Applied Molecular Evolution's AME-359 Provides Complete Protection from Lethal Cocaine Overdose in Animal Model System of Acute Cocaine Toxicity.

Business Editors & Health/Medical Writers

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SAN DIEGO--(BUSINESS WIRE)--Jan. 9, 2003

Optimized BChE Demonstrates Greater Than 250-Fold Improvement in

Potency in In Vivo Studies Compared with Wild-type Enzyme

Applied Molecular Evolution, Inc. (AME) (Nasdaq:AMEV) today announced that it has demonstrated protection from lethal cocaine overdose in a preclinical study of an optimized form of Butyrylcholinesterase (BChE), a naturally occurring human serum enzyme that catalyzes the hydrolysis, or breakdown, of cocaine in the bloodstream. The AMEsystem(TM) was utilized to engineer AME-359, a new molecule having greater than 250-fold improvement in potency over the wild-type enzyme as demonstrated by AME in an animal model system.

"AMEsystem(TM) technology was leveraged with financial support from the National Institutes of Health to demonstrate proof-of-concept that AME can potentially create new, important therapeutics from natural proteins that exist in the human body. Although BChE is able to hydrolyze cocaine, its extremely slow rate of action makes it unlikely to have therapeutic efficacy at reasonable doses. Our engineering has created a similar but novel molecule that may have potential as a treatment for cocaine overdose," commented William D. Huse, M.D., Ph.D., President, CEO and Chairman of AME. "AME-359 may potentially address the unmet medical need of acute cocaine overdose by accelerating the clearance of cocaine from the bloodstream. AME-359 therefore represents an entirely new approach to treating a critical condition with serious medical and socioeconomic consequences."

In the animal model, rats were infused with two mg/kg per minute of cocaine for up to 15 minutes. Without treatment, 100% of the rats died in approximately 12 minutes. Treatment with doses up to 50 mg/kg of wild-type BChE provided no protection from lethality. By contrast, AME-359 provided 50% survival at 0.2 mg/kg and 100% survival at 0.5 mg/kg demonstrating complete protection from the lethal cocaine overdose. These results suggest that AME has engineered improvements in BChE's catalytic rate that improve the enzyme's ability to neutralize the toxic effects of cocaine in vivo by greater than 250-fold.

Applied Molecular Evolution, Inc., (AME) is a leader in applying directed molecular evolution to improve healthcare by optimizing and developing human biotherapeutics. Directed molecular evolution is a process for optimizing genes and proteins for specific commercial purposes. Since its inception, AME's principal focus has been on applying its proprietary AMEsystem(TM) technology platform to human biotherapeutics, the largest market for directed molecular evolution. Biotherapeutics, or biopharmaceuticals, are protein pharmaceuticals such as antibodies, cytokines, hormones and enzymes. AME uses its proprietary technology to develop improved versions of currently marketed, FDA-approved biopharmaceuticals as well as novel human biotherapeutics. For more information, please visit www.AME.biz.

This press release contains forward-looking statements that are subject to risks and uncertainties that could cause actual results to differ materially from those set forth in the forward-looking statements, including uncertainties related to product development, uncertainties related to the need for regulatory or other government approvals, dependence on proprietary technology, uncertainty of market acceptance of the Company's products, uncertainties related to business opportunities, the receipt of future payments, including royalties, the continuation of customer relationships and other risks cited in the Company's Annual Report on Form 10-K for the year ended December 31, 2001, and other SEC Filings. These forward-looking statements speak only as of the date hereof. The Company disclaims any intent or obligation to update these forward-looking statements.