GENOPTIX, INC. FIRST AMENDMENT TO AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

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Exhibit 4.10

GENOPTIX, INC.

FIRST AMENDMENT TO
AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

This FIRST AMENDMENT TO AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT (this "Amendment") by and among GENOPTIX, INC., a Delaware corporation (the "Company") and the investors listed on the signature pages hereof (each, an "Investor", and together, the "Investors") dated as of May 9, 2005 (the "Investor Rights Agreement") is entered into as of August 3, 2005 by and among the Company and the Investors. Capitalized terms used herein which are not defined herein shall have the definition ascribed to them in the Investor Rights Agreement.

RECITALS

WHEREAS, the Company and the Investors have previously entered into the Investor Rights Agreement, pursuant to which the Investors possess certain registration, right of first refusal, information and other investor rights;

WHEREAS, the Company is entering into a Follow-On Series 1-D Preferred Stock Purchase Agreement with the purchasers named therein (the "Purchasers" and each individually, a "Purchaser") of even date herewith (the "Follow-On Purchase Agreement"), pursuant to which the Purchasers will purchase up to an aggregate of 12,618,296 shares of the Company's Series 1-D Preferred Stock at the Closing (as defined in the Follow-On Purchase Agreement);

WHEREAS, in connection with the Follow-On Purchase Agreement, the Company and Investors desire to amend the Investor Rights Agreement so to include the Purchasers as "Investors" therein and to make the other changes described herein;

WHEREAS, the Purchasers desire to become parties to the Investor Rights Agreement as amended by this Amendment;

WHEREAS, Section 5.6 of the Investor Rights Agreement provides that the Investor Rights Agreement may be amended with the written consent of the Company and the holders of a majority of the Registrable Securities (as defined in the Investor Rights Agreement); and

WHEREAS, the undersigned Investors are the holders of at least a majority of all of the Registrable Securities.

AGREEMENT

NOW, THEREFORE, in consideration of the foregoing and the promises and covenants contained herein and in the Investor Rights Agreement, and for other good and valuable consideration, the receipt of which is hereby acknowledged, the parties hereto agree as follows:

1. Amendments.

(a) Section 2.11 of the Investor Rights Agreement is hereby deleted and replaced and superseded in its entirety with the following:

"2.11 Amendment of Registration Rights. Any provision of this Section 2 may be amended and the observance thereof may be waived (either generally or in a particular instance and either retroactively or prospectively), only with the written consent of the Company and the Holders of at least fifty-five percent (55%) of the Registrable Securities then outstanding. Any amendment or waiver effected in accordance with this Section 2.11

shall be binding upon each Holder and the Company. By acceptance of any benefits under this Section 2, Holders of Registrable Securities hereby agree to be bound by the provisions hereunder."

(b) Section 2.12 of the Investor Rights Agreement is hereby deleted and replaced and superseded in its entirety with the following:

"2.12 Limitation on Subsequent Registration Rights. Other than as provided in Section 5.11, after the date of this Agreement, the Company shall not, without the prior written consent of the Holders of at least fifty-five percent (55%) of the Registrable Securities then outstanding, enter into any agreement with any holder or prospective holder of any securities of the Company that would grant such holder registration rights pari pasu with or senior to those granted to the Holders hereunder, other than the right to a Special Registration Statement."

(c) Section 5.6 of the Investor Rights Agreement is hereby deleted and replaced and superseded in its entirety with the following:

"5.6 Amendment and Waiver.

(a) Except as otherwise expressly provided, this Agreement may be amended or modified only upon the written consent of the Company and the holders of at least fifty-five percent (55%) of the Registrable Securities.

(b) Except as otherwise expressly provided, the obligations of the Company and the rights of the Holders under this Agreement may be waived only with the written consent of the holders of at least fifty-five percent (55%) of the Registrable Securities.

(c) For the purposes of determining the number of Holder or Investors entitled to vote or exercise any rights hereunder, the Company shall be entitled to rely solely on the list of record holders of its stock as maintained by or on behalf of the Company."

