SENL-B19

Iomab-B significantly improved outcomes in TP53 positive patients with a median overall survival of 5.49 months versus 1.66 months in those not receiving Iomab-B (hazard ratio = 0.23, p-value=0.0002) in the Phase 3 SIERRA Trial The results demonstrate Iomab-B's ability to overcome the negative impact of a TP53 mutation in these patients who otherwise would have limited treatment options and dismal prognosis Five presentations include two upcoming oral presentations detailing improved outcomes in SIERRA trial patients ages 65+ and demonstration of robust engraftment with Iomab-B NEW YORK, Feb. 23, 2024 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, today highlighted results from three poster presentations at the 2024 Tandem Meetings | Transplantation & Cellular Therapy (TCT) Meetings of ASTCT® (American Society for Transplantation and Cellular Therapy and CIBMTR® (Center for International Blood and Marrow Transplant Research) being held in San Antonio, Texas. The posters detailed results and findings from the Phase 3 SIERRA trial of Iomab-B (131I-Apamistamab) including; improved rates of Complete Remission (CR), durable Complete Remission (dCR) and survival in patients with a TP53 mutation, key aspects of radiopharmaceutical dosimetry as related to Iomab-B, and early results from a Phase 1 study demonstrating safety and lymphodepletion from Iomab-ACT conditioning with CD19 CAR-T therapy. Dr. Avinash Desai, Actinium's Chief Medical Officer, said, "Patients with a TP53 mutation have a desperate need for viable treatment options to improve outcomes. As seen in the SIERRA trial, Iomab-B led bone marrow transplant can overcome the negative impact of a TP53 mutation, producing complete remissions in more than 50% of patients as well as significant durable complete remissions. This is in stark contrast to the 0% complete remission and durable complete remission rate seen in the TP53 positive patients on the control arm who received best available treatment based on physician's choice. We are excited to further highlight these important outcomes to the transplant community and look forward to presenting additional findings from the SIERRA trial in our upcoming oral presentations." The presented Iomab-B Phase 3 SIERRA trial results and highlights include: Response Rate by TP53 Mutational Status and Treatment CR = Complete Remission Improved Survival with Iomab-B Upcoming Iomab-B Phase 3 SIERRA Trial 2024 TCT Oral Presentations: Title: 131I-Apamistamab Improves Outcomes in Patients 65 Years and Older with Relapsed or Refractory AML Date & Time: Saturday, February 24, 2024, at 11:45 AM Title: Targeted Myeloablative Radiation Using 131I-Apamistamab Prior to Allogeneic Hematopoietic Cell Transplant for Patients with R/R AML Results in Robust Engraftment Date & Time: Saturday, February 24, 2024, at 10:30 AM In addition, Actinium presented results from its ongoing phase 1 trial using Iomab-ACT as conditioning prior to CD19 CAR-T therapy for patients with relapsed or refractory B-cell Acute Lymphoblastic Leukemia or Diffuse Large B-cell Lymphoma. Importantly, no patients (0/4) developed immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade, a major safety measure of the study, as ICANS is observed in 25% or more of pts w/ R/R B-ALL and DLBCL treated with various CAR T-cell products. Iomab-ACT demonstrated transient depletion of peripheral blood lymphocytes and monocytes. Persistence of CAR T-cells up to 8 weeks and minimal non-hematologic toxicities have been observed to date. About the TCT Tandem Meetings The Tandem Meetings I Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR are the combined annual meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR). Administrators, clinicians, data manager / clinical research professionals, fellows-in-training, investigators, laboratory technicians, MD/PhDs, nurses, nurse practitioners, pharmacists, physician assistants, and other allied health professional attendees benefit from a full scientific program that addresses the most timely issues in hematopoietic cell transplantation and cellular therapy. About Actinium Pharmaceuticals, Inc. Actinium develops targeted radiotherapies to meaningfully improve survival for people who have failed existing oncology therapies. Advanced pipeline candidates Iomab-B (pre-BLA & MAA (EU)), an induction and conditioning agent prior to bone marrow transplant, and Actimab-A (National Cancer Institute CRADA pivotal development path), a therapeutic agent, have demonstrated potential to extend survival outcomes for people with relapsed and refractory acute myeloid leukemia. Actinium plans to advance Iomab-B for other blood cancers and next generation conditioning candidate Iomab-ACT to improve cell and gene therapy outcomes. Actinium holds more than 220 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron. For more information, please visit: Forward-Looking Statements This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time. Investors: investorrelations@actiniumpharma.com View original content to download multimedia: SOURCE Actinium Pharmaceuticals, Inc. Company Codes: AMEX:ATNM

--Researchers found CAR T-cell therapy may serve as effective alternative for patients with these disorders -- PHILADELPHIA, Nov. 17, 2023 /PRNewswire/ -- Immunotherapies that target the CD20 antigen have revolutionized how patients with a variety of blood cancers and hematologic disorders have been treated. However, many patients develop resistance to these treatments due to a loss of the antigen that's being targeted. Now, a new study from researchers at Children's Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania (Penn) has found that gene splicing occurring within these cells can cause significant changes in CD20 protein levels that render the therapies ineffective. The findings, published today by the journal Blood, also demonstrate that patients with very low levels of CD20 may still be responsive to CAR-T therapy, something that was previously thought not possible. These findings may lead to more appropriate choices for therapy that maximize benefits to patients affected by a variety of blood cancers. CD20 is a cell-surface protein involved in the fine-tuning of B cell responses to foreign agents like viruses. It is expressed exclusively on the surface of normal and malignant B cells and is not expressed by other cell types in the body. This makes CD20 an attractive target for monoclonal antibody therapies which have been used to treat a variety of B-cell lymphomas, including follicular lymphoma, Burkitt lymphoma, diffuse large B cell lymphomas and high-grade B-cell lymphomas. Despite anti-CD20 therapies revolutionizing the way these conditions are treated, some patients with these conditions do not respond to antibodies targeting CD20, while others initially respond before eventually developing resistance. Prior research had shown that a loss of CD20 reduced the effectiveness of these immunotherapies, since it would remove their intended target. However, the mechanism by which CD20 levels can be reduced were poorly understood. Researchers at CHOP suspected that CD20 messenger RNA was not being properly translated into the CD20 protein expressed on the surfaces of cells. "It does not matter how much mRNA is being made, it's how effectively it is translated that matters," said senior study author Andrei Thomas-Tikhonenko, PhD, chief of the Division of Cancer Pathobiology and a professor with the Department of Pathology and Laboratory Medicine at CHOP and Penn. "In this study, we found that certain isoforms of the mRNA responsible for producing CD20 were impacted by splicing in a way that the proteins were not being made at the levels necessary for these immunotherapies to do their job." In the study, researchers focused on the MS4A1 gene, which encodes for CD20. The gene undergoes splicing, or stitching together of its building blocks called exons, to produce several mRNA isoforms, which may encode the identical amino acid sequence, but differ in the efficiency with which the protein is made. The researchers identified four variants in total among normal and malignant cells. Of the four variants, V1 and V3 were by far the most abundant, yet only V3 is efficiently translated into CD20. In contrast, variant V1 had trouble recruiting ribosomes responsible for making proteins, making it difficult for monoclonal antibodies to target affected cells. Surprisingly, CHOP researchers and their Penn collaborators, including Drs. Steven Schuster and Marco Ruella, also found that CAR T-cells were still able to effectively kill both V3- and V1-expressing cells. CAR T-cell therapy modifies patient's own immune cells to kill cancer cells. Historically, CAR T-cell therapy presented challenges and was thought not to be effective in these malignancies, but the study showed that it was more effective in targeting both variants compared with the monoclonal antibody mosunetuzumab, which was only effective against V3-expressing cells. "If a patient has relapsed because CD20 levels are downregulated, CAR T-cell therapy may still be an option, as it requires a lower threshold of the protein in order to be effective," said first study author Zhiwei Ang, PhD, Research Associate Scientist in the Thomas-Tikhonenko lab. "These findings may help clinical staff offer more precise options when treating these hematologic malignancies." This study was supported by grants from the National Institutes of Health grants U01 CA232563, U01 CA232563-S3, U01 CA232486, U01 CA243072, and T32 CA009615, United States Department of Defense grant CA180683P1, The V Foundation for Cancer Research grant T2018-014, The Emerson Collective grant 886246066, the Leukemia & Lymphoma Society, the Joshua Kahan Endowed Chair in Pediatric Leukemia Research and the Mildred L. Roeckle Endowed Chair in Pathology at CHOP. Ang et al, "Alternative splicing of its 5'-UTR limits CD20 mRNA translation and enables resistance to CD20-directed immunotherapies." Blood. 142 (2023) pp. 1724-1739. DOI: 10.1182/blood.2023020400. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the 595-bed hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as an inpatient hospital campus with a dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Ben Leach Children's Hospital of Philadelphia (609)634-7906 [email protected] SOURCE Children's Hospital of Philadelphia