Trueline's scientists recognized that if the HCK protein could be switched “off”, leukemic stem cells would lose a key survival mechanism, and chemo-resistant cancers would now become vulnerable. TTX-114 is the outcome of a structure-based optimization effort and will be clinically evaluated in hematological malignancies and certain lymphomas.
Following chemotherapy, leukemic cells can hide in the protective environment of bone marrow - rendering even the most powerful agents ineffective. An enzyme called HCK (hematopoietic cell kinase) has recently been shown to direct cancerous cells into hiding
Gene transcriptional analysis of patient-derived leukemic stem cells identified HCK as a master switch that turns “on” during the refractory or relapse stages of acute myeloid leukemia. Importantly, HCK plays a minor role in healthy, developing blood cells which enhances the likelihood of clinical safety with an HCK/BTK inhibitor.
BTK is a key partner of HCK in ensuring lymphoma cell survival. TTX-114 is designed to target both, HCK and BTK, tackling the Achilles' heel of cancer survival to overcome resistance to current standard of care.