Eying “Extra” DNA As Cancer Driver, Boundless Bio Debuts With $46M

Xconomy San Diego — 

In the nucleus of human cells sit our chromosomes, comprised mainly of tightly wound DNA. In some cells, however, some pieces of genetic material that exist within the nucleus are not attached to a chromosome—and a new company, Boundless Bio, believes these “extra” pieces of DNA play a key role in driving some especially aggressive solid-tumor cancers.

The San Diego-based biotech came out of stealth mode Thursday with an announcement that it had raised a $46.4 million Series A financing round to fund the development of cancer drugs targeting tumors that have what’s known as extrachromosomal DNA.

Zach Hornby, former chief operating officer of cancer drug maker Ignyta, is Boundless’s CEO and president. Its financing was co-led by Arch Venture Partners and City Hill Ventures.

San Diego biotech veteran Jonathan Lim, co-founder and former CEO of Ignyta, which Roche acquired in December 2017 for $1.7 billion, is managing partner at City Hill and a venture partner at Arch. He also co-founded another cancer-focused biotech, Erasca, last year, in which City Hill also invested.

Discoveries related to extrachromosomal DNA, or ecDNA, by Paul Mischel—a UC San Diego pathologist, professor, and member of the Ludwig Institute for Cancer Research—have set the direction for the company’s drug development plans, according to Hornby.

“It’s not that often that a whole new way of thinking about cancer biology comes around,” Hornby said in a phone interview.

EcDNA are large circular pieces of genetic material, and are identified “with high frequency” in nearly half of all solid-tumor cancers, according to Boundless. The company says it believes ecDNA to be a key driver of cancer in tumors that are difficult to treat, and that the extra genetic material gives those cells advantages when it comes to tumor growth, progression, and even resistance to existing treatments.

Boundless says it has figured out how to identify tumors with ecDNA, and how to target them with drugs.

It’s a departure from other cancer drug makers that often look to target mutated proteins being produced by cancer genes, like Ignyta did before selling to Roche when it was developing entrectinib (Rozlytrek) for people whose tumors have fusions of NTRK genes and ROS1 proteins to other genes. Entrectinib earned regulatory approval in the US last month. Boundless, meanwhile, aims to stop cells from creating ecDNA in the first place, Hornby says. That could be achieved by affecting the machinery that creates ecDNA, the metabolic state of the cell, or the repair pathways that the cell needs to keep the DNA alive, given its vulnerable state, unattached to a chromosome.

“We’re targeting the actual process by which the oncogene products arrive in the first place,” Hornby says. “We’re cutting out the cell’s ability to create oncodrivers and mechanisms of evasion and resistance, and looking at it through this new lens has revealed novel targets—targets that, to our knowledge, no one has ever tried to pharmaceutically pursue, or drug.”

He says the company—which has 15 employees, and plans to have about 20 by year’s end—is a few years away from entering human testing.

Hornby is joined in the Boundless C-suite by Jason Christiansen, another Igynta alum, as its chief technology officer, and by Scott Moorefield, who was most recently global business development director at Roche, as its chief business officer.

In addition to Mischel, the UCSD pathologist who is the company’s primary scientific founder, Boundless lists numerous other researchers as scientific founders, including The Scripps Research Institute’s Ben Cravatt, who has co-founded a number of biotechs in San Diego.

Vertex Ventures, GT Healthcare Capital Partners, the Tavistock Group’s Boxer Capital, and Alexandria Venture Investments also invested in the Boundless financing.