Document:

EX-4.3

 Exhibit 4.3 

JUNO THERAPEUTICS, INC. 

SECOND AMENDMENT 
 to

 FOURTH AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT 

This Second Amendment (this “Amendment”), dated January 29, 2016, to the Fourth Amended and Restated
Investors’ Rights Agreement, dated December 5, 2014, and as amended July 27, 2015 (as so amended, the “Agreement”) by and among Juno Therapeutics, Inc., a Delaware corporation (the
“Company”), and the Investors party thereto, is entered into by and among the Company and each of the Investors set forth on the signature pages hereto. Capitalized terms used but not otherwise defined herein shall have the
meanings assigned thereto in the Agreement. 
 RECITALS 

A. On January 8, 2016, the Company entered into an Agreement and Plan of Reorganization, by and among the Company, AbVitro Inc.
(“AbVitro”), and certain other parties, pursuant to which the Company issued shares of Common Stock to the stockholders of AbVitro (the “AbVitro Stockholders”) as partial consideration for the
acquisition of AbVitro. 
 B. The parties to the Agreement desire to amend the Agreement to, among other things, provide for the joinder, as
of the date of this Agreement, of the AbVitro Stockholders as Investors for purposes of Sections 2 and 6 of the Agreement. 
 NOW THEREFORE,
in consideration of the mutual covenants set forth herein, the parties hereto agree as follows: 
 1. Amendments.  

(a) The recitals of the Agreement are hereby amended by the addition of the following: 

“F. On January 8, 2016, the Company entered into an Agreement and Plan of Reorganization (the “Acquisition
Agreement”), by and among the Company, AbVitro Inc. (“AbVitro”), and certain other parties, pursuant to which the Company issued shares of Common Stock to the stockholders of AbVitro (the “AbVitro
Stockholders”) as partial consideration for the acquisition of AbVitro. The parties to the Agreement desire to amend the Agreement to, among other things, provide for the joinder of the AbVitro Stockholders as Investors solely for
purposes of Sections 2 and 6 hereunder.” 
 (b) Section 1.1(h) of the Agreement is hereby amended and restated in its entirety as
follows: 
 ““Holder” shall mean any Investor who holds Registrable Securities for so long as it holds
Registrable Securities and any holder of Registrable Securities to whom the registration rights conferred by this Agreement have been duly and validly transferred in accordance with Section 2.11 of this Agreement; provided, however, no AbVitro
Stockholder shall be considered a Holder for purposes of Section 3, Section 4 or Section 5 of this Agreement.” 

 (c) Section 1.1(l) of the Agreement is hereby amended and restated in its entirety as
follows: 
 ““Initiating Holders” shall mean any
Holder or Holders who in the aggregate hold not less than a majority of the outstanding Registrable Securities, excluding for such purposes the AbVitro Stockholders.” 

(d) Section 1.1(r) of the Agreement is hereby amended and restated in its entirety as follows: 

““Registrable Securities” shall mean (i) shares of Common Stock issued or issuable pursuant to the
conversion of the Shares, (ii) any Common Stock issued as a dividend or other distribution with respect to or in exchange for or in replacement of the shares referenced in (i) above, (iii) any shares of Common Stock issued or issuable
to FHCRC pursuant to the FHCRC Side Letter, (iv) any shares of Common Stock issued to ZetaRx pursuant to the Asset Purchase Agreement, (v) any shares of Common Stock issued or issuable to MSKCC pursuant to the MSKCC Side Letter,
(vi) following, and contingent upon the occurrence of, the joinder of the Additional Investor to this Agreement upon the License Effective Date pursuant to Section 6.1, any shares of Common Stock issued or issuable to the Additional
Investor pursuant to the Additional Stock Purchase Agreement or the License Agreement; and (vii) any shares of Common Stock issued to the AbVitro Stockholders pursuant to the Acquisition Agreement; provided, however, that
Registrable Securities shall not include any shares of Common Stock described in clause (i)-(vii) above which have previously been registered or which have been sold to the public either pursuant to a registration statement or Rule 144, or
which have been sold in a private transaction in which the transferor’s rights under this Agreement are not validly assigned in accordance with this Agreement.” 

