frexalimab + rilzabrutinib + brivekimig

frexalimab + rilzabrutinib + brivekimig is an investigational combination therapy being developed by Sanofi for the treatment of proteinuric glomerular diseases, including focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). The regimen integrates three distinct mechanisms of action: frexalimab, a monoclonal antibody that inhibits the CD40/CD40L costimulatory pathway; rilzabrutinib, an oral, reversible, covalent inhibitor of Bruton's tyrosine kinase (BTK); and brivekimig, a bispecific Nanobody (VHH) targeting both tumor necrosis factor-alpha (TNFα) and OX40 ligand (OX40L). By simultaneously modulating B-cell signaling, T-cell costimulation, and pro-inflammatory cytokine pathways, the combination aims to address the complex immune dysregulation underlying glomerular injury and reduce proteinuria. It is currently being evaluated in Phase 2 clinical trials.