Expert’s Profile

Founder and chair of CTS

Ryosei Leo Kawai, PhD

Leo Kawai is an international scientist and distinguished expert of translational drug research and development with 27 years of experience in the pharmaceutical industry. He has served in senior leadership roles at multiple global R&D sites in Switzerland, the US, and Japan focusing on Drug Metabolism and Pharmacokinetics (DMPK), clinical pharmacology, modeling & simulation, and translational medicine in global scope, as well as development strategy for regulatory approval in Japan.

Leo Kawai was formerly the leader in model aided drug discovery and development as Head of Pharmacokinetics and Pharmacometrics at Novartis AG, Switzerland, and continued to innovate development standards as Head of Clinical Pharmacology / Exploratory Clinical Development in Japan, also as Senior Expert Modeler in the Modeling & Simulation Department at Novartis Institute of Biomedical Research in the US. Following his successful 21-year career with Novartis, he served as Principal, Executive Director of the Translational Medicine and Clinical Pharmacology Department of Daiichi Sankyo Co. Ltd. in Tokyo, then, played the role of Head of Clinical Science Japan at Bayer Yakuhin Ltd.

Dr. Kawai was a member of the Editorial Advisory Board for the Journal of Pharmacokinetics and Pharmacodynamics, an Associate Editor for Drug Metabolism and Pharmacokinetics, a Council Member in the Japanese Society for the Study of Xenobiotics, and was recipient of the JSSX Fellow in 2008, the Kitagawa Memorial Award in 2010.

 

EDUCATION

1983 – 1986             PhD, Graduate School of Pharmacy

Chiba University, Chiba, Japan

1981 – 1983             MS, School of Pharmacy

Chiba University, Chiba, Japan

1977 – 1981             BS, School of Pharmacy

Chiba University, Chiba, Japan

EXPERIENCE

03/2019 – Present Chuo Translational Science LLC

Founder, Chair

12/2018 – Present NDA Partners LLC

Expert Consultant

08/2017 – 04/2019 CMIC Co., Ltd.

Senior Consultant

  • Assisted pharmaceutical companies to conduct rational drug development in Japan by generating high level strategy with scientific and business insight, substantiating CTN (clinical trial notification; IND in Japan), and interacting with PMDA (Japanese equivalent to US FDA). Provided also wide scope of clients (pharma, biotech, healthcare, governmental agency) with cutting-edge technology, knowledge and/or hands-on research aids relevant to pharma R&D (discovery to NDA in global view) to support their business innovations.
08/2014 – 07/2017 Bayer Yakuhin KK

Head of Clinical Science Japan

  • Developed clinical pharmacology team in Asia into part of a global Clinical Science that could strategically contribute globally to early development, including 1st in human study in Japan.
  • Facilitated early-to-late portfolio programs, focusing on oncology, cardiovascular, hematology, ophthalmology, women’s health, and radiology. Responsible for oncology early development in Japan.
  • Outlined development strategy, conducted initial (Phase 1) trials/clinical pharmacological assessment, and filed a global CTD in Japan through interaction with PMDA.
09/2011 – 07/2014 Daiichi Sankyo Co. Ltd. (Tokyo, Japan)

Principal, Executive Director of Translational Medicine and Clinical Pharmacology Department

  • Senior expert and advisor in translational medicine. Supported early clinical stages of cardiovascular, metabolism, and oncology projects, as well as functional growth in the scope of M&S and biomarkers.
  • International project team leader for a novel respiratory therapy, responsible for global KOL management, integration of global resource/expertise, and responding to functional/regional conflicts.
03/2007 – 08/2011 Novartis Institute of Biomedical Research, Inc. (Cambridge, Massachusetts)

Senior Expert Modeler, Modeling & Simulation Department

  • Coordinated cross-organizational PKPD assessment network in the R&D Division by establishing and promoting common internal guidelines and maximizing the modeling and simulation value in R&D.
  • Drove or assisted M&S and clinical pharmacology studies in global development program and regulatory correspondences.
10/2000 – 03/2007 NovartisPharma KK (Tokyo and Tsukuba/Ibaraki, Japan)

Head of Clinical Pharmacology / Exploratory Clinical Development

  • Established a clinical pharmacology department at the Tokyo site and introduced population PK and pharmacogenetics into clinical trials in Japan, creating also novel development paradigms (e.g., Japanese clinical studies out of Japan, bridging strategy, multi-regional clinical trial, etc.)
  • Expanded exploratory clinical development function (translational medicine) to conduct proof-of-concept studies in Japan.
  • Managed clinical (Tokyo) and preclinical DMPK function (Tsukuba).
08/1996 – 10/2000 Novartis AG (Basel, Switzerland)

Head of Pharmacokinetics and Pharmacometrics

  • Established and managed PKPD modeling expert group with a core expertise in PBPK and nonlinear mixed effect model (NONMEM) to translate preclinical pharmacology and PK data into early clinical study design and assessment.
  • Applied extensively PBPK-PD modeling to specific development projects, offering a rational approach to demonstrate proof-of-concept in early clinical programs.
03/1993 – 08/1996 Sandoz Tsukuba Research Institute (Ibaraki, Japan)

PK Section Head, Drug Metabolism and Pharmacokinetics Department

  • Established site as an early translational science center to support compound selection and optimization, and become a global leader for preclinical PKPD modeling.
  • Established PK Group and was globally responsible for mechanistic preclinical PK studies and PBPK model development, as well as regulatory interaction to gain optimal market authorization in Japan.
09/1990 – 03/1993 Sandoz Pharma AG (Basel, Switzerland)

Lab Head, Biopharmaceutics Department

  • Developed and promoted PBPK model for drug development. Proposed strategic ADME (experimental) profiling and model-aided interspecies scaling to be applied to early drug development.
  • Contributed to the development of cyclosporine and its derivatives for transplantation and autoimmune diseases.
09/1987 – 09/1990 National Institutes of Health (Bethesda, Maryland)

Post-doctoral Fellow, Nuclear Medicine PET Section

  • Participated in PET program as an imaging data modeler. Collaborated with chemists, physicians, and statisticians to design and develop new ligands, while exploring imaging strategy and improving clinical applications.
04/1986 – 09/1987 Nomura Research Institute (Kanagawa, Japan)

Consultant Scientist

Conducted and reported preclinical research and ADME studies.

HONORS AND AWARDS

2010                         JSSX Kitagawa Memorial Award

2008                         JSSX Fellow (Awarded by Japanese Society for the Study of Xenobiotics)

1987 – 1990             Fogarty Fellow, National Institutes of Health (NIH)

PROFESSIONAL SOCIETIES

Japanese Society for the Study of Xenobiotics (JSSX)

2012 – 2013            Council Member

2006 – 2008             Council Member and Chair, DMPK International Promotion Committee

EDITORIAL BOARDS

2013 – Present         Drug Metabolism and Pharmacokinetics, Advisory Board

2006 – 2012             Drug Metabolism and Pharmacokinetics, Associate Editor

2003 – 2008             Journal of Pharmacokinetics and Pharmacodynamics, Advisory Board

