EX-4.5



 Exhibit 4.5 

AMENDMENT NO. 1 TO 
 THE
THIRD AMENDED AND RESTATED 
 INVESTORS’ RIGHTS AGREEMENT 

THIS AMENDMENT NO. 1 TO THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT (this “Amendment”) is made and
effective as of May 31, 2013, by and among Akebia Therapeutics, Inc., a Delaware corporation (the “Company”), and the “Investors” as defined in that certain Third Amended and Restated Investors’ Rights Agreement,
dated as of May 10, 2013, by and among the Company and the Investors a party thereto (the “Agreement”). Capitalized terms not defined herein have the meanings given them in the Agreement. 

RECITALS 
 WHEREAS,
on May 10, 2013, the Agreement was entered into by the Company and the Investors in connection with the transactions and agreements contemplated in that certain Series C Preferred Stock Purchase Agreement by and between the Company and certain
parties as listed therein, dated as of May 10, 2013 (the “Series C Stock Purchase Agreement” and the transactions and agreements contemplated therein collectively the “Series C Transaction”); and 

WHEREAS, in connection with an Additional Closing (as defined in the Series C Stock Purchase Agreement) to the Series C Transaction
dated May 31, 2013, the Company and the Investors holding more than the Appropriate Percentage (as defined in the Agreement) of the Registrable Securities (as defined in the Agreement) outstanding desire to amend the Agreement in accordance
with the terms and conditions more fully set forth in this Amendment. 
 NOW, THEREFORE, in consideration of the foregoing premises
and the mutual covenants hereinafter set forth, and other good and valuable consideration had and received, the parties hereto, upon the terms and subject to the conditions contained herein, hereby agree as follows: 

1. Amendment of Section 6.6. Section 6.6 of the Agreement is hereby amended by deleting it in its entirety and replacing it
with the following: 
 Amendments and Waivers. Any term of this Agreement may be amended and the observance of any term of this
Agreement 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 more than the Appropriate Percentage of the Registrable Securities then
outstanding; provided, that the Company may in its sole discretion waive compliance with Section 2.12(c) (and the Company’s failure to object promptly in writing after notification of a proposed assignment allegedly in violation of
Section 2.12(c) shall be deemed to be a waiver); and provided, further, that any provision hereof may be waived by any waiving party on such party’s own behalf, without the consent of any other party. Notwithstanding the foregoing, this
Agreement may not be amended or terminated and the observance of any term hereof may not be waived with respect to any Investor without the written consent of such Investor, unless such 

  
 1 








 
amendment, termination, or waiver applies to all Investors in the same fashion (it being agreed that a waiver of the provisions of Section 4 with respect to a particular transaction shall be
deemed to apply to all Investors in the same fashion if such waiver does so by its terms, notwithstanding the fact that certain Investors may nonetheless, by agreement with the Company, purchase securities in such transaction). Notwithstanding the
foregoing, the provisions of (a) Section 2.8(d), commencing with its words “provided, however”, may not be amended or waived without the written consent of (i) the Company and (ii) the holders of ninety percent
(90%) of the shares of Common Stock issuable upon conversion of the then outstanding shares of Preferred Stock and (iii) (A) Satter Investment Management, LLC so long as Satter Investment Management, LLC or any of its Affiliates holds
any Preferred Stock or Common Stock issued upon conversion of any of such Preferred Stock, (B) Novartis Bioventures Ltd. so long as Novartis Bioventures Ltd. holds any Preferred Stock or Common Stock issued upon conversion of any of such
Preferred Stock, and (C) Novo A/S so long as Novo A/S holds any Preferred Stock or Common Stock issued upon conversion of any of such Preferred Stock; (b) Section 3.3 may not be amended to terminate a designated right therein to
appoint an observer to the Board of Directors without the written consent of the Company and at least fifty percent (50%) of the shares of Common Stock issuable upon conversion of the then outstanding shares of Preferred Stock held by the
Persons entitled to appoint such observer; (c) Sections 4.1 and 4.2 may not be waived without the written consent of the holders of more than seventy percent (70%) of the shares of Common Stock issuable upon conversion of the then
outstanding shares of Preferred Stock; and (d) Section 5.8, Section 6.6(a) and this Section 6.6(d) may not be amended or waived without the written consent of (i) the Company, (ii) the holders of ninety percent
(90%) of the shares of Common Stock issuable upon conversion of the then outstanding shares of Preferred Stock and (iii) (A) Satter Investment Management, LLC so long as Satter Investment Management, LLC or any of its Affiliates holds
any Preferred Stock or Common Stock issued upon conversion of any of such Preferred Stock, (B) Novartis Bioventures Ltd. so long as Novartis Bioventures Ltd. holds any Preferred Stock or Common Stock issued upon conversion of any of such
Preferred Stock, and (C) Novo A/S so long as Novo A/S holds any Preferred Stock or Common Stock issued upon conversion of any of such Preferred Stock. The Company shall give prompt notice of any amendment or termination hereof or waiver
hereunder to any party hereto that did not consent in writing to such amendment, termination, or waiver. Any amendment, termination, or waiver effected in accordance with this Section 6.6 shall be binding on all parties hereto,
regardless of whether any such party has consented thereto. No waivers of or exceptions to any term, condition, or provision of this Agreement, in any one or more instances, shall be deemed to be or construed as a further or continuing waiver of any
such term, condition, or provision. 
 2. Amendment of Section 2.8(d). The last sentence of Section 2.8(d) of the Agreement
is hereby amended by deleting the parenthetical which reads “(net of any Selling Expenses) paid by such Holder)” and replacing it with the parenthetical which reads “(net of any Selling Expenses paid by such Holder)”. 

