Iomab-ACT Program: Next Generation Targeted Conditioning for GeneTx and CAR-T

Iomab-ACT is comprised of apamistamab, the same anti-CD45 antibody as Iomab-B, but utilizes lower, nonmyeloablative levels of I-131 to achieve lymphodepletion for cellular therapies such as CAR-T or reduced intensity conditioning for gene therapies. We intend to continue to develop the Iomab-ACT program designed specifically for use prior to CAR-T and gene therapies, ultimately with a value proposition of improving overall access and outcomes for patients who need cellular or gene therapies. We are studying Iomab-ACT in collaboration with MSKCC, for conditioning prior to CAR-T therapy for patients with relapsed or refractory B-cell acute lymphoblastic leukemia (“B-ALL”) or diffuse large B-cell lymphoma (“DLBCL”). This study funded by a NIH grant is the first-of-its-kind study to use a radiotherapeutic-based conditioning regimen with CAR-T therapy. We have completed treatment of an initial cohort of three patients and have expanded to a second cohort that continues to be conducted under an extension of our NIH grant. The Iomab-ACT program builds on Actinium's expertise in targeted conditioning gained from its development of apamistamab-I-131 for bone marrow transplant (BMT) conditioning (Iomab-B), which has been studied in multiple clinical trials in over 300 patients including the completed Phase 3 SIERRA trial.

CAR-T is a revolutionary medical approach that has led to paradigm shifts in the treatment of patients with certain cancers. The rapidly evolving and crowded field of CAR-T is now filled by dozens of companies, including some of the largest pharmaceutical and biotechnology companies, who are working on over 200 CAR-T programs. Despite significant advances in the field of CAR-T, little innovation has been applied to a critical aspect of the CAR-T treatment process called lymphodepletion.

Actinium's Iomab-ACT program is intended to be a universal next generation targeted lymphodepletion solution for CAR-T. Actinium's approach is multi-modal and is intended to lymphodeplete and reduce the patient's tumor burden while also optimizing the tumor microenvironment by targeting regulatory T cells, myeloid derived suppressor T cells and cytokine secreting macrophages. All of these cells express CD45 and would therefore be targeted by Iomab-ACT. In doing so, Actinium believes the Iomab-ACT program has the potential to improve CAR-T efficacy and response duration through improved cell expansion and persistence. Also, through the reduction in macrophages and other cells, Actinium believes it can reduce toxicities such as cytokine release syndrome (CRS) and neurotoxity, which are potentially fatal and black box warning for approved CAR-T products.

Actinium believes Iomab-ACT has the potential to address many limitations of CAR-T that are not addressed by current non-targeted, non-optimized lymphodepletion regimens such as Fludarabine and Cyclophosphamide (Flu/Cy) as highlighted below.

Through targeted conditioning for lymphodepletion via the Iomab-ACT program, Actinium hopes it can improve CAR-T patient access and outcomes.

To learn more about Actinium's Iomab-ACT program for next generation lymphodepletion please contact IomabACT@actiniumpharma.com.