PTT-3213 / Pathios Therap - LARVOL DELTA

Association of G-coupled protein receptor 65 (GPR65), a novel therapeutic target, with immune cell subsets in metastatic renal cell carcinoma (mRCC) (ESMO-IO 2025) - P1/2 | "Non-negative Matrix Factorization clustering in IMmotion151 revealed enrichment of T-effector/proliferative programs in GPR65high (p<0.00001); this same cluster previously has shown improved ORR and PFS with atezolizumab + bevacizumab versus sunitinib in IMmotion151. In RCC explants, PTT-3213 reduced anti-inflammatory cytokines (e.g., IL-10) and increased chemoattractant cytokines (e.g., CCL3), indicating pro-inflammatory, anti-tumor TME with GPR65 inhibition.Conclusions GPR65 expression marks a highly immune infiltrated yet functionally restrained TME, correlating with PD-L1 expression and T-effector signatures. These findings position GPR65 as a putative therapeutic target and support combination strategies in mRCC, aligning with an ongoing phase 1 trial of a GPR65 inhibitor in solid tumors (NCT06634849).Legal entity responsible for the study The authors."

Immune cell • IO biomarker • Metastases • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CCL3 • CD4 • CD8 • IL10 • PD-L1

Inhibition of acid sensing by GPR65 normalises gene expression in macrophages, increases immune cell infiltration in tumors, and restrains subcutaneous MC38 growth in mice (SITC 2022) - "Oral administration of our exemplar compound PTT-3213 in subcutaneous MC38 tumor-bearing mice caused gene expression changes consistent with those observed in primary macrophages in vitro , indicative of a dramatic impact on the TME...Ethics Approval Protocols or procedures involving the care and use of animals in studies in China were reviewed and approved by the Institutional Animal Care and Use Committee of Crown Bioscience. During studies, the care and use of animals was conducted in accordance with the regulation of the Association for Assessment and Accreditation of Laboratory Animal Care Studies involving the welfare and use of animals within the UK complied with the UK Animals Scientific Procedures Act 1986 (ASPA) in line with Directive 2010/63/EU of the European Parliament and Council of 22/September/2010 on the protection of animals used for scientific purposes and UK Home Office guidance on the implementation of the Act and applicable codes of practice for the..."

IO biomarker • Preclinical • Oncology • Solid Tumor • CD4 • CD8