New Sionna trial tests NBD1 stabilizer SION-719 with Trikafta
Study will enroll adults with F508del mutation to assess safety, CFTR activity
Sionna Therapeutics has launched a clinical trial to test its experimental therapy SION-719 in combination with Trikafta (elexacaftor/tezacaftor/ivacaftor), which is currently the standard-of-care treatment for cystic fibrosis (CF).
According to a company press release, the Phase 2a study (NCT07108153) will enroll adults with CF who carry two copies of F508del — the most common CF-causing mutation — and who are already on a stable dose of Trikafta. Participants will be randomly assigned to receive either SION-719 or a placebo in addition to Trikafta. The study aims to evaluate the safety and pharmacological properties of these medications used in combination, as well as assess sweat chloride levels to measure CFTR protein function.
The study is currently recruiting at sites in the U.S.; sites in Australia are also expected to enroll participants. Top-line results are expected by mid-2026.
How SION-719 works
CF is caused by mutations in the gene that encodes CFTR, a protein that’s important for mucus production. In people with CF, the protein is absent or doesn’t work correctly, which leads to the production of thick, sticky mucus that builds up in organs to cause most disease symptoms.
CFTR modulators are medications that boost the activity of the defective CFTR protein in people with certain mutations. Trikafta contains a combination of three CFTR modulators and is widely approved for those with F508del and other responsive mutations.
The F508del mutation makes part of the CFTR protein — known as nucleotide-binding domain 1 (NBD1) — unstable, leading it to lose its function. Current CFTR modulators like Trikafta don’t target this specific part of the protein. SION-719 is designed to specifically stabilize this region.
“The NBD1 domain of the CFTR protein plays a critical role in the folding, stability and trafficking of CFTR to a cell’s surface, but none of the currently approved CF therapies directly stabilize NBD1,” said Charlotte McKee, MD, Sionna’s chief medical officer.
“We are confident in the potential of NBD1 and believe that adding SION-719 to the standard of care could demonstrate clinically meaningful improvement in CFTR function,” McKee said. “If the trial is successful, we believe it would represent an important step in validating the NBD1 mechanism and would provide evidence that NBD1 stabilization is mechanistically unique from, and synergistic with, the components of standard of care.”
Earlier Phase 1 testing in healthy volunteers found that SION-719 was overall well tolerated. Pharmacological data suggested it may enhance the clinical benefits of Trikafta, according to Sionna.
Sionna is also developing another NBD1-targeting modulator, SION-451. The company recently launched a Phase 1 study (NCT07035990) testing SION-451 combined with other experimental modulator therapies in healthy volunteers.
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