Vertex Exercises Cystic Fibrosis Gene Editing Options from CRISPR Therapeutics

Cystic fibrosis (CF) is a rare, life-shortening genetic disease. It is caused by mutations in the CFTR gene that lead to a defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) protein. Children must inherit two defective CFTR genes—one from each parent—to have CF. There are approximately 2,000 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic test, lead to CF by creating non-working or too few CFTR proteins at the cell surface. The defective function or absence of CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the early 30s.

Vertex has exercised its option to in-license three targets from CRISPR Therapeutics as part of a 2015 collaboration. The targets include the cystic fibrosis transmembrane conductance regulator (CFTR) gene and two that are undisclosed. 

The option exercise was noted in CRISPR’s third quarter financial results. Under the terms of their agreement, Vertex now has exclusive global rights to develop and commercialize products related to these targets. In return, CRISPR will receive $30 million in upfront cash and is eligible to receive up to $410 million in development, regulatory, and commercial milestones and royalties on net product sales for each of the three targets. While the 2015 research collaboration has ended, Vertex has optioned five programs, including one in sickle cell anemia and one in beta thalassemia, which saw the first patient with a severe form of beta thalassemia being dosed with the partners’ ex vivo gene therapy.

The option exercise comes just months after Vertex struck a new strategic collaboration and license agreement with CRISPR Therapeutics, paying the biotech $175 million upfront for the exclusive worldwide rights to the company’s existing and future intellectual property including foundational CRISPR/Cas9 technology, novel endonucleases, single and double cut guide RNAs, and AAV vectors for DMD and DM1 gene editing products. The total value of the deal could reach $1 billion depending on the successful achievement of specified research, development, regulatory, and commercial milestones, plus royalties on sales for the DMD and DM1 programs. At IND filing, CRISPR has the option to forego the DM1 milestones and royalties to co-develop and co-commercialize all DM1 products globally.

Vertex’s growing portfolio of approved therapies now includes the recently approved triple combination Trikafta, which has the potential to treat up to 90 percent of cystic fibrosis patients. 

Photo: Jeffrey Leiden, CEO of Vertex