Galapagos NV, a clinical-stage biotechnology company, recently delivered a joint presentation with AbbVie during the 38th annual conference of the European Cystic Fibrosis Society held in Brussels, Belgium. The presentation revealed co-developed technologies to address CF, part of Galapagos’ pipeline that includes three Phase 2 programs, two Phase 1 trials, five pre-clinical studies, and 20 discovery small-molecule and antibody programs for cystic fibrosis, inflammation, and other indications.
Dr. Corina Balut of AbbVie presented the study titled “Development of Trafficking Assays to Evaluate Novel Corrector-Potentiator Combinations,” which revealed new assays that are being developed by both companies to test the effects of corrector molecules in the rescue of CFTR-F508del — a mechanism of action that could offer promising therapeutic value for CF patients. The presentation also disclosed information regarding new insights into the influence of each component in these combined “cocktails.”
Among these “cocktails” is the CFTR with an MSD discovery platform, which the companies believe can provide a more sensitive and accurate method to study the endocytosis and degradation rate of plasma membrane CFTR.
This new assay also describes the effect of various correctors at the surface of cells, allowing company researchers to better understand how the compound works.
The companies’ co-development projects are the result of a partnership agreement to develop and commercialize molecules addressing CFTR gene mutations in patients with cystic fibrosis. These include the potentiator GLPG1837, which is currently in a Phase 1 trial and is expected to enter a Phase 2 study in class III mutation patients before end 2015, and the corrector GLPG2222, which is in the pre-clinical candidate stage and is expected to enter Phase 1 before the end of 2015.
Galapagos and AbbVie hope to nominate a second novel corrector by Q3 2015 and complete the triple combination therapy discovery phase. This second novel corrector is expected to enter Phase 1 in Q2 2016.
Cystic fibrosis is a life-threatening disorder that causes severe damage to the lungs and digestive system. An inherited condition, cystic fibrosis affects the cells that produce mucus, sweat and digestive juices. These secreted fluids are normally thin and slippery. In cystic fibrosis, a defective gene causes the secretions to become thick and sticky. Instead of acting as a lubricant, the secretions plug up tubes, ducts and passageways, especially in the lungs and pancreas.
The CFTR gene, also known as “cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7),” provides instructions for making the CTFR protein. This protein functions as a channel across the membrane of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. The channel transports negatively charged particles called chloride ions into and out of cells. The transport of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus.
Mucus is a slippery substance that lubricates and protects the lining of the airways, digestive system, reproductive system, and other organs and tissues. The CFTR protein also regulates the function of other channels, such as those that transport positively charged particles called sodium ions across cell membranes. These channels are necessary for the normal function of organs such as the lungs and pancreas.
Given the key role that the CTFR mutation plays in cystic fibrosis, both Galapagos and Abbvie feel that their novel, co-developed technologies are well-positioned to potentially make a substantial impact in effectively treating patients with the disease.