CD40-L Blockade for Prevention of Acute Graft-Versus-Host Disease

The approach builds upon extensive evidence supporting the benefit of CD40L blockade in
disrupting key signaling events associated with immune activation. The trial addresses a
pressing clinical need, namely prevention of Graft-Versus-Host Disease (GVHD) after
hematopoietic cell transplantation (HCT) and promotion of donor-recipient immune tolerance.
The safety profile of this anti-CD40L antibody overcomes major prior limitations, and the
planned biologic studies will provide significant mechanistic insight.

Inclusion Criteria:

- Hematologic malignancy or blood disorder requiring allogeneic HCT

- Adequate vital organ function

- Karnofsky Performance Status Score (KPS) ≥ 80%

- Participants must have an available 8/8 HLA-A, -B, -C, and -DRB1 matched-related or
unrelated donor

Exclusion Criteria:

- Active infection not controlled with appropriate antimicrobial therapy

- HIV, hepatitis B or C infection

- HCT-CI (comorbidity index) > 4

- Anti-thymocyte globulin, or cyclophosphamide administered within 14 days before or
planned to receive with HCT conditioning or as part of GVHD prophylaxis in the 14 days
after HCT