Declan Mulkeen - Increasing the impact of MRC research

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MRC Open Council - Cardiff - July 2011

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  • Medical research, and health related industries – are, if you look across all areas of science, and industry – clear strengths in the UK. Both in bringing benefits of research to patients, and in turning research into economically important industry, the UK has a very good track record. The challenges … we need to do better – competition we need to do it faster and with better productivity – pace of science is accelerating – in some areas, such as pharmaceuticals, the pace of new products emerging is slowing down we need to do it differently – open discovery small mol pharmaceutical model ? stratification of disease and treatment Govt has backed science - high expectations
  • Benlysta : First new Lupus drug in 56 years. Was made possible due to a technique called combinatorial antibody libraries developed at MRC’s LMB. In 2009 it was reported as in Phase III trials, in 2010 reported as undergoing marketing authorisation, and we now know that it has been approved by the FDA (March 2011) as the first new treatment for Lupus in 50 years. Estimates of the market for Benlysta have already been published at around $1.9bn. ICM software : This product, used in brain monitoring for neurosurgery and intensive care was developed back in 2006; by 2010 it was being used in 40 centres worldwide.
  • - invested in allowing good ideas to develop longer in academia, or with academic / industry partnership – recognising that more is needed to compete for private investment - created better ways of aligning MRC plans with industry … top level forum … and new initiative, in Immunology and Inflammation, where we developed strategy together, best of academic and industry ideas - made sure ideas that need public sector funding can progress smoothly all the way from MRC early phase studies to late phase NIHR HTA programmes - helped to build new capabilities in Universities, responding to industry which does more and more of its research in partnership with Universities - MRCT CTD screening and medicinal chemistry - increased postgrad CASE training positions with industry, and in the last year have made progress in getting more of these into smaller companies - made it easier for companies to work alongside MRC awards – much more flexible rules MICA - taking care not to duplicate what industry is good at, and especially not to recreate in academia, strategies that have failed in industry.
  • - invested in allowing good ideas to develop longer in academia, or with academic / industry partnership – recognising that more is needed to compete for private investment - created better ways of aligning MRC plans with industry … top level forum … and new initiative, in Immunology and Inflammation, where we developed strategy together, best of academic and industry ideas - made sure ideas that need public sector funding can progress smoothly all the way from MRC early phase studies to late phase NIHR HTA programmes - helped to build new capabilities in Universities, responding to industry which does more and more of its research in partnership with Universities - MRCT CTD screening and medicinal chemistry - increased postgrad CASE training positions with industry, and in the last year have made progress in getting more of these into smaller companies - made it easier for companies to work alongside MRC awards – much more flexible rules MICA - taking care not to duplicate what industry is good at, and especially not to recreate in academia, strategies that have failed in industry.
  • Dr Matt Jones is an MRC Senior Non-Clinical Fellow in the School of Physiology and Pharmacology, University of Bristol. His research into neuronal networks and control of cognitive behaviour is underpinned by a number of productive industrial collaborations. “ I’ve always collaborated with industry,” says Matt. “A range of companies have provided access to the pharmacological tools, disease models and techniques that I need for my research. Ultimately, if you want to have a positive impact on patients, then you need industry’s support.” Indeed, Matt’s first postdoctoral position was at the MRC National Institute for Medical Research , funded by an industrial collaboration grant linking the MRC and Glaxo Wellcome, now GlaxoSmithKline (GSK). It gave him access to early transgenic mouse models of Alzheimer’s disease, an area he was just moving into