Document:

Amendment No. 1 to Shareholder's Agreement

 Exhibit 4.3 
 AMENDMENT TO SHAREHOLDERS’ AGREEMENT 
 THIS AMENDMENT AGREEMENT is dated
for reference as of June 25, 2013 among Aquinox Pharmaceuticals Inc. (the “Canadian Company”), Aquinox Pharmaceuticals (USA) Inc. (the “U.S. Company”) and certain shareholders of the Canadian Company and U.S. Company
identified as such on the signature page thereto (the “Shareholders”). 
 WHEREAS: 

 

	A.	The Canadian Company, the U.S. Company and certain shareholders of the Canadian Company and the U.S. Company entered into an Amended & Restated
Shareholders’ Agreement made as of March 19, 2013 (the “Shareholders’ Agreement”) relating to the establishment of certain rights and obligations in respect of the conduct of the affairs of the Canadian Company and the
U.S. Company, the holding and sale of their respective securities, and certain other matters; 

  

	B.	The Shareholders’ Agreement may only be amended by an instrument in writing duly executed by the Canadian Company, the U.S. Company and Shareholders holding not
less than 60% of the Common Shares (as that term is defined in the Shareholders’ Agreement) that are subject to the Shareholders’ Agreement on a Fully Converted Basis (as that term is defined in the Shareholders’ Agreement);

  

	C.	The undersigned Shareholders hold more than 60% of the Common Shares (as that term is defined in the Shareholders’ Agreement) that are subject to the
Shareholders’ Agreement on a Fully Converted Basis; and 

  

	D.	The parties wish to amend the Shareholders’ Agreement as set forth herein. 

 NOW THEREFORE THIS AGREEMENT WITNESSES that in consideration of the premises, the mutual covenants and agreements set forth in this Agreement and other good and valuable consideration (the receipt
and sufficiency of which is hereby acknowledged by each of the parties), the parties hereby agree as follows: 
  

	1.	Amendment. The Shareholders’ Agreement is amended by modifying Sections 3.1(a) and 3.1(b) of the Shareholders’ Agreement as follows:

  

	 	3.1	Composition of the Board of Directors 

  

	 	(a)	Each Shareholder agrees to vote, or cause to be voted, all Shares owned by such Shareholder, or over which such Shareholder has voting control, from time to time and at
all times, in whatever manner as shall be necessary to ensure that the size of the Board of the U.S. Company shall be set and remain at six Directors. Each Shareholder agrees to vote, or cause to be voted, all Shares owned by such
Shareholder, or over which such Shareholder has voting control, from time to time and at all times, in whatever manner as shall be necessary to ensure that the following persons shall be elected to the Board of the U.S. Company:

  

	 	(i)	the then current Chief Executive Officer of the Companies (the “Common Director”); 

  
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	 	(ii)	at any time during which VW Shareholders collectively own 10% or more of the outstanding Common Shares on a Fully Diluted Basis, one individual designated by the
VW Shareholders (the “VW Director”); 

  

	 	(iii)	at any time during which JJDC or its Affiliates collectively own 10% or more of the outstanding Common Shares on a Fully Diluted Basis, one individual designated by
JJDC (the “JJDC Director”); 

  

	 	(iv)	at any time during which PVI or its Affiliates collectively own 10% or more of the outstanding Common Shares on a Fully Diluted Basis, one individual designated by PVI
(the “PVI Director”); and 

  

	 	(v)	onetwo individuals, each of whom is not an employee of either of the Companies and has been approved and designated by Investor Approval
(theeach, an “Independent Director”), 

 and each Director designated as a
Director pursuant to clauses (ii) to (iv) above shall, for purposes of this Agreement, be referred to as an “Investor Nominee Director”. If a person or group exercising the right to designate a Director pursuant to clauses
(ii) to (iv) above ceases to hold 10% or more of the outstanding Common Shares on a Fully Diluted Basis, any Director appointed by such person or group pursuant to this Section 3.1(a) shall immediately resign as Director and, if such
Director does not immediately resign as Director, the Shareholders shall forthwith take all actions required to be taken to remove such Director from the Board and appoint an additional Independent Director. 

