ATNM: ATNM-400 active in ARPI‐resistant prostate cancer models; flexible dosing and favorable safety shown

AI Summary

Actinium presented preclinical SNMMI data showing ATNM-400, a non‐PSMA Ac‐225 antibody radioconjugate, remains potent in cells and tumors resistant to all three approved ARPIs (enzalutamide, apalutamide, darolutamide), achieving 94% tumor growth inhibition as a single agent (vs ~32% and 5% for apalutamide and darolutamide) and producing durable complete responses in combination in ≥57% of mice (4/7 and 5/7) in an ARPI‐resistant 22Rv1 model. The agent matched or exceeded PSMA‐targeted radioligands across PSMA‐high/low/negative models (comparable to 225Ac‐PSMA‐617 and superior to 177Lu‐PSMA‐617 at much lower administered activity), showed consistent tolerability across single‐bolus and repeat dosing with minimal blood/liver/kidney signals, and—because its target is not expressed in salivary glands—is not expected to cause xerostomia; clinical benefit remains unproven as these are preclinical results.

Positives

ATNM-400 retained potency in cells and tumors resistant to enzalutamide, apalutamide and darolutamide
As monotherapy achieved 94% tumor growth inhibition in an ARPI‑resistant model vs 32% and 5% for apalutamide and darolutamide
Matched or exceeded PSMA‑directed radioligands across PSMA‑high/low/negative models with flexible dosing and minimal off‑target toxicity; target not expressed in salivary glands (xerostomia not expected)

Negatives

All data are preclinical (cell and mouse models); human safety and efficacy are untested
Efficacy combination data are from small cohorts (e.g., 4/7 and 5/7 complete responses), so results are preliminary
Clinical and regulatory translation risk remains (forward‑looking statements noted)