BioPharma, Startups

Startup Boundless Bio brings in $105M to break the circle behind cancer growth

Boundless Bio’s research has uncovered a previously unknown driver of cancer growth and drug resistance. With $105 million in Series B financing, the biotech is on a path to bring to the clinic small molecules that address this target, called extrachromosomal DNA.

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Floating inside some cancer cells are bits of circle-shaped genetic material that are separate from chromosomes. Scientists observed them for decades, thinking they were just cellular debris without any function, according to Zach Hornby, CEO of Boundless Bio. More recent research revealed that these circular units of DNA indeed have a function, and they play a key role in making cancer more aggressive and difficult to treat.

Boundless Bio has spent three years studying how these circles, called extrachromosomal DNA (ecDNA), help cancers grow and develop resistance to currently available treatments. That work has yielded drug candidates that take an alternative approach compared to therapies that target specific cancer proteins. The startup is charting a course to bring its programs into human testing and on Wednesday it announced a $105 million Series B round of financing to support its plans.

The science underpinning Boundless Bio’s drugs is based on research that started at UC San Diego. The startup’s scientific founder, Paul Mischel, a pathologist, was trying to understand why some targeted therapies don’t work for some patients, Hornby said. His research led him to gene amplification, the process by which multiple copies of a gene are produced, a common occurrence in cancer. Mischel found that the gene amplification was not happening on chromosomes as expected. Instead, it was happening in the nucleus on DNA that looked like circles—ecDNA.

“These are fully functional DNA that is separate from chromosomes,” Hornby said. “That was a whole new revelation that there was genomic biology separate from chromosomes.”

Gene amplification-driven tumors are different than cancers that stem from genetic mutations or fusions, according to Boundless Bio. The circle shapes of ecDNA pass their genetic material from mother cells to daughter cells unevenly, leading to new genetic diversity that enables a cancer to rapidly adapt to changing conditions. Those adaptations include developing resistance to various cancer treatments. That means cancers driven by gene amplification are also less likely to respond to precision medicines that address a specific genetic target.

Boundless Bio developed a proprietary technology, called Spyglass, that interrogates gene amplification-driven tumors. By comparing ecDNA-driven tumors to those that are not driven by ecDNA, the company was able to identify promising drug targets that are key to the life cycle of ecDNA. While many cancer drugs take a direct strike by specifically targeting certain proteins, Boundless Bio employs a less direct approach called synthetic lethality. Rather than directly inhibiting ecDNA, Boundless Bio’s small molecules target something else in a cell that the ecDNA rely on. Hitting this target has the effect of taking out ecDNA, Hornby said.

EcDNA is found in many types of cancer, more commonly in solid tumors compared to hematological malignancies, Hornby said. Just as important, ecDNA is generally not found in normal cells, so a drug that stops ecDNA likely won’t harm healthy tissue. In 2019, Mischel and other scientific founders of Boundless Bio published research in the journal Nature that described how ecDNA’s circular shape supports amplification of cancer genes. Last August, the company published additional research in the journal Nature Genetics describing how ecDNA and gene amplification is associated with many different types of cancers.

Boundless Bio’s research has produced three programs, each addressing distinct targets that when blocked, stop ecDNA, Hornby said. The first program is expected to produce a drug candidate by the end of this year, which could lead to an investigational new drug application filing by the end of next year. If the research stays on track, Hornby estimates the company could begin clinical testing in early 2023 with one or more programs.

Meanwhile, the company is also developing a companion diagnostic. In order to treat patients whose cancers are driven by ecDNA, it’s important to identify which patients have these cancers, Hornby said. That diagnostic will be based on molecular sequencing.

The new biology uncovered by Boundless Bio has drawn some interest from larger pharmaceutical companies. To date, Hornby said he has kept those queries at bay, choosing instead to focus the company on developing its technology platform. But now that Boundless Bio has a better understanding of ecDNA science and what its technology can do, Hornby said the startup could consider striking up alliances with other companies.

Before Wednesday, Boundless Bio last raised money in 2019 when it emerged from stealth with a $46 million Series A round of funding. Hornby said the new capital is expected to be enough to support the company for the next three years. He added that it’s a Series B financing, not a crossover round. Crossover financings, which include firms that invest in both public and private companies, are often a signal a company is preparing for an IPO. Hornby said that Boundless Bio’s Series B financing is large enough that the company would not need to raise another round of funding before going public—if it chooses to do so.

RA Capital Management and Nextech Invest co-led Boundless Bio’s latest financing. Other participants include Fidelity Management & Research Company, Redmile Group, Wellington Management, Surveyor Capita, PFM Health Sciences, and Logos Capital. Also participating were earlier investors ARCH Venture Partners, City Hill Ventures, Vertex Ventures HC, GT Healthcare Capital Partners, Boxer Capital of Tavistock Group, and Alexandria Venture Investments. In conjunction with the financing, Jakob Loven, Partner at Nextech Invest, will join the Boundless Bio Board of Directors.

Photo by Flickr user Neil Williamson via a Creative Commons license