Cellectis boosts its coffers in revised off-the-shelf CAR-T deal with Servier
Years before the CAR-T therapies Kymriah and Yescarta hit the market, two French companies joined forces in a quest to bring off-the-shelf immunotherapies based on gene-edited allogeneic CAR-T cells to fruition.
Now, the players Cellectis and partner Servier have amended the terms of their collaboration, six years after they first inked a deal to co-develop Cellectis’ lead product candidate, UCART19, in addition to five other product candidates targeting solid tumors.
Under the 2014 deal, Cellectis received $10 million upfront and was eligible to get up to $140 million for each of the six product candidates potentially developed. Years later, Servier exercised its option to acquire exclusive global rights to further develop and commercialize UCART19. Servier and Allogene, an outfit run by Kite vets Arie Belldegrun and research chief David Chang, now are working on the therapy together and the CD19 therapy is currently is in an early-stage trial for the treatment of relapsed/refractory acute lymphoblastic leukemia.
On Wednesday, Cellectis handed the global license to develop and sell all next-generation gene-edited allogeneic CAR T-cell candidates targeting CD19 to Servier. In doing so, Cellectis will receive an additional $26.7 million upfront and is eligible to get up to $410 million per product in milestone payments, in addition to royalties.
Meanwhile, Cellectis is set to regain exclusive control over the five undisclosed allogeneic CAR-T cell targets previously covered by the initial Servier agreement.
Existing CAR-T therapies are engineered to work in this way: Cells are extracted from the patient and then manipulated in a lab where chimeric antigen receptors are added to direct the patient’s own T cells to snuff out specific cancer cells once re-infused back into the patient. By targeting CD19, a marker present on almost all B cells, CAR-T therapies have shown remarkable potency and durability in a number of blood cancers, including acute lymphoblastic leukemia (ALL).
Despite their abundant promise, the adoption of CAR-T therapies — Novartis’ Kymriah and Gilead’s Yescarta — has underwhelmed initial expectations. The uptake of Kymriah was plagued by manufacturing problems, and despite Novartis’ attempt to expand its capacity, sales continue to disappoint commercially, giving Yescarta an edge in the market.
Meanwhile, big side effects — notably life-threatening episodes of cytokine release syndrome and neurotoxicity — as well as the therapies’ expensive price tags have also limited their use. A raft of drug developers including Cellectis, Servier and Allogene are working on a fix for some of these constraints by developing off-the-shelf CAR-T therapies, designed to smoothen manufacturing complexities by using healthy donor cells.