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.

Krishna Polu, M.D., Equillium’s former Chief Medical Officer, discusses how itolizumab uniquely modulates both the activity and trafficking of teff cells.