Acadia Pharmaceuticals and Stoke Therapeutics will collaborate to discover, develop and commercialize novel RNA-based medicines for rare genetic neurodevelopmental diseases of the central nervous system (CNS). The collaboration includes Rett syndrome, SYNGAP1 syndrome, and a third undisclosed target.
Under the terms of the agreement, Stoke will receive an upfront payment of $60 million from Acadia and is eligible to receive up to $907 million in milestones as well as royalties on future sales.
The deal involves Stoke’s proprietary platform – TANGO (Targeted Augmentation of Nuclear Gene Output). TANGO is designed to restore missing proteins by increasing protein output from healthy genes. To do this, Stoke researchers design antisense oligonucleotides (ASOs) that bind to pre-mRNA and help the target genes produce more protein. The company’s initial application for TANGO is in diseases where one copy of a gene functions normally and the other is mutated, also called haploinsufficiencies.
“Stoke’s RNA-based approach to upregulating healthy proteins offers very exciting new possibilities for the treatment of rare, neurodevelopmental diseases like Rett syndrome,” said Steve Davis, Chief Executive Officer of Acadia Pharmaceuticals. “Combining Stoke’s capabilities with Acadia’s extensive expertise in neuroscience drug development and commercialization enables us to push harder and faster in exploring some of the new frontiers in rare central nervous system disorders.”
“Rett syndrome and SYNGAP1 syndrome are two severe, intractable diseases of the central nervous system and both are associated with developmental delays, motor function loss, autism, seizures and other comorbidities that impact quality of life for patients and their families,” said Edward M. Kaye, Chief Executive Officer of Stoke Therapeutics.
He added that, “Acadia shares our deep commitment to improving outcomes for people living with neurodevelopmental disorders. We believe their late-stage development and commercialization capabilities, in addition to their neuroscience expertise, complement our discovery research efforts and clinical learnings from our work in Dravet syndrome. Together, we believe we have a significant opportunity to improve treatment options by delivering new disease-modifying medicines to people who need them.”
For the SYNGAP1 program, the two companies will jointly share global research, development and commercialization responsibilities and share 50/50 in all worldwide costs and future profits. In addition, Stoke is eligible to receive potential development, regulatory, first commercial sales and sales milestones.
With the Rett syndrome (MECP2) and the undisclosed neurodevelopmental program, Stoke will lead research and pre-clinical development activities, while Acadia will lead clinical development and commercialization activities. Acadia will fully fund the research and pre-clinical development activities related to these two targets and Stoke is eligible to receive potential development, regulatory, first commercial sales and sales milestones as well as tiered royalty payments on worldwide sales starting in the mid-single digit range and escalating to the mid-teens based on revenue levels.
Rett syndrome is a rare, debilitating neurological disorder that occurs primarily in females following apparently normal development for the first six months of life. The condition is often misdiagnosed as autism, cerebral palsy, or non-specific developmental delay. Rett syndrome is caused by mutations on the X chromosome on MECP2, and there are more than 200 different mutations on this gene that can cause the condition.
SYNGAP1 syndrome is a rare neurological disorder characterized by moderate to severe intellectual disability that is evident in early childhood. Mutations in SYNGAP1 were first identified in 2009 and since then, an increasing number of children with the condition have been identified.