Vofatamab (B-701) is a highly specific human anti-FGFR3 antibody, for the treatment of bladder cancer, also referred to as urothelial cell carcinoma (UCC). Vofatamab is highly selective for FGFR3 and does not bind to the other fibroblast growth factor receptors (FGFRs 1,2 and 4). It is being used to inhibit signaling through this pathway in bladder cancers that express wild-type or mutated FGFR3 and has potential for application in other FGFR3 expressing cancers.

Fibroblast Growth Factor Receptor is a cell surface receptor for ligands called fibroblast growth factors (FGFs). FGFs regulate the growth and differentiation of cells through complex combinatorial signaling pathways, including binding with a family of 4 tyrosine kinase FGF receptors (FGFRs). In humans, there are 22 FGFs and 4 FGF receptors (FGFR1, FGFR2, FGFR3, and FGFR4). Each of the FGFRs has an extracellular domain for ligand binding, a transmembrane domain, and an intracellular split tyrosine kinase domain. The extracellular ligand-binding region of FGFR3 has three immunoglobulin-line domains (IgD1 – 3).

The receptor FGFR3 in its native state is a monomer. The binding of FGF ligands to FGFR3 leads to receptor dimerization, which then triggers a downstream cascade of cellular events, starting with phosphorylation of the intracellular domain of the FGFR3 receptor which in turn results in triggering a number of intracellular pathways, which ultimately regulate the growth and differentiation of cells.

Vofatamab (B-701) is a human IgG1 monoclonal antibody that is specific for the FGFR3 and does not interact with the other FGFRs, i.e., FGFR1, FGFR2, or FGFR4. It is being used as an investigational treatment for medical conditions that are caused by activation of wild-type or mutated forms of FGFR3.