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Merrimack’s GI Cancer Agents Show Promise

Published Online: Friday, September 20, 2013
Merrimack Logo Merrimack Pharmaceuticals is combining biology, computing, and engineering in order to gain a comprehensive understanding of the dynamics of different types of cancer and then use that information to develop new therapeutics.

The company says its approach focuses on three biological characteristics of tumors: signaling networks that drive tumor growth; signaling adaptations that occur when tumors become resistant to treatment; and tumor micro-anatomy and micro-environment. Each of these strategies has helped Merrimack develop different biologic agents.

For example, by concentrating on signaling adaptations, the company was able to develop MM-111, a first-in-class bispecific antibody that is able to bind with both specificity and avidity to HER2- and HER3-expressing tumor cells. While the role of HER2 is well established in breast cancer, Merrimack was able to determine that HER3 is a key tumorigenic node involved in many different types of cancer, with involvment in the growth and development of cancers as well as ways in which cancer cells develop resistance to targeted therapies and chemotherapy.

Merrimack Key

Merrimack Pipeline

Agent Indication Description Target Phase
MM-121 NSCLC, breast cancer, ovarian cancer Monoclonal antibody ErbB3 II
MM-111 Gastric cancer (2nd line, 2 indications) Bispecific antibody ErbB3, ErbB2 II
MM-151 Regractory advanced solid tumors Oligoclonal antibody EGFR I
MM-141 Cancer, nonspecific Bispecific tetravalent antibody IGF-1R, ErbB3 I
MM-131 Cancer, nonspecific Multispecific antibody Undisclosed Preclinical
MM-398 Pancreatic cancer (2nd line, 2 indications), colorectal cancer, glioma Nanotherapeutic Encapsulated irinotecan III
MM-302 Advanced, HER2+ breast cancer Antibody-targeted nanotherapeutic HER2-targeted encapsulated doxorubicin I
MM-310 Cancer, nonspecific Antibody-targeted nanotherapeutic Undisclosed Preclinical

Source: www.merrimackpharma.com

In August, MM-111 received orphan drug status from the FDA for the treatment of both esophageal cancer and gastric as well as gastroesophageal junction (GEJ) cancers. Estimates vary, but various scientific studies have found that the HER2 cell surface receptor is overexpressed in 7% to 34% of gastric cancers, and HER3 expression is associated with poor prognosis in patients with the disease and perhaps contributes to resistance to current treatment options. A phase II study to assess the efficacy of MM-111 in these tumor types is currently enrolling patients. Another product of Merrimack’s research approach is MM-398, which was developed using the company’s investigations into the micro-anatomy of a tumor, with a focus on how the vasculature, immune system, extracellular factors, and interaction with noncancer cells and neighboring tissues can affect the development of the tumor. MM-398 is a nanotherapeutic that delivers the chemotherapy drug irinotecan via encapsulation in a liposomal sphere. The natural blood flow of the tumor directs the drug to the site of the tumor to minimize exposure of the drug to noncancer cells.

The results of a phase II study of MM-398 in pancreatic cancer were published in August in the British Journal of Cancer. The study met its primary endpoint with 75% of patients surviving at least 3 months, with 25% of patients in the study surviving for at least one year. The median overall survival was 5.2 months, and 50% of patients showed evidence of disease control. A global, randomized, open-label phase III trial called NAPOLI-1 is assessing MM-398 with or without 5-FU and leucovorin versus the control arm of 5-FU and leucovorin in patients with metastatic pancreatic cancer after gemcitabine failure. Enrollment is expected to be completed later this year.

Overall, a total of eight different therapeutic agents are in various stages of development at Merrimack, and while many are in early stages, some of these drugs are being considered for specific tumor types, including non-small cell lung cancer, breast cancer, and colorectal cancer, in addition to the aforementioned tumor types.


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