Actinium Presents Data Showing ATNM-400 is More Efficacious than Pluvicto and is Highly Efficacious after Pluvicto Resistance in Prostate Cancer Tumor Models at the American Association for Cancer Research Annual Meeting

-  Results highlight ATNM-400's potential as a transformative therapeutic option for prostate cancer patients with unmet clinical needs as expression of the target receptor for ATNM-400 persists following Pluvicto therapy and ATNM-400 demonstrates sustained tumor control after Pluvicto stops working

-  ATNM-400 showed greater tumor growth inhibition compared to Pluvicto in prostate cancer models with 99.8% tumor growth inhibition achieved with a single 40 µCi/kg dose of ATNM-400 demonstrating the potential to be offered as an alternative option

-  ATNM-400 was well tolerated with no apparent toxicities at two different dose levels, with efficient clearance from essential organs

NEW YORK, April 28, 2025 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, today announced preclinical results with ATNM-400 in prostate cancer models presented at the American Association for Cancer Research (AACR) Annual Meeting. ATNM-400 is a novel, non-PSMA targeting, first in class targeted radiotherapy utilizing the Actinium-225 (Ac-225) radioisotope that Actinium is evaluating in prostate cancer models prior to and following treatment with Pluvicto. Pluvicto (Lu-177-PSMA-617) is a prostate-specific membrane antigen (PSMA) directed radiotherapy radiolabeled with the beta-particle emitter, Lutetitium-177 (Lu-177) is approved for patients with metastatic castration-resistant prostate cancer. Pluvicto is marketed and sold by Novartis and generated sales of $1.39 billion in 2024.

ATNM-400 is a highly innovative, first-in-class prostate cancer candidate in comparison to Pluvicto and the majority of radiotherapies in development for prostate cancer which target PSMA and are either non-differentiated or barely differentiated, as it targets a distinct non-PSMA receptor. The receptor specifically targeted by ATNM-400 is highly expressed in metastatic castration-resistant prostate cancer (mCRPC) and continues to be expressed at a high level even after Pluvicto treatment which does not appear to impact target expression levels.  ATNM-400 leverages the alpha-particle emitter Ac-225, which is more potent than Lu-177, can cause lethal double-stranded irreversible DNA breaks, and has a shorter path length that could result in fewer off-target effects.

Key Data and Highlights From the ATNM-400 AACR Presentation

In vivo studies demonstrated that ATNM-400 is more efficacious than Pluvicto and produced a statistically significant (p < 0.0001) reduction in tumor volume in 22Rv1 prostate cancer models demonstrating its transformative therapeutic potential.

In mice bearing Pluvicto-failed tumors, ATNM-400 was administered on day 14 following Pluvicto treatment, demonstrating robust antitumor activity and tumor growth inhibition in Pluvicto- resistant tumor models.

• Expression of the target receptor for ATNM-400 persists following Pluvicto therapy and ATNM-400 demonstrates sustained tumor control after Pluvicto stops working
  
  
• ATNM-400 demonstrated greater efficacy than Pluvicto in prostate cancer models with 99.8% tumor growth inhibition achieved with a single 40 µCi/kg dose of ATNM-400 supporting its potential to be offered as an alternative option
  
  
• ATNM-400 internalizes rapidly, exhibiting potent cytotoxicity and prostate cancer cell killing via double strand DNA breaks that are produced by the Ac-225 alpha-particle emitting radionuclide payload of ATNM-400
  
  
• Biodistribution analyses showed sustained uptake in the tumor up to the 216-hour time point, with rapid clearance from the blood by the 48-hour time point and clearance from essential organs including the kidneys, intestines and liver
  
  
• ATNM-400 was well tolerated with body weight recovery and no apparent toxicity at both doses evaluated in vivo

Sandesh Seth, Actinium's Chairman and CEO, said, "We are thrilled to unveil these exciting results demonstrating the transformative therapeutic potential of ATNM-400. There is a significant unmet need for a therapy that can address patients who are treated with Pluvicto and progress, which we only expect to increase following the recent approval of Pluvicto in the earlier line, pre-taxane setting. Consistent with our focus on leading-edge innovation, ATNM-400 is highly novel given it is a non-PSMA target receptor, which is highly expressed in mCRPC, and as we have presented at AACR, continues to be expressed following Pluvicto therapy. ATNM-400 capitalizes on the potency and precision of the Ac-225 isotope payload that can overcome resistance via lethal double strand DNA breaks. Our enthusiasm for ATNM-400 was validated by the significant interest this data received at AACR and we look forward to validating the potential of this exciting radiotherapy candidate as we advance its development with additional data expected later this year".

The ATNM-400 AACR presentation is available for viewing on the Presentations & Webinars page of Actinium's website HERE.

Title: ATNM-400 is a novel Actinium-225 antibody radioconjugate with strong efficacy in preclinical models of prostate cancer
Abstract Number: 578

About Actinium Pharmaceuticals, Inc.

Actinium is a pioneer in the development of targeted radiotherapies intended to meaningfully improve patient outcomes. Actinium is advancing its lead product candidate Actimab-A, a CD33 targeting therapeutic, as potential backbone therapy in acute myeloid leukemia (AML) and other myeloid malignancies leveraging the mutation agnostic alpha-emitter radioisotope payload Actinium-225 (Ac-225). Actimab-A has demonstrated potential activity in relapsed and refractory acute myeloid leukemia (r/r AML) patients in combination with the chemotherapy CLAG-M including high rates of Complete Remissions (CR) and measurable residual disease (MRD) negativity leading to improved survival outcomes and is being advanced to a pivotal Phase 2/3 trial. In addition, Actinium is engaged with the National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) for development of Actimab-A in AML and other myeloid malignancies. The first clinical trial under the CRADA will evaluate the triplet combination comprised of Actimab-A, Venetoclax (Abbvie/Roche) an oral Bcl-2 inhibitor and ASTX-727 (Taiho Oncology, an Otsuka holdings company) a novel oral hypomethylating agent (HMA) in frontline acute myeloid leukemia (AML) patients. Additionally, Actinium is developing Actimab-A as a potential pan tumor therapy in combination with PD-1 checkpoint inhibitors including KEYTRUDA^® and OPDIVO^® by depleting myeloid derived suppressor cells (MDSCs), which represents a potential multi-billion-dollar addressable market. ATNM-400 is Actinium's novel non-PSMA targeting Ac-225 radiotherapy for prostate cancer, which is supported by preclinical data demonstrating higher efficacy than Pluvicto (PSMA-617-Lutetium-177) and potent efficacy in Pluvicto resistant prostate cancer models. Iomab-ACT, Actinium's next generation conditioning candidate, is being developed with the goal of improving patient access and outcomes for potentially curative cell and gene therapies. Iomab-B is an induction and conditioning agent prior to bone marrow transplant in patients with r/r AML, which Actinium is seeking a potential strategic partner for the U.S. In addition, the company's R&D efforts are primarily focused on advancing several preclinical programs for solid tumor indications. Actinium holds 230 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron.

For more information, please visit: https://www.actiniumpharma.com/

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.

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SOURCE Actinium Pharmaceuticals, Inc.