EXCLUSIVE LICENSE AGREEMENT



 Exhibit 10.1 
  
 Confidential Materials omitted and filed separately with the 
 Securities and Exchange Commission. Asterisks denote omissions. 
  
 EXCLUSIVE LICENSE AGREEMENT 
  
 BETWEEN 
  
 CHILDREN’S MEDICAL CENTER CORPORATION 
  
 AND 
  
 ICAGEN, INC. 
  
 This Agreement is made and entered into as of the date last written below
(the Effective Date), by and between Children’s Medical Center Corporation, a charitable corporation duly organized and existing under the laws of the Commonwealth of Massachusetts and having its principal office at 300 Longwood Avenue, Boston,
Massachusetts, 02115, U.S.A. (hereinafter referred to as “CMCC”), and ICAgen, Inc., a business corporation organized and existing under the laws of the State of Delaware and having its principal place of business located at 4222 Emperor
Boulevard, Suite 460, Durham, NC 27703 (hereinafter referred to as “Licensee”). 
  
 WHEREAS, CMCC is the owner of the CMCC Patent Rights which are identified in Appendix A and/or has the right to grant exclusive licenses under said CMCC Patent Rights for the Field of Use, subject only to a
royalty-free, nonexclusive license heretofore granted to the United States Government for those patents developed with U.S. Government funding; 
  
 WHEREAS, CMCC has the right to license its interest in the Sheffield Patent Rights which are identified in Appendix B for the Field of Use, subject only
to a royalty-free, nonexclusive license heretofore granted to the United States Government for those patents developed with U.S. Government funding; 
  
 WHEREAS, CMCC desires to have the Licensed Patent Rights utilized in the public interest and is willing to grant a license thereunder on the terms and
conditions described herein; 
  
 WHEREAS, Licensee has represented
to CMCC that Licensee is ready, willing and able, subject to obtaining necessary regulatory approvals and on the terms and conditions set forth herein, to engage in the commercial development, production, manufacture, marketing and sale of Licensed
Products and/or the use of Licensed Processes and that it shall commit itself (either directly or through Affiliates, Sublicensees or contractees) to a thorough, vigorous and diligent program of exploiting the Licensed Patent Rights in accordance
with the terms and conditions described herein so that public utilization shall result therefrom; and 
  
 WHEREAS, Licensee desires to obtain an exclusive license under the Licensed Patent Rights for the Field of Use on the terms and conditions of this
Agreement. 









 NOW, THEREFORE, in consideration of the premises and the mutual covenants contained herein, the parties
hereto agree as follows: 
  
 ARTICLE I. DEFINITIONS 
  
 For the purpose of this Agreement, the following words and phrases shall have
the meanings set forth below: 
  
 1.1 “Affiliate” shall
mean any company or other legal entity controlling, controlled by or under common control with Licensee. For purposes of the definition of “Affiliate” the term “control” shall mean: (i) in the case of a corporate entity, the
direct or indirect ownership of at least a majority of the stock or participating shares entitled to vote for the election of directors of that entity; (ii) in the case of a partnership, the power customarily held by a general partner to direct the
management and policies of such partnership; or (iii) in the case of a joint venture, whether in corporate, partnership or other legal form, a more than nominal economic interest and managerial role. 
  
 1.2 “Combination Product(s) or Process(es)” shall mean a product or
process that includes a Licensed Product or Licensed Process sold in combination with another component(s) whose manufacture, use or sale by an unlicensed party would not constitute an infringement of the Licensed Patent Rights. 
  
 1.3 “Field of Use” shall mean human and veterinary therapeutics and
diagnostics, but excluding NEWCO’s Field of Use. 
  
 1.4
“First Commercial Sale” shall mean with respect to each country: (i) the first sale of any Licensed Product or Licensed Process by Licensee, following approval of such Licensed Product’s or Licensed Process’s marketing by the
appropriate governmental agency, if any such approval is necessary, for the country in which the sale is to be made; or (ii) when governmental approval is not required, the first sale in that country of the Licensed Product or Licensed Process.

  
 1.5 “Gross Compensation” shall mean all
consideration received by Licensee and Affiliates from third parties for the manufacture, sale, commercialization, and/or sublicensing of the Licensed Patent Rights, the Technology and the Sublicensed Technology. Gross Compensation shall include:

  
 (a) all payments received by Licensee and/or
Affiliates as upfront payments, license fees, milestone payments, royalties, rentals, user fees or other sums received for the manufacturing, sales, commercialization and/or sublicensing of the Technology, and/or the Sublicensed Technology; for
further clarification, Gross Compensation does not include other sums received for solely sponsoring research or development, or as a bona fide equity or debt investment in Licensee or any of its Affiliates; and 
  
 (b) all non-cash compensation received by Licensee and/or
Affiliates such as stock, partnership interests, or other equity interests in a business entity when such equity interest is received by Licensee or Affiliates in return for the manufacturing, sales, 

  

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commercialization and/or sublicensing of the Technology and/or the Sublicensed Technology. 
  
 1.6 “Licensed Patent Rights” shall mean all of the following intellectual property which CMCC owns or has rights
to during the term of this Agreement: 
  
 (a) The
United States and foreign patents and/or patent applications listed in Appendix A and Appendix B attached hereto and incorporated herein by reference and divisionals and continuations thereof. 
  
 (b) The United States and foreign patents issued from the
applications listed in Appendix A and Appendix B and from divisionals and continuations of those applications. 
  
 (c) Claims of United States and foreign continuation-in-part applications, and of the resulting patents, which claim subject matter
specifically described and enabled in the United States and foreign patent applications described in Appendix A and Appendix B. 
  
 (d) Claims of all later filed foreign patent applications, and of the resulting patents, which claim subject matter specifically described
and enabled in the United States patent and/or patent applications described in subparagraphs (a), (b) or (c) of this Article I, Paragraph 1.6. 
  
 (e) Any reissues, divisions, amendments or extensions of the United States or foreign patents described in subparagraphs (a), (b), (c) or
(d) of this Article I, Paragraph 1.6. 
  
 1.7 “Licensed
Product” shall mean any product or part thereof: 
  

	 	1.	The manufacture, use of, importation of, sale of or offer for sale of which would infringe any Valid Claim contained in the Licensed Patent Rights in any country; or


  

	 	2.	The manufacture of which uses a “Licensed Process” 

  
 1.8 “Licensed Process” shall mean any process that would infringe any Valid Claim contained in the Licensed Patent Rights in any country.

  
 1.9 “NCEs” shall mean the compounds covered in whole
or in part by Sheffield Patent Rights. 
  
 1.10 “Net
Sales” shall mean gross receipts received by Licensee or Licensee’s Affiliates for sales of Licensed Products and/or Licensed Processes produced hereunder, less the sum of the following: 
  

	 	1.	Discounts, rebates allowances and adjustments actually allowed in amounts customary in the trade. 

  

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	 	2.	Sales taxes, tariff duties and/or use, excise, value-added, and similar government taxes directly imposed and with reference to particular sales. 

  

	 	3.	Outbound transportation, shipping, importation, and delivery charges (including insurance premiums related to transportation and delivery) prepaid or actually allowed.


  

	 	4.	Amounts allowed or credited on actual returns. 

  

	 	5.	Price reductions or rebates imposed by government authorities. 

  
 No deductions shall be made for commissions paid to individuals whether they are with independent sales agencies or regularly employed by Licensee and on
its payroll or for the cost of collections. Licensed Products and Licensed Processes shall be considered “sold” and “received” when actually collected. Notwithstanding anything herein to the contrary, the following shall not be
considered a sale of a Licensed Product or Licensed Process under this Agreement: (i) the transfer of a Licensed Product or Licensed Process to an Affiliate for sale by the Affiliate in a transaction that will be royalty bearing; (ii) the transfer
of a Licensed Product or Licensed Process to a third party without consideration to Licensee in connection with the development or testing of a Licensed Product or Licensed Process; or (iii) the transfer of a Licensed Product or Licensed Process to
a third party without consideration in connection with the marketing or promotion of the Licensed Product or Licensed Process. 
  
 1.11 “NEWCO’s Field of Use” shall mean the use of the NCE’s in the field of cancer, actinic keratosis and Kaposi’s sarcoma.

  
 1.12 “Sheffield Patent Rights” shall mean the
patents and patent applications set forth in Appendix B hereto. 
  
 1.13 “Sublicensee” shall mean a person or entity unaffiliated with Licensee to whom Licensee has granted an arm’s length sublicense under this Agreement. 
  
 1.14 “Sublicensed Technology” shall mean any and all patentable and unpatentable technology, Licensed Products,
Licensed Processes, compounds, devices, models, things, know-how, methods, documents, materials, copyrightable works, and all other information in CMCC’s custody and under CMCC’s control relating to the Licensed Patent Rights supplied by
ION to CMCC. 
  
 1.15 “Technology” shall mean
CMCC’s rights, as of the Effective Date hereof, to any and all patentable and unpatentable technology, Licensed Products, Licensed Processes, compounds, devices, models, things, know-how, methods, documents, materials, copyrightable works, and
all other information in CMCC’s custody and under CMCC’s control relating to the Licensed Patent Rights, but excluding Sublicensed Technology. 
  
