Preclinical data in four well-established
preclinical models of pain associated with tissue inflammation and
nerve injury demonstrate AV-101’s robust effects similar to
gabapentin but with a better side effect profile
Phase 1 data demonstrate AV-101 is
well-tolerated, with no meaningful difference in adverse events
between AV-101 and placebo at any dose tested
Vistagen (Nasdaq: VTGN), a late clinical-stage biopharmaceutical
company aiming to transform the treatment landscape for individuals
living with anxiety, depression, and other central nervous system
(CNS) disorders, today announced that the European Patent Office
(EPO) issued a Notice of Intention to Grant a patent related to the
use of AV-101 for the treatment of neuropathic pain. AV-101 is the
Company’s investigational oral prodrug of 7-chloro-kynurenic acid
(7-Cl-KYNA), a potent and selective full antagonist (i.e.,
inhibitor) of the glycine coagonist site of the
N-methyl-D-aspartate receptor (NMDAR). The patent, once granted,
will not expire until at least 2034 and will become part of
Vistagen’s global patent portfolio on therapeutic uses and
manufacturing techniques for AV-101.
AV-101 Preclinical Data in Pain Models
Preclinical data previously published in the peer-reviewed
journal, The Journal of Pain,1 demonstrate robust antinociceptive
effects, similar to gabapentin, but with a better side effect
profile in several preclinical models of hyperalgesia and
allodynia. In the study, AV-101 prodrug was systematically
administered in four rat models of pain to examine its analgesic
and behavioral profile. Dose-dependent anti-hyperalgesia effects
were shown in the four models of pain. Compared to the control
drugs tested (gabapentin and MK-801), AV-101 has similar robust
anti-nociceptive effects but, contrary to the control drugs tested,
AV-101 had no discernable negative side effects. The preclinical
study was conducted by Tony L. Yaksh, PhD, Professor of
Anesthesiology and Pharmacology at the University of California,
San Diego.
Further preclinical research conducted by Dr. Yaksh comparing
AV-101 to pregabalin in the Chung ligation model of pain, an
accepted gold standard preclinical model for chronic neuropathic
pain caused by nerve damage, demonstrated that AV-101 had a
significant dose response with similar efficacy in this rat model
of a mononeuropathy as compared to pregabalin, which was used as an
active comparator. The statistically significant positive
preclinical results suggest AV-101’s potential to treat multiple
hyperpathic pain states.2
AV-101 Phase 1 Clinical Data
Additionally, clinical data from both the single and multi-dose
Phase 1 studies previously published in the peer-reviewed
publication, Scandinavian Journal of Pain,3 indicated that oral
AV-101 was well-tolerated, with no meaningful difference in adverse
events at any dose between AV-101 and placebo. Although the AV-101
study was not designed to achieve statistical significance in
reducing pain in healthy volunteers, there were consistent
reductions for allodynia pain and mechanical and heat hyperalgesia.
The study was conducted by Mark S. Wallace, MD, Professor of
Anesthesiology and Pain Management Specialist at the University of
California, San Diego.4
The preclinical data involving gabapentin and pregabalin, paired
with the favorable safety and tolerability profile of AV-101 in all
clinical studies completed to date, as well as previously reported
positive preclinical results in levodopa-induced dyskinesia (LID)
associated with Parkinson’s therapy, demonstrate potential for
Phase 2 development of AV-101 as a new non-opioid treatment
alternative for multiple CNS disorders.
Vistagen plans to seek potential strategic collaborations to
further advance the clinical development and commercialization of
AV-101.
About AV-101
AV-101 (4-Cl-KYN) is an investigational oral prodrug of
7-chloro-kynurenic acid (7-Cl-KYNA), a potent and selective full
antagonist of the glycine binding site of the NMDAR that modifies
the function of the NMDAR. Unlike classic channel-blocking NMDAR
antagonists such as ketamine and amantadine, 7-Cl-KYNA is not an
ion channel blocker, which the Company believes is the reason for
the compound’s comparatively improved safety and tolerability
profile. In clinical and nonclinical testing completed to date,
AV-101 has demonstrated good oral bioavailability and an excellent
pharmacokinetic (PK) profile. No binding of AV-101 or 7-Cl-KYNA to
off-site targets was identified by an extensive receptor screening
study. Moreover, in all clinical trials completed to date, AV-101
has been well-tolerated with no serious adverse psychological side
effects or other safety concerns that are often observed with
classic channel-blocking NMDAR antagonists. Moreover, clinical
studies to date also suggest an improved side effect profile vs.
other non-opioid drugs approved to treat conditions associated with
pain, such as gabapentin (approved to treat post-herpetic neuralgia
and adjunctively to treat partial onset epileptic seizures) and
pregabalin (approved to treat neuropathic pain associated with
diabetic peripheral neuropathy and post-herpetic neuralgia), both
of which produce sedation in some patients.
