Breath Test for Cancer: Biomarker Screening is Underway

The thought that compounds in the breath could be measured and assessed to diagnose different aspects of pathology is an exciting prospect.

As part of the search for diagnostic tests that don’t rely on invasive tissue biopsies, breath biopsies are an attractive possibility for cancer diagnostic tests.

Like liquid biopsies, a breath test for cancer would remove risk and discomfort for patients, and makes continual monitoring more accessible.

To learn more about the breathalyzer platform being used in clinical trials to detect early cancer biomarkers, we spoke to Chris Claxton, head of investor relations at Owlstone Medical.

Michele Wilson (MW): Can you tell us about your mission at Owlstone Medical, and how the company came about?

Chris Claxton (CC): It is a stark reality that 1 in 2 people will get cancer. Some cancers are common but mortality is relatively low. In other cancers, survival rates are high because of effective screening programmes and treatments. The greatest problem lies with cancers, such as lung and colon cancer, which affect millions of people yet survival rates remain very poor. At Owlstone Medical, we recognize that better ways to treat cancer must be found, but more importantly, better ways to detect cancer earlier, when chances of a cure are dramatically higher. In cancer, survival rates when detected early are 10 times better and treatment costs are 10 times lower than if diagnosed late. We are addressing this by unlocking the enormous promise of breath-based diagnostics through the development and application of Breath Biopsy®, with the aim of saving 100,000 lives and $1.5 billion in healthcare costs.

In 2004, Owlstone Inc. was spun-out to develop and commercialize Field Asymmetric Ion Mobility Spectrometry (FAIMS), which was originally developed at the Engineering Department of Cambridge University by three individuals including Owlstone Medical CEO Billy Boyle, who ultimately became the founders of Owlstone Inc. That company proceeded to become a highly successful and profitable business that attracted substantial investment and contracts with the US Department of Defence, Department of Homeland Security and the UK Ministry of Defence.

Although the focus was initially on security and military applications initially, management had always been interested in exploring potential applications of the technology in healthcare. Given the very different development needs and customer bases of these two markets, it was decided to spin the medical business into a new entity and so in July 2016, Owlstone Medical was formed to develop and commercialize the platform specifically for diagnostic applications.

MW: Can you give us an overview of breath biopsies and the ReCIVA Breath Sampler?

CC: Every time you breathe out, 1,000s of chemicals called volatile organic compounds (VOCs), produced as the end product of metabolic processes within the body or as a result of chemicals from external sources such as diet or medication, are released. Owlstone Medical’s Breath Biopsy® platform operates by capturing and analyzing these VOCs, looking for the changes that can be characteristic of specific disease or indicate environmental exposure.

The Breath Biopsy platform includes: ReCIVA®, a proprietary non-invasive sample collection device; the company’s microchip FAIMS sensor; the world’s only commercial Breath Biopsy Laboratory, and the development of the world’s largest Digital Breath Biobank.

The ReCIVA® Breath Sampler can take stable breath samples anywhere, as the analysis of the sample is performed separately. Depending on the particular disease under investigation, the VOCs of interest could be present in different breath fractions. Pressure and CO2 sensors in ReCIVA®, provide real-time monitoring of the patient's breathing, allowing the relevant fractions to be selected and accurately collected, and which is controlled and powered by tethering the device to a laptop or tablet. Once the sample is collected it is shipped to our Breath Biopsy lab in Cambridge in the UK (we plan to open similar labs in the US and China) where the analysis is performed.

Developing a standardized device for breath sample collection was key to enabling breath analysis to be effectively deployed in clinical trials. The ReCIVA® Breath Sampler is now CE marked and in use in over 100 academic research groups and clinical labs around the world, including the LuCID Clinical Trial for lung cancer detection, the InTERCEPT colorectal cancer trial, and in collaboration with CRUK in the PAN cancer trial.

MW: Which lab techniques enabled the development of your platform?

CC: The core technology behind Breath Biopsy is Field Asymmetric Ion Mobility Spectrometry (FAIMS).

FAIMS is a variant of ion mobility spectrometry – a method of distinguishing charged gaseous molecules according to differences in the speed that they move through a buffer gas under the influence of an oscillating electric field.

MW: What was the biggest hurdle you had to overcome to get to this stage?

CC: The concept of using breath to diagnose disease is not a new one, however the application of breath biomarkers in medical diagnostics has been hampered in the past by a range of challenges. There’s a reason that with a very few exceptions we don’t go to the doctor’s office for breath testing today, and that is because the development of breath-based diagnostics is difficult. There is no single problem Owlstone Medical had to overcome in order to develop Breath Biopsy, but instead we had to build the entire workflow end to end. How are samples collected? How are they stabilized? How are they shipped? How is external contamination dealt with? How are samples analyzed? These are all issues that we had to tackle holistically.

In particular, we recognized that reproducibility is key for any analytical technique, and standardization of sample collection is a vital step in guaranteeing the comparability of results from different analysis methods. Therefore, the design for the Breath Sampler technology was inspired by discussions with more than 100 multi-disciplinary experts in breath diagnostics.

Today, with the platform established, the key challenge lies in biomarker discovery. Linking the 1000s of chemicals on breath with specific conditions such that they become effective biomarkers. This is the work that we are primarily engaged in, working with our academic and pharma partners. 

MW: How is the breath biopsy industry tracking as a whole? Which other diseases could potentially be diagnosed through a breath biopsy?

CC: Breath biopsy is a growing field generating more and more interest as across the life sciences. There is a tremendous drive to detect disease earlier and to help make the discovery and deployment of novel therapeutics mode effective. This need is what has led to the rapid growth of liquid biopsy and now those same drivers are impacting the breath space.

Cancer has been our starting point due to the acute need for screening tests that can be used to detect disease earlier. Our most advanced trial is the LuCID trial, looking for biomarkers for the early detection of lung cancer and to distinguish between malignant and benign nodules on the lungs. We are currently over half way through and up to 4,000 patient recruitment, taking place at 26 sites in the UK and Europe. No results have been published, but we are hoping to be able to issue preliminary results late this year or early next.

Additionally, we have underway the InTERCEPT trial for colon cancer screening, and in collaboration with CRUK (Cancer Research UK) we have launched the PAN Cancer Trial, studying early detection of different cancer types in breath. The clinical trial has initiated in patients with suspected oesophageal and stomach cancers and will expand to prostate, kidney, bladder, liver and pancreatic cancers in the coming months.

Beyond cancer we are working with partners in a wide range of disease areas. For example, our partnerships with AstraZeneca and GSK (GlaxoSmithKline) are in asthma and COPD (chronic obstructive pulmonary disease). We are also launching tests in the areas of environmental exposure and drug metabolism.

Chris Claxton was speaking to Michele Wilson, Science Writer for Technology Networks.