Background/Rationale

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 CD95 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.

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.

 

Image of Epithelial Cell Death
 

Phase II Clinical Trials

Apogenix is in advanced discussions with clinical centers across Europe to evaluate asunercept for the treatment of COVID-19 in two controlled phase II clinical trials in Europe. In Austria, Apogenix will participate in an open-label, randomized, controlled study organized as an “investigator initiated trial” (IIT) in hospitalized COVID-19 patients. The Austrian study will recruit 100 patients. In an Apogenix-sponsored trial across Europe, the plan is to recruit 400 patients. This trial is also designed as an open-label, randomized, controlled study in hospitalized COVID-19 patients. Apogenix is currently evaluating the expansion of this trial to include clinical centers in the US. Patient recruitment is scheduled to begin in Q2/2020.

The primary endpoint of both trials is the time to sustained improvement by one category from admission on the WHO 7-point clinical performance scale, which will be measured daily until day 29. Efficacy endpoints include improvements of WHO scale, oxygenation, viral clearance, length of hospitalization, and mortality at days 15 and 29. The final data analysis is expected in Q1/2021.