Document:

License Agreement

 Exhibit 10.10 
 Portions of this exhibit marked [*] are omitted and are requested to be treated confidentially. 
 LICENSE AGREEMENT 
 THIS AGREEMENT is effective as of the
     day of             , 2001 (the “Effective Date”) by and among Pharmaceutical Product Development, Inc., a North Carolina
corporation having a place of business at 3151 South Seventeenth Street, Wilmington, NC 28412 (hereinafter “PPD”) and its wholly owned subsidiary GenuPro, Inc., d/b/a PPD GenuPro, a North Carolina corporation having a place of business at
3900 Paramount Parkway, Morrisville, North Carolina 27560 (hereinafter “GenuPro”), and Alza Corporation, a Delaware corporation having a place of business at 1900 Charleston Road, Mountain View, CA 94043 (hereinafter “Licensee”).
PPD, GenuPro and Licensee are sometimes referred to herein individually as a “Party” and collectively as the “Parties.” 
 WITNESSETH THAT: 
 WHEREAS, GenuPro and PPD have performed research and development with
respect to dapoxetine pursuant to a Development and Commercialization Agreement between Eli Lilly and Company (“Lilly”), PPD and GenuPro dated May 22, 1998 (the “Lilly Agreement”); 
 WHEREAS, pursuant to the Lilly Agreement, both PPD and Lilly have forfeited the right to develop and commercialize dapoxetine in the Field and GenuPro has
obtained a license from Lilly to develop and commercialize dapoxetine in the Field under the Lilly Patents, Lilly Know-How and Lilly Manufacturing Know-How (as later defined herein); 
 WHEREAS, GenuPro and/or PPD are the owner(s) of the entire right, title and interest in the GenuPro Patents and GenuPro Know-How (as later defined herein); and 
 WHEREAS, GenuPro wishes to have rights under the Lilly Patents, Lilly Know-How, Lilly Manufacturing Know-How, GenuPro Patents and GenuPro Know-How further
developed and marketed at the earliest possible time; 
 WHEREAS, Licensee wishes to enter into an agreement to obtain exclusive licenses to the
Lilly Patents, Lilly Know-How, Lilly Manufacturing Know-How, GenuPro Patents and GenuPro Know-How in the Field from GenuPro in order to practice the invention claimed therein and to make, use and sell in the commercial market the therapeutic product
made in accordance therewith; and 
 WHEREAS, GenuPro and PPD are willing to grant such licenses to Licensee under the terms and conditions set
forth in this Agreement. 
 NOW, THEREFORE, PPD, GenuPro and Licensee hereby agree as follows: 
  

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 ARTICLE I - DEFINITIONS 
 1.01. “Adverse Event” means any adverse event associated with the use of a Compound, CTM Product or Licensed Product in humans, whether or
not considered drug-related, including the following: an adverse event occurring in the course of the use of a drug product in professional practice; an adverse event occurring from drug overdose whether accidental or intentional; an adverse event
occurring from drug abuse; and an adverse event occurring from drug withdrawal; and any failure of expected pharmacological action. 
 1.02.
“Affiliate” of a Party hereto shall mean any entity that controls, is controlled by or is under common control with such Party. For purposes of this definition, a Party shall be deemed to control another entity if it owns or controls,
directly or indirectly, at least fifty percent (50%) of the voting equity of another entity (or other comparable ownership interest for an entity other than a corporation) or if it has management control of the other entity. 
 1.03. “Combination Product” means any product in any dosage form that contains, in addition to a Licensed Product, one or more other active
ingredients having significant prophylactic or therapeutic activity. 
 1.04. “Compound” means the GenuPro Compound, a
Peripheral Compound or a SAR Compound. 
 1.05. “Confidential Information” means any and all information relating to Licensed
Products or their development, manufacture, use or sale (including Product-Related Improvements and Know-How) disclosed, directly or indirectly, by one Party to another Party, whether in writing or orally, (a) prior to the Effective Date
pursuant to the terms of the Confidential Disclosure Agreement in effect between the Parties dated June 5, 2000 (“CDA”), or (b) during the term of this Agreement. 
 1.06. “Controlled” means, with respect to any compound, material, information or intellectual property right, that the Party owns or has a license to such compound, material, information
or intellectual property right and has the ability to grant to the other Party access, a license or a sublicense (as applicable under this Agreement) to such compound, material, information or intellectual property right as provided for herein
without violating the terms of any agreement or other arrangements with any Third Party existing at the time such Party would be first required hereunder to grant the other Party such access, license or sublicense. 
 1.07. “CTM Product” means Compound together with any formulation ingredients in a finished pharmaceutical dosage form suitable for
administration and dosing to humans in clinical trials, but not in suitable form for commercial sale (for example, without limitation, not in packaged form such as blister packs or other containers and not including external packaging and package
inserts). 
 1.08. “Development Plan” means a development plan prepared by Licensee, its Affiliate or sublicensee, by
which Licensee intends to achieve regulatory agency registration of Licensed Product, including, but not be limited to, a description of the CMC, preclinical, clinical, and regulatory activities, with estimated timelines necessary to achieve such
approval in the Field in the Territory. 
  

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 1.09. “Diligent Efforts” means the carrying out by Licensee or its sublicensee of
obligations or tasks in a manner consistent with the efforts Licensee devotes to a product of similar market potential, profit potential or strategic value, based on the conditions then prevailing with respect to the product and the relevant market
and consistent with reasonable business practices in the industry.  
 1.10. “Enforceable Claim” means a claim included
in an issued and unexpired patent that has not been: (i) abandoned or disclaimed; or (ii) declared invalid or unenforceable by a decision of a court or other governmental agency of competent jurisdiction, which decision is unappealable or
unappealed within the time allowed for appeal. 
 1.11. “Field” means the treatment only in humans of the therapeutic
indications within the urogenital area including premature ejaculation, primary urinary incontinence, urge, stress and mixed incontinence, urinary urgency, interstitial cystitis, neurogenic bladder, bladder sphincter dyssynergia and irritative
symptoms of benign prostate hypertrophy (“BPH”), hypoactive sexual desire, hyperactive sexual desire, impotence, retarded ejaculation, delayed orgasm and anorgasmia; provided, however, that “Field” shall not include diseases of
the kidney. 
 1.12. “First Commercial Sale” means the first transaction following regulatory approval in which Licensee, its
Affiliate or sublicensee transfers physical possession and title to a Licensed Product to a Third Party in exchange for value and after which transfer the seller has no right or power to determine the Third Party’s resale price. Transfer for
research, development or testing purposes shall not constitute the First Commercial Sale. 
 1.13. “Generic Product” means,
with respect to a particular Licensed Product, a dapoxetine-containing product approved for the same indication as such Licensed Product (a) wherein such approval is based on an Abbreviated New Drug Application (“ANDA”) or an
equivalent of an ANDA or (b) wherein the dapoxetine in such product (in bulk or finished form) is made by Lilly or under license (directly or indirectly) from Lilly. 
 1.14. “GenuPro Compound” means: [*]. 
 1.15. “GenuPro Intellectual
Property” shall have the meaning set forth in Section 8.01(a). 
 1.16. “GenuPro Know-How” means any Know-How,
other than Lilly Know-How or Lilly Manufacturing Know-How, Controlled by GenuPro or PPD during the term of this Agreement. GenuPro Know-How includes, without limitation, all Know-How related to the composition of matter of Compounds, or their
manufacture or use. 
 1.17. “GenuPro Patents” means all Patents, other than Lilly Patents, that are Controlled by GenuPro or
PPD during the term of this Agreement and that claim Compounds or Licensed Products or the development, manufacture, intermediates made during the manufacture thereof, purification, use or formulation thereof. GenuPro Patents include without
limitation patents that claim GenuPro Intellectual Property. 
 1.18. “HSR Act” means Hart-Scott-Rodino Antitrust Improvement
Act. 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

  

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 1.19. “Joint Development Committee” or “JDC” means a committee composed as
set forth in Section 4.04 and having the duties set forth in Section 4.05. 
 1.20. “Key Country” means [*].

 1.21. “Know-How” means any unpatented or unpatentable inventions, information, data, drawings, plans, specifications and
designs relating to Compounds, CTM Products or Licensed Products including, in particular, any marketing information, pre-clinical, clinical, toxicology, analytical, regulatory, ADME information and/or data. 
 1.22. “Licensed Product” means a Patented Product or a Non-Patented Product. 
 1.23. “Lilly Know-How” means any Know-How, other than Lilly Manufacturing Know-How, which Lilly licensed to GenuPro under the Lilly Agreement. 
 1.24. “Lilly Manufacturing Know-How” means any Know-How that relates to the manufacture of Compound or Licensed Product, including
processes and analytical methods therefor, and that Lilly licensed to GenuPro under the Lilly Agreement. 
 1.25. “Lilly
Patents” means all Patents licensed by Lilly to GenuPro under the Lilly Agreement that claim a Compound or Licensed Product or method of making or using a Compound or Licensed Product, including without limitation the Patents listed on
Schedule 1.25. 
 1.26. “Marketing Plan” means an annual marketing plan prepared by Licensee, its Affiliate or sublicensee,
that includes, but is not limited to, a description of Licensee’s commercial objectives for the year with respect to Licensed Product in the Field in the Territory and strategy by which Licensee intends to achieve such objectives. 

1.27. “NDA” shall mean a New Drug Application filed with the United States Food and Drug Administration in conformance with applicable
laws and regulations. 
 1.28. “Net Sales” means the total amount billed or invoiced in United States dollars (or converted
thereto in accordance with the Agreement) on sales of the Licensed Product by Licensee, its Affiliates, sublicensees and/or Affiliates of sublicensees in the Territory to Third Parties, less the following deductions (i) trade, cash and quantity
discounts actually taken on such Licensed Product; (ii) taxes on sales (such as sales or use taxes) to the extent added to the sale price and set forth separately as such in the total amount invoiced; (iii) freight, insurance and other
transportation charges to the extent added to the sale price and set forth separately as such in the total amount invoiced; and (iv) reserves for amounts to be repaid or credited by reason of rejections, defects, recalls or returns or because
of retroactive price reductions, chargebacks, rebates or commissions, made in accordance with generally accepted accounting principles and Licensee’s accounting policies. Sales between Licensee and its Affiliates and sublicensees shall not be
treated as Net Sales hereunder. 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

  

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 1.29. “New Formulation or Use” shall have the meaning set forth in Section 5.08(c).

 1.30. “Non-Patented Product” means any product that: (a) is in suitable form for commercial sale, (b) contains or
comprises a Compound, and (c) the manufacture, use or sale of which would not, in the absence of the licenses granted herein, infringe an Enforceable Claim of any GenuPro Patent or Lilly Patent issued in the country in which such product
is sold. For clarity, a particular product may be a Patented Product when sold in one country and a Non-Patented Product when sold in another country. 
 1.31. “Patent” means (i) unexpired letters patent (including inventor’s certificates) which have not been held invalid or unenforceable by a court of competent jurisdiction from which no appeal can be taken or has
been taken within the required time period, including without limitation any substitution, extension, registration, confirmation, reissue, re-examination, renewal or any like filing thereof and (ii) pending applications for letters patent,
including without limitation any continuation, division or continuation-in-part thereof and any provisional applications. 
 1.32.
“Patented Product” means any product that: (a) is in suitable form for commercial sale, (b) contains or comprises a Compound, and (c) the manufacture, use or sale of which would, in the absence of the licenses granted
herein, infringe an Enforceable Claim of any GenuPro Patent or Lilly Patent issued in the country in which such product is sold. For clarity, a particular product may be a Patented Product when sold in one country and a Non-Patented Product when
sold in another country. 
 1.33. “Peripheral Compound” means any compound that is an isomer, homolog, analog or prodrug of the
GenuPro Compound and that is made, identified or characterized at any time by Licensee, PPD, GenuPro or Lilly (to the extent to which GenuPro or PPD has rights to such compounds made, identified or characterized by Lilly). The term
“isomers” includes compounds of identical elemental composition (empirical formulae) and specifically encompassing chain, geometrical, sterochemical, keto-enol, optical and position isomerism. The term “homologs” includes carbon
compounds, conforming to the same general formula and in which each member differs from another by a constant linear increment of the atomic groups –CH2- or –CH2-CH2-. The term “analogs” includes compounds which are structurally
closely related to the GenuPro Compound or a compound that is a bioisostere or a halogen, alcohol, ester, ether or acid substituted variant of the GenuPro Compound. 
 1.34. “Phase III Clinical Study” means a trial involving administration of a Compound to sufficient numbers of human patients with the goal of establishing that the Compound is safe and
efficacious for its intended use, to define warnings, precautions and adverse reactions that are associated with the drug or label expansion of such Compound, and to be considered as a pivotal study for submission of an NDA. 
 1.35. “Product-Related Improvement” means any invention, patentable or not, information or data which (a) is not the composition of
matter of a Compound, (b) relates to a Compound, and (c) is either (i) made, identified, conceived, reduced to practice or generated at any time solely or jointly by Licensee’s employees or agents in the course of performance of
the Project or further development of Licensed Product during the term of this Agreement or (ii) made, identified, conceived, reduced to practice or generated solely or jointly by Licensee’s, PPD’s or

  

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GenuPro’s employees or agents in the course of performance of the Project or further development of Licensed Product during the term of this Agreement. Product-Related Improvements include
but are not limited to New Formulations or Uses, dosage forms of Compounds or methods of synthesis or manufacturing. 
 1.36.
“Product-Related Improvement Patents” shall have the meaning set forth in Section 8.01(b). 
 1.37. “Project”
means a development and clinical trial program to be directed primarily by Licensee or its Affiliates or sublicensees, the aim of which is to achieve commercialization of a Licensed Product for indications in the Field in the Territory.

 1.38. “SAR Compound” means the Compound which results from any structure activity relationship studies which may be
conducted by Licensee or GenuPro as part of any other studies conducted pursuant to this Agreement. Performance of such studies shall be at Licensee’s sole discretion. SAR Compounds will relate to the GenuPro Compound or a Peripheral Compound.
 
 1.39. “Serious Adverse Event” means any Adverse Event occurring at any dose that results in any of the following
outcomes: death, a lifethreatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that
may not result in death, be life-threatening, or require hospitalization may be considered a Serious Adverse Event when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical
intervention to prevent one of the outcomes listed in this definition. 
 1.40. “Territory” shall mean all countries of the
world. 
 1.41. “Third Party” means any person or entity other than PPD, GenuPro or Licensee or an Affiliate of PPD, GenuPro or
Licensee. 
 ARTICLE II - LICENSES AND EXCLUSIVITY 
 2.01. Other Licensing Arrangement. The Parties to this Agreement acknowledge that the scope of rights granted to Licensee under the Lilly Patents, Lilly Know-How and Lilly Manufacturing
Know-How are limited by and can be no greater than the rights granted to GenuPro under the Lilly Agreement. 
 2.02. Sublicense to Lilly
Patents, Lilly Know-How and Lilly Manufacturing Know-How.  
 (a) Effective as of the Effective Date, GenuPro
hereby grants Licensee an exclusive, royalty bearing sublicense (with the right to further sublicense as provided in Section 2.04) under the Lilly Patents and Lilly Know-How to develop, use, offer for sale and sell Licensed Products in the
Territory solely in the Field. 
 (b) Effective as of the Effective Date, GenuPro hereby grants Licensee an exclusive,
royalty bearing sublicense (with the right to further sublicense as provided in Section 2.04) of GenuPro’s non-exclusive license under the Lilly Patents, Lilly Know-How and Lilly

  

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Manufacturing Know-How, to make, have made and import Licensed Products in the Territory solely in the Field. For the avoidance of doubt, GenuPro is sublicensing to Licensee under this
Section 2.02(b) all of GenuPro’s rights under Section 6.07 of the Lilly Agreement with respect to Licensed Products, which such rights are non-exclusive. 
 (c) The Parties acknowledge and agree that, provided Licensee does not promote or pursue regulatory approval for the use of Licensed Products outside the Field, the sale of Licensed Product to a
Third Party who uses it outside the Field shall not be a breach by Licensee of the Field restrictions in the sublicenses set forth in this Section 2.02. 
 2.03. License to GenuPro Intellectual Property. 
 (a)
Effective as of the Effective Date, GenuPro and PPD hereby grant Licensee an exclusive, royalty bearing license (with the right to sublicense as provided in Section 2.04) under the GenuPro Patents and GenuPro Know-How, to develop, make,
have made, use, sell, offer for sale, have sold and import Licensed Products in the Territory solely in the Field. 
 (b)
Effective at such time as GenuPro or PPD acquires rights to practice any GenuPro Patents or GenuPro Know-How outside the Field, GenuPro and PPD hereby grant Licensee an exclusive, royalty-bearing (pursuant to Section 5.03) license (with the
right to sublicense as provided in Section 2.04) under the GenuPro Patents and GenuPro Know-How, to develop, make, have made, use, sell, offer for sale, have sold and import Licensed Products in the Territory outside the Field. 
 2.04. Right to Sublicense. With respect to the sublicenses and licenses granted to Licensee in Sections 2.02 and 2.03 above, such sublicenses
and licenses shall include the right of Licensee to sublicense to any party, including without limitation an Affiliate, so long as such sublicense is consistent with the terms of this Agreement. Licensee shall be responsible for the performance by
its sublicensee(s) of all obligations imposed under the terms of this Agreement. 
 2.05. No Other Rights. Except as otherwise
expressly provided herein, this Agreement does not grant Licensee any license or other right under Lilly Patents, Lilly Know-How, Lilly Manufacturing Know-How, GenuPro Patents or GenuPro Know-How. 
 2.06. Exclusivity. During the term of this Agreement, PPD and GenuPro and their Affiliates will not conduct (itself or directly or indirectly
with a Third Party) any material development or commercialization activities (or grant any rights to Third Parties to do so) with respect to the Compounds or any product containing or comprising a Compound, other than under this Agreement.

 ARTICLE III - SUPPLIES OF LICENSED PRODUCT 
 3.01. Licensee Supply Requirements. Licensee shall at its own expense provide all quantities of Compound, CTM Product and Licensed Product that Licensee needs in order to develop,
commercialize and market Licensed Product in the Field in the Territory. 
 3.02. Transfer of Material. GenuPro shall in good
faith and at no charge to Licensee promptly following the Effective Date, but in any event within ten (10) days of the Effective

  

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Date if this Agreement, transfer to Licensee all GenuPro Compound and CTM Product in its possession as of the Effective Date of this Agreement. The amounts of each are listed on Schedule 3.02.
Such transfer of material shall be accompanied by applicable quality and regulatory information necessary to permit use of such materials in clinical testing. 
 3.03. Assistance in Third Party Contractor Identification. Upon request by Licensee, GenuPro shall take reasonable steps to assist Licensee to identify and qualify a Third Party contractor
for the supply of quantities of Compound or CTM Product to Licensee and direct services by such Third Party contractor. 
 ARTICLE IV - INITIATION AND CONDUCT OF PROJECT 
 4.01. General Principle. During the term of this
Agreement, as among Licensee, PPD and GenuPro, Licensee shall be responsible for development and marketing of Compounds in such countries of the Territory as it deems appropriate, consistent with its obligations under this Agreement. Licensee will
use Diligent Efforts to submit applications for regulatory approval to market a Licensed Product in the [*] and [*]. Licensee will select in its sole discretion, prior to NDA submission, at least [*] Key Countries in which
Licensee shall use Diligent Efforts to submit applications for regulatory approval to market a Licensed Product, wherein [*] of such countries are [*]. Licensee shall have responsibility for obtaining all necessary regulatory approvals
to do so, and Licensee, or its subcontractors, shall hold legal title of any Investigational New Drug Application (“IND”) and NDA filed by Licensee with the United States Food and Drug Administration, or any equivalents of such items in
countries within the Territory, and shall assume full responsibility for all development and marketing activities pursuant to and in support of such application. 
 4.02. Transfer of Know-How. To facilitate Licensee’s accomplishment of the responsibilities set forth in Section 4.01 above, within thirty (30) days of the Effective Date of
this Agreement GenuPro shall in good faith supply Licensee with copies of the GenuPro Know-How, Lilly Know-How and Lilly Manufacturing Know-How pertinent to the development of the GenuPro Compound in the Field that GenuPro is able to provide using
commercially reasonable efforts and which is in the possession of GenuPro on the Effective Date, and shall transfer to Licensee the legal title to any IND on the GenuPro Compound presently on file in GenuPro’s name with the FDA and any
comparable filings in other countries of the Territory. GenuPro shall also facilitate transfer of GenuPro Compound manufacturing-related information (including any associated quality and analytical information) to Licensee from those Third Parties
from which GenuPro or PPD has received quotations for manufacturing GenuPro Compound that GenuPro is not under any obligation to keep confidential from a third party. GenuPro will provide Licensee with all relevant information available and known to
GenuPro or PPD concerning the safety, handling, use, disposal and environmental effects of the GenuPro Compound or as may be useful to Licensee to conduct the Project, including but not limited to any communications with regulatory agencies.

  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

  

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 4.03. Development and Commercialization. Licensee shall use Diligent Efforts (and shall cause
any sublicensees or subcontractors participating in the subject matter of this Agreement to use Diligent Efforts) to develop and introduce Licensed Product to commercial market and to market Licensed Product thereafter. 
 4.04. Joint Development Committee. Within thirty (30) days of the Effective Date of this Agreement, GenuPro and Licensee shall assemble a
JDC. Initially, the JDC will be composed of at least two, but no more than four, representatives each from GenuPro or its Affiliates and Licensee. The initial members of the JDC will be those representatives the names of whom will be provided to the
other Party within ten days after the Effective Date. Each Party will promptly notify the other Party in writing of any change in its appointed representatives. The chairperson of the JDC will be one of Licensee’s representatives. 

4.05. Duties of JDC. Licensee shall have full control over implementation of the development and marketing of Licensed Product throughout
the term of this Agreement. The duties of the JDC shall include, but not be limited to, (a) monitoring the progress of the Development Plan and Marketing Plan; and (b) providing GenuPro with detailed annual updates describing the progress
made in implementing the Development Plan and Marketing Plan. Licensee shall consult GenuPro members of the JDC to obtain assistance with completion of the Development Plan and Marketing Plan. The JDC may consult additional GenuPro representatives
(who GenuPro shall deem appropriate at its sole discretion) on an as-needed basis should issues arise where the JDC reasonably believes GenuPro personnel have expertise particularly relevant to the issue being addressed. Notwithstanding the above, a
GenuPro JDC member shall have the right to consult with the JDC where the GenuPro JDC member reasonably believes input from GenuPro is appropriate in order to protect GenuPro’s interests in the subject matter of this Agreement. To accomplish
its objectives, the JDC will meet quarterly, or more often if mutually agreed upon by the Parties, during the term of the Development Plan and will meet at least annually thereafter. The JDC may meet in person or by telephone conference. In-person
JDC meetings will be at a site designated by Licensee and will alternate between a site on the west coast and a site on the east coast of the continental United States. Each Party will bear all expenses of its personnel arising from attending such
meetings. Among other duties, one of Licensee’s JDC members shall prepare written minutes of each such meeting, which minutes will, without limitation, record the updates given at the meetings describing the progress made in implementing the
Development Plan and Marketing Plan. 
 4.06. Adverse Event Reporting. PPD and GenuPro will report all Serious Adverse Events of
which it becomes aware to Licensee as soon as possible, but within 48 hours in any event. Licensee will report Adverse Events and Serious Adverse Events to GenuPro in accordance with reporting requirements provided for in Section 2.06 and
Schedule 2.06 of the Lilly Agreement, and changes recorded in the letter to Dr. Winston Satterlee of PPD dated January 7, 1999 and the letter from Lilly to Dr. Paul Covington of PPD dated March 19, 1999. 
  

