VistaGen Therapeutics (NASDAQ: VTGN) Featured Research Report

11 A EGIS C APITAL C ORP. PH10 neuroactive nasal spray PH10 is a synthetic neurosteroid (Pregn-4-en-20-yne-3-one), delivered intranasally, that is being developed for a wide variety of depression-related indications. The initial indication for PH10 is major depressive disorder (MDD), although other depression disorders such as postpartum depression (PPD), suicidal ideation (SI), and others, could follow. We believe VistaGen will next seek to advance PH10 through Phase 2B for the treatment of MDD in the US, and anticipate commencement of this trial in late 2021. The World Health Organization (WHO) counts 300mm people as suffering from depression, and in the U.S. The National Institute of Mental Health estimated that 17.2mm adults had at least one major depressive episode in 2017. MDD differs from a depressed mood in that it consists of chronic, pervasive feelings of unhappiness and suffering, leading to impaired functioning. Developed from pherine compounds, PH10 is an odorless, neuroactive nasal spray that actives chemosensory receptors that trigger neural pathways in the brain, and is thought to produce antidepressant effects. The pathway consists of microgram doses of API engaging nasal chemosensory neurons (NCNs) which activate olfactory bulb neurons (OBNs) on the base of the brain, which in turn connect through neurons to the central limbic amygdala (where mood is regulated). 2 In a Phase 2A study, PHD10 (self-administered at 6.4 micrograms of dose) was considered safe and led to rapid onset of antidepressant effects, sustained over an 8-week period, as measured by the Hamilton Depression Rating Scale-17 (HAM-D-17) with a p-value of 0.022 (statistically meaningful). 2 Importantly, when considering how PH10 could fit into the treatment paradigm, we reference the rapidity of action and safety profile shown from the Phase 2A trial. In particular, we think the ability to have a rapid-onset antidepressant, including one free from the side effect profile inherent in ketamine-based treatments, could see meaningful use, in our view. This becomes especially true in light of the high remission rates (67%) patients experience on the existing commercial-stage therapies. VistaGen Therapeutics, Inc. October 8, 2020