 1.16 “Valid Claim” shall mean any claim of an issued patent which has not been held invalid or unenforceable in an unappealed or unappealable by
right decision by a court of competent jurisdiction, or a claim of a pending foreign patent application which has been pending not more than [**] years from its filing date in the country in which it is pending. 
  

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 ARTICLE II. GRANT 
  

2.1 CMCC hereby grants to Licensee and its Affiliates the worldwide right and exclusive license, including the right to grant sublicenses, under the
Licensed Patent Rights to make, have made, use, market, lease, import, offer for sale, sell and otherwise commercialize the Licensed Products and to practice the Licensed Processes in the Field of Use to the end of the term for which the Patent
Rights are granted, unless sooner terminated as provided in this Agreement. 
  
 2.2 CMCC hereby grants to Licensee and its Affiliates the worldwide right and license, with the right to grant sublicenses exclusively under the Sublicensed Technology in the Field of Use and hereby further grants to
Licensee and its Affiliates the worldwide right and license, with the right to grant sublicenses nonexclusively under the Technology (except for the Patent Rights, for which the license is exclusive), to make, have made, use, market, offer to sell,
sell, import or otherwise commercialize Licensed Products and to practice the Licensed Processes. Nothing in this grant, however, shall prevent CMCC from disseminating information included within the Sublicensed Technology or the Technology solely
for non-commercial research purposes with Licensee’s prior written consent, which shall not be unreasonably withheld or delayed, so long as Licensee’s commercial interests are not prejudiced by such dissemination. 
  
 2.3 The licenses granted hereunder shall not be construed to confer rights
upon Licensee by implication, estoppel, or otherwise as to any technology not specifically encompassed by the terms Technology and Sublicensed Technology. It is agreed and understood that the licenses granted hereunder do not confer any right upon
Licensee to any technology owned or controlled by Pharm-Eco Laboratories, Inc., including but not limited to any technology relating to methods of manufacturing the NCE’s, and that may be known to CMCC. 
  
 2.4 Notwithstanding anything above to the contrary, CMCC shall retain a
royalty free, nonexclusive, irrevocable license to practice (including the right to have made solely for its own non-commercial research purposes) the Sublicensed Technology and the Technology for non-commercial research purposes only, and to
provide materials under the Sublicensed Technology and the Technology to other non-profit research organizations under material transfer agreements which provide that such materials shall be used solely for non-commercial research purposes only;
provided however, that if Licensee has notified CMCC in writing that a particular compound or compounds are being considered as potential clinical compound candidates, CMCC shall not distribute such clinical candidate compounds to any third
party without Licensee’s written consent. 
  
 2.5
Notwithstanding anything above to the contrary, the license granted hereunder shall be subject to the rights of the United States government, if any, under Public Laws 96-517, 97-226, and 98-620, codified at 35 U.S.C. sec. 200-212 and any
regulations promulgated thereunder. 
  
 2.6 The granting and
acceptance of this Agreement is subject to “Harvard’s Statement of Policy in Regard to Inventions, Patents and Copyrights” dated March 17, 1986; and (ii) Public Law 96-517 and Public Law 98-620. Nothing in this Agreement shall prevent
HARVARD, 

  

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CMCC or their employees from seeking additional funding; however, in no event shall any rights under an agreement with non-profit or non-commercial sponsors
of research conflict with or affect in any way the right and license granted hereunder to Licensee by CMCC. Any rights granted in this Agreement greater than permitted under Public Law 96-517, 97-226 or 98-620 shall be subject to modifications as
may be required to conform to provisions of those statutes. 
  
 2.7 Licensee agrees that HARVARD retains the right to make and to use the information and technology relating to the Sheffield Patent Rights set forth in Appendix B for research purposes only and not for any commercial purpose. In the event
that, pursuant to Section 3.5 of the license agreement between Ion Pharmaceuticals, Inc., and CMCC dated July 1999, ION notifies CMCC of the name and address of the scientist and the not-for-profit institution to which HARVARD has transferred any
materials comprising the Sublicensed Technology, then CMCC shall promptly notify Licensee of such name and address. 
  
 2.8 Licensee understands and agrees that the licenses granted hereunder will be revoked if the activities of Licensee, its Sublicensees, Affiliates or
agents under the licenses granted in this Section II infringe upon NEWCO’s Field of Use. By “infringe,” it is meant that Licensee, its Sublicensees, Affiliates or agents conduct a clinical trial, advertise or sell a product for use in
NEWCO’s Field of Use or engage in activities which are determined, by a competent court or administrative body from which no further appeal can be or has been taken, to infringe, directly, contributorily or as inducement, the Sheffield Patent
Rights in NEWCO’s Field of Use. 
  
 2.9 Licensee agrees that
Licensed Products leased or sold in the United States shall be manufactured substantially in the United States. 
  
 2.10 In order to establish exclusivity for Licensee, CMCC hereby agrees that it shall not, without Licensee’s prior written consent, grant to any
other party a license to make, have made, use, lease, import, offer for sale and/or sell Licensed Products or to use the Licensed Processes in the Field of Use during the period of time in which this Agreement is in effect, except as otherwise
specified in this Agreement or as required by law to grant rights to the United States Government. 
  
 ARTICLE III. SUBLICENSING 
  
 3.1 Licensee shall have the right to enter into sublicensing agreements with respect to any of the rights, privileges, and licenses granted hereunder, subject to the terms and conditions hereof. Such sublicenses will
terminate upon the termination of Licensee’s rights granted herein unless events of default are cured by Licensee or Sublicensee within [**] days of notification by CMCC of default and/or as provided by the terms of this Agreement. Any
sublicensing agreement shall include an audit right by HARVARD of the same scope as provided by Article VI hereof. No such sublicensing agreement shall contain any provision which would cause it to extend beyond the term of this Agreement.

  
 3.2 Licensee agrees that any sublicense granted by it shall
provide that the obligations to CMCC of Articles II (Grant), VI (Reports and Records), VIII (Infringement), IX (Insurance and Indemnification), XII (Export Controls), XIII (Non Use of Names), XIV (Assignment), XV (Dispute Resolution), XVI (Term and
Termination) and XVIII (Miscellaneous Provisions) of this 

  

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Agreement shall be binding upon the sublicensee as if it were a party to this Agreement. Licensee further agrees to attach a copy of this Agreement to all
sublicense agreements. 
  
 3.3 Licensee agrees to provide to CMCC
notice of any sublicense granted hereunder and to forward to CMCC promptly upon execution a copy of any and all fully executed sublicense agreements. Licensee further agrees to forward to CMCC annually a copy of such reports received by Licensee
from its sublicensees during the preceding twelve (12) month period as shall be pertinent to a royalty accounting under the applicable sublicense. 
  
 3.4 All sublicenses granted by Licensee hereunder shall include a requirement that the sublicensee use its commercially reasonable efforts to bring the
subject matter of the sublicense into commercial use as promptly as is reasonably possible. 
  
 3.5 Licensee shall advise CMCC in writing of any consideration received from sublicensees under this Agreement. Licensee shall not accept from any sublicensee anything of value in lieu of cash payments to discharge
sublicensee’s payment obligations under any sublicense granted under this Agreement, without the express written permission of CMCC, which permission shall not be unreasonably withheld. 
  
 3.6 CMCC agrees that if Licensee has provided to CMCC notice that Licensee
has granted a sublicense to a sublicensee under this Agreement, then in the event CMCC terminates this Agreement for any reason, CMCC shall provide to such sublicensee no less than thirty (30) days prior to the effective date of said termination,
written notice of said termination at the address specified by Licensee to CMCC in Licensee’s notice to CMCC under Paragraph 3.3 of this Article III. CMCC agrees that upon the sublicensee’s notice as described below and provided the
sublicensee is not in breach of its sublicense, CMCC shall grant to such sublicensee license rights and terms equivalent to the sublicense rights and terms which the Licensee shall have granted to said sublicensee; provided that the sublicensee
shall remain a sublicensee under this Agreement for a period of at least sixty (60) days following receipt of notice from CMCC. Sublicensee shall during said sixty (60) day period provide to CMCC notice wherein the sublicensee: (i) reaffirms the
terms and conditions of this Agreement as it relates to the rights the sublicensee has been granted under the sublicense; (ii) agrees to abide by all of the terms and conditions of this Agreement applicable to sublicensees and to discharge directly
all pertinent obligations of Licensee as it relates to the sublicense which Licensee is obligated hereunder to discharge; and (iii) acknowledges that CMCC shall have no obligations to the sublicensee other than its obligations set forth in this
Agreement with regard to Licensee. 
  
 ARTICLE IV. DUE DILIGENCE

  
 4.1 Licensee (either directly or through Affiliates,
contractees or Sublicensees) shall use its good faith and diligent efforts to bring one or more Licensed Products and/or Licensed Processes to market as soon as reasonably practicable, consistent with sound and reasonable business practices and
judgment. Thereafter, Licensee agrees that until expiration or termination of this Agreement, Licensee shall continue active and diligent efforts to keep Licensed Products and/or Licensed Processes reasonably available to the public. In the event
Licensee decides not to exploit a Licensed Patent Right in a particular country, it shall promptly inform CMCC in writing and shall surrender to CMCC its license to that Licensed Patent Right in that country. 
  

