SAN FRANCISCO—Orchard Therapeutics started 2018 with two clinical-stage assets and a preclinical pipeline that was, in CEO Mark Rothera’s words, “not that large.” Now, after picking up GlaxoSmithKline’s rare disease gene therapy unit and becoming a commercial-stage company, Orchard is looking to bring its treatment for “bubble boy syndrome” to the U.S. and ramp up its clinical work.
Orchard acquired the GSK assets in exchange for a 19.9% stake in Orchard and undisclosed milestones and royalties. These included the EMA-approved Strimvelis, which treats ADA-SCID, a rare genetic disorder that causes immunodeficiency, as well as late-stage candidates for metachromatic leukodystrophy (MLD) and Wiskott-Aldrich syndrome (WAS).
The company, based in Boston and London, now has five clinical-stage gene therapies and 10 preclinical programs.
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“I would say we have the world-leading gene therapy pipeline today … partly because it’s very advanced, but also very deep,” Rothera said at the J.P. Morgan Healthcare Conference. The company plans regulatory filings for its three leading clinical programs within the next three years and will move one of its preclinical assets into the clinic in 2019, he said.
And with $375 million total raised, Orchard has a big year ahead. Of course, a key use of the cash will be clinical and manufacturing work, but a good chunk of it—about $90 million, Rothera reckons—will fund Orchard’s 150,000-square-foot manufacturing site in Fremont, California.
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The company has already signed on the contract manufacturing organizations (CMOs) for the launch of its ADA-SCID, MLD and WAS treatments, but is looking to “take charge” of its “own destiny.” The site won’t be running until 2021, and Orchard plans to continue working with CMOs to make its treatments, but the combination of having its own facility as well as manufacturing partners “provides some redundancy, that you want a bit of,” Rothera said.
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With Strimvelis already marketed in Europe, Orchard is focusing on getting OTL-101, its ACA-SCID treatment, to patients in the U.S., where there is no gene therapy for the disease. It's planning to file for FDA approval in 2020. Eventually, OTL-101 will supplant Strimvelis, which is approved for use at one treatment center in Milan. OTL-101, like the rest of Orchard’s pipeline, uses a newer, lentiviral vector, and unlike Strimvelis can be cryopreserved.
“It’s not patients who will do the traveling, it’s the cells,” Rothera said.
In addition to requiring travel, Strimvelis, which was developed as a fresh cell product, has a small window of time to extract a patient’s stem cells, insert a working copy of the disease-causing gene and put the cells back into the patient—about six hours. This means quality control can be difficult.
“[The new technology] allows potentially weeks to make sure of the right number of cells, viability, sterility, the right [vector copy number.] When you give it back to the patient, the chance of it working looks much, much clearer,” Rothera said.
After bringing gene therapy to ADA-SCID patients in the U.S., Orchard will look to Europe and other parts of the world.
“At that point, patients will have a choice [between Strimvelis and OTL-101,” Rothera said. “I’m sure which way that’s going to go.”