Document:

Amended and Restated Agreement, dated June 2, 1997

 Exhibit 10.05 
  
 Confidential treatment has been requested for portions of this Exhibit. The copy filed herewith omits the information subject to the confidentiality request. Omissions
are designated as ***. A complete version of this Exhibit has been filed separately with the Securities and Exchange Commission. 
  
 EXECUTION COPY 
  
 AMENDED AND RESTATED 
 COLLABORATIVE RESEARCH, DEVELOPMENT 
 AND MARKETING AGREEMENT 
  
 Between 
  
 MITOTIX, INC. 
  
 and 
  
 THE DUPONT MERCK PHARMACEUTICAL COMPANY

  
 dated as of June 2, 1997 

 TABLE OF CONTENTS 
  

							
	 ARTICLE 1.
	  	DEFINITIONS	  	1
	 1.1
	  	“Affiliate”	  	1
	 1.2
	  	“Allowable Expense”	  	2
	 1.3
	  	“Alternate UBC Plan”	  	2
	 1.4
	  	“Antisense”	  	2
	 1.5
	  	“Annual CDK Research Plan”	  	2
	 1.6
	  	“Annual Research Plan and Budget”	  	2
	 1.7
	  	“Calendar Quarter”	  	2
	 1.8
	  	“Calendar Year”	  	2
	 1.9
	  	“Cdc 27/Cdc 16 License”	  	2
	 1.10
	  	“CDK Collaboration”	  	2
	 1.11
	  	“CDK Research Operating Committee”	  	2
	 1.12
	  	“CDK Development Compounds”	  	2
	 1.13
	  	“CDK-D Development Compounds”	  	2
	 1.14
	  	“CDK-non-D Development Compounds”	  	2
	 1.15
	  	“CDK Field”	  	3
	 1.16
	  	“CDK-D Field”	  	3
	 1.17
	  	“CDK-non-D Field”	  	3
	 1.18
	  	“CDK Patent Rights”	  	3
	 1.19
	  	“CDK Products”	  	3
	 1.20
	  	“CDK Research Program”	  	3
	 1.21
	  	“CDK Targets”	  	3
	 1.22
	  	“CDK-D Targets”	  	3
	 1.23
	  	“CDK-non-D Targets”	  	4
	 1.24
	  	“Collaboration”	  	4
	 1.25
	  	“Collaborative Policy Setting Committee”	  	4
	 1.26
	  	“Cyclin E License”	  	4
	 1.27
	  	“Cyclin D License”	  	4
	 1.28
	  	“Competitive Product”	  	4
	 1.29
	  	“Development Partner”	  	4
	 1.30
	  	“Distributor”	  	4
	 1.31
	  	“DuPont Merck Inventions”	  	4
	 1.32
	  	“Effective Date”	  	4
	 1.33
	  	“Extended UBC Collaboration”	  	5
	 1.34
	  	“Extension Notice”	  	5
	 1.35
	  	“First Commercial Sale”	  	5
	 1.36
	  	“Gene Therapy”	  	5
	 1.37
	  	“Immunoassay Product”	  	5
	 1.38
	  	“IND”	  	5
	 1.39
	  	“Initial UBC Term”	  	5
	 1.40
	  	“Inventions”	  	5
	 1.41
	  	“IPO”	  	5
	 1.42
	  	“Know-how”	  	5
	 1.43
	  	“Mitotix Inventions”	  	5

  

 (i) 

							
	 1.44
	  	“Mitotix Pending License Agreements”	  	5
	 1.45
	  	“Mitotix License Agreements”	  	5
	 1.46
	  	“Mitotix Product”	  	6
	 1.47
	  	“Net Sales”	  	6
	 1.48
	  	“New UBC Target”	  	7
	 1.49
	  	“NDA”	  	7
	 1.50
	  	“Percentage Contribution”	  	7
	 1.51
	  	“pl6 License”	  	7
	 1.52
	  	“PRAD1 License”	  	7
	 1.53
	  	“Product Patent Rights”	  	7
	 1.54
	  	“Radiopharmaceutical”	  	7
	 1.55
	  	“Radiopharmaceutical Product”	  	7
	 1.56
	  	“Research Operating Committees”	  	7
	 1.57
	  	“Research Year”	  	8
	 1.58
	  	“Royalty-Bearing Products”	  	8
	 1.59
	  	“Royalty Term”	  	8
	 1.60
	  	“Strategic Countries”	  	8
	 1.61
	  	“Target”	  	8
	 1.62
	  	“Third Party”	  	8
	 1.63
	  	“UBC Collaboration”	  	8
	 1.64
	  	“UBC Deferral Payment”	  	8
	 1.65
	  	“UBC Development Compounds”	  	8
	 1.66
	  	“UBC Extension Payment”	  	8
	 1.67
	  	“UBC Field”	  	9
	 1.68
	  	“UBC Operational Disengagement Plan”	  	9
	 1.69
	  	“UBC Operating Profit”	  	9
	 1.70
	  	“UBC Patent Rights”	  	9
	 1.71
	  	“UBC Pricing Date”	  	9
	 1.72
	  	“UBC Products”	  	9
	 1.73
	  	“UBC Research, Development and Pre-Launch Marketing Costs”	  	9
	 1.74
	  	“UBC Research Operating Committee”	  	9
	 1.75
	  	“UBC Research Program”	  	9
	 1.76
	  	“UBC Targets”	  	9
	 1.77
	  	“UBC9 License”	  	10
	 1.78
	  	“Unique Product”	  	10
	 1.79
	  	“Valid Patent Claim”	  	10
			
	 ARTICLE 2.
	  	SCOPE AND STRUCTURE OF THE COLLABORATIONS	  	10
			
	 ARTICLE 3.
	  	CDK COLLABORATION-CDK RESEARCH PROGRAM	  	10
	 3.1
	  	Conduct of the CDK Research Program	  	10
	 	  	3.1.1	  	General Terms	  	10
	 	  	3.1.2	  	Annual Research Plan	  	11
	 	  	3.1.3	  	Transfer of Technical Information and Know-How	  	11
	 	  	3.1.4	  	DuPont Merck Compounds	  	11
	 	  	3.1.5	  	Subcontracts	  	12
	 	  	3.1.6	  	Data	  	12

  

 (ii) 

							
	 	  	 3.1.7
	  	Quarterly Reports by Mitotix and DuPont Merck	  	12
	 3.2
	  	Funding of the CDK Research Program	  	13
	 	  	3.2.1	  	Annual Payment	  	13
	 	  	3.2.2	  	Incentive Research Funding	  	13
	 3.3
	  	Expiration or Termination of the CDK Research Program and Result of	  	 
	 	  	 Such Termination
	  	14
			
	 ARTICLE 4.
	  	CDK COLLABORATION: CDK DEVELOPMENT PROGRAM	  	14
	 4.1
	  	Designation of CDK Development Compounds	  	14
	 4.2
	  	Clinical Development and Marketing	  	14
	 4.3
	  	Development Information	  	14
			
	 ARTICLE 5.
	  	GENERAL DESCRIPTION OF THE UBC COLLABORATION	  	15
	 5.1
	  	Scope of UBC Collaboration	  	15
	 5.2
	  	Initial Term and Option to Extend	  	15
	 	  	5.2.1	  	Initial Term	  	15
	 	  	5.2.2	  	Option to Extend; UBC Extension Payment	  	15
	 	  	5.2.3	  	UBC Deferral Payment	  	16
	 5.3
	  	UBC Research Program	  	16
	 5.4
	  	Research and Development Funding Commitments	  	16
	 	  	5.4.1	  	First Three Research Years	  	16
	 	  	5.4.2	  	Fourth Research Year and Thereafter	  	17
	 	  	5.4.3	  	Changes to Mitotix’s Funding Commitment	  	17
	 	  	5.4.4	  	Alternate UBC Plan	  	17
	 	  	5.4.5	  	Invoicing	  	18
	 	  	5.4.6	  	Records	  	19
	 5.5
	  	Termination of UBC Collaboration if DuPont Merck Does Not Extend the UBC Collaboration and Result of Such Termination	  	19
	 5.6
	  	Certain Royalty Rights	  	20
	 5.7
	  	UBC Operational Disengagement Plan	  	20
	 5.8
	  	New UBC Targets	  	22
	 5.9
	  	Terms of Equity Investment	  	22
	 	  	5.9.1	  	General Provisions Relating to Price of Equity Investment	  	22
	 	  	5.9.2	  	Investment Prior to an Initial Public Offering	  	23
	 	  	5.9.3	  	Investment After an Initial Public Offering	  	23
			
	 ARTICLE 6.
	  	THE UBC COLLABORATION - UBC RESEARCH PROGRAM	  	24
	 6.1
	  	Conduct of the UBC Research Program	  	24
	 	  	6.1.1	  	General Terms	  	24
	 	  	6.1.2	  	Annual UBC Research Plan and Budget	  	24
	 	  	6.1.3	  	DuPont Merck Compounds	  	25
	 	  	6.1.4	  	Subcontracts	  	25
	 	  	6.1.5	  	Data	  	25
	 	  	6.1.6	  	Quarterly Reports by Mitotix and DuPont Merck	  	26
	 6.2
	  	Expiration or Termination of the UBC Research Program and Result of Such Termination	  	26
	 	  	6.2.1	  	Termination of Initial UBC Term	  	26

  

 (iii) 

							
	 	  	6.2.2	  	Expiration Following Extension of the UBC Collaboration and Commencement of Alternate UBC Plan	  	26
	 	  	6.2.3	  	Termination of the UBC Research Program Following Extension of the UBC Collaboration and Prior to the Commencement of the Alternate UBC Plan	  	26
	 	  	6.2.4	  	Termination of the UBC Research Program Following Commencement of the UBC Operational Disengagement Plan	  	28
			
	 ARTICLE 7.
	  	UBC COLLABORATION: UBC DEVELOPMENT PROGRAM	  	28
	 7.1
	  	Description of UBC Development Compounds	  	28
	 7.2
	  	Clinical Development and Marketing	  	28
	 	  	7.2.1	  	When the Alternate UBC Plan is Not in Effect	  	28
	 	  	7.2.2	  	Clinical Development and Marketing Under the Alternate UBC Plan	  	28
	 7.3
	  	Development Information	  	29
			
	 ARTICLE 8.
	  	MITOTIX’S RIGHT TO CO-PROMOTE	  	29
	 8.1
	  	Mitotix’s Co-promotion Option	  	29
			
	 ARTICLE 9.
	  	MANAGEMENT OF THE COLLABORATIONS	  	30
	 9.1
	  	Collaborative Policy Setting Committee	  	30
	 	  	9.1.1	  	General	  	30
	 	  	9.1.2	  	Chair	  	30
	 	  	9.1.3	  	Minutes	  	30
	 9.2
	  	Research Operating Committees	  	30
	 	  	9.2.1	  	Chairs	  	31
	 	  	9.2.2	  	Minutes	  	31
	 9.3
	  	Disagreements	  	31
	 9.4
	  	Project Leaders	  	32
	 9.5
	  	Availability of Employees	  	32
	 9.6
	  	Visit of Facilities	  	32
			
	 ARTICLE 10.
	  	LICENSE GRANTS AND RIGHTS OF FIRST NEGOTIATION	  	32
	 10.1
	  	Grant of License Rights to DuPont Merck in CDK Field	  	32
	 	  	10.1.1	  	Exclusive License in CDK Field	  	32
	 	  	10.1.2	  	Conversion to Non-Exclusive	  	33
	 	  	10.1.3	  	Election to Terminate License Grant	  	33
	 	  	10.1.4	  	Additional In-Licensed CDK Technology	  	33
	 	  	10.1.5	  	Release of Certain CDK Targets and Certain Royalty Payments	  	33
	 10.2
	  	Grant of License Rights to DuPont Merck in the UBC Field	  	34
	 	  	10.2.1	  	Exclusive License in the UBC Field	  	34
	 	  	10.2.2	  	Conversion to Non-Exclusive	  	34
	 	  	10.2.3	  	Election to Terminate License Grant	  	34
	 	  	10.2.4	  	Additional In-Licensed UBC Technology	  	34
	 10.3
	  	Reservation of Rights	  	36
	 10.4
	  	Grant of License Rights to Mitotix	  	36
	 	  	10.4.1	  	License to Perform Obligations	  	36

  

 (iv) 

							
	 	  	10.4.2	  	License to DuPont Merck Inventions	  	36
	 10.5
	  	DuPont Merck Rights of First Negotiation	  	37
	 	  	10.5.1	  	Right of First Negotiation with Respect to Antisense and/or Gene Therapy	  	37
	 	  	10.5.2	  	Right of First Negotiation with Respect to CDK-non-D Targets	  	37
			
	 ARTICLE 11.
	  	MILESTONES AND ROYALTIES	  	38
	 11.1
	  	Milestone Payments	  	38
	 	  	11.1.1	  	Development Events	  	39
	 	  	11.1.2	  	Notice of Achievement of Milestones	  	41
	 	  	11.1.3	  	Radiopharmaceutical Products and Immunoassay Products	  	41
	 	  	11.1.4	  	Non-Strategic Countries	  	41
	 11.2
	  	Royalties Payable to Mitotix on Net Sales	  	41
	 	  	11.2.1	  	Royalty Payable to Mitotix on Net Sales in Strategic Countries	  	42
	 	  	11.2.2	  	Conditions on Royalty Payments	  	42
	 11.3
	  	Royalties Payable to Mitotix on Net Sales to Distributors in Non-Strategic Countries	  	43
	 11.4
	  	Royalties Payable to Mitotix on Net Sales by Development Partners and other Sublicensees in Japan and Other Non-Strategic Countries	  	43
	 11.5
	  	Profit Sharing on Sales of UBC Products	  	43
			
	 ARTICLE 12.
	  	ROYALTIES PAYABLE TO DUPONT MERCK	  	44
	 12.1
	  	General	  	44
	 12.2
	  	Royalties Payable to DuPont Merck on Net Sales	  	44
	 	  	12.2.1	  	Royalty Payable to DuPont Merck on Net Sales in Strategic Countries	  	44
	 	  	12.2.2	  	Conditions on Royalty Payments	  	45
	 12.3
	  	Royalties Payable to DuPont Merck on Net Sales to Distributors in Non-Strategic Countries	  	45
	 12.4
	  	Royalties Payable to DuPont Merck on Net Sales by Development Partners and other Sublicensees in Japan and Other Non-Strategic Countries	  	45
			
	 ARTICLE 13.
	  	PAYMENT TERMS	  	46
	 13.1
	  	General	  	46
	 13.2
	  	Royalty Reports, Exchange Rates	  	46
	 13.3
	  	Payment of Profit Sharing Amounts	  	46
	 13.4
	  	Audits	  	47
	 13.5
	  	Payment Terms	  	48
	 13.6
	  	Exchange Controls	  	48
	 13.7
	  	Payment Method	  	48
	 13.8
	  	Interest on Late Payments	  	48
	 13.9
	  	Overriding Provisions of License Agreements	  	49
			
	 ARTICLE 14.
	  	PATENTS	  	50
	 14.1
	  	Ownership of Inventions	  	50

  

 (v) 

							
	 14.2
	  	Provisions Concerning the Filing, Prosecution and Maintenance of CDK Patent Rights, UBC Patent Rights and Inventions	  	51
	 	  	14.2.1	  	CDK Patent Rights, UBC Patent Rights and Inventions Owned by Each Party	  	51
	 	  	14.2.2	  	Joint Inventions Relating to CDK Targets and UBC Targets	  	51
	 	  	14.2.3	  	Joint Inventions Relating to CDK Products and UBC Products	  	51
	 	  	14.2.4	  	Consultation Regarding Joint Inventions	  	51
	 	  	14.2.5	  	Patent Costs	  	52
	 14.3
	  	Cooperation	  	52
	 14.4
	  	No Other Technology Rights	  	52
	 14.5
	  	Enforcement of Patent Rights	  	52
	 14.6
	  	Defense of Individual Infringement Actions Involving Use of the Targets	  	53
	 14.7
	  	Defense of Joint Infringement Actions Involving Use of the Targets	  	53
	 14.8
	  	Contribution	  	54
	 14.9
	  	Third Party Patents	  	54
	 14.10
	  	Infringement of Mitotix Inventions or Joint Inventions Covering CDK Products or UBC Products	  	54
			
	 ARTICLE 15.
	  	CONFIDENTIALITY	  	55
	 15.1
	  	Nondisclosure Obligations	  	55
	 15.2
	  	Samples	  	56
	 15.3
	  	Terms of this Agreement and Existence of UBC Collaboration	  	56
	 15.4
	  	Publications	  	57
			
	 ARTICLE 16.
	  	REPRESENTATIONS AND WARRANTIES	  	57
	 16.1
	  	Authorization	  	57
	 16.2
	  	License Agreements with Third Parties	  	58
	 16.3
	  	Patent Validity	  	58
	 16.4
	  	Exclusivity and Freedom-to-operate	  	58
			
	 ARTICLE 17.
	  	INDEMNITY	  	58
	 17.1
	  	DuPont Merck Indemnity Obligations	  	58
	 17.2
	  	Mitotix Indemnity Obligations	  	59
	 17.3
	  	Procedure	  	59
	 17.4
	  	Insurance	  	60
			
	 ARTICLE 18.
	  	TERM AND TERMINATION	  	60
	 18.1
	  	Expiration	  	60
	 18.2
	  	Termination for Cause	  	60
	 	  	18.2.1	  	Bankruptcy	  	60
	 	  	18.2.2	  	Material Breach	  	60
	 	  	18.2.3	  	Failure to Retain Qualified Scientists	  	60
	 18.3
	  	Effect of Termination	  	60
	 18.4
	  	Failure to Pursue	  	61
			
	 ARTICLE 19.
	  	MISCELLANEOUS	  	61

  

 (vi) 

							
	 19.1
	 	 Force Majeure
	  	61
	 19.2
	 	 Assignment
	  	62
	 19.3
	 	 Severability
	  	62
	 19.4
	 	 Notices
	  	62
	 19.5
	 	 Applicable Law
	  	63
	 19.6
	 	 Dispute Resolution
	  	63
	 19.7
	 	 Entire Agreement
	  	63
	 19.8
	 	 Headings
	  	64
	 19.9
	 	 Independent Contractors
	  	64
	 19.10
	 	 Agreement Not to Solicit Employees
	  	64
	 19.11
	 	 Waiver
	  	64
	 19.12
	 	 Counterparts
	  	64
	 19.13
	 	 Definition and Effect of Change of Control
	  	64

  

 (vii) 

 APPENDICES 
  

			
	 Appendix A:
	  	CDK Patent Rights and Certain Mitotix License Agreements
		
	 Appendix B:
	  	CDK Work Plan
		
	 Appendix C:
	  	CDK Primary and Secondary Screens
		
	 Appendix D:
	  	UBC Patent Rights and Certain Mitotix License Agreements
		
	 Appendix E:
	  	Mitotix Pending License Agreements
		
	 Appendix F:
	  	UBC Work Plan
		
	 Appendix G1:
	  	Co-promotion of CDK Products and Co-promotion of UBC Products when the Alternate UBC Plan has been put into Effect
		
	 Appendix G2:
	  	Co-promotion of UBC Products when the Alternate UBC Plan is not in Effect
		
	 Appendix H:
	  	UBC Products - Definition of Percentage Contribution
		
	 Appendix I:
	  	Definition of UBC Operating Profit
		
	 Appendix J:
	  	Examples of Milestone Payment Obligations

  

 (viii) 

 AMENDED AND RESTATED 
 COLLABORATIVE RESEARCH, DEVELOPMENT 
 AND MARKETING AGREEMENT 
  
 THIS AMENDED AND RESTATED COLLABORATIVE RESEARCH, DEVELOPMENT AND MARKETING
AGREEMENT dated as of June 2, 1997 (the “Agreement”) is made between MITOTIX, INC., a Delaware corporation having its principal place of business at One Kendall Square, Building 600, Cambridge, Massachusetts 02139 (“Mitotix”),
and THE DUPONT MERCK PHARMACEUTICAL COMPANY, a Delaware general partnership having its principal place of business at 974 Centre Road, Wilmington, Delaware 19807 (“DuPont Merck”). 
  
 R E C I T A L S 
  
 Mitotix and DuPont Merck are parties to a Collaborative Research, Development
and Marketing Agreement, dated as of December 6, 1995 (the “Initial Agreement”), pursuant to which Mitotix and DuPont Merck agreed, inter alia, (i) to utilize certain biological targets in order to identify and develop small
molecules that can be used as active agents in therapeutic products for the treatment of diseases resulting from inappropriate cell division, proliferation, or longevity; and (ii) to collaborate on research with respect to such biological targets
and on the discovery, worldwide development, and commercialization of CDK Products and UBC Products (both as defined below) for therapeutic purposes. 
  
 Mitotix and DuPont Merck desire to amend and restate the Initial Agreement to extend the Initial UBC Term (as defined below) and to make certain other
changes as provided herein. 
  
 NOW THEREFORE, in consideration of
the foregoing and of the covenants herein contained, the parties hereto mutually agree to amend and restate the Initial Agreement as follows: 
  
 ARTICLE 1. DEFINITIONS 
  
 The terms in this Agreement with initial letters capitalized, whether used in the singular or the plural, shall have meaning set forth below or, if not
listed below, the meaning as designated in places throughout this Agreement. 
  
 1.1 “Affiliate” shall mean any corporation or other entity which controls, is controlled by, or is under common control with a party to this Agreement. A corporation or other entity shall be regarded
as in control of another corporation or entity if it owns or directly or indirectly controls more than fifty percent (50%) of the voting stock or other ownership interest of the other corporation or entity, or if it possesses, directly or
indirectly, 

  

 
the power to direct or cause the direction of the management and policies of the corporation or other entity or the power to elect or appoint more than fifty
percent (50%) of the members of the governing body of the corporation or other entity. For purposes of this Agreement, DuPont Merck shall not be deemed to be an Affiliate of E.I. DuPont de Nemours & Co. or Merck & Co., Inc. or any of their
subsidiaries. 
  
 1.2 “Allowable Expense” shall
have the meaning set forth in Appendix I. 
  
 1.3
“Alternate UBC Plan” shall mean the research, development and marketing plan for the UBC Products that is described in Section 5.4.4. 
  
 1.4 “Antisense” shall mean inhibiting or preventing in vivo expression of a gene product in a human or animal through the use of
an oligonucleotide or modified oligonucleotide which binds to RNA or DNA. 
  
 1.5 “Annual CDK Research Plan” shall have the meaning set forth in Section 3.1.2 below. 
  
 1.6 “Annual Research Plan and Budget” shall have the meaning set forth in Section 6.1.2 below. 
  
 1.7 “Calendar Quarter” shall mean the respective periods of
three (3) consecutive calendar months ending on March 31, June 30, September 30 and December 31. 
  
 1.8 “Calendar Year” shall mean each successive period of twelve (12) months commencing on January 1 and ending on December 31.

  
 1.9 “Cdc 27/Cdc 16 License” shall mean the
license agreement dated as of July 12, 1995 between Mitotix and Harvard University. 
  
 1.10 “CDK Collaboration” shall have the meaning set forth in Section 2 below. 
  
 1.11 “CDK Research Operating Committee” shall mean the joint committee composed of representatives of Mitotix and DuPont Merck described
in Section 9.2 of this Agreement. 
  
 1.12 “CDK
Development Compounds” shall mean, collectively, the CDK-D Development Compounds and the CDK-non-D Development Compounds. 
  
 1.13 “CDK-D Development Compounds” shall mean compounds selected by DuPont Merck through the use of the CDK-D Targets for clinical
development in the CDKD Field. 
  
 1.14 “CDK-non-D
Development Compounds” shall mean compounds selected by DuPont Merck through the use of the CDK-non-D Targets for clinical development in the CDK-non-D Field. 
  

 2 

 1.15 “CDK Field” shall mean, collectively, the CDK-D Field and the CDK-non-D Field.

  
 1.16 “CDK-D Field” shall mean the use of
CDK-D Targets for the discovery, identification and development of CDK-D Development Compounds for all therapeutic indications and the use, manufacture, distribution, marketing and sale for all indications of therapeutic and Radiopharmaceutical
agents incorporating CDK-D Development Compounds. The use of the CDK-D Targets for Antisense, Gene Therapy and all non-Radiopharmaceutical diagnostic applications is specifically excluded from the CDK-D Field. 
  
 1.17 “CDK-non-D Field” shall mean the use of CDK-non-D
Targets for the discovery, identification and development of CDK-non-D Development Compounds for oncology indications and the use, manufacture, distribution, marketing and sale for oncology indications of therapeutic and Radiopharmaceutical agents
incorporating CDK-non-D Development Compounds. The use of CDK-non-D Targets for Antisense, Gene Therapy and all non-Radiopharmaceutical diagnostic applications is specifically excluded from the CDK-non-D Field. 
  
 1.18 “CDK Patent Rights” shall mean those United States
patents and patent applications and the international patent applications owned or licensed by Mitotix which may be useful in the CDK Field and which are identified in Appendix A and any division, continuation, continuation-in-part thereof,
any foreign patent applications corresponding to any such applications or any United States or foreign patents or the equivalent thereof issuing thereon or any reissue or extension thereof. CDK Patent Rights shall also include those United States
patents and patent applications and the international patent applications which may be useful in the CDK Field for which Mitotix may acquire, from a Third Party during the term of the CDK Research Program, license rights and the right to grant
sublicenses (including rights acquired pursuant to the Mitotix Pending License Agreements), and any division, continuation, continuation-in-part thereof, any foreign patent applications corresponding to any such applications or any United States or
foreign patents or the equivalent thereof issuing thereon or any reissue or extension thereof. 
  
 1.19 “CDK Products” shall mean pharmaceutical and Radiopharmaceutical compositions incorporating CDK-D Development Compounds or CDK-non-D Development Compounds whether such compounds are selected for
development, developed, marketed or sold during the term of the CDK Research Program or thereafter. 
  
 1.20 “CDK Research Program” shall mean the research program described generally in Article 3 below and in the research work plan set
forth in Appendix B hereto, as revised from time to time as provided in this Agreement. 
  
 1.21 “CDK Targets” shall mean collectively Targets included within the CDK-D Targets and the CDK-non-D Targets. CDK Targets shall specifically exclude cdc25 phosphatase and complexes thereof and all
Targets included within the UBC Targets. 
  
 1.22 “CDK-D
Targets” shall mean the following Targets: all cyclin Ds, associated cyclin dependent kinases, complexes thereof, and functional equivalents (all homologues of 

  

 3 

 
cyclin Ds and associated cyclin dependent kinases) thereof; physically direct biochemical modulators of cyclin Ds or homologues thereof and of associated
cyclin dependent kinases; and any targets of modulation of p16, functional homologues of p16, or other natural cell cycle modulators of cyclin Ds, their functional homologues, associated cyclin dependent kinases or complexes thereof. 
  
 1.23 “CDK-non-D Targets” shall mean all non-D cyclins,
associated cyclin dependent kinases, complexes thereof, and functional equivalents (all non-D cyclin homologues and associated cyclin dependent kinases) thereof; physically direct biochemical modulators of non-D cyclins or homologues thereof and of
associated cyclin dependent kinases; and any targets of modulation of natural cell cycle modulators of non-D cyclins, their functional homologues, associated cyclin dependent kinases or complexes thereof. 
  
 1.24 “Collaboration” shall have the meaning set forth in
Section 2 below. 
  
 1.25 “Collaborative Policy Setting
Committee” shall mean the joint committee composed of representatives of Mitotix and DuPont Merck described in Section 9.1 of this Agreement. 
  
 1.26 “Cyclin E License” shall mean the license agreement dated as of September 5, 1995 between Mitotix and Fred Hutchinson Cancer
Research Center. 
  
 1.27 “Cyclin D License”
shall mean the license agreement dated as of October 22, 1992 between Mitotix and Cold Spring Harbor Laboratory. 
  
 1.28 “Competitive Product” means a product directed at the same Target and having the same mechanism of action as a Royalty-Bearing
Product or a Mitotix Product and which together with all other such products sold in a particular country, achieves sales in any Calendar Quarter equal to *** of the total gross sales or gross unit sales in such quarter of the Royalty-Bearing
Product or Mitotix Product, as the case may be. 
  
 1.29
“Development Partner” shall mean a Third Party that is either (i) licensed by DuPont Merck to conduct all or a significant portion of the clinical development with respect to a particular Royalty-Bearing Product and to market and
sell such Royalty Bearing-Product in a non-Strategic Country or (ii) licensed by Mitotix to conduct all or a significant portion of the clinical development with respect to a particular Mitotix Product and to market and sell such Mitotix Product in
a non-Strategic Country. 
  
 1.30 “Distributor”
shall mean a Third Party that is either (i) engaged by DuPont Merck to market and distribute Royalty-Bearing Products or (ii) engaged by Mitotix to market and distribute Mitotix Products. 
  
 1.31 “DuPont Merck Inventions” shall have the meaning set forth in Section 14.1 below. 
  
 1.32 “Effective Date” shall mean December 6, 1995.

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omitted portions. 

  

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 1.33 “Extended UBC Collaboration” shall have the meaning set forth in Section 5.2 below.

  
 1.34 “Extension Notice” shall have the
meaning set forth in Section 5.2.2 below. 
  
 1.35 “First
Commercial Sale” shall mean the first sale for use or consumption by the general public of a product in a country after required marketing and pricing approval has been granted by the governing health authority of such country. 

 
 1.36 “Gene Therapy” shall mean the introduction of a
gene, together with associated regulatory elements, if any, into human cells (whether in vivo or ex vivo) in order to treat or prevent disease through the endogenous expression of the gene product in humans. Gene shall mean a DNA or
RNA sequence of human or other origin that encodes a protein or other molecule. 
  
 1.37 “Immunoassay Product” shall mean an assay which contains a Development Compound or a metabolite derived therefrom as a standard reference and is sold by DuPont Merck, its Affiliates, Development
Partners, Distributors or sublicensees in connection with a particular CDK Product or UBC Product for use in monitoring the level of the CDK Product or UBC Product, as the case may be, administered to a patient. All Immunoassay Products shall be
Royalty Bearing Products. 
  
 1.38 “IND” shall
mean an investigational new drug application filed with the United States Food and Drug Administration prior to beginning clinical trials in humans. 
  
 1.39 “Initial UBC Term” shall have the meaning set forth in Section 5.2 below. 
  
 1.40 “Inventions” shall have the meaning set forth in
Section 14.1 below. 
  
 1.41 “IPO” shall have the
meaning set forth in Section 5.9.2 below. 
  
 1.42
“Know-how” shall mean all confidential technical information in the possession of Mitotix or DuPont Merck during the term of this Agreement relating to the CDK Targets, the UBC Targets or relating to the discovery, development,
manufacture, marketing and sale of the CDK Products or the UBC Products. 
  
 1.43 “Mitotix Inventions” shall have the meaning set forth in Section 14.1 below. 
  
 1.44 “Mitotix Pending License Agreements” shall mean those agreements under negotiation between Mitotix and a Third Party as of the
Effective Date under which Mitotix will license patent rights or know-how that may be useful in the CDK Field or the UBC Field. The Mitotix Pending License Agreements are identified in Appendix E. Upon execution, such Mitotix Pending License
Agreements shall be deemed to be Mitotix License Agreements. 
  
 1.45 “Mitotix License Agreements” shall mean those license agreements entered into by Mitotix and a Third Party on or prior to the Effective Date under which Mitotix has 

  

 5 

 
exclusively licensed patent rights or know-now that may be useful in the CDK Field or the UBC Field. The Mitotix License Agreements are listed in Appendix
A and Appendix D. 
  
 1.46 “Mitotix
Product” shall mean (i) any Antisense or Gene Therapy product sold by Mitotix for oncology indications incorporating a compound that was discovered or selected for development by Mitotix through the use of the CDK Targets or the UBC Targets
and was first identified within *** years following the termination of the CDK Research Program (with respect to the use of the CDK Targets) or within *** years following the termination of the UBC Research Program (with respect to the use of the
UBC Targets), and (ii) any products meeting the description of Mitotix Products set forth in Section 5.6, Section 5.8, Section 6.2 3(a)(i) or in Section 10.1.5. 
  

1.47 “Net Sales” with respect to any product (UBC Product, Royalty-Bearing Product or Mitotix Product) shall mean the gross invoiced
sales price of such product sold to independent Third Party customers, including but not limited to Distributors, in bona fide, arms-length transactions, less actual (to the extent not already deducted in the amount invoiced): 
  
 (a) quantity, cash, or other trade discounts actually accrued or taken;

  
 (b) bad debt expense; 
  
 (c) custom duties, surcharges and taxes and other governmental charges
incurred, if any, directly related to the sale; 
  
 (e) amounts
repaid or credited by reason of rejections, return of goods, or retroactive price reductions; 
  
 (f) amounts incurred resulting from governmental, or an agency thereof, mandated rebate programs; 
  
 (g) third party rebates and chargebacks actually accrued or allowed; 
  
 (h) freight and insurance costs incurred in transporting such product to such customers; and 
  
 (i) as agreed by the parties, any other specifically identifiable amounts
included in gross sales that were or ultimately will be credited and that are substantially similar to those listed herein above. 
  
 The amount of Net Sales for any period shall be determined on the basis of sales recorded in such period in accordance with generally accepted accounting principles. The
transfer of any product by DuPont Merck or Mitotix, or one of their Affiliates, to another Affiliate of such party shall not be considered a sale; in such cases, Net Sales shall be determined based on the invoiced sales price by the Affiliate to an
independent Third Party customer, less the deductions allowed under this Section. 

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omitted portions. 

  

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 In the case of a Combination Product (said Combination Product being a pharmaceutical or
Radiopharmaceutical product which contains one or more pharmacologically active ingredients in addition to the Royalty-Bearing Product, UBC Product, or Mitotix Product as the case may be) only, Net Sales shall be calculated on the basis of the
invoice price for the product (Royalty-Bearing Product, UBC Product, or Mitotix Product as the case may be) containing the same weight of product and sold alone without other active ingredients. In the event that the product is not sold alone
without other active ingredients, then Net Sales shall be the Net Sales of the Combination Product, determined as set forth above, multiplied by the fraction A/(A+B) where A is the seller’s cost of acquiring or manufacturing the product
(Royalty-Bearing Product, UBC Product, or Mitotix Product as the case may be) and B is the seller’s cost of acquiring or manufacturing the other active ingredient(s) in the Combination Product, determined in accordance with generally accepted
accounting principles. 
  
 1.48 “New UBC Target”
shall mean a UBC Target that was not identified by Mitotix, DuPont Merck or a Third Party prior to the Effective Date and for which a novel screen and selectivity assays have been developed and validated for a specific therapeutic program as part of
the UBC Collaboration. A Target shall not be a New UBC Target until approved by the Collaborative Policy Setting Committee as a New UBC Target as described in Section 5.8. 
  
 1.49 “NDA” shall mean a new drug application filed with the United States Food and Drug Administration
after completion of human clinical trials to obtain marketing approval for a Royalty-Bearing Product, or the corresponding application for authorization for marketing for a Royalty-Bearing Product filed in any other country in accordance with the
applicable laws and regulations of that country. 
  
 1.50
“Percentage Contribution” shall have the meaning set forth in Section 5.4.1 and Appendix H. 
  
 1.51 “p16 License” shall mean the license agreement dated as of July 1, 1995 between Mitotix and Cold Spring Harbor Laboratory.

  
 1.52 “PRAD1 License” shall mean the license
agreement dated as of August 25, 1995 between Mitotix and the General Hospital Corporation. 
  
 1.53 “Product Patent Rights” shall have the meaning set forth in Section 14.10. 
  
 1.54 “Radiopharmaceutical” shall mean any use for human in vivo medical imaging purposes. 
  
 1.55 “Radiopharmaceutical Product” shall mean any CDK
Product or UBC Product used for human in vivo medical imaging purposes. 
  
 1.56 “Research Operating Committees” shall mean collectively the CDK Research Operating Committee and the UBC Research Operating Committee. 
  

 7 

 1.57 “Research Year” shall mean each twelve-month period during the Collaboration, with
the first Research Year beginning on January 1, 1996. 
  
 1.58
“Royalty-Bearing Products” shall mean (i) all CDK Products, (ii) all Radiopharmaceutical Products that are UBC Products, (iii) effective upon the initiation of the Alternate UBC Plan, all UBC Products; (iv) effective upon the deemed
commencement of the Alternate UBC Plan for financial purposes following the commencement of the UBC Operational Disengagement Plan pursuant to Section 5.7, all UBC Products and (v) all Immunoassay Products; provided, however, that
Royalty Bearing Products shall not include: (i) CDK Products incorporating compounds that are first identified more than *** years following the earlier of (X) the termination of the license grant set forth in Section 10.1.1 pursuant to Section
10.1.3 or (Y) the termination of the Agreement; and (ii) UBC Products incorporating compounds that are first identified more than *** years following the earlier of (X) the termination of the license grant set forth in Section 10.2.1 pursuant to
Section 10.2.3 or (Y) the termination of this Agreement. In addition, any product meeting the description of a Royalty Bearing Product set forth in Section 6.2.3(a)(ii) shall be a Royalty Bearing Product. 
  
 1.59 “Royalty Term” shall mean, with respect to each product
in each country, the period of time equal to the longer of (a) ten (10) years from the date of the First Commercial Sale of such product in such country or (b) if the manufacture, use or sale of such product in such country is covered by a Valid
Patent Claim owned by or exclusively licensed to the party responsible for the relevant royalty payment, the term for which such Valid Patent Claim or any new Valid Patent Claim remains in effect. 
  
 1.60 “Strategic Countries” shall mean the United States of
America, Canada, France, Germany, Italy, the United Kingdom and Spain. 
  
 1.61 “Target” shall mean a specific, identified biomolecule, including a protein, polynucleotide, carbohydrate, lipid, or any combination thereof. 
  
 1.62 “Third Party” shall mean any person or entity other than Mitotix or DuPont Merck and their respective
Affiliates. 
  
 1.63 “UBC Collaboration” shall
have the meaning set forth in Articles 2 and 5. 
  
 1.64
“UBC Deferral Payment” shall have the meaning set forth in Section 5.2.3. 
  
 1.65 “UBC Development Compounds” shall mean compounds selected by the Collaborative Policy Setting Committee through the use of UBC Targets for clinical development in the UBC Field, unless the
Alternate UBC Plan is in effect, in which case “UBC Development Compounds” shall mean compounds selected by DuPont Merck through the use of UBC Targets for clinical development in the UBC Field. 
  
 1.66 “UBC Extension Payment” shall have the meaning set
forth in Section 5.2.3. 

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omitted portions. 

  

 8 

 1.67 “UBC Field” shall mean use of the UBC Targets for the discovery, identification and
development of UBC Development Compounds and the use, manufacture, distribution, marketing and sale for all indications of therapeutic and Radiopharmaceutical agents incorporating UBC Development Compounds. The use of the UBC Targets for Antisense,
Gene Therapy and all non-Radiopharmaceutical diagnostic applications is specifically excluded from the UBC Field. 
  
 1.68 “UBC Operational Disengagement Plan” shall have the meaning set forth in Section 5.7. 
  
 1.69 “UBC Operating Profit” shall have the meaning set forth
in Appendix I hereof. 
  
 1.70 “UBC Patent
Rights” shall mean those United States patents and patent applications and the international patent applications owned or licensed by Mitotix which may be useful in the UBC Field and which are identified in Appendix D and any
division, continuation, continuation-in-part thereof, any foreign patent applications corresponding to any such applications or any United States or foreign patents or the equivalent thereof issuing thereon or any reissue or extension thereof. UBC
Patent Rights shall also include those United States patents and patent applications and the international patent applications which may be useful in the UBC Field for which Mitotix may acquire, from a Third Party during the term of the UBC Research
Program, license rights and the right to grant sublicenses, and any division, continuation, continuation-in-part thereof, any foreign patent applications corresponding to any such applications or any United States or foreign patents or the
equivalent thereof issuing thereon or any reissue or extension thereof. 
  
 1.71 “UBC Pricing Date” shall have the meaning set forth in Section 5.9.1. 
  
 1.72 “UBC Products” shall mean pharmaceutical and Radiopharmaceutical compositions incorporating UBC Development Compounds whether such
compounds are selected for development, developed, marketed or sold during the term of the UBC Research Program or thereafter. 
  
 1.73 “UBC Research, Development and Pre-Launch Marketing Costs” shall have the meaning set forth in Appendix H. 
  
 1.74 “UBC Research Operating Committee” shall mean the joint
committee composed of representatives of Mitotix and DuPont Merck described in Section 9.2 of this Agreement. 
  
 1.75 “UBC Research Program” shall mean the research program described generally in Section 6.1 and in the research workplan set forth in
Appendix F hereto, as revised from time to time as provided in this Agreement. 
  
 1.76 “UBC Targets” shall mean the following Targets: (i) all ubiquitin-mediated proteolytic pathways, including enzymes and ligands involved in the ubiquitin-mediated degradation of proteins and (ii)
all HPV-mediated ubiquitinylation, E6, E6AP, binding ligands thereof, associated complexes thereof, and direct biochemical modulators thereof. In 

  

 9 

 
the event that cdc25 proves to be a candidate for a New UBC Target as set forth in Section 1.44, it will be presented to the Collaborative Policy Setting
Committee as such for evaluation as described in Section 5.8. 
  
 1.77 “UBC9 License” shall mean the license agreement dated as of March 8, 1995 between Mitotix and Harvard University. 
  
 1.78 “Unique Product” shall have the meaning set forth in Section 11.1.1. 
  
 1.79 “Valid Patent Claim” shall mean a claim of an issued and unexpired patent which has not been revoked
or held unenforceable or invalid by a decision of a court or other governmental agency of competent jurisdiction, unappealable or unappealed within the time allowed for appeal, and which has not been admitted to be invalid or unenforceable through
reissue or disclaimer or otherwise. 
  
 ARTICLE 2. SCOPE AND
STRUCTURE OF THE COLLABORATIONS 
  
 Mitotix and DuPont Merck wish
to establish two collaborative alliances both with the objective and intent of discovering, developing and marketing compounds that therapeutically or for Radiopharmaceutical use affect or bind to the defined Targets within the defined research and
development fields. One collaboration will focus on research and development with respect to the CDK Targets (the “CDK Collaboration”) and the other will focus on research and development with respect to the UBC Targets (the “UBC
Collaboration”). During the course of the collaborations, Mitotix and DuPont Merck will communicate regularly and will assume different rights and responsibilities for the discovery, development and commercialization of CDK Products and UBC
Products, based on the phase of development and commercialization and the territory involved, all as more specifically described below and in the Appendices hereto. Throughout this Agreement the CDK Collaboration and the UBC Collaboration shall be
referred to collectively as “the Collaboration.” 
  
 ARTICLE 3. CDK COLLABORATION-CDK RESEARCH PROGRAM 
  
 3.1
Conduct of the CDK Research Program. 
  
 3.1.1 General Terms. The CDK Research Program will be conducted in good scientific manner, and in compliance with all applicable good laboratory practices, and applicable legal requirements, to attempt to achieve efficiently and
expeditiously the objectives described in the work plan set forth in Appendix B hereto. Throughout the CDK Research Program, including any extensions thereof as provided in Section 3.3, Mitotix shall assign eight full-time equivalent
qualified scientists to perform the work set forth in each Annual CDK Research Plan (as defined below). The name, curriculum vitae, and percentage of time devoted to working on the CDK Research Program for each scientist comprising such eight
full-time equivalent scientists shall be provided to DuPont Merck within thirty (30) days of the Effective Date and not later than sixty (60) days prior to the start of each subsequent 

  

 10 

 
Research Year. The mixture of skills and levels of expertise represented by such scientists shall be appropriate to the scientific objectives of the CDK
Research Program at any point in time and shall not, without the consent of DuPont Merck, differ substantially from the mixture of skills and levels of expertise among the full-time equivalent scientists assigned to Mitotix proprietary research
projects having similar objectives. The names of such scientists and the percentage of time to be devoted by each to working on the CDK Research Program shall be identified in each Annual CDK Research Plan. The selection of such scientists shall be
subject to DuPont Merck approval, such approval not to be unreasonably withheld. Mitotix and DuPont Merck shall proceed diligently with the work set out in each Annual CDK Research Plan by using their respective good faith efforts considering, in
the case of Mitotix, the funding received from DuPont Merck hereunder. 
  
 3.1.2 Annual Research Plan. The CDK Research Program will be conducted under an annual research plan which describes the work to be pursued by Mitotix and DuPont Merck during the Research Year (the “Annual
CDK Research Plan”). The first Annual CDK Research Plan shall be prepared by the CDK Research Operating Committee and approved by DuPont Merck with the concurrence of the Collaborative Policy Setting Committee within forty-five (45) days after
the Effective Date. Subsequent Annual CDK Research Plans shall be prepared by the CDK Research Operating Committee, for submission to, and approval by, DuPont Merck with the concurrence of the Collaborative Policy Setting Committee, not later than
sixty (60) days prior to the start of each Research Year. 
  
 3.1.3 Transfer of Technical Information and Know-How. Within three (3) months after the Effective Date, Mitotix shall provide DuPont Merck with technical information, Know-how, and upon reasonable request by
DuPont Merck, materials that are not otherwise available, necessary to enable DuPont Merck to utilize the primary and secondary screens for CDK Targets that have been validated by Mitotix as of such date; such primary and secondary screens are
identified in Appendix C attached hereto. As additional primary and secondary screens for the CDK Targets become available and are validated, Mitotix shall promptly provide DuPont Merck with additional technical information, Know-how, and
upon reasonable request by DuPont Merck, materials that are not otherwise available, to enable DuPont Merck to utilize such additional primary and secondary screens. All such technical information and Know-how provided by Mitotix under this Section
shall be treated as “Information” under Article 15. 
  
 3.1.4 DuPont Merck Compounds. The Collaborative Policy Setting Committee shall determine which party shall be responsible for conducting the primary screening of compounds. Following primary screening,
compounds which meet the specifications set forth by the CDK Research Operating Committee for suitable candidates for continued preclinical development shall be provided to Mitotix. Mitotix shall conduct secondary screening of such compounds and
conduct additional preclinical work with respect to such compounds, all as set forth in the applicable Annual CDK Research Plan. Mitotix will promptly provide to DuPont Merck all data from such screening and preclinical work in accordance with
Section 3.1.7 and as otherwise reasonably requested by DuPont Merck in support of the development of CDK Development Compounds. Such compounds provided by DuPont Merck will be used by Mitotix solely for screening and preclinical work within the CDK
Field, as approved by DuPont Merck, and for no other purpose. Any know-how 

  

 11 

 
incidentally developed at Mitotix outside of the CDK Field using a DuPont Merck compound shall be promptly disclosed to DuPont Merck. Any know-how and patent
rights developed by Mitotix using a DuPont Merck compound provided hereunder shall be considered Know-how and CDK Patent Rights, respectively. DuPont Merck shall at all times own all rights to the compounds it provides to Mitotix hereunder,
including without limitation, all rights with respect to the manufacture, use, or sale of such compounds. In accordance with the foregoing, Mitotix agrees to (i) disclose to DuPont Merck any inventions it conceives or makes with respect to the
manufacture, use or sale of compounds provided by DuPont Merck to Mitotix hereunder; (ii) assign to DuPont Merck all patent rights with respect to such inventions and (iii) execute any necessary papers and otherwise reasonably cooperate with DuPont
Merck in securing patents on such inventions. Upon expiration or termination of the CDK Research Program, Mitotix shall, upon the request of DuPont Merck, return or destroy all compounds provided to Mitotix by DuPont Merck in the performance of the
CDK Research Program. 
  
 3.1.5
Subcontracts. Subject to the provisions of Article 15 and, if applicable, the p16 License, and as set forth in the Annual CDK Research Plan and Budget or otherwise approved by the Collaborative Policy Setting Committee, Mitotix and DuPont
Merck may subcontract portions of the CDK Research Program to be performed by them in the normal course of their business to a Third Party upon prior written notice to the other; provided, however, that such Third Party has entered
into an appropriate confidentiality agreement with Mitotix and/or DuPont Merck obligating such Third Party to be bound by the confidentiality obligations contained in this Agreement, or such subcontracting would not require the transfer of
confidential information to the Third Party. 
  
 3.1.6 Data. Mitotix and DuPont Merck shall each maintain records in sufficient detail and in good scientific manner appropriate for patent purposes and as will properly reflect all work done and results achieved in the performance of
the CDK Research Program (including all data in the form required to be maintained under any applicable governmental regulations). Such records shall include books, records, reports, research notes, charts, graphs, comments, computations, analyses,
recordings, photographs, computer programs and documentation thereof, computer information storage means, samples of materials and other graphic or written data generated in connection with the CDK Research Program. Mitotix and DuPont Merck shall
each provide the other the right to inspect such records, and shall provide copies of all requested records, to the extent reasonably required for the performance of the requesting party’s obligations under this Agreement; provided, however,
that each party shall maintain such records and the information of the other contained therein in confidence in accordance with Article 15 below and shall not use such, records or information except to the extent otherwise permitted by this
Agreement. 
  
 3.1.7 Quarterly Reports bv
Mitotix and DuPont Merck. Within thirty (30) days following the end of each Calendar Quarter, Mitotix and DuPont Merck shall each provide to the members of the CDK Research Operating Committee a written report summarizing in reasonable detail
the preclinical work performed by it under the CDK Research Program during the preceding Calendar Quarter. 
  

 12 

 3.2 Funding of the CDK Research Program. 
  
 3.2.1 Annual Payment. 
  
 (a) In consideration of Mitotix’s performance of its
obligations under the CDK Research Program, DuPont Merck shall pay Mitotix a research fee at the rate of *** Dollars *** per Research Year during the term of the CDK Research Program, including any extension thereof pursuant to Section 3.3;
provided, however, that no research fee shall be due to Mitotix from DuPont Merck during the six month period from January 1, 2000 through June 30, 2000. The parties acknowledge that such funding is intended to cover the cost of the eight
full-time equivalent scientists that Mitotix has committed to the CDK Research Program at the rate of *** Dollars *** per scientist. The research fee for each Research Year shall be paid in equal quarterly payments throughout the Research
Year (or any portion thereof), with the first payment of ***Dollars ***to be paid to Mitotix on the Effective Date. Such research funding by DuPont Merck in support of the CDK Research Program shall be contingent upon Mitotix providing and retaining
the eight qualified full-time equivalent scientists described in Section 3.1.1 and Mitotix making a good faith effort in accordance with industry standards to achieve the goals of the CDK Collaboration as set forth annually in the Annual CDK
Research Plan. 
  
 (b) Without limiting DuPont
Merck’s rights or remedies, DuPont Merck shall have the right to reduce the level of funding described above to reflect the failure by Mitotix to provide or retain the eight qualified full-time equivalent scientists or to make a good faith
effort in accordance with industry standards to achieve the goals of the CDK Collaboration. DuPont Merck may exercise such right to reduce funding upon six (6) months’ prior written notice to Mitotix of its intention to do so, stating the
reasons why DuPont Merck believes Mitotix has either failed to provide or retain the required scientists or to make the required effort, provided that Mitotix has not taken good faith commercially reasonable steps during such six (6) month
period to diligently correct such deficiencies. If such funding is discontinued completely as a result of this Section 3.2.l(b), then the CDK Research Program shall be deemed to have terminated and the provisions of Section 3.3 shall apply.

  
 (c) In the event of a Change of Control
(defined in Section 19.13) and the failure of Mitotix (or its successor) to adhere to the provisions of Section 19.13, as reasonably determined by DuPont Merck, DuPont Merck may elect to discontinue payment of the research funding to Mitotix upon
three (3) months prior written notice to Mitotix. Upon such discontinuation of funding, Mitotix shall no longer be obligated to provide research support for the CDK Research Program, and the CDK Research Program shall be deemed to have terminated.

  
 (d) 3.2.2 Incentive Research Funding.
In the event safety assessment studies with respect to a CDK Development Compound are completed with a result that human clinical trials for such CDK Development Compound commence on or before December 31, 1997, then DuPont Merck shall pay Mitotix
*** upon the commencement of such human clinical trials, in support of the CDK Research Program. DuPont Merck shall use 

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omitted portions. 

  

 13 

 commercially reasonable efforts to commence such human clinical trials on or before such date. 
  
 3.3 Expiration or Termination of the CDK Research Program and Result of
Such Termination. Unless sooner terminated pursuant to Section 3.2.l(b) or Section 3.2.l(c) above, the term of the CDK Research Program shall commence on January 1, 1996 and shall continue through June 30, 2000. DuPont Merck shall have the
option to extend the CDK Research Program for up to three (3) additional consecutive one-year periods. In order to exercise its option to extend the CDK Research Program, DuPont Merck shall provide Mitotix with written notice of the extension of the
CDK Research Program at least six (6) months prior to the commencement of each such additional one-year period. Upon the expiration or termination of the CDK Research Program the terms of Sections 10.1.2 and 10.1.3 shall apply. 
  
 ARTICLE 4. CDK COLLABORATION: CDK DEVELOPMENT PROGRAM 
  
 4.1 Designation of CDK Development Compounds. Based upon the
preclinical work conducted by Mitotix and DuPont Merck, DuPont Merck shall determine, with collaborative input from Mitotix through the Collaborative Policy Setting Committee, whether to designate a compound as a CDK Development Compound. DuPont
Merck shall provide Mitotix prompt written notice of its decision. DuPont Merck will be responsible for directing the preclinical and clinical development of compounds in the CDK Field in the CDK Collaboration. 
  
 4.2 Clinical Development and Marketing. The clinical development of a
CDK Development Compound starting with the commencement of human clinical trials for such CDK Development Compound and continuing through obtaining regulatory approvals of any resulting CDK Product shall be the sole responsibility of DuPont Merck
and shall be conducted at the sole expense of DuPont Merck, with input from Mitotix through the Collaborative Policy Setting Committee. Subject to Mitotix’s co-promotion option set forth in Article 8, DuPont Merck shall have sole responsibility
for and shall bear all expenses associated with the marketing and sale of all CDK Products. For each CDK Development Compound, DuPont Merck shall use its good faith commercially reasonable efforts to evaluate and develop such compound or CDK Product
in a timely manner in accordance with industry standards and DuPont Merck internal practices and shall advise the Collaborative Policy Setting Committee as to the status of the development of each CDK Development Compound. Consistent with industry
standards and DuPont Merck internal practices, DuPont Merck shall use its good faith commercially reasonable efforts to conduct at its own expense, such human clinical trials as are necessary to obtain all regulatory approvals to manufacture and
market CDK Products and to seek and obtain all necessary regulatory approvals to market and promptly commence worldwide marketing of each CDK Product. 
  
 4.3 Development Information. DuPont Merck shall keep Mitotix informed as to the progress of DuPont Merck in the development and testing of all CDK
Development Compounds and CDK Products and the preparing, filing and obtaining of the approvals necessary for marketing. Within thirty (30) days following the end of each Calendar Quarter 

  

 14 

 
following the designation of a CDK Development Compound, DuPont Merck shall provide to Mitotix a reasonably detailed report which shall describe the progress
of the development and testing of the CDK Products incorporating such CDK Development Compounds. DuPont Merck may satisfy its reporting obligation hereunder by providing an oral report to the Collaborative Policy Setting Committee within such thirty
(30) day period, provided that a written report of the oral presentation is delivered to Mitotix no later than thirty (30) days after the oral report is made to the Collaborative Policy Setting Committee. In addition, DuPont Merck shall provide
Mitotix with a minimum of three (3) months’ advance notice of the contemplated filing of an IND or an NDA. DuPont Merck shall provide Mitotix with a report on all material regulatory submissions at least forty-five (45) days prior to the date
of such submissions, or any major amendments or supplements thereto within ten (10) business days of filing thereof. DuPont Merck shall provide to Mitotix in a timely manner copies of any material regulatory submission, or amendments thereof,
reasonably requested by Mitotix or, alternatively shall provide Mitotix reasonable access to each such material regulatory submission or amendments thereof at DuPont Merck’s offices, for review and copying by Mitotix. 
  
 ARTICLE 5. GENERAL DESCRIPTION OF THE UBC COLLABORATION 
  
 5.1 Scope of UBC Collaboration. In the performance of the UBC
Collaboration hereunder, DuPont Merck and Mitotix will collaborate in research on the UBC Targets and on the discovery and development of therapeutic agents which act on such UBC Targets, as set forth in this Agreement. The goal of the UBC
Collaboration is to discover and develop products efficiently while allowing Mitotix to grow development capabilities in the United States in accordance with the specific terms of this Agreement. It will be the responsibility of the Collaborative
Policy Setting Committee to ensure that the division of research and development efforts are consistent with this goal. The financial goal of the UBC Collaboration is for each party to share in the UBC Operating Profit as outlined in Section 11.5
and Appendix I in proportion to the contribution each party has made to the UBC Research, Development and Pre-Launch Marketing Costs of such UBC Products, as set forth in this Agreement and described in Appendix H. 
  
 5.2 Initial Term and Option to Extend. 
  
 5.2.1 Initial Term. The UBC Collaboration shall
commence on January 1, 1996 and continue in effect through April 30, 2000 (the “Initial UBC Term”). 
  
 5.2.2 Option to Extend; UBC Extension Payment. DuPont Merck shall have the option to extend the term of the UBC
Collaboration by (i) providing Mitotix written notice of its intention to do so (the “Extension Notice”) and (ii) making a *** Dollar *** equity investment in Mitotix prior to the expiration of the Initial UBC Term, payable
as set forth in Section 5.2.3 and upon the terms set forth in Section 5.9. If Mitotix receives the Extension Notice and the *** Dollar *** equity investment by DuPont Merck prior to the termination of the Initial UBC Term, the UBC Collaboration
shall continue as the “Extended UBC Collaboration.” 

	***	Certain information on this page 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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 5.2.3 UBC Deferral Payment. The Initial Agreement provided that the Initial UBC
Term would continue in effect through April 30, 1998. In consideration of Mitotix’s agreement to extend the Initial UBC Term by two years, DuPont Merck shall pay Mitotix an aggregate of *** Dollars *** (the “UBC Deferral Payment”).
The UBC Deferral Payment shall be paid in nine equal quarterly installments, with the first payment of *** Dollars *** to be received by Mitotix within ten (10) business days of January 1, 1998; provided, however, that DuPont Merck’s
obligation to pay each installment shall be contingent on Mitotix providing and retaining the ten qualified full-time equivalent scientists described in Section 6.1.1 and Mitotix making a good faith effort in accordance with industry standards to
achieve the goals of the UBC Collaboration; and provided, further, that if Mitotix has reduced the number of qualified scientists devoted to working on the UBC Research Program at the written request of DuPont Merck, then DuPont Merck shall
be required nonetheless to make each installment of the UBC Deferral Payment. Upon DuPont Merck’s election to extend the UBC Collaboration as set forth in Section 5.2.2, all installments of the UBC Deferral Payment received prior to the date of
such extension shall be applied toward the *** Dollar *** equity investment in Mitotix described in Section 5.2.2 and the balance of such equity investment (the “UBC Extension Payment”) shall be paid by wire transfer to an account
designated by Mitotix. If DuPont Merck elects not to extend the UBC Collaboration or fails to pay the balance of the equity investment, any prior installments of the UBC Deferral Payment shall be deemed to be research funding and shall not result in
the issuance of equity to DuPont Merck. The UBC Deferral Payment shall not be included in calculating the amount of UBC Research, Development and Pre-Launch Marketing Costs funded by DuPont Merck pursuant to Section 5.4, but costs incurred by
Mitotix in providing and retaining the qualified full-time equivalent scientists described in Section 6.1.1 shall be included in calculating the amount of UBC Research, Development and Pre-Launch Marketing Costs funded by Mitotix. 
  
 5.3 UBC Research Program. During the UBC Collaboration, the parties
shall conduct the UBC Research Program as set forth in Article 6 below. As set forth in Section 6.2 below, the term of the UBC Research Program shall commence on January 1, 1996 and shall terminate as of the expiration of the Initial UBC Term,
unless DuPont Merck exercises its option to extend the UBC Collaboration pursuant to Section 5.2. As set forth in Section 6.2, if DuPont Merck exercises its option to extend the UBC Collaboration pursuant to Section 5.2, then the UBC Research
Program shall continue for the remaining Research Year in which DuPont Merck exercises its option to extend and continue for an additional three (3) Research Years, (unless, as set forth in Section 6.2.3, where the Alternate UBC Plan is not in
effect, the Collaborative Policy Setting Committee determines that the UBC Research Program should terminate earlier), after which DuPont Merck shall have the option to extend the UBC Research Program for up to three (3) additional consecutive
one-year Research Years. 
  
 5.4 Research and Development
Funding Commitments. 
  
 5.4.1 First Three
Research Years. During the first three (3) Research Years after the Effective Date, each party shall fund an agreed upon amount of all UBC Research, Development and Pre-Launch Marketing Costs set forth in the Annual UBC Research Plan

	***	Certain information on this page 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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 and Budget; provided, however, Mitotix shall fund not less than thirty percent (30%) and DuPont
Merck shall fund not more than seventy percent (70%) of all UBC Research, Development and Pre-Launch Marketing Costs set forth in the Annual UBC Research Plan and Budget. Each party shall use good faith commercially reasonable efforts to meet its
funding commitment set forth herein. The percentage share of the total amount of UBC Research, Development and Pre-Launch Marketing Costs incurred by a party at any point in time during the UBC Collaboration shall hereafter be referred to as a
party’s “Percentage Contribution”. The Percentage Contribution at any point in time shall be calculated based on the net present value of the UBC Research, Development and Pre-Launch Marketing Costs incurred from the Effective Date,
as set forth in Appendix H. At the end of each Research Year the parties shall calculate the Percentage Contribution. At the end of the third Research Year it is the expectation of the parties that Mitotix’s Percentage Contribution shall
not be less than thirty percent (30%) and DuPont Merck’s Percentage Contribution shall not be more than seventy percent (70%). 
  
 5.4.2 Fourth Research Year and Thereafter. Commencing with the fourth Research Year and continuing for each Research Year
thereafter, Mitotix will fund at a level to maintain its Percentage Contribution between twenty percent (20%) and thirty percent (30%), and DuPont Merck will fund at a level to maintain its Percentage Contribution between seventy percent (70%) and
eighty percent (80%) of all UBC Research, Development and Pre-Launch Marketing Costs for each Research Year, with the goal of achieving as described in Appendix H, a 30% and 70% Percentage Contribution by Mitotix and DuPont Merck,
respectively, by the time of First Commercial Sale of a UBC Product. 
  
 5.4.3 Changes to Mitotix’s Funding Commitment. In Mitotix’s sole discretion, it may reduce its funding commitment during any Research Year in order to decrease its Percentage Contribution from thirty
percent (30%) to a minimum of twenty percent (20%). However, if after any Research Year, Mitotix allows its Percentage Contribution to fall below thirty percent (30%), Mitotix’s Percentage Contribution calculated at the end of the Research Year
in which it decreased its funding commitment shall become the new target Percentage Contribution for Mitotix and Mitotix shall not be permitted to increase its Percentage Contribution beyond such new target amount. 
  
 5.4.4 Alternate UBC Plan. 
  
 (a) Mitotix may, at any time prior to the entry of the last
patient into the pivotal clinical efficacy trial on which the NDA filing for the first UBC Product would be based, provide DuPont Merck with written notice of its election to commence the Alternate UBC Plan, and the Alternate UBC Plan shall commence
upon DuPont Merck’s receipt of such written notice. In addition, if at any time Mitotix permits its Percentage Contribution to decrease to less than twenty percent (20%), then effective upon the end of the Research Year in which Mitotix’s
Percentage Contribution falls below twenty percent (20%), the Alternate UBC Plan shall commence. 
  
 (b) Upon the commencement of the Alternate UBC Plan (i) the UBC Research Program shall continue and all future planning and funding with
respect to the UBC Research, Development and Pre-Launch Marketing Costs shall be the sole responsibility of 

  

 17 

 
DuPont Merck, (ii) Mitotix shall provide research and development support of the UBC Research Program (up to a level of eight qualified full time equivalent
scientists and substantially similar to the corresponding level of support provided by Mitotix under the CDK Research Program) in accordance with the Annual UBC Research Plan and Budget, and subject to DuPont Merck’s funding of such research
and development support, and Mitotix shall invoice DuPont Merck, in accordance with the terms set forth in Section 5.4.5, for all UBC Research, Development and Pre-Launch Marketing Costs incurred by Mitotix in performing its obligations under the
Annual UBC Research Plan and Budget (as revised as necessary to reflect the commencement of the Alternate UBC Plan), (iii) all UBC Products shall be deemed to be Royalty-Bearing Products, (iv) the provisions of Article 6 and 7 shall remain in
effect, except that the decision-making power of the parties shall be as set forth under the CDK Collaboration, and (v) DuPont Merck shall reimburse Mitotix on a straight dollar for dollar basis (i.e. not time adjusted) for all UBC Research,
Development and Pre-Launch Marketing Costs incurred by Mitotix from the Effective Date until the commencement of the Alternate UBC Plan; provided, however, that Mitotix shall not be entitled to such reimbursement under clause (v) above if (a)
Mitotix permits its Percentage Contribution to decrease to less than twenty percent (20%) after the entry of the last patient into the pivotal clinical efficacy trial on which the NDA filing for the first UBC Product is based, or (b) no UBC Product
is ever sold. Such reimbursement under clause (v) shall be made in equal quarterly payments over a three (3) year period commencing with the First Commercial Sale of a UBC Product, provided, however, that no such quarterly payment shall
exceed thirty percent (30%) of the Net Sales of the UBC Product in that quarter. 
  
 5.4.5 Invoicing. At the beginning of the fourth and each subsequent Research Year, based upon the tasks assigned to each party by
the Collaborative Policy Setting Committee pursuant to the Annual UBC Research Plan and Budget and the amount of the annual budget that is expected to be spent by each party in connection with the performance of its obligations under the Annual UBC
Research Plan and Budget, the parties shall mutually determine in writing whether it is necessary for either party to invoice the other so that each party funds the UBC Research, Development and Pre-Launch Marketing Costs for the Research Year in
accordance with the Percentage Contribution targets set forth above. In addition, at the beginning of each Research Year following the commencement of the Alternate UBC Plan, based upon the tasks assigned to Mitotix by the Collaborative Policy
Setting Committee pursuant to the Annual UBC Research Plan and Budget and the amount of the annual budget that is expected to be spent by Mitotix in connection with the performance of its obligations under the Annual UBC Research Plan and Budget,
Mitotix will invoice DuPont Merck for the UBC Research Development and Pre-Launch Marketing Costs it is expected to incur during the Research Year. The amount that is to be invoiced to any one party, if any, shall be invoiced in four equal quarterly
amounts throughout the Research Year. Within fifteen (15) days of a receipt of an invoice from a party hereunder, the receiving party shall make payment in full under the invoice in United States dollars by check, wire transfer of funds, or other
means acceptable to the party to whom payment is to be made. Adjustments as necessary to reflect the expenses actually incurred by each party shall be made as promptly as possible following the end of each Research Year quarter and shall be
reflected in the determination of invoice amounts for the subsequent quarter. 
  

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 5.4.6 Records. Each party shall keep complete and accurate records of the UBC
Research, Development and Pre-Launch Marketing Costs incurred by it in each Research Year, which records shall be retained for three (3) years after the end of the Research Year to which they relate. The records shall conform to generally accepted
accounting principles consistently applied and shall be in accordance with procedures to be agreed upon between the parties, as outlined in Appendix H and Appendix I. Each party shall have the right at its own expense during the term
of this Agreement and during the subsequent three-year period to appoint an independent certified public accountant reasonably acceptable to the other party to inspect said records. Upon reasonable notice from a party, the other party shall make its
records available during regular business hours for inspection by the independent certified public accountant at the place or places where such records are customarily kept, to the extent reasonably necessary to verify the occurrence of the
expenditures. The right of inspection shall not be exercised more than once in any Calendar Year. The parties agree to hold in strict confidence all information concerning such expenditures and all information learned in the course of any audit or
inspection, except to the extent necessary for a party to enforce any rights it may have pursuant to this Agreement or if disclosure is required by law. The failure of either party to request verification of any expenditures during the three (3)
year period the parties are required to retain the records for any Research Year shall be considered acceptance of the accuracy of the reports concerning such expenditures. 
  
 5.5 Termination of UBC Collaboration if DuPont Merck Does Not Extend the UBC Collaboration and Result of Such
Termination. If DuPont Merck does not exercise the option to extend the UBC Collaboration pursuant to Section 5.2, the UBC Collaboration will terminate as of the expiration of the Initial UBC Term. In the event of such termination of the UBC
Collaboration: 
  
 (a) the license granted to DuPont Merck under
Section 10.2.1 shall immediately terminate and be of no further force and effect, 
  
 (b) all Mitotix rights to the UBC Targets, including any New UBC Targets shall immediately revert to Mitotix, 
  
 (c) Mitotix shall have, without any further action by the parties, a worldwide, exclusive license in the UBC Field, with the right to sublicense, to any
and all rights in (a) any Know-how and DuPont Merck Inventions gained or discovered by DuPont Merck during the UBC Collaboration relating specifically to the UBC Targets, including any New UBC Targets; and (b) all Joint Inventions in the UBC Field
relating specifically to UBC Targets; provided however, that such exclusive license shall become non-exclusive after the expiration of a ten (10) year period following the termination of the Initial UBC Term, 
  
 (d) Mitotix shall have, without any further action by the parties, a
worldwide non- exclusive license in the UBC Field to any Know-how and DuPont Merck Inventions gained or developed by DuPont Merck during the UBC Collaboration relating to assays or otherwise useful in the UBC Field, 
  

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 (e) any Confidential Information delivered to DuPont Merck by Mitotix for use in the UBC Collaboration
shall be promptly returned to Mitotix, 
  
 (f) notwithstanding the
foregoing, DuPont Merck shall retain all rights to, and no rights are granted to Mitotix with respect to, compounds delivered to Mitotix pursuant to Section 6.1.3 or otherwise disclosed to Mitotix, including without limitation all DuPont Merck
know-how and patent rights relating to such compounds, 
  
 (g)
Mitotix shall promptly return to DuPont Merck all compounds delivered to Mitotix pursuant to Section 6.1.3 and any information delivered to Mitotix by DuPont Merck relating to DuPont Merck compounds for use in the UBC Collaboration shall be promptly
returned to DuPont Merck, and 
  
 (h) DuPont Merck shall not,
either individually, or with an Affiliate or Third Party pursue any research, development, manufacturing, sales or marketing efforts in the UBC Field for a period of twenty four (24) months following the termination of the UBC Collaboration.

  
 5.6 Certain Royalty Rights. If Mitotix or a Third Party
licensee of Mitotix, sells a therapeutic or Radiopharmaceutical product in the UBC Field that incorporates a compound that was: 
  
 (a) (x) first identified within ten (10) years after the termination of the UBC Collaboration through the use of the UBC Targets and (y) discovered
or selected for development in reliance upon the Know-how or DuPont Merck Inventions exclusively licensed to Mitotix pursuant to Section 5.5(c) above, or 
  

(b) (x) first identified within four (4) years after the termination of the UBC Collaboration through the use of the UBC Targets and (y)
discovered or selected for development in reliance upon the Know-how in existence prior to the termination of the UBC Collaboration, 
  
 then such product shall be a Mitotix Product and Mitotix shall pay the royalties set forth in Article 12 upon the sale of such Mitotix Product. 
  
 5.7 UBC Operational Disengagement Plan. 
  
 In the event of a Change of Control (defined in Section 19.13) and the
failure of Mitotix (or its successor) to adhere to the provisions of Section 19.13, as reasonably determined by DuPont Merck, (i) DuPont Merck may elect (subject to the restrictions in Section 19.13) to commence the UBC Operational Disengagement
Plan effective upon three (3) months prior written notice to Mitotix or (ii) if the Change of Control occurs prior to the expiration of DuPont Merck’s option to extend the UBC Collaboration under Section 5.2, DuPont Merck may, effective upon
three (3) months prior written notice to Mitotix, elect to terminate the UBC Collaboration and such termination shall have the effect set forth in Section 5.5. If DuPont Merck elects to commence the UBC Operational Disengagement Plan, DuPont
Merck’s option to extend the UBC Collaboration under Section 5.2 shall 

  

 20 

 
remain in effect. If DuPont Merck does not exercise the option to extend the UBC Collaboration pursuant to Section 5.2, the terms of Section 5.5 shall apply.

  
 Upon commencement of the UBC Operational Disengagement Plan,
the Collaborative Policy Setting Committee shall dissolve with respect to the UBC Collaboration and all research and development activities under the UBC Collaboration shall become the sole responsibility of DuPont Merck. Under the UBC Operational
Disengagement Plan, DuPont Merck will assume responsibility for all operational elements of the UBC Collaboration, but the financial elements of the UBC Collaboration shall not be altered. 
  
 Following commencement of the UBC Operational Disengagement Plan, upon
request by DuPont Merck, the UBC Research Program may be continued under DuPont Merck’s direction and Mitotix shall provide research and development support for the UBC Research Program in accordance with an Annual UBC Research Plan and Budget
and subject to DuPont Merck’s funding of such research and development support. In such event, such research and development support by Mitotix shall be provided up to a level of eight qualified full time equivalent scientists and substantially
similar to the corresponding level of support provided by Mitotix under the CDK Research Program. Upon commencement of the UBC Operational Disengagement Plan, upon request by DuPont Merck, Mitotix shall discontinue its operational activities in
support of the UBC Collaboration. 
  
 Following commencement of
the UBC Operational Disengagement Plan, upon request by DuPont Merck, Mitotix shall provide DuPont Merck with all materials, technical information and know-how necessary or useful to enable DuPont Merck to continue the UBC Research Program (to the
extent not transferred earlier) and shall provide DuPont Merck with reasonable assistance in transferring assays to DuPont Merck. Upon request by DuPont Merck, all compounds and information in tangible form received by Mitotix from DuPont Merck
shall be returned to DuPont Merck. 
  
 Following the commencement
of the UBC Operational Disengagement Plan, Mitotix shall continue to have the right to fund UBC Research, Development and Pre-Launch Marketing Costs incurred by DuPont Merck so as to maintain Mitotix’s Percentage Contribution above twenty
percent (20%) in accordance with Section 5.4, and if Mitotix does so, Mitotix shall continue to have the right to receive a share of the UBC Operating Profit in accordance with Section 11.5 and Appendices H and I. In the event that
Mitotix permits its Percentage Contribution to decrease to less than twenty percent (20%), the Alternate UBC Plan shall be deemed to have commenced, for purposes of the financial provisions only, such that (i) all UBC Products shall be deemed to be
Royalty-Bearing Products, and (ii) DuPont Merck shall reimburse Mitotix on a straight dollar for dollar basis (i.e. not time adjusted) for all UBC Research, Development and Pre-Launch Marketing Costs incurred by Mitotix from the Effective Date until
the deemed commencement of the Alternate UBC Plan hereunder; provided, however, that Mitotix shall not be entitled to such reimbursement under clause (ii) above if (a) the entry of the last patient into the pivotal clinical efficacy trial on
which the NDA filing for the first UBC Product would be based did not occur prior to the Change of Control and Mitotix permits its Percentage Contribution to decrease to less than twenty percent (20%) after the commencement of the UBC Operational
Disengagement Plan and after the entry of such patient, or (b) no UBC Product is ever sold. Such reimbursement 

  

 21 

 
under clause (ii) shall be made in equal quarterly payments over a three (3) year period commencing with the First Commercial Sale of a UBC Product,
provided, however, that no such quarterly payment shall exceed thirty percent (30%) of the Net Sales of the UBC Product in that quarter. 
  
 5.8 New UBC Targets. The parties agree that the UBC Collaboration will focus on an area of science that is relatively undefined as of the Effective
Date, and that it is possible that more than one New UBC Target may be discovered during the course of the UBC Collaboration. Within ninety (90) days after the Collaborative Policy Setting Committee has accepted a new target as a New UBC Target it
shall notify the parties in writing of its determination as to whether such New UBC Target shall be pursued as part of the UBC Collaboration. If the Collaborative Policy Setting Committee determines to include a New UBC Target within the UBC
Collaboration, the New UBC Target shall become a UBC Target for the purposes of this Agreement. If the Collaborative Policy Setting Committee determines in writing not to include a particular New UBC Target within the UBC Collaboration, Mitotix
shall have all rights to use such New UBC Target either independently or in collaboration with a Third Party within the UBC Field, and such New UBC Target will not be included in the definition of UBC Target and will not be subject to the license
grant set forth in Section 10.2.1. If Mitotix, either independently or in collaboration with a Third Party, uses such New UBC Target to discover or select for development a compound that is first identified within four (4) years following the
release of such New UBC Target by DuPont Merck and that is ultimately incorporated within a therapeutic or Radiopharmaceutical product, then such product shall be a Mitotix Product and Mitotix shall pay the royalties set forth in Article 12 upon any
sale of such Mitotix Product. Any royalty payments made by Mitotix to DuPont Merck under this Section shall not be deemed to be a UBC Research, Development and Pre-Launch Marketing Cost for purposes of Section 5.4 hereof. 
  
