cathy tralau -stewart phd head of drug discovery drug discovery centre imperial college
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The Imperial Drug Discovery Centre; enabling translation of academic projects towards clinical validation. Cathy Tralau -Stewart PhD Head of Drug Discovery Drug Discovery Centre Imperial College www.imperial.ac.uk /medicine/ drugdiscoverycentre. Drug Discovery Landscape. - PowerPoint PPT PresentationTRANSCRIPT
The Imperial Drug Discovery Centre;
enabling translation ofacademic projects towards clinical
validationCathy Tralau-Stewart PhDHead of Drug DiscoveryDrug Discovery Centre
Imperial College
www.imperial.ac.uk/medicine/drugdiscoverycentre
Drug Discovery Landscape
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Pharma 2020: The Vision PWC 2010
Future of drug discovery
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‘in the next 10 years, pharma spend will continue to decrease and most of pre-clinical candidate drug discovery will be done in academia’
Dr Dave TapolczayCEO MRC Technology 2009
‘>50% of future pipeline will come from outside major pharma’
David Redfern CSO, GSK, Feb 2011
‘Research-led Pharma needs new innovative models’
John LechleiterPresident & CEO Eli LillyFeb 2011
• ‘Investors will not tolerate sub-optimal returns on R&D’
• ‘This will be the last generation of high R&D spend unless return to investors is greater’
• ‘Ten year doomsday scenario- No R&D only generics’
What future for UK science base?
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The Future of Healthcare Industries
• Fewer and more consolidated health care companies
• Focused on developing low risk assets • Competition to in-license the ever-decreasing
number of advanced assets• Without focus, there will be a reduced supply
of innovative drugs to treat real un-met need
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Published by AAAS
M. A. Fischbach et al., Science 325, 1089 -1093 (2009)
Between 1962 and 2000, no major classes of antibiotics were introduced
and resistance is a major issue
7AE Clatworthy et al (2007) Nature Chemical Biology p 541
~ 30 years
~ 3 years
Why Do Drug Discovery in Academia ?
Pull: Pharma require products for their pipelines
Push: Translate publicly funded research to the clinic
Ability: Demonstrate research excellence
Moral case: Need for new approaches to diseaseReward: Potential for commercial reward and publications
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Academic v Industrial skill base
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Academic/ Clinical
• In-depth disease knowledge• Novel pathway knowledge• Clinical expertise & access• Innovative approaches
Industrial
• Drug discovery Know-how• Quantitative robust assays• Data security• Candidate definition
Complementary skills and capabilities
Profile of a drug candidate
Active• phenotypic activity reflecting clinical endpoint• defined target (receptor, enzyme, ion channel)
Selective• against targets associated with toxicity
Bioavailable• available at site of action • suitable elimination kinetics
Safe• Significant adverse effects only occur at higher dose than the effective
dose10
Licenseable assets
1. Candidate with human PoC or Phase I safety (IP)
2. Pre- Clinical Candidate with required safety/ toxicology/ pharmacokinetics & efficacy profile (IP)
3. Candidate molecule with defined optimised target profile
4. Lead series (+/- backup)
5. Novel target or effect
Time (years)
Valu
e
6-10
4-6
2-4
2-3
0
Drug Discovery takes 10 years +
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Discovery Development
Basic research: years 0-3
Pre-Clinical: years 4-6
Clinical: years 7-10
Drug to public: years 11+
1000’s 100’s 10’s 1’s
Disease
Target Hypothesis
Protein, Assay, Screen, Hit
Lead, Med Chem, Pharmacology, ADMET,
Candidate, Tox, FTIH
PoC (Phase 2), Phase 3, File
DRUG
Academic expertise Industrial expertiseLack of expertise
The Drug Discovery Centre (DDC)
Most academic institutions do not have capabilities or expertise to achieve this alone
However, Imperial College had the foresight to invest in creating a a Drug Discovery Centre of expertise
The DDC;• Supports the translation of research into quality drug discovery
projects
• Is a recognized leader in the developing ‘discipline’ of academic drug discovery
• Is a Cross-Faculty Centre hosted by The Faculty of Medicine, (Experimental Medicine)
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A flexible cost efficient academic virtual biotech
• Projects sourced from Imperial’s 2000 + researchers
• Multidisciplinary expertise in-house
• Limited expensive lab capabilities
• Compound library (x1800 biologically active)
• Chemoinformatics
• Screening lab
• Outsource specific expertise, skills and capabilities from extensive world-wide array of Contract Research Organisations (CROs)
• Project and outsourcing management essential
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DDC team: respected, expert, multi-disciplinary
Expertise Background
Pharmacology Cathy Tralau-Stewart PhD
20 years Glaxo, GlaxoWellcome, GSK
Medicinal Chemistry Albert Jaxa-Chamiec PhD
30 years Pfizer, Searle, SK&F, Glaxo, GSK
Molecular Modeling & Medicinal Chemistry Caroline Low PhD 20 years James Black
Foundation / J&JCell Biology & Project
Management Hayley Cordingley PhD 10 years GSK
Assay Development & Screening Katie Chapman PhD 2 years GSK
Chemistry & Project Management Matt Fuchter PhD
Imperial, CSIRO Melbourne & Royal School of Pharmacy
Drug Metabolism and Pharmacokinetics Richard Starkey Servier, Shire
Chemistry Post-doc Katie Judd PhD Bath
Biology Post-doc Katherine Scott PhD Manchester 15
DDC Outputs
The DDC has expertise to• Create chemical tools for basic research• Create small molecule starting points for drug discovery• Develop target biology • Develop robust bioassays to test drug candidates• Create candidate molecules
We create “Composition of Matter” patents• the starting point for Industrial Drug Development campaigns
We aim to develop new approaches to drug discovery• To shorten the 10-15 year timeframe from the bench to the clinic• Tackle the hard problems - no “low hanging fruit” left• Create the next generation of drugs
Contract studies- engaging expertise as required
• Synthetic chemistry • Peptide & protein synthesis • DMPK ~ in vitro and in vivo• Receptor/ enzyme selectivity
screens • HTS
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A cost-effective and efficient approach which enables access industry expertise
and capabilities
DDC contribution to projects
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Target IdentificationTarget Valdation
Hit discovery
Hit to Lead Lead optimisation
Candidate Pre-clinicalClinical
Increasing value
Medicinal chemistry/modeling
Synthetic chemistry
Drug metabolism & pharmacokinetics
Assay design/screening (virtual/real)
In vitro/in vivo pharmacology
Grant applications
Project Management
Portfolio by phase Jan 2011
Mlaria
DDC delivery
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Translation in action
Tool compounds•Malaria•Heart failure
•Kidney fibrosis
Hit discovery•Malaria•5 cancer projects
•Transplant rejection
Hit to Lead•Biological therapeutic(breast cancer)
•Solid tumors
Lead optimisation•Ovarian cancer
•Rheumatoid arthritis
•Multiple myeloma
Pre-clinical•Breast cancer(BS194 and back ups)
Spin out•Navion - external investment,
biological (breast cancer)
Increasing value
Traditional drug discovery ‘process’
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Discovery Development
Basic research: years 0-3
Pre-Clinical: years 4-6
Clinical: years 7-10
Drug to public: years 11+
1000’s 100’s 10’s 1’s
Disease
Target Hypothesis
Protein, Assay, Screen, Hit
Lead, Med Chem, Pharmacology, ADMET,
Candidate, Tox, FTIH
PoC (Phase 2), Phase 3, File
DRUG
Projects : 24 ……………………………………….…….1
Drug Discovery Cycle
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Click icon to add picture AssetsClinicians who also run research groupsLab work on human tissueBirthplace of new technologies
GapsInter-disciplinary skillsAccess to toolsLack of flexibilityDrug discovery knowledge
Drug discovery linking directly to the clinic
Benefit of phenotypic human based assays
eg;• Identified compounds which reverse the
resistant phenotype in paired human platinum sensitive & resistant ovarian tumour cell lines (Hani Gabra & Euan Stronach)
• Identified compounds which effectively inhibit TNF in human rheumatoid synovial membranes using human white blood cells (Sandra Sacre, Brian Foxwell & Marc Feldmann)
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Patient Access – Imperial College Healthcare NHS Trust
•One million patients pass through our London hospitals each year•Charing Cross Hospital•Hammersmith Hospital•St Mary’s Hospital•Queen Charlotte’s & Chelsea Hospital•Western Eye Hospital•Large patient population for recruitment into clinical trials•Imperial College Clinical Trials Unit - access to a large and ethnically diverse patient population in major London hospitals (2.3 million local population)
The Drug Discovery Centre translates academic
research
Academics discover novel targets
Partnership with industry to ensure translation to the clinic
Drug Discovery Centre expertise; from biology to candidate
Imperial College Drug Discovery Centre
www.imperial.ac.uk/medicine/drugdiscoverycentre
7th Floor Biochemistry, South Kensington
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