EOS Network participates in a focus group for the Quantitative Biomarker Identification for EoE (QuBIE) trial conducted by Cyted. This trial is exploring a promising tool that can potentially improve diagnostic and treatment care for Eosinophilic Oesophagitis (EoE). We talked with Sarah Killcoyne, the head of research and development at Cyted, who also serves as the Chief Investigator for the QuBIE study.

About Sarah Killcoyne

I’m currently the Director of Research and Development at Cyted here in the UK, where we provide a diagnostic service for early cancer detection using a sponge-on-a-string device called EndoSign®. My background is in computational cancer biology, so I come from a background in modelling for the identification of both the diagnosis and prognosis of cancers.

I did my initial training in biology at Colorado State University, US, and I worked for about ten years at a research Institute in Seattle studying a variety of diseases. One of the projects we were involved in was the Cancer Genome Atlas Project. This project was the first and largest cancer genome sequencing and analysis project to date, started in 2005. From there, I went to the Luxembourg Centre for Systems Biomedicine to complete my PhD.

I came to Cambridge to work with Rebecca Fitzgerald at the University of Cambridge to better understand specific cancers, such as oesophageal.

Rebecca Fitzgerald is a Professor of Cancer Prevention at the University of Cambridge and Director of the Early Cancer Institute. She still practices medicine as an Honorary Consultant in Gastroenterology at Addenbrooke's Hospital, Cambridge.

What is a 'Sponge-On-A-String' test?

A sponge with an attached string is both in a capsule and expanded compared to the ruler. Courtesy of Sarah Killcoyne.

At Rebecca’s lab, I was introduced to her device, a capsule sponge (now developed by Cyted as an EndoSign®  device) used to help diagnose patients with Barrett’s oesophagus, a pre-cancer disease. It consists of a small capsule about the size of a multivitamin with a dissolvable outside. The capsule is attached to the string. 

When you swallow the capsule, it dissolves and releases a small medical-grade sponge in your stomach. The released sponge is small, soft, and squishy. The nurse then pulls the sponge up, collecting cells along the entire oesophagus. 

Using the sponge was a massive change for patients with Barret’s disease. Before that, if you had reflux or Barrett’s, the primary way you were diagnosed and evaluated was using endoscopy, which is much more invasive than the sponge. 

Barrett's disease, also known as Barrett's oesophagus, is a condition in which the cells lining the lower part of the oesophagus change. This happens because of long-term exposure to stomach acid and bile that reflux into the oesophagus. Barrett's disease is not cancer, but it increases the risk of developing a rare type of oesophageal cancer called adenocarcinoma.

How might an EndoSign® be used for EoE?

sponge on a string test swallowing the capsule photo

Sarah Killcoyne swallows a capsule during the capsule sponge test.

The sponge in the EndoSign® device collects cells along with the entire length of the oesophagus, which means that we get a really rich biological sample for diagnosing not just pre-cancer but other diseases as well. EoE is effectively just a collection of cells in the oesophagus (in this case, eosinophils) that should stand out and be pretty uncommon compared to what’s normally there.

Eosinophils are a type of white blood cell that fights infections and allergic reactions but can also cause tissue damage and inflammation.

Eosinophilic Oesophagitis (EoE) is a chronic immune system disease that affects the oesophagus, the food pipe - the tube that connects the mouth to the stomach. It is caused by an allergic reaction to certain foods or allergens, which leads to a buildup of eosinophils in the lining of the oesophagus. This condition causes inflammation, scarring, narrowing, and difficulty swallowing. 

Patients with EoE currently require endoscopy, which is very invasive. Ideally, patients should get it fairly regularly. 

If we can use an EndoSign® device at least to monitor a patient who has EoE to see whether or not the eosinophils are actually in the oesophagus, we should be able to help diminish the number of endoscopies. 

It would also improve their care because we could regularly evaluate patients’ diseases. Since swallowing the capsule is much simpler than performing an endoscopy, we can monitor patients over time, doing a much less invasive test.

Data we can obtain through EndoSign® compared to an endoscopy

oesophagus biopsy photo

Oesophagus tissue biopsy. Photo courtesy of Sarah Killcoyne

Endoscopy is a medical procedure that allows doctors to observe the inside of the body without performing major surgery. An endoscope is a flexible tube with a light and camera attached, allowing doctors to view pictures of the digestive tract on a colour TV monitor. This procedure examines the interior of a hollow organ or cavity of the body.

Endoscopies involve using body openings such as the mouth (gastroscopy) or anus (colonoscopy). The only preparation is avoiding all food and liquids for a number of hours before the endoscopy.

In endoscopy, they take tissue samples (biopsies) of the oesophagus, but they can also see other visual changes of the oesophagus such as narrowing,  rings and furrows. So, there are additional benefits to endoscopy. 

Besides being less invasive than endoscopy, the EndoSign®’s benefits are that we collect cells across the entire oesophagus. 

It’s a very specific test as we are just looking at the oesophagus, not trying to look at all the possible diseases you can see in your blood, for instance.

We can target looking for eosinophils - or even for other immune cells/biomarkers that might be related to EoE and try to identify if those are present in increased numbers. If trials correlate to what is seen in endoscopy, we will have a simpler test that is effective for patients to use.

What is a biomarker, and why are they useful?

biomarkers examples

Examples of biomarkers: Blood pressure measurement (Objective indicator), Covid-19 antigen test (Provides a clear range or binary response), and Blood glucose level measurements (Measurable, quantifiable and reproducible).

Cyted Focus Group Presentation, 2023

A part of why we want to do this is to look for what’s called a biomarker. 

Biomarkers are any biological features we can use to quantitatively determine a patient’s health. For example, a blood glucose test for diabetics is a biomarker; we can measure how low or high a patient’s glucose is and tell us if they need more or less insulin.