  
 2 








 3. Miscellaneous Amendments. The Agreement is amended hereby so that any reference therein
to the Agreement shall be deemed to be a reference to the Agreement as amended by this Amendment. 
 4. Continuance of Agreement.
Except as specifically amended by this Amendment, the Agreement shall remain in full force and effect. 
 5. Governing Law. The laws
of the State of Delaware govern all matters arising out of or relating to this Amendment, including, without limitation, its interpretation, construction, performance, and enforcement, without giving effect to such state’s conflicts of law
principles or rules of construction concerning the drafter hereof. 
 6. Counterparts. This Amendment may be executed in two or more
counterparts, including by facsimile or PDF signature, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. 

[Signature Page Follows] 

  
 3 








 Exhibit 4.5 

IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first written above. 

 

			
	AKEBIA THERAPEUTICS, INC.
		
	By:	 	/s/ Joseph H. Gardner
		 	Joseph H. Gardner, Ph.D.
		 	President and Chief Executive Officer


  

	
	Address:
	
	 Suite 420,
 9987 Carver Road,

Cincinnati, OH 45242




  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	NOVARTIS BIO VENTURES LTD.
		
	By:	 	/s/ H.S. Zivi
		 	Name: Simon Zivi
		 	Title: Deputy Chairman


  

			
	
		
	By:	 	/s/ Rebecca White
		 	Name: Rebecca White
		 	Title: Authorized Signatory


  

	
	Address:
	
	 NOVARTIS BIOVENTURES LTD.
 Attn: Henri Simon
Zivi
 131 Front Street
 Hamilton HM 12

Bermuda

	
	 But for mail, to:
  

Novartis Bio Ventures Ltd.
 Attn: Henri Simon Zivi

PO Box HM 2899
 Hamilton HM LX Bermuda

	
	 And, also send a copy to:
  

Novartis Venture Fund
 Attn: Campbell Murray

Five Cambridge Center, Suite 603
 Cambridge, MA
02142




  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	 VENTURE INVESTORS EARLY STAGE
 FUND
IV LIMITED PARTNERSHIP

	
	By: VIESF IV GP, LLC, its General Partner
		
	By:	 	/s/ Paul M. Weiss
		 	Name: Paul M. Weiss, Ph.D.
		 	Title: Managing Director


  

	
	Address:
	
	 505 South Rosa Road
 Madison, WI
53719-1262
 Attn: Paul Weiss, Managing Director
 Phone:
(608) 441-2700
 Fax: (608) 441-2727
 Email:
paul@ventureinvestors.com




  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	TRIATHLON MEDICAL VENTURES FUND, L.P.
	
	By: Triathlon Medical Ventures, LLC
	Title: its General Partner
		
	By:	 	/s/ John M. Rice
		 	John M. Rice
		 	Managing Partner


  

	
	Address:
	
	 300 E-Business Way
 Suite 200

Cincinnati, OH 45241




  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	KEARNY VENTURE PARTNERS, L.P.
		
	By:	 	/s/ Anupam Dalal
		 	Name: Kearny Venture Associates, LLC
		 	Title: its General Partner


  

	
	Address:
	
	 Attn: Anupam Dalal
 Kearny Venture Associates
LLC
 88 Kearny Street, Suite 1800
 San Francisco, CA
94108-5530



  

			
	KEARNY VENTURE PARTNERS 
ENTREPRENEURS FUND, L.P.
		
	By:	 	/s/ Anupam Dalal
		 	Name: Kearny Venture Associates, LLC
		 	Title: its General Partner


  

	
	Address:
	
	 Attn: Anupam Dalal
 Kearny Venture Associates
LLC
 88 Kearny Street, Suite 1800
 San Francisco, CA
94108-5530




  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	THOMAS WEISEL HEALTHCARE VENTURE PARTNERS, L.P.
	
