CEO and co-founder Rosana Kapeller told BioWorld that Rome Therapeutics Inc.’s $50 million series A will fund early work in an “exploding” new area of biology: the repeatome – “the dark genome” or “junk DNA,” as many previously deemed the roughly 60% of the human genome that consists of repetitive sequences of nucleic acids.
“For the longest time, people thought [repeats] didn’t do anything, that they were just pieces of DNA that were dormant,” Kapeller said, but new technology has proved that isn’t so.
Exploiting its know-how in oncology, virology, immunology and machine learning, the Rome team has identified several promising drug targets and launched multiple discovery programs. The financing was led by Google Ventures (GV) and Arch Venture Partners, with participation from Partners Innovation Fund (PIF)
Described as a rich and complex ecosystem, the repeatome contains the remnants of ancient viruses that have integrated into the genome. The virus-like strands of genetic material are activated by stress. “Cancer cells co-opt this mechanism – they don’t want to die,” Kapeller said. “They basically modify the RNA back into DNA, and the DNA gets reintegrated into the genome,” which confers survival benefit. Computational biologist and theoretical physicist Benjamin Greenbaum developed a decoding algorithm and came up with an “extremely focused way to map the repeatome,” she said. His insights and those of clinical oncologist David Ting led to Rome (a contraction of the word repeatome).
Ting, who focuses on understanding RNA expression patterns in cancer, is the associate clinical director for innovation at the Massachusetts General Hospital (MGH) Cancer Center and an assistant professor at Harvard Medical School. Greenbaum, for his part, uses techniques from statistical physics, information theory and evolutionary biology to understand the interaction of tumors with the immune system and to explore virus evolution. He is an associate member of Memorial Sloan Kettering Cancer Center, where he is an associate attending computational oncologist and inaugural program leader in computational immune-oncology. Julius Knowles, a partner at PIF and a member of Rome’s board, worked with the scientific co-founders on planning the company. Its formation was driven by Ari Nowacek, a partner with Arch. The founding intellectual property came from MGH and the Icahn School of Medicine at Mount Sinai, where Greenbaum has worked.
Kapeller incubated Rome, of Cambridge, Mass., during her tenure as an entrepreneur-in-residence at GV, where she is currently a fellow. She was previously chief scientific officer of Cambridge, Mass.-based Nimbus Therapeutics Inc., a subsidiary of which was acquired in 2016 by Gilead Sciences Inc., of Foster City, Calif., for $400 million up front and $800 million in development-related milestone payments. Gilead brought aboard the lead acetyl-coA carboxylase (ACC) inhibitor program at Nimbus, including a phase II-ready and preclinical allosteric ACC inhibitors aimed at treating nonalcoholic steatohepatitis, hepatocellular carcinoma, and other metabolic and liver diseases.
“Originally when I left Nimbus, I thought I was going to work on the intersection of machine learning and drug discovery,” Kapeller said. “I’m still very fascinated by that. I think machine learning is going to have a huge impact on our industry,” as will work on the repeatome, in her view. “We believe this could be a mechanism by which you could induce sustained remission in incurable cancers and life-threatening autoimmune diseases,” she said, like antiretroviral therapies changed HIV, insulin came to the rescue of people with diabetes, and statins as well as calcium channel blockers helped people with their cardiovascular symptoms. “Suddenly, diseases that would kill you became chronic and manageable,” she said. “That’s our mission.”
Kapeller likened the situation in repeatome research to that of cell biology when she began her career 30 years ago. “Basically, you knew there was a receptor on the surface of cells and there was a signal, a black-box signal that was transmitted to the nucleus, but nobody understood how that happened.” Scientists figured it out, and biopharma used that knowledge. “In a way, this [work by Rome] is exactly the opposite, studying a way for the nucleus to send information to the outside,” she said. The approach opens new stretches of the genome for discovery of therapeutics. “I believe we’re going to develop some great drugs out of it. Initially, we’re going to be small molecule-focused, but we’re going to be therapeutic modality-agnostic in the future,” she said. Cancer and autoimmune diseases will be targeted first, with efforts to activate and suppress immune activity, respectively. “It’s the same mechanism going in different directions,” she said. “The proof is when we get into humans and start testing the hypothesis.” There will be a push in neurodegenerative illness, too. The new money will “hopefully take us a long way but we’re not disclosing the timelines right now,” she added.
Rome, with 10 employees, is “weathering [the COVID-19 crisis] fairly well, because we are working with contract research organizations around the world,” Kapeller said. “If one group has to shut down, there’s another group that can take over. I wouldn’t say that it is business as usual,” but the firm is maintaining 70% to 80% of its productivity, she said.