Sino-American Pharmaceutical Professionals Association-New England (SAPA-NE)
SAPA-New England 4th Annual Conference 2001
Drug Discovery: Industry Trends and Business Climate
Co-organized by Harvard Business School Healthcare and Biotech Club
Lead Sponsor: ArQule, Inc.
In Part Sponsored by Northeastern Section of ACS
PROGRAM
June 8-9, 2001
Burden Hall Auditorium, Harvard Business School
Soldiers Field Road
Boston, MA 02163
Website: http://www.sapa-ne.org
or
www.sapaweb.org
Conference Chair:
Jenny Li, Staff Investigator
ArQule, Inc.
Conference Co-Chair and Section Chair:
Shiwen Lin, Ph.D.
Cheng Zhang, Ph.D.
Jun Xian, Ph.D.
InfiMed Therapeutics Inc.
Tel: 617-864-0807, e-mail: slin@infimedrx.com
Millennium Pharmaceuticals, Inc.
Tel: 617-577-3574, e-mail: czhang@mpi.com
Genome Therapeutics Corporation
Tel: 781-398-2343, e-mail: jun.xian@genomecorp.com
Conference Organizing Committee:
Huimin Chen, Ph.D.
Li Chen, Ph.D.
Daming Gou, Ph.D.
Jun Huangpu, Ph.D. MBA
Gang Li, Ph.D.
Ms. Jenny Li
Mr. Kechun Li
Shiwen Lin, Ph.D.
Sean Lu, Ph.D.
Mr. Wuchun Shen
Yongchun Shen, Ph.D.
Wenge Wang, Ph.D.
Yihan Wang, Ph.D.
Erxi Wu, Ph.D.
Mr. Dong Wang,
Ph.D. Candidate
Jun Xian, Ph.D.
Yibin Xiang, Ph.D.
Yajun Xu, Ph.D.
Cheng Zhang, Ph.D.
Zhongli Zheng, Ph.D.
Xiaotian Zhu, Ph.D.
Genetics Institute, SAPA-NE, Director of Membership
Hoffman-La Roche, SAPA, President-elect
Rhodia ChiRex, SAPA-NE, Treasurer
Harvard Business School, Healthcare & Biotech Club
Prime Organics, Inc., SAPA-NE, Director of Public
Relation
ArQule Inc., SAPA-NE, President-elect
Eisai Research Institute, SAPA-NE, 1999 Term President
InfiMed Therapeutics Inc., SAPA-NE, Director of FundRaising
Sigma-RBI, SAPA-NE, Director of Scientific Symposium
The Boston Consulting Group, SAPA-NE Web Master
Eisai Research Institute, SAPA-NE, 2000 Term President
Genetics Institute, SAPA-NE, Director of Social Event
ARIAD Pharmaceuticals, Inc., SAPA-NE, President
Harvard Medical School, SAPA-NE, Coordinator
Dept. of Chem., MIT, SAPA-NE, Coordinator
Genome Therapeutic Corporation, SAPA-NE, Director of
Career Development
Genome Therapeutic Corporation, SAPA-NE, Chair of
Advisory Committee
Millennium Pharmaceuticals, Inc., SAPA-NE, Coordinator
Millennium Pharmaceuticals, Inc., SAPA-NE, Secretary
General
Biogen, Inc., SAPA-NE, Co-Chair of Advisory Committee
Amgen, Inc., SAPA-NE, 1999-2000 Term Director
Greetings from Conference Chair
Welcome to SAPA-NE (Sino-American Pharmaceutical Professionals Association, New
England Section) 4th Annual Conference: Drug Discovery: Industry Trends and Business
Climate.
Recent advances in genomics are bringing about a revolution in our understanding of the
molecular mechanisms of disease and creating an explosive number of new biological targets for
the development of new drugs. Fulfilling the promise of genomics, however, will require similar
advances in the technology and systems used to discover and test small molecules interacting
with these targets. Advances in drug discovery technologies hold the key to unlock the value of
genomics. Things are changing more rapidly than ever. “High through-put lead optimization”, a
relatively new term a few years ago, has become a popular phrase everywhere in our industry.
If you believe the trend is clear, the classical questions are still here. How to optimize
ADMET properties? How to interpret and handle the enormous information generated by our
tremendous efforts? How to improve the efficiency of the discovery process? These are no simple
questions and most importantly, people who discover the niche will be successful in their career
endeavor. Have you heard the discovery story of Merck’s VIOXX, an anti-inflammatory drug and
Celebrex’s rival? Dr. Peppi Prasit, the key scientist who is responsible for its discovery, got the
idea from a local conference. “Although the compound (in the poster) wasn’t chemically fit in
people. Dr. Prasit immediately went back to his lab, cooked up the mysterious molecule and put it
to Merck’s new test…” Information exchange helps! SAPA-NE has organized this conference by
bringing together leaders from east to west, who will share their experiences and discuss current
trends and strategies in the drug discovery industry. Our program includes presentations from a
variety of perspectives including senior management from the pharmaceutical and biotechnology
industries, research scientists, and business development professionals. The conference also
includes an exhibition of new products and technologies for drug discovery and a career fair. I
encourage you to take advantage of this tremendous opportunity to hear the latest trends in drug
discovery and get some ideas of significant innovations in the drug discovery process that address
these challenges.
SAPA is a federally registered non-profit organization striving to promote and facilitate
the exchange of scientific information and to contribute to the whole society. On behalf of SAPANE, I’d like to take this opportunity to thank our speakers whose sole compensation is the
satisfaction of the ultimate contribution to the improvement of well being of human beings.
SAPA-NE is grateful to the lead sponsor, ArQule, Inc. and other corporate sponsors for their
vision and strong support in many ways and for their generous funding to this conference and
other SAPA-NE activities all year round. Special thanks go to NESACS and Harvard Business
School Healthcare and Biotech Club for their shared value and support. And congratulations to
you for your smart decision to participate this conference. I hope you will meet some outstanding
leaders in our industry and make new friends at this conference. Together we can make a better
world. Thank you very much.
