In 1989, Bill Huse, M.D., Ph.D., founded the company in San Diego, California and incorporated it as Ixsys, Inc. Operations began in 1990, with five employees. It was the first company to focus on the technology now called directed evolution to engineer proteins that had improved functions. The company was renamed Applied Molecular Evolution, Inc., in 2000 and went public later that year.

Collaborations were a key element of AME’s growth over the years. Bristol-Myers Squibb was AME’s first collaborative partner, beginning in the early 1990s, and the companies worked on tumor-antigen-targeting products. AME also collaborated with Biosynexus, CancerVax, Centocor, Chiron, MedImmune and Seattle Genetics. In 2001, AME and Lilly entered their initial collaboration, a product development agreement to optimize two protein therapeutics for Lilly. By the time it became a wholly owned subsidiary of Lilly in 2004, AME had completed all projects with other collaborators. AME’s 110 employees now devote all their time to Lilly projects.