(e) Section 2.3(a) of the Agreement is hereby amended and restated in its entirety as follows: 

“Request for Form S-3 Registration. After its initial public offering, the Company
shall use its commercially reasonable efforts to qualify for registration on Form S-3 or any comparable or successor form or forms. After the Company has qualified for the use of Form S-3, in addition to the rights contained in the foregoing
provisions of this Section 2 and subject to the conditions set forth in this Section 2.3, if the Company shall receive from a Holder or Holders of Registrable Securities other than any AbVitro Stockholder a written request that the Company
effect any registration on Form S-3 or any similar short form registration statement with respect to all or part of the Registrable Securities (such request shall state the number of shares of Registrable
Securities to be disposed of and the intended methods of disposition of such shares by such Holder or Holders), the Company will take all such action with respect to all Registrable Securities (including Registrable Securities held by AbVitro
Stockholders) as required by Section 2.1(a)(i) and Section 2.1(a)(ii).” 

  
 2 

 (f) Section 2.11 of the Agreement is hereby amended by amending and restating subclause
(iii) thereof in its entirety as follows: 
 “(iii) the transferee or assignee of such rights assumes in writing the obligations of
such Holder under this Agreement, including without limitation the obligations set forth in Section 2.9 (provided, however, solely with respect to the AbVitro Stockholders, the obligations set forth in Section 2.1(h)-(j) of the
Agreement and Joinder between the Company and such AbVitro Stockholder shall be assumed by such transferee or assignee and deemed to apply rather than the restrictions on transfer set forth in Section 5 of this Agreement).” 

(g) Exhibit A to the Agreement is hereby amended to add each of the Investors set forth on Exhibit A hereto. 

2. Entire Agreement. This Amendment, together with Agreement and the exhibits hereto and thereto, constitutes the full and entire
understanding and agreement between the parties with regard to the subjects hereof and supersedes in the entirety any prior understandings or agreements among the parties with regard to the same, and no party shall be liable or bound to any other in
any manner by any representations, warranties, covenants and agreements except as specifically set forth herein. For avoidance of doubt, the terms of the Amendment and Waiver dated July 27, 2015 shall remain in effect and shall apply to the
Agreement as amended hereby. 
 3. Counterparts. This Agreement may be executed in any number of counterparts, each of which shall be
an original, but all of which together shall constitute one instrument. 
 (signature page follows) 

  
 3 

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	JUNO THERAPEUTICS, INC.
	a Delaware corporation
		
	By:	 	 /s/ Hans E. Bishop

	Name:	 	Hans E. Bishop
	Title:	 	Chief Executive Officer

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	INVESTOR:
	
	ARCH Venture Fund VII, L.P.
	By:	 	ARCH Venture Partners VII, L.P.
	Its:	 	General Partner
	By:	 	ARCH Venture Partners VII, LLC
	Its:	 	General Partner
	
	 /s/ Keith Crandell

	Managing Director
	
	 Keith Crandell

	(Print name of signatory)

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	INVESTOR:
	
	CL ALASKA L.P.
	By:	 	Crestline SI (GP), L.P., its General Partner
	By:	 	Crestline Investors, Inc., its General Partner
		
	By:	 	 /s/ John Cochran

		
	Name:	 	 John Cochran

		
	Title:	 	 Vice President

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	INVESTOR:
		
	By:	 	 /s/ Francois Vigneault

	Name:	 	Francois Vigneault, Ph.D.
		
	Address:	 	 [omitted]

		 	  

		
	Fax:	 	  

		
	Email:	 	 [omitted]

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	INVESTOR:
		
	By:	 	 /s/ George Church

	Name:	 	George Church
		
	Address:	 	 [omitted]

		 	  

		
	Fax:	 	  

		
	Email:	 	 [omitted]

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	INVESTOR:
		
	By:	 	 /s/ Jeffrey M. Ostrove

	Name:	 	Jeffrey M. Ostrove, Ph.D.
		
	Address:	 	 [omitted]

		 	  

		
	Fax:	 	  

		
	Email:	 	 [omitted]

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	SANTE HEALTH VENTURES II, LP
	By: SHV Management Services II, L.P., its General
Partner
	By: SHV Management Services II, LLC, its General Partner

 
					
			
		 	By:	 	 /s/ Kevin Lalande

		 		 	Kevin Lalande, its Managing Member
			
		 	Address:	 	 [omitted]

		 	  

		 	  

			
		 	Fax:	 	 [omitted]

			
		 	Email:	 	 [omitted]

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	INVESTOR:
		
	By:	 	 /s/ Brian Booth

	Name:	 	Brian Booth
		
	Address:	 	[omitted]
		
