Biothera Announces Clinical Study to Evaluate Combination Therapy of Imprime PGG and Merck’s Checkpoint Inhibitor Keytruda in Patients with Non-Small Cell Lung Cancer

On December 10, 2015 Biothera Pharmaceutical Inc., reported plans for a Phase 1b/2 clinical study in non-small lung cancer (NSCLC) patients to evaluate the ability of Biothera’s Imprime PGG to enhance responses to pembrolizumab (Keytruda), the anti-PD-1 antibody from Merck (NYSE:MRK), known as MSD outside the United States and Canada (Press release, Biothera Pharmaceuticals, DEC 10, 2015, View Source [SID1234562110]). Merck will provide funding and clinical supplies of pembrolizumab for the investigator-initiated study under the direction of Lawrence Feldman, M.D., of the University of Illinois at Chicago. The trial is expected to begin in the first quarter of 2016.

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Imprime PGG is a first-in-class, systemically administered beta glucan PAMP (pathogen associated molecular pattern) that triggers a robust, integrated immune response shown to enhance the anti-tumor efficacy of checkpoint inhibitors (PD-1, PD-L1 antibodies), anti-angiogenic antibodies and tumor-targeting monoclonal antibodies (mAbs). To date, Imprime PGG has shown promising efficacy in combination with mAbs in two Phase 2 studies of patients with NSCLC.

"Preclinical results for the combination therapy with Imprime PGG show the potential to expand the number of patients who can respond to Keytruda, as well as enhance the robustness of their response," said Dr. Feldman, Associate Professor of Medicine, College of Medicine at the University of Illinois at Chicago and principal investigator for the study. "The results for combination therapy with Imprime PGG have been encouraging, and I look forward to the progress of the upcoming study."

Biothera research has demonstrated that Imprime PGG activates key immune responses, including enhancement of dendritic cell maturation and presentation of antigen and co-stimulatory signals to T cells. The effect is to establish a critical link between the innate and adaptive immune systems, resulting in an expansion of T cell populations and inducing the production of the anti-tumor cytokine interferon gamma (IFN-γ). Imprime PGG also has been demonstrated to increase PD-L1 expression on tumor cells and tumor-associated macrophages, which also may enhance patient responses to pembrolizumab.

"Imprime PGG acts as an ignition switch to drive a coordinated response involving both the innate and adaptive immune systems to recognize and kill cancer cells," said Jose Iglesias, M.D., Chief Medical Officer, Biothera Pharmaceutical Inc. "In the anticipated Phase 1b/2 study, Imprime is expected to perform a dual role of enhancing antigen presentation, which helps more T cells target cancer, and upregulating PD-L1 expression to provide pembrolizumab more opportunities to disrupt or inhibit PD-1/PD-L1 interaction."

The Phase 1b/2 study is scheduled to begin dosing of patients in Q1 2016, with plans to enroll up to 58 patients with NSCLC following their progression on first line platinum-based chemotherapy. The phase 1b element of the trial is a dose-escalation study of up to 12 patients receiving Imprime PGG in combination with pembrolizumab. The phase 2 element of the study will test whether the addition of Imprime PGG to pembrolizumab increases median progression free survival and overall survival in up to 46 subjects.