Safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral allosteric TYK2 inhibitor ESK-001 using a randomized, double-blind, placebo-controlled study design.

ESK-001 is a highly selective allosteric inhibitor of tyrosine kinase 2 (TYK2), which plays an essential role in mediating cytokine signaling in multiple immune-mediated diseases. In 2 phase I studies, a first-in-human single ascending dose (SAD) and multiple ascending dose (MAD) study and a multiple-dose (MD) study, we evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of orally administered ESK-001 in healthy participants using a randomized, double-blind, placebo-controlled study design. ESK-001 was rapidly absorbed with systemic exposures generally increasing dose-proportionally across all cohorts.