Marketing Rights

EXHIBIT 4.9

First Amendment to
Amended and Restated Investor Rights Agreement

     This First Amendment to the Amended and Restated Investor Rights Agreement (the “Amendment”) is made effective as of October 31, 2005, and is entered into by and among SGX Pharmaceuticals, Inc., a Delaware corporation, previously known as Structural GenomiX, Inc. (the “Company”), certain holders of the Company’s Series A Preferred Stock (“Series A Preferred”), and certain holders of the Company’s Series B Preferred Stock (“Series B Preferred”) (which parties are hereinafter collectively referred to as the “Original Parties”).

     Whereas, the Original Parties have previously entered into that certain Amended and Restated Investor Rights Agreement, dated April 21, 2005 (the “Investor Rights Agreement”);

     Whereas, the Company, Silicon Valley Bank (“SVB”) and Oxford Finance Corporation (“Oxford”) have entered into a Loan and Security Agreement dated September 16, 2005 (the “Loan Agreement”); and

     Whereas, pursuant to the Loan Agreement, the Company agreed to issue certain warrants to SVB and Oxford and to solicit the requisite consent of the parties to the Investor Rights Agreement to add SVB and Oxford as parties to the Investor Rights Agreement to provide such parties with those certain incidental, or “Piggyback,” registration rights pursuant to and as set forth therein.

     Now, therefore, in consideration of the foregoing premises and the mutual covenants and conditions herein, the parties hereto hereby agree that:

1.		Capitalized terms not defined herein shall have the meaning ascribed to them in the Investor Rights Agreement.
2.		SVB and Oxford shall become parties to the Investor Rights Agreement and the definition of “Holder” in Section 1 of the Investor Rights Agreement shall include SVB and Oxford; provided, however, that neither SVB nor Oxford (nor any permitted transferee or assignee of SVB or Oxford) shall be deemed a Holder for purposes of Section 2.2 or 2.4 of the Investor Rights Agreement.
3.		The definition of “Registrable Securities” in Section 1.1 of the Investor Rights Agreement shall be replaced in its entirety with the following:

     ““Registrable Securities” means the (a) Common Stock of the Company issued or issuable upon conversion of the Shares; (b) Bridge Converted Common Stock; (c) Common Stock of the Company issued or issuable upon conversion of the Conversion Securities (as those securities are defined in the Convertible Promissory Note issued by the Company to mHoldings Trust (“mHoldings”) dated December 21, 2001 (the “Millennium Note”) (or in the event the Conversion Securities (as those securities are defined in the Millennium Note) consist of the Company’s Common Stock, the Conversion Securities (as those securities are defined in the Millennium Note)); (d) Common Stock of the Company issued or issuable upon conversion of the Warrant Securities (or in the event the Warrant

Securities consist of the Company’s Common Stock, the Warrant Securities), provided, however, that any such shares of Common Stock or Warrant Securities issued upon exercise of the Lender Warrants (or upon conversion of the Warrant Securities issued upon exercise thereof) shall not be deemed Registrable Securities for purposes of Section 2.2 or 2.4 hereof; and (e) 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, such above-described securities. Notwithstanding the foregoing, Registrable Securities shall not include any securities sold by a person to the public either 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.

The definition of “Shares” in Section 1.1 of the Investor Rights Agreement shall be replaced in its entirety with the following:

     ““Shares” shall mean (a) the Series A Stock and Series B Stock now held or hereafter acquired by the Investors listed on Exhibit A hereto and their permitted assigns; (b) the Pre-Series B Conversion Preferred Stock held by the Investors listed on Exhibit A hereto and their permitted assigns; (c) the Company securities issuable upon exercise of the Warrant and the Lenders Warrants (the “Warrant Securities”); and (d) the Conversion Securities (as those securities are defined in the Millennium Note) issued pursuant to the Millennium Note to mHoldings (or its permitted assigns).”

5.

The following definition shall be added to Section 1.1 of the Investor Rights Agreement immediately following the definition of “Initial Offering”:

     ““Lender Warrants” shall mean those certain warrants issued to Silicon Valley Bank and Oxford Finance Corporation (or their respective permitted assigns) pursuant to that certain Loan and Security Agreement dated as of September 16, 2005 by and among the Company, Silicon Valley Bank and Oxford Finance Corporation.”

6.		By executing this Amendment, each of SVB and Oxford agree to be bound by the provisions of the Investor Rights Agreement, as amended by this Amendment (and as may be subsequently amended from time to time), including without limitation the provisions of Section 2.13 thereof.
7.		This Amendment may be executed in any number of counterparts, each of which shall be an original, but all of which together shall constitute one instrument. Except as specifically amended by this Amendment, the terms and conditions of the Investor Rights Agreement shall remain unchanged and in full force and effect. This Amendment shall be governed by and construed in accordance with the laws of the State of California as applied to contracts among California residents entered into and performed entirely within California.

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Company:

SGX Pharmaceuticals, Inc.
By:		/s/ Michael Grey
		Name:		Michael Grey
		Title:		President and Chief Executive Officer

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
ALEXANDRIA REAL ESTATE EQUITIES, L.P.,
a Delaware limited partnership
By:		ARE-QRS CORP.,
		a Maryland corporation, general partner
		By:		/s/ Etsuko Mason
				Etsuko Mason
				Vice President, Treasurer and
				Assistant Secretary

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		Bavp, L.P.
By:		/s/ Louis C. Bock
Print Name:		Louis C. Bock
Title:		Managing Director

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		Caduceus Private Investments, LP
By:		/s/ Eric A. Bittelman
Print Name:		Eric A. Bittelman
Title:		CFO, OrbiMed Capital LLC, General Partner

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Coleman Swenson Hoffman Booth IV L.P.
By:		Its General Partner,
		CSHB Ventures IV L.P.
By:		/s/ Larry H. Coleman   Its: General Partner
Print Name:		Larry H. Coleman
Title:		General Partner

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		Walter T. Dec
By:		/s/ Walter T. Dec
Print Name:		Walter T. Dec
Title:		Sir

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		/s/ Ken Dill Joland Schreurs
By:
Print Name:		Ken Dill Joland Schreurs
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		Frederick Frank
By:		/s/ Frederick Frank
Print Name:		Frederick Frank
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		GC&H Investments
By:		/s/ John L. Cardoza
Print Name:		John L. Cardoza
Title:		Executive Partner

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :
By:		/s/ Wayne A. Hendrickson
Print Name:		Wayne A. Hendrickson
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		C. S. Henney
By:		/s/ Christopher S. Henney
Print Name:
Title:		Chairman

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		James M. Hesbough
By:		/s/ James M. Hesbough
Print Name:
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		/s/ Barry Honig
By:
Print Name:		Barry H. Honig
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Index Venture Management SA
on behalf of
Index Employee Investment Plan
By:		/s/ David Rimer
Print Name:		David Rimer
Title:		Director

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		/s/ Joshua Lederberg
By:
Print Name:
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		Charles E. Mather
By:		/s/ Charles E. Mather
Print Name:		Charles E. Mather
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		K. Flynn McDonald
By:		/s/ K. Flynn McDonald
Print Name:		K. Flynn McDonald
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :
By:		/s/ Stelios Papadopoulos
Print Name:		Stelios Papadopoulos
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		Prospect Venture Partners, L.P.
By:		/s/ Alex Barkas
Print Name:		Alex Barkas
Title:		Managing Member, Prospect
		Management Co. LLC, general
		partner of Prospect Venture
		Partners, L.P.

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		Peter Reikes
By:		/s/ Peter Reikes
Print Name:		Peter Reikes
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		George E. Rossmann
By:		/s/ George E. Rossmann
Print Name:
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		Rutter Investments, LP
By:		/s/ William J. Rutter
Print Name:		William J. Rutter
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		William J. Rutter
By:		/s/ William J. Rutter
Print Name:		William J. Rutter
Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name:		William J. Rutter Revocable Trust
By:		/s/ William J. Rutter

Print Name:		William J. Rutter

Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		/s/ Andrej Sali

By:

Print Name:

Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :

By:		/s/ John P. Schmidt

Print Name:		John P. Schmidt

Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		Scinet Development & Holdings, Inc.

By:		/s/ John E. Lamier

Print Name:		John E. Lamier

Title:		President

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		SGC Partners I LLC

By:		/s/ Christopher A. White

Print Name:		Christopher A. White

Title:		Director

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		Spring Creek Partners

By:		/s/ Duane R. Bach

Print Name:		Duane R. Bach

Title:		GP

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
DLJ Capital Corporation
		/s/ Vijay K. Lathi
		By:		Vijay K. Lathi
		Its:		Attorney in Fact
DLJ ESC II, L.P.
		By:		DLJ LBO Plans Management Corporation
		Its:		General Partner
		/s/ Vijay K. Lathi
		By:		Vijay K. Lathi
		Its:		Attorney in Fact
Sprout Capital VIII, L.P.
		By:		DLJ Capital Corporation
		Its:		Managing General Partner
		/s/ Vijay K. Lathi
		By:		Vijay K. Lathi
		Its:		Attorney in Fact
Sprout Plan Investors, L.P.
		By:		DLJ LBO Plans Management Corporation II
		Its:		General Partner
		/s/ Vijay K. Lathi
		By:		Vijay K. Lathi
		Its:		Attorney in Fact

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

Sprout Venture Capital, L.P.
		By:		DLJ Capital Corporation
		Its:		General Partner
		/s/ Vijay K. Lathi
		By:		Vijay K. Lathi
		Its:		Attorney in Fact

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
VECTOR LATER-STAGE EQUITY FUND II, L.P.
By:		VECTOR FUND MANAGEMENT II, L.L.C.
Its:		General Partner
By:		/s/ Barclay A. Phillips
		Barclay A. Phillips
Its:		Managing Director

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
VECTOR LATER-STAGE EQUITY FUND I, (QP), L.P.
By:		VECTOR FUND MANAGEMENT II, L.L.C.
Its:		General Partner
By:		/s/ Barclay A. Phillips
		Barclay A. Phillips
Its:		Managing Director

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Name :		Vulcan Ventures Inc.

By:		/s/ W. Lance Conn

Print Name:		W. Lance Conn

Title:		EVP, Investment Management

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Silicon Valley Bank
Signature:		/s/ Susan L. Worsham

Print Name:		Susan L. Worsham

Title: Deal Team Leader

Oxford Finance Corporation
Signature:

Print Name:

Title:

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this First Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Silicon Valley Bank
Signature:

Print Name:

Title:

Oxford Finance Corporation
Signature:		/s/ M.J. Altenburger

Print Name: Michael J. Altenburger

Title: Chief Financial Officer

[Signature Page to First Amendment to Amended and Restated Investor Rights Agreement]

Second Amendment to
Amended and Restated Investor Rights Agreement

     This Second Amendment to the Amended and Restated Investor Rights Agreement (the “Amendment”), is made effective as of March 27, 2006, and is entered into by and among SGX Pharmaceuticals, Inc., a Delaware corporation, previously known as Structural GenomiX, Inc. (the “Company”), certain holders of the Company’s Common Stock or warrants to purchase shares of the Company’s Common Stock (which parties are hereinafter collectively referred to as the “Original Parties”), and Novartis Pharma AG (“Novartis”).

     Whereas, the Company and the Original Parties have previously entered into that certain Amended and Restated Investor Rights Agreement, dated April 21, 2005, as amended (the “Investor Rights Agreement”);

     Whereas, upon the closing of the Company’s initial public offering, Sections 3 and 4 of the Investor Rights Agreement terminated and are of no further force and effect;

     Whereas, the Company and Novartis have entered into a Stock Purchase Agreement of even date herewith (the “Purchase Agreement”) and the Company and Novartis Institutes for Biomedical Research, Inc. have entered into a License and Collaboration Agreement of even date herewith; and

     Whereas, pursuant to the Purchase Agreement, the Company has agreed to sell and issue $5,000,000 of the Company’s Common Stock to Novartis and to add Novartis as a party to the Investor Rights Agreement to provide Novartis certain registration rights pursuant to and as set forth therein.

     Now, therefore, in consideration of the foregoing premises and the mutual covenants and conditions herein, the parties hereto hereby agree that:

1.

Capitalized terms not defined herein shall have the meaning ascribed to them in the Investor Rights Agreement.

2.

The Company and the Original Parties holding the requisite 66-2/3% of the Registrable Securities hereby agree to amend the Investor Rights Agreement as set forth in this Amendment, and such Original Parties further hereby consent to and waive their rights under Section 2.12 of the Investor Rights Agreement and under any other applicable provision of the Investor Rights Agreement with respect to the registration rights granted to Novartis as set forth herein.

3.

Novartis shall become a party to the Investor Rights Agreement and the definition of “Holder” in Section 1 of the Investor Rights Agreement shall include Novartis, for all purposes under the Investor Rights Agreement.

4.

The definition of “Registrable Securities” in Section 1.1 of the Investor Rights Agreement shall be replaced in its entirety with the following:

     ““Registrable Securities” means the (a) Common Stock of the Company issued or issuable upon conversion of the Shares; (b) Bridge Converted Common Stock; (c) Common Stock of the Company issued or issuable upon conversion of the

Conversion Securities (as those securities are defined in the Convertible Promissory Note issued by the Company to mHoldings Trust (“mHoldings”) dated December 21, 2001 (the “Millennium Note”) (or in the event the Conversion Securities (as those securities are defined in the Millennium Note) consist of the Company’s Common Stock, the Conversion Securities (as those securities are defined in the Millennium Note)); (d) Common Stock of the Company issued or issuable upon conversion of the Warrant Securities (or in the event the Warrant Securities consist of the Company’s Common Stock, the Warrant Securities), provided, however, that any such shares of Common Stock or Warrant Securities issued upon exercise of the Lender Warrants (or upon conversion of the Warrant Securities issued upon exercise thereof) shall not be deemed Registrable Securities for purposes of Section 2.2 or 2.4 hereof; (e) the 637,755 shares of Common Stock of the Company (the “Novartis Shares”) issued to Novartis Pharma AG (“Novartis”); and (f) 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, such above-described securities. Notwithstanding the foregoing, Registrable Securities shall not include any securities sold by a person to the public either 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.”

5.

The word and number “ninety (90)” set forth in Section 2.4(c) of the Investor Rights Agreement are hereby deleted in their entirety and replaced with the word and number “sixty (60)”.

6.

Section 2.6(a) of the Investor Rights Agreement is hereby deleted and replaced in its entirety with the following:

         “(a) Prepare and file with the SEC a registration statement with respect to such Registrable Securities and use its best efforts to cause such registration statement to become effective, and, upon the request of the Holders of a majority of the Registrable Securities registered thereunder, keep such registration statement effective for up to one hundred twenty (120) days (or, in the case of a Registration Statement on Form S-3, one hundred eighty (180) days) or, if earlier, until the Holder or Holders have completed the distribution related thereto.”

7.

A new sentence is hereby added before the last sentence of Section 2.11 of the Investor Rights Agreement which reads as follows:

         “Notwithstanding the foregoing, to the extent any amendment or waiver pursuant to this Section 2.11 would adversely affect the rights of Novartis, such amendment or waiver shall not be effective against Novartis without the prior written consent of Novartis; provided, however, that a waiver of any provision of Section 2.3 (Piggyback Registrations) shall not require the prior written consent of Novartis unless such waiver would adversely affect the rights of Novartis in a disproportionate manner than the rights of the other Holders hereunder.”

8.

A new subsection 5.6(e) of the Investor Rights Agreement is hereby added which reads as follows:

     “(e) To the extent any amendment or waiver of this Agreement would adversely affect the rights of Novartis, such amendment or waiver shall not be effective against Novartis without the prior written consent of Novartis; provided, however, that a waiver of any provision of Section 2.3 (Piggyback Registrations) shall not require the prior written consent of Novartis unless such waiver would adversely affect the rights of Novartis in a disproportionate manner than the rights of the other Holders hereunder.”

9.		By executing this Amendment, Novartis agrees to be bound by the provisions of the Investor Rights Agreement, as amended by this Amendment (and as may be subsequently amended from time to time, subject to Section 5.6(e)), including without limitation the provisions of Section 2.13 thereof.
10.		Notwithstanding Section 2.7 of the Investor Rights Agreement, all registration rights granted to Novartis under Section 2 of the Investor Rights Agreement shall terminate and be of no further force and effect at the earlier of (a) five (5) years after the date of the Company’s Initial Offering or (b) after the Company’s Initial Offering, at such time as (i) Novartis is entitled to sell all of its shares pursuant to SEC Rule 144(k) and (ii) Novartis owns less than one percent (1%) of the Registrable Securities.

11.

The Company hereby acknowledges that, as a result of the 1-for-2 reverse stock split of the Company’s Common Stock effected in January 2005, the number of shares of Registrable Securities set forth in Section 2.10 of the Investor Rights Agreement is equal to 6,322 shares of Registrable Securities as of the date hereof.

12.

Notwithstanding Section 5.8 of the Investor Rights Agreement, all notices to Novartis required or permitted hereunder or under the Investor Rights Agreement shall be in writing and shall be deemed effectively given: (a) upon personal delivery to Novartis; (b) when sent by confirmed electronic mail or facsimile if sent during normal business hours of the recipient; if not, then on the next business day; (c) five (5) days after having been sent by registered or certified mail, return receipt requested, postage prepaid; or (d) three (3) days after deposit with a nationally recognized overnight courier, specifying next or two-day delivery, with written verification of receipt. All communications to Novartis shall be sent to the address as set forth on the signature pages hereof or at such other address as Novartis may designate by ten (10) days advance written notice to the Company.

