On March 27, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported ATNM-400, a novel, non-PSMA targeting, first in class radiotherapy for prostate cancer utilizing the Actinium-225 (Ac-225) radioisotope (Press release, Actinium Pharmaceuticals, MAR 27, 2025, View Source [SID1234651544]). Initial preclinical data from ATNM-400 will be presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held on April 25 – 30, 2025, in Chicago, IL. The ATNM-400 AACR (Free AACR Whitepaper) abstract will include the results from in vitro and in vivo studies including biodistribution imaging and efficacy analyses with various dose levels of ATNM-400. Actinium continues to advance ATNM-400 with additional data expected from Pluvicto-resistant prostate cancer models at AACR (Free AACR Whitepaper). Pluvicto (Lu-177-PSMA-617) is a prostate-specific membrane antigen (PSMA) directed targeted radiotherapy that uses the beta-particle emitting radioisotope Lutetitium-177 (Lu-177) that is approved for patients with metastatic prostate cancer. Pluvicto is marketed and sold by Novartis and generated sales of $1.39 billion in 2024. ATNM-400 is differentiated from Pluvicto as it targets a different marker than PSMA that has been shown to be overexpressed in patients with prostate cancer and uses the alpha-particle emitter Ac-225, which is more potent than Lu-177 but has a shorter path length, which could result in fewer off-target effects.

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Sandesh Seth, Actinium’s Chairman and CEO, said, "The current era of radiotherapy is built on the clinical and commercial success of Pluvicto in prostate cancer. The field is now looking to address patients that do not respond or progress after Pluvicto therapy. We believe ATNM-400 can address this high unmet need and we are incredibly excited by our data to date. As anticipated, we have seen robust tumor control and ATNM-400 has shown to be well tolerated in preclinical studies, which we believe is due to the precise and potent cell-killing of Ac-225. We are also highly excited by the results of our biodistribution studies that showed selective tumor uptake with minimal uptake in normal tissues. By focusing on a non-PSMA target, we also believe ATNM-400 has the potential to address some of the toxicities reported with Pluvicto and other PSMA targeting radiotherapies such as xerostomia. We are eager to present our ATNM-400 data at AACR (Free AACR Whitepaper) and to continue to advance this highly novel prostate cancer candidate."

Highlights from the abstract include:

ATNM-400 selectively binds to prostate cancer cells, undergoes rapid internalization, and induces dose-dependent cytotoxicity
In prostate cancer xenograft mouse models, ATNM-400 accumulated in tumors for up to 144 hours, while showing minimal uptake in normal tissues
Small animal SPECT/CT imaging with Indium-111-labeled antibody confirmed selective tumor accumulation and clearance from healthy tissues
A single dose of ATNM-400 achieved 68.5% tumor growth inhibition at 20 µCi/kg and 99.8% at 40 µCi/kg, with all doses being well tolerated
ATNM-400 AACR (Free AACR Whitepaper) Presentation Details

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

Abstract Number: 578

Session: PO.ET08.01 – Theranostics and Radiotheranostics

Date & Time: April 27, 2025 – 2:00 pm – 5:00 pm