researching, and Matt remains in touch with those early collaborators. “ I’m less wary of industry than many academics tend to be,” he admits. “Approaches do vary from company to company but common scientific interests and goals mean I’ve always found industrial collaborations invigorating. For non-clinicians, industry can provide a bridge to patient data and they have a much better appreciation of what’s important in the clinic.” After several years at the Massachusetts Institute of Technology , where he learned state-of-the art electrophysiological techniques used to record neuronal network activity during behaviour, Matt returned to the UK in 2006 to start his own lab applying the technique in models of psychiatric disease. His first Principal Investigator position was funded by a Research Councils UK Academic Fellowship alongside an Integrative Pharmacology Fellowship co-funded by the Association of the British Pharmaceutical Industry. “As soon as I got to Bristol,” says Matt, “I contacted everyone I knew in UK industry and said: ‘This is what I’m doing, is it of any interest?’ It’s vital for academics to be proactive.” As a result, Matt has cultivated collaborations with Eli Lilly & Co, Janssen, GSK, Pfizer and others, always driven by scientific need. “I’m fortunate that our research on neural networks and cognition is riding a wave at the moment,” says Matt. “Saying that, it’s not enough just to be in the right place at the right time – you need to know that you are. So a broad network of contacts is vital. It’s an exciting time for me and for the field. But it’s a bleak picture in industry where improved psychiatric treatments are concerned – there are few new drugs in the pipeline and there’s a growing appreciation that companies need to be supporting research into fundamental mechanisms of brain function.” Through his contacts and collaborations, most of the PhD students in Matt’s lab have some involvement with industry through MRC Industrial CASE studentships or similar schemes . “It benefits the student because they get experience of industry,” says Matt. “It benefits me because I get to access the tools and expertise that industry has. And it benefits the company because they get access to our unique electrophysiology and broader view of mechanisms of cognition.” As part of his MRC Fellowship, Matt will spend time at Lilly’s Centre for Cognitive Neuroscience (CCN, directed by Dr Mark Tricklebank of Lilly), using proprietary technology to study altered sleep states that contribute to cognitive symptoms in schizophrenia. “The Lilly CCN model of jointly supervised postdoctoral Fellows and a broad range of academic collaborations has set a powerful precedent,” he says. “It’s been hugely productive and enjoyable and, alongside academic-industry links, has also fostered new academic collaborations amongst the universities involved.” Matt has also been successful in getting further funding for a collaborative project with Janssen, who will support a PhD student and postdoc in his lab. The University of Bristol is part of the Severnside Alliance for Translational Research (SARTRE), which took part in a pilot scheme whereby they locally managed one of the MRC’s translational research funding schemes: the Developmental Pathway Funding Scheme (DPFS). Through SARTRE , Janssen became interested in psychiatric research in Matt’s lab at Bristol and at the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff. Following a one-year pilot, DPFS-funded work contributed to Matt and Professor Lawrence Wilkinson (Cardiff University, also a member of the Lilly CCN) securing an MRC grant to study the neurobiology of a gene linked to schizophrenia . “This is just one example of how a broad network of collaborations spanning industry and academia can fuel future research,” says Matt. Given his success in working with industry, does Matt have any advice for academics who want to follow his lead? “All my industry collaborations have been about answering specific scientific questions that can help people – disregard academic and industrial stereotypes to focus on your common goals and you will certainly find common benefits. The landscape has changed in industry in the last five years, especially in psychiatric research. The business of industrial R&D is always in flux but they know that academic collaborations offer an invaluable knowledge and skills base and – provided the expectations of both parties are realistic – good value for money . Perhaps academics need advertise their wares a little more actively.”