Jenny Li, Conference Chair
President-elect, SAPA-NE
Drug Discovery – Industry Trends and Business Climate
Time: 8:00 am - 5:30 pm , June 8-9, 2001
Place: Burden Hall Auditorium, Harvard Business School
Soldiers Field Road, Boston, MA 02163
8:00 am - 9:00 am
9:00 am - 12:00 am
12:00 am –1:30 pm
1:30 pm - 5:30 pm
5:30 pm - 6:30 pm
10:00 am - 5:30 pm
6:30 pm - 8:00 pm
8:00 pm – 9:30 pm
Registration
Morning Session
Lunch
Afternoon Session
Social hour
Exhibition and Job Fair
Reception
Dinner
Morning Session (Plenary Speeches)
Host: Dr. Michael Singer, Group Leader, Sigma-RBI
Secretary of Northeastern Section of ACS (NESACS)
9:00 am - 9:10 am
Conference Chair’s Announcement, Jenny Li, President-elect of
SAPA-NE, Staff Investigator, ArQule, Inc.
Opening Remark: Dr. Tim B. Frigo, President of NESACS
9:10 am – 10:00 am
Dr. Stephen A. Hill, President & CEO, ArQule, Inc.
“The New Medicines of the Future - Where Will They Come
From?”
10:00 am - 10:40 am Dr. Donna M. Huryn, Director, Department of Chemical Sciences,
Wyeth-Ayerst Research, Princeton, NJ
“Design and Synthesis of VLA-4 Antagonists”
10:40 am - 10:55 am Coffee Break
10:55 am - 11:35 am Dr. Maria Webb, VP of Discovery Biology, Pharmacopeia, Inc.
“Applications and Successes of Large, Diverse Combinatorial
Libraries in Drug Discovery”
11:35 am - 11:50 am SAPA-NE 2000-2001 Outstanding Contribution Awards
11:50 am - 1:30 pm
Lunch
Afternoon Session (Plenary Speeches)
Host: Dr. Yaping Hong, Associate Research Fellow, Sepracor Inc.
1:30 pm - 2:10 pm
Dr. Ken Korzekwa, VP of Research, Camitro Corporation
“Modeling Biochemistry’s Versatile Processes: Cytochrome P450
Models for Drug Discovery and Development”
2:10 pm - 2:50 pm
Dr. Bingfang Yan, D.V.M., Associate Professor, Dept. of
Biomedical Sciences, University of Rhode Island
“Regulation of Drug-Metabolizing Enzymes by Nuclear Receptor
Activation: Serious Considerations in Drug Development”
2:50 pm - 3:10 pm
Coffee Break
3:10pm - 3:50 pm
Dr. Kelvin W. Chan, Head, eADME, Drug Metabolism &
Pharmacokinetics, Aventis Pharmaceuticals, Inc.
“The Role of ADME/PK in Drug Discovery”
3:50 pm - 4:30 pm
Dr. Chris H. Senanayake, Senior Director of Chemical Process
Research, Sepracor Inc.
“Rapid Access to Drug Synthesis via Catalytic and Asymmetric
Processes”
4:30 pm - 5:10 pm
Dr. Fred J. Vinick, Senior Vice President of Drug Discovery,
Genzyme Corporation
“Small Molecule Drug Discovery at Genzyme Corporation”
5:30 pm – 6:30 pm
Social Hour
Parallel Session
Section Chair: Dr. Jun Xian, Genome Therapeutics Corporation
10:00 am - 5:30 pm
Trade Exposition of Novel Technology and New Products for
Drug Discovery
10:00 am - 5:30 pm
Job Clearing House
The 2nd Day
Business Development
8:30 am - 9:00 am
Registration and Breakfast
9:00 am - 9:10 am
Conference Chair Opening Remark for Business Development
Host: Dr. Jun Huangpu, MBA, Harvard Business School
9:10 am – 9:50 am
Dr. Roland R. Franke, CEO, Natural Pharmaceuticals, Inc.
“Success Factors in Technology Commercialization”
9:50 am - 10:30 am
Dr. Joseph C. Hogan, President and CEO, Alveus Systems, Inc.
“A Molecular Level Systems Engineering Approach to Chemical
Markets”
10:30 am - 10:40 am Coffee Break
10:40 am - 11:20 am Dr. Sheila DeWitt, Director, Business Development, ArQule, Inc.
“A Career Transition from Science to Business Development from Big Pharma to Biotech”
12:00 pm - 1:30 pm
Lunch
Afternoon Session (Plenary Speeches and Penal Discussions)
Host: Dr. Yibin Xiang, Director of Chemistry, Genome
Therapeutics Corp., Chair of SAPA-NE Advisory Committee
1:30 pm - 2:10 pm
Dr. Kenneth I. Kaitin, Director, Tufts Center for the Study of Drug
Development
“The Changing Environment for Pharmaceutical Innovation”
2:10 pm - 2:50 pm
Ms. Rongling Deng, WHO Fellow, Tufts Center for the Study of
Drug Development, SDA Officer
“New Drug Approval and Innovative Atmosphere in China”
2:50 pm – 3:00 pm
Coffee Break
3:00 pm - 5:30 pm
Discussion with Delegation of China Senior Pharmaceutical
Executives and Government Regulatory Agencies
Wang Jian Ping, Director, Dept. of Biotech. and Pharmaceutical
Science & Technology Commission of Shanghai Municipality
Fu Da Xu, Assoc. Director of Project Management, Shanghai
Center of Research & Development of New Drugs
Wang Huisheng, VP, Shanghai Clone Biotech. Co., Ltd.
Jiang Guangping, General Manager, Biolink Informatics Inc.
Cheng Yong, Vice President of Marketing & Sale, United Gene
Holdings, Ltd.
Chen Qi Yu, VP, Shanghai Fortune Industrial Joint-Stock Co., Ltd.
Dr. Qi Bao, Senior Consultant and Manager Pharmaceuticals
Group, China Concept
Guo Chungang, Assoc. Prof., the State Dept. Of Toxicology
Wang Kaimin, Prof. & Consultant of SDA, China
Parallel Session
Section Chair: Dr. Jun Xian, Genome Therapeutics Corporation
10:00 am - 5:30 pm
Trade Exposition of Novel Technology and New Products for
Drug Discovery
10:00 am - 5:30 pm
Job Clearing House
The New Medicines of the Future – Where Will They
Come from ?
Stephen A. Hill, President & CEO
ArQule, Inc.
