Therapeutic Focus

ADDRESSING A SIGNIFICANT UNMET NEED

Stoke’s initial focus is the treatment of genetic epilepsies. Epilepsy is the fourth most common neurologic disease and affects more than 50 million people worldwide. More than 50% of epilepsies have a genetic basis and more than 30% of patients are resistant to existing therapies. Many of these patients have haploinsufficiencies that we believe are amenable to our technology platform. Symptoms include not only refractory seizures but also severe cognitive and developmental delays and other neurological comorbidities. Current treatments for Dravet syndrome only address the occurrence of seizures. There are no medicines available to treat the underlying cause of any genetic epilepsy.

Our lead program addresses Dravet syndrome, a severe and progressive genetic epilepsy that affects roughly 35,000 patients across the U.S., Canada, Japan, Germany, France and the United Kingdom; it is not concentrated in a particular geographic area or ethnic group. Currently, Dravet patients are typically treated with multiple antiepileptic drugs. Unfortunately, these therapies do not adequately control seizures in 90% of patients, and they do not address other aspects of the disease, including cognitive regression or developmental stagnation, ataxia, speech impairment, sleep disturbances and an increased risk of sudden unexpected death in epilepsy (SUDEP). There are no genetically-targeted therapies currently available to address the underlying cause of Dravet syndrome.

Approximately 85% of Dravet syndrome cases are caused by spontaneous, heterozygous loss of function mutations in a gene called SCN1A. This gene encodes the voltage-gated sodium channel type 1 alpha subunit (NaV1.1). By upregulating NaV1.1 protein expression from the non-mutant copy of the SCN1A gene in patients, Stoke hopes to provide the first gene-specific, disease-modifying approach to prevent the occurrence of seizures and reduce significant non-seizure comorbidities, including developmental deficits.

There are an estimated 10,000 diseases caused by a genetic abnormality in a single gene
Stoke has identified approximately 2,900 monogenic diseases that may be amenable to our TANGO approach
Our lead program addresses Dravet syndrome, a severe and progressive genetic epilepsy

As the potential for precision therapies in epilepsy becomes clear, genetic testing for patients is critical. Stoke Therapeutics is part of an innovative, cross-company collaboration that aims to provide faster diagnosis for young children with epilepsy. Together with Invitae, BioMarin and Xenon Pharmaceuticals, the collaboration sponsors a no-cost epilepsy gene panel testing program for health care providers (HCPs) to order for any child up to 60 months old who has had an unprovoked seizure. HCPs can find out more about the program at www.BehindTheSeizure.com.

BUTTERFLY is an observational study of Dravet syndrome patients initiated by Stoke. This non-interventional two-year study, being conducted at approximately 20 sites in the U.S., observes patients ages 2-18 years with mutations in the SCN1A gene. For more information, please follow this link or contact BUTTERFLYStudy@iqvia.com.