Wowwwww 6 maal Cl transport tov Orkambi....
Galapagos advances triple combination therapy in cystic fibrosis
Galapagos NV
1 minute ago
GlobeNewswire
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GLPG2665, a next-generation (C2) corrector, together with the other two components of the triple combination, show up to six-fold greater chloride transport than Orkambi1) in vitro
Triple combination therapy of C2 with GLPG2222 and GLPG1837 expected to address 80% of mutations in the CF population
Multiple series of C2 correctors identified, each with unique mode of action
GLPG2665 enters pre-clinical development and completes the first Galapagos-AbbVie triple combination therapy
Mechelen, Belgium; 15 October 2015: Galapagos NV (Euronext & NASDAQ: GLPG) announced today that GLPG2665 has been selected as the first next generation corrector compound candidate. Galapagos discovered multiple C2 corrector compound series, each with a different chemical scaffold and corresponding unique and complementary mode of action. GLPG2665 is the first candidate to complete the potential triple combination therapy for the delta F508 (class II) mutation in cystic fibrosis. GLPG2665 will now enter pre-clinical development, and is expected to enter Phase 1 studies by mid 2016. GLPG2665 in combination with corrector GLPG2222 and potentiator GLPG1837 consistently have shown restoration of healthy activity level in human bronchial epithelial (HBE) cells of patients with the Class II F508del mutation. The combination resulted in chloride transport up to six-fold greater than Orkambi in HBE cells with the homozygous F508del mutation. Poor functioning of the CFTR channel is the major deficit in patients with cystic fibrosis.
"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."
Advancement of the third component of the triple combination therapy into development brings the Galapagos-AbbVie collaboration closer to its goal of bringing disease-modifying therapies to CF patients. Galapagos expects to enter Phase 2 studies with potentiator GLPG1837 in Class III mutation patients and a Phase 1 study with corrector GLPG2222 in healthy volunteers by filing before year-end.
About the Galapagos - AbbVie collaboration in cystic fibrosis
In September 2013 Galapagos signed an agreement with AbbVie in which they will work collaboratively to develop and commercialize oral drugs that address the main mutations in CF patients, including F508del and G551D. Under the terms of the agreement, AbbVie made an upfront payment of $45 million to Galapagos. Upon successful completion by Galapagos of clinical development through to completion of Phase II, AbbVie will be responsible for Phase III, with financial contribution by Galapagos. Galapagos achieved a $10 million milestone in 2014 and is eligible to receive up to $350 million in total additional payments for developmental and regulatory milestones, sales milestones upon the achievement of minimum annual net sales thresholds and additional royalty payments on net sales, ranging from mid-teens to 20%.
About cystic fibrosis (CF)
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 27. 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.