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 4.2 The parties acknowledge that Licensee has provided to CMCC prior to the date of execution of this
Agreement a written commercialization development plan (“Development Plan”) setting forth the initial indications and markets for Licensed Products and Licensed Processes, including to the extent practicable: (i) time-delimited targets for
pre-clinical development, clinical trials, regulatory approval, manufacturing and marketing that represent reasonable efforts, consistent with industry norms for similar technology and applications, to bring Licensed Products and Licensed Processes
to the marketplace; and (ii) actual or projected financial resources and/or strategic alliances that will be required to implement the Development Plan. The Development Plan is attached hereto as Appendix C and is hereby incorporated herein by
reference. 
  
 4.3 Licensee and any Sublicensee or Affiliate shall
use its good faith and diligent efforts to accomplish the milestones set forth in the Development Plan and to manufacture and distribute Licensed Products and Licensed Processes. 
  
 4.4 CMCC shall not unreasonably withhold its assent to any revision of the objective(s) set forth in the Development Plan
when requested in writing by Licensee and supported by reasonable evidence: (i) of technical difficulties or delays in the clinical studies or regulatory process that Licensee could not have reasonably avoided; or (ii) that Licensee, its Affiliates
and/or Sublicensees have expended good faith and diligent efforts and adequate resources to meet said objective. 
  
 4.5 In the event CMCC reasonably believes that Licensee is not reasonably and diligently seeking to achieve the objectives set forth in the Development
Plan in a timely manner, CMCC shall so notify Licensee in writing. Licensee shall have the option, exercisable by written notice to CMCC provided within ten (10) days after receipt of any such notice, to either: (i) receive a [**] grace period to
reasonably establish that Licensee is expending its good faith and diligent efforts and adequate resources to achieve said objectives; or (ii) agree to CMCC’s termination of this Agreement as provided hereafter. In the event Licensee agrees to
termination of this Agreement, CMCC shall immediately terminate the license granted to Licensee under this Agreement. In the event Licensee fails to reasonably establish its diligence as provided above prior to expiration of the [**] grace period,
CMCC shall have the right to terminate the license granted to Licensee under this Agreement or to convert the license granted to Licensee hereunder to a nonexclusive license on financial terms and conditions mutually agreed to by CMCC and Licensee.

  
 4.6 In the event that CMCC believes that Licensee fails to
meet the objective(s) set forth in the Development Plan in a timely manner, CMCC shall notify Licensee thereof in writing, and Licensee shall have [**] days following such notification to establish to that (i) it has met such objective(s); or (ii) a
revision to the Development Plan is necessary and appropriate as contemplated above. In the event that Licensee fails to reasonably establish that it has met such objectives and Licensee has not submitted a revision to the Development Plan, then the
issue of whether the objectives have been met shall be submitted to arbitration in accordance with the provisions of Article XV of this Agreement and this Agreement shall remain in effect until the arbitrator renders a decision and for a period
thereafter sufficient to carry out the decision. In the event Licensee fails to reasonably establish that the objectives have been met and has submitted a revision to the development plan, but Licensor reasonably believes Licensee 

  

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has failed to reasonably establish the need for such revision to the Development Plan and the appropriateness of such revision, the issues of whether the
objectives have been met and the need for and scope of the revision shall be submitted to arbitration in accordance with the provisions of Article XV of this Agreement. In such case, the revision shall be given immediate effect. This Agreement,
including such revision, shall remain in effect until the arbitrator renders a decision and for a period thereafter sufficient to carry out the decision. In considering the issues of need for and scope of the revision, the arbitrator shall be guided
by considerations of the actual cause of the need for revision so that if the need for revision occurs despite the good faith efforts consistent with industry norms of Licensee, then the arbitrator shall find in favor of Licensee, as to the need for
the revision. If the arbitrator does not find in favor of Licensee on whether the objectives have been met or on the need for a revision to the Development Plan, CMCC shall have the right in its discretion to, within [**] days of the
arbitrator’s decision, either terminate the license granted to Licensee under this Agreement or to convert the license granted to Licensee hereunder to a non-exclusive license on financial terms and conditions mutually agreed to by CMCC and
Licensee. 
  
 4.7 Licensee shall fund research at Children’s
Hospital in accordance with the terms of the Sponsored Research Agreement between Licensee and CMCC to be negotiated in good faith by the parties hereto. Such Sponsored Research Agreement shall include the terms set forth in Appendix D hereto. In
the event Licensee terminates the Sponsored Research Agreement within [**] years of its initiation without cause or Hospital terminates said agreement under Paragraphs 8 (b), (c), or (d) of that agreement, this License shall remain in full force
until such time and thereupon shall terminate. In the event Licensee terminates the Sponsored Research Agreement for cause as defined in Article 8 (d), (f), or (j), licenses or options granted pursuant to the Sponsored Research Agreement may not be
terminated by CMCC. 
  
 4.8 Licensee shall provide to CMCC and to
HARVARD written annual reports within sixty (60) days after June 30 of each calendar year which shall include but not be limited to: reports of progress on research and development, regulatory approvals, manufacturing, sublicensing, marketing and
sales during the preceding twelve (12) months as well as plans for the coming year (“Annual Plan”). If progress differs from that anticipated in the Annual Plan, Licensee shall explain the differences and propose a modified plan for
HARVARD’s review. If HARVARD is dissatisfied with the modified plan, then HARVARD and Licensee shall meet to develop a mutually agreed upon plan. HARVARD has agreed to maintain as confidential all information designated as confidential by
Licensee which is provided to HARVARD under this Paragraph. HARVARD has agreed not to use such confidential information for any purpose other than the evaluation of CMCC’s or Licensee’s compliance under this Agreement and agrees not to
disclose such information to anyone who is not a direct employee of HARVARD’s Office of Technology and Licensing or who has not signed a non-disclosure agreement with HARVARD covering the confidential information, which shall be in form and
substance reasonably acceptable to CMCC and Licensee. Copies of such nondisclosure agreements shall be provided to CMCC and Licensee promptly after execution. 
  

4.9 HARVARD shall have the right to terminate or render this Agreement non- exclusive, only as to the Appendix B Licensed Patent Rights, if CMCC or
Licensee, or one of Licensee’s Affiliates or Sublicensees are not engaged in research, development, clinical trials, product approval, manufacturing, or marketing of Licensed Products or Licensed Processes, or 

  

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licensing of the Appendix B Licensed Patent Rights. Prior to invoking the right to terminate or render this Agreement non-exclusive, HARVARD shall give
written notice to CMCC and to Licensee and a [**] opportunity for CMCC or Licensee to demonstrate that it, its affiliate, or sublicensee is using reasonable efforts to comply with its obligations under this Paragraph. If after the [**] period, CMCC
or Licensee fail to demonstrate such compliance, HARVARD may notify CMCC and Licensee of its intent to either terminate or render this Agreement non-exclusive only as to the Appendix B Licensed Patent Rights. 
  
 4.10 Subject to the other provisions of this Article IV, CMCC’s sole
remedy for Licensee’s failure to meet its obligations under this Article IV shall be termination of this Agreement. 
  
 ARTICLE V. ROYALTIES AND OTHER PAYMENTS 
  
 5.1 For the rights, privileges and exclusive licenses granted hereunder, Licensee shall pay to CMCC the following amounts in the manner hereinafter
provided until the end of the term of the last to expire Licensed Patent Right, unless this Agreement shall be sooner terminated as hereinafter provided: 
  
 (a) A license issue fee of [**] Dollars ($[**]), which license issue fee shall be deemed earned on the date of the execution of this
Agreement. 
  
 (b) A License Maintenance Fee of
[**] Dollars ($[**]),[**] Dollars ($[**]) of which shall be payable within [**] days of the first anniversary of the date of execution of this License Agreement and, [**] Dollars ($[**]) of which shall be payable [**] thereafter. 
  
 (c) Licensee shall make the following milestone payments to
CMCC upon the completion of the following events by Licensee (“Licensee Milestones”): 
  
 (i) Payment of [**] Dollars ($[**]) upon [**] by Licensee, but not more than one payment shall be required for each Licensed Product or
Licensed Process in the event that more than one [**] is required for the same Licensed Product or Licensed Process. 
  
 (ii) Payment of [**] Dollars ($[**]) upon [**] with respect to a Licensed Product or a Licensed Process. 
  
 (iii) The Licensee Milestones will be creditable toward
running royalties due CMCC for Net Sales by Licensee, up to, and no more than, [**]% of the Net Sales due in any given payment period. 
  
 (iv) Notwithstanding anything to the contrary herein, it is understood by the parties that if Licensee ceases to develop a Licensed
Product or Licensed Process prior to the payment of all milestones specified in this paragraph 5.1 (such Licensed Product being referred to as a “Canceled Product”) and Licensee decides to develop a different Licensed Product or Licensed
Process for the same labeled indication as the Canceled Product, then Licensee shall, with respect to 

  

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such other Licensed Product or Licensed Process, be obligated to pay only that/those milestone payment(s) which were not made with respect to the Canceled
Product; provided however, that if Licensee does at some time in the future develop such canceled product, then appropriate and prompt adjustment with respect to milestone payments shall be made hereunder. 
  
