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…?