Translational Research in Inflammatory Respiratory Disease

Translational Research in Inflammatory Respiratory Disease

NOCRI simplifies access to the UK s world-leading clinical research infrastructure

Foreword Collaborative research accelerates the development of new treatments, devices and diagnostics to tackle complex healthcare needs. Creative engagement between the NHS, universities and industry forms a powerful alliance to drive translational medicine. This alliance is vital. It ensures that advances in basic science progress swiftly into benefits for patients and the economy. NIHR Translational Research Partnerships are the embodiment of this collaborative approach. Supported by NOCRI, the TRPs accelerate the development of solutions to meet real patient needs. If your early phase programmes are targeted at inflammatory respiratory diseases, then contact the NOCRI team to discuss how the NIHR TRPs can help. Professor Dame Sally C Davies Chief Medical Officer and Chief Scientific Adviser, Department of Health This booklet highlights the way NIHR Translational Research Partnerships can help broker early phase collaboration between industry, the NHS and universities to the benefit of all parties. The NIHR Office for Clinical Research Infrastructure (NOCRI) makes this process easier for industry, enabling the generation of new ideas and leaps in research. We have a clear and managed approach to collaborations, including tools to shorten the contracting process and a dedicated Operations Manager. This helps companies to achieve their translational research objectives more efficiently. Mark Samuels Managing Director, NOCRI NOCRI connects the country s expert investigators, technologies and research facilities to deliver high quality clinical research. If you would like to know more about how NOCRI can help you to establish academic-nhsindustry collaborations, please e-mail the NOCRI Translational Research Partnerships office at trp@nihr.ac.uk, or call +44 (0) 203 328 6744. 3

Introduction to NOCRI NOCRI makes it easy to access the UK s clinical research infrastructure, which includes world-leading scientists in world-class facilities. With 60 million people in the National Health Service, we connect companies to investigators with access to well-characterised cohorts of patients. NOCRI is a unique resource for the global life sciences industry - improving the quality, efficiency and success of translational research. We achieve this by providing: fast and easy access to the UK s clinical research infrastructure rapid connection to expert investigators and cutting edge technologies a managed process for collaborative research. We focus on facilitating successful outcomes, from making rapid introductions through to supporting collaborations to ensure delivery of research. 4

Introduction to Translational Research Partnerships The NIHR Translational Research Partnerships (TRPs) were developed at the request of the life sciences industry. The Partnerships combine the finest minds and capabilities from 36 universities and NHS organisations into a single structure. Underpinned by world class NIHR clinical research infrastructure, they create a unique resource to drive translational research in defined therapeutic areas, address unmet medical needs and take on the challenges of an evolving drug, device and diagnostic development model. All participating centres work to a set of unified and streamlined operating procedures that are supported by a dedicated team within NOCRI. Together, this enables us to define, design and deliver research projects better and faster through improved communication with industrial partners and a cost-effective delivery model. The TRPs bring together the UK s leading academics and the life sciences industry, in order to drive translational research The Translational Research Partnership concept draws strength from the UK s long tradition of creating breakthroughs in translational and early phase clinical research. In the field of respiratory medicine, UK scientists used their expertise in the molecular mechanisms of asthma to identify anti-il-5 therapy as an effective treatment for patients with eosinophilic asthma, leading to a paradigm shift towards stratified medicine in this field. This is but one example from a long list of achievements held by the UK s translational and early phase clinical research industry. 5

Building on these successes, the Partnerships bring together some of the world s best clinical researchers and translational research capabilities, placing us in a unique position to translate pre-clinical data into successful clinical research and development. Our activities span the complete range of translational research, including pre-clinical models, exploratory trials, phase I and II proof of concept clinical drug trials and other studies for medical technology and diagnostic applications. The Partnerships are supported by a dedicated team within NOCRI which acts as a single point of contact and facilitates the set-up of all research projects. Where necessary, NOCRI also works with potential commercial partners to identify suitable public funding schemes aimed at collaborations in translational science and exploratory development. Study design is informed by formidable expertise and capabilities: cutting edge expertise in exploratory development protocols, biomarkers, pathophysiology, disease mechanisms and patient selection expertise at the interface of pre-clinical and clinical research, including pre-clinical models of disease, human disease tissues and validation and optimisation of biomarkers enabling technologies and infrastructure, including advanced imaging, biobanks and dedicated research facilities cohorts of well-characterised patients available for clinical development studies. 6

