Cystic fibrosis (CF) is a multisystem disease of the lungs, sinuses, pancreas, and gastrointestinal tract, and is caused by dysfunction or deficiency of the cystic fibrosis transmembrane conductance regulator protein (CFTR), an epithelial anion channel that regulates salt and water balance in tissues and maintains homoeostasis of the airway surface liquid layer of the lungs. To address the most prevalent patient population (F508del mutation), two biomolecular modulators are required, correctors to increase CFTR levels at the cell surface, and potentiators to allow the effective opening of the CFTR channel. Despite approved potentiator and poteniator/corrector combo therapies, there remains high need to develop more potent and efficacious correctors to provide robust clinical efficacy for the large patient population.<br/>As part of a broad AbbVie Galapagos CF collaboration, we have identified a highly potent series of CFTR correctors. In this presentation, I will describe structure activity relationship (SAR) studies that guided the discovery and selection of ABBV/GLPG-2222 was advanced into clinical trials and the back up effort on THP series.

Discovery of ABBV/GLPG-2222, a potent, efficacious CFTR corrector for the treatment of cystic fibrosis and back up effort on THP series

256th National Meeting (2018)

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