Boundless Bio, a company interrogating and targeting extrachromosomal DNA (ecDNA) in aggressive cancers, today announced the completion of a $46.4 million Series A financing. Boundless Bio is leveraging new discoveries about the role of ecDNA in driving cancer growth, resistance, and recurrence to develop the first ecDNA-targeting medicines and transform outcomes for patients with high copy number, focal gene amplification cancers, which historically have been very difficult to treat. The company's joint lab and office headquarters is based in the biotech hotbed of the Torrey Pines region of San Diego, California.

The financing round was co-led by ARCH Venture Partners and City Hill Ventures, with participation from Vertex Ventures, GT Healthcare Capital Partners, Boxer Capital of the Tavistock Group, Alexandria Venture Investments, and other undisclosed investors. The funds raised will be used to cement a leadership position in the emerging field of ecDNA biology by continuing to build technology capable of identifying and characterizing ecDNA-driven tumors; identifying and validating novel cancer targets; and developing targeted, proprietary treatments that exploit ecDNA's unique vulnerabilities. Initial programs are directed to high copy number, focal gene amplification solid tumors, where ecDNA are believed to be a primary driver.

Biotech veteran Zachary Hornby is President, Chief Executive Officer, and a Director of Boundless Bio. Mr. Hornby was previously Chief Operating Officer of Ignyta, Inc., from its inception through its acquisition and integration by Roche. Jonathan Lim, M.D., former co-founder and CEO of Ignyta, serves as the company's Chairman.

"Boundless Bio aims to improve cancer care by bringing a whole new class of weapons to the cancer-fighting armamentarium that exploit the emerging field of ecDNA biology," said Hornby. "When DNA in cancer cells comes off chromosomes in the form of ecDNA, it replicates more rapidly and is more transcriptionally active, allowing cancer cells to grow and resist treatment. We are creating powerful medicines that counterattack this ecDNA phenomenon by eliminating cancer cells' ability to employ ecDNA to survive."

"By targeting ecDNA biology, Boundless Bio is translating some of the most exciting and differentiated recent discoveries in cancer research to develop an entirely new class of medicines for patients with cancer," said Jonathan Lim, M.D., Managing Partner at City Hill Ventures and Venture Partner at ARCH Venture Partners. "We are excited to join this exceptional group of investors in supporting the company's efforts to bring this potentially game-changing technology to bear on gene amplification cancers that have historically evaded treatment."

Scientific Approach

Boundless Bio was founded by a team of pioneering cancer researchers, led by Paul Mischel, M.D., a Distinguished Professor at the University of California San Diego (UC San Diego) School of Medicine and member of the Ludwig Institute for Cancer Research, who is a forerunner in understanding the role of ecDNA in cancer pathogenesis and evolution. Mischel led efforts to interrogate ecDNA, which are identified with high frequency in nearly half of all solid tumor cancers and thought to be one of the key drivers of the most aggressive cancers - specifically, those characterized by high copy number amplifications of oncogenes. ecDNA are large circles of DNA, located outside the chromosomes but within the nucleus of a cell, which contain multiple genes and encode regulatory and other types of sequences. If the ecDNA encode genes that translate to proteins that are advantageous for cell survival, such as oncogenes, the ecDNA provide a distinct advantage to cells that contain several copies; this can then drive tumor growth, progression, and resistance to standard treatment options.

In addition to Dr. Mischel, the company's distinguished scientific founders include:

-Vineet Bafna, Ph.D., Professor of Computer Science & Engineering, UC San Diego;
-Howard Chang, M.D., Ph.D., Virginia and D.K. Ludwig Professor of Cancer Genomics and Genetics at Stanford University;
-Ben Cravatt, Ph.D., Professor and Gilula Chair of Chemical Biology at The Scripps Research Institute;
-Prashant Mali, Ph.D., Assistant Professor of Bioengineering at UC San Diego; and
-Roel Verhaak, Ph.D., Professor and Associate Director of Computational Biology at The Jackson Laboratory.

"Guided by our developing understanding of ecDNA, our scientific founders have created a new architectural map of the cancer genome to demonstrate why some cancers aggressively evolve and resist existing treatment approaches," said Dr. Mischel. "We have developed technology capable of identifying, characterizing, and ultimately, drugging, ecDNA-driven tumors. Boundless Bio has brought together a team of pioneering, committed, and collaborative individuals to tackle the hardest-to-treat cancers."

Leadership team

In addition to CEO Zachary Hornby, the Boundless Bio leadership team comprises experienced life sciences executives and drug development professionals, including:

-Jason Christiansen, Ph.D., Chief Technology Officer;
-Scott Moorefield, Ph.D., Chief Business Officer;
-Tony Pinkerton, Ph.D., Vice President, Chemistry; and
-Meredith Wesley, Vice President, Talent and Culture.

The company's board members are leaders in the life sciences with an extensive history of successful cancer research, drug development, and company-building:

-Jonathan Lim, M.D., Chairman and Co-Founder;
-Kristina Burow, Managing Director, ARCH Venture Partners;
-Ho Cho, Ph.D., Vice President of Biotherapeutics, Celgene;
-Ben Cravatt, Ph.D., Co-Founder;
-Zachary Hornby; CEO and President; and
-Carolyn Ng, Ph.D., Managing Director, Vertex Ventures

"Boundless Bio's exceptionally talented leadership team has deep expertise in cancer drug research and development, as well as strong company building experience," said Kristina Burow, Managing Director of ARCH Venture Partners. "We have tremendous confidence in their ability to create life-improving therapies for patients with previously intractable cancers."

About ecDNA

Extrachromosomal DNA, or ecDNA, are large circles of DNA containing genes that are outside the cells' chromosomes and can make many copies of themselves. The ecDNA can be rapidly replicated within the cell, causing high numbers of oncogene copies, a trait that can be passed to daughter cells in asymmetric ways during cell division. Cells have the ability to upregulate or downregulate the ecDNA and resulting oncogenes to ensure survival under selective pressures, including chemotherapy or radiation, making ecDNA one of cancer cells' primary mechanisms of recurrence and treatment evasion. ecDNA are rarely seen in healthy cells, but are found in a large number of all solid tumor cancers. They are a key driver of the most aggressive and difficult-to-cancers-specifically, those characterized by high copy number amplification of oncogenes.

About Boundless Bio

Boundless Bio is a biotechnology company focused on interrogating a novel area of cancer biology, extrachromosomal DNA (ecDNA), to deliver transformative therapies to patients with previously intractable cancers. For more information, visit www.boundlessbio.com.