Pre-clinical research Early-phase clinical research Late-phase clinical research Pre-Clinical Modules Patient Tissues Biomarkers Phase 1 PoM Patient stratification Point of intervention PoC Selected University and NHS Partners NIHR Biomedical Research Centres & Units Clinical Research Facilities Translational Research Partnerships NIHR Clinical Research Networks NOCRI Structure and key capabilities of NIHR Translational Research Partnerships (PoM: proof of mechanism; PoC: proof of concept) 7

How we work with you The Inflammatory Respiratory Disease TRP is a consortium of nine centres where each centre is formed by a university and its associated NHS organisations, represented by an Academic Lead. The Partnership centres were selected by an international review panel based on their recognised expertise and capabilities in the designated field. A collaboration agreement binds the Partnership together, ensuring that all centres work to common business processes and timelines. A dedicated TRP team within NOCRI acts as the single point of contact for a commercial partner and coordinates all steps from first contact through to delivery of the signed project, thus ensuring that TRP projects deliver to time and target. NOCRI enables the quick exploration of research opportunities by facilitating scientific exchange through setup of meetings and assisting in the negotiation of required agreements and contracts. We provide standard templates for non-disclosure agreements (NDAs) and contractual arrangements, including the model industry collaborative research agreement (micra), which has been accepted by all participating universities and NHS organisations and endorsed by trade associations such as the Association of the British Pharmaceutical Industry and the UK BioIndustry Association. These templates facilitate rapid sign-off and turnaround. Through our streamlined processes we aim to complete all necessary steps from NDA agreement, to study start within a period of eight months. 8

In essence, the Partnership aims to act as one institution by providing a single point of contact and entry in to the nine centres of excellence. Collectively the centres provide exemplary scientific expertise, strong track-records in working with the life sciences industry and first class clinical research facilities provided by the NIHR Biomedical Research Centres/Units, NIHR and NIHR/Wellcome Trust Clinical Research Facilities and partner Contract Research Organisations. The Partnerships are committed to delivering research faster and better. For further information on the Partnerships, please e-mail the NOCRI Translational Research Partnerships office at trp@nihr.ac.uk, or call +44 (0) 203 328 6744. Non-Disclosure Agreement (NDA) Expression of Interest and Project Proposal Final project plan and study protocol Sign contractual agreement (micra or mcta) MHRA & Ethics (REC) approvals; NHS permissions NOCRI operational support Design and define project and collaboration model Agree costs and funding IRAS Submission Study start TRP operational process and milestones for project setup 9

University College London Hospitals NHS Foundation Trust; Royal Free London NHS Foundation Trust; University College London Professor Wisia Wedzicha University Hospital Southampton NHS Foundation Trust; University of Southampton Professor Ratko Djukanovic Belfast Health and Social Care Trust; Queen s University Belfast Professor Stuart Elborn University Hospitals of Leicester NHS Trust; University of Leicester Professor Chris Brightling Inflammatory Respiratory Disease TRP King s Health Partners Academic Health Science Centre Professor Tariq Sethi Oxford University Hospitals NHS Trust; University of Oxford Dr Ling-Pei Ho Manchester Academic Health Science Centre Professor Ashley Woodcock 10 Nottingham University Hospitals NHS Trust; University of Nottingham Dr Tim Harrison Royal Brompton and Harefield NHS Foundation Trust; Imperial College London; Imperial College Healthcare NHS Trust Professor Peter Barnes

