On April 28, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported preclinical results with ATNM-400 in prostate cancer models presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Actinium Pharmaceuticals, APR 28, 2025, View Source [SID1234652253]). ATNM-400 is a novel, non-PSMA targeting, first in class targeted radiotherapy utilizing the Actinium-225 (Ac-225) radioisotope that Actinium is evaluating in prostate cancer models prior to and following treatment with Pluvicto. Pluvicto (Lu-177-PSMA-617) is a prostate-specific membrane antigen (PSMA) directed radiotherapy radiolabeled with the beta-particle emitter, Lutetitium-177 (Lu-177) is approved for patients with metastatic castration-resistant prostate cancer. Pluvicto is marketed and sold by Novartis and generated sales of $1.39 billion in 2024.

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In vivo studies demonstrated that ATNM-400 is more efficacious than Pluvicto and produced a statistically significant (p < 0.0001) reduction in tumor volume in 22Rv1 prostate cancer models demonstrating its transformative therapeutic potential.

ATNM-400 is a highly innovative, first-in-class prostate cancer candidate in comparison to Pluvicto and the majority of radiotherapies in development for prostate cancer which target PSMA and are either non-differentiated or barely differentiated, as it targets a distinct non-PSMA receptor. The receptor specifically targeted by ATNM-400 is highly expressed in metastatic castration-resistant prostate cancer (mCRPC) and continues to be expressed at a high level even after Pluvicto treatment which does not appear to impact target expression levels. ATNM-400 leverages the alpha-particle emitter Ac-225, which is more potent than Lu-177, can cause lethal double-stranded irreversible DNA breaks, and has a shorter path length that could result in fewer off-target effects.

Key Data and Highlights From the ATNM-400 AACR (Free AACR Whitepaper) Presentation

In vivo studies demonstrated that ATNM-400 is more efficacious than Pluvicto and produced a statistically significant (p < 0.0001) reduction in tumor volume in 22Rv1 prostate cancer models demonstrating its transformative therapeutic potential.

In mice bearing Pluvicto-failed tumors, ATNM-400 was administered on day 14 following Pluvicto treatment, demonstrating robust antitumor activity and tumor growth inhibition in Pluvicto- resistant tumor models.

Expression of the target receptor for ATNM-400 persists following Pluvicto therapy and ATNM-400 demonstrates sustained tumor control after Pluvicto stops working

ATNM-400 demonstrated greater efficacy than Pluvicto in prostate cancer models with 99.8% tumor growth inhibition achieved with a single 40 µCi/kg dose of ATNM-400 supporting its potential to be offered as an alternative option

ATNM-400 internalizes rapidly, exhibiting potent cytotoxicity and prostate cancer cell killing via double strand DNA breaks that are produced by the Ac-225 alpha-particle emitting radionuclide payload of ATNM-400

Biodistribution analyses showed sustained uptake in the tumor up to the 216-hour time point, with rapid clearance from the blood by the 48-hour time point and clearance from essential organs including the kidneys, intestines and liver

ATNM-400 was well tolerated with body weight recovery and no apparent toxicity at both doses evaluated in vivo
Sandesh Seth, Actinium’s Chairman and CEO, said, "We are thrilled to unveil these exciting results demonstrating the transformative therapeutic potential of ATNM-400. There is a significant unmet need for a therapy that can address patients who are treated with Pluvicto and progress, which we only expect to increase following the recent approval of Pluvicto in the earlier line, pre-taxane setting. Consistent with our focus on leading-edge innovation, ATNM-400 is highly novel given it is a non-PSMA target receptor, which is highly expressed in mCRPC, and as we have presented at AACR (Free AACR Whitepaper), continues to be expressed following Pluvicto therapy. ATNM-400 capitalizes on the potency and precision of the Ac-225 isotope payload that can overcome resistance via lethal double strand DNA breaks. Our enthusiasm for ATNM-400 was validated by the significant interest this data received at AACR (Free AACR Whitepaper) and we look forward to validating the potential of this exciting radiotherapy candidate as we advance its development with additional data expected later this year".

The ATNM-400 AACR (Free AACR Whitepaper) presentation is available for viewing on the Presentations & Webinars page of Actinium’s website HERE.

Title: ATNM-400 is a novel Actinium-225 antibody radioconjugate with strong efficacy in preclinical models of prostate cancer
Abstract Number: 578