AMENDMENT NO.1 TO AMENDED AND RESTATED COLLABORATION AGREEMENT BETWEEN GENZYME CORPORATION AND DYAX CORP.

<Page>

                                                               Exhibit 10.35.1

              AMENDMENT NO.1 TO AMENDED AND RESTATED COLLABORATION

              AGREEMENT BETWEEN GENZYME CORPORATION AND DYAX CORP.

        This Amendment No. 1 (the "Amendment") to the Amended and Restated

Collaboration Agreement dated May 31, 2002 (the "Agreement") by and between

Genzyme Corporation, with its principal office at One Kendall Square, Cambridge,

Massachusetts 02139 ("Genzyme"), and Dyax Corp., with a principal office at 300

Technology Square, Cambridge, Massachusetts 02139 ("Dyax") is effective as of

September 30, 2003 ("Amendment Effective Date"). Terms not otherwise defined

herein shall have the respective meanings attributed to them in the Agreement.

        WHEREAS, Genzyme and Dyax are parties to the Agreement, pursuant to

which the parties agreed to collaborate in developing DX-88 for the treatment of

hereditary angioedema and other inflammatory diseases; and

        WHEREAS, Genzyme and Dyax now wish to modify the terms of their

collaboration and amend certain provisions of the Agreement;

        NOW, THEREFORE, in consideration of the promises and agreements set

forth herein, and for other good and valuable consideration, Genzyme and Dyax

hereby agree as follows:

1.      The parties acknowledge and agree that on June 26, 2003, Genzyme

elected to exercise its Buy-In Option. As a result, all rights and obligations

of Genzyme contained in the Agreement that are contingent upon Genzyme's

exercise of its Buy-In Option shall hereafter be deemed to be current and fully

enforceable rights and obligations.

2.      Section 1.15 of the Agreement ("Field") shall be amended and restated

as follows:

        "FIELD" shall mean any and all therapeutic uses of a Collaboration