AV-101 for MDD - Mechanism of Action

Based on evidence of effectiveness of the NMDA (N-methyl-d-aspartate) receptor antagonist ketamine, the glutamatergic system plays a key role in mood disorders. We believe that specific ways of targeting the NMDA subtype glutamate receptor can produce a new generation of NMDA receptor antagonists with better safety and tolerability for the treatment of major depressive disorder. AV-101's mechanism of action is functionally similar to ketamine in that both are NMDA receptor antagonists. However, ketamine is a classic channel-blocking NMDA receptor antagonist. AV-101 is an oral NMDA receptor GlyB antagonist that inhibits NMDA receptor function rather than blocking it. We believe this difference (modulating NMDA receptor activity rather than blocking it), together with the activation of AMPA receptor pathways, can potentially bypass the adverse psychological side effects and safety concerns associated with ketamine treatment for MDD while still achieving fast-acting antidepressant effects. 

PH94B for SAD - Mechanism of Action

Intranasal PH94B is a first-in-class neuroactive steroid (a "pherine") that engages nasal chemosensory receptors which, in turn, trigger rapid activation of the limbic system areas of the brain associated with social anxiety disorder (SAD). This mechanism of pharmacological action, the rapid onset of efficacy, and the excellent safety and tolerability profile shown in clinical trials make PH94B an excellent product candidate for PRN (as-needed) treatment for individuals with SAD.

PH10 for MDD - Mechanism of Action

PH10 is also a first-in-class neuroactive steroid (a pherine) administered as a nasal spray that binds locally on nasal chemosensory receptors and triggers responses in the hypothalamus, amygdala, prefrontal cortex and hippocampus. It is believed to initiate nerve impulses that follow defined pathways to directly affect brain function. Similar to PH94B, PH10 does not circulate systemically in the blood. In a small exploratory Phase 2a study in individuals with MDD, PH10 showed a large, rapid-onset antidepressant effect, without psychological side effects or safety concerns.