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. InfiMed Therapeutics Inc. Tel: 617-864-0807, e-mail: [email protected] Cheng Zhang, Ph.D. Millennium Pharmaceuticals, Inc. Tel: 617-577-3574, e-mail: [email protected] Jun Xian, Ph.D. Genome Therapeutics Corporation Tel: 781-398-2343, e-mail: [email protected]

Conference Organizing Committee:

Huimin Chen, Ph.D. Genetics Institute, SAPA-NE, Director of Membership Li Chen, Ph.D. Hoffman-La Roche, SAPA, President-elect Daming Gou, Ph.D. Rhodia ChiRex, SAPA-NE, Treasurer Jun Huangpu, Ph.D. MBA Harvard Business School, Healthcare & Biotech Club Gang Li, Ph.D. Prime Organics, Inc., SAPA-NE, Director of Public Relation Ms. Jenny Li ArQule Inc., SAPA-NE, President-elect Mr. Kechun Li Eisai Research Institute, SAPA-NE, 1999 Term President Shiwen Lin, Ph.D. InfiMed Therapeutics Inc., SAPA-NE, Director of Fund- Raising Sean Lu, Ph.D. Sigma-RBI, SAPA-NE, Director of Scientific Symposium Mr. Wuchun Shen The Boston Consulting Group, SAPA-NE Web Master Yongchun Shen, Ph.D. Eisai Research Institute, SAPA-NE, 2000 Term President Wenge Wang, Ph.D. Genetics Institute, SAPA-NE, Director of Social Event Yihan Wang, Ph.D. ARIAD Pharmaceuticals, Inc., SAPA-NE, President Erxi Wu, Ph.D. Harvard Medical School, SAPA-NE, Coordinator Mr. Dong Wang, Dept. of Chem., MIT, SAPA-NE, Coordinator Ph.D. Candidate Jun Xian, Ph.D. Genome Therapeutic Corporation, SAPA-NE, Director of Career Development Yibin Xiang, Ph.D. Genome Therapeutic Corporation, SAPA-NE, Chair of Advisory Committee Yajun Xu, Ph.D. Millennium Pharmaceuticals, Inc., SAPA-NE, Coordinator Cheng Zhang, Ph.D. Millennium Pharmaceuticals, Inc., SAPA-NE, Secretary General Zhongli Zheng, Ph.D. Biogen, Inc., SAPA-NE, Co-Chair of Advisory Committee Xiaotian Zhu, Ph.D. 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 SAPA- NE, 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 Registration 9:00 am - 12:00 am Morning Session 12:00 am –1:30 pm Lunch 1:30 pm - 5:30 pm Afternoon Session 5:30 pm - 6:30 pm Social hour 10:00 am - 5:30 pm Exhibition and Job Fair 6:30 pm - 8:00 pm Reception 8:00 pm – 9:30 pm 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: [email protected]

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 pre- requisite 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, Wyeth-AyerstChemical Sciences Research CN 8000 Princeton, NJ 08543 Tel: (732)-274-4025 Fax: (732)-274-4129 Email: [email protected] 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 counter- receptor, 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 Anti- Infective 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: [email protected]

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: [email protected]

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: [email protected]

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: [email protected]

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: [email protected]

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 best- selling 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: [email protected]

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: [email protected]

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 [email protected]

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: [email protected]

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: [email protected]

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: [email protected]

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 SAPA- NE 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)

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

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 [email protected] www.rhodiachirex.com

The Drug Substance Company Corporate Sponsors and Vendors:

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. ArQule, Inc Zymark

Beckman Coulter PerkinElmer

Promega BioDevice Phenomenex Matrix Northeastern Section of ACS Biological Equipment Specialties IGEN Sigma-RBI BioSource