Belatacept Conversion in Proteinuric Kidney Transplant Recipients

Background: Proteinuria develops in about 30% of kidney transplant recipients and is a strong
predictor of graft loss. The amount of proteinuria has a direct correlation with the risk of
graft failure. Novel therapies are urgently needed to reduce proteinuria and prevent graft
loss in transplant recipients, since ACE inhibitors carry a number of limitations in the
transplant setting, including significant reduction in renal function, anemia and
hyperkalemia.

Preliminary data: B7-1 is expressed at significant levels in about 10% of kidney allograft
biopsies with predominance in patients with proteinuria.

Hypothesis: We hypothesize that B7-1 targeting therapy may reduce proteinuria and improve
graft survival in proteinuric transplant recipients that have B7-1 staining on allografts. In
addition, the absence of CNI nephrotoxicity and the potential protective effect of Belatacept
on DSA production may be of benefit in this subset of transplant patients.

Objectives:

Primary: Determine the effect of Belatacept conversion in reducing proteinuria by 25% at 12
months in renal transplant recipients (≥1gram/d) that are either B7-1-positive or negative on
kidney biopsy.

Secondary: Assess the effect of Belatacept conversion in the percent change of renal function
from baseline to 12 months; donor-specific anti-HLA antibodies presence and intensity (MFI);
correlation of B7-1 positivity on immunofluorescence on biopsy with B7-1-expression in urine
extracellular vesicles; adverse events; acute rejection episodes; blood pressure control; new
onset diabetes; hyperlipidemia; graft survival; and patient survival.