So itacitinib is a JAK1-specific JAK kinase inhibitor and JAK kinases are involved in signaling through many cytokine receptor family genes and also activation of gamma interferon signaling. So this is a major signaling pathway for inflammation. And so we found in the lab many years ago that blocking that pathway with either JAK1-specific or JAK1/JAK2-balanced inhibitors would actually reduce the rates of graft-versus-host disease in mice dramatically...
So itacitinib is a JAK1-specific JAK kinase inhibitor and JAK kinases are involved in signaling through many cytokine receptor family genes and also activation of gamma interferon signaling. So this is a major signaling pathway for inflammation. And so we found in the lab many years ago that blocking that pathway with either JAK1-specific or JAK1/JAK2-balanced inhibitors would actually reduce the rates of graft-versus-host disease in mice dramatically. Again, the treatment for it to be maximally effective had to be given prophylactically. So that observation has resulted in eventually ruxolitinib, a family member to be approved for the treatment of acute graft-versus-host host disease. It was a first drug ever approved for the treatment of acute graft-versus-host disease. Itacitinib is a kissing cousin selectively, inhibiting only JAK1, but also doing in general, the same thing as ruxolitinib. And that is to block this interferon signaling pathway. And we thought that by instituting this early on after transplant, we’d do two things. We would block the cytokine release syndrome, which occurs when donor haploidentical T-cells rapidly expand in the recipient, which we showed, in fact, all of CRS was gone. And the second thing is that we would also then also block GVHD, which we showed. So the rates of GVHD were very much reduced for both acute and chronic. The rate of CRS went to zero and the vast majority of patients survived leukemia-free. So this needs to be extended for the bigger population of patients which we’re doing. And then the question is… This will have a big study showing this, and then the question is, will that require a randomized trial to actually prove its efficacy or are the results so good that the FDA will extend the label or approve itacitinib for this indication?