(d) Section 5.11 of the Investor Rights Agreement is hereby deleted and replaced and superseded in its entirety with the following:

"5.11 Additional Investors. Notwithstanding anything to the contrary contained herein, if the Company shall issue Equity Securities in accordance with Section 4.5(c), (f), (h) or (i) of this Agreement, any purchaser of such Equity Securities may become a party to this Agreement by executing and delivering an additional counterpart signature page to this Agreement and shall be deemed an "Investor," a "Holder" and a party hereunder."

(e) Exhibit A of the Investor Rights Agreement is hereby deleted and replaced and superseded in its entirety with Exhibit A attached hereto.

2. Waiver of Rights of First Refusal. The rights set forth in Section 4.1 of the Investor Rights Agreement to purchase shares of Equity Securities (as defined in the Investor Rights Agreement) of the Company are hereby waived, for and on behalf of all Major Investors (as defined in the Investor Rights Agreement) with respect to the issuance of 12,618,296 shares of Series 1-D Preferred at the Closing pursuant to the Follow-On Purchase Agreement.

3. Counterpart Signature Page. By executing this Amendment, each of the Purchasers agrees to be bound by the provisions of the Investor Rights Agreement, as amended by this Amendment, and to be deemed "Investors," "Holders" and parties hereunder and thereunder.

4. Effect of Amendment. Except as expressly modified by this Amendment, the Investor Rights Agreement shall remain unmodified and in full force and effect.

5. Governing Law. This Amendment shall be governed by and construed in accordance with the laws of the State of Delaware as applied to agreements among Delaware residents entered into and to be performed entirely within the State of Delaware.

6. Counterparts. This Amendment may be executed in any number of counterparts and signatures delivered by facsimile, each of which shall be deemed an original, but all of which together shall constitute one instrument.

[REMAINDER OF THIS PAGE INTENTIONALLY LEFT BLANK]

IN WITNESS WHEREOF, the parties have executed this FIRST AMENDMENT TO AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT as of the date set forth above.

COMPANY:		INVESTORS:
GENOPTIX, INC.		CHICAGO GROWTH PARTNERS VIII, L.P.
By:	/s/ ▇▇▇▇ ▇. NOVA ▇▇▇▇ ▇. Nova, Ph.D.	By: Its:	Chicago Growth Management VIII, L.P. General Partner
	President, Chief Executive Officer &	By:	Chicago Growth Management, L.L.C.
	Co-Founder	Its:	General Partner
Address:	▇▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇	By:	/s/ ▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇▇▇▇▇▇▇
	▇▇▇ ▇▇▇▇▇, ▇▇ ▇▇▇▇▇	Title:	Managing Director
		▇▇▇▇▇▇▇ ▇▇▇▇▇ CAPITAL PARTNERS VII QP, L.P.
		By:	▇▇▇▇▇▇▇ ▇▇▇▇▇ Capital Management VII, L.P.
		Its:	General Partner
		By:	▇▇▇▇▇▇▇ ▇▇▇▇▇ Capital Management VII, L.L.C.
		Its:	General Partner
		By:	/s/ ▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇▇▇▇▇▇▇
		Title:	Managing Director
		▇▇▇▇▇▇▇ ▇▇▇▇▇ CAPITAL PARTNERS VII, L.P.
		By:	▇▇▇▇▇▇▇ ▇▇▇▇▇ Capital Management VII, L.P.
		Its:	General Partner
		By:	▇▇▇▇▇▇▇ ▇▇▇▇▇ Capital Management VII, L.L.C.
		Its:	General Partner
		By:	/s/ ▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇▇▇▇▇▇▇
		Title:	Managing Director
		ALLIANCE TECHNOLOGY VENTURES III, L.P.
		By:	ATV III Partners, LLC
		Its:	General Partner
		By:	/s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇
		Name:	▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇
		Title:	General Partner

[SIGNATURE PAGE TO FIRST AMENDMENT TO
AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT]

