actinium-225-TGW211

Actinium-225-TGW211 is a next-generation, first-in-class HER2-directed radioimmunoconjugate being developed as a targeted radiopharmaceutical for the treatment of HER2-positive solid tumors. It links actinium-225, a potent alpha-emitting radionuclide, to a trastuzumab-based antibody targeting Human Epidermal Growth Factor Receptor 2 (HER2), utilizing Tagworks Pharmaceuticals’ proprietary Click-to-Release linker platform. This technology allows the antibody conjugate to bind and internalize into HER2-positive tumors, after which a small molecule trigger can be administered to selectively cleave circulating antibody and rapidly eliminate the radionuclide from the body, improving the tumor-to-blood dose ratio and reducing off-tumor toxicity. Early clinical development (Phase 0/1, CleavHER trial) uses indium-111 for imaging and dosimetry, but the platform is explicitly being developed for therapeutic use with actinium-225 as the payload. The indication is for patients with HER2-positive solid tumors, particularly those resistant to standard therapies. The therapy is administered intravenously, and preclinical studies suggest the platform may enhance efficacy while lowering systemic toxicity compared to conventional radioimmunotherapy[1][7][12].