The Cystic Fibrosis Foundation will invest up to $5 million in Carmine Therapeutics to continue lab research of a method to deliver a potential gene therapy to people with cystic fibrosis that would temporarily eliminate the symptoms of CF in the lungs.

Carmine received an initial investment of $3.5 million from the Foundation, and the company will receive an additional $1.5 million if it reaches certain milestones. This new investment follows a $766,000 award made in December 2021. This support of Carmine is part of the Foundation’s  Path to a Cure initiative, an ambitious research agenda to accelerate treatments and drug development for the underlying cause of the disease and ultimately deliver a cure. The Foundation decided to increase funding based on encouraging data from earlier lab work.

“Gene delivery is a problem that we need to solve to successfully get genetic-based therapies into people with CF, which is our best hope for a permanent cure,” said Steven Rowe, MD, executive vice president and chief scientific officer of the Cystic Fibrosis Foundation. “The additional funding provided to Carmine by the Foundation will support the preliminary work necessary to see if this potential delivery method is viable in CF.”

CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that result in the production of a dysfunctional CFTR protein or no protein at all. Gene therapy — also known as gene transfer — is a process in which a new, correct version of the CFTR gene would be delivered into cells in a person’s body to make normal CFTR proteins.

For gene therapy to work in cystic fibrosis, it needs to get inside the cells in the body. Gene delivery is particularly difficult in the lungs because of the thick mucus caused by CF and the lung’s natural immune system response to anything foreign. Researchers are targeting the lungs because they are the most severely affected by CF.

Researchers have been experimenting with using non-harmful viruses to deliver the healthy CFTR gene into lung cells. However, other scientists, like those at Carmine, are testing methods that do not rely on viruses. Carmine’s program plans to use extracellular vesicles — bits of cell membrane that naturally bud off from cells to form tiny particles that mediate cell-to-cell communication. Carmine is obtaining extracellular vesicles from donated red blood cells. Once loaded with the gene therapy, these particles can be either inhaled or infused through an IV.

This method of delivering healthy CFTR genes shows promise because it harnesses a natural process in the body that is unlikely to trigger an immune system response — like viral methods often do — and could be safer to use. In addition, the extracellular vesicles can carry the full-length CFTR gene unlike viruses, which are not large enough.

Expanding our options for effective gene delivery greatly enhances our ultimate chance of success with gene therapy for cystic fibrosis. Investments such as these follow the Foundation’s venture philanthropy model of providing companies early-stage funding to develop breakthrough treatments for adults and children with cystic fibrosis. The approach has super-charged CF drug discovery and development by de-risking and accelerating new technologies in CF, resulting in more than 16 approved therapies — including four treatments for the underlying cause of CF.