Creating a world leading infection R&D hub in the UK

As the world is rocked by one of the greatest healthcare challenges in living memory, how we treat infectious diseases is becoming one of the key medical questions of our age. Hannah Randles, Health and Life Sciences Champion at Liverpool City Region’s Growth Platform explains how the region’s infectious diseases ecosystem is driving innovation in tackling a global challenge. A new public-private consortium born out of the Liverpool City Region, in the North West of the UK, and backed by UKRI’s Strength in Places Fund, has been established t ofast-track the discovery and development of new products and treatments for infectious diseases. The COVID-19 pandemic has brought into sharp focus the devastating impact that the lack of effective treatments for infectious diseases can have on society. Coupled with the worldwide rise in antimicrobial-resistant superbugs, hospital-acquired infections, and diseases such as Zika, Ebola, TB, malaria and HIV, which are still claiming millions of lives every year, the pandemic has placed the need for better infectious disease prevention and treatment at the top of the global agenda. But the world’s Infectious Disease Therapeutics (IDT) pipeline has been weakened. Driven by the high cost, high risk, and low reward of innovating to create essential therapeutics, such as antibiotics, drugs and public health insecticides, which shifted to a high-volume low-margin commodity format several decades ago. This response to infectious disease treatment has derailed research and development pipelines for these essential products and deskilled the industrial base, which refocused on more lucrative markets, such as oncology. Despite the £107 billion global market for new products to help the world to tackle the infectious disease challenge, the risk/reward ratio for IDTs following standard R&D pathways, with high levels of late stage product failure, is still unattractive for industry. Efforts to rejuvenate the pipeline of IDTs are hampered by outdated methodologies and high rates of late stage product failures. This lack of new IDTs has left us highly exposed and facing a therapeutic pipeline that is on the verge of collapse, with billions of people across the globe at risk of infectious diseases with no treatment. The ‘catastrophic threat’ of antibiotic resistance is now globally recognised as one of the world’s most pressing healthcare challenges, only adding to the urgent need to create new IDT pipelines. Unless risk is reduced by the introduction of new predictive methodologies and open shared innovation platforms, our ability to prevent and treat many infectious diseases will soon be compromised, leaving the world in an ever more perilous scenario. The devastating global impact of COVID-19 has helped to create a renewed focus on the importance of effective infectious disease management, and sparked a revolution with the potential to radically change the pathway to market for new antibiotics, drugs, vaccines and public health insecticides for the prevention and treatment of these human diseases. The Liverpool city region - a centre of R&D excellence The UK is at the forefront of the global challenge to tackle COVID-19 and create new treatments for infectious diseases and the Liverpool City Region has emerged as a world-leading location for the development, testing and manufacture of treatments for infectious diseases. Combined with nearby counties Cheshire and Warrington, the city region delivers £2 billion of R&D activity in the infectious diseases space per annum – representing by far the biggest centre for infectious diseases research in the UK, and one of the biggest centres in Europe. The city region’s outstanding expertise in infectious diseases R&D has created a dynamic eco-system with world-leading capability across drug discovery, diagnostics and clinical trials, all the way through to biopharmaceutical vaccine manufacturing capability, as one of the largest biopharmaceutical manufacturing clusters in Europe. Home to globally respected organisations tackling infectious diseases including the Liverpool School of Tropical Medicine (LSTM), the region’s facilities coupled with a pedigree in infectious disease R&D, place it at the forefront of the sector. The Liverpool City Region has the largest concentration of translationally-focused public sector R&D expertise in infectious diseases in the UK. It has an extensive track record of establishing public-private partnerships and is working with major organisations in the area of infection including the World Health Organization, the Department for International Development, and The Bill & Melinda Gates Foundation. The city region has access to patient populations (and pathways for drug and diagnostic evaluation and implementation) in the UK and across Africa, Asia and South America. It also offers access to the people, skills and supply-chains to support the journey from drug discovery through to manufacturing and delivering vaccines. The region’s infectious disease ecosystem has led to the creation of a new consortium which is responding to the global infectious diseases challenge by leveraging the North West UK’s expertise to create the global location of choice for infection R&D in the Liverpool City Region. The consortium plans to create a new treatment pipeline, which promises to radically transform the world’s response to infectious diseases. Leading the charge Led by the Liverpool School of Tropical Medicine (LSTM), the infection innovation consortium (iiCON) brings together the UK’s leading public and private organisations focused in infectious disease R&D, including Liverpool University Hospitals NHS Foundation Trust, Unilever UK, the University of Liverpool, Evotec and the AMR Centre, which are based at Alderley Park, Cheshire. The combined infectious diseases, antibiotic and hygiene R&D portfolio of the six consortium partners currently exceeds £2 billion. The expertise of each partner is highly complementary and covers the full spectrum of product discovery, development, manufacture, marketing and impact assessment – representing a concentration of expertise not replicated anywhere else in the UK. The consortium also has an exceptional skill base, an understanding of and access to the disruptive technologies needed to bolster the IDT pipeline, and networks with local, national and international stakeholders. In addition, academic groups in Liverpool are at the vanguard of developing innovative approaches to product development, with improved specification of disease and pathogen target product profiles through interrogation of human disease data and delivering evidence-based recommendations for product use post-license. In recognition of this unique combination of skill, expertise and academic excellence, iiCON has received an £18.6 million grant from the UK