Sionna Therapeutics shares plunged 92 percent in pre-market trading after its Phase 2a cystic fibrosis trial of SION-719 failed to meet its key activity endpoint. The company is not advancing SION-719 as an add-on to standard of care and is evaluating next steps for its SION-451 dual combination program.
Sionna Therapeutics shares plunged 92 percent in pre-market trading after its Phase 2a cystic fibrosis trial of SION-719 failed to meet its key activity endpoint.
"We are disappointed in the unexpected results from the Phase 2a trial," Mike Cloonan, President and Chief Executive Officer of Sionna, said. "We are further evaluating the data to decide on next steps for the SION-451 dual combination."
The PreciSION CF trial (NCT07108153) showed a -1.0 mmol/L mean placebo-adjusted sweat chloride change (p=0.7) when SION-719 was added to Trikafta (elexacaftor/tezacaftor/ivacaftor) for 14 days. Sweat chloride is an important measure of CFTR function, the protein that is defective in cystic fibrosis. The randomized, double-blind, placebo-controlled, crossover trial enrolled 15 adult participants with CF homozygous for F508del on a stable dose of Trikafta. Sionna identified potential confounders, including higher than anticipated variability in individual sweat chloride levels and differences in Trikafta exposure between the SION-719 and placebo periods. The company is evaluating the impact of these factors on the interpretation of the trial data.
SION-719 was generally well tolerated, with most treatment-emergent adverse events mild to moderate, no serious adverse events, and no meaningful trends in liver function test abnormalities. Based on these results, Sionna does not plan to advance SION-719 as an add-on to standard of care. The company received the topline data on Friday, Aug. 7, and is continuing to analyze the results.
Sionna also reported results from a Phase 1 healthy volunteer trial (NCT07035990) evaluating SION-451 in dual combinations with SION-2222 (galicaftor), a transmembrane domain 1-directed CFTR corrector, and with SION-109, an intracellular loop 4-directed CFTR corrector. All 120 participants dosed across both combinations achieved the safety, tolerability, and pharmacokinetic objectives, including target exposures defined prior to the Phase 2a results. SION-451 plus SION-2222 was identified as the preferred dual combination, though one participant discontinued due to rash and two discontinued due to elevated liver function tests and flu-like symptoms. The SION-451 plus SION-109 regimens were all generally well tolerated.
Sionna ended Q2 with approximately $268.3 million in cash, cash equivalents, and marketable securities. The company intends to take actions to preserve capital while evaluating next steps for the SION-451 program.
The trial failure removes SION-719 as a potential add-on therapy to Trikafta, the dominant CF treatment from Vertex Pharmaceuticals, and raises questions about the company's NBD1 stabilization approach, which aims to restore CFTR function to near-normal levels in people with CF. The 92 percent stock decline reflects investor concerns about the viability of the pipeline, though the $268.3 million cash position provides some runway. Investors will watch the company's conference call at 8:00 a.m. ET today for further details on the confounder analysis and the future of the SION-451 dual combination program.
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