Document:

EX-10.11

 Exhibit 10.11 

AMENDMENT NO. 2 to 

RESEARCH, DEVELOPMENT AND COMMERCIALIZATION AGREEMENT, 

DATED MAY 24, 2004, by and between VERTEX PHARMACEUTICALS INCORPORATED and CYSTIC FIBROSIS FOUNDATION THERAPEUTICS INCORPORATED 

This Amendment No. 2 (the “Second Amendment”) is made as of January 1, 2006 (the “Effective Date”)
by and between Vertex Pharmaceuticals Incorporated, a Massachusetts corporation with its principal offices at 130 Waverly Street, Cambridge, Massachusetts 02139-4242 (“Vertex”), and Cystic Fibrosis Foundation Therapeutics
Incorporated, a Delaware corporation with its principal offices at 6931 Arlington Road, Bethesda, Maryland 20814 (“CFFT”). 

This Second Amendment amends the Research, Development and Commercialization Agreement, dated May 24, 2004, by and between Vertex and
CFFT (the “Existing Agreement”), as amended by Amendment No. 1 to the Existing Agreement, dated January 6, 2006, by and between Vertex and CFFT (the “First Amendment”). Any reference herein to the
“Existing Agreement, as amended”, refers to the Existing Agreement and the First Amendment, unless the context otherwise requires. Vertex and CFFT are referred to herein individually as a “Party” and collectively as
the “Parties.” 
 Background 

In 1998, CFFT made an award to Aurora Biosciences Corporation (“Aurora”) to conduct a feasibility study using high throughput
screening for cystic fibrosis targets. On May 19, 2000, CFFT selected and provided support for Aurora to conduct high throughput screening with respect to the cystic fibrosis transmembrane conductance regulator (“CFTR”) target
identified by CFFT. Since that time, Aurora, and then after its merger into Vertex, Vertex, have been conducting a research program with CFFT’s support aimed at identification and design of “Potentiator” and “Corrector”
compounds, both of which are directed as a principal mode of therapeutic action at modulation of the biological effect of CFTR in different ways and with different anticipated results. 

 On May 24, 2004, the Parties executed the Existing Agreement. The Existing Agreement
contemplated that during the course of the research program, Vertex, with CFFT’s agreement, would select either the Potentiator or the Corrector approach as its Primary Program (as defined in the Existing Agreement), to which a majority of
resources under the research program would be directed, and the other approach would be designated as an Alternative Program (as defined in the Existing Agreement), to which the balance of resources would be directed. 

In 2005, with the concurrence of CFFT, Vertex selected the Potentiator approach as the Primary Program, and designated a certain Potentiator
Compound (“VX-770”) as a Development Candidate under the terms of the Existing Agreement. 

The Parties believe that it may be possible to create Corrector Compounds of significant potential value as therapeutics. To further that
effort, on January 6, 2006, the Parties executed the First Amendment. Among other things, the First Amendment provided for continued funding for research relating to Corrector Compounds. 

In connection with the First Amendment, the Parties executed a Term Sheet (the “Term Sheet”) outlining the financial terms
upon which CFFT might consider funding for the accelerated development of Potentiator Compounds. 
 This Second Amendment is intended
to set forth the Parties’ agreement with respect to additional funding for the accelerated development of Potentiator Compounds, and to amend the Existing Agreement and the First Amendment accordingly. 

  
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 Amendment 

In consideration of the mutual covenants set forth in this Second Amendment, and other good and valuable consideration, the receipt of which
is hereby acknowledged, the Parties agree as follows: 
 Section 1. Acceleration Funding Agreement 

This Second Amendment is intended to constitute the Potentiator Funding Agreement contemplated by the First Amendment (referenced as the
“Acceleration Funding Agreement” in the Term Sheet). Capitalized terms not otherwise defined in this Second Amendment shall have the meaning ascribed to them in the Existing Agreement, as amended. If specific provisions of this
Second Amendment are inconsistent with specific provisions of the Existing Agreement, as amended, the provisions of this Second Amendment, with respect to the subject matter of this Second Amendment, shall control. Otherwise, the Existing Agreement,
as amended, shall continue to be applicable. 
 Section 2. Development and Development Funding. 

2.1. Potentiator JDC Organization and Operation. 

2.1.1 Potentiator JDC Membership. As soon as practicable after the Effective Date, Vertex will establish a Potentiator Joint Development
Committee (the “Potentiator JDC”) consisting of not fewer than 8 members, as may be determined from time to time by the Potentiator JDC. The Potentiator JDC shall continue to function until FDA approval of a Potentiator Drug
Product. During the period ending December 31, 2008, the Potentiator JDC shall include an equal number of representatives designated by each of Vertex and CFFT. Thereafter, CFFT shall be entitled to four (4) representatives on the
Potentiator JDC. In addition to members appointed by CFFT, the Potentiator JDC is expected to have members from the 

  
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 various functional groups (e.g., research, preclinical safety, clinical, regulatory, marketing) that
are or will be expected to be involved from time to time in development and launch of VX-770 or any other Potentiator Backup Compound that is substituted for VX-770
(collectively VX-770 and such Potentiator Backup Compounds are referred to hereinafter as “VX-770”). Vertex will appoint the Potentiator JDC Chair. In
addition to Potentiator JDC members, attendees of Potentiator JDC meetings may include such Vertex or CFFT representatives as may be required for presentation to or discussion with the Potentiator JDC from time to time. 

2.1.2 Potentiator JDC Operation. The Potentiator JDC will be the principal organization through which the development of VX-770 is planned and evaluated, subject to appropriate review and approval at senior management levels as required by Vertex from time to time. The Potentiator JDC will be responsible for preparation and
implementation of the development plan described in Section 2.1.3, below, with respect to VX-770. The Potentiator JDC will typically meet at least quarterly, depending on the level of current development
activity. Each of Vertex and CFFT shall have one vote on the Potentiator JDC. The objective of the Potentiator JDC shall be to reach agreement by consensus on all matters overseen by the Potentiator JDC. However, except as hereinafter provided, in
the event of a deadlock with respect to any action, the vote of the Potentiator JDC Chair rendered after reasonable and open discussion among the members of the Potentiator JDC shall be final and controlling. 