 (d) Running royalties on a country-by-country basis in an
amount equal to [**] percent ([**]%) of Net Sales by Licensee or an Affiliate of Licensed Products or Licensed Processes derived from a new chemical entity disclosed by CMCC to Licensee and which, but for this Agreement would infringe a Valid Claim
of the Licensed Patent Rights. Running royalties on a country-by-country basis in an amount equal to [**] percent ([**]%) of Net Sales by Licensee or an Affiliate of Licensed Products or Licensed Processes derived from a new chemical entity
discovered by Licensee or its Affiliate and which, but for this Agreement would infringe a Valid Claim of the Licensed Patent Rights. 
  
 5.2 In the event Licensee or its Affiliate has granted sublicenses under this Agreement, Licensee or its Affiliate will pay CMCC [**] percent ([**]%) of
Gross Compensation received by Licensee or its Affiliate from said Sublicensees on a country-by-country basis for Licensed Products or Licensed Processes derived from a new chemical entity disclosed by CMCC to Licensee or its Affiliate which, but
for this Agreement would infringe a Valid Claim of the Licensed Patent Rights in the country, and [**] percent ([**]%) of Gross Compensation received by Licensee or its Affiliate from said Sublicensees for Licensed Products or Licensed Processes
derived from a new chemical entity discovered by Licensee, its Affiliate or Sublicensee, and which, but for this Agreement would infringe a Valid Claim of the Licensed Patent Rights in the country. 
  
 5.3 No multiple royalties shall be payable because any Licensed Product or
Licensed Process, its manufacture, use, lease or sale which, but for this Agreement would infringe a Valid Claim of more than one patent licensed under this Agreement. 
  

 5.4 To the extent that Licensee or its Affiliates obtains subsequent to the date of this Agreement licenses to third party patents or other
intellectual property that it or they reasonably believes are necessary to produce or sell Licensed Products or Licensed Processes, Licensee may deduct from the running royalty on Net Sales due to CMCC [**] percent [**]%) of the Net Sales as
appropriate on a country by country basis due in respect of such third party patents or intellectual property, but only up to an amount equal to [**] percent ([**]%) of the Net Sales or share of Gross Compensation due hereunder for the same payment
period. 
  
 5.5 For purposes of calculating royalties, in the
event that a Licensed Product or Licensed Process includes both component(s) which, but for this Agreement would infringe a Valid Claim of the Licensed Patent Rights (“Patented Component”) and a component which is diagnostically useable or
therapeutically active alone or in a combination which does not require the Patented Component, and such component is not covered by a Valid Claim of a Licensed Patent Right (“Unpatented Component”), then Net Sales of the Combination
Product or Combination Process shall be calculated using one of the following methods; provided that in no 

  

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event shall royalties payable to CMCC hereunder be reduced to less than [**] percent ([**]%) of those otherwise due hereunder: 
  
 (a) By multiplying the Net Sales of the Combination Product
or Combination Process during the applicable royalty accounting period (“accounting period”) by a fraction, the numerator of which is the aggregate gross selling price of the Patented Component(s) contained in the Combination Product or
Combination Process if sold separately, and the denominator of which is the sum of the gross selling price of both the Patented Component(s) and the Unpatented Component(s) contained in the Combination Product or Combination Process if sold
separately; or 
  
 (b) In the event that no such
separate sales are made of the Patented Component(s) or the Unpatented Components during the applicable accounting period, Net Sales for purposes of determining royalties payable hereunder shall be calculated by multiplying the Net Sales of the
Combination Product or Combination Process by a fraction, the numerator of which is the fully allocated production cost of the Patented Component(s) and the denominator of which is the sum of the fully allocated production costs of the Patented
Component(s) and the Unpatented Component(s) contained in the Combination Product or Combination Process. Such fully allocated costs shall be determined by using Licensee’s standard accounting procedures, which procedures must conform to
standard cost accounting procedures. 
  
 5.6 Royalty payments
shall be paid in United States dollars in Boston, Massachusetts, or at such other place as CMCC may reasonably designate consistent with the laws and regulations controlling in any foreign country. If the currency conversion shall be required in
connection with the payments of royalties or other amounts hereunder, the conversion shall be made by using the exchange rate prevailing at the Bank of Boston on the last business day of the calendar quarterly reporting period to which such royalty
payments relate. 
  
 5.7 The royalty payments set forth in this
Agreement shall, if overdue, bear interest until payment at a per annum rate of four percent (4%) above the prime rate in effect at the Bank of Boston on the due date. The payment of such interest shall not foreclose CMCC from exercising any other
rights it may have as a consequence of the lateness of any payment. 
  
 ARTICLE VI. REPORTS AND RECORDS 
  
 6.1 Licensee shall
keep, and shall require its Affiliates and Sublicensees to keep, full, true and accurate books of account in accordance with generally accepted accounting principles and containing sufficient detail to enable CMCC to determine the royalty and other
amounts payable to CMCC under this Agreement. Said books of account shall be kept at Licensee’s principal place of business or the principal place of business of the appropriate division of Licensee to which this Agreement relates. Said books
and the supporting data shall be retained for at least three (3) years following the end of the calendar year to which they pertain. 
  
 6.2 Licensee agrees to permit an auditor selected by CMCC or HARVARD and reasonably acceptable to Licensee to have access, during the term of this
Agreement and for a period of three (3) years thereafter, and during ordinary business hours after reasonable advance 

  

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written notice to Licensee, to such records as may be necessary, in the opinion of such auditor, to determine the correctness of any report and/or payment
made under this Agreement. Such an auditor shall be at CMCC’s or HARVARD’s, as appropriate, expense and shall occur not more than once per year. The auditor shall treat all information to which it has access under this paragraph as
confidential and shall not disclose such information to any third party. 
  
 6.3 Licensee shall deliver to CMCC true and accurate reports by February 15th, for the period July 1 through December 31 of the previous year, and on August 15th, for the period January 1st through June 30th of the
current year, giving such particulars of the business conducted by Licensee, its Affiliates and its Sublicensees under this Agreement as shall be pertinent to a royalty accounting hereunder and to verify Licensee’s activities with respect to
achieving the objectives of the Development Plan described in Article IV above. These reports shall include at least the following: 
  

	 	1.	Gross Compensation received by Licensee by country. 

  

	 	2.	Noncash, nonliquid compensation portions of Gross Compensation. 

  

	 	3.	Amount calculated due to CMCC. 

  

	 	4.	Number of Licensed Products and Licensed Processes manufactured and sold. 

  

	 	5.	Aggregate billings for Licensed Products and Licensed Processes sold. 

  

	 	6.	Applicable deductions. 

  

	 	7.	Total royalties due. 

  

	 	8.	Names and addresses of all sublicensees of Licensee. 

  

	 	9.	Licensed Products manufactured and sold to the U.S. Government. No royalty obligations shall arise from sales or use by, for or on behalf of the U.S. Government in view of a
royalty-free, nonexclusive license that may heretofore have been granted to the U.S. Government. 

  
 6.4 With each such report submitted under subparagraph 6.3, Licensee shall pay to CMCC the compensation due and payable under this Agreement. If no
payments shall be due, Licensee shall so report. 
  
 ARTICLE VII.
PATENT PROSECUTION 
  
 7.1 CMCC shall apply for, seek prompt
issuance of, and maintain during the term of this Agreement the Licensed Patent Rights set forth in Appendix A. CMCC shall be diligent in its participation in applying for, seeking prompt issuance of, and maintaining during the term of this
Agreement the Licensed Patent Rights set forth in Appendix B, as permitted under CMCC’s Agreement with HARVARD and HARVARD’s Agreement with ION. (HARVARD and ION make decisions jointly respecting the Licensed Patent Rights set forth in
Appendix B, and 

  

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HARVARD has assigned its rights to make such joint decisions to CMCC.) The prosecution, filing and maintenance of all applications and patents on the
Licensed Patent Rights shall be the primary responsibility of CMCC. CMCC shall promptly provide Licensee with copies of all substantive correspondence received by CMCC or CMCC’s attorneys or agents from the U.S. Patent and Trademark Office or
any foreign patent office. Licensee shall have reasonable opportunities to advise CMCC and shall cooperate with CMCC in the prosecution, filing and maintenance of the Licensed Patent Rights. 
  
 7.2 Licensee shall reimburse to CMCC for Licensee’s proportional share
of fees and costs relating to the filing, prosecution and maintenance of the Licensed Patent Rights shown in Appendix A and Appendix B incurred after the date of this Agreement, which proportional share shall be the portion of the fees and costs
payable by CMCC, including any amounts payable by CMCC under the Assignment and Sublicense Agreement between CMCC and Ion Pharmaceuticals, Inc., dated September 14, 1999. CMCC shall provide to Licensee an itemized invoice of all such fees and
Licensee shall pay to CMCC all amounts due under said invoice within thirty (30) days of the date of said invoice. Licensee shall also reimburse CMCC for Licensee’s proportional share, as defined above, of fees and costs relating to the filing,
prosecution and maintenance of the Licensed Patent Rights shown in Appendix A and Appendix B incurred after July 21, 1998 and before the Effective Date of this Agreement, up to a maximum of $[**]. Licensee shall have the right to request, on a
case-by-case and country-by-country basis that a particular action due in such case in such country not be carried out. Such request shall be made no later than the later to occur of thirty (30) days before the due date of such action or thirty (30)
days after Licensee receives notice of such due date. Such timely request shall relieve Licensee of its obligation of payment for such action. In the event that Licensee makes such a request concerning a particular case in a particular country,
Licensee’s license hereunder solely as to that particular case in that particular country shall terminate. 
  
