autotaxin

SEONGNAM, South Korea and ATLANTA, March 28, 2024 /PRNewswire/ -- Bridge Biotherapeutics (KQ288330), a South Korean clinical-stage biotech company developing novel drugs for cancer, fibrosis, and inflammation, announced a research collaboration with Dr. Jessica M. Konen's Lab at Emory University School of Medicine. 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. About Bridge Biotherapeutics, Inc. Bridge Biotherapeutics Inc., based in the Republic of Korea and the U.S., is a publicly traded, clinical-stage biotech company founded in 2015. Bridge Biotherapeutics is engaged in the discovery and development of novel therapeutics, focusing on therapeutic areas with high unmet needs, including fibrotic diseases and cancers. The company is developing BBT-877, a novel autotaxin inhibitor for the treatment of fibrotic diseases including idiopathic pulmonary fibrosis (IPF), and BBT-207, a potent targeted cancer therapy for non-small cell lung cancer (NSCLC) with EGFR C797S mutations. Learn more at . About Autotaxin Autotaxin (ATX), a protein of approximately 900 amino acids discovered in the early 1990s, is an important enzyme for generating the lipid-signaling molecule, lysophosphatidic acid (LPA). Autotaxin's lysophospholipase D activity converts lysophosphatidylcholine (LPC) into LPA, which engages in signaling via LPA receptors. LPA signaling results in cell proliferation, migration, secretion of cytokines and chemokines, and reduction of cell apoptosis. Ultimately, autotaxin has a pathogenic role in processes of inflammation and fibrosis, making it an attractive drug target. SOURCE Bridge Biotherapeutics, Inc.

SEONGNAM, South Korea and AURORA, Colo., March 26, 2024 /PRNewswire/ -- Bridge Biotherapeutics (KQ288330), a South Korean clinical-stage biotech company developing novel drugs for cancer, fibrosis, and inflammation, announced a research collaboration with Dr. Raul Torres's Lab at the University of Colorado School of Medicine. The collaboration will focus on exploring the potential of BBT-877, a novel autotaxin (ATX) inhibitor, as an immuno-oncology treatment for cancer. Throughout his previous and ongoing research, Dr. Raul Torres, Professor of Immunology and Microbiology at the University of Colorado School of Medicine, has shown that lysophosphatidic acid (LPA) plays a role in modulating CD8 T cell immunosurveillance and metabolism, ultimately disrupting the body's anti-tumor immunity.[i] LPA, a lipid that increases in its concentration across various cancer types, interacts with six different G protein-coupled receptors (LPA receptor 1-6, LPAR 1-6) to activate pathways and downstream signaling molecules leading to inflammation and fibrosis. According to recent research by Dr. Torres, the engagement of LPAR5 to LPA leads to the inhibition of cytotoxic function of CD8 T cells, thereby allowing cancer cells to evade immune surveillance. Silencing the inhibitory signaling of the LPA-LPAR5 pathway by reducing LPA levels is expected to enhance CD8 T cell immunity and improve effectiveness in killing cancer.[ii] The joint research effort is focused on BBT-877, a novel ATX inhibitor that has been found to reduce LPA production by as much as 90% in human studies. The goal is to assess BBT-877's potential as an immuno-oncology treatment. Early findings suggest that it may boost the immune system's ability to attack cancer cells by enhancing antigen-specific target cell killing, reducing LPA-mediated activation of LPAR5, and suppressing T cell dysfunction, leading to stronger anti-tumor immunity. "We are excited to collaborate with Dr. Torres's Lab to investigate the potential of BBT-877 as a novel immuno-oncology treatment," said James Lee, CEO of Bridge Biotherapeutics. "Dr. Torres's groundbreaking research on the role of the LPA-LPAR axis and T cell antigen receptor signaling in anti-tumor immunity has suggested the potential of autotaxin inhibitors to expand its indication into immuno-oncology," he added. Dr. Raul Torres, Professor at the University of Colorado School of Medicine, stated, "By collaborating with Bridge Biotherapeutics, we aim to deepen our understanding of the intricate mechanisms underlying anti-tumor immunity with regards to the LPA-LPAR axis and to translate scientific findings into novel therapeutic strategies that can enhance immune responses against cancer." Under the terms of the collaboration, Bridge Biotherapeutics will provide financial support and access to BBT-877, while Dr. Raul Torres's Lab will contribute its expertise in immunology and cancer biology. Together, the two entities will conduct preclinical studies to evaluate the therapeutic potential of BBT-877 in enhancing anti-tumor immunity. About Bridge Biotherapeutics, Inc. Bridge Biotherapeutics Inc., based in the Republic of Korea and the U.S., is a publicly traded, clinical-stage biotech company founded in 2015. Bridge Biotherapeutics is engaged in the discovery and development of novel therapeutics, focusing on therapeutic areas with high unmet needs, including fibrotic diseases and cancers. The company is developing BBT-877, a novel autotaxin inhibitor for the treatment of fibrotic diseases including idiopathic pulmonary fibrosis (IPF), and BBT-207, a potent targeted cancer therapy for non-small cell lung cancer (NSCLC) with EGFR C797S mutations. Learn more at . About Autotaxin Autotaxin (ATX), a protein of approximately 900 amino acids discovered in the early 1990s, is an important enzyme for generating the lipid-signaling molecule, lysophosphatidic acid (LPA). Autotaxin's lysophospholipase D activity converts lysophosphatidylcholine (LPC) into LPA, which engages in signaling via LPA receptors. LPA signaling results in cell proliferation, migration, secretion of cytokines and chemokines, and reduction of cell apoptosis. Ultimately, autotaxin has a pathogenic role in processes of inflammation and fibrosis, making it an attractive drug target. Company Codes: Korea:288330