It’s the same as doing a heart test, an EEG, or even a blood pressure test. These are all biomarkers. They give you a quantitative and repeatable way to evaluate a patient’s health. 

With the sponge, we aim to identify new biomarkers specific to patients with uncontrolled EoE.

For patients who have EoE that has been treated, but perhaps the treatment isn’t working, we would like to be able to identify that from the sponge, using a quantifiable biomarker, rather than having to do a visual pathology inspection of the sponge or in endoscopy.

Using these biomarkers, we could potentially diagnose patients before the severity of  EoE leads to A&E visits.

Ideally, moving forward, we would also be able to say which drugs are mostly likely to work for a patient. We would be able to do this because we would have a panel, or set, of biomarkers that relates to what patients have responded to before.

We do this by looking at a large number of biomarkers initially. But from these, we can identify the most specific to the disease.

We have done some internal experimental collections of sponges where people at the company have volunteered to swallow the sponge. I’ve personally participated several times now.

When these sponges were sent to the pathologist, they identified two people with EoE. One of them, myself, we already knew, had EoE, and the pathologist didn’t know, so that was a good validation of the sponge itself. 

Also, a second person was identified as having potential EoE, and they have since gone on to get a formal diagnosis via endoscopy.

The good thing about that is they were diagnosed before they had any of the severe complications that most EoE patients have. Often, people won’t get diagnosed with EoE until they’ve been into A&E with what’s called the food bolus obstruction, where a patient swallows food and it just gets stuck in their oesophagus.

Food bolus obstruction is a severe complication that may result in endoscopy, where the obstruction can be removed.

The second participant that was identified before severe complications, and they are now undergoing treatment early. This means their oesophagus will hopefully be healthier longer: it won’t stiffen, and it won’t cause them as many swallowing issues. Which would be ideal for more patients.

Patient Involvement

I think there will be some nervousness among patients about trying to swallow the capsule. 

We’ve had really good results with patients with Barrett’s and patients with reflux who might suspect they have Barrett’s in terms of being able to swallow this, saying it’s very comfortable.

But EoE patients are a little different. They have varying degrees of their ability to swallow even small tablets, and I think there’s going to be a little bit of nervousness about trying something new.

So, we’ve been working with EOS Network and Guts UK to discuss with a group of patients as a focus group on how we run the trial in terms of recruiting patients. But most importantly, how we talk to patients about the trial and the test. And even, to some degree, what tests we do.

The patients themselves are very keen to see developments in the area of the EoE because there hasn’t been a lot. They’ve been really critical and helped us understand how best not just to message patients but also how best to help patients understand what we hope to do and how we hope to help them.

It is also important for us to understand how patients want to be helped and what they hope to see from the trial.

So, as a good example, we thought the patients were going to be resistant to signing up for this because they were going to have to undergo endoscopies, particularly if they were asked to do two. But when we brought it up to the focus group of patients, they were very clear that they would not see a problem with signing up, but they would want to do it twice to make sure that we got good data. And to make sure that the EndoSign®'s data was comparable to biopsies before and after treatment.

I’m looking forward to starting this trial and getting patients through it. But also going back to the focus group and showing them the kinds of data that we’ve been able to generate. Because they’re very interested and I think they’re going have some really great insights as to what it means for them. 

Aims and results of the study

sponge on a string test photo

Sarah Killcoyne during the EndoSign® test.

The study aims to identify patient-specific biomarkers that can predict the effectiveness of different treatments/diets for EoE. This could potentially allow patients to bypass ineffective treatments and reduce the number of necessary invasive biopsies. Early identification of the disease can help patients start treatments sooner, potentially preventing long-term complications. 

What would help to build on this study to help patients understand much sooner what treatments will be most effective for them? 

Right now, there’s a limited number of treatments for EoE patients, and all of those treatments have varying effectiveness. This means that at the moment, to determine whether treatment works for you, you have to take it for at least two months. 

And then go back to get another endoscopy and also to report all of your symptoms to say whether or not you think that treatment was working.

So if the treatment is not working, you’ve just spent two months taking a drug or diet that did you absolutely no good. If we can identify from a patient biomarker profile, treatment A will work for them, but treatment B won’t. Then maybe we can skip past treatment B and get the patient on a better regimen sooner.

A group of EoE patients do what’s called dietary therapy. They have to cut out certain foods to see if they might be getting EoE by reacting to it allergically.

Again, those patients just have to try. It’s a trial-and-failure problem. So, if we can offer them a sponge while they’re going through this trial to determine which food they are most reactive to, we can help them tailor how they treat their disease much sooner and much more effectively than if they have to wait for an endoscopy, which can take weeks to obtain right now. 

Taking a step back as well, patients mostly don’t get diagnosed until they’ve had EoE for many years. 

If we can identify more patients sooner, as we did on our internal sponge trial, which had nothing to do with EoE at the time, then we can help people a lot sooner as well, keeping them out of A&E. 

We can get them on treatments sooner to help prevent long-term effects like narrowing or stiffening the oesophagus, which can make swallowing more difficult.

These things will benefit patients moving forward. 

When can we see the results of the study, and how can we join it?

Hopefully, late this year. We expect to build on this, so we hope to conduct a wider study next year so that more patients could potentially be involved and ultimately move forward into getting this into the NHS. 

That will take longer, but the more people we can get involved with over the next two years, the better any test we develop will be.

If you have EOE, consider joining the trial. Talk to your consultant, or go to one of the three trusts - Nottingham University Hospitals NHS Trust, East and North Hertfordshire NHS Trust and County Durham & Darlington NHS Foundation Trust.

EndoSign® Website

EOS Network facilitated Cyted's EoE study

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