After recalibrating its production strategy in the late 2010s to better align with the realities of the CAR-T market, Gilead Sciences’ Kite Pharma is gearing up to hit the ground running for approval of its next-generation multiple myeloma cell therapy later this year.
And looking further afield, Kite is eyeing the potential of in vivo CAR-T, which could further simplify the manufacturing and logistical constraints of this class and bring medicine to more patients, said Laura Alquist, Kite’s senior vice president and global head of technology operations, when she spoke with Fierce at the recent U.S. Biomanufacturing Summit in San Francisco.
Having ranked second in the CAR-T market behind Novartis with its B-cell lymphoma treatment Yescarta, Kite, like many other cell therapy developers, quickly faced the early realities of limited manufacturing capacity, a small patient pool and infrastructure hurdles that hindered the early rollout of potentially curative cancer treatments.
Concept of manufacturing
When it comes to aligning commercial scale-up with the innovation happening across Kite’s pipeline, Alquist acknowledged that the company has “learned some lessons along the way,” noting that Kite is now leveraging “close collaboration between research and process development at an early stage.”
By co-locating clinical manufacturing with the process development (PD) team, Kite has streamlined the technology transfer process and reduced time-to-clinic, according to Alquist.
“The handover from research to process development to clinical manufacturing is very seamless, and we are seriously considering how to bring it to commercial scale,” she explained.
Regarding the strategic priorities that Kite’s manufacturing organization should consider, Alquist noted that “speed to market is critical, especially when there is a potentially curative, life-changing treatment,” pointing to therapies like Yescarta, which has secured several label updates and expansion into follicular lymphoma, and Kite’s Tecartas, which has been approved for mantle cell lymphoma and acute lymphoblastic leukemia.
“We can continue to build robustness into our processes, but sometimes it’s a trade-off for speed, so we’re constantly balancing that,” she said.
Early in the history of commercial CAR-T, manufacturing constraints related in part to the supply of viral vectors also limited the success of first-generation therapies.
Gilead, which acquired Kite in 2017, was an early investor in its cell therapy capabilities, which now includes three commercial manufacturing sites and has brought viral vector production in-house to alleviate concerns of shortages, Alquist explained.
Perhaps the most notable example of the company’s sophisticated manufacturing strategy, Kite announced in 2019 that it would build a 67,000-square-foot facility at its Oceanside, Calif., biopharmaceutical site to bring vector manufacturing in-house. Prior to this move, the company relied on contractors for needed materials.
“Vector’s in-house production ensures a reliable supply of key CAR T components and can support both commercial and clinical manufacturing for patient treatment,” Alquist said.
“Our dedicated resources for incorporating and designing viral vector methodologies and processes are currently supplying retroviral vectors to Kite’s CAR T facility, and we are currently advancing manufacturing of lentiviral vectors to support our pipeline products,” she continued.
Preparation of anitocell
Alquist spoke with Fierce as Kite prepares for approval of its third CAR-T, Anitocel, in partnership with Arcellx, toward the end of the year. Ahead of the potential launch, Kite’s commercial facility in Frederick, Maryland, is already being used to supply the drug to the company’s clinical programs and is preparing to scale up to bring the product to market, Alquist said.
Kite announced the design for the facility in 2019, drawing up plans for the 279,000-square-foot facility about 20 miles west of Baltimore. When the FDA approved construction of the facility in 2022, Kite declared that the facility, along with factories in Southern California and Amsterdam, would constitute the world’s largest “dedicated in-house cell therapy manufacturing network.”
Anitocel’s expected turnaround time (representing the timeline from when a patient’s cells are harvested, genetically engineered in the lab, and then reinjected into the patient) is 14 to 17 days, comparable to treatments such as Yescarta, Kite’s global head Cindy Peretti told Fierce Biotech last year.
ambition in vivo
As for the upcoming manufacturing innovations that are garnering attention for Alquist, Kite executives pointed to an area in which the company is currently operating: in vivo CAR-T therapy, calling the potential of this approach “incredibly disruptive” and saying they believe the field is “on the cusp of another great advancement.”
Unlike traditional autologous CAR-T, in vivo therapy uses gene therapy to fine-tune T cells while they are still in the patient, potentially offering a simpler form of treatment. Gilead entered the space last summer with its $350 million acquisition of in vivo player Interius BioTherapeutics.
Meanwhile, Kite also paid $120 million upfront to Chinese biotech Pregene in a separate in vivo CAR-T development agreement.
“Probably over the next 10 years, there will be a greater balance between the inside and outside of the body,” Alquist surmised. “It’s not going to come right away and cannibalize us in vitro, but I think it’s a great opportunity to think about how we can provide more traditional treatments.”
Alquist noted that aside from the therapeutic efficacy of in vivo CAR-T, the evolution of this class “doesn’t come with all the complex logistics for patients, manufacturing, and supply chain.”
“It’s really going back to more traditional manufacturing, the vectors themselves, and being able to deliver them and distribute them much more easily compared to traditional self-medication,” she said.
“As an off-the-shelf treatment that does not initially require the patient’s immune cells, in vivo could increase access to a larger number of patients, be delivered to patients faster, and potentially eliminate the need for preconditioning chemotherapy,” Alquist added.
Elsewhere, regarding Kite and Gilead’s broader positioning against the backdrop of U.S.-originated policies and tariffs, Alquist noted that Kite has a “regional” manufacturing network with factories in the U.S. and Europe, the latter also serving the Middle East and a distribution center in Japan.
Beyond geopolitical considerations, “our goal was to be as close to the patients as possible,” Alquist said.