PUBLICATIONS

Journal Articles (International peer reviewed/ Japanese journals not included)
  • Kawai, R., Fujuta, S. & Suzuki, T., 1985. Simultaneous quantitation of lidocaine and its four metabolism by high-performance liquid chromatography – Application to studies in vitro and in vivo metabolism of lidocaine in rats. Journal of Pharmaceutical Sciences, 74, pp.1219-1224.
  • Suzuki, T., Fujita, S. & Kawai, R., 1984. Precursor-metabolite interaction in the metabolism of lidocaine. Journal of Pharmaceutical Sciences, 73, pp.136-138.
  • Kawai, R., Fujita, S. & Suzuki, T., 1986. A new lidocaine metabolite, diethylamino-2-hydroxymethyl-6-methylacetanilide. Drug Metabolism and Disposition, 14, pp.277-279.
  • Fujita, S. et al., 1985. Age associated alteration of lidocaine metabolism is position selective. Biochemical and Biophysical Research Communications, 126, pp.117-122.
  • Kiesewetter, D.O. et al., 1990. Preparation and biological evaluation of 18F-labeled bonzoamide analogs as potential dopamine D2 receptor ligands. Nuclear Medicine and Biology, 17, pp.347-356.
  • Kawai, R. et al., 1990. BBB transport and rapid tissue binding of the opiate antagonist cyclofoxy: Comparison of active and inactive enantiomers. American Journal of Physiology, 259, pp.1278-1287.
  • Kawai, R. et al., 1990. Blasberg. Kinetic analysis of the opiate antagonist cyclofoxy in rat brain: Simultaneous infusion of active and inactive enantiomers. Journal of Pharmacology and Experimental Therapeutics, 255, pp.826-835.
  • Sawada, Y. et al., 1991. Kinetic analysis of transport and opioid receptor binding of [3H](-)-cyclofoxy in rat brain in vivo: Implications for human studies. Journal of Cerebral Blood Flow & Metabolism, 11, pp.183-203.
  • Kawai, R. et al., 1991. Regional brain measurement of Bmax and KD with the opiate antagonist cyclofoxy: Equilibrium studies in the conscious rat. Journal of Cerebral Blood Flow & Metabolism,11, pp.529-544.
  • Hiramatsu, Y. et al., 1993. Kinetic analysis of rat parotid gland muscarinic receptors in vivo: comparison with brain and heart. American Journal of Physiology, 264, pp.541-552.
  • Hiramatsu, Y. et al., 1994. Kinetic analysis of rat exocrine gland muscarinic receptors in vivo. Journal of Pharmacology and Experimental Therapeutics, 269, pp.1205-1212.
  • Bruelisauer, A. et al., 1994. Absorption and disposition of SDZ IMM 125, a new cyclosporine derivative, in rats after single and repeated administration. Drug Metabolism and Disposition, 22, pp.194-199.
  • Kawai, R. et al., 1994. Physiologically based pharmacokinetic study on a cyclosporin derivative, SDZ IMM 125. Journal of Pharmacokinetics and Pharmacodynamics, 22, pp.327-365.
  • Charnick, S.B. et al., 1995. Physiologically based pharmacokinetic modeling as a tool for drug development. Journal of Pharmacokinetics and Biopharmaceutics, 23, pp.217-229.
  • Song, S.H. et al., 1998. Dose-Dependent Effects of PSC 833 on Its Tissue Distribution and on the Biliary Excretion of Endogenous Substrates in Rats. Drug Metabolism and Disposition, 26, pp.1128-1133.
  • Kawai, R. et al., 1998. Physiologically Based Pharmacokinetics of Cyclosporine A: Extension to Tissue Distribution Kinetics in Rats and Scale-up to Human. Journal of Pharmacology and Experimental Therapeutics, 287, pp.457-468.
  • Comets, E. et al., 1999. Nonparametric analysis of the absorption profile of octreotide in rabbits from long-acting release formulation OncoLAR. Journal of Controlled Release, 59(2), pp.197-205.
  • Song, S.H. et al., 1999. Effect of PSC833, a P-gp modulator on the disposition of vincristine and digoxin in rats. Drug Metabolism and Disposition, 27, pp.689-694.