ATV III AFFILIATES FUND, L.P.
	By:	ATV III Partners, LLC
	Its:	General Partner
By:	/s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇
Name:	▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇
Title:	General Partner
ENTERPRISE PARTNERS V, L.P.
	By:	Enterprise Management Partners V, LLC
	Its:	General Partner
By:	/s/ ▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇
Name:	▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇, M.D.
Title:	Managing Director
▇▇▇▇▇▇-▇▇▇▇▇▇▇▇▇ CAPITAL FOCUS II, L.P.
	By:	▇▇▇▇▇▇-▇▇▇▇▇▇▇▇▇ Partners II, L.L.C.
	Its:	General Partner
By:	/s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇
	▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇, Principal
TD JAVELIN CAPITAL FUND II, L.P.
	By:	TD II Regional Partners, Inc.
	Its:	General Partner
By:	/s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇
	▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇, Vice President
TD LIGHTHOUSE CAPITAL FUND, L.P.
	By:	TD II Regional Partners, Inc.
	Its:	General Partner
By:	/s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇
	▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇, Vice President

[SIGNATURE PAGE TO FIRST AMENDMENT TO
AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT]

		EXCELSIOR VENTURE PARTNERS III, LLC
		By:	/s/ ▇▇▇ ▇. ▇▇▇▇▇▇▇▇
		Name:	▇▇▇ ▇. ▇▇▇▇▇▇▇▇
		Title:	Vice President
		LOTUS BIOSCIENCE INVESTMENT HOLDINGS, LTD.
		By:	/s/ ▇▇▇▇ ▇▇▇▇▇ ▇▇▇ /s/ ▇▇▇▇ ▇▇▇ ▇▇▇
		Name:	▇▇▇▇ ▇▇▇▇▇ ▇▇▇ ▇▇▇▇ ▇▇▇ ▇▇▇
		Title:	Directors
		GC&H INVESTMENTS
		By:	/s/ ▇▇▇▇ ▇. ▇▇▇▇▇▇▇
		Name:	▇▇▇▇ ▇. ▇▇▇▇▇▇▇
		Title:	Managing Member
		▇▇▇▇ ▇▇▇▇▇▇
		/s/ ▇▇▇▇ ▇▇▇▇▇▇
		▇▇▇▇▇ FAMILY TRUST DATED 10/12/81
		By:	/s/ ▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇ ▇▇▇▇▇ Trustee
		▇▇▇▇▇▇ & ▇▇▇▇ ▇▇▇▇▇ FAMILY L.P.
		By:	/s/ ▇▇▇▇▇▇ ▇. ▇▇▇▇▇ ▇▇▇▇▇▇ ▇. ▇▇▇▇▇ General Partner

[SIGNATURE PAGE TO FIRST AMENDMENT TO
AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT]

		▇▇▇▇▇▇ FAMILY TRUST
		By:	/s/ ▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇, ▇▇.
		Name:	▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇, ▇▇.
		Title:	Trustee

		▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇
		/s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇

		▇▇▇▇▇▇▇ VENTURES
		By:

		Name:

		Title:

		COMERICA INCORPORATED
		By:	/s/ ▇▇▇ ▇. ▇▇▇▇▇▇▇
		Name:	▇▇▇ ▇. ▇▇▇▇▇▇▇
		Title:	Vice President

[SIGNATURE PAGE TO FIRST AMENDMENT TO
AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT]

