MM-151 is an oligoclonal therapeutic consisting of a mixture of three fully human monocolonal antibodies designed to bind and inhibit signaling of the Epidermal Growth Factor Receptor (EGFR). EGFR-mediated signaling promotes the growth and survival of cancer cells and has long been recognized as an important drug target in several types of cancer, including colon, lung, breast, pancreatic, and head and neck cancers. Unlike other EGFR-targeted therapies, MM-151 is a mixture of three independent antibodies, binding to three non-overlapping sites on EGFR to maximize inhibition of ligand-dependent and independent signaling.
The decision to design a therapy for maximal EGFR inhibition was a product of Merrimack’s Network Biology approach. Current EGFR-based therapies only inhibit EGFR signaling about 95%. While this dramatic reduction in EGFR signaling was certainly an important achievement, we realized through biological modeling that the remaining 5% of activity has the potential to still provide sufficient survival signals to allow the tumor to continue to grow and propagate. With this insight, we designed MM-151 to inhibit the activity of the EGFR receptor as much as possible, resulting in an almost complete blockade of EGFR-mediated pro-survival signals. The use of three antibodies not only results in maximal receptor inhibition, but also addresses resistance to EGFR-targeted therapies that may develop through compensatory activity of other EGFR ligands. By having three separate antibodies, MM-151 has been shown in preclinical studies to have the ability to simultaneously block these binding sites from additional ligands, proactively inhibiting potential escape mechanisms.
Currently, Merrimack is conducting a Phase 1 clinical study of MM-151 in patients with solid tumors, with a focus on colorectal cancer, non-small cell lung cancer and triple negative breast cancer. The purpose of this trial is to assess the initial safety and tolerability of escalating doses of MM-151 in a small set of patients, including a determination of the maximum tolerated dose and any dose limiting adverse events.
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