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MRC Open Council - Cardiff - July 2011
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Increasing the impact of MRC research
Declan MulkeenDirector, Research ProgrammesJuly 2011
Humanised antibodies – four decades
1973 Mouse antibodies isolated by César Milstein and George Köhler (MRC Laboratory of Molecular Biology)
1986 Michael Neuberger and Sir Greg Winter ‘humanise’ mouse antibodies
Sir Greg develops and patents technology for producing antibodies in vitro
2003 MRC-developed Humira® licensed to treat UK arthritis patients
2008 21 monoclonal antibody drugs on market for treating breast cancer, leukaemia, asthma, arthritis, psoriasis and transplant rejection
2011 Antibodies make up 1/3 of new drugs for cancer, arthritis and asthma; global antibody market estimated to be worth $40bn
Division of Signal TransductionTherapy, Dundee
Sir Philip CohenDirector, MRC Protein Phosphorylation Unit
• 1998: £6.5m, 5 years (Astra, Zeneca, Pfizer, SmithKline Beecham, NovoNordisk and later Boehringer Ingelheim)
• 2003: £15.2m, 5 years (AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Merck and Co, Merck KGaA, Pfizer)
• 2008: renewal of core funding brings total investment from private sector to over £40m
• Protein phosphorylation now one of the largest areas of research worldwide
• 2009: Market for drugs that act on kinases = $15.2bn
Wellcome Trust Project Grants 2006Developed 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
Basic Research
Applied Research
HealthcarePractice & Policy
1st translational gap 2nd translational gap
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" £237k
Mood Disorders Centre (University of Exeter): Cognitive therapy for depression
Outcomes• 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. • 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. • 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). • This treatment material has been copyrighted. • 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.• 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).• The work has been cited in the NICE guideline update on depression (2009)
Wellcome 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 CentreFounded 2003 by Professor Edward Watkins and Professor Willem Kuyken
Collaborations with the private sector
• In 2010, MRC-funded research reported over 650 partnerships with the private sector
• 327 different organisations, based in around 20 different countries
• Co-funding agreements at time of award account for
one-quarter
• 24% are based in the UK• 10% elsewhere in Europe• 10% in the USA, and 48% are global (>2 centres in
different countries)
Companies built from MRC research
• 35 companies have been formed since 2006
• ~ 400 new highly skilled jobs
• 7 have been merged into or acquired by other organisations often with the release of significant investment. For example:
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.
Outcomes from funding: 2010
The MRC pipeline: 2010
Eg Benlysta
Eg ICM software
Strengthening translation 2007-11
• Stronger translational pathway
• Reinforcing exploratory and collaborative research
The Translational Pathway
Developmental Pathway Funding Scheme (DPFS)Preclinical development (£13m/yr)
Developmental Clinical Studies (DCS)Phase I-II (£17m/yr)
MRC-NIHR Efficacy, Mechanism and Evaluation (EME)Phase (v. late IIb)-III (£13m/yr)
Translational Stem Cell Research Committee (TSCRC)
multiple DPFS if required
Collaborative development
• MenBioVax: meningitis vaccine developed by ImmBio with TSB funding following a collaborative programme with Bristol Medical School
• MRC DPFS funding to take MenBioVax through preclinical studies
“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
DCS Case Study: Sodium nitrite for ischaemia-reperfusion injury in myocardial infarction
Lundberg et al. 2008
Collaborative and exploratory research
• Gaps in research skills
• Easier movement between academia and industry
• Underpinning science• Models• Biomarkers
• New ways of coordinating
• Facilities and resources
Inflammation and Immunology Initiative
A new way of funding from the MRC
• Collaboration with ABPI: Disease-focused workshops
• COPD• Rheumatoid arthritis
Brought together experts from academia and industry
Identified research priorities Ear-marked funds for research consortiums to
address barriers and exploit opportunities MRC invested £9.5m over four years
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)
• School of Physiology and Pharmacology, University of Bristol
• Research into neuronal networks and control of cognitive behaviour
• Industrial collaborations with Eli Lilly, Janssen, GSK, Pfizer…
• “A range of companies have provided access to the pharmacological tools, disease models and techniques that I need.”
Dr Matt JonesMRC Senior Non-Clinical Fellow
“Ultimately, if you want to have a
positive impact on patients, then you
need industry’s support.”
What Fellows tell us about industry
Questionnaire• Career placements in
industry?• 0%!
• Why?• 40% Unaware & unable• 60% Irrelevant
• Would you apply for a Senior Fellowship with an industry component?
• 21% Yes
• Issues and risks• “Wanted to focus on establishing my
lab” • “Too early” “Too basic”• “Need to know who and how”• “Translational research is too risky at
this stage of my academic career”
• Opportunities• “Modelling & simulation in drug
development”• “Vital access to novel compounds &
facilities”• “Develop new RNAi based compounds
and therapy”• “Rational drug development”
[n=52 responses from 69 CDA Fellows]
Where next ?
The next steps …..
• Support areas where science is driving major change• Stratified Medicine• Regenerative Medicine
• Coordination - Heath Departments, TSB, Research Councils• Critical mass • International visibility • Simplicity
• Make it easier to engage with industry throughout a research career
• Widen range of companies and innovation sectors engaged with MRC• Links to Small and Medium sized companies
Thank you
TSB
Basic medicalresearch
Prototype discovery and design
Pre-clinical development
Early clinical trials
Late clinical trials
Developmental PathwayFunding 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”
MRC translational research funding
MRC Translational Funding (@ end 2010)
Scheme Number Value Number Value
LeadingTherapeuticAreas
LeadingModalities
Last 12 monthsSince Inception Since Inception
DPFS 97 c. £33m 21 c. £12mCancer,Infection,Neurological
Small Molecule,DiagnosticNon-Imaging,Protein/Peptide
DCS 13 c. £19m 10 c. £14mCardiovascular, Infection,Stroke
Protein/Peptide,Small Molecule,Vaccine
TSCRC 17 c. £11m 6 c. £4m
Eye,Oral and GI,Inflammatory andImmune System,Musculoskeletal
RegenerativeMedicine
TOTAL 127 c. £64m 37 c. £30m