On April 22, 2026 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported preclinical results for ATNM-400 across prostate, lung, and breast cancer models presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in San Diego, CA. ATNM-400 is a novel, first-in-class targeted radiotherapy utilizing the Actinium-225 (Ac-225) radioisotope that targets a non-PSMA membrane antigen overexpressed in advanced and therapy-refractory solid tumors across multiple oncology indications.

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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 (NSCLC), 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 (Ac-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.

Key Data and Highlights From the ATNM-400 AACR (Free AACR Whitepaper) Presentation

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:

In Prostate Cancer

Demonstrates in vivo efficacy across prostate cancer models with low, medium, and high PSMA expression, including PSMA-negative models.
Shows superior anti-tumor efficacy versus vehicle control, unconjugated antibody, and 177Lu–PSMA-617 (active ingredient in PLUVICTO) in both high -PSMA, (C4-2) and low (22Rv1) PSMA-expressing models, addressing both patients unlikely to respond to PSMA-targeted radioligand therapy (low-PSMA, 22Rv1) and those who relapse on it (C4-2).
Activity in PSMA-negative (DU145) models supports a differentiated profile, suggesting ATNM-400 could address mCRPC patients who are ineligible for or have progressed on PSMA-targeted radioligand therapy due to low or absent PSMA expression— a population with no currently approved targeted radiotherapy option.

In Lung Cancer

New data in the NCI-H1975 EGFR-mutant NSCLC model – a clinically relevant model of osimertinib-resistant disease – 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. These results extend the Company’s prior data demonstrating 100% complete tumor regression with the ATNM-400 plus osimertinib combination.
ATNM-400 monotherapy demonstrates greater anti-tumor activity than Dato-DXd (TROP-2 ADC approved in EGFR-mutant lung cancer) and izalontamab brengitecan (HER3-EGFR bispecific ADC in development for EGFR-mutant lung cancer). ATNM-400 also demonstrates greater anti-tumor activity than the EGFR-cMET bispecific antibody amivantamab (RYBREVANT) as shown in prior studies.

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 (ENHERTU). These results extend the Company’s SABCS 2025 data and position ATNM-400 as a potential alternative for patients who cannot tolerate HER2 ADCs due to interstitial lung disease, a known class-related toxicity.

In the same post-trastuzumab failure setting, ATNM-400 produces durable tumor growth inhibition after treatment discontinuation which exceeds both vehicle control and trastuzumab deruxtecan, supporting the potential for less frequent dosing and more durable disease control than ADCs.Sandesh Seth, Actinium’s Chairman and CEO, said, "The data we presented at AACR (Free AACR Whitepaper) are an important new piece of a much larger picture for ATNM-400. As a single agent, ATNM-400 continues to demonstrate activity across prostate, lung, and breast cancer in the treatment-resistant settings that represent the greatest unmet need, and also in combinations which can expand the available opportunity to additional patient populations. These data build on our previously disclosed results showing significant tumor regression when ATNM-400 is combined with osimertinib in EGFR-mutant lung cancer, and when combined with enzalutamide in prostate cancer, with similar combination potential emerging in breast cancer. What is becoming increasingly clear is that ATNM-400’s target antigen is upregulated by standard-of-care therapies, which creates a strong mechanistic rationale for ATNM-400 to rescue patients who progress approved agents and also to extend the benefit of these approved agents through combinations. We look forward to continuing to advance ATNM-400 toward the clinic with additional data to come in 2026."

The ATNM-400 AACR (Free AACR Whitepaper) presentation is available for viewing on the Presentations & Webinars page of Actinium’s website HERE.

Title: Preclinical Development of ATNM-400, a First-in-Class Actinium-225 Radioconjugate with Pan-Tumor Efficacy in Solid Tumors

Abstract Number: 5824

(Press release, Actinium Pharmaceuticals, APR 22, 2026, View Source [SID1234664695])