France-based OSE Immunotherapeutics announced receipt of orphan drug designation from the US FDA for pegrizeprument (VEL-101), a pegylated monovalent antibody fragment targeting CD28, in the prevention of organ rejection in heart transplant patients. The designation may provide development incentives including tax credits, user-fee exemptions, and, if ultimately approved for the indication, seven years of US orphan exclusivity.
Pegrizeprument (FR104) is a pegylated Fab fragment — a monovalent antibody fragment conjugated with polyethylene glycol to extend circulating half-life — directed against CD28, a co-stimulatory receptor on effector T cells. Its mechanism operates on two levels: direct blockade of CD28-mediated T cell co-stimulatory signaling, and indirect preservation of the CTLA-4 immunosuppressive pathway. Because pegrizeprument binds CD28 selectively without occupying the shared ligand-binding site used by CTLA-4, the regulatory arm of the immune response remains intact. This structural approach distinguishes it from belatacept, a CTLA-4-Ig fusion protein that competes with both CD28 and CTLA-4 for their shared B7 ligands, and which has been associated with an elevated risk of post-transplant lymphoproliferative disorder in certain patient populations.
The molecule originated from research at Institut National de la Santé et de la Recherche Médicale (INSERM) in France, where the selective anti-CD28 Fab fragment concept was developed through fundamental T cell co-stimulation immunology. OSE Immunotherapeutics subsequently licensed the technology from INSERM and, in 2021, entered an exclusive licensing and co-development agreement with Veloxis Pharmaceuticals — a transplant-focused specialty company and subsidiary of Asahi Kasei Corporation — which assumed lead development responsibility, particularly for clinical advancement in the United States. OSE retains milestone and royalty interests under that arrangement.
Pegrizeprument has completed Phase I/II study, assessed in acute rejection prophylaxis and renal function in a de novo renal transplant population receiving an allograft from standard criteria donors.