Fate Therapeutics Presents Updated Preliminary Data on iPSC-Derived CAR-T for Active Lupus Nephritis

Key Points

• Fate Therapeutics reported preliminary Phase 1 data for FT819, an off-the-shelf anti-CD19 CAR T-cell product candidate, in systemic lupus erythematosus with lupus nephritis.
• Both patients with active lupus nephritis evaluated at Month 6 after FT819 and bendamustine conditioning achieved a complete renal response or primary efficacy renal response.
• Across 29 autoimmune patients receiving a single FT819 dose after less-intensive conditioning, the company reported no dose-limiting toxicities or cytokine release syndrome above Grade 2.

Fate Therapeutics, a clinical-stage biopharmaceutical company developing induced pluripotent stem cell (iPSC)-derived cellular immunotherapies for cancer and autoimmune diseases, announced updated preliminary Phase 1 data for FT819 in patients with systemic lupus erythematosus (SLE) with lupus nephritis (LN). FT819 is an off-the-shelf, CD19-targeting chimeric antigen receptor (CAR) T-cell product candidate. The findings came from the ongoing FT819-102 study.

In the active LN cohort receiving FT819 after bendamustine conditioning, both patients evaluable at Month 6 achieved a complete renal response (CRR) or primary efficacy renal response (PERR). This conditioning regimen was selected for the ongoing Phase 2 RECLAIM-LN study. Patients discontinued standard-of-care therapy per protocol, although hydroxychloroquine and low-dose prednisone were permitted.

Safety findings

Fate reported safety findings across 29 autoimmune patients, including patients with SLE, who received a single dose of FT819 following less-intensive, fludarabine-free conditioning:

• No dose-limiting toxicities, immune effector cell-associated neurotoxicity syndrome (ICANS), graft-versus-host disease (GvHD), immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), or deaths were reported.
• No cytokine release syndrome (CRS) above Grade 2 was observed. Grade 1–2 CRS occurred in 5 patients (17.2%).
• Grade ≥3 infections occurred in 2 patients (6.9%), both urinary tract infections. Grade ≥3 cytopenias occurred in 6 patients (20.7%).

Renal response and B-cell findings

In the two patients with active LN treated with FT819 plus bendamustine who reached Month 6, mean urine protein-to-creatinine ratio (UPCr) decreased by approximately 50% from baseline. A CRR was sustained through Month 24 in the single patient who had reached that time point.

In the broader Regimen A cohort, which used either cyclophosphamide or bendamustine conditioning, Fate reported a 50% renal response at Month 6 among six evaluable patients with LN. Patients discontinued immunosuppressant medications before FT819 treatment, with hydroxychloroquine and low-dose prednisone permitted.

The company also reported improvements in disease activity and fatigue. Clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores declined as early as Month 1 in patients with active LN and in the overall SLE population (n=11), with reductions maintained in patients with longer follow-up. Physician Global Assessment (PGA) scores fell by approximately 75% from baseline by Month 6. Patient-reported Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) scores improved twofold from baseline by Month 6, with mean scores moving out of the range associated with moderate-to-severe fatigue.

Fate reported durable B-cell depletion in 11 patients and targeting of B cells in secondary lymphoid tissue in three patients. During B-cell reconstitution, B-cell levels reached the normal range in many patients. At Month 6, the reconstituted population had a higher proportion of naïve B cells and a lower proportion of class-switched memory B cells (n=5).

The 50 most abundant B-cell receptor clones present at baseline were absent by Month 1 after FT819 treatment and did not re-emerge through Month 6. The company described the loss of these dominant clones, which may include disease-driving autoreactive B cells, together with naïve B-cell reconstitution as suggestive of an immune reset.

RECLAIM-LN and manufacturing

The ongoing Phase 2 RECLAIM-LN study (FT819-201), described by Fate as potentially registrational, is evaluating FT819 in patients with refractory, moderate-to-severe SLE with LN using bendamustine conditioning. The regimen avoids fludarabine, which is cleared by the kidneys and requires dose adjustment in patients with impaired renal function.

FT819 is manufactured from a clonal master iPSC bank rather than from each patient’s own cells. Fate says the product can be stored in inventory for on-demand use and is produced at a low cost of goods.

The research also received funding from CIRM through grants CLIN2-16303 and CLIN2-20291.

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