HZ-V055

HZ-V055 is an orally bioavailable, selective pan-Ras molecular glue inhibitor developed by Healzen. It is designed to target the active (ON) state of mutant Ras proteins, including Kras G12C, G12D, and G12V, by facilitating the formation of a ternary complex with cyclophilin A (CypA). This complex sterically blocks the interaction between mutant Ras and its downstream effectors, such as BRAF, thereby inhibiting oncogenic signaling pathways that drive tumor growth and metastasis. Preclinical studies have demonstrated that HZ-V055 possesses significantly higher selectivity for mutant Ras over wild-type Ras compared to first-generation inhibitors like RMC-6236, potentially leading to a wider therapeutic window and reduced toxicities in skin and gastrointestinal tissues. HZ-V055 has shown robust anti-tumor activity in multiple models of pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) and is currently in the IND-enabling stage of development.