On October 13, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of differentiated targeted radiotherapies, reported that compelling preclinical data for ATNM-400, its novel, first-in-class antibody radioconjugate armed with the potent alpha-emitter Actinium-225 (Ac-225), has been accepted for presentation at the 32nd Annual Prostate Cancer Foundation (PCF) Scientific Retreat being held on October 23 – 25, 2025 in Carlsbad, CA (Press release, Actinium Pharmaceuticals, OCT 13, 2025, View Source [SID1234656594]). The presentation will highlight ATNM-400’s ability to induce robust, durable anti-tumor activity in metastatic castration-resistant prostate cancer (mCRPC) models, including tumors resistant to standard-of-care therapies such as the androgen receptor pathway inhibitor (ARPI), enzalutamide (Xtandi, Astellas/Pfizer) and the PSMA-targeted therapy, 177Lu-PSMA-617 (active agent in Pluvicto, Novartis) as well as superior efficacy compared to 225Ac-PSMA-617.

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ATNM-400 PCF Presentation Information

Title: ATNM-400, a first-in-class Actinium-225 antibody radioconjugate, demonstrates potent anti-tumor activity and overcomes resistance to enzalutamide and 177Lu-PSMA-617 in prostate cancer models

Poster Session Date and Time: Thursday, October 23, 2025, 7:30 – 10:30 PM P.T.

Following the PCF presentation, the ATNM-400 poster will be available for viewing online on Actinium’s investor relations page HERE.

Addressing Critical Unmet Needs in mCRPC

Prostate cancer patients who progress to mCRPC face limited treatment options. While ARPI therapies like enzalutamide and PSMA-targeted radiotherapies like Pluvicto have extended survival, resistance and disease progression remain major challenges.

ATNM-400 directly addresses this unmet need by targeting a distinct, non-PSMA tumor antigen strongly linked to treatment resistance, rapid disease progression, and poor survival outcomes in prostate cancer. Leveraging a high-affinity antibody against the novel target, combined with the potent cell-killing power of alpha radiation via the Ac-225 isotope payload, ATNM-400 offers a mechanistically differentiated approach beyond current PSMA-directed therapies. The target antigen of ATNM-400 is overexpressed following ARPI therapy and is associated with a shorter time to castration resistance. This positions ATNM-400 as a differentiated treatment option in the post-ARPI setting, where it has been shown to overcome enzalutamide resistance and enhance the efficacy of ARPI combinations. In preclinical models, synergy with enzalutamide resulted in robust, durable tumor control and significantly improved overall survival. This innovative strategy aims to overcome limitations of current treatments and provide new hope for patients facing advanced prostate cancer.

"ATNM-400’s ability to maintain anti-tumor activity in both PSMA-expressing and PSMA-resistant models, while also synergizing with ARPI therapy, underscores its potential as a differentiated, next-generation alpha therapy for prostate cancer," said Sandesh Seth, Chairman and Chief Executive Officer, Actinium Pharmaceuticals, Inc. "We look forward to highlighting ATNM-400 at PCF and engaging with prostate cancer KOLs as we work to further advance ATNM-400."

About ATNM-400

ATNM-400 is a novel, first-in-class Ac-225 antibody radioconjugate targeting a distinct non-PSMA protein strongly implicated in prostate cancer progression and treatment resistance. Unlike 177Lu-PSMA-617, the active agent in Pluvicto and the majority of radiotherapies under development, which rely on PSMA targeting, ATNM-400 is designed to maintain efficacy in PSMA-low or PSMA-resistant disease, a major unmet clinical need. Ac-225 delivers high-linear-energy-transfer alpha particles that induce irreparable double-strand DNA breaks, offering superior potency over beta emitters like Lutetium-177 (177Lu), and has a shorter tissue path length that may reduce off-target toxicity. Additionally, the antigen specifically targeted by ATNM-400 continues to be expressed at a high level even after androgen receptor inhibitor (ARPI) therapy and ATNM-400 has shown to overcome resistance to the ARPI therapy enzalutamide and work synergistically in combination with enhanced tumor control including complete tumor regression.

Prostate cancer is the most 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 and do not respond or develop resistance to Pluvicto. In the U.S., 40,000 – 60,000 mCRPC patients annually progress after ARPI therapy, which as a class had sales of over $10.0 billion in 2024 including enzalutamide (Xtandi) which led the ARPI class with sales of over $5.9 billion in 2024, highlighting a significant unmet need. Actinium intends to evaluate ATNM-400 in other solid tumor indications beyond prostate cancer.