MM-111 is a bispecific antibody designed to target cancer cells that are characterized by overexpression or amplification of ErbB2 (HER2).  ErbB2 overexpression is known to occur in certain patients with breast, lung, stomach and other types of cancer.  MM-111 has two antibody arms, a targeting arm that binds to ErbB2 with high affinity and a therapeutic arm that binds to ErbB3 and represents the first bispecific antibody targeting two receptors on the same cell to enter clinical development. Computational simulations from our Network Biology research program suggest that the bispecific format of MM-111 is an optimal approach to inhibiting ErbB3 signaling in ErbB2-overexpressing tumors.

Both ErbB2 and ErbB3 are members of the ErbB family of receptors, which are part of a complex molecular network whose activation is commonly linked with cancer.  Increased levels of ErbB2 in the cells of a patient’s tumor can be associated with disease recurrence and poor prognosis for the patient. In addition, the importance of ErbB3 in cancer progression is now widely appreciated and the inability of currently marketed ErbB2-targeted therapies to inhibit ErbB3 signaling has been implicated in disease progression. MM-111 is differentiated from Herceptin® and other ErbB2-targeted therapies because it is not therapeutically treating ErbB2 but rather using ErbB2 as a marker to specifically target cancer cells and deliver treatment to the patient via ErbB3. In preclinical studies, MM-111 has demonstrated significant efficacy and specificity in ErbB2 overexpressing tumors.

In concert with the therapeutic development of MM-111, Merrimack is using its understanding of the ErbB network and the mechanism of action of MM-111 to develop a companion diagnostic strategy to classify a patient as more or less likely to benefit from the drug based on the molecular profile of that patient’s tumor.

Preclinical data on MM-111 as a monotherapy has been presented at the 2009 Annual Meeting of the American Association of Cancer Research, the 2008 San Antonio Breast Cancer Symposium and IBC’s 2008 International Conference on Antibody Engineering (please click on the links below to view these posters).

In June 2009, MM-111 entered clinical development in a Phase 1/2 trial enrolling patients with tumors that overexpress ErbB2. The Phase 2 portion of the study will be restricted to breast cancer patients specifically. 

For more information on current clinical trials, please go to www.clinicaltrials.gov and type in "MM-111" in the search box.

2009 AACR Posters on MM-111
MM-111: a novel ErbB3 antagonist with potent antitumor activity in ErbB2 over-expressing malignancies

Computational Modeling and Simulation Guide the Development of MM-111, a Bispecific Antibody Targeting ErbB3 in ErbB2-Over expressing Tumors

2008 Posters on MM-111

San Antonio Breast Cancer Symposium:
MM-111: a novel bispecific antibody targeting ErbB3 with potent antitumor activity in ErbB2 over-expressing malignancies

IBC’s 19th Annual Antibody Engineering Conference:
Engineering of a novel bispecific antibody, MM-111, which selectively inhibits ErbB3 in ErbB2 positive tumors and has potent anti-tumor activity