2.1.3 Development Plan. The Potentiator JDC shall review the implementation of an overall development plan for VX-770. The development plan shall describe the proposed clinical trial activities, non-clinical development activities, and supply and manufacturing activities for VX-770. The initial development plan considered by Vertex for VX-770 (the “VX-770 Benchmark Potentiator Development
Plan”) and the development plan currently being 

  
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 implemented by Vertex (the “VX-770 Accelerated Potentiator
Development Plan”), are attached hereto as Exhibits 2.1.3A and 2.1.3B, respectively. The VX-770 Accelerated Potentiator Development Plan reflects a significant acceleration into 2006 or
2007 of certain development activities previously planned for later in the development process, with the objective of significantly accelerating the time to NDA filing if VX-770 is successful. The VX-770 Accelerated Potentiator Development Plan will be reviewed and may be further refined from time to time by the Potentiator JDC, based in part on data generated in early
pre-clinical and clinical trials. However, the Parties intend that separate clinical trails will be conducted for the G5551D and dF508 CF patients, as provided in Exhibit 2.1.3B, and to that end the IND
which Vertex filed on March 14, 2006 provides for separate Phase I clinical trials targeting G5551D and dF508 CF patient groups. The actual design of those Phase I and any further clinical trails may be influenced by FDA feedback, clinical and
nonclinical trial data and other scientific and medical information. Any change in the clinical plans will be reviewed by Vertex with the Potentiator JDC with the aim of reaching consensus before being implemented. 

2.1.4 Meeting Materials. The Potentiator JDC will consider all information that is material to an assessment of the status,
direction and progress of the development program for VX-770, including clinical trial protocols, a summary of the IND package, enabling animal toxicity data reports, clinical trial protocols, clinical trials
final reports, summary data and reports. The Potentiator JDC will review progress reports prepared by Vertex, which shall be submitted to the Potentiator JDC prior to each meeting and which shall include a summary in written text of progress made
during the preceding three month period under the VX-770 Accelerated Potentiator Development Plan. The chemical structure of VX-770 will be disclosed at the written
request of CFFT to one CFFT employee reasonably acceptable to Vertex who is a 

  
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 JDC member and who executes a customary form of confidentiality agreement directly with Vertex, undertaking
to maintain the chemical structure in confidence. Vertex will also disclose the chemical structure of VX-770 to CFFT’s chemistry advisors to whom it has previously disclosed the structure, under
confidential disclosure agreements previously executed with each such advisor, provided that such agreements explicitly cover the additional disclosure or are appropriately modified to that effect. The Potentiator JDC Chair will ensure that minutes
are prepared and distributed to each member of the Potentiator JDC after each meeting. Subject to the restrictions on disclosure of chemical structures set forth above, CFFT’s representatives on the Potentiator JDC will receive all documents
and information distributed or communicated to members of the Potentiator JDC. In any event, all information presented to the JDC or otherwise disclosed to CFFT by or at the direction of Vertex shall be deemed confidential to Vertex and subject to
the confidentiality provisions of the Existing Agreement. 
 2.2 Therapeutic Development Network. CFFT will use its good faith
efforts to foster discussions between the Therapeutic Development Network (“TDN”) and Vertex so that the TDN may enter into appropriate agreements with Vertex to provide to Vertex resources and expertise of the TDN to support
development efforts for VX-770. 
 2.3 Budget and Funding. Exhibit 2.3A contains a
summary “Benchmark Potentiator Budget” that sets forth the estimated costs of the VX-770 Benchmark Potentiator Development Plan originally proposed by Vertex, and a further summary budget, the
“Accelerated Potentiator Budget,” that sets forth the estimated costs of the VX-770 Accelerated Potentiator Development Plan, in each case for the period commencing January 1, 2006 and
ending December 31, 2007 (the “CFFT Accelerated Potentiator Funding Term”). A more detailed budget for the VX-770 Accelerated Potentiator Development Plan for 2006, based on 

  
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 Vertex’s most current activity and cost assumptions, is also attached as Exhibit 2.3B. Vertex
will provide comparable budgetary information for 2007 as soon as it becomes available in late 2006. CFFT agrees to bear $13.3 million of the actual Development Costs (as defined below) for VX-770 under
the VX-770 Accelerated Potentiator Development Plan; provided that (i) CFFT’s aggregate funding obligation (the “CFFT Accelerated Potentiator Funding”) shall not exceed
50% (fifty percent) of that portion of Vertex’s Development Costs incurred during the CFFT Accelerated Potentiator Funding Term that are in excess of the aggregate Development Costs summarized in the Benchmark Potentiator Budget for the CFFT
Accelerated Potentiator Funding Term; and (ii) CFFT’s funding obligation for the year 2006 shall not exceed $7.9 million unless CFFT otherwise agrees in writing. The budget for the
VX-770 Accelerated Potentiator Development Plan may be revised by the Potentiator JDC from time to time; except that the amount of CFFT Accelerated Potentiator Funding shall not be increased without the
written consent of CFFT. For purposes of this Amendment 2, the dates specified in Section 4.3 of the Existing Agreement for Vertex to provide CFFT with an accounting of all internal FTE’s and outsource costs will be changed to no later
than January 31, 2007 and 2008, respectively; and Vertex shall exercise its good faith efforts to furnish CFFT with such accounting as early in January as is possible. Funding will be reviewed by Vertex and CFFT at the end of each calendar year
during the CFFT Accelerated Potentiator Funding Term, and any amounts paid by CFFT during the calendar year that are in excess of the CFFT Accelerated Potentiator Funding amounts required under this Second Amendment will be credited against
CFFT’s 2007 funding obligations hereunder (if paid on account of activities during 2006), or promptly refunded by Vertex (if paid on account of activities during 2007). 

  
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 For the purpose of this Second Amendment, “Development Costs” shall mean
all internal and external costs associated with the VX-770 Accelerated Potentiator Development Plan, including but not limited to all (i) costs and expenses invoiced by third parties,
whether for goods or services associated with the development plan, and (ii) FTE costs of Vertex development scientists and management personnel with respect to time properly allocated to the
VX-770 Accelerated Potentiator Development Plan activities. Such internal costs may include, but not be limited to, (a) laboratory work; (b) regulatory planning, oversight
and review; (c) quality assurance activities; (d) pharmaceutical supply chain activities; (e) negotiations with clinical trial sites, institutional review boards, and suppliers;
(f) development plan research; (g) program management activities; (h) intellectual property creation and protection; (i) holding scientific discussions;
(j) traveling to and attending appropriate seminars and symposia; and (k) carrying out Potentiator JDC activities, provided, however, costs associated with (i) and (j) above shall only be allocated to the VX-770 Accelerated Potentiator Development Plan activities if they are attributable to personnel who spent more than half of their working time on such activities. Activities included in calculating FTE’s shall
not include negotiation of this Second Amendment or modifications or extensions of this Second Amendment or the Existing Agreement, as amended, or administrative activities such as accounting, invoicing, personnel related activities or the like.
FTEs allocated to activities under the VX-770 Accelerated Potentiator Development Plan shall be accounted for at the rate of $325,000 per FTE per annum. Payments for internal and external costs shall be
invoiced and paid pursuant to Section 4.3 of the Existing Agreement. 

  
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 At its sole discretion, and except as to amounts previously due to Vertex, CFFT shall have
the right to terminate the CFFT Accelerated Potentiator Funding Term and CFFT’s funding obligation hereunder effective December 31, 2006 or June 30, 2007 upon not less than sixty (60) days’ prior written notice to Vertex;
provided, however, that in the event of such a termination, the provisions of this Second Amendment will cease to apply effective as of the date of such termination (and, with respect to provisions of the Existing Agreement, as amended, which
were otherwise modified or amended by the provisions of this Second Amendment, such provisions shall be read without regard to any amendment or modification set forth in this Second Amendment). 

Section 3. Amendments to Corrector Contributions and Royalty Rates. 

3.1 Corrector Contributions. Effective as of January 6, 2006, Section 4.2 of the Existing Agreement, as amended, is further
amended as follows: the text in Section 4.2 up to and including the Initial Corrector Budget Chart is deleted, and, in its place the following is inserted: 

CFFT will fund seventy percent (70%) of the Initial Corrector Budget and Vertex will fund thirty percent (30%) of the Initial Corrector
Budget. Based on the approved Initial Corrector Budget of $27.3 million (which includes the $675,000 of Potentiator research funding referenced in the Research Plan), CFFT will make the payments to Vertex specified below during the specified
periods. 
  

									
	 	  	INITIAL CORRECTOR BUDGET
(millions $)	 
	 Research Period
	  	Aggregate
Budget
Amount	 	  	CFFT Financial
Commitment	 
	 January 1, 2006 — December 31, 2006
	  	$	12.6M	 	  	$	8.82M	 
	 January 1, 2007 — March 31, 2008
	  	$	14.7M	 	  	$	10.29M	 

 The text in the balance of Section 4.2 of the First Amendment (i.e., following the Initial Corrector Budget Chart)
remains unchanged. 
 3.2 Royalty Rates. Section 5.3.1 of the Existing Agreement is amended, as of the Effective Date, as
follows: 

  
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 (i) The number “4%” referenced in the royalty table
appearing in Section 5.3.1 of the Existing Agreement, as amended, is deleted, and in its place shall be inserted “6%”; 

(ii) The paragraph following the royalty table in Section 5.3.1 of the Existing Agreement, as amended, is deleted;
and in its place, the following is inserted: 
 Following the year in which cumulative Net Sales of all Drug Products in the Field first
exceed $1 billion, measured from the date of the First Commercial Sale of any such Drug Products, (a) the royalty rate for the first $250 million in annual Net Sales of such Drug Products in subsequent years shall be increased from
six percent (6%) to eight percent (8%); and (b) the calculation of Net Sales for any calendar year thereafter for purposes of computing the royalties referenced in Section 5.3.1, shall include all Net Sales of all Drug Products during that
year, for use in the Field, under the Existing Agreement, as amended to and including this Amendment. 
 (iii)
Section 5.3.2 of the Existing Agreement, as amended, is redesignated as Section 5.3.3, and the following new Section 5.3.2 is inserted: 

5.3.2 Additional Royalty. Vertex shall pay an additional royalty to CFFT in an amount equal to twice the amount of actual CFFT
Accelerated Potentiator Funding paid to Vertex under this Second Amendment, in two installments as set forth below. The additional royalty is assumed for illustrative purposes to be based on actual CFFT Accelerated Potentiator Funding of
$13.3 million, and based on that assumption a total of $26.6 million would be payable in the following amounts, in each case within thirty days after the first quarter in which cumulative Net Sales of Potentiator Drug Products have reached
the following levels: 
  

									
	 Cumulative Net Sales
	  	  
	 	  	Additional Royalty Amount	 
	$100 million	  				  	$	13.3 million	 
	$200 million	  				  	$	13.3 million	 
		  				  	  
	  
	 
	 Total:
	  				  	$	26.6 million	 

 For example, if the first Potentiator Drug Product is launched by Vertex on October 1, 2009, and
Cumulative Net Sales of that Drug Product reach $100 million by March 31, 2010, an Additional Royalty Amount of $13.3 million would then be payable to CFFT in addition to any other royalties due and payable under the Agreement.
Thereafter, if Cumulative Net Sales of Potentiator Drug Product reach $200 million on September 30, 2010, a further Additional Royalty Amount of $13.3 million would be payable to CFFT. 