  • Declan Mulkeen - Increasing the impact of MRC research

    1. 1. Increasing the impact of MRC research Declan Mulkeen Director, Research Programmes July 2011
    2. 2. Humanised antibodies – four decades <ul><li>1973 Mouse antibodies isolated by C ésar Milstein and George Köhler (MRC Laboratory of Molecular Biology) </li></ul><ul><li>1986 Michael Neuberger and Sir Greg Winter ‘humanise’ mouse antibodies </li></ul><ul><li>Sir Greg develops and patents technology for producing antibodies in vitro </li></ul><ul><li>2003 MRC-developed Humira ® licensed to treat UK arthritis patients </li></ul><ul><li>2008 21 monoclonal antibody drugs on market for treating breast cancer, leukaemia, asthma, arthritis, psoriasis and transplant rejection </li></ul><ul><li>2011 Antibodies make up 1/3 of new drugs for cancer, arthritis and asthma; global antibody market estimated to be worth $40bn </li></ul>
    3. 3. Division of Signal Transduction Therapy, Dundee <ul><li>Sir Philip Cohen </li></ul><ul><li>Director, MRC Protein Phosphorylation Unit </li></ul><ul><li>1998 : £6.5m, 5 years (Astra, Zeneca, Pfizer, SmithKline Beecham, NovoNordisk and later Boehringer Ingelheim) </li></ul><ul><li>2003 : £15.2m, 5 years (AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck and Co, Merck KGaA, Pfizer) </li></ul><ul><li>2008 : renewal of core funding brings total investment from private sector to over £40m </li></ul><ul><li>Protein phosphorylation now one of the largest areas of research worldwide </li></ul><ul><li>2009 : Market for drugs that act on kinases = $15.2bn </li></ul>
    4. 4. Wellcome Trust Project Grants 2006 Developed Professor Edward Watkins research NIHR South-West CLAHRC (2007) Provision of institutional programmatic support to support the further translation of this work into a viable treatment. Total value of Peninsula CLAHRC £10m MRC Experimental Medicine Grant (2007) “ Cognitive training as a facilitated self-help intervention for depression” Allowed for growth of research team and shift in focus from experimental research to evaluation of therapy via RCT . £464k MRC Brain Sciences Trial Platform Grant (2005) “ Preventing depression relapse in NHS practice using Mindfulness-Based Cognitive Therapy&quot; £237k Mood Disorders Centre (University of Exeter): Cognitive therapy for depression <ul><ul><li>Outcomes </li></ul></ul><ul><ul><li>Proof-of-principle evidence that training depressed individuals to think about their problems in a more concrete way reduces their symptoms of depression. Pilot work in a multiple case series has demonstrated in patients with major depression that is safe, tolerable, and acceptable. </li></ul></ul><ul><ul><li>The final stages of the current MRC grant have tested out the efficacy of the intervention in a small scale controlled trial (n =121). The results of the main outcome analysis indicate that the cognitive training guided self-help treatment adds significant clinical benefit in terms of reducing depression relative to treatment-as-usual alone, and that it is of equivalent efficacy to a relaxation based guided self-help treatment in reducing depression, but superior in changing depressogenic thinking such as rumination. </li></ul></ul><ul><ul><li>The project has therefore developed a novel treatment derived from experimental findings that is easily accessible, cost-effective and able to be disseminated, and could be made widely available (for example via Improving Access to Psychological Treatments IAPT initiative). </li></ul></ul><ul><ul><li>This treatment material has been copyrighted. </li></ul></ul><ul><ul><li>The report of the main outcome of the trial has now been prepared as a paper and submitted to a high impact peer-reviewed journal for publication. </li></ul></ul><ul><ul><li>Collaborations with researchers in the Netherlands (2009) has extended this work to a new population (adolescents at risk) and to a prevention treatment (rather than an acute treatment). </li></ul></ul><ul><ul><li>The work has been cited in the NICE guideline update on depression (2009) </li></ul></ul>W ellcome Trust Capital Grant to build the new Sir Henry Wellcome Mood Disorders Centre at Exeter (due to open in 2011) £3.6m Health Technology Assessment (2010) “ Preventing depressive relapse in NHS Practice through mindfulness-based cognitive therapy (MBCT)” £2.1m Mood Discorders Centre Founded 2003 by Professor Edward Watkins and Professor Willem Kuyken Basic Research Applied Research Healthcare Practice & Policy 1st translational gap 2nd translational gap
    5. 5. Collaborations with the private sector <ul><li>In 2010, MRC-funded research reported over 650 partnerships with the private sector </li></ul><ul><li>327 different organisations, based in around 20 different countries </li></ul><ul><li>Co-funding agreements at time of award account for one-quarter </li></ul><ul><li>24% are based in the UK </li></ul><ul><li>10% elsewhere in Europe </li></ul><ul><li>10% in the USA, and 48% are global (>2 centres in different countries) </li></ul>
    6. 6. Companies built from MRC research <ul><li>35 companies have been formed since 2006 </li></ul><ul><li>~ 400 new highly skilled jobs </li></ul><ul><li>7 have been merged into or acquired by other organisations often with the release of significant investment. For example: </li></ul>Thiakis Ltd ., an Imperial College spin out company was formed in 2004 to develop discoveries from the MRC funded laboratory of Professor Steve Bloom for the treatment of obesity and associated conditions. Thiakis raised £10 million funding in 2006, and was sold to Wyeth for £20 million followed by additional potential milestones payments totalling up to £80 million, in December 2008. Domantis was an MRC spin out established by Sir Gregory Winter, and Dr Ian Tomlinson from MRC LMB with seed funding from MVM Ltd. to develop Human Domain Antibodies™. At the end of 2006 GSK acquired Domantis for £230 million. MRC received £7.3 million from sale of its interest.
