Title: Development of RxSelex: A microbiome-based predictive diagnostic of IBD biologics treatment outcome
Funder: Department of Health and Social Care

Abstract: MEDICAL NEED: Clinical management of chronic diseases such as IBD is frequently inefficient, with few products to help physicians select personalized treatment strategies. In IBD, the bulk of patients who fail first line drugs are considered for biologics therapy, with most initially receiving anti-TNF&alpha; drugs, of which multiple generic versions are now in the formulary. However, up to 40% of patients do not respond to initial treatment. Among initial responders, 13%&ndash;46% lose response over the subsequent year. While physicians switch drugs aiming to find an effective long-term therapy, patients continue suffering and valuable healthcare resources are wasted. PROJECT VISION: To solve this issue, AlphaBiomics is developing RxSelex, a highly disruptive diagnostic that uniquely draws upon the immunomodulatory role of the microbiome and combines next-generation-sequencing of patient stool with machine learning to predict how patients will respond to biologics. The resulting RxSelex report guides the doctor and patient in selecting a personally optimized treatment plan. KEY OBJECTIVES: Funds are sought to validate AlphaBiomics RxSelex prediction model against two carefully curated and geographically distinct cohorts of 150 IBD patients each, collected by leading gastroenterology centres in the United Kingdom and the Netherlands. In addition, funds are requested to (i) validate RxSelex assay protocols, (ii) integrate the patient perspective and (iii) deploy commercial, IP and regulatory strategies for access to the NHS and other markets. IMPACT: Introducing RxSelex into the NHS care pathway will improve IBD patient outcomes, increase care efficiencies and offer compelling value for payers. Securing this funding will allow AlphaBiomics to bring RxSelex to within 12 months of NHS launch in 2022, with full CE-marked product expected to follow in 2023 for initial roll out in EU and then US markets.

Lay abstract: Crohn s disease and ulcerative colitis are the major forms of inflammatory bowel disease (IBD), a group of persistent and long-term diseases. These diseases are characterized by an abnormal reaction of the body s immune system, known as inflammation, in all or part of the digestive system. Treatment options for IBD depend on how severe symptoms are, and how much of the bowel is affected. The treatment includes use of medication, however, if this does not bring symptom relief, called remission, then major surgery is frequently required. Patients experiencing severe IBD who have not achieved remission with the usual medication are typically treated with a biologic drug which stops inflammation. Unlike chemical medications, this new type of medicine is made out of materials also found in living organisms. Initially, all patients with IBD who do not gain remission are treated with the same type of biologic drug, but it is known that patients respond differently. Some may benefit, whereas others do not, or even have unwanted side effects. Those who do not respond are treated with an alternative biologic drug or may require surgery because inflammation has worsened. This trial-and-error approach is unsatisfactory for patients whose symptoms are not relieved. There is therefore a pressing need to better match individual patients with safe and effective biologic drugs that work for them. The gut microbiome (the large and complex community of typically harmless bacteria in our intestines) has an important influence over biologic drug response. Yet, no products exist which probe the microbiome to forecast biologic drug response in IBD. AlphaBiomics will develop a test, known as a diagnostic, that predicts whether or not individual patients with IBD are likely to respond positively to biologic drugs. This is done by measuring important stool microbiome components, ensuring the appropriate drug is prescribed. The benefits achieved using this test are substantial, for example increased patient quality of life, together with improved cost benefits to the NHS, society, and the economy. AlphaBiomics will use National Institute for Health Research (NIHR) funding to turn the results from an ongoing NIHR-funded programme into a diagnostic test called RxSelex that predicts treatment response. NIHR funds will be used to verify that RxSelex correctly predicts treatment response of patients in two countries, the United Kingdom and the Netherlands, to develop laboratory tests and computer programs needed for RxSelex, and also to analyse its impact on patients experiencing IBD and on the NHS. Patients are involved throughout by advising and guiding researchers based on their unique and invaluable insights and experiences. These critical steps will place AlphaBiomics in a strong position to generate evidence required to bring RxSelex to market and to speed adoption by the NHS and healthcare systems globally.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: ORAL AND GASTROINTESTINAL