From a biology perspective, there are advantages to using patient cells that have never been frozen, which impacts cell health. The “fresh” CAR-T cells produced in the Cocoon show strong and steady growth once they are infused back into the patient, says Stoffels, which helps to minimize a common side effect of CAR-T therapy, called cytokine release syndrome—an overly aggressive response to immunotherapy that cause fevers, nausea, and fatigue. “The fact that you can do this in seven days allows people with a very short life expectancy to still to get this type of therapy,” he says. “The first patient treated with CAR-T cells from the Cocoon system, who came to the hospital with acute respiratory distress and a severe relapse of his tumor is still in very good shape. This could have never been done with the classical CAR-T in a centralized manufacturing.”
Stoffels says that “decentralization, simplification, and automation of the whole process will reduce the cost of CAR-T significantly,” though he won’t specify by how much. “Time and labor drive a lot of the cost of CAR-T therapies. If you put four or five Cocoon systems in a room in a hospital, you can do 200 patients per year, with just a few people.”
Even so, Galapagos is facing a crowded field of competitors. There are currently 1,128 clinical trials of CAR-T therapies listed at ClinicalTrials.gov, with 275 either recruiting or having completed Phase 2 or 3. There are also a handful of other companies developing systems similar to the Cocoon, such as CliniMACS Prodigy device, which can also be used in the centralized facility, and is in Phase 1/2 trials in the U.S. for patients with B cell Acute Lymphoblastic Leukemia. Meanwhile, companies including Allogene, Precision BioSciences, and Caribou Biosciences are all working on so-called allogenic CAR-T treatments that eliminate wait times by using “off-the-shelf” T cells. And ultimately, the industry may move toward in vivo CAR-T: Rather than manufacturing CAR-T cells outside the body, the therapy will deliver DNA or RNA that reprograms T-cells or other immune cells directly in the patient’s body. Ensoma, Vector BioPharma, Umoja Biopharma, Interius BioTherapeutics, Capstan, and Moderna are among the companies working in this area.
Galapagos will not be immune from shortages of chemical reagents and other raw materials that impact other companies. Distributed manufacturing also comes with drawbacks, says Young from Calibr: “All of the challenges with not having enough highly trained technicians to do this gets amplified if you are working across multiple hospital centers. The technicians don’t need to be as highly trained, because the systems need a lot less manual manipulation. But any time you distribute this out to all these hospital centers, you’re losing a degree of control over all of that.”
But Stoffels has done the impossible before, repeatedly, and seems undeterred. “I’ve worked my whole life on trying to make medicines accessible,” he says. “That is also a mission here. The new science allows us to do new, difficult, and different things. And if you don’t start, you never get there.”