NEW YORK – Watchmaker Genomics said on Wednesday that it has entered a multiyear, co-exclusive licensing agreement with Exact Sciences to develop and commercialize a bisulfite-free DNA methylation analysis technology called TAPS (TET-assisted pyridine borane sequencing).
As part of the agreement, Watchmaker will share exclusive rights to TAPS with Exact, which obtained the technology through its acquisition of Base Genomics in 2020. Watchmaker hopes this will allow it to expand its next-generation sequencing product offering to include DNA methylation analysis for both research and clinical applications.
Originally developed by researchers at the University of Oxford's Ludwig Institute for Cancer Research, TAPS promises to detect both 5-methylcytosine and 5-hydroxymethylcytosine with single-base resolution while circumventing the shortcomings of traditional bisulfite sequencing. The technology spurred the establishment of Base Genomics, an Oxford-based startup that garnered $11.5 million in seed funding before being acquired by Exact.
"We were pretty excited about those early publications and some of the subsequent publications that were leveraging the TAPS technology," said Watchmaker Cofounder and CEO Trey Foskett. "It became clear to us that this was a technology that we could continue to help [Exact] improve as well as commercialize."
According to Foskett, one component of the co-exclusive licensing agreement with Exact is to help develop the TAPS chemistry into commercial products. Watchmaker is bringing its expertise in enzyme engineering and next-generation sequencing reagent manufacturing to the table, he noted.
"I think Exact saw us as a good partner for the commercialization, productization, and development of the [TAPS] chemistry from something that could work on somebody's lab bench to something that hopefully works on everybody's lab bench in the near future," said Watchmaker CSO and Cofounder Brian Kudlow.
Specifically, the company plans to leverage its protein engineering platform in order to enhance the TET enzyme used in TAPS, he said, as well as the amplification polymerases involved in the workflow.
Additionally, Watchmaker aims to make TAPS a "reproducible, manufacturable, QC-able, and scalable" technology that is suitable for commercial production, he said. "A huge amount of work just goes into really taking something that was run as an academic exercise to making it something that can work every time for a broader market."
By adding TAPS to its technology arsenal, Watchmaker is also hoping to expand its NGS product offering to enable multimodal genomic and epigenomic analysis, as well as to expand its customer base in both the research and clinical space, Foskett said.
Currently, the Boulder, Colorado-based life sciences tools company offers a series of library prep kits for both RNA and DNA sequencing, which Foskett said could be "very complementary" to the TAPS workflow. Additionally, the company is setting its sights on "enabling applications" for TAPS, he added, such as the opportunity to combine somatic variant detection with methylation analysis in the same library prep process.
An initial goal for the company is to commercialize TAPS into a kitted assay that can be marketed toward the broader research community, he said. Beyond that, the company hopes to collaborate with partners in the clinical space to steer the technology toward diagnostic applications, specifically in oncology.
Foskett noted that the current collaboration agreement with Exact does offer Watchmaker "effectively the exclusive rights to sublicense." It also does not exclude Watchmaker from developing products for clinical or oncology applications — even for early cancer detection and minimal residual disease (MRD) testing — if it is "under the right circumstances and with the right partner," he said.
While Watchmaker is betting on the epigenetic analysis market with TAPS, other companies are also developing technologies for methylation analysis. For instance, earlier this year, Biomodal, a University of Cambridge spinoff formerly known as Cambridge Epigenetix, launched a sequencing sample prep kit that promises to simultaneously detect canonical DNA bases (A, C, G, T) and modified cytosines in one workflow using the so-called "five-letter seq" technology.
Furthermore, single-molecule sequencing technologies, such as those from Pacific Biosciences and Oxford Nanopore Technologies, are also promoting their ability to simultaneously profile genetic and epigenetic signals.
Compared with conversion-based methylation detection methods, Kudlow said he believes the reduced complexity afforded by the TAPS workflow can result in less sequencing while preserving more library complexity. However, he did acknowledge that how TAPS will stack up against competing technologies is "yet to be determined."
Additionally, Foskett said the company is "super excited" about direct methylation detection approaches and believes the single-molecule sequencing platforms can potentially be "complementary" to TAPS.
One limitation of the direct methylation detection methods is that they typically require high sequencing coverage and large DNA input, he noted, making it challenging to work with cell-free DNA or formalin-fixed paraffin-embedded (FFPE) samples.
Assuming both companies fulfill the obligations of the co-exclusivity agreement, Foskett said they will have access to TAPS throughout the lifetime of the IP.
In addition, the two partners have established a long-term strategic supply agreement, under which Watchmaker will provide Exact with access to its portfolio of sequencing reagents and precision enzymes. "These products have the potential to enhance the performance of Exact Sciences’ tests while significantly reducing associated costs," Watchmaker said in a statement.
In an email, Isaac Kinde, Exact’s VP of technology assessment, said that the company "[looks] forward to working with Watchmaker and leveraging its abilities in high-quality enzyme production to complement our research and development efforts in bringing new and more sensitive cancer detection technologies to patients."
Exact declined to answer specific questions regarding the newly forged partnership, including how the company plans to improve the TAPS technology on its part, or how it plans to develop TAPS into cancer testing products.