	Fax:	 	 NA

		
	Email:	 	[omitted]

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	INVESTOR:
	
	SVP FINANCIAL GROUP
		
	FAX:	 	  

		
	Name:	 	 Mike Kruse

		
	Position:	 	 Treasurer

		
	Address:	 	[omitted]
		
	By:	 	 /s/ Mike Kruse

		
	Email:	 	[omitted]

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	INVESTOR:
	
	PRESIDENT AND FELLOWS OF HARVARD COLLEGE
		
	By:	 	 /s/ Isaac T. Kohlberg

	Name:	 	 Isaac T. Kohlberg

		 	Senior Associate Provost
		 	Chief Technology Development Officer
		 	Office of Technology Development
	Position:	 	 Harvard University

		
	Address:	 	[omitted]
		
	Fax:	 	  

		
	Email:	 	 [omitted]

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	INVESTOR:
		
	By:	 	 /s/ Mirza Cifric

	Name:	 	Mirza Cifric
		
	Address:	 	[omitted]
		
	Fax:	 	  

		
	Email:	 	[omitted]

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	INVESTOR:
		
	By:	 	 /s/ Teresa Broering

	Name:	 	Teresa Broering
		
	Address:	 	[omitted]
		
	Fax:	 	  

		
	Email:	 	[omitted]

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	INVESTOR:
		
	By:	 	 /s/ David Fabrizio

	Name:	 	David Fabrizio
		
	Address:	 	[omitted]
		
	Fax:	 	  

		
	Email:	 	[omitted]

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 The parties are signing this Amendment as of the date stated in the introductory clause. 

 

			
	INVESTOR:
	
	BIOINNOVATION, LLC
		
	By:	 	 /s/ Peter D. Parker

	Name:	 	Peter D. Parker
	Title:	 	Manager
		
	Address:	 	[omitted]
		
	Fax:	 	  

		
	Email:	 	[omitted]

 (Signature page to Amendment to Fourth Amended and Restated Investors’ Rights Agreement)

 EXHIBIT A 

INVESTORS – ABVITRO STOCKHOLDERS 

Sante Health Ventures II, L.P. 
 BioInnovation, LLC 

Francois Vigneault 
 George Church 

Mirza Cifric 
 President and Fellows of Harvard College 

Teresa Broering 
 David Fabrizio 

Jeffrey M. Ostrove, Ph.D. 
 Brian Booth 

Silicon Valley BankEX-10.4(C)

 Exhibit 10.4(C) 

AMENDMENT NO. 2 TO COLLABORATION AGREEMENT 

This Amendment No. 2 to Collaboration Agreement (the “Amendment No. 2”), effective as of October 16, 2013 (the
“Amendment No. 2 Effective Date”), is made by and between Fred Hutchinson Cancer Research Center, a Washington non-profit organization having offices at 1100 Fairview Ave. N., Seattle, WA 98109 (“FHCRC”), and
Juno Therapeutics, Inc., a Delaware corporation having offices at 307 Westlake Ave. North, Suite 300, Seattle, WA 98109 (“Juno”). 

WHEREAS, the parties entered into that certain Collaboration Agreement dated October 16, 2013, as amended by Amendment No. 1 thereto
dated November 19, 2014 (collectively, the “Original Agreement”); and 
 WHEREAS, the parties wish to amend the
Original Agreement under the terms and conditions herein. 
 NOW THEREFORE, in consideration of the premises and mutual promises set forth
in this Agreement, and other good and valuable consideration, the exchange, receipt and sufficiency of which are acknowledged, FHCRC and Juno hereby agree as follows: 

1. Definitions. The term “Agreement” as used in this Amendment No. 2 and in the Original Agreement shall mean the
Original Agreement as amended hereby. Except as otherwise set forth herein, the capitalized terms used herein and in the Original Agreement shall have the meaning set forth in the Original Agreement. 