Expertise NIHR Translational Research Partnerships are strongly positioned to ensure scientific ideas are applied to patient need earlier than would otherwise have been possible, by concentrating expertise and fast-tracking ideas. Key facts The Inflammatory Respiratory Disease TRP provides: expertise in a range of inflammatory respiratory diseases including amongst others asthma, allergy, COPD, cystic fibrosis, idiopathic pulmonary fibrosis, acute lung injury and respiratory infection experts in experimental medicine with outstanding track records in undertaking clinical research, each of whom have easy access to well-defined patient cohorts and state of the art facilities, including NIHR funded infrastructure advice and facilities to conduct first-into-man and first-into-disease projects; suggestions and execution of ex vivo validatory work on human tissue samples and efficient delivery of phase I and phase IIA trials and other studies translational expertise to design and undertake early phase studies to deliver data that match a drug target to an appropriate therapy area and establish proof of concept the potential to revolutionise drug development by harnessing academic expertise, state of the art clinical and laboratory facilities and applying an original and cost-effective operational model The research centres that make up the NIHR Translational Research Partnerships have been selected to work together based on their proven ability to deliver in experimental medicine and translational research. By working together in this way, the Partnerships bring a unique breadth of expertise to industry s translational research questions. The head of each NIHR Inflammatory Respiratory Disease TRP centre outlines their establishments capabilities on the following pages. 11

Individual Centre Information Professor Peter Barnes Honorary Consultant Physician at the Royal Brompton & Harefield NHS Foundation Trust Head of Respiratory Medicine, Imperial College London The NIHR Biomedical Research Unit in Respiratory Disease at The Royal Brompton and Harefield NHS Foundation Trust and Imperial College London; Imperial College Healthcare NHS Trust Disease Expertise The Royal Brompton & Harefield NHS Foundation Trust is internationally recognised across the spectrum of lung disease, with particular expertise in severe asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis, primary ciliary dyskinesia, interstitial lung diseases, sleep medicine, acute and chronic respiratory failure and rare lung diseases. Research Capabilities Our research capabilities include exhaled inflammatory biomarkers, skeletal muscle biopsies, imaging, extensive lung physiology techniques, nasal and bronchoscopic sampling, sputum induction, bronchial challenges, as well as a large range of preclinical techniques including mouse models of asthma and COPD. We host comprehensive core facilities including an NIHR Respiratory Biomedical Research Unit, an in/out-patient 24 hour Clinical Research Facility, biobank, and sample collection/processing. Across Imperial College there is the capacity to host a full range of early phase clinical studies from Phase I volunteer studies through to Phase III multi-centre international trials. We work closely and collaboratively with the Respiratory Theme of the NIHR Imperial Biomedical Research Centre, and for human volunteer studies, we are able to access the NIHR / Wellcome Trust Clinical Research Facility at Imperial College Healthcare NHS Trust in Hammersmith. Patient Cohorts We host respiratory clinics providing adult and paediatric services and staffed by leading clinical researchers. We act as a tertiary referral centre for the whole of the UK and have some of the largest services nationally (e.g. severe asthma, bronchiectasis, sleep medicine) and in several cases internationally (e.g. cystic fibrosis and interstitial lung disease). 12

Professor Chris Brightling Wellcome Senior Research Fellow and Clinical Professor in Respiratory Medicine, University of Leicester Honorary Consultant Respiratory Physician at the University of Leicester and Glenfield Hospital The NIHR Biomedical Research Unit in Respiratory Disease at the University Hospitals of Leicester NHS Trust and the University of Leicester Disease Expertise We have strong expertise in asthma and COPD. In addition, we host clinics in airway inflammation, allergy, pleural diseases and tuberculosis. Research Capabilities Leicester is an international hub for multi-centre trials, and acts as the reference lab for sputum analysis, imaging in airway diseases, exercise testing and activity monitoring. We host an NIHR Respiratory Biomedical Research Unit which includes an in-patient bedded unit. We bring significant expertise in the pathogenesis of airway diseases and their underlying mechanisms, with various pre-clinical models of disease, including primary cells from bronchoscopies and lung resections as well as strong clinical trial capabilities. Patient Cohorts We effectively combine paediatric cohorts of severe asthmatics with the capability to assess inflammatory profiles in children. 13

