GLPG2451 + GLPG2222 + GLPG2737

A triple combination of the investigational small molecules GLPG2451, GLPG2222, and GLPG2737 developed for the treatment of cystic fibrosis, specifically targeting patients homozygous (and some heterozygous) for the F508del CFTR mutation. GLPG2451 is a potentiator that increases the open probability of the CFTR channel. GLPG2222 is a Type 1 CFTR corrector that helps correct folding and trafficking of mutant CFTR. GLPG2737 is a structurally novel Type 2 CFTR corrector, designed to further increase the amount of functional CFTR protein at the epithelial cell surface. This triple combination aims to maximize restoration of chloride transport through complementary mechanisms. In clinical studies, the triple combination showed an increased chloride transport versus dual combinations, albeit with individual dosing challenges and limited clinical benefit reported due to insufficient potentiator exposure. All components are investigational and studied primarily by Galapagos in clinical trials, most notably in the FALCON and PELICAN studies[1][2][3][5][7][8].