On June 23, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported new preclinical data from its first-in-class, non-PSMA targeting radiotherapy prostate cancer candidate ATNM-400, that leverages the potent alpha-particle emitter Actinium-225 (Ac-225) isotope, at the Society of Nuclear Medicine & Molecular Imaging (SNMMI) annual meeting being held June 21st – 24th, 2025, in New Orleans, Louisiana (Press release, Actinium Pharmaceuticals, JUN 23, 2025, View Source [SID1234654066]). The data presented at SNMMI showed ATNM-400 has superior potency compared Xtandi (enzalutamide) and is highly efficacious in Xtandi resistant prostate models. Xtandi is an androgen receptor inhibitor (ARPI) therapy developed and marketed by Astellas and Pfizer that is approved for three stages of prostate cancer and generated sales of $5.9 billion in 2024. Actinium also presented additional new data showing ATNM-400 is more efficacious than PSMA-617 labeled with both Lutetium-177 (Lu-177) and Ac-225 and that ATNM-400 also overcomes resistance to Pluvicto (Lu-177-PSMA-617). Pluvicto is developed and marketed by Novartis and generated sales of $1.4 billion in 2024. ATNM-400 represents a transformational therapeutic candidate being developed to overcome limitations of current prostate cancer therapies such as Xtandi and Pluvicto and improve outcomes over what is currently achievable. Key data and highlights from the ATNM-400 SNMMI presentation include:
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ATNM-400 Target Expression Profile and Disease Biology
The ATNM-400 target is implicated in prostate cancer disease biology and contributes directly to disease progression, with expression correlating with shorter time to castration resistance and poorer survival in castrate resistant prostate cancer (CRPC) patients making it differentiated from PSMA, which serves primarily as a surface marker
The target for ATNM-400 is also reported to be elevated in prostate cancer patients who develop resistance to the ARPI therapy Xtandi
ATNM-400 shows consistent tumor uptake, rapid clearance from the blood and clearance from vital organs including intestines, liver, and kidneys
Target expression is retained post Pluvicto treatment in prostate cancer models
ATNM-400 Compared to Xtandi (enzalutamide)
ATNM-400 exhibited potent killing of all Xtandi resistant prostate cancer cells that remained following treatment with Xtandi, with Xtandi only killing 50% of the resistant prostate cancer cells
ATNM-400 monotherapy and in combination with Xtandi had superior anti-tumor efficacy in vivo compared to Xtandi alone in a prostate cancer model; all treatments were well-tolerated with no change in body weight
ATNM-400 inhibited tumor growth of Xtandi resistant tumors whereas re-treatment with Pluvicto or additional enzalutamide did not
ATNM-400 Compared to PSMA targeted Radiotherapy
ATNM-400 was more potent than both Pluvicto (177Lu-PSMA-617) and 225Ac-PSMA-617 in prostate cancer cell killing
At therapeutically relevant doses, ATNM-400 exhibited more efficacious tumor growth inhibition compared to both Pluvicto and 225Ac-PSMA-617 in prostate cancer in vivo model
As previously reported, ATNM-400 was able to overcome Pluvicto resistance, halting tumor growth in prostate cancer tumors that failed Pluvicto therapy and producing potent tumor cell killing
Sandesh Seth, Actinium’s Chairman and CEO, said, "We are committed to advancing ATNM-400 to address the high unmet needs that remain in prostate cancer. These new data presented at SNMMI demonstrate the therapeutic potential of ATNM-400 as both a monotherapy and in combination with both androgen receptor inhibitors and PSMA radiotherapy, two leading prostate cancer treatment modalities. With ATNM-400’s target being a disease-driving protein involved in tumor progression and therapeutic resistance combined with the potency and precision of the Ac-225 isotope payload, we believe ATNM-400 has a transformational profile rooted in prostate cancer disease biology, which is strongly supported by our data. We are thrilled to highlight ATNM-400’s first-in-class data at SNMMI and highly encouraged by the strong interest from KOL’s across the prostate cancer and nuclear medicine communities. As Actinium continues to advance our efforts with novel targeted radiotherapies, ATNM-400 is the ideal cornerstone of our emerging solid tumor pipeline."
The ATNM-400 SNMII presentation is available for viewing on the Presentations & Webinars page of Actinium’s website HERE.
Title: First-in-class antibody radioconjugate ATNM-400 exhibits potent anti-tumor activity and overcomes resistance to enzalutamide and 177Lu-PSMA-617 in prostate cancer models
About ATNM-400
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), contributes directly to disease progression and poorer survival outcomes, and continues to be expressed at a high level even after androgen receptor inhibitor and Pluvicto treatment. ATNM-400 leverages the alpha-particle emitter Ac-225, which is more potent than Lu-177, can cause lethal irreversible double-stranded DNA breaks, and has a shorter path length that could result in fewer off-target effects.