ATNM-400 from Actinium Pharmaceuticals (ATNM) shows breakthrough promise in resistant breast cancer

Actinium Pharmaceuticals, Inc. (NYSE American: ATNM) has announced new preclinical data for its lead radiopharmaceutical candidate ATNM-400, a first-in-class Actinium-225 antibody radioconjugate, showing strong tumor-suppressing effects in models of triple-negative breast cancer and hormone receptor or HER2-positive subtypes that have developed resistance to standard therapies. The data will be presented on December 11, 2025, during the San Antonio Breast Cancer Symposium, one of the most prominent oncology events globally, drawing attention from clinicians, researchers, and investors.

The American radiopharma developer said the new dataset strengthens the rationale for using ATNM-400 in breast cancer patients who have progressed after tamoxifen or trastuzumab. Unlike conventional antibody-drug conjugates, the ATNM-400 candidate delivers targeted alpha-particle radiation to tumors, leveraging the high potency and short path length of Actinium-225 emissions. In doing so, the therapy aims to bypass common dose-limiting toxicities such as interstitial lung disease, which often constrain HER2-targeting ADCs like trastuzumab deruxtecan.

Actinium Pharmaceuticals has positioned ATNM-400 as a differentiated approach not only for endocrine- and HER2-resistant patients but also for those with triple-negative breast cancer, a subtype notorious for poor prognosis and high relapse rates. The company noted that approximately 40 percent of patients with TNBC experience rapid recurrence, often without viable therapeutic options after initial treatment failure. ATNM-400 showed robust anti-tumor effects in TNBC models, supporting its potential entry into first-in-human trials targeting this unmet need.

What makes ATNM-400 a novel therapeutic option in treatment-resistant breast cancer?

Breast cancer continues to be the most common cancer in women, with over 70 percent of cases being hormone receptor positive. Despite advancements in endocrine therapies like tamoxifen, recurrence remains a major issue, affecting 20 to 30 percent of patients. Similarly, a significant subset of HER2-positive breast cancers eventually become resistant to trastuzumab and other HER2-targeted treatments.

Actinium Pharmaceuticals developed ATNM-400 to specifically target a tumor antigen that is overexpressed in patients who have developed resistance to these frontline treatments. This target is also associated with increased disease progression, metastasis, and worse clinical outcomes. By attaching Actinium-225 to an antibody that recognizes this resistance-linked antigen, ATNM-400 delivers localized radiation directly into tumor cells while minimizing damage to healthy tissue.

This strategy contrasts with ADCs that carry chemotherapeutic payloads, which often result in broader systemic exposure and off-target effects. The company emphasized that ATNM-400’s design could expand treatment options for patients unable to tolerate ADC-related toxicities, particularly lung-related complications such as ILD.

In preclinical testing, the therapy inhibited tumor growth across multiple resistant models, demonstrating its potential as a monotherapy or in combination with existing drugs. The company will present these findings during a dedicated SABCS session on December 11 at 5:00 PM CT.

How is Actinium positioning ATNM-400 as a pan-tumor radiopharmaceutical platform?

Beyond its breast cancer data, Actinium Pharmaceuticals has highlighted ATNM-400’s potential in metastatic castration-resistant prostate cancer and non-small cell lung cancer. In both cases, the therapy targets the same resistance-associated antigen, which remains highly expressed even after treatment with androgen receptor inhibitors or PSMA-targeted radiotherapies in prostate cancer and EGFR inhibitors in NSCLC.

In prostate cancer models, ATNM-400 has demonstrated superior efficacy compared to enzalutamide and 177Lu-PSMA-617, the active agent in Pluvicto, while also retaining activity in tumors that had developed resistance to these agents. Moreover, the therapy exhibited synergy when used in combination with enzalutamide, suggesting utility in various stages of prostate cancer treatment.

Similarly, in NSCLC, the radiopharmaceutical candidate outperformed multiple approved agents, including osimertinib, amivantamab, and Dato-DXd, and showed robust efficacy in post-EGFR-resistance models. Preclinical evidence also supported the therapy’s use in combination with osimertinib, indicating a potentially valuable role in sequential or combination strategies.

These results have positioned ATNM-400 as a versatile alpha-emitting therapeutic candidate with cross-indication potential, moving beyond traditional antigen targets like PSMA or EGFR and instead focusing on treatment resistance biology.

What are the broader implications for Actinium’s pipeline strategy?

While ATNM-400 is leading Actinium Pharmaceuticals’ preclinical expansion into solid tumors, the company’s most advanced clinical asset is Actimab-A, a CD33-targeting radioconjugate designed for acute myeloid leukemia. Supported by data showing complete remission rates and MRD negativity in combination with CLAG-M chemotherapy, Actimab-A is entering a pivotal Phase 2/3 trial and is considered a potential backbone therapy in relapsed or refractory AML.

