Preclinical Data Showing Synergy of Biothera Pharmaceuticals’ Imprime PGG and a CD40 Agonist in a Pancreatic Cancer Model Presented at Keystone Symposia
EAGAN, MN — March 26, 2018 — Biothera Pharmaceuticals, Inc. and the Abramson Cancer Center of the University of Pennsylvania announced today the presentation of new preclinical data demonstrating the combination of Imprime PGG and a CD40 agonist antibody stimulated T cell-dependent anti-tumor activity in a pancreatic cancer model. The data were presented at the ongoing Keystone Symposia Conference – Cancer Immunotherapy: Combinations in Montreal, Quebec, Canada.
While some solid tumors show remarkable sensitivity to immunotherapy, pancreatic ductal adenocarcinoma (PDAC) is remarkably resistant. This poor responsiveness may reflect multiple barriers to T cell activation, including ineffective tumor antigen presentation by myeloid cells. To enhance T cell activity, researchers at the University of Pennsylvania and Biothera Pharmaceuticals, Inc. combined two myeloid-directed immune agonists (Imprime PGG + CD40 antibodies) that would potentially synergize to reverse the poorly immunogenic state of pancreatic cancer. Imprime PGG is Biothera’s Phase 2 cancer immunotherapy, a pathogen associated molecular patterning (PAMP) molecule that repolarizes immunosuppressive myeloid cells in the tumor microenvironment and effectively enhances the capabilities of antigen presenting cells. CD40 agonistic antibodies are being clinically developed by several pharmaceutical companies to potentiate the co-stimulatory activity of antigen-presenting cells and to promote anti-cancer T cell immunity.
In a preclinical PDAC model, the combination of Imprime PGG and a CD40 agonist antibody induced complete and durable regressions in a majority of mice. Tumor-free mice also resisted tumor re-challenge suggesting the establishment of immune memory. This therapeutic effect was completely abrogated by CD4/CD8 cell depletion, indicating that the combination of Imprime PGG with the CD40 agonist worked by activation T cell-based immunity.
“The activity of this combination is quite striking and warrants further investigation,” said Gregory Beatty, Ph.D., M.D., Director of Translational Research, University of Pennsylvania Pancreatic Cancer Research Center, who reported the preclinical data as part of his presentation, “Strategies for Incorporate CD40 Agonists in Cancer Therapy.” Dr. Beatty’s lab conducted the research with support from Biothera Pharmaceuticals.
“Dr. Beatty’s research is particularly exciting as this is the first work to show synergy between Imprime PGG and anti-CD40 agonists in driving a robust T cell-based anti-cancer response,” said Jeremy Graff, Ph.D., Chief Scientific Officer and Senior Vice President, Research, at Biothera Pharmaceuticals.
Biothera researchers also presented Biothera Pharmaceuticals’ data at Keystone from ex vivo human and in vivo xenograft and syngeneic tumor models showing Imprime PGG re-orients the functionality of immunosuppressive myeloid cells (myeloid-derived suppressor cells and tumor-associated macrophages) and increases effector functionality of the tumor-infiltrating CD8 T cells. Collectively, these data show that systemic Imprime PGG therapy can re-model the normally immunosuppressive tumor microenvironment and enhance the effectiveness of checkpoint inhibitor therapy. The Biothera poster presentation was titled, “Imprime PGG modulates the functionality of immunosuppressive myeloid components of the tumor microenvironment and drives enhanced anti-tumor efficacy in combination with anti-PD1 antibody.”
About Biothera Pharmaceuticals, Inc.
Biothera Pharmaceuticals is a privately held clinical stage immuno-oncology company developing Imprime PGG, a Phase 2 cancer immunotherapy that has been shown in preclinical studies to enhance the efficacy of anti-cancer immune responses in combination with immune checkpoint inhibitor, tumor-targeting and anti-angiogenic antibodies. Biothera Pharmaceuticals has clinical research agreements with Merck to evaluate Imprime PGG and KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in Phase 2 studies in advanced melanoma, metastatic triple negative breast cancer and head and neck squamous cell cancer. This therapeutic combination also is the focus of a Big Ten Cancer Research Consortium Phase 1b/2 trial in patients with non-small cell lung cancer. In addition, Biothera Pharmaceuticals has a clinical collaboration agreement with Genentech to study Imprime PGG in combination with TECENTRIQ® (atezolizumab) and AVASTIN® (bevacizumab) in metastatic colorectal cancer.
Biothera Pharmaceuticals, Inc.