Timing Is an Essential Element of Cell & Gene Therapy Product Development

Xconomy Philadelphia — 

The science underpinning the latest investigational cell and gene therapies is complex enough. But the rapid advance of technologies that support development of these kinds of drugs presents logistical considerations, too.

“Drug development is an interesting process because it takes five to 10 years to get a drug to market and invariably, somewhere along that line, the technology’s a little outdated before it even is approved, and there’s new things out there that are better,” said Jeffrey Castelli, chief portfolio officer and head of gene therapy at Amicus Therapeutics (NASDAQ: FOLD). “You look at some of the gene therapies that are now just ready coming to market and you think, wow, that’s a pretty outdated gene therapy approach—but you really get locked in as you’re moving your product toward development.”

Castelli was among the executives who spoke as part of a panel at Xconomy’s online Xcelerating Life Sciences Philadelphia forum last week.

Amicus, headquartered in Cranbury Township, NJ, operates a gene therapy R&D center in Philadelphia. To keep its therapies from becoming stale prior to commercialization, the company keeps an eye on new technologies that arise, Castelli said. But some innovations invariably surface too late to incorporate.

“We really try to implement them early on, and then make sure that when we have our second wave of programs and products we’ve incorporated some of the innovation,” he said. “But you do get locked into your approach along the way, and there’s more and more switching costs as you move along that pathway.”

To guide that process Tom Wilton, chief business officer at Philadelphia-based cell therapy company Carisma Therapeutics, says it’s essential to collect and analyze data early on to guide the path of drug development.

“As a relatively small company … you’ve really got to focus the majority of your resource on pushing forward that lead program and getting it into the clinic,” he said. “Later this year we’ll get a lot of data back from that first-in-human clinical study, the first time anyone’s ever taken an engineered macrophage into the clinic. … What that should give us then is a set of criteria and priorities around what we need to bring forward in a next-generator program.”

To date the company’s consideration of new technologies has been perhaps a bit more opportunistic—“everything from gene editing the macrophages to novel binders to different combination strategies”—but once Carisma has the initial clinical data in hand, that will narrow its focus, Wilton said.

“There’s always a tendency [with a first-generation product] to say we could do this to this, we could do this to this, but you have to lock it down, you have to get into the clinic and get that data set to really understand what your priorities are and where you need to focus, and that’s what we’re planning to do.”

As experimental products move into later stages of development, another consideration arises, the panelists said: Producing them at scale.

For cell and gene therapy companies, figuring out when to lock in the space needed to make these drugs so it is available when needed for clinical trials or commercialization is difficult to determine precisely, especially given the shortage of manufacturers versed in some of the advanced technologies needed to do so.

“There is a capacity shortage right now in cell and gene therapy manufacturing,” said Audrey Greenberg, co-founder and executive managing director of Discovery Labs, an MLP Ventures-backed biotech coworking and incubator space in King of Prussia, PA. “There’s estimates that it’s five times [current cumulative bioreactor volumetric capacity] now and will be 50 times in five years given the FDA pipeline and the dollars flowing into these companies.”

Discovery Labs is building out a $1.1 billion gene and cell treatment manufacturing operation plus developing a contract development manufacturing organization to provide services to companies in the sector.

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