Professor Ratko Djukanovic Professor of Medicine, University of Southampton Honorary Consultant Physician, University Hospital Southampton NHS Foundation Trust Director, Southampton NIHR Respiratory Biomedical Research Unit The NIHR Biomedical Research Unit in Respiratory Disease at Southampton University Hospitals NHS Foundation Trust and the University of Southampton Disease Expertise Southampton brings clinical and research expertise in asthma, cystic fibrosis and respiratory intensive care in children and adults and in COPD. Research Capabilities We host world class laboratories for proteomic and lipidomic analysis of patient samples, multimodal imaging (including CT, SPECT, nuclear medicine, bronchoscopic ultrasound, in vivo airway laser confocal microscopy) and quantitative post-processing applied to lung disease to study structure and aerosol deposition. We host a NIHR Respiratory Biomedical Research Unit and our NIHR/Wellcome Trust Clinical Research Facility can host patient stays lasting several days, including overnight, and its bronchoscopy suites operating under negative pressure enable the study of infected patients. Isolation chambers for allergen challenge and virus infection studies in volunteers, coupled with induced sputum, make it possible to study airways disease exacerbations. We undertake allergen, methacholine, histamine and AMP bronchial challenge models and have a wide range of pre-clinical models including epithelial culture models, lung parencyhmal and bronchial explants models. Patient Cohorts Clinical databases are used to support patient recruitment into early phase trials within our specialist trial facilities. These databases cover asthma, COPD, cystic fibrosis, interstitial lung disease and primary ciliary dyskinesia. 14

Professor Stuart Elborn Director of the Centre for Infection and Immunity in the School of Medicine, Dentistry and Biomedical Sciences, Queen s University Belfast Belfast Health and Social Care Trust and Queen s University Belfast Disease Expertise We are a recognised centre of excellence in cystic fibrosis, asthma, COPD, acute lung injury and bronchiectasis. Research Capabilities We host state of the art laboratories, including a dedicated Clinical Research Facility and have close affiliations with our on-site Contract Research Organisation. Our laboratory has developed novel clinical and laboratory endpoints including lung clearance index biomarkers for patient and healthy volunteer studies. We utilise several pre-clinical models of disease, including the Lipopolysaccharide (LPS) inhalation model of acute lung injury in healthy volunteers of pulmonary inflammation (Human LPS challenge) and an ex vivo lung perfusion model for acute lung injury. Belfast s infrastructure supports preclinical studies and early phase trials, and runs many trials every year. Patient Cohorts Clinics in Belfast include the full range of inflammatory respiratory conditions and specialist clinics in difficult asthma, cough and primary immunodeficiency. 15

Dr Tim Harrison Clinical Associate Professor, Nottingham Respiratory Research Unit, University of Nottingham and Nottingham University Hospitals NHS Trust Nottingham University Hospitals NHS Trust and the University of Nottingham Disease Expertise Nottingham hosts significant research expertise in asthma across the full spectrum of disease severity. We also have recognised expertise in idiopathic pulmonary fibrosis. Research Capabilities Nottingham has expertise in pre-clinical models of respiratory disease and clinical research trials in patients with a wide spectrum of respiratory diseases including asthma, COPD, cystic fibrosis, lung fibrosis and lymphangioleiomyomatosis (LAM). Our facilities are equipped to invasively and non-invasively assess airway inflammation, including bronchoscopy and tissue culture and advanced lung imaging facilities, comprising MRI and hyperpolarised lung imaging. We have dedicated facilities within the respiratory department and access to a six bed clinical research facility. Patient Cohorts We hold clinical databases for potential trial recruitment in COPD, asthma and interstitial lung disease and we host the UK lymphangioleiomyomatosis centre. 16

