RAS-AlphaTAC · KRAS-AlphaTACs: a novel class of biotherapeutics to target KRAS

The RAS pathway is the most frequently activated signaling node in human cancer. Activating KRAS mutations are found in approximately one in seven human cancers. KRAS signaling is also activated in a significant subset of human cancers that lack KRAS mutations. Targeting KRAS has been a central goal during the past four decades, and the efforts have intensified over the past years, ignited by the approval of the KRAS-G12C inhibitors. A targeted KRAS degradation approach is an attractive solution for blocking KRAS activity, and within the Ub-RASDisease project, we explored the degradability of wild-type and mutant KRAS proteins. In parallel, my group initiated studies to combine the Alphabody technology with the targeted protein degradation approach by designing an AlphaTAC as a novel therapeutic modality. The goal of this project is to generate and pre-clinically validate AlphaTACs targeting KRAS for degradation. This will strengthen the Proof of concept on the AlphaTAC utility in targeted protein degradation and provide support for establishing a proprietary platform in view of the creation of a new spin-off company.