FDA clears IND application for 225Ac-FL-020 in mCRPC

The FDA has cleared an investigational new drug (IND) application for the prostate-specific membrane antigen (PSMA)-targeting radionuclide drug conjugate (RDC) ²²⁵Ac-FL-020 for investigation as a potential treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), announced Full-Life Technologies, the developer of the therapy, in a news release.¹

Preclinical data on the therapy were recently presented at the 2024 Annual Meeting of the AACR.

Acceptance of the IND application will initiate the launch of phase 1 clinical trials of the therapy in the US and globally, which the company plans to begin in 2024. The upcoming phase 1 trial will evaluate the safety, tolerability, and preliminary anti-tumor activity of ²²⁵Ac-FL-020 in patients with mCRPC.

“The IND application clearance is a significant regulatory milestone in our development plan for ²²⁵Ac-FL-020”, said Steffen Heeger, MD, MSc, Chief Medical Officer of Full-Life Technologies, in the news release.1 “This important step underscores our overall commitment to the therapeutic potential of radiopharmaceuticals and once again highlights the value of the team´s effort, dedication, and cross-functional collaboration. We are excited to initiate the phase I clinical program, which provides the first opportunity to gather human data on ²²⁵Ac-FL-020's safety and anti-tumor activity.”

²²⁵Ac-FL-020 is an actinium-225 (²²⁵Ac)-based PSMA radioligand therapydesigned to selectively attack cancer cells. Preclinical data on the therapy were recently presented at the 2024 Annual Meeting of the American Association for Cancer Research in San Diego, California.²

The preclinical study first assessed the binding affinity of the non-labeled vector FL-020 against PSMA in vitro, showing that FL-020 bound to LNCaP cells with an IC₅₀ value of 51.55 nM in PSMA high LNCaP tumor-bearing nude mice. The authors also noted high and sustained tumor uptake and fast systemic clearance with Indium-111 (¹¹¹In)-FL-020.

Further, the study indicated high selectivity of FL-020, with off-target screening showing that less than 50% of inhibition of binding or activity was observed by FL-020 at 10 µM against 85 targets, including receptors, ions, channels, enzymes, and transporters.

The investigators also compared the anti-tumor activity of ²²⁵Ac-FL-020 in LNCaP xenograft models to that of 225Ac-PSMA-617. Findings showed that ²²⁵Ac-FL-020 demonstrated superior anti-tumor activity to 225Ac-PSMA-617 at the dose level of 10 KBq/mouse in the LNCaP xenograft model. Additionally, the therapy had a favorable safety profile as indicated by body weight and hematological parameters.

Based on these data, the authors concluded,² “Taken together, these results collectively demonstrate that ²²⁵Ac-FL-020 is a potent and selective PSMA-targeting radioligand therapy candidate with superior anti-tumor activity and a favorable safety profile warranting further clinical development.”

References

1. Full-Life Technologies announces clearance from FDA of IND application for 225Ac-FL-020 for the treatment of metastatic castration-resistant prostate cancer. News release. Full-Life Technologies. Published online and accessed May 30, 2024. https://www.full-life.com/media/press-releases/24

2. Liu F, Zhang J, Yang J, et al. 225Ac-FL-020 is a novel PSMA-targeting radionuclide drug conjugate (RDC) with superior in vivo anti-tumor activity. Presented at: 2024 Annual Meeting of the American Association for Cancer Research (AACR). April 5-10, 2024. San Diego, California. Abstract 6023