ATNM News & Events

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.

Actinium Pharmaceuticals highlighted data presented at the American Association for Cancer Research, or AACR, Annual Meeting supporting transcriptional reprogramming as a central mechanism driving the mutation-agnostic anti-leukemic activity of Actimab-A, or lintuzumab-Ac225, in acute myeloid leukemia, or AML. Preclinical translational data demonstrated that lintuzumab-Ac225 delivers potent cytotoxic activity across AML models harboring common mutations, including FLT3, NPM1, KMT2A, and TP53, as well as in primary patient samples. Importantly, combining Actimab-A with standard-of-care therapies - the menin inhibitor revumenib, the FLT3 inhibitor gilteritinib, and the hypomethylating agent azacitidine - resulted in enhanced leukemic cell killing in vivo across all tested models, independent of mutation status. These results support a combination-driven clinical strategy aimed at improving depth and durability of response. The findings provide the mechanistic foundation for Actimab-A's observed clinical activity and, together with the manageable safety profile demonstrated across prior Actimab-A trials in more than 150 AML patients, reinforce its suitability as a combination backbone across multiple treatment settings. Actimab-A is Actinium's lead clinical radiotherapy delivering Actinium-225, a potent alpha-emitter radioisotope payload that produces lethal double-strand DNA breaks to kill CD33-expressing AML cells. In the relapsed/refractory AML setting Actimab-A in combination with the intensive chemotherapy regimen CLAG-M produced an 83% overall response rate and 75% MRD-negativity in a Phase 1 trial which forms the basis of a Phase 2/3 registrational study for which Actinium has FDA alignment and is seeking a development partner. Actimab-A is also being studied in newly diagnosed patients via the ongoing NCI-sponsored frontline triplet trial of Actimab-A with venetoclax and ASTX-727; and has shown promise in post-remission and MRD-directed settings; as well as myelodysplastic syndrome and other CD33-expressing myeloid malignancies. Combination treatment produced consistent pathway-level changes compared with monotherapy. Gene set enrichment analyses showed enhanced myeloid differentiation signatures with the addition of Actimab-A (lintuzumab-Ac225) to revumenib, gilteritinib, and azacitidine. Together, these findings show that Actimab-A combinations don't just add cytotoxicity - they reprogram AML cells from proliferation toward differentiation and apoptosis, providing the mechanistic basis for deeper, more durable MRD-negative responses and reinforcing Actimab-A's role as a universal combination backbone across AML.

Actinium Pharmaceuticals announced the presentation of new preclinical data for ATNM-400, its first-in-class Actinium-225 based antibody radioconjugate, at the 2025 San Antonio Breast Cancer Symposium. The poster, titled "Anti-Tumor Activity of ATNM-400, a First-in-Class Actinium-225 Antibody Radioconjugate, in Hormone-Positive, Triple-Negative, Tamoxifen-Resistant and Trastuzumab-Resistant Breast Cancer Models," showcases the following key findings: Potent Efficacy Across Breast Cancer Subtypes: ATNM-400 demonstrated significant tumor-growth inhibition in HR+ and TNBC in vivo models, with all treatment regimens well tolerated and no significant changes in body weight observed. Potent Activity in Standard-of-care Treatment-Resistant Breast Cancer Models: Trastuzumab-resistant BT474-Clone5 breast cancer cells or Tamoxifen-resistant MCF7-Tam1 breast cancer cells exhibited increased target expression, resulting in enhanced in vitro cytotoxicity with ATNM-400. Combining ATNM-400 with either trastuzumab or tamoxifen resulted in greater cytotoxicity versus monotherapy and produced in vivo tumor regression in the trastuzumab-resistant model. Mechanistic Evidence of Irreversible DNA Damage: Activation of phosphorylation of AKT was observed in trastuzumab resistant BT474-Clone5 breast cancer cells, as well as a significant increase in the total level of the ATNM-400 target antigen in the in vivo trastuzumab-resistant breast cancer model. ATNM-400 treatment of these trastuzumab-resistant breast cancer cells caused significant increase in phosphorylated H2AZ, consistent with alpha-particle-driven double-strand DNA damage. Favorable Biodistribution: Sustained tumor uptake in a breast cancer model through 144 hours and rapid clearance from normal organs supports a potentially differentiated safety profile. Pan-Tumor Potential: These results, together with previously published ATNM-400 data in prostate and lung cancer, reinforce the program's broad applicability across solid tumors.

Actinium Pharmaceuticals announced preclinical data for ATNM-400, a first-in-class Actinium-225 antibody radioconjugate, in hormone receptor positive, HER2 positive and triple-negative breast cancer that will be presented at the San Antonio Breast Cancer Symposium, SABCS, being held December10-14, 2025 in SanAntonio, Texas. The data demonstrates significant anti-tumor activity in breast cancer models resistant to standard-of-care therapies including endocrine therapy tamoxifen and HER2-targeted therapy trastuzumab as well as potent tumor growth inhibition in TNBC models. The data highlight ATNM-400's potential to address critical unmet needs in patients who have exhausted treatment options following endocrine therapy or HER2-targeted therapy failure. These data add to ATNM-400's robust preclinical data package that also encompasses metastatic castrate-resistant prostate cancer and non-small cell lung cancer.