A Rising Star in Biopharma: Industry Veterans Challenge the "Undruggable" Frontier with a Bold IPO

Seizing the IPO Window: Cystic Fibrosis Drugmaker Goes Public

On February 10, 2025, U.S.-based biopharmaceutical company Sionna Therapeutics announced the completion of its $219.2 million initial public offering (IPO) on the Nasdaq stock exchange under the ticker symbol "SION." This makes Sionna the latest pharmaceutical company to capitalize on the IPO window, following Chinese firms Ascentage Pharma, Metsera, and Maze Therapeutics.

Founded in 2019, Sionna Therapeutics is a clinical-stage biopharmaceutical company dedicated to developing innovative treatments for cystic fibrosis (CF) with the goal of transforming the current treatment landscape for CF patients.

Cystic fibrosis is caused by mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, leading to a reduction or complete loss of CFTR protein function. The CFTR gene and its corresponding protein were first discovered in 1989 by Chinese-American scientist Lap-Chee Tsui.

According to the Cystic Fibrosis Foundation (CFF), approximately 106,000 people across 94 countries have been diagnosed with CF, including around 33,000 adults and children in the United States. First documented in the 1930s, CF was once associated with a life expectancy of less than a year. While advances in treatment have improved patient outcomes, CFF data from 2023 indicate that between 2019 and 2023, the median predicted survival age for CF patients in the U.S. remained at 61 years.

Vertex Pharmaceuticals Dominates the CF Market

Currently, the global cystic fibrosis drug market is dominated by a single player—Vertex Pharmaceuticals. Vertex’s breakthrough CF drug, Kalydeco (ivacaftor), was first approved in the U.S. in 2012 as a CFTR potentiator that enhances the function of defective CFTR protein. Although it only benefits about 4% of CF patients, it was the first drug to directly target the underlying cause of CF.

Vertex later introduced several more CF treatments, including its 2019 triple-combination therapy, Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor), which is effective for approximately 90% of CF patients. In 2024, Trikafta (marketed as Kaftrio in Europe) generated a record $10.239 billion in global sales. In December 2024, the U.S. FDA approved Vertex’s next-generation triple-combination therapy, Alyftrek (vanzacaftor/tezacaftor/deutivacaftor).

Notably, around 90% of CF patients carry at least one copy of the ΔF508 mutation—a deletion of phenylalanine at position 508 in the CFTR protein’s nucleotide-binding domain 1 (NBD1). This mutation causes severe CF, as patients with ΔF508 often have little to no CFTR function in their epithelial cells. Trikafta is the current standard of care for these patients.

However, a major challenge in CF treatment remains: none of the approved CFTR modulators can directly stabilize NBD1.

Sionna Aims to Tackle the "Undruggable" Target

Sionna sees an opportunity to develop therapies targeting NBD1 to provide clinically meaningful benefits for CF patients. While NBD1 has long been recognized as a key target for restoring normal CFTR function, it has historically been considered "undruggable."

According to Sionna’s IPO prospectus, at least two-thirds of CF patients on Trikafta (the standard of care) fail to achieve normal CFTR function, as measured by a sweat chloride concentration below 30 mmol/L. Despite treatment, CFTR function may continue to decline over time, leading to respiratory infections, lung deterioration, and worsening lung function. More than 6,000 patients have discontinued CFTR modulators, and some Trikafta users have had to reduce their dosage due to tolerability issues.

Sionna aims to provide additional treatment options for CF patients, support novel mechanisms of action with clinical benefits, and offer alternative solutions for patients who experience side effects with Trikafta.

Biopharma Veterans Join Forces: Backed by CFF, Led by Former Sanofi and Vertex Executives

Sionna was co-founded by Dr. Greg Hurlbut (former Head of Protein Conformational Diseases and Rare Pulmonary Disease Research at Sanofi Genzyme) and Dr. Mark Munson (former Head of Medicinal Chemistry at Sanofi US). They spent over a decade researching NBD1 at Sanofi. Dr. Hurlbut was also the principal investigator of a $32 million CFF grant supporting small-molecule drug development targeting ΔF508-CFTR.

Before Sionna’s formation, the Cystic Fibrosis Foundation had spent more than a decade funding Sanofi’s early-stage ΔF508 corrector discovery efforts, laying the groundwork for Sionna’s pipeline.

In December 2019, Sionna licensed Sanofi’s CFTR modulator assets in a global exclusive agreement, covering three pipeline candidates: SION-719, SION-109, and SION-451. Sanofi received a $1.5 million upfront payment, $300,000 in reimbursed research costs, and is eligible for up to $40 million in milestone payments.

At the same time, Sionna reached a separate agreement with CFF, compensating the foundation to secure or defer certain rights under its prior agreement with Sanofi. Sionna has already paid CFF a $200,000 upfront fee and issued 300,300 Series Seed Preferred shares worth $1 million. CFF is also eligible for up to $40 million in milestone payments.

Additionally, Sionna’s Chief Medical Officer, Dr. Charlotte McKee, was previously Vice President of Clinical Development at Vertex, where she played a key role in launching multiple CFTR modulators. The company’s Scientific Advisory Board includes Dr. Taiyin Yang, a Chinese-American scientist and member of the U.S. National Academy of Engineering.

