Company Collaborating with Researchers at the University of Nottingham on Optimization and Evaluation of Novel Small Molecule GPR65 Inhibitors in Preclinical Brain Tumor Models
OXFORD, UK – September 27, 2023
Pathios Therapeutics Limited (“Pathios”), a biotech company focused on the development of first-in-class therapies for cancer, today announced that the company has been awarded a £567K (~US$727K) grant from Innovate UK, the UK government’s innovation agency. The grant funding will enable the company to expand its development of novel small molecule GPR65 inhibitors into the area of a possible treatment of malignant brain tumors. The project is being conducted in collaboration with researchers from the University of Nottingham and is focused on optimizing small molecule GPR65 inhibitors to penetrate the central nervous system (CNS) and evaluate those optimized compounds in preclinical models of brain cancer.
The treatment of patients with malignant brain tumors remains a high unmet medical need. While chemotherapy has modestly improved survival rates among these patients, the need for truly impactful treatments remains. Immunotherapy has demonstrated some promise in this area, though overcoming the immunosuppressive tumor microenvironment (TME) remains a key challenge.
Pathios is pursuing a novel immuno-oncology approach to the treatment of cancer focused on counteracting the immunosuppressive polarization of immune cells, including tumor associated macrophages (TAMs), that is triggered by an acidic TME. This is achieved by the design and development of inhibitors of GPR65, an acid sensing G protein-coupled receptor that is exclusively expressed on immune cells and is associated with driving the immunosuppressive immune cell phenotype in the TME that prevents immune-mediated killing of cancer cells. Pathios’ internal human genetic analysis demonstrates that reductions in GPR65 function are associated with significantly improved survival across a range of solid tumor types, positioning it as a unique immuno-oncology target for therapeutic intervention.
With this grant, Pathios is utilizing an extensively developed proprietary assay platform to optimize CNS penetration of small molecule GPR65 inhibitors for the treatment of human malignant gliomas. Optimized GPR65 inhibitors are being tested in a human ex vivo co-culture system model of human glioblastoma in collaboration with University of Nottingham researchers, followed by in vivo efficacy evaluation in mouse models.
“Recent research suggests that a portion of glioblastoma patients do not respond to approved immuno-oncology drugs due to the immunosuppression of immune cells in the TME by the acidic microenvironment inherent to all solid tumors, including brain cancers.” said Stuart Hughes, Ph.D., chief executive officer of Pathios. “We believe there is promise in applying our novel immuno-oncology approach to cancers of the brain with a CNS-penetrating small molecule GPR65 inhibitor. We are excited to be working alongside the talented team at the University of Nottingham on this important preclinical research, which we hope will pave the way for future clinical studies.”
“We are excited to be supporting the research and development of this novel therapy for malignant brain tumours. By working with Pathios we aim to support their preclinical development and
expedite the progress of their inhibitors into the clinic,” said Alan McIntyre, Associate Professor of Faculty of Medicine & Health Sciences, at the University of Nottingham. “This is important as malignant brain tumours are difficult to treat. In addition, this approach offers a new avenue to overcome the therapy resistance caused by the acidic microenvironment, frequently found in malignant brain tumours.”
About Acidity in the Tumor Microenvironment
The acidic tumor microenvironment, inherent to many cancers, causes a profound immunosuppression of infiltrating immune cells. This environment disarms the anti-cancer immune response and negates the effectiveness of current immunotherapies. This is particularly evident in tumor associated macrophages (TAM), where acidity is sensed by the cell-surface receptor GPR65, leading to an induction of the transcriptional repressor ICER (inducible cAMP early repressor) and the widespread suppression of a host of pro-inflammatory mediators and anti-tumorigenic genes.
About Pathios Therapeutics
Launched in 2017, Pathios is a drug discovery and development company focused on translating innovative science into new medicines. Pathios was founded by a team of experienced biotech and pharmaceutical industry professionals, entrepreneurs, and clinicians. The company is focused on developing small molecule inhibitors of the pH-sensing G protein-coupled receptor GPR65 to counteract the GPR65 mediated immunosuppressive polarization of immune cells, including tumor associated macrophages, that is triggered by an acidic tumour microenvironment present in most cancers. To date, Pathios has raised a total of US$33M in Series A funding from the leading venture capital firms, Canaan Partners and Brandon Capital. Pathios is headquartered at the Innovation Centre on Milton Park, a key science precinct south of Oxford, UK.
For more information, please visit www.pathios.com.
About the University of Nottingham
Ranked in the Top 100 globally and 17th in the UK by the QS World University Rankings 2024, the University of Nottingham is a founding member of Russell Group of research-intensive universities. Studying at the University of Nottingham is a life-changing experience, and we pride ourselves on unlocking the potential of our students. We have a pioneering spirit, expressed in the vision of our founder Sir Jesse Boot, which has seen us lead the way in establishing campuses in China and Malaysia – part of a globally connected network of education, research and industrial engagement.
The University is among the best universities in the UK for the strength of our research, positioned seventh for research power in the UK according to REF 2021. The birthplace of discoveries such as MRI and ibuprofen, our innovations transform lives and tackle global problems such as sustainable food supplies, ending modern slavery, developing greener transport, and reducing reliance on fossil fuels.
The University is a major employer and industry partner – locally and globally – and our graduates are the second most targeted by the UK’s top employers, according to The Graduate Market in 2022 report by High Fliers Research. We lead the Universities for Nottingham initiative, in partnership with Nottingham Trent University, a pioneering collaboration between the city’s two world-class institutions to improve levels of prosperity, opportunity, sustainability, health and wellbeing for residents in the city and region we are proud to call home. More news: https://www.nottingham.ac.uk/news/
About Innovate UK
Innovate UK drives productivity and economic growth by supporting businesses to develop and realise the potential of new ideas. We connect businesses to the partners, customers and investors that can help them turn ideas into commercially successful products and services and business growth. We fund business and research collaborations to accelerate innovation and drive business investment into R&D. Our support is available to businesses across all economic sectors, value chains and UK regions. Innovate UK is part of UK Research and Innovation. For more information visit https://www.ukri.org/councils/innovate-uk/
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