First Volunteer Dosed in Phase 1 Trial of SION-638

Sionna's oral treatment has been shown to bind to the NBD1 region of CFTR protein

Teresa Carvalho, MS avatar

by Teresa Carvalho, MS |

Share this article:

Share article via email
A young person in athletic clothes shouts into a megaphone cone.

The first participant has been dosed in a Phase 1 clinical trial evaluating Sionna Therapeutics‘ SION-638, an investigational oral treatment for cystic fibrosis (CF).

The trial aims to assess the safety and pharmacokinetics — the movement into, through, and out of the body — of SION-638 in healthy volunteers. The start of dosing follows the recent clearance of the company’s Investigational New Drug (IND) application by the U.S. Food and Drug Administration.

CF is caused by mutations in the CFTR gene that provides instructions for building CFTR, a protein channel that normally controls the flow of water and chloride ions (salt) into and out of cells.

This flow is key to producing mucus, which is important for the functioning of several organs, such as the lungs and digestive tract. CFTR mutations lead to thick and sticky mucus accumulating in the airways, favoring bacterial infections, and inflammation.

Recommended Reading
This is an illustration of scientists amid a montage of medical and anatomical images.

#NACFC2022 – SION-638 Restored CFTR Protein Function

“While people with CF are living longer and more fulfilling lives, many continue to need ancillary medications and are at increased risk for exacerbations [sudden symptom worsening] and other serious complications,” Charlotte McKee, MD, Sionna’s chief medical officer, said in a press release.

The most common CFTR mutation is known as F508del. About nine in 10 CF patients have at least one copy of the CFTR gene with this mutation, which affects a specific region of the CFTR protein, known as the first nucleotide-binding domain 1, or NBD1. It makes the CFTR protein unfold and, consequently, the protein is rapidly degraded and is unable to function.

“Despite advances in CF treatment, the unmet need is high as current therapies can only partially correct the function of the CFTR protein, which means many patients are still at risk of experiencing exacerbations, complications, and a burden on daily life,” said Mike Cloonan, Sionna’s president and CEO.

SION-638 is a small molecule that, according to preclinical studies, binds to the NBD1 region with high affinity, thereby improving CFTR’s stability and functionality.

“We have achieved an important milestone of advancing SION-638, a first-in-class NBD1 modulator, into a Phase 1 study. We are encouraged by data from clinically predictive CF models demonstrating the potential to normalize folding, maturation, and function of the CFTR protein, and we look forward to evaluating our ability to drive improved outcomes for people with CF in clinical trials,” Cloonan said.

The treatment also was shown to increase the amount of mutated CFTR protein that was transported to the cell’s surface. SION-638’s effect was increased when it was combined with the approved CFTR modulators elexacaftor, tezacaftor, and ivacaftor.

These modulators make up Trikafta, approved in the U.S. to treat CF patients, ages 6 and older, with the F508del mutation (among other mutations). Work in an airway cell model showed combining SION-638 with Trikafta’s components improved CFTR’s function more than Trikafta alone.

Sionna is also developing other molecules to correct CFTR protein defects.

“We have not yet achieved the full promise of CFTR modulators, and it is important to continue advancing research that may lead to additional treatment options and further improvements in CFTR function in the years to come,” McKee said.

A Conversation With Rare Disease Advocates

Your CF Community

Visit the Cystic Fibrosis News Today forums to connect with others in the CF community.