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 ARTICLE V - FEES AND ROYALTIES 
 5.01. License Fees. As consideration for the exclusive licenses set forth in Sections 2.02 and 2.03, GenuPro shall be entitled to a one-time,
upfront payment from Licensee, upon the later of (a) ten (10) days after the expiration of all applicable waiting periods under the HSR Act and (b) the Effective Date, of a license fee of [*]. 
 5.02. Milestones.  
 (a) Clinical Milestone Payments. 
 (i) Initiation of Phase III Clinical Trials.
Licensee will notify GenuPro in writing upon its first initiation of a Phase III Clinical Study in the Field involving a CTM Product within fourteen (14) days of such initiation. Within thirty (30) days of such initiation, Licensee
will pay GenuPro a one-time milestone payment of [*]. 
 (ii) Filing of NDA. Licensee will
notify GenuPro, in writing, within fourteen (14) days of the first acceptance by the FDA of a filing of an NDA for the use of a Licensed Product in the Field in the U.S. Within thirty (30) days of such acceptance, Licensee will pay GenuPro
a one-time milestone payment of [*] if such acceptance occurs on or before [*], or [*] if such acceptance occurs after [*]. 
 (iii) Approval of NDA. Licensee will notify GenuPro, in writing, of its first written approval of an NDA by the FDA for the use of a Licensed Product in the Field, within fourteen
(14) days of Licensee’s receipt thereof. Within thirty (30) days of Licensee’s receipt of such written approval, Licensee will pay GenuPro a one-time milestone payment of [*] if such approval occurs on or before
[*], or [*] if such approval occurs after [*]. 
 (iv) First [*] Approvals In
[*]. Licensee will notify GenuPro, in writing within fourteen (14) days of Licensee’s receipt thereof, of the first [*] written approvals of all regulatory filings (including any pricing approval that is required for
commercial launch of a product) required to market a Licensed Product in the Field in countries in [*]. Within thirty (30) days of Licensee’s receipt of each such written approval, Licensee will pay GenuPro a milestone payment of
[*] per country, if such approval occurs on or before [*] or [*] per country if such approval occurs after [*]. Licensee shall make a maximum of [*] payments pursuant to this Section 5.02(a)(iv) . The total of
such payments shall equal: [*]. 
 (b) Net Sales-based Milestone Payments. Licensee shall pay to GenuPro
one-time milestone payments in accordance with the following schedule, based on total Net Sales for four consecutive calendar quarters, such payment to be made within forty-five (45) days after the first time such milestone has been achieved
(the Parties recognize that one or more milestones hereunder may be achieved before expiration of four consecutive quarters). In no event shall Licensee be obligated to pay to GenuPro more than $50,000,000 under this Section 5.02(b).

  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

  

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 Milestone Payment Schedule. 
  

			
	Consolidated annual Net Sales level(s) of Licensed Products in
the Territory to which milestone payments shall be applied	  	Amount of one-time milestone payment per consolidated annual Net Sales level(s)
		
	Net Sales greater than [*]	  	[*]
		
	Net Sales greater than [*]	  	[*]
		
	Net Sales greater than [*]	  	[*]
		
	Net Sales greater than [*]	  	[*]

 5.03. Royalties. Subject to the
terms and conditions of this Agreement, Licensee shall pay to GenuPro a royalty in accordance with the schedule set forth in this Section 5.03, subject to the following conditions:  
 (a) Patented Products without Competition From Generic Products. If a Patented Product is sold in a country where a
Generic Product is not then being sold in such country, then a royalty, in accordance with the royalty schedule set forth below, based on the consolidated annual Net Sales of such Patented Product by Licensee, its Affiliates, and sublicensees in
such countries (the “Patented Country Net Sales”) shall be paid by Licensee to GenuPro: 
  

			
	Consolidated annual Patented Country Net Sales level(s) of Patented Products in the Territory to which royalty rates(s) shall
be applied	  	Royalty rate(s) per annual Patented Country Net Sales level(s)
		
	On the portion of annual Patented Country Net Sales less than or equal to [*]	  	[*] of Net Sales
		
	On the portion of annual Patented Country Net Sales equal to or greater than [*] but not greater than [*]	  	[*] of Net Sales
		
	On the portion of annual Patented Country Net Sales equal to or greater than [*]	  	[*] of Net Sales

  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

  

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 (b) Patented Products with Competition by Generic Products. If a Patented
Product is sold in a country where a Generic Product is also sold at such time, then a royalty of [*] of the Net Sales of the Patented Product in such country shall be paid by Licensee to GenuPro. 
 (c) Non-Patented Products with Competition by Generic Products. If a Non-Patented Product is sold in a country where a Generic
Product is also sold at such time, then a royalty of [*] of the Net Sales of the Non-Patented Product in such country shall be paid by Licensee to GenuPro. 
 (d) Non-Patented Products without Competition by Generic Products. If a Non-Patented Product is sold in a country where a Generic Product is not then being sold in such country, then a
royalty, in accordance with the royalty schedule set forth below, based on the consolidated annual Net Sales of such Non-Patented Product by Licensee, its Affiliates, and sublicensees in such countries (the “Non-Patented Country Net
Sales”) shall be paid by Licensee to GenuPro: 
  

			
	Consolidated annual Non-Patented Country Net Sales level(s) of Non-Patented Products in the Territory to which royalty rates(s) shall be applied	  	Royalty rate(s) per annual Non-Patented Country Net Sales level(s)
		
	On the portion of annual Non-Patented Country Net Sales less than or equal to [*]	  	[*] of Net Sales
		
	On the portion of annual Non-Patented Country Net Sales equal to or greater than [*] but not greater than [*]	  	[*] of Net Sales
		
	On the portion of annual Non-Patented Country Net Sales equal to or greater than [*]	  	[*] of Net Sales

 5.04. Royalty Reduction.
In the event that a Third Party markets, for the same indication as a Licensed Product, a product containing or comprising a Peripheral Compound or an SAR Compound (as “Peripheral Compound” and “SAR Compound” are defined in
the Lilly Agreement rather than in this Agreement) of the GenuPro Compound and such Third Party is Lilly or acquired rights to such compound from Lilly, then the rate at which Licensee is obligated to pay royalties to GenuPro with respect to such
Licensed Product under Section 5.03 shall be reduced [*] during the time that such Third Party is marketing such product. 
  

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 5.05. Royalty Period. Licensee’s obligation to pay royalties to GenuPro under
Section 5.03 shall begin, on a country by country basis, upon the date of the First Commercial Sale in such country of such Licensee’s Licensed Product and shall end upon termination of sale of the Licensed Product in such country.

 5.06. Payments to Third Parties. Licensee shall have a royalty credit equal to [*] of all amounts paid by Licensee to
Third Parties with respect to licenses to intellectual property rights covering a Licensed Product or its manufacture or use in the Field. Such royalty credit may be applied against royalties due under Section 5.03 with respect to such Licensed
Product, provided that the royalty paid by Licensee after the application of any credit shall not, as a result of such adjustment, be less than [*] of the royalty rate which would otherwise apply under Section 5.03 to such Licensed
Product, unless the royalty reduction set forth in Section 5.04 applies to such Licensed Product. 
 5.07. Payments to Lilly.
If Licensee licenses from Lilly intellectual property rights that cover a Licensed Product or its development, manufacture, use, sale or offer for sale in the Field, then PPD shall pay directly to Lilly on behalf of Licensee, and in accordance with
the payment provisions of such license, all amounts owed by Licensee to Lilly as a result of such license. 
 5.08. Method of
Calculation. The calculation of the amount of annual royalties due under the provisions of Section 5.03 shall be subject to and in accordance with the following provisions: 
 (a) Frequency. Royalties shall be calculated and paid on a quarterly basis. Licensee shall provide GenuPro with a
statement of royalties owed to GenuPro within forty-five (45) days after the end of each calendar quarter other than the last quarter in any calendar year, and the quarterly royalty payment shall be made at the time of such statement. At the
end of each calendar year, aggregate royalties shall be calculated on aggregate annual sales to determine additional royalty payments owed to GenuPro by Licensee. Within sixty (60) days after the end of each calendar year, Licensee shall
provide GenuPro with a statement of such additional aggregate royalty payments owed to GenuPro and a written report showing the method by which the royalty payments for such year were calculated, including a breakdown of gross sales and Net Sales
for each Licensed Product sold, including any exchange rates used. If there are no sales of Licensed Product in a country in a given year, then no statement shall be included in such yearly report. Licensee shall submit any additional aggregate
royalty payments to GenuPro together with such statement and written report. 
 (b) Combination Products. Licensee
shall pay GenuPro royalties with respect to any Combination Product at a royalty rate that is equal to a percentage (which shall not exceed 100%) of the otherwise applicable royalty rate under Section 5.03. Such percentage shall be equal to
[*]. If the numerator and denominator cannot be determined in the manner set forth above, then the Parties shall enter into good-faith negotiations regarding the amount of such percentage. 
  

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 (c) New Formulations. In the event that Licensee develops a new formulation or
dosage form of a License Product that requires clinical studies for regulatory approval or [*] (a “New Formulation or Use”), Licensee shall pay royalties to GenuPro on such New Formulation or Use at the same rate as set forth in
Section 5.03 hereof, provided that the amount of royalties otherwise due under this Section 5.08(c) will not be paid until Licensee [*]. New Formulation or Use shall include [*].  
 (d) Sales upon Invoicing. A sale of Licensed Product shall be deemed to have occurred upon the invoicing of such Licensed
Product to a Third Party; or if not invoiced, then when delivered, shipped, or paid for, whichever first occurs. Regardless of the number of patents or other components of Know-How that cover a Licensed Product, only one royalty shall be payable
upon sale of a Licensed Product. 
 (e) Other Consideration. In the case of a sale or other disposal of
Licensee’s Licensed Product for value other than in an arm’s-length transaction exclusively for money, such as barter or counter-trade, the amount of such sale shall be calculated using the fair market value of such Licensed Product (if
higher than the stated sales price) in the country of disposition. 
 ARTICLE VI - Royalty Records, Verification and
Payment 
 6.01. Books and Records. Licensee shall keep and shall require any Affiliates and sublicensees selling Licensed
Products to keep proper records and books of account, in accordance with generally accepted accounting practices, showing the Net Sales of Licensed Products upon which the royalty payments of Licensee are based, and all other information necessary
for the accurate determination of payment to be made hereunder. 
 6.02. Audit. On reasonable written notice, GenuPro, at its own
expense, shall have the right, no more than once a year, to have an independent certified public accountant inspect and audit the books and records of Licensee, including any Net Sales reports received from its Affiliates and its sublicensees,
during usual business hours for the sole purpose of, and only to the extent necessary for, determining the correctness of royalty payments due under this Agreement. Such examination with respect to any fiscal year shall not take place later than
three years following the expiration of such period. The expense of any such audit shall be borne by GenuPro; provided, however, that, if the audit with respect to a particular calendar year discloses an error in excess of [*] or [*],
whichever is greater, in favor of the Licensee, then Licensee shall pay, in addition to the amount of any underpayment, the cost of the audit. Licensee shall include substantially the same audit rights in any sublicense it grants in order to ensure
correctness of payments due hereunder. 
 6.03. Foreign Payments. Royalties based on Net Sales outside of the U.S. shall be
payable in the United States in dollars. Dollar amounts shall be calculated in the foreign currency for the country in which sales are recorded and will be translated into dollars as published by the Wall Street Journal on the last business day of
the quarter for which such payments are due. Payments in dollars shall be paid by wire transfer to GenuPro. 
  

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 ARTICLE VII - CLINICAL DEVELOPMENT COLLABORATION 
 Upon Licensee’s request, the Parties shall negotiate in good faith a separate written agreement whereby PPD shall perform specified clinical research
activities (including Phase II, Phase III or Phase IV clinical studies). 
  

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 ARTICLE VIII - INTELLECTUAL PROPERTY 
 8.01. Ownership of Peripheral Compounds and Product-Related Improvements.  
 (a) GenuPro shall own all right, title and interest in and to all intellectual property rights covering [*] (“GenuPro
Intellectual Property”). 
 (b) Licensee shall own all right, title and interest in and to [*]. 

8.02. Patent Prosecution. 
 (a) GenuPro shall have the right to control the preparation, filing, prosecution, maintenance and defense of GenuPro Patents and be responsible for all costs associated with the GenuPro Patents.
Licensee shall provide GenuPro and any person designated by GenuPro, any reasonable assistance required to perfect the rights defined in Section 8.01(a) . GenuPro shall provide Licensee with drafts of all proposed patent filings (including,
without limitation, patent applications, amendments and responses to official actions) at least 30 days before filing and shall take into account any comments provided by Licensee to GenuPro within 30 days after Licensee’s receipt of the
applicable draft. If GenuPro decides not to file or maintain any applications or patents on a country-by-country basis or patent family basis any GenuPro Patent, GenuPro shall give Licensee reasonable notice of same and after receipt of such notice,
Licensee may, at its expense, file or maintain such applications or patents at its own expense, and GenuPro shall assign such patents and patent applications to Licensee that Licensee elects to file or maintain. 
 (b) Licensee shall have the right to control the preparation, filing, prosecution, maintenance and defense thereof and be responsible
for all costs associated with [*]. GenuPro shall provide Licensee and any person designated by Licensee, any reasonable assistance required to perfect the rights defined in Section 8.01(b). Subject to the last sentence in this
Section 8.02(b), if Licensee decides not to file or maintain any applications or patents on a country-by-country basis or patent family basis any [*], Licensee shall give GenuPro reasonable notice of same and after receipt of such
notice, GenuPro may, at its expense, file or maintain such applications or patents at its own expense, and Licensee shall assign such patents and patent applications to GenuPro that GenuPro elects to file or maintain. The previous sentence shall not
apply to any decision of Licensee that is based on its determination, in its sole discretion, that the value of a particular [*] will most likely be maximized by a form of intellectual property protection other than patent protection, or that
a particular filing would detract from the overall value of the patent estate. 
 (c) PPD and GenuPro covenant to
exercise all rights they have under the Lilly Agreement to ensure that the Lilly Patents are competently prosecuted and maintained in force. If PPD and GenuPro become aware of a potential abandonment of a Lilly Patent that cannot be avoided by
PPD’s and GenuPro’s actions, PPD or GenuPro shall provide prompt notice to Licensee of such potential abandonment and the circumstances surrounding it. 
  

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 8.03. Notification. At each JDC meeting, Licensee shall notify GenuPro of any Peripheral
Compound, SAR Compound or Product-Related Improvement made by Licensee’s employees since the previous meeting (or, in the case of the first meeting of the JDC, since the Effective Date), and PPD and GenuPro shall disclose to Licensee all
GenuPro Know-How made during such period. 
 8.04. Assignment. 
 (a) Licensee hereby irrevocably assigns to GenuPro any intellectual property rights Licensee may obtain which GenuPro shall own
pursuant to Section 8.01(a) . GenuPro shall have the right to obtain and to hold in it own name, patents or such other protection as may be appropriate to the subject matter, and any extensions and renewals thereof. Licensee shall provide
GenuPro and any person designated by GenuPro any reasonable assistance required to perfect the rights defined in this Section 8.04(a). 
 (b) GenuPro hereby irrevocably assigns to Licensee any rights GenuPro may obtain which Licensee shall own pursuant to Section 8.01(b). Licensee shall have the right to obtain and to hold
in it own name, patents or such other protection as may be appropriate to the subject matter, and any extensions and renewals thereof. GenuPro shall provide Licensee and any person designated by Licensee any reasonable assistance required to perfect
the rights defined in this Section 8.04(b). 
 8.05. Trademarks. Licensee shall own all trademarks developed by Licensee used
to identify a Licensed Product. 
 ARTICLE IX - PATENT AND INFRINGEMENT 
 9.01. Scope of Rights under Other Arrangements. Notwithstanding anything to the contrary in this Article 9, the Parties acknowledge that the
scope of rights to initiate or defend claims of patent infringement or invalidity regarding Lilly Patents are limited by and must be consistent with the terms of Article 9 of the Lilly Agreement. 
 9.02. Infringement of Patent Rights. 
 (a) Each Party to this Agreement shall notify the other in writing promptly of any actual, potential or suspected infringement (collectively “alleged infringement”) of the Product-Related
Improvement Patents as they relate to Licensed Products of which such Party becomes aware and shall promptly provide the other Party with available evidence of such alleged infringement. In such event, the Parties shall discuss the most appropriate
action to take. If and when the Parties to this Agreement have the right to initiate an infringement claim, then the Parties shall reasonably cooperate with each other in an attempt to terminate such third-party infringement through means other than
litigation. If, within sixty (60) days after the date of notification of infringement, attempts to abate such infringement are unsuccessful, then Licensee may, at its own initiative and expense, bring and conduct an infringement action against
such Third Party, and Licensee shall be entitled to any recoveries, damages or awards obtained in such action (through settlement, court order, or otherwise). If Licensee refuses to bring an infringement action against the Third Party, then GenuPro
may, at its own initiative and expense,

  

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bring and conduct such action, and GenuPro shall be entitled to any recoveries, damages or awards obtained in such action (through settlement, court order, or otherwise). 
 (b) Each Party to this Agreement shall notify the other in writing promptly of any actual, potential or suspected infringement
(collectively “alleged infringement”) of the GenuPro Patents or Lilly Patents as they relate to Licensed Products of which such Party becomes aware and shall promptly provide the other Party with available evidence of such alleged
infringement. If a Lilly Patent is the subject of such alleged infringement, GenuPro shall inform Lilly so that Lilly may pursue its prosecution rights pursuant to Sections 9.02 and 9.04 of the Lilly Agreement. At such time as the JDC decides it is
appropriate, GenuPro shall request, in accordance with Section 9.02(b) or 9.04(b) of the Lilly Agreement that Lilly take legal action against such infringement. If Lilly commences an infringement action regarding a Lilly Patent or a GenuPro
Patent, Licensee shall be entitled to that portion of any recovery described in Section 9.02(a)(ii)(3) or 9.04(a)(ii)(3) of the Lilly Agreement, as applicable. If GenuPro obtains the right to prosecute an action of infringement pursuant to
Section 9.02(b) or 9.04(b) of the Lilly Agreement or if a GenuPro Patent is the subject of such alleged infringement, the Parties shall discuss the most appropriate action to take. If and when the Parties to this Agreement have the right to
initiate an infringement claim, then the Parties shall reasonably cooperate with each other in an attempt to terminate such third-party infringement through means other than litigation. If, within sixty (60) days after the date of notification
of infringement, attempts to abate such infringement are unsuccessful, then GenuPro may, at its own initiative and expense, bring and conduct an infringement action against such Third Party, any recoveries, damages or awards obtained in such action
(through settlement, court order, or otherwise) shall be allocated in accordance with Section 9.02(b)(ii) or 9.04(a)(ii) of the Lilly Agreement, as applicable. GenuPro shall not settle any action in a manner that is prejudicial to any of
Licensee’s rights under GenuPro Patents or Lilly Patents licensed hereunder without Licensee’s prior written approval, which approval shall not be unreasonably withheld. If GenuPro refuses to bring an infringement action against the Third
Party or refuses to continue such a suit, then Licensee may, at its own initiative and expense, bring, conduct and/or continue such action (and GenuPro grants Licensee the right to do so in its name), and Licensee shall be entitled to any
recoveries, damages or awards obtained in such action (through settlement, court order, or otherwise). 
 9.03. Infringement of Third
Party Patent Rights. If a Party’s conduct under this Agreement becomes the basis of a claim of infringement of any patent or other proprietary right of any Third Party, such Party shall promptly give notice to the other Party and the
Parties shall confer to consider the claim and an appropriate course of action. If and when a Party to the instant Agreement have the right to defend an infringement claim, each Party shall have the right to conduct the defense against any such
claim or infringement action brought against it, and shall have the right and authority to settle any such claim or action after consultation with the other Party, provided that such defending Party shall not make any admission or take any action
that would prejudice any of the other Party’s patent rights without the prior written approval of the other Party, which approval shall not be unreasonably withheld. The other Party shall cooperate with the defending Party, as reasonably
requested by it, in connection with the defense against such claim or action, at the defending Party’s expense. [*]  
  

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 9.04. Patent Marking. To the extent permitted by applicable laws and regulations, Licensee
agrees to mark, and to cause any Affiliate or sublicensee to mark, Licensee’s Licensed Products (through a marking on containers, packaging or labels, or an Orange Book or like listing) made, sold, or otherwise disposed of by it or them with
any notice of patent rights necessary or desirable under applicable law to enable patent rights to be enforced to their full extent in any country where such Party’s Licensed Products are to be sold. 
 ARTICLE X - CONFIDENTIAL INFORMATION 
 10.01. Obligations. Each Party (the “Receiving Party”) will maintain the Confidential Information disclosed by the other Party (the “Disclosing Party”), confidential
throughout the Project and for a period continuing through [*] years after the termination of this Agreement. However, such obligation of confidentiality shall not apply to any Confidential Information that: 
 (a) is, as of the Effective Date, in the public domain or subsequently enters the public domain through no fault of the Receiving
Party; 
 (b) was known to the Receiving Party prior to disclosure by the Disclosing Party hereunder and was acquired
without breach of any obligation to the Disclosing Party and can be documented by written records; 
 (c) is disclosed to
the Receiving Party by a Third Party lawfully in possession of same and having the right to disclose same; 
 (d) is
independently developed by Receiving Party, as demonstrated by written evidence, without reference to information disclosed by Disclosing Party; 
 (e) is disclosed pursuant to the Disclosing Party’s prior written approval; 
 (f) is required to be disclosed by a governmental authority provided reasonable notice of the impending disclosure is provided to the Disclosing Party, and the Disclosing Party has agreed to such disclosure in writing or has
exhausted its right to contest such disclosure; 
 (g) is disclosed to a Third Party in order to allow Disclosing Party
to defend against litigation with a Third Party, to file and prosecute patent applications or to comply with governmental regulations; 
 (h) is required to be disclosed in order to allow Receiving Party to obtain regulatory agency approval to market a Licensed Product in the Field within the Territory; 
 (i) is required by a governmental entity to be disclosed (for example, without limitation, on product labeling or a product insert)
in order to market a Licensed Product in the Field within the Territory; 
 (j) is disclosed to a Third Party in
connection with developing, testing, evaluating or applying for or securing regulatory agency approval of Licensed Product in the Field within the 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

  

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 Territory, provided such Third Party has agreed in writing to be bound by confidentiality terms at least as
stringent as those in this Agreement; or 
 (k) is disclosed to a Third Party who has entered into, or is contemplating
entering into a written agreement with Receiving Party regarding commercialization of Licensed Product for an indication or indications in the Field within the Territory, provided such Third Party has agreed in writing to be bound by confidentiality
terms at least as stringent as those in this Agreement. 
 10.02. Limitations on Publications. The Parties agree that no one Party
shall publish the results of any studies, whether conducted by its own employees or in conjunction with a Third Party, carried out pursuant to this Agreement or Confidential Information received from the other Party that is relating to the Project,
without the prior written approval of the other Party. Each Party agrees to provide the other Party with a copy of any proposed abstracts, presentations, manuscripts, or any other disclosure which discloses clinical study results pursuant to this
Agreement or Confidential Information received from the other Party relating to the Project at least [*] days prior to their intended submission for publication and agrees not to submit or present such disclosure until the Party not seeking
to disclose such information provides its prior written approval. Such written approval will not be unreasonably withheld unless such proposed disclosure could reasonably harm or impair a Party’s intellectual property assets or may reasonably
cause commercial harm to a Party. 
 ARTICLE XI - WARRANTIES 
 11.01. Warranties By GenuPro and PPD. GenuPro and PPD represent and warrant to Licensee the following: 
 (a) GenuPro has the full right and power to grant the licenses set forth in Sections 2.02 and 2.03 in the manner and to the extent
set forth in this Agreement (including Licensee’s right to further sublicense), free and clear of any adverse assignment, grant or other encumbrances inconsistent with such grant. 
 (b) The GenuPro Compound has been developed to the “Proof of Concept” stage as defined under the Lilly Agreement and
GenuPro provided notice thereof to Lilly on September 29, 1999 in compliance with the procedures set forth in Section 4.01 of the Lilly Agreement. 
 (c) Neither GenuPro nor PPD nor an Affiliate of either has received any notice or other communication from Lilly regarding the exercise by Lilly of its rights under Section 4.01 of the Lilly
Agreement with respect to the GenuPro Compound and Lilly no longer has the right to provide such notice. 
 (d) PPD has
not exercised its rights under Section 4.02 of the Lilly Agreement with respect to the GenuPro Compound.  
 (e) PPD has no rights under Section 4.02 of the Lilly Agreement with respect to the GenuPro Compound. 
  

