As is often the case, it was a personal and devastating encounter with disease that brought Paul Mischel, a founder of newly launched Boundless Bio Inc., to the life sciences. When he lost his father to cancer, he dedicated his career to finding a cure.

Mischel, a pathologist at the Ludwig Institute for Cancer Research, University of San Diego, found his research leading to a big question: Why do cancer cells evolve so quickly in real time in the body when it takes human and other cells many generations to evolve? Mischel worked to discover the role of extrachromosomal DNA (ecDNA) and its role in driving cancer growth, resistance and recurrence, and to developing ecDNA-targeting medicines to treat patients with high copy number and focal gene amplification cancers. He helped design and develop technology capable of identifying and characterizing ecDNA-driven tumors, which are characterized by high copy number amplifications of oncogenes.

That path also led to the creation of Boundless Bio, which just raised $46.4 million in a series A financing. Zach Hornby, San Diego-based Boundless' president and CEO, told BioWorld that the company may be the only one devoted to this new avenue of biology research.

"It's a powerful mechanism," Hornby said. "Mischel made this discovery in 2014 and published it Nature in 2017. In 2018, Mischel brought the science to [co-founder] Ben Cravatt and they went to Arch [Venture Partners] and said it's potentially transformational. In 2018, they were seeded with a modest amount of money. In early 2019, Arch deemed it ready for a full series A. I joined in May, and the financing was completed in June."

The financing round was co-led by Arch and City Hill Ventures, along with Vertex Ventures, GT Healthcare Capital Partners, Boxer Capital of the Tavistock Group, Alexandria Venture Investments, and other undisclosed investors. Hornby was formerly the chief operating officer of Ignyta Inc. and stayed through its integration by Roche Holding AG, which bought the company for $1.7 billion and got entrectinib, a tyrosine kinase inhibitor for patients with fusions of the ROS1 and NTRK genes. (See BioWorld, Dec. 27, 2017)

Jonathan Lim, Ignyte's co-founder and former CEO, is chairman of Boundless' board and a co-founder.

The series A is only the beginning of the fundraising, but Hornby said he's keeping his eyes firmly in front of him and not too far ahead.

"Fortunately, we now have a good runway and we're not overly focused on a series B," Hornby said. "I feel optimistic that if we make reasonable traction, we'll be well positioned to start in the clinic in 2021. ... This allows us some time to put our heads down and validate the biology and to generate proof of concept."

The company intends to be opportunistic about partnering with other companies working with ecDNA, "if it drives the biology forward," Hornby said. "As we identify new targets that are implicated in ecDNA biology, we'll look to see if anyone else has tried these targets and, if so, what chemical matter is available for in-licensing. If there's no chemical matter out there, we'll initiate discovery ourselves."

The company moved into its lab and office facility just this week in Torrey Pines.

"We have a 10,000-square-foot facility, we've hired PhD scientists," Hornby said. "We have 15 employees now, we'll go up to 20 by the end of the year. We'll be conducting biology and chemistry in the lab and be collaborating with our founders, all six of them."

The company name came from chat among the founders about the people they wanted to recruit and the ethos they wanted to establish.

Hornby added that the founders want to hire "people with unlimited zeal and passion, boldness, energy, and the need to follow the science wherever it goes. The word 'boundless' means we can't be constrained by convention."

Hornby said he found himself interested in the company for the "pure intellectual stimulation of it. These cancers are some of the highest unmet needs out there. This biology could explain them. It felt like a fun challenge to grapple with."

Hornby said he expects to get into the clinic in "several years" and is working to identify the company's lead targets.

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