Nimbus founder Rosana Kapeller has a new company, with $50M and an eye on the ‘repeatome’
Rosana Kapeller left Nimbus two years ago determined, after 2 decades and 3 companies, that her next spot would be as CEO. Today, after a 7-month sabbatical and a stint at a top VC firm, the jocular computational biology pioneer is back. And with full control.
“I really wanted to… make a unique organization, a unique culture,” Kapeller told Endpoints News. “I wanted that challenge.”
And a challenge it will be, both scientifically and because, well, there’s a pandemic keeping much of her 10-person team working from her home. “This is a hard time to start a company,” she acknowledged.
Still, Kapeller is confident, placing her faith both in the ambitious science of her new company and in her own experience as a businesswoman, dating back to her upbringing in a business-focused family in Brazil. The new company is ROME Therapeutics and it’s launching out of stealth mode with $50 million in Series A funding from GV — where Kapeller served as entrepreneur-in-residence for the last year — ARCH Ventures, and Partners Innovation Fund. The biotech is one of a series that have arisen in the past few years to target parts of what was once deemed “junk DNA”: the 97-99% of genetic code that doesn’t code for proteins. Although scientists have known for decades now that at least parts of this vast nucleic flotsam serve key functions, untangling those functions has been a major hurdle. Drugging them has been an even larger one.
ROME will target one segment of this erstwhile junk called the “repeatome.” The name has yet to catch on — a PubMed search produced 22 results and the Wikipedia page is a single paragraph attributed to one PLOS paper out of France — but the field has slowly gained steam since a 2011 Science paper, on which ROME co-founder David Ting was lead author.
The repeatome refers to some 50% of human DNA that is made up of sequences that repeat over and over again — like a musical or literary motif — and that don’t make any proteins. Some of these, as scientists have long known, are retroviruses that infected us and embedded their codes in our DNA over millions of years of evolutions. Other sequences, though, are “virus-like,” said Ting. Most of the time these sequences are blocked from doing anything, trapped by methyl agents or histones that wrap like chains around DNA. But in some instances — such as some cancers — distressed cells take the chains off and translate the sequences into RNA. Those RNA sequences don’t make any proteins. But they look like RNA viruses and activate the innate immune system as a virus would, calling it to attack a tumor.
“These repeats are like the first responders, telling the body these cells are becoming uncontrollable — control it,” Kapeller said.
Two problems can emerge. First, cancer cells can develop ways of reverse transcribing these RNA sequences back into their genome, both silencing the immune signals and adding to the cancer’s genetic variability. In some autoimmune conditions, the opposite problem is at play, Kapeller said. Healthy cells send off these RNA repeats, triggering a damaging immune response.
Kapeller talks about ROME’s role as restoring “yin and yang”: Keeping the immune signals going in cancer and turning them off in autoimmune diseases. ROME has not yet revealed how they plan on doing that, but when Ting first hypothesized that cancers were transcribing these signals, he started a clinical trial with a common HIV drug on 4th line colon cancer patients. The HIV drug, which is meant to stop the HIV virus from reverse transcribing itself, appeared to inhibit the cancer’s ability to reverse transcribe the RNA signals. The patients on the study maintained their condition, a rarity for that form and stage of cancer.
“Somehow cancer has repurposed this process to replicate and grow into tumor,” Ting told Endpoints, describing his discovery. “It was kind of an accident, an accident of something we were told was junk and finding the junk was actually doing something.”
That something evaded scientists in part because early DNA sequencers lacked the ability to pick up and analyze these vast codexes of DNA and study which repeats were being transcribed into RNA. To do so, ROME will rely on two new but established techniques, sequencing of long stretches of DNA and sequencing of the RNA being transcribed inside a cell, alongside a machine learning approach set up by theoretical physicist Benjamin Greenbaum. In part, that’s what made it a fitting project for Kapeller, who did computational work at Millennium and Ailleron and then was enlisted by Atlas Ventures to launch Nimbus, one of the first major computational biotechs.
Although it will be Kapeller’s first stint as a CEO, it will hardly be her first time in leadership. Nimbus lacked a CEO for its first 4.5 years, she notes, leaving control of the biotech between herself and the board. She says that she’s learned a few things from her experience with past companies: That control and command doesn’t work, transparency is necessary, and diversity and putting women in management matters. She brings an MD-PhD’s understanding of patients, she said, and she took something besides business acumen back from her hometown of Rio de Janeiro: a certain warmth.
“I’m from Brazil and Brazilians love to use humor a lot,” Kapellar said.
For instance, she led off the company’s first meeting with their PR firm with a slide of herself and her co-founders in Roman gladiator costumes. She’s reluctant to mention those jokes in interviews, though, weary after enough years as an executive of how it might be translated.
With the science, she’s bolder. They’re one of the first jumping into a still-emerging field, she said, and their goal is sustained remission: cancer and autoimmune treatments that won’t stop working after a few months, or years.
This is “completely uncharted territory,” Kapeller said.