EXHIBIT 10.46 FIRST AMENDMENT DATED AS OF DECEMBER 4, 2006 TO PRODUCT DEVELOPMENT AND LICENSE AGREEMENT

Exhibit 10.46

[*Confidential treatment has been requested as to certain portions of this document. Each such portion, which has been omitted herein and replaced with an asterisk [***], has been filed separately with the Securities and Exchange Commission.]

FIRST AMENDMENT

DATED AS OF DECEMBER 4, 2006

TO

PRODUCT DEVELOPMENT AND LICENSE AGREEMENT

BY AND BETWEEN

NASTECH PHARMACEUTICAL COMPANY INC.

AND

PROCTER & GAMBLE PHARMACEUTICALS, INC.

DATED AS OF JANUARY 27, 2006

[*Confidential treatment has been requested as to certain portions of this document. Each such portion, which has been omitted herein and replaced with an asterisk [***], has been filed separately with the Securities and Exchange Commission.]

FIRST AMENDMENT
TO
PRODUCT DEVELOPMENT AND LICENSE AGREEMENT

     This First Amendment to the Product Development and License Agreement (the “First Amendment”) is entered into as of December 4, 2006 by and between PROCTER & GAMBLE PHARMACEUTICALS, INC., a corporation organized under the laws of Ohio (“P&G”), and NASTECH PHARMACEUTICAL COMPANY INC., a corporation organized under the laws of Delaware (“Nastech”), as an amendment to the Product Development and License Agreement (the “Agreement”) entered into as of January 27, 2006 by and between P&G and Nastech. All capitalized terms used herein shall have the meanings given in the Agreement.

     WHEREAS, P&G and Nastech wish to amend the Agreement in the manner set forth herein.

     NOW, THEREFORE, for and in consideration of the mutual covenants contained herein, the parties hereto agree as follows:

     1.  Amendment .

     1.01. Article I of the Agreement is hereby amended by adding the following as definitions therein:

     “ [***] TERM” means the period commencing upon [***] .

     “ [***] TERM FUNDING” means amounts payable by P&G [***] .

     “FIRST AMENDMENT” means the First Amendment to the Product Development and License Agreement, dated as of December 4, 2006, as the same may be amended, modified or extended.”

     “PHASE II POC STUDY” means a proof-of-concept study to be conducted substantially in accordance to the protocols outlined in the Development Plan [***] .

     “ [***] STUDY” means [***] .”

     “THIRD PARTY DEVELOPMENT COSTS” means costs which are included in the Development Plan budget and which are incurred for services performed by Third Parties.

     1.02 [***] .

[*Confidential treatment has been requested as to certain portions of this document. Each such portion, which has been omitted herein and replaced with an asterisk [***], has been filed separately with the Securities and Exchange Commission.]

     1.03. Section 2.8.4 shall be added to the Agreement, which Section shall read in its entirety as follows:

          “2.8.4 The following provisions shall apply notwithstanding anything to the contrary in this Section 2.8:

                    (a)  [***] .

          (b) [***] ”

     1.04 Section 4.10 shall be added to the Agreement, which Section shall read in its entirety as follows:

     “4.10 [***] ”

     1.05. Section 13.4 to the Agreement shall be amended to read in its entirety as follows:

     “13.4 TERMINATION BY P&G WITHOUT CAUSE. P&G may terminate for any reason as follows:

     (I)  [***] ;

     and, should subsection (I) not be applicable, (II) (i) upon [*