  
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 (iv) The following new Section 5.3.4 is inserted: 

Net Sales under this Section 5.3 shall not in any event include any Net Sales of Drug Products that are the subject of the royalty
obligations set forth in the Section 5.3.3 or in Section 10.5.5. 
 Section 4. Existing Agreement Ratified. 

In all other respects, the Existing Agreement, as amended, is hereby ratified and confirmed. 

[Signature Page Follows] 

  
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 In witness whereof, the Parties hereto have executed this Agreement as of the day and
year first above written. 
  

									
	VERTEX PHARMACEUTICALS	  		 	CYSTIC FIBROSIS FOUNDATION
	INCORPORATED	  		 	THERAPEUTICS INCORPORATED
					
	By:	 	 /s/ Kenneth S. Boger
	  	        	 	By:	 	 /s/ Robert Beall

	Title: Senior VP and General Counsel	  		 	Title: President/CEO
	Date: 15 Mar 06	  		 	Date: March 16, 2006

  
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 Exhibit 2.1.3A 

[Gant chart setting forth benchmark Development Plan.] 

  
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 Exhibit 2.1.3B 

[Gant chart setting forth accelerated Development Plan.] 

  
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 Exhibit 2.3B 

Funding of VX-770 Development 

Budget Summary: The budget for the VX-770 Benchmark Potentiator Development Plan (“Benchmark Potentiator
Budget”) attached hereto as Exhibit 2.1.3A is as follows: 
  

									
	 	  	2006	 	  	2007	 
	 Benchmark Budget
	  				  			
	 Internal
	  	$	6.34 M	 	  	$	7.54 M	 
	 External
	  	 	4.64 M	 	  	 	5.19 M	 
		  	  
	  
	 	  	  
	  
	 
	 Total
	  	$	10.98M	 	  	$	12.73M	 

 The budget for the VX-770 Accelerated Potentiator Development Plan (the
“Accelerated Potentiator Budget”) attached hereto as Exhibit 2.1.3B is as follows: 
  

									
	 	  	2006	 	  	2007	 
	 Accelerated Budget
	  				  			
	 Internal
	  	$	13.18 M	 	  	$	13.82 M	 
	 External
	  	 	13.73 M	 	  	 	27.06 M	 
		  	  
	  
	 	  	  
	  
	 
	 Total
	  	$	26.91 M	 	  	$	40.88 M	 

 [Chart setting forth Detailed Accelerated Potentiator Budget.]EX-10.12

 Exhibit 10.12 

Execution Copy 
 CERTAIN
IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THIS EXHIBIT BECAUSE IT 
 IS BOTH (I) NOT MATERIAL AND (II) WOULD LIKELY CAUSE
COMPETITIVE HARM IF 
 PUBLICLY DISCLOSED. [***] INDICATES THAT INFORMATION HAS BEEN REDACTED. 

AMENDMENT NO. 5 to 

RESEARCH, DEVELOPMENT AND COMMERCIALIZATION AGREEMENT, 

DATED MAY 24, 2004, by and between VERTEX PHARMACEUTICALS INCORPORATED and CYSTIC 

FIBROSIS FOUNDATION THERAPEUTICS INCORPORATED 

This Amendment No. 5 (the “Fifth Amendment”) is made effective as of April 1, 2011 (the “Effective
Date”) by and between Vertex Pharmaceuticals Incorporated, a Massachusetts corporation with its principal offices at 130 Waverly Street, Cambridge, Massachusetts 02139-4242 (“Vertex”), and Cystic Fibrosis Foundation
Therapeutics Incorporated, a Delaware corporation with its principal offices at 6931 Arlington Road, Bethesda, Maryland 20814 (“CFFT”). 

This Fifth Amendment amends the Research, Development and Commercialization Agreement, dated May 24, 2004, by and between Vertex and CFFT
(the “Original Agreement”), as amended by Amendment No. 1 to the Original Agreement, dated January 6, 2006 (the “First Amendment”), Amendment No. 2 dated January 1, 2006 (the “Second
Amendment”), Amendment No. 3 dated November 20, 2006 (the “Third Amendment”), and Amendment No. 4 dated August 20, 2007 (the “Fourth Amendment”). Any reference herein to the
“Original Agreement, as amended”, refers to the Original Agreement and all amendments, excluding this Fifth Amendment, unless the context otherwise requires. Vertex and CFFT are referred to herein individually as a
“Party” and collectively as the “Parties.” 

 Background 

In 1998, CFFT made an award to Aurora Biosciences Corporation (“Aurora”) to conduct a feasibility study using high throughput
screening for cystic fibrosis targets. On May 19, 2000, CFFT selected and provided support for Aurora to conduct high throughput screening with respect to the cystic fibrosis transmembrane conductance regulator (“CFTR”) target
identified by CFFT. From that time until March 31, 2008 (the “Original Research Term”), Aurora, and then after its merger into Vertex, Vertex, conducted a research program with CFFT’s support aimed at identification and
design of “Potentiator” and “Corrector” compounds, both of which are directed as a principal mode of therapeutic action at modulation of the biological effect of CFTR in different ways and with different anticipated results. 

On May 24, 2004, the Parties executed the Original Agreement. The Original Agreement contemplated that during the course of the research
program, Vertex, with CFFT’s agreement, would select either the Potentiator or the Corrector approach as its Primary Program (as defined in the Original Agreement, as amended), to which a majority of resources under the research program would
be directed, and the other approach would be designated as an Alternative Program (as defined in the Original Agreement, as amended), to which the balance of resources would be directed. 

In 2005, with the concurrence of CFFT, Vertex selected the Potentiator approach as the Primary Program, and designated a certain Potentiator, VX-770, as a Development Candidate under the terms of the Original Agreement, as amended. On March 16, 2006, the Parties executed the Second Amendment, which provided for funding for the accelerated development
of Potentiator Compounds. On November 20, 2006, the Parties executed the Third Amendment, which allocated on-going CFFT funding to the Vertex Potentiator Back-up
Program. 
 To further the discovery of Corrector Compounds of significant potential value as therapeutics, on January 6, 2006, the
Parties executed the First Amendment, which provided, among other things, for continued funding for research relating to Corrector Compounds. On August 20, 2007, the Parties executed the Fourth Amendment, which
re-allocated certain of the Corrector Research Program funding in order to support accelerated preclinical development of the Corrector Development Candidate VX-809.
Upon termination of the Original Research Term, the Original Agreement, as amended, expired pursuant to Section 10.1, and certain provisions, set forth in Section 10.4 of the Original Agreement, as amended, survived. 