19 Presidential Way
Woburn, MA 01801
Tel: 781 994 0311
Fax: 781 503 0009
Email: sahill@arqule.com
Abstract
The Pharmaceutical industry has been a major success story over the last century. In many ways
our industry began with an understanding of the chemistry and biology of natural products, and
evolved via synthetic chemistry towards the rational design of target specific molecules. How
will the recent excitement around genomics, the explosion of information, increased data
processing capacity and speed, and the continued need for novel medicines shape the
pharmaceutical business of the future? Whilst predicting the future is probably futile, being
prepared for changes in the way medicines are researched developed and marketed will be a prerequisite for the successful companies of the future. Today's research and development
productivity cannot hope to fuel the expected growth of our biggest companies. Small companies
may lack the scale and critical mass to be successful. What will be the relationship between
biotechnology and traditional pharmaceutical businesses? I personally believe that small
molecules, which can be administered orally, will remain at the core of the prescription medicine
market. Therefore biologically relevant chemistry must remain at the core of our discovery
efforts. How do we make that chemistry more effective and more efficient? This is the challenge
for companies like ArQule and many others. We are beginning to address this challenge in many
innovative ways and I believe there is indeed reason for believing that our industry will continue
to thrive in the next century- but only if we are bold and innovative.
Biography
Stephen Hill, B.M.B. Ch., M.A., F.R.C.S. joined the Company as President and CEO on April 1,
1999. Dr. Hill served as the Head of Global Drug Development at F. Hoffmann-La Roche Ltd.
since 1997. He joined Roche in 1989 as Medical Adviser to Roche Products in the United
Kingdom. He held several senior positions there, including that of Medical Director, with
responsibility for clinical trials of compounds across a broad range of therapeutic areas, including
those of CNS, HIV, cardiovascular, metabolic, and oncology products. Subsequently, he served
as Head of International Drug Regulatory Affairs at Roche headquarters in Basel, Switzerland,
where he led the regulatory submissions for seven major new chemical entities globally. He also
was a member of Roche's Portfolio Management, Research, Development and Pharmaceutical
Division Executive Boards. Prior to Roche, Dr. Hill served for seven years with the National
Health Service in the United Kingdom, in General and Orthopedic Surgery. Dr. Hill is a Fellow
of the Royal College of Surgeons of England, and holds his scientific and medical degrees from
St. Catherine's College at Oxford University.
Design and Synthesis of VLA-/VCAM
Antagonists
Donna M. Huryn, Ph.D., Director,
Chemical Sciences
Wyeth-Ayerst
Research
CN 8000
Princeton, NJ 08543
Tel: (732)-274-4025
Fax: (732)-274-4129
Email: hurynd@war.wyeth.com
m
Abstract
The adhesion molecule, VLA-4, plays a key role in the initiation and maintenance of the
inflammatory process. Its interaction with its native receptor VCAM-1, an endothelial cell surface
protein, leads to inflammatory cell recruitment. The disruption of the VLA-4/VCAM interaction
represents a new therapeutic approach to inflammatory diseases such as asthma, atherosclerosis,
multiple sclerosis, and rheumatoid arthritis. We have previously identified small molecules based
on tosyl-proline-phenylalanine which inhibit the interaction between VLA-4 and its counterreceptor, VCAM-1. The genesis of these compounds will be discussed, as will their evolution to
compounds exhibiting potent, and selective VLA-4 antagonism.
Biography
Donna M. Huryn is Director of in the Department of Chemical Sciences at Wyeth-Ayerst
Research. Prior to joining Wyeth-Ayerst, she held scientific positons at Hoffmann-La Roche. She
received her undergraduate degree at Cornell University, and Ph.D. from the University of
Pennsylvania working with Professor Amos B. Smith. Dr. Huryn’s current research includes the
design and synthesis of therapeutics in the CNS area, as well as Inflammation, Cancer and AntiInfective areas.
Applications and Successes of Large, Diverse
Combinatorial Libraries in Drug Discovery
Maria Webb, Ph.D., Vice President, Discovery Biology
Pharmacopeia, Inc
PO Box 5350
Princeton, NJ 08543-5350
Tel: (609) 452-3622
Fax: (609) 655-4187
Email: mwebb@pharmacop.com
Abstract
Genomics had lead to the identification of ~ 40,000 human genes, and proteomics will identify
many more proteins from polymorphisms, transcript splicing and post-translational modifications.
It is unclear precisely how many proteins will be drug targets for therapeutic intervention, but it is
clear that our industry will face a growing number of targets with increasing complexity in the
next ten years. Lead Identification and Optimization of drug-like small molecules at these targets
are critically necessary steps in successful models of drug discovery. Although encoding and
solid phase chemical synthesis technologies, as well as uHTS technologies, have made it possible
to create and efficiently screen large chemical libraries of several million distinct compounds, it
has been hypothesized that small collections of representative molecules are sufficient for Lead
Identification. I will show data that indicates that it is often necessary to screen large collections
of drug-like molecules, and that these molecules are capable of advancement to the clinic.
Biography
Maria Webb is Vice President of Drug Discovery Biology at Pharmacopeia in Princeton NJ
where the focus is lead identification and optimization using Pharmacopeia’s platform
technologies of combinatorial chemistry and high-throughput screening technologies. She
received her Ph.D. in 1983 in Physiology from the Pennsylvania State University where she
worked on steroid receptor physiology. From 1983 to 1985 she was an NIH fellow in Dr. Gerald
Litwack’s lab at Temple University Medical School where she worked on steroid receptor
biochemistry. In 1985, she moved to Hershey Medical Center of The Pennsylvania State
University where she was a Research Assistant Professor working in steroid receptor regulation
of transcription. In 1989, she moved to Bristol-Myers Squibb where she worked on numerous
programs as part of the Cardiovascular Division including GPCR drug discovery programs
targeted at thromboxane, angiotensin II and endothelin receptors before coming to Pharmacopeia
in 1996.
Modeling Biochemistry’s Versatile Processes: Cytochrome
P450 Models for Drug Discovery and Development
Ken Korzekwa, Ph.D.,Vice President of Research
Camitro Corporation
4040 Campbell Avenue
Menlo Park, CA 94043
Tel: (650) 614-7028
Fax: (650) 327-4639
Email: kkorzekwa@camitro.com
Abstract
A common characteristic of most biochemical processes is a high degree of specificity. For
example, most enzymes and receptors will only bind compounds with very specific
characteristics. However, some biochemical processes have evolved to be versatile. For example,
drug-metabolizing enzymes can bind and metabolize a wide variety of substrates. In general,
most processes involved in ADME (absorption, distribution, metabolism, and elimination) tend to
be nonselective. Consequently, modeling these processes requires unique approaches. Camitro is
developing an integrated platform of computational models for the prediction of ADME/Tox
properties of pharmaceutical drug candidates. Our models permit the high-throughput analysis of
virtual compounds or libraries before synthesis at very early stages in the drug discovery process,
thereby reducing the need for and complementing the interpretation of iterative compound
synthesis and experimentation cycles. An overview of our modeling efforts will be provided,
focusing on models for the cytochrome P450 enzymes.
