On July 31, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported additional preclinical data supporting its ATNM-400 radiotherapy prostate cancer candidate at the 4th Annual Targeted Radiopharmaceuticals Summit (TRP) being held July 29 – 31, 2025 in San Diego, CA (Press release, Actinium Pharmaceuticals, JUL 31, 2025, View Source [SID1234654691]). ATNM-400 is a novel, first-in-class targeted radiotherapy designed to deliver potent Actinium-225 (Ac-225), an alpha-emitter radioisotope, to prostate cancer cells by targeting a non-Prostate Specific Membrane Antigen (PSMA), disease-driving protein overexpressed in advanced and treatment-resistant disease. Unlike PSMA-targeted agents that primarily serve as imaging and targeting tools, the ATNM-400 target is directly implicated in tumor progression, survival signaling, and resistance to androgen receptor (AR) pathway inhibitor (ARPI) therapy. The presentation titled, "Building a Transformative Ac-225 Portfolio for Next-Generation Precision Oncology" on Wednesday, July 30, 2025, highlighted new PET imaging data showing tumor-specific uptake of ATNM-400, robust tumor control and improved survival outcomes in preclinical studies.

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ATNM-400 Demonstrated Sustained Tumor-Specific Uptake

PET imaging confirmed tumor-specific uptake of the ATNM-400 antibody

The ATNM-400 antibody showed sustained tumor uptake up to 216 hours with rapid clearance from normal tissues
ATNM-400 Produced Robust Tumor Control, Improved Survival and Superior Efficacy After Pluvicto Resistance

ATNM-400 is more efficacious than Pluvicto (Lu-177-PSMA-617) with potent tumor control

ATNM-400 significantly improved survival compared to Pluvicto with continued follow-up ongoing

ATNM-400 is highly effective in prostate cancer tumors with acquired Pluvicto resistance, halting tumor growth and producing potent tumor cell killing after Pluvicto stops working, highlighting its potential in advanced disease settings that are resistant to standard treatments
Enhanced Efficacy of ATNM-400 with Enzalutamide Supports Potential for Novel Combinations

ATNM-400 demonstrated significant in vitro tumor cell killing when used in combination with AR-targeting agents, such as enzalutamide (Xtandi)

The ATNM-400 enzalutamide combination produced superior anti-tumor efficacy and durable tumor control compared to enzalutamide alone with 40% of prostate cancer tumor-bearing animals having complete cures

Actinium previously highlighted that ATNM-400 inhibited tumor growth of enzalutamide resistant tumors whereas re-treatment with Pluvicto or additional enzalutamide did not

Actinium highlighted that follow-up continues to further evaluate the durability of ATNM-400’s anti-tumor efficacy in prostate cancer with additional data expected in the second half of 2025. Actinium’s TRP presentation can be accessed via the Investor Relations page of Actinium’s website HERE.

Sandesh Seth, Actinium’s Chairman and CEO, said, "We are highly encouraged by the growing body of data supporting the therapeutic potential of ATNM-400 and the significance of its target being directly implicated in tumor progression, survival signaling, and resistance to ARPI therapy. The new data presented at TRP highlight the utility of the differentiated mechanism of action of ATNM-400 via the Ac-225 alpha-emitter payload evidenced by durable tumor control, improved survival rates compared to Pluvicto, and efficacy in enzalutamide and Pluvicto resistant models. We believe ATNM-400 has the potential to redefine the treatment paradigm in the high-value, advanced disease, and metastatic castrate-resistant prostate cancer settings, which impact tens of thousands of patients annually. We look forward to presenting additional data in the second half of this year and further highlighting ATNM-400’s differentiated potential in treatment settings with high unmet needs."

About ATNM-400

ATNM-400 is a highly innovative, first-in-class, non-PSMA targeting Actinium-225 (Ac-225) radiotherapy candidate for prostate cancer. In comparison to Pluvicto (Lu-177-PSMA-617) and the majority of radiotherapies in development for prostate cancer, which target prostate specific membrane antigen (PSMA) and are either non-differentiated or barely differentiated, ATNM-400 targets a distinct non-PSMA disease-driving protein overexpressed in advanced and treatment-resistant disease. The receptor specifically targeted by ATNM-400 is highly expressed in metastatic castration-resistant prostate cancer (mCRPC), contributes directly to disease progression, poorer survival outcomes, and continues to be expressed at a high level even after androgen receptor inhibitor (ARPI) and Pluvicto treatment. ATNM-400 leverages the alpha-particle emitter Ac-225, which can cause lethal irreversible double-stranded DNA breaks and is more potent compared to the beta-particle emitter Lutetium-177 (Lu-177) used by Pluvicto, as well as a shorter path length that could result in fewer off-target effects.

Prostate cancer is the most commonly diagnosed cancer in men, with ~1.5 million new cases globally and over 313,000 expected in the U.S. in 2025. While early-stage disease is typically managed with surgery, radiation, and ARPI therapy, up to 20% of cases progress to mCRPC – a lethal stage with limited treatment options. Targeted radiotherapy is a growing field in prostate cancer, dominated by PSMA-targeting agents like Pluvicto, which had sales of over $1.3 billion in 2024, yet many patients either lack PSMA expression or develop resistance to Pluvicto. In the U.S., 40,000–60,000 mCRPC patients annually progress after ARPIs such as Xtandi, which had sales of over $5.9 billion in 2024, highlighting a significant unmet need.