13.

This Amendment may be executed in any number of counterparts, each of which shall be an original, but all of which together shall constitute one instrument. Except as specifically amended by this Amendment, the terms and conditions of the Investor Rights Agreement shall remain unchanged and in full force and effect. This Amendment shall be governed by and construed in accordance with the laws of the State of California as applied to contracts among California residents entered into and performed entirely within California.

     In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Company:
SGX Pharmaceuticals, Inc.
By:		/s/ Michael Grey
Name:		M G Grey
Title:		President and CEO

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]

In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Novartis Pharma AG
Signature: /s/ Joseph E. Mamie		Signature: /s/ Dr. Matthias S. Runge
Print Name: Joseph E. Mamie		Print Name: Dr. Matthias S. Runge
Title: Head Operational Treasury		Title: Head Legal Pharma Ophthalmics &
		Oncology Region Europe

Address:

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]

     In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:

Entity Name: Millennium Pharmaceuticals, Inc.

By: /s/ Joel Goldberg

Print Name: Joel Goldberg

Title: Assoc. General Counsel

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]

In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Entity Name:		ATLAS VENTURE FUND III, L.P.
		ATLAS VENTURE ENTREPRENEURS’ FUND III, L.P.
		By:		Atlas Venture Associates III, L.P.
				its general partner
		By:		Atlas Venture Associates III, L.P.
				its general partner
By: /s/ Axel Bicham
Print Name: Axel Bicham
Title:
		ATLAS VENTURE FUND IV, L.P.
		ATLAS VENTURE PARALLEL FUND IV – A, C.V.
		ATLAS VENTURE ENTREPRENEURS’ FUND IV, L.P.
		By:		Atlas Venture Associates IV, L.P.
				its general partner
		By:		Atlas Venture Associates IV, Inc.
				its general partner

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]

In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:

Entity Name: BAVP, L.P.

By: /s/ Louis C. Bock

Print Name: Louis C. Bock

Title: Managing Director

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]

In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Entity Name: Sprout Capital VIII, L.P.
SPROUT CAPITAL VIII, L.P.
By:		DLJ Capital Corporation
Its:		Managing General Partner
By:		/s/ Vijay K. Lathi
		Vijay K. Lathi
		Attorney in Fact

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]

In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Entity Name: Sprout Venture Capital, L.P.
SPROUT VENTURE CAPITAL, L.P.
By:		DLJ Capital Corporation
Its:		General Partner
By:		/s/ Vijay K. Lathi
		Vijay K. Lathi
		Attorney in Fact

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]

In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Entity Name: Sprout Plan Investors, L.P.
SPROUT PLAN INVESTORS, L.P.
By:		DLJ LBO Plans Management Corporation II
Its:		General Partner
By:		/s/ Vijay K. Lathi
		Vijay K. Lathi
		Attorney in Fact

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]

In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Entity Name : DLJ ESC II, L.P.
DLJ ESC II, L.P.
By:		DLJ LBO Plans Management Corporation
Its:		General Partner
By:		/s/ Vijay K. Lathi
		Vijay K. Lathi
		Attorney in Fact

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]

In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Entity Name : DLJ Capital Corporation
DLJ CAPITAL CORPORATION
By:		/s/ Vijay K. Lathi
		Vijay K. Lathi
		Attorney in Fact

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]

In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:
Entity Name :

By: /s/ Alex Barkas

Print Name: Alex Barkas

Title: Managing Member of the General Partner of

Prospect Venture Partners

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]

In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:

Entity Name : Index venture Associates I Limited As General Partner of

Index Ventures I (jersey) L.P.
Index Ventures I (Delaware) L.P.
Index Ventures I Parallel Entrepreneur Fund (Jersey) L.P.

Index Ventures I (SLP) Limited As General Partner of

Index Ventures I GMBH & co KG

By: /s/ Kate Wilson                              

Print Name: Kate Wilson

Title: Director

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]

In Witness Whereof, the parties hereto have executed this Second Amendment to the Amended and Restated Investor Rights Agreement effective as of the day and year first set forth above.

Investors/Holders:

Entity Name : Index Venture Management SA               

By: /s/ Neil Rimer/Nunu Tadesse                                          

Print Name: Neil Rimer/Nunu Tadesse

Title: Directors

[Signature Page to Second Amendment to Amended and Restated Investor Rights Agreement]