EX-4.3



 Exhibit 4.3 

AMENDMENT NO. 2 
 TO

 INVESTORS’ RIGHTS AGREEMENT 

THIS AMENDMENT NO. 2 TO THE INVESTORS’ RIGHTS AGREEMENT (this “Agreement”) is made as of April 25, 2016 by and
among Intellia Therapeutics, Inc., a Delaware corporation (the “Company”), and parties listed on the signature pages hereto. Capitalized terms used but not defined herein shall have the meanings ascribed thereto in the
Investors’ Rights Agreement, dated as of August 20, 2015, as amended on April 11, 2016 (as amended or otherwise modified from time to time, the “Investors’ Rights Agreement”), by and among the Company and the
other parties thereto. 
 WITNESSETH 

WHEREAS, the Company and the Investors are parties to the Investors’ Rights Agreement; 

WHEREAS, pursuant to Subsection 6.6 of the Investors’ Rights Agreement, the Investors’ Rights Agreement may be
amended by the written consent of (a) the Company and (b) stockholders then holding shares of Preferred Stock representing at least sixty-seven percent (67%) of the combined voting power of the Preferred Stock (calculated on an
as-converted to Common Stock basis) (the “Requisite Holders”); 
 WHEREAS, the undersigned represent the Requisite
Holders necessary to amend the Investors’ Rights Agreement; and 
 WHEREAS, the Company and the Requisite Holders desire to
amend certain provisions of the Investors’ Rights Agreement. 
 NOW, THEREFORE, in consideration of the mutual promises and
covenants contained in this Agreement, the parties hereto, intending to be legally bound, agree as follows: 
 1. Amendment of Subsection
1.24 of the Investors’ Rights Agreement . Pursuant to Subsection 6.6 of the Investors’ Rights Agreement, Subsection 1.24 of the Investors’ Rights Agreement is hereby amended and restated in its entirety to read
as follows: 
 “1.24 “Registrable Securities” means (i) the Common Stock issuable or issued upon conversion
of the Preferred Stock; (ii) any Common Stock issued as (or issuable upon the conversion or exercise of any warrant, right, or other security that is issued as) a dividend or other distribution with respect to, or in exchange for or in
replacement of, the shares referenced in clause (i) above; and (iii) any Common Stock held by Regeneron Pharmaceuticals, Inc. (“Regeneron”) or Novartis (as defined below); excluding in all cases, however, any Registrable
Securities sold by a Person in a transaction in which the applicable rights under this Agreement are not assigned pursuant to Subsection 6.1, and excluding for purposes of Section 2 any shares for which registration rights have
terminated pursuant to Subsection 2.13 of this Agreement.” 







 2. Investors’ Rights Agreement. By execution of this Agreement, the Company
and the Requisite Holders executing the same, holding in the aggregate a sufficient number of shares of stock to amend the Investors’ Rights Agreement in accordance with Subsection 6.6 thereof, hereby agree that the
provisions set forth in the Investors’ Rights Agreement are hereby amended as set forth herein. The Investors’ Rights Agreement, as amended by this Agreement, contains the entire agreement among the parties with respect to the subject
matter thereof and hereof and shall be read and construed together as a single agreement. Except to the extent amended hereby, all of the terms, provisions and conditions of the Investors’ Rights Agreement are hereby ratified and confirmed and
shall remain in full force and effect as of the date specified therein. 
 3. Counterparts. This Agreement may be executed in
two or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. Counterparts may be delivered via facsimile, electronic mail (including .pdf) or other transmission method
and any counterpart so delivered shall be deemed to have been duly and validly delivered and be valid and effective for all purposes. 

4. Titles and Subtitles. The titles and subtitles used in this Agreement are used for convenience only and are not to be considered in
construing or interpreting this Agreement. 
 5. Severability. The invalidity or unenforceability of any provision hereof shall in no
way affect the validity or enforceability of any other provision. 
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 IN WITNESS WHEREOF, the parties have executed this Amendment No. 2 to Investors’ Rights
Agreement as of the date first written above. 
  

			
	THE COMPANY:
	
	INTELLIA THERAPEUTICS, INC.
		
	By:	 	 /s/ Nessan Bermingham

	Name:	 	Nessan Bermingham
	Title:	 	CEO and President


 [Amendment No. 2 to Investors’ Rights Agreement – Intellia Therapeutics, Inc.] 







 IN WITNESS WHEREOF, the parties have executed this Amendment No. 2 to Investors’ Rights
Agreement as of the date first written above. 
  

			
	INVESTORS:
	
	ATLAS VENTURES FUND IX, L.P.
	
	By: Atlas Venture Associates, IX, L.P., Its General Partner
	
	By: Atlas Venture Associates, IX, LLC, Its General Partner
		
	By:	 	 /s/ Frank Castellucci

	Name:	 	Frank Castellucci
	Title:	 	General Counsel


 [Amendment No. 2 to Investors’ Rights Agreement – Intellia Therapeutics, Inc.] 







 IN WITNESS WHEREOF, the parties have executed this Amendment No. 2 to Investors’ Rights
Agreement as of the date first written above. 
  

			
	INVESTORS:
	
	NOVARTIS INSTITUTES FOR
	BIOMEDICAL RESEARCH, INC.
		
	By:	 	 /s/ Scott A. Brown

	Name: Scott A. Brown
	Title: VP, General Counsel


 [Amendment No. 2 to Investors’ Rights Agreement – Intellia Therapeutics, Inc.] 







 IN WITNESS WHEREOF, the parties have executed this Amendment No. 2 to Investors’ Rights
Agreement as of the date first written above. 
  

			
	INVESTORS:
	
	CARIBOU THERAPEUTICS HOLDCO, LLC
		
	By:	 	Caribou Biosciences, Inc.
		 	Its Manager
		
	By:	 	 /s/ Rachel E. Haurwitz

	Name: Rachel E. Haurwitz
	Title: President & CEO


 [Amendment No. 2 to Investors’ Rights Agreement – Intellia Therapeutics, Inc.] 







 IN WITNESS WHEREOF, the parties have executed this Amendment No. 2 to Investors’ Rights
Agreement as of the date first written above. 
  

					
	INVESTORS:
	
	ORBIMED PRIVATE INVESTMENTS V, L.P.
		
	By:	 	OrbiMed Capital GP V LLC,
		 	its General Partner
			
		 	By:	 	OrbiMed Advisors LLC,
		 		 	its Managing Member
		
	By:	 	 /s/ Carl Gordon

	Name: Carl Gordon
	Its: Member
	
	ORBIMED GLOBAL HEALTHCARE MASTER FUND, L.P.
		
	By:	 	OrbiMed Global Healthcare GP LLC,
		 	its General Partner
			
		 	By:	 	OrbiMed Advisors LLC,
		 		 	its Managing Member
		
	By:	 	 /s/ Carl Gordon

	Name: Carl Gordon
	Title: Member


 [Amendment No. 2 to Investors’ Rights Agreement – Intellia Therapeutics, Inc.]