Posted: 1 May 2024
Pathios Therapeutics Limited (“Pathios”), a biotech company focused on the development of first-in-class therapies for cancer, today announced that the company has raised $25 million in the first close of a Series B financing. The financing consists of a new strategic investment from Bristol Myers Squibb, as well as support from existing investors including Canaan and Brandon Capital. Proceeds from the raise will be used to support the continued development of Pathios’ unique approach to cancer immunotherapy focused on the inhibition of GPR65, a novel target that has been genetically associated with a range of immunologically-mediated diseases. As part of these efforts, the company expects to advance PTT-4256, its lead internally discovered, oral, highly potent, and selective small molecule inhibitor of GPR65, into human clinical trials in advanced solid cancers by the end of 2024. Additionally, Pathios will leverage the proceeds from the financing to expand its team, including executive leadership, to align with its continued evolution into a clinical-stage company.
“The support of a syndicate comprised of premier life science investors Canaan and Brandon Capital and a global leader in oncology in Bristol Myers Squibb adds both capital and expertise as we look to generate clinical evidence to support our conviction that GPR65 inhibition will open the door to an entirely new approach to immunotherapy,” said Tom McCarthy Ph.D., co-founder and executive chair of Pathios. “It is particularly gratifying to know that our investors share our belief not only in the foundational science we are pursuing but also the significant range of potential therapeutic applications for the platform, both broadly across the field of cancer and into other immunologically mediated diseases. We are eager to leverage the proceeds from this raise to continue our work and successfully advance PTT-4256 into the clinic later this year.”
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 tumor microenvironment (TME). It does so by attacking a ubiquitous cancer immune evasion pathway through the targeting of GPR65, an acid sensing G protein-coupled receptor that has been shown to foster immunosuppressive polarization of immune cells. GPR65 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. Furthermore, there are strong genetic associations between GPR65 activity and a variety of other immunologically-mediated diseases, offering the opportunity to expand its research and development into other high-value therapeutic areas with significant unmet need.
“Our belief in the anti-tumor potential of our GPR65 inhibition platform is built upon two key pillars: the extensive validation of the target through human genetic analysis and the ubiquitous and fundamentally causal role that GPR65 plays in human cancer biology by creating a TME that is immunologically-favourable to tumor growth,” said Stuart Hughes, Ph.D., chief executive officer of Pathios. “This funding will now enable us to evaluate our scientific hypothesis in the clinic, providing the opportunity to illuminate the activity of this novel target in humans for the first time. While our initial clinical study will have all the hallmarks of a first-in-human trial, it will also feature a biomarker-rich design that allows for the measurement of clinical target engagement.”
Preclinical data on PTT-4256 presented at the American Association for Cancer Research (AACR) Annual Meeting 2023 demonstrated that the compound possesses excellent drug-like properties and impressive monotherapy anti-tumor activity. Importantly, PTT-4256 was shown to be highly effective in counteracting the effects of low pH (i.e. high acidity) that polarize human and mouse macrophages toward an immunosuppressive state. This PTT-4256-induced relief of immune suppression was associated with dose-dependent increases in a range of pro-inflammatory genes that are consistent with an anti-tumor immune response, evidence of an infiltration of T cells and natural killer (NK) cells into the TME, and prevention of the activation of immunosuppressive cytokines. Together, this activity led to impressive monotherapy efficacy for PTT-4256 in syngeneic mouse cancer models following oral dosing.
