SION - Previewing preciSION Study - Is NBD1 Stabilization Truly a Birth of a New Paradigm or Just Another Mirage in the Cystic Fibrosis Treatment Landscape?

Research evidence excerpt

SION - Previewing preciSION Study - Is NBD1 Stabilization Truly a Birth of a New Paradigm or Just Another Mirage in the Cystic Fibrosis Treatment Landscape?

is plenty of room for improvements for Trikafta-controlled CF patients. Additionally,

while not comprehensively discussed in this deep-dive, SION-451 (NBD1 stabilizer) is being investigated in a Phase I HV study (n~24)

SION BUY asstudiesa dualarecombinationslated to readwithoutSION'sthis summerproprietary(likelyCFTRmid-to-latemodulatorsAugust- SION-2222timeframe for(TMD1preciSION,corrector)per andour estimate).SION-109We(ICL4continuecorrector).to believeBoth

Sionna Therapeutics, Inc. SION has the potential to revolutionize the cystic fibrosis treatment paradigm with its first-in-class NBD1 stabilizers. For more in-depth

Sector: Biotechnology discussion on cystic fibrosis, NBD1 targeting, and SION's clinical development, please see our Initiation. In our scenario analysis, we

see 2-3x upside potential/60% downside risk on this readout. We reiterate our BUY rating and $50 price target. Company Update

Share Price $38.83

Price Target $50.00 Scenario Analysis: Framing Our Expectations for the preciSION Study

Mgmt has consistently guided for ~10 mmol/L improvements in SwCl levels. Per our conversations with the buy-side, the Street appears

Market Data to be divided on this threshold. Here, we present our bull/bear thesis, along with our scenario analysis (see Figure 1 below).

52-Week Range $13.81 - $48.45

Base: If SION-719 delivers ~8-10 mmol/L SwCl reduction (meaningfully more than Alyftrek's 3.2 mmol/L reduction in the same Shares Out (M) 45.2 •

F508del/F508del CF patient population), this would provide credibility that NBD1 stabilization is partially orthogonal to existing CFTR Market Cap (M) $1,753

modulation.