Lintuzumab Ac-225

New KRAS-mutant data show ATNM-400 outperformed standard-of-care inhibitors sotorasib and adagrasib as a monotherapy. Treatment with these agents increased expression of the ATNM-400 target greater than 3.5x and enhanced their effect in combination Additional data in the EGFR-mutant setting demonstrated powerful synergy with osimertinib due to enhanced target expression in treated animals resulting in complete tumor regression in the combination arm The data with EGFR and KRAS mutations which account for approximately 40-50 percent of all NSCLC cases provide compelling evidence of the potential of ATNM-400 as a monotherapy or in combination with inhibitory agents against these mutations ATNM-400 is a radioconjgate comprising an antibody coupled to Actinium-225 which causes cell death via double stranded DNA breaks independent of cellular mechanisms and offers broad potential as a mutation agnostic agent in NSCLC where its target is expressed in over 90 percent of tumors with greater expression as resistance emerges NEW YORK, June 3, 2026 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE American: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, on June 2, 2026, presented new preclinical data on ATNM-400 in non-small cell lung cancer (NSCLC) at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2026 Annual Meeting in Los Angeles, California. The new KRAS-mutant data, together with a growing body of EGFR-mutant data, demonstrate ATNM-400's activity across the two major mutation driver classes in NSCLC and support a distinct strategic opportunity. ATNM-400 can be developed as a potential mutation-agnostic backbone for the broader NSCLC market, alone or in combination with standard-of-care therapies, rather than as another mutation-specific drug for a narrow subset. NSCLC accounts for roughly 85% of the more than two million lung cancer cases diagnosed globally each year, a market more than twice the size of prostate cancer. It is also highly heterogeneous: no single mutation dominates, so treatments are fragmented across mutation-specific therapies such as EGFR, KRAS, BRAF, ALK and others, each marketed by different companies, each addressing only a molecular subset, and each ultimately limited by acquired resistance. ATNM-400, Actinium's first-in-class Actinium-225 (Ac-225) antibody radioconjugate, is designed to break out of that single-mutation paradigm. Rather than blocking a specific mutant protein, it delivers a high-linear-energy-transfer alpha-particle payload that induces dense, irreversible double-strand DNA breaks and tumor-cell death independent of a tumor's driver mutation or signaling pathway, the mechanistic basis of its mutation-agnostic activity. ATNM-400's target antigen, from previously published immunohistochemistry studies, is present in approximately 98% of NSCLC tumors and highly expressed in approximately 70% of those tumors. It is conserved across EGFR-, KRAS-, and other driver-defined subgroups, and further increased in tumors that have become resistant to EGFR, KRAS, and immune-checkpoint therapies. In new KRAS-mutant studies presented at SNMMI, sotorasib (active ingredient in LUMAKRAS®/Amgen) and adagrasib (active ingredient in KRAZATI®/BMS) increased ATNM-400's target up to 3.5- and 3.8-fold, respectively, and adding ATNM-400 deepened tumor-cell killing beyond either inhibitor alone. These results demonstrate the same target-expression increasing, synergy-enabling biology shown previously with the EGFR inhibitor osimertinib, which produced tumor growth inhibition of 107% when combined with ATNM-400. These combination benefits also broaden ATNM-400's commercial opportunity. The franchises it could enhance are substantial; the KRAS inhibitor class in NSCLC is projected to exceed $5 billion in peak sales, and the EGFR-mutant segment has peak sales estimates over $15 billion, led by osimertinib (active ingredient in TAGRISSO®/AZ), which generated $7.3 billion in 2025. This positions ATNM-400 to participate in these established markets by enhancing the standard of care, while also reaching the broader NSCLC population beyond any single mutation. Sandesh Seth, Actinium's Chairman and CEO, said, "Today's data further strengthen our conviction that ATNM-400 represents a fundamentally different approach to treating NSCLC solid tumors. While most targeted therapies are designed for a single mutation-defined patient population, ATNM-400 combines the mutation-independent cell-killing power of Actinium-225 with a target that is broadly expressed across tumors and becomes even more abundant as resistance emerges. The consistency of activity we have now demonstrated across both EGFR- and KRAS-driven NSCLC supports our vision for ATNM-400 as a potential mutation-agnostic backbone therapy that can be used alone or in combination across large patient populations. We believe this opportunity could extend beyond lung cancer and may position ATNM-400 as a foundational therapy across multiple solid tumor indications." Highlights from the SNMMI 2026 Poster