Boundless Bio uncloaks with $46M to create new cancer drugs aimed at extrachromosomal DNA

Boundless Bio finds its roots in a simple question—how do cancer cells evolve so quickly? In seeking an answer, Boundless founder Paul Mischel, M.D., revisited questions that had been considered put to rest. One of those questions was about the architectural nature of the cancer genome. 

“The seminal discovery he made was that within a cancer cell, DNA does not always reside on chromosomes, as it would in a normal cell,” Boundless Bio CEO Zachary Hornby told FierceBiotech. “Cancer DNA finds the ability to hive off of chromosomes and form these separate structures that are circular and are called extrachromosomal DNA.” 

Mischel and his team found that a group of cancer-driving mutations called gene amplifications occur in the extrachromosomal DNA, or ecDNA for short. Amplifications are an increase in the number of copies of genes. When this happens in oncogenes, or cancer-driving genes, it can cause cancer cells to grow or become resistant to cancer drugs. 

While the biotech industry has managed to drug other cancer-promoting mutations, such as gene fusions, tumors with high copy number amplification mutations have so far eluded efforts to drug them. 

Armed with $46 million in series A funding, Boundless is looking to change it. It aims to understand how ecDNA forms, perpetuates and transcribes into proteins and then use that knowhow to identify new targets for a new class of cancer drugs. 

“Instead of looking at the cancer gene protein product as a drug target, maybe we can try to drug the process by which cancer genes amplify and are transcribed,” Hornby said. 

ARCH Venture Partners and City Hill Ventures led the round, with Vertex Ventures, GT Healthcare Capital Partners, Boxer Capital of the Tavistock Group and Alexandria Venture Investments also chipping in. 

Hornby, formerly the chief operating officer of Ignyta, divided Boundless’ plan into three buckets. 

“One is drug discovery efforts against novel targets we’ve identified, and we do indeed have those underway. We have screening efforts underway to identify new molecular entities,” he said. “Bucket number two is using the tools and technologies we’ve already developed to identify new cancer targets. We’ve identified an initial list of novel targets that we are currently validating and prioritizing.” 

Bucket number three is continuing to build its toolbox for interrogating and understanding ecDNA biology. 

San Diego-based Boundless is launching with about 15 staffers, with plans to reach 20. Its initial focus going into will be finding new targets and developing its technology, so that’s where hiring will focus, too. 

“But with the knowledge that the ultimate value creation for patients is in advancing drug candidates that we can take into the clinic, over time, that will be our square focus,” Hornby said.