Our CNS pipeline includes three differentiated new generation CNS drug candidates with potential to go beyond the current standard of care for anxiety, depression and other CNS disorders. Each of our drug candidates, PH94B, PH10 and AV-101, has a novel mechanism of action, a favorable safety profile observed in all clinical studies to date, and therapeutic potential in multiple mental health and neurology markets.

PH94B Nasal Spray for Anxiety Disorders

PH94B is an innovative investigational synthetic pherine nasal spray with potential to treat multiple anxiety disorders without the side effects and safety concerns associated with benzodiazepines. PH94B’s rapid-onset mechanism of action is fundamentally different from benzodiazepines and all other FDA-approved anti-anxiety medications. Developed from proprietary compounds called pherines and administered at non-systemic microgram level doses as an odorless nasal spray, PH94B binds to nasal chemosensory receptors which are believed to activate neural circuits in the limbic amygdala that suppress fear and anxiety. Following a statistically significant Phase 2 public speaking (p=0.002) and social interaction (p=0.009) study of PH94B in adults with social anxiety disorder (SAD), and a successful meeting with the U.S. Food and Drug Administration (FDA), we are currently preparing for pivotal Phase 3 development of PH94B for the acute treatment of anxiety in adults with SAD.

The FDA has granted Fast Track designation for development of PH94B for acute treatment of SAD, believed to be the first such designation ever granted by the FDA for a SAD drug candidate. In an acute treatment manner analogous to use of a rescue inhaler before a predictable asthma attack or a migraine drug before onset of a migraine episode, PH94B has potential to be used as needed by a person with SAD before an anxiety-provoking stressor.

Based on the results of Phase 2 studies, PH94B has the potential to be the first FDA-approved acute treatment of anxiety for millions who suffer from SAD worldwide. In addition, PH94B has therapeutic potential in multiple additional anxiety disorders, including, among others, postpartum anxiety, preoperative anxiety, PTSD, and panic disorder.

PH10 Nasal Spray for Depression Disorders

PH10 is a synthetic investigational pherine nasal spray with a novel, designed with a potential rapid-onset mechanism of action that is fundamentally different from all current treatments for depression. Developed from proprietary compounds called pherines and administered at microgram level doses as an odorless nasal spray, PH10 binds to nasal chemosensory receptors which are believed to activate neural circuits in the brain that produce antidepressant effects. Specifically, a microgram level dose of PH10 engages nasal chemosensory neurons (NCNs). NCNs activate olfactory bulb neurons (OBNs) on the base of the brain. OBNs send neural connections to neurons in the central limbic amygdala, the brain center where mood is regulated. Neurons in the limbic amygdala stimulate release of excitatory neurotransmitters (e.g., norepinephrine) resulting in rapid-onset antidepressant effects. PH10 was designed to not require systemic uptake and distribution to produce its rapid-onset antidepressant effects. In a small randomized, double-blind, placebo-controlled exploratory Phase 2A clinical study in major depressive disorder (MDD), at a 6.4 mcg dose, rapid-onset antidepressant effects were observed and sustained for 8 weeks (p=0.022), without psychological side effects or safety concerns associated with ketamine-based therapy.

AV-101, an Oral NMDAR Glycine Site Antagonist for Depression and Neurological Disorders

AV-101 (4-Cl-KYN) is an investigational prodrug designed to be orally administered and to target the N-methyl-D-aspartate receptor (NMDAR), an ionotropic glutamate receptor in the brain. Abnormal NMDAR function is associated with numerous CNS diseases and disorders. AV-101’s active metabolite, 7-chloro-kynurenic acid (7-Cl-KYNA), has been observed to be a potent and selective full antagonist of the glycine co-agonist site of the NMDAR that inhibits the function of the NMDAR, but does not block NMDAR function like ketamine and other NMDAR antagonists. AV-101 has been observed in clinical trials to be orally bioavailable, well-tolerated and not cause dissociative or hallucinogenic psychological side effects or safety concerns similar to those that may be caused by other NMDAR antagonists. In light of these and findings from a wide range of preclinical studies, we believe that AV-101, in combination with FDA-approved probenecid, has potential to become a new oral treatment alternative for multiple large CNS markets.

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