 7.3 In the event CMCC elects not to pursue, maintain or retain a particular Licensed Patent Right licensed to Licensee hereunder, CMCC shall so notify
Licensee in sufficient time for Licensee to assume the filing, prosecution and/or maintenance of such application or patent at Licensee’s expense. In such event, CMCC shall provide to Licensee any authorization necessary to permit Licensee to
pursue and/or maintain such Licensed Patent Right. Licensee shall have no further royalty obligations under this Agreement with respect to any such Licensed Patent Right. 
  

 ARTICLE VIII. INFRINGEMENT 
  
 8.1 Licensee and CMCC shall each inform the other promptly in writing of any alleged infringement known to it by a third party of the Licensed Patent
Rights in the Field of Use and of any available evidence thereof. 
  
 8.2 Subject to the ION/NEWCO Sublicense Agreement dated December 3, 1997, Licensee or its Affiliate or Sublicensee shall have the first right, but not the obligation, to institute and prosecute at its own expense any infringement of the
Licensed Patent Rights which falls, within the Field of Use. If Licensee, its Sublicensee or its Affiliate fails to bring such action or proceedings within a period of two (2) months after receiving written notice of the infringement or if within
such time Licensee notifies CMCC that it intends not to bring such action, then CMCC shall have the right, but not the obligation, to prosecute at its own expense 

  

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any such infringement of the Licensed Patent Rights. If Licensee, its Affiliate or Sublicensee brings such action then Licensee may reduce, by up to [**]
percent ([**]%), the royalty due to CMCC which is earned under the Licensed Patent Rights by [**] percent ([**]%) of the amount of the expenses and costs of such action, including attorney fees. In the event that such [**] percent ([**]%) of
such expenses and costs exceeds the amount of royalties withheld by Licensee for any calendar year, Licensee may to that extent reduce the royalties due to CMCC from Licensee in succeeding calendar years, but never by more than [**] percent ([**]%)
of the royalty due in any one year. Recoveries or reimbursements from such action shall first be applied to reimburse CMCC, Licensee, its Affiliate, or its Sublicensee, ION and HARVARD, as applicable, for litigation costs, and then to reimburse CMCC
for royalties withheld. If CMCC brings such action, then any remaining recoveries or reimbursements shall be retained by CMCC, after payment of any amounts due to HARVARD pursuant to the HARVARD/ION License Agreement. If Licensee, its Affiliate or
its Sublicensee brings such action, then any remaining recoveries or reimbursements to CMCC by Licensee due shall be treated as Gross Compensation, after payment of any amounts due to HARVARD pursuant to the HARVARD/ION License Agreement.
Notwithstanding anything to the contrary in the foregoing, Licensee shall reimburse CMCC, ION or HARVARD, as appropriate, for any costs incurred by CMCC, ION or HARVARD as part of an action brought by Licensee, its Affiliates or Sublicensees,
irrespective of whether CMCC, ION or HARVARD become co-plaintiffs. CMCC shall reimburse Licensee for any costs Licensee incurs as part of an action brought by CMCC or its affiliates, irrespective of whether Licensee becomes a co-plaintiff.

  
 8.3 Licensee shall have no right to institute or prosecute any
infringement of the Sheffield Patent Rights which falls within NEWCO’s Field of Use. 
  
 8.4 Subject to the ION/NEWCO Sublicense Agreement dated December 3, 1997, in the event that NEWCO or its successors institutes an action for infringement of the Licensed Patent Rights in Licensee’s Field of Use,
CMCC hereby assigns to Licensee any recoveries due to CMCC resulting from such action. 
  
 8.5 If CMCC is deemed to be an indispensable party in a suit brought by Licensee, pursuant to this paragraph, CMCC agrees to be named as a co-plaintiff. If HARVARD or ION is deemed to be an indispensable party in a
suit brought by Licensee pursuant to this paragraph, then CMCC will endeavor to secure ION’s and HARVARD’s agreement to be named as a co-plaintiff. 
  
 8.6 In the event that a declaratory judgment action alleging invalidity, unenforceability or noninfringement of any of the Licensed Patent Rights shall be
brought against Licensee, CMCC, at its option, shall have the right, within thirty (30) days after commencement of such action, to intervene and participate in the defense of the action at its own expense. 
  
 8.7 In any infringement suit which either party may institute to enforce the
Licensed Patent Rights pursuant to this Agreement, the other party hereto shall, at the request and the expense of the party initiating such suit, cooperate in all reasonable respects and, to the extent reasonably possible, have its employees
testify when requested and make available relevant records, papers, information, samples, specimens, and the like. 
  

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 8.8 Licensee shall during the exclusive period of this Agreement have the sole right subject to the terms
and conditions hereof to sublicense any alleged infringer for future use of the Licensed Patent Rights. Any up-front fees paid to Licensee as part of such a sublicense shall be treated as Gross Compensation as set forth in Article V. 
  
 8.9 If a third party obtains a judgment (consent or otherwise) against
Licensee or its Affiliate, as applicable, or obtains a settlement agreement from Licensee or its Affiliate, as applicable, for infringement of a patent based on the manufacture, use, offer to sell, sale, lease or importation of Licensed Products or
Licensed Processes, the costs of Licensee’s or its Affiliate’s, as applicable, defense of the third party’s claims will be offset against [**] percent ([**]%) of the future royalties each year until Licensee or its Affiliate, as
applicable, is completely reimbursed for all attorneys fees, court costs, legal fees, damages and/or settlement amounts paid. In addition, in such event and upon payment by Licensee of all amounts due CMCC through the effective date of termination,
the Licensee or its Affiliate, against which the judgment is obtained or which enters into the settlement agreement shall have the right to immediately terminate this agreement as to itself. Upon such termination, CMCC shall have no recourse against
that Licensee or Affiliate, as applicable, for exercising its right to terminate. CMCC shall, at the request and expense of Licensee, its Affiliate or Sublicensee, as applicable cooperate with Licensee, its Affiliate or Sublicensee, as applicable in
any such third party action by making its employees available to testify and by producing relevant, non-privileged records, papers, information, samples, specimens and the like. CMCC shall endeavor to secure Harvard’s and Ion’s consent to,
at Licensee’s, its Affiliate’s or Sublicensee’s, as applicable, request and expense, cooperate with Licensee, its Affiliate or Sublicensee, as applicable in any such third party action by making its employees available to testify and
by producing relevant, non-privileged records, papers, information, samples, specimens and the like. 
  
 8.10 In the event that a governmental agency in any country or territory compels CMCC to grant a license, or Licensee, its Affiliate or Sublicensee, as
applicable, to grant a sublicense to any non-governmental third party under the Licensed Patent Rights, then Licensee, its Affiliate or Sublicensee, as applicable, shall have the benefit during the term of such license, in such territory or country
only, of any of the terms granted to such third party which are more favorable than the terms set forth in this Agreement, only if the third party is actually and substantially commercializing Licensed Products or Licensed Processes. This provision
shall apply to a license granted to a governmental agency only if that governmental agency grants a sublicense to a non-governmental third party. 
  
 ARTICLE IX. UNIFORM INDEMNIFICATION 
 AND
INSURANCE PROVISIONS 
  
 9.1 Each party shall promptly notify the
other of any claim, lawsuit, or other proceeding related to the Licensed Patent Rights. Licensee shall indemnify, defend and hold harmless CMCC, its corporate affiliates, current or future directors, trustees, officers, faculty, medical and
professional staff, employees, students and agents and their respective successors, heirs and assigns (the “Indemnitees”), against any liability, damage, loss or expense (including reasonable attorney’s fees and expenses of
litigation) incurred by or imposed upon the Indemnitees or any one of them in connection with any claims, suits, actions, demands or judgments arising out of any theory of product liability (including, but not limited to, actions in 

  

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the form of tort, warranty, or strict liability) concerning any product, process or service made, used or sold pursuant to any right or license granted under
this Agreement. Any Indemnitee shall promptly notify Licensee of any suit, claim or action for which indemnification may be sought. Licensee shall have the right, but not the obligation, at its own expense, to control the defense of any such suit,
claim or action. Indemnitees shall not settle any such suit, claim or action without Licensee’s consent. Licensee’s indemnification hereunder shall not apply to any liability, damage, loss or expense to the extent that it is directly
attributable to the negligent activities, deliberate misrepresentations or willful misconduct of the Indemnitees or Additional Indemnities. 
  
 9.2 Licensee or Licensee’s Sublicensees and Affiliates shall indemnify, defend and hold harmless ION and its officers, employees, directors,
affiliates and agents and HARVARD and its trustees, officers, medical and professional staff, employees, students and agents and ION’s and HARVARD’s respective successors, heirs and assigns (the “Additional Indemnitees”) from and
against any liability, damage, loss or expense (including reasonable attorneys’ fees and expenses of litigation) incurred by or imposed upon any of the Additional Indemnitees in connection with any claims, actions, suits, demands, judgments or
other proceeding relating to this Agreement and arising out of the design, manufacture, sale, use in commerce, lease or promotion by Licensee, its Affiliates, Sublicensees or agents, of any product, process or service relating to, or developed
pursuant to, this Agreement. Any Additional Indemnitee seeking indemnification hereunder shall promptly notify Licensee of any suit, claim or action for which indemnification may be sought. Licensee shall have the right, but not the obligation, at
its own expense, to control the defense of any such suit, claim or action, using attorneys reasonably acceptable to Harvard. Additional Indemnitees shall not settle any such suit, claim or action without Licensees consent, which consent shall not be
unreasonably withheld or delayed. Licensee’s indemnification hereunder shall not apply to any liability, damage, loss or expense to the extent that it is directly attributable to the negligent activities, deliberate misrepresentations or
willful misconduct of the Indemnitees or Additional Indemnities. 
  