 5.9 Terms of Equity Investment. 
  
 5.9.1 General Provisions Relating to Price of Equity
Investment. The number of shares of Mitotix stock to be issued to DuPont Merck in exchange for the UBC Deferral Payment shall be calculated as of the date Mitotix receives each installment of the UBC Deferral Payment. The number of shares of
Mitotix stock to be issued to DuPont Merck in exchange for the UBC Extension Payment shall be calculated as of the date Mitotix receives the Extension Notice, provided that Mitotix receives the UBC Extension Payment no later than thirty (30)
days after it receives the Extension Notice. If Mitotix receives the UBC Extension Payment more than thirty (30) days following receipt of the Extension Notice, then the number of shares to be issued in exchange for the UBC Extension Payment shall
be calculated as of the date Mitotix receives the UBC Extension Payment. Each calculation date referred to in the preceding three sentences is hereinafter referred to as the applicable “UBC Pricing Date.” In any case where the number of
shares issuable to DuPont Merck is determined by reference to prices paid by investors in Mitotix or reported trading prices, such prices shall be appropriately adjusted to reflect stock splits, stock dividends, combinations, mergers and other
recapitalizations affecting shares of Mitotix capital stock. 
  

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 5.9.2 Investment Prior to an Initial Public Offering. If Mitotix has not completed
an initial public offering of its common stock (an “IPO”) at the time the UBC Extension Payment is received by Mitotix, then DuPont Merck shall receive, in exchange for the UBC Deferral Payment and the UBC Extension Payment, redeemable,
convertible shares of the next available class of preferred stock with rights, preferences and privileges substantially similar to the rights, preferences and privileges attached to the Series C Convertible Preferred Stock of Mitotix, except that
the liquidation preference associated with such new class of stock will be junior to all prior series of preferred stock. With respect to each UBC Pricing Date, the number of shares of preferred stock issuable to DuPont Merck shall be determined by
dividing the amount of the UBC Deferral Payment made on that date or the UBC Extension Payment by the price at which Mitotix most recently (as of such UBC Pricing Date) sold shares of preferred stock to investors, provided, however, that if
Mitotix did not receive gross proceeds of at least *** from such most recent sale of stock to investors, then the price shall be the weighted average purchase price of all shares of stock sold by Mitotix during the period beginning on the Effective
Date (including the shares sold to DuPont Merck on the Effective Date) and ending on the applicable UBC Pricing Date, excluding shares of stock and options to purchase shares of stock issued to employees and directors of and consultants to Mitotix
and shares issued to non-profit institutions in exchange for technology rights in arms-length negotiated transactions in which no other material investor in Mitotix has any direct or indirect interest in the shares issued to the non-profit
institution; and provided, further, that the price of such shares shall in no event be less than $3.00 per share nor more than $7.00 per share (subject to appropriate adjustment for stock splits, stock dividends, combinations, mergers and
other recapitalizations affecting shares of Mitotix capital stock.) 
  
 5.9.3 Investment After an Initial Public Offering. If Mitotix has completed an IPO before the UBC Extension Payment is received by Mitotix, then DuPont Merck shall receive, in exchange for the UBC Deferral
Payment and the UBC Extension Payment, shares of Mitotix common stock. With respect to each UBC Pricing Date occurring prior to an IPO, the number of shares of common stock issuable to DuPont Merck shall be determined by dividing the amount of the
UBC Deferral Payment made on that date by the price determined pursuant to Section 5.9.2. With respect to each UBC Pricing Date occurring after an IPO, the number of shares shall be determined by dividing the amount of the UBC Deferral Payment made
on that date or the UBC Extension Payment by the average of the closing prices reported for Mitotix’s common stock during the thirty (30) trading days ending on the second trading day prior to the applicable UBC Pricing Date. The shares issued
to DuPont Merck pursuant to this Section 5.9.3 shall be afforded registration rights substantially similar to those granted to DuPont Merck with respect to shares purchased by it under and pursuant to the Series C Convertible Preferred Stock
Purchase Agreement, entered into among Mitotix, DuPont Merck and others (the “Purchase Agreement”), except that, (i) in addition to the registration rights granted DuPont Merck under Sections 7.4 and 7.5 of the Purchase Agreement, DuPont
Merck may require registration of all or part (but at least 50%) of the shares purchased by it under this Section 5.9.3 for sale in a firm commitment underwritten offering by an underwriter selected by DuPont Merck and reasonably acceptable to
Mitotix, in which offering all registration expenses are borne by Mitotix and all underwriting discounts and selling commissions are borne by DuPont Merck, (ii) supplementing DuPont Merck’s rights under Section 7.4 of the Purchase Agreement in
the 

	***	Certain information on this page 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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 case of a “piggy-back” registration in which the managing underwriter in such offering is
entitled to exclude shares held by selling shareholders from the offering, Mitotix will use good faith efforts to cause all other holders of “piggy-back” registration rights to agree that their shares will be subject to exclusion from the
offering before any shares held by DuPont Merck are excludable. The additional rights to be granted to DuPont Merck under clause (i) of the preceding sentence will expire when the shares purchased by DuPont Merck under this Section 5.9.3 become
eligible for sale pursuant to Rule 144(k) under the Securities Act of 1933, or any successor provision. 
  
 ARTICLE 6. THE UBC COLLABORATION - UBC RESEARCH PROGRAM 
  
 6.1 Conduct of the UBC Research Program. 
  
 6.1.1 General Terms. The UBC Research Program shall be conducted in good scientific manner, and in compliance with all applicable
good laboratory practices, and applicable legal requirements, to attempt to achieve efficiently and expeditiously the objectives described in the work plan set forth in Appendix F hereto. Throughout the UBC Research Program, Mitotix and
DuPont Merck shall each assign a minimum of four full-time equivalent qualified scientists to perform the work set forth in the Annual UBC Research Plan and Budget (as defined below); provided, however, that DuPont Merck shall not be
obligated to pay any installment of the UBC Deferral Payment unless Mitotix has assigned, throughout the Initial UBC Term, a minimum of ten full-time equivalent qualified scientists to perform such work; and provided, further, that if Mitotix
has reduced the number of qualified scientists devoted to working on the UBC Research Program at the written request of DuPont Merck, then DuPont Merck shall be required nonetheless to make each installment of the UBC Deferral Payment. The name and
percentage of time devoted to working on the UBC Research Program for each scientist comprising such requisite number of full-time equivalent scientists for each party shall be provided in each Annual UBC Research Plan and Budget. The mixture of
skills and levels of expertise of such scientists shall be appropriate to the scientific objectives of the UBC Research Program. Mitotix and DuPont Merck shall proceed diligently with the work set out in the Annual UBC Research Plan and Budget by
using their respective good faith efforts considering the funding commitments of both parties hereunder. 
  
 6.1.2 Annual UBC Research Plan and Budget. The UBC Research Program shall be conducted under an annual UBC research plan and budget
which describes the work to be pursued by Mitotix and DuPont Merck during the Research Year (the “Annual UBC Research Plan and Budget”). The first Annual UBC Research Plan and Budget shall be prepared by the UBC Research Operating
Committee and approved by the Collaborative Policy Setting Committee within forty-five (45) days after the Effective Date. Subsequent Annual UBC Research Plans and Budgets shall be prepared by the UBC Research Operating Committee, for submission to,
and approval by, the Collaborative Policy Setting Committee, not later than sixty (60) days prior to the start of each Research Year. The Collaborative Policy Setting Committee shall determine which party shall be responsible for conducting the
primary screening of compounds, continued biological discovery, target validation, biochemical and cell-based assay refinement, and new assay development and screening 

  

 24 

 
activities for UBC Targets, and where such activities will be conducted. Mitotix and DuPont Merck will share in the chemistry efforts, in vivo model
development and animal pharmacology within the UBC Field. 
  
 6.1.3 DuPont Merck Compounds. Following primary screening, compounds which meet the specifications set forth by the UBC Research Operating Committee for suitable candidates for continued preclinical evaluation
shall be provided to Mitotix. Mitotix shall conduct secondary screening of such compounds, and shall conduct additional preclinical work with respect to such compounds, all as set forth in the Annual UBC Research Plan and Budget. Mitotix will
promptly provide to DuPont Merck all data from such screening and preclinical work in accordance with Section 6.1.6 and as otherwise reasonably requested by DuPont Merck in support of the development of UBC Development Compounds. Such compounds
provided by DuPont Merck will be used by Mitotix solely for screening and other preclinical work within the UBC Field in accordance with the Annual UBC Research Plan and Budget and for no other purpose. Any know-how incidentally developed by Mitotix
outside of the UBC Field using a DuPont Merck compound provided hereunder shall be promptly disclosed to DuPont Merck. Any know-how and patent rights developed by Mitotix using a DuPont Merck compound shall be considered to be Know-how and UBC
Patent Rights, respectively. DuPont Merck shall at all times own all rights to the compounds it provides to Mitotix hereunder, including without limitation, all rights with respect to the manufacture, use, or sale of such compounds. In accordance
with the foregoing, Mitotix agrees to (i) disclose to DuPont Merck any inventions it conceives or makes with respect to the manufacture, use or sale of compounds provided by DuPont Merck to Mitotix hereunder; (ii) assign to DuPont Merck all patent
rights with respect to such inventions and (iii) execute any necessary papers and otherwise reasonably cooperate with DuPont Merck in securing patents on such inventions. Upon expiration or termination of the UBC Research Program, Mitotix shall,
upon the request of DuPont Merck, return or destroy all compounds provided to Mitotix by DuPont Merck in the performance of the UBC Research Program. 
  
 6.1.4 Subcontracts. Subject to the provisions of Article 15, and as set forth in the Annual UBC Research Plan and Budget or
otherwise approved by the Collaborative Policy Setting Committee, Mitotix and DuPont Merck may subcontract portions of the UBC Research Program to be performed by them in the normal course of their business to a Third Party upon prior written notice
to the other; provided, however, that such Third Party has entered into an appropriate confidentiality agreement with Mitotix and/or DuPont Merck obligating such Third Party to be bound by the confidentiality obligations contained in this
Agreement, or such subcontracting would not require the transfer of confidential information to the Third Party. 
  
 6.1.5 Data. Mitotix and DuPont Merck shall each maintain records in sufficient detail and in good scientific manner appropriate for
patent purposes and as will properly reflect all work done and results achieved in the performance of the UBC Research Program (including all data in the form required to be maintained under any applicable governmental regulations). Such records
shall include books, records, reports, research notes, charts, graphs, comments, computations, analyses, recordings, photographs, computer programs and documentation thereof, computer information storage means, samples of 

  

 25 

 
materials and other graphic or written data generated in connection with the UBC Research Program. Mitotix and DuPont Merck shall each provide the other the
right to inspect such records, and shall provide copies of all requested records, to the extent reasonably required for the performance of the requesting party’s obligations under this Agreement; provided, however, that each party shall
maintain such records and the information of the other contained therein in confidence in accordance with Article 15 below and shall not use such records or information except to the extent otherwise permitted by this Agreement. 
  
 6.1.6 Quarterly Reports by Mitotix and DuPont Merck.
Within thirty (30) days following the end of each Calendar Quarter, Mitotix and DuPont Merck shall each provide to the members of the UBC Research Operating Committee a written report summarizing in reasonable detail the work performed by it under
the UBC Research Program during the preceding Calendar Quarter. 
  
 6.2 Expiration or Termination of the UBC Research Program and Result of Such Termination. 
  
 6.2.1 Termination of Initial UBC Term. The term of the UBC Research Program shall commence on January 1, 1996 and shall terminate
as of the expiration of the Initial UBC Term, unless DuPont Merck exercises its option to extend the UBC Collaboration pursuant to Section 5.2. Upon the termination of the UBC Research Program pursuant to this Section 6.2.1, the provisions of
Section 5.5 shall apply. 
  
 6.2.2 Expiration
Following Extension of the UBC Collaboration and Commencement of Alternate UBC Plan. If DuPont Merck exercises its option to extend the UBC Collaboration and the Alternate UBC Plan is in effect in accordance with the terms of Section 5.4.4, then
the UBC Research Program shall continue for the remaining Research Year and continue for an additional three (3) Research Years. DuPont Merck shall have the option to extend the UBC Research Program for up to three (3) additional consecutive one-
year Research Years. In order to exercise its option to extend the UBC Research Program, DuPont Merck shall provide Mitotix with written notice of extension of the UBC Research Program at least six (6) months prior to the commencement of each such
additional one-year period. Upon the expiration of the UBC Research Program pursuant to this Section 6.2.2, the terms of Sections 10.2.2 and 10.2.3 shall apply. 
  
 6.2.3 Termination of the UBC Research Program Following Extension of the UBC Collaboration and Prior to
the Commencement of the Alternate UBC Plan. If DuPont Merck exercises its option to extend the UBC Collaboration under Section 5.2 and the Alternate UBC Plan is not in effect, then the UBC Research Program shall continue for the remaining
Research Year following DuPont Merck’s exercise of such option and for an additional three (3) Research Years unless the Collaborative Policy Setting Committee determines in writing that the UBC Research Program should terminate earlier. DuPont
Merck shall have the option to extend the UBC Research Program for up to three (3) additional consecutive one-year Research Years. In order to exercise its option to extend the UBC Research Program, DuPont Merck shall provide Mitotix with written
notice of extension of the UBC Research Program at least six (6) months prior to the commencement of each such additional one-year period. Upon the expiration of the UBC Research Program 

  

 26 

 
pursuant to this Section 6.2.3, the terms of Section 10.2.2 and 10.2.3 shall apply, in addition to the following: 
  
 (a) Upon termination of the UBC Research Program under this
Section 6.2.3, neither party shall engage in further research activities in the UBC Field without first notifying the other party of the UBC Targets it wishes to pursue. Within ninety (90) days after receipt of such notice, the recipient shall
notify the other party if it wishes to collaborate on such research, in which event the parties will perform the research together as part of the UBC Collaboration in accordance with Articles 5 and 6. If the recipient does not respond in writing
within such ninety (90) day period or responds in writing that it does not wish to collaborate, then the party who wishes to continue research may do so on the following basis: 
  
 (i) In the case of continuation of the research by Mitotix, Mitotix shall have all rights to use the UBC
Targets that were so identified to DuPont Merck by Mitotix, either independently or in collaboration with a Third Party, within the UBC Field, or otherwise, and such UBC Targets will not be included in the definition of UBC Target and will not be
subject to the license grant set forth in Section 10.2.1. If Mitotix, either independently or in collaboration with a Third Party, uses such UBC Targets to discover or select for development a compound that is first identified within four (4) years
following expiration of the UBC Research Program and that is ultimately incorporated within a therapeutic or Radiopharmaceutical product, then such product shall be a Mitotix Product and Mitotix shall pay the royalties set forth in Article 12 upon
any sale of such Mitotix Product. Mitotix’s costs of performing such research and any royalty payments made by Mitotix to DuPont Merck under this paragraph shall not be deemed to be a UBC Research, Development and Pre-Launch Marketing Cost or
Allowable Expense. 
  
 (ii) In the case of
continuation of the research by DuPont Merck, DuPont Merck’s costs of performing such research shall not be deemed to be a UBC Research, Development and Pre-Launch Marketing Cost or Allowable Expense and Mitotix will not be entitled to share in
UBC Operating Profits from sales of any UBC Products developed from use of such UBC Targets by DuPont Merck. If DuPont Merck, either independently or in collaboration with a Third Party, uses such UBC Targets to discover or select for development a
compound that is first identified within four (4) years following the earlier of (x) the termination of the license grant set forth in Section 10.2.1 pursuant to Section 10.2.3 or (y) the termination of this Agreement and that is ultimately
incorporated within a UBC Product, then such product shall be a Royalty-Bearing Product and DuPont Merck shall pay the royalties set forth in Article 11 upon any sale of such Royalty-Bearing Product. Notwithstanding the inclusion of such product
within the definition of Royalty-Bearing Products, DuPont Merck shall not be obligated to pay any milestone payments to Mitotix under Article 11 with respect to such product. DuPont Merck’s costs of performing such research and any royalty
payments made by Mitotix to DuPont Merck under this paragraph shall not be deemed to be a UBC Research, Development and Pre-Launch Marketing Cost or Allowable Expense. 
  
 (b) Upon conversion of the license granted to DuPont Merck in Section 10.2.1 to a non-exclusive license
pursuant to Section 10.2.2, the provisions of paragraph (a) 

  

 27 

 
above shall no longer apply as to any additional research that a party wishes to pursue in the UBC Field. 
  
 6.2.4 Termination of the UBC Research Program Following
Commencement of the UBC Operational Disengagement Plan. If DuPont Merck elects to commence the UBC Operational Disengagement Plan and at any time thereafter determines not to request that Mitotix provide research and development support
for the UBC Research Program as set forth in Section 5.7, the UBC Research Program shall be deemed to have terminated and the provisions of Sections 10.2.2 and 10.2.3 shall apply. 
  
 ARTICLE 7. UBC COLLABORATION: UBC DEVELOPMENT PROGRAM 
  
 7.1 Description of UBC Development Compounds. Based upon the preclinical work conducted by Mitotix and DuPont Merck
and the recommendation of the UBC Research Operating Committee, (i) unless the Alternate UBC Plan is in effect, the Collaborative Policy Setting Committee shall determine whether to designate a compound as a UBC Development Compound, and (ii) if the
Alternate UBC Plan is in effect, DuPont Merck shall determine whether to designate a compound as a UBC Development Compound. 
  
 7.2 Clinical Development and Marketing. 
  
 7.2.1 When the Alternate UBC Plan is Not in Effect. 
  
 (a) If the Alternate UBC Plan is not in effect, the clinical development of a UBC Development Compound
outside of the United States following a decision by the Collaborative Policy Setting Committee to designate a compound as a UBC Development Compound and continuing through obtaining regulatory approvals of any resulting UBC Product shall be the
sole responsibility of DuPont Merck with input from Mitotix through the Collaborative Policy Setting Committee. With respect to the clinical development of a UBC Development Compound in the United States, the Collaborative Policy Setting Committee
shall determine the participation of Mitotix and DuPont Merck; provided, however, that Mitotix shall have the right, at its discretion, to participate in such development in a manner consistent with Mitotix’s then current Percentage
Contribution and its co-promotion rights set forth in Appendix G2, and DuPont Merck shall be responsible for at least seventy percent (70%) of the development activities. It is agreed that Mitotix’s personnel expenses in support of the
clinical development of a UBC Development Compound shall not exceed the lesser of (i) Mitotix’s Percentage Contribution times the total personnel expenses in support of the clinical development of such UBC Development Compound or (ii) thirty
percent (30%) of such total personnel expenses, unless otherwise determined by Collaborative Policy Setting Committee. The personnel provided by Mitotix in support of the UBC Collaboration shall possess the experience and qualifications appropriate
to the objectives of the UBC Collaboration in accordance with industry standards. 
  
 7.2.2 Clinical Development and Marketing Under the Alternate UBC Plan. If the Alternate UBC Plan is in effect, then DuPont Merck
shall have sole responsibility for conducting, at its own expense, all clinical, regulatory, marketing, and sales work associated 

  

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with a UBC Development Compound, subject to Mitotix’ co-promotion rights in the United States, as set forth in Appendix G1. For each such UBC
Development Compound, DuPont Merck shall use good faith commercially reasonable efforts to evaluate and develop such compound in a timely manner in accordance with industry standards and DuPont Merck internal practices and shall advise the
Collaborative Policy Setting Committee as to the status of the development of each UBC Development Compound. Consistent with industry standards and DuPont Merck internal practices, DuPont Merck shall use its good faith commercially reasonable
efforts to conduct at its expense such human clinical trials as are necessary to obtain all regulatory approvals to manufacture and market UBC Products which are subject to the Alternate UBC Plan and to seek and obtain all necessary regulatory
approvals to market and promptly commence worldwide marketing of each such UBC Product. 
  
 7.3 Development Information. If the Alternate UBC Plan is in effect and/or as to all clinical development of a UBC Development Compound outside the United States, (i) DuPont Merck shall keep Mitotix informed as
to the progress of DuPont Merck in the development and testing of all UBC Development Compounds and UBC Products and the preparing, filing and obtaining of the approvals necessary for marketing, (ii) within thirty (30) days following the end of the
first month of each Calendar Quarter following the designation of a UBC Development Compound, DuPont Merck shall provide to Mitotix a reasonably detailed report which shall describe the progress of the development and testing of the UBC Products
incorporating such UBC Development Compounds. DuPont Merck may satisfy its reporting obligation hereunder by providing an oral report to the Collaborative Policy Setting Committee within such thirty (30) day period, provided that a written report of
the oral presentation is delivered to Mitotix no later than thirty (30) days after the oral report is made to the Collaborative Policy Setting Committee. In addition, DuPont Merck shall provide Mitotix with a minimum of three (3) months’
advance notice of the contemplated filing of an IND or an NDA, and DuPont Merck shall provide Mitotix with a report on all material regulatory submissions at least forty-five (45) days prior to the date of such submissions, or any major amendments
or supplements thereto within ten (10) business days of filing thereof. DuPont Merck shall provide to Mitotix in a timely manner copies of any material regulatory submission, or amendments thereof, reasonably requested by Mitotix or, alternatively
shall provide Mitotix reasonable access to each such material regulatory submission or amendments thereof at DuPont Merck’s offices, for review and copying by Mitotix. 
  
 ARTICLE 8. MITOTIX’S RIGHT TO CO-PROMOTE 
  
 8.1 Mitotix’s Co-promotion Option. Mitotix shall have the option to co-promote each CDK Product and UBC Product
in the United States under the terms set forth in Appendix Gl and Appendix G2. respectively. In the event that Mitotix determines to exercise its option to co-promote a CDK Product or UBC Product in the United States, Mitotix and
DuPont Merck will negotiate, execute and deliver a co-promotion agreement containing the principles of agreement set forth in Appendix Gl and Appendix G2, respectively, and such other terms and conditions as DuPont Merck and Mitotix
may 

  

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mutually agree upon. If the Alternate UBC Plan is in effect, Mitotix’s co-promotion rights will be limited to such rights described for CDK Products in
Appendix G1. 
  
 ARTICLE 9. MANAGEMENT OF THE COLLABORATIONS

  
 9.1 Collaborative Policy Setting Committee. 

 
 9.1.1 General. A joint committee comprised of not
more than four named senior representatives of DuPont Merck and not more than four named senior representatives of Mitotix (the “Collaborative Policy Setting Committee”) shall be appointed and shall meet not less than semi-annually during
the term of the Collaboration. Each representative shall be appointed by the applicable party. The first meeting will be held no later than forty-five (45) days after the Effective Date. Meetings shall be at times and places agreed to by Mitotix and
DuPont Merck, alternating between Cambridge, Massachusetts and Wilmington, Delaware, or such other locations or in such other form (e.g., telephone or video conference) as the members of the Collaborative Policy Setting Committee shall agree.
At such meetings, the principal function of the Collaborative Policy Setting Committee will be to discuss the CDK Collaboration and the UBC Collaboration and to set priorities thereunder, to approve the Annual CDK Research Plan and the Annual UBC
Research Plan and Budget, to discuss the compounds chosen for development, and to discuss the quality and productivity of the personnel assigned to each project. The Collaborative Policy Setting Committee may also discuss at such meetings the
preclinical or clinical development of CDK Development Compounds and UBC Development Compounds, as well as any anticipated regulatory filings with respect to possible CDK or UBC Products. Members of the Collaborative Policy Setting Committee may be
represented at any meeting by another member of the Collaborative Policy Setting Committee, or by a deputy. Any approval, determination or other action agreed to by all of the members of the Collaborative Policy Setting Committee or their deputies
present at the relevant Collaborative Policy Setting Committee meeting shall be the approval, determination or other action of the Collaborative Policy Setting Committee, provided that at least two representatives of each party are present at such
meeting. 
  
 9.1.2 Chair. The
Collaborative Policy Setting Committee shall be jointly chaired by a DuPont Merck and a Mitotix representative to the Committee. Each chair shall be appointed by the applicable party, rather than by a vote of the committee. 
  
 9.1.3 Minutes. The Collaborative Policy Setting
Committee shall keep accurate minutes of its deliberations which record all proposed decisions and all actions recommended or taken. The responsibility for drafting the minutes shall rotate between the joint chairs. Draft minutes shall be sent to
all members of the Collaborative Policy Setting Committee within thirty (30) working days after each meeting. Draft minutes shall then be edited by the chair who drafted the minutes and shall be issued to the members of the Collaborative Policy
Setting Committee in final form. All records of the Collaborative Policy Setting Committee shall be available to both parties. 
  
 9.2 Research Operating Committees. A CDK Research Operating Committee and a UBC Research Operating Committee, each comprised of not more than four
representatives 

  

 30 

 
of DuPont Merck and not more than four representatives of Mitotix shall be appointed and each committee shall meet as it determines necessary, but not less
than three times during each Research Year. Each representative shall be appointed by the applicable party. Over time, it is anticipated that the UBC Research Operating Committee will begin to act as a development committee as it takes on
responsibility for overseeing the day-to-day development of the UBC Development Compounds and the UBC Products. Meetings shall be held at times and places agreed to by Mitotix and DuPont Merck, alternating between Cambridge, Massachusetts and
Wilmington, Delaware, or such other locations or in such other form (e.g., telephone or video conference) as the members of the committee shall agree. The Research Operating Committees will be responsible for overseeing the day-to-day
implementation of goals of the respective Research Programs as determined by the Collaborative Policy Setting Committee and preparing the Annual CDK Research Plan and the Annual UBC Research Plan and Budget. Members of each Research Operating
Committee may be represented at any meeting by another member of the respective Research Operating Committee or by a deputy. Any approval, determination or other action agreed to by all members of a Research Operating Committee or their deputies
present at the relevant Research Operating Committee shall be the approval, determination or other action of such Research Operating Committee, provided that at least a majority of the representatives of each party are present at such meeting.

  
 9.2.1 Chairs. The CDK Research
Operating Committee shall be jointly chaired by a representative of Mitotix and a representative of DuPont Merck. During the Initial UBC Term, the UBC Research Operating Committee shall be chaired by a Mitotix representative to the committee. During
the Extended UBC Collaboration, the UBC Research Operating Committee shall be jointly chaired by a representative of Mitotix and a representative of DuPont Merck. Each chair shall be appointed by the applicable party, rather than by a vote of the
committee. 
  
 9.2.2 Minutes. Each
Research Operating Committee shall keep accurate minutes of its deliberations which record all proposed decisions and all actions recommended or taken. The chairs shall be responsible for the preparation of draft minutes, and when a Research
Operating Committee is jointly chaired, the responsibility for drafting the minutes shall rotate between the joint chairs. Draft minutes shall be sent to all members of the Research Operating Committee within thirty (30) working days after each
meeting. Draft minutes shall be edited by the chair who drafted the minutes and shall be issued to the members of the Research Operating Committee and the members of the Collaborative Policy Setting Committee in final form. All records of each
Committee shall at all times be available to both parties. 
  
 9.3
Disagreements. All disagreements within the Collaborative Policy Setting Committee or either of the Research Operating Committees shall be subject to the following: 
  
 (a) the representatives of the committee will negotiate in good faith for a period of not less than sixty (60) days to
attempt to resolve the dispute; disagreements within either of the Research Operating Committees shall be presented to the Collaborative Policy Setting Committee and shall be negotiated in good faith by the Collaborative Policy Setting Committee to
attempt to resolve the dispute; 
  

 31 

 (b) failing resolution at the above level, the representatives of the disputing Collaborative Policy
Setting Committee shall promptly present the disagreement to the Chief Executive Officer of Mitotix and the President, DuPont Merck Research Laboratories, and such executives shall meet or discuss in a telephone or video conference each party’s
view and make a good faith effort to resolve the disagreement; 
  
 (c) failing resolution at the above level, the parties shall attempt to resolve the disagreement by promptly presenting the disagreement to the Chairman of Mitotix and the Chief Executive Officer of DuPont Merck, and such executives shall
meet or discuss in a telephone or video conference and make a good faith effort to resolve the disagreement. 
  
 9.4 Project Leaders. At least once a year Mitotix and DuPont Merck shall provide each other with the names of the key employees within their
organizations who are working on the UBC Collaboration and the CDK Collaboration. In addition, each party shall appoint a project leader for the CDK Collaboration and a project leader for the UBC Collaboration. Project leaders shall be the primary
contact between the parties with respect to each collaboration and shall serve on the respective Research Operating Committee. Each party shall notify the other within thirty (30) days of the date of this Agreement of the appointment of its project
leader and shall notify the other party as early as practicable regarding any change in the appointment. 
  
 9.5 Availability of Employees. Each party agrees to make its employees and consultants reasonably available to consult with the other party on
issues arising during the Collaboration and in connection with any request from any regulatory agency, including regulatory, scientific, technical and clinical testing issues. 
  
 9.6 Visit of Facilities. Representatives of Mitotix and DuPont Merck may, upon reasonable notice and at times
reasonably acceptable to the other party, visit the facilities where the CDK Research Program or the UBC Research Program is being conducted, and consult informally, during such visits and by telephone, with personnel of the other party performing
work on the respective Research Program. If requested by the other party, Mitotix and DuPont Merck shall cause appropriate individuals working on the CDK Research Program or the UBC Research Program or on CDK or UBC Products to be available for
meetings at the location of the facilities where such individuals are employed at times reasonably convenient to the party responding to such request. 
  
 ARTICLE 10. LICENSE GRANTS AND RIGHTS OF FIRST NEGOTIATION 
  
 10.1 Grant of License to DuPont Merck in CDK Field. 
  
 10.1.1 Exclusive License in CDK Field. Except as otherwise provided, herein, Mitotix hereby grants DuPont Merck an exclusive
worldwide right and license (with the right to sublicense) under the CDK Pastent Rights, Mitotix Inventions, Joint Inventions, and Know-how (i) utilize the CDK-D Targets in the CDK-D-Field, (ii) to develop, make have made, use and sell CDK Products
and Immunoassay Products in the CDK-D Field, (iii) utilize the CDK-non-D Targets in the CDK-non-D Field and (iv) develop, make have made, 

  

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use and sell CDK Products and Immunoassay Products in the CDK-non-D Field. No license is granted to DuPont Merck under this Section 10.1.1 to utilize the
CDK-D Targets or the CDK-non-D Targets for Antisense, Gene Therapy or non-Radiopharmaceutical diagnostic applications. 
  
 10.1.2 Conversion to Non-Exclusive. Unless sooner terminated, the license granted to DuPont Merck in Section 10.1.1(i) and (iii)
shall become a non-exclusive license without any further action on the part of Mitotix or DuPont Merck seven (7) years after the expiration of the CDK Research Program, including any extensions thereof. Following the conversion of such license to a
non-exclusive license, Mitotix shall have the right to develop, make, have made, use and sell products in the CDK Field and in the CDK non-D Field. 
  
 10.1.3 Election to Terminate License Grant. Upon written notice to Mitotix, DuPont Merck may elect to terminate the license granted
to DuPont Merck in Section 10.1.1 at any time following the expiration or termination of the CDK Research Program pursuant to Sections 3.2.l(b), 3.2.l(c) or 3.3. above; provided, however, that upon such election, DuPont Merck shall retain an
exclusive license under the Mitotix Inventions, Joint Inventions and applicable Know-how solely to develop, make, have made, use and sell CDK Products incorporating compounds that at the time of termination of the CDK Research Program have been
designated as CDK Development Compounds. 
  
 10.1.4 Additional In-Licensed CDK Technology. If, from time to time during the term of the CDK Research Program, DuPont Merck shall determine that it is necessary or desirable and in the best interest of the CDK Collaboration to
license certain patent rights or know-how from a Third Party for use in the CDK Field, DuPont Merck shall so notify the Collaborative Policy Setting Committee and Mitotix in writing. DuPont Merck shall promptly commence negotiations with such Third
Party to determine the cost of licensing such patent rights and/or know-how. In the event that DuPont Merck enters into a license agreement with a Third Party which includes a license grant under such patent rights and/or know-how to use CDK Targets
for Antisense, Gene Therapy and non- Radiopharmaceutical diagnostic applications, and/or to use CDK-non-D Targets outside the CDK-non-D Field, DuPont Merck shall sublicense the patent rights and know-how for such uses to Mitotix, and such sublicense
shall survive termination of this Agreement. All costs and expenses incurred by DuPont Merck in obtaining any license referred to in this Section, including but not limited to upfront license payments, milestone payments, royalty payments and legal
fees and disbursements, shall be borne by DuPont Merck, unless such costs and expenses are attributable to applications sublicensed to Mitotix pursuant to the provisions above, in which case, such costs and expenses shall be the responsibility of
Mitotix. 
  
 10.1.5 Release of Certain CDK
Targets and Certain Royalty Payments. If at any time during the CDK Collaboration, the Collaborative Policy Setting Committee determines that a specific CDK Target will not be pursued as part of the CDK Collaboration, DuPont Merck, at its sole
discretion, may release the CDK Target to Mitotix, and shall provide Mitotix with written notice of its decision. If DuPont Merck releases such CDK Target to Mitotix, the CDK Target will no longer be included in the definition of CDK Targets and
will no longer be subject to the license grant set forth in Section 10.1.1. Thereafter, Mitotix or a Third Party licensee of Mitotix shall be permitted to use and license 

  

 33 

 
Third Parties to use the released CDK Target without restriction; provided, however, that if any product is ultimately sold by Mitotix or its licensee
within the CDK Field that incorporates a compound first identified within four (4) years following the release of the CDK Target by DuPont Merck and discovered or selected for development through the use of such released CDK Target, then such
product shall be a Mitotix Product and Mitotix shall pay the royalties set forth in Article 12 upon any sale of such Mitotix Product. 
  
 10.2 Grant of License Rights to DuPont Merck in the UBC Field. 
  
 10.2.1 Exclusive License in the UBC Field. Except as otherwise provided herein, Mitotix hereby grants
DuPont Merck an exclusive worldwide right and license (with the right to sublicense) under the UBC Patent Rights, Mitotix Inventions, Joint Inventions and the Know-how to (i) utilize the UBC Targets in the UBC Field and (ii) to develop, make, have
made, use and sell UBC Products and Immunoassay Products in the UBC Field. No license is granted to DuPont Merck under this Section 10.2.1 to utilize the UBC Targets for Antisense, Gene Therapy or non-Radiopharmaceutical diagnostic applications.

  
 10.2.2 Conversion to Non-Exclusive.
Unless sooner terminated, the license granted to DuPont Merck in Section 10.2.1 (i) shall become a non-exclusive license without any further action on the part of Mitotix or DuPont Merck seven (7) years after the expiration of the UBC Research
Program, including any extensions thereof. Following the conversion of such license to a non-exclusive license, Mitotix shall have the right to develop, make, have made, use and sell products in the UBC Field. If DuPont Merck does not exercise its
option to commence the Extended UBC Collaboration, the license granted to DuPont Merck in Section 10.2.1 shall terminate as provided in Section 5.5. 
  
 10.2.3 Election to Terminate License Grant. Upon written notice to Mitotix, DuPont Merck may elect to terminate the license granted
to DuPont Merck in Section 10.2.1 at any time following the expiration or termination of the UBC Research Program pursuant to Sections 6.2.1, 6.2.2 or 6.2.3 above; provided, however, that upon such election, DuPont Merck shall retain an
exclusive license under the Mitotix Inventions, Joint Inventions and applicable Know-how solely to develop, make, have made, use and sell UBC Products incorporating compounds that at the time of termination of the UBC Research Program have been
designated as UBC Development Compounds. 
  
 10.2.4 Additional In-Licensed UBC Technology. 
  
 (a) If, from time to time during the term of the UBC Research Program prior to DuPont Merck’s exercise of its option to commence the Extended UBC Collaboration, Mitotix shall determine that it is necessary or
desirable and in the best interest of the UBC Collaboration to license certain patent rights or know-how from a Third Party for use in the UBC Field, Mitotix shall so notify DuPont Merck and the Collaborative Policy Setting Committee in writing.
Mitotix shall promptly commence negotiations with such Third Party to determine the cost of licensing such patent rights and/or know-how. Mitotix shall enter into a license agreement with such Third Party upon terms and conditions approved in
writing by the Collaborative Policy Setting Committee and shall sublicense its rights thereunder within the UBC Field to DuPont Merck. All costs and expenses incurred 

  

 34 

 
by Mitotix in obtaining any license referred to in this Section, including but not limited to up front license payments, milestone payments, royalty payments
and legal fees and disbursements, shall be treated as UBC Research, Development and Pre-Launch Marketing Costs or Allowable Expenses, as appropriate, unless the Alternate UBC Plan is in effect, in which case, such costs shall be promptly reimbursed
to Mitotix by DuPont Merck; provided, however, that any such costs and expenses incurred by Mitotix with respect to such license agreements attributable to applications outside the UBC Field shall be paid by Mitotix and shall not be
treated as UBC Research, Development and Pre-Launch Marketing Costs or Allowable Expenses and shall not be reimbursed by DuPont Merck. Mitotix will not be required to issue stock or rights to acquire stock in connection with any such license, except
upon terms acceptable to Mitotix in its sole discretion. 
  
