12 January 2022 - - US-based biopharmaceutical company Acadia Pharmaceuticals Inc. (NASDAQ: ACAD) and US-based biotechnology company Stoke Therapeutics, Inc. (NASDAQ: STOK) have entered a collaboration to discover, develop and commercialize novel RNA-based medicines for the potential treatment of severe and rare genetic neurodevelopmental diseases of the central nervous system, the companies said.

The collaboration includes SYNGAP1 syndrome, Rett syndrome (MECP2), and an undisclosed neurodevelopmental target of mutual interest.

Under the terms of the agreement, Stoke will receive an upfront payment of USD 60m from Acadia and is eligible to receive up to USD 907m in milestones as well as royalties on future sales.

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.

For 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.

SYNGAP1 syndrome is a rare neurological disorder characterized by moderate to severe intellectual disability that is evident in early childhood.

Mutations in the SYNGAP1 gene (which produces the SynGAP protein) were first identified in 2009 and since then, an increasing number of children with SYNGAP1 syndrome have been identified.

Normal levels of SynGAP protein are essential for proper brain function and development. Mutations in the SYNGAP1 gene also play an important role in the development of epileptic encephalopathies.

The severity and onset of symptoms can vary from patient to patient. SYNGAP1 syndrome is characterized by developmental delay or intellectual disability, generalized epilepsy, and autism spectrum disorder and other behavioral abnormalities.

More than 80% of cases of SYNGAP1 syndrome are caused by a haploinsufficiency of the SYNGAP1 gene. SYNGAP1 syndrome is estimated to account for 1% to 2% of all intellectual disability cases.

There are currently no approved treatments for SYNGAP1 syndrome.

Currently, there are no FDA-approved medicines for the treatment of Rett syndrome.

TANGO (Targeted Augmentation of Nuclear Gene Output) is Stoke's proprietary research platform. Stoke's initial application for this technology are diseases in which one copy of a gene functions normally and the other is mutated, also called haploinsufficiencies.

In these cases, the mutated gene does not produce its share of protein, resulting in disease. Using the TANGO approach and a deep understanding of RNA science, Stoke researchers design antisense oligonucleotides that bind to pre-mRNA and help the functional (or wild-type) genes produce more protein.

TANGO aims to restore missing proteins by increasing or stoking protein output from healthy genes, thus compensating for the mutant copy of the gene.

Stoke Therapeutics (NASDAQ: STOK), is a biotechnology company dedicated to addressing the underlying cause of severe diseases by upregulating protein expression with RNA-based medicines.

Using Stoke's proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides to selectively restore protein levels. Stoke's first compound, STK-001, is in clinical testing for the treatment of Dravet syndrome, a severe and progressive genetic epilepsy.