Exhibit 10.3

[ * ] = Certain confidential information contained in this document, marked by brackets, has been omitted and filed separately with the Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

A MENDMENT N O . 2 TO THE C OLLABORATION A GREEMENT

BETWEEN

E XELIXIS , I NC ., AND B RISTOL -M YERS S QUIBB C OMPANY

T HIS A MENDMENT N O . 2 (“ Amendment No. 2 ”) to the Agreement (defined below) is effective as of October 1, 2009 (the “ Amendment No. 2 Effective Date ”) by and between Exelixis, Inc. , a Delaware corporation having an address at 170 Harbor Way, P.O. Box 511, South San Francisco, California 94083-0511 (“ Exelixis ”) and Bristol-Myers Squibb Company , a Delaware corporation having an address at 345 Park Avenue, New York, New York 10154 (“ BMS ”). Exelixis and BMS may be referred to individually as a “ Party ” and collectively as the “ Parties ”.

W HEREAS , Exelixis and BMS entered into that certain Collaboration Agreement executed as of December 15, 2006, and as amended to be effective on January 11, 2007 (the Collaboration Agreement, as amended, the “ Agreement ”), for the purposes of applying Exelixis’ technology and expertise to the discovery, lead optimization and characterization of small molecule compounds that directly bind and modulate certain oncology targets, with a goal of filing Investigational New Drug applications for such small molecule compounds, and to provide for the development and comm