At the dawn of 2019, it was all systems go for Orchard Therapeutics. The company had just pulled off a $200 million IPO, picked up GlaxoSmithKline’s stable of rare disease gene therapies and planned to break ground on a $90 million manufacturing site in California. Now, under the wing of a new CEO, the company has reined it in and is growing in a more considered manner.
In May, two months after Bobby Gaspar, M.D., Ph.D., took over, Orchard laid out a plan to focus less on ultrarare diseases in favor of more prevalent ones, adding new work in dementia and Crohn’s disease and pulling funding from its programs in beta thalassemia and ADA-severe combined immunodeficiency (SCID), often called "bubble boy disease." That plan included axing the new manufacturing site as well as cutting 25% of its workforce.
“We took a view that to prioritize what we were doing right now, deliver on that and invest in some R&D on the larger indications … That is where the full value of Orchard lies and the full value of hematopoietic stem cell gene therapy lies,” Gaspar, who’s no stranger to Orchard, told FierceBiotech. The pediatrician co-founded the company in 2015 after treating the first patient with an ex vivo, stem-cell-based gene therapy in a clinical trial two years earlier and then served as its chief scientific officer before stepping up to CEO.
“It doesn’t mean to say we don’t look at developing [our ADA-SCID] program at a later stage,” Gaspar added. Having developed the treatment in academia and taken care of patients with the disease, he’s seen firsthand the effect it can have on patients. “But it’s about making choices at this stage,” he said.
One of those choices is neurometabolic diseases, for which Orchard is prioritizing four programs. The diseases are rare, but not as rare as ADA-SCID.
These comprise metachromatic leukodystrophy, a life-threatening inherited disease of the body’s metabolic system; Wiskott Aldrich syndrome, a life-threatening inherited immune disorder; mucopolysaccharidosis type I, a rare, inherited neurometabolic disease; and mucopolysaccharidosis type IIIA, (also known as Sanfilippo syndrome type A), a life-threatening neurometabolic disease characterized by intellectual disability and loss of motor function.
The idea is to use its gene therapies to tackle conditions that aren’t served by other types of treatments and use what it learns to go into more common diseases. It will iron out certain details, like how to manufacture vectors and scale production, in a smaller population before trying to do the same in a larger one, Gaspar said.
As for its California manufacturing site? Orchard’s previous CEO, Mark Rothera, billed the now-nixed facility as a way to “take charge” of its “own destiny” and not rely on partners to manufacture its treatments. Gaspar agrees on the importance of in-house manufacturing but is pushing that piece off into the future.
“We didn’t need that level of manufacturing capability, so what we wanted to do was defer that investment into the later stage, when we actually would need that level of in-house manufacturing capacity,” he said. In the meantime, it’s working with CDMOs in the near and medium terms and diverting some of the money it would have spent on the site toward its R&D efforts so, eventually, it will have a pipeline that will need its own manufacturing space.