Successful Academia-Pharma Collaboration Drug Discovery and Clinical Development

Transcription

1 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)

2 Center Project Center Project Center for Advanced Medical Research and Development Clinical Cell Therapy Medical Apparatus Development Gene Therapy Regulatory Science Center for Regulatory Epigenome and Diseases Regulatory Epigenome Disease Genomics and Epigenomics United Centers for Advanced Research and Translational Medicine (ART) Center for Drug Discovery and Exploratory Clinical Study Center for Neuroscience Molecular Medicine and Therapy Chemical library and medicinal chemistry Medicinal bioregulation Drug metabolism and Pharmacokinetics Regulatory Science Exploratory Clinical study Molecular Imaging Developmental Neuroscience Clinical Neuroscience Translational Neuroscience Center for Oxygen Medicine Center for Metabolic Diseases Center for Advanced and Integrated Renal Science Center for Integrated Research for Women s Health Oxidative Stress medicine and Therapy Hypoxia Medicine and Therapy Metabolic Diseases Metabolic Disease Complications Chronic kidney disease Renal pathophysiology Integrated research for women s health Center for Prion Research Center for Cancer Research Neurological Science Neurochemistry Cell Proliferation Cancer stem cell Center for Immunological Science Center for Sports Medicine & Science Immune development and homeostasis Allergy and autoimmunity Peak Performance Sports Injury

3 Project-oriented, cross-cutting research organization ART style Open innovation Traditional vertical structure Academic unit A Professor Assoc. professor Lecturer Assistant Academic unit B 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 Core center B Professor (C,L,N) Assoc. professor (A,B,D) Lecturer (C,G) Assistant (P,S,Z) Core center D Academic unit C Professor Assoc. professor Lecturer Assistant Academic unit D Professor Assoc. professor Lecturer Assistant Professor (A,C) Assoc. professor (A,B,D) Lecturer (Q,V,W) Assistant (C,F,G) Professor (Y,E) Assoc. professor (F) Lecturer (K,M,U,Z) Assistant (H,J,E) Human resource (PJ leader) & Projects

4 Current status Technology Licensing Organization (TLO) Center/Organization for the clinical study Support Support Intellectual properties(ips) form basic research Clinical Trial Guidance and motivation at an early stage of research Comprehensive, hands-on supports

5 Old model Basic Research Intellectual properties (IPs) Insufficient Useful compounds Pharmacokinetics (PK) Pharmacodynamics (PD) Toxicity Transfer to the Pharma Proof of concept in human Project manager Patent attorney Regulatory expert Ideal model IPs Clinical Data Assets of academia Transfer to the Pharma

6 Fact Medicines are not always developed for fields in which they are needed

7 Academia-Pharma collaboration What are their respective roles? Exploratory clinical trial Academia Traditional development for the marketing approval application Industry Knowledge of disease pathophysiology Safe investigational compound Lead Optimiza tion Preclinical Ⅰ Ⅱ Ⅲ Sub missi on Human (Patient) Eliminate ineffective compounds Select useful compounds which act on human physiology and pharmacology

8 New ICH Harmonized Tripartate Guideline European Union, Japan and the USA Epoch-making step for the drug discovery and development in academia!

9 Exploratory clinical trial Pharmacokinetics (microdose trial) Tissue distribution (microdose trial with PET-CT) Pharmacodynamics (using biomarkers) 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) Miyata et al, Nature Review Nephrology, 2011

10 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)

11 Cross-disciplinary approach Pathology Computer Science Pharma cology Low Molecular & Compound Development (probe) Drug Discovery Biology Structural Biology Chemistry

12 In silico approach by structure based drug design Our examples PAI-1 Oxygen sensor Oxidative stress sensor Miyata et al, Nature Review Nephrology, 2011

13 Inhibitors of plasminogen activator inhibitor (PAI)-1 Antiobesity Anticancer Antiinflammation Potential benefits Cell regeneration Antithrombosis Antifibrosis

14 Human PAI-1 protein structure

15 Open innovation Possible in acadmia (basic research), but still rare in Academia-Pharma collaboration Investigational new compound Useful Biomarkers Open Resources Molecular imaging

16 Lack of the an adequate framework to nurture academic seeds for clinical trials Discovery & Screening Lead optimi zation Pre- Clinical Phase Ⅰ Phase Ⅱ Phase Ⅲ Submission Regurations (GLP, GMP) POC Death Valley for translational medicine Pharmaceutical industry MEXT, METI JST NEDO Governmental fund Who should invest and develop?

17 Ideal 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..

18 Clinical development in the academic network from the global perspective US (Northwestern univ.) Japan (Tohoku univ.,etc) IPs (material) GMP compound GLP Pre-clinical data Ph-I (Japanese) Ph-IIa Alopecia IPs (Indication) Ph-I (US) Ph-IIa PCOS Ph-IIa Cell regeneration Ph-IIa Thrombosis Ph-IIa Kidney disease Ex. PAI-inhibitor

19 Academia-Pharma collaboration? 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.