The purpose of Parts D and E of this Phase 1 study are to evaluate the safety, tolerability, and pharmacokinetics of multiple dose combinations of SION-451 and complementary modulators SION-2222 and SION-109 in healthy participants.

This is a Phase 1 randomized, double-blind, placebo-controlled study. Parts D and E will evaluate the safety, tolerability, and pharmacokinetics of multiple dose combinations of SION-451 and complementary modulators SION-2222 and SION-109 in healthy participants. Parts A, B, and C of this study have completed dosing.

Part D will involve multiple dosing of SION-451 and SION-2222 in combination. Part E will involve multiple dosing of SION-451 and SION-109 in combination.

Inclusion Criteria:

1. Healthy male or female adult participants aged 18 to 55 years, inclusive, at the time of consent.
2. Weight of at least 45 kg and body mass index between 18.0 and 32.0 kg/m2, inclusive, at Screening.
3. Participant is willing to abstain from alcohol, caffeine, smoking and nicotine-containing products for 72 hours prior to Day -1 through the duration of the study. Participant is willing to abstain from eating cruciferous vegetables, charcoal-grilled meats, and poppy seeds for 48 hours prior to dosing throughout the duration of the study.
4. Participant has read, understood, and voluntarily provided written informed consent
5. Participant has an understanding, ability, and willingness to fully comply with study procedures and restrictions.

Exclusion Criteria:

1. Participant has clinically significant, in the opinion of the investigator, current or recurrent illness, such as cardiovascular (including but not limited to known structural cardiac abnormalities, family history of long QT syndrome, or cardiac syncope or recurrent, idiopathic syncope), neurologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine, or psychiatric disease or disorder, or other abnormality which may affect safety or clinical laboratory evaluations.
2. Participant has a history of malignancy, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of recurrence for at least 1 year.
3. Participant has clinically significant abnormalities, in the opinion of the investigator, on ECG, physical examination, or vital sign assessment at Screening or Day -1.
4. Participant has any single reading of QTcF >470 ms (females) or >450 ms (males) at Screening or Day -1.
5. Chronic or habitual alcohol (>10 standard drinks per week) or tobacco (>10 cigarettes per week) use or use of recreational drugs (>1 use per month). The Investigator may exclude a participant with lower levels of alcohol, tobacco, or recreational drug use based on discretion and the pattern or history of use.