Fueled by $111 Million, Sionna Therapeutics Takes Aim at Cystic Fibrosis

Newly-launched Sionna Therapeutics is stepping up to the plate and challenging Vertex Pharmaceuticals in the cystic fibrosis space. Backed by OrbiMed, Sionna hit the ground with a pipeline of first-in-class small molecules designed to fully restore the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in CF patients.

Sionna is making its public debut with $111 million in Series B financing that will support the development of its assets aimed at stabilizing CFTR's first nucleotide-binding domain (NBD1). Sionna noted in its announcement that the leading cause of CF is the genetic mutation ΔF508, which affects NBD1 stability and CFTR function. There are approximately 2,000 known mutations in the CFTR gene.

There are over 100,000 people living with the disease across the globe. Of those, an estimated 90% have the ΔF508 genetic mutation that occurs within the NBD1 domain of CFTR. This mutation causes NBD1 to unfold at body temperature and impairs CFTR function, the company noted. Within the next year, Sionna intends to file an Investigative New Drug Application with the U.S. Food and Drug Administration for its first NBD1 targeted program, SION-638. The company is also developing SION-109, which targets NBD1's interface with the intracellular loop 4 (ICL4) region and the transmembrane domain 1 of CFTR

Mike Cloonan, president and CEO of Sionna, said NBD1 is a well-known and researched target in cystic fibrosis, but has, until now, been considered undruggable.

“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. Our mission at Sionna is to significantly improve the health and quality of life for people who continue to suffer from the life-long consequences and burden of living with CF,” Cloonan, who previously served as chief operating officer of Sage Therapeutics, said in a statement.

Sionna said that in clinically predictive in vitro CF models, its NBD1-targeted small molecules, working alongside complementary modulators, have shown the ability to normalize folding, maturation, and stability of the CFTR protein affected by the ΔF508 genetic mutation. The company said this allows “proper trafficking of CFTR to the cell surface,” as well as the normal regulation of the flow of ions and water.

The absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. Most CF patients die in their mid-20s.

“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,” Sionna said in its announcement.

In addition to Cloonan, who spent time at Biogen before Sage, Sionna’s executive team includes Vertex Pharmaceuticals veteran Charlotte McKee, who will serve as chief medical officer; Chief Scientific Officer John Maco, who served as head of integrated drug discovery at Sanofi; company co-founder Greg Hurlbut, former head of rare pulmonary disease research at Sanofi, who will serve as vice president of drug discovery; and Mark Munson, also a company co-founder, who serves as vice president of medicinal chemistry. Munson is also a Sanofi veteran, most recently serving as head of medicinal chemistry.

The Series B financing was led by OrbiMed. Other participants included T. Rowe Price Associates, Inc., Q Healthcare Holdings, LLC., and a subsidiary of QIA, the sovereign wealth fund of Qatar. Other investors include RA Capital, TPG's The Rise Fund, Atlas Venture and the Cystic Fibrosis Foundation. The $111 million from the latest funding round provides Sionna with funds of about $150 million.