of ≥30%.
At 36 weeks, MGL-3196 achieved multiple key secondary endpoints
including a sustained highly significant (p<0.001) reduction in
liver fat compared to placebo as measured by MRI-PDFF; mean
relative fat reduction for MGL-3196 was 37% versus 8.9% for
placebo. MGL-3196 was associated with a greater percentage of
subjects with a 2-point improvement in NAS (56% of 73 patients vs
32% of 34 placebo subjects, p=0.02). NASH resolution (NR) was seen
in 27% of MGL-3196 compared with 6% of placebo subjects, p=0.02.
MGL-3196 patients with ≥ 30% fat reduction on Week 12 MRI-PDFF
demonstrated a higher percentage of 2-point improvement in NAS
(70%, p=0.001) and NR (39%, p=0.001) compared with placebo,
demonstrating a strong relationship between early reduction in
liver fat as demonstrated by week 12 MRI-PDFF and NASH improvement
on liver biopsy at Week 36. In patients with NASH Resolution, 35%
of the MGL-3196 treated patients and no placebo patients had more
advanced NASH (baseline NAS ≥5).
At Week 36, MGL-3196 treated patients showed sustained reduction
of fibrosis biomarkers. In MGL-3196 patients with NASH resolution,
fibrosis also resolved in 50% of patients and was decreased
statistically significantly reduced relative to all placebo
patients.
There were statistically significant reductions in liver enzymes
in MGL-3196 treated patients compared to placebo treated patients;
reductions of greater magnitude were achieved with longer duration
of MGL-3196 treatment. Statistically significantly more
MGL-3196 treated patients than placebo treated patients had
normalization of ALT (alanine transaminase).
Similar to week 12, at week 36 there were sustained,
statistically significant reductions in low-density lipoprotein
cholesterol (LDL-C), triglycerides, ApoB and lipoprotein(a).
MGL-3196 was well tolerated in this trial with mostly mild and a
few moderate AEs which were balanced between drug treated and
placebo patients. An increase in incidence of mild transient
diarrhea in MGL-3196-treated, often a single episode, at the start
of treatment. Diarrhea incidence was not increased later in the
study.
Based on liver enzyme inclusion criteria, some patients are
receiving extended treatment beyond 36 weeks for up to 36
additional weeks. All patients in this 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.
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 now demonstrated in two Phase 2
double-blind, placebo-controlled trials in NASH and HeFH 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. Based on evidence of these
pleiotropic actions, coupled with an excellent safety profile,
Madrigal plans to initiate a Phase 3 clinical program in NASH and
dyslipidemias.
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
(Tables Follow)
Madrigal Pharmaceuticals, Inc. |
Condensed Consolidated Statements of
Operations |
(in thousands, except share and per share
amounts) |
(unaudited) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended |
|
Six Months Ended |
|
June 30, |
|
June 30, |
|
|
2018 |
|
|
2017 |
|
|
|
2018 |
|
|
2017 |
|
Revenues: |
|
|
|
|
|
Total
revenues |
$ |
- |
|
$ |
- |
|
|
$ |
- |
|
$ |
- |
|
Operating
expenses: |
|
|
|
|
|
Research
and development |
|
5,109 |
|
|
6,816 |
|
|
|
10,307 |
|
|
11,196 |
|
General
and administrative |
|
2,717 |
|
|
1,623 |
|
|
|
4,588 |
|
|
3,318 |
|
Total
operating expenses |
|
7,826 |
|
|
8,439 |
|
|
|
14,895 |
|
|
14,514 |
|
Loss from
operations |
|
(7,826 |
) |
|
(8,439 |
) |
|
|
(14,895 |
) |
|
(14,514 |
) |
Interest income (expense), net |
|
1,166 |
|
|
92 |
|
|
|
1,871 |
|
|
168 |
|
Other income |
|
200 |
|
|
- |
|
|
|
200 |
|
|
- |
|
Net
loss |
$ |
(6,460 |
) |
$ |
(8,347 |
) |
|
$ |
(12,824 |
) |
$ |
(14,346 |
) |
|
|
|
|
|
|
Basic and
diluted net loss per common share |
$ |
(0.45 |
) |
$ |
(0.69 |
) |
|
$ |
(0.90 |
) |
$ |
(1.20 |
) |
Basic and
diluted weighted average number of common shares outstanding |
|
14,383,720 |
|
|
12,039,005 |
|
|
|
14,256,501 |
|
|
11,997,602 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Madrigal Pharmaceuticals, Inc. |
Condensed Consolidated Balance
Sheets |
(in thousands) |
(unaudited) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
June 30, |
December 31, |
|
|
|
|
|
2018 |
|
|
2017 |
|
|
|
|
|
|
|
|
|
|
Assets |
|
|
|
|
|
Cash, cash equivalents
and marketable securities |
$ |
490,305 |
|
$ |
191,527 |
|
|
|
|
Other current
assets |
|
968 |
|
|
485 |
|
|
|
|
Other non-current
assets |
|
255 |
|
|
301 |
|
|
|
|
Total
assets |
$ |
491,528 |
|
$ |
192,313 |
|
|
|
|
|
|
|
|
|
|
Liabilities and
Equity |
|
|
|
|
|
Current
liabilities |
$ |
5,436 |
|
$ |
10,054 |
|
|
|
|
Long-term
liabilities |
|
- |
|
|
- |
|
|
|
|
Stockholders’
equity |
|
486,092 |
|
|
182,259 |
|
|
|
|
Total
liabilities and stockholders’ equity |
$ |
491,528 |
|
$ |
192,313 |
|
|
|
|
|
|
|
|
|
|
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