FT819 shows first clinical activity in systemic sclerosis

FT819 is a gene-edited, induced pluripotent stem cell (iPSC)-derived anti-CD19 CAR T-cell product designed for off-the-shelf use in autoimmune disease. The product was generated using targeted genome engineering. CRISPR was used to insert the CAR transgene into the TRAC locus, while simultaneously disrupting both copies of the TRAC gene to eliminate endogenous T-cell receptor expression. This design provides uniform CAR expression and reduces the risk of graft-versus-host disease.

The updated Phase 1 basket study has now enrolled 30 patients across multiple autoimmune indications, including five patients with systemic sclerosis. Preliminary efficacy analyses were available for four patients with moderate-to-severe, treatment-resistant disease. All four achieved at least an rCRISS25 (Revised Composite Response Index in Systemic Sclerosis) response three months after treatment, while one patient reached rCRISS100. Improvements were observed across multiple disease measures, including modified Rodnan Skin Score (mRSS), clinician and patient global assessments, forced vital capacity (FVC) and HAQ Disability Index, suggesting broad clinical benefit despite the small cohort.

The safety profile remained favourable. No cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), graft-versus-host disease, hypogammaglobulinaemia, dose-limiting toxicities or deaths were reported. One patient developed immune thrombocytopenia (ITP), which was managed with steroids and intravenous immunoglobulin.

The presentation also strengthens the case for outpatient administration. Three of the five patients with systemic sclerosis were treated either entirely as outpatients or discharged within 24 hours of infusion, consistent with the programme’s goal of avoiding intensive lymphodepleting chemotherapy. In addition, translational analyses again demonstrated profound peripheral B-cell depletion together with depletion of B cells in lymphoid tissue, supporting the proposed mechanism of immune resetting.

The findings were presented by Natalie J. Shiff from Fate Therapeutics on 9 July 2026 at the International Society for Stem Cell Research (ISSCR) 2026 Annual Meeting.