SL-279252 (PD1-Fc-OX40L) is currently in a Phase 1 clinical trial in subjects with advanced solid tumors or lymphomas.
SL-279252 is a bi-functional fusion protein that contains the extracellular domain (ECD) of PD1 linked to the ECD of OX40L through an IgG4 Fc linker protein. Proper folding of the OX40L side of the ARC leads to a trimer of OX40L molecules, which, when bound to OX40, potently stimulates an activation pathway in immune cells.
The ARC molecule consists of PD1 linked to OX40L through an Fc linker protein and binds to PDL1 on tumor cells and OX40 on T cells. This results in the blockade of PD1 signaling in T cells while simultaneously activating the OX40 activation pathway, leading to activated T cells in the tumor microenvironment.