  
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 As of the date of this Fifth Amendment, Vertex is continuing the clinical development of the
Potentiator VX-770, the Corrector VX-809, and a combination regimen of both VX-770 and
VX-809. Vertex also is developing the Corrector VX-661, which was discovered during the Original Research Term, and intends to identify
VX-661 as a Development Candidate in accordance with Section 3.1 of the Original Agreement, as amended. VX-809 and VX-661,
together with any additional Correctors discovered by Vertex during the Original Research Term are referred to in this Fifth Amendment as “First Generation Correctors.” 

In furtherance of its charitable purpose to cure and/or mitigate the effects of cystic fibrosis, CFFT intends to provide the additional
funding specified in this Fifth Amendment for the research and development of Correctors for cystic fibrosis. This Fifth Amendment sets forth the Parties’ agreement with respect to such (a) additional funding from CFFT to support clinical
development of VX-661, (b) additional funding from CFFT for a new research term to conduct further research relating to discovery of additional Corrector Compounds, such newly-discovered compounds to be
referred to herein as “Second Generation Correctors,” and (c) clinical development of Second Generation Corrector(s), in accordance with the Original Agreement, as amended, together with this Fifth Amendment; and to amend the
Original Agreement, as amended, accordingly. 

  
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 Capitalized terms not otherwise defined in this Fifth Amendment shall have the meaning
ascribed to them in the Original Agreement, as amended. Terms used in this Fifth Amendment to refer to a Drug Product which is prepared from a specific Drug Product Candidate or Category of Drug Candidate, for example, Drug Product prepared from VX-770 or Second Generation Correctors, shall be referred to herein by identifying the Drug Product Candidate or category, such as VX-770 Drug Product or Second Generation
Corrector Drug Product. If specific provisions of this Fifth Amendment are inconsistent with specific provisions of the Original Agreement, as amended, the provisions of this Fifth Amendment, with respect to the subject matter of this Fifth
Amendment, shall control. Otherwise the Original Agreement, as amended, to the extent its provisions have survived the termination of the Original Research Term, shall continue to be applicable. 

Amendment 
 In
consideration of the mutual covenants set forth in this Fifth Amendment, and other good and valuable consideration, the receipt of which is hereby acknowledged, the Parties agree as follows: 

Section 1. First Generation Corrector Development and Development Funding. 

1.1 VX-661 as Drug Product Candidate. The Parties agree that
VX-661 will be designated as a Development Candidate, and that Vertex has commenced a Development Program with respect thereto. The Corrector JDC in place for VX-809
development shall serve as the JDC for VX-661. 
 1.2 Development Plan. The Corrector JDC
shall review implementation of the overall development plan for VX-661. The development plan shall describe the proposed clinical trial activities, non-clinical
development activities, and supply and manufacturing activities for VX-661. Any change in the development plan for VX-661 will be reviewed [***]. 

  
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 1.3 Budget and Funding. Exhibit 1.3(a) contains a summary that sets forth
certain estimated costs of the proposed VX-661 development activities for the period through the completion of the [***]. CFFT agrees to fund up to [***]. The proposed activities and
budget[***] for the VX-661 development program may be revised by the Corrector JDC from time to time, provided that the amount of [***] to be reimbursed by CFFT shall not be increased without the
written consent of CFFT. 
 [***]. On the Effective Date CFFT shall pay Vertex [***] (of the total [***] to be funded)
[***]. For purposes of this Fifth Amendment, Vertex will provide CFFT with [***] reports within [***] (commencing with the second calendar quarter of 2011) showing expenses incurred and invoices received under the VX-661 development program during the quarter just ended against budgeted expenses for that quarter (which, for the second calendar quarter of 2011, shall include any expenses for activities undertaken during the
first calendar quarter of 2011 that were invoiced [***]). Payments due for [***] shall be made by CFFT to Vertex [***] within [***] following receipt by CFFT of an invoice for such
VX-661 External Development Costs accompanied by usual and customary documentation of such costs, including copies of Third Party invoices supporting such costs and evidence that the costs relate to the VX-661 development program. All payments shall be made without deduction for withholding or similar taxes in United States dollars to the credit of such bank account as may be designated in writing to CFFT. Any
payments that fall due on a date that is a legal holiday in The Commonwealth of Massachusetts may be made on the next following day that is not a legal holiday in The Commonwealth. 

  
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 If the development program for VX-661 is
discontinued or the VX-661 External Development Costs incurred to advance VX-661 through completion of the [***] are less than [***], CFFT agrees, subject
to termination rights by CFFT in accordance with this Fifth Amendment, that any funds remaining from the original [***] funding commitment hereunder will be available to reimburse Vertex for the actual external development costs related to
continued development of First Generation Correctors, on the invoicing and payment terms set forth in this Section 1.3 as if it were with respect to VX-661 External Development Costs. 

