A new collaboration gets its start with CAR-T
NEW YORK—A global strategic collaboration has been announced between Pfizer Inc. and Paris-based Cellectis for the development of Chimeric Antigen Receptor T-cell (CAR-T) immunotherapies in oncology. Cellectis, through the use of its CAR-T platform technology, is focusing its efforts on both liquid (B cell malignancies) and solid tumors (12 antigenic targets).
Per the terms of the agreement, Pfizer will have exclusive rights to develop and commercialize CAR-T therapies in oncology, directed at a total of 15 targets it has selected. The two companies will collaborate on preclinical research, with Pfizer to assume responsibility for the development and commercialization of any CAR-T therapies for its selected targets. This agreement also covers a total of 12 targets chosen by Cellectis, with similar terms: both companies will be working together on the preclinical research for four of Cellectis’ selected targets, while Cellectis will handle the work independently on an additional eight targets and be responsible for clinical development and commercialization of any CAR-T therapeutics for its chosen targets. Pfizer will have right of first refusal to the four Cellectis-selected targets. Cellectis is looking to open a U.S. site in order to work more closely with Pfizer’s scientists.
The agreement stipulates that Pfizer will pay Cellectis $80 million up front, in addition to funding for research and development costs associated with Pfizer’s selected targets and the four targets of Cellectis’ that Pfizer will be working on. Cellectis also stands to receive development, regulatory and commercial milestone payments of up to $185 million per Pfizer product, as well as tiered royalties on net sales of any products Pfizer commercializes.
Pfizer will also enter into an equity agreement under which it will purchase roughly 10 percent of the Cellectis capital through newly issued shares at 9.25 Euro per share, subject to approval by two-thirds of the votes cast by Cellectis shareholders. At present, Cellectis shareholders representing 52.8 percent of its voting rights have undertaken to vote in favor of the issuance. Should the equity sale fail to gain shareholder approval, Pfizer has the option of terminating the collaboration agreement.
“This leading immuno-oncology collaboration aimed at delivering immunotherapies is built upon Cellectis’ advanced genome-editing and cell engineering capability and Pfizer’s cutting-edge biotherapeutic cancer therapy platform,” Dr. Mikael Dolsten, president of R&D at Pfizer, said in a press release. “Combining the innovation and scientific expertise of Cellectis with Pfizer’s deep oncology and immunology experience creates a world-class partnership designed to deliver a new generation of CAR-T immunotherapies for cancer patients with urgent medical needs.”
T cells can be grafted with a CAR, an artificial molecule “that, when present at the surface of immune effector cells, will enable them to recognize a desired protein (antigen) and trigger the killing of cells harboring this antigen at their surface,” similar to how the immune system handles a standard infection. Cellectis harvests large numbers of cells from the immune systems of healthy individuals, cells that are then genetically reprogrammed to specifically target and kill cancer cells. The resulting T cells are known as allogeneic or “donor-derived” T cells and are engineered to prevent attacks on healthy tissue and to prove resistant to the most commonly used lymphodepleting chemotherapies.
As for the CARs, they are engineered by combining domains from different proteins, each of which allow the CARs to perform specific functions. The most common CAR formation, Cellectis explains on its website, “comprises an extracellular domain containing a region that recognizes the targeted antigen and a spacer region that links it to the transmembrane domain … followed by an intracellular domain, responsible for transmitting an activation signal to the cell upon antigen recognition, causing the CAR-engineered cell to attack the tumor cell. The target-binding moiety is usually derived from an antibody, while the intracellular portion can include, besides the domain leading to cell activation and cytotoxic response, one or more domains from co-stimulatory receptor proteins that could enhance the proliferative capacity and survival of the ‘therapeutic’ cells.”
“We believe our CAR-T platform technology has the potential to offer a real advantage over other approaches to T-cell receptor engineering, and this collaboration with Pfizer is an important step towards realizing the full potential of this technology in harnessing the body’s own immune system to fight cancer,” Dr. Andre Choulika, Cellectis’ chairman and CEO, commented in a statement. “This alliance provides access to Pfizer’s state-of-the-art therapeutic development capabilities and provides a unique opportunity to advance this innovative work with the goal of developing best-in-class CAR-T therapeutics. We look forward to working closely with the team at Pfizer on researching and developing novel CAR-T therapies that could potentially change the way cancer is treated.”
According to Cellectis, its allogeneic T cells “may be used to overcome the limitations of autologous (patient-derived) adoptive immunotherapies, eventually making it possible to treat many cancer patients using a standardized, off-the-shelf therapeutic product.” The company adds that “Adoptive immunotherapy using T cell CARs is our flagship project.”