[ICYMI] Revisiting SION Coverage Launch, Thoughts On Summer Data

Research evidence excerpt

[ICYMI] Revisiting SION Coverage Launch, Thoughts On Summer Data

Sionna Therapeutics (SION)

The Wedbush View: Remain Outperform rated on SION. We initiated coverage of SION on

5/4/26 [LINK TO OUR INITIATION REPORT]. While this occurred during the midst of 1Q26

reporting, investor feedback tilted positively with interest in SION's upcoming readouts. Recall,

SION will report two updates this summer: 1) top-line Phase 2a PreciSION data for SION-719 as

an add-on to Trikafta in CF patients, 2) top-line Phase 1 SION-451 data in healthy volunteers. We

also checked in with SION CFO Elena Ridloff this week. Herein, we revisit highlights from our

discussion with CFO Ridloff and investor discussion topics we've fielded since our launch. We

continue to hold a positive bias on SION ahead of the Summer 2026 readouts as we see NBD1

stabilization as a unique strategy to modulate CFTR activity.

Key points of discussion:

Underlying Phase 2a PreciSION design, baseline characteristics. A key question centers on

starting sweat chloride (SwCl) values for PreciSION subjects. We note one meta-analysis (Xu et

al., 2023) of Trikafta clinical trials demonstrated at entry (prior to treatment initiation)

participants had a mean baseline SwCl level of 94.55 mmol/L. Following initiation of Trikafta

treatment, subjects experienced an average absolute change in SwCl of -41.82 mmol/L after four

weeks. The figure shown below illustrates the range of 4-week SwCl changes from an earlier

meta-analysis. Two of the studies are outliers to an extent; however, the remaining results are

relatively consistent. This equates to an average reduction of -43mmol/L (excluding the outliers).

Figure: Absolute Changes of Sweat Chloride (SwCl) After Four Weeks in Trikafta Studies

Source: Xu et al., 2023

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