MM-121, Merrimack’s lead candidate, is a fully human monoclonal antibody that targets the ErbB3 receptor.  MM-121 is the first selective ErbB3 antagonist to enter human clinical development.

ErbB3 is a novel target within the ErbB/EGFR/HER pathway, which is well-known to be hyperactivated or dysregulated in cancer which leads to uncontrolled cell growth in multiple cancer types.  Merrimack data demonstrates that ErbB3 is an ultra-sensitive target in this pathway, involved in signaling mediated both by ErbB3 ligands such as heregulin (HRG) and EGFR ligands like betacellulin (BTC).  Additionally, ErbB3 is believed to play a central role in resistance to both targeted therapies (e.g. trastuzumab, erlotinib, gefitinib) and chemotherapy in a number of tumor types. Merrimack data indicates that MM-121 is effective in tumor models that are resistant to other ErbB targeted therapies and chemotherapies. 

Preclinical data on MM-121 shows that it effectively inhibits ErbB3 phosphorylation across multiple cancer cell lines including lung, ovarian, prostate, renal, breast, and colon.  MM-121 is differentiated from other therapeutics targeting the ErbB network, such as cetuximab, trastuzumab or lapatinib, by targeting the ErbB3 receptor rather than EGFR/ErbB1 and/or ErbB2/HER2.

In concert with the therapeutic development of MM-121, Merrimack is developing a companion diagnostic that will assess the molecular profile of a tumor to classify a patient as a likely responder or non-responder.  Preclinical data on MM-121 as both a monotherapy and combination therapy has been presented at a number of conferences including the 2009 and 2008 Annual Meetings of the American Association of Cancer Research (please click on the links below to view these posters).

A Phase 1 trial of MM-121 was initiated in late 2008 and is being conducted at 3 centers in the United States.  A Phase 1/2 trial of MM-121 in combination with a targeted therapy is expected to begin in late 2009.  Additionally, Merrimack anticipates initiating Phase 2 development of MM-121 as a monotherapy in early 2010. 

For more information on current clinical trials, please go to www.clinicaltrials.gov and type in "MM-121" in the search box.

Publications:

An ErbB3 Antibody, MM-121, Is Active in Cancers with Ligand-Dependent Activation

Full Text: Therapeutically Targeting ErbB3: A Key Node in Ligand-Induced Activation of the ErbB Receptor–PI3K Axis

PODCAST: Science Signaling interviews Ulrik Nielsen, Merrimack's Chief Scientific Officer, on how mathematical modeling of signaling pathways can be used to identify candidate targets for cancer therapies.

AACR 2010
Efficacy of MM-121 in ER+ and triple negative breast cancer studies

Prediction of xenograft response to MM-121, and anti-ErbB3 inhibitor, using computational modeling and measurements of five biomarkers

13th World Conference on Lung Cancer
MM-121 a first in class anti-ErbB3 antibody, shows efficacy in preclinical models of lung cancer: A potentially new treatment modality for human lung cancer

2009 AACR Posters on MM-121
In vivo effect of combination therapy: an anti ErbB3 antibody, MM-121, plus selected cancer therapies

Computational modeling guided the identification of beneficial combinations of MM121 and other targeted therapies.

2008 AACR Posters on MM-121
MM-121: a human monoclonal antibody ErbB3 antagonist 2008

Computational modeling and simulation lead to the development of MM-121, a human monoclonal antibody ErbB3 antagonist