At its sole discretion, CFFT shall have the right to terminate its funding obligation under this Section 1.3, effective upon written
notice provided to Vertex [***]. Upon any such funding termination: (a) CFFT shall be responsible to fund only those costs incurred for activities initiated by Vertex and for which Vertex has incurred
non-terminable obligations to a Third Party prior to the funding termination; (b) the royalty rates for Net Sales of VX-661 Drug Product and VX-809 Drug Product set forth in Section 5.3.1(b), [***], as illustrated by the examples set forth in Exhibit 1.3(c); and (c) Section 10.6 of the Original Agreement, as amended by this
Fifth Amendment, shall terminate and CFFT shall have none of the rights set forth in such Section 10.6. 
 Section 2. Second Generation
Corrector Research and Development Program Funding. 
 2.1 Research Plan and Program. Beginning on the Effective Date,
the “Research Program” will refer to research undertaken under the terms of this Fifth Amendment pursuant to the research plan for Second Generation Corrector Research (which shall be the “Research Plan” referred to
in Section 2.4 of the Original Agreement, as amended, and the research conducted under the Research Plan shall be the “Research Program” under the Original Agreement, as amended, and under this Fifth Amendment), an initial
version of which is attached hereto as Exhibit 2.1 (the “Second Generation Corrector Research Plan”). The “Research Term” shall begin on the Effective Date and end on the Research Termination Date (as defined
in this Fifth Amendment). 

  
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 2.2 Budget; Funding Obligation; Payments. The budget for the Research Program
[***] (as defined in this Fifth Amendment) is attached hereto as Exhibit 2.2(a) (as revised during the term of the Research Program, the “Second Generation Corrector Research Budget”). CFFT agrees to fund up to
[***] of the costs of the Research Program for Second Generation Correctors as set forth herein and in the Second Generation Corrector Research Budget, including Vertex internal costs and external costs, for research and development
activities, which for purposes of this Fifth Amendment, shall include all research and development activities undertaken with respect to a Second Generation Corrector or Correctors from [***]. 

For purposes of this Fifth Amendment, Vertex will provide CFFT with [***] reports within [***] (commencing with the second
calendar quarter of 2011) showing expenses incurred and invoices received under the Research Program during the quarter just ended against budgeted expenses for that quarter. The first such report shall be due after completion of the second calendar
quarter of 2011, and will cover the period from [***] through the end of that quarter. 
 Payments due under the Second Generation
Corrector Research Budget on account of internal FTEs shall be made by CFFT [***]. Internal FTE costs will be calculated at an annual rate of $[***] per FTE. On the Effective Date CFFT shall pay [***] (of the total [***]
to be funded), [***]. 

  
 7 

 Payments due on account of external costs of the Research Program shall be made by CFFT to
Vertex [***] within [***] days following receipt by CFFT of an invoice for such external costs accompanied by usual and customary documentation of such costs, including copies of Third Party invoices supporting such costs and evidence
that the costs relate to the Research Program. For all non-United States Dollar expenditures, documentation of the currency conversion rate shall be provided. Each invoice shall also include a quarterly “true-up” of internal FTEs. Accounting and invoicing for expenditures for the Research Program shall be maintained and provided separately from those for the VX-661
development program. 
 On or before January 31 of each year during the Research Term, Vertex will provide CFFT with an accounting of
all internal FTE costs and external research costs (including documentary evidence of external FTEs and other costs, which shall include a yearly FTE true-up) incurred under the Research Program during the
most recently concluded calendar year. If CFFT’s funding for any reporting period is in excess of the amount set forth in the Second Generation Corrector Research Budget for that period, the excess amount will be carried over and applied as a
credit against CFFT’s required funding in future periods, subject to the limit of CFFT’s funding obligation set forth above. If CFFT’s funding for any reporting period is less than the amount set forth in the Second Generation
Corrector Research Budget for that period, the balance remaining will be carried over and added to the budgeted amount for the next reporting period. If there is any unexpended funding provided by CFFT at the termination of the Research Program, it
shall be promptly returned to CFFT. To the extent not inconsistent with the provisions of this Amendment, the provisions of Section 4.5 of the Original Agreement, as amended, will apply to the Research Program. 

  
 8 

 CFFT agrees to fund up to [***] of external development costs for Second Generation
Correctors, as set forth in the estimated development budget in Exhibit 2.2(b), which for purposes of this Fifth Amendment shall include all costs and expenses invoiced by Third Parties, whether for goods or services, associated with the
development of a Second Generation Corrector or Correctors at any time after an IND is opened for such Second Generation Corrector or Correctors. Vertex will provide CFFT with [***] reports within [***] showing external expenses
incurred in development of Second Generation Corrector(s) during the quarter just ended against budgeted expenses for that quarter. Payments due for such expenses shall be made by CFFT to Vertex [***] within [***] days following
receipt by CFFT of an invoice for such expenses accompanied by usual and customary documentation of such costs. 
 For illustrative
purposes, Exhibit 2.2(c) shows the total combined costs to be funded by CFFT for (i) the Second Generation Corrector Research Program (as set forth in greater detail in Exhibit 2.2(a)) and (ii) the estimated external
development costs for the clinical development of Second Generation Correctors (as set forth in greater detail in Exhibit 2.2(b)). 

All payments made by CFFT under this Section 2.2 shall be made without deduction for withholding or similar taxes in United States
dollars to the credit of such bank account as may be designated in writing to CFFT. Any payments that fall due on a date that is a legal holiday in The Commonwealth of Massachusetts may be made on the next following day that is not a legal holiday
in The Commonwealth. 
 2.3 Conduct of Research. Vertex will dedicate a minimum average of [***] FTE scientists (on an
annualized basis) to the Research Program during its term[***]. 
 2.4 Termination of Research and/or Development Funding. The
Research Term shall end on [***], unless the Research Program is otherwise extended or terminated in accordance with this Fifth Amendment (the “Research Termination Date”). After the Research Termination Date, CFFT shall be
responsible to fund only those expenses that do not exceed the Second Generation Corrector Research Budget for activities initiated by Vertex prior to the Research Termination Date and for which Vertex has either incurred non-terminable obligations to a Third Party, or which require a minimal amount of time and/or resources to complete after the Research Termination Date. 

  
 9 

 CFFT may in its sole discretion upon [***] notice provided any time after the first
anniversary of the Effective Date terminate its funding obligation for the Research Program. In addition, at its sole discretion, CFFT shall have the right to terminate its funding obligations for external development costs for Second Generation
Correctors [***]. Upon any such funding termination: (a) CFFT shall be responsible to fund those internal costs incurred for research activities, if any, initiated by Vertex prior to the termination and/or external costs for activities
initiated by Vertex and for which Vertex has incurred non-terminable obligations to a Third Party prior to the funding termination; (b) the royalty rates set forth in Sections 5.3.1(c)[***] shall
be reduced [***]; and (c) Section 10.6 of the Original Agreement, as amended by this Fifth Amendment, shall terminate and CFFT shall have none of the rights set forth in such Section 10.6. 

Section 3. Amendments to Royalty Rates. 

3.1 Royalty Rates. Section 5.3.1 of the Original Agreement, as amended, is deleted, and in its place the following shall be
inserted: 
 “5.3.1 Net Sales in the Field 

(a) Vertex shall pay to CFFT the following royalties on Net Sales 

[***]: 
  

	 	•	 	 [***] 

  

	 	•	 	 [***] 

  

	 	•	 	 [***]; 

[***]. 

  
 10 

 (b) [***]: 

 

	 	•	 	 [***]  

  

	 	•	 	 [***]. 

[***]. 

(c) [***]: 
  

	 	•	 	 [***] 

  

	 	•	 	 [***]. 

[***]. 

3.2 Section 5.3.2 of the Original Agreement, as amended, is amended by designating the original language as subparagraph (a), and
adding the following as subparagraph (b): 
 (b) “Vertex also shall pay [***] in two equal installments, as set
forth below. [***] which would be payable in the following amounts, in each case within [***] after the [***] in which cumulative Net Sales of Drug Products containing VX-661 or VX-809 have reached the following levels: 
  

					
	 [***]
	  		  	 [***]

	 [***]
	  		  	 [***]

	 [***]
	  		  	 [***]

		  	 [***]
	  	[***]”

  
 11 

 Section 4. Miscellaneous Provisions. 

Section 4.1 Interruption. Section 10.6 of the Original Agreement, as amended, shall be deleted in its entirety,
and the following substituted therefore: 
 10.6 Interruption. 

10.6.1 Definitions. For purposes of this Agreement, the terms defined in this Section 10.6.1 shall have the
following meanings: 
 10.6.1.1 “Ceased”, with respect to the development of a Development Candidate, will
mean that Vertex has ceased commercially reasonable development activity, in accordance with the standards of commercial reasonableness set forth in Section 3.1 of the Original Agreement, as amended, with respect to that Development Candidate
for a period of twelve consecutive months. 
 10.6.1.2 “Follow-on”
[***]. 
 10.6.1.3 “Lead” [***]. 

10.6.1.4 “Permitted Reason” shall mean, with respect to any Second Generation Corrector: 

(a) Vertex has not completed a clinical study of such Second Generation Corrector designed to establish so-called “proof-of-concept (“POC”), but either (i) Vertex obtained evidence that such compound is unlikely
to achieve Successful POC; or (ii) such compound failed to demonstrate Successful Pre-Clinical CFTR Correction Activity; or 

(b) Vertex completed clinical studies designed to establish POC for the compound and the compound failed to achieve Successful
POC. 
 10.6.1.5 “Successful Pre-Clinical CFTR Correction Activity”
shall mean, with respect to any compound, demonstration that the compound [***]; and (b) [***]. [***]. 

  
 12 

 10.6.1.6 “Successful POC” shall mean demonstration by a
compound [***] of [***]. 
 10.6.1.7 “Vertex” for the purpose of this Section 10.6 only
shall mean Vertex or any of its Affiliates, licensees, sublicensees, assignees or partners. 
 10.6.2 Interruption;
License to CFFT. If, prior to commercialization by Vertex of a Second Generation Corrector, Vertex has ceased development with respect to all Correctors (first generation and second generation), there shall be deemed to be an
“Interruption.” In the event of an Interruption, the following license in favor of CFFT shall become effective: 

(a) if Vertex is not commercializing any First Generation Corrector at the time of the Interruption, then CFFT shall have an
irrevocable, exclusive worldwide license [***], with the right to sublicense, under the Vertex CF Technology, to develop, manufacture, have manufactured, use, sell, offer to sell and import those Compounds in the Field; or 

(b) if Vertex is commercializing a First Generation Corrector at the time of the Interruption, then CFFT shall have an
irrevocable, exclusive worldwide license [***], with the right to sublicense, under the Vertex CF Technology, to develop, manufacture, have manufactured, use, sell, offer to sell and import those Compounds in the Field; 

provided, however, the license under this Section 10.6.2(b) shall not encompass any Corrector for which Vertex ceased
Development for a Permitted Reason. 
 [***]. 

  
 13 

 10.6.3. Termination of Interruption Rights. This Section 10.6
shall terminate, and CFFT shall have no further rights hereunder, immediately upon the First Commercial Sale of a Second Generation Corrector Drug Product, and as otherwise provided in this Fifth Amendment. 

Section 4.2 Termination upon Vertex
Change-in-Control. CFFT shall have the right, exercisable in its sole discretion, to terminate all of its funding obligations under this Fifth Amendment upon a Change-in-Control of Vertex, subject to CFFT’s obligations to fund previously committed amounts in accordance with the provisions of this Fifth Amendment. In the event of
any such termination prior to an Interruption (as defined above), the provisions of Section 10.6 shall be terminated and have no further force or effect. For purposes of this Section 4.2, a “Change-in-Control” shall mean that any “person” or “group,” as such terms are used in Sections 13(d) and 14(d)(2) of the Securities Exchange Act of 1934 (the
“Act”), becomes a beneficial owner, as such term is used in Rule 13d-3 promulgated under the Act, of securities of Vertex representing more than [***] of the combined voting power of
the outstanding securities of Vertex having the right to vote in the election of directors; or (b) all or substantially all the business or assets of Vertex are sold or disposed of, or Vertex or a subsidiary of Vertex combines with another
company pursuant to a merger, consolidation, or other similar transaction, other than (i) a transaction solely for the purpose of reincorporating Vertex or one of its subsidiaries in a different jurisdiction or
recapitalizing or reclassifying Vertex’s stock; or (ii) a merger or consolidation in which the shareholders of Vertex immediately prior to such merger or consolidation continue to own at least a majority of the outstanding voting
securities of Vertex or the surviving entity immediately after the merger or consolidation. 

