Novartis advanced their 2nd gen siponimod to phase III in SPMS not RRMS, so I will leave it out for now. As for the others, ponesimod also has some activity at S1P3 and that should be bad from the AE angle. Ceralifimod has the same activity at S1P1 and S1P5 that should help with efficacy but the price is in safety. My guess is the better choice is to target S1P1 mainly, as did Receptos and GSK (but GSK did not move their candidate beyond phase I, which implies they have seen unwanted AE).
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