79 Effects of an oral selective sphingosine 1-phosphate receptor modulator in a mouse model of sle

Background and aims Ozanimod (RPC1063) is a specific and potent small molecule modulator of S1P 1 , 5R that has shown therapeutic benefit in clinical trials of relapsing multiple sclerosis and ulcerative colitis. Its metabolite, RP-101075, shares ozanimod’s specificity profile at the S1P receptor family in vitro , and its pharmacokinetic (PK) and pharmacodynamic profile in vivo . Methods The (NZB×NZW)F1 model was used in therapeutic dosing mode to assess the benefit of an S1P 1,5R modulator in systemic lupus erythematosus (SLE), compared to cyclophosphamide. Results As predicted for an S1P 1,5R modulator, treatment with 0.3, 1 and 3 mg/kg RP-101075 resulted in a dose-dependent reduction in circulating T and B cells, achieving 62%–99% decrease across all doses tested. Compared to vehicle treated animals, 3 mg/kg RP-101075 reduced proteinuria over the duration of the study (34±5 vs 18±1 U*week; p Conclusions Given that RP-101075 shares the pharmacokinetic profile of ozanimod and reduces circulating lymphocytes similarly, ozanimod warrants clinical evaluation as a potential treatment for SLE.