The natural role of the CD95 ligand (CD95L) is to maintain immune homeostasis by induction of apoptotic T cell death. Dysregulation of CD95L has been reported in various diseases such as cancer and viral infections (influenza, SARS, MERS, and COVID-19).
Throughout disease progression of viral infections such as influenza or COVID-19, CD95L causes severe dysregulation of the immune system. This results in two major pathological problems – reduced lymphocyte counts (lymphopenia) and inflammatory cell death, leading to pneumonia and acute respiratory distress syndrome (ARDS), respectively.
Published data show that CD95L levels are increased in the lung of ARDS patients and cause the inflammatory death of epithelial cells. The addition of CD95L inhibitors prevents epithelial cell death in ARDS and thereby offers new therapeutic options for ARDS. Apogenix has developed a proprietary diagnostic CD95L antibody to determine CD95L expression levels in COVID-19 patients to serve as a potential biomarker for the use of CD95L inhibitors.
Newly published evidence indicates that CD95L plays a role in the induction of life-threatening lymphopenia and inflammatory cell death in COVID-19 patients. Studies in Chinese COVID-19 patients consistently report that the severity of lymphopenia correlates with the severity and the outcome of the disease.
Asunercept is a fully human Fc-fusion protein that specifically binds to CD95L, thereby preventing apoptotic cell death of immune cells or epithelial cells. By blocking CD95L, asunercept could reduce CD95L-mediated lymphopenia and the excess of inflammatory cell death reported in ARDS patients. By directly targeting two critical pathogenic mechanisms, asunercept could therefore represent a unique therapeutic approach for viral infections such as COVID-19.