 9.3 Licensee agrees, at its own expense, to provide attorneys reasonably acceptable to CMCC to defend against any actions brought or filed against any party indemnified hereunder with respect to the subject of indemnity contained herein,
whether or not such actions are rightfully brought. 
  
 9.4 (a)
During the period of time in which research or development for any Licensed Products or Licensed Process is conducted on the premises of Licensee, its Affiliates or Sublicensees, and during the period of time in which any clinical trials are being
conducted for any Licensed Products or Licensed Processes, Licensee, its Affiliates or Sublicensees shall at its sole cost and expense, shall have procured and maintained policies of comprehensive general liability insurance with a nationally
recognized carrier in amounts not less than $2,000,000 per incident and $2,000,000 annual aggregate. Such insurance policies shall name each of CMCC, ION and HARVARD as additional insured parties with the same scope of coverage for each coverage
required for Licensee. 
  
 9.4(b) Beginning at the time as any
such product, process or service is being commercially distributed or sold (other than for the purpose of obtaining regulatory approvals) by Licensee or by a Sublicensee, Affiliate or agent of Licensee, Licensee shall, at its sole cost 

  

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and expense, procure and maintain commercial general liability insurance in amounts not less than $2,000,000 per incident and $2,000,000 annual aggregate and
naming the Indemnitees, ION and HARVARD as additional insureds. Such commercial general liability insurance shall provide (i) product liability coverage and (ii) contractual liability coverage for Licensee’s indemnification under Article IX,
Paragraphs 9.1 through 9.3 of this Agreement. 
  
 9.4(c) If
Licensee elects to self-insure all or part of the limits described above in 9.4(a) and 9.4(b) (including deductibles or retentions which are in excess of $250,000 annual aggregate), such self-insurance program must be acceptable to CMCC and the Risk
Management Foundation of the Harvard Medical Institutions, Inc. The minimum amount of insurance coverage required under this Article IX, Paragraph 9.4 shall not be construed to create a limit of Licensee’s liability with respect to its
indemnification under Article IX, Paragraphs 9.1 through 9.3 of this Agreement. 
  
 9.5 Licensee shall provide CMCC with written evidence of such insurance upon request of CMCC. Licensee shall provide CMCC with written notice at least thirty (30) days prior to the cancellation, non-renewal or
material change in such insurance. If Licensee does not obtain replacement insurance providing comparable coverage within such thirty (30) day period, CMCC shall have the right to terminate this Agreement effective at the end of such thirty (30) day
period without notice of any additional waiting periods. 
  
 9.6
Licensee shall maintain such commercial general liability insurance during (i) the period that any such product, process or service is being commercially distributed or sold (other than for the purpose of obtaining regulatory approvals) by Licensee
or by a Sublicensee, Affiliate or agent of Licensee and (ii) a reasonable period after the period referred to above, which in no event shall be less than fifteen (15) years. 
  
 9.7 Article IX, Paragraphs 9.1 through 9.6 shall survive expiration or termination of this Agreement. 
  
 9.8 OTHER THAN WARRANTIES SET FORTH HEREIN, CMCC MAKES NO WARRANTY, EXPRESS
OR IMPLIED, INCLUDING, WITHOUT LIMITATION, ANY IMPLIED WARRANTY OF MERCHANTABILITY OR ANY IMPLIED WARRANTY OF FITNESS FOR A PARTICULAR PURPOSE WITH RESPECT TO ANY PATENT, TRADEMARK, SOFTWARE, TRADE SECRET, TANGIBLE RESEARCH PROPERTY, INFORMATION OR
DATA LICENSED OR OTHERWISE PROVIDED TO LICENSEE HEREUNDER AND HEREBY DISCLAIMS THE SAME. 
  
 ARTICLE X. CMCC REPRESENTATIONS WARRANTIES AND COVENANTS 
  
 10.1 CMCC warrants that it has the lawful right and authority to enter into this Agreement without the consent or authority of another person or entity. 
  
 10.2 CMCC warrants that it owns or has rights in the Licensed Patent Rights sufficient to allow it to grant the licenses
granted hereunder without conflict with or violation of any agreement between CMCC and any third party. 
  

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 10.3 CMCC warrants that to the best of the knowledge of CMCC’s Intellectual Property Office, the
Licensed Patent Rights are in good standing, i.e., that all proper assignments have been made transferring to CMCC its proper interest right, title and interest in the Licensed Patent Rights, that all annuities have been paid in respect of
the Licensed Patent Rights, and that none of the Licensed Patent Rights is the subject of any protest, opposition, interference, re-examination, reissue, litigation, or any other inter parties proceeding. 
  
 10.4 CMCC warrants that to the best of the knowledge of CMCC’s
Intellectual Property Office, as of the Effective Date of this Agreement the Licensed Patent Rights constitute all the patents and patent applications with a CMCC inventor common to the Licensed Patent Rights owned by it that, but for this agreement
would be infringed by the manufacture, offer to sell, sale, use, lease or importation of Licensed Products. 
  
 10.5 CMCC warrants that it has provided to Licensee true and correct copies of all agreements (“the Relevant Agreements”) in its possession,
including any amendments or modifications thereto, that actually or potentially affect any right, title or interest in the Licensed Patent Rights. Appendix E is a list of all such Relevant Agreements. 
  
 10.6 CMCC covenants that it will not, without Licensee’s consent, modify
any of the Relevant Agreements or take any action thereunder in a manner which would affect Licensee’s rights under the Licensed Patent Rights. 
  
 ARTICLE XI. CONFIDENTIALITY 
  
 11.1 Each Party shall keep confidential all confidential information of the other Party, or as applicable its Affiliates or Sublicensees communicated to
such Party, or as applicable its Affiliates or Sublicensees pursuant to this Agreement. For purposes of this Section, information shall be deemed to be communicated to CMCC only if such information is communicated to CMCC’s Office of
Technology. CMCC shall not undertake obligations of confidentiality for information communicated by Licensee to CMCC employees other than Office of Technology staff. The confidentiality obligations of either party shall not apply, however, to:

  
 (a) information which is generally available
to the public or which becomes available to the public through no fault of the receiving party, or as applicable its Affiliates or Sublicensees; 
  
 (b) information that is required by law to be disclosed by the receiving Party, or as applicable its Affiliates or Sublicensees, provided
that such Party has advised the other Party, or as applicable its Affiliates or Sublicensees, of the demand, subpoena, interrogatory or other legal process sufficiently in advance of such disclosure as to allow the other Party, or as applicable its
Affiliates or Sublicensees to attempt to obtain a protective order or other remedy, if available, and if such Party, or as applicable its Affiliates or Sublicensees does obtain such a remedy, the information shall continue to be treated as
confidential information; 
  
 (c) information
that was known or used by the receiving Party, or as applicable its Affiliates or Sublicensees prior to its disclosure to the receiving Party, or as 

  

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applicable its Affiliates or Sublicensees by the other Party, or as applicable its Affiliates or Sublicensees; 
  
 (d) information which is otherwise lawfully disclosed to the
receiving Party, or as applicable its Affiliates or Sublicensees by sources other than the other Party, or as applicable its Affiliates or Sublicensees who are rightfully in possession of such information and have no duty to keep such information
confidential; or 
  
 (e) information which is
independently developed, as evidenced by written documents, by or for the receiving party, or as applicable its Affiliates or Sublicensees, without reference to or reliance upon information communicated to such Party, or as applicable its Affiliates
or Sublicensees by the other Party. 
  
 11.2 Nothing in this
Section shall be construed as prohibiting Licensee from disclosing Confidential Information which Licensee, in its sound business judgment is reasonably necessary for the purpose of commercializing Licensed Products or Licensed Processes, including
without limitation, disclosure to business partners, potential business partners, government agencies, investors and potential investors. 
  
 ARTICLE XII. EXPORT CONTROLS 
  
 It is understood that CMCC is subject to United States laws and regulations controlling the export of technical data, computer software, laboratory
prototypes and other commodities (including the Arms Export Control Act, as amended and the Export Administration Act of 1979), and that its obligations hereunder are contingent on compliance with applicable United States export laws and
regulations. The transfer of certain technical data and commodities may require a license from the cognizant agency of the United States Government and/or written assurances by Licensee that Licensee shall not export data or commodities to certain
foreign countries without prior approval of such agency. CMCC neither represents that a license shall not be required, nor that if required, it shall be issued Licensee is responsible for taking any steps necessary to comply with such regulations.