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 (f) GenuPro has provided to Lilly and PPD, in compliance with the procedures set
forth in Section 4.04 of the Lilly Agreement, notice of GenuPro’s intent to sign this Agreement. PPD has not submitted a counteroffer to GenuPro in accordance with its right under Section 4.04 of the Lilly Agreement and has waived its
right to submit such a counteroffer. PPD has been notified in writing by Lilly that Lilly will not exercise its right to submit a counteroffer under Section 4.04 of the Lilly Agreement. The terms of this Agreement are not materially different
from the terms submitted to Lilly on November 1, 2000 and the additional information submitted to Lilly on November 15, 2000. Lilly has no further rights under Section 4.04 of the Lilly Agreement with respect to the transaction
contemplated by this Agreement. 
 (g) Lilly has in fact granted to GenuPro the licenses set forth in Sections 6.03 -6.07
of the Lilly Agreement and such licenses are currently in full force and effect. To the best of their knowledge, Schedule 1.25 includes all intellectual property of Lilly that is applicable to Compounds. 
 (h) Neither GenuPro nor PPD nor an Affiliate of either has received any notice or other communication from Lilly regarding any breach
by GenuPro or PPD of their obligations under the Lilly Agreement, including without limitation the diligence obligations set forth in Section 2.03 of the Lilly Agreement. 
 (i) GenuPro and PPD have licensed to Licensee in this Agreement all rights that GenuPro and PPD have with respect to Compounds and
Licensed Products, including without limitation those rights received pursuant to the Lilly Agreement. 
 (j) Neither
GenuPro nor PPD shall assert in any way any patent or other intellectual property right Controlled by GenuPro or PPD against Licensee or its sublicensees or Affiliates, or their customers (direct or indirect), agents or contractors with respect to
the development, manufacture, use, import, offer for sale or sale of a Licensed Product. 
 (k) GenuPro and PPD have
disclosed to Licensee in writing all Peripheral Compounds and SAR Compounds (as defined in the Lilly Agreement) that relate to the GenuPro Compound and that have been made prior to the Effective Date and are in their possession as of the Effective
Date. Such Peripheral Compounds and SAR Compounds include all such compounds disclosed to GenuPro or PPD by Lilly pursuant to Section 8.04 of the Lilly Agreement. 
 (l) GenuPro and PPD have shown to Licensee the complete, unredacted text of all provisions of the Lilly Agreement that apply to the GenuPro Compound, except certain financial information. The
information that GenuPro and PPD redacted from the “Field” definition in the version of the Lilly Agreement provided to Licensee describes uses for proprietary Lilly compounds unrelated to dapoxetine. 
  

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 (m) All GenuPro Patents and GenuPro Know-How comprise “Joint Improvements”
as defined in the Lilly Agreement. Neither GenuPro nor PPD Control any Know-How or Patents relating to Compounds, CTM Products or Licensed Products that are not classified as “Joint Improvements” under the Lilly Agreement and are not
subject to the exclusive license to Lilly set forth in the last sentence of the second paragraph of Section 6.03 of the Lilly Agreement. [*] 
 (n) To the best of their knowledge, the Compounds, CTM Products and Licensed Products and methods of making or using them do not infringe or misappropriate the intellectual property rights of
any Third Party, and no royalties are owed to any Third Party with respect to such compounds and products. Neither GenuPro nor PPD nor an Affiliate of either has received any notice or other communication alleging that a Compound, CTM Product or
Licensed Product infringes or misappropriates the intellectual property rights of a Third Party. 
 (o) PPD and GenuPro
are not aware of any Third Party patent rights relating to the Manufacturing Know-How, and Lilly has not brought any such Third Party patent rights to the attention of PPD or GenuPro pursuant to Lilly’s obligation under Section 5.04 of the
Lilly Agreement. In the event that Lilly brings such Third Party patent rights to the attention of PPD or GenuPro during the term of this Agreement, PPD and GenuPro shall promptly and fully disclose such information in writing to Licensee.

 (p) PPD and GenuPro are not aware of any intellectual property rights Controlled by Lilly that (i) are not
licensed to GenuPro pursuant to the Lilly Agreement and sublicensed to Licensee pursuant to this Agreement, and (ii) are necessary to develop, make, have made, use, import, offer for sale or sell a Licensed Product. 
 (q) PPD and GenuPro have disclosed to Licensee all material adverse data relating to the Compounds and their safety in animals and
humans, development status and regulatory status known to GenuPro as of the Effective Date of this Agreement. 
 (r) PPD
and GenuPro are not aware of any lawsuits (either former or current) which arose from clinical trials performed by PPD, GenuPro or Lilly using the CTM Product. Neither GenuPro nor PPD nor an Affiliate of either has received any notice or other
communication regarding a claim arising from a clinical trial performed by PPD, GenuPro or Lilly upon CTM Product. 
 (s)
GenuPro is validly existing and in good standing under the laws of the state of its incorporation and has the corporate power and authority to enter into this Agreement. This Agreement has been duly executed and delivered by GenuPro and
constitutes the valid and binding obligation of GenuPro, enforceable against it in accordance with its terms except as enforceability may be limited by bankruptcy, fraudulent conveyance, insolvency, reorganization, moratorium and other laws relating
to or affecting creditors’ rights generally and by general equitable principles. The execution, delivery and performance of this Agreement have been duly authorized by all necessary action on the part of GenuPro, its officers and directors.

  

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 11.02. Warranties by Licensee. Licensee represents and warrants to GenuPro the following:
Licensee is validly existing and in good standing under the laws of the state of its incorporation and has the corporate power and authority to enter into this Agreement. This Agreement has been duly executed and delivered by Licensee and
constitutes the valid and binding obligation of Licensee, enforceable against it in accordance with its terms except as enforceability may be limited by bankruptcy, fraudulent conveyance, insolvency, reorganization, moratorium and other laws
relating to or affecting creditors’ rights generally and by general equitable principles. The execution, delivery and performance of this Agreement have been duly authorized by all necessary action on the part of Licensee, its officers and
directors. 
 11.03. Employee Agreements. Each Party warrants that it has entered into a proprietary information and inventions
agreement with each of its employees prior to the time that any such employee shall receive Confidential Information from a Disclosing Party or begin work related to this Agreement. Such agreement shall minimally set forth employee obligations to
assign inventions to the inventing Party and to maintain confidentiality of Confidential Information consistent with the terms of this Agreement. Each Party shall enter into a similar agreement with any Third Party retained by the Party to perform
services hereunder prior to the time that such Third Party receives any Confidential Information from a Disclosing Party or begins work related to this Agreement. 
 ARTICLE XII - TERM AND TERMINATION 
 12.01. Term. Unless otherwise
terminated by operation of law or in accordance with the provisions of this Article XII, the licenses granted herein and the obligations assumed hereunder with respect to the Licensed Product shall commence as of the Effective Date of this Agreement
and shall continue in full force and effect until all payment obligations of Licensee to GenuPro under this Agreement relating to the Licensed Product are terminated. 
 12.02. Hart-Scott-Rodino Act. Licensee may terminate this Agreement, effective immediately, if the Parties do not receive approval of their filing under the HSR Act with respect to this
Agreement by 60 days after the Effective Date. 
 12.03. Material Breach. This Agreement will be terminable upon the material
default of either Party. In the event of such material default by a Party (“Defaulting Party”), the other Party (“Non-Defaulting Party”) shall give the Defaulting Party written notice of the default and its election to terminate
this Agreement at the expiration of a cure period one hundred eighty (180) days from the date of the notice. If the Defaulting Party fails to resolve the default during the cure period by: (a) curing the default, (b) providing a
written explanation satisfactory to the Non-Defaulting Party that a default has not occurred, or (c) entering into a written agreement with the Non-Defaulting Party for the cure or other resolution of the default, then the Non-Defaulting Party
may terminate this Agreement by giving written notice to the Defaulting Party. The termination will be effective upon Defaulting Party’s receipt of such terminating notice. All termination rights shall be in addition to and not in substitution
for any other remedies that may be available to the Non-Defaulting Party. Termination pursuant to this section will not relieve the Defaulting Party from liability and damages to the Non-Defaulting Party for default. Waiver by either Party of a
single default or a succession of defaults will not deprive such Party of any

  

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right to terminate this Agreement arising by reason of any subsequent default. If GenuPro should terminate this Agreement under this Section 12.03, Licensee shall irrevocably lose any and
all licenses granted to Licensee by GenuPro pursuant to Sections 2.02 and 2.03. Licensee also shall (and shall cause any subcontractors or sublicensees under contract with Licensee to) transfer to GenuPro (and into GenuPro’s name where
appropriate) at no cost to GenuPro all quantities of Compound, CTM Product, or Licensed Product, as well as all Know-How, Product-Related Improvements and Lilly Manufacturing Know-How in Licensee’s possession related to Licensed Product
including, but not limited to, all regulatory files and filings related thereto, any patents or patent applications encompassing Product-Related Improvements. Licensee shall irrevocably assign its intellectual property rights in Product-Related
Improvements to GenuPro. GenuPro shall have the right to obtain and to hold in it own name, patents or such other protection as may be appropriate to the subject matter, and any extensions and renewals thereof. Licensee shall provide GenuPro and any
person designated by GenuPro any reasonable assistance required to perfect such rights. Notwithstanding the foregoing, if Licensee challenges GenuPro’s right to terminate this Agreement, no transfer of rights under this Section 12.03 shall
occur unless and until GenuPro’s right to terminate has been affirmed in an arbitration pursuant to Section 12.09. 
 12.04.
Termination for Insolvency. If either GenuPro or Licensee: (a) makes a general assignment for the benefit of creditors or becomes insolvent (for the purposes of this Agreement, “insolvent” shall mean the inability of a
Party to pay its debts as they become due in the ordinary course of business), (b) files an insolvency petition in bankruptcy, (c) petitions for or acquiesces in the appointment of any receiver, trustee or similar officer to liquidate or
conserve its business or any substantial part of its assets, (d) commences under the laws of any jurisdiction any proceeding involving its insolvency, bankruptcy, reorganization, adjustment of debt, dissolution, liquidation or any other similar
proceeding for the release of financially distressed debtors, or (e) becomes a Party to any proceeding or action of the type described above in (c) or (d) and such proceeding or action remains undismissed or unstayed for a period of
more than sixty (60) days, then the other Party may by written notice terminate this Agreement in its entirety with immediate effect. 
 12.05. Residual Obligation upon Termination. Termination of this Agreement for any reason whatsoever will not release or discharge either Party from the performance of any obligation, the payment of any debt or responsibility
for any liability which may have previously accrued and remains to be performed, paid or discharged, at the date of such termination. However, upon termination no further obligations under this Agreement shall be incurred by the Parties. Moreover,
termination of this Agreement shall not release either Party of the obligations of confidentiality set forth in Section 10.01. Sections 12.05, 12.06, 12.07, 12.08, 12.09, 13.01, 13.06, 13.09, 13.14, 13.15, and 13.17 and Articles I, VIII and XI
shall survive any expiration or termination of this Agreement.  
 12.06. Additional Remedies. Termination of this
Agreement under Sections 12.03 or 12.04 shall not be exclusive or prejudicial to any other rights or remedies each Party may have on account of such breach or default under this Agreement or otherwise. 
  

 24 

 12.07. Remaining Licensed Product. Upon any termination of this Agreement, Licensee shall have
the right for [*] to sell all Licensed Product then on hand, and to complete all orders for such Licensed Product then on hand, and royalties shall be paid to GenuPro with respect to such Licensed Product as though this Agreement had not
terminated. 
 12.08. Pre-Arbitration Efforts. In the event of any controversy or claim arising from or relating to any provision
of this Agreement, or any term or condition hereof, or the performance by a Party of its obligations hereunder, or its constructive or its actual or alleged breach, the Parties shall try to settle their differences amicably between themselves. If
the representatives of the Parties are unable to reach agreement on any such issue, the issue shall be submitted for consideration, in the case of Licensee, to its General Counsel, or its designee, and in the case of GenuPro, to its General Counsel,
or its designee. If such representatives are unable to agree within fourteen (14) days, then the issue shall be submitted for consideration to, in the case of Licensee, to the Chief Operating Officer, and, in the case of GenuPro, to its Chief
Executive Officer. If such representatives are unable to agree within fourteen (14) days, then any disputes remaining unresolved between the Parties, except as otherwise provided in this Agreement, shall be finally resolved by binding
arbitration, as set forth below. 
 12.09. Arbitration 
 (a) Arbitration Jurisdiction. Any dispute or controversy arising out of or relating to this Agreement not able to be resolved
between the Parties as provided in Section 12.08 will be finally decided by arbitration in accordance with the then-current Licensing Agreement Arbitration Rules of the American Arbitration Association; provided, however, that the code of civil
procedure of the state in which arbitration is being held shall apply to any such proceeding. If GenuPro commences an arbitration proceeding, it will be conducted in Santa Clara County, California, if Licensee commences an arbitration proceeding, it
will be conducted in Wilmington, North Carolina. The Parties agree that any arbitration panel will include members knowledgeable as to evaluation of pharmaceutical technology. 
 (b) Arbitration Procedures. Whenever a Party decides to institute arbitration proceedings, it shall give written notice to the
other Party. A single arbitrator mutually chosen by the Parties shall conduct the arbitration. If the Parties cannot agree upon a single arbitrator within fifteen (15) days after the institution of the arbitration proceeding, then the
arbitration will be conducted by a panel of three arbitrators appointed in accordance with applicable AAA rules; provided, however, that each Party shall within thirty (30) days after the institution of the arbitration proceedings appoint one
arbitrator, with the third arbitrator being chosen by the other two arbitrators. If only one Party appoints an arbitrator, then such arbitrator shall be entitled to act as the sole arbitrator to resolve the controversy. All arbitrator(s) eligible to
conduct the arbitration must agree to render their opinion(s) within thirty (30) days after completion of the final arbitration hearing. The arbitrator(s) shall have the authority to grant injunctive relief and specific performance, and to
allocate between the Parties the costs of arbitration in an equitable manner; provided, however, that each Party shall bear its own costs, attorneys fees and witness fees. 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

  

 25 

 Notwithstanding the terms of this Section, a Party shall also have the right to obtain, prior to the
arbitrator(s) rendering the arbitration decision, provisional remedies, including injunctive relief or specific performance, from a court having jurisdiction thereof. The arbitrator(s) will, upon the request of either Party, issue a written opinion
of the findings of fact and conclusions of law and shall deliver a copy to each of the Parties. Decisions of the arbitrator(s) shall be final and binding on all of the Parties. Judgment upon the award rendered may be entered in the highest court or
forum, state or federal, having jurisdiction; provided, however, that the provisions of this Section will not apply to decisions on the validity of patent claims or to any dispute or controversy as to which any treaty or law prohibits such
arbitration. 
 ARTICLE XIII - MISCELLANEOUS 
 13.01. Indemnification and Insurance. 
 (a)
Indemnification.  
 (i) Except to the extent an action is described in this subsection
(i) involves gross negligence or intentional misconduct by Licensee, its officers, directors, employees and/or agents, GenuPro and PPD shall indemnify, hold harmless and defend Licensee, its officers, employees and/or agents against any and all
claims, suits, losses, damage, costs, fees (including reasonable attorney’s fees) and expenses resulting from or arising out of GenuPro’s or PPD’s activities contemplated under this Agreement, including, but not limited to, breach of
their warranties and obligations hereunder. GenuPro’s and PPD’s obligation to indemnify, hold harmless and defend shall include, but not be limited to, claims, demands, judgments or costs whether for money damages or equitable relief by
reason of alleged personal injury (including death) to any person or alleged property damage. 
 (ii)
GenuPro and PPD shall indemnify, hold harmless and defend Licensee, its officers, employees, agents, sublicensees, Affiliates, customers (direct or indirect) and/or contractors against any and all claims, suits, losses, damage, costs, fees
(including reasonable attorney’s fees) and expenses resulting from or arising out of any allegation by Lilly or its Affiliate or licensee that the development, manufacture, use, import, offer for sale or sale of a Licensed Product in the
Territory in the Field infringes or misappropriates any intellectual property rights Controlled by Lilly or licensed by Lilly to such Affiliate or licensee. 
 (iii) GenuPro and PPD shall indemnify, hold harmless and defend Licensee, its officers, employees, agents,
sublicensees, Affiliates, customers (direct or indirect) and/or contractors against any and all claims, suits, losses, damage, costs, fees (including reasonable attorney’s fees) and expenses resulting from or arising out of any allegation by a
Third Party that the practice of the license set forth in Section 2.02(b) results in infringement of a patent right owned or Controlled by such Third Party, provided that Lilly was obligated under Section 5.04 of the Lilly Agreement to
inform GenuPro of such Third Party patent right and Lilly breached such obligation. 
 (iv) Except to the
extent an action is described in this subsection (iv) involves gross negligence or intentional misconduct by GenuPro or PPD, their officers, directors, employees and/or agents, Licensee shall indemnify, hold harmless and defend GenuPro and PPD

  

 26 

 
or their officers, employees and/or agents against any and all claims, suits, losses, damage, costs, fees (including reasonable attorney’s fees) and expenses resulting from or arising out of
Licensee’s activities contemplated under this Agreement, including, but not limited to, breach of its warranties and obligations hereunder. Licensee’s obligation to indemnify, hold harmless and defend shall include, but not be limited to,
claims, demands, judgments or costs whether for money damages or equitable relief by reason of alleged personal injury (including death) to any person or alleged property damage. 
 (b) Insurance. Prior to Licensee initiating any clinical trial (other than clinical trials for which PPD is acting as a
clinical research organization, in which case PPD will obtain such insurance and provide documentation to Licensee and GenuPro), Licensee shall have and maintain such type and amounts of liability insurance covering the development activities
contemplated hereunder and that are normal and customary in the pharmaceutical industry generally for Parties similarly situated. Within five (5) days of GenuPro’s written request, Licensee shall provide GenuPro with a copy of its
policy(ies), along with any amendments and revisions thereto. In addition, Licensee shall furnish to GenuPro certificates evidencing the insurance coverage within five (5) days of GenuPro’s written request. Each of the certificates shall
provide that the coverage will not be canceled until at least thirty (30) days after written notice has been given by Licensee to GenuPro. 
 13.02. HSR Filing. Each Party agrees to make an appropriate filing with the FTC under the HSR Act as soon as possible after the Effective Date and to respond to any questions of the FTC with respect thereto as soon as
practicable, in order to obtain prompt FTC clearance of the transactions proposed by this Agreement. Each Party shall use their best efforts to expedite the filing. The Parties will share equally the HSR Act filing fee and will request early
termination of the waiting period. 
 13.03. Amendment. This Agreement may not be amended, supplemented or otherwise modified
except by an instrument in writing signed by an authorized representative of both Parties. 
 13.04. Lilly Agreement. Licensee
hereby adopts the Lilly Agreement, to the extent applicable to Licensee and related to the GenuPro Compound. 
 13.05. Entire
Agreement. The Parties acknowledge and agree that this Agreement includes the Schedules and constitutes the entire agreement and understanding relating to the subject matter of this Agreement. As such, the instant Agreement supersedes all
previous communications, proposals, representations and agreements, whether oral or written, including the Confidentiality Agreement, relating to the subject matter of this Agreement. 
 13.06. Severability. Each Party agrees that, should any provision of this Agreement be determined by a court of competent jurisdiction to violate or contravene any applicable law or policy,
such provision will be modified by the court to the extent necessary to comply with the applicable law or policy, and such modified provision and the remainder of the provisions hereof will continue in full force and effect; and if such provision
cannot be so modified, it shall be severed from this Agreement and the remaining provisions shall be equitably adjusted if necessary, and shall remain in full force and effect. 
  

 27 

 13.07. Waiver. The waiver of a breach hereunder may be effected only by a writing signed by
the waiving Party and shall not constitute a waiver of any other breach. 
 13.08. Notices. Any notice required or permitted to be
given or delivered hereunder or by reason of the provisions of this Agreement shall be in writing and shall be deemed to have been properly served if: (a) delivered personally, (b) delivered by a recognized overnight courier service
instructed to provide next-day delivery, (c) sent by certified or registered mail, return receipt requested and first class postage prepaid, or (d) sent by facsimile transmission followed by confirmation copy delivered by a recognized
overnight courier service the next day. Such notices, demands and other communications shall be sent to the addresses set forth below, or to such other addresses or to the attention of such other person as the recipient Party has specified by prior
written notice to the sending Party. Date of service of such notice shall be: (i) the date such notice is personally delivered or sent by facsimile transmission (with issuance by the transmitting machine of confirmation of successful
transmission), (ii) three days after the date of mailing if sent by certified or registered mail, or (iii) one day after date of delivery to the overnight courier if sent by overnight courier. Unless otherwise specified in writing, the
mailing addresses of the Parties shall be as described below. 
  

			
	For:	  	 GenuPro
 PPD GenuPro

c/o PPD, Inc.
 3151 South 17th Street

Wilmington, NC 28412
 Facsimile:
(910) 343-5920
 Attn: Chief Executive Officer
 Facsimile: (910) 772-6951
 Attn: General Counsel

		
	For:	  	 For: ALZA Corporation
 1900
Charleston Road
 Mountain View, CA 94043
 Facsimile: (650) 564-7848
 Attn: General Counsel

 13.09. Governing Law. This Agreement shall be governed by, and construed in accordance with, the laws of the State of California, United States, excluding any choice of law rules which may
direct the application of the law of any patents encompassed within the scope of this Agreement shall be determined in accordance with the applicable laws of the countries in which such patents have issued. 
 13.10. Assignability. This Agreement and the licenses granted herein shall be binding upon and inure to the benefit of the successors in
interest of the respective Parties, whether by acquisition, merger or purchase of all or substantially all of the assets of such Party. Except as contemplated in the foregoing, neither Party shall assign any benefit and/or burden under this
Agreement without prior written consent of the other Party. Each Party agrees to grant such consent if such Party reasonably determines that the proposed assignment will not materially adversely affect it, provided that the assignee agree in writing
that it will comply with all applicable provisions of

  

 28 

 
this Agreement. Nothing in this Section 13.10 shall be deemed to prevent Licensee from subcontracting its obligations under this Agreement to any Third Party to the extent that such
subcontracting is envisioned for the activities contemplated under this Agreement or is otherwise unanimously agreed upon by the JDC. 
 13.11. Release of Information. No Party to this Agreement may release any information to any Third Party regarding the terms of this Agreement without the prior written consent of the other Party. Without limitation, this
prohibition applies to press releases, educational and scientific conferences, promotional Licensed Products, governmental filings, and discussions with public officials and the media. This provision, however, does not apply to any publications or
disclosures which may be required: (i) by law, including requests for a copy of this Agreement or related information by tax authorities; (ii) for recording purposes; (iii) by investment bankers, lawyers, accountants and other
professional advisors (provided such disclosure is made under strict confidentiality and the detail of terms disclosed is kept to the absolute minimum required by such professionals); and (iv) by Eli Lilly and Company in connection with the
Development and License Agreement. Each Party agrees that it shall fully cooperate with the other with respect to all disclosures regarding this Agreement to the Securities and Exchange Commission and any other governmental or regulatory agencies,
including requests for confidential treatment of proprietary information of either Party included in any such disclosures. 
 13.12.
Relationship of the Parties. The Parties are independent contractors and nothing in this Agreement is intended or shall be deemed to constitute or create a partnership, agency or employer-employee relationship between the Parties.

 13.13. Dollars. All references to “dollars” hereunder are to United States dollars. 
 13.14. Jointly Prepared. This Agreement has been prepared jointly and shall not be strictly construed against either Party. 
 13.15. Headings. The captions or headings of the Sections are inserted only as a matter of convenience or for reference and shall have no
effect on the meaning of the provisions hereof. 
 13.16. Counterparts. This Agreement may be executed in one or more
counterparts, each of which shall be an original, but all of which taken together shall constitute one and the same agreement. 
 13.17.
Schedules. Each Schedule attached hereto shall be incorporated into and be a part of this Agreement. 
 IN WITNESS WHEREOF, the
Parties have executed this Agreement through duly authorized representatives as of the date first set forth herein. 
  

									
	 GenuPro, Inc.
	 		  	Alza Corporation
					
	 By:
	 	 	 		  	By:	  	 
					
	 Name:
	 	 	 		  	Name:	  	 
					
	 Title:
	 	 	 		  	Title:	  	 

  

 29 

			
	Pharmaceutical Product Development, Inc.
		
	By:	 	 
		
	Name:	 	 
		
	Title:	 	 

  

 30 

 Schedule 1.25 
 [*] 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

  

 i 

 Schedule 3.02 
  

	1.	Drug Substance 

  

			
	 •   Dapoxetine HCl Batch 175MH1
	  	6.57 kg (GMP batch used for CTM Product)
		
	 •   Dapoxetine HCl Batch 291MH0
	  	1.567kg (GMP status not confirmed)
		
	 •   Dapoxetine HCl Batch 176MH1
	  	1.6 kg (GMP status not confirmed)

  

	2.	Formulated CTM Product 

  

							
	 Placebo
	  		  		  	
				
	 •   12 count
	  	 930 bottles
	  		  	
				
	 •   50 count
	  	 228 bottles
	  		  	
				
	 10mg Capsules
	  		  		  	
				
	 •   Bulk capsules
	  	 4366 capsules
	  		  	
				
	 •   12 count
	  	 930 bottles
	  		  	
				
	 •   50 count
	  	 613 bottles
	  		  	
				
	 20mg Capsules
	  		  		  	
				
	 •   Bulk capsules
	  	 5024 capsules
	  		  	
				
	 •   12 count
	  	 930 bottles
	  		  	
				
	 •   50 count
	  	 613 bottles
	  		  	
				
	 30mg Capsules
	  		  		  	
				
	 •   12 count
	  	 1230 bottles
	  		  	
				
	 •   50 count
	  	 316 bottles
	  		  	

  

 i 

 Portions of this exhibit marked [*] are omitted and 
 are requested to be treated confidentially. 
 Amendment No. 1 To LICENSE AGREEMENT  
 This Amendment No. 1 to License
Agreement (“Amendment No. 1”) is effective as of the 26th day of December, 2003 (the “Amendment Effective Date”) by and among Pharmaceutical Product Development, Inc., a North Carolina corporation having a place of business
at 3151 South Seventeenth Street, Wilmington, NC 28412 (hereinafter “PPD”) and its wholly owned subsidiary GenuPro, Inc., d/b/a PPD GenuPro, a North Carolina corporation having a place of business at 3900 Paramount Parkway, Morrisville,
North Carolina 27560 (hereinafter “GenuPro”), and ALZA Corporation, a Delaware corporation having a place of business at 1900 Charleston Road, Mountain View, CA 94043 (hereinafter “Licensee”). PPD, GenuPro and Licensee are
sometimes referred to herein individually as a “Party” and collectively as the “Parties.” 
 WITNESSETH
THAT: 
 WHEREAS, GenuPro, PPD and Licensee have entered into a LICENSE AGREEMENT (the “Agreement”) effective
as of the 2nd day of January, 2001 relating to the
development and commercialization of dapoxetine. 
 WHEREAS, GenuPro, PPD and Licensee wish to amend and supplement certain rights and
obligations as set forth under the terms of the Agreement under the terms and conditions set forth in this Amendment No. 1. 
 NOW,
THEREFORE, GenuPro, PPD and Licensee hereby agree as follows: 
 1. All capitalized terms used but not otherwise defined herein will have the
meanings ascribed to them in the Agreement. 
 2. Section 5.01 (License Fees) is amended by adding the following sentence to the end of
that section: “Licensee will make an additional one-time license fee payment to GenuPro of [*] within fifteen (15) days after Licensee’s receipt of this fully executed Amendment No. 1; provided, however, that such
payment will be fully refunded to Licensee in the event that Licensee terminates the Agreement prior to January 31, 2004 pursuant to Section 12.10 herein. 
 3. Section 5.02(a)(iii) (Approval of NDA) is amended by deleting the last sentence and replacing it with the following: “Within thirty (30) days of Licensee’s receipt of such written
approval, Licensee will pay GenuPro a one-time milestone payment of [*].” 
 4. Section 5.05 (Royalty Period) is amended
by adding the following sentence to the end of the section: “Notwithstanding the foregoing and subject to the limitations below, Licensee will have no obligation to pay royalties that would otherwise be owed to GenuPro under Section 5.03
based on worldwide Net Sales of Licensed Products for the period beginning on the date on which the first NDA approval in the United States is received for a Licensed Product and ending upon the expiration of [*] following the calendar
quarter in which such first NDA approval is 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

  

 1 

 received (the “Royalty Suspension Period”); provided, however, that the Royalty Suspension Period
will terminate immediately when the cumulative aggregate amount of royalties that would otherwise have been due to GenuPro pursuant to Section 5.03 and this Section 5.05 on Licensed Products, if such royalties had been paid without giving
effect to the first part of this sentence, equals the first to occur of (a) [*] on or before [*], or (b) [*] at any time thereafter. For clarity, the parties acknowledge and agree that
Licensee’s obligation to pay royalties to GenuPro under Section 5.03 shall resume immediately upon the expiration or earlier termination of the Royalty Suspension Period, but that Licensee will never have an obligation to pay royalties
that were not required to be paid during the Royalty Suspension Period. 
 5. Article V (Fees and Royalties) is amended by adding the following
new Section 5.09 to the end of the Article: 
 “5.09 [*]  
 6. Section 12.05 (Residual Obligation upon Termination) is amended in that the last sentence is deleted and replaced with the following: “Sections
5.09, 12.05, 12.06, 12.07, 12.08, 12.09, 13.01, 13.06, 13.09, 13.14, 13.15, and 13.17 and Articles I, VIII and XI shall survive any expiration or termination of this Agreement.” 
 7. Article XII is amended by adding the following new Section 12.10 to the end of that Article: 
 “Section 12.10 Special Right of Termination by Licensee. Licensee may terminate this Agreement on or before January 31, 2004, at its sole discretion, based on the results of in-life
animal carcinogenicity studies being performed on a certain Licensed Product by providing written notice of such termination to GenuPro or PPD on or before January 31, 2004.” 
 8. Section 13.11 (Release of Information) is amended in that the current existing paragraph in Section 13.11 will be referred to as subsection (a) and the following is added as new
subsection (b): 
 “(b) Notwithstanding anything in subsection (a) above to the contrary, PPD or GenuPro may make a
public disclosure regarding the Agreement that is factual and either is approved by Licensee, in its reasonable discretion, in advance or in the opinion of PPD’s or GenuPro’s counsel is required to be made by law, provided that in each
case, PPD or GenuPro shall provide Licensee a written copy of the intended disclosure at least 5 business days prior to the date of the disclosure or public announcement and that PPD and GenuPro incorporate any changes reasonably requested by
Licensee prior to making any such disclosure. 
 Except as otherwise amended herein, the Agreement shall remain in full force and effect.

  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

  

 2 

 IN WITNESS WHEREOF, the Parties have executed this Amendment No. 1 through duly authorized
representatives as of the date first set forth herein. 
  

									
	GenuPro, Inc.	 		 	ALZA Corporation
					
	By:	 	 	 		 	By:	 	 
					
	Name:	 	 	 		 	Name:	 	 
					
	Title:	 	 	 		 	Title:	 	 
			
	Pharmaceutical Product Development, Inc.	 		 	
					
	By:	 	 	 		 		 	
					
	Name:	 	 	 		 		 	
					
	Title:	 	 	 		 		 	

  

 3Buy-back Agreement

 EXHIBIT 10.11 
  
 Portions of this exhibit marked [*] are requested to be treated confidentially. 
  
 AGREEMENT 
  
 THIS AGREEMENT (“Agreement”) is entered
into as of July 13, 2005 between Takeda San Diego, Inc., a Delaware corporation having its principal place of business at 10410 Science Center Drive, San Diego, CA 92121, (formerly known as Syrrx, Inc.) (“TSD”), TAKEDA
PHARMACEUTICAL COMPANY LIMITED, a corporation organized under the laws of Japan, having its principal place of business at 1-1 Doshomachi 4-chome, Chuo-ku, Osaka, Japan (hereinafter “TPC”), Development Partners, LLC, a
Delaware limited liability company having its principal place of business at 3151 South 17th Street, Wilmington, NC 28412 (“PPD”), and Pharmaceutical Product Development, Inc., a North Carolina corporation having its
principal place of business at 3151 South 17th Street, Wilmington, NC 28412 (“PPD, Inc.”). TSD, TPC, and PPD and PPD, Inc. are sometimes referred to herein individually as a “Party” and collectively as the
“Parties”. 
  
 WHEREAS, TSD,
PPD and PPD, Inc. entered into a Collaboration Agreement (as defined below); 
  
 WHEREAS, pursuant to the Collaboration Agreement, PPD acquired the exclusive worldwide right to co-develop serine protease dipeptidyl peptidase IV inhibitors with TSD; 
  
 WHEREAS, Takeda America Holdings, Inc., a New York
corporation having its principal place of business at New York, NY (“Takeda”), acquired TSD effective March 16, 2005; 
  
 WHEREAS, the Parties now desire to, among other things, (i) terminate the Collaboration Agreement, (ii) reallocate ownership and
responsibilities for the future development and commercialization of Products (as defined below) and the rights related thereto; and (iii) provide for up-front and milestone cash payments and royalty payments based on Net Sales of Products (as
defined below) to PPD by TSD, all in accordance with the terms and conditions of this Agreement; 
  
 NOW, THEREFORE, in consideration of the foregoing and the premises and conditions set forth herein, the Parties agree as follows:

  
 ARTICLE 1 
  
 DEFINITIONS 
  
 1.1 “Affiliate” means, (a) with respect to TSD, (i) TPC;
(ii) Takeda or (iii) a particular person, corporation, partnership, or other entity that controls, is controlled by or is under common control with TSD, TPC or Takeda; and (b) with respect to PPD, (i) PPD, Inc. or (ii) a particular person,
corporation, partnership, or other entity that controls, is controlled by or is under common control with PPD or PPD, Inc. For the purposes of 

 the definition in this Section 1.1, the word “control” (including, with correlative meaning, the
terms “controlled by” or “under the common control with”) means the actual power, either directly or indirectly through one or more intermediaries, to direct the management and policies of such entity, whether by the ownership of
at least fifty percent (50%) of the voting stock of such entity, or by contract or otherwise. 
  
 1.2 “BLA” means a biologics license application with the FDA as more fully described at 21 CFR § 601.2, or successor equivalent. 
  
 1.3 “Collaboration Agreement” means the collaboration
agreement entered into among PPD, PPD, Inc. and TSD (then Syrrx, Inc.) effective as of November 19, 2003 to discover, develop, and commercialize serine protease dipeptidyl peptidase IV inhibitors as human drug products. 
  
 1.4 “Collaboration Compound” means any serine protease
dipeptidyl peptidase IV inhibitor [*] that (a) has [*] as measured internally by TSD using a [*] assay specific for the Target; or (b) has [*] and has not been shown to have [*] the Target, a list of which has been delivered to PPD by TSD.

  
 1.5 “Collaboration Patent Estate” means
(a) those Patents set forth in Schedule 1.5 and any continuation, division, continuation-in-part or foreign equivalents thereof, and (b) any Patents and any continuation, division, continuation-in-part or foreign equivalents thereof that
claim a Collaboration Compound, regardless of the nature of the claim (i.e. composition of matter, process, method, etc.). 
  
 1.6 “Combination Product” means a formulation including two or more active pharmaceutical ingredients, or a package including two or
more different pharmaceutical products, which includes Compound as one of the active pharmaceutical ingredients but does not include a Takeda Proprietary Compound as one of the active pharmaceutical ingredients. 
  
 1.7 “Compound” means (a) any Collaboration Compound; and
(b) any serine protease dipeptidyl peptidase IV inhibitor discovered by TSD [*] that falls within the scope of the Collaboration Patent Estate. For sake of clarity, an inhibitor of the Target is specifically excluded from the definition of a
Compound if such inhibitor (a) has [*] and has been shown to have [*] the Target, or (b) was Controlled by Takeda or an Affiliate of Takeda other than TSD [*]. 
  

1.8 “Confidential Information” shall have the meaning set forth in Section 8.1. 
  
 1.9 “Control” means, with respect to an item of
Information, Material or Intellectual Property right that a Party owns or has a license to, that the Party has the ability to disclose, assign and/or grant a license or sublicense as provided for by this Agreement under such Information, Material or
Intellectual Property right without violating the terms of any agreement or other arrangement with any Third Party. 
  
 1.10 “CTM” means a Product that is in a finished pharmaceutical dosage form that is (a) suitable for administration and dosing to
humans in clinical trials, but (b) not suitable for commercial sale (for example, without limitation, not in packaged form such as blister packs or other containers and not including external packaging and package inserts). 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 1.11 “Development Plan” means the 322 Development Plan and such other development plans
that TSD or its Affiliates may prepare in the future (for other Compounds), by which TSD or its Affiliates intend to achieve Regulatory Approval of a Product, including, but not limited to, a description of the CMC, preclinical, clinical, and
regulatory activities, with estimated timelines necessary to achieve such approval in the Field in the Territory. 
  
 1.12 “322 Development Plan” means the Development Plan for SYR110322 as shown in Schedule 1.12. 
  
 1.13 “Diligent Efforts” means the carrying out by TSD,
its Affiliate or its licensees or subcontractors of obligations or tasks in a sustained manner consistent with the commercially reasonable efforts TSD and its Affiliates devote to a research, development or marketing project for a pharmaceutical
product or products of similar market potential, profit potential or strategic value resulting from its own research efforts, based on conditions then prevailing. Diligent Efforts includes, but is not limited to the requirement that TSD and its
Affiliates use commercially reasonable efforts to carry out its obligations in accordance with timelines set forth in a Development Plan by: (a) promptly assigning responsibility for such obligations to specific employee(s) who are held accountable
for progress and monitor such progress on an on-going basis, (b) setting and consistently seeking to achieve specific and meaningful objectives for carrying out such obligations, and (c) consistently making and implementing decisions and allocating
resources designed to advance progress with respect to such objectives. The Parties understand and agree that delays outside the control of TSD may occur with regard to the clinical development of Compounds and that the occurrence of such
delays, in and of themselves, shall not be grounds for PPD to claim that a material breach of this Agreement has occurred so long as TSD used Diligent Efforts to avoid the occurrence of such delays, and is using Diligent Efforts to reduce the impact
of such delays following their occurrence. 
  
 1.14
“Drug Substance” means a Compound together with any formulation ingredients, that is suitable for administration and dosing to animals, other than humans. 
  
 1.15 “Effective Date” means the last date on which the Parties executed this Agreement. 
  
 1.16 “EMEA” means the European Medicine Agency.

  
 1.17 “EU” means the European Union
established under the Maastricht Treaty on February 7, 1992, as amended from time to time. 
  
 1.18 “FDA” means the United States Food and Drug Administration, or a successor federal agency thereto. 
  
 1.19 “Field” means all treatments of humans using a Product. 
  
 1.20 “Finished Product” means a Product in a finished
pharmaceutical dosage form that is suitable for commercial sale (for example, without limitation, in packaged form such as blister packs or other containers and including external packaging and package inserts). 
  
 1.21 “First Commercial Sale” means the first sale of a
Product by TSD, its Affiliates or its licensees for use, consumption or resale of such Product in a country 

 where Regulatory Approval of such Product has been obtained by TSD, its Affiliates or its licensees. Sale of
a Product by TSD to an Affiliate of TSD or a licensee of TSD shall not constitute a First Commercial Sale unless such Affiliate or such licensee is the end user of the Product. 
  
 1.22 “Good Clinical Practices” or “GCP” means current Good Clinical Practices as specified in
the United States Code of Federal Regulations, at the time of testing, and all FDA and ICH guidelines, including the ICH Consolidated Guidelines on Good Clinical Practices. 
  
 1.23 “Good Laboratory Practices” or “GLP” means current Good Laboratory Practices as
specified in the United States Code of Federal Regulations at 21 CFR §58 at the time of testing and all applicable ICH guidelines. 
  
 1.24 “Good Manufacturing Practices” or “GMP” means current Good Manufacturing Practices and standards as provided for (and
as amended from time to time) in European Community Directive 91/356/EEC (Principles and Guidelines of Good Manufacturing Practice for Medicinal Products) and in the Current Good Manufacturing Practice Regulations of the United States Code of
Federal Regulations Title 21 (21 CFR §§210-211) in relation to the production of pharmaceutical intermediates and active pharmaceutical ingredients, as interpreted by ICH Harmonized Tripartite Guideline, Good Manufacturing Practice Guide
for Active Pharmaceutical Ingredients, and subject to any arrangements, additions or clarifications agreed from time to time between the Parties. 
  
 1.25 “HSR Act” means Hart-Scott-Rodino Antitrust Improvement Act of 1976, as amended. 
  
 1.26 “IND” means an Investigational New Drug Application
for a Product filed with the FDA necessary to commence human clinical trials in conformance with applicable laws and regulations. 
  
 1.27 “Information” means information, results and data of any type whatsoever, in any tangible or intangible form whatsoever,
including without limitation, databases, inventions, practices, methods, techniques, specifications, formulations, formulae, knowledge, know-how, skill, experience, test data including pharmacological, biological, chemical, biochemical,
toxicological and clinical test data, analytical and quality control data, stability data, studies and procedures, and patent and other legal information or descriptions. 
  

 1.28 “Intellectual Property” means (a) all Regulatory Documentation, all Regulatory Filings and all Regulatory
Approvals; and (b) any and all inventions, developments, results, know-how and other Information (including physical, chemical or biological materials) made, conceived or reduced to practice by PPD or its Affiliates before the Effective Date or
during the Term of this Agreement, whether alone or jointly with TSD and its Affiliates or a Third Party that (i) relates to the composition of matter, manufacture or use of a Compound, or (ii) is incorporated into any Product or its use, or (iii)
is necessary for the discovery, identification, manufacture, development, or commercial use or sale of any Product. 
  
 1.29 “Joint Development Committee” or “JDC” means a committee composed as set forth in Section 4.5 and having the duties
set forth in Section 4.6. 
  
 1.30 “MAA”
means Marketing Authorization Application submitted to the EMEA. 

 1.31 “Marketing Authorization” means any Regulatory Approval required to market and
sell a Product in any country. 
  
 1.32 “Marketing
Plan” means an annual marketing plan prepared by TSD, its Affiliates or licensees or subcontractors, that includes, but is not limited to, a prospective description of TSD’s commercial objectives for the upcoming year with respect to a
Product throughout the Territory and the strategy by which TSD intends to achieve such objectives. 
  
 1.33 “Material” means any tangible material that comprises, consists of, or incorporates a Collaboration Compound and any precursor, prodrug, metabolite, ionized form (e.g., salt),
solvate (e.g., hydrate), stereoisomer (e.g., enantiomer, diastereomer, mixture of isomers), resonant form, or tautomer thereof. 
  
 1.34 “NDA” means a New Drug Application submitted and filed with the FDA necessary for approval of a Product in conformance with
applicable laws and regulations. 
  
