Merrimack Pharmaceuticals, Inc announced that it has reached an agreement with Sanofi to regain worldwide rights to develop and commercialise MM-121, a monoclonal antibody designed to block ErbB3 (HER3) activation in patients with heregulin-positive tumours and improve response to standard of care treatments.

In partnership with Sanofi, Merrimack completed an extensive Phase 2 programme 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 tumours 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. Data from these studies were recently presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting. To view the clinical posters presented at ASCO 2014.

"We are grateful for Sanofi's support over the last five years and believe that the data generated through this partnership validate the potential for MM-121 to help patients most at risk for progression on current therapies. Regaining MM-121 is an opportunity to capitalise on our leadership position among the other oncology companies that are pursuing ErbB3," said Robert Mulroy, President and chief executive officer at Merrimack. "With these data and the feedback we've received from our committed investigators, we believe MM-121 has the potential to be a foundational therapy for use across multiple solid tumour types and we plan to continue its development through subsequent strategic partnerships. Our next step is to discuss our Phase 2 data and potential registration paths with the FDA."

Sanofi will continue to fund the existing MM-121 Phase 2 programme 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. Top line results of that study are below.

Results from the Second Cohort of a Phase 2 Study of MM-121 in Combination with Paclitaxel in Neoadjuvant Breast Cancer

Merrimack and Sanofi completed a randomised (2:1), exploratory Phase 2 study testing MM-121 in combination with paclitaxel followed by doxorubicin and cyclophosphamide. The study was conducted in two populations of patients with either ER/PR positive (ER/PR+) HER2 negative breast cancer (n=101) or triple negative breast cancer (TNBC) (n=99). There was no formal quantitative endpoint specified for this study.

In November 2013, Merrimack released initial top line results from the ER/PR+ HER2 negative cohort. Those results demonstrated that patients who received the combination of MM-121 and paclitaxel achieved a pCR rate of 10.6% (95% CI [5.2; 20.3]) compared to 3.3% (95% CI [0.6; 16.7]) for the control arm. Top line results from this second cohort of patients with TNBC showed that patients who received the combination of MM-121 and paclitaxel achieved a pCR rate of 42.9% (95% CI 30.8; 55.9) compared to 51.7 (95% CI 34.4; 68.6) for the control arm. Translational analysis is ongoing for both cohorts and the full data set will be reported at a future medical conference. Preliminary analysis of approximately 50 per cent of the pretreatment biopsies suggests a link between heregulin levels and pCR rates.

For the TNBC cohort, rates for serious adverse events were 28.1per cent vs. 15.6 per cent and rates for grade 3 or higher adverse events were 50.0 per cent vs. 31.3 per cent between the treatment and control arms, respectively. As reported previously, in the ER/PR+ HER2 negative cohort, similar frequencies were reported for adverse events of any grade between the treatment and control arms, with no unexpected toxicities experienced and no increase in serious adverse events. Grade 3 or worse adverse events in the ER/PR+ HER2 negative cohort were 55.2per cent on treatment arm versus 53.1per cent on control arm.

MM-121 is a fully human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumour growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, MM-121 is designed to block ErbB3 signaling in order to restore or enhance the anti-tumour effect of a combination therapy partner.

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 programme was designed to establish clinically useful biomarkers that were initially identified using Merrimack's systems biology approach and confirmed in preclinical studies.