August 1, 2014 (Vol. 34, No. 14)

Gail Dutton

Targeted Sequencing Technology Enhances Gene Mutation Identification and Discovery

In transforming itself from a reagents supplier to a next-generation sequencing (NGS) applications company, Enzymatics is advancing the genomics industry. While Enzymatics continues to support and expand its fast-growing core business—reagents and kits for original equipment manufacturers—it is also taking advantage of a new technology—Anchored Multiplex PCR (AMP™) chemistry.

AMP, which was developed by researchers at Massachusetts General Hospital, formed the basis of ArcherDx, a startup that was acquired by Enyzmatics almost a year ago. With AMP, Enzymatics intends to move up the value chain, providing not just raw tools, but diagnostic tests for specific genetic mutations.

The AMP-targeted sequencing technology, known as Archer™, generates enriched libraries of targets of interest. And, because it focuses on only those targets, Enzymatics officials claim that researchers can identify more complex mutations more quickly than when using whole-genome analysis.

When Enzymatics’ executives met Archer’s co-founders, all the assembled parties realized two things. First, Archer’s analytics platform and AMP chemistry had the power to thrust NGS toward industrial-scale commercialization for mass markets as well as research. Second, Enzymatics had the experience and resources to make that happen rapidly.

“We have a track record of supporting dynamic, high-growth technologies and taking them to the next level,” emphasizes Stephen Picone, Enzymatics’ co-founder and chief strategy officer. “We knew the AMP chemistry would make a significant impact in healthcare. It has a high human impact, so it made sense to bring the two businesses together.”

“Although ArcherDx technically was an acquisition, we think of it as a merger,” Picone adds. “We applied our focus to put the Enzymatics machine behind the powerful Archer application. So far, it seems to be an ideal match. With our combined strength, we executed Archer’s three-year business plan in one year.”


Enzymatics’ Archer Technology embodies advances in three areas of next-generation sequencing: assay, workflow, and analysis. The reagents, the kitting solution, and the Archer product itself are shown here.

AMP: Purpose-Built for Oncology

“AMP is the first target-enrichment method for NGS that is purpose-built for cancer,” Jason Myers, Ph.D., CSO for Enzymatics and co-founder of ArcherDx, tells GEN. AMP allows the detection of known and novel gene fusions in a single multiplex assay without requiring prior knowledge of breakpoints or fusion partners. This capability enables researchers to capture and uniformly amplify only the targets of interest.

Specifically, the AMP chemistry identifies and detects gene rearrangements, single nucleotide variants, insertions, deletions, copy number variants, or changes in RNA abundance, enabling the identification of rare, recurrent mutations. Unlike traditional library-preparation methods, AMP ligates half-functional adapters before amplification with target-specific primers on one end and an adapter complimentary primer on the other end, thus enriching novel and uncharacterized sequences. Complex mutations, therefore, are identified with one assay.

Archer focuses on carcinomas, hematological malignancies, and sarcomas and is very scalable. It looks at hundreds of genes, “and has the potential to look at thousands of genes simultaneously,” Dr. Myers says. The current products, however, focus on areas of actionable information and are, hence, panels that can be used to detect and identify those genes most closely associated with cancers.

“It displaces FISH, IHC, and some PCR procedures as well as its NGS predecessors,” Dr. Myers notes. For example, where FISH detects gene fusions, AMP detects and also identifies those fusions. “Archer often is an order of magnitude faster than comparable products, and it’s about 30 times less expensive than traditional assays.”

Additionally, as early adopters are seeing, “AMP is quickly scalable,” asserts Ian Ratcliffe, CEO and chairman of the board. “We can turn around custom gene panels in weeks, rather than months.”

Released in February, adoption of Archer technology is advancing rapidly. “It’s an important part of precision medicine,” Picone says. Several of the top cancer centers in the United States are actively developing assays around AMP, and many others also are implementing Archer technology in their research. According to Dr. Myers, pharmaceutical companies also are using Archer to identify biomarkers for companion diagnostics and to discover mutations in cancer.

Enzymatics’ first assay kit for Archer was introduced spring 2014 to detect ALK, RET, and ROS1 fusions. These mutations are involved in non-small cell lung carcinoma and can be identified with as little as 20 ng of nucleic acid. An assay kit for mixed lineage leukemia has also been developed, and Dr. Myers says he expects four other assay kits to be launched by year’s end.

Strategic Growth

Currently, Archer technology is available for research use only. Enzymatics plans to expand the Archer platform into additional markets, initially focusing on translocations—suitable targets, Picone maintains, because they pose “some of the most challenging problems in oncology.” The company also plans to extend this target-enrichment platform to other markets, including germ line and infectious disease, while new Archer versions will continue to simplify workflow to reduce complexity and increase efficiency.

During the coming year, Enzymatics’ focus will expand beyond translocations to also address other cancer-related mutations. As Dr. Myers points out, “Pathologists want an assay that looks at all the mutations—point mutations, copy number variations, and translocations—simply and simultaneously.”

“Enzymatics is ideally positioned to identify new enzymes and sequencing-based technologies to add to our portfolio,” Ratcliffe insists. “Archer is a case study of the company’s ability to identify and accelerate great technologies into the market. We will continue to deliver world-class products and customer support through our reagent and kitting businesses, while continually evaluating strategic opportunities for growth. There’s a lot of opportunity ahead to build a substantial, versatile life science company that serves the research and applied markets.” 

Enzymatics

Location: 100 Cummings Center, Suite 407J, Beverly, MA 01915

Phone: (978) 927-7027

Websitewww.enzymatics.com

Principal: Ian Ratcliffe, CEO and chairman of the board

Number of Employees: 125

Focus: Enzymatics is a developer and manufacturer of application- and NGS-focused kits for Archer™ Anchored Multiplex PCR technology, as well as the underpinning reagents, assays, and software.

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