Presentation Poster Titled: ATNM-400: A First-in-Class Actinium-225 Antibody Radioconjugate Demonstrating Durable, Mutation-Agnostic Anti-Tumor Activity in Non-Small Cell Lung Cancer Models New data demonstrated ATNM-400's potential as a mutation-agnostic antibody radioconjugate therapy for NSCLC: Across a panel of four lung cancer cell lines spanning EGFR- and KRAS-driver mutations, ATNM-400 bound and was internalized specifically by the three target-positive lines (NCI-H1975, NCI-H358 and Calu-3) but not by the target-negative line (A549), confirming that its activity is driven by target expression rather than by any particular mutation. In a KRAS G12C model (NCI-H358), PET imaging of radiolabeled ATNM-400 showed the drug concentrating in the tumor with low uptake in healthy tissue, visually confirming that it reaches its target in a living animal and delivers its alpha payload where intended while largely sparing normal organs. In a KRAS G13D model (Calu-3), a single dose of ATNM-400 drove tumor regression (124% and 135% inhibition at two dose levels), indicating marked antitumor potencywith full body-weight recovery. Deep responses from one dose with a clean tolerability profile point to a wide therapeutic window and dosing flexibility, favorable attributes for clinical translation. Treatment with both approved KRAS inhibitors (sotorasib and adagrasib) raised ATNM-400's target expression dose-dependently—up to roughly 3.5- to 3.8-fold—reaching statistical significance at every dose (p < 0.0001). The effect occurred with both agents, indicating a class-wide consequence of KRAS G12C inhibition that builds a rationale for combining ATNM-400 with these therapies. ATNM-400 plus sotorasib or adagrasib decreased cancer-cell viability beyond either inhibitor alone. The data demonstrate that ATNM-400 has development potential not only as a monotherapy but also in combination with these leading KRAS therapies and possibly the entire KRAS-mutant class. In an EGFR-mutant model (NCI-H1975), ATNM-400 monotherapy achieved 75% tumor growth inhibition versus 40% for osimertinib; combined with osimertinib it reached 107% inhibition with complete cures in 100% of mice. Osimertinib raised target expression, providing a clear rationale for the combination. About Actinium Pharmaceuticals, Inc. Actinium is a pioneer in targeted radiotherapies designed to improve outcomes for patients with cancer. The company employs a biology-driven approach to develop differentiated radiopharmaceuticals for solid tumors and hematologic malignancies. Its mission is to transform cancer treatment through innovative radioconjugates that maximize therapeutic efficacy while minimizing toxicity to healthy tissue by combining expertise in tumor biology, translational medicine, and radiochemistry. Since inception, Actinium has focused on developing innovative radiotherapies. Its pipeline reflects this strategy across three areas: (1) solid tumor therapeutics including ATNM-400 and Actimab-A with pan-tumor potential; (2) Actimab-A as a therapeutic backbone for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in collaboration with the National Cancer Institute (NCI); and (3) targeted conditioning agents including Iomab-B for bone marrow transplant and Iomab-ACT for cell and gene therapy conditioning. ATNM-400 targets a novel antigen distinct from PSMA and has demonstrated preclinical activity across metastatic castration-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC), and breast cancer. Actimab-A has shown improved survival in relapsed/refractory AML with CLAG-M and is advancing toward a Phase 2/3 trial, with additional development ongoing through a CRADA with the NCI. Actinium is also advancing preclinical solid tumor programs and holds approximately 250 patents and patent applications, including intellectual property related to cyclotron-based production of Ac-225. For more information, please visit www.actiniumpharma.com. Forward-Looking Statements This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements, including statements as related to regaining compliance with the rules of the NYSE American and submission of a compliance plan, are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on Form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time. Investors: investorrelations@actiniumpharma.com View original content to download multimedia:https://www.prnewswire.com/news-releases/actinium-presents-new-atnm-400-data-in-kras-and-egfr-mutant-models-at-snmmi-2026-supporting-a-mutation-agnostic-opportunity-in-non-small-cell-lung-cancer-302789401.html SOURCE Actinium Pharmaceuticals, Inc. Released June 3, 2026

