MM-111 is a first-in-class bispecific antibody that has been shown in preclinical studies to bind with both specificity and avidity to HER2 and HER3 expressing tumor cells. The HER2 arm is responsible for initial tumor cell targeting and docking, while the therapeutic HER3 arm is designed to block heregulin-induced cell signaling. HER3 was identified by Merrimack’s Network Biology approach as being a key tumorigenic node in many different types of cancer. Ligand-induced signaling of HER3 activates cellular pathways that promote the development, growth and progression of cancer. In addition, HER3 activation serves as a compensatory mechanism by which cancer cells develop resistance to targeted therapies as well as many chemotherapies.
MM-111 is designed to allow the specific inhibition of HER3 signaling in cancer cells having elevated HER2 expression, a subtype representing a large population of gastric and breast cancers. Additionally, opportunity exists to investigate combining MM-111 with other HER2-targeted therapies, such as trastuzumab and lapatinib, where MM-111 could function to prevent the development of HER3-mediated resistance to these therapies.
At this time, MM-111 is being investigated in gastric cancer in a Phase 2 clinical trial combined with paclitaxel in patients having intermediate levels of HER2 expression, and with paclitaxel and trastuzumab in patients having elevated levels of HER2 expression. Merrimack has developed a diagnostic strategy to quantitatively detect the levels of heregulin, HER2 and HER3 in an individual tumor. This ability, coupled with an understanding of how these protein levels affect MM-111’s function, could provide an opportunity to identify patients likely to respond to MM-111-based therapies.