Company: SION
Filing Date: 2025-03-20
Form Type: 10-K
Source: 0002036042-25-000005
Chunk: 19

Company: Sionna Therapeutics, Inc.
Filing Date: 2025-03-20
Form: 10-K
Item: Item 1
Chunk 19
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 and 450 mg, as well as single doses of 75 mg and 25 mg with food to provide a preliminary assessment of the effect of food on PK. Three MAD cohorts had been completed as of the data cutoff date, evaluating 75 mg, 150 mg, and 300 mg of SION-451 BID over 10 dosing days. As of the data cutoff date, all data remained blinded to individual subject treatment assignment. 

SION-451 was generally well tolerated at all dose levels administered based on interim Phase 1 clinical data as of the data cutoff date of January 14, 2025. There were no SAEs, and most TEAEs were mild to moderate (Grade 1 or Grade 2). No TEAEs led to the discontinuation of trial drug. The most common TEAEs, occurring in more than one subject, were headache, abdominal pain, contact dermatitis, influenza, presyncope, fatigue and upper respiratory tract infection. All TEAEs occurring in >1 subject were Grade 1 or Grade 2, and many were in an isolated dose cohort that was impacted by an outbreak of respiratory infection in the Phase 1 unit. One Grade 1 TEAE of increased transaminases had been observed, in a subject with influenza A infection. No dose limiting TEAEs or safety trends of concern have been observed, including in the additional MAD cohorts completed after the interim data cutoff date. 

Increasing exposure was observed with increasing single and multiple doses as of the interim data cutoff date. The concentration targets for SION-451 as both an add-on to SOC and as part of a dual combination with SION-2222 or SION-109 were achieved with single and multiple doses. A PK summary of SION-451 as of the cutoff date of January 14, 2025 is shown in Figures 16 and 17 below. The observed PK was consistent with BID dosing. 

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Figure 16. Preliminary Phase 1 PK Summary for SION-451 in the SAD Portion of the Trial 

(Each solid line shows mean concentration data from a dosing cohort. Dotted lines represent average PK concentration exposure targets that have the potential, based on our preclinical CFHBE model, to provide clinically meaningful benefit, if SION-451 is administered in a proprietary dual combination with either SION-2222 or SION-109, or as an add-on to SOC.) 

 Figure 17. Preliminary Phase