A range of preclinical and Phase 1 clinical studies suggest
AV-101’s therapeutic potential in multiple CNS indications,
including levodopa-induced dyskinesia, neuropathic pain, and
seizures. The U.S. FDA has granted Fast Track designation for
development of AV-101 as a potential non-opioid treatment for
neuropathic pain. Vistagen plans to seek strategic partnering
support to further advance the potential clinical development and
commercialization of AV-101.
About Vistagen
Vistagen (Nasdaq: VTGN) is a late clinical-stage
biopharmaceutical company aiming to transform the treatment
landscape for individuals living with anxiety, depression, and
other CNS disorders. Vistagen is advancing therapeutics with the
potential to be faster-acting and with fewer side effects and
safety concerns than those currently available for the treatment of
anxiety, depression, and multiple CNS disorders. Vistagen's
pipeline includes six clinical-stage product candidates, including
fasedienol (PH94B), itruvone (PH10), PH80, PH15, and PH284, each an
investigational agent belonging to a new class of drugs known as
pherines, as well as AV-101, which is an oral prodrug of an
antagonist of the N-methyl-D-aspartate receptor (NMDAR). Pherines
are neuroactive nasal sprays designed with an innovative proposed
mechanism of action that activates chemosensory neurons in the
nasal cavity and can beneficially impact key neural circuits in the
brain without systemic absorption or direct activity on neurons in
the brain. Vistagen is passionate about transforming mental health
care and redefining what is possible in the treatment of anxiety,
depression, and several other CNS disorders. Connect at
www.Vistagen.com.
1 Yaksh, T.L., et al. (2017). “Characterization of the Effects
of L-4-Chlorokynurenine on Nociception in Rodents.” The Journal of
Pain 18:1184-1196. https://doi.org/10.1016/j.jpain.2017.03.014 2
Vistagen, data on file 3 Wallace, M. et. al. (2017). “Randomized,
double-blind, placebo-controlled, dose-escalation study:
Investigation of the safety, pharmacokinetics, and antihyperalgesic
activity of L-4-chlorokynurenine in healthy volunteers.”
Scandinavian Journal of Pain 17(1): 243-251.
https://doi.org/10.1016/j.sjpain.2017.05.004 4 Dr. Mark S. Wallace
serves as an advisor to Vistagen
Forward-looking Statements
This press release contains certain forward-looking statements
within the meaning of the federal securities laws. These
forward-looking statements involve known and unknown risks that are
difficult to predict and include all matters that are not
historical facts. In some cases, you can identify forward-looking
statements by the use of words such as “may,” “could,” “expect,”
“project,” “outlook,” “strategy,” “intend,” “plan,” “seek,”
“anticipate,” “believe,” “estimate,” “predict,” “potential,”
“strive,” “goal,” “continue,” “likely,” “will,” “would” and
variations of these terms and similar expressions, or the negative
of these terms or similar expressions. Such forward-looking
statements are necessarily based upon estimates and assumptions
that, while considered reasonable by Vistagen and its management,
are inherently uncertain. As with all pharmaceutical products,
there are substantial risks and uncertainties in the process of
development and commercialization and actual results or development
may differ materially from those projected or implied in these
forward-looking statements. Among other things, there can be no
guarantee that the scope of protection and enforceability provided
by any patents issued for any of the Company’s drug candidates,
including AV-101, will be sufficient to deter competition, or that
any of the Company’s drug candidates, including AV-101, will
successfully replicate past preclinical studies and/or clinical
trials, complete ongoing or future clinical trials, receive
regulatory approval or be commercially successful. Other factors
that may cause such a difference include, without limitation, risks
and uncertainties relating to the Company’s ability to pursue
and/or secure collaborative support for continued clinical
development of AV-101; other risks and uncertainties related to
delays in launching, conducting and/or completing ongoing and
planned clinical trials; fluctuating costs of materials and other
resources and services required to conduct the Company’s ongoing
and/or planned clinical and nonclinical trials; market conditions;
the impact of general economic, industry or political conditions in
the United States or internationally; and other technical and
unexpected hurdles in the development, manufacture and
commercialization of the Company’s drug candidates. These risks are
more fully discussed in the section entitled “Risk Factors” in the
Company’s most recent Annual Report on Form 10-K for the fiscal
year ended March 31, 2023, and in its most recent Quarterly Report
on Form 10-Q for the quarter and six months ended September 30,
2023, as well as discussions of potential risks, uncertainties, and
other important factors in our other filings with the U.S.
Securities and Exchange Commission (SEC). The Company’s SEC filings
are available on the SEC’s website at www.sec.gov. Additionally,
you should not place undue reliance on these forward-looking
statements in the future, because they apply only as of the date of
this press release and should not be relied upon as representing
the Company’s views as of any subsequent date. The Company
explicitly disclaims any obligation to update any forward-looking
statements, other than as may be required by law. If the Company
does update one or more forward-looking statements, no inference
should be made that the Company will make additional updates with
respect to those or other forward-looking statements.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231227642635/en/
Investors: Mark McPartland Senior Vice President, Investor
Relations (650) 577-3606 markmcp@vistagen.com
Media: Nate Hitchings SKDK nhitchings@skdknick.com
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