Galicaftor

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. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech 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. Exclusive Improving the Healthcare Financial Experience to Help Care Flow Zelis CEO Amanda Eisel shares her perspective on how the company is solving the problems of a fragmented health financial system to benefit all. By Stephanie Baum 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. Image: Jackie Niam, Getty Images

Cystic fibrosis biotech Sionna Therapeutics will raise $191 million in its upsized Nasdaq debut on Friday, and metabolic disease biotech Aardvark Therapeutics outlined plans for a potential $89 million IPO. Sionna will begin trading as $SION on Friday to help it fund the development of treatment candidates that it in-licensed from Sanofi and AbbVie for $1.5 million upfront in 2019 and $5 million upfront in 2024, respectively. The Boston-area biotech sold 10.58 million shares versus an original plan of 8.82 million shares. It priced at $18 apiece, the high end of the range it marketed this week. Aardvark, meanwhile, penciled in a price range of $16 to $18 per share for its proposed entry onto the Nasdaq as $AARD . If the metabolic disease biotech prices at the midpoint of that range and sells all 5.88 million of its marketed shares, it could garner about $89 million in net proceeds, according to a Thursday evening SEC filing . Sionna’s transition to a public company comes as the biotech plans to report topline Phase 1 data on its NBD1 stabilizers SION-719 and SION-451 — which derive from Sanofi — in the first half of this year. The drug developer will then select one of those for a Phase 2a in the second half of 2025, according to its IPO documents. It also has clinically tested assets from AbbVie , including a CFTR corrector called galicaftor and a CFTR potentiator known as navocaftor. Six-year-old Sionna isn’t in a funding crunch. Its $182 million Series C from last year was slated to fuel the company through 2026, CEO Mike Cloonan previously told Endpoints News . The company still had about $180 million at the end of September. But with multiple clinical programs underway in a condition that has been cornered by Vertex for two decades, and the public markets appearing to get a little bit warmer, Sionna decided to plow ahead with its IPO. Its Friday float follows last week’s Nasdaq launches from Metsera and Maze . More publicly traded hopefuls are on deck. One of them, immunology startup Odyssey Therapeutics, revealed its IPO ambitions the same day as Sionna last month. But Odyssey has yet to reveal the scope of its proposed offering, perhaps signaling that it’s running into challenges during the process. RA Capital, TPG Growth, Atlas Venture and OrbiMed were its largest financial backers. Sionna’s experimental small molecules target the most common genetic mutation for patients with cystic fibrosis: ΔF508, chief medical officer Charlotte McKee previously told Endpoints . “NBD1 is the domain in which that ΔF508 actually lives,” she said. “Vertex has very successfully, to this point, found drugs that bind around NBD1,” McKee said last July. She joined Sionna in 2021 after six years at Vertex, where she worked on CF clinical development. “The current modulators stabilize and bind around this domain, but they don’t directly stabilize, so you’ve still got this critical place where the thing that goes wrong is actually living. That still causes a significant amount of instability and dysfunction that’s being left on the table at this point with the current modulators.”