Vertex beefs up its cystic fibrosis pipeline with $1.2B Parion R&D pact

Vertex CMO Jeffrey Chodakewitz

With its cystic fibrosis combo drug awaiting a likely approval at the FDA, Vertex ($VRTX) is beefing up its pipeline in the field, paying $80 million upfront and promising up to $1.1 billion more in milestones to partner with Parion Sciences on a new class of CF-related drugs.

The Durham, NC-based Parion has been working on ENaC inhibitors, including P-1037 and P-1055. In preclinical experiments, 1037 demonstrated an ability to clear mucus from the cell surface, an activity that promises to improve lung function in cystic fibrosis patients. And that makes it a promising addition to Vertex's drug portfolio.

Vertex is grabbing worldwide rights to the two drugs, along with other possible drug candidates, in the pact. In return, Parion gets up to $490 million in development and regulatory milestones, up to $370 million in milestones for pulmonary conditions beyond CF, plus $230 million in bonus milestones if Vertex decides to develop an additional ENaC inhibitor from Parion's research program.

Parion recently launched a Phase IIa study of 1037 in 120 CF patients with CFTR mutations. And now the new partners will kick off an additional Phase IIa study that adds P-1037 to Vertex's lumacaftor and ivacaftor, recruiting patients with two copies of the F508del mutation.

Just a few weeks ago an FDA advisory committee voted 12 to 1 in favor of Vertex's treatment, which combines the investigational lumacaftor with ivacaftor, marketed on its own as Kalydeco. Vertex's new treatment targets the roughly 8,500 patients whose CF is caused by the so-called F508del mutation in their CFTR genes, making up the disease's largest population. Kalydeco, first approved in 2012, is cleared to treat CF patients with different CFTR mutations, a group totaling roughly 2,000.

Vertex has been retooling its business over the last two years, moving out of hep C, where Gilead ($GILD) now dominates. Ironically, Gilead was once partnered with Parion on 1037 and other ENaC inhibitors, but Gilead bowed out of the pact last year and returned the drugs to Parion.

Epithelial sodium channel--or ENaC--inhibitors block the sodium channels on airway surfaces. In pulmonary diseases like COPD and CF, blocking the ENaC channel demonstrated an ability to promote fluid secretion and rehydrate the mucus layers, restoring airway clearance and reducing infection, improving lung function.

"This collaboration with Parion complements our ongoing work in CF and supports our two key goals in this disease--to increase the number of people eligible for new CF medicines and to enhance the benefit of treatment," said Dr. Jeffrey Chodakewitz, the CMO at Vertex. "The goal of these planned studies of P-1037 is to determine whether ENaC inhibition can improve lung function in people with CF, including those with mutations unlikely to respond to treatment with the investigational combination of lumacaftor and ivacaftor. Beyond CF, this agreement helps to diversify our pipeline by providing opportunities to evaluate P-1037 as part of Phase IIa studies in multiple other diseases that impact the lungs."

- here's the release