  • Tanaka, C., Kawai, R. and Rowland, M., 2000. Dose-Dependent Pharmacokinetics of cyclosporin A in rats: events in tissues. Drug Metabolism and Disposition, 28, pp.582–589.
  • Tanaka, C., Kawai, R. and Rowland, M., 1999. Physiologically-based pharmacokinetics of cyclosporine A: Reevaluation of dose-nonlinear kinetics in rats. Journal of Pharmacokinetics and Biopharmaceutics, 27, pp.597-623.
  • Comets, E. et al., 2000. Modeling the Kinetics of Release of Octreotide from Long-Acting Formulations Injected Intramuscularly in Rabbits. Journal of Pharmaceutical Sciences, 89, pp.1123-1133.
  • Comets, E. et al., 2003. Population pharmaco-dynamic analysis of octreotide in acromegalic patients. Clinical Pharmacology & Therapeutics, 73, pp.95-106.
  • Luyten, MA. et al., 2004. A Mouse Model to Assess Endothelial Activation In Vivo by Targeted Insertion of Alkaline Phosphatase into the E-selectin Gene. Drug Development Research, 63, pp.54–65.
  • Koseki, N. et al., 2007. Development and validation of a method for quantitative determination of valsartan in human plasma by liquid chromatography-tandem mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 43, pp.1769-74.
  • Laplanche, R. et al., 2007. Physiologically Based Pharmacokinetic (PBPK) Modeling of Everolimus (RAD001) in Rats Involving Non-Linear Tissue Uptake. Journal of Pharmacokinetics and Pharmacodynamics, 34(3), pp.373-400.
  • Murai, K. et al., 2009. Deactivation of anti-cancer drug letrozole to a carbinol metabolite by polymorphic cytochrome P450 2A6 in human liver microsomes. Xenobiotica, 39, pp.795–802.
  • Kawai, R., 2009. Mechanism-based PKPD projection in Exploratory Drug Development. Drug Metabolism and Pharmacokinetics, 24, pp.1–2.
  • Kawai, R. ed., 2009. Theme Issue on Mechanism-based PKPD Projections in Exploratory Drug Development. Drug Metabolism and Pharmacokinetics, 24, pp.1–90.
Book Chapters
  • Kawai, R. & Lemaire, M., 1993. Role of Blood Cell Uptake on Cyclosporin Pharmacokinetics. In J. P. Tillement & H. Eckert, eds. Proceeding of international symposium on Blood Binding and Drug Transfer. Paris: EFC Publishing, pp. 89–108.
  • Kawai, R., 1993. Bases of Predictions for Human Pharmacokinetics: Use of Physiologically Based Model in Animal Scale-up. In Y. Sugiyama, ed. Methods and Techniques in Pharmacokinetic Studies – from preclinical to phase I. Tokyo: Journal for the Society for the Study of Xenobiotics, pp. 109–145.
  • Kawai, R., 2006. Utility of PK/PD Modeling in Drug Development: Bridging from Nonclinical to Clinical. In Y. Sugiyama & K. Tsutani, eds. Clinical Pharmacology-based Drug Development Strategy. Tokyo: Hirokawa Publishing Company, pp. 37–52.
Invited Lectures (International Conferences)
  • Kawai and M. Lemaire. “Role of Blood Cell Uptake on Cyclosporin Pharmacokinetics”, International Symposium on Blood Binding and Drug Transfer. Basel, Switzerland, September 18-19, 1992.
  • Kawai. “Physiologically-Based Pharmacokinetics (PBPK) Model as a Tool for Drug Development” in Advances in Pharmaceutical Science, Singapore National University, Singapore, December 8-10, 1994.
  • Kawai. “Physiologically-Based Pharmacokinetics (PBPK) Models” in Sandoz PK/PD Pharmacometrics Workshop, at Paris, France, April 20-22, 1994.
  • Kawai. “Physiologically based pharmacokinetic modelling as an interface media druging drug development” in Pharmacokinetics & Pharmacodynamics in the pharmaceutical industry (PK/PD 97), at London, UK, March 17-18, 1997.
  • Kawai. “Physiologically based pharmacokinetic (PBPK) modelling of Dry Powder Inhalation Drugs” in Pharmacokinetic/Pharmacodynamic Analysis, at London, UK, May 11-12, 1998.
