NEW YORK (GenomeWeb) – Now a publicly traded company with its first assay on the market, Biocartis has set an ambitious agenda to expand its product menu and to build out its flagship molecular diagnostics instrument.
In the past year, the company went public on the Euronext Brussels exchange and launched its first in vitro diagnostics platform, called Idylla, along with the first assay for the instrument targeting BRAF mutations. Now flush with €115 million ($128 million) in proceeds from its initial public offering, the Belgian firm is set to launch additional assays for oncology and infectious diseases, and a dedicated platform for sepsis testing.
Additionally, Biocartis is developing liquid biopsy assays for cancer detection while also developing new versions of Idylla and preparing its entry into the US market. The platform is available currently only in Europe and a few other select geographies.
"The next key activity of the company is to make sure that we develop at a reasonable speed, the oncology and infectious disease menu," Biocartis Founder, Executive Chairman, and CEO Rudi Pauwels told GenomeWeb recently, adding that about half of the proceeds from the IPO will go toward product development.
According to Pauwels, Biocartis plans to launch four to five assays each year for the next several years for use on Idylla. The automated sample-in, result-out system is designed to work in any laboratory setting, allowing for decentralized molecular testing, and generates results in between 40 minutes and 2.5 hours. According to the company the platform can currently simultaneously detect up to 30 molecular targets in a single cartridge, and the company is developing specific test protocols to detect more than 30 targets per sample.
Its launch marked a milestone for Biocartis following nine years of development dating back to work at Royal Philips Electronics, which developed and owned the technology before selling it to Biocartis in early 2010. The launch of Idylla had earlier been slated for late 2012.
Transitioning from a technology development shop to a commercial entity with a focus exclusively on the IVD market, Biocartis has "come out of the gate," said Pauwels, who stepped away as CEO in 2011 but returned to the role in 2013 after Nayan Greg Parkekh resigned. "The Idylla system is ready, the first assay is on the market, [and] manufacturing is there."
Assays ahead
In initially targeting BRAF mutations for its first assay, Pauwels said that the BRAF testing space may not be the biggest, but "it is an extremely clinically useful example of high-precision, targeted medicine."
He added that the cancer space provides an opportunity for Biocartis to combine fast results with "good multiplexing" focused on biomarkers that are clinically actionable and reimbursable.
In order to evaluate the clinical utility of the BRAF test, Biocartis collaborated with European labs and hospitals, ran more than 600 melanoma tumor samples on Idylla, and then compared the results with other routinely used methods, including home-brewed tests, as well as US Food and Drug Administration-approved tests.
According to Pauwels, the BRAF assay never missed a mutation and even found some that the other technologies didn't. Biocartis confirmed its results with ultra-deep sequencing or some other "specialty" method, he said.
Since bringing the test to market, Biocartis has forged about a dozen distribution deals covering Europe, where it has a presence in every country. Pauwels said that with only one assay in its portfolio, Biocartis has taken a slower approach to its commercialization plans, but that will change as a result of its IPO. About 15 percent of the proceeds, or more than €17 million, will go toward expanding the company's sales and marketing efforts, he said.
Next in Biocartis' pipeline is a KRAS test for colon cancer, anticipated to be available in Europe during the summer. It will use formalin-fixed, paraffin-embedded tissue and investigate all 21 mutations in one cartridge, with results available in less than two hours.
Slated for launches later in the year are an NRAS assay, a combo NRAS/BRAF test, and an NRAS/BRAF/EGFR492 assay. Each assay will be for colon cancer detection.
Further into the future, a lung cancer panel is expected in 2016, as well as a panel for microsatellite instability.
Those assays are based on real-time PCR technology, but Biocartis also anticipates launching cell-free, or liquid biopsy, tests for KRAS and NRAS mutations, as well as a liquid biopsy panel for lung cancer, next year.
The liquid biopsy assays will be designed to enable physicians to monitor the cancer in a patient, Pauwels said. In the infectious disease space, viral load tests for ailments such as HIV and hepatitis C have enabled patient monitoring and radically changed patient care, Pauwels said. However, similar tests for cancer have so far proven elusive.
"We are still looking at disease progression, maybe the mass of tumors, and that is something you measure every three, six, nine months," he said, adding such an approach contradicts precision medicine, which is based on matching the most effective drug to individual patients.
Biocartis' initial focus is on dynamic modeling, meaning "we have, now, molecular profiling of the cancer, we know what the cancer-driving mutations are … Now, can we look after a few months whether [the number of BRAF mutations] goes down or comes up," he said.
Biocartis is currently developing a cartridge for Idylla that can process plasma and measure BRAF and KRAS mutations with the idea that the liquid biopsy assays would be available for research use only. At the recent American Society of Clinical Oncology annual meeting, Biocartis presented data indicating that BRAF mutations monitored in plasma from metastatic melanoma patients on Idylla were "significantly associated with treatment response and progression," the firm said in a statement.
In a meeting abstract, Biocartis and its collaborators at University Hospital Brussels said that they analyzed 232 plasma samples from 41 patients with metastatic melanoma for circulating levels of mutant BRAF.
