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UTR-HER2-NSCLC-T790M is an investigational RNA-based therapeutic developed by UTR Therapeutics for the treatment of HER2-positive, EGFR T790M-mutant non-small cell lung cancer (NSCLC). The therapy is specifically designed to address resistance to tyrosine kinase inhibitors like osimertinib and monoclonal antibodies like trastuzumab. Its mechanism of action involves the use of engineered destabilized 3'UTR AU-rich elements (ARE) of the ERBB2 gene. By replacing the stable endogenous 3'UTR with unstable poly-U-rich elements, the therapeutic induces the degradation of HER2/ERBB2 mRNA transcripts and subsequent protein depletion through nonsense-mediated decay pathways. Preclinical data using iron oxide nanocage delivery has demonstrated efficacy in reducing tumor growth and inhibiting metastasis in resistant NSCLC models. It is currently in the IND-enabling phase of development.
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