Our CNS pipeline includes three differentiated clinical-stage drug candidates with potential for convenient, at-home use, rapid-onset therapeutic benefits, and exceptional safety in multiple large and growing mental health and neurology markets where current treatments fall short of patient needs.
PH94B Neuroactive Nasal Spray
PH94B neuroactive nasal spray, initially in development for social anxiety disorder (SAD), is a synthetic investigational neurosteroid with a novel, rapid-onset mechanism of action that is fundamentally different from all current drug treatments for SAD. Developed from proprietary compounds called pherines and administered at non-systemic microgram doses as an odorless nasal spray, PH94B binds to nasal chemosensory receptors which activate neural circuits in the brain that suppress fear and anxiety. Specifically, PH94B engages nasal chemosensory receptors that trigger a subset of neurons in the main olfactory bulbs (OB). OB neurons then stimulate inhibitory GABAergic neurons in the limbic amygdala, decreasing release of norepinephrine, and facilitating fear extinction activity of the limbic-hypothalamic parasympathetic system.
PH10 Neuroactive Nasal Spray
PH10 neuroactive nasal spray is a synthetic investigational neurosteroid with a novel, rapid-onset mechanism of action that is fundamentally different from all current treatments for MDD. Developed from proprietary compounds called pherines and administered at microgram doses as an odorless nasal spray, PH10 binds to nasal chemosensory receptors which activate neural circuits in the brain that produce antidepressant effects. Specifically, PH10 binds to nasal chemosensory receptors that trigger a subset of neurons in the main olfactory bulb (OB). OB neurons then stimulate neurons in the limbic amygdala that release norepinephrine and increase activity of the limbic-hypothalamic sympathetic nervous system.
AV-101, an Oral NMDAR Glycine Site Antagonist
AV-101 (4-Cl-KYN) belongs to a new generation of investigational medicines in neuropsychiatry and neurology known as NMDA (N-methyl-D-aspartate) glutamate receptor modulators. The NMDA receptor is a pivotal receptor in the brain and abnormal NMDA function is associated with multiple CNS diseases and disorders, including MDD, epilepsy, levodopa-induced dyskinesia, neuropathic pain and many others. AV-101 is an oral prodrug of 7-chlorokynurenic acid (7-Cl-KYNA), which binds uniquely at the glycine site of the NMDA receptor and has potential to be a new at-home treatment for multiple CNS indications involving NMDA receptors, each with high unmet need.
Recent discoveries from successful AV-101 preclinical studies demonstrate a 7-fold concentration increase in the brain of AV-101 prodrug, and, more importantly, a 35-fold increase of 7-Cl-KYNA, AV-101's active metabolite, when AV-101 is administered adjunctively with probenecid, a safe and well-known oral anion transport inhibitor used to treat gout. This data suggest that it may be possible to increase therapeutic concentrations and duration of 7-Cl-KYNA in the brain, and thus increase NMDAR antagonism in MDD patients with an inadequate response to standard antidepressants when AV-101 and probenecid are combined.