 

	(b)	(i) Upon execution of this Agreement, the Board of the U.S. Company will be constituted as follows: 

 

					
	  	 	 Name of Director:
	  	 
		 	David Main	  	Common Director
		 	Kenneth Galbraith	  	VW Director
		 	Asish Xavier	  	JJDC Director
		 	Elaine V. Jones, Ph.D.	  	PVI Director
		 	Daniel Levitt	  	Independent Director
		 	Robert Pelzer	  	Independent Director

  

	 	(ii)	If a Director ceases to be a Director for any reason, each Shareholder agrees to vote, or cause to be voted, all Shares owned by such Shareholder, or over which such
Shareholder has voting control, from time to time and at all times, in whatever manner as shall be necessary to ensure that the Board composition set out above in Section 3.1(a) is maintained. 

  
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	2.	Investor Approval. Each of the undersigned Shareholders acknowledges and agrees that each of Daniel Levitt and Robert Pelzer have been approved and designated as
Independent Directors by Investor Approval. 

  

	3.	Governing Law. This Agreement is a contract made under and shall be governed by and construed in accordance with the laws of the Province of British Columbia and
the laws of Canada applicable therein. Any action, suit or proceeding arising out of or relating to this Agreement shall be brought in the courts of the Province of British Columbia, and each of the Parties hereby irrevocably submits to the
jurisdiction of such courts. 

  

	4.	Effectiveness. This Amendment Agreement shall become effective upon the execution hereof by each of the parties hereto. 

 

	5.	Counterparts. This Agreement may be executed in several counterparts (including by fax), each of which when so executed shall be deemed to be an original and
shall have the same force and effect as an original but such counterparts together shall constitute but one and the same instrument. 

 IN WITNESS WHEREOF the parties have executed this Agreement as of the date first written above. 
  

									
	AQUINOX PHARMACEUTICALS INC.	 	 	 	AQUINOX PHARMACEUTICALS (USA) INC.
					
	Per:  	 	/s/ David Main	 	 	 	Per:	 	/s/ David Main
		 	(Authorized Signatory)	 		 		 	(Authorized Signatory)
			
	VENTURES WEST 8 LIMITED PARTNERSHIP, by its General Partner, Ventures West 8 Management Ltd.	 		 	B.C. ADVANTAGE FUNDS (VCC) LTD.
					
	Per:	 	/s/ Gary Bridger	 	 	 	Per:	 	/s/ Frank Holler
		 	(Authorized Signatory)	 		 		 	(Authorized Signatory)
					
	Per:	 	/s/ Kenneth Gailbraith	 	 	 	 	 	 
		 	(Authorized Signatory)	 		 		 	

  
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	14159, L.P.	 	 	 	667, L.P.
					
	By:	 	Baker Bros. Advisors, LLC, management
company and investment adviser to 14159,
L.P., pursuant to authority granted to it by
14159 Capital, L.P., general partner
to
14159, L.P., and not as the general partner	 	 	 	By:	 	Baker Bros. Advisors, LLC, management
company and investment adviser to 667,
L.P., pursuant to authority granted to it by
Baker Biotech Capital, L.P., general
partner
to 667, L.P., and not as the general partner
					
	By:  	 	 /s/ Scott Lessing
	 		 	By:	 	 /s/ Scott Lessing

		 	 Scott Lessing

President
	 		 		 	 Scott Lessing

President

			
	BAKER BROS. INVESTMENTS II, L.P.	 		 	BAKER BROTHERS LIFE SCIENCES, L.P.
					
