Pfizer’s desire to collaborate with Cellectis on its chimaeric antigen receptor T-cell (CART) programmes is easily explained: immuno-oncology is a scorching area, and CART projects have received much attention of late. Pfizer’s confidence in the technology has spurred the French group’s share price to jump an enormous 67% to €10.38 ($14.09).
Less explicable is Pfizer’s decision to opt for a licensing deal rather than simply buying Cellectis outright. At $80m, the upfront fee is a sizeable chunk – 40% – of the company's market cap at yesterday’s close and Pfizer is hardly short of ex-US cash. Mathieu Simon, executive vice-president at Cellectis, tells EP Vantage that a buyout was never on the cards: “We were not interested in any type of M&A transaction. The board and management made it very clear [to Pfizer] that we want to remain independent,” he says.
As things stand, Pfizer has exclusive development and sales rights to CART therapies aimed at 15 molecular targets of its choice, each of which may yield more than one product candidate, Mr Simon says. A further 12 targets will be picked by Cellectis. The companies will work together on preclinical research on the Pfizer targets and four of Cellectis’s; Pfizer will have right of first refusal to these. Cellectis will work independently on the other eight.
Should the technology pan out, Cellectis is in line for a huge payday: it is eligible for milestone payments of up to $185m per Pfizer product, plus tiered royalties. If even one of these products goes the distance, Pfizer would have done far better to have bought Cellectis.
It does have a foot in the door, at least. Pfizer intends to buy a 10% stake in the company through newly issued shares at €9.25 apiece, a transaction to which 52.8% of Cellectis investors have so far agreed.
The other mystery centres on Cellectis’s technology itself. CART therapies are intended for B-cell cancers such as leukaemia, and usually involve modifying a patient’s T-cells ex vivo to make them target CD19, an antigen expressed on B-cells, before reinfusing the cells into the patient. Theoretically any antigen could be targeted, but all those currently in development appear to be aimed at CD19.
Cellectis rejects this autologous approach in favour of allogeneic cells: the modified cells administered to the patient come from a separate donor. The advantages of an off-the-shelf approach are clear: if the technology is proven to work the ease of production, storage and convenience could give Cellectis and Pfizer the edge over autologous projects such as those from Novartis and Kite Pharma, as well as various academic groups (ASH – Novartis pulls the CART in autologous T-cell therapy, December 9, 2013).
Mr Simon says that the technology Cellectis uses to alter T-cells so that they kill B-cells is also employed to modify them to be rejection-proof. In other words, the company can remove the cell-surface antigens that mark the donated cells as foreign.
Cellectis has also convinced Servier of the merits of its allogeneic cells. In February it licensed its lead leukaemia project, UCART19, plus five other candidates targeting solid tumours to the French firm. This time the terms were much lower, at $10m up front with up to $140m in milestones plus royalties (Cellectis banks on US support, March 26, 2014).
Pfizer does not have immuno-oncology expertise in-house – part of the reason it wanted AstraZeneca was to get technology in this area that originally came from MedImmune, which Astra bought in 2007. It is possible that the US giant thought it best to let Cellectis oversee CART R&D independently, but it seems likelier that it tried and failed to snare the whole company.