On March 28, 2024 Bridge Biotherapeutics (KQ288330), a South Korean clinical-stage biotech company developing novel drugs for cancer, fibrosis, and inflammation, reported a research collaboration with Dr. Jessica M. Konen’s Lab at Emory University School of Medicine (Press release, Bridge Biotherapeutics, MAR 28, 2024, View Source [SID1234641588]).

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The collaboration will explore the potential therapeutic benefits of combination therapy of BBT-877, a novel autotaxin (ATX) inhibitor, with anti-PD-1 immunotherapy for the treatment of non-small cell lung cancer (NSCLC) in patients harboring KRAS and P53 (KP) mutations who are resistant to anti-PD-1 blockade.

As a member of the cancer immunology research program at Winship Cancer Institute of Emory University, Dr. Konen’s research has shown that autotaxin has a direct impact on the body’s immune response to tumors. Specifically, higher levels of ATX expression are associated with a decrease in the number of tumor-infiltrating CD8 T cells and an increase in inflammatory gene signatures, including those related to the cytolytic activity of CD8 T cells. Furthermore, an activated tumor-immune microenvironment upregulates ATX and thus provides opportunities for acquired resistance to anti-PD-1 treatment.[i]

From their in vitro studies, the company and the laboratory found that BBT-877 induces CD4 and CD8 T cell proliferation and activation markers, with a robust increase in CD8 T cells that express Granzyme B. The ongoing research collaboration is dedicated to investigating the potential benefits of combining BBT-877 with anti-PD-1 therapy as a treatment approach.

"We are excited to collaborate with Dr. Konen’s team at Emory University School of Medicine to explore the potential of BBT-877 in overcoming resistance to anti-PD-1 therapy in NSCLC patients with KRAS and P53 mutations as a combination therapy with immuno-oncology agents," said James Lee, CEO of Bridge Biotherapeutics. "We believe that Dr. Konen’s research on the role of autotaxin in immunosuppression has the potential to significantly improve treatment outcomes for those patients who are resistant to anti-PD-1 therapy."

"This collaboration presents a promising opportunity to translate our scientific understanding of autotaxin’s role in immunotherapy resistance into a novel therapeutic approach for KRAS/P53 mutant NSCLC patients," said Dr. Jessica Konen, Department of Hematology and Medical Oncology Instructor at Emory University School of Medicine. "We are pleased to work with Bridge Biotherapeutics to explore indication expansion into NSCLC through a combination of BBT-877 with anti-PD-1 agent and potentially offer new hope to those patients."

Under the terms of the collaboration, Bridge Biotherapeutics will provide financial support and access to BBT-877, while Dr. Jessica Konen’s Lab will contribute its expertise in immunology and oncology. Together, the two entities will conduct preclinical studies to evaluate the therapeutic potential of BBT-877 in enhancing anti-tumor immunity.