NEW YORK – Oxford Nanopore Technologies has been working on a tuberculosis drug resistance sequencing assay that it hopes will become its first in vitro diagnostic test developed in house.
Dubbed Ampore-TB, the assay will enable TB drug resistance profiling directly from sputum samples in about six hours using the GridIon platform and an automated analysis pipeline supported by Epi2me, Oxford Nanopore’s cloud-based bioinformatics platform.
An Oxford Nanopore spokesperson told GenomeWeb that Ampore-TB is currently undergoing internal validation and is slated to be released globally as a research-use-only product later this year. The company plans to obtain regulatory approval for the test under the European Union’s In Vitro Diagnostic Regulation and from the US Food and Drug Administration but did not disclose a timeline.
The GridIon platform will meet the ISO 13485 standard in 2025, the spokesperson also noted, but that instrument will not be specific to TB testing and will only be available to specified partners.
According to Emma Stanton, senior VP of clinical at Oxford Nanopore, a major reason for the company to select Ampore-TB as its first prospective IVD test is "a very clear call to action" from the World Health Organization, which published a new guideline in March recommending the use of targeted next-generation sequencing for the diagnosis of drug-resistant TB.
The guideline specifically highlighted Oxford Nanopore’s Ampore-TB, along with the Deeplex Myc-TB test from Genoscreen in France and the TBseq assay from Hangzhou ShengTing Medical Technology in China.
Oxford Nanopore has yet to disclose Ampore-TB’s technical specs. Stanton declined to comment on the final format of the assay, citing the early stage of its development.
According to the WHO’s guideline, Ampore-TB, which analyzes sputum samples, is a targeted NGS test developed for the simultaneous identification of mycobacterial species and the detection of Mycobacterium tuberculosis complex (MTBC) genetic variants that have been linked to antimicrobial resistance. The guideline noted that Ampore-TB has met the performance criteria to profile resistance to rifampicin, isoniazid, fluoroquinolones, linezolid, amikacin, and streptomycin.
The assay sequences 27 amplicons, including 24 drug resistance targets, a genotyping target, a non-tuberculous mycobacteria identification target (hsp65), and an internal control, using the Oxford Nanopore GridIon device.
Additionally, the guideline noted that the Ampore-TB workflow includes pre-installed analysis software that can automatically generate a report of the test results.
Stanton said Ampore-TB is being developed by Oxford Nanopore internally, with some IP licensed from the UK's Quadram Institute, which the company has been collaborating with to develop the workflow. Once the test is ready, Oxford Nanopore plans to leverage its existing partnership with French in vitro diagnostics firm BioMérieux to help roll it out globally, tapping into the partner's logistics network.
"[BioMérieux’s] role is in helping us to commercialize and distribute the test; they are not developing the test," said Stanton. "Essentially, we will give them the fully developed test, and they will be responsible for distributing it."
"After a year-long partnership with Oxford Nanopore, significant progress has been made towards developing a research-use-only (RUO) sequencing product for detecting drug resistance in tuberculosis," Charles Cooper, executive VP and chief medical officer of BioMérieux, wrote in an email. "This achievement results from an excellent collaboration between the teams involved. It marks an important milestone in the development of an in vitro diagnostic (IVD) test."
While Cooper’s statement appears to suggest BioMérieux is involved in the development of Ampore-TB, an Oxford Nanopore spokesperson confirmed that the test is completely developed in-house by the company. The spokesperson also said BioMérieux is "sharing their indispensable experience on infectious disease diagnostics" with Oxford Nanopore.
Stanton said Oxford Nanopore will have to get regulatory approval from each of the countries it plans to sell Ampore-TB in. The goal is to launch the test in waves, she said, and her team has already begun conversations with regulatory authorities of those countries where the test will first become available.
She did not disclose the names of those countries and did not comment on Oxford Nanopore's plans for regulatory approvals in low- and middle-income countries, where TB testing is in highest demand.
Ampore-TB is not the only sequencing-based TB test highlighted by the WHO. The TBseq test from China’s Hangzhou ShengTing Medical Technology, for instance, also uses the Oxford Nanopore MinIon or GridIon platform. Meanwhile, Genoscreen’s Deeplex Myc-TB can be performed using the Nextera XT and DNA Flex library preparation kits and the Illumina ISeq 100, MiniSeq, MiSeq, or NextSeq sequencers, according to the guidelines.
Besides the advantages of nanopore sequencing for TB testing, such as its fast turnaround time and accessibility, the WHO guideline also pointed out some "feasibility challenges" for the technology, including library preparation being "quite complex" and "the need for improved computer analysis and storage capacity."
Beyond targeted NGS, WHO’s guideline also highlighted various other molecular technologies for rapid TB diagnosis and resistance detection, including moderate-complexity automated nucleic acid amplification technologies (NAATs) for the detection of TB and resistance to rifampicin and isoniazid, lateral flow antigen detection tests, low-complexity automated NAATs for the detection of resistance to isoniazid and second-line anti-TB agents, and line-probe assays.
The development of Ampore-TB is spearheaded by Oxford Nanopore Diagnostics, a subsidiary of Oxford Nanopore that was established in 2022 but has largely remained silent since then.
"We haven't spoken about [OND] a lot in the public domain," said Stanton, who heads the subsidiary. While the creation of OND was "necessary for many legal, contractual, and regulatory requirements," she said, her team is "deliberately embedded across in the parent organization" and works closely with the rest of the company.
According to Stanton, the OND team includes people working in regulatory affairs and quality assurance. It also has employees with "domain expertise" across various clinical areas, as well as "other people who [have] experience from our competitors in taking sequencing platforms into clinical markets," she added.
Beyond its in-house development efforts, Stanton said an integral part of Oxford Nanopore’s clinical strategy is to forge partnerships with other institutions and companies. Although Ampore-TB is on track to become the company’s first own IVD product, infectious disease is "the smallest target addressable market" for the firm, she said, adding that the company is also eyeing other disease areas such as oncology and transplant diagnostics, as well as rare diseases and other genetic disorders.
Stanton highlighted a series of clinical partnerships the firm has already forged, such as an agreement with Day Zero Diagnostics to develop a diagnostic solution for sepsis, collaborations with Hungarian firm Omixon and Dutch company GenDx to develop HLA transplant diagnostic tests, and a deal with Swiss manufacturer 4bases to develop tests for BRCA1 and BRCA2 breast and ovarian cancer susceptibility genes.
At its annual user meeting in London this week, Oxford Nanopore is holding a dedicated "Clinical and Biopharma Day" for the first time that is distinct from the main event, signaling the company’s increasing focus on clinical and applied markets.
Still, with Ampore-TB’s IVD timeline unclear, it appears that Oxford Nanopore has a way to go to become a diagnostic test manufacturer.
"Whilst we are on a path to have diagnostics, this is really about showcasing and sharing where we are [with the technology]," Stanton said. "It's a Clinical and Biopharma Day, not a Diagnostics Day, quite deliberately."