Biography
Ken Korzekwa is Vice President of Research at Camitro Corporation. He joined Camitro from the
University of Pittsburgh, where he was Associate Professor of Medicine in the Center for Clinical
Pharmacology and Director of the Center’s Drug Discovery Program from 1995-1999. His
research activities at Pittsburgh focused on four major areas: enzyme kinetics of drug metabolism,
in vitro-iv vivo correlations in drug metabolism, predictive models for toxicological risk
assessment, and steroid metabolism. While at Pittsburgh he also provided consulting on multiple
occasions to pharmacokinetics/drug metabolism groups at major pharmaceutical companies. Prior
to joining the University of Pittsburgh, he spent three years as a Staff Fellow and PRAT Fellow in
the Laboratory of Chemical Pharmacology, NHLBI, NIH, under Dr. James Gillette, and five
years as a Senior Staff Fellow in the Laboratory of Molecular Carcinogenesis, National Cancer
Institute, NIH. Dr. Korzekwa has been actively involved in theoretical and experimental studies
of P450 metabolism for more than 10 years. He has published extensively on the enzymology and
mechanism of cytochrome P450 mediated human drug metabolism and toxicity. He was the
recipient of the Best Paper Award in 1990 in Drug Metabolism and Disposition awarded by the
Drug Metabolism Division of the American Society for Pharmacology and Experimental
Therapeutics. Dr. Korzekwa serves on the Editorial Review Board for the journals Chemical
Research and Toxicology and Journal of Biochemical Toxicology. He received his Ph.D. in
Medicinal Chemistry from the University of Washington and his undergraduate degree in
Chemical Engineering from the University of New Mexico.
Regulation of Drug-Metabolizing Enzymes by Nuclear Receptor
Activation: Serious Considerations in Drug Development
Bingfang Yan, D.V.M., Ph.D. Associate Professor
Department of Biomedical Sciences
University of Rhode Island
41 Lower College Road
Kingston, RI 02881
Tel: (401) 874-5032
Fax: (401) 874-5048
Email: byan@uri.edu
Abstract
Cytochrome P450 (CYP) enzymes rank first among the phase I biotransformation enzymes in
terms of catalytic versatility and the number of xenobiotics they metabolize. Therefore, CYP
enzymes determine the intensity and duration of action of drugs and play key roles in the detoxication and bioactivation of xenobiotics. Many therapeutical agents are shown to increase the
expression of CYP enzymes, thus cause serious drug-drug interactions. The Food and Drug
Administration requests all new drugs be tested for CYP induction, and pharmaceutical industries
are very interested in establishing CYP induction profiles of drug candidates early so that appropriate decisions can be made for further development. Studies of molecular signaling have
demonstrated that CYP induction is primarily achieved by receptor-mediated transactivation.
These receptors include the aryl hydrocarbon receptor, the constitutive androstane receptor, the
pregnane X receptor and the peroxisome proliferator-activated receptor-. In this presentation,
the mechanisms of action of these receptors will be discussed, and receptor-based screening procedures will be described.
Biography
Bingfang Yan is an associate professor of Biomedical Sciences at the University of Rhode Island.
He received D.V.M. degree in 1982 from Huazhong Agricultural University and Ph.D. degree in
1994 from the University of Kansas Medical Center. His research interest is in drug-metabolizing
enzymes in general, cytochrome P450 systems and carboxylesterases in particular. His lab uses
cellular and molecular techniques and animal models to study catalysis, prodrug activation and
xenobiotic-regulation mediated by nuclear receptors. Currently he is the principal investigator for
two major projects supported by the National Institutes of Health.
The Role of ADME/PK in Drug Discovery
Kelvin W. Chan, Ph.D.
Head, eADME
Drug Metabolism & Pharmacokinetics
Aventis Pharmaceuticals, Inc.
Route 202-206
P.O. Box 6800
Bridgewater, NJ 08807-0800
Tel: (908) 231-3878
Fax: (908) 231-2594
Email: kelvin.chan@aventis.com
Abstract
Advances in genomics, proteomics, combinatorial chemistry, and high throughput screening have
synergistically increased our ability to generate large number of compounds that show in vitro
activity towards the pharmacological targets. This has created an enormous challenge for
pharmaceutical companies to define strategies for selecting the most “drug-like” compounds for
further development. Historically, 63% of chemical entities failed in development due to poor
biopharmaceutical properties or toxicity. Consequently, the absorption, distribution, metabolism,
excretion (ADME), and pharmacokinetic (PK) properties of lead candidates are being
characterized and optimized increasingly early in the discovery phase. Unfortunately, the
throughput of ADME and PK screens lags behind that of activity screening and will become one
of the bottlenecks in optimizing drug candidates. This presentation will discuss a general strategy
for screening ADME/PK properties of lead compounds and using liquid chromatography/mass
spectrometry to increase the throughput of ADME/PK studies.
Biograhpy
Kelvin W. Chan is the Head of early ADME (US) of Drug Metabolism & Pharmacokinetics at
Aventis Pharmaceuticals, Inc. He had held previous positions in Drug Safety & Metabolism and
Analytical Chemistry at Wyeth-Ayerst Research (1990-2000) and Syntex Research (1984-1990).
His research interests have included high throughput strategies to provide metabolism and
pharmacokinetic input to the discovery and refinement of new drug candidates, and chemical
structure elucidation by the various spectroscopic techniques. He graduated with a Ph.D. in
Analytical Chemistry from the University of Illinois and received post-doctoral training at
Cornell University. Kelvin was an elected officer of the North Jersey ACS Mass Spectrometry
Discussion Group (Treasurer, 1992-1993; Chair-Elected, 1993-1994; Chairman, 1994-1995). He
has more than 60 invited lectures, presentations at national and international conferences, or peer
reviewed publications.
Rapid Access to Drug Synthesis via Catalytic and
Asymmetric Processes
Chris H. Senanayake, Ph. D.
Senior Director of Chemical Process Research, Sepracor Inc.
