Bill Sandborn: Yeah, so what you see with both ozanimod and etrasimod from their Phase 2 programs is they had a lower dose that achieved roughly 30% reduction in ALC from baseline and a higher dose that received €“ that resulted in 50% to sort of 54%, 55% reduction in the ALC, and with each drug you saw a linear dose response from the 30% reduction to the 50% to 55% reduction. If you look analogously in multiple sclerosis, in Phase 2 trials they explored with €“ there’s four different drugs approved for S1P, and in Phase 2 they explored you know across the range from 20% or 30% ALC reduction all the way to 79% ALC reduction. And then in Phase 3, a range across sort of 55% with ozanimod on the low side of multiple sclerosis up to 73% to 79% with different doses of Gilenya on the higher side of ALC reduction.
And across all of these, whether you look at clinical remission and endoscopy across low to mid lymphocyte reduction in ulcerative colitis or annualized relapse rate, a clinical measure of multiple sclerosis, a reduction in T1 enhancing brain lesion reduction on MRI with multiple sclerosis. You see, linear relationships between the degree of lymphocyte reduction and clinical outcome measures on one hand or sort of structural outcome measures on the other. And at least in multiple sclerosis you don’t really plateau those effects until you get up to at least 65% ALC reduction in probably the low 70’s. So what we believe is that the range above 55% reduction is unexplored in ulcerative colitis and given what’s been seen with multiple sclerosis, we think it’s very logical that what’s been seen with multiple sclerosis going to 70% something reduction, and the linear relationship between load intermediate lymphocyte reduction and ulcerative colitis, that it’s very logical to think that you could add to the magnitude of efficacy that was seen with etrasimod, and so we’re really looking for 20% plus efficacy across the important outcome measures, but the primary endpoint will be clinical remission and you know, if you think about most of the existing drugs, the difference between drug and placebo is about 10%, so a 20% plus delta becomes really critically meaningful, especially for a safer role therapy.
Jeff Jones : Great! No, I appreciate that color and it sounds fairly analogous to the way you’re thinking about the TYK2 scenario. I’ll jump back into the queue. Thanks, guys.
A – Raju Mohan: Thanks Jeff.
Operator: Thank you. Our next question will come from Chris Shibutani with Goldman Sachs. Your line is open.
Chris Shibutani: Thank you very much. Good afternoon. If I could return to 958 and some of the context with competitor data that we saw the AAD meeting, but maybe approach it more from the question of not efficacy, but on the overall tolerability profile as well. Looking to see how you view some of the relative information that we learned. In particular in terms of any potential that you might see something in the way of CPK elevation, how are you thinking about that potentially in the ongoing Phase 2 studies. And related to that, now that we have sort of a new visibility on the competitive data set and what’s happening, I believe theoretically there’s still potential for you to make modifications to your Phase 2 programs across the different indications. How are you thinking about that? Is there potential for tweaks to any of the program designs? Thank you.
