P1006: Characterization of Tl-895: A Novel Bruton Tyrosine Kinase Inhibitor (Btki) in Clinical Development for Chronic Lymphocytic Leukemia (Cll) and Myelofibrosis (Mf)

Abstract

Background:BTK, a key component of B-cell receptor (BCR) signaling, promotes the interaction of CLL cells with the tumor microenvironment contributing to disease-related lymphadenopathy, splenomegaly, hepatic infiltration, and elevated lymphocyte counts (Montresor 2018). In MF, activated JAK2 increases BTK and NFκ B signaling leading to aberrant CD34 + cell trafficking and dysregulated cytokines (Nimmagadda 2019; Fisher 2019). Novel and improved BTK inhibitors may induce deeper and more durable responses in CLL and offer the potential to improve clinical outcomes in MF. TL-895 is a highly potent, selective, orally available, covalent, small molecule inhibitor of BTK and bone marrow tyrosine kinase X-linked (BMX). TL-895 is being studied in patients (pts) with CLL (NCT02825836) and is the first BTKi being investigated in pts with MF (NCT04655118).