2.2.3. Ozanimod

Ozanimod has a high a ffinity for S1PR-1 and to a lesser extent for S1PR-5. It selectively crosses the BBB with brain to blood ratio of 10-16:1 [30] and its a ffinity for the S1PR-1 is comparable to FGM-P and SPM [30]. Like FGM-P and SPM, it induces rapid internalization and degradation of S1PR-1 in rodents and produces reduction in circulating B and T cell lymphocytes [30,84]. Compared to FGM and SPM, there is more rapid lymphocyte reconstitution after it is discontinued. The t1/2 elimination of its major active metabolites, cc112273 and cc1084037, is only 11 days (see Table 2) [85]. Of note, OZM treatment significantly improves EAE scores in mice, even in the presence of restored blood lymphocyte counts [30], supporting a direct CNS therapeutic role. We are unaware of extensive preclinical studies of OZM modulation of S1PR-5, its effects on OPCs, OLGs or myelination, or BBB integrity.
