sphingosine 1 phosphate s1p receptor modulators possess a unique mechanism of action as disease modifying therapy for multiple sclerosis ms subtype 1 s1p receptors are expressed on the surfaces of lymphocytes and are important in regulating egression from lymph nodes the s1p receptor modulators indirectly antagonize the receptor s function and sequester lymphocytes in lymph nodes fingolimod was the first s1p agent approved in the usa in 2010 for relapsing ms after two phase iii trials freedoms and transforms demonstrated potent efficacy and good safety and tolerability post marketing experience as well as a third phase iii trial freedoms ii also showed favorable results more selective s1p receptor agents ponesimod act128800 siponimod baf312 ozanimod rpc1063 ceralifimod ono 4641 gsk2018682 and mt 1303 are still in relatively early stages of development but phase i and ii trials showed promising efficacy and safety however these observations have yet to be reproduced in phase iii clinical trials.