EXHIBIT A

SCHEDULE OF INVESTORS

NAME AND ADDRESS		SERIES 1-A PREFERRED	SERIES 1-B PREFERRED	SERIES 1-C PREFERRED	SERIES 1-D PREFERRED
1.	ENTERPRISE PARTNERS V, L.P. 2223 ▇▇▇▇▇▇▇ ▇▇ ▇▇ ▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇ ▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇, M.D.	3,759,398	6,737,746	2,796,072	3,281,923
2.	ALLIANCE TECHNOLOGY VENTURES III, L.P. ▇▇▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇ ▇▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇▇▇▇ ▇▇▇▇▇	3,684,211	3,851,743	2,025,750	2,377,748
3.	ATV III AFFILIATES FUND, L.P. ▇▇▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇ ▇▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇▇▇▇ ▇▇▇▇▇	75,188	78,606	22,531	26,446
4.	▇▇▇▇▇▇-▇▇▇▇▇▇▇▇▇ CAPITAL FOCUS II, L.P. c/o ▇▇▇▇▇▇-▇▇▇▇▇▇▇▇▇ & Co., Inc. Two ▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇	563,910	336,886	239,942	281,635
5.	TD JAVELIN CAPITAL FUND II, L.P. c/o ▇▇▇▇▇▇-▇▇▇▇▇▇▇▇▇ & Co., Inc. Two ▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇	563,910	561,478	299,766	351,854
6.	TD LIGHTHOUSE CAPITAL FUND, L.P. c/o ▇▇▇▇▇▇-▇▇▇▇▇▇▇▇▇ & Co., Inc. Two ▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇	563,910	870,290	382,021	448,402
7.	LOTUS BIOSCIENCE INVESTMENT HOLDINGS, LTD. ▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇ ▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇ ▇▇▇▇ Attn: ▇▇▇▇▇▇▇ ▇▇▇▇/▇▇▇▇ ▇▇▇▇▇	375,940	393,033	203,400	238,743
8.	EXCELSIOR VENTURE PARTNERS III, LLC c/o U.S. Trust of CT ▇▇▇ ▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇, ▇▇▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇▇ ▇. ▇▇▇▇	942,481	1,403,696	620,580	728,413
9.	▇▇▇▇▇ FAMILY TRUST DATED 10/12/81 ▇▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇ ▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇ ▇▇▇▇▇	24,000	47,000	20,000	23,475
10.	▇▇▇▇▇▇ AND ▇▇▇▇ ▇▇▇▇▇ FAMILY LP ▇▇▇▇ ▇▇ ▇▇▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇ ▇▇ ▇▇▇▇▇, ▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇▇▇ ▇. ▇▇▇▇▇	37,532	39,130	20,278	23,802

A-1

11.	▇▇▇▇▇▇ FAMILY TRUST ▇▇ ▇▇▇ ▇▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇ ▇▇, ▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇ ▇▇.	18,797		29,741		27,995	32,859
12.	GC&H INVESTMENTS LLC ▇▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇ ▇▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇ ▇▇▇▇▇▇▇	75,188		78,388		40,622	47,681
13.	▇▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇	16,918		25,196		11,140	13,076
14.	COMERICA INCORPORATED Attn: Warrant Administrator ▇▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇^▇▇ ▇▇▇▇▇, ▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇	12,000	(1)	16,798	(2)	0	276,025	(3)
15.	▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇ ▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇▇ ▇▇▇▇▇	0		12,262		3,244	3,808
16.	HARBOUR VENTURES ▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇	0		11,199		5,599	6,572
17.	CHICAGO GROWTH PARTNERS VIII, L.P. ▇▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇▇▇▇▇	0		0		0	6,309,148
18.	▇▇▇▇▇▇▇ ▇▇▇▇▇ CAPITAL PARTNERS VII QP, L.P. ▇▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇▇▇▇▇	0		0		0	6,075,018
19.	▇▇▇▇▇▇▇ ▇▇▇▇▇ CAPITAL PARTNERS VII, L.P. ▇▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ Attn: ▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇▇▇▇▇	0		0		0	234,130
TOTALS:		10,701,383		14,476,394		6,718,940	20,504,733

(1): Represents shares issuable upon exercise of that certain Warrant dated November 26, 2002, originally issued to purchase 12,000 shares of Series B Preferred Stock that was amended in connection with the Series B-2 Preferred Stock financing to become a warrant to purchase 12,000 shares of Series B-1 Preferred, and further amended in connection with the Series 1-C Preferred financing to become a warrant to purchase 12,000 shares of Series 1-A Preferred. Such shares are not included in the "Totals" set forth below.
(2): Represents shares issuable upon exercise of that certain Warrant dated November 26, 2002 to purchase 16,798 shares of Series B-2 Preferred that was amended in connection with the Series 1-C Preferred financing to become a warrant exercisable for 16,798 shares of Series 1-B Preferred. Such shares are not included in the "Totals" set forth below.
(3): Represents shares issuable upon exercise of that certain Warrant to purchase 276,025 shares of Series 1-D Preferred issued to Comerica Bank in connection with the Debt Financing. Such shares are not included in the "Totals" set forth below.

A-2

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Exhibit 4.10

EXHIBIT A SCHEDULE OF INVESTORS

GENOPTIX, INC. FIRST AMENDMENT TO AMENDED AND RESTATED INVESTOR RIGHTS AGREEMENT

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