 (b) After DuPont Merck’s exercise of its option to commence the Extended UBC Collaboration and prior to the commencement of the Alternate UBC Plan, this Section 10.2.4(b) shall apply. If the Collaborative Policy
Setting Committee determines that it is necessary or desirable and in the best interest of the UBC Collaboration for Mitotix or DuPont Merck to license certain patent rights or know-how from a Third Party for use in the UBC Field, the Collaborative
Policy Setting Committee shall so notify Mitotix and DuPont Merck in writing and shall instruct one of the parties to promptly commence negotiations with such Third Party to determine the cost of licensing such patent rights and/or know-how. Upon
written approval of the Collaborative Policy Setting Committee such party may enter into a license agreement with such Third Party upon terms and conditions approved in writing by the Collaborative Policy Setting Committee. If Mitotix is the
licensee, Mitotix shall exclusively sublicense its rights thereunder within the UBC Field to DuPont Merck. If DuPont Merck is the licensee, DuPont Merck shall exclusively sublicense its rights thereunder with respect to uses of UBC Targets for
Antisense, Gene Therapy and non-Radiopharmaceutical diagnostic applications to Mitotix, and such sublicenses shall survive termination of this Agreement; provided, however, such sublicense shall not survive termination of this Agreement by
DuPont Merck if such termination is under Section 18.2.2 hereof. All costs and expenses paid to Third Parties by the licensing party in obtaining any license referred to in this Section 10.2.4(b), including but not limited to upfront license
payments, milestone payments, royalty payments and legal fees and disbursements, shall be treated as UBC Research, Development and Pre-Launch Marketing Costs or Allowable Expenses, as appropriate, provided, however, that (i) any such costs
and expenses incurred by Mitotix with respect to such license agreements attributable to applications outside the UBC Field shall be the responsibility of Mitotix and shall not be treated as UBC Research, Development and Pre-Launch Marketing Costs
or Allowable Expenses and shall not be reimbursed by DuPont Merck and (ii) any such costs and expenses incurred by DuPont Merck with respect to such license agreements attributable to applications outside of the UBC Field shall be the sole
responsibility of DuPont Merck and shall not be treated as UBC Research, Development and Pre-Launch Marketing Costs or Allowable Expenses unless such costs and expenses are attributable to applications sublicensed to Mitotix pursuant to the
provisions above, in which case, such costs and expenses shall be the responsibility of Mitotix and shall not be treated as UBC Research, Development and Pre-Launch Marketing Costs or Allowable Expenses and shall not be reimbursed by DuPont Merck.
Neither party will be required to issue stock or rights to acquire stock in connection with any such license, except upon terms acceptable to such party in its sole discretion. 
  

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 (c) After DuPont Merck’s exercise of its option to commence the Extended UBC
Collaboration and after the Alternate UBC Plan is in effect, this Section 10.2.4(c) shall apply. If DuPont Merck shall determine that it is necessary or desirable and in the best interest of the UBC Collaboration for DuPont Merck to license certain
patent rights or know-how from a Third Party for use in the UBC Field, DuPont Merck shall so notify the Collaborative Policy Setting Committee and Mitotix in writing. DuPont Merck shall promptly commence negotiations with such Third Party to
determine the cost of licensing such patent rights and/or know-how. In the event that DuPont Merck enters into a license agreement with a Third Party which includes a license grant to use such patent rights and/or know-how for Antisense, Gene
Therapy and non-Radiopharmaceutical diagnostic applications, DuPont Merck shall sublicense the patent rights and know-how for such uses to Mitotix, and such sublicenses shall survive termination of this Agreement; provided, however,
such sublicenses shall not survive termination of this Agreement by DuPont Merck if such termination is under Section 18.2.2 hereof. All costs and expenses incurred by DuPont Merck in obtaining any license under this Section 10.2.4(c) shall be borne
by DuPont Merck, unless such costs and expenses are attributable to applications sublicensed to Mitotix pursuant to the provisions above, in which case, such costs and expenses shall be the responsibility of Mitotix. 
  
 10.3 Reservation of Rights. Notwithstanding the license grants set
forth in Sections 10.1 and 10.2 above, (i) Mitotix at all times reserves a non-exclusive license under the CDK Patent Rights, UBC Patent Rights, Mitotix Inventions, Joint Inventions and Know-how solely to permit Mitotix to perform its obligations
and exercise its rights under this Agreement, including but not limited to its rights of co-promotion with respect to the CDK Products and the UBC Products as set forth in Article 8, and (ii) Mitotix at all times reserves its rights under the CDK
Patent Rights, UBC Patent Rights, Mitotix Inventions, Joint Inventions and Know-how to use the CDK Targets and UBC Targets outside of the CDK Field and the UBC Field, respectively, including but not limited to uses relating to Antisense, Gene
Therapy and non-Radiopharmaceutical diagnostic applications. 
  
 10.4 Grant of License Rights to Mitotix. 
  
 10.4.1 License to Perform Obligations. DuPont Merck hereby grants Mitotix a non-exclusive worldwide license under the DuPont Merck Inventions and Know-how solely to permit Mitotix to perform its obligations and
exercise its rights under this Agreement, including but not limited to Mitotix’s obligation to conduct screening of the CDK Development Compounds and the UBC Development Compounds. Mitotix specifically agrees that it will use compounds
delivered by DuPont Merck under this Agreement (see Sections 3.1.4 and 6.1.3) solely for the purpose of performing its obligations under this Agreement and for no other purpose. Such DuPont Merck compounds will not be transferred to any Third Party
without the prior written approval of DuPont Merck. 
  
 10.4.2 License to DuPont Merck Inventions. DuPont Merck hereby grants Mitotix an exclusive (except as to DuPont Merck) worldwide license (with the right to sublicense) under any DuPont Merck Inventions and Joint Inventions solely to
permit Mitotix to use the CDK Targets and the UBC Targets to discover, develop, make, have made, use and sell Antisense or Gene Therapy products in the oncology field. 
  

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 10.5 DuPont Merck Rights of First Negotiation. 
  
 10.5.1 Right of First Negotiation with Respect to
Antisense and/or Gene Therapy. Mitotix shall provide DuPont Merck advance written notice, (the “Antisense/Gene Therapy Notice”) of its intention to grant a license to any Third Party to (i) use the CDK Targets or the UBC Targets
for Antisense, Gene Therapy and non-Radiopharmaceutical diagnostic applications and/or (ii) to discover, develop, make, have made, use and/or sell Antisense, Gene Therapy or non-Radiopharmaceutical diagnostic products incorporating compounds
selected through the use of the CDK Targets or the UBC Targets. DuPont Merck shall have a period of thirty (30) days from its receipt of the Antisense/Gene Therapy Notice to provide Mitotix with written notice of its desire to enter negotiations
with Mitotix regarding such a license. Upon (i) the failure of DuPont Merck to provide such written notice of its desire to enter negotiations with Mitotix in response to the Antisense/Gene Therapy Notice within thirty (30) days of DuPont
Merck’s receipt thereof, (ii) the failure of DuPont Merck and Mitotix to agree upon a memorandum of intent within one hundred twenty (120) days of DuPont Merck’s receipt of the Antisense/Gene Therapy Notice, or (iii) the failure of Mitotix
and DuPont Merck to execute a definitive agreement within one hundred eighty (180) days of DuPont Merck’s receipt of the Antisense/Gene Therapy Notice, Mitotix shall be free to license a Third Party; provided, however, if Mitotix offers
terms and conditions which are, taken as a whole, equal to or less favorable to Mitotix than the last offer made by Mitotix to DuPont Merck, then Mitotix shall offer such terms and conditions to DuPont Merck under the procedure described above.

  
 10.5.2 Right of First Negotiation with
Respect to CDK-non-D Targets. During the term of the CDK Research Program, including any extensions thereof, Mitotix shall provide DuPont Merck advance written notice (the “CDK-non-D Notice”) of its intention to grant a license to any
Third Party to (i) to use the CDK-non-D Targets outside the CDK-non-D Field and/or (ii) to discover, develop, make, have made, use and/or sell therapeutic products incorporating compounds selected through the use of the CDK-non-D Targets for
indications other than oncology indications. DuPont Merck shall have a period of thirty (30) days from its receipt of the CDK-non-D Notice to provide Mitotix with written notice of its desire to enter negotiations with Mitotix regarding such a
license. Upon (i) the failure of DuPont Merck to provide such written notice of its desire to enter negotiations with Mitotix in response to the CDK-non-D Notice within thirty (30) days of DuPont Merck’s receipt thereof, or (ii) the failure of
DuPont Merck and Mitotix to agree upon a memorandum of intent within one hundred twenty (120) days of DuPont Merck’s receipt of the CDK-non-D Notice, or (iii) the failure of Mitotix and DuPont Merck to execute a definitive agreement within one
hundred eighty (180) days of DuPont Merck’s receipt of the CDK-non-D Notice, Mitotix shall be free to license a Third Party, provided, however, if Mitotix offers terms and conditions to a Third Party which are, taken as a whole, equal to
or less favorable to Mitotix than the last offer made by Mitotix to DuPont Merck, then Mitotix shall offer such terms and conditions to DuPont Merck under the procedure described above. 
  

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 ARTICLE 11. MILESTONES AND ROYALTIES PAYABLE TO MITOTIX 
  
 11.1 Milestone Payments. 
  
 (a) In consideration of Mitotix’s work on the CDK
Research Program, and if the Alternate UBC Plan is initiated or deemed to be initiated for financial purposes following commencement of the UBC Operational Disengagement Plan, in consideration of Mitotix’s work on the UBC Research Program, and
the licenses granted to DuPont Merck hereunder, DuPont Merck shall pay the amounts set forth in the chart below to Mitotix upon the achievement of each of the following milestones; provided, however, that no milestone payments shall be due on
(i) CDK Products incorporating compounds that are first identified more than two (2) years following the earlier of (x) the termination of the license grant set forth in Section 10.1.1 pursuant to Section 10.1.3 or (y) the termination of this
Agreement, and (ii) UBC Products incorporating compounds that are first identified more than two (2) years following the earlier of (x) the termination of the license grant set forth in Section 10.2.1 pursuant to Section 10.2.3 or (y) the
termination of this Agreement. 
  
 (b) No
milestone payments shall be due with respect to UBC Products prior to commencement of the Alternate UBC Plan. If the Alternate UBC Plan becomes effective, or is deemed to be effective for financial purposes following commencement of the UBC
Operational Disengagement Plan, after any of the following milestones have been achieved with respect to any UBC Product, then no milestone payment shall be due for such previously achieved milestone with respect to such UBC Product. 
  

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 11.1.1 *** 
  

					
	 Milestone

	  	Column 1 (1)

	  	Column 2 (2)

			
	 1.      IND Filing in the United States
	  	***	  	***
			
	 2.      Enrollment of at least 50% of the predicted number of patients for the first clinical trial for efficacy
evaluation involving fewer than 100 patients per trial
	  	***	  	***
			
	 3.      Enrollment of 50% of the predicted number of patients for the first clinical trial for efficacy
evaluation involving more than 100 patients per trial
	  	***	  	***
			
	 4.      Filing of the first NDA in the United States
	  	***	  	***
			
	 5.      Approval of the first NDA in the United States
	  	***	  	***

  

	(1)	DuPont Merck shall pay Mitotix the amounts set forth in this column upon the achievement of the stated milestone for the first Royalty-Bearing Product CDK Product to achieve such
milestone and, if the Alternate UBC Plan is activated or is deemed to be activated for financial purposes following commencement of the UBC Operational Disengagement Plan, upon the achievement of the stated milestone for the first Royalty-Bearing
Product UBC Product to achieve such milestone. 

  

	(2)	DuPont Merck shall pay Mitotix the amounts set forth in this column upon the achievement of the stated milestone for each subsequent Royalty-Bearing Product CDK Product which is a
Unique Product (as defined below) to achieve such milestone and, if the Alternate UBC Plan is activated or is deemed to be activated for financial purposes following commencement of the UBC Operational Disengagement Plan, upon the achievement of the
stated milestone for each subsequent Royalty-Bearing Product UBC Product to achieve such milestone which is a Unique Product. 

  

	(3)	If an NDA for the first Royalty-Bearing Product is filed in any non-U.S. Strategic Country before an NDA is filed in the United States for the Royalty-Bearing Product, then DuPont
Merck shall pay Mitotix the sum of *** for each NDA filed in a non-U.S. Strategic Country for the Royalty-Bearing Product; provided, however, that 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 39 

 DuPont Merck shall not be obligated to pay Mitotix more than a total of *** with respect to the filing of
NDAs worldwide for the first Royalty-Bearing Product. 
  

	(4)	If an NDA for the subsequent Royalty-Bearing Product is filed in any non-U.S. Strategic Country before an NDA is filed in the United States for the Royalty-Bearing Product, then
DuPont Merck shall pay Mitotix the sum of *** for each NDA filed in a non-U.S. Strategic Country for the Royalty-Bearing Product; provided, however, that DuPont Merck shall not be obligated to pay Mitotix more than a total of $2,000,000 with
respect to the filing of NDAs worldwide for the subsequent Royalty- Bearing Product. 

  

	(5)	If an NDA for the first Royalty-Bearing Product is approved in any non-U.S. Strategic Country before an NDA is approved in the United States for the Royalty-Bearing Product then
DuPont Merck shall pay Mitotix the sum of *** for each NDA approved in a non-U.S. Strategic Country for the Royalty-Bearing Product; provided, however, that DuPont Merck shall not be obligated to pay Mitotix more than a total of *** with
respect to the approval of NDAs worldwide for the first Royalty-Bearing Product. 

  

	(6)	If an NDA for the subsequent Royalty-Bearing Product is approved in any non-U.S. Strategic Country before an NDA is approved in the United States for the Royalty- Bearing Product
then DuPont Merck shall pay Mitotix the sum of *** for each NDA approved in a non-U.S. Strategic Country for the Royalty-Bearing Product; provided, however, that DuPont Merck shall not be obligated to pay Mitotix more than a total of *** with
respect to the approval of NDAs worldwide for the subsequent Royalty-Bearing Product. 

  
 The guiding principle behind the payment of milestone payments shall be that for each Unique Product in the CDK Collaboration one, and only one, milestone
payment shall be paid for each milestone event achieved and if the Alternate UBC Plan is in effect or is deemed to be in effect for financial purposes following the commencement of the UBC Operational Disengagement Plan, for each Unique Product in
the UBC Collaboration, one, and only one, milestone payment shall be paid for each milestone event achieved. A “Unique Product” refers to a Royalty-Bearing Product that the Collaborative Policy Setting Committee agrees has a distinctly
different Target and mechanism of action relative to any Royalty-Bearing Product for which a milestone payment has been previously paid to Mitotix by DuPont Merck. Thus, if two or more Royalty-Bearing Products are in development simultaneously, or
one is subsequently dropped from clinical development, that utilize the same Target and mechanism of action all such Royalty-Bearing Products will be treated as one Unique Product and only one milestone will be paid for each milestone event
achieved. If two or more Royalty-Bearing Products are in development simultaneously, but utilize a different Target and mechanism of action, each of these products will be treated as a separate Unique Product and each will be eligible for milestone
payments. 
  
 In addition, DuPont Merck shall pay a milestone
payment in the amount of *** upon NDA approval for each Royalty-Bearing Product which has the same Target and mechanism of action as a Unique Product for which milestone payments have 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 40 

 previously been paid, but is approved for a new indication relative to such Unique Product. As used in the preceding
sentence, “new indication” refers to a new and distinct primary disease (for example, cancer versus psoriasis) and does not, for example, refer to types or classes of diseases (for example, colon versus breast cancer) or the subsequent
approval of a claim for an expanded or different patient population with the same primary disease as for the initially approved claim. 
  
 In addition, DuPont Merck shall pay a milestone payment in the amount of *** upon NDA approval for each Royalty-Bearing Product which has the same Target
and mechanism of action as a Unique Product for which milestone payments have previously been paid, but is approved for a new mode of delivery (i.e., PO versus IV) relative to such Unique Product. 
  
 All milestone payments will be paid according to column 2 in the above table,
except that the first Royalty-Bearing Product CDK Product which is a Unique Product and, if the Alternate UBC Plan is in effect or is deemed to be in effect for financial purposes following the commencement of the UBC Operational Disengagement Plan,
the first Royalty-Bearing Product UBC Product which is a Unique Product to reach any of the five milestone events is to be paid in accordance with column 1 above. 
  
 Appendix J sets forth examples of how the milestone payments are to be made in accordance with this Section 11.1.

  
 11.1.2 Notice of Achievement of
Milestones. DuPont Merck shall notify Mitotix in writing within ten (10) business days following the occurrence of each event described in Section 11.1.1 above and shall, within thirty (30) days following the occurrence of such event, pay to
Mitotix in United States dollars by wire transfer or other means acceptable to Mitotix, the amounts due upon the occurrence of such events. The milestone payments made to Mitotix pursuant to Section 11.1.1 are not refundable under any circumstances
and will not be credited against royalty payments due Mitotix under Section 11.2. 
  
 11.1.3 Radiopharmaceutical Products and Immunoassav Products. Subject to Section 13.9, DuPont Merck shall not be obligated to pay
milestone payments under this Section 11.1 with respect to any Royalty-Bearing Products which are Radiopharmaceutical Products or Immunoassay Products. 
  
 11.1.4 Non-Strategic Countries. DuPont Merck shall have no milestone payment obligations to Mitotix with respect to non-Strategic
Countries. 
  
 11.1.5 Additional
Obligations. DuPont Merck shall also be responsible for additional milestone and royalty payments, if any, under the Mitotix License Agreements, but only to the extent set forth in Section 13.9. 
  
 11.2 Royalties Payable to Mitotix on Net Sales. All royalties payable
under this Section 11.2 shall be paid throughout the Royalty Term. 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 41 

 11.2.1 Royalty Payable to Mitotix on Net Sales in Strategic Countries. In
consideration of the licenses granted to DuPont Merck hereunder, DuPont Merck shall pay to Mitotix annual royalties for each Calendar Year on (i) Net Sales by DuPont Merck, its Affiliates and sublicensees of each Royalty-Bearing Product in the
Strategic Countries, and (ii) Net Sales by DuPont Merck and its Affiliates of each Royalty-Bearing Product in the non-Strategic Countries where DuPont Merck does not use a Distributor or sublicensee to conduct such sale. Such royalty shall be
payable based upon the annual Net Sales in a Calendar Year of each individual Royalty-Bearing Product at the rates and in the amounts set forth below: 
  
 (a) *** percent (***%) of aggregate Net Sales of the Royalty-Bearing Product, for annual Net Sales of such Royalty-Bearing Product of up
to four hundred million dollars ($400,000,000); 
  
 (b) *** percent (***%) of the aggregate Net Sales of the Royalty-Bearing Product, for annual Net Sales of such Royalty-Bearing Product of between four hundred million dollars ($400,000,000) and seven hundred million dollars
($700,000,000); 
  
 (c) *** percent
(***%) of aggregate Net Sales of the Royalty-Bearing Product, for annual Net Sales of such Royalty-Bearing Product above seven hundred million dollars ($700,000,000). 
  
 Notwithstanding the above, (i) if (x) a royalty is owed under this Section 11.2.1 with respect to sales of a Royalty-Bearing
Product in any country in which the Royalty-Bearing Product is not covered by a Valid Patent Claim owned by DuPont Merck or exclusively licensed to DuPont Merck and (y) a Competitive Product is sold in such country, then the royalty payable pursuant
to this Section 11.2.1 based upon sales of the Royalty-Bearing Product in such country shall be *** percent (***%); and (ii) if a Third Party Competitive Product is sold in such country, then the royalty rates set forth above shall be reduced by ***
percent (***%), but in no event shall such royalty rates fall below *** percent (***%). 
  
 11.2.2 Conditions on Royalty Payments. Royalties on each Royalty-Bearing Product at the rate set forth above shall be payable on a
country-by-country basis during the Royalty Term subject to the following conditions: 
  
 (a) only one royalty shall be due with respect to the same unit of Royalty- Bearing Product. 
  
 (b) no royalties shall be due upon the sale or other
transfer among DuPont Merck and its Affiliates, but in such cases the royalty shall be due and calculated upon DuPont Merck’s or its Affiliate’s Net Sales of Royalty-Bearing Product to a Third Party; 
  
 (c) no royalties shall accrue on the disposition of
Royalty-Bearing Product in reasonable quantities by DuPont Merck or its Affiliates as bona fide samples or as donations to non-profit institutions or government agencies for non-commercial purposes; 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 42 

 (d) notwithstanding the above royalty rates, upon DuPont Merck request, the parties agree
to discuss in good faith a reduction of such royalty rate in any given country in the event the level of development, patent protection, or general commercial environment affects the commercial viability of the Royalty-Bearing Product under such
royalty rate; and 
  
 (e) if DuPont Merck
utilizes one of its general partners or any of their subsidiaries as a Distributor and the prices charged to such general partner or subsidiary of a general partner are less than those ordinarily charged to other Third Party Distributors of the same
product, then any sales to such partner or subsidiary of a partner shall be treated as sales to an Affiliate rather than as sales to a Distributor. 
  
 11.3 Royalties Payable to Mitotix on Net Sales to Distributors in Non-Strategic Countries. In consideration of the licenses granted to DuPont Merck
hereunder, DuPont Merck shall pay to Mitotix a royalty equal to *** percent (***%) of the Net Sales of all Royalty Bearing Products sold to its Distributors in each non-Strategic Country where DuPont Merck uses a Distributor to conduct such sale.

  
 11.4 Royalties Payable to Mitotix on Net Sales by
Development Partners and other Sublicensees in Japan and Other Non-Strategic Countries. DuPont Merck agrees to use good faith commercially reasonable efforts to enter into a license agreement with a Third Party in Japan pursuant to which the
Third Party will perform as Development Partner for one or more Royalty-Bearing Products in Japan and will market and sell such Royalty-Bearing Product(s) in Japan. In connection with such arrangement and other similar arrangements that DuPont Merck
may pursue in non-Strategic Countries, DuPont Merck shall pay Mitotix *** percent (***%) of all royalties that DuPont Merck receives from such Development Partners or other sublicensees on sales of the Royalty-Bearing Product(s). DuPont Merck shall
not owe any amount to Mitotix based upon DuPont Merck’s receipt from a Development Partner or other sublicensees of upfront license payments or milestone payments unless such amounts are creditable against future royalties owed DuPont Merck
from such Development Partner or sublicensee. In such cases, Mitotix shall be entitled to receive *** percent (***%) of such amount as it is credited against royalties earned. DuPont Merck shall not owe any amount to Mitotix based upon DuPont
Merck’s receipt of equity payments from a Development Partner or sublicensee. Notwithstanding the above, if DuPont Merck engages a Development Partner in a country in which DuPont Merck maintains a development organization and a pharmaceutical
sales force with the reasonable capability to develop and market the Royalty-Bearing Product, DuPont Merck shall pay royalties to Mitotix on the Net Sales made by such Development Partner as if the Royalty- Bearing Product had been sold by DuPont
Merck itself. 
  
 11.5 Profit Sharing on Sales of UBC
Products. Unless the Alternate UBC Plan is in effect or is deemed to be in effect for financial purposes following the commencement of the UBC Operational Disengagement Plan, Mitotix and DuPont Merck shall share in the UBC Operating Profits
(defined in Appendix I) from sales of UBC Products worldwide in accordance with their respective Percentage Contributions as set forth in Appendices H and I hereof. In order to effectuate such profit sharing with respect to
sales of UBC Products, Mitotix and DuPont Merck agree that prior to the First Commercial Sale of such UBC 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 43 

 Products one or more partnerships or similar entities will be formed if required to facilitate and support the allocation
of the UBC Operating Profit, in accordance with applicable tax laws and regulations. 
  
 ARTICLE 12. ROYALTIES PAYABLE TO DUPONT MERCK 
  
 12.1 General. All royalties payable under this Article 12 shall be paid throughout the Royalty Term. 
  
 12.2 Royalties Payable to DuPont Merck on Net Sales. 
  
 12.2.1 Royalty Payable to DuPont Merck on Net Sales in Strategic Countries. In consideration of the licenses granted to Mitotix
hereunder, Mitotix shall pay to DuPont Merck annual royalties for each Calendar Year on (i) Net Sales by Mitotix, its Affiliates and sublicensees of each Mitotix Product in the Strategic Countries and (ii) Net Sales by Mitotix and its Affiliates of
each Mitotix Product in the non-Strategic Countries where Mitotix does not use a Distributor or sublicensee to conduct such sale. Such royalty shall be payable based upon the annual Net Sales in a Calendar Year of each individual Mitotix Product at
the rates and in the amounts set forth below: 
  
 (a) *** percent (***%) of aggregate Net Sales of the Mitotix Product, for annual Net Sales of such Mitotix Product of up to four hundred million dollars ($400,000,000); 
  
 (b) *** percent (***%) of the aggregate Net Sales of the Mitotix Product, for annual Net Sales of such
Mitotix Product of between four hundred million dollars ($400,000,000) and seven hundred million dollars ($700,000,000); 
  
 (c) *** percent (***%) of aggregate Net Sales of the Mitotix Product, for annual Net Sales of such Mitotix Product above seven hundred
million dollars ($700,000,000). 
  
 Notwithstanding the above, (i)
if (x) a royalty is owed under this Section 12.2.1 with respect to sales of a Mitotix Product in any country in which the Mitotix Product is not covered by a Valid Patent Claim owned by Mitotix or exclusively licensed to Mitotix and (y) a
Competitive Product is sold in such country, then the royalty payable pursuant to this Section 12.2.1 based upon sales of the Mitotix Product in such country shall be *** percent (***%); and (ii) if a Third Party Competitive Product is sold in such
country, then the royalty rates set forth above shall be reduced by *** percent (***%), but in no event shall such royalty rates fall below *** percent (***%). 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 44 

 12.2.2 Conditions on Royalty Payments. Royalties on each Mitotix Product at the
rate set forth above shall be payable on a country-by-country basis during the Royalty Term subject to the following conditions: 
  
 (a) only one royalty shall be due with respect to the same unit of Mitotix Product; 
  
 (b) no royalties shall be due upon the sale or other
transfer among Mitotix and its Affiliates, but in such cases the royalty shall be due and calculated upon Mitotix’s or its Affiliate’s Net Sales of Mitotix Product to a Third Party; 
  
 (c) no royalties shall accrue on the disposition of Mitotix
Product in reasonable quantities by Mitotix or its Affiliates as bona fide samples or as donations to non-profit institutions or government agencies for non-commercial purposes; and 
  
 (d) notwithstanding the above royalty rates, upon Mitotix request, the parties agree to discuss in good
faith a reduction of such royalty rate in any given country in the event the level of development, patent protection, or general commercial environment affects the commercial viability of the Mitotix Product under such royalty rate. 
  
 12.3 Royalties Payable to DuPont Merck on Net Sales to Distributors in
Non-Strategic Countries. In consideration of the licenses granted to Mitotix hereunder, Mitotix shall pay to DuPont Merck a royalty equal to *** percent (***%) of the Net Sales of all Mitotix Products sold to Distributors in each
non-Strategic Country where Mitotix uses a Distributor to conduct such sale. 
  
 12.4 Royalties Payable to DuPont Merck on Net Sales by Development Partners and other Sublicensees in Japan and Other Non-Strategic Countries. Mitotix agrees to use good faith commercially reasonable
efforts to enter into a license agreement with a Third Party in Japan pursuant to which the Third Party will perform as Development Partner for one or more Mitotix Products in Japan and will market and sell such Mitotix Product(s) in Japan. In
connection with such arrangement and other similar arrangements that Mitotix may pursue in non-Strategic Countries, Mitotix shall pay DuPont Merck *** percent (***%) of all royalties that Mitotix receives from such Development Partners or other
sublicensees on sales of the Mitotix Product(s). Mitotix shall not owe any amount to DuPont Merck based upon Mitotix’s receipt from a Development Partner or other sublicensees of upfront license payments or milestone payments unless such
amounts are creditable against future royalties owed Mitotix from such Development Partner or sublicensee. In such cases, Mitotix shall be entitled to receive *** percent (***%) of such amount as it is credited against royalties earned. Mitotix
shall not owe any amount to DuPont Merck based upon Mitotix’s receipt of equity payments from a Development Partner or sublicensee. Notwithstanding the above, if Mitotix engages a Development Partner in a country in which Mitotix maintains a
development organization and a pharmaceutical sales force with the reasonable capability to develop and market the Mitotix Product, Mitotix shall pay royalties to DuPont Merck on the Net Sales made by such Development Partner as if the Mitotix
Product had been sold by Mitotix itself. 

	***	Certain information on this page 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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 ARTICLE 13. PAYMENT TERMS 
  
 13.1 General. Where relevant, the following payment terms and conditions shall apply to all payments made by one
party to the other under this Agreement, whether such payments are made as milestone payments, royalty payments or profit sharing payments. 
  
 13.2 Royalty Reports, Exchange Rates. During the term of this Agreement following the First Commercial Sale of a Royalty-Bearing Product or a
Mitotix Product, as the case may be, the party owing royalties as a result of such First Commercial Sale (the “Paying Party”) shall furnish to the party having a right to receive royalties as a result of such First Commercial Sale (the
“Receiving Party”) a written quarterly report showing, on a country by country basis, (i) the gross sales of all Royalty-Bearing Products or Mitotix Products, as the case may be, sold to Third Party customers, including Distributors, by
the Paying Party, its Affiliates and sublicensees, during the reporting period and the calculation of Net Sales from such gross sales; (ii) the royalty payments received from a Paying Party Development Partner and the royalty payments which would
have been due from a Paying Party Development Partner except for the credit such Paying Party Development Partner received for upfront payments, milestone payments or other payments made to the Paying Party during the reporting period; (iii) the
royalties and other payments payable in United States dollars which shall have accrued hereunder in respect of the items described in (i) and (ii) above; (iv) withholding taxes, if any, required by law to be deducted in respect of the items
described in (i) and (ii) above; (v) the dates of the First Commercial Sales of any Royalty Bearing Product or Mitotix Product, as the case may be, during the reporting period; and (vi) the exchange rates used in determining the amount of United
States dollars due. All payments to be made under this Agreement shall be made in United States dollars. In the case of sales outside the United States, the rate of exchange to be used in computing the amount of currency equivalent in United States
dollars due shall be the Calendar Quarter-end exchange rate, which is the exchange rate utilized by DuPont Merck in its worldwide accounting system and reflects the average exchange rate for the Calendar Quarter in which the sales are recorded.
Reports and any amounts payable shall be due on the forty fifth (45th) day following the close of each Calendar Quarter. If no royalty is due for any royalty period hereunder, the Paying Party shall so report. The Paying Party shall keep complete
and accurate records in sufficient detail to properly reflect all gross sales and Net Sales and to enable the royalties and other amounts payable hereunder to be determined. 
  
 13.3 Payment of Profit Sharing Amounts. This Section 13.3 will not apply to UBC Products if the Alternate UBC Plan is
in effect. Within sixty (60) days of the end of each Calendar Quarter following the First Commercial Sale of a UBC Product, DuPont Merck shall report to Mitotix its Net Sales of UBC Products during such Calendar Quarter and each party shall report
to the other party its Allowable Expenses incurred and any sublicense revenues received by such party during such quarter. Within thirty (30) days after exchange of such reports, each party shall present to the other its calculation of the UBC
Operating Profit for such quarter and the payment, if any, to be made by DuPont Merck to Mitotix in order to achieve a sharing of the UBC Operating Profit that is equal to each party’s Percentage Contribution, in accordance with and as set
forth in Appendices H and I hereof. In the event a partnership or similar entity is formed pursuant to Section 11.5, such allocation of UBC Operating Profit and corresponding payments will be made by the 

  

 46 

 
partnership in accordance with the applicable tax laws and regulations. With respect to the sales of UBC Products and such profit sharing, the party
receiving payments or receiving reports shall be the “Receiving Party” and the party making payment or submitting reports shall be the “Paying Party”. 
  
 13.4 Audits. Upon the written request of the Receiving Party, the Paying Party shall permit an independent certified
public accounting firm of nationally recognized standing selected by the Receiving Party, and acceptable to the Paying Party, which acceptance shall not be unreasonably withheld, to have access during normal business hours to such of the records of
the Paying Party as may be reasonably necessary to verify the accuracy of the royalty reports aad profit sharing reports hereunder in respect of any Calendar Year ending not more than thirty-six (36) months prior to the date of such request. All
such verifications shall be conducted at the Receiving Party’s expense and not more than once in each Calendar Year. These rights with respect to any Calendar Year shall terminate three (3) years after the end of any such Calendar Year.

  
 In the event such accounting firm concludes that additional
royalties or profit sharing payments were owed during such period, the additional amount shall be paid within thirty (30) days of the date the Receiving Party delivers to the Paying Party such accounting firm’s written report so correctly
concluding. The fees charged by such accounting firm shall be paid by the Receiving Party unless the audit discloses that the payments payable by the Paying Party for the audited period are more than one hundred ten percent (110%) of the payments
actually made for such period, in which case the Paying Party shall pay the reasonable fees and expenses charged by the accounting firm. 
  
 The Paying Party shall include in each sublicense agreement granted by it pursuant to this Agreement a provision requiring the sublicensee to make reports
to the Paying Party, to keep and maintain records of sales made pursuant to such sublicense agreement and to grant access to such records by the Receiving Party’s independent accountant to the same extent required of the Paying Party under this
Agreement. Upon the expiration of thirty-six (36) months following the end of any Calendar Year, the calculation of royalties payable with respect to such Calendar Year shall be binding and conclusive upon the Receiving Party; and the Paying Party
and its sublicensees shall be released from any liability or accountability with respect to royalties for such Calendar Year. 
  
 The Receiving Party agrees that all information subject to review under this Section 13.4 or under any sublicense agreement entered into pursuant to this
Agreement is confidential and will be subject to the confidentiality provisions of this Agreement, and that the Receiving Party shall cause its accounting firm to enter into an acceptable confidentiality agreement with the Receiving Party obligating
it to retain all such information in confidence. 
  
 In addition,
pursuant to the terms of the pl6 License, DuPont Merck shall maintain at its principal office usual books of account and records showing its actions under this Agreement. Once per Calendar Year, upon reasonable notice, such books and records shall
be open to inspection and copying, during usual business hours, by an independent certified public accounting firm of nationally recognized standing selected by Cold Spring Harbor Laboratory and to whom DuPont Merck has no reasonable objection, for
two years after the 

  

 47 

 
Calendar Quarter to which they pertain, for purposes of verifying the accuracy of the amounts paid to Cold Spring Harbor Laboratory by Mitotix or DuPont
Merck as a result of sales of Royalty Bearing Products deemed to be Licensed Products or Ultimate Products (each as defined in the pl6 License). If it is correctly determined that Mitotix’s payment to Cold Spring Harbor Laboratory with respect
to such sales is less than the amount owing by more than ten percent (10%) of the total amount of the amount owing as a result of DuPont Merck’s underpayment to Mitotix, DuPont Merck shall pay the amount owing plus ten percent (10%) of the
deficiency and shall pay the reasonable fees and expenses charged by the accounting firm, including travel expenses. Payment of any deficiency in the amount owing, any penalty, or any cost shall be made within ten days after the DuPont Merck
receives written notice of such accounting firm’s written report so correctly concluding. 
  
 13.5 Payment Terms. Payments shown to have accrued by each royalty report (Section 13.2) or profit sharing report (Section 13.3) provided for under this Agreement shall be due and payable on the date such
report is due. Payments hereunder in whole or in part may be made in advance of such due date. Payments determined to be owing, and any overpayments to be credited, with respect to any Calendar Quarter shall be added, together with interest thereon
accruing under this Agreement from the date of the report for the Calendar Quarter for which such amounts are owing, or credited, as the case may be, to the next quarterly payment hereunder. 
  
 13.6 Exchange Controls. Except as hereinafter provided in this
section, all license fees, research payments, milestone payments, royalties, profit sharing payments and other payments due under this Agreement shall be paid in United States dollars. If at any time legal restrictions prevent the prompt remittance
of part or all royalties or profit sharing amounts with respect to any country where a Royalty-Bearing Product, a Mitotix Product or UBC Product, as the case may be, is sold, payment shall be made through such lawful means or methods as the Paying
Party may determine. When in any country the law or regulations prohibit both the transmittal and deposit of royalties on sales in such a country, royalty payments shall be suspended for as long as such prohibition is in effect, and as soon as such
prohibition ceases to be in effect, all royalties that the Paying Party would have been obligated to transmit or deposit, but for the prohibition, shall forthwith be deposited or transmitted promptly to the extent allowable, as the case may be. If
the royalty rate specified in this Agreement should exceed the permissible rate established in any country, the royalty rate for sales in such country shall be adjusted to the highest legally permissible or government-approved rate. 
  
 13.7 Payment Method. Except as otherwise provided in this Agreement or
agreed to by the parties, all payments under this Agreement shall be made by electronic bank transfer in funds available on the date due to such account as the Receiving Party specifies to the Paying Party before such payment is due. 
  
 13.8 Interest on Late Payments. Any payments by a Paying Party that
are not paid within ten (10) days of the date such payments are due under this Agreement shall bear interest, to the extent permitted by applicable law, at two percentage points above the base rate of interest declared from time to time by The First
National Bank of Boston in Boston, Massachusetts, calculated on the number of days payment is delinquent. 
  

 48 

 13.9 Overriding Provisions of License Agreements. 
  
 (a) Notwithstanding any provision of Article 13, if the
terms of any license agreement (including the Mitotix License Agreements) under which rights are sublicensed to a party pursuant to this Agreement require the licensee to make reports or royalty payments to the original licensor at different times
than those specified herein, then the Paying Party shall make its royalty payments and reports hereunder and at such times and with such reporting details as will enable the licensee to comply with its obligations to the original licensor, if so
required by the original licensor. In addition, the provisions of Sections 14.2 through 14.9 of this Agreement are expressly subject to any countervailing provision of a Mitotix License Agreement. In the event of any conflict between the provisions
of Sections 14.2 through 14.9 of this Agreement and the provisions of any Mitotix License Agreement, the Mitotix License Agreement shall control. In addition, (i) to the extent that the material obligations of the Cyclin E License are not
substantially set forth in this Agreement, DuPont Merck agrees, when and where applicable, to be bound by the terms of the Cyclin E License, (ii) DuPont Merck agrees to comply, when and where applicable, with the terms of the pl6 License, and (iii)
DuPont Merck acknowledges that this Agreement, when and where applicable, shall be subject to and subordinate to the terms and conditions of the UBC9 License. 
  

(b) Except as specifically otherwise provided hereunder, Mitotix shall be responsible for all costs and expenses with respect to the
Mitotix License Agreements, including, but not limited to, any upfront payments, license maintenance fees, milestone payments, royalty payments and legal fees and disbursements. 
  
 (c) In the case of products developed by DuPont Merck that trigger a royalty payment pursuant to the pl6
License, DuPont Merck shall share equal responsibility for royalty payments on such products which may be owed to Cold Spring Harbor Laboratory under the pl6 License to the extent that such product is a Royalty-Bearing Product and the Royalty Term
has ended with respect to such Royalty-Bearing Product. One-half of such payment which is due shall be paid by DuPont Merck directly to Cold Spring Harbor Laboratory and the remaining one-half of such payment shall be paid by Mitotix. DuPont
Merck’s reporting obligations under Section 13.2 and Mitotix’s right to audit under Section 13.4 shall be in effect with respect to such payments to Cold Spring Harbor Laboratory under this paragraph. 
  
