Contract

[ * ] = 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.

Exhibit 10.46

January 6, 2005

Xxxxx Xxxxxxx, Ph.D.

Cystic Fibrosis Foundation Therapeutics, Inc.

0000 Xxxxxxxxx Xxxx

Xxxxxxxx, XX 00000

Dear Xx. Xxxxxxx:

The purpose of this Letter Agreement is to amend the Study Funding Agreement, dated June 17, 2003, as amended, between the undersigned parties (the “Agreement”).

By signing below, the undersigned parties agree to extend, for an additional [ * ], the time to agree upon (i) a revised Work Plan under Section 2.2 of the Agreement and (ii) a revised Exhibit B which shall reflect the revised Work Plan.

All other terms and provisions of the Agreement shall remain unchanged and are in full force and effect.

XXXXXX-XXXX PHARMACEUTICALS, INC.
By:		/s/ X. Xxxxxxx
		Xxxx X. Xxxxxxx Vice President, General Counsel
Agreed to and Acknowledged by:
CYSTIC FIBROSIS FOUNDATION THERAPEUTICS, INC.
By:		/s/ X. Xxxxx
		Xxxxxx X. Xxxxx, Ph.D. President and CEO