Radiopharm Theranostics has received regulatory approval to advance its novel radiopharmaceutical RAD 402 into first-in-human testing for advanced prostate cancer, marking a significant milestone in the development of terbium-161-based cancer therapies.
The clinical-stage biopharmaceutical company announced that Australia's Bellberry Human Research Ethics Committee has granted approval to initiate a Phase 1 clinical trial of RAD 402, a Kallikrein Related Peptidase 3 (KLK3)-targeting radiotherapeutic for patients with metastatic or locally advanced prostate cancer.
Novel Radiopharmaceutical Approach
RAD 402 represents a first-in-class approach combining a humanized IgG1 monoclonal antibody with the radionuclide terbium-161. The therapy is designed to be internalized by prostate cells after binding to KLK3 with high affinity. KLK3, which encodes prostate specific antigen (PSA), is expressed in the prostate and most adenocarcinomas of the prostate, including their metastases.
"This clearance enables us to advance RAD 402 into our first-in-human Phase 1 clinical trial, which, to my knowledge, is the first company-sponsored therapeutic trial using 161Tb," said Riccardo Canevari, CEO and Managing Director of Radiopharm Theranostics.
The therapeutic mechanism relies on terbium-161's dual emission of beta particles and Auger electrons, which Canevari described as driving the compound's potential antitumor activity. This dual emission profile distinguishes RAD 402 from other radiopharmaceutical approaches currently in development.
Preclinical Validation
Comprehensive preclinical proof-of-concept biodistribution studies conducted in mouse xenografts provided the foundation for regulatory approval. These studies demonstrated strong tumor targeting capabilities while showing limited bone and marrow uptake, addressing a key safety concern for radiopharmaceuticals. The hepatic excretion profile observed was consistent with expectations for a monoclonal antibody-based therapeutic.
"The strength of our preclinical data, combined with regulatory endorsement, underscores RAD 402's first-in-class potential," Canevari noted, emphasizing that targeting KLK3 in advanced prostate cancer represents a novel and promising mechanism of action.
Manufacturing Partnerships
Radiopharm has established key supply chain partnerships to support the clinical development of RAD 402. The company signed a supply agreement with Terthera in 2022 for the production of terbium-161, and more recently entered into an agreement with Cyclotek in 2025 for the radiolabeling of RAD 402 with the radionuclide.
Clinical Development Context
The approval positions Radiopharm to expand its clinical pipeline, which currently includes one Phase 2 trial and four Phase 1 trials across various solid tumor cancers, including lung, breast, and brain metastases. The company's platform encompasses distinct technologies spanning peptides, small molecules, and monoclonal antibodies for cancer applications.
"Receiving HREC approval marks a key milestone for Radiopharm and for patients in need of safer, more effective new treatments for prostate cancer," Canevari stated, highlighting the potential clinical impact of this regulatory milestone.
