The Cystic Fibrosis Foundation is committing up to $13 million in additional funds to SpliSense to support a Phase 2b clinical trial. The trial will evaluate the effectiveness of its inhaled antisense oligonucleotide when used in combination with Trikafta or Alyftrek, two cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies. The study will evaluate the combination treatment in people with CF who are taking these modulators and have the 3849+10Kb C-to-T splicing mutation.

Earlier parts of the Phase 2 trial tested the new treatment alone in different doses for people with this splicing mutation. Now that people with that mutation can take Trikafta (elexacaftor/tezacaftor/ivacaftor) or Alyftrek (vanzacaftor/tezacaftor/deutivacaftor), the trial will focus on whether adding the SpliSense treatment can make these modulators work better.

“This is the first inhaled genetic medicine to show statistically significant improvements in lung function, a major sign that it could benefit people with CF,” said Steven Rowe, MD, executive vice president and chief scientific officer at the Cystic Fibrosis Foundation. “We are hopeful that we will see even better results when we combine it with a modulator.”

Splicing mutations change the CFTR messenger RNA (mRNA), the set of instructions cells use to make CFTR protein, by removing or adding information. This change causes errors in the instructions and prevents the body from making normal CFTR protein.

SpliSense's antisense oligonucleotide works by attaching to the faulty mRNA and blocking the incorrect instructions. This helps the cell remove or skip the incorrect sections and make a full-length CFTR protein. 

Since 2017, the Foundation has provided a total of $17.8 million to SpliSense to develop a therapy for splicing mutations.