New data demonstrated ATNM-400 remains potently active in prostate cancer cells and tumors resistant to all three approved androgen receptor inhibitors (ARPIs) -enzalutamide (Xtandi®), apalutamide (Erleada®), and darolutamide (Nubeqa®)- directly targeting the point of failure for a high proportion of mCRPC patients ATNM-400 substantially outperformed apalutamide and darolutamide in an ARPI-resistant tumor model, and in combination with either ARPI it showed durable complete responses, supporting both monotherapy and combination strategies in refractory disease similar to prior data with enzalutamide ATNM-400 delivered superior tumor control as a single bolus or repeat dose with a consistent safety profile and minimal off-target toxicity across treatment regimens, indicating dosing flexibility and a wide therapeutic window that could de-risk clinical translation. In high PSMA expressing disease, ATNM-400 outperformed 177Lu-PSMA-617 in terms of activity and was similar to 225Ac-PSMA-617. However, as its target is not expressed in the salivary glands, ATNM-400 is not expected to cause xerostomia which is a key limitation of PSMA directed therapies NEW YORK, June 3, 2026 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE American: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, on June 2, 2026, presented new data on ATNM-400 in prostate cancer at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2026 Annual Meeting taking place in Los Angeles, California. Androgen receptor pathway inhibitors (ARPIs) such as enzalutamide (Xtandi®, Astellas/Pfizer), apalutamide (Erleada®, Johnson & Johnson), and darolutamide (Nubeqa®, Bayer) are foundational to advanced prostate cancer care, but virtually all patients eventually develop resistance and progress -with up to 50,0001 patients per year exhausting ARPI therapy- creating a large and recurring unmet need. ATNM-400, Actinium's first-in-class Actinium-225 antibody radioconjugate, targets a non-PSMA antigen linked to aggressive prostate cancer biology and delivers a high-energy alpha-particle payload that kills tumor cells through a mechanism independent of PSMA expression and androgen receptor signaling. In preclinical head-to-head studies, this PSMA-independent mechanism allowed ATNM-400 to match or exceed PSMA-targeted radioligand therapies, including 177Lu-PSMA-617 (active ingredient of Pluvicto®, Novartis) and 225Ac-PSMA-617, across PSMA-high, PSMA-low, and PSMA-negative models. _______________________________ 1 Candelieri-Surette D, Lee J, Lynch JA, et al. Epidemiology of Metastatic Castration-Resistant Prostate Cancer in Veterans Nationwide. J Natl Compr Canc Netw. 2025;23(8):307–313. doi:10.6004/jnccn.2025.7032. The new data presented at SNMMI 2026 address three key questions: whether ATNM-400 can overcome ARPI resistance in the mCRPC setting, whether it works as both a single agent and in combination, and how its dosing and safety profile support translation to patients. The data answer each: ATNM-400 remained potent against cells and tumors resistant to all three approved ARPIs, achieved 94% tumor growth inhibition as a single agent and durable complete responses in combination, and maintained a consistent, clean safety profile across both single-bolus and repeat-dose regimens. Prostate cancer is one of oncology's largest commercial opportunities: androgen receptor pathway inhibitors generate more than $12 billion in annual sales in 2025 and Pluvicto® (177Lu-PSMA-617) reached $2.0 billion in 2025, yet up to 50,0001 patients exhaust ARPI therapy each year and roughly 30% of mCRPC patients are ineligible for PSMA-directed therapy. Because ATNM-400 acts independently of both androgen receptor signaling and PSMA, it is positioned to serve the full mCRPC continuum, from patients who have failed ARPIs to the PSMA-low and PSMA-negative populations with no approved targeted radiotherapy today. Actinium estimates this represents a combined opportunity of more than 100,000 patients annually, addressable as a monotherapy or in combination with existing standards of care. Sandesh Seth, Actinium's Chairman and CEO, said, "ARPI resistance is a central problem in advanced prostate cancer as once these drugs stop working there are few good options left. The new data are compelling as ATNM-400 stayed potent in cells and tumors resistant to all three approved ARPIs, outperformed apalutamide and darolutamide on its own similar to previous data with enzalutamide, and produced durable complete responses when combined with them. Equally important for development, ATNM-400 worked across single-dose and repeat-dose regimens with a consistent, clean safety profile, giving us real flexibility as we move toward the clinic. We believe these findings position ATNM-400 as a differentiated option for patients who have run out of ARPI choices. The same resistance-targeting biology underlies the compelling activity we have reported in non-small cell lung cancer and breast cancer, positioning ATNM-400 as a potential pan-tumor backbone for large, resistance-driven patient populations, alone or in combination. We look forward to sharing additional data across these programs in the coming months as we advance ATNM-400 toward the clinic." Highlights from the SNMMI 2026 Poster Presentation Poster Titled: ATNM-400: A First-in-Class Non-PSMA Actinium-225 Antibody Radioconjugate Demonstrates Superior Efficacy to PSMA-617 Radioligands and ARPIs With Favorable Safety Profile in