After recalibrating its production strategy in the late 2010s to better meet the realities of the CAR-T market, Gilead Sciences’ Kite Pharma is preparing to hit the ground running with the potential approval of a next-generation multiple myeloma cell therapy later this year.
And looking further afield, Kite is eyeing the potential of in vivo CAR-Ts to simplify the manufacturing and logistical constraints of the class even more, potentially bringing the medicines to a greater swath of patients, Laura Alquist, SVP and global head of technical operations at Kite, said in a recent sit-down with Fierce at the American Biomanufacturing Summit in San Francisco.
Second to the CAR-T market behind Novartis with its B-cell lymphoma therapy Yescarta, Kite, like many other cell therapy developers, quickly faced the early reality check of limited manufacturing capacity, plus small patient pools and infrastructure hurdles that hamstrung the initial rollout of the potentially cure-like cancer treatments.
Manufacturing mindset
When it comes to matching the commercial scale-up to the innovations taking place across Kite’s pipeline, Alquist admitted that the company has had “some lessons learned along the way,” noting that Kite now leverages “close collaboration between research and process development early on.”
By co-locating its clinical manufacturing with its process development (PD) team, Kite has also simplified the tech transfer process and accelerated time to clinic, according to Alquist.
“That hand off is very seamless from research to process development to clinical manufacturing and really thinking through how we would take that into a commercial scale,” she explained.
As for the strategic priorities Kite’s manufacturing organization must consider, Alquist noted that “speed to market is critically important, especially when you have these life-changing therapies with the potential to deliver a cure,” alluding to therapies like Yescarta—which has secured several label updates and an expansion into follicular lymphoma—as well as Kite’s Tecartus, approved in mantle cell lymphoma and acute lymphoblastic leukemia.
“You can continue to build robustness into the process, but you’re trading off sometimes speed, and so we’re always striking that balance,” she said.
Earlier in the history of commercial CAR-Ts, manufacturing constraints—in part tied to the supply of viral vectors—also put limits on the success of first-generation therapies.
Gilead—which acquired Kite in 2017—invested early in its cell therapy capacity, which now includes three commercial manufacturing sites and internalized viral vector production to mitigate shortfall concerns, Alquist explained.
In perhaps the most prominent example of the company’s refined manufacturing strategy, Kite revealed in 2019 that it would build a 67,000-square-foot facility at its biologics site in Oceanside, California, to bring vector manufacturing in-house. Prior to that move, the company relied on contractors for the essential material.
"Internal vector production ensures reliable supply of the key CAR T component in support of both our commercial and clinical manufacturing for patient therapies," Alquist said.
"Our dedicated resources for incorporating and designing viral vector methods and processes currently supplies retroviral vector to Kite’s CAR T facilities, and we now are advancing our lentiviral vector manufacturing in support of pipeline products," she continued.
Anito-cel preparations
Alquist spoke with Fierce as Kite gears up for the potential approval of its third CAR-T, the Arcellx-partnered anito-cel, toward the end of the year. Ahead of the potential launch, Kite’s commercial facility in Frederick, Maryland—already tapped to supply the medicine for the company’s clinical program—is preparing to scale up for the product’s market rollout, Alquist said.
Kite unveiled designs on the facility back in 2019, drafting plans for a 279,000-square-foot facility some 20 miles west of Baltimore. When the FDA signed off on the site in 2022, Kite proclaimed that the facility—alongside its plants in Southern California and Amsterdam—constituted the world’s “largest, dedicated in-house cell therapy manufacturing network.”
The expected turnaround time for anito-cel—which describes the timeline under which a patient's cells are removed, genetically reengineered in the lab and then reinfused back into the patient—sits at 14 to 17 days, comparable to therapies like Yescarta, Kite’s global head Cindy Perettie told Fierce Biotech last year.
In vivo ambitions
As for upcoming manufacturing innovations that have caught Alquist’s attention, the Kite exec pointed to an area in which her company is now operating—in vivo CAR-T therapy—calling the potential of the approach “incredibly disruptive” and noting that she believes the field is “at the cusp of another major breakthrough.”
Unlike traditional, autologous CAR-Ts, in vivo therapies utilize gene therapy to tweak T cells while still inside the patient, potentially offering a much simpler form of treatment. Gilead dove into the space with a $350 million buyout of in vivo player Interius BioTherapeutics last summer.
Meanwhile, Kite also paid $120 million upfront to China biotech Pregene in a separate in vivo CAR-T development pact.
“There’s probably more of a balance between in vivo and ex vivo over the next decade,” Alquist speculated. “It’s not going to come over and cannibalize ex vivo right away, but I do think it is an incredible opportunity to think about how we could deliver those therapies more traditionally.”
Aside from the therapeutic promise of in-vivo CAR-Ts, Alquist noted that the evolution of the class “doesn’t have all the complex logistics for the patient and for manufacturing and for the supply chain.”
“It truly goes back to more traditional manufacturing, the vectors themselves, and being able to deliver those and distribute them much more easily compared to a traditional autologous therapy,” she said.
"As an off-the-shelf therapy that would not require patients’ immune cells first, in vivo creates the opportunity logistically to increase access for more patients and to deliver to them sooner," Alquist added.
Elsewhere, regarding Kite and Gilead’s broader positioning against the policy and tariff backdrop stemming from the United States, Alquist noted that Kite built its manufacturing network “regionally,” with plants in the U.S. and Europe, the latter of which also serves the Middle East, as well as a distribution center in Japan.
Beyond geopolitical considerations, “our goal was to be as close to patients as possible,” Alquist said.