ATNM-400

Next-Generation, Non-PSMA Prostate Cancer Radiotherapy

Prostate cancer is the most common cancer in men, with approximately 1 in 8 men diagnosed with prostate cancer during their lifetime. According to the American Cancer Society, an estimated 313,780 new cases of prostate cancer will be diagnosed in the United States in 2025. The global incidence of prostate cancer is approximately 1.5 million new cases annually. Approximately 20% of prostate cancer cases are more aggressive forms that progress to metastatic disease, which is associated with significantly worse survival outcomes. Radiotherapy is commonly used to treat prostate cancer, and in 2022, the PSMA-targeting radiotherapy Pluvicto was approved by the FDA and the European Medicines Agency for the treatment of patients with metastatic castration-resistant prostate cancer. Pluvicto is marketed and sold by Novartis and generated sales of $1.39 billion in 2024. ATNM-400 is differentiated from Pluvicto as it targets a different marker than PSMA that has been shown to be overexpressed in patients with prostate cancer and uses the alpha-particle emitter Ac-225, which is more potent than Lu-177 but has a shorter path length, which could result in fewer off-target effects such as xerostomia.

ATNM-400 is a highly innovative, first-in-class prostate cancer candidate in comparison to Pluvicto and other radiotherapies in development for prostate cancer, 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) and continues to be expressed at a high level even after Pluvicto treatment.

In vivo studies demonstrated that ATNM-400 is more efficacious than Pluvicto and produced a statistically significant (p < 0.0001) reduction in tumor volume in 22Rv1 prostate cancer models. In mice bearing Pluvicto-failed tumors, ATNM-400 was administered on day 14 following Pluvicto treatment, demonstrating robust antitumor activity and tumor growth inhibition in Pluvicto-resistant tumor models.

The left graph is titled "ATNM-400 Shows Signifiicantly Higher Anti-Prostate Cancer Activity than Pluvicto", it shows ATNM-400 with lower tumor volumes after the midpoint between ten and fifteen days post treatment. The second graph is labeled "ATNM-400 Demonstrates Potent Efficacy in Pluvicto Resistance Prostate Tumor Models", it shows ATNM-400 with lower tumor volume after forty days of treatment.

  • ATNM-400 internalizes rapidly, exhibiting potent cytotoxicity and prostate cancer cell killing via double strand DNA breaks
  • Biodistribution analyses showed sustained uptake in the tumor up to the 216-hour time point, with rapid clearance from the blood by the 48-hour time point and clearance from essential organs including the kidneys, intestines and liver
  • ATNM-400 was well tolerated with body weight recovery and no apparent toxicity at both the 20 µCi/kg and 40 µCi/kg doses evaluated in vivo
  • ATNM-400 demonstrated dose-dependent antitumor activity with 68.5% tumor growth inhibition via a single 20 µCi/kg dose and 99.8% tumor growth inhibition with a single 40 µCi/kg dose with extended survival at the 40 µCi/kg dose

The ATNM-400 poster can be downloaded here.