Omega Therapeutics Publishes OTX-2002 Preclinical Data in Nature Communications

Omega Therapeutics, Inc., a biotechnology firm specializing in programmable epigenomic mRNA medicines, has published preclinical data in Nature Communications on the efficacy of OTX-2002 in treating hepatocellular carcinoma (HCC), the most prevalent form of primary liver cancer. The data illustrate the potential of Omega's precision epigenomic control approach to regulate the MYC gene, a target previously considered undruggable.

Mahesh Karande, President and CEO of Omega Therapeutics, explained that their OMEGA platform leverages advanced understanding of DNA architecture and epigenomic regulation. This enables the design of an epigenomic controller that can intentionally target nearly any gene and modulate its expression. OTX-2002, specifically, has shown precise engagement with the c-MYC oncogene, leading to its downregulation at both mRNA and protein levels, which in turn has demonstrated significant anti-tumor effects in various preclinical HCC models.

The unique functionality of OTX-2002 stems from its design as a bicistronic mRNA-encoded epigenomic controller that is delivered via liver-targeting lipid nanoparticles. This allows it to downregulate MYC expression pre-transcriptionally by inducing two distinct epigenetic modifications at different loci within the MYC gene. Given MYC's role in regulating cell proliferation, differentiation, and apoptosis and its involvement in over half of all human cancers, the implications of this approach are significant.

Key findings from the publication, titled “Targeted Transcriptional Downregulation of MYC Using Epigenomic Controllers Demonstrates Antitumor Activity in Hepatocellular Carcinoma Models,” include:

- Rapid reduction in MYC mRNA and protein levels,
- Decreased viability of multiple HCC cell lines,
- Dose-dependent reduction in tumor size and growth rate in preclinical HCC models,
- Synergistic antitumor activity when combined with tyrosine kinase inhibitors or immune checkpoint inhibitors,
- Positive impact on the tumor microenvironment, shown by a decrease in inhibitory regulatory T cells in immune-competent mice bearing HCC tumors.

OTX-2002 is currently being evaluated in the Phase 1/2 MYCHELANGELO™ I trial, which includes adult patients with HCC and other MYC-associated solid tumors.

The OMEGA platform is central to Omega Therapeutics' capabilities, combining data science, rational drug design, and customized delivery to control epigenetic processes and reprogram cellular physiology. This platform allows for the precise targeting of specific genomic loci within insulated genomic domains to durably modulate the expression of single or multiple genes, making it possible to address the root cause of numerous diseases.

Omega Therapeutics, founded in 2017 by Flagship Pioneering, aims to revolutionize genomic medicine. The company has developed a robust pipeline of therapeutic candidates derived from its OMEGA platform, targeting a wide range of diseases, including those in oncology, regenerative medicine, and multigenic diseases such as inflammatory and cardiometabolic conditions. The leadership team at Omega, known for innovation and operational excellence, is committed to advancing this new class of programmable epigenomic mRNA medicines to potentially cure or treat a wide array of diseases.

In summary, Omega Therapeutics' recent publication highlights the promising potential of OTX-2002 and the OMEGA platform in treating HCC by targeting and downregulating the MYC gene. This development underscores the broader implications of epigenomic mRNA medicines in addressing diseases that have been challenging to treat with traditional approaches.