Document:

EX-10.49

 Exhibit 10.49 
 ***Text Omitted and Filed Separately 
 with the Securities and Exchange
Commission. 
 Confidential Treatment Requested 
 Under 17 C.F.R. Sections 200.80(b)(4) 
 and 230.406. 

AMENDMENT Nr.1 
 (to
Collaboration and License Agreement) 
 This Amendment Nr.1 (the “Amendment”) is made as of the 30th day of April
2013 (the “Amendment Nr. 1 Effective Date”), by and between: 
 ASTRAZENECA AB, a company Incorporated in Sweden
under no. 556011-7482 with offices at S-431 83, Mölndal, Sweden (“AstraZeneca”); and 
 REGULUS
THERAPEUTICS INC., a Delaware Corporation (“Regulus”) having a place of business at 3545 John Hopkins Court, San Diego, California 92121-1121, U.S.A. 

Recitals 
  

	(A)	 WHEREAS, AstraZeneca and Regulus have entered into a Collaboration and License Agreement (the “Original Agreement”), which came into force on the
14th day of August, 2012. 

 

	(B)	 WHEREAS, AstraZeneca has entered into an agreement with [...***...] for the purposes of engaging in scientific research related to the study
[...***...] 

  

	(C)	 WHEREAS, AstraZeneca has clinical samples from the [...***...] studies [...***...] on which it is entitled to generate results
(“AstraZeneca Results”) in house at AstraZeneca, at any of its Affiliates or at a third party on behalf of AstraZeneca. 

  

	(D)	 WHEREAS, AstraZeneca shall own all right, title and interest in and to all AstraZeneca Results from the [...***...] agreement.

  

	(E)	 WHEREAS, AstraZeneca and Regulus desire to undertake miRNA analysis of the [...***...] at Regulus for the benefit of the joint collaboration pursuant to
the Research Plan attached hereto as Exhibit A. No further research shall be undertaken unless the Research Plan is amended in writing and signed by both parties. 

NOW, THEREFORE, in consideration of the mutual covenants contained in this Amendment, and other good and valuable consideration, the receipt
and sufficiency of which is hereby acknowledged, the parties, intending to be legally bound, agree as follows: 
  

	1.	 Amended Terms and Conditions 

  

	1.1	 Solely for the purposes of the miRNA analysis of the [...***...], the [...***...] generated and Program Inventions resulting therefrom will be
considered AstraZeneca Program Inventions regardless of inventorship. 

 ***Confidential Treatment Requested

	1.2	 AstraZeneca grants Regulus a perpetual, non-exclusive license to the [...***...] and AstraZeneca Program inventions for its internal research and
development purposes. 

 For the avoidance of doubt Regulus acknowledges and agrees that AstraZeneca shall be entitled
to share the 
[...***...] and its Principal Investigator to publish such results to the extent [...***...] is entitled to do so under the 
[...***...] agreement, subject to the review rights afforded to AstraZeneca under the
[...***...] agreement. 
  

	2.	Miscellaneous 

  

	2.1	Except as expressly set forth in above Section 1.1 to 1.4, all other terms and conditions of the Original Agreement shall remain unchanged in full force and effect.
	 

  

	2.2	This Amendment may be executed in any number of counterparts, each of which shall be deemed an original and all of which taken together shall be deemed to constitute one and the
same instrument. Each party acknowledges that an original signature or a copy thereof transmitted by facsimile or by pdf shall constitute an original signature for purposes of this Amendment. 	 

 THIS AMENDMENT IS EXECUTED by the authorised representatives of the Parties as
of the date first written above. 
  

									
	SIGNED for and on behalf of	 		 	SIGNED for and on behalf of
			
	AstraZeneca AB (publ)	 		 	Regulus Therapeutics Inc.
			
		 		 	By:
			
	 /s/ Marcus Schindler
	 		 	 /s/ Garry E. Menzel

	Signature	 		 	Signature
					
	Name:  	 	Marcus Schindler	 		 	Name:  	 	Garry E. Menzel, Ph.D.
					
		 	VP iScience CVMD	 		 		 	COO & EVP, Finance
					
	Title:	 	  Authorised Signatory	 		 	Title:	 	Authorised Signatory

 ***Confidential Treatment Requested 

 EXHIBIT A 
 RESEARCH PLAN 
 [...***...] 
 ***Confidential Treatment RequestedEX-10.50

 Exhibit 10.50 
 ***Text Omitted and Filed Separately 
 with the Securities and Exchange
Commission. 
 Confidential Treatment Requested 
 Under 17 C.F.R. Sections 200.80(b)(4) 
 and 230.406. 

AMENDMENT NO. 1 TO COLLABORATION AND LICENSE AGREEMENT 
 This Amendment No. 1 to Collaboration and License Agreement (this “Amendment”) dated June 24, 2013, is by and between Regulus Therapeutics Inc., a Delaware corporation
with its principal address at 3545 John Hopkins Ct., Suite 210, San Diego, CA 92121 (“Regulus”), and Biogen Idec MA Inc., a Massachusetts corporation with its principal address at 133 Boston Post Road, Weston, MA 02493
(“BI”). Regulus and BI may each be referred to herein individually as a “Party” and collectively as the “Parties.” 

