LPA synthesis

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

SEOUL, Korea and REDWOOD CITY, Calif., Dec. 14, 2023 (GLOBE NEWSWIRE) -- GPCR Therapeutics, Inc., a clinical-stage international biopharmaceutical company, announces it enters into an out-licensing agreement with Bridge Biotherapeutics (KQ288330) for the CXCR4-LPA1 inhibitor combination method of treatment. GPCR receives an upfront payment of KRW 2 billion (approx. USD 1.5 million), and a 50:50 profit-share on future commercialization, including sub-licenses. In collaboration with Bridge Biotherapeutics, GPCR will pursue joint development and commercialization of the combination therapy. Conducting a multinational phase 2a clinical trial of BBT-877, an autotaxin inhibitor for the treatment of IPF, Bridge Biotherapeutics has been accelerating development of its proprietary IPF pipeline. Last September, GPCR published the paper on the direct interaction between two different GPCRs, CXCR4 and LPA1, in the peer-reviewed academic journal ‘Cell Communication and Signaling’(1). The target GPCRs are known to promote fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). Through various in vitro experiments, the company found that the efficacy of LPA1 inhibition can be further maximized by inhibition of CXCR4, thereby securing a scientific basis that the CXCR4- LPA1 inhibitor combination may be necessary for full anti-fibrotic activity. Based on this finding, GPCR filed a provisional patent application on the CXCR4-LPA1 inhibitor combination method of treatment. Dr. Dong Seung Seen, founder and CEO of GPCR Therapeutics, commented, “Since the publication of our paper, various global companies have expressed interest in the relationship between LPA1 and CXCR4 and its inhibitory effect. Due to the versatility of our patent, we look forward to collaborating with many IPF-targeting companies, starting with Bridge Biotherapeutics.” James Lee, founder and CEO of Bridge Biotherapeutics, said, “We are encouraged to collaborate with GPCR Therapeutics to uncover new possibilities of IPF treatment. Our collaboration will help us move forward to identifying and bringing novel treatment of IPF, such as a combination therapy of LPA1 and CXCR4 inhibitor, based on GPCR’s latest research.” IPF is a progressive chronic lung condition that causes scarring (fibrosis) of a patients’ lungs which makes breathing increasingly difficult as the lungs become stiffer and lose their elasticity. The lungs become less efficient at transferring oxygen so that when someone with IPF breathes in, the transfer of oxygen through air sacs in their lungs and into their blood stream is impaired. Lung damage from IPF is irreversible, and there is currently no treatment that stops or reverses the scarring. In the US there are around 495 cases per 100,000 people, with median survival estimated at 2–5 years from the time of diagnosis. (2) (3) References (1) Cell Communication and Signaling paper, “LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration”: (2) American Lung Association data on IPF: (3) PubMed paper on incidence and prevalence of IPF: About GPCR Therapeutics GPCR Therapeutics, Inc. is a clinical-stage international biopharmaceutical company with an innovative approach to developing therapeutics built on its proprietary GPCR data. The company’s lead small molecule asset, GPC-100/Burixafor, targets CXCR4, one of the most prevalent chemokine GPCRs overexpressed in various cancers. The company has an ongoing US Phase 2 clinical trial assessing the efficacy of the combination of GPC-100 and propranolol in patients with multiple myeloma. In addition, the company is engaged in active collaborations with domestic and international biotechnology companies. By targeting the unique pharmacology of GPCR pairs, the company aims to develop life-changing treatments for cancer and other diseases. The company has identified that CXCR4 interacts with the beta-2 adrenergic receptor (B2AR), and this GPCR pair presents an alternate signaling pathway that is synergistically dependent on CXCR4 and B2AR activation. GPCR Therapeutics has its HQ in Seoul, Korea with additional R&D facilities in the San Francisco Bay Area, USA. For more information, visit gpcr.co.kr and follow us on LinkedIn. For more information, please contact: GPCR Therapeutics (in Seoul) DaYoon Kim - Business Development Manager Tel: +82-2-878-2848 [email protected] Scius Communications (in London): Katja Stout - Founder & Managing Partner +44 778 943 5990 [email protected]