Actinium Pharmaceuticals, Inc. has announced that the company has entered into a sponsored research agreement with Memorial Sloan Kettering Cancer Center (MSKCC) to expand Actimab-A's mutation agnostic mechanism of action.

The collaboration has two specific objectives. The first objective is to study Actimab-A in combination with targeted therapies including FLT3 and menin inhibitors to define transcriptional profiles in AML cells following treatment with these combinations.

The second objective is to assess the activity of Actimab-A-based combinations on primary AML patient-derived ex vivo samples from patients with and without prior Venetoclax + hypomethylating agent (HMA) treatment. The collaboration will be done with members of MSKCC's leukemia and early drug development specialist teams.

Actimab-A has demonstrated a mutation agnostic profile with positive clinical results in high-risk relapsed and refractory (r/r) AML patients including those with a TP53 gene mutation, prior Venetoclax treatment and prior bone marrow transplant (BMT). Additionally, Actimab-A has demonstrated mechanistic synergy with improved antileukemic activity and or tumour control with FLT3 inhibitors, menin inhibitors for NPM1 mutant and KMT2A rearrangement and IDH1&2 inhibitors in preclinical studies. NPM1 and KMT2A are present in approximately 30 percent, FLT3 mutations are present in approximately 25-30 percent and IDH1&2 are present in approximately 10-20 percent of AML cases.

Commenting on the development, Sandesh Seth, Actinium's Chairman and CEO, said, “In 2025, we are reimagining and revitalising our Actimab-A program leveraging its mutation agnostic, backbone therapy profile. This collaboration with MSKCC will further expand and support novel Actimab-A combinations with targeted therapies like FLT3 and menin inhibitors in AML. As we have demonstrated in combination with CLAG-M, Actimab-A has the potential to improve patients' outcomes via its novel and differentiated mechanism to target radiosensitive AML blasts and produce lethal double strand DNA breaks via the Actinium-225 payload for which there are no known resistance or repair mechanisms.”

He further added, “We are eager to execute this collaboration and look forward to generating important data from AML patient derived models. Our goal is to address the unmet needs of over 100,000 patients with myeloid malignancies across the treatment journey with Actimab-A, which represents a multi-billion-dollar market opportunity. With recently initiated trials, this exciting research collaboration and clinical data expected in the second half of 2025, we believe we are making great progress to achieve our goal.”

Actimab-A is Actinium's lead radiotherapeutic that delivers Actinium-225, a potent alpha-emitter radioisotope payload that can produce lethal double strand DNA breaks to kill targeted cells that express CD33. CD33 is expressed ubiquitously in AML and in other myeloid malignancies, giving Actimab-A backbone therapy potential.

Actimab-A is being advanced into a pivotal Phase 2/3 in combination with the chemotherapy regimen CLAG-M in patients with relapsed or refractory AML and in newly diagnosed AML in combination with Venetoclax and ASTX-727 (Taiho Oncology, an Otsuka holdings company) a novel oral hypomethylating agent (HMA) under a cooperative research and development agreement (CRADA) with the National Cancer Institute (NCI).

Actinium is also developing Actimab-A for solid tumour indications by targeting myeloid derived suppressor cells (MDSCs), CD33 expressing immune cells, which are overexpressed in the tumour microenvironment that can limit the efficacy of PD-1 checkpoint immunotherapies and are associated with poor outcomes.