Swartz Analytical Techniques in Combinatorial Chemistry

Profile: Founded in 1983, the company designs, develops, manufactures and markets proprietary, high-performance, bioanalytical measurement systems, including consumables, that are designed to accelerate and improve the cost effectiveness of the drug discovery and development process. Its systems have applications in many aspects of the therapeutic development process, from drug discovery and clinical research through manufacturing and quality control. In 1996 the company acquired NovelTech Systems, Inc., which designs, develops, manufactures, and markets high-throughput drug screening products.

Products/technologies: Sells bioanalytical systems for research in the life sciences, supporting combinatorial chemistry, genomics, and drug discovery. Its line of microplate reader systems is aimed at the life science market. The Fluorescence Imaging Plate Reader (FLIPR) is for high-throughput screening using live cell targets. SPECTRAmax PLUS is a high-throughput spectrophotometer that combines the power and performance of a spectrophotometer with the flexibility and throughput of a microplate reader in one system. It uses new technology called PathCheck .

Contact: Andrew Galligan

Molecular Dynamics, Inc.

928 East Arques Avenue, Sunnyvale, CA 94086-4520, USA Phone: (408) 773-1222; Fax: (408) 773-1493

Toll-free in U.S.: (800) 333-5703 E-mail: info@mdyn.com

Internet: http:/ /www.mdyn.com

Stock: MDYN (NASDAQ)

Profile: The company is a developer, manufacturer, and international marketer of systems that accelerate genetic discovery and analysis. The company’s products increase scientists’ ability to visualize, quantify, and analyze genetic information. Molecular Dynamics is a founding member of the Genetic Analysis Technology Consortium (GATC), formed to develop and publish global standards and to provide a unified technology platform to design, process, read, and analyze DNA arrays. Molecular Dynamics and Amersham Pharmacia Biotech developed a microarray system that permits researchers to make and analyze high-density microarrays with increased speed, efficiency, and sensitivity. Data from a single microarray experiment provides researchers

with the ability to accurately measure gene expression levels in thousands of samples. In late 1996, the two companies launched the Microarray Technology Access Program to make available preferential, precommercial access to their microarray technology.

Products/technologies: Combines advanced laser scanning, electro-optical, and software technologies to produce optical scanners and confocal microscopes. These instrument systems are designed to improve the productivity of molecular and cell biologists by automating routine procedures, increasing speed and accuracy of quantitation, and enabling new bioanalytical techniques. MegaBACE 1000 Genetic Analysis System, a high-throughput system, uses novel capillary technology for rapid and highly parallel analysis of genetic samples. The company also has laser fluorescence confocal scanning technology for DNA analysis, as well as innovative microfluidic technologies.

Contact: Jay Flatley, President and CEO

Molecular Informatics (See PE Molecular Informatics)

Molecular Simulations Inc.

9685 Scranton Road, San Diego, CA 92121-3752, USA Phone: (619) 458-9990; Fax: (619) 458-0136

E-mail: solutions@msi.com Internet: http:/ /www.msi.com

Profile: Founded in 1984, this privately held company provides molecular modeling and simulation software for both life and materials science research. The company employs more than 280 people (approximately half of whom are Ph.D. scientists); it operates sales offices around the world and a research and development facility in Cambridge, England. MSI’s Combinatorial Chemistry Consortium addresses the full scope of the combinatorial chemistry process and is focused on maximizing the productivity of library design and analysis. In February 1998, Molecular Simulations Inc. and Pharmacopeia Inc. announced a definitive agreement whereby Pharmacopeia will acquire all of the outstanding stock of MSI. The transaction is expected to be completed in the second quarter of 1998; upon completion MSI will become a wholly owned subsidiary.

Products/technologies: MSI’s software combines the core atomistic simulation technologies of molecular mechanics and quantum mechanics with molecular visualization, modeling and instrument simulation. Products include C2 Diversity combinatorial chemistry software that provides a guideline for design and analysis of combinatorial libraries; and SAR information in library design of large (100,000 ) enumerated libraries. In October 1997, the company announced the first commercial release of WebLab ViewerPro, which brings molecular visualization and analysis to desktop personal computers. The product runs on Windows 95 or NT, Power Macintosh, and Silicon Graphics platforms, and is used to build and view molecules, proteins, and crystalline materials, helping scientists to understand molecular structures and properties. Cerius 3.0 drug design software contains features for drug design, including the integration of organic and aromatic chemistry for the improved rendering of pharmaceutical compounds, faster rotation speeds, and a combinatorial chemistry module. MSI implemented a web-based architecture that will expand the availability of MSI software products and libraries to any scientist using a web browser on a desktop computer.

Contact: Brenda Pfeiffer, Corporate Communications

Neugenesis

Manoa Innovation Center, 2800 Woodlawn Dr., Suite 251, Honolulu, HI 96822-1865, USA

Phone: (808) 539-3801; Fax: (808) 539-3804 or 539-3625 E-mail: info@neugenesis.com

Internet: http:/ /www.neugenesis.com

Profile: A private company, Neugenesis was founded in 1992 by several key individuals who recognized the potential commercial value of Neurospora for biotechnology applications. It has nine employees and occupies a 1600 square foot facility for its headquarters and R&D facilities. The company uses proprietary combinatorial biology technology to discover and develop new biotherapeutics, both alone and in partnership with other biopharmaceutical companies.

Products/technologies: These include a combinatorial biology drug discovery platform for the development, improvement, and production of therapeutic proteins; recombinant protein production systems for monomeric, dimeric, and heteromeric proteins. Neugenesis’ combinatorial biology technology (the

CombiKARYON ) is a way to create diversity in complex proteins. Two important features are directed vs. random libraries to reduce the level of screening required and provide more efficient libraries overall; and shape/ space enrichment whereby new proteins created through the Neugenesis system will exhibit improvements yet maintain the core structure of the protein.

Contact: Lynn M. Uehara, VP, Business Development

NeuralMed, Inc.

2525 Meridian Parkway, Suite 240, Durham, NC 27713, USA Phone: (919) 549-0270; Fax: (919) 549-0271

E-mail: info@neuralmed.com Internet: http:/ /www.neuralmed.com

Profile: The company was founded in 1994 in Pittsburgh, Pennsylvania, by a group of engineers, statisticians, and business executives from several companies specializing in data mining applications. In early 1996, NeuralMed relocated to Research Triangle Park, North Carolina, to better access the scientific and engineering talent of the area. Its staff has expertise in data mining technologies, software systems development, system support, and consulting. Also, it has a broad range of experience in both the private and public sectors, including international expertise and university teaching.

Products/technologies: Has delivered various applications, including combinatorial chemistry predictions, by use of five neural network algorithms for building predictive models.

Contact: Tom Stallings, President and CEO

Neurogen Corp.

35 N.E. Industrial Road, Branford, CT 06405, USA Phone: (203) 488-8201; Fax: (203) 481-8683 E-mail: info@nrgn.com

Internet: http:/ /www.bio.com/co/Neurogen.html

Stock: NRGN (NASDAQ)

Profile: Organized around scientists from Yale University and industry, the company was founded in 1988. It is engaged in the design and development

of a new generation of drugs that the company expects will provide improved treatment for a broad variety of neuropsychiatric disorders, including anxiety, obesity, schizophrenia, sleep disorders, dementia, depression, stress-related disorders and epilepsy.

Products/technologies: These include a combinatorial chemistry library. Its AIDD (Accelerated Intelligent Drug Design) program is a proprietary blend of combinatorial chemistry with high throughput screening, robotics, and informatics. New drug candidates are developed through the integration of cutting edge neurobiology, medicinal chemistry and molecular biology, and AIDD.

Contact: Stephen Davis

NeXstar Pharmaceuticals, Inc.

2860 Wilderness Pl., Suite 200, Boulder, CO 80301, USA Phone: (303) 444-5893; Fax: (303) 444-0672

E-mail: Kdoherty@NeXstar.com Internet: http:/ /www.nexstar.com

Stock: NXTR (NASDAQ)

Profile: Founded in 1995 with the merger of NeXagen and Vestar, the company utilizes proprietary compounds to develop therapeutics and diagnostics to serve unmet medical needs. From NeXagen, NeXstar acquired the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) combinatorial chemistry technology.

