In April 2018, Promethera announced the acquisition of Swiss biopharmaceutical company Baliopharm. The transaction complemented Promethera’s pipeline with an innovative antibody-based drug candidate that specifically binds to the tumor necrosis factor receptor 1 (TNF-R1). With the TNF-alpha pathway being implicated in the progression of many inflammatory diseases, including chronic liver diseases leading to fibrosis, a therapeutic antibody approach is a valuable strategy in its own right as well as in combination with Promethera’s cell-based medicines such as the HepaStem technology. The program is currently in preclinical development.
In initial studies performed using a parental full-length monoclonal antibody, blocking TNF-R1 selectively led to a reduction in key disease parameters. Atrosimab has been derived and optimized from the parental antibody used in these initial studies. The maturation process resulted in several favorable characteristics including a 3,6-fold stronger inhibition of TNF-R1 activation than the parental antibody, a 5-fold more effective inhibition of TNF-alpha induced cell death and a 6-fold more potent inhibition of TNF-alpha mediated release of pro-inflammatory cytokines IL-6 and IL-8. Additionally, Atrosimab has been designed to feature a longer half-life than standard Fab and scFv fragments.