GNS396 in Acute Myeloid leukemia: GNS 396 shows potent anti-proliferation activity when assayed against the NCI60 panel of human tumor cell lines, notably against AML cell lines, as well as an original dose-responses cytotoxic activity against AML cell lines subpopulation displaying high ALDH activity (ALDH activity is a marker of CSCs), in addition GNS396 is active even against primary tumor highly resistant to Cytarabine. Furthermore GNS396 shows a synergic effect in combination with AML standard of care (Cytarabine). In vivo GNS396 induces significant reduction of leukemia growth in preclinical AML model.
GNS396 offer great promise for AML treatment and prevention of relapse in AML patients. By simultaneously targeting the tumorigenic (by GNS396) and non-tumorigenic populations (by both GNS396 and Cytarabine), both leukemia cell heterogeneity and plasticity could be overcome. This compound is selected as drug candidate for future investigation in AML clinical trial in combination with standard of care.