	By: Thomas Weisel Capital Management LLC
	Title: its Managing Member


  

			
		
	By:	 	/s/ Anupam Dalal
		 	Name: Anupam Dalal
		 	Title: Managing Director


  

	
	Address:
	
	 88 Kearny Street, Suite 1800
 San Francisco,
CA 94108




  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	ATHENIAN VENTURE PARTNERS III L.P.
		
	By:	 	/s/ Karl Elderkin
		 	Name: Karl O. Elderkin
		 	Title: President


  

			
	AVP OHIO TECHNOLOGY I L.P.
		
	By:	 	/s/ Karl Elderkin
		 	Name: Karl O. Elderkin
		 	Title: President


  

	
	Address:
	
	 340 West State Street
 Unit 29/Suite I37D

Athens OH 45701




  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	AGECHEM VENTURE FUND L.P.
		
	By:	 	/s/ Louis Lacasse
		 	Name: Louis Lacasse
		 	Title: President


  

	
	Address:
	
	 Attn: Louis Lacasse, President
 1 Westmount
Square, Suite 800
 Montreal, Quebec, Canada
 H3Z
2P9




  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	 CINCINNATI CORNERSTONE INVESTORS

AKB, LLC

		
	By:	 	/s/ Robert W. Coy, Jr.
		 	Robert W. Coy, Jr.
		 	President


  

	
	Address:
	
	 30 West 3rd Street, 6th Floor

Cincinnati, OH 45202-3559




  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	FAMILY AKEBIA INVESTMENTS LLC
		
	By:	 	/s/ Milton Berlinski
		 	Name: Milton Berlinski
		 	Title: Managing Member


  

	
	Address:
	
	 1185 Park Avenue #11G
 New York, NY
10128




  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	MUNEER A. SATTER REVOCABLE TRUST
		
	By:	 	/s/ Muneer A. Satter
		 	Name: Muneer A. Satter
		 	Title: Trustee
	
	THE SATTER FOUNDATION
		
	By:	 	/s/ Muneer A. Satter
		 	Name: Muneer A. Satter
		 	Title: Trustee
	
	SATTER FAMILY TRUST
		
	By:	 	/s/ Muneer A. Satter
		 	Name: Muneer A. Satter
		 	Title: Investment Advisor
	
	SATTER CHILDREN’S TRUST I
		
	By:	 	/s/ Muneer A. Satter
		 	Name: Muneer A. Satter
		 	Title: Investment Advisor
	
	Address:
	
	c/o Satter Investment Management, LLC
	676 N. Michigan Avenue, Suite 4000
	Chicago, IL 60611
	Attn: Muneer A. Satter



  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	KRISTEN HAYLER HERTEL REVOCABLE TRUST
		
	By:	 	/s/ Kristen Hayler Hertel
		 	Name: Kristen Hayler Hertel
		 	Title: Trustee
	
	Address:
	
	c/o Satter Investment Management, LLC
	676 N. Michigan Avenue, Suite 4000
	Chicago, IL 60611
	Attn: Muneer A. Satter



  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	ANNE-CAROLE WITORT INSURANCE TRUST
		
	By:	 	/s/ Muneer A. Satter
		 	Name: Muneer A. Satter
		 	Title: Trustee
	
	ROSE SHEREEN FUQUA INSURANCE TRUST
		
	By:	 	/s/ Muneer A. Satter
		 	Name: Muneer A. Satter
		 	Title: Investment Advisor
	
	RABI H. SATTER INSURANCE TRUST
		
	By:	 	/s/ Muneer A. Satter
		 	Name: Muneer A. Satter
		 	Title: Investment Advisor
	
	JOHN WOOD TRUST
		
	By:	 	/s/ Muneer A. Satter
		 	Name: Muneer A. Satter
		 	Title: Investment Advisor
	
	Address:
	
	c/o Satter Investment Management, LLC
	676 N. Michigan Avenue, Suite 4000
	Chicago, IL 60611
	Attn: Muneer A. Satter



  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 








 IN WITNESS WHEREOF, the parties have caused this Amendment to be executed as of the date first
written above. 
  

			
	ABDUS SATTER INSURANCE TRUST
		
	By:	 	/s/ Muneer A. Satter
		 	Name: Muneer A. Satter
		 	Title: Trustee
	
	GORDON AND BARBARA ANNE HERTEL INSURANCE TRUST
		
	By:	 	/s/ Muneer A. Satter
		 	Name: Muneer A. Satter
		 	Title: Trustee
	
	Address:
	
	c/o Satter Investment Management, LLC
	676 N. Michigan Avenue, Suite 4000
	Chicago, IL 60611
	Attn: Muneer A. Satter



  
 SIGNATURE PAGE TO
AMENDMENT NO. 1 TO 
 THE THIRD AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT