Flagship unveils 'genome-tuning' biotech Omega Therapeutics

DNA genomics precision medicine
Because its approach could work for so many disease areas, Omega Therapeutics plans to ink some partnerships as well as work on its own pipeline. (Pixabay)

Flagship Pioneering launched Omega Therapeutics, a company aiming to take 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. 

Richard Young, Ph.D., and Rudolf Jaenisch, M.D., first described how 3D closed loops of DNA control genomic activity in 2015. Long strands of DNA make these loops because they have to fit into the cell’s nucleus—the loops help “organize and package two meters of DNA” to fit into a space that is about 5 micrometers, or five millionths of a meter, across, the researchers said in a statement at the time. Each loop is an “insulated neighborhood” of one or more genes and their regulatory elements. 

Omega is targeting these neighborhoods, called Insulated Genomic Domains (IGDs), with a platform that could be applied to a variety of ailments. 

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“If you think about it, other than some viral and other infections, pretty much all human disease is due to the dysregulation of genomic expression,” Omega CEO Mahesh Karande, a Novartis alum and former CEO of Macrolide, told FierceBiotech. “Disease mostly occurs because of dysregulation of the genome, by genes not being expressed at the right level. They’re over- or under-expressed. We are able to tune that expression to the native level it’s supposed to be at.” 

The Cambridge, Massachusetts-based biotech is mapping IGDs to different diseases and figuring out which of these neighborhoods plays a role in different diseases. From there, it will create treatments it calls Omega Controllers that adjust gene expression to healthy levels. 

This adjustment happens without making permanent changes to the genome by switching genes on or off, cutting disease-causing genes out or putting in a healthy version of a faulty gene. 

“In nature, generally things are not all the way on or all the way off, but rather turned to a very specific range in a healthy setting,” said Omega Chief Scientific Officer Thomas McCauley, Ph.D., the former CSO of Macrolide and Translate Bio. "Our Omega Controllers are able to target IGDs using the map that Mahesh mentioned and target the right place on that IGD to restore gene function at the right level.” 

RELATED: Flagship launches Foghorn Therapeutics with $50M commitment 

Because the approach could work for so many disease areas, Omega plans to ink some partnerships as well as work on its own pipeline, said David Berry, M.D., Ph.D., a general partner at Flagship, in a statement. Omega’s treatments could be used to boost the efficacy of in vivo and ex vivo therapies, he said. 

In the in vivo space, checkpoint inhibitors are a potential candidate. 

“Many of them are not as effective as you’d like them to be. Sometimes immuno-oncology agents act only on 30% of the patient population,” Karande said. 

Omega could identify specific genes in patients that affect how they respond to these treatments. For example, if a gene is expressed in patients who don’t respond to a certain immuno-oncology drug, Omega might knock down the expression of that gene to make that drug more effective. On the ex vivo side, Karande envisions Omega’s technology being used when cell therapies are being engineered outside the body.

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