Stoke Therapeutics, Inc. is focused on advancing its clinical-stage program, zorevunersen (STK-001), for Dravet syndrome. The company has completed two Phase 1/2a open-label studies for zorevunersen and has ongoing Open Label Extension (OLE) studies in the U.S. and the U.K. Stoke plans to provide a regulatory update on Phase 3 registrational plans for zorevunersen by year-end.
Regulatory Update and Clinical Progress
In August 2024, the U.S. Food and Drug Administration (FDA) removed the partial clinical hold on higher doses of zorevunersen in the MONARCH and SWALLOWTAIL studies in the U.S., allowing for continued chronic dosing. Stoke Therapeutics continues discussions with the FDA and global regulatory agencies regarding a single global Phase 3 study of zorevunersen, with an update expected by year-end.
Edward M. Kaye, M.D., Chief Executive Officer of Stoke Therapeutics, stated, "Key to our regulatory discussions are the assessments of behavior and cognition in patients with Dravet syndrome. In our studies of zorevunersen, we have demonstrated substantial and sustained effects across multiple measures of disease, starting within the first year of treatment. These data give us confidence in our Phase 3 planning and the potential for zorevunersen to go beyond seizure management by addressing the root cause of the disease."
The company plans to present data at the American Epilepsy Society (AES) 2024 Annual Meeting, pending acceptance of the abstracts. The company is preparing to share new data from all patients treated in the clinical studies with initial 70mg doses followed by 45mg maintenance dosing in studies of zorevunersen. A Phase 3 regimen of two or three loading doses of 70mg followed by maintenance doses of 45mg is currently under discussion with global regulatory agencies.
Financial Position
As of September 30, 2024, Stoke Therapeutics had $269.2 million in cash, cash equivalents, and marketable securities. For the three months ended September 30, 2024, revenue recognized from the License and Collaboration Agreement with Acadia Pharmaceuticals was $4.9 million, compared to $3.3 million for the same period in 2023. The net loss for the three months ended September 30, 2024, was $26.4 million, or $0.47 per share, compared to $24.5 million, or $0.55 per share, for the same period in 2023.
About Zorevunersen
Zorevunersen is an investigational new medicine for the treatment of Dravet syndrome currently being evaluated in ongoing clinical trials. Stoke believes that zorevunersen, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. Zorevunersen is designed to upregulate Na v 1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene to restore physiological Na v 1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure comorbidities. Zorevunersen has been granted orphan drug designation by the FDA and the EMA, and rare pediatric disease designation by the FDA as a potential new treatment for Dravet syndrome.
Collaboration with Acadia Pharmaceuticals
Stoke Therapeutics continues its collaboration with Acadia Pharmaceuticals for the development of RNA-based medicines targeting SYNGAP1, MECP2 (Rett syndrome), and an undisclosed neurodevelopmental target. The collaboration includes co-development and co-commercialization efforts for SYNGAP1.