Prostate Cancer Models New data presented at SNMMI 2026 highlight several findings central to ATNM-400's development in prostate cancer: In a low-PSMA, moderate-target tumor model (22Rv1), a single bolus dose of ATNM-400 (40 or 30 µCi/kg) delivered superior tumor control versus fractionated dosing, and a repeat 30 µCi/kg regimen sustained tumor control and survival through day 60 with all regimens outperforming 177Lu-PSMA-617 and showing minimal deviation from vehicle in blood, liver, and kidney safety markers. Flexible, well-tolerated dosing gives clinicians multiple ways to balance efficacy and safety and points to a wide therapeutic window. ATNM-400 produced potent, dose-dependent killing of prostate cancer cells that are resistant to enzalutamide, apalutamide, and darolutamide, driving cell viability toward zero after each ARPI had failed, while the ARPIs alone left the resistant cells largely intact. Demonstrating activity specifically after ARPI failure addresses the most common point of progression in advanced prostate cancer and supports ATNM-400 as a treatment option for patients with few alternatives. As monotherapy in an ARPI-resistant tumor model (22Rv1), ATNM-400 achieved 94% tumor growth inhibition versus just 32% for apalutamide and 5% for darolutamide, roughly three- to eighteen-fold greater tumor control than the ARPIs themselves. Working on its own in tumors that no longer respond to standard ARPIs positions ATNM-400 as a potential stand-alone therapy after resistance, not only an add-on. In combination with either apalutamide or darolutamide in the same ARPI-resistant model, ATNM-400 delivered durable tumor control at 107% tumor growth inhibition, with complete responses in at least 57% of mice (4/7 and 5/7). Turning resistant tumors into complete responses by pairing ATNM-400 with the very drugs that had failed supports a combination strategy that could extend the commercial and clinical value of approved ARPIs. In a high-PSMA, high-target tumor model (C4-2), ATNM-400 matched or exceeded both PSMA-targeted radioligands-comparable to 225Ac-PSMA-617 and superior to 177Lu-PSMA-617-while being given at roughly one-thousandth the administered radioactivity of 177Lu-PSMA-617 (40 µCi/kg versus 40 mCi/kg), with durable survival and favorable tolerability. Because ATNM-400 acts independently of PSMA, this activity carries across PSMA-high, PSMA-low, and PSMA-negative models, reaching the PSMA-variable patients that PSMA-directed radioligand therapy serve least well. Moreover as the ATNM-400 target is not expressed in the salivary glands xerostomia, a limitation of PSMA directed therapies and especially PSMA-Ac-225 based agents, is not expected. About Actinium Pharmaceuticals, Inc. Actinium is a pioneer in targeted radiotherapies designed to improve outcomes for patients with cancer. The company employs a biology-driven approach to develop differentiated radiopharmaceuticals for solid tumors and hematologic malignancies. Its mission is to transform cancer treatment through innovative radioconjugates that maximize therapeutic efficacy while minimizing toxicity to healthy tissue by combining expertise in tumor biology, translational medicine, and radiochemistry. Since inception, Actinium has focused on developing innovative radiotherapies. Its pipeline reflects this strategy across three areas: (1) solid tumor therapeutics including ATNM-400 and Actimab-A with pan-tumor potential; (2) Actimab-A as a therapeutic backbone for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in collaboration with the National Cancer Institute (NCI); and (3) targeted conditioning agents including Iomab-B for bone marrow transplant and Iomab-ACT for cell and gene therapy conditioning. ATNM-400 targets a novel antigen distinct from PSMA and has demonstrated preclinical activity across metastatic castration-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC), and breast cancer. Actimab-A has shown improved survival in relapsed/refractory AML with CLAG-M and is advancing toward a Phase 2/3 trial, with additional development ongoing through a CRADA with the NCI. Actinium is also advancing preclinical solid tumor programs and holds ~250 patents and patent applications, including intellectual property related to cyclotron-based production of Ac-225. For more information, please visit www.actiniumpharma.com. Forward-Looking Statements This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements, including statements as related to regaining compliance with the rules of the NYSE American and submission of a compliance plan, are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time. Investors: investorrelations@actiniumpharma.com View original content to download multimedia:https://www.prnewswire.com/news-releases/actinium-pharmaceuticals-oral-presentation-at-snmmi-2026-highlights-atnm-400-overcoming-resistance-to-all-three-approved-androgen-receptor-inhibitors-and-offers-flexible-well-tolerated-dosing-in-prostate-cancer-models-302789403.html SOURCE Actinium Pharmaceuticals, Inc. Released June 3, 2026