Our late-stage product candidate, belumosudil (KD025), is an orally administered, selective inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2), a signaling pathway that modulates immune and fibrotic processes. A pivotal study of belumosudil is ongoing in patients with chronic graft-versus-host disease (cGVHD), a complication following hematopoietic cell transplantation (HCT) that results in multi-organ inflammation and fibrosis. A Phase 2 clinical trial of belumosudil is also underway in systemic sclerosis (SSc), a chronic immune disorder characterized by fibrosis of the skin and internal organs. ROCK mediates cell movement, shape, differentiation and function. Kadmon’s research has helped define the role of ROCK in the pathogenesis of many diseases, including immune and fibrotic diseases. Specifically, our research has demonstrated that belumosudil helps to resolve immune dysregulation by down-regulating pro-inflammatory Th17 cells and increasing regulatory T (Treg) cells.
ROCK is downstream of major pro-fibrotic mediators and regulates multiple fibrotic processes, including stress fiber formation, myofibroblast activation and pro-fibrotic gene transcription. Belumosudil down-regulated key fibrotic processes in preclinical models, including profibrotic gene transcription, stress fiber formation, myofibroblast activation and collagen deposition.