Orchard Therapeutics says it is launching a cryopreserved formulation of its lead candidates to overcome the limitations of fresh hematopoietic stem cell gene therapies.

Orchard Therapeutics’ pipeline includes Strimvelis, the former GSK autologous ex vivo hematopoietic stem cell (HSC) gene therapy approved by the EMA in 2016, along with five clinical stage programs.

The firm launched its initial public offering (IPO) last year and in its first public year-end financial conference call last week spoke of the potential upcoming milestones including moving its three lead programs in ADA-SCID (adenosine deaminase severe combined immunodeficiency), MLD (metachromatic leukodystrophy) and WAS (Wiskott–Aldrich syndrome) to regulatory filings in the US and Europe over the next three years.

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But another key strategy discussed by management is the launching of a cryopreserved formulation of the gene modified HSCs.

“The trial for our three lead programs for ADA-SCID, MLD and WAS were initiated using a fresh-cell product, but if approved, we like others, plan to commercialize these products using a cryopreserved formulation,” Bobby Gaspar, cofounder and CSO said on the call (transcript here).

“By extending the product’s shelf life, we’re able to focus the process around the patient. We can collect the cells at their local treatment center, ship the cells to a manufacturing facility, genetically modify and cryopreserve the HSCs, and then ship them back to the patients’ local treatment center to be reintroduced into the patient.”

CFO Frank Thomas added the industry generally is moving towards cryopreservation as its preferred formulation, and Orchard is undertaking bridging studies for its programs to move into this space.

“We understand the limitation for using fresh formulation and we like others want to launch the commercial products with the cryopreserved formulation as that will give greater accessibility to patients,” he said.

“We’ve actually already treated only 30 patients with cryopreserved formulation across our different studies. So the bridging work is underway for those four, three programs, and what we’re planning to do is to show in vitro CMC comparability between the fresh and the cryopreserved formulation. And we will evaluate the hematopoietic stem cell disease study for cell number, the liability, the sterility of the products and also the VCN [vector copy number] numbers in that product as well.”

Manufacturing

The firm also spoke about investment in its own gene therapy network, specifically the build-out of a 150,000 square-foot facility in Fremont, California, announced in December 2018.

“For our first three potential launches, our commercial manufacturing platform is based on the CMO [contract manufacturing organization] partnership networks we have established with some of the leaders in the field, including Lonza, MolMed and Oxford BioMedica,” said CEO Mark Rothera.

“Given the importance of building in-house manufacturing capabilities and the breadth of our portfolio, we announced the lease of a facility in Freemont California at the end of last year. The new facility will complement our existing CMO network and will enhance our ability to develop and deliver ex-vivo lentiviral gene therapies for a wide range of diseases on a global scale.”