Actinium highlights expanded data set for ATNM-400 in prostate cancer

Actinium Pharmaceuticals (ATNM) reported new preclinical data from its non-PSMA targeting radiotherapy prostate cancer candidate ATNM-400, that leverages the potent alpha-particle emitter Actinium-225 isotope, at the Society of Nuclear Medicine & Molecular Imaging annual meeting being held June 21st – 24th, 2025, in New Orleans, Louisiana. The data presented at SNMMI showed ATNM-400 has superior potency compared Xtandi and is highly efficacious in Xtandi resistant prostate models. Actinium also presented additional new data showing ATNM-400 is more efficacious than PSMA-617 labeled with both Lutetium-177 and Ac-225 and that ATNM-400 also overcomes resistance to Pluvicto. ATNM-400 represents a 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: 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 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: 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 weightl 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 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.