In 2000, EPIX Pharmaceuticals harnessed cutting-edge technology developed at Tel Aviv University to create a computer-based approach to drug discovery for diseases and ailments involving membrane proteins. Recognizing that this approach might help open up novel avenues to study and ultimately correct the defective protein CFTR, the CF Foundation met with EPIX to explore a potential collaboration.
In 2005, with significant financial support and expertise from Cystic Fibrosis Foundation Therapeutics (CFFT), the nonprofit drug discovery and development arm of the CF Foundation, EPIX researchers got to work.
Using EPIX proprietary PREDICT™ technology, researchers aimed to create a 3-D model of CFTR and then determine how small molecules could bind to the protein and reverse the effects of mutations in CFTR that cause cystic fibrosis. “With greater knowledge of the 3-D structure, we have a higher chance of identifying potential drugs to treat CF. We have applied our PREDICT™ technology to membrane proteins and have four clinical programs that resulted from our approach. Our CFTR program could one day have a meaningful impact on CF patients’ lives, and that is truly exciting,” said Chen Schor, chief business officer at EPIX.
Currently, EPIX scientists are working to identify sites within the CFTR protein that may be good targets for treatment and then EPIX expects to use their unique computer-based screening approach to search all EPIX’s compound libraries for drugs that may work on those sites. Already they are beginning to see the fruits of their labor. In 2006, EPIX scientists identified a potential binding site on the CFTR protein structure that lends itself to an in silico (computer simulation) screening approach. This past March, EPIX completed the first round of in silico screening, and has selected a set of more than 500 molecules for biological testing at a third party laboratory. By August, EPIX had successfully identified a potential compound through the application of their computational-medicinal chemistry approach to drug discovery and development. This compound could increase the levels of the CFTR protein, which may improve the activity of the CFTR protein. The discovery of this compound marks another milestone in the Foundation’s collaboration with EPIX.
“The scientific team has really pulled out all the stops to deliver results, and they have achieved two major milestones earlier than originally planned—one by nearly a year. With active compounds emerging already, our collaboration with EPIX is indeed promising. We hope to identify at least one and possibly several potential drug candidates, which would be designed to restore the proper function of the CFTR protein,” said Diana Wetmore, vice president of alliance management at the CF Foundation.
“We truly enjoy working with the Foundation team—they bring a lot of expertise to the table and this results in a very productive program focused on treating CF patients,” concluded Schor.