Avrobio is using 'pods' to create gene therapies, and it believes the approach could change the game altogether
Where other companies have gone big, Avrobio is going small. Its manufacturing operation is no different.
Instead of trying to keep up with the validation of new facilities — and spending money and precious time in the process — the company has opted for a different approach: small, automated pods that can be installed in rented clean rooms anywhere. Though production output isn’t as high as other companies, Avrobio avoids brick-and-mortar and is able to stay flexible and nimble to respond to fluctuations.
“We believe it’s the only way to globalize,” said Geoff MacKay, Avro’s founder and CEO. “We had no appetite to build big facilities everywhere in the world.”
The company based in Cambridge, MA is focused on single-dose personalized gene therapy to cure Fabry disease, Gaucher disease type 1 and cystinosis through the platform its dubbed plato. Unlike other gene therapies that are delivered straight into patients, AvroBio’s lentiviral-based therapies are delivered ex vivo into patients’ stem cells before proliferation and then infusion back into patients.
The pods — typically used in hospitals for bone marrow transplants — come from Miltenyi Biotec, and MacKay and his team repurpose the tech for use in modifying the patients’ stem cells. The pods are housed in CMO clean rooms all over the world, from Houston to Melbourne, San Jose and Maastricht, but the biotech eventually plans to scale up capacity for its own in-house version of the technology.
MacKay believes a localized manufacturing chain is crucial because it allows for each patients’ stem cells to be stored in relative proximity to the patient. The model also allows a greater degree of flexibility — each discrete pod can be used for a wide variety of therapies — and easy scalability.
“The beauty here is that you validate the pod, but regulators are agnostic about where you house the pod, because the environment doesn’t change,” MacKay said. “It’s the exact same steps, the exact same environment, so you kind of just sidestep all of the complexities of getting new manufacturing facilities online.”
It’s also a boon for AvroBio, which at the clinical stage is approaching the point at which most gene therapy companies start thinking of investing heavy capital in their own plants. Without the need for a huge footprint, that could AvroBio capital flexible as it moves into the next stage of trials.
“When you’re a biotech company in early development, the cost of capital is obviously precious, and if you don’t have to spend hundreds of millions of dollars with a VC type cost of capital, that’s great … Normally, you don’t have that type of luxury,” MacKay said.
Avrobio currently has 3 products in clinical trials. Its gene therapy for Fabry disease is currently being studied in two clinical trials: 1 Phase I trial in Canada, and a Phase II trial in Australia, the US and Canada. It also has a therapy for Gaucher disease type 1 that is in Phase I in Canada and Australia, and a cystinosis study in a Phase I/II trial at the University of California, San Diego.
Toward the end of 2018, the gene therapy company saw its stock plummet, dropping down 52% after its data surrounding Fabry disease treatment showed that vector copy numbers dropped in peripheral blood in all of its patients between 1 and 18 months.
Recently, the company announced new data that showed at least in a few patients, the therapy saw 100% reduction in kidney substrate, the endpoint the FDA uses for approval. There has been strong safety and efficacy data in all 14 patients in the trial, and so far, a year from dosing, 10 patients in clinical trials show no waning efficacy.