Adrian Krainer was shopping for groceries two days before Christmas in 2016 when a colleague called with terrific news.
The federal government had just approved the first drug for spinal muscular atrophy, the leading genetic cause of death in infants. Krainer, a molecular genetics professor at Cold Spring Harbor Laboratory on Long Island, N.Y., had worked on the scientific underpinnings of the medicine for more than 15 years. Now Biogen Inc., the Cambridge biotech that shepherded it to approval, could start selling the life-saving drug, called Spinraza.
It was Krainer’s first foray into drug development and the pinnacle of his career. He celebrated with his wife by popping a bottle of Veuve Clicquot Champagne that they had been saving for New Year’s Eve.
Now the 59-year-old native of Uruguay hopes to repeat the achievement, this time as a founder of — and scientific guru to — a biotech startup in Bedford called Stoke Therapeutics Inc.
Krainer started the firm in 2014 with a Cold Spring post-doctoral fellow and protege, Isabel Aznarez. It was spun off from his laboratory before Spinraza’s approval and revealed it had received millions in investor funding this January. Stoke’s first target is a rare and catastrophic inherited form of epilepsy called Dravet syndrome. Company executives hope to start clinical trials of a medicine by 2020.
“When Spinraza was being developed, I didn’t want to be super optimistic because you never know what obstacles you’ll find along the way,’’ Krainer said at the headquarters of Stoke, in which he has equity and serves on the board of directors. “In that case, the planets aligned beautifully. I don’t see any reason why it won’t be the case for Dravet.”
Of course, the odds are always stacked against any experimental drug winning approval. Stoke, however, has several things going for it, including $40 million in venture capital from Apple Tree Partners of New York and a CEO, Dr. Edward Kaye, who led another biotech that focused on genetic medicines for rare neuromuscular diseases.
Kaye ran Cambridge-based Sarepta Therapeutics Inc. in 2016, when the Food and Drug Administration approved its Exondys 51 drug. That was the first treatment for Duchenne muscular dystrophy, a deadly muscle-wasting disease. FDA approval came after months of delays and a dispute within the agency over the drug’s effectiveness.
“I’m the closer,” said Kaye, who has known Krainer for years. “I’m the one who takes an interesting idea and then takes it to the clinic and gets a drug approved.”
Kaye said Stoke wants to use an RNA-splicing technology similar to the one Krainer developed and tested in mice for Spinraza. That approach drew the attention of C. Frank Bennett, senior vice president of research at Ionis Pharmaceuticals, a drugmaker in Carlsbad, Calif. Ionis then collaborated with Cold Spring on development of the medicine and licensed it to Biogen.
“We’re standing on the shoulders of Spinraza,” said Kaye, who says the precedent of that medicine will shorten the amount of time until clinical trials can start for Dravet patients. “It’s not 10 or 15 years away. We’re talking within the next couple of years we’re going to be in patients.”
Dravet is a rare and severe form of epilepsy, occurring in roughly 1 in 20,000 to 40,000 births. It’s caused by a single defective gene. Seizures generally start in the first year of life and initially are often associated with a fever.
Infants have normal development when seizures begin, but as the episodes recur, most suffer developmental disabilities. Dravet is difficult to treat, even with anticonvulsant medicines, and can sometimes be fatal.
As in the case with Spinraza and spinal muscular atrophy, Stoke scientists want to get at the genetic roots of the disease rather than treat its symptoms. They hope to develop a drug that will adjust RNA splicing to help the defective gene make more protein. Like Spinraza, the medicine would be injected into the spinal canal periodically, and, scientists hope, provide long-lasting benefits. They have already started testing medicine in mice genetically altered to suffer epileptic seizures.
‘When Spinraza was being developed . . . the planets aligned beautifully. I don’t see any reason why it won’t be the case for Dravet.’
Stoke calls its patented scientific approach Targeted Augmentation of Nuclear Gene Output, or TANGO. The acronym is a nod to the dance that’s popular in Uruguay. Like Krainer, Aznarez grew up in that South American country.
Aznarez was the one who came up with the idea to start a business based on her mentor’s insights.
“I went and talked to Adrian and said, ‘Adrian, what do you think about instead of developing drugs and giving them away . . . why don’t we do it ourselves?’” Aznarez, 46, recalled.
“She’s more entrepreneurial than I am,” Krainer said.
Aznarez has moved to Boston and is working full time at Stoke as the head of biology. Krainer, who earned his PhD at Harvard, is continuing to work at Cold Spring Harbor, which has licensed TANGO to Stoke and has equity in the company. Stoke has about two dozen employees.Jonathan Saltzman can be reached at email@example.com