Therapeutic monitoring of BRAF mutant cell-free DNA was performed on 33 patients who were treated with BRAF/MEK targeted therapies Yervoy (ipilimumab) or Keytruda (permbrolizuman). Among other things, the researchers found that during BRAF/MEK targeted therapy, an increase in the BRAF mutant ctDNA fraction was detected in seven of 12 patients prior to disease progression on imaging, and in two of 12 patients concomitant with disease progression on imaging.
A month later, an increase in BRAF mutant ctDNA fraction predicted disease progression in 67 percent of cases, and within the following two months, an increase in BRAF mutant ctDNA fraction predicted disease progression in 100 percent of cases, the researchers said.
At the same time, undetectable BRAF mutant ctDNA predicted the absence of disease progression in as many as 91 percent of the cases.
Based on the results, Biocartis and its collaborators determined that "BRAF mutant ctDNA likely reflects the BRAF mutant proliferative tumor burden and holds promise as a therapeutic monitoring tool for [patients] with advanced BRAF V600 mutant melanoma."
In addressing the oncology market, Biocartis' goal is not to compete with firms such as Foundation Medicine, which look at hundreds of genes in one assay, Pauwels said. Because his firm is coming into the space a little later, its strategy is to use markers that are clinically actionable, physicians know how to interpret, are in the care guidelines, and are reimbursable.
"We couldn't [develop] a platform, and then spend two or three years arguing with insurance companies," he said.
Pauwels said that the price for its oncology assays will be between €120 and €350, compared to the thousands of euros for similar assays offered by competitors.
"We want to make sure they will be below their true economic costs of running the assays," he said. "It's really a philosophical choice … if we innovate, we must also innovate [so that] the healthcare system is sustainable."
Meanwhile, the value proposition of Idylla in infectious disease is that it would be able to look at panels of different pathogens, or syndromic panels. With one panel, Biocartis would be able to differentiate diseases with similar symptoms, Pauwels said.
"We want to bring for particular clinical situations — let's say respiratory tract infections, GI infections — panels that cover a wide range of viruses," he said. "We want to have one blood drop and one drop sample, 200 ml, to measure all of that."
The Idylla cartridge, he said, has five individually controlled PCR chambers "and each can be analyzed by six different colors." With precise temperature control, Biocartis can apply high resolution melt analysis in combination with "proper assay design" to enable Idylla assays to report 30 different parameters.
Biocartis anticipates launching assays for influenza, respiratory syncytial virus, and influenza virus surveillance next year, and viral load tests for hepatitis B and C, and HIV in 2017.
In late May, Biocartis and Fast-track Diagnostics announced they would collaborate on developing multiplex tests for infectious diseases for use on Idylla. The first assay is expected to be a respiratory panel for detecting viral and bacterial targets in upper respiratory tract infections.
Also, Biocartis has what Pauwels said, in essence, is a developer edition of Idylla with special software and cartridges to facilitate assay development with collaborators such as Johnson & Johnson.
At the Clinical Virology Symposium in May, researchers from J&J subsidiary Janssen Diagnostics and Biocartis presented data for tests for hepatitis C viral load, influenza A/B and RSV, and influenza surveillance, demonstrating high specificities.
Additionally, during the summer Biocartis plans to submit to the FDA its Ebola assay for emergency use authorization.
Going after sepsis
Lastly, the company plans to bring new technology aimed at sepsis with a version of the Idylla platform called Idylla Enrich that would be able to identify sepsis-causing pathogens and generate results in about two hours.
Pauwels explained that the challenge in sepsis is the ultra-low concentration of such pathogens to be found in whole blood, making detection difficult even with molecular methods.
Biocartis is developing Idylla Enrich to work with 5 to 10 ml sample of whole blood that is placed in a cartridge containing new proprietary chemistry "that essentially is solving the needle-in-the-haystack problem by destroying the hay and keeping the needles intact," Pauwels said.
The cartridge will destroy everything that is human in the whole blood, such as red blood cells, white blood cells, and free DNA. "All of that will be degraded," Pauwels said, and what remains in the cartridge will then be filtered through a size-exclusion filter. Because the system takes a generic approach, it wouldn't require a capture probe, he said.
He declined to provide further details about the method, but said that it has demonstrated a nearly 100 percent recovery rate with 10 colony-forming units per ml. "So we have been showing that we can physically indeed collect … a handful of bacteria versus the blood from the system."
The chemistries have been developed as has the basic technology, and the company is in the industrialization phase of development with an anticipated launch in 2017 or 2018. "It's a big program for Biocartis," Pauwels said.
Also on the instrument front is the development of a high-throughput version of Idylla that could be run 24/7. As diagnostic development costs continue to rise, "it would be a great advantage if you have to do your development only once," Pauwels said, adding that the new platform will be developed to be "extremely scalable."