 (d) In the case of products developed by DuPont Merck that
trigger a royalty payment pursuant to the pl6 License, DuPont Merck shall be responsible for royalty payments on such products which may be owed to Cold Spring Harbor Laboratory under the pl6 License, but only to the extent that DuPont Merck is not
obligated to make any royalty or profit-sharing payments to Mitotix with respect to such product. Any such payment which is due shall be paid by DuPont Merck directly to Cold Spring Harbor Laboratory. 
  
 (e) In the case of products developed by DuPont Merck that
trigger a royalty payment pursuant to the Cyclin E License, DuPont Merck shall be responsible for royalty payments on such products which may be owed to Fred Hutchinson Cancer Research Center under the Cyclin E License, but only to the extent that
DuPont Merck is not obligated 

  

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to make any royalty or profit-sharing payments to Mitotix with respect to such product. Any such payment which is due shall be paid by DuPont Merck directly
to Fred Hutchinson Cancer Research Center. 
  
 (f) Subject to Section 13.9(i), in the case of products developed by DuPont Merck that trigger a milestone payment pursuant to the pl6 License, DuPont Merck shall be responsible for milestone payments on such products which may be owed to
Cold Spring Harbor Laboratory under the pl6 License, but only to the extent that the pl6 License requires a milestone payment for NDA filing with respect to such product and DuPont Merck is not obligated to make any milestone payments to Mitotix
with respect to such product. Any such payment which is due shall be paid by DuPont Merck directly to Cold Spring Harbor Laboratory. 
  
 (g) Subject to Section 13.9(i), in the case of products developed by DuPont Merck that trigger a milestone payment pursuant to the Cyclin
E License, DuPont Merck shall be responsible for milestone payments on such products which may be owed to Fred Hutchinson Cancer Research Center under the Cyclin E License, but only to the extent that DuPont Merck is not obligated to make any
milestone payments to Mitotix with respect to such product. Any such payment which is due shall be paid by DuPont Merck directly to Fred Hutchinson Cancer Research Center. 
  
 (h) Subject to Section 13.9(i), in the case of products developed by DuPont Merck that trigger a milestone
payment pursuant to the UBC9 License, DuPont Merck shall be responsible for milestone payments on such products which may be owed to Harvard University under the UBC9 License, but only to the extent that DuPont Merck is not obligated to make any
milestone payment to Mitotix with respect to such product. Any such payment which is due shall be paid by DuPont Merck directly to Harvard University. 
  
 (i) Notwithstanding the foregoing, any and all milestone and royalty payments which may be owed to Mitotix’s licensor under the
Mitotix License Agreements with respect to UBC Products which are subject to profit sharing under Section 11.5 shall be paid by Mitotix. Such milestone and royalty payments shall be UBC Research Development and Pre-Launch Marketing Costs or
Allowable Expenses, as appropriate. 
  
 ARTICLE 14. PATENTS

  
 14.1 Ownership of Inventions. All right, title and
interest in all writings, inventions, discoveries, improvements and other technology, whether or not patentable or copyrightable, and any patent applications, patents or copyrights based thereon (collectively, the “Inventions”) that are
made or conceived during and as a result of the Collaboration solely by employees of Mitotix or others acting on behalf of Mitotix (“Mitotix Inventions”) shall be owned by Mitotix. All Inventions that are made or conceived during and as a
result of the Collaboration solely by employees of DuPont Merck or others acting on behalf of DuPont Merck (“DuPont Merck Inventions”) shall be owned by DuPont Merck. All Inventions that are made or conceived during and as a result of the
Collaboration, jointly by employees or others acting on behalf of Mitotix and DuPont Merck (“Joint Inventions”) shall 

  

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be owned jointly by DuPont Merck and Mitotix. Each party shall promptly disclose to the other party the making, conception or reduction to practice of
Inventions by employees or others acting on behalf of such party. Each party represents and agrees that all employees and other persons acting on its behalf in performing its obligations under this Agreement shall be obligated under a binding
written agreement to assign to such party, or as such party shall direct, all Inventions made or conceived by such employee or other person, or in the case of non-employees working for other companies or institutions on behalf of a party, Mitotix or
DuPont Merck, as applicable, shall have the right to license all Inventions made by such non-employees on behalf of Mitotix or DuPont Merck, as applicable, in accordance with the policies of said company or institution. Mitotix and DuPont Merck
agree to enforce such agreements (including, where appropriate, by legal action) considering, among other things, the commercial value of such Inventions. 
  
 14.2 Provisions Concerning the Filing, Prosecution and Maintenance of CDK Patent Rights, UBC Patent Rights and Inventions. 
  
 14.2.1 CDK Patent Rights, UBC Patent Rights and
Inventions Owned by Each Party. Mitotix shall be responsible for filing, prosecution and maintenance of patent applications covering CDK Patent Rights and UBC Patent Rights owned or licensed by Mitotix, to the extent permitted by the
Mitotix License Agreements. Each party shall be responsible for filing, prosecution and maintenance of patent applications covering Inventions owned by such party. If a party does not file a patent application covering an Invention owned by such
party within six months of the creation or discovery of such Invention, then the other party shall have the right to file a patent covering such Invention in the name of the party that created or discovered such Invention. 
  
 14.2.2 Joint Inventions Relating to CDK Targets and UBC
Targets. Mitotix shall have the right to file, prosecute and maintain patent applications covering Joint Inventions relating to CDK Targets and UBC Targets in the names of both parties. If Mitotix does not file an application covering such Joint
Invention within six months of the creation or discovery of such Joint Invention, then DuPont Merck shall have the right to file a patent covering such Joint Invention relating to CDK Targets and UBC Targets in the names of both parties. 

 
 14.2.3 Joint Inventions Relating to CDK Products and
UBC Products. DuPont Merck shall have the right to file, prosecute and maintain patent applications covering Joint Inventions relating to CDK Products and UBC Products, including but not limited to patents covering compounds, formulations,
pharmaceutical compositions, methods of use, and methods of synthesis, in the names of both parties. If DuPont Merck does not file an application covering such Mitotix Invention or Joint Invention within six months of the creation or discovery of
such Joint Invention, then Mitotix shall have the right to file a patent covering such Joint Invention in the names of both parties. 
  
 14.2.4 Consultation Regarding Joint Inventions. A party filing a patent application with respect to Joint Inventions shall consult
with the other as to the preparation and filing, prosecution and maintenance of such patent application and patents, and such party shall furnish to the other party copies of documents relevant to such preparation, filing, 

  

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prosecution or maintenance sufficiently prior to filing such document or making any payment due thereunder to allow for review and comments by the non-filing
party. 
  
 14.2.5 Patent Costs. Mitotix
shall bear all costs associated with filing, prosecuting and maintaining patent applications covering CDK Patent Rights and UBC Patent Rights owned or licensed by Mitotix, unless such costs are being borne by a licensor under a Mitotix License
Agreement. Each party shall bear all costs associated with filing, maintaining and prosecuting any patents or patent applications relating to Inventions owned by such party or filed in the name of the other party. Each party shall bear fifty percent
(50%) of all costs associated with filing, maintaining or prosecuting patents or patent applications relating to Joint Inventions. If either party elects at any time not to continue to und its portion of the costs associated with filing, maintaining
or prosecuting patents or patent applications relating to Joint Inventions, the party shall so notify the other party in sufficient time for the other party to assume all such costs; provided, however, that the electing party shall remain
obligated to pay for or to reimburse the other party for any costs with respect to patents or patent applications relating to the Joint Inventions incurred prior to such election. The electing party will relinquish all rights it may have in the
Joint Invention and will execute any and all documents reasonably necessary to permit the party assuming such costs to file, maintain and prosecute patents or patent applications relating to the Joint Invention in its own name. 
  
 14.3 Cooperation. Each party shall make available to the other party
or to the other party’s authorized attorneys, agents or representatives, its employees, agents or consultants to the extent necessary or appropriate to enable the appropriate party to file, prosecute and maintain patent applications and
resulting patents with respect to Inventions and for periods of time sufficient for such party to obtain the assistance it needs from such personnel. Where appropriate, each party shall sign or cause to have signed all documents relating to said
patent applications or patents at no charge to the other. 
  
 14.4
No Other Technology Rights. Except as otherwise expressly provided in this Agreement, under no circumstances shall a party hereto, as a result of this Agreement, obtain any ownership interest in or other right to any technology, know-how,
patents, pending patent applications, compounds, products, antibodies, cell lines or cultures, or animals of the other party, including items owned, controlled or developed by the other party, or transferred by the other party to said party at any
time pursuant to this Agreement. 
  
 14.5 Enforcement of Patent
Rights. Mitotix and DuPont Merck shall promptly notify the other in writing of any alleged or threatened infringement of CDK Patent Rights in the CDK Field or of UBC Patent Rights in the UBC Field of which they become aware. Mitotix and DuPont
Merck shall then confer and may agree jointly to prosecute any such infringement. Mitotix shall control the joint litigation in the event of any dispute between the parties with respect to any aspect of the litigation. If the parties do not agree on
whether or how to proceed with enforcement activity within (i) ninety (90) days following the notice of alleged infringement or (ii) ten (10) business days before the time limit, if any, set forth in the appropriate laws and regulations for the
filing of such actions, whichever comes first, then either party may act in its own name to commence litigation with respect to the alleged or threatened infringement. In the event a party brings an infringement action, the other 

  

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party shall cooperate fully, including, if required to bring such action, the furnishing of a power of attorney. Neither party shall have the right to settle
any patent infringement litigation under this Section in a manner that diminishes the rights or interests of the other party without the express written consent of such other party. 
  
 The costs of any joint litigation commenced pursuant to this Section, including attorneys’ fees and expenses, shall be
borne equally by the parties (unless they agree to a different cost sharing arrangement in any particular matter), with such costs to be accounted for by equalizing payments to be made on a quarterly basis. Only out-of-pocket costs shall be
accounted for and reimbursed under this Section, without any allocation for internal resources devoted to the litigation. Except as otherwise agreed to by the parties as part of a cost sharing arrangement, any recovery realized as a result of such
joint litigation shall be shared equally by the parties (unless they agree beforehand to a different sharing of such recovery). 
  
 14.6 Defense of Individual Infringement Actions Involving Use of the Targets. If Mitotix or DuPont Merck, or any of their respective Affiliates,
shall be individually named as a defendant in a legal proceeding by a Third Party for infringement of a patent because of the use of CDK Targets in the CDK Field or the use of the UBC Targets in the UBC Field, the party which has been sued shall
promptly notify the other party in writing of the institution of such suit. The party which has been sued shall be entitled to control the defense of such suit, and all out-of-pocket expenses including out-of-pocket costs, outside attorney fees,
adverse judgments or settlement amounts incurred on account of DuPont Merck or Mitotix as the case may be shall be paid as set forth under Section 14.8 below. For Royalty-Bearing Products, DuPont Merck may deduct its share of such out-of-pocket
expenses, for the purpose of determining the amount of Net Sales of Royalty-Bearing Products sold in the country where such infringement action is maintained. Such deduction shall continue from year-to-year until such out-of-pocket expenses have
been deducted in full. The controlling party may not settle such suit or otherwise consent to an adverse judgment in such suit that diminishes the rights or interests of the non-controlling party without the express written consent of the
non-controlling party. The party which has been sued shall keep the other party at all times reasonably informed as to the status of the suit. The party which is not controlling such legal proceedings shall have the right to be represented by
advisory counsel of its own selection (and such counsel’s opinion shall be reasonably considered by the controlling party), at its own expense, and shall cooperate fully in the defense of such suit and reasonably cooperate in furnishing to the
party controlling such legal proceedings all evidence and assistance in its control. 
  
 14.7 Defense of Joint Infringement Actions Involving Use of the Targets. If Mitotix and DuPont Merck, or any of their respective Affiliates, shall be jointly named as defendants in a legal proceeding by a Third
Party or shall be joined in the same litigation for infringement of a patent because of the use of CDK Targets in the CDK Field or use of UBC Targets in the UBC Field, DuPont Merck shall be entitled to control the defense of such suit, and all
out-of-pocket expenses including out-of-pocket costs, outside attorney fees, adverse judgments or settlement amounts incurred on account of DuPont Merck or Mitotix or both shall be paid as set forth under Section 14.8 below. For Royalty-Bearing
Products, DuPont Merck may deduct its share of such out-of-pocket expenses, for the purpose of determining 

  

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the amount of Net Sales of Royalty-Bearing Products sold in the country where such infringement action is maintained. Such deduction shall continue from
year-to-year until such out-of-pocket expenses have been deducted in full. Mitotix shall have the right to be represented by counsel of its own selection, but at its sole expense, and shall cooperate fully in the defense of such suit and reasonably
cooperate in furnishing to DuPont Merck all evidence and assistance in its control. DuPont Merck shall, however, not be entitled to settle such suit or otherwise consent to an adverse judgment in such suit without the express written consent of
Mitotix if such settlement or adverse judgment diminishes any right or interest of Mitotix hereunder. 
  
 14.8 Contribution. With respect to all such out-of-pocket expenses (including out- of-pocket costs, outside attorneys fees, judgments, or
settlement amounts) payable with respect to legal proceedings covered by Sections 14.6 and 14.7, Mitotix shall contribute fifty percent (50%) of the amount owed or expended and DuPont Merck shall pay the remainder. 
  
 14.9 Third Party Patents. If DuPont Merck, in its reasonable judgment,
is required to obtain a license from any Third Party under any patent in order to use the CDK Targets in the CDK Field or use the UBC Targets in the UBC Field, and to pay a royalty under such license, and the infringement of such patent cannot
reasonably be avoided by DuPont Merck without such a license, DuPont Merck’s obligation to pay royalties for a Royalty-Bearing Product based on such use under Article 12 hereof shall be reduced by the amount of the royalty payable by DuPont
Merck under such additional license, provided, however, that the royalties otherwise payable under Article 12 hereof shall not be reduced in any such event by more than one-half (1/2). If DuPont Merck is required by a court of competent
jurisdiction to pay a royalty to any Third Party under any patent with respect to use of the CDK Targets in the CDK Field or use of the UBC Targets in the UBC Field, DuPont Merck’s obligation to pay royalties for a Royalty-Bearing Product based
on such use under Article 12 hereof shall be reduced by the amount of the royalty payable by DuPont Merck to such Third Party, provided, however, that the royalties otherwise payable under Article 12 hereof shall not be reduced in any such
event by more than one-half (1/2). 
  
 14.10 Infringement of
Mitotix Inventions or Joint Inventions Covering CDK Products or UBC Products. 
  
 (a) Mitotix and DuPont Merck each shall immediately give notice to the other of any potential infringement by a Third Party of any patent
rights covering Mitotix Inventions and Joint Inventions relating to CDK Products or UBC Products, including but not limited to patents covering compounds, formulations, pharmaceutical compositions, methods of use, and methods of synthesis,
(collectively, “Product Patent Rights”) of which they become aware or of any certification of which they become aware filed under the United States “Drug Price Competition and Patent Term Restoration Act of 1984” claiming that
Product Patent Rights covering a CDK Product or UBC Product are invalid or unenforceable or that infringement will not arise from the manufacture, use or sale of a CDK Product or UBC Product by a Third Party. 
  
 (b) DuPont Merck as exclusive licensee of such Product
Patent Rights will have the right to settle with the infringer or to bring suit or other proceeding at its expense 

  

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against the infringer in its own name or in the name of Mitotix where necessary, after consultation with Mitotix. Mitotix shall be kept advised at all times
of such suit or proceedings brought by DuPont Merck. Mitotix may, in its discretion, join with DuPont Merck as party to the suit or other proceeding, provided that DuPont Merck shall retain control of the prosecution of such suit or proceedings in
such event. Mitotix agrees to cooperate with DuPont Merck in its efforts to protect such Product Patent Rights, including joining as a party where necessary. 
  

(c) If DuPont Merck does not settle with the infringer of such Product Patent Rights or bring suit or other proceeding against the
infringer, upon DuPont Merck’s prior written approval Mitotix may in its discretion, bring suit or other proceeding at its expense against the infringer. Mitotix shall first consult with DuPont Merck as to whether such act(s) by a Third Party
reasonably constitute infringement and whether it is commercially advisable to bring such suit or proceeding as reasonably determined by DuPont Merck. In the event that Mitotix brings such suit or other proceeding, DuPont Merck shall be kept advised
at all times of such suit or proceedings. In such event, DuPont Merck may, in its discretion, join with Mitotix as party to the suit or other proceeding, provided that Mitotix shall retain control of the prosecution of such suit or proceedings. In
the event that Mitotix brings such suit or proceeding, DuPont Merck agrees to cooperate with Mitotix in its efforts to protect Product Patent Rights, including joining as a party where necessary. 
  
 (d) With respect to any suit or other proceeding against an
infringer of the Product Patent Rights covering a CDK Product or a UBC Product when the Alternate UBC Plan is in effect, this Section 14.10(d) shall apply. Each party will bear its own expenses with respect to any suit or other proceeding against an
infringer of the Product Patent Rights. Any recovery in connection with such suit or proceeding will first be applied to reimburse Mitotix and DuPont Merck for their out-of-pocket expenses, including attorney’s fees. The balance of any recovery
shall be distributed as follows: (i) as to ordinary damages, DuPont Merck shall receive an amount equal to its lost profits or a reasonable royalty on the sales of the infringer (whichever measure of damages the court shall have applied), less a
reasonable approximation of the royalties that DuPont Merck would have owed to Mitotix on sales of products that DuPont Merck lost to the infringer, which amount shall be received by Mitotix, and (ii) as to special or punitive damages, such amount
shall be allocated between the parties in the same proportion as ordinary damages are allocated pursuant to clause (i). 
  
 (e) With respect to any suit or other proceeding against an infringer of the Product Patent Rights covering a UBC Product when the
Alternate UBC Plan is not in effect, this Section 14.10(e) shall apply. Each party will bear its own expenses with respect to any suit or other proceeding against an infringer of the Product Patent Rights and such expenses shall be Allowable
Expenses. Any recovery in connection with such suit or proceeding will be shared in accordance with the party’s respective Percentage Contribution. 
  
 ARTICLE 15. CONFIDENTIALITY 
  
 15.1 Nondisclosure Obligations. Except as otherwise provided in this Article 15 and subject to Section 19.13, during the term of this Agreement and
for a period of ten (10) 

  

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years thereafter, both parties shall maintain in confidence and use only for purposes permitted by this Agreement (i) confidential information and data
received from the other party resulting from or related to the use of CDK Targets or UBC Targets for the development of CDK Development Compounds or UBC Development Compounds, respectively; and (ii) all information and data not described in clause
(i) above but supplied by the other party under this Agreement marked “Confidential.” 
  
 For purposes of this Article 15, information and data described in clause (i) or (ii) shall be referred to as “Information.” To the extent it is
reasonably necessary or appropriate to fulfil its obligations or exercise its rights under this Agreement, a party may disclose Information it is otherwise obligated under this Section not to disclose to its Affiliates, sublicensees, consultants,
outside contractors and clinical investigators, and in the case of DuPont Merck, the DuPont Merck Partnership Board on a need-to-know basis on condition that such Affiliates and Third Parties agree to keep the Information confidential for the same
time periods and to the same extent as such party is required to keep the Information confidential under this Agreement; and a party or its sublicensees may disclose such Information to government or other regulatory authorities to the extent that
such disclosure is reasonably necessary to obtain patents or authorizations to conduct clinical trials with and to commercially market any product. The obligation not to disclose Information shall not apply to any part of such Information that (i)
is properly in the public domain; (ii) is disclosed to the receiving party by a Third Party who may lawfully do so and is not under an obligation of confidentiality to the disclosing party; (iii) is known by the receiving party at the time of its
receipt, and not through a prior disclosure by the disclosing party, as documented by business records; or (iv) can be shown by written documents to have been independently developed by the receiving party without reference to the Information
received from the disclosing party and without breach of any of the provisions of this Agreement. 
  
 15.2 Samples. Samples of compounds synthesized, purified or developed in the course of the CDK Research Program or the UBC Research Program shall
not be supplied or sent by either party to any Third Party unless protected by an appropriate materials transfer and confidentiality agreement in accordance with the provisions and objectives of this Agreement. 
  
 15.3 Terms of this Agreement and Existence of UBC Collaboration.
Mitotix and DuPont Merck each agrees (i) not to disclose any terms or conditions of this Agreement to any Third Party without the prior consent of the other party, except as required by applicable law and (ii) not to disclose to any Third Party that
Mitotix and DuPont Merck are collaborating in the UBC Field unless the Extended UBC Collaboration is in effect, or unless the parties agree otherwise. Notwithstanding the foregoing, (i) DuPont Merck and Mitotix shall agree in writing upon the
substance of information that can be used in a press release to describe the terms of this transaction, and DuPont Merck and Mitotix may disclose such information, as modified by prior written mutual agreement from time to time; provided that
the disclosing party shall provide the other party with a copy of each such press release, (ii) each party shall be entitled to issue press releases or to otherwise to announce significant achievements in preclinical research, regulatory
approval and/or the development process for CDK Products or UBC Products; provided, however, that such disclosures shall be subject to prior written approval by the other party, (iii) Mitotix may disclose the terms of this 

  

 56 

 
Agreement to licensors of rights sublicensed hereunder, to potential licensees of rights that Mitotix has the power to grant under this Agreement and to
potential investors in Mitotix (and professional advisors of such investors) who require such information for due diligence purposes, provided that in each case where disclosure is made under this clause (iii), Mitotix shall take all
reasonable steps to minimize the extent of such disclosure, shall make such disclosures under appropriate confidentiality restrictions and shall inform DuPont Merck of the disclosures made. 
  
 15.4 Publications. During the term of this Agreement, Mitotix and
DuPont Merck each acknowledge the other party’s interest in publishing certain of its results to obtain recognition within the scientific community and to advance the state of scientific knowledge. Each party also recognizes the mutual interest
in obtaining valid patent protection and in protecting business interests and trade secret information. Consequently, either party, its employees or consultants wishing to make a publication (including any oral disclosure made without obligation of
confidentiality) relating to work performed by such party as part of the Collaboration (the “Publishing Party”) shall deliver to the other party (the “Reviewing Party”) a copy of the proposed written publication at least sixty
(60) days prior to submission for publication or presentation, or an abstract of such oral disclosure at least thirty (30) days prior to submission of the abstract or the oral disclosure, whichever is earlier. The Reviewing Party shall have the
right (a) to propose modifications to the publication to protect proprietary information and (b) to request a reasonable delay in publication or presentation in order to protect proprietary information. 
  
 If the Reviewing Party requests such a delay, the Publishing Party shall
delay submission or presentation of the publication for a period of ninety (90) days to enable patent applications protecting each party’s rights in such information to be filed or to otherwise revise the publication to protect proprietary
information. If no request for delay or modification of the proposed publication is made within the applicable sixty (60) or thirty (30) day period referred to in the preceding paragraph, the Publishing Party shall be free to proceed with the
publication or presentation. If the Reviewing Party requests modifications to the publication, the Publishing Party shall edit such publication to prevent disclosure of trade secret or proprietary business information prior to submission of the
publication or presentation. In addition, the contributions of the parties to the work described in the publication shall be expressly noted in such publications or other public disclosures by acknowledgment or co-authorship, whichever is
appropriate. 
  
 ARTICLE 16. REPRESENTATIONS AND WARRANTIES

  
 16.1 Authorization. Each party warrants and represents
to the other that it has the legal right and power to enter into this Agreement, to extend the rights and licenses granted to the other in this Agreement, and to fully perform its obligations hereunder, and that it has not made nor will it make any
commitments to others in conflict with or in derogation of such rights or this Agreement. Except as otherwise disclosed, each party further represents to the other that it is not aware of any legal obstacles, including patent rights of others, which
could prevent it from carrying out the provisions of this Agreement. 
  

 57 

 16.2 License Agreements with Third Parties. Mitotix warrants and represents to DuPont Merck that
each Mitotix License Agreement authorizes a sublicensee thereunder to perform under the license agreement in place of Mitotix, or provides for the assignment of the sublicense to the Third Party licensor, in the event that Mitotix were to breach its
obligations under the license agreement or to file for bankruptcy, and in such case the license agreement will remain in effect between the sublicensee and the Third Party licensor provided that DuPont Merck is not in breach of this Agreement
or any terms of the applicable Mitotix License Agreement. Mitotix shall use good faith commercially reasonable efforts to negotiate each Mitotix Pending License Agreement to include a provision which authorizes a sublicensee thereunder to perform
under the license agreement in place of Mitotix in the event that Mitotix were to breach its obligations under the license agreement or to file for bankruptcy, and in such case the license agreement will remain in effect between the sublicensee and
the Third Party licensor. If DuPont Merck shall be required to make payment directly to a Third Party licensor in order to preserve the rights sublicensed to DuPont Merck under a Mitotix License Agreement, DuPont Merck shall be entitled to reduce
any payments otherwise due Mitotix under this Agreement, by an amount equal to what DuPont Merck is obligated to pay to the Third Party licensor. Mitotix represents and warrants that Appendices A, D and E are accurate and complete and
identify all Mitotix License Agreements and Mitotix Pending License Agreements, respectively. Mitotix shall use all good faith commercially reasonable efforts to successfully complete at its own expense the Mitotix Pending License Agreements.
Mitotix warrants and represents that it shall use all good faith efforts to fully perform all of its obligations under the Mitotix License Agreements. Mitotix shall provide prompt notice to DuPont Merck of any dispute involving the Mitotix License
Agreements. 
  
 16.3 Patent Validity. Nothing in this
Agreement shall be construed as a warranty or representation by either party as to the validity or scope of any CDK Patent Rights or UBC Patent Rights. Mitotix represents and warrants that Appendix A and Appendix D are accurate and
complete and identify all patent rights owned or licensed to Mitotix as of the Effective Date which are necessary or useful for the use of the CDK Targets and UBC Targets in accordance with the objectives of this Agreement. 
  
 16.4 Exclusivity and Freedom-to-operate. Mitotix represents and
warrants that, except for certain material transfer agreements with academic institutions under which Mitotix has the first option to license any research results, no other person or organization presently has any effective option or license from
Mitotix to use the CDK Patent Rights or UBC Patent Rights, or is authorized to use the Mitotix Know-how, in the CDK Field or UBC Field. Mitotix represents and warrants that, to the best of its knowledge and belief, the use of the CDK Patent Rights,
UBC Patent Rights, and Mitotix Know-how in the CDK Field and UBC Field as contemplated in this Agreement does not infringe any Third Party patents or other rights. 
  
 ARTICLE 17. INDEMNITY 
  
 17.1 DuPont Merck Indemnity Obligations. In the absence of Mitotix’s negligence or a breach of warranty by Mitotix, DuPont Merck agrees to
defend, indemnify and hold 

  

 58 

 
Mitotix, its Affiliates and their respective employees and agents harmless from all claims, losses, damages or expenses arising as a result of (a) actual or
asserted violations of any applicable law or regulation by DuPont Merck, its Affiliates or sublicensees by virtue of which CDK Products or UBC Products manufactured, distributed or sold shall be alleged or determined to be adulterated, misbranded,
mislabeled or otherwise not in compliance with any applicable law or regulation; (b) claims for bodily injury, death or property damage attributable to the manufacture, distribution, sale or use of CDK Products or UBC Products by DuPont Merck, its
Affiliates or sublicensees; (c) a CDK Product or UBC Product recall ordered by a governmental agency or required by a confirmed CDK Product or UBC Product failure as reasonably determined by the parties hereto; or (d) claims that any CDK Product or
UBC Product infringes the intellectual property rights of a Third Party. 
  
 17.2 Mitotix Indemnity Obligations. In the absence of DuPont Merck’s negligence or a breach of warranty by DuPont Merck, Mitotix agrees to defend, indemnify and hold DuPont Merck, its Affiliates and parent
companies and their respective employees and agents harmless from all claims, losses, damages or expenses relating to Mitotix’s performance under this Agreement and arising as a result of the negligence, unlawful act, or willful misconduct of
Mitotix or its subcontractors or agents, and not caused by the negligence of DuPont Merck. 
  
 17.3 Procedure. Should a party or any of its Affiliates or its employees or agents (the “Indemnitee”) intend to claim indemnification under this Article 17, such Indemnitee shall promptly notify the
other party (the “Indemnitor”) in writing of any loss, claim, damage, liability or action in respect of which the Indemnitee intends to claim such indemnification, and the Indemnitor shall be entitled to assume the defense thereof with
counsel selected by the Indemnitor and approved by the Indemnitee, such approval not to be unreasonably withheld; provided, however, that if representation of Indemnitee by such counsel first selected by the Indemnitor would be inappropriate
due to a conflict of interest between such Indemnitee and any other party represented by such counsel, then Indemnitor shall select other counsel for the defense of Indemnitee, with the fees and expenses to be paid by the Indemnitor, such other
counsel to be approved by Indemnitee and such approval not to be unreasonably withheld. The indemnity agreement in this Article 17 shall not apply to amounts paid in settlement of any loss, claim, damage, liability or action if such settlement is
effected without the consent of the Indemnitor, which consent shall not be withheld unreasonably. The failure to deliver notice to the Indemnitor within a reasonable time after the commencement of any such action, if prejudicial to its ability to
defend such action, shall relieve such Indemnitor of any liability to the Indemnitee under this Article 17, but the omission so to deliver notice to the Indemnitor will not relieve it of any liability that it may have to any Indemnitee otherwise
than under this Article 17. The Indemnitee under this Article 17, its employees and agents, shall cooperate fully with the Indemnitor and its legal representatives in the investigation of any action, claim or liability covered by this
indemnification. In the event that each party claims indemnity from the other and one party is finally held liable to indemnify the other, the Indemnitor shall additionally be liable to pay the reasonable legal costs and attorneys’ fees
incurred by the Indemnitee in establishing its claim for indemnity. 
  

 59 

 17.4 Insurance. DuPont Merck and Mitotix shall each maintain product liability insurance with
respect to development, manufacture and sales of CDK Products or UBC Products by DuPont Merck or Mitotix Products by Mitotix, respectively, in such amount as DuPont Merck or Mitotix, respectively, customarily maintains with respect to sales of its
other products. DuPont Merck or Mitotix, as applicable, shall maintain such insurance for so long as it continues to manufacture or sell any CDK Products, UBC Products or Mitotix Products, and thereafter for so long as DuPont Merck or Mitotix, as
applicable, maintains insurance for itself covering such manufacture or sales. In the case of DuPont Merck, such insurance may be self-insurance. 
  
 ARTICLE 18. TERM AND TERMINATION 
  
 18.1 Expiration. Unless terminated earlier pursuant to Section 18.2 below, this Agreement shall expire on the expiration of all royalty and profit
sharing obligations under this Agreement. 
  
 18.2 Termination
for Cause. This Agreement may be terminated upon the occurrence of any of the following. 
  
 18.2.1 Bankruptcy. Either party may terminate this Agreement upon or after the bankruptcy, insolvency, dissolution or winding up of
the other party (other than dissolution or winding up for the purposes of reconstruction or amalgamation). 
  
 18.2.2 Material Breach. Either party may terminate this Agreement upon or after the breach of any material provision of this
Agreement by the other party if the breaching party has not commenced to cure such breach within thirty (30) days after notice thereof by the other party and has not thereafter proceeded diligently to cure such breach within a reasonable time. In no
event shall such reasonable time to cure such breach exceed one hundred eighty (180) days from the date of such notice. 
  
 18.2.3 Failure to Retain Qualified Scientists. DuPont Merck may terminate this Agreement in the event that Mitotix is unable to
retain sufficient qualified scientists to provide commercially reasonable support for the CDK Collaboration or UBC Collaboration or to fulfill its obligations in the CDK Research Program, as described in Sections 3.1.1 and 3.2; provided, however,
that DuPont Merck shall not have the right to terminate under this Section 18.2.3 unless (a) Mitotix is given six (6) months prior written notice by DuPont Merck of DuPont Merck’s intent to terminate, stating the reasons and justification
for such termination, and (b) Mitotix has not taken good faith commercially reasonable steps during such six (6) months period to correct such stated deficiencies. 
  
 18.3 Effect of Termination. Expiration or termination of this Agreement shall not relieve the parties of any
obligation accruing prior to such expiration or termination. Without limiting the foregoing, in the event of expiration or termination of this Agreement, for any reason (i) all licenses granted to DuPont Merck hereunder will terminate, except that
DuPont Merck shall retain an exclusive license under the Mitotix Inventions, Joint Inventions and applicable Know-how solely to develop, make, have made, use and/or sell any CDK 

  

 60 

 
Product or UBC Product incorporating compounds that at the time of termination or expiration of the Agreement have been designated as a Development Compound
(ii) the provisions of Articles 11 and 12 will survive termination of the Agreement such that DuPont Merck will continue to have milestone and royalty obligations to Mitotix with respect to Royalty-Bearing Products where applicable; and Mitotix and
DuPont Merck will continue to share in UBC Operating Profits in accordance with Section 11.5 where applicable; and Mitotix will continue to have royalty obligations to DuPont Merck with respect to Mitotix Products; (iii) the provisions of Section
13.9 will survive termination of the Agreement such that DuPont Merck will continue to have milestone and royalty obligations to certain Mitotix licensors where applicable, and (iv) the provisions of Section 5.5 will survive termination of the
Agreement. 
  
 18.4 Failure to Pursue. If DuPont Merck is
not diligently pursuing the discovery or development of either CDK Products or UBC Products using good faith commercially reasonable efforts in accordance with industry standards and consistent with the usual practice followed by DuPont Merck in
pursuing the discovery or development of its other similar pharmaceutical products, then Mitotix shall have the right to terminate the license right granted to DuPont Merck pursuant to Section 10.1.1 (in the event that DuPont Merck is not diligently
pursuing the discovery or development of any CDK Products) or Section 10.2.1 (in the event that DuPont Merck is not diligently pursuing the discovery or development of any UBC Products). Mitotix shall not have the right to terminate under this
Section 18.4 unless (a) DuPont Merck is given six (6) months prior written notice by Mitotix of Mitotix’s intent to terminate, stating the reasons and justification for such termination and recommending steps which DuPont Merck should take in
such development, and (b) DuPont Merck has not taken good faith commercially reasonable steps during such six (6) month period to diligently pursue the discovery or development of such CDK Products or UBC Products. Notwithstanding the foregoing,
Mitotix shall in no event have the right to terminate such license if the development of such product is not being pursued on the basis that a competitive product is being diligently developed by DuPont Merck pursuant to this Agreement, or DuPont
Merck reasonably determines in good faith and consistent with industry standards that such product is unlikely to yield satisfactory results in clinical trials or regulatory submissions, or that such product is commercially unattractive. Upon the
termination of any such license grants, all rights licensed to DuPont Merck thereunder shall be returned to Mitotix. Upon Mitotix’s termination of one or more of the above-referenced licenses, and at the request of Mitotix, DuPont Merck shall
enter into good faith negotiations with Mitotix regarding the grant of a license to Mitotix to pursue further development of the Development Compound Mitotix asserts is not being diligently pursued by DuPont Merck in the CDK Field or the UBC Field.

  
 ARTICLE 19. MISCELLANEOUS 
  
 19.1 Force Majeure. Neither party shall be held liable or responsible
to the other party nor be deemed to have defaulted under or breached this Agreement for failure or delay in fulfilling or performing any term of this Agreement when such failure or delay is caused by or results from causes beyond the reasonable
control of the affected party including but not limited to fire, floods, embargoes, war, acts of war (whether war is declared or not), 

  

 61 

 
insurrections, riots, civil commotions, strikes, lockouts or other labor disturbances, acts of God or acts, omissions or delays in acting by any governmental
authority or the other party. Either party shall provide the other party with prompt written notice of any delay or failure to perform that occurs by reason of force majeure and the parties shall discuss in good faith any solution to such situation.

  
 19.2 Assignment. This Agreement may not be assigned or
otherwise transferred by either party without the consent of the other party; provided, however, that either Mitotix (subject to Section 19.13) or DuPont Merck may, without such consent, assign this Agreement and its rights and obligations
hereunder to its Affiliates or in connection with the transfer or sale of all or substantially all of its business, or in the event of its merger or consolidation or change in control or similar transaction. Any purported assignment in violation of
the preceding sentences shall be void. Any permitted assignee shall assume all obligations of its assignor under this Agreement. 
  
 19.3 Severabilitv. Each party hereby agrees that it does not intend to violate any public policy, statutory or common laws, rules, regulations,
treaty or decision of any government agency or executive body thereof of any country or community or association of countries. Should one or more provisions of this Agreement be or become invalid, the parties hereto shall substitute, by mutual
consent, valid provisions for such invalid provisions which valid provisions in their economic effect are sufficiently similar to the invalid provisions that it can be reasonably assumed that the parties would have entered into this Agreement with
such valid provisions. In case such valid provisions cannot be agreed upon, the invalidity of one or several provisions of this Agreement shall not affect the validity of this Agreement as a whole, unless the invalid provisions are of such essential
importance to this Agreement that it is to be reasonably assumed that the parties would not have entered into this Agreement without the invalid provisions. 
  
 19.4 Notices. Any consent, notice or report required or permitted to be given or made under this Agreement by one of the parties hereto to the
other shall be in writing, and delivered personally or by facsimile (and promptly confirmed by personal delivery or overnight courier) or by a nationally-recognized overnight courier, addressed to such other party at its address indicated below, or
to such other address as the addressee shall have last furnished in writing to the addressor and shall be effective upon receipt by the addressee. 
  

			
	If to	    	 
	Mitotix:	    	 Mitotix, Inc.

	 	    	 One Kendall Square, Building 600

	 	    	 Cambridge, MA 02139

	 	    	 Attention: President

	 	    	 Telephone: (617) 225-0001

	 	    	 Telecopy: (617) 225-0005

  

 62 

			
	 with a copy to:
	    	 Maureen Manning, Esquire
 Palmer & Dodge
 One Beacon Street
 Boston, MA 02108
 Telephone: (617) 573-0210
 Telecopy: (617) 227-4420

  

			
	 If to
	    	 
	DuPont Merck:	    	 The DuPont Merck Pharmaceutical Company
 Experimental Station, E400
 Route 141 and Henry Clay Road
 Wilmington, DE 19880-0400
 Attention: President, DuPont Merck Research Laboratories
 Telephone: 302-695-7008
 Fax: 302-695-4497

  

			
	 with a copy to:
	    	 Associate General Counsel
 Legal Department
 The DuPont Merck Pharmaceutical Company
 974 Centre Road, DuPont Merck Plaza,
WR722
 Wilmington, DE 19807-2802
 Fax: 302-892-8536

  
 19.5 Applicable
Law. This Agreement shall be governed by and construed in accordance with the laws of the State of Delaware without reference to any rules of conflict of laws, except that all questions concerning the construction or effect of patent rights will
be construed in accordance with the laws of the country granting those rights. 
  
