Ovid & UConn to collaborate on next-gen genetic therapy for Angelman Syndrome

Under the terms of the research collaboration, Ovid will work closely with UConn’s Stormy J. Chamberlain, Ph.D., and gain exclusive access to identified genetic sequences for a potential shRNA-based therapeutic. Ovid plans to validate select sequences and leverage its translational medicine capabilities and drug development expertise in Angelman syndrome to advance an shRNA-based therapeutic into clinical studies. Dr. Chamberlain is a recognized leader in the field of Angelman syndrome and UBE3A research and currently serves as the John and Donna Krenicki Associate Professor of Genomics and Personalized Healthcare in UConn’s Genetics and Genome Sciences Department. In addition, Dr. Chamberlain chairs the Angelman Syndrome Foundation (ASF) Scientific Advisory Committee and is a member of the Dup15q Alliance Scientific Advisory Board. Ovid will also work closely with UConn’s Noelle Germain, Ph.D., Assistant Professor of Genetics and Genome Sciences on these efforts.

The most common cause of Angelman syndrome is the loss of function of the gene that codes for ubiquitin protein ligase E3A (UBE3A), which plays a critical role in nerve cell communication, resulting in impaired tonic inhibition. An shRNA-based therapeutic may address this underlying genetic cause of Angelman syndrome by reducing the expression of UBE3A-antisense, potentially restoring the function of UBE3A. This genetic approach may be used in combination with OV101 (gaboxadol), Ovid’s novel, small-molecule delta (δ)-selective GABAA receptor agonist, to restore tonic inhibition and address the underlying symptomology of individuals with Angelman syndrome. OV101 is currently being evaluated in the pivotal Phase 3 NEPTUNE trial in Angelman syndrome, with topline results expected in 4Q-2020. In addition, Ovid is also exploring OV881, a microRNA approach that may reduce the expression of UBE3A-antisense and potentially restore UBE3A expression.

Angelman syndrome affects approximately 1 in 12,000 to 1 in 20,000 people globally. There are no approved therapies by the U.S. Food and Drug Administration (FDA), European Medicines Agency or rest-of-world for Angelman syndrome, and treatment primarily consists of behavioral interventions and pharmacologic management of symptoms.

Ovid lead candidate OV101 gets FDA Rare Pediatric Disease Designation in Angelman syndrome

OV101 is believed to be the only delta (δ)-selective GABAA receptor agonist in development and is currently being evaluated in the Company’s pivotal Phase 3 NEPTUNE trial in Angelman syndrome, with topline results expected in the fourth quarter of 2020.

If a new drug application (NDA) for OV101 in Angelman syndrome is approved, Ovid may be eligible to receive a priority review voucher from the FDA, which can be redeemed to obtain priority review for any subsequent marketing application or may be transferred and/or sold to other companies for their programs, such as has recently been done by other voucher recipients.

The U.S. Patent and Trademark Office has granted Ovid patents directed to methods of treating Angelman syndrome and Fragile X syndrome using OV101. The issued patents expire in 2035 without regulatory extensions.

Angelman syndrome is a rare genetic condition that is characterized by a variety of signs and symptoms. Characteristic features of this condition include delayed development, intellectual disability, severe speech impairment, problems with movement and balance, seizures, sleep disorders and anxiety. The most common cause of Angelman syndrome is the loss of function of the gene that codes for ubiquitin protein ligase E3A (UBE3A), which plays a critical role in nerve cell communication, resulting in impaired tonic inhibition. Individuals with Angelman syndrome typically have normal lifespans but are unable to live independently. Therefore, they require constant support from a network of specialists and caregivers. Angelman syndrome affects approximately 1 in 12,000 to 1 in 20,000 people globally.

There are no approved therapies by the FDA, European Medicines Agency (EMA), or rest of world for Angelman syndrome, and treatment primarily consists of behavioral interventions and pharmacologic management of symptoms.

Angelman syndrome is associated with a reduction in tonic inhibition, a function of the delta (δ)-selective GABAA receptor that allows a human brain to decipher excitatory and inhibitory neurological signals correctly without being overloaded. If tonic inhibition is reduced, the brain becomes inundated with signals and loses the ability to separate background noise from critical information.