**The Northern Ireland Precision Biomarkers and Therapeutics Consortium (NIPBT)** is a partnership of Life and Health Science (LHS) companies and Academia, aligned to the strategies of both the Departments of Health and Economy of the NI devolved government to enhance health and wealth creation for NI citizens. Currently, NI has a significant presence in the LHS sector: Almac,Randox and a growing cluster of innovation-driven SMEs. This is complemented by academic strengths at Queen's University Belfast in experimental medicine, drug delivery, cancer research, health data analysis, and the Precision Medicine Centre of Excellence (PMCOE); as well as Ulster University's track record in the development of medical diagnostic technologies. The UK Life Sciences Industrial Strategy 2017 reported that Northern Ireland excels in Precision Medicine, advocating the sector for strategic development. However, the **2018 Steer Report** concluded that the regional LHS sector is currently disjointed and segregated, limiting its potential to enhance the region's prosperity. These are the specific challenges that NIPBT will address in order to transform NI into an internationally-leading region for precision medicine services and product development. These challenges will be addressed via three key objectives: **1\. Integration:** Create an R&D hub that seeds and fosters collaboration, synergies and innovation. **2\. Capacity Building:** Address key common gaps in scarce technology/expertise and further develop the region's existing, internationally-competitive research capabilities in core areas. **3\. Sustainability:** Deliver focused skills and career development networks, ensuring sustainable growth of the LHS sector leading to increased attractiveness of the region for foreign investment. To address these objectives, NIPBT will develop an industry-focused **Future Medicines Institute (FMI)** to drive commercially-relevant R&D; **a collaborative hub that will be the first in NI for this sector**. Combining cutting-edge health data analytics with state-of-the-art equipment/expertise, the FMI will be a vital catalyst for the regional LHS sector. NIPBT will capitalise on investment in the regional LHS sector already made by lnvestNI and lnnovateUK (e.g. Almac, Randox, PMCOE) and new capital investments financed under the Innovation Pillar of the **Belfast Region City Deal**; demonstrating clear alignment and synergy with the region's economic and health strategies. The result of this investment will be development of new platform technologies, diagnostics and therapeutics that will stimulate local economic growth, reverse the region's "brain- drain" and ultimately deliver innovative healthcare products and solutions to enhance patient outcomes locally and globally.

The enzyme Neutrophil Elastase (NE) is associated with the severity of several respiratory diseases, including Chronic Obstructive Pulmonary Disease (COPD), where repeated cycles of infection and inflammation leads to active NE release from immune cells, causing lung damage. Active NE is predictive of lung function loss and is the most informative biomarker to monitor disease activity. ProAxsis has developed a novel point-of-care test (NEATstik) which allows active NE to be quickly measured within 10 minutes. Researchers in Dundee have shown that a positive NEATstik test identifies patients suffering from a lung bacterial infection, who are most likely to benefit from antibiotics. Additionally, they used NEATstik to identify patients at highest risk of suffering from exacerbations over the following year. Thus, NEATstik can support appropriate antibiotic prescribing, and monitoring of their effect, to ensure that respiratory disease patients receive the treatment that is most likely to work for them. An additional key advantage of NEATstik is that it could be used in the patient's home, thereby avoiding unnecessary trips to hospital, a key consideration in the post-COVID environment. To make this viable, enhancements are needed for the sample processing required for conduct of the test. Further valuable information could be gained if the NEATstik result was combined with other respiratory health measures. This is a collaborative project between ProAxsis Limited, who developed NEATstik, the Centre for Process and Innovation (CPI), a world-renowned product engineering expert centre and Wanda Health, specialists in integrating new technologies into remote patient monitoring systems. Together, the partners will significantly enhance the sample processing required for NEATstik, and integrate the test alongside multiple other respiratory health measures into a remote patient monitoring tool, allowing patients to conduct the test at home, and their healthcare professionals to observe the NEATstik test result alongside other important health data.