 1.35 “Net
Sales” means the total gross amount billed or invoiced in United States dollars (or converted into US dollars in accordance with this Agreement) by TSD, its Affiliates, or licensees for sales of Products to a Third Party less, to the extent
included within the amount invoiced to and paid by the customer, deductions for: (a) transportation charges, and other charges, such as insurance, relating thereto, (b) sales and excise taxes, customs and any other taxes, all to the extent imposed
upon the sale of the Products and paid by the selling party and not refundable in accordance with applicable law (but not including taxes assessed against the income derived from such sale), (c) rebates or allowances actually granted or allowed to
group purchasing organizations, managed health care organizations and to governments, including their agencies, or to trade customers, in each case that are not Affiliates or licensees of TSD, (d) quantity discounts, cash discounts or chargebacks
actually granted, allowed or incurred in the ordinary course of business in connection with the sale of the Products, and (e) allowances or credits to customers, not in excess of the selling price of the Products, on account of governmental
requirements, rejection, outdating recalls or return of the Products. Such amounts shall be determined from the books and records of TSD maintained in accordance with GAAP or another generally accepted accounting method agreed by the Parties,
consistently applied. In the event a Product is sold as part of a Combination Product or a Takeda Combination Product, Net Sales for purposes of determining royalty and milestone payments hereunder, shall be as follows:  
  
 (i) Net Sales in United States of
Combination Products and Takeda Combination Products [*]: As long as [*], Net Sales of a Combination Product or a Takeda Combination Product, as the case may be, for purposes of determining royalty and milestone payments hereunder, shall be [*]%
of Net Sales of such Combination Product or Takeda Combination Product, as the case may be. For sake of clarity, [*] shall not, in and of themselves, cause a Combination Product or a Takeda Combination Product to be [*] pursuant to this Subsection
1.35(i). 
  
 (ii) Net
Sales in United States of Takeda Combination Products Not Subject to Section 1.35(i) [*]: In regard to Takeda Combination Products that are not subject to Section 1.35(i), for the [*] period commencing on [*], Net 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Sales of such Takeda Combination Product for purposes of determining royalty and milestone
payments hereunder, shall be [*]% of Net Sales of such Takeda Combination Product. For sake of clarity, [*] shall not, in and of themselves, cause a Takeda Combination Product to be [*] pursuant to this Subsection 1.35(ii). 
  
 (iii) Net Sales in United States of
Combination Products or Takeda Combination Products Not Subject to Sections 1.35(i-ii) [*]: In regard to Combination Products and Takeda Combination Products that are not subject to Sections 1.35(i-ii), for the [*] period commencing on [*], Net
Sales of such Combination Product or Takeda Combination Product, as the case may be, for purposes of determining royalty and milestone payments hereunder, shall be [*]% of Net Sales of such Combination Product or Takeda Combination Product, as the
case may be. For sake of clarity, [*] shall not, in and of themselves, cause a Combination Product or a Takeda Combination Product to be [*] pursuant to this Subsection 1.35(iii). 
  
 (iv) Net Sales in United States of Takeda Combination Products Not Subject to
Sections 1.35(i-iii) [*]: In regard to Takeda Combination Products that are not subject to Sections 1.35(i-iii), for the period commencing on [*], Net Sales of a Takeda Combination Product for purposes of determining royalty and milestone
payments hereunder, shall be [*]% of Net Sales of such Takeda Combination Product. 
  
 (v) Net Sales in United States of Combination Products Not Subject to Section 1.35(i) or Section 1.35(iii) [*]: In
regard to Combination Products that are not subject to Section 1.35(i) or Section 1.35(iii), for the period commencing on [*], Net Sales of such Combination Product for purposes of determining royalty and milestone payments hereunder, shall be [*]%
of Net Sales of such Combination Product. 
  
 (vi) Net Sales outside of United States of Takeda Combination Products and Combination Products: Net Sales outside of the United States for Takeda Combination Products and Combination Products, for the purpose of determining royalty
and milestone payments hereunder, shall be determined on a country by country basis by multiplying the actual Net Sales of the Takeda Combination Product or Combination Product by the fraction [*], where A is [*] and B is [*]. Where available in a
given country, the [*] or [*] for the other product(s) in the given country will be used as [*]. In the event that such [*] cannot be determined for either the Product or other product(s) in the Combination Product or the Takeda Combination Product,
Net Sales for purposes of determining royalty payments hereunder shall be calculated by multiplying the Net Sales of the Combination Product or Takeda Combination Product by the fraction [*], where C is [*] and D is [*], determined in accordance
with GAAP or another generally accepted accounting method agreed by the parties, consistently applied. PPD shall have the right to inspection to verify the accuracy of the calculation of the Net Sales in accordance with Section 6.5. 
  
 A sale of Product shall be deemed to have occurred upon the invoicing of such
Product to a Third Party; or if not invoiced, then when delivered, shipped, or paid for, whichever 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 first occurs, provided that there shall be no double counting of sales if a sale is deemed to have occurred
when Product is delivered to a Third Party. For purposes of clarification, a sale of a Product shall be deemed to be made in a particular country when the Product sold is intended for use by consumers in such country. In the case of a sale or other
disposal of a Product for value other than in an arm’s-length transaction exclusively for money, such as barter or counter-trade, the amount of such sale shall be calculated using the fair market value of such Product (if higher than the stated
sales price) in the country of disposition. 
  
 1.36
“Party” or “Parties” shall have the meaning set forth in the first paragraph of this Agreement. 
  
 1.37 “Patent” means (a) an unexpired letters patent (including inventor’s certificates) issued anywhere in the world which has
not been held invalid or unenforceable by a court of competent jurisdiction from which no appeal can be taken or has been taken within the required time period, including without limitation any substitution, extension, registration, confirmation,
reissue, re-examination, renewal or any like filing thereof, or (b) a pending application for a letters patent pending anywhere in the world, including without limitation any continuation, division or continuation-in-part thereof and any provisional
applications. 
  
 1.38 “Permitted Seller”
means TSD and any Affiliate, licensee or sublicensee having the right to sell Product, including without limitation, TPC and any permitted licensee of TPC. 
  

1.39 “Phase II Trial” means a clinical trial of a Product on patients, including possibly pharmacokinetic and dose ranging
studies, the principal purposes of which are to make a preliminary determination that such Product is safe for its intended use and to obtain sufficient information about such Product’s efficacy to permit the design of further clinical trials,
and generally consistent with 21 CFR §312.21(b). 
  
 1.40
“Phase III Trial” means that portion of the clinical development program that provides for the pivotal human clinical trials of a Product, which trial(s) is/are designed to (a) establish that such Product is safe and efficacious
for its intended use; (b) define warnings, precautions and adverse reactions that are associated with the Product in the dosage range to be prescribed; (c) be a pivotal study for submission of a NDA; and (d) be generally consistent with 21 CFR
§312.21(c). 
  
 1.41 “Phase III Development
Costs” means all development costs incurred by either Party with TSD’s prior approval under the Collaboration Agreement for (a) direct support of the performance of a Phase III Trial or (b) process development for a Product in a Phase
III Trial. For clarity, Phase III Development Costs include costs to formulate and manufacture Phase III Trial CTM. 
  
 1.42 “PMDA” means the Pharmaceutical and Medical Devices Agency in Japan. 
  
 1.43 “PPD Product” means a human therapeutic product
that comprises SYR110322, SYR110619, [*] that PPD develops under this Agreement by electing to exercise its option as to a PPD Product pursuant to Article 12. 
  

1.44 “Product” means a human therapeutic product that comprises, consists of, or 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 incorporates a Compound that has less than [*], or has [*] and has not been shown to have [*] the Target,
including a prodrug, metabolite, ionized form (e.g., salt), solvate (e.g., hydrate), stereoisomer (e.g., enantiomer, diastereomer, mixture of isomers), resonant form, or tautomer of such Compound together with any formulation ingredients, regardless
of the formulation or mode of administration of such Product. For sake of clarity, Product includes Combination Products and Takeda Combination Products. 
  
 1.45 “Regulatory Approval” means any and all approvals (including supplements, amendments, pre- and post-approvals, pricing and
reimbursement approvals), licenses, registrations or authorizations of any national, supra-national (e.g., the European Commission or the Council of the EU), regional, state or local regulatory agency, department, bureau, commission, council or
other governmental entity, that are necessary for the manufacture, distribution, use or sale of a Product in a regulatory jurisdiction. 
  
 1.46 “Regulatory Documentation” means, with respect to a Product, all regulatory filings and supporting documents created, submitted
to the FDA or any equivalent agency or government authority outside of the United States (including any supra-national agency such as in the EU) relating to such Product, and all data contained therein, including, without limitation, the contents of
any IND(s), NDA(s), BLA(s), Drug Master File, correspondence to and from the FDA or any equivalent agency or governmental authority outside of the United States, minutes from meetings (whether in person or by audio conference or videoconference)
with regulatory authorities, registrations and licenses, regulatory drug lists, advertising and promotion documents shared with regulatory authorities, adverse event files, complaint files and manufacturing records. 
  
 1.47 “Regulatory Filing” means the NDA or BLA or IND or
any foreign counterparts thereof and any other filings required by any regulatory agency, department, bureau, commission, council or other governmental entity in a regulatory jurisdiction relating to the study, development, manufacture or
commercialization of any Product. 
  
 1.48 “Serious
Adverse Event” means any adverse event related to a Product that results in any of the following outcomes: death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a
persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered a Serious Adverse Event when, based upon
appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. 
  
 1.49 “Takeda Combination Product” means a formulation including two or more active pharmaceutical
ingredients, or a package including two or more different pharmaceutical products, which includes a Compound and at least one Takeda Proprietary Compound. 
  
 1.50 “Takeda Proprietary Compound” means an active pharmaceutical ingredient that (i) [*], (ii) is not a Compound, (iii) either (x)
is Controlled exclusively or 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 semi-exclusively in a country or a region by TSD, TPC or Takeda or an Affiliate thereof, or (y) TSD, TPC or
Takeda or an Affiliate thereof has or had exclusive or semi-exclusive rights to commercialize and market such active pharmaceutical ingredient in a country or a region, and (iv) has been incorporated into a pharmaceutical product (including a
Product) that was introduced into the commercial market. ACTOS is one example of a Takeda Proprietary Compound. 
  
 1.51 “Target” means human serine protease dipeptidyl peptidase IV (DP4). 
  
 1.52 “Term” shall have the meaning assigned to it in
Section 10.1. 
  
 1.53 “Territory” means
throughout the world. 
  
 1.54 “Third Party”
means any individual, corporation, partnership, limited liability company or other entity other than (i) TSD, (ii) PPD or (iii) an Affiliate of either of them. 
  
 ARTICLE 2 
  
 COLLABORATION AGREEMENT 
  
 2.1 Termination of Collaboration Agreement. 
  
 (a) TSD and PPD agree that the Collaboration Agreement is hereby terminated in its entirety as of the Effective Date. As of the Effective
Date, the Collaboration Agreement shall have no further force or effect (including, subject to Section 2.1(a)(iii), any provisions that would otherwise survive) and no Party thereto shall have any further right or obligation thereunder except that:

  
 (i) PPD shall assign, and TSD shall assume, in
an Assignment and Assumption Agreement substantially in the form of Schedule 2.1(a)(i)(1), all contracts with Third Parties under or in connection with the Collaboration Agreement, including investigator sites, that are in existence as of the
Effective Date, to the extent assignable; provided, that PPD and TSD shall each use reasonable efforts to obtain any necessary consents from Third Parties promptly after the Effective Date. Schedule 2.1(a)(i)(2) lists all Third Party contracts in
existence as of the Effective Date. PPD confirms that it has provided TSD with true and correct copies of all Third Party contracts in existence as of the Effective Date and as listed in Schedule 2.1(a)(i)(2). 
  
 (ii) TSD shall have the obligations of payment for services to
be performed by PPD pursuant to the Collaboration Agreement as set forth in Section 5.4 of this Agreement; and 
  
 (iii) Articles 12, 14, 15, 16, and 17 and Sections 3.4(e)(ii) and 11.1 of the Collaboration Agreement shall survive termination. 

 
 (b) Without limiting the generality of the foregoing,
following the Effective Date, and except as specifically set forth herein, PPD shall not, directly or indirectly, have any liability or obligation for any cost or expense related to any Compound or Product, including but not limited to costs or
expenses for research, development, manufacturing, or commercialization of any Compound or any Product. 
  
 2.2 Reversion of License Rights in the Collaboration Agreement. Except as otherwise provided in Section 2.1(a) of this Agreement, as of the Effective Date, (a) all 

 rights and licenses granted by TSD to PPD under the Collaboration Agreement shall terminate and revert to
TSD, and (b) all rights and licenses granted by PPD to TSD under the Collaboration Agreement shall terminate and revert to PPD. 
  
 2.3 End of Collaboration Agreement Report. As soon as possible, but no later than thirty (30) days from the Effective Date, PPD shall provide to TSD a
written report summarizing the status of SYR110322 Phase II Trial and API production for Phase III through the Effective Date. The provision of such report shall not relieve PPD from its obligations under Section 3.3. Such report shall identify any
and all material written Information related to the API and Phase II Trial known to PPD as of the Effective Date. PPD shall also provide to TSD a final report for the SYR110619 Phase I trial on or about July 31, 2005. Following delivery of such
reports, TSD shall have a right to reasonably request through the JDC additional information from PPD relating to the SYR110322 and SYR110619 development programs and results, and PPD shall provide such information. 
  
 2.4 Mutual Release From Claims Arising Under the Collaboration Agreement.
Each Party, on behalf of itself and its predecessors, successors, parents, subsidiaries, Affiliates, segments or divisions, and present and former shareholders, officers, directors, employees, agents, assigns and representatives and their heirs,
family members and executors, hereby releases the other Party and its predecessors, successors, parents, subsidiaries, Affiliates, segments or divisions, and present and former members, shareholders, officers, directors, agents, employees,
representatives, attorneys, and assigns from any and all claims, demands, obligations, or liability of whatever kind, that it has, had, or may have against the other Party, whether asserted or otherwise and whether known or unknown, for any claims,
actions, or matters of any kind arising through the Effective Date in relation to the Collaboration Agreement, provided however, that such release shall not extend to any claims, demands, obligations, or liability of whatever kind, that it may have
against the other Party either under this Agreement or under the Collaboration Agreement arising after the Effective Date, or claims for indemnity under Article 15 of the Collaboration Agreement for matters covered under such indemnification
provisions that arose before the Effective Date. 
  
 2.5
California Civil Code Section 1542. The Parties represent that they are not aware of any claims other than the claims that are released by this Agreement. The Parties also acknowledge that they have been advised by legal counsel and each Party
hereby waives the provisions of California Civil Code Section 1542, which provides as follows: 
  
 A GENERAL RELEASE DOES NOT EXTEND TO CLAIMS WHICH THE CREDITOR DOES NOT KNOW OR SUSPECT TO EXIST IN HIS FAVOR AT THE TIME OF EXECUTING THE
RELEASE, WHICH IF KNOWN BY HIM MUST HAVE MATERIALLY AFFECTED HIS SETTLEMENT WITH THE DEBTOR. 

 ARTICLE 3 
  
 ASSIGNMENT and LICENSE 
  
 3.1 Assignment. Subject to all of the terms and conditions of this Agreement, PPD hereby irrevocably sells, assigns,
delivers, conveys, transfers and sets over to TSD, its successors and assigns the entire right, title and interest to Intellectual Property that PPD or an Affiliate of PPD Controls as of the Effective Date or during the Term of this Agreement.

  
 3.2 License. To the extent that PPD is unable to assign
any Intellectual Property Controlled by PPD or an Affiliate of PPD as of the Effective Date or during the Term of this Agreement, PPD hereby grants and shall grant to TSD a perpetual, worldwide, exclusive license (even as to PPD), with the right to
grant sublicenses as is reasonably necessary for TSD to achieve Rgulatory Approval and commercialize Products, to such Intellectual Property. To the extent that PPD is unable to grant an exclusive license to any Intellectual Property Controlled by
PPD or an Affiliate of PPD as of the Effective Date or during the Term of this Agreement, PPD hereby grants and shall grant to TSD a perpetual, worldwide, non-exclusive license, with the right to grant sublicenses as is reasonably necessary for TSD
to achieve Rgulatory Approval and commercialize Products, to such Intellectual Property. TSD agrees to perform under and abide by the terms and conditions of any underlying licenses to such Intellectual Property. 
  
 3.3 Delivery of Documents and Materials. Promptly following the Effective
Date, PPD shall deliver to TSD any and all data and documentation in PPD’s Control related to the development of a Compound or Product, and not in the possession of TSD, on the Effective Date. Following the Effective Date, PPD shall promptly
notify TSD if it later discovers any data or documentation in PPD’s Control related to the development of a Compound or Product that was not previously delivered to TSD and shall promptly deliver such to TSD. Promptly following the Effective
Date, PPD shall transfer to TSD the legal title to the associated INDs presently on file and any comparable filings in other countries of the Territory for SYR110322 and SYR110619. PPD shall transfer to TSD ownership of all Drug Substance, CTM and
Finished Product of SYR110322 and SYR110619 and any other Material in its possession as of the Effective Date of this Agreement, the amounts of which are listed on Schedule 3.3. 
  
 3.4 Notice of New Intellectual Property Developed by PPD After the Effective Date. PPD shall promptly provide TSD with
notice of any Intellectual Property that PPD develops following the Effective Date. PPD will promptly provide to TSD information and access to personnel reasonably requested by TSD that is necessary for seeking protection of such Intellectual
Property. All expenses incurred by TSD associated with seeking protection of Intellectual Property shall be paid by TSD. 
  
 ARTICLE 4 
  
 DEVELOPMENT 
  
 4.1 Control over Development. Subject to Section 4.3 and its obligations to use Diligent Efforts, TSD shall, directly or through its Affiliates or
licensees or subcontractors, have full control over implementation of all aspects of a Product’s development, marketing and commercialization throughout the Term of this Agreement, and shall be solely responsible for all costs and expense
associated therewith. 

 4.2 Design and Modifications to the Development Plan. Except as set forth in Section 4.3, TSD shall
consult PPD with regard to the design and implementation of a Development Plan as well as modifications to a Development Plan and take PPD’s suggestions into consideration. Except as set forth in this Section 4.2 and Section 4.3, TSD shall have
the right, in its sole reasonable discretion, to modify a Development Plan after TSD consults with PPD about any proposed material changes to a Development Plan and TSD shall give full consideration to any reasonable comments or suggestions by PPD.
TSD shall at all times exercise Diligent Efforts in the design, development, implementation, and modification of a Development Plan. 
  
 4.3 Development and Commercialization of SYR110322. During the term of this Agreement, TSD shall be responsible for the remainder of clinical and
non-clinical development of SYR110322 in accordance with the 322 Development Plan, and TSD shall be solely responsible for all costs and expenses associated therewith. TSD shall have the right to modify the 322 Development Plan from time to time as
reasonably necessary, [*]. TSD will use Diligent Efforts to submit applications for regulatory approval to market a Product comprising SYR110322 in the United States, EU and Japan, and will use Diligent Efforts to file an MAA in the European Union
for a Product comprising SYR110322 with the EMEA within [*] of acceptance of an NDA filing for a Product comprising SYR110322. Upon approval in a country, TSD shall use Diligent Efforts to market such Product in such country. TSD shall promptly
notify PPD in writing of the First Commercial Sale of a Product in each country. TSD shall use Diligent Efforts to exploit the lifecycle of the Product including, where appropriate, carrying out clinical trials and/or other studies on the Product
and obtaining Marketing Authorizations. TSD shall use Diligent Efforts to commercialize Product, including deploying sales personnel as necessary to promote the Product, taking into account the sales volume of the Product, the number of competitors,
the regulatory environment, and the potential for sales in a geographic area. TSD shall use Diligent Efforts to maximize the Net Sales of Products. 
  
 4.4 Development and Commercialization of Backup Product. Should TSD cease to develop and commercialize a Product comprising SYR110322 despite using
Diligent Efforts, then TSD shall use Diligent Efforts (and shall cause any Affiliates, licensees or subcontractors participating in the subject matter of this Agreement to use Diligent Efforts) to develop and introduce a Product comprising one of
SYR110619 [*] to the commercial market and to market such Product. Should TSD cease to develop and commercialize such Product despite using Diligent Efforts, then TSD shall use Diligent Efforts (and shall cause any licensees or subcontractors
participating in the subject matter of this Agreement to use Diligent Efforts) to develop and introduce a Product comprising [*] SYR110619 [*] to the commercial market and to market such Product. With respect to this Section 4.4, TSD will use
Diligent Efforts to submit applications for regulatory approval to market the SYR110619 [*] Product in the United States, EU and Japan. Should TSD cease to develop and commercialize such Product despite using Diligent Efforts, then TSD shall not
have any further obligation to develop alternative Compound(s) under this Agreement. 
  
 4.5 Joint Development Committee. Within thirty (30) days of the Effective Date, PPD and TSD shall assemble a JDC. Initially, the JDC will be composed of at least two, but no more than six,
representatives, with an equal number appointed by each of PPD and TSD, or their Affiliates. A list shall be provided to the other Party within thirty (30) days after the Effective Date. Each Party will promptly notify the other Party in writing of
any change in its appointed representatives. The chairperson of the JDC will be one of TSD’s or its Affiliate’s representatives. 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 4.6 Duties of JDC. The duties of the JDC shall include, but not be limited to, (a) reporting the
progress of all Development and Marketing Plans; (b) providing updates describing the progress made in designing and implementing new Development or Marketing Plan(s); (c) discussing potential modifications to any Development Plan; (d) reporting the
results of any efforts, if any, to evaluate potential therapeutic applications for Compounds other than type II diabetes; and (e) providing updates on discovery, non-clinical and preclinical, clinical development or marketing of Compounds other than
SYR110322. TSD shall promptly provide PPD with copies, through the JDC, of all Development Plans and Marketing Plans. TSD shall also provide PPD with copies through the JDC of all Regulatory Filings, Regulatory Documentation and communications with
regulatory agencies within ten (10) days of mailing or receipt of Regulatory Filings, Regulatory Documentation or communications, as the case may be, with a regulatory agency. TSD shall provide to PPD copies of all final clinical study reports. A
PPD JDC member shall have the right to consult with the JDC if the PPD JDC member reasonably believes information is needed from TSD in order to protect PPD’s interests, as the case may be, in the subject matter of this Agreement, and TSD
through the JDC shall reasonably cooperate in connection therewith. To accomplish its objectives, the JDC will meet quarterly, or more often if mutually agreed upon by the Parties, during the term of any Development Plan or during any period of
post-marketing regulatory activity, and will meet at least annually thereafter. The JDC may meet in person or by telephone or video conference. In-person JDC meetings will be held in Chicago, IL or such other sites that the Parties may mutually
agree upon. Each Party will bear all expenses of its personnel arising from attending such meetings. Among other duties, one of TSD’s JDC members shall prepare and promptly circulate to the other JDC members written minutes of each such
meeting, which minutes will, without limitation, record the updates given at the meetings describing the progress made in discovery, development, and commercialization of a Product. Both Parties acknowledge and agree that they intend to be as
transparent as reasonably possible with each other on all material issues relating to development and commercialization of Product, and that the forum for achieving such transparency shall be the JDC. 
  
 4.7 Decision Making By the JDC. TSD shall have a sole and final vote on
any issue and matter in the JDC after taking into account TSD’s obligation to use Diligent Efforts as set forth in Article 4. 
  
 4.8 Serious Adverse Event. TSD shall immediately inform PPD in writing of the occurrence of any Serious Adverse Event with regard to a Product.

  
 4.9 Clinical Development Collaboration. TSD agrees to
utilize PPD exclusively for clinical and bioanalytical CRO services related to the Phase II and Phase III Trials of Products that are conducted in support of obtaining Regulatory Approval in the U.S. and in the EU, in all cases, under terms and
conditions mutually acceptable to the Parties; provided that (a) PPD provides such services at [*] rates which are applied between PPD, Takeda Global Research and Development Center, Inc. (“TGRD”) and Takeda Europe Research &
Development Centre Ltd. (“TeuR&D), and (b) PPD demonstrates that it has and is maintaining the requisite technical expertise and capacity to reliably provide such services in a professional and competent manner. TSD will consider in good
faith using PPD for CRO services related to Phase IV trials 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 of the Products and biostatistics and data management services related to Phase II-IV trials of the
Products. CRO services performed by PPD pursuant to this Section 4.9 shall be governed by that certain Global Master Agreement, Clinical Research Management Services (Phase II-IV) dated July 1, 2004, that certain Global Master Agreement,
Bioanalytical Laboratory Services dated September 1, 2004 and that certain Global Master Agreement, Biostatistics and Data Management Services (Phase II-IV) dated July 13, 2005, each of which is executed among TGRD, TeuR&D and PPD Development,
LP (the “Takeda MSAs”). Schedule 4.9 includes a description of initial services that will be performed by PPD under the 322 Development Plan. Individual task orders, which more fully describe the specific types of services and
activities to be undertaken by PPD for each study under the 322 Development Plan, will be executed under the appropriate Takeda MSA. Each task order will be signed by TSD, as an affiliate of TGRD and TeuR&D. If PPD is asked to perform CRO
services for multiple Products at the same time, PPD shall conduct such CRO services for such multiple Products pursuant to the Development Plan for each such Product, and pursuant to guidance from TSD regarding the coordination between such
Products as necessary. In case of conflict between this Agreement and the Takeda MSAs regarding the assignment or license of Intellectual Property to TSD, the terms of this Agreement shall prevail. 
  
 ARTICLE 5 
  
 CONSIDERATION 
  
 5.1 Upfront Payment. Within thirty (30) days after the Effective Date,
TSD shall pay to PPD the sum of Fifteen Million Dollars ($15,000,000). 
  
 5.2 Milestone Payments. 
  
 (a) TSD
shall make the milestone payments set forth below to PPD within thirty (30) days of the occurrence of the related milestone events with regard to a Product. Each such milestone payment shall not come due until the related milestone event occurs and
shall only be payable upon the first occurrence of the related milestone event. Once TSD provides PPD with payment for the occurrence of a given milestone event, TSD shall have no further obligation to make any further milestone payments to PPD for
any future occurrence of such milestone event whether with the same Product or a different Product. TSD shall give PPD notice of the occurrence of a milestone event within five (5) business days of the occurrence of such milestone event. 

 

			
	 Milestone Event

	  	 Milestone Payment

	 First dosing of any Product to a subject in a
 Phase III Trial
	  	 Fifteen million dollars
 ($15,000,000)

	 [*]
	  	[*] million dollars ($[*])
	 [*]
	  	[*] million dollars ($[*])
	 [*]
	  	[*] million dollars ($[*])
	 [*]
	  	[*] million dollars ($[*])
	 [*]
	  	[*] million dollars ($[*])
	 [*]
	  	 [*] million [*] thousand
 dollars ($[*])

  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 (b) TSD shall pay to PPD milestone payments in accordance with the schedule set forth below
with regard to Products, based on total worldwide Net Sales of all Products for the first consecutive twelve month period during which such sales milestone event is achieved, such payment to be made within thirty (30) days after achievement of such
milestone event. Each of the milestone payments listed in Section 5.2(b) shall be payable only once under this Agreement regardless of the number of Products that individually achieve the sales milestone event in a given twelve month period or the
number of times a given Product achieves such sales milestone event in a given twelve month period. 
  

			
	 Sales Milestone Event

	  	 Milestone Payment

	 First time that aggregate worldwide Net Sales
 of all Products in a twelve consecutive month
 period exceed [*] dollars ($[*])
	  	[*] dollars ($[*])
	 First time that aggregate worldwide Net Sales
 of all Products in a twelve consecutive month
 period exceed [*] dollars ($[*])
	  	[*] dollars ($[*])

  
 5.3 Royalties. In accordance with the terms of Article 6 of this Agreement, TSD shall pay the following running earned royalties on a Compound by
Compound basis on cumulative annual (a fiscal year starting on April 1) Net Sales as set forth below for each Product sold. For purposes of clarification and illustration, examples of royalty calculations are set forth on Schedule 5.3. 

 
 Such royalties shall be payable on cumulative Net Sales on a
Compound by Compound basis and on a country-by-country basis beginning upon the First Commercial Sale of a Product in the country until the later of (a) the [*] year anniversary of the First Commercial Sale of that Product in that country or (b) [*]
following [*]. For the avoidance of doubt and except as provided in (a) of the preceding sentence, no royalties shall be payable by TSD with respect to Net Sales of Product after the date that is [*]. Royalties under this Section 5.3 shall be based
on cumulative Net Sales of Products containing the same Compound, as calculated in accordance with Section 1.35. 
  
 During the [*] period following expiration of all Patents in the Collaboration Patent Estate which [*], the specified royalty rate shall be
reduced [*]. For example, if there is at least one Patent in the Collaboration Patent Estate issued in a country that [*] and the applicable royalty rate is [*]%, then for a period of [*] following [*], the royalty rate will be [*]%. 
  
 Independent but including the preceding paragraph, the royalty
rates set forth in this Section 5.3 shall be reduced by [*] percent ([*]%) if [*]. For example, if the stated royalty rate is [*]%, then the royalty rate is [*]% if [*] and [*]% if the Product [*]. 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

	 	(a)	U.S. Net Sales. 

  

			
	 Annual Net Sales in the United States

	    	 Royalty rate(s) per annual U.S. Net Sales

	 On the portion of annual Net Sales less than [*] US dollars ($[*])
	    	[*] percent ([*]%) of Net Sales
		
	 On the portion of annual Net Sales equal to or greater than [*] US dollars ($[*]) but not greater than [*] US dollars
($[*])
	    	[*] percent ([*]%) of Net Sales
		
	 On the portion of annual Net Sales greater than [*] US dollars ($[*])
	    	[*] percent ([*]%) of Net Sales

  

	 	(b)	EU Net Sales. 

  

			
	 Annual Net Sales in the EU

	    	 Royalty rate(s) per annual EU Net Sales

	 On the portion of annual Net Sales less than [*] US dollars ($[*])
	    	[*] percent ([*]%) of Net Sales
		
	 On the portion of annual Net Sales equal to or greater than [*] US dollars ($[*]) but not greater than [*] US dollars
($[*])
	    	[*] percent ([*]%) of Net Sales
		
	 On the portion of annual Net Sales greater than [*] US dollars ($[*])
	    	[*] percent ([*]%) of Net Sales

  

	 	(c)	Japan Net Sales. 

  

			
	 Annual Net Sales in Japan

	    	 Royalty rate(s) per annual Japanese Net Sales

	 On the portion of annual Net Sales less than [*] US dollars ($[*])
	    	 [*] percent ([*]%) of Net Sales

		
	 On the portion of annual Net Sales equal to or greater than [*] US dollars ($[*]) but not greater than [*] US dollars
($[*])
	    	 [*] percent ([*]%) of Net Sales

		
	 On the portion of annual Net Sales greater than [*] US dollars ($[*])
	    	 [*] percent ([*]%) of Net Sales

  

	 	(d)	Rest of World Net Sales. 

  

			
	 Annual Net Sales in all countries (in the aggregate) other than the
 United States, EU and Japan

	    	 Royalty rate(s) per annual Net Sales in all countries (in the aggregate)
 other than the United States, EU and Japan

	 On the portion of annual Net Sales less than [*] US dollars ($[*])
	    	 [*] percent ([*]%) of Net Sales

		
	 On the portion of annual Net Sales equal to or greater than [*] US dollars ($[*]) but not greater than [*] US dollars
($[*])
	    	 [*] percent ([*]%) of Net Sales

		
	 On the portion of annual Net Sales greater than [*] US dollars ($[*])
	    	 [*] percent ([*]%) of Net Sales

  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 5.4 Costs and Expenses. The Parties shall apportion costs and expenses as follows: 
  
 (a) PPD shall be solely responsible for all direct and indirect
costs and expenses (including internal personnel and other internal costs and expenses) related to Phase II Trials pursuant to the Collaboration Agreement accrued prior to [*]; and 
  
 (b) TSD shall reimburse PPD for [*]% of all Phase III Development Costs accrued before [*] and PPD shall be
responsible for the remaining [*]% of such costs. 
  
 (c) Within six (6) months of the Effective Date, PPD shall submit a final request for reimbursement for any and all monies PPD seeks reimbursement for from TSD under Section 5.4(b) hereof. Schedule 5.4 lists all expenses that are
outstanding under Section 5.4(b) as of the Effective Date. TSD shall pay to PPD such amounts owed no later than thirty (30) days after receipt of such final request from PPD. 
  
 5.5 Third Party License Payments. If TSD, its Affiliates or licensees pay an upfront payment, milestone, royalty or
other payment to a Third Party in consideration for immunity from or license to such Third Party’s intellectual property rights with respect to the Product, then [*] percent ([*]%) of such payment shall be credited to TSD against the subsequent
royalty payment that comes due to PPD under Article 5, provided however, that no royalty payment to PPD under Article 5 shall be reduced by more than [*] percent ([*]%). For sake of clarity, a license to a specific pharmaceutical active ingredient
other than a Compound used in a Combination Product or a Takeda Combination Product shall not be treated as a Third Party License payment under this Section 5.5. Notwithstanding the foregoing, PPD shall reimburse TSD $500,000 for the [*].

  
 5.6 Payments Non-Refundable. All payments to PPD under
this Article 5 and Article 6 are noncreditable and nonrefundable, and TSD shall not have any right to set off any amounts provided to be paid under this Article 5 or Article 6. 
  
 ARTICLE 6 
  
 RECORDS; REPORTS AND PAYMENTS 
  
 6.1 Payment Method; Reports. 
  
 (a) All payments to PPD pursuant to Article 5 shall be made by Federal Reserve electronic wire transfer in immediately available funds to an
account designated by PPD. All payments pursuant to Article 5 and this Section 6.1(a) shall be made in U.S. dollars. 
  
 (b) Within forty five (45) days after the close of each calendar quarter in which there are any Net Sales during the Term, TSD shall furnish
to PPD a statement of 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Net Sales of each Product for such calendar quarter setting forth the Net Sales for each country in which
Products were sold during such calendar quarter, and a calculation of royalties due pursuant to Section 5.3, together with a payment for royalties due for such quarter. TSD will mail such report to the attention of: Pharmaceutical Product
Development, Inc., 3151 South 17th Street, Wilmington, North Carolina, 28412, Attn: Corporate Controller. The amount of royalty payment due to PPD shall be paid by TSD concurrently with the remittance of each royalty report. Interest shall accrue on
any payments due under this Agreement (including royalties) not paid when due through and including the date upon which PPD has collected the funds in accordance herewith at a rate equal to the lesser of (i) the sum of [*] percent ([*]%) plus the
prime rate of interest quoted in the Money Rates (or equivalent) section of The Wall Street Journal (or any substitute source mutually agreed to by the Parties), calculated daily on the basis of a three hundred sixty (360) day year, or (ii)
the maximum interest rate allowed by applicable law. Except as set forth in Section 6.3, payments pursuant to this Section 6.1(b) shall be made in U.S. dollars. 
  

6.2 Taxes. Each Party shall pay any and all taxes levied on account of all payments it receives under this Agreement. If laws or regulations
require that taxes be withheld, the paying Party will (a) deduct those taxes from the remittable payment, (b) pay the taxes to the proper taxing authority, and (c) send evidence of the obligation together with proof of tax payment to the non-paying
Party within thirty (30) days following that tax payment. Any such payments made by the paying Party shall be treated as having been made to the non-paying Party under this Article 6. 
  
 6.3 Blocked Currency. In each country where the local currency is blocked and cannot be removed from the country,
royalty payments pursuant to Section 5.3 arising from Net Sales made in that country shall be paid to PPD in the country in local currency by deposit in a local bank designated by PPD, unless the Parties otherwise agree. 
  
 6.4 Foreign Exchange. Conversion of sales recorded in local currencies to
U.S. dollars will be done for such currencies using the average rate of exchange for the applicable quarter based upon the daily rates for such currencies at the time published in The Wall Street Journal (or any substitute source mutually
agreed to by the Parties). 
  
 6.5 Records; Inspection. TSD
shall keep, and shall require its Permitted Sellers to keep, complete, true and accurate books of accounts and records for the purpose of determining the basis and accuracy of payments to be made under this Agreement. Such records shall be kept in
accordance with generally accepted accounting principals, showing Net Sales of Product on a country-by-country and Product-by-Product bases, and TSD’s or its Permitted Sellers’ usual internal practices and procedures, consistently applied.
Such books and records shall be kept for at least five (5) years following the end of the calendar quarter to which they pertain. Such records will be open for inspection by PPD during such five (5) year period by independent accountants reasonably
acceptable to TSD, solely for the purpose of verifying the basis and accuracy of amounts in the payment statements hereunder. Such inspections shall be made no more than once each calendar year, at reasonable time and on reasonable notice and shall
be limited to information related to Products. Results of any such inspection shall be deemed to be Confidential Information of TSD. If any errors in favor of TSD are discovered in the course of such inspection, then within thirty (30) days of
written request by PPD, TSD shall pay PPD those amounts that PPD would 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 have received in the absence of such errors, plus interest pursuant to and in accordance with Section
6.1(b). Inspections conducted under this Section 6.5 shall be at the expense of PPD, unless a variation or error in favor of TSD exceeding [*] percent ([*]%) of the amount stated for the period covered by the inspection is established in the course
of such inspection, whereupon all costs relating to the inspection for such period will be paid promptly by TSD. 
  
 ARTICLE 7 
  
 INDEMNIFICATION 
  
 7.1 TSD Indemnification of PPD. TSD hereby agrees to indemnify, defend and hold harmless PPD and its Affiliates and their directors, officers, agents and employees (the “PPD Indemnitees”) from and against any and all
damages, liabilities, expenses and/or loss, including reasonable legal expenses and reasonable attorneys’ fees (“Losses”) resulting from suits, claims, proceedings or causes of action (“Claims”) brought by a
Third Party against such PPD Indemnitee based on: (i) any claim arising out of any allegation of infringement or misappropriation of a Third Party’s intellectual property relating to the subject matter of this Agreement; (ii) any breach by TSD
or its Affiliates of a representation or warranty contained in this Agreement; (iii) any breach of this Agreement or applicable law by TSD or its Affiliates; (iv) the handling, possession, development, manufacturing, marketing, distribution,
promotion, sale or use of Product; (v) any product liability or other claim arising out of any allegation of injury or death caused by any person’s use of Product; (vi) any liability or other claim (including without limitation injury or death)
arising from the use of any Drug Substance, CTM, or Product; (vii) the breach or other violation of any underlying license to the Intellectual Property licensed to TSD by PPD in Section 3.2, by TSD and its Permitted Sellers and other licensees or
subcontractors; (viii) the exercise of any right(s) under the Intellectual Property, by TSD and its Permitted Sellers and other licensees or subcontractors; (ix) any failure by TSD or its Affiliates to comply in all material respects with applicable
laws in connection with the performance of their respective obligations or the exercise or their respective rights under this Agreement; (x) the negligence or willful misconduct of TSD or its Affiliates in the performance of this Agreement; and\or
(xi) liabilities arising from the contracts listed in Schedule 2.1(a)(i)(1) that are assigned to TSD pursuant to Section 2.1(a)(i), but only to the extent such liability arises from activities under such contracts that occur after the Effective
Date; except to the extent such PPD Losses result from (1) breach by PPD or its Affiliates of a representation or warranty contained in this Agreement; and/or (2) breach of this Agreement or applicable law by the PPD Indemnitee; and/or (3) the
negligence or willful misconduct of the PPD Indemnitee in the performance of this Agreement. TSD and TPC agree to indemnify, defend and hold the PPD Indemnitees harmless from and against any and all Losses arising from any Claim against the PPD
Indemnitees as a result of [*]. 
  
 7.2 PPD Indemnification of
TSD. PPD hereby agrees to indemnify, defend and hold harmless TSD and its Affiliates and their directors, officers, agents and employees (the “TSD Indemnitees”) from and against any and all Losses resulting from Claims brought by a
Third Party against such TSD Indemnitee based on: (i) breach by PPD or its Affiliates of a representation or warranty contained in this Agreement; (ii) any breach of this Agreement or applicable law by PPD or its Affiliates; (iii) any failure by PPD
or its Affiliates to comply in all material respects with applicable laws in 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 connection with the performance of its respective obligations or the exercise or its respective rights under
this Agreement; and/or (iv) the negligence or willful misconduct of PPD or its Affiliates in the performance of this Agreement; except to the extent such Losses result from (1) breach by TSD or its Affiliates of a representation or warranty
contained in this Agreement; (2) breach of this Agreement or applicable law by the TSD Indemnitee; and/or (3) the negligence or willful misconduct of the TSD Indemnitee in the performance of this Agreement. 
  
 7.3 Notice of Request for Indemnification. In the event that an
Indemnitee is seeking indemnification under Section 7.1 or Section 7.2, it shall inform the indemnifying Party of a claim as soon as reasonably practicable after it receives notice of the Claim, shall permit the indemnifying Party to assume
direction and control of the defence of the Claim (including the right to settle the Claim solely for monetary consideration), and shall cooperate as requested by the indemnifying Party (at the expense of the indemnifying Party) in the defence of
the Claim. 
  
 7.4 Limitation on Liability. IN NO EVENT SHALL
EITHER PARTY OR ITS AFFILIATES, OR THEIR DIRECTORS, OFFICERS, EMPLOYEES OR AGENTS BE LIABLE TO THE OTHER PARTY FOR ANY INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY OR CONSEQUENTIAL DAMAGES, WHETHER BASED UPON A CLAIM OR ACTION OF CONTRACT, WARRANTY,
NEGLIGENCE, STRICT LIABILITY OR OTHER TORT, OR OTHERWISE ARISING OUT OF THIS AGREEMENT, PROVIDED HOWEVER, THAT THE FOREGOING SHALL NOT PRECLUDE A CLAIM BY PPD FOR DAMAGES CAUSED BY A MATERIAL BREACH BY TSD OF ITS OBLIGATIONS UNDER THIS
AGREEMENT FOR THOSE PAYMENTS THAT PPD WOULD HAVE REALIZED PURSUANT TO ARTICLE 5 HAD TSD COMPLIED WITH ITS OBLIGATIONS UNDER THIS AGREEMENT. 
  
 7.5 Payment of Indemnification. Upon the final, unappealable determination of liability and the amount of the indemnification payment under this
Article, the indemnifying Party will pay such amount to the Indemnified Party in immediately available funds within thirty (30) days after such determination. 
  

7.6 Clinical Trial Insurance. Prior to TSD initiating any clinical trial with respect to a Compound or Product, TSD shall have and maintain such
type and amounts of liability insurance covering the development activities contemplated hereunder and that are normal and customary in the pharmaceutical industry generally for parties similarly situated, and shall name PPD as an additional insured
thereunder. TSD shall furnish to PPD certificates evidencing the insurance coverage, including amendments and revisions thereto, within five (5) business days of PPD’s written request. 
  
 ARTICLE 8 
  
 CONFIDENTIALITY AND PUBLICITY 
  
 8.1 Nondisclosure of Confidential Information. All Information disclosed
by one Party to the other Party pursuant to this Agreement shall be “Confidential Information,” provided that it is marked or otherwise identified as “confidential” or “proprietary.” The Parties agree that
during the Term, and for a period of five (5) years thereafter, a Party receiving Confidential Information of the other Party will (a) maintain in confidence such Confidential Information to the same extent such Party maintains its own proprietary
business information of similar kind and value (but at a

 
minimum each Party shall use commercially reasonable efforts), (b) not disclose such Confidential Information to any Third Party without prior written consent of the other Party, and (c) not use
such Confidential Information for any purpose except those permitted by this Agreement. 
  
 8.2 Exceptions. The obligations in Section 8.1 shall not apply with respect to any portion of the Confidential Information that the receiving Party can show by competent written proof: 

 
 (a) Is publicly disclosed by the disclosing Party, either
before or after it is disclosed to the receiving Party hereunder; or 
  
 (b) Was known to the receiving Party, without obligation to keep it confidential, prior to disclosure by the disclosing Party; or 
  
 (c) Is subsequently disclosed to the receiving Party by a Third Party lawfully in possession thereof and
without obligation to keep it confidential; or 
  
 (d) Has been published by a Third Party; or 
  
 (e) Has been independently developed by the receiving Party without the aid, application or use of all or any part of Confidential Information. 
  
 For purposes of clarification, all Information and Intellectual Property, including without limitation all Regulatory Filings, all Regulatory
Documentation and all Regulatory Approvals assigned by PPD to TSD pursuant to Section 3.1, shall be deemed Confidential Information of TSD and shall not be subject to the exceptions set forth in (b) and/or (e) in this Section 8.2. 
  
 8.3 Authorized Disclosure. A Party may disclose the Confidential
Information belonging to the other Party to the extent such disclosure is reasonably necessary in the following instances: 
  
 (a) Prosecuting or defending litigation; 
  
 (b) Complying with applicable court order, law, governmental regulations or the rules of any national securities exchange or association; and

  
 (c) Disclosure, in connection with the
performance of this Agreement, to licensees, research collaborators, employees, consultants, or agents, each of whom prior to disclosure must be bound by similar obligations of confidentiality and non-use at least equivalent in scope to those set
forth in this Article 8. 
  
 The Parties acknowledge
that the terms of this Agreement shall be treated as Confidential Information of both Parties. Such terms may be disclosed by a Party to investment bankers, investors, potential investors, lenders and other financing parties, provided that they are
bound by similar obligations of confidentiality and non-use at least equivalent in scope to those set forth in this Article 8. In addition, a copy of this Agreement may be filed by either Party with the Securities and Exchange Commission if such
filing is required by law or regulation. In connection with any such filing, such Party shall endeavour to obtain confidential treatment of such terms and other trade secret information to the extent permitted by the Securities and Exchange
Commission. Notwithstanding the foregoing, the Parties shall have the right to publicly disclose the financial information regarding this Agreement as set forth in Schedule 8.3. 

