Ovid Therapeutics Inc., a biopharmaceutical company committed to developing medicines that transform the lives of people with rare neurological diseases, and the University of Connecticut School of Medicine, have announced a research collaboration and license agreement to accelerate the development of a next-generation short hairpin RNA (shRNA)-based therapeutic for Angelman syndrome and potentially other indications.
 
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. Ovid and UConn believe that 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 the fourth quarter of 2020.
 
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. Chamberlain is recognized 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, 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.
 
“Ovid is deeply committed to the Angelman syndrome community. We have made great progress and are excited to see the topline data from our Phase 3 NEPTUNE trial with OV101 expected in Q4 2020,” said Amit Rakhit, M.D., MBA, president and chief medical officer of Ovid Therapeutics. “We believe OV101 has the potential to serve as a core therapy for this disorder and are now focused on building a comprehensive and strategic Angelman syndrome longer term pipeline. If successful, OV101 may be used in combination with genetic approaches in the future to address the needs of Angelman syndrome.”
 
“Our lab shares in Ovid’s demonstrated commitment to advance innovative therapeutic options for Angelman syndrome,” stated Chamberlain. “An shRNA therapeutic can target the genetic cause of Angelman syndrome at its source and may offer potential advantages to other next-generation approaches, including antisense oligonucleotide therapy, via a lower rate of degradation and turnover and plasmid delivery allowing for a less-frequent dosing profile. Ovid is uniquely positioned to accelerate an shRNA therapeutic through late preclinical and clinical development, and our lab looks forward to working with the team at Ovid towards our common objective of impacting the lives of individuals living with Angelman syndrome and their families.”