Amendment Number Two to the Founding Investor Rights Agreement



 Exhibit 10.15
 AMENDMENT NUMBER TWO 
 TO THE 

FOUNDING INVESTOR RIGHTS AGREEMENT 
 This Amendment Number Two (the “Amendment”) to the Founding Investor Rights Agreement dated January 1, 2009, as amended on June 7, 2010 (the “Investor Rights
Agreement”), is entered into as of the 27th
day of October, 2010 (the “Effective Date”) by and among ALNYLAM PHARMACEUTICALS, INC., a Delaware corporation, with its principal place of business at 300 Third Street,
Cambridge, Massachusetts 02142 (“Alnylam”), ISIS PHARMACEUTICALS, INC., a Delaware corporation, with its principal place of business at 1896 Rutherford Road, Carlsbad,
California 92008 (“Isis”), and REGULUS THERAPEUTICS INC. (formerly Regulus Therapeutics LLC), a Delaware corporation, with its principal place of business at 3545 John
Hopkins Court, Suite 210, San Diego, CA 92121 (“Regulus”). 
 RECITALS 

WHEREAS, Regulus, Isis and Alnylam entered into the Investor Rights Agreement; and 

WHEREAS, Isis, Alnylam, and Regulus now desire to amend the Investor Rights Agreement as provided
herein. 
 AGREEMENT 
 NOW, THEREFORE, in consideration of the mutual covenants contained herein, and other good and valuable consideration, the receipt and sufficiency of which is hereby
acknowledged, Isis, Alnylam and Regulus each agrees as follows: 
  

	1.	DEFINITIONS 

 Capitalized
terms used herein and not defined elsewhere herein have the meanings set forth in the Investor Rights Agreement. 
  

	2.	AMENDMENT TO SECTION 5.1 


2.1 Section 5.1. The second sentence of Section 5.1 of the Investor Rights Agreement shall be amended and restated in
its entirety as follows: 
 “Each Founding Investor’s pro rata share is equal to the ratio of (a) the number of shares of
the Company’s Common Stock (including all shares of Common Stock issuable or issued upon conversion of the Shares or upon the exercise of any outstanding warrants or options) of which such Founding Investor is deemed to be a holder immediately
prior to the issuance of such Equity Securities to (b) the total number of shares of the Company’s outstanding Common Stock (including all shares of Common Stock issued or issuable upon conversion of any outstanding preferred stock of the
Company or upon the exercise of any outstanding warrants or options) immediately prior to the issuance of the Equity Securities.” 








	3.	MISCELLANEOUS 

 3.1
Other Terms. All other terms and conditions of the Investor Rights Agreement shall remain in full force and effect. 

3.2 Counterparts. This Agreement may be executed in any number of counterparts, each of which will be deemed an original, and all
of which together will constitute one and the same instrument. 
 [Remainder of Page Intentionally Left Blank] 


  
 2 








 IN WITNESS WHEREOF, the Parties hereby execute this Amendment Number Two to the Founding
Investor Rights Agreement as of the Effective Date. 
  

			
	ALNYLAM PHARMACEUTICALS, INC.
		
	 By:
	 	 /s/ illegible

		 	Name:
		 	Title:
	
	ISIS PHARMACEUTICALS, INC.
		
	 By:
	 	 /s/ B. Lynne Parshall

		 	Name: B. Lynne Parshall
		 	 Title: Chief Operating Officer and
 Chief Financial Officer

	
	REGULUS THERAPEUTICS INC.
		
	 By:
	 	 /s/ Kleanthis G. Xanthopoulos

		 	Name: Kleanthis G. Xanthopoulos
		 	Title: President and CEO