Vistagen Receives Notice of Allowance for AV-101 Canadian Patent for Treatment of Dyskinesia Related to Levodopa Therapy for Parkinson’s Disease

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 Canadian Intellectual Property Office (CIPO) issued a Notice of Allowance for a patent related to the use of AV-101 for reduction of dyskinesia (sudden uncontrolled movements) induced by the administration of levodopa (L-Dopa), the most commonly prescribed medication for treatment of Parkinson's disease (PD). AV-101 is the Company’s oral prodrug antagonist at the NMDAR (N-methyl-D-aspartate receptor) glycine site. The patent, once granted, will not expire until at least 2034. The U.S. Patent and Trademark Office (USPTO) granted a related U.S. patent for Vistagen’s AV-101 and similar patents have been granted or are pending in several additional major pharmaceutical markets.

Preclinical data previously published in the international, peer-reviewed journal, Cells, demonstrate the effects of AV-101 in a widely-used MPTP non-human primate model for reproducing motor complications of PD, including dyskinesia observed in many PD patients treated with L-Dopa. In this study, AV-101's efficacy against L-Dopa induced dyskinesia (LID) was measured through behavioral scores on a dyskinesia scale, and a Parkinsonian disability scale was used to measure L-Dopa antiparkinsonian efficacy. The study demonstrated that AV-101 significantly (p = 0.01) reduced LID without affecting the timing, extent, or duration of the therapeutic benefits of L-Dopa. No adverse events attributable to the drug were observed during the study. The preclinical study was conducted by Dr. Thérèse Di Paolo, Emeritus Professor in the Faculty of Pharmacy at Laval University in Canada and among the world's leading researchers focused on PD and LID, pursuant to Vistagen's research agreement with CHU de Québec – Université Laval Research Center in Québec, Canada.

About AV-101

AV-101 is an 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 inhibits the function of the NMDAR. Unlike ketamine, amantadine and other NMDAR antagonists, 7-Cl-KYNA is not an ion channel blocker. 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 such as ketamine and amantadine. Nonclinical results also indicate that long-term administration of AV-101 induces hippocampal neurogenesis, a hallmark of drugs that have antidepressive effects, and increases endogenous levels of KYNA, which also is a functional NMDAR glycine site antagonist. A range of preclinical and clinical studies suggest therapeutic potential in multiple indications, including levodopa-induced dyskinesia, neuropathic pain, seizures, major depressive disorder, and suicidal ideation. Vistagen is preparing for Phase 2A development of AV-101, on its own or with collaborators, as a treatment for one or more neurological disorders involving the NMDAR.