MediciNova Announces MN-001 (tipelukast) Data regarding Lipid Metabolism in NASH/NAFLD to be Presented at The Liver Meeting® 2021, the Annual Meeting of the American Association for the Study of Liver Diseases
November 11 2021 - 6:00PM
MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ
Global Market (NASDAQ:MNOV) and the JASDAQ Market of the Tokyo
Stock Exchange (Code Number: 4875), today announced that
MediciNova’s research collaborator Masatsune Ogura, M.D., Ph.D.,
Associate Professor at the Department of General Medical
Science, Chiba University Graduate School of Medicine, is
presenting results and findings of a study that investigated the
mechanism by which MN-001 (tipelukast) alters triglyceride (TG)
metabolism in hepatocytes at The Liver Meeting® 2021, the Annual
Meeting of the American Association for the Study of Liver Diseases
(AASLD) to be held online from November 12th to 15th. In this
study, HepG2 cells derived from human hepatocellular carcinoma
samples were incubated for 48 hours with arachidonic acid (AA), LXR
agonist T0901317, and MN-001 (tipelukast) each alone or in various
combinations. The amount of TG synthesis in the HepG2 cells was
calculated by extracting lipids from the HepG2 cells before and
after treatment. As a result, it was found that MN-001 had an
inhibitory effect on TG synthesis in HepG2 cells.
To further clarify part of the mechanism, mRNA
was extracted from cell samples and the mRNA expression of
molecules related to TG metabolism was measured using real-time
PCR. As a result, the expression of CD36, one of the fatty acid
transporters involved in the uptake of AA into liver cells, was
suppressed in the samples by adding MN-001. This suggests that
MN-001 reduces TG synthesis by inhibiting the AA uptake into
hepatocytes. CD36 enhances cellular fatty acid uptake in the liver
and is known to be involved in the pathogenesis of fatty liver.
The highlights of the presentation entitled
“Improvement of Intracellular Lipid Metabolism by Tipelukast in the
Pathogenesis of NASH/NAFLD" (Poster Publication # 1793) are as
follows:
- TG synthesis
(μg/mg protein) in HepG2 cells
- Compared to the
vehicle, T0901317 alone increased TG synthesis by 3.8-fold, AA
alone increased TG synthesis by 15.3-fold, and the combination of
T0901317 + AA increased TG synthesis by 24.3-fold.
- Compared to
MN-001 alone, the combination of T0901317 + MN-001 increased TG
synthesis by 1.7-fold, the combination of AA + MN-001 increased TG
synthesis by 3.7-fold, and the combination of T0901317 + AA +
MN-001 increased TG synthesis by 3.7-fold.
- CD36 mRNA
expression was downregulated in all 4 groups (vehicle, T0901317
alone, AA alone, T0901317 + AA) by adding MN-001.
- It was
suggested that downregulation of CD36 expression is an important
mechanism of MN-001. CD36 is one of the molecules responsible for
fatty acid uptake into hepatocytes. MN-001 inhibits AA uptake into
hepatocytes and suppresses TG synthesis, which is expected to
reduce TG accumulation in hepatocytes.
Kazuko Matsuda, M.D. Ph.D, MPH., Chief Medical
Officer, MediciNova, Inc., commented, “We are very pleased to
present new results and findings from our collaboration
with Dr. Ogura which elucidate MN-001’s ability to
improve lipid metabolism. In particular, its ability to suppress
CD36 expression and reduce intracellular triglyceride synthesis may
account for the role of MN-001 in NASH/NAFLD pathogenesis in
addition to the significant lowering of serum triglyceride levels
which was observed in multiple clinical trials.”
About MN-001
MN-001 (tipelukast) is a novel, orally
bioavailable, small molecule compound thought to exert its effects
through several mechanisms to produce its anti-inflammatory and
anti-fibrotic activity in preclinical models, including leukotriene
(LT) receptor antagonism, inhibition of phosphodiesterases (PDE)
(mainly 3 and 4), and inhibition of 5-lipoxygenase (5-LO). The
5-LO/LT pathway has been postulated as a pathogenic factor in
fibrosis development, and MN-001's inhibitory effect on 5-LO and
the 5-LO/LT pathway is considered to be a novel approach to treat
fibrosis. MN-001 has been shown to down-regulate expression of
genes that promote fibrosis including LOXL2, Collagen Type 1 and
TIMP-1. MN-001 has also been shown to down-regulate expression of
genes that promote inflammation including CCR2 and MCP-1. In
addition, histopathological data shows that MN-001 reduces fibrosis
in multiple animal models.
About MediciNova
MediciNova, Inc. is a clinical-stage
biopharmaceutical company developing a broad late-stage pipeline of
novel small molecule therapies for inflammatory, fibrotic, and
neurodegenerative diseases. Based on two compounds, MN-166
(ibudilast) and MN-001 (tipelukast), with multiple mechanisms of
action and strong safety profiles, MediciNova has 11 programs in
clinical development. MediciNova’s lead asset, MN-166 (ibudilast),
is currently in Phase 3 for amyotrophic lateral sclerosis (ALS) and
degenerative cervical myelopathy (DCM) and is Phase 3-ready for
progressive multiple sclerosis (MS). MN-166 (ibudilast) is also
being evaluated in Phase 2 trials in glioblastoma, patients at risk
of developing acute respiratory distress syndrome (ARDS), and
substance dependence. MN-001 (tipelukast) was evaluated in a Phase
2 trial in idiopathic pulmonary fibrosis (IPF) and is in
preparation for a second Phase 2 trial in nonalcoholic
steatohepatitis (NASH). MediciNova has a strong track record of
securing investigator-sponsored clinical trials funded through
government grants.
Statements in this press release that are not
historical in nature constitute forward-looking statements within
the meaning of the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995. These forward-looking statements
include, without limitation, statements regarding the future
development and efficacy of MN-166, MN-001, MN-221, and MN-029.
These forward-looking statements may be preceded by, followed by or
otherwise include the words "believes," "expects," "anticipates,"
"intends," "estimates," "projects," "can," "could," "may," "will,"
"would," “considering,” “planning” or similar expressions. These
forward-looking statements involve a number of risks and
uncertainties that may cause actual results or events to differ
materially from those expressed or implied by such forward-looking
statements. Factors that may cause actual results or events to
differ materially from those expressed or implied by these
forward-looking statements include, but are not limited to, risks
of obtaining future partner or grant funding for development of
MN-166, MN-001, MN-221, and MN-029 and risks of raising sufficient
capital when needed to fund MediciNova's operations and
contribution to clinical development, risks and uncertainties
inherent in clinical trials, including the potential cost, expected
timing and risks associated with clinical trials designed to meet
FDA guidance and the viability of further development considering
these factors, product development and commercialization risks, the
uncertainty of whether the results of clinical trials will be
predictive of results in later stages of product development, the
risk of delays or failure to obtain or maintain regulatory
approval, risks associated with the reliance on third parties to
sponsor and fund clinical trials, risks regarding intellectual
property rights in product candidates and the ability to defend and
enforce such intellectual property rights, the risk of failure of
the third parties upon whom MediciNova relies to conduct its
clinical trials and manufacture its product candidates to perform
as expected, the risk of increased cost and delays due to delays in
the commencement, enrollment, completion or analysis of clinical
trials or significant issues regarding the adequacy of clinical
trial designs or the execution of clinical trials, and the timing
of expected filings with the regulatory authorities, MediciNova's
collaborations with third parties, the availability of funds to
complete product development plans and MediciNova's ability to
obtain third party funding for programs and raise sufficient
capital when needed, and the other risks and uncertainties
described in MediciNova's filings with the Securities and Exchange
Commission, including its annual report on Form 10-K for the year
ended December 31, 2020 and its subsequent periodic reports on Form
10-Q and current reports on Form 8-K. Undue reliance should not be
placed on these forward-looking statements, which speak only as of
the date hereof. MediciNova disclaims any intent or obligation to
revise or update these forward-looking statements.
INVESTOR CONTACT:Geoff O'BrienVice PresidentMediciNova,
Inc.info@medicinova.com
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