111 Locke Drive
Marlborough, MA 01752-7231
Phone: 508-357-7459
Fax: 508-357-7408
Email: csenanay@sepracor.com
Abstract
Scientists worldwide have documented that, in general, enantiomers are recognized differently by enzymes,
receptors, and other binding sites in biological systems. Many studies have shown that two enantiomers of
a chiral drug usually display different biological activity while one enantiomer can be detrimental. For
example, Sepracor is developing several single-isomeric drugs such as, (R)-albuterol (levalbuterol), (R,R)formoterol, (S)-oxybutynin, etc. of existing racemic drugs which display an improved therapeutic profile.
Also, it has been documented that certain active metabolites of drugs display an enhanced therapeutic
profile over the existing drug entities. For example, fexofenadine is an active metabolite of the former bestselling nonsedating antihistamine seldane (terfenadine). Norastemizole is a potent metabolite of
antihistamine astemizole and cis-hydroxyitraconazole is an active metabolite of antifungal cis-itraconazole.
For the last few years, our group has been engaged in the development of new asymmetric methods and
catalytic processes for the synthesis of drugs such as, levalbuterol, (R,R)-formoterol, (S)-oxybutynin, (S)fexofenadine, norastemizole, cis-hydroxyitraconazole isomers, isomers of sibutramine metabolites, (R)fluoxetine, (S)-zopicolone, (S,S)-hydroxybupropion, (S)-cetirizine, and (S)-doxazosin. This lecture will
highlight several rapid synthetic approaches to produce Sepracor’s ICEs.
Biography
Dr. Chris H. Senanayake was born in Sri Lanka and received a BS degree (First Class) in Chemistry in
1982 from the University of Sri Jayawardanepura in Sri Lanka. After coming to the United States, he
completed his MS at Bowling Green State University in 1983 with Professor Thomas Kinstle in synthetic
chemistry. He obtained his Ph.D. under the guidance of Professor James H. Rigby at Wayne State
University in 1987, where he worked on the total synthesis of complex natural products such as
ophiobolanes, and completed the first total synthesis of grosshemin in the guaianolide family. He then
undertook a postdoctoral fellow with Professor Carl R. Johnson and worked on the total synthesis of polyol
systems such as amphotericin B and compactin analogous, and the synthesis of C-nucleoside precursors. In
1989 he joined Dow Chemical Co. as a Senior Research Chemist in the Department of Process and
Development. After a brief stay at Dow Chemical, he joined the Merck Process Research Group in 1990 as
a Senior Research Chemist. After a series of accomplishments in synthetic organic chemistry and obtaining
a prestigious Merck Management Award in chemistry, he was promoted to Research Fellow in 1993. In
1996 he joined Sepracor, Inc. as Director of Chemical Process Research. He was promoted to Senior
Director of Chemical Process Research in 1998. He is responsible for the design and development of
chemical processes for the commercialization of pharmaceutical drugs.
Dr. Senanayake’s current research interests focus on the development of new asymmetric methods for the
synthesis of bioactive molecules and heterocycles, and on catalytic, enzymatic, and mechanistic studies. He
is the author of >75 papers and patents in several areas of synthetic organic chemistry.
Small Molecule Drug Discovery at Genzyme Corporation
Fredric J. Vinick, Ph.D., Sr. Vice President of Drug Discovery
Genzyme Corporation
1 Kendall Square
Cambridge, MA 02139
Tel: (617) 374-7272
Fax: (617) 252-7550
Email: fredric.vinick@genzyme.com
Abstract
In this presentation we describe the Genzyme approach to drug discovery, a hybrid of methods,
new and old, which seeks to minimize risk/cost and maximize the output of drug candidates
(novel substances which are safe and efficacious in animal models of disease). We will illustrate
our strategy with data from two actual programs. We will show how Genzyme has used novel
assay design and high throughput screening to discover potent new leads with potential for the
treatment of cystic fibrosis. In contrast to this approach, we will also describe how the Genzyme
Drug Discovery Group has selected a preclinical candidate for the treatment of lysosomal storage
disorders (e.g., Gaucher’s and Fabry’s Disease) through an extremely effective chemistry/biology
collaboration with an academic laboratory.
Biography
Fredric J. Vinick was educated at Williams College (B.A. in Chemistry, 1969), Yale University
(Ph.D. in Organic Chemistry with Professor Harry Wasserman, 1973) and Columbia University
(two years of postdoctoral research in the laboratories of Prof. Gilbert Stork). Dr. Vinick was a
member of the medicinal chemistry department at Ciba Geigy Corporation from 1974-1978. He
then moved to Pfizer Central Research where over the course of a sixteen-year career, he worked
in the areas of exploratory process research, CNS medicinal chemistry and exploratory medicinal
chemistry. As the founder and director of Pfizer's New Leads group in 1986 he helped establish
high throughput screening, compound library acquisitions and high speed chemical synthesis
methods. While at Pfizer Dr, Vinick contributed to patents and publications on selective
phosphodiesterase inhibitors, nonpeptide substance P antagonists and bradykinin antagonists. In
1994 he assumed the position of Vice President, Drug Discovery at Genzyme Corporation. He is
currently Senior Vice President of Drug Discovery. Dr. Vinick continues to have a major interest
in highly efficient approaches.
Success Factors in Technology Commercialization
Roland R. Franke, Ph.D., CEO
Natural Pharmaceuticals, Inc.
100 Cummings Center, Suite 414G
Beverly MA 01915
Tel: (978) 524-8100
Fax: (978) 524-8156
Email: franke_roland@alum.mit.edu
Abstract
Technology commercialization requires a combination of critical factors that contribute to the
success of a new company. This presentation will analyze the importance of attitudes,
management teams, ownership distribution, IP management, investors and investment strategy,
location and speed to market.
Biography
Roland Franke is the CEO of Natural Pharmaceuticals, Inc., a pharmaceutical company focussed
on the GMP production of very difficult to manufacture Active Pharmaceutical Ingredient (API).
The first product of the company is paclitaxel (API), a very successful and potent anti-cancer
drug through a novel semi-synthetic pathway. Dr. Franke has been with NPI for 3 1/2 years.
Before founding NPI he has worked in the pharmaceutical consulting practice of Booz Allen &
Hamilton for 3 years.
