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Successful Academia-Pharma Collaboration
Drug Discovery and Clinical Development
Toshio MIYATA
Tohoku University Graduate School of Medicine
United Centers for Advanced Research
and Translational Medicine (ART)
United Centers for
Advanced Research and Translational
Medicine (ART) ●Developmental
Neuroscience●Clinical Neuroscience
●Translational Neuroscience
Center for Neuroscience
●Cell Proliferation●Cancer stem cell
Center for Cancer Research
●Metabolic Diseases●Metabolic Disease
Complications
Center for Metabolic Diseases
Center for Advanced Medical Research and
Development
●Clinical Cell Therapy ●Medical Apparatus
Development●Gene Therapy
●Regulatory Science
●Chronic kidney disease●Renal pathophysiology
Center for Advanced and
Integrated Renal Science
●Integrated research for women’s health
Center for Integrated Research for Women’s
Health
●Neurological Science●Neurochemistry
Center for Prion Research
●Molecular Medicine and Therapy
●Chemical library and medicinal chemistry
●Medicinal bioregulation●Drug metabolism and
Pharmacokinetics●Regulatory Science
●Exploratory Clinical study●Molecular Imaging
Center for Drug Discovery and
Exploratory Clinical Study
Center for Immunological
Science
●Immune development and homeostasis
●Allergy and autoimmunity
Center for Sports Medicine &
Science
●Peak Performance●Sports Injury
●Regulatory Epigenome●Disease Genomics and
Epigenomics
Center for Regulatory Epigenome and
Diseases
●Oxidative Stress medicine and Therapy
●Hypoxia Medicine and Therapy
Center for Oxygen Medicine
Center Project Center Project
Traditional vertical structure
ART styleOpen innovation
「Human resource (PJ leader)」& 「Projects」
Academic unit A
・Professor・Assoc. professor・Lecturer・Assistant
Core center A
・Professor (A,B,C)・Assoc. professor (D,E,F)・Lecturer (Q,S,X)・Assistant from other
faculty (C,D,E)
Core center B
Core center DCore center C
・Professor (Y,E)・Assoc. professor (F)・Lecturer (K,M,U,Z)・Assistant (H,J,E)
・Professor (A,C)・Assoc. professor (A,B,D)・Lecturer (Q,V,W)・Assistant (C,F,G)
・Professor (C,L,N)・Assoc. professor (A,B,D)・Lecturer (C,G)・Assistant (P,S,Z)
Project-oriented, cross-cutting research organization
・Professor・Assoc. professor・Lecturer・Assistant
・Professor・Assoc. professor・Lecturer・Assistant
・Professor・Assoc. professor・Lecturer・Assistant
Academic unit B
Academic unit C Academic unit D
Clinical TrialIntellectual properties(IPs)
form
basic research
Technology Licensing Organization
(TLO)Center/Organization for the
clinical study
Guidance and motivation at an early stage of researchComprehensive, hands-on supports
Support Support
Current status
Intellectual properties(IPs)
Transfer to the Pharma
Basic Research
Useful compounds
Old model
Proof of concept in human
Pharmacokinetics (PK)Pharmacodynamics (PD)
Toxicity
Transfer to the Pharma
IPs Clinical Data
Assets of academia
Ideal model
Project managerPatent attorney
Regulatory expert
Insufficient
Medicines are not always developed for fields in which they are needed…
Fact
Knowledge of disease
pathophysiology
Safe investigational
compound
Academia
Human(Patient)
LeadOptimiza
tion
Pre-clinical
Ⅰ Ⅱ ⅢSubmission
Eliminate ineffective compoundsSelect useful compounds which act on human
physiology and pharmacology
Exploratory clinical trialTraditional development for the marketing
approval application
Industry
Academia-Pharma collaboration
What are their respective roles?
New ICH Harmonized Tripartate Guideline
European Union, Japan and the USA
Epoch-making step for the drug discovery and development in academia !
Earlier access to human data
Pharmacokinetics (PK) as a micro-dosing test
Pharamadynamics (PD) with useful surrogate biomarkers
and sensitive detection technologies (e.g., PET molecular
imaging)
Pharmacokinetics (microdose trial)
Tissue distribution (microdose trial with PET-CT)
Pharmacodynamics (using biomarkers)
Miyata et al, Nature Review Nephrology, 2011
Exploratory clinical trial
Earlier access to human data should
•Improve insights into human physiology/pharmacology
•Document the drug candidate’s characteristics
•Identify therapeutic targets relevant to disease
Exploratory clinical trials in academia
Benefits
•Investigational chemical compounds
•Molecular imaging
•Biomarkers (efficacy, toxicity)
Tools
Pathology
Biology
StructuralBiology
Chemistry
ComputerScience
Pharmacology
Low MolecularCompound
(probe)
Cross-disciplinary approach
Drug Discovery&
Development
Oxygen sensorPAI-1 Oxidative stresssensor
Miyata et al, Nature Review Nephrology, 2011
In silico approach by structure based drug designOur examples
Anti-thrombosis
Anti-fibrosis
Anti-obesity
Cellregeneration
Anti-cancer
Anti-inflammation
Potentialbenefits
Inhibitors of plasminogen activator inhibitor (PAI)-1
Human PAI-1 protein structure
Investigational new compound
Molecularimaging
UsefulBiomarkers
Open innovation
Possible in acadmia (basic research),
but still rare in Academia-Pharma collaboration…
OpenResources
Lack of the an adequate framework to nurture academic seeds for clinical trials
Pharmaceutical industry
Governmental fund
MEXT, METI
JST
Discovery & Screening
Leadoptimization
Pre-Clinical
PhaseⅠ
Phase Ⅱ
Phase Ⅲ
Sub-mission
NEDO
Death Valley for translational medicine
Who should invest and develop?
Regurations (GLP, GMP) POC
To take advantage of clinical development system outside Japan while bridging with the EU, US, etc..
Ideal approach…?
To take into consideration of both advantages and disadvantages of Japan and other countries from the
global perspective!
Japan (Tohoku univ.,etc)
Ph-IIaThrombosis
Ph-IIaCell
regeneration
IPs (material)
GMP compoundGLP Pre-clinical data
Ph-IIaKidney disease
Clinical development in the academic network from the global perspective
Ph-I (Japanese)Ph-IIaPCOS
Ph-IIaAlopecia
Ph-I(US)
IPs (Indication)
US (Northwestern univ.)
Ex. PAI-inhibitor
Guidance and motivation at an early stage of research with a clear, anticipated exit as well as comprehensive, hands-on internal supports are important.
IPs, combined with clinical data, could be important assets of academia for the transfer to the Pharma.
Academia and the Pharma have its respective roles. Open innovation of science and technology for the exploratory clinical trials should be the scope of academic research.
Clinical development should be conducted in the academic network from the global perspective.
Academia-Pharma collaboration…?