  
 ARTICLE XIII. NON-USE OF NAMES 
  
 13.1 Use of Names. Licensee agrees that it and its sublicensees may
not use in any way, nor permit any other party to use in any way, the names “Children’s Medical Center Corporation”, “CMCC”, “ION,” “SHEFFIELD,” “HARVARD COLLEGE,” “HARVARD” or any
logotypes or symbols associated with CMCC, HARVARD, ION, or SHEFFIELD or the names of any of their corporate affiliates, nor any adaptation thereof, nor the name of any employee at CMCC or HARVARD, without the prior written consent of ION,
SHEFFIELD, HARVARD or CMCC (in the case of ION, SHEFFIELD, HARVARD, CMCC, as appropriate; except that such obligation of Licensee under this Paragraph 11.1, shall not apply to information (i) that Licensee or its sublicensees determines in its sole
discretion to be necessary and appropriate to satisfy its disclosure and other obligations under federal or state law, or (ii) any and all data or research work product derived or resulting from the Technology or Sublicensed Technology for the sole
purpose of complying with federal and state laws and regulatory 

  

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requirements. Licensee may state that it is licensed by CMCC under one or more patents or patent applications of the Licensed Patent Rights. 
  
 ARTICLE XIV. ASSIGNMENT 
  
 14.1 Except as otherwise provided herein, this Agreement is not assignable in
whole or in part, and any attempt to do so shall be void and of no effect. 
  
 14.2 CMCC may assign this Agreement at any time to any corporate affiliate of CMCC without the prior consent of Licensee. 
  
 14.3 Except as provided in Article XIV, Paragraph 14.4 below, Licensee may assign this Agreement to another entity only with the prior written consent of
CMCC, which consent shall not be unreasonably withheld or delayed. 
  
 14.4 Notwithstanding anything herein to the contrary, in the event Licensee merges with another entity, is acquired by another entity, or sells all or substantially all of its assets related to Licensed Products and Licensed Processes to
another entity, Licensee may assign its rights and obligations hereunder to, in the event of a merger or acquisition, the surviving entity, and in the event of a sale, the acquiring entity, without CMCC’s consent so long as: (i) Licensee is not
then in breach of this Agreement; (ii) the proposed assignee has a net worth at least equivalent to the net worth Licensee had as of the date of this Agreement; (iii) the proposed assignee has available resources and sufficient scientific, business
and other expertise comparable to Licensee in order to satisfy its obligations hereunder; (iv) Licensee provides written notice of the assignment to CMCC, together with documentation sufficient to demonstrate the requirements set forth in
subparagraphs (i) through (iii) above, at least twenty (20) days prior to the effective date of the assignment; and (v) CMCC receives from the assignee, in writing, at least ten (10) days prior to the effective date of the assignment: (a)
reaffirmation of the terms of this Agreement; (b) an agreement to be bound by the terms of this Agreement; and (c) an agreement to perform the obligations of Licensee under this Agreement. Any such notices or documentation received by CMCC hereunder
shall be held in confidence by CMCC and shall not be disclosed by CMCC to any third party. 
  
 ARTICLE XV. DISPUTE RESOLUTION AND ARBITRATION 
  
 15.1 Except for the right of either party to apply to a court of competent jurisdiction for a temporary restraining order, a preliminary injunction, or other equitable relief to preserve the status quo or prevent
irreparable harm, any and all claims, disputes or controversies arising under, out of, or in connection with the Agreement, including any dispute relating to patent validity or infringement, which the parties shall be unable to resolve within sixty
(60) days shall be resolved by final and binding arbitration in Boston, Massachusetts, in accordance with the rules of the American Arbitration Association (“AAA”) then obtaining. The arbitration shall be the exclusive forum for resolving
any such dispute and all expenses, in connection therewith (including without limitation the award of attorneys’ fees to the prevailing party), shall be paid as determined by the arbitrator. A single arbitrator shall be mutually agreed upon and
if the parties are unable to agree on a mutually acceptable arbitrator, an arbitrator shall be chosen in accordance with AAA rules. The decision of the arbitrator shall be final and binding upon the 

  

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parties hereto. Any award rendered in such arbitration shall be final and may be enforced by either party in either the courts of the Commonwealth of
Massachusetts or in the United States District Court for the District of Massachusetts, wherein subject matter jurisdiction properly resides, and each of CMCC and Licensee hereby consents and submits to exclusive personal jurisdiction in such forum.
The arbitrator shall have no power to add to, subtract from or modify any of the terms or conditions of this Agreement, nor to award punitive damages. 
  
 15.2 Notwithstanding the foregoing, nothing in this Article shall be construed to waive any rights or timely performance of any obligations existing under
this Agreement. 
  
 ARTICLE XVI. TERM AND TERMINATION 

 
 16.1 The term of this Agreement shall be (15) years or the life of the
last expiring Licensed Patent Right, whichever period is longer. 
  
 16.2 CMCC may terminate this Agreement immediately upon the bankruptcy, insolvency, liquidation, dissolution or cessation of operations of Licensee; or the filing of any voluntary petition for bankruptcy, dissolution, liquidation or
winding-up of the affairs of Licensee; or any voluntary assignment by Licensee for the benefit of creditors; or the filing of any involuntary petition for bankruptcy, dissolution, liquidation or winding-up of the affairs of Licensee which is not
dismissed within ninety (90) days of the date on which it is filed or commenced. 
  
 16.3 CMCC may terminate this Agreement upon thirty (30) days prior written notice in the event of Licensee’s failure to pay to CMCC royalties due and payable hereunder in a timely manner, unless Licensee shall
make all such payments to CMCC within said thirty (30) day period. Upon the expiration of the thirty (30) day period, if Licensee shall not have made all such payments to CMCC, the rights, privileges and licenses granted hereunder shall terminate.

  
 16.4 Except as otherwise provided in Paragraph 14.3 above,
CMCC may terminate this Agreement upon sixty (60) days prior written notice in the event of Licensee’s breach or default of any material term or condition or warranty contained in this Agreement, unless Licensee shall cure such breach within
said sixty (60) day period. Upon the expiration of the sixty (60) day period, if Licensee shall not have cured said breach, the rights, privileges and license granted hereunder shall terminate. 
  
 16.5 Licensee shall have the right to terminate this Agreement at any time
upon six (6) months’ prior written notice to CMCC, and upon payment by Licensee of all amounts due CMCC through the effective date of termination. 
  
 16.6 Upon termination of this Agreement for any reason, nothing herein shall be construed to release either party from any obligation that matured prior
to the effective date of such termination. Licensee and any sublicensee thereof may, however, after the effective date of such termination, sell all Licensed Products and complete Licensed Products in the process of manufacture at the time of such
termination and sell the same, provided that Licensee shall pay to CMCC the royalties thereon as required under this Agreement and shall submit the reports required under this Agreement on the sales of Licensed Products. 
  

 -22- 








 ARTICLE XVII. PAYMENTS, NOTICES, AND OTHER COMMUNICATIONS 
  
 17.1 All payments, notices, reports and/or other communications made in
accordance with this Agreement, shall be deemed effectively given on the date of delivery if delivered by hand, three (3) days deposit in certified or registered mail, or the next business day if sent by a national overnight business courier service
and addressed as follows: 
  
 In the case of CMCC: 
  
 Director, Technology Transfer 
 Office of Research Administration 
 Children’s Hospital 
 300 Longwood Avenue 
 Boston, MA 02115 
  
 In the case
of Licensee: 
  
 President 
 ICAgen, Inc. 
 P.O. Box 14487 
 Research Triangle Park NC 27709 
  
 or such other address as either party shall notify the other in writing. 
  
 ARTICLE XVIII. GENERAL PROVISIONS 
  
 18.1 All rights and remedies hereunder will be cumulative and not alternative, and this Agreement shall be construed and governed by the laws of the
Commonwealth of Massachusetts. 
  
 18.2 This Agreement may be
amended only by written agreement signed by the parties. 
  
 18.3
It is expressly agreed by the parties hereto that CMCC and Licensee are independent contractors and nothing in this Agreement is intended to create an employer relationship, joint venture, or partnership between the parties. No party has the
authority to bind the other. 
  
 18.4 This Agreement constitutes
the entire agreement between the parties with respect to the subject matter hereof and supersedes all proposals, negotiations and other communications between the parties, whether written or oral, with respect to the subject matter hereof.

  
 18.5 If any provisions of this Agreement shall be held to be
invalid, illegal or unenforceable, the validity, legality and enforceability of the remaining provisions of this Agreement shall not be impaired thereby. 
  
 18.6 This Agreement may be executed in any number of counterparts, each of which shall be deemed an original as against the party whose signature appears
thereon, but all of which taken together shall constitute but one and the same instrument. 
  

 -23- 








 18.7 The failure of either party to assert a right to which it is entitled or to insist upon compliance
with any term or condition of this Agreement shall not constitute a waiver of that right or excuse a similar subsequent failure to perform any such term or condition by the other party. 
  
 18.8 Licensee agrees to mark any Licensed Products sold in the United States with all applicable United States patent
numbers. All Licensed Products shipped to or sold in other countries shall be marked in such a manner as to conform with the patent laws and practices of the country of manufacture or sale. 
  
 18.9 Each party hereto agrees to execute, acknowledge and deliver such
further instruments and do all such further acts as may be necessary or appropriate to carry out the purposes and intent of this Agreement. 
  
 18.10 The paragraph headings contained in this Agreement are for reference purposes only and shall not in any way affect the meaning or interpretation of
this Agreement. 
  
 18.11 Subject to the provisions of Article XII
hereof, this agreement shall be binding upon the parties and their respective successors and assigns. 
  
 18.12 Articles III (Paragraph 3.6), IX (Paragraphs 9.1 through 9.6), X, XI and XIII shall survive the termination of this Agreement. 
  
