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Base Genomics Raises $11M to Support Commercialization of Methylation Sequencing Platform

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NEW YORK – UK epigenetics startup Base Genomics has raised $11.5 million (£9.1 million) to commercialize a new approach for DNA methylation sequencing that management believes will find applications in research and diagnostics alike.

The Oxford-based firm announced the closure of a seed financing round this week as well as plans to develop a methylation-based blood test for early-stage cancer detection. The round was led by Oxford Sciences Innovation, an early-stage investment firm also based in Oxford.

"We are doing product development to turn the invention into a real-world, robust, and scalable product that can be used across a variety of applications in research and in the clinic," said CEO Oliver Waterhouse, who previously was entrepreneur in residence at Oxford Sciences Innovation.

"Alongside that, we are doing our own clinical experiments and proof-of-concept work to show that we get highly sensitive results from oncology samples," he added. "We are particularly interested in the detection of early-stage cancer, and also the detection of minimal residual disease."

Waterhouse cofounded Base Genomics last year to commercialize technology developed at the University of Oxford's Ludwig Institute for Cancer Research. The approach, called TET-assisted pyridine borane sequencing (TAPS), enables users to detect at single-base resolution both 5-methyl cytosine and 5-hydroxymethyl cytosine, overcoming limitations with the conventional bisulfite sequencing approach for methylation analysis, which requires a large amount of input DNA and damages the DNA during the chemical reaction. Researchers described the TAPS approach in a paper in Nature Biotechnology last year.

"People have been desperate for an alternative to bisulfite [sequencing], and TAPS overcomes those issues," said Waterhouse. "We have no doubt if we execute properly, this will become the new gold standard because it has such clear advantages over the current methods that are out there for DNA methylation sequencing."

Some other seasoned hands in the technology world have been similarly impressed by TAPS. Anna Schuh, head of molecular diagnostics at the University of Oxford, has joined the management team as CMO, and Vincent Smith, a former genomic product development leader at Illumina, with a pedigree going back to Solexa, has left that firm to become CTO at Base Genomics. Yibin Liu and Chunxiao Song, co-inventors of the technology, are also part of the company's core team. Liu is the chemistry lead and Song is chemistry adviser.

"What attracted me is that the company's technology is built on a very novel, elegant, and powerful chemistry," said Smith of his new firm. "From my experience at Illumina, whose sequencing technology is built on a similarly simple and highly effective chemistry, I could see the industry-defining potential for TAPS."

According to Waterhouse, Base Genomics is now looking to expand its team to about 20 personnel. The company is based at the Bioescalator, an incubator for new companies at the University of Oxford's Old Road Campus in Headington. Commercialization is the main priority, with an eye on the clinical oncology market.

"In the initial phase, we are focused on commercializing the technology with a view toward having our own tests in the market for detecting early-stage cancer and minimal residual disease," said Waterhouse. Such assays will be developed internally, he said, though Base Genomics is considering how it can "expedite and maximize" the potential of the technology through partnerships.

Smith said that the company is currently reviewing plans to commercialize TAPS and make it available to the research community. Base Genomics will also work with collaborators to test the technology in the context of various diseases, he added.

Given his history with Solexa — Smith pressed the start button on the first automated next-generation sequencing run back in 2005 — he said that he believes TAPS has the potential to be as transformative for DNA methylation analysis as sequencing-by-synthesis was for genomic analysis.

"I think this technology has the potential to enable methylation to become as central to genomic analysis as DNA sequencing is," said Smith. "I think the best and most powerful technologies in genomics are based on novel chemistries, so it is very exciting to be involved with a company like Base at the beginning of its journey."

Waterhouse declined to specify any outside interest for the company's nascent cancer program, but reiterated it was a primary focus as the company starts to commercialize its tech.

"Given that the challenge in early cancer detection is to achieve sufficient sensitivity, the name of the game is to get as much information as you can out of the blood sample in order to detect it earlier and earlier. TAPS doesn't degrade the DNA nearly as much as bisulfite, so there is far more DNA available to be sequenced," Waterhouse said. "TAPS also retains the underlying sequence complexity, enabling simultaneous genetic and epigenetic analysis, so you can look at methylation at the same time as you look for sequence variants such as SNPs."

Smith said as the company ramps up, his team will be working to hone the TAPS technology for widespread adoption. "The challenge there is similar to the story with SBS sequencing," he noted. "The first thing you need to do is deeply understand the technology and explore every corner of it," he said. "You have to make sure you are building your chemistry and reagents with components and processes that are really well characterized and you have to test it exhaustively, stress-testing the system as much as possible. Ultimately it comes down to doing good science, as well as having the right processes and tools in place to control and measure performance."

Smith added that TAPS will remain a platform agnostic technology that can be used with short-read, high-throughput sequencing platforms like Illumina, as well as long-read platforms. Indeed, in a recent Genome Biology paper, the creators of the TAPS technology presented its application for targeted base-resolution sequencing of DNA methylation and hydroxymethylation in regions up to 10 kilobases, and said the method was compatible with both Oxford Nanopore and Pacific Biosciences sequencing.

"It should be useful with any other long-read platform that comes along, too," said Smith. "I think this technology has got legs for that reason, too."

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