Galapagos NV has announced the advancement of development plans for a triple combination Cystic fibrosis (CF) therapy consisting of GLPG2665, one of the multiple C2 correctors developed by the company, corrector GLPG2222 and potentiator GLPG1837. The new plans to develop the therapy is the result of an ongoing collaboration between Galapagos and AbbVie in an effort to discover drugs that act on major mutations in CF, such as the most common CFTR mutations F508del and G551D.
Cystic fibrosis is a chronic, life-threatening disease that affects the respiratory and digestive systems. CF is caused by mutations in the CFTR gene. The CFTR protein created by the gene normally acts as a chloride channel, transporting chloride ions across cell membranes, leading to the production of mucus that protects the lining of airways. Mutations in this protein lead to deficient chloride ion transport and, consequently, obstruction of airways and glands and deficient lung and pancreatic function.
To address this mutation, Galapagos created a portfolio of new C2 corrector compounds with different modes of action, and has chosen GLPG2665 for pre-clinical development. This decision is based on results of the triple combination therapy with this compound that demonstrated a restorative effect on human bronchial epithelial (HBE) cells in patients with the F508del (class II) mutation. Researchers also compared the therapy’s efficacy against those obtained with Orkambi, a CF drug marketed by Vertex Pharmaceuticals. Chloride transport with the combination therapy was six times greater with the triple medicine combination than the improvements observed with Orkambi in HBE cells with F508del mutation in both maternal and paternal genes (homozygous mutation). Galapagos’ triple combination therapy has the potential to treat 80% of the mutations known in CF patients. GLPG2665 is expected to enter Phase I studies next year.
“This is a critical step in the development of our cystic fibrosis portfolio,” said Onno van de Stolpe, CEO of Galapagos. “The collaboration with AbbVie delivered novel corrector GLPG2665, the first of multiple correctors to complement our triple combination therapy. The race to bring a truly disease-modifying therapy to the vast majority of patients with CF has started, which is good news for the patients. Galapagos is fully committed to advancing our combination therapy GLPG1837, GLPG2222, and GLPG2665 as rapidly as possible.”