Thursday, September 28, 2023
Pathios Therapeutics Limited, a biotechnology company dedicated to advancing innovative cancer therapies, has been awarded a grant of £567,000 (equivalent to approximately US$727,000) from Innovate UK, the United Kingdom's governmental innovation agency. This funding will facilitate the expansion of Pathios' research into novel small molecule GPR65 inhibitors as potential treatments for malignant brain tumors. This project is a collaborative effort with researchers from the University of Nottingham, focusing on optimizing these inhibitors for penetration into the central nervous system (CNS) and evaluating their efficacy in preclinical brain cancer models.
The treatment of malignant brain tumors remains a significant medical challenge, with limited effective treatment options available. While chemotherapy has shown some progress in improving survival rates, there is a pressing need for more impactful treatments. Immunotherapy has demonstrated promise, but overcoming the immunosuppressive tumor microenvironment (TME) remains a critical obstacle.
Pathios is pursuing an innovative immuno-oncology approach by addressing the immunosuppressive effects of the acidic TME on immune cells, including tumor-associated macrophages (TAMs). They are focusing on designing and developing inhibitors for GPR65, a receptor exclusively found on immune cells that senses acidity and is associated with promoting the immunosuppressive phenotype in the TME, hindering the immune system's ability to target cancer cells. Pathios' research, based on human genetic analysis, suggests that reducing GPR65 function can significantly improve survival rates across various solid tumor types, making it a unique target for immuno-oncology interventions
With the grant in hand, Pathios is utilizing a proprietary assay platform to optimize the ability of small molecule GPR65 inhibitors to penetrate the CNS for the treatment of malignant gliomas. These optimized inhibitors are undergoing testing in a human ex vivo co-culture system model of human glioblastoma in collaboration with researchers from the University of Nottingham, followed by assessments of efficacy in mouse models.
Stuart Hughes, Ph.D., CEO of Pathios, highlighted the potential of this novel immuno-oncology approach for brain cancers, particularly in addressing the immunosuppressive effects of the acidic TME. The collaboration with the University of Nottingham aims to advance this promising research and potentially pave the way for future clinical studies.
Alan McIntyre, Associate Professor of the Faculty of Medicine & Health Sciences at the University of Nottingham, expressed enthusiasm for supporting the development of this innovative therapy for malignant brain tumors. He emphasized the importance of addressing therapy resistance caused by the acidic microenvironment frequently observed in such tumors.
The acidic TME, common in many cancers, has a profound immunosuppressive effect on immune cells, undermining the body's anti-cancer immune response and limiting the effectiveness of current immunotherapies. This effect is particularly pronounced in TAMs, where acidity is detected by the GPR65 cell-surface receptor, leading to the induction of the transcriptional repressor ICER (inducible cAMP early repressor) and widespread suppression of pro-inflammatory mediators and anti-tumorigenic genes.
