Drug platforms

Hafnium (Hf)-based metal-organic complexes could enhance the sensitivity of solid tumors to radiotherapy. The complexes consist of nanoscale frameworks of six or 12 Hf atoms coordinated to molecules of 2,5-di(p-benzoato)aniline (DBA), in which the electron-dense metal units function as X-ray absorbers to generate and facilitate the diffusion of reactive oxygen species (ROS). In mouse breast and colon cancer lines and human oral and laryngeal squamous cell carcinoma lines, one of the complexes (Hf₁₂-DBA) increased radiation enhancement factor at 10% survival rate -- a measure of radiation sensitivity -- compared with hafnium oxide (HfO₂), a clinical radio-enhancer agent. In the irradiated colon cancer line, Hf₁₂-DBA increased apoptosis compared with HfO₂. In an irradiated mouse model of colorectal adenocarcinoma, intratumoral injection of Hf₁₂-DBA decreased tumor volume. Also in the model, intratumoral Hf₁₂-DBA, radiotherapy and an anti-PD-L1 antibody decreased the volume of local and distal tumors compared with radiation plus the antibody. Ongoing work by RiMO Therapeutics Inc. includes Phase I testing of another Hf-based complex of undisclosed composition, RiMO-301, to treat solid tumors, including head and neck and prostate cancers. ...