The HER3 pathway is a drug tolerance pathway, allowing cancer cells to escape death and survive the effect of other drugs. The HER3 pathway is activated by a signal, heregulin (HRG), which binds to the HER3 receptor. Merrimack has pioneered this pathway as a key node in cellular signaling networks and a prime target for cancer drug development.
MM-121 is a potent engineered monoclonal antibody designed to block the HER3 pathway by preventing the signal between heregulin and the HER3 receptor.
Consistent with cell biology data, human clinical studies in three different cancers (lung, breast, ovarian) have independently pointed to the potential value of investigating MM-121 in tumors with a high expression of heregulin. Merrimack is now prospectively testing the therapeutic effect of MM-121 in lung and breast cancer patients whose tumors have high expression of heregulin in two randomized, controlled clinical trials.