Omega halts sole clinical-stage program to prioritize Novo Nordisk collab and liver, obesity work

Omega Therapeutics is halting work on its only clinical-stage candidate as part of a strategic refocus centered on three preclinical epigenomic controller programs including a collaboration with Novo Nordisk.

The Flagship Pioneering-founded biotech has completed a phase 1 study of OTX-2002—an epigenetic controller programmed to control expression of an elusive cancer-driving gene called c-MYC—in patients with relapsed or refractory hepatocellular carcinoma (HCC) and other solid tumor types known for association with the MYC oncogene.

The preliminary efficacy safety data suggested an observed disease control rate for response-evaluable HCC patients of 50%, which Omega noted was “in-line with the historical benchmark range for completed phase 1 trials for approved TKIs and PD-1 monotherapies in HCC.”

Epigenomic controllers are programmable mRNA medicines designed to make specific epigenetic changes. In a third-quarter earnings release Nov. 14, Omega’s recently appointed chief scientific officer Jennifer Nelson, Ph.D., said the phase 1 study had “clearly demonstrated our ability to prospectively design an epigenomic controller capable of inducing prespecified changes in epigenetic signatures that alter gene expression with high specificity.”

“Expanding on these results, we have an incredible opportunity to establish epigenomic controllers as a new class of medicines with unparalleled versatility,” Nelson added.

However, this opportunity doesn’t appear to involve OTX-2002 itself. In the same release, Omega revealed the biotech will not be taking that program forward for now.

“The company is engaged in discussions with potential partners to further advance clinical development into phase 2 or may choose to resume development through internal efforts with additional funding,” Omega said.

The company is taking a similar approach to two preclinical programs it is pausing, including OTX-2101, a c-MYC-targeting epigenomic controller being developed for the treatment of non-small cell lung cancer. Also pushed aside is a potential treatment of human lung fibroblasts with CXCL1-8-targeting epigenomic controllers.

Instead, the company is prioritizing three preclinical programs, including a collaboration with Novo to target them at obesity. Another program will continue to explore how epigenomic controllers can up-regulate expression of the HNF4A gene with the aim of treating liver diseases such as metabolic dysfunction-associated steatohepatitis. Finally, the company will be working on whether it can up-regulate FGF21, a hormone believed to be involved in hyperlipidemia and obesity.

“Our prioritized pipeline leverages the differentiated capabilities of our platform and reflects the diverse potential applications of Omega’s technology,” Nelson said in the same release. “We are excited by the opportunity to demonstrate the power of precision epigenomic control in these select high-value programs and build on the clinical progress we have made.”

Flagship launched Omega in 2019 with the aim of taking genomic medicine “to the next level.” Founded on the work of two MIT professors, the company is working on treatments that adjust gene expression up or down without making permanent changes to the genome.