NEW YORK – Owlstone Medical has been developing a menu of breath-based tests using parallel approaches to detect in breath endogenous biomarkers of disease and measuring signals produced as the body metabolizes specially prepared solutions.
The Cambridge, UK-based firm is closing in on the commercialization of its Libra test that uses a volatile organic compound (VOC) probe for the early detection of liver disease while it conducts clinical trials for its Evolution test that uses a VOC probe for the early detection of lung cancer. Meanwhile, the company recently inked a five-year research agreement with the US Food and Drug Administration to develop tools to identify in breath samples VOCs that could be used in diagnostic tests.
Owlstone CEO Billy Boyle said that the research collaboration with the FDA will involve the development of methods for identifying individual compounds from breath samples, confirming that those potential biomarkers are exhaled in breath and determining the concentration ranges of those substances in healthy controls.
The company recently announced that the work will include the development of a common set of analytical methods that breath researchers could use as a reference and that the expanded use of breath-based testing could increase access to testing in rural and economically challenged areas. The collaboration also includes the development of Owlstone's Breath Biopsy VOC Atlas database of identified and quantified compounds in breath.
The FDA said in an email that the agency plans to develop the analytical chemistry methods to identify chemicals in complex gaseous mixtures, including breath samples, using gas chromatography-mass spectrometry (GC-MS). The methods will be publicly available.
The agency noted that it is not identifying individual biomarkers or developing any tests, but rather, the project is meant to help accelerate medical technology innovation through the development of common methodologies and tools that can reduce the risks of early product development and aid product design. It also noted that no funding amounts are attached to research collaboration agreements.
In addition, the FDA and the Bill and Melinda Gates Foundation announced in June a partnership with similar goals of identifying analytical methods that could aid the development of breath-based diagnostic tests.
Owlstone officials, including Boyle, wrote in an article published earlier this year in the journal Metabolomics that about 1,500 VOCs have been identified from breath samples, yet endogenous VOCs in breath have not yet been used as biomarkers in clinical testing. Without standardized methods to collect and analyze breath samples, the production of reliable VOC data has been challenging.
"If the association between the production of VOCs in the body, their presence in breath, and the relationships between specific VOCs and physiological states are established, this could support breath as a robust metabolomic platform for clinical biomarker analysis, similar to blood, urine, and fecal sampling," the authors wrote.
Among the challenges, the authors said that contamination can originate from ambient air or testing equipment, and untargeted breath biomarker discovery studies have resulted in tentatively identified VOCs that can be misidentified through differences in methodologies and instrumentation compared to the reference libraries. A multitude of researchers has worked on the detection of lung cancer through VOCs, yet "there are currently no clinically validated breath biomarkers or tests suitable for lung cancer screening due to historical issues with standardization."
Other firms have also recently reported progress in bringing to market tests that use breath samples and mass spectrometry to identify disease. Maryland-based biodefense and medical device firm Zeteo Tech, for example, recently reported the completion of a proof-of-concept study on the use of mass spectrometry to identify protease biomarkers that are associated with lower respiratory tract infections. Tampa, Florida-based startup Detect Ion said in August it had forged a partnership with the Moffitt Cancer Center for the development of tests that use mass spec to identify VOC biomarkers for the early detection of lung cancer.
Connecticut-based startup DiagMetrics, meanwhile, has been developing infectious disease and critical care tests that use exhaled breath condensate and molecules to bind with targets, and biosensors. University of Minnesota spinout Vocxi Health also has been developing a breath-based lung cancer test, although the firm is using biosensors for the detection of VOCs.
Owlstone has developed its Breath Biopsy platform for the detection of VOCs using its ReCiva Breath Sampler for the capture of VOCs on breath in cartridges that contain sorbent tubes and GC-MS for biomarker identification. In 2021, the firm launched from its UK lab a breath-based digestive health testing service that uses gas chromatography to detect concentrations of hydrogen and methane biomarkers to aid the diagnosis of conditions including small intestine bacterial overgrowth and carbohydrate absorption issues.
The company also recently launched its FDA-registered OMED Breath Analyzer, which is available in the UK and US for the quantitative measurement of hydrogen and methane in breath to aid the monitoring of digestive health and treatment progress.
Boyle said that Owlstone expects to launch in the UK late this year its Libra test for the early detection of liver cirrhosis through the metabolism of limonene in the liver. The test involves drinking a beverage containing limonene, and 40 minutes later, the patients with impaired liver function will have elevated limonene concentrations in their breath.
"If someone has chronic liver disease, then the concentration of that chemical on the breath should be much higher compared to those that are healthy," he said.
With the FDA approval this year of Madrigal Pharmaceuticals' Rezdiffra (resmetirom) as a treatment for metabolic dysfunction-associated steatohepatitis (MASH), also known as nonalcoholic steatohepatitis (NASH), "it becomes more pressing that you're able to identify those people that do have chronic liver disease so they can be selected for therapy," he said.
He said that existing blood tests for MASH are not very sensitive, and Libra has comparable performance to imaging-based alternatives.
The company also has an ongoing Phase II clinical study for its lung cancer screening test that would be used for early detection in high-risk asymptomatic patients. The commercial test will use inhaled D5-ethyl-βD-glucuronide as a probe for lung cancer. The tumor-associated enzyme β-glucuronidase will metabolize the probe into D5-ethanol that can be detected as a signal that a tumor is present.
Boyle said that blood-based early cancer detection tests are used for the detection of biomarkers that can be shed in miniscule amounts during early stages of the disease and may be absent from a sample. Owlstone, in contrast, has taken a similar approach to the methods used in a PET scan of introducing a substrate with enhanced uptake in a tumor.
"We're trying to take that same principle and say, 'Why don't we introduce a chemical probe that goes to the tumor and is targeting the specific mechanism of the tumor and then releases a signal molecule?'" he said.
The firm also announced in August that it had received a $5 million equity investment and $1.5 million in grant funding from the Gates Foundation to support the identification of breath-based biomarkers of tuberculosis and HIV and test development. Additionally, it said in May 2023 it had inked a contract with the US Department of Defense to develop its handheld instrument for the detection of bacterial and viral respiratory diseases in challenging environments.
Boyle said that Owlstone is focused on the initial launch of its tests within the UK followed by expansion into the US. He expects that the firm's Libra test will be available in the US in 2026.
For now, the company is working with the FDA to move the field of breath-based testing forward by helping to set standards for the discovery and confirmation of endogenous biomarkers. Boyle said that he expects, however, that Owlstone's approach of using exogenous probes to generate and analyze a detectable signal will for the next few years provide an easier path for companies in the space to bring tests to market.
"We're more likely to see tests on the market if those approaches are adopted," he said.