  • Kawai, C. Tanaka, EU. Koelle, K. Ochiai, C. Hauck, A. Schweitzer and W. Niederberger. “Pharmacokinetic-Pharmacodynamic Optimization of the Dosage of a Multi-drug Resistance Modifier” in Measurement and Kinetics of in vivo Drug Effects: Advances in Simultaneous Pharmacokinetic/Pharmacodynamic Modelling, 3rd International Symposium, Noordwijkerhout, the NL, May 27-30, 1998.
  • Kawai. “Physiologically-Based Pharmacokinetic (PBPK) profiling in early drug development” in PKUK98 at Manchester, UK, November 4-6, 1998.
  • Kawai. “Use of Physiologically-Based Pharmacokinetic Concept in Novartis: Challenge to Fast and Efficient Development” as plenary seminar in Minnesota University, School of Pharmacy, Minneapolis, MN, USA, July 8th, 1999.
  • Kawai. “Use of Physiologically-Based Pharmacokinetic Concept in Novartis: Challenge to Fast and Efficient Development” as plenary seminar in University of Tokyo, School of Pharmacy, Tokyo, Japan, July 16th, 1999.
  • Kawai. “Difference in the Pharmacokinetics of Compounds Between Species” in Novartis Pharma Research Conference 1999, in Florence, Italy, September 7-9, 1999.
  • Kawai. “Impact of PK variables assessed by physiologically-based PK (PBPK) models” in PAGE 2001, May 2001, Basel, Switzerland.
  • Kawai. “Mechanistic assessment of variability in pharmacokinetics” in Symposium 1 (Variability in drug disposition and response [part one] – Molecular basis of variability in drug disposition and response – Clinical implications of variability Pharmacy), PBS, World Congress 2001 in Singapore, September 3-5, 2001.
  • Kawai. “Demonstrated contributions to date during human drug development”: Workshop on “Physiologically-Based Pharmacokinetics (PBPK) in Drug Development and Regulatory Science” May 29-30, 2002, Georgetown University Conference Center, Washington, DC, USA.
  • Kawai. “Preclinical-to-clinical PK/PD Bridging in Development” in 1st International Drug Discovery and Development Summit: From Lead to Drug in Five Years, at Honolulu, Hawaii, USA, December 2-5, 2002.
  • Kawai. “Modeling and Simulation to Provide Prediction and Insight into Clinical Readout” in Symposium “Exposure-response Relationship: Mechanism-based PK-PD and the Associated Models and Simulations”, Pharmaceutical Science World Congress 2004, Kyoto, Japan, May 31-June 3, 2004.
  • Kawai. “PKPD Modeling in Drug Development” in Session 6: Perspectives in Drug Development, 13th NA ISSX – 20th JSSX joint meeting, Maui, Hawaii, USA, October 23-27, 2005.
  • Kawai. “Physiology-based PK/PD modelling of cyclosporins” Physiologically-based PK/PD modelling of therapeutic macromolecules, in the 1st Expert meeting of COST Action B 25 WG 1 (Physiologically Based Pharmacotoxicokinetics and Dynamics), Athens, Greece, December 11, 2006.
  • Kawai. “Integrating PBPK and PKPD to facilitate decision-making in drug development” in SimCYP seminar, “ADME in Drug Development: Bridging DM-PK-PD Using Modeling and Simulation”, Boston, MA, USA, June 3, 2008.
  • Kawai. “Factors Leading to Erroneous PKPD Interpretation. JSSX Symposium for the Success in Drug Development” The 1stsymposium – ‘What have we learned from the failure?’: in the 24th JSSX Annual Meeting, Kyoto, Japan, November 27- 29, 2009.
  • Kawai. “Modeling and Simulation Through Research and Development”: in World Conference on Pharmacometrics. Seoul, Korea, September 5-7, 2012.
  • Kawai. “Pharmacometrics in Pharmaceutical Industry: Perspective in Pharmacology”: in World Congress of Basic and Clinical Pharmacology. Kyoto, Japan, July 1-6, 2018.
CTS Chuo Translational Science
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