The ErbB3 receptor was identified in the late 1980’s but, primarily due to its lack of intrinsic kinase activity was largely underappreciated as a therapeutic target by the scientific community until only very recently.  Merrimack’s modeling and research efforts identified ErbB3 as a highly sensitive node in the ErbB signaling network, demonstrating a dominant role for ErbB3 in downstream AKT activation despite being kinase-inactive. Upon recognition of the importance of ErbB3 in the regulation of ErbB signaling, Merrimack began working diligently on ErbB3 in 2003 and MM-121 entered clinical development in 2008.  A combination of our scientific, development, and clinical expertise has enabled Merrimack to be the first company to initiate clinical trials of an ErbB3-targeted therapeutic.

ErbB3 and heregulin (HRG), the cognate ligand to ErbB3, have been shown to play a role in many important cellular functions across several cell types and cancers. HRG and ErbB3 are involved in tumor cell growth, invasion and angiogenesis through either overexpression or activation of autocrine or paracrine loops.  The roles of ErbB3 and HRG have been demonstrated in several cancer types, both large (e.g. breast, colon, lung, ovarian, pancreatic, renal) and orphan indications (e.g. clear cell sarcoma of soft tissue).  Importantly, ErbB3 has also been shown to be involved in resistance to both targeted therapies (e.g. trastuzumab, gefitinib) and chemotherapy in a number of tumor types.

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