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• First‑in‑human Phase 1 study evaluates HER3‑targeted ATNM‑400 in metastatic castration‑resistant prostate cancer population, including patients with and without prior PSMA‑directed therapy
• HER3‑targeted alpha radiotherapy offers a differentiated approach through a target distinct from PSMA and the potential to address treatment resistance across multiple solid tumors
NEW YORK , Oct. 23, 2026 /PRNewswire/ -- Actinium Pharmaceuticals, Inc. (NYSE American: ATNM) (Actinium or the Company), a pioneer in differentiated targeted radiotherapies with the potential to transform cancer treatment, today announced that the first‑in‑human Phase 1 study of ATNM‑400, a HER3-targeted, non-PSMA radiotherapy, in metastatic castration‑resistant prostate cancer (mCRPC) will be featured at the European Society for Medical Oncology (ESMO) Congress 2026, taking place October 23–27, 2026, in Madrid, Spain.
ATNM‑400 is an investigational, first‑in‑class Actinium-225 antibody radioconjugate targeting HER3, an antigen distinct from PSMA that is implicated in tumor survival and treatment resistance. In prostate cancer, HER3 targeting offers potential across a broad mCRPC population, including patients with PSMA‑positive, PSMA‑low or PSMA‑negative disease. This includes patients who have not received PSMA‑directed therapy and those who progress following it. The Phase 1 study pairs Zirconium‑89‑labeled ATNM‑400 imaging with the development of therapeutic Actinium‑225‑labeled ATNM‑400 to inform patient selection and dosing.
"We are excited to take this first step in our pan‑cancer strategy for ATNM‑400 with its first‑in‑human Phase 1 study in prostate cancer," said Sandesh Seth, Actinium's Chairman and CEO. "The initial results shared at EANM, including tumor retention through Day 7 with HER3‑targeted imaging and encouraging tolerability, reinforce our enthusiasm for ATNM‑400. We believe ATNM‑400's differentiated HER3‑targeting approach could benefit patients across the full mCRPC spectrum, including those with PSMA‑positive, PSMA‑low or PSMA‑negative disease, as well as patients who have not received or have progressed following PSMA‑directed therapy. This study represents an important milestone toward realizing ATNM‑400's broad potential in prostate cancer and building the clinical foundation for expansion into additional solid tumors."
First-in-human Phase 1 study in mCRPC. The multicenter, open-label dose-escalation and expansion study enrolls patients with progressive mCRPC previously treated with an androgen receptor pathway inhibitor (ARPI) and taxane‑based chemotherapy; prior lutetium is permitted but not required. Patients with positive Zirconium-89-ATNM-400 PET imaging proceed to Actinium-225-ATNM-400 treatment every six weeks for up to four cycles. The study evaluates safety and tolerability to establish a recommended Phase 2 dose, with additional assessments of dosimetry, pharmacokinetics and antitumor activity.
"Our clinical strategy uses imaging to understand where ATNM-400 distributes, how much reaches tumors and how long it is retained," said Steffen Heeger, MD, MSc, Actinium's Chief Medical Officer. "HER3 signaling can support prostate cancer cell growth and survival and has been implicated in resistance to androgen receptor‑directed therapies. This connection to disease progression and treatment resistance provides a strong biological rationale for evaluating HER3‑targeted radiotherapy in mCRPC. ATNM‑400 is designed to deliver Actinium‑225 to HER3‑expressing tumor cells, an approach we are evaluating in this first‑in‑human study."
ATNM ‑ 400 ESMO 2026 Presentation Details Abstract Title: First‑in‑human phase 1 study of ATNM‑400, Actinium-225 antibody radioconjugate, in metastatic castration‑resistant prostate cancer (mCRPC) Abstract Number: 2386eTiP Presentation Type: ePoster — Trial in Progress Category: Metastatic prostate cancer Presenter: Jeri Kim, MD (Houston, United States of America)
About ATNM ‑ 400 and HER3 ATNM‑400 is an investigational antibody radioconjugate that pairs the HER3‑targeting monoclonal antibody barecetamab with the alpha‑emitting isotope Actinium‑225. Its antibody‑based design combines antigen‑specific targeting with the potential for sustained tumor localization, supporting prolonged delivery of high‑energy alpha radiation. Tumor uptake and retention observed through Day 7 with the ⁸⁹Zr‑labeled imaging counterpart support this development rationale alongside the approximately 10‑day half‑life of ²²⁵Ac. The theranostic approach enables noninvasive visualization of antibody distribution to inform therapeutic development.
ATNM‑400 is differentiated from PSMA‑targeted radiotherapies by its focus on HER3, an antigen implicated in tumor survival and treatment resistance. PSMA‑directed approaches include Novartis' Pluvicto and a broad pipeline of investigational therapies, including Telix Pharmaceuticals' TLX591‑Tx, Clarity Pharmaceuticals' ⁶⁷Cu‑SAR‑bisPSMA, Convergent Therapeutics' CONV01‑α, AstraZeneca's AZD2265 (formerly FPI‑2265), Curium's lutetium‑177 zadavotide guraxetan (¹⁷⁷Lu‑PSMA‑I&T), ARTBIO's AB001 and AdvanCell's ADVC001. These programs span small‑molecule and antibody‑based therapies using beta‑ or alpha‑emitting isotopes. ATNM‑400 combines HER3 targeting with an Actinium‑225 antibody radioconjugate, offering a distinct biological approach with the potential to expand radiotherapy across the broad mCRPC population, including patients with PSMA‑low or PSMA‑negative disease and those who do not respond to or progress following PSMA‑directed treatment. Its HER3‑directed mechanism also supports investigation beyond prostate cancer in other HER3‑expressing solid tumors.
HER3, also known as ERBB3, is a member of the epidermal growth factor receptor family involved in signaling pathways that support tumor growth, survival and resistance to treatment. HER3‑directed antibody‑drug conjugates in clinical development include BioNTech and MediLink's BNT326/YL202, Bristol Myers Squibb and SystImmune's EGFR × HER3 bispecific ADC izalontamab brengitecan (iza‑bren), and Daiichi Sankyo and Merck's patritumab deruxtecan (HER3‑DXd). These programs underscore the clinical development interest in HER3 as an oncology target. ATNM‑400 applies a distinct payload strategy, using alpha radiation in place of a conventional cytotoxic drug. Its preclinical activity in prostate, non‑small cell lung and breast cancer models supports investigation as a potential pan‑cancer radiotherapy, as a monotherapy and in rational combinations.
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 HER3, an antigen distinct from PSMA, and is in a first‑in‑human Phase 1 study in mCRPC, with 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 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.
Investor Contact Peter (PJ) Kelleher LifeSci Advisors pkelleher@lifesciadvisors.com (617) 430-7579
Released October 23, 2026
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