Actinium’s ATNM-400 Overcomes Triple-ARPI Resistance with 94% Tumor Inhibition
ATNM•Actinium’s ATNM-400 achieved 94% tumor growth inhibition in ARPI-resistant prostate cancer models, outperforming apalutamide (32%) and darolutamide (5%), and matched or exceeded 177Lu-PSMA-617 efficacy. The alpha-emitter conjugate maintained a clean safety profile in single and repeat dosing, offering flexible regimens and addressing a cohort of over 100,000 mCRPC patients.
1. Preclinical Efficacy in ARPI-Resistant Models
Actinium’s ATNM-400 achieved 94% tumor growth inhibition as monotherapy in models resistant to enzalutamide, apalutamide and darolutamide, versus just 32% and 5% for apalutamide and darolutamide respectively. It also matched or exceeded 177Lu-PSMA-617 activity across PSMA-high, PSMA-low and PSMA-negative tumor models.
2. Combination Strategies and Durable Responses
When combined with ARPIs, ATNM-400 induced durable complete responses, demonstrating sustained tumor regression and addressing the common progression point in metastatic castration-resistant prostate cancer after ARPI failure.
3. Dosing Flexibility and Safety Profile
Single-bolus doses (30–40 µCi/kg) and repeat 30 µCi/kg regimens delivered consistent tumor control through day 60, with minimal off-target toxicity in blood, liver and kidney markers and no expected xerostomia due to non-PSMA targeting.
4. Commercial Opportunity and Clinical Translation
Targeting a non-PSMA antigen, ATNM-400 could address over 100,000 mCRPC patients annually, including those ineligible for PSMA-directed therapy, positioning it for monotherapy or combination use in a market exceeding $14 billion in annual sales.
