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UW Spinout Bellwether Bio Raises $2.8M in Seed Financing

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NEW YORK (GenomeWeb) – Bellwether Bio, a liquid biopsy startup that recently spun out of the University of Washington, has raised almost $2.8 million in seed financing.

The company, cofounded by UW professor Jay Shendure and Matthew Snyder, a former graduate student in Shendure's lab, aims to commercialize technology based on determining fragmentation patterns in circulating cell-free DNA. Snyder is chief technology officer at Bellwether Bio, while Shendure, a professor in the Department of Genome Sciences, will serve as head of the company's scientific advisory board.

W Fund, WRF Capital, and Bioeconomy Capital, as well as biotechnology and software angel investors, contributed to the seed financing. Chad Waite, managing director of OVP Venture Partners and an investment committee member at the W Fund, will join Bellwether's board of directors as an observer.

In an interview, Snyder said that the firm currently has three employees and plans to hire three to four more over the next month or two.

The UW team published a study in Cell last year, showing that by sequencing cell-free DNA to high depth and analyzing the spacing of the nucleosomes, it could identify the tissue of origin of the fragments.

The method is based on the principle that different cell types have unique patterns of nucleosomes. In the Cell study, the researchers sequenced cell-free DNA to high depth and developed a method to trace the fragmented DNA back to its original location by analyzing the nucleosome position. When they analyzed blood samples from cancer patients, they found that the different fragmentation and nucleosome patterns could be traced to different types of cancer and to the body site where the tumor originated.  

Bellwether Bio licensed the technology from UW and has continued developing it. The company initially plans to use the technology for cancer liquid biopsy applications — analyzing cell-free circulating DNA to identify the site of origin, severity, and size of the tumor, as well as prognostic factors and information about treatment response, Snyder said.

But rather than joining the fray of competing cancer liquid biopsy startups, Bellwether Bio is collaborating with existing, and as of now unnamed, companies.

Snyder said the company’s technology for analyzing fragmentation patterns is complementary to other analytical approaches that look at somatic point mutations or copy number variants in cell-free DNA.

And because Bellwether Bio's analysis can be performed on DNA sequence data, it will not require extra material or a separate instrument. "We look at the data in a different way after [the DNA has] been sequenced," Snyder said, "which will be a value-add to our partnerships moving forward."

The seed financing will support the collaborations Bellwether will be forging over the next 18 months to two years, Snyder said, including two to three collaborations in the cancer space plus one or two in other areas, for example pregnancy.

Being able to determine the tissue of origin of circulating cell-free DNA fragments could have important applications in cancer and other fields. For instance, Illumina's Grail is aiming to develop a ctDNA assay that can identify cancer in pre-symptomatic individuals. But for such an assay to be effective, it will need to be able to determine where in the body the cancer is. Likewise, being able to trace a circulating cell-free DNA fragment back to its tissue could help identify metastases or validate that a mutation is in fact present in the tumor.

Startup Cirina, founded by Dennis Lo of the Chinese University of Hong Kong, is also working on technology that would be able to trace cell-free DNA fragments back to their tissue of origin. In 2015, Lo's CUHK team published a study in the Proceedings of the National Academy of Sciences showing that methylation markers on cell-free DNA can point to the tissue of origin.

Aside from cancer, Snyder said, Bellwhether’s technology could have applications in other disease areas. In the Cell study, the UW researchers reported that one advantage of their method is that it does not rely on genetic differences between cell-free DNA from a tumor and normal cell-free DNA. As such, it could have applications in pathological conditions that do not involve  genetic mutations. For instance, heart attack, stroke, and autoimmune disorders are associated with elevated levels of cell-free DNA but not genetic variants. This method could enable the identification and monitoring of cell-free DNA for such conditions, although Snyder declined to discuss Bellwether's plans to move into these disease areas.