Merrimack Pharmaceuticals, Inc., a biopharmaceutical company has reported preclinical study results which showed that the novel therapy MM-121 restores tumour sensitivity and delays the onset of resistance to the aromatase inhibitor, letrozole, in an ER+ breast cancer model. The study was presented as part of the American Association for Cancer Research’s 2013 in Washington, DC.

MM-121 is a fully human monoclonal antibody that targets ErbB3, a cell surface receptor implicated in tumour growth and survival. By inhibiting ErbB3 signaling, MM-121 was found to restore sensitivity, delay resistance and enhance the anti-tumor effect of letrozole as a combination therapy partner.

“In nearly all cases of advanced ER+ breast cancer, endocrine therapies are initially effective, but patients eventually develop resistance to these treatments,” said Gavin MacBeath, co-founder and head of Translational Research, Merrimack Pharmaceuticals. "We are excited to see that in preclinical models, MM-121 blocked activation of its target, ErbB3, and down-regulated several signaling pathways within these tumours. We saw delayed resistance to letrozole when co-administered with the drug, and restored sensitivity when added after the tumours developed resistance to letrozole. These data help guide our thinking regarding how best to combine MM-121 with anti-hormonal therapies in the treatment of advanced ER+ breast cancer.”

The activity of MM-121 alone and in combination with letrozole was measured in an MCF7 in vivo model of post-menopausal ER+ breast cancer engineered to express aromatase. Models of ER+ breast cancer were randomized to receive letrozole, MM-121 or both MM-121 and letrozole following development of resistance to letrozole. Tumours were harvested 24 hours after initiating treatment post-randomization and at the end of the study when all treatment arms developed resistance.

Sanofi and Merrimack entered into an exclusive, global license and collaboration agreement for MM-121 in 2009.

Merrimack Pharmaceuticals is discovering, developing and preparing to commercialize innovative medicines paired with companion diagnostics for the treatment of cancer.