Itolizumab is a clinical-stage, first-in-class immune-modifying monoclonal antibody that targets the CD6-ALCAM signaling pathway to selectively downregulate pathogenic Teff while preserving Treg cells critical for maintaining a balanced immune response. Equillium is developing itolizumab for conditions where there are limited to no treatment options, including acute graft-versus-host disease, uncontrolled moderate to severe asthma and lupus nephritis.
In preclinical studies, blockade of CD6 with itolizumab led to a reduction in Teff cell proliferation and downregulation of several important pathways that contribute to Teff cell development. The downregulation of these pathways is accompanied by decreased secretion of the pro-inflammatory Teff cytokines IFN-γ, TNF-α, IL-6 and IL-17. Additionally, inhibiting the binding of ALCAM to CD6 modulates lymphocyte trafficking and results in reduced Teff cell infiltration into inflamed tissues.