 19.6 Dispute Resolution. Subject to Section 9.3, any disputes arising between the parties relating to, arising out of or in any way connected with this Agreement or any term or condition hereof, or the
performance by either party of its obligations hereunder, whether before or after termination of this Agreement, shall be promptly presented to the Chief Executive Officers of Mitotix and DuPont Merck for resolution. Such chief executive officers
shall attempt in good faith to promptly resolve such dispute. If such officers are unable to resolve such dispute, any litigation instituted by DuPont Merck shall, unless otherwise agreed to in writing by Mitotix, be filed in a Massachusetts federal
or state court located in Boston and any litigation instituted by Mitotix shall, unless otherwise agreed to in writing by DuPont Merck, be filed in a Delaware federal or state court located in Wilmington. Each party hereby irrevocably consents to
the personal jurisdiction of such courts. 
  
 19.7 Entire
Agreement. This Agreement, including the Appendices and Exhibits attached hereto, contains the entire understanding of the parties with respect to the subject matter hereof. All express or implied agreements and understandings, either oral or
written, heretofore made are expressly merged in and made a part of this Agreement. This Agreement may be amended, or any term hereof modified, only by a written instrument duly executed by both parties hereto. 
  

 63 

 19.8 Headings. The captions to the several Articles and Sections hereof are not a part of this
Agreement, but are merely guides or labels to assist in locating and reading the several Articles and Sections hereof. 
  
 19.9 Independent Contractors. It is expressly agreed that Mitotix and DuPont Merck shall be independent contractors and that the relationship
between the two parties shall not constitute a partnership, joint venture or agency, except in the event and to the extent that a partnership or similar entity is formed between the parties pursuant to Section 11.5 Neither Mitotix nor DuPont Merck
shall have the authority to make any statements, representations or commitments of any kind, or to take any action, which shall be binding on the other, without the prior consent of the other party to do so. 
  
 19.10 Agreement Not to Solicit Employees. During the term of this
Agreement and for a period of two (2) years following the termination of this Agreement, Mitotix and DuPont Merck agree not to seek to persuade or induce any employee of the other company to discontinue his or her employment with that company in
order to become employed by or associated with any business, enterprise or effort that is associated with its own business. 
  
 19.11 Waiver. The waiver by either party hereto of any right hereunder or the failure to perform or of a breach by the other party shall not be
deemed a waiver of any other right hereunder or of any other breach or failure by said other party whether of a similar nature or otherwise. 
  
 19.12 Counterparts. This Agreement may be executed in two or more counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument. 
  
 19.13
Definition and Effect of Change of Control. In the event that, any time before three (3) years after the termination or expiration, for any reason, of the UBC Research Program, any of the following events occur: (i) the acquisition of fifty
percent (50%) or more of the voting stock or other ownership interest in Mitotix, by a Third Party that DuPont Merck, in good faith, determines to be a competitor of DuPont Merck, or (ii) the acquisition, directly or indirectly, of the power to
direct or cause the direction of the management and policies of Mitotix or the power to elect or appoint fifty percent (50%) or more of the members of the governing body of Mitotix, by a Third Party that DuPont Merck, in good faith, determines to be
a competitor of DuPont Merck, or (iii) the acquisition of all or substantially all of Mitotix’s assets employed or used in the Collaboration by a Third Party that DuPont Merck, in good faith, determines to be a competitor of DuPont Merck (any
of the events discussed above shall be referred to herein as a “Change of Control”), then DuPont Merck shall, prior to the effective date of such Change of Control, or if such Change of Control occurs without the approval of the Mitotix
Board of Directors, within thirty (30) days after the first public announcement thereof, notify Mitotix of its determination that such acquisition will constitute a Change in Control. 
  
 Upon receipt of such notification, Mitotix (or its successor) shall put into place appropriate safeguards to prevent the
disclosure to the competitor of DuPont Merck Information or Know-how and technical Mitotix Information or Mitotix Know-how relating 

  

 64 

 
specifically to the Collaboration. Such safeguards will include the maintenance of the facilities and personnel used in Mitotix’s performance under this
Agreement separate from the operations and facilities of the DuPont Merck competitor. Without limitation, in no event shall chemical structures relating to the Collaboration be disclosed to the DuPont Merck competitor. 
  
 Mitotix (or its successor) shall prepare and present to DuPont Merck within
thirty (30) days after receipt of notification from DuPont Merck of its determination that such acquisition will constitute a Change of Control, a written plan of operation under which Mitotix or its successor will establish and maintain the
safeguards required by this Section and continue to perform all of its obligations under this Agreement. Within thirty (30) days after its receipt of such plan, DuPont Merck will either approve such plan or respond in writing with reasonable
suggestions for modification of the plan. The plan will be modified to include such reasonable suggestions. Following a Change of Control, Mitotix (or its successors) shall continue to make good faith commercially reasonable efforts in support of
the CDK and UBC Collaboration and shall make good faith efforts to continue the CDK and UBC Collaboration and cooperate with DuPont Merck in the same manner as before the Change of Control. 
  
 In the event of a Change of Control, DuPont Merck shall have the rights set
forth in Section 3.2.l(c) and 5.7 above. 
  
 IN WITNESS WHEREOF,
the parties have executed this Agreement as of the date first set forth above. 
  

			
	 MITOTIX, INC.

		
	By:	 	 /s/ William W. Helman

	 	 	 William W. Helman

	 	 	 Title: Chairman

  

			
	 THE DUPONT MERCK PHARMACEUTICAL COMPANY

		
	By:	 	 /s/ Paul GV Howes

	 	 	 Paul GV Howes

	 	 	 Title: President, CEO

  

 65 

 APPENDIX A 
  
 CDK PATENT RIGHTS AND CERTAIN 
 MITOTIX LICENSE
AGREEMENTS 
  

					
	 Cvclin D/p16

			
	 (1)
	  	U.S.S.N.:	  	7/701,514
	 	  	Filed:	  	May 16, 1991
	 	  	Title:	  	“D-Type Cyclin and Uses Related Thereto”1
	 	  	Inventor:	  	David H. Beach
			
	 (2)
	  	U.S.S.N.:	  	7/888,178
	 	  	Filed:	  	May 26, 1992
	 	  	Title:	  	“D-Type Cyclin and Uses Related Thereto”1
	 	  	Inventor:	  	David H. Beach
			
	 (3)
	  	U.S.S.N.:	  	8/324,526
	 	  	Filed:	  	May 26, 1992
	 	  	Title:	  	“D-Type Cyclins and Uses Related Thereto”1
	 	  	Inventor:	  	David H. Beach
			
	 (4)
	  	U.S.S.N.:	  	7/963,308
	 	  	Filed:	  	October 16, 1992
	 	  	Title:	  	“D-Type Cyclin and Uses Related Thereto”1
	 	  	Inventor:	  	David H. Beach
			
	 (5)
	  	U.S.S.N.:	  	7/991,997
	 	  	Filed:	  	December 17, 1992
	 	  	Title:	  	“Cyclin Complex Rearrangement and Uses Related Thereto”2
	 	  	Inventor:	  	David H. Beach, et al.
			
	 (6)
	  	U.S.S.N.:	  	8/154,915
	 	  	Filed:	  	November 18,1993
	 	  	Title:	  	“Cyclin Complex Rearrangement and Uses Related Thereto”2
	 	  	Inventor:	  	David H. Beach, et al.
			
	 (7)
	  	U.S.S.N.:	  	8/227,371
	 	  	Filed:	  	April 14, 1994
	 	  	Title:	  	“Cell Cycle Regulatory Protein, and Uses Related Thereto”2 
	 	  	Inventor:	  	David H. Beach, et al.

  

	1	Cyclin D License 

  

	2	pl6 License 

  

	3	Mitotix owned Patents 

  

	4	PRADl License 

  

	5	Cyclin E License 

  

 Appendix A-Page 1 

					
			
	 (8)
	  	U.S.S.N.:	  	08/246,36
	 	  	Filed:	  	May 19, 1994
	 	  	Title:	  	“D.-Type Cyclins and Uses Related Thereto”1
	 	  	Inventor:	  	David H. Beach
			
	 (9)
	  	U.S.S.N.:	  	08/248,812
	 	  	Filed:	  	May 25, 1994
	 	  	Title:	  	“Cell Cycle Regulatory Proteins, and Uses Related
Thereto”2
	 	  	Inventor:	  	David H. Beach, et al.
			
	 (10)
	  	U.S.S.N.:	  	08/253,155
	 	  	Filed:	  	June 2, 1994
	 	  	Title:	  	“D-Type Cyclins and Uses Related Thereto”1
	 	  	Inventor:	  	Giulio Draetta, Jeno Gyuris
			
	 (11)
	  	U.S.S.N.:	  	08/306,511
	 	  	Filed:	  	September 14, 1994
	 	  	Title:	  	“Cell Cycle Regulatory Protein, and Uses Related
Thereto”2
	 	  	Inventor:	  	David H. Beach, et al.
			
	 (12)
	  	U.S.S.N.:	  	08/346,147
	 	  	Filed:	  	November 29,1994
	 	  	Title:	  	“Cell Cycle Regulatory Protein, and Uses Related Thereto”2
	 	  	Inventor:	  	David H. Beach, et al.
			
	 (13)
	  	U.S.S.N.:	  	08/464,517
	 	  	Filed:	  	June 5, 1995
	 	  	Title:	  	“D-Type Cyclins and Uses Related Thereto”1
	 	  	Inventor:	  	David H. Beach
			
	 (14)
	  	U.S.S.N.:	  	08/463,772
	 	  	Filed:	  	June 5,1995
	 	  	Title:	  	“D-Type Cyclins and Uses Related
Thereto”1
	 	  	Inventor:	  	David H. Beach
			
	 (15)
	  	U.S.S.N.:	  	08/466,679
	 	  	Filed:	  	June 6, 1995
	 	  	Title:	  	“CDC37 Cell-Cycle Regulatory Protein, and Uses Related Thereto”3
	 	  	Inventor:	  	Jeno Gyuris, et al.

  

	1	Cyclin D License 

  

	2	p16 License  

  

	3	Mitotix owned Patents  

  

	4	PRAD1 License  

  

	5	Cyclin E License 

  

 Appendix A-Page 2 

					
			
	 (16)
	  	U.S.S.N.:	  	08/497,214
	 	  	Filed:	  	June 30, 1995
	 	  	Title:	  	“Cell Cycle Regulatory Proteins, and Uses Related
Thereto”2 
	 	  	Inventor:	  	David H. Beach, et al
			
	 (17)
	  	U.S.S.N.:	  	tba
	 	  	Filed:	  	October 31,1995
	 	  	Title:	  	“Inhabitors of Cyclin-Depenent
Kinases”2
	 	  	Inventor:	  	Muzammil Mansuri, et al.
			
	 (18)
	  	App. No.:	  	PCT/US92/04146
	 	  	Filed:	  	May 18, 1992
	 	  	Title:	  	“D-Type Cyclins and Uses Related Thereto”1
	 	  	Inventor:	  	David H. Beach
			
	 (19)
	  	App. No.:	  	2,103,161 (Canada)
	 	  	Filed:	  	May 18, 1992
	 	  	Title:	  	“D-Type Cyclins and Uses Related Thereto”1
	 	  	Inventor:	  	David H. Beach
			
	 (20)
	  	App. No.:	  	92 913100.1 (EPO)
	 	  	Filed:	  	May 18, 1992
	 	  	Title:	  	“D-Type Cyclins and Uses Related Thereto”1
	 	  	Inventor:	  	David H. Beach
			
	 (21)
	  	App. No.:	  	5-500242 (Japan)
	 	  	Filed:	  	May 18, 1992
	 	  	Title:	  	“D-Type Cyclins and Uses Related Thereto”1
	 	  	Inventor:	  	David H. Beach
			
	 (22)
	  	App. No.:	  	PCT/US93/09945
	 	  	Filed:	  	October 18, 1993
	 	  	Title:	  	“Cyclin Complex Rearrangement and Uses”2
	 	  	Inventor:	  	David H. Beach, et al.
			
	 (23)
	  	App. No.:	  	54440/94 (Australia)
	 	  	Filed:	  	October 18, 1993
	 	  	Title:	  	“Cyclin Complex Rearrangements and Uses”2
	 	  	Inventor:	  	DavidH. Beach, et al.

  

	1	Cyclin D License 

  

	2	p16 License 

  

	3	Mitotix owned Patents 

  

	4	PRADl License 

  

	5	Cyclin E License 

  

 Appendix A-Page 3 

					
			
	 (24)
	  	App. No.:	  	2,146,965 (Canada)
	 	  	Filed:	  	October 18, 1993
	 	  	Title:	  	“Cyclin Complex Rearrangements and Uses”2
	 	  	Inventor:	  	David H. Beach, et al
			
	 (25)
	  	U.S.S.N.:	  	93 924946.2 (EPO)
	 	  	Filed:	  	October 18, 1993
	 	  	Title:	  	“Cyclin Complex Rearrangements and Uses”2
	 	  	Inventor:	  	David H. Beach, et al
			
	 (26)
	  	App. No.:	  	510328/94 (Japan)
	 	  	Filed:	  	October 18, 1993
	 	  	Title:	  	“Cyclin Complex Rearrangements and Uses”2
	 	  	Inventor:	  	David H. Beach, et al
			
	 (27)
	  	App. No.:	  	701512/95 (Korea)
	 	  	Filed:	  	October 18, 1993
	 	  	Title:	  	“Cyclin Complex Rearrangements and Uses”2
	 	  	Inventor:	  	David H. Beach, et al
			
	 (28)
	  	App. No.:	  	PCT/US95/04636
	 	  	Filed:	  	April 14, 1995
	 	  	Title:	  	“Cell Cycle Regulatory Proteins, and Uses Related Thereto”2
	 	  	Inventor:	  	David H. Beach, et al
			
	 (29)
	  	App. No.:	  	PCT/US95/071
	 	  	Filed:	  	June 2, 1995
	 	  	Title:	  	CDK4 Binding Proteins”3
	 	  	Inventor:	  	Giulio Draetta, Jeno Gyuris
		
	 PRAD1
	  	 
			
	 (1)
	  	U.S.S.N.:	  	07/667,711
	 	  	Filed:	  	March 11, 1991
	 	  	Title:	  	“Pradl Cyclin and its cDNA”4
	 	  	Inventor:	  	Andrew Arnold
			
	 (2)
	  	U.S.S.N.:	  	tba
	 	  	Filed:	  	June 2, 1995
	 	  	Title:	  	“Pradl Cyclin and its cDNA”4
	 	  	Inventor:	  	Andrew Arnold

  

	1	Cyclin D License 

  

	2	p16 License 

  

	3	Mitotix owned Patents 

  

	4	PRAD1 License 

  

	5	Cyclin E License 

  

 Appendix A-Page 4 

					
			
	 (3)
	  	U.S.S.N.:	  	08/460,694
	 	  	Filed:	  	June 2, 1995
	 	  	Title:	  	“Pradl Cyclin and its cDNA”4
	 	  	Inventor:	  	Andrew Arnold
			
	 (4)
	  	U.S.S.N.:	  	tba
	 	  	Filed:	  	June 2, 1995
	 	  	Title:	  	“Pradl Cyclin and its cDNA”4
	 	  	Inventor:	  	Andrew Arnold
			
	 (5)
	  	U.S.S.N.:	  	08/460,655
	 	  	Filed:	  	June 2, 1995
	 	  	Title:	  	“Pradl Cyclin and its cDNA”4
	 	  	Inventor:	  	Andrew Arnold
			
	 (6)
	  	U.S.S.N.:	  	08/460,744
	 	  	Filed:	  	June 2, 1995
	 	  	Title:	  	“Pradl Cyclin and its cDNA”4
	 	  	Inventor:	  	Andrew Arnold
			
	 (7)
	  	App.No.:	  	PCT/US92/01925
	 	  	Filed:	  	March 11, 1992
	 	  	Title:	  	Pradl Cyclin and its cDNA”4
	 	  	Inventor:	  	Andrew Arnold
			
	 (8)
	  	App.No.:	  	92909340.0 (EPO)
	 	  	Filed:	  	March 11, 1992
	 	  	Title:	  	“Pradl Cyclin and its cDNA”4
	 	  	Inventor:	  	Andrew Arnold
			
	 (9)
	  	App.No.:	  	2,104,871 (Canada)
	 	  	Filed:	  	March 11, 1992
	 	  	Title:	  	“Pradl Cyclin and its cDNA”4
	 	  	Inventor:	  	Andrew Arnold
			
	 (10)
	  	App.No.:	  	tba (Japan)
	 	  	Filed:	  	March 11, 1992
	 	  	Title:	  	“Pradl Cyclin and its cDNA”4
	 	  	Inventor:	  	Andrew Arnold

  

	1	Cyclin D License  

  

	2	pl6 License  

  

	3	Mitorix owned Patents 

  

	4	PRADl License 

  

	5	Cyclin E License 

  

 Appendix A-Page 5 

					
	 Cvclin E
	  	 
			
	 (1)
	  	U.S.S.N.:	  	07/764,309
	 	  	Date Filed:	  	September 20, 1991
	 	  	Title:	  	“Human Cyclin E”5
	 	  	Inventor:	  	Roberts, Cross
			
	 (2)
	  	U.S.S. N.:	  	07/947,311
	 	  	Filed:	  	September 16, 1992
	 	  	Date Issued:	  	September 12, 1995
	 	  	Patent No.:	  	5,499,755
	 	  	Title:	  	“Human Cyclin E “5
	 	  	Inventor:	  	Roberts, Koff, Ohtsubo, Cross
			
	 (3)
	  	App. No.:	  	PCT/US92/07866
	 	  	Filed:	  	September 16, 1992
	 	  	Title:	  	“Human Cyclin E”5
	 	  	Inventor:	  	Roberts, Koff, Ohtsubo, Cross
			
	 (4)
	  	App. No.:	  	1993-506220 (Japan)
	 	  	Filed:	  	September 16, 1992
	 	  	Title:	  	“Human Cyclin E”5
	 	  	Inventor:	  	Roberts, Koff, Ohtsubo, Cross
			
	 (5)
	  	App. No.:	  	92 920511.0 (EPO)
	 	  	Filed:	  	September 16, 1992
	 	  	Title:	  	“Human Cyclin E”5
	 	  	Inventor:	  	Roberts, Koff, Ohtsubo, Cross
			
	 (6)
	  	App. No.:	  	26663/92 (Australia)
	 	  	Filed:	  	September 16, 1992
	 	  	Title:	  	“Human Cyclin E”5
	 	  	Inventor:	  	Roberts, Koff, Ohtsubo, Cross
			
	 (7)
	  	App. No.:	  	2,119,443 (Canada)
	 	  	Filed:	  	September 16, 1992
	 	  	Title:	  	“Human Cyclin E”5
	 	  	Inventor:	  	Roberts, Koff, Ohtsubo, Cross
			
	 (8)
	  	U.S.S. N.:	  	08/522,166
	 	  	Filed:	  	June 7,1995
	 	  	Title:	  	“Human Cyclin E”5
	 	  	Inventor:	  	Roberts, Koff, Ohtsubo, Cross

  

	l	Cyclin D License  

  

	2	pl6 License  

  

	3	Mitorix owned Patents  

  

	4	PRAD1 License 

  

	5	Cyclin E License 

  

 Appendix A-Page 6 

					
			
	 (9)
	  	U.S.S.N.:	  	08/485,859
	 	  	Filed:	  	June 7, 1995
	 	  	Title:	  	“Human Cyclin E”5
	 	  	Inventor:	  	Roberts, Koff, Ohtsubo, Cross
			
	 (10)
	  	U.S.S.N.:	  	08/488,382
	 	  	Filed:	  	June 7, 1995
	 	  	Title:	  	“Human Cyclin E”5
	 	  	Inventor:	  	Roberts, Koff, Ohtsubo, Cross
			
	 (11)
	  	U.S.S.N.:	  	08/480,912
	 	  	Filed:	  	June 7, 1995
	 	  	Title:	  	“Human Cyclin E”5
	 	  	Inventor:	  	Roberts, Koff, Ohtsubo, Cross

  

	1	Cyclin D License  

  

	2	p16 License  

  

	3	Mitotix owned Patents  

  

	4	PRADl License  

  

	5	Cyclin E License 

  

 Appendix A-Page 7 

 APPENDIX B  
  
 CDK WORK PLAN 
  
 The guiding principle behind the proposed workplan is that Mitotix and DuPont Merck with collaborate on the identification and development of CDK Development Compounds to
be used as therapeutic agents. The Annual CDK Research Plan will initially focus on ***. The collaborative Policy Setting Committee will broaden the focus of the CDK Research Program as it determines necessary and appropriate and will describe any
new areas of focus in subsequent Annual CDK Research Plans. The first Annual CDK Research Plan shall be prepared by the CDK Research Operating Committee and approved by DuPont Merck with the conurrence of the Collaborative Policy Setting Committee
within forty-five (45) days after the Effective Date. Subsequent Annual CDK Research Plans shall be prepared by the CDK Research Operating Committee, for submission to, and approval by, DuPont Merck with the concurrence of the Collaborative Policy
Setting Committee, not later than sixty (60) days prior to the start of each Research Year. Each Annual CDK Research Plan should include, without limitations, the following: 
  

	 	(i)	Goals and objectives for the CDK Collaboration 

  

	 	(ii)	Names and percentage of time to be working on CDK Research Program by Mitotix FTEs 

  
 Mitotix will continue biological discovery, target vbalidation, biochemical and cell-based assay refinement, and new assay development with
respect to the CDK Targets. New assay development will include both (i) selectivity assays to screen out other activity ***, subject to the direction of the Collaborative Policy Setting Committee, and (ii) genetic engineering of ceil lines to test
potential combination drug regimens. The Collaborative Policy Setting Committee shall determine which party shall be responsible for conducting the primary screening of compounds. Following primary screening, compounds which meet the specifications
set forth by the CDK Research Operating Committee for suitable condidates for continued preclinical development shall be provided to Motitx. Mitotix will have primary responsibility for conducting secondary screening of compounds with respect to CDK
Targets in the CDK Field. DuPont Merck will have primary responsibility for medicinal and strucutral chemistry of small-molecule leads, and will provide access to its chemical libraries (and other chemical libraries that it may access). Mitotix and
DuPont Merck will work together to develop any necessary in vivo and animal pharmacology models for further testing of the compounds. 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 Appendix B-Page 1 

 APPENDIX C  
  
 CDK PRIMARY AND SECONDARY SCREENS 
  
 Primary and Secondary Screens in the CDK Collaboration that have been validated by Mitorix as of the Effective Date: 
  
 *** 
  

	 	•	Actives will be tested against the following related kinase secondary screens: 

  
 *** 
  
 *** 
  
 *** 
  

	 	•	Any active leads which remain after these assays will be tested in the pharmacology enzyme panel. The enzymes in the pharmacology panel are 

  
 *** 
  
 *** 
  
 *** 
  
 *** 
  
 *** 
  
 *** 
  

	 	•	Any active leads which remain after these assays will be tested in the tertiary cell line screens. 

  
 *** 
  

	 	•	Actives will be tested against the following secondary screens: 

  
 *** 
  
 *** 
  

	 	•	Any active leads which remain after these assays will be tested in the enzyme pharmacology panel and the tertiary cell line screens. 

  
 *** 
  

	 	•	Actives will be tested again the following secondary screens: 

  
 *** 
  
 *** 
  
 *** 
  

	 	•	Any active leads which remain after these assays will be tested in the enzyme pharmacology panel and the tertiary cell line screens. 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 Appendix C-Page 1 

 APPENDIX D 
  

UBC PATENT RIGHTS AND CERTAIN 
 MITOTIX
LICENSE AGREEMENTS 
  

					
	 (1)
	  	 U.S.S.N.:
	  	 08/176,937

	 	  	 Filed:
	  	 January 4, 1994

	 	  	 Title:
	  	 “Assay and Reagents for Detecting Inhibitors of Ubiquitin-

	 	  	 	  	 dependent Degradation of Cell Cycle Regulatory Protein”1

	 	  	 Inventor:
	  	 Mark Rolfe, et al.

			
	 (2)
	  	 U.S.S.N.:
	  	 08/247,904

	 	  	 Filed:
	  	 May 23, 1994

	 	  	 Title:
	  	 “Human Ubiquitin Conjugating Enzyme”1

	 	  	 Inventor:
	  	 Marx Rolfe, et al

			
	 (3)
	  	 U.S.S.N.:
	  	 08/305,520

	 	  	 Filed:
	  	 September 13, 1994

	 	  	 Title:
	  	 “Ubiquitin Conjugating Enzymes”1

	 	  	 Inventor:
	  	 Mark Rolfe, et al.

			
	 (4)
	  	 U.S.S.N.:
	  	 08/350,468

	 	  	 Filed:
	  	 December 7, 1994

	 	  	 Titled:
	  	 “Ubiquitin Conjugating Enzymes”2

	 	  	 Inventor:
	  	 Marc Kirschner, Renee Yew, Randall King

			
	 (5)
	  	 U.S.S.N.:
	  	 08/425,299

	 	  	 Filed
	  	 April 20, 1995

	 	  	 Titled:
	  	 “Assays and Reagents for Detecting Inhibitors of Ubiquitin-
 Dependent Degradation of Cell Cycle Regulatory Proteins”3

	 	  	 Inventor:
	  	 Marc Kirschner, Randall King, Jan-Michael Peters

			
	 (6)
	  	 U.S.S.N.:
	  	 08/486,663

	 	  	 Filed:
	  	 June 7,1995

	 	  	 Title:
	  	 “Ubiquitin Conjugating Enzymes”1

	 	  	 Inventor:
	  	 Mark Rolfe, et al.

			
	 (7)
	  	 App. No.:
	  	 PCT/US95/00164

	 	  	 Filed
	  	 January 4, 1995

	 	  	 Title:
	  	 “Ubiquitin Conjugating Enzymes”1

	 	  	 Inventor:
	  	 Mark Rolfe, et al.

  

	1	Mitotix owned Patents

  

	2	UBC9 License 

  

	3	Cdc27/cdc 16 License 

  

 Appendix D-Page 1 

 APPENDIX E  
  
 MITOTIX PENDING LICENSE AGREEMENTS 
  
 The following Mitotix Pending License Agreements relating to technologies that may be useful in the CDK Field or UBC Field
are under negotiation by Mitotix as of the Effective Date: 
  

	 	(1)	Mitotix is negotiating an exclusive license to *** with ***. 

  

	 	(2)	Mitotix has applied for an exclusive license to *** from ***. 

  

	 	(3)	Mitotix is negotiating an exclusive license to *** from ***. 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 Appendix E–Page 1 

 APPENDIX F  
  
 UBC WORK PLAN 
  
 The guiding principle behind the proposed workplan and budget is that Mitotix and DuPont Merck will collaborate on the identification and development of UBC Development
Compounds to be used as therapeutic agents. The Annual UBC Research Plan and Budget will initially focus on ***. The Collaborative Policy Setting Committee will broaden the focus of the UBC Research Program as it determines necessary and appropriate
and will describe any new areas of focus in subsequent Annual UBC Research Plans and Budgets. The first Annual UBC Research Plan and Budget shall be prepared by the UBC Research Operating Committee and approved by the Collaborative Policy Secting
Committee within forty-five (45) days after the Effective Date. Subsequent Annual UBC Research Plans and Budgets shall be prepared by the UBC Research Operating Committee, for submission to, and approval by the Collaborative Policy Setting Committee
not later than sixty (60) days prior to the start of each Research Year. 
  
 Each
Annual UBC Research Plan and Budget should include without limitation the following: 
  

	 	(i)	Goals and objectives of the UBC Collaboration 

  

	 	(ii)	Specific responsibilities for each party including the names and percentage of time of Scientists to be working on the UBC Research Program 

  

	 	(iii)	Annual Budget and Estimated Percentage Contribution 

  
 Mitotix will assign at least four full-time equivalent qualified scientists to work on the UBC Research Program. 
  
 DuPont will assign at least four full-time equivalent qualified scientists to work on the UBC
Research Program. 
  
 The Collaborative Policy Setting Committee shall determine
which Party shall be responsible for conducting the primary screening of compounds. Following primary screening, compounds which meet the specifications set forth by the UBC Research Operating Committee for suitable candidates for continued
preclinical development shall be provided to Mitotix for secondary screening. 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 Appendix F–Page 1 

 APPENDIX G 
  

CO-PROMOTION OF CDK PRODUCTS AND CO-PROMOTION OF UBC PRODUCTS 
 WHEN THE ALTERNATE UBC PLAN HAS BEEN PUT INTO EFFECT 
  
 For purposes of this Appendix Gl, the term “Product” shall include CDK Products and, when the Alternate UBC Plan has been put into effect, UBC Products. 
  
 1. Timing of Mitotix’s Election to Co-Promote. DuPont Merck shall promptly notify Mitotix in writing of the filing of an NDA in the
U.S. for a Product. DuPont Merck will also furnish Mitotix with such clinical and commercial information relating to the marketing strategy for the Product, which is reasonably available to DuPont Merck at the time of NDA filing and to the extent
not provided to Mitotix earlier, as is reasonably necessary to enable Mitotix to determine whether to exercise its co-promotion option. Mitotix shall inform DuPont Merck whether or not it wishes to exercise its option to co-promote the Product
within sixty (60) days after receipt of such written notice and related information from DuPont Merck. 
  
 2. Co-Promotion Territory. The United States of America. 
  
 3. Co-Promotion Option. Mitotix’s right to co-promote Products shall consist solely of the right to perform personal detailing to appropriate target audiences, likely to be limited to physicians, at up to ten
percent (10%) of the total detailing effort at any given time for that Product in the United States. Mitotix will not be involved in any other marketing, promotion, or selling activities with regard to Products. 
  
 4. Negotiation of Co-Promotion Agreement. If Mitotix exercises its option to co-promote a
Product, the parties shall negotiate in good faith and enter into a “Co-Promotion Agreement” not less than one (1) year prior to the anticipated First Commercial Sale of the Product in the United States, as determined by DuPont Merck in
good faith. The Co-Promotion Agreement shall provide for the co-promotion of such Product by Mitotix to physicians on a fee-per-detail basis, up to a level of details per year which shall not exceed ten percent (10%) of the total number of details
for such Product in a given year. The fee-per-detail will be at a fair market value, based on industry standards for similar fee-per-detail contract detailing arrangements. 
  
 In the event that the parties cannot agree on the allocation of Mitotix’ maximum 10% detailing effort, the matter will
be taken to the Vice President, Marketing & Sales of each of the parties for resolution. If the issue remains unresolved at this level, the matter shall be taken to the President and/or CEO of each of the parties for final resolution.

  
 “Detail” or “Detailing” as used in this
Agreement shall mean, with respect to a drug product, the activity undertaken by a sales representative during a sales call on physicians in their offices, at hospitals or at other locations, including at hospital displays (excluding medical
convention exhibits and displays and other forms of communication not involving face-to-face contact by a sales representative and a physician), of describing the FDA- 

  

 Appendix G1–Page 1 

 
approved indicated uses, safety, effectiveness, contraindications, side effects, warnings and other relevant characteristics of such drug product, in a fair
and balanced manner consistent with the requirements of the Food Drug Cosmetic Act, as amended, and regulations promulgated thereunder from time to time, and using, as necessary or desirable, the applicable promotional materials for the drug
product, in an effort to increase physician prescribing preferences of the drug product for its FDA-approved indicated uses. 
  

 Appendix G1–Page 2 

 APPENDIX G2 
  
 CO-PROMOTION OF UBC PRODUCTS 
 WHEN THE ALTERNATE UBC PLAN IS NOT IN EFFECT 
  
 1. Timing of Mitotix’s Election to Co-Promote. DuPont Merck shall promptly notify Mitotix in writing of the filing of an NDA in the U.S. for a UBC Product. DuPont Merck will also furnish Mitotix with such
clinical and commercial information relating to the marketing strategy for the Product, which is reasonably available to DuPont Merck at the time of NDA filing and to the extent not provided earlier to Mitotix, as is reasonably necessary to enable
Mitotix to determine whether to exercise its co-promotion option. Mitotix shall inform DuPont Merck whether or not it wishes to exercise its option to co-promote the UBC Product within sixty (60) days after receipt of such written notice and related
information from DuPont Merck. 
  
 2. Co-Promotion Territory. The
United States of America. 
  
 3. Co-Promotion Option.
Mitotix’s right to co-promote UBC Products when the Alternate UBC Plan is not in effect shall consist solely of the right to perform a percentage of the total Selling Effort (defined below) for the UBC Product, such percentage not to exceed the
Mitotix Percentage Contribution at the time of launch of the UBC Product in the United States. Such percentage shall remain fixed unless the parties mutually agree otherwise. The costs of each party’s Selling Effort will be classified as Field
Selling Expense in accordance with Appendix J. 
  
 4. Negotiation
of Co-Promotion Agreement. If Mitotix exercises its option to co-promote a UBC Product, the parties shall negotiate in good faith and enter into a “Co-Promotion Agreement” not less than one (1) year prior to the anticipated First
Commercial Sale of the UBC Product, as determined by DuPont Merck in good faith. The Co-Promotion Agreement shall set forth terms and conditions governing the co-promotion of the product which are commercially reasonable in light of information and
assumptions pertaining at that time to the following (based on data contained in the NDA): (i) indication(s) for the product; (ii) dosage forms for the product; (iii) target audience (e.g, institutional and physician specialty); and (iv) each
company’s strengths with the target audience and appropriate managed health care audiences. Unless mutually agreed otherwise during negotiation of the Co-Promotion Agreement, the Co-Promotion Agreement shall include the following provisions:

  
 4.1. DuPont Merck shall be solely responsible for the pricing
of the product. 
  
 4.2. The parties shall detail a single brand
of the product using a trademark, branding strategy, promotional strategy, promotional investment and promotional mix selected and controlled by DuPont Merck. 
  

4.3. To the extent not prohibited by applicable laws or regulations, DuPont Merck and Mitotix shall enjoy relative corporate exposure proponional to
each parry’s Percentage Contribution (e.g., proponional prominence given to the DuPont Merck and Mitotix names on 

  

 Appendix G2–Page 1 

 
the product, product samples, promotional items, exhibits, advertisements, etc.) during the co-promotion effort. 
  
 4.4. DuPont Merck will oversee the day-to-day marketing plan for the
products, subject to guidance from a Collaborative Marketing Committee, which will consist of as many DuPont Merck representatives as deemed necessary by DuPont Merck and two representatives of Mitotix. The Collaborative Marketing Committee will
make strategic and major operational recommendations to DuPont Merck on sales, marketing, promotion and advertising, including the target subscribers whom Mitotix shall detail and the number and manner of details. 
  
 4.5. “Selling Effort”, to be further defined in the Co-Promotion
Agreement, shall mean personal sales detailing efforts mutually established between the parties and described in the marketing plan for the product. Examples of “Selling Effort” to be considered by the parties and counted as a detail are
(i) personal detailing to appropriate target audiences, (ii) broad-based technical approaches (i.e., in-service training programs), and (iii) structured group presentations to pre-screened audiences. DuPont Merck shall, in consultation with
Mitotix through the Collaborative Marketing Committee, determine the overall level and types of Selling Effort for the product which will maximize sales of the product. The parties will then agree, within the limits of Mitotix’s contractual
rights, on the allocation of the types of Selling Effort to achieve optimal utilization of each parry’s field force. The parties recognize the rapidly changing health environment in the United States and acknowledge that parameters currently
utilized for determining Selling Efforts and the results obtained therefrom may change over time, and each will take such changes into account and adopt such changes as appropriate to maximize sales of a product. In the event that the parties cannot
agree on the allocation of types of Selling Effort needed to meet the above objectives, the matter will be taken to the Vice President, Marketing & Sales of each of the parties for resolution. If the issue remains unresolved at this level, the
matter shall be taken to the President and/or CEO of each of the parties for final resolution. 
  

 Appendix G2–Page 2 

 APPENDIX H 
  
 UBC PRODUCTS 
  
 DEFINITION OF PERCENTAGE CONTRIBUTION 
  
 In summary, UBC Operating Profit (as defined in Appendix I) is to be shared between the parties based on each party’s contribution toward the funding of the expense of UBC Research, Development and Pre-Launch
Marketing Costs. The mechanism by which the Percentage Contribution will be calculated is as described below: 
  
 Target Date: The Target Date is the date the first UBC Product is expected to be launched in the first Strategic Country. The expectation is that the parties will manage to and achieve the target 70% / 30% Percentage
Contribution by the Target Date. 
  
 Set Date: The Set Date refers to the date
when the first UBC Product has been launched in all Strategic Countries. 
  
 Percentage Contribution: The Percentage Contribution refers to the percentage share of each party’s Cumulative NPV Contribution relative to the combined Cumulative NPV Contribution for both parties. 
  
 Cumulative NPV Contribution: The Cumulative NPV Contribution is determined at any time by
summing the Net Present Value (NPV) of each year’s UBC Research, Development and Pre-Launch Marketing Costs funded by each party. 
  
 Net Present Value: The Net Present Value (NPV) for each year’s UBC Research, Development and Pre-Launch costs is determined by discounting the full year’s
expenses to the Effective Date at a discount rate of 10% per annum in accordance with standard financial methodology. 
  
 For all UBC Products, the Percentage Contribution shall be calculated up through the Set Date based on each party’s continued contribution to
Research, Development, and Pre-Launch Marketing Costs. On the Set Date, a final calculation of the Percentage Contribution will be performed fixing the percentage share each party will receive of worldwide earnings from the Set Date onward for the
first UBC Product as well as all subsequent UBC Products. 
  