The formation of blood clots has been identified as a potential risk factor for a very small proportion of individuals receiving certain types of COVID-19 vaccine. A larger proportion of people who have tested positive for COVID-19 (the infectious disease caused by the coronavirus) have also experienced inappropriate blood clotting, which has resulted in more severe symptoms and unfortunately, been associated with a higher risk of virus-related death. ProAxsis is a Belfast-based company, specialising in the measurement of a group of enzymes called proteases. Increased levels of two of this group of enzymes, thrombin and factor-Xa, has been linked to the fact that some people may have an increased chance of developing blood clots. These blood clots can lead to severe health problems including strokes or organ failure. Pharmaceutical companies who are producing COVID-19 vaccines or developing new drugs to treat COVID-19 patients therefore need to find a reliable method of measuring these proteases so that "at risk" patients can be identified early and treated appropriately. In this project, ProAxsis will use its long-standing and unique expertise in the chemistry of proteases and _in vitro_ diagnostic development to create a brand new combination laboratory test. This test will measure the two key protease biomarkers, thrombin and factor-Xa, at the same time in a clinical sample, using an automated procedure known as multiplexing. ProAxsis has the team in place, and the extensive experience required, to very rapidly create and then up-scale a combination multiplex test for these highly important protease targets. Aside from providing key insights as to why certain vaccines may lead to increased rates of blood clots, this project offers substantial benefits to the patients affected by the COVID-19 virus, the healthcare professional teams providing them with clinical care, and the pharmaceutical companies developing new or repurposed drugs for treating the virus. In turn, this will support healthcare systems such as the UK's National Health Service (NHS) to decide which vaccines and drugs they should prioritise to purchase from their limited budgets, and identify which patients are most likely to respond to the new range of drugs expected to be available. This project specifically focuses on addressing the needs associated with COVID-19 vaccination and treatment, but in the future, this newly developed test could also benefit the large number of people with other conditions caused by increased blood clotting, such as strokes and heart attacks.

ProAxsis is a Northern Ireland-based company which specialises in the measurement of a group of enzymes called proteases. Current tests being developed to support the fight against COVID-19 (the infectious disease caused by coronavirus) are focused on identifying patients who currently have, or have previously had, the virus. Whilst this is clearly useful, a longer-term aim is for healthcare professionals to be able to identify which people who catch the virus are likely to suffer the worst symptoms, and when new treatments are available, which patients are likely to need and respond best to these. This will allow the healthcare professionals looking after patients who contract the COVID-19 virus to know which patients are most likely to need to spend time in hospital, and to require more extensive treatments in order to maximise the chances of them recovering. It will also allow more specific treatment for each individual patient. ProAxsis will use its long-standing and unique expertise in the chemistry of proteases and _in vitro_ diagnostic development to create a brand new combination test, which will enable two key protease biomarkers, neutrophil elastase and cathepsin G, to be specifically measured in a much larger number of samples each day than is currently possible. Early clinical studies of patients in Chinese hospitals have highlighted that both of these proteases are linked with certain risk factors associated with people having poorer outcomes when infected with the COVID-19 virus. ProAxsis has the team in place, and the extensive experience required, to very rapidly create and then up-scale tests for both of these highly important targets. This project offers substantial positive benefits to both patients affected by the COVID-19 virus, and the healthcare professional teams providing them with clinical care. It will also provide new innovative tools to show how well the drugs currently being assessed for use in COVID-19 patients will work. In turn, this will support healthcare systems such as the UK's National Health Service (NHS) to prioritise which patients are likely to need the most support for their recovery from the virus, and which drugs they should prioritise to purchase from their limited budgets.