 IN WITNESS WHEREOF, the parties have executed this Agreement as of the date
last written below. 
  

			
	 CHILDREN’S MEDICAL CENTER
 CORPORATION

		
	By:	 	[illegible]
		
	Name:	 	 
		
	Title:	 	 
		
	Date:	 	 

  

			
	 LICENSEE

		
	By:	 	 /S/    P. KAY
WAGONER

		
	Name:	 	 P. Kay Wagoner, Ph. D.

		
	Title:	 	 President & CEO

		
	Date:	 	 2/29/2000


  

 -24- 








 APPENDIX A 
  

US Patent Application Serial No. [**] 
  
 US Patent Application Serial No. [**] 
  
 US Patent Application Serial No. [**] (US Patent [**]) 
  
 International Application No. [**] 
  
 Any Continuation, Continuation-in-Part, or Divisional Application(s) of [**]: 
  

	 	1.	US Patent Application Serial No. [**]; 

  

	 	2.	International Patent Application No. [**], 

  
 which contain [**]. 









 APPENDIX B 
  

US Patent Application Serial No. [**] 
  
 International Application No. [**] 









 APPENDIX C 
  

ICAgen Sickle Cell Disease Development Plan 
  
 Confidential 
  

					
	 Development Milestone

	  	 Target Date

	  	 Cumulative Funding
Commitment (est.)


	 [**]
	  	[**]	  	 
	 [**]
	  	[**]	  	Total $[**]
	 [**]
	  	[**]	  	 
	 [**]
	  	[**]	  	Total $[**]
	 [**]
	  	[**]	  	 
	 [**]
	  	[**]	  	 










 APPENDIX D 
  

 TERMS OF SPONSORED RESEARCH AGREEMENT 
  

Icagen shall provide a total of $[**]in research grants to the Children’s Hospital researchers over a [**] period. Funding will begin six months after the
execution of the License Agreement to which this Appendix pertains and will be paid [**] in $[**] installments. This amount does not include anticipated grants for future [**] conducted with [**]. 









 APPENDIX E 
  
 INVENTION ADMINISTRATION AGREEMENT, DATED FEBRUARY 13,1995 BETWEEN THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE AND CHILDREN’S MEDICAL CENTER CORPORATION.

  
 INVENTION ADMINISTRATION AGREEMENT, DATED MAY 24, 1995 BETWEEN THE PRESIDENT
AND FELLOWS OF HARVARD COLLEGE, BRIGHAM AND WOMEN’S HOSPITAL, INC. AND CHILDREN’S MEDICAL CENTER CORPORATION. 
  
 MEMORANDUM, DATED DECEMBER 1, 1997 BETWEEN THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE AND CHILDREN’S MEDICAL CENTER CORPORATION REGARDING INVENTION ADMINISTRATION
AGREEMENT. 
  
 INVENTION ADMINISTRATION AGREEMENT DATED FEBRUARY 3, 1995 BETWEEN
THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE, BETH ISRAEL HOSPITAL AND CHILDREN’S MEDICAL CENTER CORPORATION. 
  
 AMENDMENTS DATED JANUARY 9, 1997, NOVEMBER 13, 1996, NOVEMBER 19, 1996 AND NOVEMBER 20, 1996 TO INVENTION ADMINISTRATION AGREEMENT DATED FEBRUARY 3, 1995 
  
 RESEARCH AGREEMENT BETWEEN CHILDREN’S HOSPITAL AND SHEFFIELD MEDICAL TECHNOLOGIES, INC.,
DATED JUNE 1, 1995 
  
 AMENDMENTS #1-6 TO RESEARCH AGREEMENT BETWEEN
CHILDREN’S HOSPITAL AND ION PHARMACEUTICALS, INC., DATED NOVEMBER 1, 1996 
  
 RESEARCH AND LICENSE OPTION AGREEMENT BETWEEN CHILDREN’S MEDICAL CENTER CORPORATION AND ION PHARMACEUTICALS, INC., DATED JUNE 1, 1996 
  
 LICENSE AGREEMENT BETWEEN CHILDREN’S MEDICAL CENTER CORPORATION AND ION PHARMACEUTICALS, INC., DATED NOVEMBER 1, 1996 
  
 MODIFICATION #1 TO THE LICENSE AGREEMENT BETWEEN CHILDREN’S MEDICAL CENTER CORPORATION
AND ION PHARMACEUTICALS, INC., DATED NOVEMBER 1, 1996 
  
 LICENSE AGREEMENT
BETWEEN THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE AND SHEFFIELD MEDICAL TECHNOLOGIES, INC., DATED AUGUST 22, 1994 
  
 MODIFICATION #1 TO LICENSE AGREEMENT DATED AUGUST 22, 1994 BETWEEN THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE AND SHEFFIELD MEDICAL TECHNOLOGIES, INC. 









 MODIFICATION #2 TO LICENSE AGREEMENT DATED AUGUST 22, 1994 BETWEEN THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE AND ION
PHARMACEUTICALS, INC. 
  
 MODIFICATION #3 TO LICENSE AGREEMENT DATED AUGUST 22,
1994 BETWEEN THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE AND ION PHARMACEUTICALS, INC. 
  
 RESEARCH AGREEMENT DATED AUGUST 22, 1994 BETWEEN THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE AND SHEFFIELD MEDICAL TECHNOLOGIES, INC. 
  
 AMENDMENT #1 TO THE RESEARCH AGREEMENT BETWEEN THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE AND SHEFFIELD MEDICAL TECHNOLOGIES, INC., DATED AUGUST 22, 1995 
  
 ASSIGNMENT AND LICENSE AGREEMENT BETWEEN 1266417 ONTARIO LIMITED AND ION PHARMACEUTICALS,
INC., DATED DECEMBER 3, 1997 
  
 SUB-LICENSE AGREEMENT BETWEEN 1266417 ONTARIO
LIMITED AND ION PHARMACEUTICALS, INC., DATED DECEMBER 3, 1997 
  
 ASSIGNMENT AND
SUBLICENSE AGREEMENT DATED SEPTEMBER, 1999 BETWEEN CHILDREN’S MEDICAL CENTER CORPORATION AND ION PHARMACEUTICALS, INC. 









 Intellectual Property Office 
 Children’s Hospital Boston 
 300 Longwood Avenue 
 Boston, MA 02115 
 phone 617-355-4050 fax
617-730-0146 
 IPO@childrens.harvard.edu 
 www.childrenshospital.org/ipo 
  
 August 30, 2004 
  
 Ms. Kay Wagoner 
 President & CEO 
 ICAgen, Inc. 
 4222 Emperor Boulevard, Suite 350 
 Durham, NC 27703 
  
 Dear Kay: 
  
 Thank you for providing the update on the Development Plan and Annual Plan for the Sickle Cell Program. We are delighted to learn of Icagen’s progress. 
  
 We acknowledge receipt of the updated milestone timeline and look forward to learning of
Icagen’s progression into Phase III Clinical trials. A signed copy of the amended Development Plan is enclosed as acknowledgement of receipt by our office. 
  

Please continue to keep us apprised of your progress. 
  

	
	 With kind regards,

	
	 /s/ Leslie Grushkin-Lerner, Ph.D.

	 Leslie Grushkin-Lerner, Ph.D.
 Licensing Manager











 Appendix C 
  

 Icagen Sickle Cell Disease Development Plan 
 CONFIDENTIAL 
  

					
	 Development Milestone

	  	Target Date

	 	 Cumulative Funding
Commitment (est.)


	 IND Filing with US FDA
	  	Filed	 	$[**]
	 Initiate Phase 2 Clinical Trial
	  	Completed	 	$[**]
	 Initiate Phase 3 Clinical Trial
	  	[**]	 	$[**]
	 US NDA Submission
	  	[**]	 	$[**]
	 Initiate Marketing in USA (by Icagen or via Partner)
	  	[**]	 	 
	 Initiate Marketing in First non-USA Country (by Icagen or Partner)
	  	[**]	 	 

  
 Acknowledged and Agreed to by
Children’s Medical Center Corporation: 
  

			
		
	 Name:
	 	 /s/ Donald P. Lombardi

		
	 Title:
	 	 Chief Intellectual Property Officer

		
	 Date:
	 	 August 27, 2004











 Appendix C 
  

 (revised as of July 20, 2007) 
  
 Icagen Clinical Development Plan for Senicapoc (ICA-17043) 
 CONFIDENTIAL 
  

					
	 DEVELOPMENT MILESTONE

	  	TARGET DATE

	 	CUMMULATIVE FUNDING
COMMITMENT


	 Completion of Phase III study report
	  	[**]	 	$[**]
	 Completion of preclinical and feasibility studies and expert panel reviews for additional indications
	  	[**]	 	$[**]
	 Initiation of Phase II clinical trial
	  	[**]	 	$[**]
	 Initiation of Phase III trial
	  	[**]	 	$[**]
	 US NDA submission
	  	[**]	 	[**]
	 Initiate marketing in first non-US country (with or without corporate partner)
	  	[**]	 	[**]

  
 Acknowledged and agreed to by
Children’s Medical Center Corporation 
  

			
	Name:	 	/s/ Brenda Manning
	Title:	 	Director, Intellectual Property Office
	Date:	 	July 20, 2007