Biothera’s Investigational Cancer Immunotherapy Imprime PGG Neutralizes Cancer Defense Mechanisms In The Tumor Mircoenvironment

New Preclinical Data to be presented today at Keystone Symposium in Montreal

EAGAN, Minn.--(BUSINESS WIRE)--New preclinical research from Biothera further demonstrates the ability of its cancer immunotherapy drug candidate Imprime PGG^® to initiate a cascade effect of immune responses that neutralize cancer-associated immunosuppression in the tumor microenvironment. Biothera will present the new data today in Montreal at the Keystone Symposium: Dendritic Cells and Macrophages Reunited.

“Imprime PGG, a Yeast ß-glucan Immunomodulator, Enhances Maturation and Function of Human Monocyte-Derived Dendritic Cells.”

The company’s latest research shows that Imprime PGG enhances the maturation and function of monocyte-derived dendritic cells (MoDC), which are known to contribute to tumor-induced immunosuppression. MoDCs isolated from Imprime PGG-treated whole blood expressed higher levels of the cell surface markers CD83, CD86, CD80 and HLA-DR, which are required for efficient antigen presentation. Imprime PGG’s ability to enhance MoDC maturation resulted in increased T cell proliferation and production of the anti-tumor cytokine interferon gamma – even in the presence of the potent suppressive effects of tumor-conditioned media.

“These results, along with previous data, demonstrate that Imprime PGG enhances the functions of dendritic cells as well as macrophages, the two key antigen presenting cell types that bridge innate and adaptive immunity,” said Jeremy Graff, Ph.D., Senior Vice President, Biothera Pharmaceutical Research. “Imprime PGG has the capacity to enhance the maturation of dendritic cells to promote the antitumor ability of the adaptive immune system.”

Importantly, the maturation of MoDC and the resulting increases in effector T cell expansion and interferon gamma production were only observed in blood from individuals with high levels of anti-ß-glucan antibodies (ABA). A threshold level of ABA is required to form the Imprime PGG-ABA immune complexes that bind to and efficiently prime innate immune effector cells to kill antibody-targeted cancer cells.

Previous research had also demonstrated that Imprime PGG could restrain the immunosuppressive capability of M2 macrophages, one of the key monocyte-derived cells known to foster immunosuppression within the tumor microenvironment. Together, these recent disclosures highlight the capacity of Imprime PGG to promote an anti-tumor immune microenvironment. Dr. Graff commented that the next critical steps are to evaluate these changes in syngeneic tumor models.

Biothera’s Keystone Symposium poster is #1030, “Imprime PGG, a Yeast ß-glucan Immunomodulator, Enhances Maturation and Function of Human Monocyte-Derived Dendritic Cells.” The poster presentation is scheduled from 7:00-9:00 pm EDT today.

About Biothera
Biothera, a privately held U.S. biotechnology company, is developing Imprime PGG, a late clinical stage biologic that modulates the immune response to cancer. Data from the most recent randomized phase 2 study of Imprime PGG in first line non-squamous NSCLC was featured as a late-breaking abstract in the Immunotherapy of Cancer session at ESMO 2014. In this study, which evaluated the addition of Imprime PGG to bevacizumab and carboplatin/paclitaxel versus bevacizumab and chemotherapy alone, objective response rate was 60.4% versus 43.5%, duration of response was 10.3 months versus 5.6 months and median overall survival was 16.1 months versus 11.6 months. Similarly encouraging data have been observed in both squamous and non-squamous subjects in a second randomized Phase 2 study in 1st line NSCLC in combination with cetuximab and in studies in high-risk chronic lymphocytic leukemia and metastatic colorectal cancer. Imprime PGG directly modulates the key effector cells of the innate immune system, neutrophils and monocytes/macrophage, enabling them to recognize and kill antibody-targeted cancer cells. In addition, on-going research points to a secondary, bystander effect of Imprime PGG on both innate and adaptive immune cell types known to exist in the tumor microenvironment, including T-cells, dendritic cells, M-2 macrophages and myeloid derived suppressor cells. Imprime PGG is being evaluated in a phase 3 study in late stage metastatic colorectal cancer and planning is underway for an approvable study in NSCLC.

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