Stoke focuses on treating genetic diseases by upregulating protein expression. Its lead compound, STK-001, is focused on Dravet syndrome, a rare form of epilepsy that starts in infancy.
Bedford, Massachusetts-based Stoke Therapeutics has filed for an initial public offering (IPO), hoping to raise $86 million. Stoke may be best known for its chief executive officer, Ed Kaye. Kaye served as Sarepta Therapeutics’ chief medical officer from June 2011 to April 2017. From March 2015 to September 2016, he was the company’s interim chief executive officer, and from September 2016 to June 2017 he was president and chief executive officer. When he left Sarepta, he planned to take time off before tackling another company, but said he had about six offers in a matter of weeks. He then took on the role of chief executive officer and director of Stoke.
During his tenure at Sarepta, he led the company’s often tumultuous approval of Exondys 51 for Duchenne muscular dystrophy.
Stoke plans to list on the Nasdaq under the symbol STOK. Stoke focuses on treating genetic diseases by upregulating protein expression. Its lead compound, STK-001, is focused on Dravet syndrome, a rare form of epilepsy that starts in infancy. About 10% to 20% of people with Dravet syndrome die before adulthood, with most deaths occurring before 10 years of age.
Stoke’s technology platform is called TANGO and can be used to treat a variety of genetic diseases where a single mutated gene fails to produce a necessary protein. These diseases are called autosomal dominant haploinsufficiencies. TANGO can be used to increase protein production from the remaining healthy copy of the gene.
The company has raised about $120 million in private financing to date.
In December 2018, Stoke and research collaborators from the University of Michigan presented data on Stoke’s antisense oligonucleotide (ASO) technology for treating Dravet syndrome in mice at the American Epilepsy Society 2018 conference held in New Orleans. TANGO was used to increase the target gene’s expression. In one case, up to 85% of patients with Dravet have variant mutations of Scn1a that causes insufficient production of the Nav1.1 protein. Stoke’s product is designed to raise Nav1.1 to normal levels.
In mice, the therapy increased Scn1a mRNA expression and Nav1.1 protein levels. It upregulated Sccn1a but didn’t affect other sodium channel genes. And in a single dose, it restored Nav1.1 expression to normal levels, decreasing seizures and increasing survival. The results lasted at least up to 14 weeks.
The company hopes to use funds raised to begin a Phase I/II clinical trial in the first half of 2020 and them push through clinical development to Phase III. Currently, the only drugs approved by the U.S. Food and Drug Administration (FDA) for Dravet syndrome are GW Pharmaceuticals’ Epidiolex and Biocodex’s Diacomit. They help with the disease, but don’t cure it. They seem to diminish the occurrence of seizures, but not the symptoms.
Theoretically, Stoke’s therapy would be more of a cure, although at this time there is no clinical data to back that up.
Stoke was launched in 2014 by co-founder Adrian Krainer and Isabel Aznarez. Before founding Stoke and becoming its vice president, head of biology, Aznarez was a research investigator with Krainer at Cold Spring Harbor Laboratory. Before that she was a researcher at the Hospital for Sick Children, focused on the effect of cystic fibrosis mutations on the splicing of the CFTR gene. Krainer is the St. Giles Foundation Professor at Cold Spring focused on the mechanisms of RNA splicing.
