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ChromaCode Developing Multiplexed Infectious Disease MDx Panels for Standard qPCR Instruments

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NEW YORK (GenomeWeb) – ChromaCode, a two-year-old startup company with a proprietary PCR multiplexing technology called high-definition PCR (HDPCR), plans to develop a menu of panel-based diagnostic tests as well as to support customers creating their own panels.

The firm's proprietary technology increases the multiplexing capabilities of existing real-time PCR machines of any brand up to fourfold, enabling them to run syndromic panel tests with no changes to their hardware or software, according to Patricia Wilch, the company's vice president of marketing.

ChromaCode's first assay to market will be a research-use-only tick-borne diseases panel, Wilch said. The HDPCR-based panel will be able to detect nine pathogens common to the US that are transmitted by ticks, and the company expects to launch it in August or September.

"We are a little ahead of most people out there, because today, most of the [tick-borne disease] testing is serology-based," said Wilch.

The firm plans to follow up the tick-borne diseases panel with a panel to detect drug resistance in nine different multi-drug resistant organisms, as well as other infectious disease applications in areas like women's health.

"We also want to take this technology into the oncology space, and it is also adaptable to digital PCR," Wilch added, noting that future dPCR tests would focus on oncology and genetic testing applications and could complement current next-generation sequencing applications by providing a low-cost, highly sensitive, multiplexed panel option.

In addition to making its own panels, the company also plans to partner with customers, such as large reference laboratories and hospital labs interested in developing and using syndromic panels. In that case, the firm would collaborate with a customer to develop a panel utilizing its technology, and then adapt it to the customer's system so the lab can run the panel as a routine test, Wilch said.

Typically, PCR systems have two to three color channels, and can assay one to two analytes per channel. ChromaCode's technology uses a combination of chemistry and machine learning algorithms to expand this, in part by using limiting concentrations of probes so that multiple targets can be detected in a single channel based on differing intensities of fluorescence.

ChromaCode's technology allows for plexing of up to five analytes per color channel. This can expand the capabilities of a standard PCR system, such that a five- or six-color system — such as the Bioneer Exicycler, the EliTech Elite InGenius, or the Quant Studio 5 from Thermo Fisher Scientific — would be able to detect in the realm of 25 analytes.

That multiplexing capability is on par with commercially available syndromic panels — such as US Food and Drug Administration-cleared respiratory panels from BioFire, Genmark, and Luminex, or a CE-marked product from Stat-Dx — which can detect around 20 analytes simultaneously.

However, ChromaCode says its approach has certain unique advantages over these competitors.

Greg Gosch, ChromaCode's CEO, highlighted the fact that the firm's technology allows customers to run multiplexed syndromic panels "without investing in new capital equipment." This expedites the adoption process, Wilch added, since clinicians and laboratorians can expand their menu on a system they already own.

"The fact that there's no change in the workflow whatsoever compared to running a single-plex assay, but yet [it can generate] many more results per sample, is also highly valuable," she said.

And, importantly, ChromaCode's technology can be used to run multiplex assays in 96-well plates, with a relatively short time to result, said Wilch.

"A lot of real-time PCR applications take upwards of six hours, but ours is a shorter time frame, only a couple of hours," she said. Competing products are also rapid, but may have more limited throughput in comparison because individual instruments are limited to either one test or a handful of tests at a time.    

Teasing apart data from so many color signals is quite fast with the ChromaCode system, Wilch said. "We have a proprietary software that does the analysis in the cloud in a very short amount of time – two to three minutes – and that software works hand-in-hand with our special chemistry," she said.

The core technology was originally described in a 2013 proof-of-principle Analytical Chemistry article by the inventor, Aditya Rajagopal, founder and chief technical officer at ChromaCode.

The article described the mathematical theory behind the encoding and decoding of multiplexed TaqMan PCR assays. Specifically, it used the technology to interrogate the fluorescence coming from combinations of three sequences – one from dengue virus and two from HIV – detected in one single color channel. In the article, the method was able to correctly parse these in all cases.

The authors also noted that FRET-based TaqMan probes in systems that can detect them might double the number of sequences that could be unambiguously identified in any combination.

Rajagopal helped develop the technology while he was a student at Caltech, and ChromaCode exclusively licenses it from the university. Although early development was supported by Caltech, ChromaCode has since completed Series A and Series B funding rounds, raising $15 million.

Specifically, Series A was completed in mid-2015 and the firm raised $2.5 million. The round was led by Domain Associates, whose previous successes include Amgen, Applied Biosystems, and Biosite, Gosch said, and those funds were used to open the business and complete a prototype of the HDPCR technology.

In early 2017, the firm completed a Series B round, raising $12.5 million, led by "one of the largest VC firms in healthcare, New Enterprise Associates," said Gosch. The Series B funds are being used to complete product development and prepare for commercialization in late 2018, he added.

The ChromaCode technology has also been presented in posters at recent conferences.

At the Association for Molecular Pathology annual meeting last November, the firm presented data from collaborations with researchers at USC's Keck School of Medicine and Dartmouth-Hitchcock Medical Center that showed HDPCR’s ability to expand the multiplexing capability of traditional real-time PCR instruments and described the performance of HDPCR assays for the detection of common respiratory pathogens from nasopharyngeal swab specimens.

In one of these posters, the respiratory panel was designed to detect 12 viruses – respiratory syncytial viruses A and B, influenza A, A H3, and A H1, influenza B, rhinovirus, human metapneumovirus, adenovirus, and parainfluenza virus 1, 2, and 3 — that were detected as sets of three per channel in four color channels.

The test used the QuantStudio 7, ViiA7, and ABI 7500 Fast instruments and sets of synthetic samples, and it found high positive and negative percent agreement and an overall concordance of 99 percent.

Looking ahead, the way in which a low-cost alternative for multiplexing might impact an already dynamic syndromic panel market remains to be seen.

Investment analysts at Piper Jaffray found in a recent survey that of 85 microbiology labs currently using multiplex PCR, 64 percent own BioFire systems, while 28 percent and 8 percent own Luminex Verigene and Genmark platforms, respectively. Of the 25 labs in the survey that plan to add or expand existing systems this year, 20 said they will buy a BioFire platform, with one saying it will purchase a Genmark and one planning to get a Luminex system.

Meanwhile, ChromaCode estimates that there are more than 80,000 qPCR instruments in the world that its technology could now enable to run midplex panels for both clinical and research applications.

ChromaCode will have a booth at the Association of Public Health Laboratories conference this week, Wilch said, and the firm plans to have a significant presence at the Association for Molecular Pathology annual meeting, including a booth, four posters, and a workshop.

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