BDB025

BDB025 is a first-in-class dual-mode small molecule agent designed to convert immunologically cold mismatch repair-proficient (pMMR) tumors into a hot mismatch repair-deficient (dMMR)-like state. Developed by Syntabio and Birdiebio, BDB025 acts by directly and indirectly disrupting the DNA mismatch repair (MMR) machinery, specifically targeting MSH2 and MSH6. It also induces epigenetic silencing of critical MMR genes. This coordinated mechanism induces a high microsatellite instability (MSI-H) phenotype and increases tumor mutational burden (TMB) at sub-cytotoxic dosages. By promoting T cell influx and overcoming resistance to immune checkpoint blockade, BDB025 has demonstrated the ability to sensitize pMMR colorectal cancer models to anti-PD-1 therapy.