SOUTH SAN FRANCISCO, Calif.,
Feb. 11, 2020 /PRNewswire/
-- VistaGen Therapeutics (NASDAQ: VTGN), a clinical-stage
biopharmaceutical company developing new generation medicines for
central nervous system (CNS) diseases and disorders with high unmet
medical need, today announced positive preclinical data of AV-101,
an oral NMDAR (N-methyl-D-aspartate receptor) antagonist prodrug,
administered in combination with probenecid. The new preclinical
data suggest that there is a substantially increased brain
concentration of AV-101 and its active metabolite,
7-chlorokynurenic acid (7-Cl-KYNA), when given together with
probenecid. These surprising effects were first revealed in the
Company's recent preclinical study, although they are consistent
with well-documented clinical studies of probenecid increasing the
therapeutic levels of several unrelated classes of approved
drugs.
"The remarkable preclinical data announced today demonstrate a
7-fold concentration increase in the brain of AV-101 prodrug, and,
more importantly, a 35-fold increase of 7-Cl-KYNA, AV-101's active
metabolite, when AV-101 is administered adjunctively with
probenecid. We recently identified that some of the same kidney
transporters that reduce drug concentrations in the blood, by
excretion in the urine, are also found in the blood brain barrier
and function to reduce 7-Cl-KYNA levels in the brain by pumping it
out of the brain and back into the blood. In the recent studies, we
discovered that blocking those transporters in the blood brain
barrier with probenecid resulted in a substantially increased brain
concentration of 7-Cl-KYNA," said Ralph
Snodgrass, Ph.D., President and Chief Scientific Officer of
VistaGen. "This 7-Cl-KYNA efflux-blocking effect of probenecid,
with the resulting increased brain levels and duration of
7-Cl-KYNA, suggests the potential impact of AV-101 with
probenecid could result in far more profound therapeutic benefits
for patients with major depressive disorder and other NMDAR-focused
CNS diseases and disorders than demonstrated in the Phase 2
studies of AV-101 in major depressive disorder completed last
year," added Dr. Snodgrass.
Results on AV-101 transport with adjunctive probenecid were
presented by a collaborator of VistaGen, David Dickens, Ph.D., Lecturer, Department of
Molecular and Clinical Pharmacology, University of Liverpool, at the British
Pharmacological Society's Pharmacology 2019 annual conference in
Edinburgh, UK, in December 2019.
About Probenecid
Probenecid is a safe and well-known oral drug used to treat gout
and to increase the therapeutic benefit of various antibacterial,
anticancer and antiviral drugs. It is a potent inhibitor of various
transporters, including the organic ion transporters in the kidney
and other organs. Probenecid aids in prevention of gout by
preventing the kidneys from reabsorbing uric acid from the urine,
resulting in the removal of excess uric acid from the body by
causing it to be excreted in urine. For certain antibacterial,
antiviral and anticancer drugs, probenecid inhibits organic ion
transporters in the kidney that are responsible for pumping drugs
out of the blood and into the urine. Blocking these transporters
results in reduced clearance and increased blood levels of drugs
normally excreted by the kidneys, thus increasing their
effectiveness. As recently discovered by VistaGen, some of the same
kidney transporters that reduce drug concentrations in the blood,
are also found in the blood brain barrier and function to reduce
7-Cl-KYNA levels in the brain by pumping it out of the brain and
back into the blood. In its recent studies, VistaGen discovered
that blocking those transporters in the blood brain barrier with
probenecid resulted in a substantially increased brain
concentration of 7-Cl-KYNA.
About AV-101
AV-101 (4-Cl-KYN) targets the NMDAR (N-methyl-D-aspartate
receptor), an ionotropic glutamate receptor in the
brain. Abnormal NMDAR function is associated with numerous CNS
diseases and disorders. AV-101 is an oral prodrug of
7-chloro-kynurenic acid (7-Cl-KYNA), which is a potent and
selective full antagonist of the glycine co-agonist site of the
NMDAR that inhibits the function of the NMDAR. Unlike ketamine and
many other NMDAR antagonists, 7-Cl-KYNA is not an ion channel
blocker. In all studies to date, AV-101 has exhibited no
dissociative or hallucinogenic psychological side effects or safety
concerns similar to those that may be caused by amantadine,
esketamine and ketamine. With its exceptionally few side
effects and excellent safety profile, AV-101 has potential to be an
oral new generation treatment for multiple large-market CNS
indications where current treatments are inadequate to meet high
unmet patient needs. The FDA has granted Fast Track designation for
development of AV-101 as both a potential adjunctive treatment
for MDD and as a non-opioid treatment for neuropathic
pain.
About VistaGen
VistaGen Therapeutics is a clinical-stage biopharmaceutical
company developing new generation medicines for CNS diseases and
disorders where current treatments are inadequate, resulting in
high unmet need. VistaGen's pipeline is focused on
clinical-stage CNS drug candidates with a differentiated mechanism
of action, an exceptional safety profile in all clinical studies to
date, and therapeutic potential in multiple large and growing CNS
markets. For more information, please visit www.vistagen.com
and connect with VistaGen on
Twitter, LinkedIn and Facebook.
Forward-Looking Statements
This release contains
various statements concerning VistaGen's future expectations, plans
and prospects, including without limitation, our expectations
regarding development and commercialization of AV-101 for various
therapeutic purposes, including dyskinesia in patients with
Parkinson's disease receiving levodopa-based therapy, epilepsy,
major depressive disorder, neuropathic pain and suicidal ideation.
In addition, statements concerning the Company's future
expectations may include statements regarding intellectual property
and commercial protection of each of our drug candidates. Each of
these statements constitute forward-looking statements for the
purposes of the safe harbor provisions under the Private Securities
Litigation Reform Act of 1995. These forward-looking statements are
neither promises nor guarantees of future performance and are
subject to a variety of risks and uncertainties, many of which are
beyond our control, and may cause actual results to differ
materially from those contemplated in these forward-looking
statements. Those risks include the following: (i) we may encounter
unexpected adverse events in patients during our clinical
development of any product candidate that cause us to discontinue
further development; (ii) we may not be able to successfully
demonstrate the safety and efficacy of our product candidates at
each stage of clinical development; (iii) success in preclinical
studies or in early-stage clinical studies may not be repeated or
observed future studies, and ongoing or future preclinical and
clinical results may not support further development of, or be
sufficient to gain regulatory approval to market AV-101 or any of
our product candidates; (iv) decisions or actions of regulatory
agencies may negatively affect the progress of, and our ability to
proceed with, further clinical studies or to obtain marketing
approval for our drug candidates; (v) we may not be able to obtain
or maintain adequate intellectual property protection and other
forms of marketing and data exclusivity for our product candidates;
(vi) we may not have access to or be able to secure substantial
additional capital to support our operations, including our ongoing
nonclinical and clinical development activities; and (vii) we may
encounter technical and other unexpected hurdles in the
manufacturing and development of any of our product candidates.
Certain other risks are more fully discussed in the section
entitled "Risk Factors" in our most recent annual report on Form
10-K, and subsequent quarterly reports on Form 10-Q, as well as
discussions of potential risks, uncertainties, and other important
factors in our other filings with the Securities and Exchange
Commission (SEC). Our SEC filings are available on the SEC's
website at www.sec.gov. In addition, any forward-looking
statements represent our views only as of the issuance of this
release and should not be relied upon as representing our views as
of any subsequent date. We explicitly disclaim any obligation to
update any forward-looking statements.
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SOURCE VistaGen Therapeutics