Sionna’s Drug Pipeline Progress

Sionna aims to expand CF treatment through proprietary dual-combination therapies or as adjuncts to standard care.

NBD1 Stabilizers

Sionna employs biophysical, cell-based, and virtual screening approaches, extensively utilizing structural biology to guide the optimization of novel small-molecule NBD1 stabilizers. Two highly potent small-molecule NBD1 stabilizers in its pipeline, SION-719 and SION-451, are the company's core projects. These aim to restore CFTR protein function by targeting its NBD1 domain, bringing it as "close to normal" as possible.

These small molecules are currently undergoing a randomized, double-blind, placebo-controlled Phase 1 clinical trial in Australia to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending doses in healthy participants.

As of January 14, 2025, Sionna had completed five single-ascending dose (SAD) cohorts and three multiple-ascending dose (MAD) cohorts for SION-719, with over 60 healthy participants dosed. Similarly, SION-451 had completed six SAD cohorts and three MAD cohorts, with over 70 healthy participants dosed. A mid-term analysis of the Phase 1 clinical data (as of January 14, 2025) indicated that both SION-719 and SION-451 were generally well tolerated.

Based on Sionna’s preclinical cystic fibrosis human bronchial epithelial (CFHBE) model, the company established target exposure levels for SION-719 and SION-451 to potentially provide clinically meaningful benefits when used as part of a dual combination therapy or added to the current standard of care (SOC). In these trials, the company achieved target concentrations of SION-719 and SION-451 through both single and multiple dosing. It plans to continue enrolling healthy participants in additional MAD cohorts. The primary results of these Phase 1 studies are expected to be announced in the first half of 2025, with a potential Phase 2a trial launch in the second half of 2025.

Sionna is also developing a series of complementary CFTR modulators designed to work synergistically with its NBD1 stabilizers to enhance CFTR function, a strategy validated in preclinical models.

ICL4-Targeted CFTR Corrector

Sionna recently completed a Phase 1 clinical trial evaluating SION-109, an ICL4 (Intracellular Loop 4)-targeted CFTR corrector. Across all parts of the Phase 1 study, SION-109 was generally well tolerated at all dose levels. SION-109, when used as part of a dual combination therapy with either SION-451 or SION-719, achieved target exposure through both single and multiple dosing.

All three projects mentioned above stem from Sionna’s collaboration with Sanofi and the Cystic Fibrosis Foundation (CFF).

Acquisition of Three Compounds from AbbVie – Originally Developed by a Belgian Company

In July 2024, Sionna obtained the global exclusive license for three clinical-stage compounds from AbbVie to expand its cystic fibrosis pipeline. These include the TMD1-targeted CFTR corrector Galicaftor (SION-2222, formerly ABBV-2222) and SION-2851 (formerly ABBV-2851), as well as the TMD2-targeted CFTR potentiator Navocaftor (SION-3067, formerly ABBV-3067).

In studies conducted by AbbVie, Galicaftor completed Phase 2 clinical trials and demonstrated good tolerability in both Phase 1 and 2 trials. Improvements in sweat chloride levels were observed in monotherapy, as well as enhancements in both sweat chloride and lung function when combined with Navocaftor. SION-2851 completed a Phase 1 SAD trial in healthy volunteers, while Navocaftor has been evaluated in Phase 2 trials, demonstrating its potential in combination therapy.

According to previous press releases, Sionna plans to prioritize one of these compounds in combination with SION-109 as the first potential dual-combination therapy featuring an NBD1 stabilizer. As part of this deal, Sionna paid AbbVie a $5 million upfront fee and issued 1,414,445 shares of common stock with a fair market value of $8.6 million. AbbVie is also eligible for milestone payments in later stages of development and commercialization, as well as royalties based on net product sales.

The three candidate drugs licensed to Sionna by AbbVie were originally developed by the Belgian company Galapagos, whose collaboration with AbbVie dates back to 2013. This suggests that Sionna may also be required to make certain payments to Galapagos in the future.

Sionna plans to advance the most promising candidates among its NBD1 stabilizers and complementary modulators into late-stage development. Initially, the company intends to evaluate its leading NBD1 stabilizer in a proof-of-concept trial in combination with the current standard of care, Trikafta. At the same time, Sionna will identify its proprietary dual-combination therapy most suitable for late-stage clinical trials in cystic fibrosis patients.

Sionna’s Recent Financial Data

Since its inception, Sionna has raised approximately $330 million from investors including RA Capital, TPG’s The Rise Fund, Atlas Venture, OrbiMed, and Enavate Sciences. The company has also received foundational support from the Cystic Fibrosis Foundation (CFF), which has been a committed investor and supporter of its research and development efforts.

Sionna's Recent Financial Data:

R&D Expenses for the First Nine Months of 2024:

As of December 31, 2024, Sionna held approximately $168 million in cash, cash equivalents, and marketable securities. As of the market close on February 11, 2025, the company's market capitalization was $868 million. As of the time of this report, its market capitalization stands at $629 million.