There are a number of markers of inflammation which have been associated with various diseases. One group of such markers is the cytokines which are small proteins released by different cells in the body. These cytokines work as messengers and help co-ordinate the body's fight against infection and inflammation. Cytokines are often measured in the blood of patients with illnesses such as atherosclerosis and cancer. Very recently, a number of cytokines, such as interleukin-6, have been measured in patients infected with the COVID-19 virus and have been found to be significantly increased in those who have suffered worse symptoms and unfortunately, increased death rates. This is due to a 'cytokine storm' when the person's immune system goes into overdrive and becomes out of control. This leads to very high levels of cytokines being released which in turn causes excessive inflammation and even multiple organ damage. Cytokine storms may explain why some people have severe reactions to coronaviruses whilst others end up with only mild symptoms. For lung diseases such as COVID-19, it makes more sense to measure cytokine levels in sputum, as this will be more representative of what is occurring in the lungs themselves. Therefore, the aim of this project is to adapt the existing blood-based tests for three of the key cytokines, including interleukin-6, so that they can be safely and effectively measured in sputum samples. The project will use the extensive expertise of ProAxsis in the development of sputum-based tests to create a new combination test, which enables the level of three key cytokines - Interleukin-6, Interleukin-8 and Tumour Necrosis Factor-alpha - to be measured in a small quantity of sputum. This will help healthcare professionals identify which patients infected with the COVID-19 virus are likely to suffer with the most severe symptoms. In the longer-term, it will also allow them to test the effectiveness of several of the new drugs being developed for the treatment of COVID-19\. ProAxsis will use two of its most experienced scientists to create this new sputum-based combination test within six months, and quickly move to expand its availability to other laboratories throughout the World. The company believes that this will provide a significant new tool for healthcare professionals in the fight against the COVID-19 pandemic. Since the project began, scientists have confirmed how important cytokines such as Interleukin-6 can be as biomarkers for predicting which people who catch the COVID-19 virus will suffer from the worst symptoms. However, they have also very recently shown that measuring the levels of another cytokine, Interleukin-10, in combination with Interleukin-6, provides a better prediction than just considering Interleukin-6 on its own. The Extension for Impact funding will enable the scientists at ProAxsis to use the extra three months to add Interleukin-10 in to the new sputum-based combination test, thereby improving its ability to support healthcare professionals to identify and treat people infected with the COVID-19 virus.

Neutrophil Elastase (NE) activity is associated with the severity of respiratory diseases including Cystic Fibrosis (CF) Chronic Obstructive Pulmonary Disease (COPD) and bronchiectasis. In these diseases repeated cycles of infection and inflammation result in the release of NE which causes lung damage. NE is predictive of loss of lung function and is the most informative biomarker of disease activity. NE inhibitors being developed by pharmaceutical companies as therapeutic drugs need to have their efficacy assessed within clinical samples from patients with respiratory disease. However, some adults, both from healthy and disease populations, alongside infants and young children, are unable to produce sputum. As a consequence, they are excluded from clinical trials involving these novel anti-NE therapies, that could otherwise prove beneficial. The challenge is to develop methods of measuring active NE from other biological fluids in the patients that would result in their inclusion in clinical trials. We have already commercialised an activity-based immunoassay which specifically measures active NE in sputum. This project aims to adopt this assay to be used with nasal fluid and breath condensate, which are easier to collect from most patients.

Pancreatic Insufficiency (PI) is a condition that occurs in a range of diseases including chronic pancreatitis, pancreatic cancer, diabetes, cystic fibrosis and inflammatory bowel disorders. Often, diagnosis is delayed as symptoms don't appear until almost all of the pancreatic function is lost. Pancreatic Elastase (PE), one of the enzymes normally released by the pancreas, has been identified as a biomarker of pancreatic insufficency. Measuring the active form of PE can provide information about pancreatic function and help in the prognosis of a range of PI-related diseases. Low faecal PE levels are shown to be related to poor survival in patients with pancreatic cancer, meaning that PE levels could be used to help predict survival in those diagnosed with pancreatic cancer. Diagnosis of PI before a patient shows symptoms involves invasive tests, some of these requiring hospitalisation. Other tests for PI are indirect, non-specific, unpleasant and limited. This project aims to use our technology to develop a quick and easy test to measure only the active form of PE. We plan to develop special molecules called ProteaseTags® and use them to create an activity-based immunoassay (ABI) for the detection of active PE in clinical samples with a precision that is not possible with current tests.