Specificity and safety of a targeted therapy against triple negative breast cancer

Celdara Medical, Llc, Lebanon NH

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT Despite recent advances in the treatment of breast cancer (BC), there is a pressing unmet medical need as BC remains the second leading cause of cancer-related deaths among women. Innovative new approaches are especially needed to help patients with triple-negative BC (TNBC), as TNBC's inherently aggressive clinical behavior and the lack of recognized molecular targets for therapy leads to a poorer outcome. The goal of this phase I application is to validate a high affinity inhibitor of the transcription factor RUNX2 which has great promise to be a game changer in the treatment of BC, including TNBC. RUNX2 is a validated target for breast cancer that is expressed in luminal, triple negative (TNBC) as well as HER2+ BC. Its expression is associated with poor survival and its mechanism of action is well understood. We have used computer-assisted drug design to identify our lead compound CADD522. CADD522 binds with high affinity to the DNA-binding pocket of the RUNX2 DNA-binding domain, and we have shown it to inhibit DNA binding, cell proliferation, transcriptional activity, and tumor growth. The successful development of CADD522 into the clinic will fill the significant unmet medical need for patients with metastatic BC. This application describes the work necessary to complete preclinical development, and will position CADD522 for accelerated development in the clinic. Throughout this SBIR Phase I, we will also evaluate opportunities to bring in collaborators with drug development expertise. We have already obtained support from Daiichi Sankyo (see letter), a leader in the development of new oncology therapies. The data obtained in this SBIR will be both essential and sufficient to reach the milestones that are needed to garner the support from drug development organizations that can advance our strategy into, and through, the clinic.