Apalutamide

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

Johnson & Johnson (J&J) has announced results from the final analysis of the phase 3 PROTEUS study showing that Erleada (apalutamide) plus hormone therapy (androgen deprivation therapy) significantly improved key short- and long-term clinical outcomes, versus placebo plus hormone therapy, for patients with high-risk localised or locally advanced disease. The trial met both primary endpoints. Patients treated with apalutamide plus hormone therapy were nine times more likely to have little to no cancer remaining at the time of surgery compared with hormone therapy alone (8.9% vs. 1.0% pathologic complete response/minimal residual disease). The combination also reduced the risk of developing metastasis or death by 20% and extended the time before patients required subsequent therapy to more than six years. Henar Hevia, Senior Director, EMEA Therapeutic Area Head, Oncology at Johnson & Johnson, said: “Our ambition is to continue advancing therapies into earlier lines of treatment, where intervention may have the greatest potential to alter the course of disease,” said “By building on the established role of surgery with innovative systemic approaches, like apalutamide plus hormone therapy, we are helping drive a more proactive treatment strategy, tailored to patients’ evolving needs and ultimately aimed at delivering more durable outcomes.” Surgery to remove the prostate (radical prostatectomy) is one of the standard treatments for patients with high-risk localised or locally advanced disease, alongside radiation therapy. Yet nearly half of patients who undergo curative-intent surgery will see their cancer return, requiring additional treatment and moving beyond the point where cure is possible. Additional therapies are often used only after the cancer has spread, missing a critical window to intervene earlier and improve long-term outcomes. Yusri Elsayed, Global Therapeutic Area Head, Oncology at Johnson & Johnson, commented: “These findings point to a new potential way of treating patients with high-risk localised or locally advanced prostate cancer. We are now seeing the impact of apalutamide when used earlier, alongside surgery. As the first therapy in its class to show benefit in this setting, the data reinforces apalutamide’s differentiated profile and the need to move beyond a surgery‑only approach to treating earlier and improving long‑term outcomes.” These findings will be presented in a plenary session at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting (Oral Abstract #LBA1) and published simultaneously in The New England Journal of Medicine.