Omega Therapeutics presents preclinical data on precision epigenomic control

Omega Therapeutics announced the presentation of new preclinical data demonstrating the anti-tumor effect of a MYC-targeting epigenomic controller in models of EGFR inhibitor-resistant non-small cell lung cancer at the American Association for Cancer Research Annual Meeting 2024, taking place in San Diego, California, April 5 – 10. The Company also presented preclinical data validating a novel pharmacodynamic biomarker assay for monitoring on-target engagement and activity of its clinical-stage EC candidate, OTX-2002. Abstract 1726: Targeted epigenomic control of MYC as a strategy to treat EGFR inhibitor-resistant NSCLC: Key Findings: The combination of a MYC-directed EC with osimertinib, a third generation EGFRi blocker, led to enhanced downregulation of MYC protein levels and synergistically inhibited viability of EGFR-T790M mutant NSCLC cells in preclinical models; NSCLC cells resistant to osimertinib through the EGFR C797S mutation or epithelial to mesenchymal transition retained sensitivity to epigenomic downregulation of MYC expression with NSCLC MYC-EC in multiple in vitro models; These results support potential development of a NSCLC MYC-EC in EGFR-mutant NSCLC as a combination therapy with osimertinib, and as a monotherapy in osimertinib-resistant NSCLC. Abstract 2417: Detection and quantification of site-specific DNA methylation from liquid biopsies as a pharmacodynamic biomarker of OTX-2002, a novel MYC-targeting epigenomic controller; Key Findings: Development of a new DNA methylation assay consisting of a minimal hybridization capture panel to evaluate CpG methylation events across a ~50 kilobase target region; Ultra-sensitive detection of methylation events at the MYC locus down to the theoretical limit of 1 in 104 copies of MYC; Demonstration of highly specific on-target engagement and methylation by OTX-2002 in liquid biopsies from mice bearing human hepatocellular carcinoma xenografts.