Dr. Franke has a B.S. and M.S. in synthetic organic chemistry from Freiburg University in
Germany. He did his Ph.D. work with Prof. Khorana at MIT and worked subsequently for three
years on a gene therapy project as a Howard Houghes Associate at the Rockefeller University.
He has also a M.B.A. from the Sloan School of Management with a focus on corporate finance
and entrepreneurship.
A Molecular Level Systems Engineering
Approach to Chemical Markets
Joseph C. Hogan, Jr., Ph.D.
President and CEO, Alveus Systems
1050 Winter Street, Suite 1000
Waltham, MA 02154
(T) 781 530-3808
(F) 781 530-3809
jhogan@alveussystems.com
Abstract
In recent times, powerful new technologies have been developed and applied to the
pharmaceutical drug discovery process. These include structure-based design, high-throughput
screening, combinatorial chemistry, structural design, selection and ADME/toxicity prediction
tools, genomics, proteomics, chip-based analytics and bioinformatics. These technologies have
brought significant advances to the discovery process, but major new bottlenecks have emerged
and important unmet needs remain. The application of these high-throughput principles to the
discovery, development, scale-up and production of chemistry-based products is discussed. A
molecular level systems engineering approach, targeted toward underlying commonalities of this
very large and heterogeneous market is outlined.
Biography
Joseph Hogan, Ph.D. is Founder, President and Chief Executive Officer of Alveus Systems, Inc.
This unique company is focused on integrating combinatorial and information sciences to
produce a revolutionary new convergent high-throughput discovery and development approach to
chemistry-based products and processes.
Prior to forming Alveus Systems, Dr. Hogan was the Founder of ArQule, Inc. From 1993-99 he
served as ArQule’s Chairman, Senior Vice President of R&D and Chief Scientific Officer and led
the company’s pioneering programs in the development of combinatorial chemistry, automation
and informatics technologies for the parallel solution phase synthesis and characterization of
congeneric arrays of molecules for accelerating pharmaceutical drug discovery.
Dr. Hogan has over 25 years of management experience in the design, development and
manufacturing of sophisticated chemistries, processes and products. After serving as Vice
President Chemical Products Research, Development and Engineering at the Waters Division of
Millipore, he founded and was President of Molecular Recognition, Inc. and Applied Modular
Chemistries, Inc., an MRI predecessor. Earlier he spent 14 years at Polaroid Corp. in a series of
scientific management positions, most recently as Manager of the Chemical Synthesis
Laboratory.
A Career Transition from Science to Business
Development – from Big Pharma to Biotech
Sheila H. DeWitt, Ph.D.
Director, Business Development
ArQule, Inc.
19 Presidential Way
Woburn, MA 01801-5140 USA
Phone: 781-994-0563
Fax: 781-994-0574
E-mail: sdewitt@arqule.com
Abstract
A start-up company within a large pharmaceutical company can provide unique opportunities to
experience an entrepreneurial environment for any scientist. While working as a chemist at
Parke-Davis in 1995, I had the opportunity to serve as a Vice president of Technical Development
for a spin-out company, Diversomer Technologies. When efforts to finance the company were
unsuccessful, I decided to make a career transition into business development. I will describe my
transition into business development over the last five years in two different biotechnology
companies and the opportunities – and challenges – that exist for other scientists.
Biography
Dr. DeWitt joined ArQule in February 2000 as Director of Business Development. She has held
several scientific and senior management positions at pharmaceutical, biotechnology, and
agricultural chemical companies including: FMC Agricultural Chemical Group (1986-1988),
Parke-Davis Pharmaceutical Research (1988-1995), Diversomer Technologies, a combinatorial
chemistry start-up company incubated at Parke-Davis (1995-1997), and Orchid BioSciences
(1997-2000). Dr. DeWitt earned her B.A. in Chemistry from Cornell University and her Ph.D. in
Synthetic Organic Chemistry from Duke University.
Dr. DeWitt is internationally recognized for her pioneering efforts in Combinatorial Chemistry
dating from 1992. She has been the recipient of several awards including the Michigan Leading
Edge Technologies Award (1993), Pioneer in Laboratory Robotics Award (1995), and
Association for Laboratory Automation Outstanding Service Award (1997). She is an active
member of the American Chemical Society (ACS) and the Association of Laboratory Automation
(ALA) and has served as a Committee Member for the National Research Council and co-chair
for the ACS ProSpectives Conferences. She has edited a book entitled, “A Practical Guide to
Combinatorial Chemistry”, published more 35 manuscripts, is the inventor on more than 30
patents, and has taught numerous short courses.
The Changing Environment for Pharmaceutical
Innovation
Kenneth I Kaitin, Ph.D., Director
Tufts Center for the Study of Drug Development
192 South Street, Suite 550
Boston MA 02111
Tel: (617) 636-2181
Fax: (617) 636-2425
Email: kkaitin@infonet.tufts.edu
Abstract
The current worldwide focus on containing health care expenditures and the highly competitive
environment in the pharmaceutical industry have placed substantial pressure on drug
manufacturers and regulators to improve efficiency and quality in the drug development process.
Regulatory reform in many of the world’s major markets has created a new dynamic between
drug firms and regulatory authorities. In the United States, the Prescription Drug User Fee Act of
1992 (PDUFA) has contributed to shorter FDA approval times, and with passage of the FDA
Modernization Act of 1997 (FDAMA), FDA is focusing on reducing lengthy clinical
development times. With Congressional hearings to reauthorize the collection of user fees
scheduled for winter 2002, regulatory initiatives and industry practices are coming into sharper
focus. These and other issues will be discussed in this presentation.
Biography
Dr. Kaitin is the Director of the Tufts Center for the Study of Drug Development at Tufts
University, where he studies national and worldwide trends in pharmaceutical innovation,
regulation, and public policy. He is also Assistant Professor of Pharmacology and Experimental
Therapeutics at Tufts University School of Medicine. Dr. Kaitin has written extensively on
factors that contribute to the slow pace and high cost of pharmaceutical R&D, and the impact of
regulatory and legislative initiatives to speed drug development and approval. His articles have
been published widely in medical and policy journals.
Dr. Kaitin has provided testimony before the U.S. Congress in hearings on FDA reform, and he
has worked closely with the U.S. Council on Competitiveness in the preparation of their report on
the pharmaceutical industry. He is a former President of the Drug Information Association, and
he serves on the faculty of the European Center for Pharmaceutical Medicine. He is a member of
the American Society for Clinical Pharmacology and Therapeutics, the New York Pharma Forum,
the Drug Information Association, and Regulatory Affairs Professionals, and serves on the
editorial boards of the American Journal of Therapeutics, Clinical Research and Regulatory
Affairs, and the Drug Information Journal. Dr. Kaitin received a B.S. from Cornell University
and an M.S. and Ph.D. in pharmacology from the University of Rochester.
