NASHVILLE, Tennessee—Ilan Ganot’s story starts out like that of countless other parents of boys with Duchenne muscular dystrophy (DMD): missed milestones, visits to pediatricians, then the devastating diagnosis of a disease they’d never heard of.
Afterward, Ganot was determined to do something beyond joining advocacy and awareness campaigns, as many families do.
“I started realizing that science may be in the early stages of coming up with some answers,” he said. “With a little bit of help from friends and influence from people I appreciate and am grateful for, I was helped to make some big decisions about our future as a family.”
Ganot is now the CEO of Solid Biosciences, based in Cambridge, Massachusetts. Along with his wife, Annie, the Israeli-born financial guru cofounded Solid after their son, Eytani, was diagnosed with Duchenne in 2012.
Interviewed at the Muscular Dystrophy Association’s 2022 Clinical & Scientific Conference here, Tennessee, Ganot recalled how he raised $17 million to launch Solid in the hopes of finding a cure for DMD, which affects roughly 1 in 5000 newborn boys.
“We believed, even before starting the company, that in a disease that is complicated and complex like Duchenne, where a lot of organs and a lot of aspects of daily living are affected, it helps to have focus and really understand what you’re dealing with,” Ganot told Rare Disease Advisor.
“From very early days, I was committed to bringing on board people that have expertise around this disease from all the different aspects that are needed to really make a drug development program and start a company,” he said.
A Focus on Gene Therapy
Originally from the Tel Aviv suburb of Herzliyya, the now 48-year-old investment banker attended London Business School in England and was living in New York City when Eytani was born in 2010.
“At around 6 months of age, Annie started noticing that he was slow in hitting certain developmental milestones. We had no reason to be too concerned, but we started following up on it and seeing different experts. Two years later, after I had relocated to London for work, Eytani was seen by a pediatrician who suspected something else might be going on, and he did a number of tests. One of them resulted in a Duchenne diagnosis,” he said.
“It was terrible. I remember getting the call on the trading floor, and Googling and finding out everything that’s bad about it: limited life expectancy, horrible quality of life, progressive, irreversible, everything you never want to hear about your child. Yeah, those were really sad days.”
In between having another child, Alexy Lulu, and moving to Boston to launch their company, Ganot and his wife immediately started 3-year-old Eytani on steroids under the care of Brenda Wong, MD, director of the Duchenne Program at the University of Massachusetts in Worcester.
Around that time, Ganot concluded that dystrophin regulation and exon skipping therapies would not have the kind of meaningful effect parents wanted to see in their boys, even if those therapies won approval from the US Food and Drug Administration (FDA). So, about 6 years ago, Ganot and his company turned their attention to gene therapy.
“We didn’t start off doing gene therapy. We started off looking at everything that was available, but early on we got our hands on some animal data that suggested that microdystrophin specifically could have a meaningful benefit in Duchenne,” Ganot explained.
“We licensed what we believe still is the most promising candidate of a microdystrophin construct. We packaged that into AAV9, which is something that back in 2015 was making early milestones in spinal muscular atrophy [SMA] and that ended up getting approved as Zolgensma® [onasemnogene abeparvovec-xioi].”
Encouraging Results on Microdystrophin
Following extensive testing on mice, dogs, and monkeys, in which therapeutic administration of microdystrophin by AAV was shown to restore muscle function, Solid began human trials in 2018.
“We have quite unbelievable outcomes in mice and dogs,” he explained. “Now, we treat the animals early in their life. It’s not exactly equivalent to treating patients later in their life, and oftentimes damage that’s already been done is hard to reverse. But there’s a lot of hope that the microdystrophin gene and the protein that it codes for should stabilize the muscle and definitely improve its function.|
Theoretically, such gene therapies should work at any age, though younger children are generally preferred for such trials for various reasons related to safety, availability of raw materials, and the cost of manufacturing.
Toxicity is also an issue,” he said. “What we believe is that the sooner you treat, the more likely you are to help the patient experience a better outcome.”
Solid is conducting a clinical trial (NCT03368742) for its investigative therapy, SGT-001. Two years after receiving the one-off infusion, the 9 boys participating “are expressing microdystrophin at meaningful levels, as well as showing functional outcomes that are better than the baseline and where you would have expected—and definitely better than where you would have expected to see them at the age of 10 and a half.”
On March 14, 2022, Solid reported that 2-year data from the first 3 patients in its high-dose cohort “suggest sustained or improved motor function, pulmonary function and clinically validated patient-reported outcomes compared with expected declines reported by natural history data.”
On April 27, 2022, the company said it would transition SGT-001 to a commercially scaled manufacturing process, advancing its differentiated microdystrophin, SGT-003, toward an anticipated Investigational New Drug (IND) submission to the FDA in early 2023.
The Pros and Cons of Newborn Screening
Solid reported $13.6 million in 2021 revenue as a result of its collaboration in research services and cost reimbursement with biopharmaceutical company Ultragenyx. Its research and development expenses for the first quarter of 2022 were $19.9 million—up from $14.4 million for the first quarter of 2021—and it had $180.1 million in cash and other assets on hand as of March 31, 2022.
Asked if the FDA’s May 2019 approval of onasemnogene abeparvovec to treat SMA has any implications for the eventual success of gene therapy for Duchenne, Ganot said: “I know people like to bundle rare diseases together, but they’re all very different. Of course, SMA is motor neuron and Duchenne is dystrophin deficiency. But there are similarities as well. They’re both fatal, and they both require a lot of intervention.”
Despite the obvious advantages of early diagnosis, Ganot is not among those who favor the immediate implementation of nationwide newborn screening for DMD before there’s a cure available.
“I have to tell you as somebody that has that kind of a personal experience with a rare disease of this nature, I see some merit to the argument that until there is a good treatment, maybe you don’t need to know,” he said. “The knowledge of Duchenne is not a great thing for a family. It’s not a great thing for a child.”
As for Eytani, now 11, Ganot said that at this point, his son knows a lot about his disease—but not all the details.
“He’s not particularly curious about it,” he said. “At this age, he could Google and look it up himself. We would always be honest with him if he did ask, but he doesn’t ask much.”
Ganot added: “He’s well aware of his limitations. He uses the wheelchair a lot. He’s a lot shorter [than other kids his age], and he’s obviously not strong. The disease is also affecting him cognitively as well. That said, he’s a sweet boy. He’s got two loving sisters and parents, and we do our best to keep him happy.”