On April 22, 2026 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting supporting transcriptional reprogramming as a central mechanism driving the mutation-agnostic anti-leukemic activity of Actimab-A (lintuzumab-Ac225) in acute myeloid leukemia (AML).
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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. CD33 is expressed ubiquitously in AML and other myeloid malignancies. Actimab-A has been evaluated in more than 150 AML patients across multiple treatment settings, including as monotherapy and in combination with the chemotherapy regimen CLAG-M and with the BCL-2 inhibitor venetoclax, where it has demonstrated compelling clinical activity and a manageable safety profile. Under our Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), Actimab-A is being advanced through the NCI’s National Clinical Trials Network, including an ongoing frontline triplet trial combining Actimab-A with venetoclax and the hypomethylating agent ASTX-727 in newly diagnosed AML patients. The data presented at AACR (Free AACR Whitepaper) 2026 further support Actimab-A’s mutation-agnostic mechanism of action and its synergistic activity with targeted therapies approved for patients with the most commonly expressed AML mutations.
Key Data and Highlights of the Actimab-A AACR (Free AACR Whitepaper) Presentation
New data on Actimab-A’s mechanism and combination potential in primary AML patient samples further support its positioning as a foundational backbone therapy across multiple AML treatment settings, significantly expanding its commercial opportunity across the AML treatment continuum. 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 (MDS) and other CD33-expressing myeloid malignancies.
Transcriptional Reprogramming as a Key Mechanism for Actimab-A Combination Activity
Combination treatment produced consistent pathway-level changes compared with monotherapy. Gene set enrichment analyses (GSEA) showed enhanced myeloid differentiation signatures with the addition of Actimab-A (lintuzumab-Ac225) to revumenib, gilteritinib, and azacitidine.
Across models, combinations were associated with downregulation of proliferative programs, including MYC target genes, E2F targets, and G2/M checkpoint signatures, together with enrichment of p53-associated stress response and apoptosis pathways.
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.
Broad Activity of Actimab-A as Monotherapy and in Combination in Primary AML Patient Samples
Actimab-A (LinT-Ac225) showed robust cytotoxicity in primary AML patient samples, independent of FLT3, KMT2A, NPM1, IDH1, IDH2, or TP53 mutation status, positioning Actimab-A to treat the full AML population, including TP53-mutant patients who lack effective targeted options, and to serve as a universal combination partner rather than a mutation-restricted therapy.
Combining standard-of-care therapies (SOC) – revumenib (menin-KMT2A inhibitor), gilteritinib (FLT3 inhibitor), and azacitidine (hypomethylating agent) – with Actimab-A enhanced anti-leukemic efficacy across models – demonstrating synergy with one drug from each of the three pillars of modern AML care (targeted kinase inhibitors, menin inhibitors, and hypomethylating agents) and supporting Actimab-A’s positioning as a universal combination partner across frontline, relapsed/refractory, and unfit AML populations.
Sandesh Seth, Actinium’s Chairman and CEO, said, "The data presented at AACR (Free AACR Whitepaper) 2026 represent a significant step forward in our mission to establish Actimab-A as the foundational backbone therapy across the AML treatment continuum. For the first time, we have clear molecular evidence – through transcriptional profiling – of how Actimab-A reprograms AML cells to activate p53-driven apoptosis and shut down proliferative signaling, providing the mechanistic basis for deeper, more durable MRD-negative responses and mutation-agnostic activity we have consistently observed clinically. As the only CD33-targeted radiotherapy in development for myeloid malignancies, Actimab-A uniquely leverages the broad, stable expression of CD33 and the potent, mutation-agnostic Ac-225 payload to complement – not compete with – the targeted therapies that define today’s AML standard of care. Building on compelling clinical results across more than 150 patients in multiple treatment settings, and the high visibility of our NCI CRADA – including the ongoing frontline triplet trial with venetoclax and ASTX-727 – these findings will strengthen investigator enthusiasm for Actimab-A and reinforce the significant commercial opportunity ahead as we seek a partner for the registrational Phase 2/3 Actimab-A + CLAG-M study for which we have FDA alignment. We are focused on executing across our ongoing and planned clinical programs to deliver meaningful improvements in outcomes for AML patients, who continue to face high unmet medical need that is not addressed by currently available therapies."
The Actimab-A AACR (Free AACR Whitepaper) presentation is available for viewing on the Presentations & Webinars page of Actinium’s website HERE.
Title: Actimab-A, a CD33-Targeted Actinium-225 Radioconjugate, Drives Mutation-Agnostic Anti-Leukemic Activity and Synergizes with Standard Therapies in AML Through Transcriptional Reprogramming
Abstract Number: 5827
About Actimab-A
Actimab-A (lintuzumab-Ac225) is Actinium’s lead CD33-targeted radiotherapy and the only CD33-targeted radiotherapy in clinical development for myeloid malignancies. Actimab-A pairs a humanized anti-CD33 monoclonal antibody (lintuzumab) with the potent alpha-emitter Actinium-225 (Ac-225), which delivers high-energy, short-range radiation that produces lethal double-strand DNA breaks in CD33-expressing leukemic cells while sparing surrounding healthy tissue. Because CD33 is expressed on the blasts of the large majority of AML patients and the Ac-225 payload kills cells independent of genetic background, Actimab-A is positioned as a mutation-agnostic backbone that can be combined with the targeted and non-targeted therapies that define today’s AML standard of care.
Actimab-A has been studied in more than 150 patients with AML across multiple treatment settings, including as monotherapy and in combination with the intensive chemotherapy regimen CLAG-M and with the BCL-2 inhibitor venetoclax. In a Phase 1 trial in relapsed/refractory AML, Actimab-A plus CLAG-M produced an 83% overall response rate and 75% MRD-negativity at the recommended Phase 2 dose, with meaningful overall survival benefits in a high-risk population including patients with TP53 mutations and prior venetoclax exposure, and a manageable safety profile. Under a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), Actimab-A is being advanced across the NCI’s National Clinical Trials Network – which includes approximately 2,000 clinical trial sites through groups such as ECOG, SWOG, and Alliance – and is the subject of an ongoing frontline triplet combination trial with venetoclax and the hypomethylating agent ASTX-727 (Taiho Oncology) in newly diagnosed AML patients. Actimab-A is advancing toward a Phase 2/3 registrational program, with the goal of establishing Actimab-A as a foundational backbone therapy for patients with AML, myelodysplastic syndrome (MDS), and other CD33-expressing myeloid malignancies – a patient population that continues to face high unmet medical need.
(Press release, Actinium Pharmaceuticals, APR 22, 2026, View Source [SID1234664696])