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Cellectis surges on Pfizer CAR T-cell cancer deal: $80M up front, $31M equity, $2.775B milestones

By Cormac Sheridan, Staff Writer

Shares in Cellectis SA surged more than 50 percent during early trading in Paris on Wednesday after Pfizer Inc. unveiled a strategic collaboration in cancer based on the French firm’s allogeneic chimeric antigen receptor T-cell (CAR T-cell) platform, which will involve an initial outlay of about $111 million, as well as research funding, milestones that could reach as much as $2.775 billion in total, and tiered royalties on any products that reach the market.

It’s a late, but dramatic entry to the cancer immunotherapy stage for the big pharma firm. New York-based Pfizer is paying $80 million up front and will acquire a 10 percent stake in Paris-based Cellectis, at a cost of €23.2 million (US$31.4 million), by purchasing newly issued shares priced at €9.25 per share – a substantial premium over the company’s closing share price of €6.20 immediately before the deal was disclosed.

Pfizer will also pay up to $185 million in development, regulatory and commercial milestones per product. The deal gives Pfizer exclusive rights on CAR T-cell therapies directed at up to 15 different oncology targets. Also included under the banner of the deal are another 12 targets selected by Cellectis. Pfizer will have first right of refusal on four of them, and it will provide research funding for these programs as well as for the Pfizer-designated programs. The two companies will collaborate on preclinical development of these therapies. Cellectis will work independently on the other eight.

It’s unlikely that the full scope of the deal will ever be realized. Cellectis is already busy working an alliance with Neuilly-sur-Seine, France-based Les Laboratoires Servier, which involves another six targets, including its most advanced product UCART19, a B-cell targeting therapy in development for leukemia.

However, the deal will move Cellectis’ distinctive take on CAR T-cell therapy into the fast lane. The company aims to leapfrog other developers of CAR T-cell therapies by industrializing an allogeneic approach to the field, which would substantially reduce the costs and the logistical complexities associated with present autologous or patient-specific approaches. Existing therapies that have already entered clinical trials are based on T-cells that are usually modified ex vivo by the addition of a viral vector, which results in the T-cell expressing an extracellular antigen-binding domain (typically an antibody fragment) connected, via a transmembrane domain, to a cytoplasmic signaling domain, such as the CD3 T-cell receptor zeta chain. Further iterations involve the addition of a second signaling domain and a co-stimulatory domain, to enhance the strength of the T-cell response.

Current leaders in the field include Carl June at the University of Pennsylvania, who has teamed up with Basel, Switzerland-based Novartis AG; Seattle-based Juno Therapeutics Inc., which brings together researchers from Memorial Sloan-Kettering Cancer Center, in New York; the Fred Hutchinson Cancer Center in Seattle; and the University of Washington Medical School, also in Seattle; and Cambridge, Mass.-based Bluebird Bio Inc., which has entered an alliance in the area with Celgene Inc., of Summit, N.J.

Cellectis employs the Talens (transcription activator-like effector nucleases) protein-based genome editing technology to reprogram T-cells more comprehensively. This involves the use of a tailored fusion protein comprising a selective DNA-binding Tal effector protein with a DNA cleavage domain derived from the FokI bacterial endonuclease. UCART19, its lead program, which is due to enter the clinic next year, targets the B-cell antigen CD19 and carries T-cell activation signals, like a conventional CAR T-cell construct. However, these cells also carry additional gene edits. Their CD52 receptor has been removed, which allows for potential use of alemtuzumab, a leukemia drug, without damaging the CAR T-cells. And the alpha chain of the T-cell receptor has been spliced out to prevent potential graft versus host reactions.

In Pfizer, Cellectis has found a partner whose scientific reputation has taken a battering this year, because of its perceived focus on tax inversion rather than innovation in its unsuccessful attempt to acquire London-based Astrazeneca plc.

Until recently, Pfizer has been more of a dabbler than a full-blown enthusiast in cancer immunotherapy. But it is beefing up its expertise in the area through a research agreement it entered in January with the University of Texas MD Anderson Cancer Center, in Houston. It is also collaborating with Merck & Co., of Whitehouse Station, N.J., on combination trials of its antibody PF-05082566, an agonist of the co-stimulatory receptor 4-1BB (also called CD137), and Merck’s programmed death 1 (PD-1) inhibitor MK-3475.

One side effect of the deal is a very tidy profit for a U.S. syndicate, which bought into Cellectis’ recent €20.5 million capital increase at €5.13 per share. (See BioWorld Today, April 2, 2014.)

The stock purchase requires approvals from two thirds of Cellectis shareholders. It has already secured approvals representing 52.8 of the company’s stock. The share price surge – the stock (PARIS:ALCLS) was changing hands at €10.07 by 3:20 p.m. UTC, a gain of 62 percent – indicates that this threshold will not be a significant obstacle. 

See the next edition of BioWorld Today for more on this story.