Cystic fibrosis group partners with Moderna founder for potentially curative treatment

 A prominent patient advocacy group has teamed up with Flagship Pioneering, the biotechnology incubator that founded Moderna and more than two dozen other health companies, in an effort to create potentially curative treatments for cystic fibrosis.

Unveiled Wednesday, the partnership will use funding from the Cystic Fibrosis Foundation and technologies from various Flagship-backed entities to establish single-asset companies, each focused on developing one treatment. Overall, the foundation expects to invest as much as $110 million in the collaboration, with an upfront commitment of $20 million.

Cystic fibrosis is a rare, genetic disease affecting roughly 35,000 people in the U.S. It causes a thick mucus to build up in the lungs, damaging the organ and leading to trouble breathing as well as increased risk of infection.

Though the disease remains serious and life-threatening, patients can now live longer thanks to improvements in care over the past few decades, including the availability of new drugs. Since 2012, the Food and Drug Administration has approved four medicines that, according to their developer, Vertex Pharmaceuticals, can treat approximately 90% of the cystic fibrosis population.

Still, Vertex and the Cystic Fibrosis Foundation, themselves longstanding partners, want treatments for the last 10% of patients, whose different mutations make them ineligible to the drugs on the market. Flagship, through its "Pioneering Medicines" initiative, is now trying to help the foundation find and develop such treatments.

"Their motivation was that we need to do something for this 10%," Paul Biondi, an executive director at Flagship, said in an interview.

"You can imagine how devastating that is," he added, "that there's a fantastic standard of care if you have to have one mutation, [but if you've got others] you're left out. So they feel a huge sense of urgency to come up with other therapies."

Already, Flagship has gotten buy-in from one portfolio company, Tessera Therapeutics, which touts a so-called "gene writing" technology that it claims can modify DNA in a variety of ways — from changing single units of genetic material, to inserting or deleting small segments, to writing in entire genes.

When applied to cystic fibrosis, the hope is this technology could correct defects in CFTR, the gene that's mutated in patients with the disease.

"If you could go in and just simply replace all the faulty aspects of the CFTR genes in an individual, that's exciting because essentially you cure those patients," Biondi said. "It could be that we could solve this for everybody."

While the partnership is prioritizing patients for whom there aren't drugs available, they aren't the only focus. For example, Flagship also plans to explore how targeted methods of drug delivery, as well as RNA technologies, could aid the search for more effective cystic fibrosis drugs.

The firm is perhaps best known for its work in RNA research, having built and supported Moderna, which rapidly developed a powerfully effective coronavirus vaccine.

"Similar in that RNA can create the spike protein in the COVID vaccine, the idea is you can have RNA therapies for aiding CFTR proteins in the right tissues," Biondi said. "That would be a way to at least treat it, maybe more effectively than some of the current modifiers that are out there."

Flagship is in talks with two more of its portfolio companies for the cystic fibrosis partnership, Biondi said, though it's not disclosing which ones. If the partnership generates any profits, he said they'll be shared with the companies that lent their resources.

Initially, the goal is to form one to two new companies, according to Biondi. They'll be responsible for early research and development, but once a potential treatment passes the human "proof-of-concept" stage, Flagship would probably look for another company to take on late-stage testing and commercialization.

"These companies that we create are single-asset companies, so they're not operating companies," Biondi said. "But, by having that legal, financial piece around the actual molecule, we can transact on it."

Even so, Biondi noted that Flagship could make these new companies operational, and either spin them out or outfit them with management teams and other capabilities that allow them to conduct late-stage drug development and commercial activities.

https://www.biopharmadive.com/news/flagship-cystic-fibrosis-foundation-partnership/609413/