Sionna Therapeutics has raised $111m USD to advance small molecules against a once-undruggable target with the potential to improve the treatment of cystic fibrosis (CF). Vertex has transformed the lives of many CF patients in recent years with a series of molecules but some unmet needs remain, leaving opportunities for rivals to muscle in on the market. Sionna reportedly has identified the full restoration of the function of CFTR, the chloride channel at the heart of CF, as a way to improve on the existing arsenal of therapeutic options.
“While people with CF are living longer and more fulfilling lives, the vast majority do not achieve full CFTR correction, which often means they continue to need ancillary medications and are at increased risk for infections and disease. There is a clear opportunity to improve the treatment of CF because there remains a risk of exacerbations, infections, and burden on daily life including nutritional status and the use of inhalers,” said Sionna CEO Mike Cloonan.
The question is how to fully restore CFTR function. Analysis of the question led the researchers behind Sionna to NBD1, a nucleotide-binding domain that is commonly mutated in CF patients. Deletion of F508 in NBD1 cuts trafficking of CFTR to the cell surface and the thermal stability of the binding domain.
Evidence of the role NBD1 plays in CF has attracted multiple research groups but the target has thwarted efforts to drug it. In 2016, researchers at Pfizer reported on a collaboration that delivered “discouraging” results that suggested NBD1 may lack “the features needed to build high-affinity interactions.”
Sionna claims it is the first group to crack the NBD1 puzzle, leading to the discovery of small molecules that, when used in combination with other complementary modulators, have shown the potential in vitro models to normalize folding, maturation, and stability of the CFTR protein. Exactly how Sionna has solved the mystery remains a secret.
“Our ability to target NBD1 correction is truly novel. Our team has built upon over a decade of extensive research in CF to develop a franchise of first-in-class small molecules targeting NBD1 and complementary modulators. It required years of focus and expertise,” said Cloonan.
More information is on the horizon. With OrbiMed leading a $111m series B round in Sionna, the biotech could file two investigational new drug submissions, including an application for the NBD1 program, in the next 12 months.
The Series B also attracted the support of T. Rowe Price Associates, the sovereign wealth fund of Qatar, RA Capital, TPG's The Rise Fund, Atlas Venture, and the Cystic Fibrosis Foundation. Sionna’s total funding haul now stands at around $150m.