Chronic myeloid leukemia (CML) is caused by the Philadelphia chromosome (Ph) translocation t(9;22)(q34;q11) which generates a constitutively active tyrosine kinase, BCR-ABL1. Although CML is highly responsive to therapy with tyrosine kinase inhibitors (TKIs), such as Imatinib (Gleevec), which target BCR ABL1, about 33% of the treated patients do not achieve complete cytogenetic responses (CCyR) or are unable to tolerate drug related toxicities. In most CML patients for whom TKIs are largely effective, there is the pressing concern of low level residual disease. As a result, only a small minority of patients are able to discontinue therapy, while the majority must continue therapy life-long, at considerable costs and sometimes treatment associated significant side effects. This is due to the persistence of leukemia stem cells (LSCs) which are capable of surviving despite TKI inhibition of BCR ABL1. Several survival pathways leading to BCR ABL1-independent TKI-resistance in CML have been identified.  ES-3000 reduces β-catenin.  Although not required for the maintenance of normal human hematopoietic stem cells (HSC), the wnt/β-catenin pathway is essential for the survival and proliferation of CML LSCs.  Our objective is to develop ES-3000, which targets CML LSCs through this pathway, to eradicate minimal residual disease and provide more durable responses for CML patients.