Actinium’s Antibody Radiation Conjugate Iomab-ACT Cleared for US Trial as Conditioning Therapy for SCD Allo-BMT

Actinium’s Iomab-ACT, an investigational antibody radiation conjugate (ARC) intended to serve as an alternative to chemotherapy conditioning agents, has received clearance of an investigational new drug application from the FDA for trial evaluating it as a conditioning agent for patients planning to receive allogeneic bone marrow transplant (allo-BMT) for the treatment of sickle cell disease (SCD).¹

Unlike the nontargeted chemotherapy and total body irradiation currently used for SCD patients receiving allo-BMT, Iomab-ACT is directed at CD45, an antigen expressed on immune cells. Iomab-ACT is intended to broaden eligibility for patients with SCD to receive allo-BMT to some patients who cannot receive current chemotherapy conditioning. Pending positive results in the trial, which is to be carried out in a collaboration with the Columbia University, Actinium may later evaluate Iomab-ACT as an alternative to current chemotherapy conditioning for patients planning to receive either of the 2 FDA-approved gene therapy options for SCD: Vertex Pharmaceuticals' and CRISPR Therapeutics’ exagamglogene autotemcel (exa-cel; marketed as Casgevy) and bluebird bio’s lovotibeglogene autotemcel (lovo-cel; marketed as Lyfgenia).

"Undergoing chemotherapy- or total body irradiation-based conditioning for curative allo-BMT or gene therapy often brings severe side effects for patients with SCD,” Markus Mapara, MD, PhD, a professor of medicine at Columbia University Irving Medical Center, and director of the Bone Marrow Transplantation and Cell Therapy Program at Vagelos College of Physicians and Surgeons, said in a statement.¹ “These toxicities include organ damage, infections, infertility, and the potential for secondary malignancies. Leveraging extensive data from CD45 ARC conditioning in allo-BMTs, I am thrilled to lead this pioneering study using Iomab-ACT, a nonchemotherapeutic targeted radiotherapy conditioning, for patients with SCD. This innovative approach aims to minimize toxicity while ensuring complete donor hematopoiesis engraftment. Success in this trial could revolutionize treatment, enabling the use of a low-toxicity method for the engraftment of genetically engineered autologous stem cells in SCD patients."

Actinium is also seeking to evaluate Iomab-ACT as an alternative to the chemotherapy conditioning regimens currently received by patients planning to undergo treatment with FDA-approved chimeric antigen receptor T-cell (CAR-T) therapy for oncology indications.² In March 2024, the company announced that it will be carrying out a clinical trial for this purpose in collaboration with the University of Texas Southwestern Medical Center (UT Southwestern), pending clearance from the FDA. According to Actinium, early clinical data indicates that Iomab-ACT may reduce the occurrence of immune effector cell-associated neurotoxicity syndrome or cytokine release syndrome seen with standard chemotherapy conditioning regimens to negligible levels. Similar to the expectations regarding Iomab-ACT in SCD, the ARC is expected to enable patients with blood cancers who would be ineligible for standard chemotherapy regimens to receive CAR-T therapies.

"We are honored to collaborate with Dr. Mapara on this important initiative to address the significant number of patients with SCD who do not pursue or are not able to access transplant or gene therapies due to the required chemotherapy-based conditioning and its severe toxicities,” Sandesh Seth, MS, Actinium's chairman and chief executive officer, added to the statement.¹ “SCD represents a large and high unmet need that needs better treatment options and outcomes. This exciting program in SCD adds to our recently announced commercial CAR-T trial addressing the large patient population with blood cancers that can also benefit from broader access to cellular therapy via targeted conditioning. We look forward to further expanding Iomab-ACT's already large addressable patient opportunity in transplant, cell therapy, and gene therapy conditioning."

REFERENCES
1. Actinium announces FDA clearance of Iomab-ACT targeted conditioning IND application for sickle cell disease patients undergoing bone marrow transplant in collaboration with Columbia University. News release. Actinium Pharmaceuticals, Inc. July 25, 2024. Accessed July 29, 2024.https://ir.actiniumpharma.com/press-releases/detail/484/actinium-announces-fda-clearance-of-iomab-act-targeted
2. Actinium announces clinical trial to study Iomab-ACT targeted radiotherapy conditioning with leading FDA approved commercial CAR T-cell therapy. News release. Actinium Pharmaceuticals, Inc. March 26, 2024. Accessed July 29, 2024. https://ir.actiniumpharma.com/press-releases/detail/472/actinium-announces-clinical-trial-to-study-iomab-act