RICHMOND, Calif. & VALBONNE, France—When U.S.-based Sangamo Therapeutics Inc. officially announced that it planned to acquire France’s TxCell S.A., the stock price of the latter surged by about 150 percent on July 23—the day of the announcement—and continued to trade at around that rate through the next day until the close of trading on the European markets on July 24.
TxCell is a biotechnology company that develops platforms for innovative, personalized T cell immunotherapies for the treatment of severe inflammatory and autoimmune diseases with high unmet medical need. The company has been targeting transplantation as well as a range of autoimmune diseases (both T cell- and B cell-mediated), such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel diseases and inflammatory skin diseases. As FierceBiotech noted in covering the announcement, TxCell switched its focus to CAR-Tregs across 2015 and 2016, combining its background in regulatory T cells and autoimmune disorders with CAR targeting.
Under the definitive agreement reached by the two companies on July 20, Sangamo will—following the completion of the contemplated acquisition of a majority stake of TxCell—file a simplified cash tender offer for the purchase of all then outstanding ordinary shares of TxCell, at a price of €2.58 per share in cash, or approximately €72 million (about $84.3 million), on a debt-free and cash-free basis. Subject to satisfaction of closing conditions (including in particular those relating to regulations governing foreign investments in France), Sangamo expects to complete the transaction in the fourth quarter of 2018.
For Sangamo, completion of the deal could mean a leadership position in CAR-Treg development. As one might expect, CAR-Treg is a more specialized form of CAR-T (chimeric antigen receptor T cell) therapy, which has seen increasing interest among pharma and life-sciences researchers for cancer treatment. The difference is that in CAR-Treg, the focus is on regulatory T cells (Tregs)—unlike “killer T cells” used in CAR-T cell therapy, which are aimed at attacking their target, Tregs protect their target from being attacked by the immune system. Tregs are a naturally occurring subset of T cells and are critical for maintaining immune homeostasis within the body by induction and maintenance of tolerance to self-antigens.
And why does Sangamo have an interest in Tregs genetically modified with a chimeric antigen receptor? Well, it intends to evaluate the potential of CAR-Treg therapies to prevent graft rejection in solid organ transplant and to potentially treat autoimmune diseases like Crohn’s disease and multiple sclerosis.
As Sangamo put it in the announcement of the acquisition deal, “With its highly skilled and experienced team, TxCell is a leader in the emerging field of regulatory T cell (Treg) development for immunological diseases, one of Sangamo’s stated therapeutic areas of focus for its proprietary product candidate pipeline.”
Preclinical research has provided proof of concept that antigen-specific CAR-Tregs can deliver potent immunosuppression locally to targeted tissues. By contrast, currently available anti-TNF alpha small-molecule and monoclonal antibody drugs are associated with global, non-specific immune suppression, Sangamo notes.
Sangamo expects that the proposed acquisition of TxCell would accelerate the company’s entry into the clinic with a CAR-Treg therapy. In 2019, Sangamo expects to submit a clinical trial authorization application in Europe for TxCell’s first CAR-Treg investigational product candidate for solid organ transplant, and to initiate a Phase 1/2 clinical trial later in the year. In addition, Sangamo intends to use its zinc finger nuclease (ZFN) gene-editing technology to develop next-generation autologous and allogeneic CAR-Treg cell therapies for use in treating autoimmune diseases.
“We are thrilled to announce this proposed acquisition, which would combine TxCell’s Treg expertise with our ex-vivo gene-editing capabilities, positioning Sangamo as a leader in the emerging field of CAR-Treg cell therapy,” said Sandy Macrae, CEO of Sangamo. “We believe CAR-Treg therapies will prove to be as exciting for immunology as CAR-T has been for oncology.”
“We are excited to combine with Sangamo for their experience and technical expertise in gene-edited cell therapy, and we believe Sangamo’s ZFN editing technology will facilitate the precise genetic modifications needed to create a new class of Treg-based antigen and tissue specific immunosuppressive medicines,” Stephane Boissel, CEO of TxCell, commented in a press release. “Progressing such CAR-Treg products in clinical development and towards commercialization would require expertise and financial resources that were impossible for us to get as a standalone business at a reasonable cost.”