Actinium presents data from Actimab-A studies at AACR

Actinium Pharmaceuticals (ATNM) highlighted data presented at the American Association for Cancer Research, or AACR, Annual Meeting supporting transcriptional reprogramming as a central mechanism driving the mutation-agnostic anti-leukemic activity of Actimab-A, or lintuzumab-Ac225, in acute myeloid leukemia, or AML. Preclinical translational data demonstrated that lintuzumab-Ac225 delivers potent cytotoxic activity across AML models harboring common mutations, including FLT3, NPM1, KMT2A, and TP53, as well as in primary patient samples. Importantly, combining Actimab-A with standard-of-care therapies – the menin inhibitor revumenib, the FLT3 inhibitor gilteritinib, and the hypomethylating agent azacitidine – resulted in enhanced leukemic cell killing in vivo across all tested models, independent of mutation status. These results support a combination-driven clinical strategy aimed at improving depth and durability of response. The findings provide the mechanistic foundation for Actimab-A’s observed clinical activity and, together with the manageable safety profile demonstrated across prior Actimab-A trials in more than 150 AML patients, reinforce its suitability as a combination backbone across multiple treatment settings. Actimab-A is Actinium’s lead clinical radiotherapy delivering Actinium-225, a potent alpha-emitter radioisotope payload that produces lethal double-strand DNA breaks to kill CD33-expressing AML cells. In the relapsed/refractory AML setting Actimab-A in combination with the intensive chemotherapy regimen CLAG-M produced an 83% overall response rate and 75% MRD-negativity in a Phase 1 trial which forms the basis of a Phase 2/3 registrational study for which Actinium has FDA alignment and is seeking a development partner. Actimab-A is also being studied in newly diagnosed patients via the ongoing NCI-sponsored frontline triplet trial of Actimab-A with venetoclax and ASTX-727; and has shown promise in post-remission and MRD-directed settings; as well as myelodysplastic syndrome and other CD33-expressing myeloid malignancies. Combination treatment produced consistent pathway-level changes compared with monotherapy. Gene set enrichment analyses showed enhanced myeloid differentiation signatures with the addition of Actimab-A (lintuzumab-Ac225) to revumenib, gilteritinib, and azacitidine. Together, these findings show that Actimab-A combinations don’t just add cytotoxicity – they reprogram AML cells from proliferation toward differentiation and apoptosis, providing the mechanistic basis for deeper, more durable MRD-negative responses and reinforcing Actimab-A’s role as a universal combination backbone across AML.