Ultragenyx injects $40M to grab Solid's microdystrophin transgene — while sidestepping the AAV9 vector that stirred up safety fears
Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.
Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.
With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.
“Emil Kakkis is one of my heroes,” Ganot tells Endpoints News. “I’ve been a big fan of his work and his expertise in rare disease and what a sound advisor he’s been over the years.”
The goal with the new collaboration, he adds, is to create one more potential option for Duchenne patients.
While AAV9 is an “excellent vector and delivers really well,” Pfizer’s and Solid’s experience suggested that complement activation and immune response can make it risky in indications that require high doses, Kakkis says — echoing a warning by gene therapy pioneer Jim Wilson around the same time he resigned from Solid’s board. Safety fears have spurred the FDA to put SGT-001 on hold twice, triggering layoffs and a revamp of the manufacturing protocol as well as clinical plans.
AAV8, on the other hand, clears from the bloodstream more quickly and thus appears to avoid those immunological issues. Sarepta’s work with AAV8 so far backs the belief.
Leveraging its HeLa producer cell line manufacturing platform, Ultragenyx’s first order of business now will be to get the commercial-grade manufacturing of capsids in place. Coming up with a clinical program to add to the gene therapy pipeline — which currently focuses on glycogen storage disease type Ia (GSDIa), ornithine transcarbamylase (OTC) deficiency and Wilson’s disease — will come quite a bit later.
The collaboration covers both Duchenne and other diseases resulting from a lack of functional dystrophin, including Becker muscular dystrophy.
Each product that arises from the deal is tied to $90 million in total milestones, with another $165 million reserved for sales. Ultragenyx is essentially in charge but following proof-of-concept, there would be ways for Solid to co-fund the development in exchange for profit share or higher royalties.
“We’re well behind Sarepta and Pfizer for sure, but we do believe that getting to a proper 2,000L scale manufacturing will allow us to enter the clinic and move more quickly through the development program by developing a seamless pivotal design where we go through the dosing cohorts straight into the randomized Phase III part,” Kakkis says.
Even if the frontrunners get to the market first, both Ganot and Kakkis doubt that the first one out can control it all. There are challenges related to manufacturing and distribution — not to mention uncertain prevalence of pre-existing antibodies to different AAV serotypes.
“Right now the manufacturing systems I don’t think are up to what they need to be in order to scale, and I think our system will allow us to be competitive even if we’re behind,” Kakkis says.