2. Survival of Agreement Terms. Except as expressly set forth herein, the terms and conditions of the Original Agreement shall remain
in full force and effect. In the event of any conflict between the terms and conditions of this Amendment No. 2 and the Original Agreement, the terms and conditions set forth in this Amendment No. 2 shall control with respect to the
subject matter hereof. 
 3. Section 9.2(b). Section 9.2(b) of the Original Agreement is hereby deleted and replaced in its
entirety with the following Section 9.2(b): 
 “(b) Each party agrees that until publication of the results of the Study as
permitted under this Agreement each party will have the limited right to use Study Data, whether owned by it or another party, solely for internal research purposes and patient care purposes, and that it will not disclose Study Data to any other
person or entity except: (i) as necessary, in a party’s reasonable medical judgment, for the medical care of any research subject, (ii) as necessary for protection of that party’s interests against lawsuits, allegations of
scientific misconduct, conflict of interest actions, patent infringement and interference proceedings, (iii) as permitted by this Agreement 

 

[***] Certain information in this document has been omitted and filed separately with
the Securities and Exchange Commission. Confidential treatment has been requested with respect to the omitted portions. 

  

					
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 or the applicable Project Agreement (provided that [***]; for the avoidance of doubt, this
subsection (iii) will not limit FHCRC’s rights under subsections (i), (ii), (iv) or (v) of this Section 9.2(b)), (iv) for purposes of publication or public presentation as permitted under Section 10, (v) as
required by applicable laws and regulations including laws and regulations of the FDA relating to licensure of Study Products and laws and regulations of the National Institutes of Health (NIH) relating to government grants and contracts, and
(vi) with respect to Juno, to develop and advance the commercialization of cellular immunotherapy products (itself or via commercial relationships with third parties), subject to confidentiality restrictions as provided herein and other
applicable legal requirements with respect to such data. For clarity, Juno and its Affiliates shall have the irrevocable right to (and to authorize their Sublicensees, contractors and collaborators to) access, use and reference all Study Data [***]
in connection with the development and commercialization of [***], subject to confidentiality restrictions as provided herein and other applicable legal requirements with respect to such data. Notwithstanding anything to the contrary in this
Agreement (including, without limitation, any confidentiality restrictions), Juno and its Affiliates shall have the irrevocable right to (and to authorize their Sublicensees, contractors and collaborators to) access, use, reference and include any
and all Production Data and Study Data, including clinical data, for and in regulatory filings and patent applications (and related correspondence and filings), in connection with the development and commercialization of [***]. Ownership of Project
Intellectual Property will still be determined in accordance with Section 12.2 of this Collaboration Agreement.” 
 4.
Section 15.10. The following Section 15.10 is hereby inserted as a new section immediately after Section 15.9 of the Original Agreement: 

“15.10 Certain Definitions. “Affiliate” means, with respect to a party, any person or entity that directly or
indirectly controls, is controlled by, or is under common control with such party, where “control” means ownership of fifty percent (50%) or more of the outstanding voting securities of the entity in question (or such lesser
percentage which is the maximum allowed to be owned by a foreign corporation in a particular jurisdiction) or the power to otherwise control the voting or affairs of such entity. “Sublicensee” means any third party to whom Juno has
granted a sublicense.” 
 5. Miscellaneous. This Amendment No. 2 may be executed in two or more counterparts, each of which
will be deemed an original and all of which together will constitute the same agreement, whether or not all parties execute each counterpart. This Amendment No. 2 will be effective upon full execution by facsimile or original, and a facsimile
signature will be as effective as an original signature. This Amendment No. 2 may not be altered, amended or modified in any way except by a writing (excluding email or similar electronic transmissions) signed by the authorized representatives
of both parties. The Original Agreement and this Amendment No. 2 will be governed by, interpreted and enforced in accordance with the laws of the State of Washington, without regard to conflicts of laws. 

 

[***] Certain information in this document has been omitted and filed separately with the Securities and Exchange
Commission. Confidential treatment has been requested with respect to the omitted portions. 

  

					
		 	Page 2 of 3	 	Juno Confidential

 IN WITNESS WHEREOF, the parties by their duly authorized representatives have executed this Agreement as of the
Amendment No. 2 Effective Date. 
  

									
	JUNO THERAPEUTICS, INC.	 		 	FRED HUTCHINSON CANCER RESEARCH CENTER
					
	By:	 	 /s/ Bernard J. Cassidy
	 		 	By:	 	 /s/ Nicole C. Robinson

					
	Name:	 	 Bernard J. Cassidy
	 		 	Name:	 	 Nicole C. Robinson, Ph.D.

		 		 		 		 	VP, Business Development &
					
	Title:	 	 General Counsel & Secretary
	 		 	Title:	 	 Industry Relations

					
	Date:	 	 Feb. 17, 2016
	 		 	Date:	 	 February 17, 2016

 [Signature Page to Amendment No. 2 to Collaboration Agreement] 

  

					
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