LEO O’CONNOR DECEMBER 18, 2019

NEW YORK – After years developing technology to do multiplex testing for infectious diseases, Enigma Diagnostics shuttered about two years ago without much fanfare. But thanks to a former investor in the company, Enigma’s technology may live on.

The investor, Robert Clink, had invested a large part of the £140 million ($186.8 million) that Enigma devoted to the development of its Enigma MiniLab molecular diagnostic platform, originally invented in the UK Ministry of Defence Science and Technology Laboratory. But after several years of platform and assay development, Enigma went into liquidation in 2017, short of funding needed to further develop and launch its tests, Clink said.

Clink and his colleagues are now trying to bring Enigma’s work back to life and have founded Oxfordshire, UK-based Rapid Diagnostics to purchase Enigma’s assets and technology.

“Our primary aim is to enable the technology to reach the marketplace,” said Clink, Rapid Diagnostics’ chairman and CEO.

Before Enigma went under, its platform demonstrated high accuracy at the point of care in preliminary trials. The core technology leverages single-tube magnetic bead- and fluidic-based nucleic acid sample preparation, and electrically conducting polymers — organic polymers that conduct electricity — for direct thermal cycling during PCR. It employs single-use disposable cartridges that can be stored at ambient temperature and contain all reagents necessary for sample extraction, amplification, and detection.

The system, now called the Rapid MiniLab, consists of a control unit with up to six independent processing units. Each processing module consists of six detectors and two light-emitting diode excitation sources, enabling highly multiplexed RT-PCR processing of samples, the firm said.

Diagnostic tests on the platform are conducted using disposable cartridges capable of adaptating to a broad range of test types, according to Rapid Diagnostics. The MiniLab is automated for use at the point of care without the need for separate sample preparation or pipetting steps, which is important when trained healthcare staff are not available to administer testing, Clink said.

Rapid Diagnostics’ immediate goal is to secure an equity investor and joint venture partner, and to obtain clearance for the MiniLab platform and its first assays with the China National Medical Products Administration, he added. The firm has hired Lynx Financial, a Chinese financial advisor, to help it select suitable diagnostic companies to target for investments and partnerships.

The point-of-care platform developer has an existing manufacturing and engineering facility in Didcot, Oxfordshire in the UK, and is looking to establish manufacturing and assembly facilities in China for components of a multi-drug resistant TB (MDR-TB) test that could receive clearance in the first quarter of next year from the China NMPA, Clink said.

Many diagnostic experts believe that more effective diagnosis of active TB is needed to help mitigate the growing burden of the disease, as well as rapid screening systems that are affordable and easy to use are needed.

David Boyle, a microbiologist and scientific director in the diagnostics program at PATH, said in an interview that one of the issues with getting additional tests into the market is that many companies present promising products following field evaluations of a device for which “they have no capacity to do manufacturing at any reasonable scale.”

And for active TB testing, it will be challenging for any company to compete with Cepheid because the firm has such as a large global footprint, he said.

For latent TB testing, Qiagen and Oxford Immunotec are the market leaders.

Numerous other companies are also developing products for TB detection, including Co-Diagnostics, which said recently it received regulatory clearance from Indian regulators through its joint venture CoSara Diagnostics.

Cleveland-based Diascopic said recently that it has been awarded a $225,000 grant from the National Institutes of Health to validate its portable, automated digital pathology platform for the detection of tuberculosis, and Cambridge, UK-based Rapid Biosensor Systems is targeting the clinical need for more rapid and affordable tuberculosis screening by combining breath sampling with evanescent-wave optical sensing.

The Foundation for Innovative New Diagnostics and supply chain firm LLamasoft recently announced a partnership to develop an open-access tool to identify cost-effective approaches to increase diagnostic reach in low- and middle-income countries. The tool will guide placement of diagnostics aligned with treatment capacity for tuberculosis and other diseases.

That said, any competition in the market for active TB testing is a positive development, Boyle noted, adding that if Rapid Diagnostics selects a specific geographic market like China and has its tests manufactured there, “it may have a cost advantage.”

Rapid Diagnostics did not disclose estimated pricing for its instrument and consumables but said it anticipates they will both be available at a low cost.

Cepheid in its sight

Boyle’s skepticism about Rapid Diagnostic’s ability to play against Cepheid notwithstanding, Clink said his firm envisions positioning its platform as a competitor to Cepheid’s GeneXpert tuberculosis assay, the established test in the market for active infection testing. Its MTB/RIF test can detect Mycobacterium tuberculosis infections and resistance to rifampicin within about 80 minutes.

According to Clink, though, despite the test’s popularity and market penetration, more such platforms are needed to satisfy demand in a growing market for TB testing, adding that testing needs are particularly acute in low resource regions, including in the company’s initial target market, China.

Rapid Diagnostics said that China’s NMPA has agreed to fast track the approval of its multi-drug resistant tuberculosis test, which uses sputum samples.

The technology platform had previously shown high sensitivity and specificity in clinical settings. In a 2017 study published in Tuberculosis, theChinese Center for Disease Control and Prevention investigators reported that the Enigma ML TB assay “is an accurate rapid test in terms of increased sensitivity for detecting MDR-TB patient from sputum sample[s].”

In a 2016 study published in the Journal of Clinical Microbiology, investigators at two London hospitals evaluated the performance of the Enigma MiniLab assay for influenza A and B viruses and respiratory syncytial virus, comparing it to the results of testing with a Luminex centralized laboratory respiratory virus panel. The positive and negative percent agreement for influenza A virus were 79.2 percent and 99.4 percent; for influenza B virus they were 100 percent and 100 percent; and for RSV they were 98.5 percent and 94.5 percent. The investigators said that assays such as the Enigma MiniLab “may have the potential to influence clinical decision making at the point of need and may result in a reduction in unnecessary antibiotic use, targeted use of antiviral drugs for influenza virus (and potentially also for RSV in the future), and rational use of isolation facilities.”

Clink noted that the time to result of the platform is currently 45 minutes and the firm anticipates reducing that to 35 minutes, or less, with new chemistry and additional R&D.

At Enigma, the platform developers envisioned launching highly multiplexed PCR assays including large panels to test multiple infectious diseases, but that ambitious goal combined with misallocation of funds contributed to the firm’s downfall, Clink said.

He and his colleagues have developed a more focused strategy, believing that the platform’s potential lies in developing and launching it for a narrower set of testing applications with demonstrated clinical needs — including RSV in addition to TB in human testing, and Brucella in livestock testing.

The fully automated Rapid MiniLab features similar technology to that used in the Enigma FL, or field laboratory, platform that Enigma Diagnostics designed in collaboration with the UK Ministry of Defense and launched in November 2008 for field-based testing in the veterinary and defense markets.

In 2016, Enigma announced it had received CE IVD marking for its Enigma ML system and first assay, a combined molecular test for influenza A/B and respiratory syncytial virus. That wasn’t enough to keep the company afloat, though.

Clink said he recognized that the technology had significant potential, reflected in published clinical validation results, and that prompted him to relaunch the company. Whereas Enigma Diagnostics wanted to develop and commercialize its diagnostic platform and assays by itself, Rapid Diagnostics believes that cooperation with other diagnostics companies is important to its future success. For example, the firm has identified potential partners as technology suppliers in areas where it doesn’t have a high level of expertise, such as reagent lyophilization.

In the US, it is seeking to collaborate with established diagnostic companies to help it achieve product launch, conduct market development activities, and develop a broader range of diagnostic assays. “We want to cooperate with others not only so that our products can reach the market, but so that they can do so in a better commercial sense,” Clink said.

Although the Enigma MiniLab was CE marked, placements of the system, now called Rapid MiniLab in European countries and geopraphies that accept the designation is not currently of interest to Rapid Diagnostics.

“The European market is quite congested with well-established platforms, which is why the open market in China is of more interest to us,” Clink said. Further, the firm wants to establish a firm financial footing before it expands to other geographies, he added. In the near term, Rapid Diagnostics has adequate funding to support its commercial activities, but in the medium and long term, it anticipates raising additional funds.