Actinium Pharmaceuticals announced its collaborator, Memorial Sloan Kettering Cancer Center (MSK), has commenced patient enrollment in the Phase 1 study evaluating Iomab-ACT for targeted conditioning prior to treatment with MSK's CD19 targeted CAR T-cell 19-28z. Iomab-ACT is a low dose version of Actinium's Phase 3 drug candidate Iomab-B, a CD45 targeting antibody radiation conjugate (ARC). Actinium and MSK were jointly awarded National Institutes of Health Small Business Technology Transfer grant funding for this first ever trial to evaluate ARC-based targeted conditioning prior to CAR-T therapy. The scientific rationale for this trial builds on preclinical data published in 2020 and is further supported by clinical observations from the SIERRA trial to justify combining MSK's 19-28z CAR T-cell therapy with Iomab-ACT. Manufacturing of patient CAR T-cells has commenced and patient conditioning with Iomab-ACT followed by 19-28z CAR T-cell infusion is expected early in the second quarter of 2021, with proof-of-concept data expected in the second half of 2021.

Results of a Phase 2 trial in 53 patients with relapsed and refractory B-cell acute lymphoblastic leukemia with MSK's 19-28z CAR-T published in the New England Journal of Medicine reported complete remissions in 83% (44/53) of patients, median event-free survival (EFS) of 6.1 months and median overall survival (OS) was 12.9 months at a median follow up period of 29 months (range 1 – 65 months). There was a 26% (14/53) rate of Grade 3 of greater cytokine release syndrome (CRS), with 1 patient death as a result, and 42% of patients experienced Grade 3-4 immune effector cell-associated neurotoxicity syndrome (ICANS).

"MSK's 19-28z CAR T-cell therapy has produced high response rates in patients with relapsed or refractory B-ALL who have previously undergone several lines of standard therapy. However, toxicities such as cytokine release syndrome and neurologic toxicity, as well as durability of response, remain a significant challenge. The ARC technology Iomab-ACT employs enables the delivery of targeted radiation that selective and specifically targets immune cells including those implicated in the CAR-T-associated toxicities of neurotoxicity and cytokine release syndrome. We are eager to begin treating patients in this first of its kind pilot study to explore the potential of Iomab-ACT targeted lymphodepletion to modulate the immune system and improve the safety profile of CAR T-cell therapy. We are hopeful this technology may ultimately enhance our ability to deliver CAR T-cell therapies more safely. Positive results from pilot study could have a meaningful impact on the way we condition patients for CAR-T and other adoptive cell therapies, which have transformed the treatment of patients with blood cancers," Dr. Dale Ludwig, Actinium's Chief Scientific and Technology Officer, said.

"This is a major milestone for Actinium and one we are very excited by. Adoptive cell therapies like CAR-T and gene therapies have emerged as some of the most promising areas in medicine and hold tremendous promise for patients, many of whom have limited or no treatment options remaining. This promise has led to a large and growing field of therapies where we intend to establish Iomab-ACT as the universal solution for targeted, non-chemotherapy conditioning, that harnesses the power of radiation. With Iomab-B nearing complete enrollment in the Phase 3 SIERRA trial for bone marrow transplant conditioning, starting to treat patients in this Iomab-ACT trial for CAR-T conditioning could not come at a better time. We look forward to continuing to build out our strategic business unit in targeted conditioning to best serve patients seeking potentially curative bone marrow transplant, adoptive cell therapy and gene therapy to improve patient access and outcomes," Sandesh Seth, Actinium's Chairman and CEO, said.

Iomab-ACT targets cells that express CD45, an antigen found on immune cells such as lymphocytes and macrophages as well as leukemia and lymphoma cancer cells and delivers the radioisotope warhead iodine-131 to achieve cell depletion. Iomab-ACT is intended to deplete CD45+ immune cells such as macrophages that are implicated in CAR-T related toxicities and may also have an anti-tumor effect on chemo-refractory cancers. Iomab-ACT is a low dose extension of Actinium's lead program, Iomab-B, which is being studied in a pivotal Phase 3 trial for targeted conditioning prior to a bone marrow transplant.