Using human genetics to transform cancer immunotherapy

Pathios targets the acid-sensing GPCR, GPR65, as a genetically-validated innate immune checkpoint with the potential to revolutionise oncology treatment across multiple solid tumour types.

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We target the underlying causal biology of immunosuppressive macrophages to restore a natural and coordinated immune response to cancer thus providing a groundbreaking, first-in-class immuno-oncology approach that goes beyond the state-of-the-art.


Pioneering the only approach to addressing the immunologically hostile tumour microenvironment (TME) and the underlying causal biology of myeloid immunosuppression that is built on human genetics.

The acidic tumour microenvironment inherent to all solid cancers causes a profound immunosuppression of infiltrating immune cells. This disarms the anti-cancer immune response and negates and renders current immunotherapies ineffective. This is particularly evident in tumour associated macrophages (TAMs), where acidity is sensed by the cell-surface receptor, GPR65, leading to a host of transcriptional changes in these cells that can explain many of the defining features of the immunologically hostile tumour microenvironment (TME). These include an upregulation of angiogenic and wound healing factors, a reduction of key chemokines and cytokines and a suppression of interferon and antigen presentation genes.

Pathios is developing drugs to block GPR65 signalling, thereby conditioning macrophages toward a pro-inflammatory, immune-stimulating phenotype that can reignite an effective anti-tumour immune response and harness the power of the innate immune system against cancer. Unlike most other novel approaches in immuno-oncology, targeting GPR65 has the potential to deliver profound monotherapy activity in a host of currently hard-to-treat myeloid-dominated tumours.


Pathios' AACR Poster 2023

PTT-4256 is a first-in-class GPR65 inhibitor that reverses the immuno-suppressive effects of acidic pH in macrophages, activates anti-tumorigenic pathways in the tumour microenvironment and displays single agent anti-tumour efficacy in mice.

Learn more about Pathios and our pursuit of groundbreaking therapies.

Pathios is based in Oxford, UK and brings together a team of experienced scientific leaders to deliver new therapies in cancer. Read about recent developments here.