A biotech startup called Omega Therapeutics debuts this morning touting a new approach to developing medicines based on epigenetics, a field of research that has tantalized drug makers for years but produced mixed results. Can the fledgling company surpass previous efforts and develop epigenetic drugs for a slew of different diseases?
Cambridge, MA-based Omega was formed by venture firm Flagship Pioneering in 2017, and is led by former Novartis (NYSE: NVS) executive Mahesh Karande. Its work, borne out of research from MIT biology professor Richard Young and Whitehead Institute founding member Rudolf Jaenisch, is aimed at precisely tweaking the expression of certain genes to treat disease, without causing unintended problems in the process.
“The ability to tune a gene to the right level of expression and do it durably,” says CEO Karande, “is really where we are advancing epigenetics.”
Its ambitions are broad: Omega aims to treat a slew of different conditions, from rare genetic diseases, to metabolic and inflammatory disorders, to cancer. But the 35-employee company isn’t close to that goal, and is keeping much of its immediate plans hidden for now.
“If they can achieve what they say, then it really will be transformative,” says Checkmate Pharmaceuticals founder and chief scientific officer Art Krieg, who has previously worked on drugs meant to regulate gene expression and isn’t involved with Omega. “But of course the question is, can they, and not only in a cell line, but in a mouse?”
Billions of dollars have been spent on research to understand epigenetics, the study of changes in gene expression and the complex circuitry that causes genes to make various proteins in our bodies. The idea behind this work is to identify the key molecular switches that can cause a gene to produce, or not produce, a protein—and, ideally, use that knowledge to treat a disease.
A number of companies and drug development alliances have sprouted up over the years with the intent of capitalizing on epigenetics research. The most tangible progress to date has come in blood cancers, with epigenetic drugs like vorinostat (Zolinza), decitabine (Dacogen), panobinostat (Farydak) and azacitidine (Vydaza) already in use. Another, tazemetostat, from Epizyme (NASDAQ: EPZM), is under FDA review for lymphoma. All are chemical-based drugs targeting enzymes that help regulate gene expression.
But that remains a limited purview. It’s been tough to figure out which genes and switches control what, and how to tweak them precisely without causing other problems. “It’s a very complicated area,” says Krieg. “But very powerful too.”
New computing tools and genomic insights are helping drug makers attempt to apply the technique more broadly. Flagship, for instance, teamed with Young to form another Boston-area startup, the now-publicly traded Syros Pharmaceuticals (NASDAQ: SYRS), which is developing what it terms “gene-control” drugs. Fulcrum Therapeutics (NASDAQ: FULC), which went public in July, is combining a range of methods—from stem cell technologies to computational biology, screening tools, and readily available databases of genomic information—to do this type of work. It is developing medicines for the rare disease facioscapulohumeral muscular dystrophy, the chronic blood disorders sickle cell disease and beta-thalassemia, and more.
“This is an emerging field that’s just starting to realize its full potential of treating human disease,” Fulcrum’s CEO Robert Gould, who once ran Epizyme, told Xconomy in 2016.
Still, the majority of this work is based on chemical drugs, which are blunt forces and not very specific, says Karande. Omega isn’t, and it aims to go a step further. It’s focusing on portions of DNA Young and colleagues described in this 2016 paper in the journal Cell as “insulated neighborhoods.” Omega believes these closed-looped DNA sections, which it now calls “insulated genomic domains,” are critical regulators of gene expression. Disease may occur when their shape changes or the genes within these insulated genomic domains misfire, Karande says. The company has mapped the structure and function of thousands of them.
Omega’s goal, then, is to develop medicines that get into a cell, target those DNA sections, and dial their activity either up or down, depending on whether the idea is to make more or less of a specific protein. Karande believes this approach could lead to drugs that might last longer than small molecules can, or perhaps boost the power of other drugs like cancer immunotherapies or cell therapies.
“Our ability to control an insulated genomic domain precisely is what makes us different than all of these other [epigenetics] companies,” he says.
That has yet to be proven. And Karande won’t say yet what Omega’s drugs consist of, how they’ll be delivered, what disease Omega intends to start with, or how far the company is from human testing. (That’s all coming “in the near future,” he says.) But Omega should have the chance to show all that. Like other recent Flagship startups—among them Kaleido Biosciences (NASDAQ: KLDO)—it emerges from stealth with dozens of employees and its work well underway. Omega “is not concerned” about its current financial runway, Karande says.