	By:	 	Baker Bros. Advisors, LLC, management company and investment adviser to Baker Bros. Investments II, L.P., pursuant to authority granted to it by Baker Bros. Capital, L.P., general
partner to Baker Bros. Investments II, L.P., and not as the general partner	 		 	By:	 	Baker Bros. Advisors, LLC, management company and investment adviser to Baker Brothers Life Sciences, L.P., pursuant to authority granted to it by Baker Brothers Life Sciences
Capital L.P., general partner to Baker Brothers Life Sciences, L.P., and not as the general partner
					
	By:	 	 /s/ Scott Lessing
	 		 	By:	 	 /s/ Scott Lessing

		 	 Scott Lessing

President
	 		 		 	 Scott Lessing

President

			
	JOHNSON & JOHNSON
DEVELOPMENT CORPORATION	 		 	PFIZER INC.
					
	Per:	 	 /s/ Asish K. Xavier
	 		 	Per:	 	 /s/ Barbara Dalton

		 	Asish K. Xavier	 		 		 	(Authorized Signatory)
		 	Vice President, Venture Investments	 		 		 	
				
	 AUGMENT INVESTMENTS LTD.
	 		 		 	
					
	Per:	 	 	 		 		 	
		 	 Sergey Notov
	 		 		 	

  
 4Amendment No. 2 to Shareholder's Agreement

 Exhibit 4.4 
 AMENDMENT NO. 2 TO SHAREHOLDERS’ AGREEMENT 
 THIS AMENDMENT NO. 2 TO
SHAREHOLDERS’ AGREEMENT (this “Agreement”) is dated for reference as of November 18, 2013 among Aquinox Pharmaceuticals Inc. (the “Canadian Company”), Aquinox Pharmaceuticals (USA) Inc. (the
“U.S. Company”) and certain shareholders of the Canadian Company and U.S. Company identified as such on the signature page thereto (the “Shareholders”). 
 WHEREAS: 
  

	A.	The Canadian Company, the U.S. Company and certain shareholders of the Canadian Company and the U.S. Company entered into an Amended & Restated
Shareholders’ Agreement made as of March 19, 2013, as previously amended (the “Shareholders’ Agreement”) relating to the establishment of certain rights and obligations in respect of the conduct of the affairs of the
Canadian Company and the U.S. Company, the holding and sale of their respective securities, and certain other matters; 

  

	B.	The Shareholders’ Agreement may only be amended by an instrument in writing duly executed by the Canadian Company, the U.S. Company and Shareholders holding not
less than 60% of the Common Shares (as that term is defined in the Shareholders’ Agreement) that are subject to the Shareholders’ Agreement on a Fully Converted Basis (as that term is defined in the Shareholders’ Agreement);

  

	C.	The undersigned Shareholders hold more than 60% of the Common Shares that are subject to the Shareholders’ Agreement on a Fully Converted Basis; and

  

	D.	The parties wish to amend the Shareholders’ Agreement as set forth herein. 

 NOW THEREFORE THIS AGREEMENT WITNESSES that in consideration of the premises, the mutual covenants and agreements set forth in this Agreement and other good and valuable consideration (the receipt
and sufficiency of which is hereby acknowledged by each of the parties), the parties hereby agree as follows: 
  

	1.	Amendment to Section 3.5. The first sentence of Section 3.5 of the Shareholders’ Agreement is hereby amended and restated to read in its entirety
as follows: 

 “A quorum for the transaction of business at any meeting of the Board of a Company shall be a
majority of Directors, including, if such Investor Nominee Director is then serving on the Board, each of the VW Director, the JJDC Director and the PVI Director.” 
  

	2.	Amendment to Section 3.8(f). Section 3.8(f) of the Shareholders’ Agreement is hereby amended and restated to read in its entirety as follows:

 “(f) any of the following matters, provided that such approval of the Board of the U.S. Company with
respect to such matters shall include, if such Investor Nominee Director is then serving on the Board, the affirmative vote of the JJDC Director and the PVI Director: (i) incur any material indebtedness or other material liability on behalf of
the U.S. Company; (ii) enter into any material contract to which the U.S. Company is a party or otherwise bound; (iii) retain or 

  
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terminate the services of any employee, independent contractor or other service provider of the U.S. Company; (iv) adopt or terminate any Benefit Plan (as defined in the Series C
Subscription Agreement) for the U.S. Company; or (v) initiate any legal action or proceeding on behalf of the U.S. Company; provided, however, that this Section 3.8(f) shall not be deemed to apply to a Change of Control, a public offering
of securities of the U.S. Company or any action taken pursuant to, or amendment of, this Agreement (other than this Section 3.8(f)), the Subscription Agreements, the Exchange Agreement, the Support Agreement, the Registration Rights Agreement
or the U.S. Company’s Constating Documents.” 
  

