Imprime PGG®, the phase 3 cancer immunotherapy drug from Biothera, utilizes distinct receptors and signaling pathways in monocytes to induce cytotoxic function. The research was published in the latest issue of Glycobiology.

This new research describes how structurally different forms of yeast beta glucans utilize different receptors and associated signaling pathways to activate innate immune functions. Imprime PGG is a soluble, patented, yeast-derived beta glucan that can engage and direct innate immune cells to kill cancer.

"These results further elucidate the mechanisms through which Imprime PGG specifically affects monocyte functions, and additionally demonstrate that beta-glucan structure is a critical attribute in eliciting biological effects," said Myra Patchen, Ph.D., chief scientific officer for Biothera's Pharmaceutical Group.

In the study, different forms of beta glucan were used to activate human peripheral blood mononuclear cells, specifically monocytes, and oxidative burst, one of the cytotoxic mechanisms used by innate immune cells. This research expands on previously published research in Frontiers in Immunology, where it was shown that soluble beta glucan (Imprime PGG) binds through complement receptor type 3 (CR3). This research confirms the role of CR3 in Imprime PGG-mediated oxidative burst response. In contrast, another form of yeast beta glucan (whole glucan particle) induced a similar response through a different receptor, Dectin-1. Furthermore, these physically different forms of beta glucan induced this functional response through both overlapping and distinct signaling pathways.

"Increasing our knowledge about structure and function of Imprime PGG may benefit the future development of second-generation compounds," said Dan Conners, president of Biothera's Pharmaceutical Group.

The paper is entitled, "Differential regulation of oxidative burst by distinct ?-glucan-binding receptors and signaling pathways in human peripheral blood mononuclear cells."

The authors include Nandita Bose1, Lindsay R. Wurst1, Anissa SH. Chan1, Christine M. Dudney1, Megan L. LeRoux1, Michael E. Danielson1, Paul M. Will1, Sonja E. Nodland1, Myra L. Patchen1, Jurandir J. Dalle Lucca2, Frank J. Lebeda3, and John P. Vasilakos1.

1 Biothera, Eagan, MN 55121 USA
2 US Army Institute of Surgical Research, Ft. Sam Houston, 78234 USA TX
3 US Army Medical Research and Materiel Command, Ft. Detrick, MD 21701 USA

About Imprime PGG®
Imprime PGG is a novel immunomodulatory drug in development as a cancer therapy. Innate immune cells are the most abundant immune cells in the body and are normally responsible for pathogen killing, but not anti-tumor activity. However, Imprime PGG has been shown to bind to neutrophils and monocytes and redirect their killing ability to reduce tumor growth and enhance long-term survival. This targeted mechanism is synergistic with multiple anti-tumor monoclonal antibodies, providing the potential to improve patient outcomes in a wide range of cancer indications. Imprime PGG has demonstrated marked improvements in overall response rates in multiple clinical trials for non-small cell lung cancer (NSCLC), colorectal cancer, KRAS-mutant colorectal cancer and chronic lymphocytic leukemia. Imprime PGG is currently in a Phase 3 clinical trial for advanced colorectal cancer and a second Phase 2 NSCLC study with bevacizumab (Avastin®).

For more information, visit our website at www.biothera.com/pharma.

About Biothera, the Immune Health Company
Biothera is a U.S. biotechnology company dedicated to improving immune health. The company is developing pharmaceuticals that engage the innate immune system to fight cancer.

Biothera, the Immune Health Company
David Walsh, 651-256-4606
VP, Communications
dwalsh@biothera.com