The sphingosine-1-phosphate 1 receptor (S1P1R ) is expressed by lymphocytes, 
dendritic cells, and vascular endothelial cells and plays a role in the 
regulation of chronic inflammation and lymphocyte egress from peripheral 
lymphoid organs. Ozanimod is an oral selective modulator of S1P1R and S1P5R 
receptors in clinical development for the treatment of chronic immune-mediated, 
inflammatory diseases. This first-in-human study characterized the safety, 
pharmacokinetics (PK), and pharmacodynamics (PD) of ozanimod in 88 healthy 
volunteers using a range of single and multiple doses (7 and 28 days) and a 
dose-escalation regimen. Ozanimod was generally well tolerated up to a maximum 
single dose of 3 mg and multiple doses of 2 mg/d, with no severe adverse events 
(AEs) and no dose-limiting toxicities. The most common ozanimod-related AEs 
included headache, somnolence, dizziness, nausea, and fatigue. Ozanimod 
exhibited linear PK, high steady-state volume of distribution (73-101 L/kg), 
moderate oral clearance (204-227 L/h), and an elimination half-life of 
approximately 17 to 21 hours. Ozanimod produced a robust dose-dependent 
reduction in total peripheral lymphocytes, with a median decrease of 65% to 68% 
observed after 28 days of dosing at 1 and 1.5 mg/d, respectively. Ozanimod 
selectivity affected lymphocyte subtypes, causing marked decreases in cells 
expressing CCR7 and variable decreases in subsets lacking CCR7. A dose-dependent 
negative chronotropic effect was observed following the first dose, with the 
dose-escalation regimen attenuating the first-dose negative chronotropic effect. 
Ozanimod safety, PK, and PD properties support the once-daily regimens under 
clinical investigation.