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)
Center Center for Advanced Medical Research and Development
United Centers for Advanced Research and Translational Medicine (ART)
Center for Drug Discovery and Exploratory Clinical Study
Center for Neuroscience
Center for Prion Research
Center for Cancer Research
Project
Center
Project
●Clinical Cell Therapy ●Medical Apparatus Development ●Gene Therapy ●Regulatory Science
Center for Regulatory Epigenome and Diseases
●Regulatory Epigenome ●Disease Genomics and Epigenomics
●Molecular Medicine and Therapy ●Chemical library and medicinal chemistry ●Medicinal bioregulation ●Drug metabolism and Pharmacokinetics ●Regulatory Science ●Exploratory Clinical study ●Molecular Imaging
Center for Oxygen Medicine
●Oxidative Stress medicine and Therapy ●Hypoxia Medicine and Therapy
●Developmental Neuroscience ●Clinical Neuroscience ●Translational Neuroscience
●Neurological Science ●Neurochemistry
●Cell Proliferation ●Cancer stem cell
Center for Metabolic Diseases
Center for Advanced and Integrated Renal Science Center for Integrated Research for Women’s Health
Center for Immunological Science Center for Sports Medicine & Science
●Metabolic Diseases ●Metabolic Disease Complications ●Chronic kidney disease ●Renal pathophysiology
●Integrated research for women’s health
●Immune development and homeostasis ●Allergy and autoimmunity
●Peak Performance ●Sports Injury
Project-oriented, cross-cutting research organization ART style Open innovation Traditional vertical structure Academic unit A
Academic unit B
・Professor ・Assoc. professor ・Lecturer ・Assistant
・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 C Academic unit C
Academic unit D
・Professor ・Assoc. professor ・Lecturer ・Assistant
・Professor ・Assoc. professor ・Lecturer ・Assistant
・Professor (A,C) ・Assoc. professor (A,B,D) ・Lecturer (Q,V,W) ・Assistant (C,F,G)
Core center B ・Professor (C,L,N) ・Assoc. professor (A,B,D) ・Lecturer (C,G) ・Assistant (P,S,Z)
Core center D ・Professor (Y,E) ・Assoc. professor (F) ・Lecturer (K,M,U,Z) ・Assistant (H,J,E)
「Human resource (PJ leader）」& 「Projects」
Current status Technology Licensing Organization (TLO)
Support
Intellectual properties(IPs) form basic research
Center/Organization for the clinical study
Support
Clinical Trial
Guidance and motivation at an early stage of research Comprehensive, hands-on supports
Old model Transfer to the Pharma
Intellectual properties (IPs) Insufficient
Basic Research
Useful compounds
Proof of concept in human
Pharmacokinetics (PK) Pharmacodynamics (PD) Toxicity
Project manager Patent attorney Regulatory expert
IPs
Clinical Data Assets of academia
Ideal model
Transfer to the Pharma
Fact Medicines are not always developed for fields in which they are needed‌
Academia-Pharma collaboration What are their respective roles? Traditional development for the marketing approval application
Exploratory clinical trial
Industry
Academia Knowledge of disease pathophysiology
Safe investigational compound
Lead Optimiza tion
Preclinical
Ⅰ
Ⅱ
Human (Patient)
9Eliminate ineffective compounds 9Select useful compounds which act on human physiology and pharmacology
Ⅲ
Sub missi on
New ICH Harmonized Tripartate Guideline
European Union, Japan and the USA
Epoch-making step for the drug discovery and development in academia !
Exploratory clinical trial Pharmacokinetics (microdose trial) Tissue distribution (microdose trial with PET-CT) Pharmacodynamics (using biomarkers)
Earlier access to human data 9Pharmacokinetics (PK) as a micro-dosing test 9Pharamadynamics (PD) with useful surrogate biomarkers and sensitive detection technologies (e.g., PET molecular imaging) Miyata et al, Nature Review Nephrology, 2011
Exploratory clinical trials in academia Benefits Earlier access to human data should •Improve insights into human physiology/pharmacology •Document the drug candidate’s characteristics •Identify therapeutic targets relevant to disease
Tools •Investigational chemical compounds •Molecular imaging •Biomarkers (efficacy, toxicity)
Cross-disciplinary approach
Pathology Computer Science
Pharma cology
Biology
Low Drug Discovery Molecular & Compound Development (probe)
Chemistry
Structural Biology
In silico approach by structure based drug design Our examples
PAI-1
Oxygen sensor
Oxidative stress sensor
Miyata et al, Nature Review Nephrology, 2011
Inhibitors of plasminogen activator inhibitor (PAI)-1 Antithrombosis Antifibrosis
Anticancer Potential benefits
Antiobesity
Antiinflammation Cell regeneration
Human PAI-1 protein structure
Open innovation Possible in acadmia (basic research), but still rare in Academia-Pharma collaboration‌
Investigational new compound
Open Resources Useful Biomarkers
Molecular imaging
Lack of the an adequate framework to nurture academic seeds for clinical trials
Discovery & Screening
Lead optimi zation
PreClinical
Phase Ⅰ
Regurations (GLP, GMP)
Death Valley for translational medicine
Phase Ⅱ
Phase Ⅲ
POC
Pharmaceutical industry
MEXT, METI JST NEDO
Governmental fund
Submission
Who should invest and develop?
I
deal approach‌?
To take into consideration of both advantages and disadvantages of Japan and other countries from the global perspective!
To take advantage of clinical development system outside Japan while bridging with the EU, US, etc..
Clinical development in the academic network from the global perspective
US Japan
IPs
(Tohoku univ.,etc)
Ph-IIa Alopecia
Ph-I (Japanese)
Ph-IIa Thrombosis
(Indication)
Ph-I (US)
IPs (material) GMP compound GLP Pre-clinical data
Ph-IIa Cell regeneration
(Northwestern univ.)
Ph-IIa PCOS
Ph-IIa Kidney disease
Ex. PAI-inhibitor
Academia-Pharma collaboration‌? 9 Guidance and motivation at an early stage of research with a clear, anticipated exit as well as comprehensive, hands-on internal supports are important. 9 IPs, combined with clinical data, could be important assets of academia for the transfer to the Pharma. 9 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. 9 Clinical development should be conducted in the academic network from the global perspective.