Abstract 7926: Efficacy, <i>in vivo</i> safety, and PK/PD studies for novel, oral, highly selective PTPN2/1 inhibitor (ZE00-0388)

Abstract PTPN2 inhibition is a novel immuno-oncology approach: by releasing an intracellular “brake” it increases cytokine responsiveness (e.g., IFN-γ/JAK-STAT), boosts antigen presentation, and enhances T-cell cytotoxicity, helping to overcome immune evasion in tumors resistant to PD-1 blockade.Our development candidate ZE00-0388 demonstrates potential best-in-class profile: Nanomolar potency with high selectivity for PTPN2/1 over other phosphatases, predictable PK/PD with sustained exposure above EC50, and proven target engagement. ZE00-0388 shows favorable bioavailability in all species, with best translation expected from dog to human.The combination of anti-mPD-1 and ZE00-0388 exhibited remarkable dose-dependent anti-tumor efficacy against the subcutaneous MC38 colon model. Solo treatments with ZE00-0388 demonstrated tumor growth inhibition of 81% and in combination with anti-mPD-1 complete regression of tumor in 50% of animals. ZE00-0388 has a very favorable safety profile with tolerated doses significantly above pre-clinical proof-of-concept efficacious doses, which indicates that ZE00-0388 should have a very broad therapeutic window. Citation Format: Alexei Pushechnikov, Ruben Karapetian, Stepan Mochalov, Sanja Baumann Tomovska, Nikolay Savchuk, Iain Dukes, Ruben Abagyan. Efficacy, in vivo safety, and PK/PD studies for novel, oral, highly selective PTPN2/1 inhibitor (ZE00-0388) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7926.