[Strategic evolution of drug discovery modalities: Tanabe Pharma's approach to immunology and oncology]

Tanabe Pharma is advancing innovative drug discovery by selecting and designing optimal modalities based on disease characteristics, with a focus on neurological, immunological, and oncological disorders. This review outlines key initiatives in the immunology and oncology areas. In immunology, we promote "Immunophenotype Drug Discovery", which targets patients' immunological phenotypes. Based on a cross-disease understanding of pathophysiology, various modalities such as small molecules, antibodies, and functional proteins are selected. For the plasma cell-like phenotype, selective inhibitors of immunoproteasome components LMP7/LMP2 are being pursued. For the activated T cell-like phenotype, a fusion protein combining an IL-2 variant and an agonistic anti-TNFR2 antibody is under construction. In oncology, a novel modality, Targeted Protein Degradation (TPD), has been introduced to address "undruggable" targets that are difficult to control with conventional inhibitors. TPD induces degradation of target proteins via the ubiquitin-proteasome system by bringing them into proximity with E3 ubiquitin ligases using small molecules. Leveraging insights from the BRD4 inhibitor Y-803, we has developed MT-4561, which demonstrates high degradation activity and antitumor efficacy and is currently in Phase I clinical trials. These efforts exemplify a modality-driven drug discovery approach tailored to disease-specific pathologies, aiming to provide new therapeutic options for intractable diseases through the integration of scientific knowledge and technological innovation.