Actinium Pharmaceuticals Announces Preclinical Results for ATNM-400

Actinium Pharmaceuticals announced preclinical results for ATNM-400 across prostate, lung, and breast cancer models presented at the American Association for Cancer Research, or AACR, Annual Meeting in San Diego, CA. ATNM-400 is a novel, first-in-class targeted radiotherapy utilizing the Actinium-225, or Ac-225, radioisotope that targets a non-PSMA membrane antigen overexpressed in advanced and therapy-refractory solid tumors across multiple oncology indications. ATNM-400 is a novel, first-in-class targeted radiotherapy whose differentiation stems from both its target and its isotope. The target is a non-PSMA membrane antigen associated with treatment resistance in advanced solid tumors that is overexpressed across prostate cancer, non-small cell lung cancer, and breast cancer, and is further upregulated following treatment with standard-of-care therapies - providing a strong mechanistic rationale for ATNM-400 in the treatment-resistant disease settings that represent the greatest unmet need, and for combination regimens designed to exploit this treatment-induced target upregulation. The isotope, Actinium-225, is a potent alpha emitter that, compared to beta emitters such as Lu-177, delivers high-energy radiation capable of inducing irreversible double-stranded DNA breaks, with a shorter path length that may limit off-target effects and enhance therapeutic precision. Together, this target-and-isotope combination positions ATNM-400 to overcome conventional resistance pathways and deliver durable tumor control while potentially avoiding toxicities such as interstitial lung disease that limit the use of antibody-drug conjugates - expanding the population of patients who could benefit from treatment. New preclinical data support ATNM-400 as a differentiated Ac-225 radioconjugate with potential applicability across multiple high-value solid tumor indications. ATNM-400 demonstrates a favorable tolerability profile, with no significant toxicity observed at therapeutic doses and additionally: Demonstrates in vivo efficacy across prostate cancer models with low, medium, and high PSMA expression, including PSMA-negative models; in lung cancer new data in the NCI-H1975 EGFR-mutant NSCLC model shows ATNM-400 as monotherapy or in combination with osimertinib exceeds the tumor growth inhibition of osimertinib plus chemotherapy, the current standard of care in post-osimertinib progression; and in breast cancer new head-to-head data in the BT474 Clone-5 trastuzumab-resistant HER2+ breast cancer model which is a clinically relevant model of the post-trastuzumab setting, where treatment options are limited, demonstrate that ATNM-400, both as monotherapy and in combination with trastuzumab deruxtecan, achieves anti-tumor activity comparable to the approved HER2-ADC trastuzumab deruxtecan.