CF is a rare, life-threatening, genetic disease that affects approximately 80,000 patients worldwide and approximately 30,000 patients in the United States. CF is a chronic disease that affects the lungs and digestive system. CF patients, with significantly impaired quality of life, have an average lifespan approximately 50% shorter than the population average, with the median age of death at 40. There currently is no cure for CF. CF patients require lifelong treatment with multiple daily medications, frequent hospitalizations and ultimately lung transplant, which is life-extending but not curative. CF is caused by a mutation in the gene for the CFTR protein, which results in abnormal transport of chloride across cell membranes. Transport of chloride is required for effective hydration of epithelial surfaces in many organs of the body. Normal CFTR channel moves chloride ions to outside of the cell. Mutant CFTR channel does not move chloride ions, causing sticky mucous to build up on the outside of the cell. CFTR dysfunction results in dehydration of dependent epithelial surfaces, leading to damage of the affected tissues and subsequent disease, such as lung disease, malabsorption in the intestinal tract and pancreatic insufficiency.
Galapagos and AbbVie entered into a global alliance to discover, develop and commercialize novel therapies in cystic fibrosis (CF) in September 2013. Galapagos and AbbVie aim to develop a triple CFTR combination therapy to address 90% of patients with CF. In order to bring a more effective therapy to patients, the companies have developed multiple candidates and backups for each of the three components of a potential triple combination. Triple combinations of CF compounds in the portfolio have consistently shown restoration of healthy activity levels in in vitro assays with human bronchial epithelial (HBE) cells of patients with the F508del mutation. These combinations result in a statistically significant increase in chloride transport over Orkambi in HBE cells with the homozygous F508del mutation. It is expected that a triple combination therapy from this collaboration will be tested in patients having the F508del mutation in 2017.
 Orkambi® is a prescription medicine sold by Vertex Pharmaceuticals, used for the treatment of cystic fibrosis (CF) in patients age 12 years and older who have two copies of the F508del mutation (F508del/F508del) in their CFTR gene.
On track to a triple combo therapy
Slide deck investor get-together, 27 October at the Rozen Plaza, Orlando
Dr Katja Conrath on Galapagos' CF program at UK CF Conference
Nottingham, 8 September 2016
Screening for corrector - potentiator combinations
Corina Balut, et al
The way forward in drug testing is mutation specific
Novel corrector-potentiator combinations for treating Cystic Fibrosis
Katja Conrath, et al
Presentation at Wells Fargo CF Seminar 2014
Novel potentiators for treating Cystic Fibrosis
Katja Conrath, et al