Actinium Pharmaceuticals, Inc. announced that it has entered into a research collaboration with Columbia University to study Actimab-A, its clinical-stage CD33 targeting radiotherapeutic, with engineered hematopoietic stem cells (eHSCs) modified by CRISPR/Cas9 gene editing technology to knock out CD33 expression. Dr. Siddhartha Mukherjee, MD, DPhil, Assistant Professor of Medicine at Columbia University Medical Center in the Department of Medicine and Division of Hematology/Oncology and his research group developed the technology. Technology from Dr. Mukherjee's lab has been licensed and is currently being developed by Vor Biopharma, Inc., including trem-cel (formerly VOR33).

Vor is currently using Mylotarg, a CD33 targeting antibody drug conjugate (ADC), in its clinical trial to target residual CD33 positive leukemia cells post-transplant. Under this collaboration, Actimab-A will be administered following transplantation of the eHSCs with the goal of eliminating any CD33 positive residual AML cells. eHSCs are intended to engraft and reconstitute patients' blood and immune systems with cells that do not express cancer-specific targets such as CD33.

This would then allow a patient to receive CD33 targeting therapy post-transplant to eradicate any residual CD33 positive leukemia cells and prevent relapse while sparing newly formed blood cells that do not express CD33. Actimab-A has been studied in over 150 AML patients in six clinical trials. It has the most clinical experience of any Actinium-225 based drug candidate in development.

Actinium-225 is an alpha-particle emitting radioisotope that has the most potent cell killing ability of any medical grade isotope but has a short pathlength that limits potential off-target effects. Recently, Actimab-A demonstrated high rates MRD negativity following CLAG-M therapy in relapsed or refractory AML patients with adverse risk features including over 50% with a TP53 mutation and over 50% who received prior treatment with Venetoclax. This resulted in a 53% 1-year overall survival and 32% 2-year overall survival in a patient group that has an expected overall survival of less than 3 months.