Products/technologies: Proprietary SELEX combinatorial chemistry technology that can produce aptamers, which are modified oligonucleotides that bind to cancer-specific markers. SELEX is a combinatorial chemistry technology that can create an extremely large library of aptamers of oligonucleotides (synthetic oligonucleotides) to identify those oligonucleotides with the highest specificity and affinity for the target. NeXstar’s Blended SELEX technology converts molecules with low specificity but potentially useful biological activity into high-specificity drug candidates. A planned extension of SELEX, Parallel SELEX will be used to develop orally available small-molecule drug candidates.

Contact: Michael Burke, Vice President, Business Development

Oncogene Science, Inc.

See OSI Pharmaceuticals, Inc.

Oak Samples Trading, Ltd.

5 Sapiernoye pole St., 252042 Kiev, Ukraine

Phone: 380 44 269 3467; Fax: 380 44 269-3467 (local night hours) E-mail: sdl@public.ua.net

Internet: http:/ /www.osc.edu/ccl/commercial/OST.html

Profile: Oak Samples Trading(OST) company was founded in 1994 to establish reliable links between Ukrainian chemists and their foreign colleagues. The main objectives of OST were to facilitate research information exchange and to encourage investments in Ukranian science. Today the company’s focus is on providing samples for high-throughput screening. During the course of their research, Ukrainian chemists synthesize many new compounds that are potentially active in agricultural and pharmaceutical screens.

Products/technologies: OST’s collection of small molecules was gathered from about 20 institutions throughout the Ukraine. These molecules are the results of the creative efforts of nearly 100 Ukrainian chemists. The OST collection of compounds is available as ISIS/Base-formatted diskettes (Windows) for preview prior to purchase and will be available through FTP and WWW services.

Ontogen Corp.

2325 Camino Vida Roble, Carlsbad, CA 92009, USA Phone: (619) 930-0100; Fax: (619) 930-0200 Internet: http:/ /www.ontogen.com

Profile: Ontogen is a pharmaceutical company focusing on advancing techniques for the development of small molecule therapeutics to treat cancer and diseases of the immune system. The company has approximately 45 employees.

Products/technologies: For automation of combinatorial chemistry on solid phase in a modular approach, the OntoBlock central piece of hardware consists of 96 2-ml polymeric reaction vessels containing beads on which the synthesis takes place. From there the test components are stored, are characterized, or

Oxford Asymmetry Limited

151 Milton Park, Abingdon, Oxon OX14 4SD, England Phone: 44(0)1235 861561; Fax: 44(0)1235 863139 E-mail: sales@oa-od.com

Internet: http:/ /www.oa-od.com

Profile: A privately held company, it comprises Oxford Diversity, Oxford Asymmetry, and Oxford USA. Oxford Diversity is the company’s combinatorial chemistry business; it has drug discovery experience in molecular modeling, organic chemistry, and combinatorial techniques leading to the identification of active leads. The company specializes in custom manufacturing and drug development for the pharmaceutical industry. In September 1997, Oxford Asymmetry expanded its pilot plant capacity and doubled its laboratory space. In February 1998 the company announced plans to raise funds through a listing on the London Stock Exchange.

Products/technologies: Offers a range of advanced chemical products and services required for rapid drug discovery and development, including everything from the production of diverse chemical libraries to the supply of multitonnes of bulk drug substance; and the Prospector series of combinatorial libraries.

Oxford Molecular Group, PLC (OMG)

The Medawar Centre, Oxford Science Park, Oxford OX4 4GA, UK Phone: 44 1865 784600; Fax: 44 1865 784601

E-mail: products@oxmol.com Internet: http:/ /www.oxmol.com

Stock: OMG (London Stock Exchange)

Profile: The company, whose name was changed in 1996 from IntelliGenetics, is a worldwide provider of integrated solutions for drug discovery for companies and universities. OMG was fundamental in the establishment of a new company, Cambridge Combinatorial, in February 1997 (see separate listing). In August 1997, OMG announced that it had taken an option to buy Cambridge Combinatorial. The move is intended to turn OMG from a company that designs software into one that designs new drugs. Its Collaborative Discovery division, along with its associate companies, Cambridge Combinatorial Limited and Cambridge Drug Discovery, provide research services and consulting in drug design, combinatorial chemistry and high-throughput screening.

Products/technologies: OMG offers a wide range of computer-aided molecular design (CAMD) software, advanced bioinformatics tools, cheminformatics tools, and collaborative research services. Some products now on the market include PC/GENE sequence analysis software, InteleGenetics Suite, GeneWorks , GENESEQ patent sequence DNA and protein database, MPSRCH , BIONET , MacVector sequence analysis software, RS3 Discovery software for corporate chemical information management. DIVA , a visualization and analysis tool for chemical and biological data stored in large databases, reduces the time needed for analyzing large sets of data. OMIGA, the first in a family of integrated, enterprise-wide software tools and a comprehensive sequence analysis tool, is available for Windows 95 and Windows NT 4 platforms. Through its Collaborative Discovery Division, the company provides software and service solutions to the drug discovery industry.

Contact: Dr. Tony Marchington, CEO

Packard Instrument Company, Inc.

800 Research Parkway, Meriden, CT 06450, USA Phone: (203) 238-2351; Fax: (203) 639-2172 Toll-free in U.S.: (800) 323-1891

E-mail: webmaster@packardinst.com Internet: http:/ /www.packardinst.com

Profile: Packard is a subsidiary of Canberra Industries, Meriden, Connecticut. Its instruments, reagents, and applications support are sold to organizations that conduct research and develop products in life science, diagnostics, and environmental analysis. The company employs more than 550 people worldwide with 50 employees at its corporate headquarters and 275 at its manufacturing facility in Downers Grove, Illinois.

Products/technologies: The company offers a complete line of microplate reader instrumentation. Discovery, a nonisotopic high-throughput screening analysis system, is based on a Nobel Prize–winning chemistry designed to make drug discovery faster, safer and more cost effective. Technology can be applied to a screening process called Homogeneous Time Resolved Fluorescence (HTRF), which can replace older, conventional radioisotopic processes, reducing exposure risks and waste disposal costs. The patented HTRF chemistry is from CIS Biointernational of France. Using Packard’s high capacity microplate analyzer Discovery, designed specifically for automated drug

screening, HTRF can screen 50,000 samples per day, compared to only 10,000 using conventional technology. HTRF incorporates photon-counting electronics, dual photomultiplier tubes, and time-delayed measurements to eliminate background fluorescence. MultiPROBE VersaTip technology will sense small sample volumes in microplates.

Contact: Richard McKernan, President

Pangea Systems, Inc.

1999 Harrison Street, Suite 1100; Oakland, CA 94612, USA Phone: (510) 628-0100

E-mail: info-pr@PangeaSystems.com Internet: http:/ /www.pangeasystems.com

Profile: A bioinformatics company, Pangea applies information technology to biological research. Software applications integrate data with analysis and visualization tools for biological and chemical information. Incorporated in 1993, it is a privately held company.

Products/technologies: EcoCyc 4.0 is a bioinformatics metabolic pathways

dataset for E. coli and is available through the world wide web; links approximately 2000 more genes than the previously available version. PathoLogic

creates metabolic pathway datasets of other pathogenic organisms. Gene-

World is an automated, high throughput application for analysis of DNA and protein sequences; GeneMill is a workflow management application designed for DNA sequencing laboratories. GeneThesaurus is a sequence and

annotation data warehouse containing information from multiple sources and integrates common public gene and protein sequence and protein structure databases.

Contact: Marie Martin

Panlabs, International

11804 North Creek Parkway, S., Bothell, WA 98011-8805, USA Phone: (206) 487-8200; Fax: (206) 487-3787

E-mail: panlabs@panlabs.com Internet: http:/ /www.panlabs.com

Stock (parent company): MHG.A, MHG.B (TSE)