Actinium Pharmaceuticals, Inc. announced that first-in-human data from the first dose cohort of the Phase 1 portion of the Actimab-A venetoclax Phase 1/2 combination trial in patients with relapsed or refractory Acute Myeloid Leukemia (AML) were presented at the 62ndAmerican Society of Hematology (ASH) annual meeting. The poster presentation highlighted results from the first three patients treated with the initial subtherapeutic dose level of 0.5 µCi/kg of Actimab-A and venetoclax. The enrolled patients had a median of 2 prior therapies (range 2-3) and a median bone marrow blast percentage of 30% (range 20 - >60). All 3 patients had poor risk disease with adverse cytogenetics, and each patient had an additional high-risk marker (FLT3-ITD+, antecedent JAK2+ myelofibrosis, or TP53 mutation). One patient who had multiple genetic mutations including IDH2, RUNX1, TP53 and others, achieved a complete remission with incomplete blood count recovery (CRi) after the first cycle of Actimab-A and venetoclax. Next generation sequencing at the end of the first cycle showed that patient was negative for the known IDH2 and RUNX1 mutations. This patient has continued treatment receiving the second cycle and their bone marrow remains normocellular with no excess blasts. In addition, another patient achieved a partial response after one cycle of Actimab-A and venetoclax. There were no Actimab-A related dose limiting toxicities or nonhematologic Grade 3 or greater related AEs reported in the first cohort. The trial has advanced to the second dose cohort of 1.0 µCi/kg of Actimab-A and venetoclax with patient enrollment ongoing. This Phase 1/2 trial is a multicenter, open label trial of Actimab-A (lintuzumab-Ac225) added to venetoclax for patients with CD33 positive R/R AML. A Phase 2 trial studying Actimab-A as a single agent produced a 69% overall response rate in older unfit patients with newly diagnosed AML. In a poster presentation at the American Association of Cancer Research (AACR) Annual Meeting 2019, Actimab-A was shown to be synergistic with venetoclax in venetoclax resistant cell lines, by depleting MCL-1, a protein shown to mediate resistance to venetoclax. Further, the induction of direct AML cell death via double-stranded DNA breaks by Actimab-A provides a second mechanism for enhancing synergistic potency with venetoclax. Venetoclax is a B-Cell Lymphoma 2 (BCL-2) inhibitor that is jointly developed and marketed by AbbVie and Genentech and is approved for patients with AML, Chronic Lymphocytic Leukemia (CLL), and Small Lymphocytic Leukemia (SLL). Despite its approval in AML, venetoclax has produced low response rates of 19% as a single agent in R/R AML.1 This is due in part to the type of AML, risk factors, and cytogenetics of this patient population. The Phase 2 trial results, together with a synergistic mechanism of action with venetoclax demonstrated in pre-clinical studies, are driving this combination trial with an initial focus on the high unmet needs of R/R patients including those who have relapsed or do not respond to treatment with venetoclax based regimens.