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When in ROME...
July/August 2020
by Kelsey Kaustinen  |  Email the author
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CAMBRIDGE, Mass.—Only about 2 percent of the human genome actually encodes for proteins, and that small percentage is the focus of most drug discovery efforts, while the non-coding portions of the genome have often been referred to as “junk DNA” with the assumption that it has little—or at least much less—impact than the coding regions. But research in the last decade has shown that this region is functional, if still largely unknown, and companies are beginning to explore it.
 
Once such company is biotech ROME Therapeutics, which launched in the second quarter of this year with $50 million from a Series A funding round. GV (formerly Google Ventures), ARCH Venture Partners and Partners Innovation Fund all participated in the financing. The company is headed by Dr. Rosana Kapeller, who is president, CEO and co-founder. Kapeller previously served as founding chief scientific officer at Nimbus Therapeutics, and is currently a fellow at GV.
 
ROME’s aim is to interrogate the repeatome, which comprises approximately 60 percent of the human genome and consists of repeats, or repetitive sequences of nucleic acids. The company is specifically looking to discover and develop novel therapies for cancer and autoimmune diseases.
 
“At ROME, we have set out a bold goal: to drive even the most difficult-to-treat cancers and autoimmune diseases into sustained remission,” Kapeller said. “Too many patients do not benefit from today’s therapies, or experience only a partial response that quickly fades. We believe the repeatome holds the key to longer-lasting interventions. Our scientific founders together with our team have made excellent progress in exploring this uncharted territory and identifying promising therapeutic paths. With the support of our outstanding investors and advisors, we’re moving quickly to advance our therapeutic programs.”
 
The repeatome has been found to contain remnants of ancient viruses that have merged into the human genome over hundreds of generations. As explained on ROME’s website, “The repeats themselves consist of many different families, including small simple sequence repeats, large arrays of tandem repeats in the center and ends of chromosomes (satellite and telomere DNA), and complex mobile repeats that can transpose to different locations in the genome (SINEs, LINEs and HERVs). On the surface, this landscape appears unimportant, but it contains a complex ecosystem of repeat families that can alter the very structure of our chromosomes. They can expand, contract and rearrange our genes to change the behavior of individual cells.”
 
The repeatome is active in early embryonic development, but deactivates afterwards. However, the company website notes, the repeats are reactivated during disease onset and get transcribed into RNA: “This activation sets off alarm bells in the body. The repeats are perceived as foreign invaders and can switch on the innate immune system, signaling the body to remove damaged cells and thereby quiet the repeats. In this way, repeats serve as guardians; they sound an alarm at the emergence of disease and draw the body’s natural immune defense mechanisms into the fray.”
 
“By targeting this uncharted territory, ROME has the potential to open up huge new stretches of the genome for drug discovery,” remarked Kristina Burow, managing director of ARCH Venture Partners and a member of ROME’s board of directors. “We are thrilled to be working alongside the ROME team as they seek to develop novel therapies for intractable cancers and autoimmune diseases.”
 
While no specifics are available on the company’s website and ROME did not respond to a request for additional comments, the company did note in a press release that it has already identified several drug targets and has “multiple discovery programs underway.”
 
“Rosana has brought together some of the best minds in oncology, immunology, virology and machine learning to create a novel approach to harnessing the power of the repeatome,” Dr. Krishna Yeshwant, general partner at GV and a member of ROME’s board of directors, commented in a statement. “We believe that ROME has the insights and expertise to turn cutting-edge discoveries in this field into an important new class of medicines, and we’re proud to continue working with Rosana and her team as they drive their programs forward.”
 
Code: E072001

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