Preclinical Study Results of Merrimack's MM-141 Published in Molecular Cancer Therapeutics

Merrimack Pharmaceuticals

today announced that the manuscript "MM-141, an IGF-1R- and ErbB3-Directed Bispecific Antibody, Overcomes Network Adaptations That Limit Activity of IGF-1R Inhibitors" has been published in Molecular Cancer Therapeutics and selected for the Highlights section in the current issue (Volume 13, Issue 2). This publication describes the preclinical development of Merrimack's MM-141, a novel bispecific tetravalent antibody that binds to IGF-1R and ErbB3 receptors. With this mechanism, MM-141 is able to inhibit oncogenic signaling through the PI3K/AKT/mTOR pathway, which is a driving force behind cell growth. MM-141 recently completed the monotherapy portion of a Phase 1 study in the United States and Europe. It is currently being investigated in a Phase 1 combination study and is expected to enter Phase 2 development in 2014. "We are excited that Molecular Cancer Therapeutics has highlighted how Merrimack's proprietary systems biology approach can guide the design of novel therapeutics that overcome redundancies in tumor cell resistance," said Alexey A. Lugovskoy, Ph.D., Vice President of Therapeutics at Merrimack. "MM-141 is a first-in-class molecule that is an excellent example of our approach, as it can arrest tumor cell growth in two ways: it blocks multiple inputs into the major tumor survival pathway and also depletes receptor complexes containing IGF-1R and ErbB3, which would normally allow cancer cells to proliferate." IGF-1R, the receptor activated by insulin-like growth factor 1, has the ability to induce cellular growth and proliferation. Thus, it has been implicated in promoting resistance to both chemotherapies and targeted therapies. However, the effectiveness of current IGF-1R inhibitors in the clinic has been limited, as cancer cells have the ability to develop resistance to therapies by signaling through alternative pathways. Through a systems biology-based methodology, Merrimack researchers have found that cancer cells can develop resistance to IGF-1R that is mediated through ErbB3. Therefore, dual inhibition of IGF-1R and ErbB3 pathways would be necessary to block the PI3K/AKT/mTOR pathway, resulting in the arrest of tumor cell growth. In preclinical in vitro and in vivo models, MM-141 was more active than a combination of anti-ErbB3 and anti-IGF-1R monoclonal antibodies. MM-141 was able to inhibit PI3K/AKT/mTOR signaling and potentiated the activity of cytotoxic and targeted therapies, supporting its ongoing clinical development. About MM-141 MM-141 is fully human tetravalent antibody that targets signaling of the PI3K/AKT/mTOR pathway driven through activation of IGF-1R and ErbB3/HER3. The PI3K/AKT/mTOR is a major pro-survival pathway that tumor cells use as a resistance mechanism to anti-cancer therapies. MM-141 is designed to interfere with this pathway by blocking ligand-induced signaling through the IGF-1R and ErbB3 receptors. A Phase 1 clinical study of MM-141 for the treatment of advanced solid tumors is currently underway. MM-141 is Merrimack's sixth oncology candidate to enter clinical development. About Merrimack Merrimack is a biopharmaceutical company discovering, developing and preparing to commercialize innovative medicines paired with companion diagnostics for the treatment of cancer. Merrimack applies its systems biology-based approach to biomedical research throughout the research and development process. Merrimack currently has six oncology therapeutics in clinical development. For more information, please visit Merrimack's website at www.merrimackpharma.com. Forward-Looking Statements To the extent that statements contained in this press release are not descriptions of historical facts, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements include any statements about Merrimack's strategy, future operations, future financial position and future expectations and plans and prospects for Merrimack, and any other statements containing the words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," "hope" and similar expressions. In this press release, Merrimack's forward-looking statements include statements about the potential for MM-141 to provide clinical benefit and the timing of initiation of future clinical trials. Such forward-looking statements involve substantial risks and uncertainties that could cause Merrimack's clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, availability of data from ongoing clinical trials, expectations for regulatory approvals, development progress of Merrimack's companion diagnostics and other matters that could affect the availability or commercial potential of Merrimack's drug candidates or companion diagnostics. Merrimack undertakes no obligation to update or revise any forward-looking statements. Forward-looking statements should not be relied upon as representing Merrimack's views as of any date subsequent to the date hereof. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Merrimack's business in general, see the "Risk Factors" section of Merrimack's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 8, 2013 and other reports Merrimack files with the SEC. CONTACT: Media Contacts: