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EX-99 - PRESS RELEASE - VistaGen Therapeutics, Inc. | ex99-1.htm |
8-K - CURRENT REPORT - VistaGen Therapeutics, Inc. | vtgn8k_feb112020.htm |
Exhibit 99.2
VistaGen Therapeutics Announces Positive Preclinical Data of AV-101
Combined with Probenecid Suggesting Substantially Increased Brain
Concentration Effects
When given together with VistaGen’s oral prodrug AV-101,
probenecid increased brain concentrations of AV-101 7-fold and its
active metabolite, 7-CI-KYNA, 35-fold
SOUTH SAN FRANCISCO, Calif., February 11, 2020 – 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
pre
clinical
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.
Company Contact
Mark A.
McPartland
VistaGen
Therapeutics Inc.
Phone:
+1 (650) 577-3600
Email: IR@vistagen.com
Investor Contact
Valter
Pinto / Allison Soss
KCSA
Strategic Communications
Phone:
+1 (212) 896-1254/+1 (212) 896-1267
Email: VistaGen@KCSA.com
Media Contact
Caitlin
Kasunich / Lisa Lipson
KCSA
Strategic Communications
Phone:
+1 (212) 896-1241/+1 (508) 843-6428
Email: VistaGen@KCSA.com