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Roche Adds Antibiotic Susceptibility Testing to MDx Offerings With GeneWeave Acquisition

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NEW YORK (GenomeWeb) – Roche's recent acquisition of GeneWeave Biosciences could address a blind spot in the biotech giant's molecular diagnostic offerings and engage a market that could be worth billions.

Roche is hoping that GeneWeave's technology can succeed where PCR fails: providing rule-in answers about antibiotic resistance in bacterial infections.

With multi-drug resistant infections established as a global health crisis, Roche has been looking for ways to not only identify pathogens, but also identify how to kill them. The company's wealth of experience with PCR and recent acquisitions, such as the point-of-care diagnostic platform from Iquum, work well in finding the bugs, but not so well when it comes to informing treatment options.

"This is one of the most rapidly growing areas of molecular diagnostics and to get into the area of antibiotic susceptibility testing (AST) we knew was going to take something a little different," Roche Molecular Diagnostics President Paul Brown told GenomeWeb. "PCR is good for identifying infections and even spotting genes associated with antibiotic resistance, but it doesn't work particularly well for the AST portion," he said.

"If you did AST with PCR we'd be able to tell you what drugs don't work," Brown said. "But that's not really useful for physician. They want to know what drugs do work." 

GeneWeave's technology promises to answer that question, quickly. "What we aimed to do was build a molecular diagnostic test that provided that answer in hours instead of days," GeneWeave CEO Steve Tablak told GenomeWeb. "This is a new class of diagnostics in that we look and perform a molecular test that gives us the systemic response of the bug to the antibiotics. They're really designed to target clinical questions."

GeneWeave has built a fully automated in vitro diagnostic platform to do both identification testing and AST with live-cell assays (in contrast to PCR or sequencing, where the cells are lysed to look at the molecular components). It's based on what the firm calls "Smarticles," bioactive vessels tuned to recognize specific receptors on common pathogens, then introduce a luciferase reporter into the cell.

"What we're in the process of doing is the same automating of the microbiology lab that's been done in the chemistry lab, with random access instrumentation for samples coming into the laboratory," Tablak said.

Antibiotic resistance is traditionally a question for a microbiology lab, since only culture-based testing could find the right drugs to kill the infection. 

Roche's interest in addressing the microbiology diagnostics market was due to its importance and size. "Clearly antimicrobial resistance is a public health issue," Brown said, adding that he values the classic microbiology market to be worth between $2.2 and $2.4 billion dollars. "Not much has really changed for many, many years," he said. "Areas like AST are still dominated by culture plates. It's pretty old technology."

But even those bacteria that can grow in culture take a long time to do so, something that GeneWeave wanted to improve upon. "We'd been looking and watching that space and decided that GeneWeave was far and away the best technology out there," Brown said. Roche paid $190 million for the privately-held firm upfront and could pay up to $425 million if GeneWeave meets undisclosed development milestones.

GeneWeave's technology offers speed as well as coverage of PCR's antibiotic susceptibility blind spot. "We believe it has the ability to fundamentally change way we're testing for AST," Brown said.

Not only does PCR lack the rule-in answers doctors want, it is blind to non-genetic mechanisms contributing to resistance. "The elegance of what we do is that we look at the systemic function," Tablak said.  "We do a molecular test, but we derive this phenotypic response to the antibiotic, so we're not susceptible to rapidly occurring mutations in bacteria as they evolve. He added that this could help the technology keep up in the face of a growing number of resistance mechanisms.

GeneWeave was founded in 2010 after Jason Springs, an MBA student, and Diego Rey, a doctoral student, met while at Cornell University. The firm, now located in Los Gatos, California, moved west seeking funding to develop the Smarticles technology.

There are two components to the technology, an outer casing and a payload of DNA. The outer casing has properties that allow it to find the target organism. Smarticles can be designed to target families, genuses, and individual species of bacteria, but are designed only for clinically relevant questions. For clinicians looking to detect methicillin-resistant Staphylococcus aureus (MRSA), GeneWeave has built a particle that will bind only with S. aureus and not any other bacterium, enabling detection of MRSA when the relevant antibiotics are included in the assay.

When a Smarticle finds corresponding bacteria, it will bind to a cell surface receptor and initiate transduction of its payload, a synthetic plasmid encoding DNA specifically designed to work inside the target organism and code for a luciferase enzyme. "We use the transcription and translation mechanism inside the cell to generate the reporter signal," Tablak said. "Once it's inside the bacterium, it acts like a probe to generate and amplify the signal."

This design ensures that if the clinician is looking to test for S. aureus, a positive luminescent signal is actually being made by S. aureus bacteria.

The luminescent signal, or absence of it, also helps identify antibiotic susceptibility. "Antibiotics, regardless of class, all work to the same purpose, which is to interrupt transcription and translation inside the cell," Tablak explained. "If the lights don't go on, we know [the pathogen] is susceptible to the antibiotic. If it stays on, we know it's resistant to the antibiotic at that concentration."

The entire test is run on GeneWeave's fully-automated vivoDx instrument. Tablak said the assays require less than a minute of hands on time and no sample preparation. "We can work directly inside the crude sample to find the bacteria," he said.

The platform is currently being evaluated in clinical trials and Roche hopes that its experience and resources can quickly land CE marking and US Food and Drug Administration approval for vivoDx and its first suite of assays.

In addition to MRSA, the first test being developed, GeneWeave's current pipeline for vivoDx includes assays for carbapenem- and fluoroquinolone-resistant Enterobacteriaceae and vancomycin-resistant Enterococci. But with Roche's support, Tablak expects that menu to expand. "We've got a deep bench that we're building," he said. Experience gained developing one assay is easily reused; a Smarticle developed for S. aureus can be used in both regular and drug-resistant identification assays and for multiple types of samples, like nasal swabs, blood, and tissues. 

"All the things you learn about building a gram-negative Smarticle you use in different ways," Tablak said. In this way the technology is able to address the different diagnostic needs of the clinic. New assays for different sample types still have to be cleared individually, but can be built on existing technology.

Roche's Brown said that the firm is primarily concerned with placing the instrument in microbiology laboratories, but left the door open for other applications of the Smarticle and vivoDx instrument. "It's too early to say where it will ultimately end up," Brown said. "What we're trying to do here with the GeneWeave technology is what we're trying to do in any molecular lab: improve turnaround time, speed, and workflow efficiency. We believe we will bring those to the culture lab."

"Now we've got a nicely rounded portfolio that covers what I would call the continuum of molecular diagnostics," Brown said, noting that the Iquum and GeneWeave purchases round out what he called conventional molecular diagnostics. "I'm very comfortable where we are. As always we'll remain vigilant and assess opportunities that come along on a case-by-case basis, but right now we're not specifically hunting."

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