Iomab-ACT Program: Next Generation Targeted Conditioning for GeneTx and CAR-T
The Iomab-ACT program is the use of the ARC apamistamab-I-131 and is an expansion of Actinium's strategic focus on targeted conditioning that brings Actinium into the exciting field of gene therapy (GeneTx) and Adoptive Cell Therapy (ACT) including CAR-T. 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 is being studied in an ongoing pivotal Phase 3 trial. Iomab-ACT is a natural progression of apamistamab-I-131 as conditioning is a critical step prior to bone marrow transplant, gene therapy and CAR-T. In each of these applications, the depletion of bone marrow stem cells, lymphocytes or disease or cancer cells is necessary for the new cells to engraft and the therapy to be successful. Current non-targeted chemotherapy and/or external radiation conditioning regimens are toxic, impair patients and restrict the use and efficacy of these potentially curative therapies. Actinium is committed to bringing its ARC targeted conditioning regimens to patients and advancing the fields of bone marrow transplant, GeneTx and ACT such as CAR-T.
Iomab-ACT for GeneTx
Actinium’s apamistamab-I-131 will be the first targeted conditioning regimen to be used in a clinical trial with a GeneTx. The ongoing Phase 1/2 clinical trial being conducted at UC Davis, is studying an anti-HIV stem cell gene therapy in patients with relapsed or refractory HIV-related lymphoma. The trial will use apamistamab-I-131 for conditioning going forward instead of the chemotherapy conditioning that had been previously used prior to stem cell gene therapy.
In the current clinical trial, the anti-HIV stem cell gene therapy is produced by taking a patient’s own or autologous, blood forming stem cells and genetically modifying them via gene therapy with a combination of three anti-HIV genes. The intended result is for the gene modified bone marrow stem cells to produce a new immune system and newly arising immune cells that are resistant to HIV via a single treatment. Conditioning is necessary prior to adoptive cell therapies such as gene therapy to eliminate certain cell types such as immune cells and stem cells in the bone marrow so the transplanted cells can engraft. Until now, conditioning in this trial, as is typical, used a multi-drug chemotherapy regimen administered over several days. This approach is non-targeted, associated with toxicities that impairs patients and restricts the use and efficacy of cellular therapy. Apamistamab-I-131, which requires just one therapeutic administration, will displace the non-targeted chemotherapy to condition patients in a targeted manner with the goal of reducing conditioning related toxicities and improving patient outcomes.
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.