VistaGen Therapeutics (NASDAQ: VTGN) Featured Research Report

13 A EGIS C APITAL C ORP. AV-101 AV-101 (4-Cl-KYN) is an oral prodrug targeting NMDAR, an ionotropic glutamate receptor in the brain. Unlike ketamine and other antagonists, AV-101 doesn’t block NMDAR. AV-101 has received Fast Track designation as a potential adjunctive treatment for MDD and an opioid- alternative for neuropathic pain. VistaGen has outlined a strategy to advance AV-101, in combination with probenecid (an oral uric acid lowering agent, which is known to block activity of certain organic ion efflux transporters in the kidney), through Phase 2 B clinical development in one or more CNS indications where abnormal NMDAR is implicated. 2 In a study from 2019, AV-101 failed to differentiate from placebo in a Phase 2 clinical trial, along with a standard oral antidepressant, in MDD. This was the Elevate study. Following further analysis, VistaGen concluded that the trial failure may have been due to sub-therapeutic concentrations of API in the brain. 2 Additional research conducted both by Baylor College of Medicine, and VistaGen’s own pre- clinical work suggests that combining AV-101 with adjunctive probenecid could increase the therapeutic concentrations and duration in the brain. For example, it was found in the Baylor phase 1B, that in health volunteers, higher doses of AV-101 could increase 40 Hz auditory steady state response, a measure of the integrity of inhibitory interneuron synchronization associate with NMDAR inhibition. We believe VistaGen will continue to study AV-101, including undertaking preclinical studies in various NMDAR-focused CNS indications (see pipeline). VistaGen Therapeutics, Inc. October 8, 2020