EZN-3920

EZN-3920 (also known as SPC-3920) is a third-generation locked nucleic acid (LNA)-based antisense oligonucleotide designed to target human and mouse HER3 (ErbB3) mRNA. Developed by Santaris Pharma and Enzon Pharmaceuticals, EZN-3920 complementarily binds to HER3 mRNA, triggering its degradation via RNase H activation. This downregulates HER3 expression and inhibits downstream PI3K/Akt signaling, which is a key driver of tumor growth, survival, and resistance to EGFR- and HER2-targeted therapies. In preclinical models of breast and non-small cell lung cancer (NSCLC), systemic administration of EZN-3920 demonstrated significant antitumor activity and synergized with tyrosine kinase inhibitors like gefitinib and lapatinib to overcome resistance and induce tumor regression. Development of the compound was discontinued in the preclinical stage.