Data Published by Researchers from Leading Cancer Institutes Show Polaris Group Lead Therapeutic Candidate ADI-PEG 20 Causes Tumor Cytotoxicity through Previously Unidentified Mechanism

SAN DIEGO, Dec. 1, 2014 /PRNewswire/ -- Polaris Group announced today that data from a recent publication in the Proceedings of the National Academy of Sciences of the USA (PNAS) demonstrate for the first time that treatment by Polaris lead product candidate ADI-PEG 20 (pegylated arginine deiminase) induces cytotoxic autophagy in prostate cancer cells deficient in the enzyme argininosuccinate synthetase (ASS1). Autophagy is a catabolic process used by cells to prolong survival during nutritional starvation. However, the group's research revealed that prolonged arginine depletion through ADI-PEG 20 treatment in these prostate cancer cells led to cell death through a form of atypical autophagy, involving mitochondrial dysfunction and reactive oxygen species production, nuclear DNA leakage and chromatin autophagy. The authors termed this previously unidentified mechanism "chromatophagy." ASS1 plays an important role in the synthesis of the amino acid arginine, which is required for cell growth and function. Polaris Group believes that ASS1 deficiency in certain cancer cells requires these cells to obtain arginine from the circulation in order to survive.  ADI-PEG 20 is designed to deplete arginine in the circulation and cause cancer cells to die while leaving patients' normal cells unharmed.

In a commentary published in the same issue of PNAS, Dr. Peter Szlosarek of Barts Cancer Institute, Queen Mary University of London wrote that these new data "highlight that there is still much to learn about the effects of arginine in cancer cells, and how we should exploit arginine starvation and autophagy in combination with other therapies." 

"We are excited by the discovery of this new mechanism of action for ADI-PEG 20 in its anti-cancer activities", said John Bomalaski, M.D., Executive Vice President, Medical Affairs, of Polaris. "We now have a number of Phase 1 and Phase 2 clinical trials underway with ADI-PEG 20 in cancers that are ASS1 deficient, not only as monotherapy, but also combined with one or two other agents."

About ADI-PEG 20

ADI-PEG 20 is a biologic being developed by Polaris Group to treat cancers, especially those carrying a major metabolic defect that renders such cancer cells, unlike normal cells, unable to internally synthesize arginine. Because arginine is one of the 20 amino acids that are essential for protein synthesis and survival of cells, it is believed these cancer cells become dependent upon the external supply of arginine to survive and grow. ADI-PEG 20 is designed to deplete the external supply of arginine, which causes arginine-dependent cancer cells to die while leaving the patient's normal cells unharmed. Multiple cancers have been reported to have a high degree of arginine-dependency.

About Polaris Group

Polaris Group is a privately held biopharmaceutical company that specializes in the research and development of protein drugs to treat cancer and other debilitating diseases. The company's lead therapeutic, ADI-PEG 20, is currently being evaluated in a pivotal Phase 3 trial for hepatocellular carcinoma. Polaris Group is also investigating ADI-PEG 20 as a treatment for other cancers, such as leukemia, lymphoma, melanoma, mesothelioma, non-small cell lung cancers, sarcoma, breast, ovarian, and pancreatic cancer. In addition to the ADI-PEG 20 program, Polaris Group is researching and developing other biotherapeutic agents and is advancing a small molecule drug program that utilizes a rational structure-based approach to design novel compounds that inhibit the biological function of cancer-related protein targets.

For additional information please visit www.polarispharma.com

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