At Rome Therapeutics, Kapeller Aims to Turn “Junk” Into New Drugs

Xconomy Boston — 

A new biotech, Rome Therapeutics, launched Monday with $50 million and a plan to develop novel drugs based on new insights into repeats in the non-coding stretches of the human genome.

Rome’s debut pulls back the curtain on what Rosana Kapeller, the company’s co-founder and CEO, has been up to since she left Nimbus Therapeutics in March 2018 and, later that year, joined GV (formerly Google Ventures) as an entrepreneur in residence. GV is the investment arm of Google parent company Alphabet (NASDAQ: GOOGL).

“For the longest time we have been hearing about ‘junk’ DNA—60 percent of our genome that’s comprised of repeats derived from retroviruses that integrated into our genome through evolution,” Kapeller said in a phone interview. “It always intrigued me: Why are they there, how have they participated in our evolution, and what kind of role [do] they play in human health and disease?”

Others have had these questions, too, of course, but improvements in scientific and computational tools—such as ever-improving sequencing technologies and advances in machine learning—have allowed a better understanding of these repetitive sequences of nucleic acids, or repeats, she said.

A conversation initiated by Arch Venture Partners brought together Kapeller and company co-founders David Ting, a clinical oncologist, and Ben Greenbaum, a computational biologist and theoretical physicist.

At first, Kapeller told the researchers: “This is all very interesting and fascinating, but I’m not sure you have all the data that’s necessary to convince me and others that there is a path forward here.” She requested they conduct some additional experiments.

“I asked them to go back and validate some of the targets in a more robust way than they had initially,” she said. “What I wanted to understand is, are these [repeats] active? What happens if you knock them down? One of the problems with that is you’re not working just with genes that are encoded by the 2 percent of our genome that encodes for proteins, [where] there are 2 copies of each … Here, with repeats, there are 100 copies, there’s 1,000 copies, so you can image how complex it is to be able to validate that.”

Their results convinced her that their discoveries could lay the foundation for a new company.

Kapeller says Ting and Greenbaum’s research shows that while the ecosystem of repeats is generally dormant, when illness arises, repeats play a role in activating the innate immune system—the body’s first line of defense against foreign intruders. But like so many other processes, that activation doesn’t always work as planned, and the researchers believe it plays a role in driving disease, such as cancer and autoimmune disorders.

The company, which has about 10 full-time employees, isn’t yet talking about the targets it has identified.

“We’re opening up a completely new area of biology … but … there is a roadmap,” she said. “We are being pretty pragmatic on our drug discovery plans, so initially we are being very small molecule focused, so we want to bring drugs to patients as fast as we can.”

But the underlying theme is restoring the ecosystem’s homeostasis by allowing the activation of the innate immune system to proceed as it should, in cases of cancer, and doing the opposite in the presence of autoimmune conditions.

“In cancer, we want to activate it, and in autoimmune diseases, we want to block it,” she said.

Rome’s intellectual property comes from Massachusetts General Hospital and the medical school at Mount Sinai, where Greenbaum previously worked. Ting is the associate clinical director for innovation at the Mass General Cancer Center and an assistant professor at Harvard Medical School; Greenbaum 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.

The fledgling biotech has been incubating for the past year at the GV offices in Cambridge, where Kapeller is based. The $50 million Series A round that closed this week was co-led by GV and Arch, with participation from Partners Innovation Fund. That cash will allow Rome to further advance its R&D. (The company’s name is an abbreviation of “repeatome,” the term for the slow of repeats in the human genome, as well as a reference to the “spirit of exploration and innovation” of ancient Rome.)

Kapeller was previously founding chief scientific officer at another Cambridge biotech, Nimbus Therapeutics, where she led discovery and development of a new class of drugs for nonalcoholic steatohepatitis, or NASH. In 2016 Gilead Sciences (NASDAQ: GILD) snapped up a subsidiary the biotech formed to house those compounds, including an early-stage drug, for $400 million up front and another $800 million in potential milestone payments.

The company she’s now launching is the second to debut after incubating within GV. The first, Verve Therapeutics, emerged a year ago with an ambitious plan to use gene editing to prevent heart attacks by tweaking patients’ DNA to protect heart health.

Verve is pursuing ways to alter genes with a lot of research behind them. Rome is in comparatively uncharted waters, given the newness of the research on which it is basing its programs.

Kapeller—a vocal advocate of efforts to improve gender diversity in biotech—noted that Rome is taking the path less traveled in another way, too, with a leadership team comprised entirely of women, including Donna Romero as head of chemistry and Wenyan Miao as biology and preclinical development chief.

“Although that was not done on purpose, it reflects that right now we have a robust pipeline of senior leaders who are female, and I’m very proud of that,” she said. “That could not be done 10 years ago.”