On July 9th, Fate Therapeutics announced that U.S. Food and Drug Administration has approved the first IND application for iPSC-derived allogeneic CAR-T cell therapy FT819 for the treatment of recurrent/refractory B-cell malignant tumors, including chronic lymphoblastic leukemia (CLL), acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL).

FT819 is designed to address a number of limitations related to current patient and donor-derived CAR-T cell therapy and is the first spot-type, iPSC-derived CAR-T cell product. It is designed with a variety of innovative functions designed to improve the safety and effectiveness of CAR-T cell therapy:

  • Use a clonal master iPSC line as the starting cell source, so that CAR-T cells can be produced in large quantities and supplied from stock.
  • In order to prevent graft-versus-host disease (GvHD), it completely eliminates the expression of T cell receptor (TCR).
  • It binds a new 1XX CAR signal domain, which can expand the effector function of T cells without causing failure.
  • The direct insertion of CAR transgene directly into the T-cell receptor alpha constant (TRAC) locus, which promotes unified CAR expression and enhances the potency of T cells.

“The clearance of our IND application for FT819 is a ground-breaking milestone in the field of cell-based cancer immunotherapy. Our unique ability to produce CAR T cells from a clonal master engineered iPSC line creates a pathway for more patients to gain timely access to therapies with curative potential,” said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. “Four years ago, we first set out under our partnership with Memorial Sloan Kettering led by Dr. Michel Sadelain to improve on the revolutionary success of patient-derived CAR T-cell therapy and bring an off-the-shelf paradigm to patients, and we are very excited to advance FT819 into clinical development.”

At the American Association for Cancer Research (AACR) Virtual 2020 Meeting, the Company presented preclinical data demonstrating FT819 is comprised of CD8αβ T cells with uniform 1XX CAR expression and complete elimination of endogenous TCR expression. Additionally, data from functional assessments showed FT819 has antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines that is comparable to that of healthy donor-derived CAR T cells, and persists and maintains tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia.