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                                                                     EXHIBIT 4.3

                          TRUBION PHARMACEUTICALS, INC.

                               AMENDMENT NO. 1 TO

                 AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

     This Amendment No. 1 to the Amended and Restated Investor Rights Agreement
(the "RIGHTS AGREEMENT") dated as of July 13, 2004 is entered into as of
________, 2005, by and among Trubion Pharmaceuticals, Inc., a Delaware
corporation (the "COMPANY"), Wyeth, a Delaware corporation ("WYETH"), and the
investors set forth on EXHIBIT A hereto (collectively the "INVESTORS" and each
individually an "INVESTOR").

                                    RECITALS

     A. The Company and the Investors are parties to the Rights Agreement.

     B. The Company and Wyeth have entered into a Common Stock Purchase
Agreement dated as of December ___, 2005 (the "PURCHASE AGREEMENT") pursuant to
which the Company will sell to Purchaser and Purchaser will purchase from the
Company shares of the Company's Common Stock concurrent with and conditioned
upon the closing of the Company's initial public offering (the "CLOSING"). A
condition to the Purchaser's obligations under the Purchase Agreement is that
the Rights Agreement be amended in order to provide Purchaser with certain
rights to register shares of the Company's Common Stock.

     C. Pursuant to Section 6.5 of the Rights Agreement, the written consent of
the Company and the Investors holding a majority of the Registrable Securities
(the "REQUISITE HOLDERS") is required to amend the Rights Agreement.

     D. The Company and the Requisite Holders desire to induce Purchaser to
enter into the Purchase Agreement by agreeing to the terms and conditions set
forth herein.

     NOW, THEREFORE, in consideration of the mutual promises, representations,
warranties, covenants and conditions set forth in this Agreement, the parties
hereto agree as follows:

     1. Definitions. Capitalized terms used herein without definition shall have
the meaning ascribed to them in the Rights Agreement.

     2. Addition of Purchaser as a Party to the Rights Agreement. Effective upon
the Closing pursuant to the Purchase Agreement, the parties hereby agree to add
Purchaser as a party to the Rights Agreement and Purchaser shall be deemed a
"Holder" of Registrable Securities for purposes of Sections 1, 2 and 6 of the
Rights Agreement and subject to all of the rights and obligations of such
Sections. For purposes of clarification, Purchaser shall not be entitled to the
rights or subject to the obligations set forth in Sections 3, 4 and 5 of the
Rights Agreement and Purchaser shall not be deemed an "INVESTOR" for purposes of
the Rights Agreement..

     3. Amendment to Section 1.1. The definition of "Registrable Securities" set
forth in Section 1.1 is hereby amended and restated to read in its entirety as
follows:

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          "REGISTRABLE SECURITIES" means (a) Common Stock of the Company issued
or issuable upon conversion of the Shares, (b) Common Stock of the Company
issued to Frazier Healthcare Fund ("FRAZIER"), ARCH Venture Fund ("Arch") and
Scott Minick ("MINICK") pursuant to those certain Common Stock Purchase
Agreements dated November 19, 2002 by and between the Company and each of
Frazier, Arch and Minick, (c) Common Stock of the Company issued to Wyeth
pursuant to the Purchase Agreement, and (d) any Common Stock of the Company
issued as (or issuable upon the conversion or exercise of any warrant, right or
other security which is issued as) a dividend or other distribution with respect
to, or in exchange for or in replacement of, the securities described in (a),
(b) and (c) above; provided, however, the shares referred to in clause (c) above
shall not qualify as Registrable Securities for the purposes of Sections 2.2
hereof until the 15 month anniversary of the Closing. For the avoidance of
doubt, in the event that the Company effects a registration under the Securities
Act pursuant to Section 2.2 hereof prior to the 15 month anniversary of the
Closing, in connection with such registration the Shares referred to in clause
(c) above shall qualify as Registrable Securities for the purposes of Section
2.3. Notwithstanding the foregoing, Registrable Securities shall not include any
securities sold by a person to the public pursuant to a registration statement
or Rule 144 or sold in a private transaction in which the transferor's rights
under SECTION 2 of this Agreement are not assigned.

     4. Amendment to Section 2.1(a)(ii). Section 2.1(a)(ii) is amended effective
immediately following the expiration of the "Market Stand-Off" period set forth
in Section 2.12 hereof, by deleting the last sentence thereof and substituting
therefor the following:

     "Subject to the other terms of this Agreement (including without limitation
     the restrictions on assignment of registration rights set forth in Section
     2.10 and Sections 2.1(b) and (d)), it is agreed that the restrictions
     contained in this Section 2.1(a)(ii) shall not apply to dispositions of
     Shares or Registrable Securities made pursuant to Rule 144 promulgated
     under the Securities Act."

     5. Amendment to Section 6.5. Section 6.5 is hereby amended by adding, after
the final sentence thereof, the following:

          Notwithstanding the foregoing, neither this Agreement nor any term
hereof may be amended, waived, discharged or terminated in any way that
diminishes or eliminates the rights particular to Wyeth hereunder and in a
manner different than the other holders of Registrable Securities, such action
shall require the prior written consent of Wyeth.

     6. Waiver of Right of Participation. Each Investor on behalf of itself and
all other Investors and holders of Registrable Securities hereby waives any
right of participation set forth in Section IV of the Rights Agreement with
respect to the sale and issuance of the shares of Company Common Stock to Wyeth
pursuant to the Purchase Agreement.

     7. No Other Amendments. Except as expressly amended or waived as set forth
above, the Rights Agreement shall remain in full force and effect in accordance
with its terms.

     8. Counterparts. This Amendment may be executed in any number of
counterparts, each of which shall be deemed an original and all of which
together shall constitute one document.

                            [Signature pages follow.]


                                       -2-

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     IN WITNESS WHEREOF, the parties hereto have executed this AMENDMENT NO. 1
TO THE RIGHTS AGREEMENT as of the date set forth in the first paragraph hereof.

                                        "COMPANY"

                                        TRUBION PHARMACEUTICALS, INC.
                                        a Delaware corporation


                                        By: /s/ Peter Thompson
                                            ------------------------------------
                                            Peter Thompson, M.D., FACP
                                            President and Chief Executive
                                            Officer

                      SIGNATURE PAGE TO AMENDMENT NO. 1 TO
                 AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

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     IN WITNESS WHEREOF, the parties hereto have executed this AMENDMENT NO. 1
TO THE RIGHTS AGREEMENT as of the date set forth in the first paragraph hereof.

                                        "WYETH"

                                        WYETH


                                        By: /s/ William M. Haskel
                                        ----------------------------------------
                                        Name: William M. Haskel
                                        Its: Vice President

                      SIGNATURE PAGE TO AMENDMENT NO. 1 TO
                 AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

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     IN WITNESS WHEREOF, the parties hereto have executed this AMENDMENT NO. 1
TO THE RIGHTS AGREEMENT as of the date set forth in the first paragraph hereof.

                                        "INVESTOR"

                                        PROSPECT VENTURE PARTNERS II, L.P.

                                        By: Prospect Management Co. II, LLC
                                        Its General Partner


                                        By: /s/ David Schnell
                                            ------------------------------------
                                        Name: David Schnell
                                        Title: Managing Member


                                        PROSPECT ASSOCIATES II, L.P.

                                        By: Prospect Management Co. II, LLC
                                        Its General Partner


                                        By: /s/ David Schnell
                                            ------------------------------------
                                        Name: David Schnell
                                        Title: Managing Member

                      SIGNATURE PAGE TO AMENDMENT NO. 1 TO
                 AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

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     IN WITNESS WHEREOF, the parties hereto have executed this AMENDMENT NO. 1
TO THE RIGHTS AGREEMENT as of the date set forth in the first paragraph hereof.

                                        "INVESTOR"

                                        VENROCK PARTNERS, L.P.
                                        by its General Partner, Venrock Partners
                                        Management, LLC


                                        VENROCK ASSOCIATES IV, L.P.
                                        by its General Partner, Venrock
                                        Management IV, LLC


                                        VENROCK ENTREPRENEURS FUND IV, L.P.
                                        by its General Partner, VEF Management
                                        IV, LLC


                                        By: /s/ Anders Hove
                                            ------------------------------------
                                        Name: Anders D. Hove
                                        Title: Member
                                        Address: 30 Rockefeller Plaza
                                                 Room 5508
                                                 New York, NY 10112

                      SIGNATURE PAGE TO AMENDMENT NO. 1 TO
                 AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

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     IN WITNESS WHEREOF, the parties hereto have executed this AMENDMENT NO. 1
TO THE RIGHTS AGREEMENT as of the date set forth in the first paragraph hereof.

                                        "INVESTOR"

                                        ARCH VENTURE FUND V, L.P.

                                        By: ARCH Venture Partners V, L.P.
                                            Its general partner

                                        By: ARCH Venture Partners V, L.L.C.
                                            Its general partner


                                        By: /s/ Robert Nelsen
                                            ------------------------------------
                                        Title: Managing Director


                                        ARCH V ENTREPRENEURS FUND, L.P.

                                        By: ARCH Venture Partners V, L.P.
                                            Its general partner

                                        By: ARCH Venture Partners V, L.L.C.
                                            Its general partner


                                        By: /s/ Robert Nelsen
                                            ------------------------------------
                                        Title: Managing Director


                                        HEALTHCARE FOCUS FUND, L.P.

                                        By: ARCH Venture Partners V, L.P.
                                            Its general partner

                                        By: ARCH Venture Partners V, L.L.C.
                                            Its general partner


                                        By: /s/ Robert Nelsen
                                            ------------------------------------
                                        Title: Managing Director

                      SIGNATURE PAGE TO AMENDMENT NO. 1 TO
                 AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

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     IN WITNESS WHEREOF, the parties hereto have executed this AMENDMENT NO. 1
TO THE RIGHTS AGREEMENT as of the date set forth in the first paragraph hereof.

                                        "INVESTOR"

                                        OXFORD BIOSCIENCE PARTNERS IV L.P.

                                        By: OBP Management IV L.P.


                                        By: /s/ Mark P. Carthy
                                            ------------------------------------
                                            Mark P. Carthy - General Partner


                                        MRNA FUND II L.P.

                                        By: OBP Management IV L.P.


                                        By: /s/ Mark P. Carthy
                                            ------------------------------------
                                            Mark P. Carthy - General Partner

                      SIGNATURE PAGE TO AMENDMENT NO. 1 TO
                 AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

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     IN WITNESS WHEREOF, the parties hereto have executed this AMENDMENT NO. 1
TO THE RIGHTS AGREEMENT as of the date set forth in the first paragraph hereof.

                                        "INVESTOR"

                                        FRAZIER HEALTHCARE IV, L.P.
                                        By FHM IV, LP, its general partner
                                        By FHM IV, LLC, its general partner


                                        By: /s/ Patrick Heron
                                            ------------------------------------
                                        Name: Patrick Heron
                                        Its: Authorized Representative


                                        FRAZIER AFFILIATES IV, L.P.
                                        By FHM IV, LP, its general partner
                                        By FHM IV, LLC, its general partner


                                        By: /s/ Patrick Heron
                                            ------------------------------------
                                        Name: Patrick Heron
                                        Its: Authorized Representative


                                        FRAZIER HEALTHCARE III, L.P.
                                        By FHM III, LLC


                                        By: /s/ Robert Overell
                                            ------------------------------------
                                        Name: Robert Overell
                                        Its: Authorized Representative


                                        FRAZIER AFFILIATES III, L.P.
                                        By FHM III, LLC


                                        By: /s/ Robert Overell
                                            ------------------------------------
                                        Name: Robert Overell
                                        Its: Authorized Representative

                      SIGNATURE PAGE TO AMENDMENT NO. 1 TO
                 AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT