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Dr. Stanley Crooke

Founder, Chairman & CEO

Isis Pharmaceuticals

S. Crooke

Dr. Stanley Crooke has the vision and courage that make an entrepreneur. But he also possesses the unexpected quality of patience. While it's an unusual trait in an entrepreneur, patience has been an essential element in the story of Isis Pharmaceuticals (Nasdaq: ISIS).

Crooke founded Isis in 1989, based on his belief in an untested drug technology called "antisense." Antisense drugs target ribonucleic acid, or RNA, and prevent disease-causing proteins from being produced. The company began with 30 scientists in a small office building and labs located in a garage. Thirteen years later, more than 400 employees occupy five buildings in Carlsbad.

Development of this complex technology has required years of research. But Crooke's belief in his company and the tremendous potential of antisense drugs has paid off. Isis paved the way in a field where rewards were seldom quick, and never guaranteed. As a result, the company stands at the forefront of its field. In 2001 Isis completed 17 transactions with 13 partners. Isis has nearly 900 patents worldwide, and has negotiated strategic partnerships with industry powerhouses like Eli Lilly & Co. (NYSE: LLY), Merck (NYSE: MRK) and Novartis AG (NYSE: NVS).

No other company in the antisense field has a functional genomics division, as Isis does with GeneTrove. GeneTrove's product offerings include access to its Human Gene Function database and licenses to its genomics patent portfolio.

Ibis Therapeutics forms another division of the company. Ibis focuses on the discovery of small molecule drugs that bind to RNA, and in 2001 won a government contract to develop a diagnostic tool for use in biological warfare defense. The Ibis division saw considerable success in 2001 in its drug discovery collaboration with Agouron Pharmaceuticals, a Pfizer Inc. (NYSE: PFE) company.

Isis is an organization also notable for its advocacy efforts. Last year the firm participated in a Project Concern International fund-raising event, and this year received the Health Hero award for its dedication to San Diego's Crohn's and Colitis Foundation. Isis also received the 2002 Helix Award, the highest award of corporate excellence in the international biotechnology industry, an award based on scientific innovation, company growth and corporate citizenship.

Dr. William Huse

Founder, President & CEO

Applied Molecular Evolution

W. Huse

Dr. William Huse founded Applied Molecular Evolution (Nasdaq: AMEV) in 1989, based on his own research. The goal of the company is remarkable: to accelerate the evolutionary process of selected genes. The purpose is to create new drugs to battle conditions such as cancer, arthritis, infectious disease, organ transplant rejection and even cocaine addiction.

The AMEsystem is an integrated suite of technologies for conducting all three of the fundamental steps of directed molecular evolution, and has been designed from the ground up to address the unique challenges of optimizing human therapeutic proteins. The first step, DirectAME, is a gene synthesis process that enables the rapid production of a library of variant genes based on an initial gene. The second step, ExpressAME, consists of gene expression systems that efficiently produce proteins from the genes generated using DirectAME. The third step, SelectAME, is a series of assays or screens, which facilitate the selection and identification of proteins with optimal commercial properties from the protein libraries created using ExpressAME. This entire process is repeated until a protein with the desired characteristics is produced.

In addition to internal development programs, the company has collaborated with industry-leading organizations like Eli Lilly (NYSE: LLY) and Bristol-Myers Squibb Co. (NYSE: BMY). The result of these collaborations has been that Applied Molecular Evolution is the first directed molecular evolution company with a product, Vitaxin, in human clinical trials.

In the last three years, Applied Molecular Evolution has seen considerable growth, quadrupling its number of employees. Huse recently established a subsidiary, Novasite Pharmaceuticals, to apply Applied Molecular Evolution's technologies to the discovery and optimization of small molecule drugs. Last year, Novasite entered into an agreement with Aventis to conduct a pilot study for Novasite's proprietary Expanded Target Drug Discovery system. Additionally, Applied Molecular Evolution is launching the second phase of its business strategy to internally develop second-generations of currently marketed bio-therapeutics, which will allow the company to capture far greater value from the application of Huse's technology.

Michael Perry, CEO

Rhonda Rhyne, President

Cardiodynamics

M. Perry

R. Rhyne

Cardiodynamics' BioZ is a system for monitoring heart patients without damaging, invasive procedures, and without the inconvenience and expense of a hospital stay. Developed from NASA technology, the system struggled in the marketplace until the arrival of Rhonda Rhyne and Michael Perry. Together, the two have brought the company from bankruptcy to profitability.

Strategically addressing every aspect of the company, Perry and Rhyne have overseen 16 consecutive quarters of increased sales, and an 833-percent revenue growth since 1998. Stockholders have seen 148-percent increase in value in the last three years.

Constantly innovative in their ways to market and manage the company, Perry and Rhyne have moved at lightning speed to acquire approvals and certifications for the BioZ range of products, extending the technology into overseas markets and onto the Internet. As a result, Cardiodynamics has become one of the fastest-growing companies in the field, and in 2001 the firm received the Starcom Top 25 Area Fast Growing Companies Award.

Critical partnerships with organizations such as Spacelabs (Nasdaq: SLMD), Vasomedical (Nasdaq: VASO) and the Heart & Lung Association have helped generate a 50 percent sales increase in the last year alone. 2001 also saw the issuance of two new patents and a $1,000 per unit reduction in the cost of production.

The BioZ heart monitor is based on a technology called impedance cardiography. It provides the physician with information about the heart's ability to deliver blood to the body, the force the heart exerts with each beat, and the amount of fluid in the chest. Sensors are placed on the neck and chest, and provide information about 12 different critical parameters.

The BioZ system has been clinically proven to improve patient prognoses and to decrease treatment costs. Cardiodynamics is working on the development of the BioZ.tel, which will allow the patient to transmit the data to his or her physician over a telephone line. Each development in BioZ technology not only adds to the company's product range, but also provides another tool to diagnose, monitor and treat heart disease.

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