Actinium’s ATNM-400 Delivers Breakthrough Efficacy in Resistant Prostate Cancer Models

Expanding Potential for Next-Generation Radiotherapy

Actinium Pharmaceuticals (NYSE American: ATNM) presented new preclinical data at the 32nd Annual Prostate Cancer Foundation Scientific Retreat, highlighting the strong therapeutic potential of ATNM-400, its first-in-class Actinium-225 (Ac-225) alpha radiotherapy targeting a non-PSMA antigen associated with prostate cancer progression and treatment resistance.

A Novel Approach to Overcoming Resistance

Unlike existing PSMA-targeted radiotherapies such as Pluvicto® (177Lu-PSMA-617), which lose effectiveness in patients with low or absent PSMA expression, ATNM-400 targets a distinct, non-PSMA protein that remains expressed even after androgen receptor pathway inhibitor (ARPI) or PSMA-directed therapy. This unique mechanism offers hope for patients with metastatic castration-resistant prostate cancer (mCRPC) who have exhausted current options.

In preclinical studies, ATNM-400 achieved:

• Superior tumor control and survival compared with enzalutamide and 177Lu-PSMA-617

• Durable anti-tumor activity lasting up to 100 days versus 20 days for enzalutamide

• Complete tumor regression in 40% of animals when combined with enzalutamide

• Efficacy in resistant disease models, including those unresponsive to 177Lu-PSMA-617

Actinium’s CEO, Sandesh Seth, said the findings reinforce ATNM-400’s potential to “transform the treatment paradigm for patients with mCRPC” through a biologically distinct, PSMA-independent mechanism.

Expanding to Other Tumor Types

Beyond prostate cancer, Actinium is also advancing ATNM-400 into non-small cell lung cancer (NSCLC), where it has demonstrated the ability to overcome resistance to osimertinib (Tagrisso®, AstraZeneca) in preclinical models.

A Leader in Targeted Radiotherapy Innovation

Actinium Pharmaceuticals has established itself as a pioneer in the field of targeted alpha radiotherapies, leveraging Actinium-225’s precision and potency across multiple cancers. In addition to ATNM-400, the company’s pipeline includes Actimab-A, a CD33-targeted therapeutic advancing toward Phase 2/3 trials in acute myeloid leukemia (AML)under a collaboration with the National Cancer Institute.

With ATNM-400 showing promise in both prostate and lung cancer models, Actinium is positioning itself at the forefront of next-generation radiotherapeutic innovation, aiming to bring new treatment options to patients who currently have few.