Preclinical data show promise of ATNM-400 for prostate cancer

Preclinical data shared during the 4th Annual Targeted Radiopharmaceuticals Summit (TRP) in San Diego, California, showed that the targeted radiotherapy ATNM-400 achieved robust antitumor efficacy in treatment-resistant prostate cancer tumor models.¹

According to Actinium Pharmaceuticals, ATNM-400 is “a novel Actinium-225 antibody radioconjugate for advanced prostate cancer” that “targets a non-PSMA [prostate-specific membrane antigen] protein overexpressed in [castration-resistant prostate cancer].”² The company also noted that “unlike PSMA-targeted agents that primarily serve as imaging and targeting tools, the ATNM-400 target is directly implicated in tumor progression, survival signaling, and resistance to androgen receptor pathway inhibitor (ARPI) therapy.”

"We are highly encouraged by the growing body of data supporting the therapeutic potential of ATNM-400 and the significance of its target being directly implicated in tumor progression, survival signaling, and resistance to ARPI therapy,” said Sandesh Seth, Actinium's chairman and CEO, in the news release from the company.¹ “The new data presented at TRP highlight the utility of the differentiated mechanism of action of ATNM-400 via the Ac-225 alpha-emitter payload evidenced by durable tumor control, improved survival rates compared to Pluvicto, and efficacy in enzalutamide and Pluvicto resistant models.”

In the study, tumor-specific uptake of the ATN-400 antibody in the in vivo model was confirmed via PET imaging, with sustained tumor uptake for up to 216 hours and rapid clearance from normal organs. Further, treatment with ATNM-400 was associated with dose-dependent efficacy and improved overall survival in the in vivo model.²

ATNM-400 also demonstrated robust tumor control. Data showed that ATNM-400 yielded improved survival compared with ¹⁷⁷Lu-PSMA-617 (Pluvicto), with specific efficacy in treatment-resistant models. Specifically, ATNM-400 continued to “halt tumor growth and produce potent tumor cell killing after Pluvicto stops working,” the company noted. They also added that this finding “highlight[s] its potential in advanced disease settings that are resistant to standard treatments.”

ATNM-400 was also shown to produce improved in vitro cytotoxicity compared with both 225Ac-PSMA-617 and ¹⁷⁷Lu-PSMA-617. Specifically, the IC50 value for ATNM-400 was 3.98 nCi/mL vs 17.56 nCi/mL with 225Ac-PSMA-617 and 142.1 μCi/mL with ¹⁷⁷Lu-PSMA-617 (P < .0001).²

The efficacy of ATNM-400 was enhanced when used in combination with ARPIs such as enzalutamide (Xtandi), with improved in vitro tumor cell killing with the combination. The company reported, “The ATNM-400 enzalutamide combination produced superior anti-tumor efficacy and durable tumor control compared to enzalutamide alone, with 40% of prostate cancer tumor-bearing animals having complete cures.”

Additionally, data showed that ATNM-400 was able to inhibit tumor growth in tumors resistant to enzalutamide, whereas treatment with ¹⁷⁷Lu-PSMA-617 or additional enzalutamide were not.

According to Actinium, the study remains ongoing to assess the durability of ATNM-400’s antitumor efficacy. Additional data is expected in the second half of 2025.

Overall, Seth concluded in the news release, “We believe ATNM-400 has the potential to redefine the treatment paradigm in the high-value, advanced disease, and metastatic castrate-resistant prostate cancer settings, which impact tens of thousands of patients annually. We look forward to presenting additional data in the second half of this year and further highlighting ATNM-400's differentiated potential in treatment settings with high unmet needs.”

REFERENCES

1. Actinium presents data supporting paradigm changing potential of ATNM-400 in prostate cancer demonstrating its superior efficacy and improved survival in treatment resistant tumor models versus Pluvicto and ARPI therapy, and also enhanced efficacy in combination with ARPI therapy at the 4th Annual Targeted Radiopharmaceuticals Summit. News release. Actinium Pharmaceuticals. July 31, 2025. Accessed July 31, 2025. https://ir.actiniumpharma.com/press-releases/detail/505/actinium-presents-data-supporting-paradigm-changing

2. Building a transformative Ac-225 portfolio for next-generation precision oncology. Actinium Pharmaceuticals. Accessed July 31, 2025. https://c212.net/c/link/?t=0&l=en&o=4478866-1&h=2573530962&u=https%3A%2F%2Fir.actiniumpharma.com%2Fpresentations-webinars&a=HERE