Translational Medicine(?????): Bridge Over the Valley of Death(????????)

1
Translational Medicine(?????) Bridge Over the
Valley of Death(????????)

• Edward W. Holmes, MD
• Vice Chancellor Emeritus, Health Sciences
• University of California San Diego
• President, Sanford Consortium for Regenerative
  Medicine

2
Goals of Translational Medicine(TR????)

• Advance our insight and understanding of human
  disease(????????????????)
• Use these advances to improve the health of
  individuals and populations(??????????????????????
  ???)
• Enhance economic well being of society(???????????
  ??)

3
Translational Medicine Has a Broad
Remit(TR???????????)
TransMed Starts and Ends with the
Patient TR?????????????
Clinical Medicine
Patient studies Disease Pathogenesis
Patient studies Therapeutic Intervention
Basic Research
4
What is Translational Research

• Translation does not end with the ribosome, and
  it does not begin with a clinical trial
• (TR????????????????????????????)
• Broad enterprise that spans disease pathogenesis
  to discovery of therapeutic targets to
  demonstration of clinical effectiveness
  (TR?????????????????????????????????????)

5
The Translational ContinuumTR???? From
Discovery to Delivery(????????)
Drug Target
Lead Optimiz- ation
Target Validat-ion
Clinical Trials
Clinical Delivery
Lead
GMP
The Enablers
Models Mice Primates
High Throughput and Design
G l o b a l H e a l t h
Manufacturing
Patients
Discovery Research
Medicinal Chemistry
Lead Optimization
Lead
The Human Capital
Chemist Translational Ph.D. Physician-Scientist
Ph.D. MD
Physician Scientist
Clinical Investigator
Industry
Clinicians
6
Translational Medicine(?????)
?????????
Translate Into
Commercialize Into
The Valley of Death
Fundamental Medical Discovery
Potential New Drug
?????? ???????
?????????
Approved New Theraupetic
??????????? ???????
7
Causes of the Valley of Death

• Too few well trained Physician Scientists(???????M
  D,PhD???????)
• Lack of adequate infrastructure(??????????)
• Funding to support the people and
  infrastructure(?????????????)

8
Human and Physical Capital(???????)
Translational Medicine Program(TR?????)
TCR
Basic Disease-
Investigative Clinical Trials
Clinical Research Oriented
Medicine Epidemiology
Practice of Research Health
Svcs Rsch Medicine
Physician Scientists(MD PhD)
Project Teams(?????) Regulatory
Experts (???????????? ????)
Infrastructure (????)
9
Human Capital(????) Translational Medicine
Program
TCR
Basic Disease-
Investigative Clinical Trials
Clinical Research Oriented
Medicine Epidemiology
Practice of Research Health
Svcs Rsch Medicine
Physician Scientists
10
Bridge over the Valley of Death(????????)(1)
Physician Scientists(MD, Ph.D)

• Training(??)- dual training clinical and
  scientific(???????????)
• Protected time(?????)- 80 research(??) 20
  clinical(??)
• Environment- Leadership respects and supports
  dual mission(????2????????????)
• Endangered species(?????)- international
  shortage(??????)

11
Facilities(??) Translational Medicine
Program(TM?????)
TCR
Basic Disease-
Investigative Clinical Trials
Clinical Research Oriented
Medicine Epidemiology
Practice of Research Health
Svcs Rsch Medicine
Infrastructure(????)
12
Bridge over the Valley of Death(????????) (2)
Infrastructure(????)

• Clinical Research Facilities for Patient
  Studies(??????????????)
• Access to development technologies(?????????????)
  High Through Put Screening, Medicinal Chemistry,
  Mab production, device prototype production
• Access to GMP facilities, Toxicology
  assessment(GMP???????)?????????????)

13
Team Members(???????) Translational Medicine
Program
TCR
Basic Disease-
Investigative Clinical Trials
Clinical Research Oriented
Medicine Epidemiology
Practice of Research Health
Svcs Rsch Medicine
Team Specialists(?????????) Project
Teams(?????????) Regulatory Experts(??????????????
??)
14
Bridge over the Valley of Death(????????) (3)
Team Members

• Nurses and Study Coordinators(???????????????)
• Project Team(?????)
• Regulatory Expertise(????????????????)
• Advisory Panel with industry and business
  expertise in addition to scientific
  expertise(?????????????????????????)

15
Bridge over the Valley of Death(????????) (4)
Business Development Office(??????????????)

• Intellectual Property and Technology
  Transfer(?????????)
• Legal support for contract services(???????????),
  etc
• Industrial Partnership Office(????????)

16
Key Recommendations
INDUSTRY
Interaction strengthened by new entities arising
from hospital-medical school partnerships
gtgt Grow health services, public health research
gtgt Establish flagship programmes from
bench-to-bedside (heart/ metabolic, neuro,
cancer, eye, infectious disease)
gtgt Build critical mass of human capital,
supernumerary to clinical service needs
17
Research Scholarships(?????)

• Masters of Clinical Investigation
• MD- PhD
• MBA-MD
• Research Fellowships
• ________________

18
Talent Development Programmes(?????????)

• Singapore Translational Research Investigator
  Awards (STaR)
• Clinician Scientist Awards (CSA)
• Transition Awards

19
Talent Development Programmes (?????????)

• 100 of academic salary provided(100?????????????
  ??)
• Guarantee of 70-80 of time protected for
  research(7080??????????)
• Variable laboratory support(??????????)

20
Clinical Research Institute(??????)

• One-stop centre providing infrastructure support,
  to conduct clinical trials (One-stop
  centre??????????????????????)

21
Translational and Clinical Research (TCR)
Flagship Programmes
Five TCR Programmes awarded - S25mil each
Disease Areas Awardees Host Institution
Gastric Cancer - Genomics and biomarkers trials A/Prof Yeoh Khay Guan National University of Singapore
Neuroscience - Schizophrenia and related psychoses A/Prof Chong Siow Ann Institute of Mental Health
Eye Diseases - Glaucoma and corneal disorders Prof Donald Tan Singapore Eye Research Institute
Infectious Disease - Dengue treatment and prevention A/Prof Leo Yee Sin Tan Tock Seng Hospital
Metabolic Diseases - Developmental pathways A/Prof Chong Yap Seng National University of Singapore
22
Other TCR Initiatives(??TCR???)

• Experimental Therapeutics Centre (ETC)
• Established to fill the gap between
  identification of therapeutic targets and
  synthesis of lead compounds or biologics for
  clinical trials(??????????????????????????????????
  ???????)
• Singapore Institute for Clinical Sciences (SICS)
• Research institute to bridge basic scientists at
  Bioplois with clinical investigators in
  AMCs(?????????????AMCc??????????????????)
• Restructured IRBs
• Domain specific IRBs that cover all public
  hospitals(????????????????????IRB)

23
Other TCR Initiatives

• Singapore Consortium for Cohort Studies (SCCS)
• Common infrastructure for coordination of cohort
  studies and collection of phenotypic
  data(?????????????????????????????????)
• Singapore Tissue Network (STN)
• National resource for collection, storage, and
  retrieval of human tissue samples to support
  translational and clinical research(TR?CR?????????
  ??????????????????????
• Clinical Research Imaging Center (CIRC)
• Advanced imaging technologies dedicated to human
  research studies(????????????????????)

24
Singapores Niche in Translational and Clinical
Research(TR?CR???????????????)

• Asian Phenotype(???????)
• Focus on Diseases of Interest to Singapore or
  Special Ability to Study in Singapore(????????????
  ????????????????????????)
• Investigational Medicine and POC
  Studies(?????POC??)

25
Strengthening TCR
BMS Phase 1 (2000-2005)
Oct 08 TCR Flagship 25M to be awarded for
CV/metabolism, and ID
Mar 08 CSA 4 Senior Inv 1 Inv
Nov 07 Kent Ridge Campus Joint NUHS established
Mar 08 STaR Daniel Tenen, David Virchup, Michael
Chee, Wong Tien Yin
Mar 08 Training pipeline 2 AST- PhD MCI launched
Aug 07 Outram Campus GMS launched inaugural
batch of 26 students
Mar 08 Strategic Research Infra Proposed i)
Research space (RBF, ARF, IMU)16,000sqm at KR,
23,000sqm at Outram ii) IMUs 24 beds in KR, 30
beds in Outram
Jul 07 TCR Flagship 25M for Gastric Cancer (led
by NUS)
Jul 06 Launch of BMS Phase 2 1.55B for TCR
Jul 08 TCR Flagship 25M each for Eye
Neurosciences
Feb 07 CSI 2 Snr Inv Award 4 Inv Award
Jan 08 Academic Clinical Research Orgn Duke to
establish SCRI in 08
2007 Establishment of SICS, SIgN, ETC
Feb 08 Established CBME
2007
2008
Mid 2006
2000
26
Clinical Imaging Research Centre (CIRC)

• In Apr 08, Ministry of Trade Industry approved
  S31.8mil from ST2010 to fund CIRC activities
  for 5 years.
• Construction of CIRC Phase 1 facility at the NUS
  Centre for Life Sciences began in early March
  2008 and completed on 18 September 2008.
• The Siemens 3 Tesla clinical whole body MRI
  installed in Phase 1 facility in July 2008.
• Construction for CIRC Phase 2 facility at the new
  NUS Centre for Translational Medicine has begun
  and will be completed in March 2011.
• Ongoing exploration of partnerships with MOH,
  Duke-NUS GMS etc to develop CIRC's clinical
  programmes and advancing imaging techniques such
  as PET-MR.