Actinium Pharmaceuticals has partnered with the National Cancer Institute under a Cooperative Research and Development Agreement to advance Actimab-A in combination regimens. The first of these includes Venetoclax and ASTX-727 for frontline AML, aiming to build triplet therapies with deep, durable responses.

In addition, the company is pursuing next-generation conditioning agents for cell and gene therapy via Iomab-ACT, while continuing development of Iomab-B for use as an induction and conditioning regimen prior to bone marrow transplant in r/r AML patients.

Actinium Pharmaceuticals holds a patent estate of approximately 250 issued and pending patents, including multiple protections covering Actinium-225 production and radioconjugate manufacturing.

How are institutional observers viewing ATNM-400’s positioning ahead of clinical transition?

Investors and analysts tracking the radiopharmaceutical space are increasingly focused on Actinium Pharmaceuticals’ capacity to convert its robust preclinical signals into successful human studies. The industry is witnessing growing interest in alpha emitters, and ATNM-400’s antigen specificity and safety profile differentiate it from more common beta emitters like lutetium-177. If the SABCS 2025 data delivers further validation, the therapy could become one of the first Ac-225 radioconjugates to target breast cancer resistance directly.

Experts believe the strength of the dataset, particularly in the TNBC setting, could accelerate Actinium’s push toward an Investigational New Drug application in 2026. Further preclinical studies, including toxicology and biodistribution work, are expected to solidify its clinical development path. Given the therapy’s multi-indication potential, its success could also reshape the company’s valuation and positioning within the radiopharma ecosystem.

At a time when radiotherapeutics are gaining momentum across oncology markets, ATNM-400 may offer both clinical differentiation and commercial scalability, especially as Big Pharma increasingly invests in next-generation radioligand platforms.

What are the key takeaways from Actinium Pharmaceuticals’ latest breast cancer data?

Actinium Pharmaceuticals has released preclinical results showing ATNM-400’s efficacy in breast cancer models resistant to tamoxifen and trastuzumab, with particularly strong tumor inhibition observed in triple-negative breast cancer. The therapy utilizes Actinium-225 to deliver potent radiation directly to tumors via a resistance-associated antigen. In addition to breast cancer, ATNM-400 has demonstrated activity in prostate and lung cancer models, outperforming standard therapies and showing potential for combination use.

The company’s broader pipeline includes Actimab-A for AML and conditioning agents like Iomab-ACT and Iomab-B. With a SABCS 2025 presentation scheduled for December 11 and a clinical trial transition potentially on the horizon in 2026, Actinium Pharmaceuticals is drawing significant interest from stakeholders watching the radiotherapeutic landscape evolve.

What are the key takeaways from Actinium Pharmaceuticals’ ATNM-400 breast cancer data release?

• Actinium Pharmaceuticals, Inc. (NYSE American: ATNM) has announced new preclinical data for ATNM-400, its lead Actinium-225-based radioconjugate, targeting breast cancer subtypes resistant to standard therapies.

• The data, to be presented at San Antonio Breast Cancer Symposium (SABCS) 2025, demonstrates potent anti-tumor activity in models of hormone receptor positive (HR+), HER2-positive (HER2+), and triple-negative breast cancer (TNBC), especially after tamoxifen and trastuzumab failure.

• ATNM-400 leverages alpha-particle radiation to target a tumor antigen overexpressed in resistant cancers, offering a potential alternative to antibody-drug conjugates (ADCs) like trastuzumab deruxtecan, which are limited by dose-related toxicities such as interstitial lung disease (ILD).

• Preclinical studies showed superior efficacy to standard therapies across other cancers as well, including metastatic castrate-resistant prostate cancer (mCRPC) and non-small cell lung cancer (NSCLC), where it also demonstrated synergy with drugs like enzalutamide and osimertinib.

• ATNM-400’s multi-indication potential supports its use as a monotherapy, combination, or sequential therapy in treatment-resistant settings, making it one of the few Ac-225 radiopharmaceuticals with cross-cancer utility.

• The therapy’s development comes as Actinium Pharmaceuticals builds out a broader pipeline including Actimab-A for AML and conditioning agents Iomab-ACT and Iomab-B for transplant and cell therapy readiness.

• Actimab-A is advancing into a pivotal Phase 2/3 trial and is also being explored in triplet AML combinations under a CRADA with the National Cancer Institute, reinforcing Actinium’s presence in both solid and hematologic malignancies.

• Analysts and institutional investors are watching SABCS 2025 closely as a milestone for ATNM-400’s potential IND filing in 2026, with the breast cancer data expected to guide early clinical strategy.

• Actinium Pharmaceuticals holds a broad IP portfolio around Actinium-225 manufacturing and radioconjugate development, positioning it competitively in the radiopharmaceuticals landscape.

• The company is seen as a high-potential radiopharma innovator, with ATNM-400 possibly emerging as a new therapeutic option for patients who have exhausted tamoxifen, trastuzumab, or ADC pathways.