MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ
Global Market (NASDAQ:MNOV) and the Standard Market of the Tokyo
Stock Exchange (Code Number: 4875), today announced the results of
the nonclinical studies conducted under its contract with
the Biomedical Advanced Research and Development
Authority (BARDA), part of the Administration for
Strategic Preparedness and Response (ASPR) in the U.S.
Department of Health and Human Services, to repurpose MN-166
(ibudilast) as a potential medical countermeasure (MCM) against
chlorine gas-induced lung damage such as acute respiratory distress
syndrome (ARDS) and acute lung injury (ALI). Two different
nonclinical models were used to investigate the potential clinical
utility of MN-166 (ibudilast) for the treatment of chlorine-induced
lung damage.
The primary objective of the first nonclinical
efficacy study was to determine the safety and pharmacological
activity of MN-166 (ibudilast) following ALI induced by chlorine
(Cl2) gas inhalation. In this study, single-dose and multi-dose
treatments were evaluated. The primary endpoint was the pulmonary
function measure PaO2/FiO2, which is the ratio of arterial oxygen
partial pressure to fractional inspired oxygen.
After a Cl2 gas challenge to induce moderate ALI
(mean PaO2/FiO2<200), the test subjects were divided into four
different treatment groups - two different doses of MN-166
(ibudilast) (low dose and high dose), a positive control
(rolipram), and a negative control (test article vehicle) - which
were infused intravenously (IV) over 30 minutes.
In the pilot design single-dose treatment
regimen, the test subjects were treated only once after the Cl2 gas
challenge was completed. MN-166 (ibudilast) high dose and the
positive control were more efficacious than MN-166 (ibudilast) low
dose and the negative control until 12 hours after Cl2 exposure but
this did not yield statistically significant results for overall
pulmonary function. MN-166 (ibudilast) was well tolerated and no
safety concerns were observed in the single-dose study.
A pharmacokinetic (PK) study was conducted to determine the optimal
dosing frequency of MN-166 (ibudilast) in the multi-dose study.
In the multi-dose study, based on the PK profile
in test subjects, each treatment was given every 12 hours with a
total of 4 doses after the Cl2 gas challenge. Treatment with MN-166
(ibudilast) high dose resulted in greater improvement (p=0.0001) in
the mean PaO2/FiO2 ratio than MN-166 (ibudilast) low dose,
rolipram, and negative control. The mean PaO2/FiO2 ratio decreased
(worsened) by 57% from 518.7 mmHg at baseline (the end of the
chlorine gas exposure) to 224.8 mmHg at hour 48 in the negative
control group. The mean PaO2/FiO2 ratio decreased (worsened) by 36%
from 516.0 mmHg at baseline to 327.8 mmHg at hour 48 in the MN-166
(ibudilast) high dose group. At hour 48, the last time point
measured in the study, the mean PaO2/FiO2 ratio was 46% higher
(better) in the MN-166 (ibudilast) high dose group than in the
negative control group (327.8 vs. 224.8 mmHg). Since
ARDS is defined as a PaO2/FiO2 ratio less than 300 mmHg, the mean
PaO2/FiO2 ratio values indicate that the negative control group was
still categorized as having mild ARDS at the end of the 48-hour
evaluation period but the MN-166 (ibudilast) high dose group had
recovered enough to no longer be defined as having ARDS. MN-166
(ibudilast) was well tolerated and no safety concerns were observed
in the multi-dose study.
A preliminary proof-of-concept (POC) study was
conducted to determine the feasibility of the second nonclinical
model as a tool to evaluate MN-166 (ibudilast) as a MCM for
chlorine gas exposure. After multiple attempts by MediciNova’s
subcontractor to establish the feasibility of the second Cl2-gas
induced lung injury model, it was not deemed to be a feasible model
to evaluate a drug candidate and there are no evaluable efficacy
results from the second nonclinical model POC study.
Kazuko Matsuda, MD, PhD, MPH, Chief Medical
Officer of MediciNova, Inc., commented, "We are very pleased
to report the positive results from the multi-dose nonclinical
model study in which MN-166 demonstrated a large and significant
improvement in pulmonary function and a higher survival rate. We
previously reported that MN-166 attenuated histological changes
observed in an LPS-induced ARDS nonclinical model, including
pulmonary edema in lung tissue, and protected against pulmonary
injury by reducing cellular apoptosis in lung tissue. We also
previously reported positive and significant outcomes from a
clinical trial of MN-166 in hospitalized severe COVID-19 patients
at risk of developing ARDS. Combining the positive nonclinical
chlorine gas-induced ALI model study results with the positive
results from the human clinical trial in severe COVID-19 patients
at risk of developing ARDS, we believe MN-166 has potential to
treat acute lung disease from various causes. We plan to meet with
the FDA to discuss the next steps in this development program.
Development of medical countermeasures does not require human
clinical trials to establish efficacy when these trials would not
be ethical or feasible. There is a great unmet medical need for
treatments for chlorine gas exposure as there is no drug approved
specifically for this indication. We thank BARDA for their support
of this program.”
This project has been funded in whole or in part
with federal funds from the Department of Health and Human
Services; Administration for Strategic Preparedness and
Response; Biomedical Advanced Research and Development
Authority, under contract number 75A50121C00022.
About MN-166 (ibudilast)
MN-166 (ibudilast) is a small molecule compound
that inhibits phosphodiesterase type-4 (PDE4) and inflammatory
cytokines, including macrophage migration inhibitory factor (MIF).
It is in late-stage clinical development for the treatment of
neurodegenerative diseases such as ALS (amyotrophic lateral
sclerosis), progressive MS (multiple sclerosis), and DCM
(degenerative cervical myelopathy); and is also in development for
glioblastoma, Long COVID, CIPN (chemotherapy-induced peripheral
neuropathy), and substance use disorder. In addition, MN-166
(ibudilast) was evaluated in patients that are at risk for
developing acute respiratory distress syndrome (ARDS).
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, Long COVID, and
substance dependence. MN-001 (tipelukast) was evaluated in a Phase
2 trial in idiopathic pulmonary fibrosis (IPF) and a second Phase 2
trial in non-alcoholic fatty liver disease (NAFLD) is ongoing.
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, 2022 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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