Germany-headquartered Boehringer Ingelheim brought Jascayd to EU authorisation for idiopathic pulmonary fibrosis and progressive pulmonary fibrosis. Its active substance, nerandomilast, preferentially inhibits an enzyme involved in inflammatory and fibrotic processes.
Where did nerandomilast begin? Who decided to target PDE4B specifically, and what made your team believe an inhibitor of that enzyme could succeed where earlier approaches struggled?
Christoph von der Goltz: Nerandomilast has its roots in a research programme started in Biberach, Germany, in 2000, with the molecule first made and tested in 2009. Scientists had long seen potential in blocking PDE4 to address inflammation and fibrosis, but earlier approaches were limited by side effects. PDE4B breaks down cyclic AMP (cAMP), an important intracellular messenger involved in regulating fibrosis, immune responses and vascular function. Our team pursued a more targeted idea: focus preferentially on PDE4B while limiting activity against PDE4D, which was thought to contribute to gastrointestinal side effects.
The evidence built gradually. Nerandomilast showed antifibrotic, immunomodulatory and vasoprotective activity in a range of laboratory and preclinical studies, including research using lung cells from people with idiopathic pulmonary fibrosis (IPF). That consistent body of evidence supported taking it forward into clinical development.