Omega Therapeutics Showcases Bidirectional and Multiplexed Epigenomic Control of Gene Expression in Preclinical Models of Liver Inflammation and Fibrosis

First-ever demonstration of sustained pre-transcriptional upregulation of gene expression by an epigenomic controller in both in vitro and in vivo models of liver fibrosis

Single epigenomic controller demonstrated ability to simultaneously regulate the expression of chemokines CXCL9-11 across in vitro models of liver inflammation

CAMBRIDGE, Mass., Nov. 13, 2023 (GLOBE NEWSWIRE) -- Omega Therapeutics, Inc. (Nasdaq: OMGA) (“Omega”), a clinical-stage biotechnology company pioneering the development of a new class of programmable epigenomic mRNA medicines, today announced the presentation of new preclinical data from two different programs that demonstrated sustained upregulation of gene expression and coordinated pre-transcriptional downregulation of multiple genes in models of liver fibrosis and inflammation, respectively, at the American Association for the Study of Liver Diseases’ (AASLD) The Liver Meeting 2023, taking place in Boston, Massachusetts, November 10 – 14.

“Genetic medicines have made tremendous progress towards precise downregulation of gene expression. However, to extend their reach, we need to bidirectionally control the expression of multiple genes simultaneously,” said Thomas McCauley, Ph.D., Chief Scientific Officer of Omega Therapeutics. “We believe that these new data demonstrate the power of our programmable epigenomic mRNA development candidates to control gene expression with unmatched flexibility. To our knowledge, these are the first results to show how site-specific epigenomic modulation can durably upregulate the expression of a master liver regeneration gene. Additionally, a second poster highlights our ability to multiplex gene regulation with a single construct to control a cluster of inflammatory chemokines. These exciting results highlight the progress we have made and possible applications of our approach in multiple liver diseases.”

Poster 3444-A: Induction of Hepatocyte Nuclear Factor 4 alpha (HNF4α) using novel epigenomic controllers

Key Findings

• Human cell lines treated with an epigenomic controller (EC) engineered to modulate the epigenetic profile of the P1 promoter of the HFN4α gene, a master regulator of liver development and function, showed strong increases of mRNA and protein levels.
• Upregulation of HFN4α expression following a single EC treatment persisted for ≥10 days and induced strong and durable increases in HNF4α mRNA levels in primary human hepatocytes.
• EC-mediated upregulation of HNF4α expression correlated with significantly reduced expression of clinically relevant fibrotic genes in vitro.
• Single administration of an EC in the humanized FRG mouse model resulted in induction of HNF4α mRNA levels compared to untreated FRG mice.
• EC-mediated induction of HNF4α expression in vivo in a mouse model of liver fibrosis led to decreased collagen deposition, a key marker of fibrosis.
  • Regulation of HNF4α also led to changes in expression of other fibrosis-associated genes.

Poster 2621-A: Targeting CXCL9/CXCL10/CXCL11 using novel epigenomic controllers for the treatment of inflammatory liver disease