Exelixis was founded in 1994; the scientific founders were Spyridon Artavanis–Tsakonas, at Yale at that time, and Corey Goodman and Gerry Rubin who were then at the University of California, Berkeley.

[10] The business plan was to use model organisms (fruit flies, nematodes, and zebrafish) and functional genomics to identify pathways and biological targets that could be exploited in the fields of agriculture and medicine.

[9] By 2000 it had left the radical exploratory phase behind and became focused on drug discovery and had a chemical library of 4 million compounds.

[9] In 2006 Exelixis partnered with Daiichi Sankyo on compounds that targeted mineralocorticoid receptors; esaxerenone was part of this collaboration.

Exelixis had filed an IND on XL-518 prior to the partnership, committed to funding and running the Phase I trial, and retained rights to co-market it in the US.

[20] Exelixis invested heavily in exploring cabozantinib in other cancers, betting the future of the company on the drug.