 ARTICLE 9 
  
 REPRESENTATIONS AND WARRANTIES AND COVENANTS 
  
 9.1 Representations and Warranties of the Parties. Each Party hereby
represents and warrants to the other Party that as of the Effective Date: 
  
 (a) Such Party is duly organized and validly existing and in good standing under the laws of the jurisdiction of its organization; 
  
 (b) Such Party has the full power and is duly authorized to enter into, execute and deliver this Agreement, and
to carry out and otherwise perform its obligations hereunder; 
  
 (c) This Agreement has been duly executed and delivered by, and is the legal and valid obligation binding upon such Party and the entry into, the execution and delivery of, and the carrying out and other
performance of its obligations under this Agreement by such Party (i) does not conflict with, or contravene or constitute any default under, any agreement, instrument or understanding, oral or written, to which it is a party, and (ii) does not
violate applicable law or any judgment, injunction, order or decree of any government authority having jurisdiction over it; and 
  
 (d) Such Party does not, to its knowledge, employ and will not, to its knowledge, employ, or use, a person or entity debarred under Section
306(a) or (b) of the Federal Food, Drug, and Cosmetic Act. Further, such Party, to its knowledge, does not employ and, to its knowledge, has not used a contractor or consultant that has employed, any individual or entity debarred by the FDA, or, to
the knowledge of such Party, any individual who or entity which is the subject of an FDA debarment investigation or proceeding. 
  
 9.2 Representations and Warranties of PPD. PPD hereby represents and warrants to TSD that as of the Effective Date that: 
  
 (a) To PPD’s knowledge PPD has the right and authority to
make the assignments and to grant the rights and licenses specified in Article 3 to TSD in all material respects; 
  
 (b) PPD’s interest in Intellectual Property arising under the Collaboration Agreement are free and clear of any lien, encumbrance,
security interest or restriction; 
  
 (c) PPD has not
granted any right, license or interest in, to or under the Intellectual Property inconsistent with the assignment and license rights granted to TSD under Article 3; 
  
 (d) PPD has no knowledge of any actions, suits, investigations, claims or proceedings pending or threatened
relating to the Intellectual Property; 
  
 (e) To
PPD’s knowledge, PPD has conducted research, development and other activities under the Collaboration Agreement in compliance with all applicable laws, regulations, standards, and guidelines in force in the United States, including, but not
limited to, the GCP, GLP, and GMP; 

 (f) PPD has disclosed to TSD all material Information regarding the Products in PPD’s
possession, including, but not limited to, all safety data and information; 
  
 (g) DISCLAIMER OF PPD IMPLIED WARRANTIES. EXCEPT AS EXPRESSLY PROVIDED IN THIS ARTICLE, PPD MAKES NO REPRESENTATION OR WARRANTY THAT THE USE OF INTELLECTUAL PROPERTY WILL NOT VIOLATE ANY
INTELLECTUAL PROPERTY RIGHTS OF ANY PERSON. PPD SPECIFICALLY DISCLAIMS ANY AND ALL IMPLIED OR STATUTORY WARRANTIES INCLUDING WARRANTIES OF MERCHANTABILITY AND OF FITNESS FOR A PARTICULAR PURPOSE WITH REGARD TO THE LIKELIHOOD OF SUCCESS OF PRODUCT
AFTER THE EFFECTIVE DATE, PROVIDED HOWEVER, THAT NOTHING IN THIS SECTION 9.2(g) SHALL BE CONSTRUED AS LIMITING PPD’S OBLIGATION TO DISCLOSE INFORMATION PURSUANT TO SECTION 2.3 AND 3.3 HEREUNDER TO TSD. 
  
 9.3 Covenants of PPD. For so long as there is development activity on
SYR110322, SYR110619 [*] by TSD or its Affiliates, or marketing or sales of Products by TSD, its Affiliates or licensees: 
  
 (a) PPD covenants that it will not discover, develop, or commercialize any product directed to the Target; 
  
 (b) PPD covenants that it will not acquire from any Third Party
the right to discover, develop, or commercialize any product directed to the Target; 
  
 (c) PPD covenants that it will not enter into any agreement in which any Third Party pursuant to such agreement discovers, develops, or commercializes any product directed to the Target; and 

 
 (d) PPD covenants that it will not invest in any Third Party
that, to PPD’s knowledge at the time such investment is made, is engaged or intends to engage in the discovery, development or commercialization of any product directed to the Target. 
  
 Notwithstanding the foregoing covenants, PPD may provide services to Third
Parties in connection with the preclinical and clinical development of one or more inhibitors of the Target and products containing or comprising such inhibitors, provided that (a) such services are limited to those that are usual and customary for
clinical research organizations in general and PPD in particular; and (b) PPD shall not retain (1) any right, title, interest or license in any such inhibitor; or (2) any right to receive (directly or indirectly) any consideration in connection with
the subsequent development, regulatory filings, regulatory approval, promotion or sales of such inhibitors or products (other than normal and customary fees and expenses charged by PPD for any such services). 
  
 9.4 Covenant of TSD and TPC. For the period extending from the Effective
Date until [*], TSD and TPC covenant that they will not (and will not permit their Affiliates to) (i) enter into a [*], or (ii) [*]. 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 ARTICLE 10 
  
 Term of Agreement 
  
 10.1 Term of Agreement. The term of this Agreement shall commence on the Effective Date and continue in full force and
effect until the later of the expiration of TSD’s obligation to pay royalties under Section 5.3 or the expiration of PPD’s obligation to pay royalties under Section 12.7, provided however, that the term shall expire on the twenty (20) year
anniversary of the Effective Date if at such time neither of the following events have occurred: (i) a First Commercial Sale of a Product or a first sale of a Product by PPD, its Affiliates or its licensees; or (ii) an issuance of a Patent in the
Collaboration Patent Estate (the “Term”). 
  
 10.2 Survival. Expiration of this Agreement shall not relieve any Party of any of its obligations that were incurred prior to expiration. In addition, Articles 3 (excluding Section 3.4), 7 (excluding Section 7.6) and 8, Sections 6.5,
13.2, 13.14 and 13.15, and the indemnification obligations set forth in the last sentence of Section 12.6 shall survive expiration of this Agreement. 
  
 ARTICLE 11 
  
 INTELLECTUAL PROPERTY MATTERS 
  
 11.1 Collaboration Patent Estate Maintenance. TSD shall have the sole right and responsibility in its commercially reasonable discretion at TSD’s
sole expense, for preparing, filing, prosecuting and maintaining Patents in the Collaboration Patent Estate. TSD shall keep PPD reasonably informed with respect to the status of such Patents and their prosecution. TSD shall provide to PPD, at least
on an annual basis, with a list accurately identifying the status of all Patents in the Collaboration Patent Estate. 
  
 11.2 Assistance with Intellectual Property Protection. PPD will provide to TSD information in PPD’s possession or Control and access to PPD
personnel as reasonably requested by TSD, at TSD’s sole cost, that is necessary or useful for seeking such Intellectual Property protection. All expenses incurred by TSD associated with seeking protection of Intellectual Property shall be paid
by TSD. In connection with any action involving a Patent in the Collaboration Patent Estate or a Product, PPD shall provide TSD with any information or assistance that TSD reasonably requests, at TSD’s sole cost. 
  
 11.3 Enforcement of Intellectual Property Rights 
  
 (a) If PPD believes that a Third Party is or may be infringing
a Patent in the Collaboration Patent Estate with respect to such Third Party’s serine protease dipeptidyl peptidase IV inhibitor, PPD shall immediately provide TSD notice of such belief and the related facts in reasonable detail to allow TSD to
assess the potential infringement. 
  
 (b) If a Third
Party infringes a Patent in the Collaboration Patent Estate with respect to such Third Party’s serine protease dipeptidyl peptidase IV inhibitor, TSD or its Affiliate shall have the sole right (but not the obligation) to pursue any and all
injunctive relief, and any or all compensatory and other remedies and relief (collectively, “Remedies”), against such Third Party. 

 11.4 Assistance and Cooperation. If TSD or its Affiliate pursues Remedies hereunder, PPD will use all
reasonable efforts to assist and cooperate with TSD or its Affiliate pursuing such Remedies. TSD will bear all costs and expenses relating to such pursuit. Any damages or other amounts collected with respect to such Third Party’s serine
protease dipeptidyl peptidase IV inhibitor will first be used to reimburse TSD for its out of pocket costs and expenses; and then, any remaining amount will be distributed [*]% to TSD and [*]% to PPD. 
  
 11.5 Trademarks. As between the Parties, TSD, its Affiliates or their
licensee shall own all trademarks developed by TSD or its licensee used to identify a Product sold by TSD. 
  
 ARTICLE 12 
  
 PPD OPTION TO PPD PRODUCTS 
  
 12.1 PPD Option #1 to Develop PPD Products. PPD may elect to pursue the development and commercialization of one or more of SYR110322, SYR110619, [*] as a PPD Product at such time that TSD is not
actively developing or commercializing at least one of SYR110322, SYR110619, [*] (“PPD Option #1”). 
  
 12.2 PPD Option #2 to Develop PPD Products. In the event that (a) PPD provides TSD with notice that a material breach has occurred under the Agreement with regard to TSD’s failure to use
Diligent Efforts to develop SYR110322, SYR110619, [*]; (b) TSD does not make substantial sustained efforts to effect a cure of such material breach within ninety (90) days of receipt of such written notice by PPD where such substantial sustained
efforts are reasonably likely to cure such breach; and (c) PPD provides notice that that such material breach has not been cured, then PPD may pursue the development and commercialization of the Compound that was the subject of the material breach
as a PPD Product if PPD provides notice to TSD within one (1) year from the date of written notice of such material breach (“PPD Option #2”). 
  
 12.3 PPD Election to Develop PPD Products. PPD may elect to exercise PPD Option #1 or PPD Option #2 by providing TSD with written notice indicating
the Compound(s) from among SYR110322, SYR110619, [*] which PPD desires to develop and commercialize. The Parties agree to make an appropriate filing with the Federal Trade Commission under the HSR Act, if necessary, as soon as practicable upon the
receipt by TSD of an election by PPD under this Section 12.3, and shall use their best efforts to expedite such filing. The Parties will share equally the HSR Act filing fee and will request early termination of the waiting period. 
  
 12.4 License to PPD regarding PPD Products. Subject to the terms of this
Agreement, TSD will grant to PPD as of the Effective Date a perpetual, royalty bearing, worldwide, exclusive (even as to TSD) license, with right to grant sublicenses, to all Intellectual Property owned or otherwise Controlled by TSD or its
Affiliates related to SYR110322, SYR110619, [*], to develop, make, have made, use, import, offer for sale and sell Products comprising SYR110322, SYR110619, [*] (the “PPD License”). To the extent that TSD is unable to grant an
exclusive license to any Intellectual Property Controlled by TSD or an Affiliate of TSD, such license granted by TSD to PPD will be non-exclusive with respect to such Intellectual Property. The PPD License granted by TSD to PPD pursuant to this
Section 12.4 is conditioned upon and shall only become 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 effective on a Compound by Compound basis following the exercise of PPD Option #1 or PPD Option #2 pursuant
to Sections 12.1-12.3, subject to the expiration or earlier termination of any notice and waiting period under the HSR Act, if necessary. Any costs not otherwise reimbursed by PPD for licenses to Third Party intellectual property rights acquired
pursuant to Section 5.5, to the extent transferred (TSD does not assure their transferability) from TSD to PPD at PPD’s request, shall be immediately reimbursed by PPD. 
  
 12.5 TSD Obligations Following PPD’s Exercise of Option #1 or Option #2. At such time that PPD exercises PPD Option
#1 or PPD Option #2 pursuant to Section 12.3, the PPD License shall become effective. Promptly following effectiveness of the PPD License, TSD shall deliver to PPD any and all data and documentation in TSD’s Control relating to the development
of such elected Compound. TSD shall also promptly notify PPD if it later discovers any data or documentation in TSD’s Control related to the development of such elected Compound that was not previously delivered to PPD and shall promptly
deliver such to PPD. TSD shall also transfer to PPD the legal title to the associated INDs presently on file and any comparable filings in other countries of the Territory for such elected Compound. TSD shall also transfer to PPD ownership of all
Drug Substance, CTM and Finished Product of such elected Compound and any other Material in TSD’s possession as of the time such option is exercised. 
  
 12.6 Control over development of PPD Products. Following the effectiveness of the PPD License, PPD shall have the right, at its sole discretion and
expense, to develop and commercialize such elected Compound. PPD shall be free to select Affiliates, licensees and subcontractors, in its sole discretion, to develop and commercialize PPD Products for such elected Compound, provided however, that
PPD shall be liable for all of its obligations under this Article. PPD shall also provide TSD with the same indemnification protection as TSD affords to PPD pursuant to this Agreement for Products. 
  
 12.7 Payments to TSD for PPD Products. In regard to any Compound(s) from
among SYR110322, SYR110619, [*] that PPD exercises Option #1 or PPD Option #2 pursuant to Section 12.3, then effective as of when PPD exercises such option, PPD shall have the same Milestone Payment and Royalty obligations to TSD that TSD would have
had to PPD under Article 5 of this Agreement if it were TSD developing such PPD Product instead of PPD. PPD shall pay TSD out of Net Sales of PPD Products all costs in regard to Drug Substance, CTM and Finished Product of such elected Compound and
any other Material transferred to PPD pursuant to Section 12.5. 
  
 12.8 Reversion to TSD absent PPD Diligent Efforts All rights granted to PPD under this Article shall be subject to reversion to TSD at any such time that PPD fails to utilize Diligent Efforts to develop and commercialize such elected
Compound or materially breaches its obligations under this Article including the payment obligations set forth in Section 12.7. 
  
 12.9 Exercise of PPD Option #2 not exclusive remedy. The Parties agree that PPD’s exercise of PPD Option #2 pursuant to Section 12.3 based on a
material breach shall not be exclusive or prejudicial to any other rights or remedies that PPD may otherwise have on account of the failure of TSD to use Diligent Efforts to develop SYR110322, SYR110619, [*]. 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 12.10 Specific Performance as Remedy for Breach of Section 12.5. The Parties agree that following
PPD’s proper exercise of PPD Option #1 or PPD Option #2 pursuant to Sections 12.1-12.3, should TSD fail to reasonably comply with its obligations under Section 12.5, then, following such breach, PPD shall have the right to seek specific
performance by TSD of its obligations under Section 12.5. 
  
 ARTICLE 13 
  
 MISCELLANEOUS 

  
 13.1 Entire Agreement; Amendment. This Agreement sets
forth the complete, final and exclusive agreement and all the covenants, promises, agreements, warranties, representations, conditions and understandings between the Parties hereto and supersedes and terminates all prior and contemporaneous
agreements and understandings between the Parties, including without limitation, the Collaboration Agreement. There are no covenants, promises, agreements, warranties, representations, conditions or understandings, either oral or written, between
the Parties other than as are set forth herein and therein. No subsequent alteration, amendment, change or addition to this Agreement shall be binding upon the Parties unless reduced to writing and signed by an authorized officer of each Party.

  
 13.2 Governing Law. Resolution of all disputes arising out
of or related to this Agreement or the performance, enforcement, breach or termination of this Agreement and any remedies relating thereto, shall be governed by and construed under the substantive laws of the State of New York, without regard to
conflicts of law rules that would provide for application of the law of a jurisdiction outside New York. 
  
 13.3 Notices. Any notice required or permitted to be given under this Agreement shall be in writing, shall specifically refer to this Agreement and shall be deemed to have been sufficiently given
for all purposes if mailed by first class certified or registered mail, postage prepaid, express delivery service or personally delivered. Unless otherwise specified in writing, the mailing addresses of the Parties shall be as described below.

  

			
	For TSD:	    	Takeda San Diego, Inc.
	 	    	10410 Science Center Drive
	 	    	San Diego, CA 92121
	 	    	Fax: (858) 550-0992
	 	    	Attention: General Counsel
		
	With a copy to:	    	Takeda Pharmaceutical Company Limited
	 	    	1-1 Doshomachi 4-chome, Chuo-ku, Osaka, Japan
	 	    	Fax: 81-6-6204-2055
	 	    	Attention: General Manager, Legal Department
		
	For PPD:	    	Development Partners, LLC
	 	    	3151 South 17th Street
	 	    	Wilmington, NC 28412
	 	    	Fax: (910) 762-5820
	 	    	Attention: President

			
	With a copy to:	    	Pharmaceutical Product Development, Inc.
	 	    	3151 South 17th Street
	 	    	Wilmington, NC 28412
	 	    	Fax: (910) 762-5820
	 	    	Attention: General Counsel

  
 13.4 United States Dollars. References in this Agreement to “Dollars” or “$” shall mean the legal tender of the United States of America. 
  
 13.5 No Strict Construction. This Agreement has been prepared jointly and
shall not be strictly construed against either Party. 
  
 13.6
Assignment. Neither PPD or TSD may sell, assign, transfer, convey, license, sublicense, pledge, or otherwise dispose (collectively “assignment”) this Agreement or any rights or obligations under this Agreement or any Intellectual
Property without the prior written consent of the other, provided, that (a) PPD or TSD may make such an assignment without the other Party’s consent to an Affiliate, provided that such Affiliate agrees in writing to be bound by the terms and
conditions of this Agreement, and, in the case of a transfer by TSD, any Intellectual Property so assigned by TSD or its Affiliates shall be subject to the PPD License, and (b) PPD may sell, assign, transfer, convey, license, sublicense, pledge, or
otherwise dispose to a Third Party without the other Party’s’ consent any right to milestone and/or royalty payments, or other payments that may inure to PPD’s benefit pursuant to the terms of this Agreement, and provided however,
that PPD may not assign PPD’s right to participate in the JDC pursuant to Section 4.5 or assign any rights PPD may have to perform CRO services for TSD pursuant to Section 4.9. Notwithstanding the foregoing, TSD shall have the right to
independently select and utilize Affiliates, licensees and subcontractors in its sole discretion to perform its duties under the Agreement, provided that TSD uses commercially reasonable efforts to cause such Affiliates, licensees and subcontractors
to use Diligent Efforts in performing such duties, TSD remains liable for all of its obligations under this Agreement, and any sale of Products by a Permitted Seller is included in Net Sales in accordance with Section 1.35. 
  
 13.7 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. 
  
 13.8 Further Actions. Each Party agrees to execute, acknowledge and deliver such further instruments, and to do all such other acts, as may be
necessary or appropriate in order to carry out the purposes and intent of this Agreement. 
  
 13.9 Severability. If any one or more of the provisions of this Agreement is held to be invalid or unenforceable by any court of competent jurisdiction from which no appeal can be or is taken, the
provision shall be considered severed from this Agreement and shall not serve to invalidate any remaining provisions hereof. The Parties shall make a good faith effort to replace any invalid or unenforceable provision with a valid and enforceable
one such that the objectives contemplated by the Parties when entering this Agreement may be realized. 
  
 13.10 Ambiguities. Ambiguities, if any, in this Agreement shall not be construed against any Party, irrespective of which Party may be deemed to have authored the ambiguous provision. 

 13.11 Headings. The headings for each article and section in this Agreement have been inserted for
convenience of reference only and are not intended to limit or expand on the meaning of the language contained in the particular article or section. 
  
 13.12 No Waiver. Any delay in enforcing a Party’s rights under this Agreement or any waiver as to a particular default or other matter shall not
constitute a waiver of such Party’s rights to the future enforcement of its rights under this Agreement, excepting only as to an express written and signed waiver as to a particular matter for a particular period of time. 
  
 13.13 Tax Treatment and Tax Structure Disclosure. Notwithstanding
anything herein to the contrary, any Party to this Agreement (and any employee, representative, or other agent of any Party to this Agreement) may disclose to any and all persons, without limitation of any kind, the tax treatment and tax structure
of the transactions contemplated by this Agreement and all Information, intellectual property of any kind (including opinions or other tax analyses) that are provided to it relating to such tax treatment and tax structure; provided however, that
such disclosure may not be made to the extent a lack of disclosure is reasonably necessary to comply with any applicable federal or state securities laws. For the purposes of the foregoing sentence, (a) the “tax treatment” of a transaction
means the purported or claimed federal income tax treatment of the transaction, and (b) the “tax structure” of a transaction means any fact that may be relevant to understanding the purported or claimed federal income tax treatment of the
transaction. 
  
 13.14 Dispute Resolution. (a) If a dispute
arises between the parties as to the interpretation or performance of any of the provisions of this Agreement or as to matters related to but not covered by this Agreement, then the Parties shall consult initially to try to resolve the matter
amicably. If they shall not be capable of resolving the matter within forty five (45) days of the dispute arising, the matter shall be dealt with in accordance with the provisions of Section 13.14(b). 
  
 (b) All disputes arising out of or in connection with the
Agreement shall be settled by final and binding arbitration by the American Arbitration Association (“AAA”), under its commercial rules then in effect except as provided herein. The arbitration will be conducted in New York, NY or such
other geographically neutral site within the United States that is mutually agreed by the Parties. All proceedings shall be held in English and a transcribed record prepared in English. The parties shall choose, by mutual agreement, one arbitrator
within twenty (20) days of the filing of an arbitration demand with the AAA. If the parties are unable to appoint an arbitrator within the time herein provided or any extension of time that is mutually agreed on, one arbitrator will be appointed by
PPD, one arbitrator will be appointed by TSD, and the third arbitrator will be appointed by the two arbitrators within thirty (30) days of the date on which the initial period for appointment of a sole arbitrator by mutual agreement lapsed. The
award rendered by the arbitrator shall include all costs of arbitration, reasonable attorneys’ fees and reasonable costs for expert and other witnesses, and judgment on such award may be entered in any court having jurisdiction thereof. Nothing
in this Agreement shall be deemed as preventing either party from seeking injunctive relief (or any other provisional remedy) from any court having jurisdiction over the Parties and the subject matter of the dispute as necessary to protect either
Party’s name, proprietary information, trade secrets, know-how or any other proprietary right. If the issues in dispute involve scientific or technical matters, any arbitrator chosen hereunder shall have educational training and/or experience
sufficient to demonstrate a reasonable level of knowledge in the field of biotechnology. 

 13.15 Joint Responsibility. (a) PPD and PPD, Inc. shall be jointly and severally liable for any and
all obligations of PPD hereunder. PPD, Inc. hereby unconditionally and irrevocably guarantees to TSD the performance of all of the obligations of PPD under this Agreement, including the due and prompt payment by PPD of any amounts payable under
Article 7 and Sections 12.6 and 12.7 of this Agreement and the satisfaction of each of the representations, warranties and indemnities of PPD set forth therein. In case of the failure of PPD promptly to satisfy any of its obligations under Article 7
and Sections 12.6 and 12.7 of this Agreement, PPD, Inc. hereby agrees to cause the payment of such amounts to be made promptly when and as such amounts become due and payable and as if such amounts were paid by PPD. PPD Inc.’s obligations under
this Section 13.15 shall survive any transfer of ownership of PPD, Inc. or any of its assets or the assignment by PPD, Inc. of any of its obligations under this Agreement. 
  

