Re: Amendment No. 3 to Collaboration Agreement

EXHIBIT 10.4

VIA FACSIMILE AND

OVERNIGHT MAIL

Michael R. Dougherty

President and Chief Executive Officer

Adolor Corporation

700 Pennsylvania Drive

Exton, Pennsylvania 19341

Dear Mike,

This letter amendment (“Amendment No. 3”), effective as of June 9, 2008, is in reference to the Collaboration Agreement dated April 14, 2002 (the “Collaboration Agreement”), as amended by Amendment No. 1 to the Collaboration Agreement effective on June 24, 2003 (“Amendment No. 1”) and Amendment No. 2 to the Collaboration Agreement effective on December 22, 2004 (“Amendment No. 2”) (the Collaboration Agreement, Amendment No. 1 and Amendment No.2 are collectively referred to herein as, the “Agreement”), by and between Adolor Corporation (“Adolor”) and Glaxo Group Limited (“GGL”). All capitalized terms used in this Amendment No. 3 that are not otherwise defined herein shall have the meanings given to them in the Agreement.

Notwithstanding anything to the contrary in the Agreement, the terms pursuant to which GSK shall deploy and pay incentive compensation to the GSK Sales Representatives during the period beginning on the date of the First Commercial Sale of the POI Product in the United States until December 31, 2008 (the “Launch Period”) shall be as follows:

Subject to an annual [**] percent [**] vacancy rate, GSK shall deploy not less than [**] GSK Sales Representatives to Detail the POI Product to the Target Audience in the United States during the Launch Period. The Parties acknowledge and agree that a GSK Sales Representative shall mean and include those individuals referred to internally by GSK in the United States as “Account Managers” who are hospital based. This deployment of GSK Sales Representatives as set forth in this Amendment No. 3 shall be considered as the Sales Representative FTE Requirements for GSK during the Launch Period. Further, during the Launch Period, GSK will not categorize the GSK Sales Representatives as Hospital Account Managers, Oncology Account Managers or Surgical Account Managers.