Boundless Bio raises $105M in effort to reimagine targeted cancer therapy
Boundless Bio CEO Zach Hornby was sitting in his La Jolla, CA office last fall, preparing for a board meeting when his computer pinged with an email. It was his CSO, Chris Hassig, emailing over tables and charts at the best possible time.
Their new type of cancer treatment was working. In mice, at least.
“This was a catalytic event,” Hornby told Endpoints News. The data “really said, ‘yes, we can do this.”
Hornby and his team delivered the results to the board and then started fundraising for the cash they would need to bring the new technology out of mice and into people. They emerged today with a $105 million Series B led by Nextech Invest and RA Capital Management and plans to be in the clinic by 2023.
Boundless Bio is going after cancer cells that contain extra bits of circular DNA, floating around outside the tightly wound chromosomes where the genetic code is supposed to sit. Although scientists have known about these vagabond fragments, known as extra-chromosomal DNA or ecDNA, for decades, new research has pointed to the role they may play in driving many cancers.
The ecDNA can act as a genetic reservoir for tumors. Liberated from the intricate machinery that normally regulates how DNA replicates and transcribes, they can run rampant producing oncogenes. They can mutate quickly if doctors try to throw targeted therapies at them.
Researchers believed that up to half of all tumor types and a quarter of all cancers have extra-chromosomal DNA — many of these cancers that have been overlooked by the new wave of targeted and immunotherapies. The question for Boundless, first founded in 2018 and backed by ARCH and City Hill Venture, was how one turned these new findings into drugs.
So the company has spent the last two years trying to build, in mice and lab dishes, models of tumors with ecDNA. But that was easier said than done. For cancers, the point of these rogue genes is that they can keep cells in a kind of genetic flux, and the models they built wouldn’t stay static. They’d make a tumor with ecDNA and then watch the extra-chromosomal DNA vanish. Or they’d make two lines, one ecDNA positive and one ecDNA negative and then watch the levels ecDNA rise in the negative one and fall in the positive ones.
“It kind of left us scratching our heads,” Hornby said.
Still, the company says it has now managed to pull off 20 different tumor type models in lab dishes and “multiple” different mouse models.
The goal now is to study how ecDNA tumors differ from tumors without ecDNA, using a variety of genetic and quantitative tools. Largely, Boundless will look to find and exploit vulnerabilities unique to ecDNA cancer — pathways that only these cells rely on to survive and that can be knocked out with small molecules.
They will look to pair those molecules they develop with more conventional targeted drugs. If a patient had a KRAS-positive tumor with a high number of ecDNA, for example, they could give him Amgen’s sotarisib to hit KRAS targets and Boundless’s drug to prevent the cancer from using ecDNA to evolve resistance.
Before last year’s board meeting, Boundless showed such an approach could work in mice. They plan to announce a development candidate later this year, one they hope will begin to change how the field approaches targeted therapies.
Today, Hornby said, companies approach cancer like a game of whack-a-mole, developing a targeted drug and then developing a new targeted drug when the cancer evolves resistance to the first one.
“So what we need to do is pull the plug on the game,” he said.