Fate Therapeutics, Inc. announced that the first patient with systemic lupus erythematosus (SLE) has been treated in the Phase 1 autoimmunity study of FT819, the Company?s off-the-shelf, CD19-targeted chimeric antigen receptor (CAR) T-cell program. In addition, at the American Society of Gene and Cell Therapy (ASGCT) 27th Annual Meeting, the Company presented translational data from the Phase 1 study of FT819 in relapsed /refractory B-cell malignancies (BCM) and initial clinical observations from the Phase 1 study of its FT522 off-the-shelf, CD19-targeted CAR NK cell program in relapsed /refractory B-cell lymphoma (BCL). Data from these programs highlight the scientific rationale and demonstrate key therapeutic mechanisms of activity for the treatment of B cell-mediated autoimmune disease.

The multi-center, Phase 1 autoimmunity study of FT819 is designed to assess safety, pharmacokinetics, and anti-B cell activity for patients with moderate-to-severe SLE (NCT06308978). The first patient, a 27 year-old woman diagnosed with SLE over ten years ago who has refractory disease despite having been treated with multiple standard-of-care therapies, received conditioning chemotherapy followed by a single dose of FT819 at 360 million cells. The patient was discharged after a three-day hospital stay without any notable adverse events.

In a "first-of-kind" translational assessment using a sample of the patient?s blood obtained prior to administration of conditioning chemotherapy, FT819 induced rapid and potent depletion of the patient?s CD19+ B cells in an ex vivo cytotoxicity assay. Translational Data for FT819 iPSC-derived CAR T-cell Program: FT819 is the Company?s off-the-shelf, CD19-targeted, 1XX CAR T-cell product candidate comprised of CD8aß+ T cells with a memory phenotype and high CXCR4 expression to promote tissue trafficking. Translational data presented at ASGCT from the Company?s Phase 1 BCM study show that a single dose of FT819 exhibited multiple therapeutic mechanisms implicated in generating an immune reset in patients with B cell-mediated autoimmune disease.

Clinical data highlighted at ASGCT include: Blood samples taken from 23 patients treated for relapsed /refractory B cell lymphoma showed rapid and deep CD19+ B cell depletion, with sustained suppression of B cells, in the periphery during the initial 30-day period following administration of standard conditioning chemotherapy and FT819; Patient case studies demonstrating secondary and tertiary tissue trafficking, infiltration, and activity, with complete elimination of CD19+ cells in tissue; and Patient case studies of plasma cell depletion and B-cell reconstitution showing recovery of naïve and immature phenotypes, with little to no recovery of activated memory B cells or plasmablasts. Notably, the Company also presented patient case studies demonstrating the capacity of FT819 to induce rapid, deep, and sustained B-cell depletion without the use of fludarabine as a conditioning agent. Collectively, these data support the potential of FT819 to reset the immune system of patients with autoimmune diseases, including as an add-on therapy to commonly-used treatment regimens.

Preclinical and Initial Clinical Observations for FT522 iPSC-derived CAR NK Cell Program Data: FT522 is the Company?s off-the-shelf, CD19-targeted CAR NK cell product candidate and its first to incorporate a novel alloimmune defense receptor (ADR), which is designed to increase the potency of off-the-shelf cell therapy and enable effective treatment without administration of conditioning chemotherapy to patients. Data highlighted at ASGCT include: In a novel re-challenge assay using peripheral blood mononuclear cells (PBMCs) from unmatched SLE donors, FT522 uniquely drove rapid and deep CD19+ B cell depletion, eliminated alloreactive T cells, and maintained functional persistence, indicating that FT522 can function effectively in the presence of an unmatched host immune system; In a preclinical in vivo biodistribution study, FT522 showed dose-dependent trafficking, infiltration, and residency in secondary and tertiary tissues without cytokine support at human dose equivalency levels of 250 million cells per dose and 1 billion cells per dose (based on 20 gram mouse and 65 kilogram human allometric conversion); and In initial clinical observations from the Company?s ongoing Phase 1 BCL study, the first two patients treated with FT522 showed rapid, deep, and sustained B-cell depletion in the periphery throughout the one-month treatment cycle. In addition, both patients showed enhanced persistence of FT522 in the periphery compared to clinical data observed with FT596, a prior-generation CD19-targeted CAR NK cell without ADR technology.

The Company intends to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) in the middle of 2024 for the treatment of various autoimmune diseases with FT522, including without administration of conditioning chemotherapy to patients.