Sionna Therapeutics, Inc. (NASDAQ:SION), a clinical-stage biopharmaceutical company on a mission to develop novel medicines for cystic fibrosis (CF), today reported topline data from two nucleotide binding domain 1 (NBD1) stabilizer programs, the PreciSION CF Phase 2a proof-of-concept (POC) trial of SION-719 when added to Trikafta® (elexacaftor/tezacaftor/ivacaftor) in CF participants, and the Phase 1 trial of SION-451-based proprietary dual combinations in healthy subjects.

Phase 2a PreciSION CF Trial

  • The PreciSION CF trial did not meet its key activity endpoint, with a -1.0 mmol/L mean placebo-adjusted sweat chloride change (p=0.7).
  • Potential confounders were observed in the trial, including, for example, higher than anticipated levels of variability in individual sweat chloride levels and differences in Trikafta exposure levels between the SION-719 and placebo periods. The Company is evaluating the impact of these on the interpretation of the trial data.
  • SION-719 was generally well tolerated when added to Trikafta for 14 days with most treatment emergent adverse events mild to moderate, no serious adverse events, and no meaningful trends in adverse events related to liver function tests. 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, August 7, 2026, and is continuing to analyze the results of the PreciSION CF study.



     

Phase 1 Healthy Volunteer Dual Combination Trial

  • The Phase 1 trial of SION-451 in dual combinations with either SION-2222 or SION-109 in healthy subjects achieved the safety, tolerability, and pharmacokinetic (PK) objectives, including target exposures defined prior to the Phase 2a PreciSION CF results.
  • Based on the totality of the data and target coverage observed, SION-451 + SION-2222 was identified as the preferred dual combination.
  • All SION-451 twice-daily + SION-2222 once-daily doses were generally well tolerated. One participant discontinued due to rash.
  • In the SION-451 twice-daily + SION-2222 twice-daily cohorts, most treatment emergent adverse events were mild to moderate, and no serious adverse events were reported. Two participants discontinued due to elevated liver function tests and flu-like symptoms. The SION-451 + SION-109 regimens were all generally well tolerated.
  • Sionna is evaluating next steps for the SION-451 program.



     

"We are disappointed in the unexpected results from the Phase 2a trial. We are further evaluating the data to decide on next steps for the SION-451 dual combination," said Mike Cloonan, President and Chief Executive Officer of Sionna. "We would like to thank the CF study participants, investigators, and sites for their support in the PreciSION CF study and also thank the broader CF community, our employees, and our shareholders for their support throughout the process."

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.