Grant: Project Grant

Worldwide, 2.3 million people are diagnosed with breast cancer (BC), and 685,000 die from it annually. Triple negative BC (TNBC) is the most aggressive form of BC and makes up 10-20% of all diagnoses. More people die from lung cancer (LC) than any other cancer type, with 85% of it being non-small cell lung cancer (NSCLC): 2.2 million new diagnoses annually and 1.8 million deaths, and a stage IV 5-year survival of 1%. Clearly, standards of care for TNBC and NSCLC have not yielded significant survival gains over the decades. Nectin-4 is a protein that is overexpressed in many cancers including in 60-70% of TNBC and 60% of NSCLC. Theranostic (therapeutic and diagnostic) is a nuclear medicine approach (using radioisotope tagged compounds) where a diagnostic agent is used for patient selection, dose estimation and monitoring of response to treatment of the therapeutic agent. No radiolabeled therapeutics against Nectin-4-positive NSCLC or TNBC have been reported preclinically or investigated in clinical trials. Potent radiolabeled therapeutics such as those labeled using actinium-225 have been shown to be more effective than non-radiolabeled drugs. We developed a monoclonal antibody N4MU01 against this protein and used it to develop radiolabeled diagnostic and therapeutic agents. We showed using animal models that these compounds were very effective against TNBC and NSCLC tumors. The therapeutic biologics compounds are patent-protected, making them attractive for industry uptake. For this proposal we intend to develop clinical-grade theranostic compounds and submit a phase 1 clinical trial application to Health Canada. Nuclear medicine market is currently the highest growth segment in biopharma and is poised to outsize the market for antibody drug conjugates by 2031 reaching >35 billion. The market potential for an effective radiotherapeutic targeting Nectin-4 against NSCLC and TNBC is approx $17 billion, and will have huge socioeconomic benefits for Canada & the world.