On July 7, 2021 Pathios Therapeutics Limited ("Pathios"), an innovative biotech company focused on the development of first-in-class therapies for cancer, reported the presentation of preclinical data establishing in vivo proof of concept for its small molecule GPR65 inhibitor programme (Press release, Pathios Therapeutics, JUL 7, 2021, View Source [SID1234584674]). The data will be presented during the Immuno Week meeting which is being held virtually from July 6-9th, 2021, and will form part of a session entitled "Macrophage Drug Development".
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In the research presented, Pathios evaluated the impact of PTT-3196, an orally bioavailable, potent and selective GPR65 inhibitor, on expression of key immune-related genes and tumor growth in a highly glycolytic RCC PDX model implanted in NCG mice that had been reconstituted with human immune cells. The key findings of the study were:
A dose-dependent increase in a host of genes known to be predictive of a successful response to T cell checkpoint inhibitors in the clinic including CD3D, CD3E, IL2RG, CCL5 and CXCl10
Prominent increases in a range of other genes comprising a Type I/II interferon signature including CD40, STAT1, TAP1, TAP2 and components of the inducible immunoproteasome (PSMB8, PSMB9 and PSMB10)
A reduction in tumor volume commensurate with the gene expression changes highlighted above
A suppression of pro-tumorigenic genes including TGFB, IL10 and ADORA2A
"We are extremely excited about these results. PTT-3196 is able to robustly activate the human innate immune system in a highly glycolytic, patient derived tumor microenvironment, reversing many of the pro-tumorigenic macrophage gene expression changes that result from chronic exposure to an acidic environment. The ability to bring about a gene expression signature that is predictive of clinical success with T cell checkpoint inhibitors is especially encouraging and fully validates the concept that GPR65 inhibitors counteract a critical innate immune checkpoint that we believe prevents the majority of solid cancers being able to respond to currently approved immunotherapies." Stuart Hughes, Chief Executive Officer of Pathios Therapeutics
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. To date, Pathios has secured a total of US$13.2M in Series A funding from the leading venture capital firms, Canaan Partners and Brandon Capital. The Company is focused on developing small-molecule inhibitors of the pH-sensing G protein-coupled receptor GPR65 to target immunosuppressive macrophages