Sionna Short Squeeze Fades As Raymond James Backs Cystic Fibrosis Breakthrough, RBC Warns Treatments Set High Bar

The short squeeze in Sionna Therapeutics shares that followed a 45% post-earnings rally has cooled, with shorts rising to 23.7% of free float from 21.5% as the stock slipped about 10% last week.

The biopharmaceutical firm, which is developing novel therapies for cystic fibrosis, drew conflicting sell-side views, according to The Fly, which compiled data on the short squeeze from Ortex. 

Raymond James initiated coverage with a ‘Strong Buy’ rating and $45 price target, saying Sionna has the best chance in the industry at breaking Vertex Pharmaceuticals’ stronghold in cystic fibrosis. RBC Capital Markets began at ‘Sector Perform’ with a $22 target, noting that existing treatments set a high bar and that Sionna’s next key data readouts in mid-2026 may not meaningfully de-risk the program.

Sionna is advancing two first-in-class NBD1 stabilizers, SION-719 and SION-451. Both produced positive Phase 1 safety and pharmacokinetic results in June, exceeding target exposure levels. 

The company plans to start a Phase 2a proof-of-concept trial of SION-719 as an add-on to standard of care in the second half of 2025 and a Phase 1 trial of SION-451 in two proprietary dual combinations over the same period, with topline data from both expected in mid-2026. 

Preclinical findings presented in June showed that the stabilizers, when combined with complementary modulators, enabled full correction of F508del-CFTR in models.

In second-quarter results released last month, Sionna reported a net loss of $18.1 million, or a loss of $0.41 per share, compared with a loss of $2.71 a year earlier, on higher R&D expenses of $15.4 million. 

General and administrative expenses rose to $6.5 million from $3.1 million. The company ended June with $337.3 million in cash and equivalents, which it stated should be sufficient to fund operations through 2028.

On Stocktwits, retail sentiment for Sionna was ‘bearish’ amid ‘normal’ message volume.

Sionna’s stock has declined 4% so far in 2025.

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