RARE Daily

Sionna Launches with $111 Million to Advance Small Molecules with Potential to Restore CFTR Function in Cystic Fibrosis

April 19, 2022

Rare Daily Staff

Sionna Therapeutics, founded in 2019 to develop new treatments for cystic fibrosis, officially launched   and closed a $111 million series B financing.

OrbiMed led the financing with participation from funds advised by T. Rowe Price Associates, Q Healthcare Holdings, a wholly owned subsidiary of QIA, the sovereign wealth fund of Qatar, and previous investors including RA Capital, TPG’s The Rise Fund, Atlas Venture, and the Cystic Fibrosis Foundation. Sionna has raised approximately $150 million to date.

Sionna is advancing a pipeline of first-in-class small molecules designed to fully restore the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein that is defective in cystic fibrosis (CF), by stabilizing CFTR’s first nucleotide-binding domain (NBD1). The leading cause of CF is the genetic mutation ΔF508 that affects NBD1 stability and CFTR function.

CF is a serious, potentially fatal, genetic disease caused by a mutation in the CFTR gene that leads to a buildup of mucus in the lungs and airways, impaired pancreatic function, and other organ dysfunction that can have a significant and often severe impact on health and life expectancy. Globally, there are more than 100,000 people living with CF, an estimated 90 percent of whom have the genetic mutation ΔF508 that occurs within the NBD1 domain of CFTR. This mutation causes NBD1 to unfold at body temperature and impairs CFTR function. Despite the availability of currently approved treatments and the significant progress made on other targets within CFTR, most people with ΔF508 do not achieve full CFTR function. NBD1 is essential to normalize the function of CFTR and the production of healthy, freely flowing mucus in the airways, digestive system, and other organs.

In clinically predictive in vitro CF models, Sionna’s NBD1-targeted small molecules, in combination with other complementary modulators, have demonstrated the potential to normalize folding, maturation, and stability of the CFTR protein affected by the ΔF508 genetic mutation. This allows proper trafficking of CFTR to the cell surface and normal regulation of the flow of ions and water.

The company says that by fully restoring CFTR function for patients with the ΔF508 genetic mutation to levels seen in cells of people without CF, Sionna’s pipeline has the potential to deliver best-in-class efficacy and optimal clinical benefit for people with CF.

“NBD1 is a well-known and researched target, but it has been considered undruggable until now. Based on our focused efforts and continued progress on NBD1, we see the potential to normalize CFTR function in the vast majority of people with CF,” said Mike Cloonan, president and CEO of Sionna Therapeutics.

The company plans to advance development of a franchise of small molecules targeting NBD1 and complementary modulators, including NBD1’s interface with the intracellular loop 4 (ICL4) region and the transmembrane domain 1 (TMD1) of CFTR. Sionna plans to submit Investigational New Drug applications (IND) for its first NBD1 targeted program, SION-638, and for its lead ICL4 program, SION-109, within the next 12 months.

Photo: Mike Cloonan, president and CEO of Sionna Therapeutics

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