Little girl receives breathing treatment
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In a bid to create better cystic fibrosis (CF) drugs, Sionna Therapeutics has closed a $182 million Series C financing to develop first-in-class small molecules for this indication. The company’s drugs are designed to fully restore the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein by stabilizing the first nucleotide-binding domain (NBD1). 

CF is caused by mutations in the CFTR gene. The most common of these mutations, ΔF508, causes NBD1 to unfold at body temperature and severely impairs CFTR function. While most current therapies can improve CFTR function, they do so only partially.

“We have deep experience in CF and a sharp focus on advancing the development of novel small molecules targeting NBD1 and complementary modulators that enable the potential for full restoration of CFTR function for most people living with CF,” said Mike Cloonan, president and CEO of Sionna. 

It is estimated that 70,000 people worldwide have this inherited disorder, according to the Cystic Fibrosis Patient Registry. The CF worldwide market is thought to be worth at least $5B. Vertex is the current leader in this field; its drugs have greatly extended the life expectancy among people with this disease. Can Sionna improve this?

CF is caused by mutations in the CFTR gene, which codes for an epithelial ion channel essential for producing healthy, freely flowing mucus in the airways, digestive system, and other organs. Current therapies are designed to increase CFTR function by either increasing the quantity of CFTR protein at the cell surface or by helping CFTR channels to open and allow chloride ions to cross the cell membrane.  

Sionna has presented preclinical data, including from the human bronchial epithelial cell (CFHBE) model, that demonstrate its NBD1 stabilizers can restore ΔF508-CFTR maturation, trafficking, and function to wild-type levels when combined with complementary modulators. A Phase I clinical trial of its first clinical-stage NBD1 stabilizer, SION-638, has identified doses that are generally safe and well tolerated, and target exposure (based on the CFHBE assay) was achieved at all doses, with more time above target with increasing dose.

Sionna has nominated two additional NBD1 stabilizers from its second series, SION-451 and SION-719, and plans to advance both compounds to clinical trials in 2024 pending results from ongoing Good Laboratory Practice (GLP) toxicology studies. 

The company is also continuing to advance the development of compounds targeting complementary mechanisms including SION-109, which targets NBD1’s interface with the CFTR intracellular loop 4 (ICL4) region; a Phase I clinical trial with SION-109 began in January 2024.

Cloonan said, “We are encouraged by the strong interest and validation from the excellent investors in our upsized Series C financing. This capital raise provides financial flexibility positioning us to execute our clinical development plan with funding through 2026 and multiple value-creating clinical readouts.”

Sionna’s Series C round, which was upsized and oversubscribed, was led by Enavate Sciences with additional new investors Viking Global Investors and Perceptive Advisors, as well as participation by all existing investors.

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