Sierra Oncology, Inc. reported clinical data for its lead drug candidate, momelotinib, a potent, selective and orally-bioavailable JAK1, JAK2 and ACVR1 inhibitor for the treatment of myelofibrosis. ASH 2018 Poster #4282: Protocol '1672: Translational biology study in transfusion dependent patients with myelofibrosis: This single arm, open-label study evaluated momelotinib for 24 weeks in patients with myelofibrosis who were transfusion dependent at baseline. A high rate (73%) of advanced (Grade 3) bone marrow fibrosis was noted in this population. 34.1% of patients were transfusion independent for at least 12 weeks, achieving the primary endpoint of the study. 39.0% were transfusion independent for at least 8 weeks, achieving the secondary endpoint. Median blood hepcidin levels consistently decreased 6 hours after dosing with momelotinib, with a progressive reduction in serum hepcidin evident over the entire dosing period versus baseline, consistent with the ACVR1 inhibitory activity of momelotinib. Serum iron peaked at Week 2 and subsequently decreased, consistent with restoration of iron homeostasis. Amongst those patients who achieved transfusion independence, reticulocytes, hemoglobin, transferrin and hematocrit increased through the 24 weeks, consistent with improved erythropoiesis. The platelet count also increased in those patients over that period. 77.8% of those patients who did not reach the transfusion independence endpoint achieved at least a 50% decrease in transfusion frequency for any 8-week period. Poster Title: Hepcidin Suppression by Momelotinib is Associated with Increased Iron Availability and Erythropoiesis in Transfusion-Dependent Myelofibrosis Patients. SIMPLIFY-1 Phase 3 - Transfusion Dependent to Transfusion Independent Response Rates: First line, double blind, randomized study versus ruxolitinib in JAKi naïve MF patients (N=432). 49.1% of patients who were transfusion dependent at baseline became transfusion independent for at least 12 weeks following momelotinib treatment. 58.5% were transfusion independent for at least 8 weeks. SIMPLIFY-2 Phase 3 - Transfusion Dependent to Transfusion Independent Response Rates: Second line, randomized study versus BAT (~90% ruxolitinib) in patients previously treated with ruxolitinib (N=156). 46.6% of patients who were transfusion dependent at baseline became transfusion independent for at least 12 weeks following momelotinib treatment. 46.6% were transfusion independent for at least 8 weeks. Combined Transfusion Dependent to Transfusion Independent Response Rates from SIMPLIFY-1, SIMPLIFY-2 & '1672: 44.1% of patients who were transfusion dependent at baseline (multi-study aggregate n=152) became transfusion independent for at least 12 weeks. 48.7% were transfusion independent for at least 8 weeks.