    7. 7. Outcomes from funding: 2010
    8. 8. The MRC pipeline: 2010 Eg Benlysta Eg ICM software
    9. 9. Strengthening translation 2007-11 <ul><li>Stronger translational pathway </li></ul><ul><li>Reinforcing exploratory and collaborative research </li></ul>
    10. 10. The Translational Pathway <ul><li>Developmental Pathway Funding Scheme (DPFS) </li></ul><ul><li>Preclinical development (£13m/yr) </li></ul><ul><li>Developmental Clinical Studies (DCS) </li></ul><ul><li>Phase I-II (£17m/yr) </li></ul><ul><li>MRC-NIHR Efficacy, Mechanism and Evaluation (EME) </li></ul><ul><li>Phase (v. late IIb)-III (£13m/yr) </li></ul>Translational Stem Cell Research Committee (TSCRC) multiple DPFS if required
    11. 11. Collaborative development <ul><ul><li>MenBioVax : meningitis vaccine developed by ImmBio with TSB funding following a collaborative programme with Bristol Medical School </li></ul></ul><ul><ul><li>MRC DPFS funding to take MenBioVax through preclinical studies </li></ul></ul>“ There aren’t many other sources of funding for this type of project in the UK. It brings more than just money, of course. It’s important for potential investors to be able to see that bodies like the MRC have confidence in our technology and products.” Graham Clarke, ImmBio CEO
    12. 12. DCS Case Study: Sodium nitrite for ischaemia-reperfusion injury in myocardial infarction Lundberg et al. 2008
    13. 13. Collaborative and exploratory research <ul><li>Gaps in research skills </li></ul><ul><li>Easier movement between academia and industry </li></ul><ul><li>Underpinning science </li></ul><ul><ul><li>Models </li></ul></ul><ul><ul><li>Biomarkers </li></ul></ul><ul><li>New ways of coordinating </li></ul><ul><li>Facilities and resources </li></ul>
    14. 14. Inflammation and Immunology Initiative <ul><li>A new way of funding from the MRC </li></ul><ul><li>Collaboration with ABPI: </li></ul><ul><ul><li>Disease-focused workshops </li></ul></ul><ul><ul><ul><li>COPD </li></ul></ul></ul><ul><ul><ul><li>Rheumatoid arthritis </li></ul></ul></ul><ul><ul><li>Brought together experts from academia and industry </li></ul></ul><ul><ul><li>Identified research priorities </li></ul></ul><ul><ul><li>Ear-marked funds for research consortiums to address barriers and exploit opportunities </li></ul></ul><ul><ul><li>MRC invested £9.5m over four years </li></ul></ul>
    15. 15. Research resources: eg patient cohorts ABC – A Bipolar Cohort (Newcastle): 180 London COPD Exacerbation Cohort (UCL): 250 Paediatric-Onset Inflammatory Disease Cohort and Treatment Study (PICTS) (Edinburgh): 450 Pathobiology of Early Arthritis Cohort (QMUL): 300 Type 2 diabetes in childhood (Birmingham): 85 Rapidly Evolving Multiple Sclerosis (Imperial): 200 UK Primary Sjögren’s syndrome Registry (Newcastle): 500 Wessex severe asthma cohort (Southampton) Mitochondrial Disease Patient Cohort (Newcastle; Oxford; MRC CND, London) UK TTP Registry (UCL) Population-based Ankylosing Spondylitis cohort (Swansea)
    16. 16. <ul><li>School of Physiology and Pharmacology, University of Bristol </li></ul><ul><li>Research into neuronal networks and control of cognitive behaviour </li></ul><ul><li>Industrial collaborations with Eli Lilly, Janssen, GSK, Pfizer… </li></ul><ul><li>“ A range of companies have provided access to the pharmacological tools, disease models and techniques that I need.” </li></ul>Dr Matt Jones MRC Senior Non-Clinical Fellow “ Ultimately, if you want to have a positive impact on patients, then you need industry’s support.”
    17. 17. What Fellows tell us about industry <ul><li>Questionnaire </li></ul><ul><li>Career placements in industry? </li></ul><ul><ul><li>0%! </li></ul></ul><ul><li>Why? </li></ul><ul><ul><li>40% Unaware & unable </li></ul></ul><ul><ul><li>60% Irrelevant </li></ul></ul><ul><li>Would you apply for a Senior Fellowship with an industry component? </li></ul><ul><ul><li>21% Yes </li></ul></ul><ul><li>Issues and risks </li></ul><ul><ul><li>“ Wanted to focus on establishing my lab” </li></ul></ul><ul><ul><li>“ Too early” “Too basic” </li></ul></ul><ul><ul><li>“ Need to know who and how” </li></ul></ul><ul><ul><li>“ Translational research is too risky at this stage of my academic career” </li></ul></ul><ul><li>Opportunities </li></ul><ul><ul><li>“ Modelling & simulation in drug development” </li></ul></ul><ul><ul><li>“ Vital access to novel compounds & facilities” </li></ul></ul><ul><ul><li>“ Develop new RNAi based compounds and therapy” </li></ul></ul><ul><ul><li>“ Rational drug development” </li></ul></ul>[n=52 responses from 69 CDA Fellows]
    18. 18. <ul><li>Where next ? </li></ul>
    19. 19. The next steps ….. <ul><li>Support areas where science is driving major change </li></ul><ul><ul><li>Stratified Medicine </li></ul></ul><ul><ul><li>Regenerative Medicine </li></ul></ul><ul><li>Coordination - Heath Departments, TSB, Research Councils </li></ul><ul><ul><li>Critical mass </li></ul></ul><ul><ul><li>International visibility </li></ul></ul><ul><ul><li>Simplicity </li></ul></ul><ul><li>Make it easier to engage with industry throughout a research career </li></ul><ul><li>Widen range of companies and innovation sectors engaged with MRC </li></ul><ul><ul><li>Links to Small and Medium sized companies </li></ul></ul>
    20. 20. Thank you
    21. 21. MRC translational research funding TSB Basic medical research Prototype discovery and design Pre-clinical development Early clinical trials Late clinical trials Developmental Pathway Funding Scheme Developmental Clinical Studies Targeted initiatives to alleviate bottlenecks Infrastructure/Resources Methodology Training Continued commitment to basic lab, clinical and population research Capacity building NIHR Translational Stem Cell Research Programme Translational Research Support – the “Managed Programme”
    22. 22. MRC Translational Funding (@ end 2010) Scheme Number Value Number Value Leading Therapeutic Areas Leading Modalities Last 12 months Since Inception Since Inception DPFS 97 c. £33m 21 c. £12m Cancer, Infection, Neurological Small Molecule, Diagnostic Non-Imaging, Protein/Peptide DCS 13 c. £19m 10 c. £14m Cardiovascular, Infection, Stroke Protein/Peptide, Small Molecule, Vaccine TSCRC 17 c. £11m 6 c. £4m Eye, Oral and GI, Inflammatory and Immune System, Musculoskeletal Regenerative Medicine TOTAL 127 c. £64m 37 c. £30m

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