Pathios Receives Innovate UK Smart Grant

Pathios Therapeutics has been awarded £350K (approximately US$475K) in the form a Smart Grant from Innovate UK, the UK Government’s innovation agency, to accelerate their cancer immunotherapy program targeting the innate immune checkpoint, GPR65. Pathios will collaborate on this project with researchers from the Department of Oncology at The University of Oxford to develop the tools required to enable the rapid translation of small-molecule GPR65 inhibitors for treatment-resistant melanoma.

The advent of immunotherapy agents targeting T-cell checkpoints (PD-1/CTLA-4) has brought about significant improvements in the long-term survival of many melanoma patients. However, only a subset of patients receive sustained benefit from these treatments and it remains an ongoing challenge to identify additional therapies for the remaining non-responsive population.

Recent science suggests a reason that some melanoma patients that do not respond well to anti-PD-1 therapies relates to the disarming of innate immune cells called tumor-associated macrophages (TAMs) by the acidic microenvironment that is inherent to advanced tumors. Activation of the pH-sensing receptor, GPR65, on TAMs by acidic pH leads to the suppression of a host of pro-inflammatory genes thereby shifting the characteristics of these cells from immune-stimulating to immunosuppressive. The importance of the GPR65 pathway in cancer is underscored by a small proportion of the population with inactivating polymorphisms showing stratified association with survival when analyzed in The Cancer Genome Atlas (TCGA). Pathios’ ‘Macrophage Conditioning’ approach aims to deploy small-molecule GPR65 inhibitors to reverse pH-dependent immunosuppressive signaling in the vast majority of patients who do not carry this genetic change.

With this grant, Pathios will develop a range of tools to expedite the translation of small molecule GPR65 inhibitors for use in cancer immunotherapy. This will include the development of early clinical target engagement biomarkers as well as employing a range of bioinformatics techniques to identify those patients most likely to benefit from Pathios’ GPR65-targeted approach.

"We are delighted to have secured this highly competitive funding from Innovate UK to accelerate our program against GPR65 and to continue to build our scientific links with cancer researchers at The University of Oxford. This award boosts our ongoing program and is a significant endorsement of our novel approach to targeting the innate immune system in hard-to-treat cancers. We look forward to developing the tools that will drive forward our GPR65-based ‘Macrophage Conditioning’ technology and help deliver on the company’s goal to provide a first-in-class treatment approach for those melanoma patients who currently have limited treatment options,” Stuart Hughes, Chief Executive Officer of Pathios said.