 Appendix H - Page 1 

 Prior to the Set Date, each party will share in worldwide earnings based on the Percentage Contribution
calculated at the end of the preceding year or estimated Percentage Contribution from the prior quarter if materially different. It is the expectation of both parties that the Percentage Contribution target of 70% / 30% will be managed to and
achieved by the Target Date. The following illustrates the Percentage Contribution calculation for all UBC Products up through the Set Date: 
  

															
	 	  	Annual Cost

	  	Cumulative NPV

	  	% Contribution

	 
	 	  	DuPont/
Merck

	  	Mitotix

	  	DuPont/
Merck

	  	Mitotix

	  	 DuPont /
 Merck

	 	 	Mitotix

	 
	 Year 1
	  	2.0	  	2.0	  	1.8	  	1.8	  	50	%	 	50	%
	 Year 2
	  	1.5	  	1.5	  	3.1	  	3.1	  	50	%	 	50	%
	 Year 3
	  	3.8	  	1.3	  	5.9	  	4.0	  	60	%	 	40	%
	 Year 4
	  	2.3	  	0.8	  	7.4	  	4.5	  	62	%	 	38	%
	 Year 5
	  	5.3	  	1.8	  	10.7	  	5.6	  	66	%	 	34	%
	 Target Date
	  	21.0	  	7.0	  	22.5	  	9.5	  	70	%	 	30	%
	 Year 7
	  	2.7	  	0.3	  	23.9	  	9.7	  	71	%	 	29	%
	 Set Date
	  	22.5	  	7.5	  	34.4	  	13.2	  	72	%	 	28	%

  
 If the Percentage
Contribution changes between the Target Date and the Set Date, as shown above, the share of worldwide earnings will likewise change and will be based on the Percentage Contribution calculated at the end of the prior year or estimated Percentage
Contribution from the prior quarter if materially different. The following illustrates this concept: [Note: Costs included in determining the Percentage Contribution on UBC Products are not to be included as an Allowable Expense in the calculation
of UBC Operating Profit as defined in Appendix I and vice versa. 
  

													
	 	  	(Target Date)
Launch in
Europe

	 	 	(Year T+1)
Launch in
Canada

	 	 	(Set Date)
Launch
in U.S.

	 	 	 (S + 1)All
Years
 Thereafter

	 
	 Worldwide Earnings (a)
	  	 	 	 	 	 	 	 	 	 	 	 
	 Cumulative NPV Contribution %
	  	5	 	 	8	 	 	20	 	 	25	 
	 - DuPont Merck
	  	66	%	 	70	%	 	71	%	 	72	%
	 - Mitotix
	  	34	%	 	30	%	 	29	%	 	29	%
	 Share of Worldwide Earnings
	  	 	 	 	 	 	 	 	 	 	 	 
	 - DuPont Merck
	  	3.3	 	 	5.6	 	 	14.2	 	 	18	 
	 - Mitotix
	  	1.7	 	 	2.4	 	 	5.8	 	 	7	 

  

	(a)	Excludes all Research, Development and Pre-launch Marketing Costs included in determining the Percentage Contribution. 

  

 Appendix H - Page 2 

 UBC RESEARCH, DEVELOPMENT 
 AND PRE-LAUNCH MARKETING COSTS: 
  
 For purposes of calculating the Percentage Contribution, UBC Research, Development and Pre-Launch Marketing Costs shall be compiled annually on a worldwide basis from the Effective Date up through the Set Date. After
the Set Date, all UBC Research, Development and Pre-Launch Marketing Costs will be included as Allowable Expenses (defined in Appendix J) in the determination of UBC Operating Profit. Costs included in determining the Percentage Contribution are not
to be included as an Allowable Expense in the calculation of UBC Operating Profit as defined in Appendix I and vice versa. 
  
 The definitions of expenses listed below are representative of today’s conditions and business experience. These conditions may change over time as a
result of structural changes in the respective companies, the pharmaceutical industry, or the UBC Collaboration. The parties agree to negotiate in good faith all necessary modifications to these definitions to reflect the actual experience of the
parties at that time. Modifications to any cost standard will be set at the lowest cost for each activity that is or could be provided by either party, if the level and quality of service between the two parties is comparable. If the level of
service is not comparable between the two parties, the cost standard for that service will reflect the cost of each party providing the service, as determined by the Collaborative Policy Setting Committee. 
  
 UBC Research, Development and Pre-Launch Marketing Costs shall include the following:

  
 Discovery Costs: Discovery costs will be billed at a rate of
S225,000(a) per full-time-equivalent (FTE) scientist working within the UBC field, plus all related extramural
(out-of-pocket) expenses including payments to third parties for contract research and outside consultants. 
  
 Development Costs: Upon nomination into development, Development Costs will include the direct costs as tracked by each party’s project accounting
system. These direct costs will include, but are not limited to, salaries, benefits, lab supplies, travel expenses, plus all related extramural (out-of-pocket) expenses including payments to third parties for contract research and outside
consultants, clinical grant costs, bulk drug, contract manufacturing costs, clinical supplies and FDA user fees. In addition, an appropriate share of facilities costs, Information Resources, R&D administration and cash (or cash equivalent)
incentive compensation performance bonus costs will also be allocated based on a reasonable allocation methodology agreed to by both parties. 
  

 Appendix H - Page 3 

 Post Registration Studies: Includes the cost of the Post Registration Studies 1) required by the FDA or
other regulatory agencies as part of the NDA approval, 2) required to broaden the approved indications or 3) to improve the approved labeling. The direct costs for this support will be as tracked by each party’s internal systems. These direct
costs will include, but are not limited to, salaries, benefits, lab supplies, travel expenses, plus all related extramural (out-of-pocket) expenses including payments to third parties for contract research and outside consultants, clinical grant
costs, bulk drug, contract manufacturing costs, clinical supplies and FDA user fees. In addition, an appropriate share of facilities costs, Information Resources, R&D administration and cash (or cash equivalent) incentive compensation
performance bonus costs will also be allocated. The total cost applied for Mitotix will include the cost of personnel who spend part of their time working with DuPont Merck on UBC Products. The cost of such personnel will be determined by taking
their FTE cost ($ 125,000)(a) times the percentage of their time spent on UBC Products. 
  
 Pre-Launch Expenses: Pre-Launch expenses include, but are not limited to,
all direct and indirect marketing costs incurred up through the date of launch including grant money, payments to advertising agencies, preliminary launch materials to FDA, symposia and opinion leader development activities, and use of DuPont Merck
Clinical Liasons. The cost for these activities will be as compiled by DuPont Merck internal systems. The cost of each Clinical Liason will be determined by taking their FTE cost ($125,000)(a) times the percentage of their time spent on UBC Products. In addition, the cost of two marketing personnel of Mitotix who spend part of their time on the
Collaborative Marketing Committee (as defined in Section 4.4 of Appendix G2) will be included by taking their FTE cost ($125,000)(a) times the percentage of their time spent on UBC Products plus travel expenses. 
  
 Other Expenses: All other expenses of a similar nature to the extent agreed by the parties. 

	(a)	The annual FTE cost is to be adjusted annually for inflation using the average CPI for each succeeding year beginning with 1996. 

  

 Appendix H - Page 4 

 APPENDIX I 
  
 DEFINITION OF UBC OPERATING PROFIT 
  
 The definitions of sales and expenses embodied within are representative of today’s conditions and business experience. These conditions may change
over time as a result of structural changes in the respective companies, the pharmaceutical industry, or the UBC Collaboration. The parties agree to negotiate in good faith all necessary modifications to these definitions to reflect the actual
experience of the parties at that time. Modifications to any cost standard will be set at the lowest cost for each activity that is or could be provided by either party, if the level and quality of service between the two parties is comparable. If
the level of service is not comparable between the two parties, the cost standard for that service will reflect the cost of each party providing the service, as determined by the Collaborative Policy Setting Committee. 
  
 UBC Operating Profit: UBC Operating Profits shall mean the profits or losses resulting from
the commercialization of all UBC Products worldwide and shall be equal to (i) worldwide Net Sales of all UBC Products less worldwide Allowable Expenses (defined below) incurred by Mitotix and DuPont Merck plus (ii) all revenues received from Third
parties as consideration for sublicensing of the manufacture, distribution, use and sale of UBC Products. UBC Operating Profits will be shared based on each party’s Percentage Contribution as defined in Appendix H. The following table
illustrates how UBC Operating Profits are calculated and how each party’s share of the UBC Operating Profits (assumed here to be split 70% / 30%) are realized via an earnings true-up payment. 
  
 CALCULATION OF EARNINGS SPLIT FOR UBC PRODUCTS 
  

													
	 	  	DuPont/
Merck

	 	 	Mitotix

	 	 	UBC Worldwide
Earnings

	 
	 Net Sales
	  	100	 	 	 	 	 	100	 
	 Allowable Expenses
	  	(40	)	 	(10	)	 	(50)	 
	 UBC Operating Profits
	  	60	 	 	(10	)	 	50	 
	 Earnings True-Up
	  	(25	)	 	25	 	 	 	 	 	 	 
	 UBC Operating Profits
	  	35	 	 	15	 	 	35	 	 	15	 
	 	  	 	 	 	 	 	 	70
DMPC	%
%	 	30
Mitotix	%
%

  

 Appendix I - Page 1 

 Allowable Expenses: Allowable Expenses shall include on a country-by-country basis only those expenses incurred
subsequent to commercial sale in that country (excluding Post Registration Studies unless after the Set Date). Expenses incurred prior to commercial sale in each country shall be classified as UBC Research, Development and Pre-Launch Marketing Costs
and shall be included in the calculation of Percentage Contribution. All expenses incurred after the Set Date are classified as Allowable Expenses. The following table and Exhibit 1 show how different expenses are classified at different times
relative to the launch and Set Date. 
  
 Classification of Expenses

  

							
	 	  	 Prior
 To
 Launch

	 	 After
 Launch /
 Prior to
 Set Date

	 	 After
 Set Date

				
	 R&D and Pre-Launch
	  	R&D (a)	 	R&D (a)	 	Allowable
Expense (b)
				
	 Post Registration
	  	R&D (a)	 	R&D (a)	 	Allowable
Expense (b)
				
	 Operating Expenses (c)
	  	N/A	 	Allowable
Expense (b)	 	Allowable
Expense (b)

  

	(a)	Used in the calculation of Percentage Contribution 

  

	(b)	Used in the calculation of UBC Operating Profit 

  

	(c)	Includes Manufacturing, Selling, Marketing, Distribution, Admin etc. 

  
 Prior to the Set Date, Allowable Expenses shall include (i) Manufacturing Cost of Goods, (ii) Third party Royalties, (iii)
Finished Product Distribution Expense, (iv) Field Selling Expense, (v) Direct Promotion Expense, (vi) Marketing Overhead, (vii) Regulatory Support, (viii) Medical Affairs, (ix) Administration and Other Support Services, and (x) Working Capital
Charge. Subsequent to the Set Date, Allowable Expenses shall include all of the above plus (i) Discovery Costs (ii) Development Costs, (iii) Post Registration Studies, and (iv) Pre-Launch Expenses. [Note: Costs included in Allowable Expenses are not
to be included in the Percentage Contribution as defined in Appendix H. 
  

 Appendix I - Page 2 

 The individual components of Allowable Expenses are defined as follows: 
  
 Manufacturing Cost of Goods: Manufacturing Cost of Goods shall include the
sum of variable standard manufacturing costs plus manufacturing cost variances plus an allocated share of fixed manufacturing expenses including other support functions necessary to support the technology incurred by the party performing the work.
It is the intent that to the extent possible, the amount of the allocated share of fixed and other manufacturing expense will be determined in the same manner as DuPont Merck normally employs in allocating such cost to all its production. The
methodology shall give recognition to such factors as the use of direct labor, throughput, number of batches and other relevant measures of consumption of resources. A final definition of Manufacturing Cost of Goods should be agreed to by both
parties when production of commercial quantities in a manufacturing facility is commencing. 
  
 Third party Royalties: Third party Royalties shall mean royalties or other fees or costs payable to a Third party in connection with UBC Products. 
  
 Finished Product Distribution Expense: Finished Product Distribution Expense (FPDE) includes all distribution expenses
including transportation, customs duties, insurance, fees paid to warehouses, packaging and labeling expenses. The cost of FPDE will be set at 2% of Net Sales unless actual expenditures are found to be materially lower or in excess of this amount
due to special handling etc. 
  
 Field Selling Expense: Field
Selling Expense will be calculated by multiplying the number of details times the Selling Cost Per Physician Detail in a calendar year. 
  
 Selling Cost Per Physician Detail: The Selling Cost Per Physician Detail for DuPont Merck and Mitotix details will be set at a fair market value, and will
be in the range defined by other co-promotion agreements DuPont Merck will have entered into in the five years prior. 
  
 Direct Promotion Expense: Includes all product specific promotion expenses incurred in the promotion of UBC Products including, but not limited to,
journal or direct to consumer advertising, agency fees, samples, speaker programs and other costs incurred in the promoting and marketing of UBC Products. 
  
 Marketing Overhead: Marketing Overhead shall include all costs incurred by the highest ranking member of DuPont Merck’s marketing management and his
organization’s related support for UBC Products including marketing administration, clinical development and education, FDA user fees, sales information, health economics studies, samples, marketing research, customer service, telemarketing,
bad debt expense and patent and trademark maintenance. The total cost for DuPont Merck will be applied at 6% of Net Sales, unless actual expenditures are found to be materially lower or in excess of this amount. The total cost applied for Mitotix
will include the cost of two marketing personnel who spend part of their time on the Joint 

  

 Appendix I - Page 3 

 
Marketing Team. The cost of the marketing personnel will be determined by taking their FTE cost ($125,000)(a) times the percentage of their time spent on UBC Products plus travel expenses. 
  
 Regulatory Support: Regulatory Support for DuPont Merck includes all the external and internal support necessary to maintain
the worldwide product registration for UBC Products including stability testing, preparation of annual reports, answering regulatory agency questions, preparing expert reports as required by regulatory agencies, and will involve other groups in
development as needed. The direct costs for this support will be as tracked by DuPont Merck’s project accounting system. These direct costs will include, but are not limited to, salaries, benefits, travel expenses, plus all related extramural
(out-of-pocket) expenses including payments to outside consultants, and FDA and other regulatory agency user fees. In addition, an appropriate share of facilities costs, Information Resources, R&D administration and cash (or cash equivalent)
incentive compensation performance bonus costs will also be allocated. The total cost applied for Mitotix will include the cost of Regulatory personnel who spend part of their time working with DuPont Merck on UBC Products plus travel expenses. The
cost of each Regulatory personnel will be determined by taking their FTE cost ($125,000)(a) times the percentage of
their time spent on UBC Products. 
  
 Medical Affairs: Medical
Affairs includes support necessary for adverse experience documentation and reporting, response to health professional and consumer inquiries about the product including the preparation and maintenance of the product database, administration of
Phaes IV study grants and supplies (with the exception of Post-Registration Studies as defined in Appendix I), the monitoring and review of medical literature concerning the product(s), evaluation of the need for labeling changes, coordination with
Marketing to manage promotional material review, and medical review and oversight of each of these activities. The cost for this support will be based on effort expended for UBC Products as tracked by DuPont Merck’s internal systems and will
include, but not limited to salaries, benefits, travel expenses, plus all related extramural (out-of-pocket) expenses including payments to third parties for contract research and outside consultants. In addition, an appropriate share of facilities
costs, Information Resources, R&D administration and cash (or cash equivalent) incentive compensation performance bonus costs will also be allocated. 
  
 No costs will be incurred by Mitotix since DuPont Merck will have sole responsibility for oversight for this service. 

	(a)	The annual FTE cost is to be adjusted annually for inflation using the average CPI
for each succeeding year beginning with 1996. 

  

 Appendix I - Page 4 

 Administration and Other Support Services: Includes all DuPont Merck support services such as Finance,
Legal, Information Resources, Human Resources, Public and Government Affairs. The total cost for these services will be applied at 5% of Net Sales. All claims, damages, liabilities, costs and expenses with respect to suits, claims or other legal
proceedings resulting from, arising out of or in connection with this agreement will be in addition to the 5% of Net Sales, unless actual expenditures are found to be materially lower or in excess of this amount. Administration and Other Support
Service costs provided by Mitotix will include the FTE cost of Legal and Human Resource personnel ($125,000 per FTE)(a) times the percentage of their time spent on UBC Products. 
  
 Working Capital Charge: Reflects DuPont Merck’s financing cost of working capital and will be calculated at a rate of 10% times the average annual Accounts Receivable and Inventory balance less related payables
(estimated at 25% of receivables and inventory). 

	(a)	The annual FTE cost is to be adjusted annually for inflation using the average CPI for each succeeding year beginning with 1996. 

  

 Appendix I - Page 5 

 EXHIBIT 1 - to Appendix I 
  
 ILLUSTRATION 
 EXPENSES USED IN DETERMINING THE PERCENTAGE CONTRIBUTION 
 VERSUS EXPENSES USED IN DETERMINING UBC OPERATING PROFIT 
  

			
	R&D and Pre-launch Expenses:	 	-     Expenses qualified for inclusion in determining the Percentage Contribution.
		
	Allowable Expense:	 	-     Expenses qualified for inclusion in determining worldwide earnings.

			
		
	Target Date:	 	Date when the first UBC Product will be launched in the first Strategic Country. The intention is that the target 70% : 30% Percentage Contribution will have been achieved by this
date
		
	Set Date:	 	Date when first UBC Product has been launched in all Strategic Countries. On the Set Date, the Cumulative NPV Percentage Contribution is fixed.

  
 

 
  

 Appendix I - Page 6 

 APPENDIX J 
  
 The following examples illustrate the mechanics of the milestone payments as applied to Royalty-Bearing Products. 
  
 Example A: Product 1 is followed into clinical trials by back-up Product 2 after Product 1
has been approved. Product 1 attains all milestones and is paid in accordance with column 1 for First Royalty-Bearing Product. Product 2 attains all milestones, but no milestones are paid as it is not a Unique Product. 
  
 Example B: Product 1 has attained the first three milestones when clinical development is
halted. Product 2 begins clinical development after the clinical failure of Product 1. Product 1 is paid the first three milestones from column 1. The first milestone for which Product 2 is eligible is milestone 4, which will be paid in accordance
with column 1. Assuming Product 3 is also not a Unique Product, Product 3 would only be paid a milestone on any milestone events not previously paid for Products 1 & 2. If Product 2 were to achieve milestones 4&5 before Product 3 achieved
these same milestone events, then no milestones would be paid for Product 3. 
  
 Example C: Product 1 is and Product 2 is not a Unique Product. Each achieves only the first two milestones. Product 1 being the first product receives milestone payments from column 1 for the first two milestone events. No milestones are
paid for Product 2. Product 3 is a Unique Product and is approved. As a Unique Product, Product 3 receives all of the milestone payments from column 2, and in lieu of milestone payments 3,4 & 5 from column 2, it receives milestone payments from
column 1 since it is the first product to achieve the latter milestones. 
  
 Example D: Product 1 has attained the first two milestone events when clinical development is halted. Product 2 which is one year behind is a Unique Product and likewise only achieves the first two milestone events. Since Product 1 is the
first product to achieve the first two milestone events, it is paid milestones from column 1. Since Product 2 is a Unique Product, milestones are also paid for the first two milestone events, however, these milestone payments are from column 2.
Product 3 (a back-up to Product 2) is not a Unique Product but achieves milestone events 3,4 &5. Since Product 3 is not a Unique Product, milestones are only paid on the milestone events not yet achieved by Product 2. Since no other CDK Product
has yet to achieve these same milestone events, the milestone payments for milestones 3,4 & 5 will be paid from column 1. Had a previous CDK Product achieved these same milestones, all milestone payments for Product 3 would have been from column
2. 
  

 Appendix J–Page 1 

 Example AAmendment to Amended and Restated Agreement, dated April 3, 2000

 Exhibit 10.6 
  
 Confidential treatment has been requested for portions of this Exhibit. The copy filed herewith omits the information subject to the confidentiality request. Omissions
are designated as ***. A complete version of this Exhibit has been filed separately with the Securities and Exchange Commission. 
  
 EXECUTION COPY 
  
 AMENDMENT NO. 1 TO 
 AMENDED AND RESTATED COLLABORATIVE 
 RESEARCH, DEVELOPMENT AND MARKETING AGREEMENT 
 BETWEEN MITOTIX, INC. AND 
 DUPONT PHARMACEUTICALS 
 COMPANY 
  
 This Amendment No. 1, effective April 3, 2000 (the “Effective Date”) is made to the Collaborative Research, Development and Marketing Agreement dated as of December 6, 1995, as amended and restated as of June 2, 1997 (the
“Agreement”) between Mitotix, Inc., a Delaware corporation having its principal place of business at One Kendall Square, Building 600, Cambridge, Massachusetts 02139 (“Mitotix”) and DuPont Pharmaceuticals Company, a Delaware
general partnership having its principal place of business at 974 Centre Road, Wilmington, Delaware 19807 (“DPC”). 
  
 WHEREAS, Mitotix and DPC desire to amend the Agreement to modify the rights granted under the Agreement and to make certain other changes as provided
herein; 
  
 NOW, THEREFORE, in consideration of the mutual
covenants set forth in this Amendment No. 1, the receipt and sufficiency of which is hereby acknowledged, the parties agree as follows: 
  
 1. Definitions. The terms in this Amendment with initial letters capitalized, whether used in the singular or the plural, shall have the meaning set forth in the
Agreement, or the meaning set forth below or, if not listed below, the meaning designated in places throughout this Agreement. 
  
 1.1 “Akt/Chk1/Plk Research Program” means the research program to be performed by Mitotix with respect to the Akt/Chkl/Plk Targets and
Akt/Chkl/Plk Screening Technology in accordance with the Akt/Chkl/Plk Work Plan which is attached hereto as Appendix A. 
  
 1.2 “Akt/Chkl/Plk Screening Technology” shall have the meaning set forth in Article 7 hereof. 
  
 1.3 “Akt/Chkl/Plk Targets” means collectively and individually the
Akt, Chkl and Plk Targets. Akt Target means the Akt protein and the biological processes of phosphorylation mediated by Akt, including but not limited to the phosphorylation of BAD, GSK3, PFK2, GLUT4, caspase 9 and telomerase. Chkl Target means the
Chkl protein and the biological processes of phosphorylation mediated by Chkl, including but not limited to the phosphorylation of Cdc25C. Plk Target means the Plk protein and the biological processes of phosphorylation mediated by Plk. Akt, Chkl
and Plk Targets shall include the human Akt, Chkl and Plk Target and any subtypes and isoforms thereof, as well as any homologs thereof from any other species. 
  

1.4 “DPC CDK Compound” shall have the meaning set forth in Section 4.1 hereof. 
  
 1.5 “DPC Inventions” means DuPont Merck Inventions. 
  

 1 

 1.6 “E6AP UBC Targets” shall mean the E6-AP ubiquitin protein ligase and ubiquitination
mediated by the E6-AP ligase. E6AP UBC Targets shall include but not be limited to the human E6-AP ligase and human E6-AP ligase mediated ubiquitination of p53, HHR23A, and members of the SRC family, and any subtypes and isoforms thereof, as well as
any homologs thereof from any other species. 
  
 1.7
“IkB/E6AP UBC Screening Technology” shall have the meaning set forth in Section 2.7 hereof. 
  
 1.8 “IkB UBC Targets” shall mean the LcB ubiquitin protein ligase and ubiquitination mediated by the DcB ligase. IkB UBC Targets shall include
the human IkB ligase and human IkB ligase mediated ubiquitination of IkB%, and any subtypes and isoforms thereof, as well as any homologs thereof from any other species. 
  
 1.9 “License Revenue” shall have the meaning set forth in Section 4.4(c) hereof. 
  
 1.10 “mdm2/p53 Research Program” means the research program to be
performed by Mitotix with respect to the mdm2/p53 UBC Targets and mdm2/p53 Screening Technology in accordance with the mdm2/p53 Work Plan which is attached hereto as Appendix B. 
  
 1.11 “mdm2/p53 UBC Screening Technology” shall have the meaning set forth in Section 2.6 hereof. 
  
 1.12 “mdm2/p53 UBC Targets” shall mean the mdm2 dependent
ubiquitination of p53, including the ubiquitin protein ligase that mediates the ubiquitination of p53. mdm2/p53 UBC Targets shall include the human mdm2 (hdm2) and p53 and any subtypes and isoforms thereof, as well as any homologs thereof from any
other species. 
  
 1.13 “Mitotix CDK Compound” shall
have the meaning set forth in Section 4.1 hereof. 
  
 1.14
“Mitotix CDK Products” shall have the meaning set forth in Section 4.2 hereof. 
  
 1.15 “Mitotix Library” shall mean compounds which have been synthesized, licensed or acquired by Mitotix prior to or during the UBC Research Program or CDK Research Program from external sources
independently of any information provided by DPC. 
  
 1.16
“Outside Inventions” shall have the meaning set forth in Article 5 hereof. 
  
 1.17 “Outside Know-How” shall have the meaning set forth in Article 5 hereof. 
  
 1.18 “Outside Targets” shall have the meaning set forth in Article 5 hereof. 
  
 1.19 “Protein Therapy” shall have the meaning set forth in Section 3.3 hereof. 
  
 2. UBC Collaboration. 
  
 2.1 Termination of UBC Collaboration. As of the Effective Date of this Amendment, except to the extent
expressly provided in this Amendment, the UBC Collaboration and UBC 
  

 2 

 Research Program shall be terminated. Accordingly, the Collaborative Policy Setting Committee shall no
longer operate. DPC shall no longer have any obligation to report information to Mitotix under Sections 7.2 and 7.3 of the Agreement. The parties acknowledge that DPC has not exercised its option to extend the term of the UBC Collaboration pursuant
to Section 5.2.2 of the Agreement. In addition, the parties hereby agree that the terms of Sections 5.5 and 5.6 of the Agreement shall not apply as of the Effective Date of this Amendment. 
  
 2.2 Section 2.2 is intentionally left blank. 
  
 2.3 Co-Exclusive License to DPC for UBC Screening Technology.
Except as set forth in Sections 2.6 and 2.7 hereof, and notwithstanding any provision of the Agreement to the contrary including, without limitation, Section 10.2.1 of the Agreement, Mitotix hereby grants DPC a co-exclusive (with Mitotix)
worldwide royalty-free, fully paid-up right and license (with the right to sublicense) under the UBC Patent Rights, Mitotix Inventions, Joint Inventions and Know-how solely to utilize the UBC Targets and assays (including reagents and materials used
in such assays) to identify compounds active against such UBC Targets for the purposes of research, development and commercialization of pharmaceutical and Radiopharmaceutical products incorporating such compounds for all therapeutic indications. No
license is granted to DPC under this Section 2.4 to utilize the UBC Targets for Antisense, Gene Therapy and non-Radiopharmaceutical diagnostic applications. 
  
 2.4 Co-Exclusive License to Mitotix for UBC Screenins Technology. Except as set forth in Sections 2.6 and 2.7 hereof, and notwithstanding
any provision of the Agreement to the contrary including, without limitation, Section 10.4.2 of the Agreement, DPC hereby grants to Mitotix a co-exclusive (with DPC) worldwide royalty-free, fully paid-up right and license (with the right to
sublicense) under any DPC Inventions and Joint Inventions and Know-how solely to utilize the UBC Targets and assays (including reagents and materials used in such assays) to identify compounds active against such UBC Targets for purposes of
research, development and commercialization of pharmaceutical, Radiopharmaceutical, Antisense, Gene Therapy and non-Radiopharmaceutical diagnostic products incorporating such compounds for all therapeutic indications. 
  
 2.5 Rights and Obligations With Respect to Compounds. Except
with respect to Mitotix Library compounds (as set forth in the following paragraph and Sections 2.6 and 2.7 hereof), DPC shall have exclusive rights, and Mitotix hereby grants to DPC exclusive worldwide rights, with right to sublicense, under the
UBC Patent Rights, Mitotix Inventions, Joint-Inventions and Know-how, with respect to any compounds (and any information relating to such compounds) which have been conceived, described, identified, synthesized or tested in the performance of the
UBC Collaboration and UBC Research Program. Mitotix shall not disclose any non-public information relating to such compounds to any Third Party or use such non-public information for any purpose or for its own benefit or for the benefit of any Third
Party, unless otherwise agreed by DPC. 
  
 Subject to Sections 2.6
and 2.7 hereof, each party shall have co-exclusive rights with respect to any compounds from a Mitotix Library (and any information relating to such compounds) which have been identified, synthesized or tested in the performance of the UBC
Collaboration and UBC Research Program; provided, however that DPC’s rights under this 

  

 3 

 
Section 2.5 shall be solely for uses in screening against a UBC Target licensed under Section 2.3 and solely to make, use and sell any product that
incorporates such compound where such product is active against a UBC Target licensed under Section 2.3 and for no other purpose. 
  
 Mitotix shall have the right to independently develop compounds (and any information relating to such compounds) which are identified using the rights
granted under Section 2.4, provided however, that such right shall be subject to the first sentence of this Section 2.5 and no patent or know-how rights of any kind are granted by DPC to Mitotix with respect to any such compounds. 

 
 2.6 Exclusive License to DPC for mdm2/p53 UBC Screening
Technology. Notwithstanding any provision of the Agreement to the contrary including, without limitation, Section 10.2 of the Agreement, Mitotix hereby grants to DPC an exclusive worldwide right and license (with the right to sublicense)
under UBC Patent Rights specifically claiming mdm2/p53 UBC Targets, and Mitotix Inventions, Joint Inventions and Know-how specifically directed to mdm2/p53 UBC Targets including, without limitation, all research results and data developed by either
party in the performance of the mdm2/p53 UBC Research Program funded by DPC at Mitotix (collectively the “mdm2/p53 UBC Screening Technology”) to utilize the mdm2/p53 UBC Targets and assays (including reagents and materials used in such
assays) to identify compounds active against such mdm2/p53 UBC Targets for purposes of research, development and commercialization of pharmaceutical and Radiopharmaceutical products incorporating such compounds for all therapeutic indications. No
license is granted to DPC under this Section 2.6 to utilize the mdm2/p53 UBC Targets for Antisense, Gene Therapy and non-Radiopharmaceutical diagnostic applications. 
  
 In addition, notwithstanding any provision of the Agreement to the contrary, Mitotix hereby grants to DPC an exclusive
worldwide right and license (with the right to sublicense) to any compounds from a Mitotix Library (and any information relating to such compounds) which (i) were identified as active using the mdm2/p53 UBC Screening Technology and (ii) have been
conceived, described, identified, synthesized or tested in the performance of the UBC Research Program and mdm2/p53 UBC Research Program; provided, however that DPC’s rights under this Section 2.6 shall be solely for uses in screening
against a mdm2/p53 UBC Target and solely to make, use and sell any product that incorporates such compound where such product is active against a mdm2/p53 UBC Target and for no other purpose. 
  
 DPC shall have sole responsibility for conducting, at its own expense, all
clinical, regulatory, marketing, and sales work associated with compounds identified as active using the mdm2/p53 UBC Screening Technology under this Section 2.6. For each such compound, DPC shall use good faith commercially reasonable efforts to
evaluate, develop and test such compound in accordance with industry standards and DPC internal practices and to seek and obtain all necessary regulatory approvals to market and commence worldwide marketing of each product incorporating each such
compound. 
  
 With respect to each compound identified as active
using the mdm2/p53 UBC Screening Technology under this Section 2.6 which is subject to Section 2.8(b), DPC shall inform Mitotix in writing upon the commencement of clinical testing for each such compound and, every six (6) months thereafter, DPC
shall inform Mitotix in writing as to whether DPC is continuing or 

  

 4 

 
discontinuing the development of such compound. DPC shall also inform Mitotix if DPC decides to abandon the development of such a compound at any time. DPC
shall also inform Mitotix upon the filing of an IND for the first such compound, and notwithstanding Section 15.3 of the Agreement, the parties agree that Mitotix may publicly disclose such achievement in a public disclosure that is mutually agreed
upon in writing by the parties. 
  
 2.7 Exclusive License to
Mitotix for IkB/E6AP UBC Screening Technology. Notwithstanding any provision of the Agreement to the contrary including, without limitation Section 10.4 of the Agreement, DPC hereby grants to Mitotix an exclusive worldwide right and license
(with the right to sublicense) under any DPC inventions and Joint Inventions and Know-how including, without limitation, all research results and data developed by Mitotix and DPC in the performance of the IkB/E6AP research programs funded by DPC at
Mitotix (collectively the “IkB/E6AP UBC Screening Technology”) to utilize the IkB UBC Targets and the E6AP UBC Targets and assays (including reagents and materials used in such assays) to identify compounds active against such IkB UBC
Targets and E6AP UBC Targets for purposes of research, development and commercialization of pharmaceutical, Radiopharmaceutical, Antisense, Gene Therapy and non-Radiopharmaceutical diagnostic products incorporating such compounds for all therapeutic
indications. 
  
 In addition, notwithstanding any provision of the
Agreement to the contrary, Mitotix retains exclusive worldwide rights to any compounds from a Mitotix Library (and any information relating to such compounds) which (i) were identified as active using the IkB/E6AP UBC Screening Technology and (ii)
have been conceived, described, identified, synthesized or tested in the performance of the UBC Research Program and IkB/E6AP UBC Research Program. 
  
 Mitotix shall have sole responsibility for conducting, at its own expense, all clinical, regulatory, marketing, and sales work associated with compounds
identified as active using the IkB/E6AP UBC Screening Technology under this Section 2.7. For each such compound, Mitotix shall use good faith commercially reasonable efforts to evaluate, develop and test such compound in accordance with industry
standards and Mitotix internal practices and to seek and obtain all necessary regulatory approvals to market and commence worldwide marketing of each product incorporating each such compound. 
  
 With respect to each compound identified as active using the IkB/E6AP UBC
Screening Technology under this Section 2.7 which is subject to Section 2.8(d), Mitotix shall inform DPC in writing upon the commencement of clinical testing for each such compound and, every six (6) months thereafter, Mitotix shall inform DPC in
writing as to whether Mitotix is continuing or discontinuing the development of such compound. Mitotix shall also inform DPC if Mitotix decides to abandon the development of such a compound at any time. Mitotix shall also inform DPC upon the filing
of an IND for the first such compound, and notwithstanding Section 15.3 of the Agreement, the parties agree that DPC may publicly disclose such achievement in a public disclosure that is mutually agreed upon in writing by the parties. 
  
 2.8 UBC Products. Notwithstanding any provision of the
Agreement to the contrary, the parties agree as follows. 
  
 (a) Products made, used or sold by DPC under Section 2.3 shall not be considered Royalty-Bearing Products and shall not be subject to the payment provisions of Article 11 of the Agreement. 
  

 5 

 (b) If any product is made, used or sold by DPC (or its licensee) under Section 2.6 that
incorporates a compound which is first identified within *** years following the Effective Date of this Amendment and is discovered or selected for development through use of the mdm2/p53 UBC Targets, then such product shall be considered a
Royalty-Bearing Product subject to the payment provisions of Article 11 of the Agreement, provided however, that (i) no milestone payments shall be payable with respect to such product and (ii) the royalty amount payable for such product
shall be equal to ***% of the amount otherwise payable as set forth in Article 11 of the Agreement. 
  
 (c) Products made, used or sold by Mitotix under Section 2.4 shall not be considered Mitotix Products and shall not be subject to the
payment provisions of Article 12 of the Agreement. 
  
 (d) If any product is made, used or sold by Mitotix (or its licensee) under Section 2.7 that incorporates a compound which is first identified within *** years following the Effective Date of this Amendment and is discovered or
selected for development through use of the IkB/E6AP UBC Targets, then such product shall be considered a Mitotix Product subject to the payment provisions of Article 12 of the Agreement, provided however, that (i) no milestone payments shall
be payable with respect to such product and (ii) the royalty amount payable for such product shall be equal to 25% of the amount otherwise payable as set forth in Article 12 of the Agreement. 
  
 (e) Mitotix shall not be obligated to provide DPC with a
right of first negotiation in accordance with Section 10.5.1 of the Agreement. 
  
 (f) Mitotix shall not have the option to co-promote any UBC Product. 
  
 3. CDK Collaboration. 
  
 3.1 Termination of CDK Collaboration. As of the Effective Date of this Amendment, the CDK Collaboration and CDK Research Program shall be
terminated. Accordingly, the Collaborative Policy Setting Committee shall no longer operate. DPC shall no longer have any obligation to report information to Mitotix under Sections 4.2 and 4.3 of the Agreement. Section 18.4 of the Agreement shall be
deleted and shall no longer be in effect. 
  
 With respect to any
compound in the CDK Field identified as active during the CDK Collaboration and term of the CDK Research Program, DPC shall have sole responsibility for conducting, at its own expense, all clinical, regulatory, marketing, and sales work associated
with such CDK Development Compound. For each such compound, DPC shall use good faith commercially reasonable efforts to evaluate, develop and test such compound in accordance with industry standards and DPC internal practices and to seek and obtain
all necessary regulatory approvals to market and commence worldwide marketing of each product incorporating each such compound. 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 6 

 With respect to each compound in the CDK Field identified as active during the CDK Collaboration and term
of the CDK Research Program, DPC shall inform Mitotix in writing upon the commencement of clinical testing for each such compound and, every six (6) months thereafter, DPC shall inform Mitotix in writing as to whether DPC is continuing or
discontinuing the development of such compound. DPC shall also inform Mitotix if DPC decides to abandon the development of such a compound at any time. DPC shall also inform Mitotix upon the achievement of milestones under Section 11.1.2 of the
Agreement, and notwithstanding Section 15.3 of the Agreement, the parties agree that Mitotix may publicly disclose the filing of an IND for the first such compound in a public disclosure that is mutually agreed upon in writing by the parties.

  
 3.2 CDK-non-D Field. The parties hereby agree
that the term “CDK-non-D Field” in Section 1.17 of the Agreement is modified to include all indications of therapeutic and Radiopharmaceutical agents. 
  

3.3 Co-Exclusive License to DPC for CDK Screening Technology. Notwithstanding any provision of the Agreement to the contrary including,
without limitation Section 10.1.1 of the Agreement, Mitotix hereby grants DPC a co-exclusive (with Mitotix) worldwide right and license (with the right to sublicense) under the CDK Patent Rights, Mitotix Inventions, Joint Inventions and Know-how to
utilize the CDK Targets and assays (including reagents and materials used in such assays) to identify compounds active against such CDK Targets for purposes of research, development and commercialization of pharmaceutical and Radiopharmaceutical
products incorporating such compounds for all therapeutic indications. No license is granted to DPC under this Section 3.3 to utilize CDK Targets for Antisense, Gene Therapy, non-Radiopharmaceutical diagnostic and p16 and p27 Protein Therapy
applications. 
  
 For the purposes of this Amendment, the term
“Protein Therapy” shall mean a product involving the intracellular or extracellular delivery of an exogenous polypeptide of at least 20 amino acids in length in order to treat or prevent disease. The parties agree that the Protein Therapy
applications of p16 and p27 shall be treated throughout the Agreement in the exact same manner as Gene Therapy and Antisense applications. 
  
