Our fibrosis portfolio
Fibrotic disorders represent an area of significant unmet need. In the area of lung fibrosis specifically, patients have access to few drugs, which have limited benefit and side effects that often lead to discontinuation of treatment. To address the unmet need, we are building a unique fibrosis candidate portfolio with compounds that are active on different mechanisms involved in the pathogenesis of fibrosis. Our initial focus lies on IPF and adjacent indications involving lung fibrosis, with the ambition to expand to other forms of organ and skin fibrosis.
The onset of IPF starts with damaged lung epithelium, a layer that forms a protective barrier between the environment and the underlying lung tissue. The injury that occurs at this level will trigger a wound healing process, with on the immunity side the mediation of macrophages to promote tissue regeneration. To promote the closure of the wound, the macrophages will attract and activate fibroblasts. These fibroblasts, however, accumulate in an excessive way which leads to abnormal tissue repair and the deposition of extracellular matrix components that aggravate the disease. Eventually this leads to respiratory failure. GLPG1205 (GPR84 inhibitor) is believed to interfere with the immune response of lung fibrosis. In 2020, we in-licensed chitinase inhibitor GLPG4716, in preparation for a Phase 2 in IPF, with demonstrated activity on the macrophage immune response axis. In early stage development, we are advancing two other molecules from our Toledo portfolio aimed toward the immune response, two additional novel GLPG targets with a role in fibroblast activation, and one GLPG target and an in-licensed compound form Ryvu Therapeutics directed towards the extracellular matrix (see figure below).