A 3-part Study of SYX-5219 in Healthy Volunteers and Participants With Atopic Dermatitis

This is a multi-part, adaptive, Phase 1, double-blind, first-in-human study to evaluate the safety, tolerability, and pharmacokinetics of SYX-5219 following single ascending doses (SAD), multiple ascending doses (MAD), and selected dosing in participants with atopic dermatitis (AD). Parts 1 and 2 will be conducted at a single site in the UK. Part 3 will be conducted globally at multiple sites. Part 1 (Single Ascending Dose \& Food Effect) Part 1 (SAD) will enrol up to 48 healthy participants in cohorts (3:1, active:placebo). Participants will receive single doses of SYX-5219, with a food effect evaluation including a second dosing period following washout. Part 2 (Multiple Ascending Dose) Part 2 (MAD) will enrol up to 24 healthy participants in cohorts (3:1, active:placebo). Participants will receive multiple doses of SYX-5219 over a defined treatment period. Part 3 (AD Participants) Part 3 will enrol up to 45 participants with AD across multiple global sites. Participants will be randomised (2:1) to receive SYX-5219 or placebo for up to 42 days. Prior exposure to targeted systemic therapy will be limited. Study assessments will include safety and exploratory efficacy evaluations during treatment and follow-up.