Dr Ling-Pei Ho Group Head, Lung Immunology Group Weatherall Institute of Molecular Medicine University of Oxford Consultant in Respiratory Medicine Oxford Centre for Respiratory Medicine Churchill Hospital The NIHR Biomedical Research Centre at Oxford University Hospitals NHS Trust and the University of Oxford Disease Expertise Oxford has specific expertise in interstitial lung diseases (idiopathic pulmonary fibrosis and sarcoidosis), lung and pleural infection and COPD, with particular strengths in generic exploratory lung science. Research Capabilities Research capabilities in Oxford centre around the comprehensive NIHR Biomedical Research Centre, a partnership that brings together the research expertise of the University of Oxford and the skills of clinical specialists at the Oxford Radcliffe Hospitals NHS Trust. We have a dedicated UKCRC registered Respiratory Clinical Trials Unit and state-of-the-art biomedical and GCLP-standard translational core scientific laboratories. Respiratory specialists at the Wellcome Trust Centre for Human Genetics and Weatherall Institute of Molecular Medicine ensure that the latest developments in cellular immunology, computational modelling and human genetics, and high-end biotechnology are applied to respiratory diseases. We also maintain a tissue archive that prospectively stores biopsy tissue and, resected surgical specimens from bronchoscopy, thoracoscopy and thoracic surgical resections. Patient Cohorts We have extensively-phenotyped patient and sample cohorts in COPD, idiopathic pulmonary fibrosis, pleural disease and sarcoidosis; which are connected to research-active specialist clinics in these conditions. 17

Professor Tariq Sethi Head of Respiratory Medicine, King s Health Partners The NIHR Biomedical Research Centre at Guy s & St Thomas NHS Foundation Trust and King s College London; King s Health Partners Academic Health Science Centre Disease Expertise We focus on asthma, allergy, COPD, lung fibrosis (connective tissue associated lung disease), respiratory failure, cystic fibrosis and lung cancer Research Capabilities Our research capabilities include bronchial investigation, skeletal muscle biopsies and imaging. We host state of the art laboratories and have close affiliations with our on-site Contract Research Organisation. We tackle basic laboratory proof of concept studies with animal models of asthma, allergy, lung fibrosis and lung cancer. Through our dedicated NIHR Biomedical Research Centre and NIHR Clinical Research Facility, we then take programmes through to clinical research. Patient Cohorts We can host phase I/II clinical trials in patients and healthy volunteers. We have a large cohort of patients with lung fibrosis and lung disease jointly. We are also a recognised centre for lung cancer and lung physiology plus cystic fibrosis. 18

Professor Wisia Wedzicha Professor of Respiratory Medicine at the UCL Medical School, University College London and the Royal Free London NHS Foundation Trust The NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London; Royal Free London NHS Foundation Trust Disease Expertise Within the respiratory realm, UCL brings specific expertise in COPD and especially the role of COPD exacerbations and airway infection. Research Capabilities We have expertise in detecting COPD exacerbations in the routine management of our longitudinal patient cohorts. We have particular expertise in the study of biomarkers of airway inflammation. We have access to models of pulmonary fibrosis and acute lung injury and airway epithelial cell culture. With an NIHR Biomedical Research Centre and NIHR/ Wellcome Trust Clinical Research Facility at its core, research infrastructure at UCL is able to run all forms of early phase studies, including speciality COPD exacerbation trials. Patient Cohorts Patient groups within our care include those presenting bronchiectasis, COPD, idiopathic pulmonary fibrosis and interstitial lung disease. 19

Professor Ashley Woodcock Consultant Physician at the University Hospital of South Manchester Professor of Respiratory Medicine and Head of the School of Translational Medicine at the University of Manchester. Manchester Academic Health Science Centre Disease Expertise We have expertise in a wide range of respiratory diseases including COPD, asthma and idiopathic pulmonary fibrosis. In addition, we are a recognised allergy and aspergillosis centre. Research Capabilities Manchester s North West Lung Research Centre hosts an NIHR Respiratory Clinical Research Facility with adult and paediatric research physiology laboratories. Facilities include a human performance laboratory, with complex lung function, exercise testing, bronchial challenge, food and inhaled allergen challenge. This clinical infrastructure is supported by high level bioscience laboratory infrastructure. Our Medicines Evaluation Unit is an MHRA-accredited phase I clinical trial unit that is recognised for quality and delivery of phase I and IIa trials in asthma and COPD. Patient Cohorts Allergy, asthma, COPD, fungal lung infections, and chronic cough form the core of our respiratory disease focus, with large cohorts of patients for each. 20

Notes 21

Notes

For further information visit: www.nihr.ac.uk/nocri NIHR Office for Clinical Research Infrastructure (NOCRI) A305, Richmond House 79 Whitehall London SW1A 2NS The information in this brochure is correct at time of printing. October 2012.