With CF Pact, Moderna and Vertex Aim to Spray mRNA Into the Lungs

Xconomy Boston — 

Moderna Therapeutics has spent years developing a way to coax a patient’s body to make its own protein-based drugs, with visions of treating conditions ranging from cancer to cardiology.

Add cystic fibrosis to those ambitions, as Cambridge, MA-based Moderna is announcing today a collaboration with Boston-based Vertex Pharmaceuticals (NASDAQ: VRTX), a top maker of drugs for cystic fibrosis (CF). The companies say they will use Moderna’s messenger RNA technology to discover and develop a new CF therapy that addresses the underlying cause of the disease. CF stems from a genetic mutation that leaves lungs and other organs unable to produce a protein that is key to maintaining their health and function. Without the protein, sticky mucus builds up in the lungs and other organs, with often deadly effect.

Moderna believes it can deliver into lung cells its mRNA to mimic the body’s own snippets of code, missing in CF patients, that would normally get translated into the healthy protein.

Vertex is paying Moderna $40 million upfront, half in cash and the other half as a loan that could eventually convert into equity in the Cambridge company. Moderna will lead the discovery efforts in the three-year research pact, leaning on Vertex for its expertise in the biology of CF. Moderna could earn up to $275 million in milestones from Vertex, as well as royalties on future sales of an approved CF therapy. Vertex will take the lead on preclinical, development, and commercialization work for the collaboration, while also footing the bill on collaboration-related expenses.

Vertex becomes the fourth company to sign a research deal with Moderna pursuing mRNA-based therapies. Just a week ago, Moderna signed a $200 million deal with Merck (NYSE: MRK) to work on personalized cancer vaccines, adding to a previous tie-up between the partners.

Moderna also has pacts with AstraZeneca (NYSE: AZN) for cardiovascular diseases and cancer and Alexion Pharmaceuticals for rare diseases (NASDAQ: ALXN), deals that paid Moderna $240 million and $125 million respectively.

Moderna CEO Stephane Bancel says the CF application emerged from a group within the company that explores new areas and has focused recently on the eye, lung, and brain. Within the last nine months, Bancel says the Moderna lab made “great progress” in its lung research, which prompted the company to seek out a specific disease target and a partner. Though Moderna considered cancer and asthma, the company concluded that a rare genetic lung disease would be the best opportunity.

With CF the target, Bancel says Vertex stood out because of its experience. Vertex received approval in 2012 on ivacaftor (Kalydeco), a pill developed to treat the roughly 4 percent of the CF patient population with a specific genetic mutation. A year ago, it gained FDA approval for a combination of ivacaftor and lumacaftor (Orkambi), which targets a different mutation.

Unlike other mRNA therapies being developed as injectable products, Bancel says a Moderna CF therapy will likely be administered as a spray in the mouth. Bancel says Moderna has gotten the spray to deliver mRNA into animal lung cells, although not in situations that approximate CF. That would be one of the next steps to pursue with Vertex.

Moderna and Vertex will work together to see if they can get mRNA into the lung, and then get the cells to produce functional copies of the missing cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is the underlying cause of the disease. Bancel says three years should be enough time to get a therapy from its Vertex  partnership into the clinic. “If this works in humans in clinical trials, that will make other [CF] drugs not relevant,” he says. “You will have addressed the root cause and fixed what is missing.”

That means that Vertex has its hands on technology that could render its own CF drugs and pipeline obsolete. But Moderna’s mRNA approach is far from a sure thing. Of the many programs across several disease types that Moderna has disclosed, not one has yet produced human data.

Vertex is hedging its bets and pursuing multiple approaches to treating the CF. Others are much more advanced, like the two clinical-stage compounds discovered by Durham, NC-based Parion Sciences that Vertex paid $80 million last year to acquire.

Vertex last year also signed a $105 million deal with gene-editing startup CRISPR Therapeutics, a pact that gives Vertex the option to license up to six treatments.