Because each instrument will be equipped with computer memory, it will be "quasi-autonomous," and Biocartis will be able to spec the modules based on the customer's need to run more samples, he said, adding the system would provide a new path for placing Idylla technology in settings, such as pharma conducting clinical trials, where there is a need to run higher volumes.
He also noted that separate assays would not be needed for the higher-throughput Idylla. In that sense, Biocartis is stepping away from the traditional molecular diagnostic model of batch-based systems and moving into "a category-agnostic class" where the modules that are built for the instrument use the same cartridges and the same instrument technology.
The firm is in discussions with engineering contractors to develop the high-throughput platform, and while Pauwels said no definite timeline has been determined for its launch, "it's not a five-year program."
In an effort to maximize the collective data generated on separate Idyllas, Biocartis is also developing what it calls "diagnostic grids," a web-based network that would connect different Idylla systems globally. Such a network would allow the company to monitor the platforms and allow users of the systems to share data and other information with each other.
"And that would be very interesting if you see what the challenges are in Ebola [or] pandemic flu," Pauwels said, noting that despite efforts during the past decade to create laboratories across the world, "we still see that information is coming in scattered, not standardized."
In the case of the Ebola epidemic in West Africa, he said, such "diagnostic grids" would allow Biocartis to monitor the evolution of the disease and the development and utility of assays utilizing Idylla. The firm is currently testing the use of such grids in Africa to determine the level of training required, whether the connectivity is good enough, and the logistics behind such an effort.
"So there's a lot of field work going on behind the scenes, going on at Biocartis to prepare for this idea," Pauwels said.
Post-IPO
Biocartis is funding its ambitions through its IPO, which came shortly after it raised €64.5 million in private financing in September. While the company has its share of love among private investors — less than a year before the €64.5 million financing, it raised €30 million in Series E equity financing — Pauwels said that the public markets were the next logical step in growing the company.
Before going public, though, Biocartis took steps to go leaner by spinning out its multiplexed detection technology platform called Evolution, formerly called DMAT, into a joint venture called MyCartis with Pronota.
Biocartis, Pauwels said, had determined there were fewer synergies between the Idylla business and the Evolution business than it had originally imagined. With Idylla, Biocartis "went directly into the IVD route with a separate manufacturing line, with a separate commercial infrastructure," he said, whereas Evolution was being developed as an open system that researchers could use to create their own assays.
The potential dilemma was that having two differentiated platforms, each with their own markets, would confuse investors. "It's already a big ambition that Biocartis has," Pauwels said. "If you then try to … come into the research market, which is a totally different market [with] a different approach," investors would not know how to evaluate the firm.
"At this stage, it needed to be a very clear investment story to the investors," he said. Pauwels did not completely reject the idea that Biocartis may acquire MyCartis in the future, "although I think right now Biocartis is focused maximally on … bringing more content to Idylla.
It also is building up its commercial infrastructure. In addition to selling its BRAF assay and Idylla in Europe, Biocartis has distribution deals in Australia,New Zealand, and Mexico. It currently has about 35 sales and marketing people, which includes about a dozen direct sales people, and plans to increase the sales and marketing staff to about 45 by the end of the year, Pauwels said.
Biocartis had sold about 100 Idyllas, including 80 that were deployed for the Ebola crisis inAfrica. The list price for Idylla is between €40,000 and €50,000 depending on how many systems a customer buys. Biocartis also has an instrument rental model.
The company's initial customer segment is pathology labs operating in oncology, as they are "essentially the gatekeepers and the people who prepare the FFPE samples" and analyze it before shipping it to an "adjacent lab," Pauwels said. "For those labs, we can now offer a direct solution. They can use their existing people, they don't need a specific design infrastructure, and more importantly, they can provide information quickly."
Though making the centralized lab its initial target customer may seem counter-intuitive, Pauwels said that Idylla complements instruments that such labs already have by offering them the ability to report BRAF testing results in about 90 minutes, rather than the days or a week it could take with other technologies.
The selling point of Idylla for pathology labs is that they would not have to invest in a PCR infrastructure, according to Pauwels. The labs would be able to use the same lab space, while personnel could be trained in about an hour to use the system.
For its infectious disease products, Biocartis plans to hit the hospital setting, as well as rapid response labs and microbiology labs, he added.
Aside from the Ebola assay planned for emergency use authorization, Biocartis aims to enter the US market in 2016 with a respiratory panel. Along with commercialization partner J&J, it will file the 510(k) submission with the FDA for the panel along with the Idylla platform, Pauwels said.
Also in the pipeline for the US are FDA submissions for its oncology assays and liquid biopsy assays for research use only.
Pauwels said that Biocartis does not plan to offer the BRAF assay launched in Europe as a standalone test in the US. Instead, BRAF will be included in a combo panel in the US "because it made more sense to combine it with NRAS, for example."
Regardless of the disease area or technology application, he said that one philosophy drives Biocartis' end goal, "to make qPCR sample-to-results molecular diagnostics much more accessible on a global basis," Pauwels said. "Where today, we see maybe limitations in costs [and] in required infrastructure, that's where we want to push the frontier a little bit."