CAMBRIDGE, Mass., Dec. 4, 2014 (GLOBE NEWSWIRE) -- Merrimack Pharmaceuticals, Inc. (Nasdaq:MACK) announced today that Cancer Research has published the paper "Preclinical Activity of Nanoliposomal Irinotecan is Governed by Tumor Deposition and Intratumor Prodrug Conversion" in its latest issue (Volume 74, Issue 23).
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MM-398, also known as nal-IRI, is a nanoliposomal formulation of irinotecan encapsulated in a lipid sphere. MM-398 is designed with Merrimack's nanoliposomal technology to deliver a large drug payload and to allow it to be preferentially accumulated in tumors compared to normal tissues. The publication describes how this design significantly alters the pharmacokinetic properties of irinotecan, increasing the retention time and exposure to SN-38 (the active form of the drug) in tumor cell models. MM-398's clinical program is focused around confirming these properties and their potential to improve treatment across multiple indications for the drug.
"We are pleased to publish our characterization of MM-398 in Cancer Research, which describes how we have used our systems pharmacology approach to determine how MM-398's nanoliposomal design improves antitumor activity in the preclinical setting," said Jonathan Fitzgerald, Vice President of Research at Merrimack and senior author of the publication. "Our research demonstrates that the formulation of MM-398 alters the pharmacokinetic profile of the active form of irinotecan, prolonging tumor exposure and retention compared with the free drug, and therefore provides further rationale for expanding MM-398 into a broader clinical development program. We are currently exploring translational research to determine if tumor liposome permeability and local activation of irinotecan can be used as biomarkers for MM-398 clinical activity so that we can potentially provide physicians with a tool to identify which patients may respond best to MM-398 treatment."
The preclinical data published in Cancer Research shows that the active form of the drug, SN-38, was present for more than 100 hours in tumor models following the administration of MM-398, compared to approximately 40 hours following administration of free irinotecan.
The extended exposure of tumor cells to SN-38, which is achieved by MM-398, can contribute toward the tumor inhibiting properties of MM-398. Preclinical findings also show that the uptake of liposomes and the prolonged exposure to SN-38 was observed only in tumors, which suggests that normal tissues may be generally spared from the effects of the drug.
Research presented in this publication also used a systems approach and computational modeling tools to further understand the delivery mechanism behind MM-398. Two key factors, tumor permeability to MM-398 and the activation of irinotecan into its active form by carboxylesterase enzymes (CES), were discovered to be especially important for the activation and accumulation of the drug in tumor cells. Further research for MM-398 includes focusing on these factors and integrating them as biomarkers in clinical studies, a strategy that could help identify potential patients who would respond best to the drug.
MM-398 (irinotecan liposome injection), also known as "nal-IRI," is a nanoliposomal encapsulation of the chemotherapeutic irinotecan. MM-398 has demonstrated extended circulation in comparison to free irinotecan in the clinical setting. The activated form of irinotecan is SN-38, which functions by inhibiting topoisomerase I (an essential enzyme involved in DNA transcription and replication) and promoting cell death. In 2014, Merrimack and Baxter International's biopharmaceutical business (NYSE:BAX) entered into an exclusive licensing agreement to develop and commercialize MM-398 outside of the United States and Taiwan. PharmaEngine, Inc. (Taipei, Taiwan) holds the rights to commercialize MM-398 in Taiwan.
Merrimack is a biopharmaceutical company discovering, developing and preparing to commercialize innovative medicines paired with companion diagnostics for the treatment of cancer. Merrimack seeks to gain a deeper understanding of underlying cancer biology through its systems biology-based approach and develop new insights, therapeutics and diagnostics to improve outcomes for cancer patients. Merrimack currently has six oncology therapeutics in clinical development and three additional candidates in late stage preclinical development. For more information, please visit Merrimack's website at www.merrimackpharma.com or connect on Twitter at @MerrimackPharma.
Any statements in this press release about future expectations, plans and prospects for Merrimack constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, as amended. Actual results may differ materially from those indicated by such forward-looking statements. Merrimack anticipates that subsequent events and developments will cause its views to change. However, while Merrimack may elect to update these forward-looking statements at some point in the future, Merrimack specifically disclaims any obligation to do so.
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