Research and Innovation (UKRI) Strength in Places Fund (SIPF) to deliver a major project to tackle infectious diseases, including COVID-19. The consortium has leveraged the SIPF funding to generate guarantees of around £90m in private sector funding to support the project, and plans to reconfigure the clustered research and industrial partners into a streamlined consortium that ameliorate specific bottlenecks in product development and marketing pathways of IDTs. The funding award recognises the globally renowned expertise in infectious diseases in the North West. Alongside private sector investment, it will support a five-year project to create eight specialist research platforms for infectious diseases therapeutics aiming to fast-track the discovery, development, evaluation and impact assessment of potential new products and treatments. This will support local industry and SMEs and generate substantial inward investment from multi-nationals and international funders – creating the world’s foremost centre of excellence in infection R&D in the North West of England. Creating a new IDT pipeline Efforts to rejuvenate the pipeline of IDTs are hampered by outdated methodologies and high rates of late stage product failures. The iiCON’s ambition is to revolutionise R&D pathways for companies developing new IDTs using the North West regional academic and industrial skill base to bring products to market in a more efficient, faster and cost-effective format. It aims to reduce development cost by up to £10 million per product and reduce the time to market by up to five years. The consortium will create eight specialist commercially sustainable research platforms for infectious disease therapeutics in the North West that will transform the efficiency of new product discovery, and drive forward development, evaluation and impact assessment. The project will see the consortium create and commercially market six physical and two virtual open access Platforms, using its technology and expertise to generate novel therapeutic leads, de-risk their development, reduce the time and cost to market and facilitate product registration and optimal product placement post-licence. The programme aims to catalyse a step change in regional productivity by responding to market need in a key UK economic discipline and create platforms which span early stage discovery to market entry. At the core, safe, effective and flexible human organoid and 'human challenge models' and associated technologies will reduce the risk of late stage failures of new therapeutics in Phase II or Phase III clinical trials. The consortium’s technologies will dramatically reduce industry cost and time when used at an appropriate stage in the product development cycle. The consortium will establish platforms across the whole R&D pipeline from discovery to market placement that will directly reduce the global burden of infectious disease and bring products into operational use in a faster, smarter, cheaper and more effective format. There are five key areas of focus for the new platforms: Develop an accessible high-throughput screening system with substantive small molecule and fractionated antimicrobial generating Natural Product libraries for antimicrobial, hygiene and household product discovery programmes, with backing from major pharma and North West-based consumer products companies. Develop an accessible Category 3 based high-throughput whole cell screening system for intracellular infectious agents requiring high level containment and provide improved pharmacokinetic models for new molecules. Provide access to safe and effective human challenge models. Alongside the other platforms, this will reduce the late stage failures in clinical trials, drastically reducing industries cost and time investments. Use microwave and machine learning technologies generating an accessible platform to develop non-invasive diagnostics to quality assure disease prevention products and diagnose infections. Improve the format and effectiveness of randomized control trials to reduce the time, complexity and cost of generating robust data to support international and country-based product approvals and registrations. Extending this post license to establish a model platform for assessing the optimal placement of products in settings where multiple interventions are used to tackle infection. Recognising that IDT discovery is dominated by SMEs, who optimally need partnerships with larger companies after Phase One clinical trials, the consortium has designed the Platforms to engage both groups, facilitating increased interactions at the drug optimisation and human challenge phase. From discovery to market placement the workstreams will look at hits to leads for SMEs, non-invasive diagnostics, human pathogen screening, and drug optimisation in infected human organoids. The workstreams will also focus on human challenge trials, formulation optimisation, improved randomised control trials and cognitive computer modelling of product placement. In-line with a key driver for awards from the Strength in Places Fund, the programme will also drive economic growth in the Liverpool City Region, through shared open access R&D Platforms that will attract major regional, national and international investment in a growing R&D area. A global impact The broader societal impact of the project stands to be significant, with the potential for huge benefits to health locally, nationally and internationally. Expected positive impacts from the programme range from improved evidence-based operational practices to reduced hospital and household acquired infections, better policies and practices to avoid the spread of infectious diseases alongside new products entering the infectious diseases control market. In the longer term, the new antibiotics and personal hygiene products generated from the Consortium’s activities should reduce the threat to human health in the UK from AMR - cited as one of the greatest risks to human health. The programme’s workstreams have been created with direct links to key health bodies, including Liverpool Health Partners (NHS), Public Health England and international regulatory and normative agencies in the public health insecticides, antimicrobial, diagnostics and hygiene space. These links have been specifically designed to enable the generation of an evidence-base for the health impacts of infection therapeutics to ensure that they are optimally deployed at the health system and household level. The programme delivered by the consortium will generate outputs that will directly influence and impact on the policy for product use locally, nationally and internationally – helping to transform the global response to infectious diseases. Volume 21, Issue 4 – Fall 2020 Hannah Randles is Health and Life Sciences Champion at Growth Platform, Liverpool City Region’s Growth Company.