Vertex Pharma Challenger Sionna Secures $191M in IPO Cash for Cystic Fibrosis Pipeline

Vertex Pharmaceuticals dominates the market for cystic fibrosis drugs, but Sionna Therapeutics contends the pharma company’s products still have efficacy and safety limitations. Sionna has mapped out a clinical trial strategy that could validate its different approach to the chronic respiratory disease. Now the biotech can execute those plans with $191 million from an upsized IPO.

Sionna had planned to offer more than 8.8 million shares in the range of $16 and $18 each, which would have raised nearly $150 million at the pricing midpoint. The company was able to boost the deal size to more than 10.5 million shares offered at the top of the targeted price range. Sionna’s shares debuted on the Nasdaq Friday under the stock symbol “SION.” Strong investor interest in the new stock enabled Sionna’s shares to close their first day of trading at $25 apiece, up nearly 39% from the IPO price.

In cystic fibrosis (CF), genetic mutations lead to faulty versions of CFTR, a protein key to moving ions in and out of cells. Improperly functioning CFTR leads to mucus buildup in the lungs of CF patients. Two types of drugs improve CFTR function. Correctors bind to the protein and help it fold into the proper shape. Potentiators open channels of the protein. Vertex’s drugs combine both mechanisms to improve CFTR function at the surface of a cell.

Waltham, Massachusetts-based Sionna is developing CF drugs that target NBD1, a domain on the CFTR protein. NBD1 has long been thought to be important for normalizing CFTR function because it’s the location of the F508del mutation — the most common mutation that causes CF. Sionna aims to succeed where others have fallen short developing drugs that stabilize this target.

“Approximately 90% of people with CF carry at least one copy of the F508del genetic mutation,” Sionna said in the IPO filing. “We believe stabilizing NBD1 is central to unlocking dramatic improvements in clinical outcomes and quality of life for CF patients. We have employed biophysical, cell-based and virtual screening campaigns and extensive use of structural biology to guide the optimization of novel small molecule NBD1 stabilizers.”

Sionna expects NBD1 stabilization could be used as part of a dual combination therapy or as an add-on to standard CF therapies. The company has three NBD1 stabilizers in clinical development. SION-109, which targets NBD1’s interface with the CFTR intracellular loop 4 (ICL4) region, has completed Phase 1 testing in healthy volunteers. Sionna said results showed this molecule was well tolerated and achieved exposure in the body that could support its use as part of a combination with two other Sionna stabilizers, SION-719 and SION-451. These two NBD1 stabilizers began clinical testing last summer. Interim data as of mid-January indicate that both have been well tolerated by patients so far, the company said in the filing.

Vertex’s twice-daily drug Trikafta, a combination of two correctors and one potentiator, has become a standard of care therapy for CF patients who have at least one F508del mutation in the CFTR gene. This drug, approved in 2019, has also become the company’s top-selling product. In the nine months ended Sept. 30, 2024, Trikafta (marketed as Kaftrio in Europe) accounted for $7.5 billion in sales, up 14% compared to the same period in 2023. This past December, the FDA approved Vertex’s Alyftrek, which offers the same drug combination in a once-daily pill. Neither Trikafta nor Alfytrek address NBD1.

Despite Vertex’s dominance in CF, its drugs still leave unmet medical need, Sionna said in the filing. Patients treated with Vertex’s drugs can continue to experience reduced CFTR function and declining lung function over time. Also, safety and tolerability issues lead some patients to reduce their dosage or discontinue treatment. The labels of Trikafta and Alyftrek carry black box warnings for the risk of drug-induced liver injury and liver failure.

“Our research with key opinion leaders has indicated the desire for more treatment options for CF patients, support for a new mechanism of action that could provide clinically meaningful benefit for people living with CF, and need for an alternative for those patients who experience tolerability issues on Trikafta,” Sionna said in the filing.

Sionna was co-founded in 2019 by Greg Hurlbut and Mark Munson, two scientists who spent more than a decade at Sanofi researching ways to treat CF by targeting NBD1, according to the filing. The company’s NBD1 research was licensed from Sanofi. Last July, Sionna expanded its pipeline by licensing three clinical-stage CF drugs that AbbVie developed under a partnership with Galapagos. Sionna said these molecules, two correctors and one potentiator, could be combined with its NBD1 stabilizers.

Prior to the IPO, Sionna said it had raised about $330 million from investors. The most recent financing was a $182 million Series C round announced last March. RA Capital Management is Sionna’s largest shareholder with a 22.9% post IPO stake, according to the filing. As of the end of 2024, the company said its cash position was about $168 million.

Combining its existing capital with the IPO proceeds, Sionna plans to spend about $40 million on the ongoing Phase 1 tests of SION-719 and SION-451. After completing those studies, Sionna plans to select a lead NBD1 stabilizer, conduct a drug-drug interaction trial, and then proceed to a Phase 2a proof-of-concept study. This trial, enrolling CF patients who are stable on Vertex’s Trikafta, is expected to begin in the second half of 2025.

Sionna also plans to advance the lead NBD1 stabilizer to multiple ascending dose trials in dual combinations with galicaftor (one of the in-licensed AbbVie drugs) and/or SION-109 in healthy volunteers. These studies, expected to start in the second half of this year, will inform the selection of one dual combination to advance to a Phase 2b dose-ranging study in CF patients. Sionna has budgeted $95 million to start this study and for manufacturing drug product for pivotal studies. The company expects its cash will last into 2028.

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