 (b) TSD and TPC shall be jointly and severally liable for any and all obligations of either of them hereunder. TPC hereby
unconditionally and irrevocably guarantees to PPD the performance of all of the obligations of TSD under this Agreement, including the due and prompt payment by TSD of any amounts payable under Articles 5, 6 and 7 of this Agreement and the
satisfaction of each of the representations, warranties and indemnities of TSD set forth therein. In case of the failure of TSD to promptly pay any amounts due to PPD pursuant Articles 5 or 6 of this Agreement, or to satisfy any of its obligations
under Article 7 of this Agreement, TPC hereby agrees to cause the payment of such amounts to be made promptly when and as such amounts become due and payable and as if such amounts were paid by TSD. TPC’s obligations under this Section 13.15
shall survive any transfer of ownership of TPC or any of its assets or the assignment by TPC of any of its obligations under this Agreement. 
  
 13.16 Schedules, Exhibits and Attachments. All schedules, exhibits and attachments referred to herein are intended to be and hereby are specifically
made part of this Agreement. However, if there is a conflict between a term or condition of such schedules, exhibits and attachments and this Agreement, the terms and conditions of this Agreement shall prevail. 
  
 13.17 Publicity. The Parties agree that the public announcement of the
execution of this Agreement shall be substantially in the form of the press release attached as Schedule 13.17. Any other written publication, news release or other written public announcement relating to this Agreement or to the performance
hereunder, shall first be reviewed and approved by both Parties; provided, however, that any disclosure which is required by law as advised by the disclosing Party’s counsel may be made without the prior consent of the other Party, although the
other Party shall be given prompt notice of any such legally required written disclosure and to the extent practicable shall provide the other Party an opportunity to comment on the proposed written disclosure. 
  
 13.18 Third-Party Beneficiaries; Affiliates. No Third Party is intended
or shall be deemed to be a beneficiary of any provision of this Agreement. TSD and TPC acknowledge that Affiliates of TSD and TPC have certain obligations under this Agreement, and TSD and TPC shall ensure that their respective Affiliates perform
and otherwise comply with all such obligations. Neither Party shall permit any of its Affiliates to take any action which, if taken by it, would violate its obligations hereunder. 

 [Signature page follows] 

 IN WITNESS WHEREOF, the Parties have signed this Agreement as of the date(s) set forth below.

  

			
	Takeda San Diego, Inc.
		
	 By:
	  	  

	 Name:
	  	 Steve Kaldor

	 Title:
	  	 President and Chief Scientific Officer

	 Date:
	  	  

	
	Takeda Pharmaceutical Company Limited
		
	 By:
	  	  

	 Name:
	  	 Yasuchika Hasegawa

	 Title:
	  	 President and Chief Operating Officer

	 Date:
	  	  

	
	Development Partners, LLC
		
	 By:
	  	  

	 Name:
	  	  

	 Title:
	  	  

	 Date:
	  	  

	
	Pharmaceutical Product Development, Inc.
		
	 By:
	  	  

	 Name:
	  	  

	 Title:
	  	  

	 Date:
	  	  

 Schedule 1.5 
  
 COLLABORATION PATENT ESTATE 
  

 [*] 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Schedule 1.12 
  
 322 DEVELOPMENT PLAN 
  
 [*] 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Schedule 2.1(a)(i)(1) 
  
 ASSIGNMENT AND ASSUMPTION AGREEMENT 
  
 THIS ASSIGNMENT AND ASSUMPTION AGREEMENT is made and entered into this
[            ] day of July, 2005 by and among Pharmaceutical Product Development, Inc., a North Carolina corporation, PPD Development, LP, a Texas limited partnership, and
Development Partners, LLC, a Delaware limited liability company (hereinafter collectively referred to as the “Assignor”) and Takeda San Diego, Inc., a Delaware corporation (hereinafter “Assignee”). Unless otherwise defined
herein, capitalized terms used in this Assignment and Assumption Agreement shall have the meanings assigned to them in the Agreement among the Assignor, the Assignee and Takeda Pharmaceutical Company Limited, dated as of July
[            ], 2005 (the “Agreement”). 
  
 WHEREAS, in accordance with the terms of the Agreement, Assignor is selling and assigning to Assignee, and Assignee is purchasing,
accepting assignment and assuming from Assignor, Assignor’s right, title, interest and obligations in, to and under certain contracts and other agreements of Assignor as set forth in Schedule 2.1(a)(i)(2) to the Agreement (hereinafter
“Assigned Contracts”); and 
  
 WHEREAS, Assignor and Assignee desire (i) to effect the transfer and assignment to Assignee of Assignor’s right, title and interest in, to and under the Assigned Contracts and (ii) to evidence the assumption by Assignee of all
obligations and duties thereunder. 
  
 NOW,
THEREFORE, for good and valuable consideration as set forth in the Agreement, it is agreed as follows: 
  
 1. Assignor hereby grants, conveys, sells, assigns and transfers to Assignee, its successors and assigns, forever, without reservation, all
of Assignor’s right, title and interest as of the date hereof in the Assigned Contracts. 
  
 2. Assignee hereby assumes and agrees that it will perform and discharge all liabilities and obligations of Assignor under the Assigned Contracts that arise or are to be performed from and after the date
hereof. 
  
 3. This Assignment and Assumption
Agreement has been executed and delivered pursuant to the Agreement, the terms, conditions, representations and warranties of which are incorporated by reference herein. This Assignment and Assumption Agreement shall not be deemed to modify or
supersede the Agreement in any manner whatsoever. 
  
 4, This Assignment and Assumption Agreement shall be binding upon and inure to the benefit of Assignor and Assignee and their respective successors and assigns, and shall be construed under and governed by the laws of the State of New York.
This Assignment and Assumption 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. 
  
 IN WITNESS WHEREOF, the parties hereto have caused this
Assignment and Assumption Agreement to be executed in counterparts on the date first above written. 
  

			
	 Pharmaceutical Product Development, Inc.

		
	By:	 	 
	 Name:
	 	 
	 Title:
	 	 
	
	 PPD Development, LP
 By: PPD GP, LLC
 Its: Sole General Partner

		
	By:	 	 
	 Name:
	 	 
	 Title:
	 	 
	
	 Development Partners, LLC
 By: Applied Bioscience International Inc.
 Its: Sole Manager

		
	By:	 	 
	 Name:
	 	 
	 Title:
	 	 
	
	 Takeda San Diego, Inc.

		
	By:	 	 
	 Name:
	 	 
	 Title:
	 	 

 Schedule 2.1(a)(i)(2) 
  
 THIRD PARTY CONTRACTS ASSUMED BY TSD 
  
 [*] 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Schedule 3.3 
  
 322 AND 619 MATERIAL 
  
 [*] 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Schedule 4.9 
  
 ADDENDUM FOR 322 DEVELOPMENT SERVICES 
  
 [*] 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Schedule 5.3 
  
 EXAMPLES OF ROYALTY CALCULATIONS 
  
 [*] 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Schedule 5.4 
  
 OUTSTANDING DEVELOPMENT EXPENSES 
  
 [*] 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Confidential 
  

 Schedule 8.3 
  
 AUTHORIZED PUBLIC DISCLOSURE 
  
 The parties shall have the right to disclose the following information: 
  

	•	 	 Takeda will pay PPD an upfront payment of $15 million, 

  

	•	 	 Takeda will pay PPD a development milestone of $15 million if and when the first dosing of a subject in a Phase III trial occurs,

  

	•	 	 Takeda will pay PPD additional milestone payments of up to $70.5 million upon the occurrence of certain milestone events. The parties may disclose the
milestone events, if SEC requires so. 

  

	•	 	 Commercial milestone payments of up to $33 million based on the achievement of specified worldwide sales targets for the DPP-IV compounds, and

  

	•	 	 Tiered Royalties, based on sales of the DPP-IV compounds. In the US, royalties range from middle single digit royalties to low double digit royalties.
For EU and Japan, royalties range from mid to upper single digit royalties, with similar royalties for ROW. 

 Schedule 13.17 
  
 PRESS RELEASE 
  
 Takeda Pharmaceutical Company Limited 
 PPD, Inc. 
  
 Contact for Takeda: 
 Seizo Masuda 
 +81-6-6204-2060 
 Masuda_Seizo@takeda.co.jp 
  
 Contact
for PPD: 
 Steve Smith 
 +910 772 7585 
 stephen.smith@wilm.ppdi.com 
  
 July xx, 2005 
  
 Takeda Acquires the Rights to DPP4 Inhibitors Granted to
PPDI 
  
 Osaka, Japan/Wilmington, N.C., July
xx, 2005 — Takeda Pharmaceutical Company Limited (“Takeda”) and PPD, Inc. (Nasdaq: PPDI) today announced an agreement in which Takeda acquired the development and marketing rights to all dipeptidyl peptidase IV (DPP4) inhibitors
previously granted to PPD under an agreement between PPD and Syrrx, Inc. Takeda acquired Syrrx, Inc., now known as Takeda San Diego, Inc., in March 2005. 
  
 Under the new agreement, Takeda, through Takeda San Diego, acquired all the remaining rights to develop and commercialize the DPP4
inhibitors, which rights had been shared by PPD and Takeda San Diego under the collaboration agreement dated November 19, 2003. In exchange for terminating the collaboration agreement and transferring its rights to Takeda, PPD will receive an
upfront payment of US$15.0 million, plus development and sales milestones, and royalties on sales of DPP4 inhibitors if approved for marketing. 
  
 The agreement further provides that PPD will serve as the sole provider to Takeda of Phase II and Phase III clinical development services in
the US and the EU for the DPP4 inhibitors. This will enable the DPP4 development program to continue without interruption. Further details of the financial terms of the agreement were not disclosed. 
  
 A variety of pre-clinical and clinical findings to date indicate
DPP4 inhibitors have the potential to treat type 2 diabetes. DPP4 degrades GLP-1 (Glucagon-like peptide-1), an important hormone that is released in response to the intake of food and that stimulates pancreatic beta cells to increase the secretion
of insulin and that has potential to improve beta cell function itself. DPP4 inhibitors, taken orally, work by blocking GLP-1 degradation to keep its concentration for a longer period of time. Therefore, DPP4 inhibitors are expected to be one of the
new generation agents for diabetes treatment. 
  
 “We are pleased to reach this agreement with PPD, allowing us full rights to DPP4 inhibitors created by our new colleagues at Takeda San Diego,” said Yasuchika Hasegawa, President & Chief Operating Officer of Takeda. “We
believe that these DPP4 inhibitors will enhance Takeda’s diabetes franchise in the future”. 
  
 “We too are excited with the new arrangement with Takeda for the continued development and commercialization of the DPP4 assets,”
said Fred Eshelman, Chief Executive Officer of PPD. “With the signing of this agreement, this becomes the second program under which we have advanced the clinical development of a compound and then transferred it to a third party for continued
development and commercialization, thereby further validating our compound partnering strategy. As a worldwide leader in diabetes medicines, we believe that Takeda is an outstanding partner for this program.” 
  
 ### 
  
 <About Takeda> 
 Takeda, located in Osaka, Japan, is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry,
Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products. 
 For more information on Takeda, visit our website, http://www.takeda.com 
  
 <About PPD> 
 As a leading
global provider of discovery and development services and products for pharmaceutical, biotechnology and medical device companies, PPD applies innovative technologies, therapeutic expertise and a commitment to quality to help clients maximize the
return on their R&D investments. With proven early discovery through post-market resources, the company also offers compound partnering opportunities. PPD has more than 7,100 professionals worldwide with offices in 28 countries. For more
information on PPD, visit our Web site at http://www.ppdi.com. 
  
 Except for historical information, all of the statements, expectations and assumptions contained in this news release, including the expectations and assumptions about the future development and commercialization of DPP4 inhibitors, are
forward-looking statements that involve a number of risks and uncertainties. Although PPD attempts to be accurate in making these forward-looking statements, it is possible that future circumstances might differ from the assumptions on which such
statements are based. In addition, other important factors which could cause results to differ materially include the following: risks associated with the development and commercialization of drugs; risks associated with and dependence on
collaborative relationships; rapid technological advances that make products less competitive; economic conditions and competition in the pharmaceutical industry; and the other risk factors set forth from time to time in the SEC filings for PPD,
copies of which are available free of charge upon request from the PPD investor relations department. 
  
  
 ### 
  
  

 Portions of this exhibit marked [*] are omitted and are requested to be treated
confidentially. 
  
 AMENDMENT NO. 1 TO THE
AGREEMENT 
  
 This Amendment No. 1 (the
“Amendment”), is effective as of the 10th day of October, 2005, by and among Takeda San Diego, Inc., a Delaware corporation having a place of business at 10410 Science Center Drive, San Diego, CA 92121 (“TSD”),
Takeda Pharmaceutical Company Limited, a corporation organized under the laws of Japan, having its principal place of business at 1-1 Doshomachi 4-chome, Chuo-ku, Osaka, Japan ( “TPC”), Development Partners, LLC, a
Delaware limited liability company having its principal place of business at 3151 South 17th Street, Wilmington, NC 28412 (“PPD”), and Pharmaceutical Product Development, Inc., a North Carolina corporation having its
principal place of business at 3151 South 17th Street, Wilmington, NC 28412 (“PPD, Inc.”). 
  
 WHEREAS, TSD, TPC, PPD and PPD, Inc. are parties to that certain Agreement dated July 13, 2005 (the “Agreement”); and

  
 WHEREAS, TSD, TPC, PPD and PPD, Inc. wish to
amend the Agreement in order to modify the timing and transfer of the IND for 322 and 619, modify milestone payments associated with Phase III development and clarify the contract assignment and indemnification obligations of the Parties.

  
 NOW, THEREFORE, that for and in consideration of
the foregoing premises, the mutual covenants herein contained, and other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the parties agree as follows: 
  
 1. All capitalized terms used but not otherwise defined herein
will have the meanings ascribed to them in the Agreement. 

 2. Schedule 2.1(a)(i)(2) (Third Party Contracts Assumed by TSD) is replaced in its entirety
with the attached new Schedule 2.1(a)(i)(2) in which subsection I (Renal Impairment Site Agreements) has been deleted. 
  
 3. Section 3.3 is replaced in its entirety with the following new Section 3.3: 
  
 3.3. Delivery of Documents and Materials. Promptly
following the Effective Date, PPD shall deliver to TSD any and all data and documentation in PPD’s Control related to the development of a Compound or Product, and not in the possession of TSD, on the Effective Date. Following the Effective
Date, PPD shall promptly notify TSD if it later discovers any data or documentation in PPD’s Control related to the development of a Compound or Product that was not previously delivered to TSD and shall promptly deliver such to TSD. PPD
transferred to Takeda Global Research & Development Center, Inc. (“TGRD”) the legal title to the associated INDs presently on file and any comparable filings in other countries of the Territory for SYR110322 and SYR110619 on
September 1, 2005. PPD shall transfer to TSD ownership of all Drug Substance, CTM and Finished Product of SYR110322 and SYR110619 and any other Material in its possession as of the Effective Date of this Agreement, the amounts of which are
listed on Schedule 3.3. 
  
 4. The table in
Section 5.2(a) is replaced in its entirety with the following new table for Section 5.2(a): 
  

			
	 Milestone Event

	 	 Milestone Payment

		
	 Dosing of any Product to the twentieth (20th) subject in a Phase III Trial
	 	 Fifteen million dollars ($15,000,000)

		
	 [*]
	 	 [*] million dollars ($[*])

		
	 [*]
	 	 [*] million dollars ($[*])

		
	 [*]
	 	 [*] million dollars ($[*])

		
	 [*]
	 	 [*] million dollars ($[*])

		
	 [*]
	 	 [*] million dollars ($[*])

		
	 [*]
	 	 [*] million [*] hundred thousand dollars ($[*])

  
 5. Section 7.1 is deleted in its entirety and replaced with the following: 
  
 7.1 TSD Indemnification of PPD. TSD hereby agrees
to indemnify, defend and hold harmless PPD and its Affiliates and their directors, officers, agents and employees (the “PPD Indemnitees”) from and against any and all damages, 

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 liabilities, expenses and/or loss, including reasonable legal expenses and reasonable
attorneys’ fees (“Losses”) resulting from suits, claims, proceedings, or causes of action (“Claims”) brought by a Third Party against such PPD Indemnitee arising from: (i) any allegation of infringement or
misappropriation of a Third Party’s intellectual property relating to the subject matter of this Agreement; (ii) any breach by TSD or its Affiliates of a representation or warranty contained in this Agreement; (iii) any breach of this
Agreement or applicable law by TSD or its Affiliates; (iv) the handling, possession, development, manufacturing, marketing, distribution, promotion, sale or use of Product; (v) any allegation of injury or death caused by any person’s
use of Product; (vi) any liability or other claim (including without limitation, injury or death) for the use of any Drug Substance, CTM, or Product; (vii) the breach or other violation of any underlying license to the Intellectual
Property licensed to TSD by PPD in Section 3.2, by TSD and its Permitted Sellers and other licensees or subcontractors; (viii) the exercise of any right(s) under the Intellectual Property, by TSD and its Permitted Sellers and other
licensees or subcontractors; (ix) any failure by TSD or its Affiliates to comply in all material respects with applicable laws in connection with the performance of their respective obligations or the exercise of their respective rights under
this Agreement; (x) the negligence or willful misconduct of TSD or its Affiliates in the performance of this Agreement; (xi) the contracts listed in Schedule 2.1(a)(i)(l) that are assigned to TSD pursuant to Section 2.1(a)(i), but
only to the extent such Claim arises from activities under such contracts that occur after the Effective Date; and/or (xii) the Letters of Indemnification, Phase II Clinical Research Agreements and Renal Impairment Site Agreements identified on
Schedule 7.1 attached hereto, but only to the extent a Claim arises from activities under such agreements that occur after the Effective Date. 
  
 The foregoing indemnification obligations shall not apply to the extent such PPD Losses result from (1) breach by PPD or its Affiliates
of a representation or warranty contained in this Agreement or, with respect to Section 7.1(xii) only, the Global Master Agreement, Clinical Research Management Services (Phases II-IV) dated July 13, 2005 executed by PPD, Takeda Global
Research & Development Center, Inc. and Takeda Europe Research & Development Centre Ltd. (“Clinical Agreement”); and/or (2) breach of this Agreement, applicable law or, with respect to Section 7.1(xii)
only, the Clinical Agreement by the PPD Indemnitee; and/or (3) the negligence or willful misconduct of the PPD Indemnitee in the performance of this Agreement or, with respect to Section 7.1(xii) only, the Clinical Agreement. TSD and TPC
agree to indemnify, defend and hold the PPD Indemnitees harmless from any Claim against the PPD Indemnitees as a result of [*]. 
  
 6. Attached hereto is a new Schedule 7.1 to the Agreement containing a list of Phase II Clinical Research Agreements and Letters of
Indemnification and a list of Renal Impairment Site Agreements for which TSD or an Affiliate of TSD will assume the role of sponsor as defined in 21 CFR §312.3(b) after the Effective Date. 

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 7. Section 7.3 is deleted in its entirety and replaced with the following: 

 
 7.3 Indemnification Procedure. 
  

	 	(a)	If any action is brought against a party entitled to indemnification under Section 7.1 or 7.2, as applicable, (each, an “Indemnified Party”), such
Indemnified Party or Parties shall promptly notify the party obligated to provide indemnification (an “Indemnifying Party”) in writing of the institution of such action. 

  

	 	(b)	Promptly upon receipt of notice pursuant to subparagraph (a) above, the Indemnifying Party shall promptly assume the defense of such action, including, without
limitation, the employment of counsel reasonably satisfactory to such Indemnified Party or Parties, and payment of expenses. An Indemnified Party or Parties shall have the right to employ its or their own counsel in any such case, but the fees and
expenses of such counsel shall be at the expense of such Indemnified Party or Parties, unless: 

  

	 	(i)	the employment of such counsel shall have been authorized in writing by the Indemnifying Party in connection with the defense of such action; or

  

	 	(ii)	the named parties to such action include both the Indemnified Party or Parties and the Indemnifying Party and such Indemnified Party or Parties shall have reasonably
concluded that there may be one or more legal defenses available to it or them or to other Indemnified Parties which are different from, or in addition to, those available to the Indemnifying Party. 

  
 In either of the foregoing events, such fees and expenses
shall be borne by the Indemnifying Party and the Indemnifying Party shall not have the right to direct the defense of such action on behalf of the Indemnified Party or Parties. Notwithstanding anything to the contrary set forth herein, under no
circumstances shall the Indemnifying Party be obligated to assume responsibility for the expenses for more than one counsel for all the Indemnified Parties. 
  
 (c) Notwithstanding anything contained in this Section 7.3 to the contrary, the Indemnifying Party shall not be liable for any
settlement of any such claim or action effected without its written consent, which consent shall not be unreasonably withheld. The Indemnifying Party shall have the right to settle or compromise any action, or permit a default or consent to the
entry of judgment in, or otherwise seek to terminate, any pending or threatened action, in respect of which indemnity may be sought hereunder (whether or not any Indemnified Party is a party thereto), provided such settlement, compromise,
consent, or termination includes an unconditional release of each Indemnified Party from all liability in respect of such action. In the event such an unconditional release is not obtainable for each Indemnified Party, then the Indemnifying Party
must obtain the prior written consent of any Indemnified Party not so released before the Indemnifying Party may enter into such settlement, compromise, consent or termination. 

 8. PPD represents and warrants that the Sites listed under “Phase II Clinical Research
Agreements and Letters of Indemnification” on Schedule 7.1 have not executed contracts with third party providers for services performed under the respective Clinical Research Agreements for Protocol [*] entitled, “[*]”. 

 
 9. Except as expressly provided herein, in the event of a
conflict between the terms of this Amendment and the Agreement, the terms of this Amendment shall control. 
  
 10. Except as otherwise amended herein, the Agreement shall remain in full force and effect. 
  
 IN WITNESS WHEREOF, the Parties have executed this Amendment
No. 1 through duly authorized representatives as of the date first set forth herein. 
  

							
	Takeda San Diego, Inc.	 	Takeda Pharmaceutical Company Limited
				
	By:	 	 /s/ Stephen W. Kaldor

	 	By:	 	 /s/ Yasuhiko Yamanaka

	Name:	 	 Stephen W. Kaldor

	 	Name:	 	 Yasuhiko Yamanaka

	Title:	 	 President and Chief Scientific Officer

	 	Title:	 	 General Manager, Corporate Strategy and Planning

		
	Development Partners, LLC	 	Pharmaceutical Product Development, Inc.
				
	By:	 	 /s/ Fred N. Eshelman

	 	By:	 	 /s/ Fred N. Eshelman

	Name:	 	 Fred N. Eshelman

	 	Name:	 	 Fred N. Eshelman

	Title:	 	 President

	 	Title:	 	 Chief Executive Officer

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Schedule 2.1(a)(i)(2) 
  
 THIRD PARTY CONTRACT TO BE ASSUMED BY TSD 
  
 [*] 
  

  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Schedule 7.1 
  
 CLINICAL RESEARCH AGREEMENTS AND 
 LETTERS OF INDEMNIFICATION 
  
 [*] 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC.

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