The Cystic Fibrosis Foundation is investing up to $11 million in 4D Molecular Therapeutics (4DMT) to continue testing its inhaled gene therapy in people with cystic fibrosis in a Phase 1/2 trial. Gene therapy is a potential treatment that could help all people with CF, regardless of their mutations.

4DMT invented a viral vector, using an adeno-associated virus, that is designed to target the lungs and enhance the delivery of a healthy cystic fibrosis transmembrane conductance regulator (CFTR) gene to the lung cells of people with CF. If successful, the inhaled gene therapy would result in the production of functional CFTR protein in lung cells, relieving the symptoms of CF in the lungs.

The goal of the next phase of the clinical trial is to determine whether the therapy improves lung function and can be given safely more than once without activating the immune system. Because of natural cell turnover in the lungs, the effects of gene therapy are typically not permanent and redosing is sometimes required to maintain the therapy’s benefits. Historically, this has been a big challenge with genetic therapies because immune systems can “remember” a viral delivery vehicle with the second dose, potentially triggering an immune response. 4DMT’s next-generation vector was specifically designed to overcome this problem, aiming to provide a second dose safely and efficiently.

So far, 16 people with CF have received different doses of the gene therapy in the Phase 1 clinical trial. With the Foundation’s support, 4DMT chose an optimal dose to study further and plan to provide initial doses to six more people with CF and redose up to six previous participants.

In addition to this investment, the Foundation has committed more than $20 million to 4DMT over nearly 10 years to develop novel viral vectors using adeno-associated viruses.