Autotaxin inhibitor, IOA-289, recently received the proposed INN cambritaxestat Cambritaxestat is in the Phase I AION-02 trial in combination with chemotherapy in metastatic pancreatic cancer It is the first autotaxin inhibitor to be investigated in cancer patients AMSTERDAM and GENEVA, March 7, 2024 /PRNewswire/ -- iOnctura, a pioneering, clinical-stage biotechnology company developing transformative cancer therapies, today announces that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to its autotaxin inhibitor cambritaxestat for the treatment of pancreatic cancer. After assessing its novel chemical and biological properties including an attractive non-clinical safety and efficacy profile, the US FDA has granted Orphan Drug Status, conferring certain benefits during development and commercialization. Following a separate submission process the World Health Organization has proposed the International Nonproprietary Name (INN) of cambritaxestat. Cambritaxestat is being developed as a first-in-class therapy for highly fibrotic cancer indications. The drug's lead indication is metastatic pancreatic cancer where it is being combined with standard of care nab-paclitaxel and gemcitabine in the Phase I AION-02 study. Inhibition of autotaxin is a novel treatment strategy that offers a three-pronged attack on the tumor through direct cancer cell inhibition, immune effector stimulation and inhibition of fibrotic processes, giving drugs and immune cells better access to the tumor. Translational research showing the potential of cambritaxestat in multiple cancer models, including pancreatic cancer, has recently been published in the ESMO journal Immuno-Oncology and Technology (IOTECH), Cancer Research, the Journal of Experimental & Clinical Cancer Research, and Cancers. Across these publications, cambritaxestat showed strong reduction of metastasis and tumor outgrowth in preclinical models, as well as safe and tolerable dosing in healthy volunteers. Catherine Pickering, Chief Executive Officer, iOnctura, said: "There is an urgent need to develop new therapies for pancreatic cancer which is currently the third largest cause of death by cancer in the U.S., and the fourth in Europe. Although survival of patients with pancreatic cancer has improved in recent years, it still stands at just 13% after five years. This Orphan Drug Designation will support our goal to accelerate cambritaxestat through the clinic to provide a new treatment to patients with limited options." About iOnctura iOnctura is a clinical-stage biotech developing selective cancer therapies against targets that play critical roles in multiple tumor survival pathways. This pioneering approach to drug development is expected to offer significant clinical benefits over the traditional approach of targeting a single pathway alone. iOnctura has progressed two therapeutic candidates into mid-stage clinical development: Roginolisib, an allosteric modulator of PI3Kδ; and cambritaxestat, a highly selective, non-competitive autotaxin inhibitor. IOA-359, a TGF–β pathway inhibitor is also undergoing an extensive pre-clinical program in preparation for first-in-human studies. iOnctura is backed by specialist institutional investors including M Ventures, Inkef Capital, VI Partners, Schroders Capital, European Innovation Council and 3B Future Health Fund. iOnctura BV is headquartered in Amsterdam, The Netherlands with its wholly owned Swiss subsidiary, iOnctura SA, located in Geneva, Switzerland. About cambritaxestat (IOA-289) Cambritaxestat is an orally dosed molecule that has shown preclinically to inhibit the growth and proliferation of cancer cells, stimulate immune cell infiltration into tumors and inhibit the development of fibrosis. Cambritaxestat is being developed as a first-in-class therapy for highly fibrotic cancer indications that overexpress autotaxin including pancreatic, liver, colorectal, ovarian and breast cancers. A Phase I study of cambritaxestat in combination with chemotherapy in metastatic pancreatic cancer started in Q4 2022 (NCT05586516). SOURCE iOnctura