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Merrimack Pharmaceuticals' Preclinical Research Shows MM-111 Restores Sensitivity To Chemotherapy And HER2-targeted Treatment In Gastric Cancer Model

CAMBRIDGE, Mass., April 10, 2013 /PRNewswire/ -- Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) today announced preclinical study results showing that the novel bispecific therapy MM-111 restored tumor sensitivity to the chemotherapy agent, paclitaxel, and HER2-targeted treatment, trastuzumab, in a HER2+ gastric cancer model. The research was presented as part of the American Association for Cancer Research's 2013 Annual Meeting in Washington, DC, April 6-10, 2013.

Overexpression of the HER2 (ErbB2) cell surface receptor has been reported in 10-25 percent of gastric and esophageal cancers. The HER2 receptor triggers tumor growth and survival when it binds together with an additional receptor known as HER3 (ErbB3) and another protein called heregulin. HER3 expression has been associated with poor prognosis in gastric cancer. MM-111 is designed to anchor to both receptors, HER2 and HER3, on the cell surface and block heregulin's ability to transmit tumor growth signals, thus inhibiting the tumor cell's ability to thrive.

"The protein heregulin can often cause resistance to standard chemotherapy and targeted treatments in gastric tumors that express both HER2 and HER3," said Ulrik Nielsen, PhD, Co-Founder and Chief Scientific Officer of Merrimack. "We are encouraged to see that this resistance is overcome in preclinical models when MM-111 is used in combination with trastuzumab and paclitaxel."

Merrimack is initiating a Phase 2 study testing MM-111 in combination with paclitaxel or with paclitaxel and trastuzumab for the treatment of advanced gastric, esophageal and gastroesophageal junction (GEJ) cancers.  Merrimack is also currently conducting a Phase 1 study of MM-111 across multiple HER2+ tumors, including breast, colorectal, gastric, esophageal and ovarian cancers. 

Study Results

Results of the preclinical study showed that the combination of MM-111 with trastuzumab is synergistic in a preclinical HER2-expressing gastric cancer model. Additionally, the study found that heregulin desensitizes gastric tumor cells to the effects of trastuzumab and paclitaxel.  The addition of MM-111 to the paclitaxel and trastuzumab regimen, or the addition of MM-111 to either paclitaxel or trastuzumab, restored sensitivity of tumors to treatment in the model.

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