Later this year, Umoja Biopharma will open 77,000 square feet of a 146,000 square foot manufacturing facility at the Colorado Technology Center in Louisville. Although Umoja is only in the early clinical stage of developing CAR-T therapeutics, the company got an early start on creating a facility to make the lentiviral vectors that it will need for clinical studies. Here, Ryan Crisman, PhD, co-founder and CTO of Umoja Biopharma, describes the thinking behind that decision.

“I’ve lived through the manufacturing bottlenecks in the early days of cell and gene therapy,” Crisman says. “As the science gets more and more innovative, the manufacturing becomes more and more of a potential bottleneck, and it’s definitely something to keep an eye on throughout the whole lifecycle of products.”

Umoja has an innovative platform that it plans to apply to a multi-product pipeline, which Crisman describes as “surface-engineered lentiviral particles that we directly infuse into patients.” Those particles deliver genetic information to a patient’s T cells, which then make CAR-T cells in vivo. “So instead of the one patient-one process in the current autologous CAR-T space, we’re doing one process that can treat upward of 1,000 patients by utilizing their own body to manufacture CAR-T cells.”

Taking an adaptable approach

Developing such a novel therapy requires an adaptable approach to manufacturing during development in case adjustments need to be made along the way. “By having our own internal manufacturing capabilities, we can start to look at de-risking the path to commercialization,” Crisman says. “There are a lot of horror stories in the CAR-T space when changing from a Phase I manufacturing facility to a commercial facility.” In addition, global vector shortages are frequently cited as a top bottleneck in developing cell and gene therapies. Manufacture capabilities allow Umoja to partner with companies that can use its in vivo technology platform to develop and deliver their own CAR-T products.

Still, how does a company know if it should invest early in manufacturing? “The more novel that the therapy is, the more important it is to consider earlier investment in manufacturing,” Crisman says. “Once you have your recipe, contract manufacturing organizations, CMOs, are great, but with novel therapies you’re not even quite sure what you need to be looking at, and you need to have that flexibility to adapt on the fly.” That makes internal manufacturing even more useful. “When we first started,” Crisman says, “we did a global CMO assessment and chose a top-tier CMO, but we were still learning how to bake our cake, and the CMO couldn’t figure it out with us.”

Although internal manufacturing is useful, it’s also expensive. Crisman says that it takes around $100 million to build a manufacturing facility for cell and gene therapies, plus at least $10 million a year for operating costs. “So, for new companies, a really strategic assessment needs to happen to decide if building a manufacturing asset is worth it or not,” he says. “You have to really believe in your pipeline and have a strong business strategy to support the decision.”

Early move to manufacturing takes experience

Also, making an early move to manufacturing takes experience. “In our company, we have people who have been through 12 or 15 development manufacturing builds,” Crisman says. “So, we’ve got the breadth and depth of experience to actually know how to build these successfully and operate them.”

Nonetheless, Crisman encourages constructive evaluation of a manufacturing plan. “I’d start with surrounding yourself with the people who are going to challenge assumptions and the experience to be able to help guide that assessment process,” he says. “Put some meaningful thought into whether the mission of the company can be achieved through external partnerships or if you really need that internal innovation and flexibility to be able to be effective, efficient, and successful.”

If internal manufacturing makes sense, Crisman suggests an open-minded approach to selecting a site. “Think a little outside the box on location,” he says. “I know a lot of folks who thought about building in the traditional biotech hubs, but there are some other really good spots in the U.S.” For Umoja, Colorado provides just what the company needs to move forward on its crucial mission.

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