Our second product candidate, VIB4920, is a fusion protein designed to bind to CD40L on activated T cells, blocking their interaction with CD40-expressing B cells. We believe this approach could inhibit the stimulation of dendritic cells and monocytes, thereby reducing the production of molecules that cause inflammation endemic to T and B cell-driven diseases.
Encouraged by results from a Phase 1b trial in rheumatoid arthritis which demonstrated proof of concept, we have decided to further pursue the development of VIB4920. We have selected Sjögren’s syndrome and kidney transplant rejection as initial indications, both of which are associated with the CD40/CD40L co-stimulatory pathway.
Sjögren’s syndrome is a chronic, systemic autoimmune disease involving inflammation and destruction of the salivary and lacrimal (tear duct) glands, which contribute to the hallmark dry mouth/dry eye symptoms. Aside from other serious complications, including extreme fatigue and chronic pain, Sjögren’s syndrome is often accompanied by additional autoimmune diseases, such as systemic lupus erythematosus (SLE) or rheumatoid arthritis. It’s estimated that one million people in the United States suffer from Sjögren’s—most of whom are women in their late 40s. There is no cure, and supportive treatment is aimed at relieving extensive dryness.
Beyond Sjögren’s, the blockage of the CD40/CD40L pathway may be effective in preventing kidney transplant rejection. Current regimens used to prevent rejection following kidney transplant commonly rely on a combination of CD28/B7 pathway blockade with belatacept and calcineurin inhibitors. While generally effective, these regimens are associated with slow deterioration of kidney function as a result of calcineurin inhibitor toxicity. We are also studying VIB4920 in a proof of concept study in combination with belatacept to determine if it is able to produce similar or reduced rates of kidney transplant rejection compared to current calcineurin-based regimens, while avoiding the renal toxicity associated with calineurin inhibitors.