SNDX-4321

SNDX-4321 is a novel, mutant-selective, CNS-penetrant, allosteric epidermal growth factor receptor (EGFR) inhibitor being developed by Syndax. It is designed to treat EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC), specifically targeting patient populations with significant unmet needs such as those with L858R mutations, CNS metastases, atypical activating mutations, or acquired resistance to existing therapies (including C797S resistance mutations). Unlike ATP-site directed third- and fourth-generation EGFR inhibitors (e.g., osimertinib), SNDX-4321 binds at an allosteric pocket adjacent to the ATP site that is only accessible in the presence of L858R and certain other EGFR mutations. This allosteric mechanism allows for high selectivity and a 'double drugging' approach when combined with ATP-competitive inhibitors like osimertinib. The molecule was in-licensed from the Dana-Farber Cancer Institute, and Syndax holds an exclusive worldwide license to develop and commercialize it.