Research Update

The Science of Adding Tomorrows
By Andrea N. Flynn, PhD
Associate Research Scientist
New York University

The CF Foundation has pioneered the venture philanthropy approach to drug discovery by investing in partnerships with biotechnology and pharmaceutical companies.  The Foundation’s partnership with Vertex Pharmaceuticals led to FDA approval of the first drug to target the basic defect in cystic fibrosis – Kalydeco™.  The FDA approved Kalydeco, previously VX-770, in January 2012 for patients, ages 6 and older, with two copies of the G551D mutation. The success of Kalydeco has demonstrated that screening libraries of chemical compounds can identify new drugs that target the basic defect of cystic fibrosis.

Of the over 1,800 mutations that cause CF, 4% of patients have the G551D mutation. While this mutation allows the CFTR chloride channel protein to reach the cell surface, it doesn’t allow for chloride transport.  Kalydeco, a CFTR potentiator, improves chloride transport through the CFTR chloride channel.  Nearly 90% of all people with CF have at least 1 copy of the DF508 mutation.  Unlike the G551D mutation, the DF508 mutation prevents the CFTR protein from making it to the cell membrane where it can transport chloride.  The CF Foundation is committed to indentifying new drugs, called correctors, that allow the CFTR protein to move to its proper place at the cell surface.  

Cystic Fibrosis Foundation Therapeutics (CFFT) has entered into a 6-year collaboration with Pfizer, the world’s largest research-based pharmaceutical company, to discover new drugs that specifically target the DF508 mutation.  The CF Foundation will provide both scientific and financial support, with an investment up to $58 million.  While the CF Foundation’s initial partnership with Vertex screened a library of 250,000 compounds, this latest partnership with Pfizer will allow for the screening of over 5 million compounds.

Never one to put all its eggs in one basket, the CF Foundation has also partnered with Genzyme, a Sanofi company, and Proteostasis Therpeutics to identify drugs for the DF508 mutation.  Furthermore, the CF Foundation will continue its collaboration with Vertex, and Phase 3 clinical trials of Kalydeco in combination with VX-809, a corrector compound, will begin early this year in people with two copies of the DF508 mutation.  

The CF Foundation is also dedicated to identifying new drugs for non-sense mutations.  Non-sense mutations interrupt production of the CFTR protein and result in an incomplete and non-functional CFTR chloride channel protein.  The CF Foundation will continue its partnership with PTC Therapeutics and is dedicated to finding a cure for all individuals with cystic fibrosis.   

You can track the progress of these therapies and more using the Drug Development Pipeline. Fundraising through a Great Strides team is a fantastic way to support these exciting drug development programs!