PLA2R-CAART is being developed to treat patients with PLA2R-associated membranous nephropathy (MN), a B cell-mediated autoimmune disease that affects the kidneys. B cells produce autoantibodies, which are believed to form immune complexes that are deposited at the glomerular basement membrane, causing damage of the filtration barrier, and leading to proteinuria. Over time, PLA2R-associated MN may cause kidney failure and end-stage renal disease.
PLA2R-CAART targets B cells that produce autoantibodies against phospholipase A2 receptor (PLA2R), a single-pass transmembrane protein expressed in the glomerulus of the kidney.
Primary MN is an immune-mediated kidney disease that affects approximately 15,000 patients in the United States and is associated with autoantibodies directed to PLA2R in 70-80% of patients. Since the discovery of anti-PLA2R autoantibodies in 2009, evidence has shown that these autoantibodies accumulate as immune complexes in the glomeruli of the kidney and damage the filtration barrier, leading to nephrotic syndrome as characterized by proteinuria. Many patients with PLA2R-associated MN are at risk for progression to kidney failure. Immunosuppressive therapies are commonly used, with rituximab increasingly employed to treat medium to high-risk patients. However, high unmet need remains as a significant fraction of patients either relapse or fail to respond following treatment with immunosuppressive therapies. We believe PLA2R-CAART could selectively deplete the PLA2R-autoantibody producing B cells that cause disease, providing a potentially safe, effective and durable therapeutic option for patients with PLA2R-associated MN.