	3.	Governing Law. This Agreement is a contract made under and shall be governed by and construed in accordance with the laws of the Province of British Columbia and
the laws of Canada applicable therein. Any action, suit or proceeding arising out of or relating to this Agreement shall be brought in the courts of the Province of British Columbia, and each of the Parties hereby irrevocably submits to the
jurisdiction of such courts. 

  

	4.	Effectiveness. This Amendment Agreement shall become effective upon the execution hereof by each of the parties hereto. 

 

	5.	Counterparts. This Agreement may be executed in several counterparts (including by fax), each of which when so executed shall be deemed to be an original and
shall have the same force and effect as an original but such counterparts together shall constitute but one and the same instrument. 

 IN WITNESS WHEREOF the parties have executed this Agreement as of the date first written above. 
  

									
	AQUINOX PHARMACEUTICALS INC.	 		 	AQUINOX PHARMACEUTICALS (USA) INC.
					
	Per:	 	/s/ David J. Main	 		 	Per:	 	/s/ David J. Main
		 	(Authorized Signatory)	 		 		 	(Authorized Signatory)
			
	 VENTURES WEST 8 LIMITED
 PARTNERSHIP, by its General Partner,
 Five Corners Capital Inc.
	 		 	B.C. ADVANTAGE FUNDS (VCC) LTD.
					
	Per:	 	/s/ Gary Bridger	 		 	Per:	 	/s/ Frank Holler
		 	(Authorized Signatory)	 		 		 	(Authorized Signatory)
					
	Per:	 	 	 		 		 	
		 	(Authorized Signatory)	 		 		 	

  
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	14159, L.P.	 		 	667, L.P.
					
	By:	 	Baker Bros. Advisors, LLC, management company and investment adviser to 14159, L.P., pursuant to authority granted to it by 14159 Capital, L.P., general partner to 14159, L.P., and
not as the general partner	 		 	By:	 	Baker Bros. Advisors, LLC, management company and investment adviser to 667, L.P., pursuant to authority granted to it by Baker Biotech Capital, L.P., general partner to 667, L.P.,
and not as the general partner
					
	By:	 	 	 		 	By:	 	 
		 	Scott Lessing	 		 		 	Scott Lessing
		 	President	 		 		 	President
			
	BAKER BROS. INVESTMENTS II, L.P.	 		 	BAKER BROTHERS LIFE SCIENCES, L.P.
					
	By:	 	Baker Bros. Advisors, LLC, management company and investment adviser to Baker Bros. Investments II, L.P., pursuant to authority granted to it by Baker Bros. Capital, L.P., general
partner to Baker Bros. Investments II, L.P., and not as the general partner	 		 	By:	 	Baker Bros. Advisors, LLC, management company and investment adviser to Baker Brothers Life Sciences, L.P., pursuant to authority granted to it by Baker Brothers Life Sciences
Capital L.P., general partner to Baker Brothers Life Sciences, L.P., and not as the general partner
					
	By:	 	 	 		 	By:	 	 
		 	Scott Lessing	 		 		 	Scott Lessing
		 	President	 		 		 	President
			
	 JOHNSON & JOHNSON
 DEVELOPMENT CORPORATION
	 		 	PFIZER INC.
					
	Per:	 	/s/ Asish K. Xavier	 		 	Per:	 	/s/ Barbara Dalton
		 	Asish K. Xavier	 		 		 	(Authorized Signatory)
		 	Vice President, Venture Investments	 		 		 	
			
	AUGMENT INVESTMENTS LTD.	 		 	
					
	Per:	 	 	 		 		 	
		 	Sergey Notov	 		 		 	

  
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