DUBLIN – Pfizer Inc. and Les Laboratoires Servier SAS both moved quickly to secure an interest in Cellectis SA's UCART19 allogeneic CAR T-cell therapy, which recently attained clinical proof of concept, in spectacular fashion, in acute lymphoblastic leukemia (ALL).

Neuilly-sur-Seine, France-based Servier, which is exercising a pre-existing option on the program, is paying $38 million up front and could pay more than $300 million more in milestone payments. Paris-based Cellectis also stands to receive research funding and sales royalties.

New York-based Pfizer, meanwhile, is getting U.S. rights to the program, by entering a co-development and co-commercialization deal with Servier. Financial terms on that side of the three-way deal have not been disclosed, but the two firms will split the development costs. The deal deepens Pfizer's relationship with Cellectis, following the strategic alliance the two companies entered last year. That involves up to 15 oncology targets and up to $2.775 billion in milestones, plus $80 million up front and about $32 million in equity investment. (See BioWorld Today, June 19, 2014.)

Servier had gotten to the B-cell-targeting UCART19 program first, however, as part of a six-target deal it entered with Cellectis back in February 2014. The therapy is about to enter phase I trials in chronic lymphocytic leukemia (CLL) as well as ALL. But it has already grabbed headlines on the back of its successful treatment, on a compassionate-use basis, of an 11-month-old girl at Great Ormond Street Hospital (GOSH) in London.

The child, called Layla, had a highly aggressive form of ALL. She had exhausted all available options, including a stem cell transplant and Amgen Inc.'s CD19-directed bispecific T-cell engager antibody Blincyto (blinatumomab), and was facing palliative care. Working with Cellectis's development partner, the University College London (UCL), the GOSH team administered a single dose of UCART19, which induced remission, at least within the limited period of follow-up they reported, with no apparent perturbation of her cytokine levels or any other significant toxicity. The case report will be presented on Dec. 5 at the American Society for Hematology meeting in Orlando, Fla.

The data vindicate Cellectis's allogeneic approach to CAR T-cell therapy, particularly as Layla's treating team was unable to raise sufficient CD19 cells in order to generate an autologous CAR T-cell population. UCART19 cells are generated using the TALENS (transcription activator-like effector nucleases) genome-editing technology, to disrupt T-cell receptor expression, in order to reduce the risk of graft-vs.-host disease, and to delete the CD52 receptor, in order to render the administered CAR T cells insensitive to alemtuzumab, a CD52-targeting antibody. The latter maneuver enables clinicians to administer the drug in order to suppress host-mediated rejection of the mismatched CD19-expressing CAR T cells.

Cellectis has long touted the vastly improved logistics associated with using an off-the-shelf, allogeneic CAR T-cell therapy over autologous approaches. If Cellectis can also build a case that some patients who are ineligible for autologous CAR T-cell therapy could benefit from an allogeneic alternative, it could build a powerful position in this emerging field. It is, of course, still some way behind its autologous rivals. Seattle-based Juno Therapeutics Inc. has commenced a phase II U.S. registration trial of its CD19-targeting JCAR015 therapy in ALL and has studies under way in B-cell non-Hodgkin's lymphoma. It is also testing two other CD19-directed therapies, JCAR017 and JCAR014, in pediatric or young adult CD19-positive leukemia and in various B-cell malignancies, respectively.

Santa Monica, Calif.-based Kite Pharma Inc. has begun two registration trials of KTE-C19 in mantle cell lymphoma and non-Hodgkin's lymphoma, and it plans to commence two further pivotal studies in ALL before year-end. Basel, Switzerland-based Novartis AG has reported positive interim data from an ongoing trial of CTL019 in patients with diffuse large B-cell lymphoma (50 percent response rate in 12 patients) and follicular lymphoma (100 percent response rate in seven patients).

Pfizer's involvement in UCART19 will doubtless accelerate its progress through clinical development. For Pfizer, the deal comes hot on the heels of good news concerning its other big bet in immuno-oncology. On Wednesday, the FDA granted breakthrough designation to the anti-PD-L1 antibody avelumab in metastatic Merkel cell carcinoma, a rare form of skin cancer, giving it and partner Merck KgaA a shot at being first to market in that niche indication. Avelumab attracted a whopping $850 million up-front payment as the principal asset in a potential $2.85 billion immuno-oncology alliance Darmstadt, Germany-based Merck entered with Pfizer last year. It is also undergoing two phase III trials as a first-line treatment in non-small-cell lung cancer, and phase III studies in ovarian cancer and urothelial cancer are due to get under way shortly. (See BioWorld Today, Nov. 18, 2015.)

Although Pfizer is still playing catch-up in immuno-oncology – and has paid dearly to gain a position in the field – what's beginning to look like an astute partnering strategy is starting to lend its efforts real momentum.