Vistagen Receives Notice From European Patent Office Of Intention To Grant Patent For AV-101 To Treat Neuropathic Pain

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.