Sionna Therapeutics (SION) Study result summary

PreciSION CF Phase 2a trial results

• The Phase 2a trial of SION-719 as an add-on to Trikafta in adults with CF homozygous for F508del did not meet its key activity endpoint, showing a mean placebo-adjusted sweat chloride change of -1.0 mmol/L (p=0.7), which was not statistically significant or clinically meaningful.

• The trial enrolled 15 participants, mean age 35.1 years, all stable on Trikafta, using a randomized, double-blind, placebo-controlled crossover design.

• SION-719 was generally well tolerated, with most adverse events mild to moderate and no serious adverse events reported.

• Variability in individual sweat chloride levels and differences in Trikafta exposure between periods were observed as potential confounders.

• Based on these results, development of SION-719 as an add-on to standard of care will not continue.

SION-451 dual combination program

• The Phase 1 trial evaluated SION-451 in combination with SION-2222 or SION-109 in 120 healthy volunteers, meeting safety, tolerability, and pharmacokinetic objectives.

• SION-451 BID and SION-2222 QD was identified as the preferred regimen due to favorable tolerability and exposure.

• Most adverse events in the preferred regimen were mild to moderate, with no serious adverse events or significant liver function issues; a few discontinuations occurred due to rash, elevated liver function tests, or flu-like symptoms.

• Safety profile was consistent with prior single agent trials.

• The study enabled selection of SION-451 + SION-2222 as the preferred dual combination for further evaluation.

Ongoing analysis and next steps

• Detailed analysis of the Phase 2a data is ongoing to understand confounding factors, exposure-response relationships, and translational framework adjustments.

• The team is investigating the impact of Trikafta exposure variability and sweat chloride measurement variability on outcomes.

• Further insights into the path forward for SION-451 + SION-2222 will be provided after comprehensive data review.

• No immediate changes to the translational framework are planned until the data interrogation is complete.

• Continued evaluation of SION-719 data will inform next steps for the SION-451 clinical program.