Date: 2014-06-19
Type of information: Licensing agreement
Compound: MM-121
Company: Merrimack Pharmaceuticals (USA -MA) Sanofi (France)
Therapeutic area: Cancer - Oncology
Type agreement: licensing
Action mechanism: MM-121 is a fully human monoclonal antibody that targets ErbB3, a cell surface receptor implicated in tumor growth and survival. It inhibits ligand-induced signaling through HER3.21 By targeting ErbB3, the antibody blocks heregulin (HRG1-Beta1) binding to HER3, induces HER3 internaliztion and degradation, and blocks BTC-induced phosphorylation of HER3, leading to inhibition of HRG1-Beta1- and BTC-induced survival signaling.20 SAR256212 activity has been evaluated in a broad range of preclinical tumor xenograft models. MM-121 has been investigated in four Phase 2 and six Phase 1 clinical studies covering a broad spectrum of patient populations and drug combinations. An extensive translational component of the MM-121 clinical program was designed to establish clinically useful biomarkers that were initially identified using Merrimack\'s systems biology approach and confirmed in preclinical studies.
Disease: heregulin-positive tumors
Details: * On October 1, 2009, Merrimack Pharmaceuticals and sanofi-aventis announced the signing of an exclusive worldwide licensing agreement for the development and co-commercialization of MM-121. MM-121 is currently in Phase 1 clinical testing. Merrimack will execute the development of MM-121 through Phase 2 proof of concept for each indication and sanofi-aventis will be responsible for development thereafter. Merrimack retains the right to co-promote the therapy in the United States. Merrimack developed MM-121 after identifying the importance of ErbB3 through its Network Biology approach, a fully integrated drug discovery and development technique that combines biology, engineering, and computational modeling to better understand the underlying complexity of disease pathways. The information derived from Network Biology informs the strategic decisions guiding early pharmaceutical discovery as well as helping to advance candidates through pre-clinical, clinical development and towards commercialization.
Financial terms: Under the terms of the agreement, sanofi-aventis will make an upfront payment of $60 million and will be responsible for all development costs. Merrimack is eligible for an additional $470 million in milestone payments as well as tiered double-digit royalties on sales of MM-121.
Latest news: * On June 19, 2014, Merrimack Pharmaceuticals announced that it has reached an agreement with Sanofi to regain worldwide rights to develop and commercialize MM-121, a monoclonal antibody designed to block ErbB3 (HER3) activation in patients with heregulin-positive tumors and improve response to standard of care treatments. In partnership with Sanofi, Merrimack completed an extensive Phase 2 program for MM-121 which was designed to assess the role of ErbB3 in a number of cancer indications in both the metastatic and neoadjuvant settings. In advanced settings of ovarian cancer, ER/PR+ HER2 negative breast cancer and non-small cell lung cancer, Merrimack was able to identify that heregulin, the principal ligand that binds to and activates the ErbB3 receptor, is associated with poor response to standard of care therapy and that adding MM-121 may restore sensitivity in these most at-risk patients. Consistent across three metastatic cancer indications with three different standard of care therapies, patients in these trials with heregulin-positive tumors experienced a statistically significant reduction in their risk of progression when they received a combination with MM-121. Heregulin-driven drug resistance pathways were found to be active in approximately 30-50 percent of patients tested.
Sanofi will continue to fund the existing MM-121 Phase 2 program for the next six months. The neoadjuvant cohort of a Phase 2 study testing MM-121 in combination with paclitaxel in patients with triple negative breast cancer is the final study to be completed through this collaboration.