 3.4 Co-Exclusive License to Mitotix for CDK Screening Technology. Notwithstanding any provision of the Agreement to the contrary including,
without limitation, Section 10.1.5 of the Agreement, each CDK Target under the Agreement shall be deemed to be released as of the earlier of (i) the date such CDK Target was released by DPC under Section 10.1.5 of the Agreement or (ii) the Effective
Date of this Amendment, and such released CDK Targets shall continue to be included in the definition of CDK Targets subject to the license grant set forth in Section 3.3 hereof. DPC hereby grants Mitotix a co-exclusive (with DPC) worldwide right
and license (with the right to sublicense to a Third Party collaborator of Mitotix) under any DPC Invention and Joint Invention and Know-how solely to utilize the CDK Targets and assays (including reagents and materials used in such assays) to
identify compounds active against such CDK Targets for purposes of research, development and commercialization of pharmaceutical, Radiopharmaceutical, Antisense, Gene Therapy, non-Radiopharmaceutical diagnostic and p16 and p27 Protein Therapy
products incorporating such compounds for all therapeutic indications. 
  

 7 

 3.5 Rights With Respect to Compounds. Notwithstanding the foregoing, except with respect to
Mitotix Library compounds (as set forth in the following paragraph) and as set forth in Sections 4.1 and 4.2 of this Amendment, DPC shall have exclusive rights, and Mitotix hereby grants to DPC exclusive worldwide rights, with right to sublicense,
under the CDK Patent Rights, Mitotix Inventions, Joint-Inventions and Know-how, with respect to any compounds (and any information relating to such compounds) which have been conceived, described, identified, synthesized or tested in the performance
of the CDK Collaboration and CDK Research Program. Mitotix shall not disclose any non-public information relating to such compounds to any Third Party or use such non-public information for any purpose or for its own benefit or for the benefit of
any Third Party, unless otherwise agreed by DPC. 
  
 With respect
to compounds in a Mitotix Library, Mitotix hereby grants to DPC an exclusive worldwide right and license (with the right to sublicense) to any compounds from a Mitotix Library which have been identified, synthesized or tested in the performance of
the CDK Collaboration and CDK Research Program; provided, however that DPC’s rights under this Section 3.5 shall be solely for uses in screening against a CDK Target licensed under Section 3.3 and solely to make, use and sell any product
that incorporates such compound where such product is active against a CDK Target licensed under Section 3.3 and for no other purpose. 
  
 3.6 CDK Products. Notwithstanding any provision of the Agreement to the contrary, the parties agree that: 
  
 (a) CDK Products and Immunoassay Products made, used or sold
by DPC under Section 3.3 hereof shall be considered Royalty-Bearing Products subject to the payment provisions of Article 11 of the Agreement, provided however, that Royalty-Bearing Products shall not include any CDK Product or Immunoassay
Product, respectively, incorporating compounds that are first identified through the use of the CDK Targets by either party more than *** years following the termination of the CDK Research Program; 
  
 (b) If any product is ultimately sold by Mitotix or its
licensee under Section 3.4 that incorporates a compound (other than a Mitotix CDK Compound) first identified within *** years following the release of the CDK Target by DPC and discovered or selected for development through the use of such
CDK Target, then such product shall be a Mitotix Product and Mitotix shall make payments as set forth in Article 12 of the Agreement upon the sale of such Mitotix Product; 
  
 (c) Article 8 of the Agreement is hereby amended such that DPC shall not be obligated to provide Mitotix the
option to co-promote each CDK Product incorporating compounds identified as active during the term of the CDK Research Program in the United States; and 
  
 (d) Mitotix shall not be obligated to provide DPC with a right of first negotiation with respect to CDK Targets under Section 10.5.1 of
the Agreement or CDK-non-D Targets under Section 10.5.2 of the Agreement. 
  
 3.7 Enforcement of CDK Patent Rights. Notwithstanding any provision of the Agreement to the contrary including, without limitation, Section 14.5 of the Agreement, the 

  

 8 

 
parties shall mutually agree upon the patent enforcement/licensing strategy with respect to the CDK Patent Rights in the CDK Field. The parties acknowledge
that under such strategy DPC shall be permitted to license the CDK Patent Rights in the CDK Field to any Third Party (other than Development Partners of DPC) which is infringing or alleged to be infringing the CDK Patent Rights (a “Third Party
Infringer”) and DPC shall be solely responsible at its discretion for the granting of any such license and for implementing such patent enforcement/licensing strategy. DPC shall not take any action with respect to the patent enforcement and/or
licensing of the CDK Patent Rights to a Third Party Infringer except pursuant to such patent enforcement/licensing strategy. All compensation from the sublicensing by DPC pursuant to such strategy under the CDK Patent Rights to a Third Party
Infringer shall be shared by the parties as follows: *** percent (***%) to DPC and *** percent (***%) to Mitotix. Subject to the patent enforcement/licensing strategy, DPC shall have the right at its sole discretion to grant sublicenses under the
CDK Patent Rights in exchange for a license to a research tool or other rights from the sublicensee (as a cross-license) rather than for cash revenue, provided that Mitotix shall have the right, in its discretion to (i) receive a license to such
research tool or other rights from such sublicensee on the same terms as DPC or (ii) receive *** percent (***%) of the equivalent fair cash value of such research tool to be agreed upon by the parties in good faith. 
  
 4. License to CDK Compounds. 
  
 4.1 Selection of CDK Compounds. The parties acknowledge that
certain CDK inhibitor compounds have been identified, synthesized or tested by DPC and/or Mitotix during the Collaboration and that the set of such compounds (as mutually agreed by DPC and Mitotix) shall be allocated to DPC and Mitotix according to
the following selection process. The details of the selection process shall be as mutually agreed by the parties. DPC shall retain rights to a specified group of compounds, comprised of compounds which are anticipated to be nominated as development
candidates and closely related chemical analogs, not to exceed a total of twelve compounds (each a “DPC CDK Compound”) and Mitotix shall select a specified group of compounds not to exceed twelve compounds from the remaining compounds in
the set (each a “Mitotix CDK Compound”). In order for Mitotix to make reasonably informed selections of compounds in the foregoing process, Mitotix shall have the right to review all information related to the set of CDK compounds
(including, without limitation, patent applications, biological data, chemical structure and synthesis information), subject to the confidentiality obligations of Article 15 of the Agreement and DPC shall make available to Mitotix reasonable
assistance to enable Mitotix to interpret such information. The parties agree to complete the selection process no later than by July 31, 2000. 
  
 DPC shall have exclusive rights to independently develop the DPC CDK Compounds. Mitotix shall have exclusive rights to independently develop the Mitotix
CDK Compounds. Notwithstanding any provision of the Agreement to the contrary, the DPC CDK Compounds are hereby deemed to be CDK Development Compounds. CDK Development Compounds shall include any compounds selected by DPC through use of the CDK
Targets licensed under Section 3.3, for clinical development in the CDK Field. 
  
 4.2 Exclusive License to Mitotix CDK Compounds. Notwithstanding any provision of the Agreement to the contrary, DPC hereby grants to Mitotix an exclusive, worldwide right and license (with the right to
sublicense) under any intellectual property rights of DPC related to 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 9 

 Mitotix CDK Compounds (including, without limitation, all patents, inventions, know-how and other information) to use the
Mitotix CDK Compounds for all pharmaceutical uses and to develop, make, have made, use and sell products incorporating such Mitotix CDK Compounds for all pharmaceutical uses (“Mitotix CDK Products”). In addition, notwithstanding any
provision of the Agreement or this Amendment to the contrary, DPC hereby grants to Mitotix a non-exclusive royalty-free, fully paid-up worldwide right and license (with the right to sublicense solely to a Mitotix licensee of a Mitotix CDK Product or
a Mitotix Product, as applicable) under any DPC patent rights covering any method of treatment or method of use of a Mitotix CDK Compound or Mitotix Product which would otherwise be infringed by the manufacture, use or sale of the Mitotix CDK
Product or Mitotix Product, solely to permit Mitotix (or its licensee) to manufacture, use or sell such Mitotix CDK Product or Mitotix Product. 
  
 With respect to each Mitotix CDK Compound, Mitotix shall have sole responsibility for conducting, at its own expense, all clinical, regulatory, marketing,
and sales work associated with such compounds. For each such Mitotix CDK Compound, Mitotix shall use good faith commercially reasonable efforts to evaluate, develop and test such compound in accordance with industry standards and Mitotix internal
practices and to seek and obtain all necessary regulatory approvals to market and commence worldwide marketing of each Mitotix CDK Product. The provisions of Article 13 of the Agreement shall apply to Mitotix CDK Products in the same way as
applicable to Mitotix Products. 
  
 With respect to each Mitotix
CDK Compound, Mitotix shall inform DPC in writing upon the commencement of clinical testing for each such compound and, every six (6) months thereafter, Mitotix shall inform DPC in writing as to whether Mitotix is continuing or discontinuing the
development of such compound. Mitotix shall also inform DPC if Mitotix decides to abandon the development of such a compound at any time. Mitotix shall also inform DPC upon the achievement of the milestones set forth in Section 4.4(a) hereof, and
notwithstanding Section 15.3 of the Agreement, the parties agree that DPC may publicly disclose the filing of an IND for the first such compound in a public disclosure that is mutually agreed upon in writing by the parties. 
  
 4.3 Non-exclusive License to DPC of Mitotix Riehts Related to DPC CDK
Compounds. Notwithstanding any provision of the Agreement or this Amendment to the contrary, to the extent a product incorporating a DPC CDK Compound or other CDK Development Compound which is made, used or sold by DPC (or its Affiliate or
licensees) would infringe a Mitotix patent right covering any method of treatment or method of use of a DPC CDK Compound or other CDK Development Compound, Mitotix hereby grants DPC a non-exclusive royalty-free, fully paid-up worldwide right and
license (with the right to sublicense solely to a DPC licensee of a CDK Development Compound) under any such Mitotix patent right, solely to permit DPC (or its licensee) to manufacture, use or sell such CDK Development Compound. 
  
 4.4 Payments to DPC for Mitotix CDK Products. 
  
 (a) Milestones. In consideration of the license
granted to Mitotix under Section 4.2 hereof, Mitotix shall pay the amounts set forth below to DPC upon the first 

  

 10 

 
achievement of each of the following milestones with respect to the first Mitotix CDK Product by Mitotix or its Affiliates: 
  

					
	 Milestone

	  	Payment

	 
	 IND Filing in U.S.
	  	$	*	**
	 Initiation of pivotal Phase III clinical trial
	  	$	*	**
	 Approval of first NDA in U.S.
	  	$	*	**
	 First Commercial Sale in U.S.
	  	$	*	**
	 First Commercial Sale in each of the United Kingdom, France, Germany, Spain, Canada, Japan
	  	$	*	**

  
 For
each subsequent achievement of a milestone by a Mitotix CDK Product containing a different active ingredient, Mitotix shall pay to DPC milestone payments equal to 25% of the amount set forth, provided however, that the IND filing milestone
payment for each subsequent Mitotix CDK Product shall be deferred and shall only be payable at such time that U.S. Phase II clinical trials are commenced for such subsequent Mitotix CDK Product. 
  
 (b) Royalties. In consideration of the license
granted to Mitotix under Section 4.2 hereof, Mitotix shall pay to DPC annual royalties for each Calendar Year on Net Sales by Mitotix and its Affiliates of each Mitotix CDK Product. Such royalty shall be payable based upon the annual Net Sales in a
Calendar Year of each individual Mitotix CDK Product at the rates and in the amounts set forth below: 
  
 (1) *** percent (***%) of aggregate Net Sales of the Mitotix CDK Product, for annual Net Sales of such Mitotix CDK Product of up to four
hundred million dollars ($400,000,000); 
  
 (2) *** percent (***%) of the aggregate Net Sales of the Mitotix CDK Product, for annual Net Sales of such Mitotix CDK Product of between four hundred million dollars ($400,000,000) and seven hundred million dollars
($700,000,000); 
  
 (3) *** percent (***%)
of the aggregate Net Sales of the Mitotix CDK Product, for annual Net Sales of such Mitotix CDK Product above seven hundred million dollars ($700,000,000). 
  
 Notwithstanding the above, (A) if (x) a royalty is owed under this Section 4.4 with respect to sales of a Mitotix CDK Product in any
country in which the Mitotix CDK Product is not covered by a Valid Patent Claim owned by Mitotix or exclusively licensed to Mitotix and (y) a Competitive Product is sold in such country, then the royalty payable pursuant to this Section 4.4 based on
sales of the Mitotix CDK Product in such country shall be *** percent (***%); and (B) if a Third Party Competitive Product is sold in such country, then the royalty rates set forth above shall be reduced by *** percent (***%), but in no event shall
such royalty rates fall below *** percent (***%). 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 11 

 Royalties on each Mitotix CDK Product at the rate set forth above shall be payable on a
country-by-country basis during the Royalty Term subject to the following conditions: 
  
 (i) only one royalty shall be due with respect to the same unit of Mitotix CDK Product; 
  
 (ii) no royalties shall be due upon the sale or other
transfer among Mitotix and its Affiliates, but in such cases the royalty shall be due and calculated upon Mitotix’s or its Affiliate’s Net Sales of Mitotix CDK Product to a Third Party; 
  
 (iii) no royalties shall accrue on the disposition of
Mitotix CDK Product in reasonable quantities by Mitotix or its Affiliates as bona fide samples or as donations to non-profit institutions or government agencies for non-commercial purposes; and 
  
 (iv) notwithstanding the above royalty rates, upon Mitotix
request, the parties agree to discuss in good faith a reduction of such royalty rate in any given country in the event the level of development, patent protection or general commercial environment affects the commercial viability of the Mitotix CDK
Product under such royalty rate. 
  
 If Mitotix,
in its reasonable judgment, is required to obtain a license from any Third Party under any patent having claims covering the active pharmaceutical ingredient of the Mitotix CDK Product for any pharmaceutical use, and to pay a royalty under such
license, and the infringement of such patent cannot reasonably be avoided by Mitotix without such a license, Mitotix’s obligation to pay royalties for such Mitotix CDK Products under Section 4.4 hereof shall be reduced by the amount of the
royalty payable by Mitotix under such additional license; provided, however that the royalties otherwise payable under Section 4.4 hereof shall not be reduced in any such event by more than ***. If Mitotix is required by a court of competent
jurisdiction to pay a royalty to any Third Party under any patent having claims covering the active pharmaceutical ingredient of the Mitotix CDK Product for any pharmaceutical use, Mitotix’s obligation to pay royalties for such Mitotix CDK
Product under Section 4.4 hereof shall be reduced by the amount of the royalty payable by Mitotix to such Third Party, provided, however, that the royalties otherwise payable under Section 4.4 hereof shall not be reduced in any such event by
more than ***. 
  
 (c) License Revenue. As
used herein, the term “License Revenue” shall mean the aggregate of the following payments received by Mitotix from a sublicensee of a Mitotix CDK Compound: (i) up-front cash or license fees; (ii) proceeds received by Mitotix from the sale
of securities of Mitotix at greater than fair market value that is in lieu of, or in addition to, up-front cash or license fees; (iii) milestones paid to Mitotix; (iv) royalty revenue received based on net sales of Mitotix CDK Product by the
sublicensee; (v) other consideration received for which the equivalent fair cash value of such consideration can reasonably be determined by the parties, including but not limited to, rights in products or compounds; and (vi) FTE funding above

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 12 

 $*** per FTE per year (such $*** amount being adjusted annually on January 1 by the annual change in the
Consumer Price Index for all urban consumers (CPI-U) for the Northeast)]. 
  
 The term “License Revenue” shall not include (a) committed payments to Mitotix in support of research and/or development activities performed by or on behalf of Mitotix which are less than $*** per FTE per
year (such $*** amount being adjusted annually on January 1 by the annual change in the Consumer Price Index for all urban consumers (CPI-U)] for the Northeast); (b) reimbursement of actual, documented, out-of-pocket research and/or development
expenses paid to Mitotix for research and/or development expenses incurred by or on behalf of Mitotix; (c) [proceeds received by Mitotix from the sale of securities of Mitotix at fair market value]; and (d) [payment to Mitotix that relate to an
extension of credit or a loan], provided however in the event that any credit or loan is extended to Mitotix and forgiven by the sublicensee, then the amount forgiven shall be included in License Revenue. [For purposes of determining fair market
value of securities under this Section 4.4(c), the following rules shall apply: (1) if Mitotix at the time of such issuance does not have a class of securities registered under the Securities Exchange Act of 1934, as amended (“Exchange
Act”), fair market value shall mean the price per share of similar securities sold in the most recently completed bona fide financing in which at least $2,000,000 was received by Mitotix in the aggregate, and (2) if Mitotix at the time of such
issuance has a class of securities registered under the Exchange Act, then (A) if the securities so issued are of the same class as securities of Mitotix then traded on a national securities exchange, in over-the-counter trading or other similar
trading system, then fair market value shall be the average trading price over the 20-day period preceding the date of issuance, and (B) if the securities are not of the same class as securities of Mitotix then so publicly traded (as described
above), then the fair market value shall be the amount determined in good faith by an independent certified public accounting firm of nationally recognized standing selected by Mitotix, taking into account advice from the Board of Directors of
Mitotix. 
  
 In consideration of the license granted to Mitotix
under Section 4.2 hereof, in the event a Mitotix CDK Compound is sublicensed by Mitotix, Mitotix shall pay to DPC the following percentage of the total aggregate License Revenue paid to Mitotix by the sublicensee, such percentage share based on the
development stage at which Mitotix executes a sublicense agreement with a sublicensee: 
  

			
	 Development Stage When Mitotix Executes Sublicense

	  	Percentage of License
Revenue to DPC

	 Prior to initiation of multiple dose Phase Ib/II clinical trial
	  	***%
		
	 After initiation of multiple dose Phase Ib/II clinical trial, but prior to initiation of first pivotal Phase III clinical
trial
	  	***%
		
	 After initiation of first pivotal Phase III clinical trial, but prior to the filing of NDA in U.S. and total investment by Mitotix (on fully
loaded basis) of at least $10 million
	  	***%
		
	 After filing NDA in U.S. and total investment by Mitotix (on fully loaded basis) of at least $20 million
	  	***%

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 13 

 provided, however that in no event will the percentage share of the aggregate License Revenue
payable to DPC exceed the aggregate value of the milestones and royalty payments set forth in this Section 4.4(a) and (b) above which would have been payable to DPC if Mitotix had itself developed and sold the Mitotix CDK Product. The aggregate
value of the milestones and royalty payments which would have been payable to DPC if Mitotix had itself developed and sold the Mitotix CDK Product shall be determined based upon the projected Net Sales by the sublicensee (or its licensee, affiliate
or agent) of the applicable Mitotix CDK Product as determined by an independent Third Party mutually agreed upon in good faith by the Parties. In the event that use of projected Net Sales in determining the percentage share of License Revenue to be
paid to DPC results in a payment to DPC that is less than the percentage share set forth above and the actual Net Sales exceed the projected Net Sales of the applicable Mitotix CDK Product as determined by the independent Third Party, then at such
time as the actual Net Sales exceed the projected Net Sales, Mitotix shall make additional payments to DPC on a quarterly basis until the percentage share of License Revenue that is paid to DPC equals the amount that would have been paid to DPC if
actual Net Sales had been used. Payments shall be made to DPC by Mitotix on a quarterly basis based on the License Revenue received by Mitotix in the preceding quarter. 
  
 5. Technology Outside Both the UBC Field and the CDK Field. 
  
 For the purposes of this Amendment, the following terms shall have the following meanings: 
  
 “Outside Inventions” shall mean all writings, inventions,
discoveries, improvement and other technology, whether or not patentable or copyrightable, and any patent applications, patent or copyrights based thereon that were made or conceived during and as a result of the research funded by DPC at Mitotix
outside both the UBC Field and the CDK Field during the term of the CDK Research Program; 
  
 “Outside Know-how” shall mean all confidential technical information in the possession of Mitotix or DPC during the term of the Agreement relating to Outside Targets or relating to the discovery,
development, manufacture, marketing and sale of products discovered through the use of the Outside Targets outside both the UBC Field and the CDK Field; and, 
  
 “Outside Targets” shall mean Targets discovered in the performance of the research funded by DPC at Mitotix during the term of the CDK Research
Program which are not UBC Targets or CDK Targets. 
  
 Except as
set forth in Sections 6 and 7 below, and notwithstanding any provision of the Agreement to the contrary, each party hereby grants the other party a co-exclusive (with the granting party) royalty-free, fully paid-up, worldwide right and license (with
the right to sublicense) under the granting party’s intellectual property rights claiming Outside Inventions and Outside Know-how solely to utilize the Outside Targets and assays (including reagents and materials used in such assays) to
identify compounds active against such Outside Targets for purposes of research, develop and commercialization of products incorporating such compounds for all therapeutic indications. 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 14 

 6. Compounds Outside Both the UBC Field and the CDK Field. Except as set forth in Sections 4 and 7 hereof, and
notwithstanding any provision of the Agreement to the contrary, Mitotix hereby grants DPC an exclusive, royalty-free, fully paid-up, worldwide right and license (with the right to sublicense) under the Outside Inventions and Outside know-how to any
compounds which (i) are identified as active using the Outside Targets and (ii) have been conceived, described, identified, synthesized or tested in the performance of research funded by DPC at Mitotix during the term of the CDK Research Program.
With respect to compounds in a Mitotix Library, Mitotix hereby grants to DPC an exclusive worldwide right and license (with the right to sublicense) to any compounds from a Mitotix Library which have been identified, synthesized or tested in the
performance of the research funded by DPC at Mitotix outside both the UBC Field and the CDK Field during the term of the CDK Research Program; provided, however that DPC’s rights under this Section 6 shall be solely for uses in screening
against an Outside Target and solely to make, use and sell any product that incorporates such compound where such product is active against an Outside Target and for no other purpose. 
  
 7. New Kinase Targets and Compounds. Notwithstanding any provision of the Agreement to
the contrary, Mitotix hereby grants DPC an exclusive, royalty-free, fully paid-up worldwide right and license (with the right to sublicense) under any intellectual property rights specifically claiming Akt/Chk1/Plk Targets, and Mitotix Inventions,
Joint Inventions and Know-how specifically directed to Akt/Chk1/Plk Targets (including, without limitation, all research results, data and materials developed by either party in the performance of the Akt/Chk1/Plk Research Program funded by DPC at
Mitotix) (collectively the “Akt/Chk1/Plk Screening Technology”) to utilize the Akt/Chk1/Plk Targets and assays (including reagents and materials used in such assays) to identify compounds active against such Akt/Chk1/Plk Targets for
purposes of research, development and commercialization of pharmaceutical and Radiopharmaceutical products incorporating such compounds for all therapeutic indications. 
  
 In addition, Mitotix hereby grants DPC an exclusive, royalty-free, fully paid-up worldwide right and license (with the right
to sublicense) to any compounds which (i) are identified as active using the Akt/Chk1/Plk Screening Technology and (ii) have been conceived, described, identified, synthesized or tested in the performance of research funded by DPC at Mitotix during
the CDK Research Program and Akt/Chk1/Plk Research Program. With respect to compounds in a Mitotix Library, Mitotix hereby grants to DPC an exclusive worldwide right and license (with the right to sublicense) to any compounds from a Mitotix Library
which have been identified, synthesized or tested in the performance of the CDK Collaboration and CDK Research Program; provided, however that DPC’s rights under this Section 7 shall be solely for uses in screening against an
Akt/Chk1/Plk Target and solely to make, use and sell any product that incorporates such compound where such product is active against an Akt/Chk1/Plk Target and for no other purpose. 
  
 8. Equity Investment 
  
 8.1 Issuance of Common Stock to DPC. Notwithstanding any provision of the Agreement to the contrary, DPC hereby subscribes for, and Mitotix
hereby issues to DPC, *** shares of Common Stock of Mitotix, $.001 par value (the “Shares”), as partial consideration for certain rights and licenses granted to Mitotix pursuant to this Amendment. Mitotix shall deliver to DPC a certificate
representing such Shares within 10 days following the 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 15 

 Effective Date of this Amendment registered in the name of DPC and dated as of the Effective Date of this Amendment. In
the event that the transactions contemplated by the Amended and Restated Agreement and Plan of Merger dated as of February 24, 2000 by and among GPC AG - Genome Pharmaceuticals Corporation, Genome Acquisition Corporation and Mitotix, Inc. are
consummated, then DPC shall be entitled to receive the same consideration received by all other holders of capital stock of Mitotix under such agreement. Accordingly, it is hereby represented and warranted that upon consummation of such transaction
the Shares shall be converted to shares of GPC Biotech AG (formerly GPC AG - Genome Pharmaceuticals Corporation) using the same conversion factor as applied to the Series C Convertible Preferred Stock of Mitotix currently held by DPC and such shares
of GPC Biotech AG shall be promptly issued to and delivered to DPC (i.e., the number of shares of GPC Biotech AG issued to DPC shall equal such conversion factor multiplied by ***). 
  
 8.2 Representation and Warranties by DPC Regarding Investment in the Shares. DPC hereby represents and
warrants to Mitotix that the following is true and correct as of the date hereof: 
  
 (a) Financial Matters. The financial condition of DPC is such that it is in a position to hold the Shares purchased by it for an
indefinite period of time and to bear the economic risk of an investment in the Shares, and DPC has the capability to evaluate the merits and risks of its investment in the Shares. DPC has extensive knowledge and experience in financial and
investment matters, including investment in securities that are non-listed, unregistered and are not traded on the Nasdaq National or SmallCap Market, nor on the National Association of Securities Dealers, Inc.’s (the “NASD”)
automated quotation system. 
  
 (b)
Brokers. DPC has no contract, arrangement or understanding with any broker, finder or similar agent with respect to the investment in the Shares. 
  
 (c) Access to Information. DPC and its representatives have been granted access to information concerning Mitotix sufficient to
make an investment decision with respect to the subscription for the Shares and has had the opportunity to question and to receive answers from executive officers of Mitotix concerning the terms and conditions of the Shares and the affairs of
Mitotix and has received any additional information which it has requested. 
  
 (d) Accredited Investor. DPC is an “accredited investor” as defined in Rule 501(a) of Regulation D promulgated by the U.S. Securities and Exchange Commission under the Securities Act of 1933 (the
“Act”). 
  
 (e) Investment
Intent. DPC understands that the Shares have not been registered under the Act by reason of a claimed exemption under the provisions of the Act which depends, in part, upon DPC’s investment intention. In this connection, DPC hereby
represents that it is subscribing for the Shares for its own account for investment and not with a view toward the resale or distribution to others. DPC understands that it may not sell or otherwise transfer the Shares unless they are registered
under the Act or unless an exemption from such registration is available, and that in the absence of an effective registration statement covering the Shares or an available exemption from registration under the Act, the Shares must be held
indefinitely. 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 16 

 (f) Restrictive Legend. DPC consents to the placement of a legend on any
certificate or other document evidencing the Shares that such Shares have not been registered under the Act or any state securities or “blue sky” laws and setting forth or referring to the restrictions on transferability and sale thereof.

  
 (g) Authorization; Enforceability. DPC
has all corporate right, power and authority to enter into this Amendment and to consummate the transactions contemplated hereby. All corporate action on the part of DPC and its directors and necessary for the authorization, execution, delivery and
performance of this Amendment by DPC has been taken. This Agreement has been duly executed and delivered by the DPC and constitutes a legal, valid and binding obligation of DPC, enforceable against DPC in accordance with its terms, subject to laws
of general application relating to bankruptcy, insolvency and the relief of debtors and rules of law governing specific performance, injunctive relief or other equitable remedies, and to limitations of public policy. 
  
 8.3 Representations and Warranties by Mitotix Regarding Issuance of the
Shares. Mitotix hereby represents and warrants to DPC that the following is true and correct as of the date hereof: 
  
 (a) Organization, Good Standing and Qualification. Mitotix is a corporation duly organized, validly existing and in good standing
under the laws of the State of Delaware and has full corporate power and lawful authority to conduct its business as presently conducted. Mitotix is duly qualified to do business as a foreign corporation and is in good standing in Massachusetts and
in each jurisdiction in which the nature of the business conducted by it, or the properties owned, leased or operated by it, makes such qualification necessary and where the failure to be so qualified would have a material adverse effect upon the
business, prospects and financial condition of Mitotix. 
  
 (b) Authorization; Enforceability. Mitotix has all corporate right, power and authority to enter into this Amendment and to consummate the transactions contemplated hereby. All corporate action on the part of
Mitotix and its directors and necessary for the authorization, execution, delivery and performance of this Amendment by Mitotix, and the authorization, sale, issuance and delivery of the Shares contemplated hereby has been taken. This Agreement has
been duly executed and delivered by Mitotix and constitutes a legal, valid and binding obligation of Mitotix, enforceable against Mitotix in accordance with its terms, subject to laws of general application relating to bankruptcy, insolvency and the
relief of debtors and rules of law governing specific performance, injunctive relief or other equitable remedies, and to limitations of public policy. Upon the issuance and delivery of the Shares as contemplated by this Agreement, such securities
will be duly and validly authorized and issued, fully paid and nonassessable. The issuance and sale of the Shares contemplated hereby will not give rise to any preemptive rights or rights of first refusal on behalf of any person. 
  
 9. FTE Research Funding. DPC shall continue to provide FTE funding to Mitotix
in accordance with Sections 3.2 and 5.4 of the Agreement; provided, however, that Mitotix shall be relieved of its obligation to provide the specified numbers of full-time equivalent scientists for the UBC Research Program and the CDK
Research Program pursuant to Section 3.2.1(a); and provided further, that Mitotix shall provide a sufficient number of full-time equivalent scientists 

  

 17 

 
as reasonably necessary to complete the Akt/Chk1/Plk Research Program and the mdm2/p53 Research Program. 
  
 10. Percentage of Sublicensee Royalty Revenue from Mitotix Products to DPC.
Notwithstanding any provision of the Agreement to the contrary including, without limitation, Section 12.2 of the Agreement, in the event of sales of Mitotix Products in Strategic Countries by sublicensees of Mitotix, Mitotix’s sole obligation
to DPC shall be to pay DPC *** percent (***%) of all royalties that Mitotix receives from such sublicensees; provided, however, that DPC shall not receive an amount hereunder which is less than *** (***%) of Net Sales of such Mitotix Products by
such sublicensees. 
  
 11. Effect of Termination. Notwithstanding Section
18.3 of the Agreement, the parties hereby agree that, in the event of expiration or termination of the Agreement, for any reason (i) all licenses granted to DPC hereunder will terminate, except that DPC shall retain the co-exclusive and exclusive
licenses pursuant to Sections 2.3, 2.5, 2.6, 3.3, 3.5, 6 and 7 hereof under the Mitotix Inventions, Joint Inventions and applicable Know-how solely to develop, make, have made, use and/or sell any CDK Product or UBC Product or Immunoassay Product
incorporating compounds that at the time of termination or expiration of the Agreement have been designated as a Development Compound, (ii) all licenses granted to Mitotix hereunder will terminate, except that Mitotix shall retain the co-exclusive
and exclusive licenses pursuant to Sections 2.4, 2.7, 3.4 and 4.2 under DPC Inventions, Joint Inventions and applicable Know-how solely to develop, make, have made, use and/or sell any CDK Product or UBC Product or Immunoassay Product or Mitotix CDK
Product incorporating compounds that at the time of termination or expiration of the Agreement have been designated as a Development Compound, (iii) the provisions of Articles 11 and 12 will survive termination of the Agreement such that DPC will
continue to have payment obligations to Mitotix with respect to Royalty-Bearing Products where applicable, and Mitotix will continue to have payment obligations to DPC with respect to Mitotix Products, where applicable; and (iv) the provisions of
Section 13.9 will survive termination of the Agreement such that DPC will continue to have milestone and royalty obligations to certain Mitotix licensors where applicable. 
  
 12. Headings. The headings of the Sections and Articles of this Amendment are inserted for reference only, and are not to be
considered as part of this Amendment in construing this Amendment. 
  
 13.
Effect of this Amendment. To the extent that any of the terms of this Amendment conflict with or modify any terms of the Agreement, the terms of this Amendment shall supercede and replace the terms of the Agreement. To the extent that any of
the terms of the Agreement conflict with any of the provisions of this Amendment, the terms of the Agreement shall be amended and/or construed by the parties in a way to be consistent with the provisions of this Amendment. To the extent that the
provisions of the Agreement do not conflict with the provisions of this Amendment, such provisions of the Agreement shall continue in full force and effect. 
  
 14. Public Announcements. The parties shall consult with each other and reach mutual written agreement before making any public announcement concerning this
Amendment or the Agreement or its subject matter. A joint press release to announce the signing of this 

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omitted portions. 

  

 18 

 Amendment shall be agreed to in writing and the parties agree to coordinate the dissemination of this press release.

  
 IN WITNESS WHEREOF, the parties have executed this Amendment
No. 1 as of the date first set forth above. 
  

			
	 MITOTIX, INC.

		
	By:	 	 /s/ William Helman

	 	 	 William Helman

	 Title:
	 	 Chairman

  

			
	 DUPONT PHARMACEUTICALS COMPANY

		
	By:	 	 /s/ Paul A. Friedman

	 	 	 Paul A. Friedman, M.D.

	 Title:
	 	 President, DuPont Pharmaceuticals Research Laboratories

  

 19 

 Appendix A: 
  
 *** Work Plan 
  
 Goals 
  
 1. Attempt to produce or purchase (where
possible) sufficient quantities of the three enzymes *** for enzyme characterization, assay development and HTS. 
  
 2. Test prospective substrates for the three enzymes with the goal of identifying a working substrate for assay development. 
  
 3. Where a working substrate has been identified, produce or purchase sufficient quantities
of the substrate for assay development and HTS. 
  
 4. Where a working substrate
has been identified, characterize each enzyme kinetically with the working substrate. 
  
 5. Once appropriate reagents for developing an assay have been obtained, perform proof-of-principle experiments to test the feasibility of developing an HTS-compatible assay for each kinase. 
  
 6. Where feasible, develop a high-throughput screen for each kinase. 
  
 7. Validate each kinase screen that is developed for HTS. 
  
 8. Screen the DuPont library in each kinase screen that passes validation. 
  
 9. For each kinase screen that undergoes HTS, deliver list of confirmed active compounds to
DuPont. 
  
 Activities 
  
 The assays will be developed using formats appropriate for HTS. The most likely assay formats
to be chosen will be the DELFIA format or FlashPlates format. The DELFIA format requires a phosphopeptide-specific antibody and is fluorescence-based. The FlashPlate format does not require specific antibodies and involves using 32P or 33P
radioisotopes. 
  
 Each assay that is developed will be validated on the screening
system to be used for HTS. The validation process will determine whether the screen is reliable enough to be used for HTS and will establish important screening parameters. 
  
 The high-throughput screens will be run in 384-well plates either on workstations or a fully robotic system. 
  
 Approximate durations expected for each of the key activities are as shown below: 

 
 Assay development: 8 weeks 
 Assay validation: 4 weeks 
 HTS: 8 weeks

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 20 

 Plan for each enzyme target: 
  
 *** 
  
 Mitotix has purchased the *** enzyme from a commercial source. A biotinylated peptide substrate of ***, known as “Crosstide” has been identified and tested. An antibody has been obtained from a commercial source that binds to
Crosstide once it has been phosphorylated by ***. An assay has been developed by the DELFIA format and will be validated and run on workstations. 
  
 *** 
  
 Mitotix has expressed and purified the *** enzyme. An assay has been developed in the FlashPlate format using a biotinylated peptide substrate that contains a sequence of ***. The latter peptide cannot be used in the assay because it is
part of technology restricted under a licensing agreement between Mitotix and ***. An alternative susbtrate for *** will be sought that can be used for assay development. Kinetic properties of the enzyme will be characterized using different
substrates. The most likely format for the *** screen will be the FlashPlate format. 
  
 *** 
 Mitotix
has virus encoding human ***. No known substrate exists for *** that can be used for assay development. The work will focus on optimizing the expression and kinase activity of ***. A purification scheme for *** will be developed. 

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omitted portions. 

  

 21 

 Appendix B: 
  
 *** Work Plan 
  
 Research work plan for the *** project 
  
 GOALS: 
  
 Assay and Screening: 
  

	 	•	Validate *** HTS. 

  

	 	•	Screen DuPont compound library and Mitotix compound library. 

  

	 	•	Delivery of a list of confirmed active compounds to DuPont 

  
 Biochemistry: 
  

	 	•	Continue characterization of *** dependent
ubiquitination of *** 

  
 Molecular Biology: 
  

	 	•	The cDNAs encoding two ring finger proteins, Siahl and A07, will be cloned. 

  

	 	•	Vectors for the production of Siahl and A07 in bacteria and insect cells will be constructed and protein expression will be evaluated. 

  
 ACTIVITIES: 
  
 Assay and Screening 
  
 Mitotix will perform the validation testing of the *** HTS. Following the successful completion of the validation phase, the HTS will be executed. The Mitotix compound
library will be screened in addition to the DuPont library. Confirmation testing of active compounds will follow. A list of active compounds identified and confirmed will be delivered to DuPont. 
  
 Biochemistry 
  
 The efforts at Mitotix will continue to focus on the characterization of the *** dependent ubiquitination of ***. The reaction mechanism of
*** driven ubiquitination will be explored with specific emphasis on evaluating the potential involvement of thiol
ester conjugates between *** and ubiquitin. Experiments carried out at Mitotix and DuPont have established that the ubiquitinated species of *** produced in the current assay do not result from polyubiquitination but rather from multiple mono-ubiquitinations. Thus, we will be focused on examining the reaction conditions and components in an
attempt to generate polyubiquitinated ***. These experiments will include the titration of reaction components as well as an examination of a role for the *** *** in the ubiquitination of ***. In addition, the recombinant*** and *** used in the standard reaction will be substituted with endogenous *** and *** purified from cellular extracts to test the possibility that the former may lack a modification or association with a cellular protein which is necessary for
the promotion of polyubiquitination. 

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 22 

 As described below, expression vectors for the production of two ring finger proteins and a putative substrate will be
constructed. The ability of these proteins to function in ubiquitination assays measuring either Siahl or A07 autoubiquitination or Siahl dependent ubiquitination of DCC will be explored. 
  
 Molecular Biology 
  
 *** belongs to a class of proteins which contain the structural motif know as the ring finger. The ring fingers of a number of proteins in this family have
recently been implicated in Ubc mediated autoubiquitination. The cDNAs encoding two of these proteins, Siahl and A07, will be cloned. Vectors for the production of Siahl and A07 in bacteria and insect cells will be constructed and protein expression
will be evaluated. Reports in the literature implicate Siahl in the ubiquitination of the DCC protein. A cDNA encoding the cytoplasmic domain of DCC will therefore be cloned. As above, expression vectors will be constructed and protein production
assessed. 

	***	Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has been requested with respect to the
omitted portions. 

  

 23

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