Merrimack’s human antibody engineering platform provides us with the ability to create monoclonal (MM-121), bispecific (MM-111 and MM-141) and oligoclonal (MM-151) antibody therapies targeting the complex signaling pathways that drive cancer. These therapies are developed to inhibit specific nodes responsible for tumor growth and survival, as well as treat the adaptations of a cancer cell that lead to resistance against specific therapies.
Example: MM-121 is a fully human monoclonal antibody that targets ErbB3, a cell surface receptor believed to drive cellular pathways promoting the development, growth and progression of cancers. Our Systems Biology approach identified ErbB3 as an important node that mediates resistance to chemotherapies in a range of cancers. Through the inhibition of ErbB3 signaling, MM-121 is designed to enhance the anti-tumor effect of combination therapies, as well as to delay resistance and restore sensitivity to chemotherapies.
Example: MM-111 is designed to inhibit HER3 (ErbB3) signaling in HER2-overexpressing tumor cells, as the overexpression of these two proteins has been associated with poor prognosis in a variety of cancer types. As a bispecific antibody, MM-111 relies on its anti-HER2 arm for initial tumor cell targeting and docking, while its therapeutic anti-HER3 arm blocks heregulin induced-HER3 signaling. MM-111 is currently in a Phase 2 clinical study for patients with HER2-expressing advanced gastroesophageal carcinomas.