LICENSE AGREEMENT

EXHIBIT 10.11

CERTAIN MATERIAL (INDICATED BY AN ASTERISK) HAS BEEN OMITTED FROM THIS DOCUMENT PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT. THE OMITTED MATERIAL HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.

AMENDMENT NO. 1

to the

LICENSE AGREEMENT
dated as of March 31, 2004

     THIS AMENDMENT NO. 1 (the “ FIRST AMENDMENT ”), dated and effective as of the 22nd day of December, 2004, to that certain LICENSE AGREEMENT dated as of March 31, 2004 (the “ AGREEMENT ”), by and between DUKE UNIVERSITY, a nonprofit educational and research institution organized under the laws of North Carolina (“ DUKE ”), and OREXIGEN PHARMACEUTICALS, INC., a Delaware corporation (hereinafter “ OREXIGEN ”). Unless otherwise defined herein, capitalized terms used but not defined herein shall have the meaning set forth in the AGREEMENT and the AGREEMENT shall be amended to incorporate any additional definitions provided for in this FIRST AMENDMENT, including definitions in the recitals hereto.

     WHEREAS, OREXIGEN and CYPRESS BIOSCIENCE, INC., a Delaware corporation (“ CYPRESS ”), intend to enter into that certain LICENSE AGREEMENT (the “ CYPRESS AGREEMENT ”), pursuant to which OREXIGEN shall grant a SUBLICENSE (the “ CYPRESS SUBLICENSE ”) to CYPRESS, subject to this FIRST AMENDMENT, and CYPRESS is a signatory to this FIRST AMENDMENT solely for the purposes of Section 2 of this FIRST AMENDMENT;

     WHEREAS, DUKE and OREXIGEN desire to amend the AGREEMENT as set forth herein;

     NOW, THEREFORE, in consideration of the premises and the mutual agreements hereinafter set forth, the parties hereby agree as follows:

     1.  Amendment to Section 1.19 . Section 1.19 of the AGREEMENT is hereby amended to read in its entirety as follows:

     1.01 “NET SALES” shall mean:

and each of (a) (b), and (c), above shall be less the sum of the following:

No deductions to NET SALES shall be made for commissions paid to individuals whether they are associated with independent sales agencies or regularly employed by OREXIGEN (and/or SUBLICENSEES, as the case may be) and on its payroll, or for cost of collections. DUKE LICENSED PRODUCTS, OREXIGEN LICENSED PRODUCTS, DUKE LICENSED PROCESSES, OREXIGEN LICENSED PROCESSES, DUKE LICENSED SERVICES, and OREXIGEN LICENSED SERVICES shall be considered “sold” when the consideration for provision thereof is received by OREXIGEN (and/or SUBLICENSEES, as the case may be). DUKE LICENSED PRODUCTS, OREXIGEN LICENSED PRODUCTS, DUKE LICENSED PROCESSES, OREXIGEN LICENSED PROCESSES, DUKE LICENSED SERVICES, and OREXIGEN LICENSED SERVICES used by OREXIGEN (and/or SUBLICENSEES, as the case may be) for clinical field trials, provided as free-of-charge-samples for distribution to customers or end users, or for OREXIGEN’s own internal non-commercial research (and/or SUBLICENSEES, as the case may be) shall not be included in NET SALES.

Except as provided below, if a DUKE LICENSED PRODUCT, DUKE LICENSED PROCESS or a DUKE LICENSED SERVICE is sold in combination with another active component or components not otherwise claimed in the DUKE PATENT RIGHTS, and OREXIGEN (or any appertaining SUBLICENSEE) does not pay a royalty for such component that will result in a reduced RUNNING ROYALTY pursuant to Section 3.01(b) , then the NET SALES, for purposes of determining royalties on the combination, will be calculated by multiplying the NET SALES of the combination by the fraction A/(A+B), where A is the invoice price of the DUKE LICENSED PRODUCT, DUKE LICENSED PROCESS or DUKE LICENSED SERVICE if sold separately and B is the total invoice price of any other active component or components in the combination if sold separately. If the DUKE LICENSED PRODUCT, DUKE LICENSED PROCESS or DUKE LICENSED SERVICE and

the other active component or components in the combination are not sold separately, the NET SALES, for purposes of determining royalties on the combination, will be calculated by multiplying the NET SALES of the combination by the fraction determined b