  
 14 

 Section 4.3 Publicity. The provisions of Section 6.3
of the Original Agreement shall apply to this Fifth Amendment as if it were being entered into as part of the Original Agreement, as amended. The Parties will agree on the timing and content of a press release relating to this Fifth Amendment. 

Section 4.4 Third Party Testing. 

Upon receipt of a Testing Request (as defined below) from CFFT, Vertex will supply to an Agreed Lab (as defined below) reasonably adequate
quantities of the Lead and/or the Follow-on (as such terms are defined in Section 10.6.1, as revised by this Fifth Amendment), as necessary to enable the Agreed Lab to conduct in vitro testing of the
efficacy and potency of either or both of such Compounds [***] (for purposes of this Section 4.4, the “Vertex Assay”). All such testing will be undertaken at the expense of CFFT in addition to any funding otherwise
provided hereunder. 
 An “Agreed Lab” is a commercial testing laboratory unaffiliated with either CFFT or Vertex and
reasonably acceptable to both, which (a) specializes in rendering services to the pharmaceutical industry and has nationally recognized expertise in the testing of pharmaceutical compounds; (b) has a superior reputation for integrity in
dealing with the proprietary information of others and would be free of any real or apparent conflict of interest in performing the services which are the subject of this Section 4.4; and (c) is bound by the terms of a confidentiality
agreement with Vertex which is customary in form and content, which covers the testing contemplated by this Section 4.4, and which permits the Agreed Lab to report directly to CFFT and Vertex the results which it obtains with respect to
efficacy and potency of the Lead and/or Follow-on. The Agreed Lab will adhere strictly to testing protocol approved by Vertex and shall be required to report all testing results directly to both CFFT and
Vertex. [***]. 

  
 15 

 A “Testing Request” is a written request relating to the testing of either
the Lead or Follow-on, which is delivered by CFFT to Vertex within the [***] period beginning upon receipt by CFFT of notification from Vertex of its identification of such Compound as Development
Candidate. 
 Vertex and CFFT acknowledge that the use of a commercially available assay equivalent to the Vertex Assay for the testing of
the Lead and Follow-on may yield results which are less robust than the results obtained by use of the Vertex Assay. The Parties also acknowledge that the transfer of the Vertex Assay to an Agreed Lab may be
difficult, and the results less than satisfactory, without a commitment of substantial time and effort by Vertex which, if undertaken, may adversely impact the progress of the Research Program. Therefore, the parties agree that Vertex’s
responsibility for the testing provided under this Section 4.4 shall be limited as follows: (a) Vertex will cooperate with CFFT in the selection of an Agreed Lab , as may be requested by CFFT, and thereafter will assist in the
determination whether commercially available assays conducted by the Agreed Lab are likely to provide satisfactory results; (b) Vertex will provide the Agreed Lab with requisite amounts of each Compound, in connection with Testing Requests from
CFFT as provided above, out of any supplies which Vertex may have on hand; (c) Vertex will provide telephone consulting to appropriate representatives of the Agreed Lab concerning applicable assay methodology; (d) if the parties conclude
that conventional testing will not yield adequate results, and upon the written request of CFFT rendered with due regard to the [***] to establish an assay based on proprietary protocols from Vertex, Vertex will provide the Vertex Assay to
the Agreed Lab sufficiently in advance of any testing provided for in this Section 4.4 to accommodate such testing, under provisions of confidentiality, restricted access and non-use (for other than
testing hereunder), and will ensure that appropriate Vertex representatives are available by telephone from time to time to answer questions and otherwise assist the Agreed Lab representatives in their efforts to establish the Vertex Assay. Vertex
shall in no event be responsible for any failure by the Agreed Lab to establish an effective assay using Vertex’s protocols, nor shall any time periods provided herein for action by CFFT be extended by reason of any such failure. 

  
 16 

 Section 5. Original Agreement Ratified; Certain Expired Provisions Reinstated. 

In all other respects, the Original Agreement, as amended, to the extent unexpired, is hereby ratified and confirmed. The following provisions,
which expired under the Original Agreement, as amended, as a result of the conclusion of the Original Research Term, are hereby reinstated effective on the Effective Date solely for the purposes and to the extent applicable to the subjects addressed
in this Fifth Amendment: 2.4.1, 2.6, 2.7, 2.8, 10.1, 10.4, and Article XIII, and all other provisions that have expired as of the Effective Date, whether set forth in the Original Agreement or any amendment to the Original Agreement, shall have no
force or effect as a result of the execution of this Fifth Amendment. 
 [Signature Page Follows] 

  
 17 

 In witness whereof, the Parties hereto have executed this Agreement as of the day and
year first above written. 
  

									
	VERTEX PHARMACEUTICALS,	 		 	CYSTIC FIBROSIS FOUNDATION
	INCORPORATED	 		 	THERAPEUTICS, INCORPORATED
					
	By:	 	 /s/ Matthew W. Emmens
	 		 	By:	 	 /s/ Robert J. Beall

	Title:	 	Chairman, CEO & President	 		 	Title:	 	President & CEO
	Date:	 	April 4, 2011	 		 	Date:	 	April 4, 2011

  
 18 

 Exhibit 1.3(a) 

[***] 

  
 19 

 Exhibit 1.3(b) 

[***] 

  
 20 

 Exhibit 1.3(c) 

[***] 

  
 21 

 Exhibit 2.1 

Second Generation Corrector Research Plan 

[***] 

  
 22 

 Exhibit 2.2(a) 

[***] 

  
 23 

 Exhibit 2.2(b) 

[***] 

  
 24 

 Exhibit 2.2(c) 

[***] 

  
 25 

 Exhibit 2.4 

[***] 

  
 26

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