New Drug Approval and Innovative Atmosphere in China
Ms. Rongling Deng, M.Sc., WHO Fellow
Tufts Center for the Study of Drug Development
192 South Street, Suite 550
Boston MA 02111
Tel: 617-636-2184
Fax: 617-636-2425
Email: rongling.deng@tufts.edu
Abstract
In past ten years, Chinese pharmaceutical industry has made significant achievement. Since the
pharmaceutical patents enacted on January 1, 1993, China has realized the importance and
necessity of pharmaceutical and biopharmaceutical innovations. China authority has taken steps
of measures and adjusted its strategies to develop a fairly competitive environment. Chinese
pharmaceutical industry has taken responsibility for searching completely new therapeutics in a
variety of disease areas. In this presentation, speaker will introduce new drug regulatory
administration and application procedures in China, review new drug approval in past ten years
and analyze current situation of new drug development in China.
Biography
Ms. Rongling Deng is a W.H.O Fellow at Tufts Center for the Study of Drug Development. Ms.
Deng received her BS and MS in the Department of Pharmaceutics at West China Medical
University. Before she came to Tufts Center for the Study of Drug Development, she was a senior
reviewer for ten years in Sichuan Drug Administration. She is very familiar with the history and
the procedures of drug development in China.
The Status and Development in Shanghai Biotech &
Pharmaceutical Industry
Mr. Wang Jianping, Senior Engineer and Director
Department of Science & Technology
Commission of Shanghai Municipality
Abstract
Since the end of 1993, Shanghai government has decided to make biotechnology and
pharmaceutical industry the most important direction of its development. Nowadays, under the
guidance of the government's policy and energetic engagement with enterprises and research
institutes, Shanghai has made great progress in the study of theories, technological applications,
exploration and industrialization of small scale research. In addition, the industry scale, the
product pipeline, the quality of operation and the total layout of the industry itself are changing
for the better.
In the next five years, Shanghai government will determine that biotechnology and the
pharmaceutical industry are new strategic targets. Shanghai will create new drug development
framework and mainly develop biotechnology and natural drug products with emphasis on the
drug market. We warmly welcome investments from both domestic and overseas and continue to
promote the pharmaceutical industry that will benefit all parties involved.
Biography
Mr. Wang Jianping graduated from Shanghai Jiao Tong University. He is currently a Senior
Engineer and Director of the Department of Science & Technology Commission of Shanghai
Municipality. He is also Assistant Director in the Biotechnology & Pharmaceutical Industry
Office of Shanghai Municipality. He has been engaged for a long time in the management of both
science and technology research and development. His responsibilities include routine
management of affairs, drafting medium and industry in Shanghai, formulating policies to
promote priority of projects and the coordination of programs in the development of biological
medical projects.
At the Crossroads: China’s Pharmaceutical Market
Dr. Qi Bao, Senior Consultant and Manager
Pharmaceuticals Group, China Concept
Abstract
The Chinese pharmaceutical market, its main drivers, various sectors and the regulatory environment are
discussed. Huge regional and urban-rural disparities in drug expenditure and lifestyles characterize the
market, which is driven by a combination of factors such as greater utilization of drugs, increase in urban
population, rapidly aging population and changing disease profile and healthcare reforms. The market is
and in the near future will be dominated by the hospital sector although the over-the-counter (OTC) drugs
poise to carve an increasing share of the market. The market dominance by generic products and the shift
towards locally produced drugs are set to continue in the foreseeable future as a result of government
policies in healthcare reforms and price control. The recent development and future prospect of
government’s healthcare reform program are discussed as is its impacts upon the medical industry. The
domestic pharmaceutical industry has been struggling to pull itself out of the inflexibility and restraints
under the planned economy and is undergoing painful structural changes. These changes are vital for its
continued survival as China’s WTO accession draws closer. SOE reforms in the industry, foreign
investments, the problems with intellectual property rights and the convoluted distribution system are
discussed along with the issues facing the government’s drive to develop the industry in the western
regions of China. Within the industry, three sectors are identified as future high growth areas: 1) Biotech
sector, 2) OTC sector, 3) Traditional Chinese Medicine (TCM). Each of these sectors is examined in details
with regard to its market structure, growth areas/products and the its main problems. The pros and cons of
their development plans are also discussed.
Biography
Dr. Qi Bao, Senior Consultant, Manager of Pharmaceuticals Group. Qi is the pharmaceuticals sector
specialist at China Concept. He resides in London but divides his time among China Concept’s London,
Beijing and Hong Kong Offices. He graduated from Shandong Medical University in China and obtained
his Ph.D. in medicine at the Royal Postgraduate Medical School in London. Following several years in
pharmaceutical research project management, he undertook and completed a MBA study at Cranfield
School of Management in England. After his Ph.D., Qi worked as a clinical researcher and then project
leader at Hammersmith Hospital and the National Institute for Medical Research in London for 7 years.
During the period, he led a number of high-profile international clinical projects involving project teams
from France, Germany, Denmark, USA, China and the UK and had many publications in peer-reviewed
journals. Following his MBA, Qi joined China Concept Consulting where he leads the pharmaceuticals
group and all projects in the sector. Working closely with the regulatory authorities in both China and
Europe, and the industry, he has led a number of market research and public affairs projects at China
Concept for clients in the pharmaceutical industry and investment-banking sector. He was a main
editor/translator of China Pharmaceuticals Guide, a joint publication by The Information Center of SDA,
China Concept Consulting and Informa Pharmaceuticals in London. Qi is also the Editor-in-Chief of
www.ChinaPharmaNews.com, a joint-venture online news service in English provided by China Concept
in association with SDA on latest developments in the Chinese pharmaceutical market. Qi serves as the
Secretary General of Chinese Medical Society UK.
SAPA-NE 2000-2001 Outstanding Contribution Award
Dr. Huimin Chen: SAPA-NE Director of Membership, Genetics Institute
Accomplishments:
Dr. Chen took great efforts to reorganize the SAPA-NE membership database which
ensured the timely renewal of all old memberships and facilitated the communication
between the executive committee and SAPA members. He organized and chaired the
SAPA-NE March 24 Intellectual Property Symposium. He also re-established the SAPANE coordinator team and helped to hold a couple of coordinator meetings. Dr. Chen
published a general gene therapy paper as well as reporting a few SAPA events for the
SAPA newsletter.
Dr. Jun Xian: SAPA-NE Director of Career Development, Genome Therapeutics Corp.
Accomplishments:
Dr. Xian collected information to facilitate the use of our organization as a platform to
help our members in their career development. He also organized and chaired SAPA-NE
Nov’00 career workshop which attracted over 100 members including 16 company
recruiters from Genzyme, Biogen, Genetics Institute, Millennium, etc., to post job listings
and meet our members. He also collected and updated job listing information from other
companies on our website which helped our members to obtain job offers. He was also in
charge of the trade exhibition and job clearing house sessions in several of our other
symposia, especially at the annual meeting.
Mr. Wuchun Shen: SAPA-NE Manager of IT, Boston Consulting Group Inc.
Accomplishments:
For the past 3 years, Mr. Shen has been a great supporter and advisor to SAPA-NE's
various IT initiatives including the design of the membership database, establishment and
development of SAPA-NE's website, and the implementation of online registration,
forum, job posting service, etc. By providing many technological insights and expertise
to the SAPA-NE chapter, he dedicated much of his time and personal contributions to
facilitate and maintain the website as well as communication between the SAPA-NE
executive committee and its members. His dedication and commitment in this effort has
been appreciated by many SAPA members.
Dr. Yaping Hong: SAPA-NE Coordinator, Sepracor Inc.
Accomplishments:
Dr. Hong is one of our most active members. He was a speaker at one of the SAPA drug
discovery symposia and helped to organize several SAPA-NE symposia by inviting
speakers to the meetings or acting as a host. He also provided valuable consultation for
our organizational development in moving SAPA to the US mainstream and contributed
greatly towards our fund-raising efforts.
Ms. Christine Quern: Director of Business Development, ArQule, Inc.
Accomplishments:
Ms. Quern has assisted greatly in the preparation of the 4th SAPA-NE Annual Conference
and put forth tremendous efforts in its mailer design and conference promotion. She also
initiated and implemented the on-line registration set-up combined with the ArQule
website as well as playing a key role between SAPA-NE executive committee and the
lead sponsor company, ArQule, Inc..
Ms. Jean Duffy
Accomplishments:
Ms. Duffy participated in several SAPA-NE career service sessions. She displayed many
career opportunities in her organization and communicated directly with our members in
a personal manner that was highly appreciated with our members. Jean was a good
example in demonstrating communication between biotech/pharmaceutical employers
and SAPA members.
Corporate Award:
ArQule Inc., the lead sponsor of SAPA-NE 4th Annual Conference.
SAPA-New England Events (1999-2001)
08/07/1999 Rutgers University SAPA 7th Annual Conference
08/28/1999 MIT SAPA-NE 1st Election Party
09/10/1999 Sichuan Garden SAPA-NE EC Meeting
09/26/1999 Boston City Hall Celebration of 50th Anniversary of PRC
10/02/1999 Blue Hill Reservation SAPA-NE 1st Coordinator Outing
11/06/1999 MIT SAPA-NE Biopharmaceutical Forum
11/06/1999 MIT SAPA-NE EC Meeting
11/14/1999 King School Passport Renewal
12/17/1999 Yangtze River Restaurant SAPA-NE EC Meeting
01/22/2000 MIT SAPA-NE 2nd Celebration of Chinese New Year
02/13/2000 Royal East Meeting with William Au (Guangzhou International Bioisland)
02/27/2000 MIT SAPA-NE EC Meeting
03/11/2000 MIT SAPA-NE 2nd Business Development Symposium
04/11/2000 Biogen Dalian Delegation
05/06/2000 Yangtze River Restaurant SAPA-NE EC Meeting
05/11/2000 Beijing International Biotechnology Conference
06/24/2000 MIT SAPA-NE 3rd Annual Conference
08/05/2000 Rutgers University SAPA 8th Annual Conference
09/15/2000 SAPA NE Election/Member Reunion Party
09/22/2000 MIT SAPA-NE EC Meeting
10/14/2000 Blue Hill Reservation SAPA-NE 2nd Coordinator Outing
11/03/2000 YumYum Restaurant SAPA-NE EC Meeting
11/11/2000 MIT SAPA-NE Career Workshop
01/28/2001 MIT SAPA-NE 3rd Celebration of Chinese New Year
02/24/2001 International Buffet SAPA-NE EC Meeting
03/17/2001 Royal Dynasty Restaurant SAPA-NE EC Meeting
03/24/2001 MIT SAPA-NE Intellectual Property Symposium
04/22/2001 Harvard Business School SAPA-NE EC Meeting
05/18/2001 MIT Whitehead Institute SAPA-NE EC Meeting
06/08-9/2001 Harvard Business School SAPA-NE 4th Annual Conference
Rhodia ChiRex, A Corporate Sponsor of SAPA-NE
The mission:
to commercialize new drugs
The method:
our chemistry services
Rhodia ChiRex is a leading company in the field of pharmaceutical active
ingredient outsourcing, offering a combination of proprietary chiral and
non-chiral process chemistry technologies, contract process research,
development services, and commercial-scale contract manufacturing.
Our sustainable competitive advantage is based on:
Experienced and highly competent people
Customer intimacy and responsiveness
Reliability through tight control of our commitments
Breadth and competitiveness of our technologies and processes
Full range of capabilities from laboratory to commercial scale
Rhodia ChiRex Inc.
56 Roland Street
Boston, MA 02129
1-617-628-5246
hr@rhodiachirex.com
www.rhodiachirex.com
The Drug Substance Company
Corporate Sponsors and Vendors:
ArQule, Inc
Ariad Pharmaceuticals
Biogen Inc.
Cereon Genomics
Pfizer Inc.
Genzyme Corp.
Waters Corp.
Eisai Inc.
Genetics Institute
Genome Therapeutics
Vertex Pharmaceuticals
Rhodia ChiRex
Sepracor Inc.
Prime Organics, Inc.
Beckman Coulter
Promega
BioDevice
Phenomenex
Matrix
Northeastern Section of ACS
Biological Equipment Specialties
IGEN
Sigma-RBI
BioSource
Zymark
PerkinElmer