WHEREAS, the Parties entered into that certain Collaboration and License Agreement dated as of August 15, 2012 (the
“Agreement”; capitalized terms used but not defined herein shall have the meanings ascribed to such terms in the Agreement); and 
 WHEREAS, the Parties desire to amend the Agreement to reflect certain agreed changes to the Research Plan and to memorialize their mutual understanding and commitment with respect to publicity.

 NOW, THEREFORE, in consideration of the mutual promises and covenants set forth below and other good and valuable
consideration, the receipt and sufficiency of which is hereby acknowledged, the Parties hereby agree as follows: 

1.        Article 6 (Financial Provisions) of the Agreement is hereby amended by adding
the following at the end of Section 6.3 (Milestones): 

           “The Parties hereby agree that the original
proposed payment for the milestone event described as [...***...] was not earned in accordance with the original terms of the Agreement and the Research Plan, attached as Schedule A to the Agreement. The Parties have agreed to
revise the terms of Phase 1 of the Research Plan and proceed with the Revised Phase 1 (as defined below in paragraph 3). As consideration for Regulus (a) completing, in the reasonable, independent opinion of BI, the Revised Phase 1 Activity and
Revised Phase 1 Experiment described in paragraph 3 below, BI shall, upon completion of such activity and experiment and upon receipt of an invoice detailing the actual costs and expenses of such activity and experiment, remit to Regulus the total
amount of such actual costs and expenses (such amount not to exceed [...***...]), and (b) achieving, in the reasonable, independent opinion of BI, the criteria for success of such Revised Phase 1, BI shall pay Regulus the amount equal to
(i) [...***...] less (ii) the amount remitted to Regulus pursuant to sub-clause (a) above; for example, if the actual costs and expenses are [...***...], BI shall pay 

***Confidential Treatment Requested 

  
 1 

 Regulus an additional [...***...] as consideration for achieving, in the reasonable
opinion of BI, the criteria for success of such Revised Phase 1. 
 2.        Article
8 of the Agreement is hereby amended to include the following as a new Section 8.3: 

           “8.3    Public
Announcements.  Except to the extent required to comply with applicable law, regulation, rule or legal process or as otherwise permitted in accordance with this Section 8.3, neither Party, nor any of such Party’s
Affiliates, shall make any public announcements, press releases or other public disclosures concerning this Agreement (including this Amendment) or the terms or the subject matter hereof without the prior written consent of the other Party, which
will not be unreasonably withheld, conditioned or delayed. Neither Party shall use the other Party’s name in a press release or other public disclosure or publication without first obtaining the prior written consent of the Party to be named
and providing an advanced draft of such press release or other public disclosure or publication for review by the Party to be named and giving due consideration to all reasonable comments to such draft press release or publication provided by the
Party to be named. Each Party (a) shall give the other Party a reasonable opportunity to review any and all contemplated filings with the SEC that reference the existence of and/or the terms of the Agreement or that reference the other Party in
any manner, with sufficient time prior to submission of such filings for such other Party to provide comments on any such contemplated filing, and (b) shall give due consideration to any reasonable comments to such filing provided by the other
Party.” 
 3.        The Research Plan, attached as Schedule A to the
Agreement, is hereby amended to provide for the following revised Phase 1. Serum microRNA profiling of RRMS patient samples (“Revised Phase 1”) as follows: 

 

	 	a.	The Revised Phase 1 Activity shall be as follows: [...***...] 

  

	 	b.	The Revised Phase 1 Experiment shall be as follows: [...***...] 

  

	 	c.	The Revised Phase 1 Criteria for success shall be as follows: [...***...] Success is defined by 
[...***...] 

***Confidential Treatment Requested 

  
 2 

 4.        Except as amended by this Amendment, the
terms and conditions of the Agreement shall remain in full force and effect. 

5.        The provisions of Article 11 of the Agreement shall also apply to the terms of
this Amendment mutatis mutandis. 
 6.        This Amendment shall be construed
and the respective rights of the Parties determined according to the substantive laws of the State of New York notwithstanding the provisions governing conflict of laws under such New York law to the contrary. 

7.        This Amendment may be executed in counterparts, including by facsimile or by electronic
copies delivered by email, each of which counterparts, when so executed and delivered, shall be deemed to be an original, and all of which counterparts, taken together, shall constitute one and the same instrument. 

[Signature Page Follows] 

  
 3 

 IN WITNESS WHEREOF, the Parties have executed this Amendment as of the date first set forth
above. 
  

							
		 	REGULUS THERAPEUTICS INC.	 	
				
		 	By:	 	 /s/ Kleanthis G. Xanthopoulos
	 	
		 	Name:	 	 Kleanthis G. Xanthopoulos, Ph.D.
	 	
		 	Title:	 	 President and Chief Executive Officer
	 	

							
			
		 	BIOGEN IDEC MA INC.	 	
				
		 	By:	 	 /s/ Teresa Compton
	 	

							
		 	Name:	 	 Teresa Compton
	 	

							
		 	Title:	 	 Vice President
	 	

  
 [Signature
Page to Amendment No. 1 to Collaboration and License Agreement]

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