Document:

Exhibit 10.12

 

EXECUTION COPY

 

Confidential Materials omitted and filed separately with the Securities and Exchange Commission.  Double asterisks denote omissions.

 

COMMERCIALIZATION AGREEMENT

 

This Commercialization Agreement (this “Agreement”) is entered into as of 29 April 2013 (the “Effective Date”), by and between uniQure Biopharma B.V., formerly known as Amsterdam Molecular Therapeutics (AMT) B.V., a Dutch corporation, with its offices at Meibergdreef 61, 1105 BA Amsterdam, The Netherlands (“uniQure”), and Chiesi Farmaceutici S.p.A., an Italian corporation, with its offices at Via Palermo, 26/A, 43122 Parma, Italy (“Chiesi”). uniQure and Chiesi are sometimes referred to herein individually as a “Party” and collectively as the “Parties”.

 

WHEREAS, uniQure is a company engaged in the research and clinical development of human gene based therapies. Its lead product, “Glybera”, for the treatment of lipoprotein lipase deficiency was approved by the European Commission in November 2012;

 

WHEREAS, Chiesi is a pharmaceutical company engaged in the research, development, sales and marketing as well as distribution of ethical medicinal products;

 

WHEREAS, uniQure desires to appoint Chiesi, on an exclusive basis, to obtain and maintain the best possible Price and Reimbursement Approval (as defined below) and to Commercialize (as defined below) the Product (as defined below) in the Territory (as defined below), in accordance with the terms and conditions set forth below, and Chiesi desires to accept uniQure’s exclusive appointment.

 

NOW, THEREFORE, uniQure and Chiesi hereby agree as follows:

 

ARTICLE I

DEFINITIONS; INTERPRETATION

 

Capitalized terms used herein shall have the meanings assigned to them as follows.

 

1.1                               “Affiliate” shall mean, with respect to a Party, any Person Controlled by, in Control of, or under common Control with such Party.

 

1.2                               “Additional Rights” has the meaning set forth in Section 7.5(a).

 

1.3                               “Agreement” has the meaning set forth in the first and opening paragraph of this Agreement.

 

1.4                               “Alliance Manager” has the meaning set forth in Section 4.4.

 

1.5                               “Applicable Laws” shall mean all applicable laws, statutes, codes, rules and regulations, judgments, order and ordinances, including any rules, regulations, guidelines or other requirements of any Regulatory Authority within the Territory, that may be in effect from time to time.

 

1.6                               “Approved Activities” has the meaning set forth in Section 8.1(b).

 

 

CONFIDENTIAL

 

1.7                               “Average Net Sales Price” shall mean the average net sales price of a particular Product in the Territory, calculated on a monthly basis, by dividing the Net Sales of the Product in the Territory effected in a particular calendar month by the number of patient doses of the Product accounting for the Net Sales in such calendar month.

 

1.8                               “Business Day” shall mean a day on which banking institutions in Amsterdam, The Netherlands and Parma, Italy, are open for business, excluding any Saturday or Sunday.

 

1.9                               “Certificate of Analysis” shall mean the certificate substantially in the form attached hereto as Schedule 1.9 evidencing the analytical test conducted on a specific lot of Product and setting forth, among other items, the items tested, Specifications, and test results.

 

1.10                        “Certificate of Compliance” shall mean the certificate substantially in the form attached as Schedule 1.10 stating that a specific lot of Product complies with the warranties set forth in Section 5.2.

 

1.11                        “Chiesi” has the meaning set forth in the first and opening paragraph of this Agreement.

 

1.12                        “Claims” has the meaning set forth in Section 6.1.

 

1.13                        “Co-Development and License Agreement” shall mean that certain Co-Development and License Agreement for Hemophilia B concluded separately between the Parties on the date hereof.

 

1.14                        “Collaboration” shall mean the relationship between and activities conducted by the Parties under this Agreement and all other agreements between the Parties referenced herein (other than the Confidentiality Agreement), including the Co-Development and License Agreement (collectively, the “Collaboration Agreements”).

 

1.15                        “Collaboration Agreements” has the meaning set forth in Section 1.14.

 

1.16                        “Commercialization” shall mean any and all activities, whether before or after Regulatory Approval, directed to the marketing, detailing and promotion of the Product and shall include pre-launch, launch and post-launch marketing, promoting, detailing, marketing research, medical affairs, managed markets, distributing, offering to commercially sell and commercially selling the Product, importing, exporting or transporting the Product for commercial sale and regulatory affairs with respect to the foregoing, including the filing and obtaining of Price and Reimbursement Approval for the Product, but shall not include Manufacturing nor any development activities. When used as a verb, “Commercializing”, “Commercialize” and “Commercialized” shall mean to engage in Commercialization.

 

1.17                        “Commercially Reasonable Efforts” shall mean, with respect to the efforts to be expended by a Party with respect to a goal, reasonable, diligent, good faith efforts to accomplish such goal as a similarly situated (with respect to size and assets) pharmaceutical company would use to accomplish a similar goal under similar circumstances so as to achieve such goal as expeditiously as possible; provided that, with

 

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respect to the Commercialization of the Product, such efforts shall be substantially equivalent to those efforts and resources that a similarly situated (with respect to size and assets) pharmaceutical company would typically devote to its own internally discovered products of similar market potential at a similar stage in their product life so as to achieve such goal as expeditiously as possible (which, with respect to activities for which Chiesi is responsible, shall be without regard to any amounts paid or payable to uniQure with respect to the Product under this Agreement or the Co-Development and License Agreement). Without prejudice to the foregoing and with respect to Chiesi, Commercially Reasonable Efforts shall at least include the efforts as further described in Schedule 8.1(a).

 

1.18                        “Confidential Information” shall mean all confidential or proprietary information of a Party, including information regarding such Party’s or its Affiliates’ or licensors’ products, business, business plans, financial status, biological substances, chemical substances, formulations, techniques, methodology, equipment, sources of supply and patent positioning and information belonging to such Party’s Affiliate or a Third Party and provided to the other Party under this Agreement. The terms and conditions of this Agreement shall be deemed “Confidential Information” of both Parties. All information disclosed by uniQure prior to the Effective Date pursuant to the Two Way Confidentiality Disclosure Agreement between Amsterdam Molecular Therapeutics (AMT) B.V. and Chiesi Farmaceutici S.p.A. dated 22 July 2010 (the “Confidentiality Agreement”) shall be deemed “Confidential Information” of uniQure hereunder.

 

1.19                        “Confidentiality Agreement” has the meaning set forth in Section 1.18.

 

1.20                        “Confirmed Firm Order” has the meaning set forth in Section 2.4(c).

 

1.21                        “Control” or “Controlled” shall mean, (a) when used in reference to any Confidential Information, Patent or other Intellectual Property Rights, the possession (whether by ownership or license (other than solely pursuant to a license under this Agreement)) by such Party or any of its Affiliates, of the legal authority or right to grant to the other Party access or a license or sublicense to such Confidential Information, Patent or other Intellectual Property Rights as provided herein, without violating the terms of any agreement or arrangement with any Third Party, or (b) when used in reference to Section 1.1, (i) the possession, directly or indirectly, of the power to direct the management or policies of a Person, whether through ownership of voting securities, by contract or otherwise; (ii) ownership of fifty percent (50%) or more of the voting securities entitled to vote for the election of directors in the case of a corporation, or fifty percent (50%) or more of the equity interest in the case of any other type of legal entity; or (iii) status as a general partner in any partnership, or any other arrangement whereby a Person controls or have the right to control the board of directors or equivalent governing body of a corporation or other Person. Notwithstanding the foregoing, any portfolio company of any stockholder of such Person (which stockholder is a venture capital fund or private equity fund) shall not be deemed to be “under common Control with” such Person.

 

1.22                        “Controlling Party” has the meaning set forth in Section 7.5(b).

 

1.23                        “Cover” or “Covered” shall mean, with respect to any Patent and the subject matter at issue, that, but for a license granted under a Valid Claim of such Patent, the manufacture, use, sale, offer for sale or importation of the subject matter at issue

 

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would infringe such Valid Claim, or, in the case of a Patent that is a patent application, would infringe a Valid Claim in such patent application if it were to issue as a patent.

 

1.24                        “Delivery Notification” has the meaning set forth in Section 2.5(b).

 

1.25                        “Discretionary Manufacturing Changes” has the meaning set forth in Section 3.4(b).

 

1.26                        “Effective Date” has the meaning set forth in the first and opening paragraph of this Agreement.

 

1.27                        “EMA” shall mean the European Medicines Agency and any successor agency thereto.

 

1.28                        “EU” shall mean the European Union.

 

1.29                        “EU Member States” shall mean Austria, Belgium, Bulgaria, Cyprus, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, the Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom.

 

1.30                        “Executive Officers” shall mean the Chief Executive Officer of Chiesi or a senior officer designated by Chiesi, and the Chief Executive Officer of uniQure or a senior officer designated by uniQure.

 

1.31                        “Existing Third Party Licenses” has the meaning set forth in Section 7.4.

 

1.32                        “EXW” shall mean “ex works” as defined by the International Chamber of Commerce (Incoterms 2010).

 

1.33                        “Failure to Supply” has the meaning set forth in Section 2.6(a).

 

1.34                        “FDA” shall mean the US Food and Drug Administration and any successor agency thereto.

 

1.35                        “Field” shall mean the treatment of lipoprotein lipase deficiency.

 

1.36                        “Firm Order” shall mean a written (including facsimile or email) irrevocable firm purchase order for the Product, which order shall include the precise name of the Product ordered and the quantity of the Product ordered (such quantity to be equal or above the Minimum Order Quantity).

 

1.37                        “First Commercial Sale” shall mean the first sale by Chiesi, an Affiliate of Chiesi, or a Sub-distributor of Chiesi, as the case may be, of the Product to a Third Party in the Territory; provided, however, that neither (a) transfers of the Product between Chiesi and its Affiliates or Sub-distributors nor (b) supply of the Product for clinical trial purposes, shall constitute a First Commercial Sale.

 

1.38                        “Force Majeure Event” has the meaning set forth in Section 11.6.

 

1.39                        “Forecast” has the meaning set forth in Section 2.4(a).

 

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1.40                        “FTE” shall mean an annual average of at least [**] hours allocated to one or more persons allocated to the Commercialization of the Product (including product specialists, KAMs, MSLs, medical, regulatory, pharmacovigilance, market access and marketing personnel) in the Territory (both at an headquarter and country level).

 

1.41                        “Fully Loaded Cost of Goods” shall mean the fully loaded cost of goods of the Product as defined in Schedule 2.3.

 

1.42                        “GDPs” shall mean the current good distribution practices promulgated by any Regulatory Authorities or Applicable Laws throughout the Territory that are applicable to the Product.

 

1.43                        “Gene Therapy” shall mean the introduction and expression of genetic material in cells of a person in order to cure a disease or to minimize disease symptoms.

 

1.44                        “Glybera Manufacturing Cost Reimbursement” has the meaning set forth in Section 2.3(c)(i).

 

1.45                        “GMPs” shall mean the current good manufacturing practices promulgated by any Regulatory Authorities or Applicable Laws throughout the Territory that are applicable to the Product.

 

1.46                        “Improvements” shall mean any improvements to the Product Controlled by uniQure during the Term, such as future formulations, dosages, dosage forms, delivery modes and line extensions of the Product, packaging of the Product, labeling of the Product, and developments in the Product itself.

 

1.47                        “Indemnified Party” has the meaning set forth in Section 6.3(i).

 

1.48                        “Indemnifying Party” has the meaning set forth in Section 6.3(i).

 

1.49                        “Intellectual Property Rights” shall mean all patents (including the Patents), trademarks (including the Trademark), trade names, service marks, trade dress, trade secrets and copyrights, including, without limitation, any renewal, extension or other rights therefor, and applications, provisionals, divisionals, reexaminations, continuations in part, divisions, continuations, reissues, additions, substitutions and registrations for any of the foregoing and all corresponding foreign patents and patent applications of each of the foregoing, technical information, devices, processes, procedures, discoveries, techniques, formulae, software, designs, drawings, data, methods, protocols, products, apparatuses and other materials, compositions, mask works, domain names, schematics, manufacturing processes, know-how, moral rights, software programs or applications, manufacturing and production processes and techniques, research and development information, drawings, specifications, designs, plans, proposals, technical data, results of experimentation and testing (whether or not patentable) in written, electronic, physical (including in the form of tangible compounds or cell lines), oral or any other form, financial and marketing plans, customer and supplier lists and information, and all other intellectual property or proprietary rights.

 

1.50                        “JCC” has the meaning set forth in Section 4.2(a).

 

1.51                        “JSC” has the meaning set forth in Section 4.1(a).

 

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1.52                        “Losses” has the meaning set forth in Section 6.1.

 

1.53                        “Lost Profit” has the meaning set forth in Section 2.6.

 

1.54                        “Manufacture” and “Manufacturing” shall mean all activities related to the production, manufacture, processing, filling, finishing, packaging, labeling, shipping and holding of the Product or any intermediate thereof, including process development, process qualification and validation, scale up, pre-clinical, clinical and commercial manufacture and analytical development, product characterization, stability testing, quality assurance and quality control. When used as a verb, “Manufacture” shall mean to engage in Manufacturing.

 

1.55                        “Marketing Authorization” shall mean the authorization issued by the relevant Regulatory Authority necessary to place on the market the Product in any country or regulatory jurisdiction in the Territory (including the centralized approval of a Marketing Authorization Application in the EU). For clarity, a Marketing Authorization shall not include any applicable Price and Reimbursement Approvals.

 

1.56                        “Marketing Authorization Application” shall mean an application submitted to a Regulatory Authority for marketing approval of a drug or biologic product, including (a) a Marketing Authorization Application in the EU under Regulation (EC) No. 726/2004 or Directive 2001/83/EC, (b) any non-EU equivalent of the foregoing in any other country in the Territory, and (c) all supplements and amendments that may be filed with respect to any of the foregoing.

 

1.57                        “Marketing Plan” has the meaning set forth in Schedule 8.1(a).

 

1.58                        “Minimum FTEs” has the meaning set forth in Schedule 8.1(a).

 

1.59                        “Minimum Order Quantity” has the meaning set forth in Section 2.4(d).

 

1.60                        “Net Sales” shall mean the total amount of invoiced sales of the Product in the Territory by or on behalf of Chiesi or its Affiliates or Sub-distributors to Third Parties (including wholesalers, hospitals, end users and others), in bona fide arm’s length transactions, less the following deductions, in each case related specifically to the Product and customary in the trade and actually allowed and taken by such Third Parties and not otherwise recovered by or reimbursed to Chiesi: (a) cash discounts allowed and actually taken; (b) 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; (c) freight and insurance to the extent added to the sale price and set forth separately as such in the total amount invoiced; (d) amounts repaid or credited by reason of rejections, defects, recalls, expirations, or returns; and (e) any governmental mandated charge backs, rebates, and discounts. No deductions shall be made for (x) commissions paid to individuals, whether they are with independent sales agencies or regularly employed by Chiesi or any of its Affiliates, and on its payroll, (y) the cost of collections, and (z) any advertising and promotional expenses. In no event shall Chiesi have a right to apply any discounts or deductions on the Product, resulting from Chiesi entering into “package deals” whereby Chiesi sells more than one product (in addition to the Product) to a customer and offers “package deal discounts”.

 

1.61                        “Non-Controlling Party” has the meaning set forth in Section 7.5(b).

 

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1.62                        “Party” and “Parties” has the meaning set forth in the first and opening paragraph of this Agreement.

 

1.63                        “Patents” shall mean any patent or patent application, including utility patents, utility models, design patents, provisional applications, certificates of invention, and all divisionals, continuations, continuations-in-part, substitutions, reissues, reexaminations, renewals, extensions (including any supplemental protection certificate) or additions to any patent or patent application that Cover the Product owned or Controlled by either of the Parties as of the Effective Date or during the Term. Schedule 1.63 sets forth a list of Patents that Cover the Product in the Territory owned or Controlled by uniQure as of the Effective Date, such list to be updated or confirmed upon the date this Agreement has become effective pursuant to Section 9.1(b).

 

1.64                        “Person” shall mean any natural person or any corporation, company, partnership, limited liability company, joint venture, firm, agency or other entity, including a Party.

 

1.65                        “Price and Reimbursement Approval” shall mean any approval or authorization of any Regulatory Authority establishing a pricing- and payment scheme or a reimbursement scheme for the Product in any country or jurisdiction of the Territory.

 

1.66                        “Product” shall mean the medicinal product set forth in Schedule 1.66, and any Improvements thereof.

 

1.67                        “Product Complaint” shall mean any oral or written communication of dissatisfaction issued by any Regulatory Authority regarding the identity, quality, durability, reliability or performance of any Product, including appearance, low fills, foreign materials, foreign product, defective packaging or defective labeling.

 

1.68                        “Profit” has the meaning set forth in Section 2.6.

 

1.69                        “Publishing Party” has the meaning set forth in Section 10.5(a).

 

1.70                        “Purchase Price” has the meaning set forth in Section 2.3(b).

 

1.71                        “Quality Agreement” has the meaning set forth in Section 3.3(a).

 

1.72                        “Registry” shall mean an organized system that uses observational study methods to collect uniform data (clinical and other) to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure, and that serves one or more predetermined scientific, clinical, or policy purposes and meets the requirements of the EMA.

 

1.73                        “Regulatory Approval” shall mean any and all approvals (including, where required, any applicable Price and Reimbursement Approvals), licenses, registrations or authorizations of any Regulatory Authority necessary for the Commercialization or use of a Product in a country or jurisdiction, including Marketing Authorizations.

 

1.74                        “Regulatory Authority” shall mean any federal, national, multinational, state, provincial or local regulatory agency, department, bureau or other governmental entity with authority over the testing, Regulatory Approval, manufacture, use, storage,

 

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import, promotion, marketing or sale of a drug or biologic product in a country or jurisdiction, including the EMA.

 

1.75                        “Regulatory Plan” has the meaning set forth in Section 3.2.

 

1.76                        “Required Manufacturing Changes” has the meaning set forth in Section 3.4(a).

 

1.77                        “SDEA” has the meaning set forth in Section 3.3(b).

 

1.78                        “Specifications” shall mean the composition, quality and specifications regarding the Product as may be amended, modified or supplemented from time to time in accordance with the terms hereof. The initial Specifications are annexed as Schedule 1.78.

 

1.79                        “Sub-distributor” shall mean a Third Party that is granted a sub-distribution or other Commercialization right in the Territory by Chiesi in accordance with this Agreement.

 

1.80                        “Subject Disclosure” has the meaning set forth in Section 10.3(b).

 

1.81                        “Target Price” has the meaning set forth in Schedule 8.1(a).

 

1.82                        “Term” has the meaning set forth in Section 9.1(a).

 

1.83                        “Territory” shall mean (i) the EU Member States, Iceland, Liechtenstein and Norway and (ii) Albania, Andorra, Bosnia, Croatia, Macedonia, Monaco, Montenegro, Republic of San Marino, Serbia (including Kosovo), Switzerland and Vatican City ((i) and (ii), collectively, “Territory A”) as well as (iii) Algeria, Brazil, China, Egypt, Mexico, Morocco, Pakistan, Russia and ex-CIS countries (i.e. Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kirghizstan, Moldova, Tajikistan, Turkmenistan, Ukraine and Uzbekistan), Tunisia and Turkey (“Territory B”).

 

1.84                        “Territory A” has the meaning set forth in Section 1.83.

 

1.85                        “Territory B” has the meaning set forth in Section 1.83.

 

1.86                        “Third Party” shall mean any Person other than uniQure, Chiesi, or their respective Affiliates.

 

1.87                        “Trademark” has the meaning set forth in Section 2.2(a)(i).

 

1.88                        “uniQure” has the meaning set forth in the first and opening paragraph of this Agreement.

 

1.89                        “uniQure Intellectual Property Rights” shall mean all Intellectual Property Rights Controlled by uniQure on the Effective Date or during the Term which would be infringed by the Commercialization of the Product as provided for in this Agreement.

 

1.90                        “Valid Claim” shall mean any claim within an issued and unexpired Patent or within a pending Patent application that (i) is not expired, lapsed, or abandoned, (ii) is not dedicated to the public, disclaimed, or admitted to be unenforceable or invalid; and (iii) has not been invalidated, held unenforceable or cancelled by a court or administrative

 

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agency of competent jurisdiction in an order or decision from which no appeal has been or can be taken, including through opposition, re-examination, reissue, disclaimer or otherwise.

 

1.91                        “Interpretation”. Any reference in this Agreement to an Article, Section, subsection, paragraph, clause, or Schedule shall be deemed to be a reference to any Article, Section, subsection, paragraph, clause, or Schedule, of or to, as the case may be, this Agreement. Except where the context clearly otherwise requires, (a) wherever used, the use of any gender will be applicable to all genders, (b) the singular shall include the plural and vice versa, (c) any definition of or reference to any agreement, instrument or other document refers to such agreement, instrument other document as from time to time amended, supplemented or otherwise modified (subject to any restrictions on such amendments, supplements or modifications set forth herein or therein), (d) any reference to any Applicable Laws refers to such Applicable Laws as from time to time enacted, repealed or amended, (e) the words “herein”, “hereof” and “hereunder”, and words of similar import, refer to this Agreement in its entirety and not to any particular provision hereof, (f) the words “include”, “includes” and “including” are deemed to be followed by the phrase “but not limited to”, “without limitation” or words of similar import, (g) the word “or” has the inclusive meaning (i.e., “and/or”), (h) the word “day” means a calendar day, the word “month” means a calendar month, and the word “year” means, and the word “annual” refers to, a calendar year, (i) the word “quarterly” refers to a calendar quarter, (j) each accounting term used herein that is not specifically defined herein has the meaning given to it under the International Financial Reporting Standards, and (k) the captions or headings of the Schedule, Articles, Sections or other subdivisions hereof are inserted only as a matter of convenience or for reference and shall have no effect on the meaning of the provisions hereof.

 

ARTICLE II

APPOINTMENT, SUPPLY OF PRODUCTS

 

2.1                               Appointment, Consideration.

 

(a)                                 Subject to the terms hereof, uniQure hereby appoints Chiesi as its distributor with the exclusive right to Commercialize the Product solely in the Field in the Territory during the Term.

 

(b)                                 Chiesi shall be entitled to appoint any of its Affiliates or, subject to the prior written consent of uniQure, which shall not be unreasonably withheld, Third Parties as sub-distributor to the extent required for Commercialization of the Product in the Field in the Territory. In this event, Chiesi shall procure, and shall remain ultimately responsible for, compliance by such Affiliates or Sub-distributors with all the relevant obligations of Chiesi hereunder.

 

(c)(1)                   Subject to the condition precedent pursuant to Section 9.1(b), Chiesi shall pay to uniQure, after receipt of a proper invoice, a one-time, non-refundable fee of EUR 2,000,000.00 (in words: two million Euro) in recognition of uniQure’s past expenditure developing the Product, within [**] Business Days after this Agreement has become effective pursuant to Section 9.1(b).

 

(c)(2)                   In consideration of the licenses, rights and interest granted under this Agreement, and in addition to any other payments due hereunder, Chiesi shall pay to

 

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uniQure, after receipt of a proper invoice, the following commercial milestone payments, in each case within [**] days after the end of the corresponding calendar year:

 

(A)                               EUR [**] (in words: [**] Euro) when cumulated Net Sales of the Product achieve EUR [**] (in words: [**] Euro) in a calendar year;

 

(B)                               EUR [**] (in words: [**] Euro) when cumulated Net Sales of the Product achieve EUR [**] (in words: [**] Euro) in a calendar year;

 

(C)                               EUR [**] (in words: [**] Euro) when cumulated Net Sales of the Product achieve EUR [**] (in words: [**] Euro) in a calendar year;

 

(D)                               EUR [**] (in words: [**] Euro) when cumulated Net Sales of the Product achieve EUR [**] (in words: [**] Euro) in a calendar year.

 

Within [**] days after the end of each calendar year, Chiesi shall inform uniQure of the occurrence or, as the case may be, non-occurrence, of any such milestone event.

 

For the avoidance of doubt, each milestone is payable once, up to a maximum of EUR 42,000,000.00 (in words: forty two million Euro) in milestone payments and only one milestone is payable for any given calendar year. For clarity, the highest unpaid payment possible shall be paid with respect to a particular calendar year, and any payment not made because a higher payment was due shall be available for payment if the relevant Net Sales threshold is achieved in a subsequent year. For example, if, in calendar year 2014, Product sales of EUR [**] (in words: [**] Euro) are first achieved and Product sales had not achieved EUR [**] (in words: [**] Euro) in calendar year 2013, then EUR [**] (in words: [**] Euro) shall be due with respect to the sales in 2014 and if, in 2015, Product sales achieve at least EUR [**] (in words: [**] Euro), but less than EUR [**] (in words: [**] Euro), then the EUR [**] (in words: [**]  Euro) payment shall be due with respect to the sales in 2015.

 

(d)                                 Chiesi shall keep complete and accurate records of Product sold or otherwise made available as appropriate to determine the amount of commercial milestones and other payments to be paid to uniQure. These records shall be retained for at least [**] years after delivery of the Product pursuant to Section 2.5. uniQure shall have the right [**] at uniQure’s expense to retain an independent certified public accountant selected by uniQure, and reasonably acceptable to Chiesi, to review such records in the location(s) where such records are maintained by Chiesi upon reasonable notice and during regular business hours and under obligations of confidence. Results of such review shall be made available to both Parties. If the review indicates that there was an underpayment of any amount payable to uniQure, the amount of such underpayment shall be remitted to uniQure within [**] days after such review, together with interest calculated in the manner provided in paragraph (f) below. If the underpayment is equal to or greater than [**] percent ([**]%) of the amount that was otherwise due, Chiesi shall pay all of uniQure’s reasonable out-of-pocket expenses of such review. If the review

 

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indicates that there was an overpayment of any amounts by Chiesi, Chiesi may apply the amount of such overpayment to any future payment due to uniQure under Section 2.3.

 

(e)                                  All payments to be made under this Agreement shall be made in EUR by wire transfer to the account designated by uniQure in writing. If amounts (e.g. Average Net Sales Price or Fully Loaded Cost of Goods) relevant for the calculation of any payments to be made under this Agreement are in a currency other than Euros, such amounts shall be expressed in their Euro equivalent, calculated on the last Business Day of the calendar months to which the applicable amounts relate using the currency converter at www.oanda.com. Unless otherwise expressly set forth herein, all payments to uniQure are to be executed without any further deduction within [**] days after receipt by Chiesi of the invoice with respect thereto.

 

(f)                                   Any payment to uniQure under this Agreement that is not paid on or before the date such payment is due shall bear interest at the lesser of (i) [**] per year, or (ii) the highest rate permitted by Applicable Laws, calculated on the number of days such payments are overdue.

 

(g)                                  Any payment to be made under this Agreement shall be made plus value-added tax, if applicable.

 

(h)                                 To the extent that any payments hereunder by Chiesi to uniQure are subject to tax, Chiesi shall pay such tax; provided, however, that, with respect to any payments subject to withholding tax, Chiesi shall pay the applicable withholding tax amount to the relevant taxing authority and promptly provide uniQure with all necessary documentation for uniQure to recover such tax. Chiesi will take all reasonable and lawful steps to minimize the amount of any such withholding tax obligation and uniQure shall promptly provide all information and documentation in its possession necessary for doing so.

 

2.2                               Trademark, Labeling.

 

(a)                                 Trademark.

 

(i)                                     The Product will be Commercialized by Chiesi in the Field in the Territory exclusively under the trademark “Glybera” (as defined in Schedule 2.2(a)) or, subject to the prior written consent of uniQure, such alternative trademark identified by Chiesi (the “Trademark”). In the event that Chiesi provides sufficient written evidence to uniQure that the use of an alternative trademark is required under Applicable Laws to lawfully Commercialize the Product in any country or jurisdiction of the Territory and if Chiesi identifies any trademark other than “Glybera” for this purpose, then Chiesi shall be entitled to Commercialize the Product under such alternative trademark without the prior written consent of uniQure. In the event that Chiesi identifies any trademark other than “Glybera” for other material commercial reasons, Chiesi shall provide sufficient written evidence for such reasons to uniQure and shall not be entitled to Commercialize the Product under an alternative Trademark without the prior written consent of uniQure, such consent not to be unreasonably withheld. Chiesi shall inform uniQure promptly of the need of such alternative trademark, such notice to be accompanied by the aforementioned written evidence and a list of at least [**] alternative trademarks identified by Chiesi and suitable for Commercialization of the Product throughout the entire Territory.

 

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(ii)                                  In case the Product is Commercialized by Chiesi under the Trademark “Glybera”, uniQure hereby grants to Chiesi the exclusive, royalty-free, perpetual, irrevocable, right and license (subject to Section 9.3 below) to use the Trademark “Glybera” to Commercialize the Product solely in the Field in the Territory, with the right to grant sublicenses to Sub-distributors according to Section 2.1(b). Further, uniQure hereby grants to Chiesi the non-exclusive, royalty-free, right and license to use uniQure’s trade name (as defined in Schedule 2.2(a)) in each country of the Territory during the Term solely for the purpose of identifying uniQure as the manufacturer and Marketing Authorization holder of the Product as contemplated in this Agreement.

 

(iii)                               Chiesi acknowledges that, subject to the foregoing licenses, uniQure shall own all right, title and interest in and to the Trademark “Glybera” inside and outside the Field, whether inside or outside of the Territory as well as any goodwill associated with the Trademark “Glybera”. Chiesi shall ensure appropriate use of the trademark “Glybera” at all times in the entire Territory and observe the applicable trademark use guidelines issued by uniQure, as amended from time, attached in Schedule 2.2(b). Chiesi shall not, during the Term or thereafter, register, use, or attempt to obtain any right in and to (A) the trademarks “Glybera” and “uniQure”, or (B) any name, logo or trademark confusingly similar thereto. If Chiesi or any of its Affiliates or Sub-distributors challenges the validity of any such trademark during the Term, uniQure may terminate this Agreement in accordance with the provisions of Section 9.2(d). uniQure undertakes to maintain and defend the Trademark “Glybera” in each country inside the Territory during and, for as long as Chiesi retains licenses thereto, after the Term at its own cost. In the event that at any time during such term uniQure intends not to continue prosecution or maintenance of such Trademark anywhere inside the Territory, it shall inform Chiesi at least [**] days prior to doing so and shall, upon request of Chiesi transfer all right, title and interest in such Trademark in such country or jurisdiction to Chiesi for further prosecution and maintenance by Chiesi in Chiesi’s name and at Chiesi’s costs and Chiesi shall reimburse uniQure for any reasonable external costs incurred by uniQure for such transfer.

 

(iv)                              uniQure acknowledges that except as otherwise expressly provided in this Agreement, Chiesi shall own all right, title and interest in and to any Trademark other than the trademark “Glybera” as well as any goodwill associated therewith. In case the Product is Commercialized by Chiesi under such alternative Trademark, Chiesi hereby grants to uniQure an exclusive, royalty-free, perpetual, irrevocable, right and license (subject to Section 9.3 below) to use such Trademark to Manufacture and Commercialize the Product outside the Territory, with the right to grant sublicenses. uniQure shall not, during the Term or thereafter, register, use, or attempt to obtain any right in and to (A) such Trademark and the “Chiesi” trademark, or (B) any name, logo or trademark confusingly similar thereto. If uniQure or any of its Affiliates challenges the validity of any such trademark during the Term, Chiesi may terminate this Agreement in accordance with the provisions of Section 9.2(d). Chiesi undertakes to obtain, maintain and defend such Trademark in each country inside and, as requested by uniQure, outside of the Territory during and, for as long as uniQure retains licenses thereto, after the Term at its own cost. In the event that at any time during such term Chiesi intends not to continue prosecution or maintenance of such Trademark anywhere inside or outside of the Territory it shall inform uniQure at least [**] days prior to doing so and shall, upon request of uniQure transfer all right, title and interest in such Trademark in such country or jurisdiction to uniQure for further prosecution and 

 

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maintenance by uniQure in uniQure’s name and at uniQure’s costs and uniQure shall reimburse Chiesi for any reasonable external costs incurred by Chiesi for such transfer.

 

(b)                                 Labeling.

 

(i)                                     uniQure as Marketing Authorization holder of the Product in Territory A shall be ultimately responsible for the content and type of all labeling and packaging (and any changes or supplements thereto) for the Product to be Commercialized by Chiesi in the Field in Territory A. Notwithstanding the foregoing, the Parties agree that, subject to Section 3.1, (A) Chiesi shall provide all reasonable assistance to uniQure in connection with the labeling and packaging for the Product (e.g. use of Chiesi in-house capacity for the translation of package leaflets), and (B) the Product to be Commercialized by Chiesi in the Field in Territory A shall include, to the extent legally permitted, a reference to Chiesi as Commercialization partner, and shall take into account, to the extent legally permitted, Chiesi’s livery. Details shall be agreed upon between the Parties in the Regulatory Plan. Chiesi shall take out at its costs any necessary insurance required under Applicable Laws as a result of Chiesi being referred to as a Commercialization partner on the Product, and shall reimburse uniQure for any costs associated with changes to the labeling and packaging of the Product in accordance with the foregoing.

 

(ii)                                  Chiesi as Marketing Authorization holder of the Product in Territory B shall be ultimately responsible for the content and type of all labeling and packaging (and any changes or supplements thereto) for the Product to be Commercialized by Chiesi in the Field in Territory B. Notwithstanding the foregoing, the Parties agree that, subject to Section 3.1, (A) uniQure shall provide all reasonable assistance to Chiesi in connection with the labeling and packaging for the Product, and (B) the Product to be Commercialized by Chiesi in the Field in Territory B shall include, to the extent legally permitted, a reference to uniQure as originator and manufacturer of the Product, and shall take into account, to the extent legally permitted, uniQure’s livery. Details shall be agreed upon between the Parties in the Regulatory Plan. uniQure shall take out at its costs any necessary insurance required under Applicable Laws as a result of uniQure being referred to as originator and manufacturer on the Product, and shall reimburse Chiesi for any costs associated with changes to the labeling and packaging of the Product in accordance with the foregoing.

 

(iii)                               If, according to local mandatory regulatory requirements, uniQure is not eligible as Marketing Authorization holder of the Product in any country of Territory A, or Chiesi is not eligible as Marketing Authorization holder of the Product in any country of Territory B, Chiesi or, as the case may be, its Sub-distributor, or uniQure, shall become the Marketing Authorization holder of the Product in such country of the Territory. In such case, Chiesi or, as the case may be, its Sub-distributor, or uniQure, shall be ultimately responsible for the content and type of all labeling and packaging (and any changes or supplements thereto) for the Product to be Commercialized by Chiesi in the Field in such country of the Territory, and sentences 2 to 4 of paragraph (i) or (ii) above shall apply, respectively.

 

2.3                               Purchase of the Product.

 

(a)                                 Orders.  During the Term, Chiesi shall purchase from uniQure one hundred percent (100%) of Chiesi’s requirements for the Product for Commercialization 

 

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in the Field in the Territory. Purchase shall be made pursuant to Firm Orders submitted by Chiesi to uniQure from time to time in accordance with Section 2.4.

 

(b)                                 Purchase Price.  The purchase price for the individual Product ordered shall be the greater of (i) [**] and (ii) [**] (the “Purchase Price”).

 

(c)                                  Invoicing, Payment.  uniQure shall invoice Chiesi for all quantities of Product as follows:

 

(i)                                     As upfront payment to the Purchase Price, Chiesi shall pay to uniQure the Fully Loaded Cost of Goods, reduced by the cost items incurred by uniQure only after receipt of the corresponding Delivery Notification as identified in Schedule 2.3, for each patient dose of the Product delivered (i.e. through storage at uniQure’s warehouse) in accordance with Section 2.4 (“Glybera Manufacturing Cost Reimbursement”). uniQure shall promptly inform Chiesi of the occurrence of each such event.

 

(ii)                                  Chiesi shall pay the difference between the Purchase Price and the Glybera Manufacturing Cost Reimbursement within [**] days following the delivery of a particular patient dose of the Product in accordance with Section 2.5.

 

(iii)                               Section 2.1(e) to (h) shall apply.

 

2.4                               Forecasts; Firm Orders.

 

(a)                                 Forecasts.  Chiesi shall provide uniQure a non-binding forecast by [**], detailing the quantity of Product required for 2013. Every [**] months thereafter (i.e. no later than [**]) Chiesi shall provide uniQure a non-binding forecast detailing the quantity of Product per [**] required for the respective following [**] months period. Chiesi shall make all forecasts in good faith given market and other information available to Chiesi.

 

(b)                                 Firm Orders.  Chiesi shall purchase the Product solely by Firm Orders. Firm Orders consist of the number of patient doses for a period of [**] months specified per month. Chiesi shall submit each such Firm Order to uniQure at least [**] months in advance of the anticipated release date as specified in each Firm Order. Chiesi shall submit Firm Orders for the Product [**] times per calendar year no later than [**]. Notwithstanding the foregoing and the condition precedent set forth in Section 9.1(b), Chiesi shall submit the first Firm Order no later than [**] days after the Effective Date. Any terms or conditions contained in any Firm Order, acknowledgment, invoice, bill of lading, acceptance, or other writing or document issued by either Party, whether or not in conflict with the terms of this Agreement, shall be null and void without further notice required to be given by the other Party.

 

(c)                                  Order Processing.  In order to become effective, each Firm Order placed by Chiesi shall be confirmed by uniQure by facsimile or email showing the confirmed quantity indicated in each Firm Order and delivery (i.e. through storage at uniQure’s warehouse) date of the Product within [**] Business Days of receipt (the “Confirmed Firm Order”), provided that, if uniQure does not provide an acknowledgment of the Confirmed Firm Order within such period, uniQure shall be deemed to have confirmed the corresponding Firm Order. uniQure shall not be obliged to accept and 

 

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fulfill any Firm Orders which exceed [**] percent ([**]%) of the Product quantity indicated in each relevant forecast. uniQure shall ensure availability of confirmed quantities of the Product within [**] months after uniQure’s receipt of the corresponding Firm Order, provided, however, that in case a Firm Order exceeds [**] percent ([**]%) of the Product quantity indicated in each relevant forecast for the relevant period, and uniQure accepts such Firm Order, uniQure and Chiesi shall agree to a new release date and uniQure shall be entitled to release any amounts of Product exceeding the above threshold within [**] months after uniQure’s receipt of such Firm Order. uniQure shall store such Product at uniQure’s warehouse at uniQure’s cost.

 

(d)                                 Batch Sizes.  All quantities of Product ordered by Chiesi shall be consistent with uniQure’s current minimum batch sizes for the applicable Product (the “Minimum Order Quantity”), or multiples thereof, as set forth in Schedule 2.4(d). Notwithstanding the foregoing, uniQure agrees to support and cooperate with Chiesi to accept, fulfill and deliver order quantities at amounts less than the Minimum Order Quantity, in the event that Chiesi’s good faith internal evaluations or the requirements of customers for the Product support or require smaller quantity Firm Orders.

 

2.5                               Shipment and Delivery.

 

(a)                                 Terms.  Within [**] Business Days following receipt of a Delivery Notification from Chiesi, UniQure shall manufacture the finished dosage form of the Product for the quantities specified in the Delivery Notification (not to exceed the quantities in the respective Confirmed Firm Order), and ship such quantities of Product directly to the customers of Chiesi, together with a corresponding invoice to Chiesi. The Parties shall agree, after [**] the Effective Date, on a reduction of the [**] Business Day period set forth above. All quantities of Product shall be delivered EXW uniQure’s facility in Amsterdam. Chiesi shall obtain at its cost all necessary export or import licenses and permits to export or import the relevant quantities of the Product into the relevant country or jurisdiction of the Territory. Title and risk of loss and damage for any Product delivered pursuant to this Agreement shall pass to Chiesi at the time the same are tendered by uniQure to the carrier for delivery to Chiesi’s customers. uniQure shall pack Product for shipment in accordance with uniQure’s standard procedures and Applicable Laws, unless otherwise specified in writing by Chiesi within the scope of mandatory Applicable Laws [**] days prior to such shipment, in which event any extra costs incurred by uniQure on account of the packaging changes requested by Chiesi shall be promptly reimbursed by Chiesi.

 

(b)                                 Delivery Notification.  For each supply of Product to each of its customers, Chiesi shall ensure and confirm to uniQure in writing (each a “Delivery Notification”) that (i) the Product has obtained Price and Reimbursement Approval in the relevant part of the Territory, except for Germany until the relevant Price and Reimbursement Approval has been obtained, and (ii) the healthcare professionals involved in the treatment of a patient have received the educational pack and the patient to be treated with the supplied Product is included in the Registry.

 

(c)                                  Release.  uniQure shall perform release testing pursuant to the Specifications and in accordance with uniQure’s standard procedures regarding the Manufacturing of Product. After each shipment of Product, uniQure shall release the Product and provide to Chiesi a Certificate of Analysis and a Certificate of Compliance 

 

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and such other documents as may be required by Applicable Laws or mutually agreed by the Parties.

 

(d)                                 Minimum Remaining Shelf-life and Returns.  Product returns shall be the sole responsibility of Chiesi and uniQure shall have no obligation with respect to any such returned Product, provided that the releasing Qualified Person should be informed of return and final disposition and all Products supplied by uniQure hereunder shall have a minimum remaining shelf life upon delivery equal to no less than [**] months of the shelf-life set forth in the relevant Specifications or such longer period as required by a relevant customer in the Territory.

 

2.6                               Failure to Supply.

 

(a)                                 In the event that it becomes apparent to uniQure that it will be unable to fulfill any Confirmed Firm Order for the Product (“Failure to Supply”), uniQure shall, immediately after learning of such event or circumstances, notify Chiesi in writing of uniQure’s Failure to Supply, along with a reasonable explanation of the reason, to the extent then known to uniQure, for uniQure’s Failure to Supply and with a specific indication of the quantity of Product affected by such Failure to Supply and anticipated timing of delivery of the Product. Promptly after Chiesi’s receipt of any such notice, the Parties shall agree upon mutually acceptable revised quantities and delivery dates with respect to the Product subject to such Confirmed Firm Order or, to the extent this is not possible in light of the specific or then unknown reason for uniQure’s Failure to Supply, shall discuss in good faith measures to further investigate the root cause and, as the case may be, appropriate steps to overcome such Failure to Supply.

 

(b)                                 Notwithstanding paragraph (a), in the event that Chiesi cannot fulfill any firm orders for the Product received from any Third Parties as a consequence of uniQure’s Failure to Supply, except if such Failure to Supply is caused as a result of any Force Majeure Event, then Chiesi shall be entitled to an indemnification payment equal to Chiesi’s Lost Profit for the period during which Chiesi has been affected by the Failure to Supply. Any indemnification payment made to Chiesi under this paragraph for Failure to Supply shall be reimbursed in full to uniQure, in case any patient who suffered from the Failure to Supply is then subsequently treated. Such indemnification payments and reimbursements, if any, shall be calculated on a calendar year basis, such calculation to be made within [**] days after the end of the corresponding calendar year and any resulting amount to be paid within [**] days after such calculation has been made.  uniQure, in relying on the above Force Majeure Event exceptions, shall provide reasonably detailed particulars of the reasons underlying any such Force Majeure Event to Chiesi and shall allocate its existing stocks of the Product between uniQure, its Affiliates, Chiesi and other distributors of the Product, on a pro-rata basis, based upon order volumes for the Product for the prior [**]month period.

 

(c)                                  For the purpose of this Section 2.6, “Profit” shall be calculated, on a per Product basis, as the difference between (a) the relevant Average Net Sales Price that would have applied to the Product affected by the Failure to Supply and (b) the applicable Purchase Price for the Product affected by the Failure to Supply calculated as per Section 2.3 above, and “Lost Profit” shall mean the accumulated Profit for all quantities of Product affected by the Failure to Supply.

 

(d)                                 Without prejudice to the foregoing paragraphs (a) to (c), if

 

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(i)                                     uniQure’s Failure to Supply affects at least [**] consecutive Confirmed Firm Orders for a period of no less than nine (9) months, and

 

(ii)                                  the reason for uniQure’s Failure to Supply could be established during the Parties’ discussion pursuant to paragraph (a) above, and such reason was specifically related to uniQure’s ability to Manufacture the Product at its current manufacturing site (i.e. the Failure to Supply could reasonably be expected to be overcome if the Product was Manufactured at a different manufacturing site),

 

upon either Party’s request, the Manufacturing of the Product shall be transferred to (A) uniQure’s US manufacturing site, provided such site is operational at the relevant point in time, and further provided uniQure, within [**] following such request, does not opt against such transfer, and (B) otherwise (i.e. if uniQure opts against such transfer within the foregoing [**] period) to any other Third Party manufacturer mutually agreed to by uniQure and Chiesi. uniQure shall efficiently and promptly transfer to its US manufacturing site or, as the case may be, such Third Party manufacturer all information, licenses and rights controlled by uniQure and necessary to Manufacture and supply the Product to Chiesi hereunder during the continuance of uniQure’s Failure to Supply. Such transfer shall ensure uniQure’s ongoing control over the information, licenses and right so transferred, shall include the steps outlined in Schedule 2.6, and shall occur through email and videoconference interactions, as well as face-to-face meetings as required to ensure efficient transfer of technologies and capabilities.

 

If uniQure’s US manufacturing site or, as the case may be, such Third Party manufacturer is unable to Manufacture the Product within [**] months after uniQure has started the technology transfer to such person, Chiesi shall have the right to terminate this Agreement with three (3) month notice in writing, except if uniQure’s Failure to Supply is caused as a result of a Force Majeure Event. Such termination shall not become effective if, during such three (3) month notice period, uniQure has notified Chiesi of the ability of its US manufacturing site or, as the case may be, such Third Party manufacturer to Manufacture the Product. Upon termination of this Agreement by Chiesi pursuant to this Section 2.6(d), the provisions of Section 9.3(b) (i), (ii) and (iv) shall apply.

 

(e)                                  Without prejudice to the foregoing paragraphs (a) to (c), if

 

(i)                                     uniQure’s Failure to Supply affects at least [**] consecutive Confirmed Firm Orders for a period of no less than nine (9) months, and

 

(ii)                                  the reason for uniQure’s Failure to Supply (A) could be established during the Parties’ discussion pursuant to paragraph (a) above, but such reason was not specifically related to uniQure’s ability to Manufacture the Product at its current manufacturing site (i.e. the Failure to Supply could not reasonably be expected to be overcome if the Product was Manufactured at a different manufacturing site), or (B) could not be established during the Parties’ discussion pursuant to paragraph (a) above during at least the foregoing nine (9) months period, and

 

(iii)                               uniQure’s Failure to Supply is not caused as a result of a Force Majeure Event,

 

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Chiesi may terminate this Agreement with three (3) month notice in writing. Such termination shall not become effective if, during such three (3) month notice period, uniQure has notified Chiesi of the end of its Failure to Supply and has provided to Chiesi at least [**] of the outstanding Confirmed Firm Orders. Upon termination of this Agreement by Chiesi pursuant to this Section 2.6(e), the provisions of Section 9.3(b) (i), (ii) and (iv) shall apply.

 

(f)                                   Without prejudice to the foregoing paragraphs (a) to (e), if within [**] months after uniQure has notified Chiesi in writing of uniQure’s Failure to Supply, any Person is unable to Manufacture and supply the Product to Chiesi hereunder, then for any possible future supply of the Product to Chiesi hereunder, the percentage set out in Section 2.3(b)(i) above shall be reduced to [**] percent ([**]%) for any individual Product ordered after the end of uniQure’s Failure to Supply for a period equivalent to the duration of uniQure’s Failure to Supply (i.e. if uniQure’s Failure to Supply lasted for [**] months, the reduced percentage of [**] percent ([**]%) shall apply to any individual Product ordered during the [**] months period after the end of uniQure’s Failure to Supply).

 

ARTICLE III

QUALITY, REGULATORY AND PHARMACOVIGILANCE MATTERS

 

3.1                               Permits.

 

(a)                                 uniQure shall be responsible for any filing, holding and maintenance associated with all Marketing Authorizations for the Product in Territory A, and Chiesi shall be responsible for any filing, holding and maintenance associated with all Marketing Authorizations for the Product in Territory B. Notwithstanding the foregoing, if, according to local mandatory regulatory requirements, uniQure is not eligible as Marketing Authorization holder of the Product in any country of Territory A, or Chiesi is not eligible as Marketing Authorization holder of the Product in any country of Territory B, Chiesi or, as the case may be, its Sub-distributor, or uniQure, shall become the Marketing Authorization holder of the Product in such country of the Territory. Details regarding each Party’s responsibilities and obligations and the exchange of information in the process of filing, holding and maintaining any Marketing Authorizations for the Product in the Territory shall be agreed upon between the Parties in the Regulatory Plan. Notwithstanding the foregoing and except as otherwise set forth in this Agreement, including the Regulatory Plan, the Quality Agreement and the SDEA, each Party shall, at such Party’s sole cost and expense, maintain in full force and effect all other Regulatory Approvals required by Applicable Laws to carry out such Party’s duties and obligations under this Agreement.

 

(b)                                 Without prejudice to the generality of paragraph (a) above, (i) uniQure and Chiesi shall share equally the cost associated with the Registry in the EU, the PIP (Pediatric Investigation Plan) and any Phase IV clinical study regarding the Product mutually agreed between the Parties, (ii) uniQure shall be responsible for any filing, holding and maintenance fees associated with Marketing Authorizations and Marketing Authorization Applications in Territory A, including in the countries outside of the EU Member States, as further agreed between the Parties during the Term in accordance with Schedule 3.1, CMC (Chemistry, Manufacturing, and Controls), and pharmacovigilance regarding the Product in the Territory (except for the Registry), and (iii) Chiesi shall be responsible for any filing, holding and maintenance fees associated with Marketing 

 

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Authorizations and Marketing Authorization Applications in Territory B as further agreed between the Parties during the Term in accordance with Schedule 3.1, any changes (other than Required Manufacturing Changes and Discretionary Manufacturing Changes which are governed by Section 3.4 below) Chiesi shall request with respect to the Product, and reporting of safety data regarding the Product in Territory B.

 

3.2                               Regulatory Plan and Responsibility.  The Parties shall adopt a regulatory plan relating to the Product (the “Regulatory Plan”) a draft of which shall be attached as Schedule 3.2 and which shall be finalized by the Parties as soon as possible after the Effective Date, but in any event within [**] weeks thereafter. The Regulatory Plan shall be approved by the JCC and may be updated from time to time through the JSC or the JCC.

 

3.3                               Quality Agreement and Safety Data Exchange Agreement.

 

(a)                                 As soon as possible after the Effective Date, but in any event within [**] days after the Effective Date, the Parties shall enter into a quality agreement regarding the Product (the “Quality Agreement”), whereby the Parties shall define their respective responsibilities in relation to GDPs and quality matters, Specifications, release and supply of the Product. In the event of a conflict between the terms of this Agreement and the Quality Agreement, the terms of this Agreement shall govern.

 

(b)                                 Without prejudice to the generality of Section 3.1(b) above, as soon as possible after the Effective Date, but in any event within [**] days after the Effective Date, the Parties shall enter into a safety data exchange agreement (the “SDEA”) that defines the roles and responsibilities of each Party in terms of pharmacovigilance and the detailed safety exchange required to permit compliance by each Party with safety reporting requirements to Regulatory Authorities in the Territory. In the event of a conflict between the terms of this Agreement and the SDEA, the terms of this Agreement shall govern.

 

3.4                               Change Management.

 

(a)                                 For changes to the Specifications or Manufacture processes of the Product that are required by Applicable Laws in the Territory (collectively, “Required Manufacturing Changes”), uniQure and Chiesi shall cooperate in making such changes in a timely manner.

 

(b)                                 For changes to the Specifications or Manufacture processes of the Product that are not Required Manufacturing Changes (collectively, “Discretionary Manufacturing Changes”), uniQure and Chiesi must each agree in writing to any Discretionary Manufacturing Changes before such change is implemented, provided that neither Party shall unreasonably withhold its consent to such Discretionary Manufacturing Changes.

 

(c)                                  Unless otherwise agreed between the Parties, through the JSC or JCC, uniQure’s quality system, as further defined in the Quality Agreement, shall be utilized by the Parties in reviewing and implementing any changes under this Section 3.4.

 

(d)                                 The commercially reasonable costs, including obsolete raw materials, work-in-process, product packaging and labeling materials, (i) associated with 

 

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Required Manufacturing Changes shall be shared equally between uniQure and Chiesi, and (ii) associated with Discretionary Manufacturing Changes shall be borne by the Party initiating such changes.

 

3.5                               Stability Testing; Validation. uniQure shall perform stability testing, process validation or cleaning validations with respect to the Product in accordance with uniQure’s standard procedures, as further defined in the Quality Agreement, and Applicable Laws. Any additional testing reasonably requested by Chiesi shall be performed by uniQure at the expense of Chiesi.

 

3.6                               Recalls; Product Complaints.

 

(a)                                 uniQure shall have the sole authority and responsibility to respond to any Regulatory Authority, to respond to Product Complaints and to handle all recalls and market withdrawals of the Product in accordance with Applicable Laws, provided, that in all cases, unless otherwise required to comply with any Applicable Laws or any decision, order, request or directive of a Regulatory Authority, Chiesi shall release no communication into the marketplace regarding such Product Complaints, recalls or market withdrawals without first obtaining uniQure’s consent to such communication, which shall not be unreasonably withheld. Other complaints related to the Product, in particular complaints not related to regulatory matters, shall be managed solely by Chiesi.

 

(b)                                 Each Party shall promptly (but in any case, not later than [**] Business Days) notify the other Party in writing of any decision, order, request or directive of a Regulatory Authority to recall, withdraw or field correct any Product. UniQure shall promptly (but in any case, not later than [**] Business Days) notify Chiesi of any voluntary decision to recall, withdraw or field correct any Product. uniQure shall be solely responsible for determining whether to issue a recall, withdrawal, or field correction (but shall comply with all Applicable Laws in making such determination) and for the cost and expense of any such recall, withdrawal or field correction; provided, that uniQure shall give due consideration to all comments timely made by Chiesi relating to the Manufacture or testing of the Product and shall notify Chiesi in writing if uniQure declines to address any such comments, stating the reason therefor. If any recall, market withdrawal or field correction is not due to uniQure’s Manufacture of the Product, then uniQure shall be relieved of uniQure’s obligations to supply the Product hereunder until the cause of such recall, withdrawal or field correction has been resolved to the satisfaction of the Parties and the applicable Regulatory Authority, and during such period such relief shall be deemed a Force Majeure Event for the purposes of this Agreement.

 

(c)                                  Notwithstanding the foregoing paragraphs (a) and (b), but without prejudice to any obligations of uniQure under mandatory Applicable Laws, to the extent possible with view to any timelines applicable under Applicable Laws, the Parties, through the JSC or JCC, shall mutually discuss any of the foregoing events (i.e. response to any Regulatory Authority, response to Product Complaints, recalls, market withdrawals, field corrections) and agree on a joint communication in relation to such event both to any Regulatory Authority and the marketplace taking into account both the regulatory and commercial implications associated with such event and communication.

 

3.7                               Notice of Government Inspections.  Each Party agrees that, to the extent such Party becomes aware of the results, observations or outcome of any inspections or 

 

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audits of the facilities or operations involved in the Manufacture or Commercialization of the Product conducted by a Regulatory Authority, such Party will notify the other Party of any such information as it directly relates to the Product within [**] Business Days after obtaining the information and shall provide the other Party with a copy of any written materials provided by the Regulatory Authority in connection with such inspection or audit. Each Party will provide the other with copies of reports of quality audits conducted by such Party with respect to the Product and will apprise the other Party of material Manufacture, marketing, promotion, sales, or other issues affecting supply or Commercialization of the Product.

 

3.8                               Government Inquiries.  If either Party shall be contacted by any Regulatory Authority for any regulatory purpose pertaining specifically to this Agreement or to the Product, such Party shall immediately notify the other Party. Either Party may permit unannounced inspections of the Product or facilities by a Regulatory Authority with competent jurisdiction and may respond to the extent necessary to comply with such Party’s obligations under Applicable Laws.

 

3.9                               Inspections / Audit of Records and Facilities.  Unless otherwise required by Applicable Laws or any decision, order, request or directive of a Regulatory Authority, [**](or in case of uniQure’s facilities being inspected, up to [**] times a year [**]), for a period of no more than [**] Business Days and by no more than [**] designated personnel, each Party shall have reasonable access during normal business hours to the other Party’s regulatory files as they relate to the Manufacture and Commercialization of the Product in the Territory to (a) review all such records, correspondence, notices, documents, and other materials (including warning letters and letters of adverse findings) and (b) inspect the other Party’s facilities for compliance with this Agreement, in particular to inspect and audit uniQure’s standard procedures regarding the Manufacturing of Products. Any inspection shall not unreasonably disrupt the normal operations of the inspected Party and shall be announced with a notice period of at least [**] months prior to such audit.

 

3.10                        Price and Reimbursement Approvals.  Subject to Section 8.1(a) and(c) below, taking into account uniQure’s unique experience and understanding of Gene Therapy generally and the Product specifically, both Parties agree that Chiesi and uniQure shall jointly consult and prepare the pricing strategy for the Price and Reimbursement Approvals of the Product in the Field in the Territory to be filed and obtained by Chiesi. For the avoidance of doubt and in accordance with Section 8.1(c) below, such consultation shall not establish or create any obligation of Chiesi to set a certain or fixed price for the Product.

 

ARTICLE IV

GOVERNANCE; DECISION MAKING

 

4.1                               Joint Steering Committee.

 

(a)                                 Formation and Membership.  Within [**] days after the Effective Date, Chiesi and uniQure shall establish a joint steering committee (the “JSC”) to manage the Collaboration. The JSC to be established under this Agreement shall be identical to the one to be established under the Co-Development and License Agreement. The JSC shall be comprised of [**] executives or senior employees of Chiesi and [**] executives or senior employees of uniQure with appropriate experience and level of decision-making

 

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authority. From time to time, in addition to the JCC described below, the Parties may establish one or more subcommittees of the JSC to oversee particular projects or activities (e.g., activities under the Co-Development and License Agreement, financial reporting). Each such subcommittee shall be comprised of an equal number of representatives from each Party with appropriate experience and level of decision-making authority. Each subcommittee shall meet with a frequency to be agreed on by the Parties. Each Party may change any one or more of its representatives on the JSC or any subcommittee at any time upon written notice to the other Party.

 

(b)                                 Responsibilities.  The JSC shall be responsible for:

 

(i)                                     providing overall direction of the Collaboration;

 

(ii)                                  attempting to resolve disputes arising under the Collaboration Agreements; and

 

(iii)                               performing such other tasks and undertaking such other responsibilities as may be set forth in the Collaboration Agreements.

 

(c)                                  Meetings.

 

(i)                                     The JSC shall meet at least [**], by tele- or video-conference or in person, with the meetings in approximately [**] to be held in-person. The location of in-person JSC meetings shall alternate between the headquarters offices of each Party, with the first meeting to take place at [**] within [**] days after the Effective Date.

 

(ii)                                  Each Party shall use reasonable efforts to cause its representatives to attend the meetings of the JSC and any subcommittees. In addition, each Party may, at its discretion, invite a reasonable number of non-voting employees or officers, and, with the consent of the other Party, consultants or scientific advisors, to attend meetings of the JSC or any subcommittee, or the relevant portion thereof; provided that, its representatives and any such other employees, officers, consultants or scientific advisors are bound by written obligations of confidentiality that are at least as stringent as those set forth in this Agreement. Each Party shall bear all travel and living expenses of its representatives and other employees, officers, consultants or scientific advisors incurred to attend the meetings of the JSC or any subcommittee.

 

(iii)                               Either Party may also request, by providing written notice to the other Party, that a special meeting of the JSC be convened for the purpose of resolving disputes in connection with, or for the purpose of reviewing or making a decision pertaining to, any material matter within the purview of the JSC, the examination or resolution of which cannot reasonably be postponed until the next scheduled JSC meeting. Such meeting shall be convened at such time as may be mutually agreed upon by the Parties, but in any event shall be held within [**] days after the date of such notice.

 

(d)                                 Administrative Matters.  The right to appoint the chairperson of the JSC shall alternate on an annual basis between Chiesi and uniQure, with [**] having the right to appoint the chairperson for the first year of the Term. The Alliance Managers shall work with the chairperson to develop JSC meeting agendas. The chairperson shall be responsible for calling meetings of the JSC and for leading the meetings. A JSC

 

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member of the chairing Party shall serve as secretary of such meetings. The secretary shall promptly prepare and distribute to all members of the JSC draft minutes of the meeting for review and comment, including a list of any actions or decisions approved by the JSC, with the goal of distributing final approved minutes of each JSC meeting within [**] days after the meeting. Neither the chairperson nor the secretary shall have any greater authority than any other representative on the JSC and the Party appointing the chairperson and the secretary shall not have any greater authority than the other Party by virtue of its right to make such appointments. The chairperson shall include on the agenda any items proposed by either Party.

 

(e)                                  Decision Making.  Each Party, through its representatives, shall have one (1) vote on the JSC and each subcommittee. Both Parties must vote in the affirmative to allow the JSC or a subcommittee to take any action that requires the approval of the JSC or the subcommittee. Decision on any matter may be taken at a meeting, by teleconference, videoconference or by written agreement. If a subcommittee is unable to resolve any dispute, or to unanimously agree on any matter, within its responsibilities, such dispute or matter shall be referred to the JSC for resolution. Either Party may convene a special meeting of the JSC in accordance with Section 4.1(c)(iii) for the purpose of resolving any dispute within the JSC’s jurisdiction that represents a material issue the resolution of which cannot reasonably await until the next scheduled meeting of the JSC.

 

(f)                                   Dispute Resolution by Executive Officers.

 

(i)                                     If the JSC is unable to resolve any dispute within the responsibilities of the JSC specified in Section 4.1(b) within [**] days after a Party provides notice to the other Party of the existence of such dispute, such dispute or other matter shall be referred to the Executive Officers for resolution. If a dispute is referred to the Executive Officers for resolution pursuant to the preceding sentence, the Executive Officers shall attempt in good faith to resolve such dispute within [**] days. In resolving any disputes under this Section 4.1(f), each Party shall act in good faith, subject to the terms and conditions of the Collaboration Agreements, and in a commercially reasonable manner without favoring other products being developed or commercialized by or on behalf of such Party or its Affiliates outside of the Collaboration.

 

(ii)                                  If the Executive Officers are unable to reach a consensus in accordance with paragraph (i) above, (A) uniQure shall have final decision-making authority with respect to all matters related to research or development in relation to the Product, with reasonable input from Chiesi taking into account Territory-specific matters, (B) Chiesi shall have final decision-making authority with respect to all matters related to Commercialization of the Product in the Territory, with reasonable input from uniQure taking into account uniQure’s global Product strategy, (C) subject to Sections 3.1 and 3.2, both Parties agree that on regulatory matters with respect to the Product they will jointly work towards a regulatory strategy for the Product in the countries of the Territory which are not EU Member States, and (D) any matter not falling within any of the foregoing categories (A) to (C) shall be decided by binding arbitration pursuant to Section 11.9 below.

 

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4.2                               Joint Commercialization Committee.

 

(a)                                 Formation and Membership.  Within [**] days after the Effective Date, Chiesi and uniQure shall establish, as a subcommittee of the JSC, a joint commercialization committee (the “JCC”) to manage the overall relationship between the Parties under this Agreement. The JCC shall be comprised of [**] executives or senior employees of Chiesi and [**] executives or senior employees of uniQure with appropriate experience and level of decision-making authority. From time to time, the Parties may establish one or more subcommittees of the JCC to oversee particular projects or activities (e.g., regulatory, supply, forecast, global brand integration). Each such subcommittee shall be comprised of an equal number of representatives from each Party with appropriate experience and level of decision-making authority. Each subcommittee shall meet with a frequency to be agreed on by the Parties. Each Party may change any one or more of its representatives on the JCC or any subcommittee at any time upon written notice to the other Party.

 

(b)                                 Responsibilities.  The JCC shall be responsible for:

 

(i)                                     periodically reviewing the Regulatory Plan and suggesting or approving such updates or amendments to the Regulatory Plan as the JCC deems appropriate, including all budgets relating to activities to be conducted hereunder and amendments thereto;

 

(ii)                                  ensuring consistency and coordination, to the maximum possible extent, between Commercialization activities to be conducted by uniQure in the Field outside the Territory and by Chiesi in the Field in the Territory;

 

(iii)                               providing overall strategic direction with respect to Commercialization and regulatory activities for the Product, including activities conducted under the Regulatory Plan;

 

(iv)                              overseeing Commercialization and regulatory activities for the Product;

 

(v)                                 discussing and addressing any supply chain or other delivery issues that have arisen or might arise relating to the Product;

 

(vi)                              attempting to resolve disputes arising under this Agreement that are referred to the JCC by either Party or any subcommittee; and

 

(vii)                           performing such other tasks and undertaking such other responsibilities as may be set forth in this Agreement or as may be delegated to it by the JCC.

 

(c)                                  Meetings.

 

(i)                                     The JCC shall meet at least [**], by tele- or video-conference or in person, with the meetings in approximately [**] to be held in-person. The location of in-person JCC meetings shall alternate between the headquarters offices of each Party, with the first meeting to take place at [**] within [**] days after the Effective Date.

 

(ii)                                  Each Party shall use reasonable efforts to cause its representatives to attend the meetings of the JCC and any subcommittees. In addition,

 

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each Party may, at its discretion, invite a reasonable number of non-voting employees or officers, and, with the consent of the other Party, consultants or scientific advisors, to attend meetings of the JCC or any subcommittee, or the relevant portion thereof; provided that, its representatives and any such other employees, officers, consultants or scientific advisors are bound by written obligations of confidentiality that are at least as stringent as those set forth in this Agreement. Each Party shall bear all travel and living expenses of its representatives and other employees, officers, consultants or scientific advisors incurred to attend the meetings of the JCC or any subcommittee.

 

(iii)                               Either Party may also request, by providing written notice to the other Party, that a special meeting of the JCC be convened for the purpose of resolving disputes in connection with, or for the purpose of reviewing or making a decision pertaining to, any material matter within the purview of the JCC, the examination or resolution of which cannot reasonably be postponed until the next scheduled JCC meeting. Such meeting shall be convened at such time as may be mutually agreed upon by the Parties, but in any event shall be held within [**] days after the date of such notice.

 

(d)                                 Administrative Matters.  [**] shall have the right to appoint the chairperson of the JCC. The Alliance Managers shall work with the chairperson to develop JCC meeting agendas. The chairperson shall be responsible for calling meetings of the JCC and for leading the meetings. A [**] JCC member shall serve as secretary of such meetings. The secretary shall promptly prepare and distribute to all members of the JCC draft minutes of the meeting for review and comment, including a list of any actions or decisions approved by the JCC, with the goal of distributing final approved minutes of each JCC meeting within [**] days after the meeting. Neither the chairperson nor the secretary shall have any greater authority than any other representative on the JCC and [**] shall not have any greater authority than [**] by virtue of its right to make such appointments. The chairperson shall include on the agenda any items proposed by either Party.

 

(e)                                  Decision Making.  Each Party, through its representatives, shall have one (1) vote on the JCC and each subcommittee. Both Parties must vote in the affirmative to allow the JCC or a subcommittee to take any action that requires the approval of the JCC or the subcommittee. Decision on any matter may be taken at a meeting, by teleconference, videoconference or by written agreement. If a subcommittee is unable to resolve any dispute, or to unanimously agree on any matter, within its responsibilities, such dispute or matter shall be referred to the JCC for resolution. Either Party may convene a special meeting of the JCC in accordance with Section 4.2(c)(iii) for the purpose of resolving any dispute within the JCC’s jurisdiction that represents a material issue the resolution of which cannot reasonably await until the next scheduled meeting of the JCC.

 

(f)                                   Dispute Resolution.  If the JCC is unable to resolve any dispute within the responsibilities of the JCC specified in Section 4.2(b) within [**] days after a Party provides notice to the other Party of the existence of such dispute, then,(A) the respective representative(s) of each Party in the JCC may exercise the final decision-making authority of each Party pursuant to Section 4.1(f)(ii)(A) or, as the case may be, Section 4.1(f)(ii)(B) also at the JCC level or decide to refer such dispute to the JSC for decision, and (B) any matter not falling within any of the categories of Section

 

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4.1(f)(ii)(A) or, as the case may be, Section 4.1(f)(ii)(B) shall be referred to the JSC for decision.

 

4.3                               Alliance Managers.  Each Party shall appoint an employee (or an employee of its Affiliate) to serve as an alliance manager (“Alliance Manager”) with responsibility for overseeing that the Parties’ activities are conducted in accordance with the Collaboration Agreements, and for being the primary point of contact between the Parties with respect to all such activities. The Alliance Managers to be appointed under this Agreement shall be identical to the ones to be appointed under the Co-Development and License Agreement. The Alliance Managers are responsible for driving the Collaboration progress and the resolution of issues between the Parties. The Alliance Managers may be members, but in any event may attend the meetings of the JSC, JCC or any other JSC subcommittee, and be responsible for communicating with and reporting to the JSC, JCC and any other JSC subcommittee on all relevant matters.

 

ARTICLE V

REPRESENTATIONS, WARRANTIES AND COVENANTS

 

5.1                               Mutual Representations, Warranties and Covenants. Each Party hereby represents, warrants and covenants to the other Party, as of the Effective Date and, where expressly stated, at all times during the Term, as follows:

 

(a)                                 Such Party: (i) is duly formed and in good standing under the laws of the jurisdiction of its formation, (ii) has the power and authority and the legal right to enter into this Agreement and perform its obligations hereunder, and (iii) has taken all necessary action on its part required to authorize the execution and delivery of this Agreement and the performance of its obligations hereunder;

 

(b)                                 Upon execution, this Agreement will have been duly executed and delivered on behalf of such Party and constitutes a legal, valid and binding obligation of such Party and is enforceable against it in accordance with its terms;

 

(c)                                  The execution and delivery of this Agreement and the performance of such Party’s obligations hereunder: (i) do not conflict with or violate any requirement of Applicable Laws or any provision of the articles of incorporation, bylaws or limited partnership agreement of such Party; and (ii) do not conflict with, violate, or breach, or constitute a default or require any further consent under, any contractual obligation or court or administrative order by which such Party is bound;

 

(d)                                 During the Term, to its knowledge, such Party will not, in the conduct of its activities under this Agreement, (i) employ or use any contractor or consultant that employs any individual or entity debarred by the FDA (or subject to a similar sanction of EMA), or (ii) employ any individual who or entity that is the subject of an FDA debarment investigation or proceeding (or similar proceeding of EMA);

 

(e)                                  During the Term, such Party shall perform its activities pursuant to this Agreement in compliance in all material respects with Applicable Laws;

 

(f)                                   During the Term, neither Party shall grant any right or license to any Third Party relating to any of the Intellectual Property Rights it Controls which would

 

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conflict with, or limit the scope of, any of the rights or licenses granted or to be granted to the other Party hereunder.

 

5.2                               Additional Representations, Warranties and Covenants of uniQure. uniQure hereby represents, warrants and covenants as of the Effective Date, and, where expressly stated, at all times during the Term, that:

 

(a)                                 During the Term, at the time the same are tendered to the carrier for delivery to Chiesi’s customers, the Product sold to Chiesi pursuant to this Agreement (i) shall be Manufactured, stored, handled and released in compliance with all Applicable Laws, including GMPs; (ii) shall meet the applicable Specifications and (iii) shall not be adulterated or misbranded or otherwise defective within the meaning of any Applicable Laws;

 

(b)                                 Schedule 1.63 attached hereto is a complete and correct list of all Patents that Cover the Product in the Territory and, subject to Section 9.1(b), are Controlled by uniQure as of the Effective Date;

 

(c)                                  uniQure Controls all uniQure Intellectual Property and, subject to Section 9.1(b), has the full right, power and authority to grant to Chiesi the rights and licenses necessary to perform Chiesi’s activities under this Agreement in the Territory;

 

(d)                                 To uniQure’s knowledge, the Commercialization of the Product in the Territory, as anticipated hereunder, does not infringe upon any Intellectual Property Rights of any Third Party;

 

(e)                                  uniQure has not received any written allegation from a Third Party that any of the Patents issued on the Effective Date which is Controlled by UniQure and Covering the Product in the Territory is invalid or unenforceable and, to uniQure’s knowledge, none of such Patents is infringed by any Third Party.

 

5.3                               Additional Representations, Warranties and Covenants of Chiesi. Chiesi hereby represents, warrants and covenants as of the Effective Date, and, where expressly stated, at all times during the Term, that any and all Delivery Notification requirements set forth in Section 2.5(b) shall be fulfilled before any quantities of the Product are supplied to any of its customers.

 

5.4                               No Other Representations or Warranties.  EXCEPT AS OTHERWISE EXPRESSLY SET FORTH IN THIS AGREEMENT, NEITHER PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING ANY WARRANTY THAT ANY PATENT RIGHTS ARE VALID OR ENFORCEABLE, AND EXPRESSLY DISCLAIMS ALL IMPLIED WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE AND NON-INFRINGEMENT. WITHOUT LIMITING THE GENERALITY OF THE FOREGOING, EACH PARTY DISCLAIMS ANY WARRANTIES WITH REGARDS TO: (A) THE SAFETY, USEFULNESS FOR ANY PURPOSE OR NON-INFRINGEMENT OF ANY PRODUCT; OR (B) THE VALIDITY, ENFORCEABILITY OR NON-INFRINGEMENT OF ANY INTELLECTUAL PROPERTY RIGHTS IT PROVIDES OR LICENSES TO THE OTHER PARTY UNDER THIS AGREEMENT.

 

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5.5                               No Reliance by Third Parties.  The representations and warranties of a Party set forth in this Article 5 are intended for the sole and exclusive benefit of the other Party hereto, and may not be relied upon by any Third Party.

 

ARTICLE VI

INDEMNIFICATION; INSURANCE

 

6.1                               Indemnification by Chiesi.  Chiesi shall indemnify, defend and hold harmless uniQure and its Affiliates, and its and their respective directors, officers, employees and agents, from and against any and all liabilities, damages, losses, costs and expenses, including the reasonable fees of attorneys and other professional Third Parties (collectively, “Losses”), arising out of or resulting from any and all Third Party suits, claims, actions, proceedings or demands (“Claims”) to the extent based upon:

 

(i)                                     any breach of any representation, warranty or covenant made by, or any material obligation of, Chiesi under this Agreement;

 

(ii)                                  the gross negligence, recklessness or willful misconduct of Chiesi or its Affiliates and its or their respective directors, officers, employees and agents;

 

(iii)                               any theory of product liability (including without limitation tort, warranty, or strict liability) that is applicable in the Territory with respect to the death, personal injury, or illness of any Person in the Territory, and arising directly from Chiesi’s or its Affiliates’ or Sub-distributors’ Commercialization of the Product in the Territory;

 

provided that Chiesi shall not be obligated pursuant to this Section 6.1 if and to the extent uniQure is required to indemnify Chiesi under Section 6.2 below.

 

6.2                               Indemnification by uniQure. uniQure shall indemnify, defend and hold harmless Chiesi and its Affiliates, and its and their respective directors, officers, employees and agents, from and against any and all Losses, arising out of or resulting from any and all Claims to the extent based upon:

 

(i)                                     any breach of any representation, warranty or covenant made by, or any material obligation of, uniQure under this Agreement;

 

(ii)                                  the gross negligence, recklessness or willful misconduct of uniQure or its Affiliates and its or their respective directors, officers, employees and agents;

 

(iii)                               any theory of product liability (including without limitation tort, warranty, or strict liability) that is applicable in the Territory with respect to the death, personal injury, or illness of any Person in the Territory, and arising directly from uniQure’s or its Affiliates’ development, design, Manufacture, storage, release and handling of the Product;

 

(iv)                              Claims that the (i) Commercialization of the Product; or (ii) exercise of any rights or licenses granted to Chiesi and its Affiliates in accordance with this Agreement; violates or infringes upon the Intellectual Property Rights of any Third Party;

 

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provided that uniQure shall not be obligated pursuant to this Section 6.2 if and to the extent Chiesi is required to indemnify uniQure under Section 6.1 above.

 

6.3                               Procedure.

 

(a)                                 A Party entitled to indemnification under this Article VI (an “Indemnified Party”) shall give prompt written notification to the Party from whom indemnification is sought (the “Indemnifying Party”) of the commencement of any Claim for which indemnification may be sought or, if earlier, upon the assertion of any such Claim by a Third Party (it being understood and agreed, however, that the failure by an Indemnified Party to give notice of a Claim as provided in this Section 6.3(i) shall not relieve the Indemnifying Party of its indemnification obligation under this Agreement except and only to the extent that such Indemnifying Party is actually damaged as a result of such failure to give notice).

 

(b)                                 Within [**] days after delivery of such notification, the Indemnifying Party may, upon written notice thereof to the Indemnified Party, assume control of the defense of such Claim with counsel reasonably satisfactory to the Indemnified Party.

 

(c)                                  If the Indemnifying Party does not assume control of such defense, the Indemnified Party shall control such defense and, without limiting the Indemnifying Party’s indemnification obligations, the Indemnifying Party shall reimburse the Indemnified Party for all reasonable costs and expenses, including reasonable attorney’s fees, incurred by the Indemnified Party in defending itself, within [**] days after receipt of any invoice therefor from the Indemnified Party, such invoice to be issued no more often than quarterly.

 

(d)                                 The Party not controlling such defense may participate therein at its own expense; provided that, if the Indemnifying Party assumes control of such defense and the Indemnified Party in good faith concludes, based on advice from counsel, that the Indemnifying Party and the Indemnified Party have conflicting interests with respect to such Claim, the Indemnifying Party shall be responsible for the reasonable fees and expenses of counsel to the Indemnified Party in connection with its participation in the defense action.

 

(e)                                  The Party controlling such defense shall keep the other Party advised of the status of such Claim and the defense thereof and shall consider recommendations made by the other Party with respect thereto.

 

(f)                                   The Indemnified Party shall not agree to any settlement of any Claim without the prior written consent of the Indemnifying Party, which shall not be unreasonably withheld, delayed or conditioned. The Indemnifying Party shall not, without the prior written consent of the Indemnified Party, agree to any settlement of such Claim, or consent to any judgment in respect thereof, that does not include a complete and unconditional release of the Indemnified Party from all liability with respect thereto, that imposes any liability or obligation on the Indemnified Party or that acknowledges fault by the Indemnified Party.

 

6.4                               Limitation of Liability.  EXCEPT WITH RESPECT TO ANY BREACH BY A PARTY OF ITS OBLIGATIONS UNDER ARTICLE X, EXCEPT AS

 

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PROVIDED FOR IN SECTION 2.6, EXCEPT FOR ANY DAMAGES ARISING FROM A PARTY’S WILLFUL MISCONDUCT AND EXCEPT TO THE EXTENT A PARTY MAY BE REQUIRED TO INDEMNIFY THE OTHER PARTY UNDER THIS ARTICLE VI WITH RESPECT TO THIRD PARTY CLAIMS, NEITHER PARTY SHALL BE LIABLE FOR ANY (AND EACH PARTY HEREBY DISCLAIMS ALL) SPECIAL, EXEMPLARY, CONSEQUENTIAL, PUNITIVE OR OTHER INDIRECT DAMAGES, INCLUDING LOST REVENUE AND LOST PROFITS, WHETHER BASED UPON WARRANTY, CONTRACT, TORT, STRICT LIABILITY OR OTHER LEGAL THEORY. EXCEPT WITH RESPECT TO ANY BREACH BY UNIQURE OF ITS OBLIGATIONS UNDER ARTICLE X, EXCEPT AS PROVIDED FOR IN SECTION 2.6, EXCEPT FOR ANY DAMAGES ARISING FROM UNIQURE’S WILLFUL MISCONDUCT AND EXCEPT TO THE EXTENT UNIQURE MAY BE REQUIRED TO INDEMNIFY CHIESI UNDER THIS ARTICLE VI WITH RESPECT TO THIRD PARTY CLAIMS, THE TOTAL LIABILITY OF UNIQURE, ITS AFFILIATES, AND THEIR RESPECTIVE OFFICERS, EMPLOYEES, AND AGENTS ARISING OUT OF OR IN RELATION TO THIS AGREEMENT, WHETHER BASED UPON WARRANTY, CONTRACT, TORT, STRICT LIABILITY OR OTHER LEGAL THEORY, SHALL FURTHER BE LIMITED TO AN AMOUNT OF EUR 10,000,000.00 (IN WORDS: TEN MILLION EURO) (REFLECTING THE AMOUNT PAYABLE UNDER UNIQURE’S INSURANCE PURSUANT TO SECTION 6.5) FOR THE CORRESPONDING DAMAGE EVENT. CHIESI SHALL REASONABLY COOPERATE WITH UNIQURE IN OBTAINING SUCH INSURANCE, AT UNIQURE’S COST.

 

6.5                               Insurance.  Each Party shall procure and maintain at its cost insurance, including product liability insurance, adequate to cover its obligations hereunder and which are consistent with normal business practices of comparable companies with respect to similar obligations and liabilities, at all times during the Term. In addition, uniQure shall further procure and maintain, at uniQure’s cost, insurance adequate to cover its obligations under the in-license agreement with Xenon Pharmaceuticals Inc. dated 18 June 2001 and Chiesi shall reasonably cooperate with uniQure in obtaining such insurance. It is understood that such insurance shall not be construed to create any limit of either Party’s obligations or liabilities with respect to its indemnification obligations hereunder. Each Party shall provide the other, upon request, with evidence of such insurance.

 

ARTICLE VII

INTELLECTUAL PROPERTY

 

7.1                               Ownership. uniQure shall own or otherwise Control all right, title and interest in and to any uniQure Intellectual Property Rights.

 

7.2                               Enforcement. uniQure shall have the exclusive right and the obligation, to institute infringement actions against any Third Parties (other than Sub-distributors) based on any Patents and other Intellectual Property Rights Covering the Product in the Territory. Chiesi shall execute all necessary and proper documents and take such actions as shall be appropriate to allow uniQure to institute and prosecute such infringement actions and shall otherwise cooperate, at uniQure’s expense, in the institution and prosecution of such actions. Upon reasonable request of Chiesi, uniQure (i) shall provide to Chiesi all reasonable information in connection with such infringement actions; (ii) shall allow a qualified representative of Chiesi to attend as an observer at relevant

 

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negotiations and hearings, if and to the extent such attendance is both legally permitted and reasonably acceptable for uniQure and (iii) shall consider any measures suggested by Chiesi in connection with such infringement actions, it being understood that uniQure, without any obligation to state reasons for its decision, shall not be obliged to accept, fulfill or maintain such measures.

 

7.3                               Right to Commercialize.

 

(a)                                 During the Term and subject to the terms of this Agreement, in particular Section 9.1(b), uniQure hereby grants to Chiesi and its Affiliates a royalty-free right and license, with the right to grant sublicenses only to Sub-distributors, in the Territory to uniQure Intellectual Property Rights that are required to Commercialize the Product in the Territory under and in accordance with the terms of this Agreement. Such right and license shall be exclusive except in cases where, based on agreements between uniQure and Third Parties existing on the Effective Date, uniQure is not capable of granting exclusive but only non-exclusive licenses (e.g. because uniQure itself has only obtained non-exclusive rights and licenses from Third Party licensors).

 

(b)                                 Chiesi shall not have the right to carry out any research or development with respect to the Product, or, subject to Sections 2.6, 9.3(b) and 9.3(c), to Manufacture the Product, or have the Product Manufactured by an Affiliate or Third Party.

 

7.4                               Compliance with Third Party Agreement.

 

(a)                                 The grants by uniQure under uniQure Intellectual Property Rights set forth in Section 7.3(a) include the sublicense of certain uniQure Intellectual Property Rights that are not owned by uniQure. Chiesi’s rights and licenses under, or with respect to, uniQure Intellectual Property Rights, including any Patent prosecution or enforcement undertaken by the Parties pursuant to Section 7.2, are limited to the rights granted by Third Party licensors to uniQure under the respective in-license agreements between such Third Party licensors and uniQure (“Existing Third Party Licenses”) and are subject to all applicable restrictions, limitations and obligations imposed on uniQure or its sub-licensees in such Existing Third Party Licenses, a copy of which agreements is attached hereto as Schedule 7.4. Chiesi shall comply, and cause its Affiliates and Sub-distributors to comply, with all such restrictions, limitations and obligations mutatis mutandis. To the extent there is a conflict between the terms of any Existing Third Party License and the rights granted to Chiesi hereunder, the terms of such Existing Third Party License shall control solely with respect to the Patents and know-how owned or controlled by the applicable Third Party licensor. Notwithstanding anything to the contrary in this Agreement, either Party may not exercise any of its rights under this Agreement (including any right to any cure period (including under Section 9.2(b)) or to delay performance of an obligation (including under Section 11.6)) in any manner that would result in any licensor having a right to terminate an Existing Third Party License, or that would cause the other Party to be in breach of any of its obligations under any Existing Third Party License.

 

(b)                                 During the Term, uniQure shall comply with the Existing Third Party Licenses in effect which are then applicable to the activities under this Agreement with respect to the Product (and in particular shall not commit any breach that would entitle the Third Party licensor to terminate such an Existing Third Party License) and

 

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shall not terminate any such Existing Third Party License without Chiesi’s prior written consent. In addition, during the Term, uniQure shall promptly notify Chiesi of any written notice of breach or termination received by uniQure with respect to any such Existing Third Party License and, to the extent that uniQure does not cure such breach at least [**] Business Days before the date on which the relevant licensor could terminate such Existing Third Party License due to such breach by uniQure, Chiesi shall have the right (to the extent consistent with such Existing Third Party License) to cure any such breach on uniQure’s behalf and in such a case, Chiesi shall have the right to deduct (i) any and all arm’s length payments made on behalf of uniQure for the above purpose, from the next due payments to be made hereunder plus (ii) interest on such payments calculated pursuant to Section 2.1(f) above.

 

(c)                                  The license granted by uniQure in Section 7.3(a) with respect to the Patents licensed under the Existing Third Party Licenses are subject to rights reserved by the licensors and the US government as set forth in the Existing Third Party Licenses.

 

7.5                               Additional Rights Acquired after Effective Date.

 

(a)                                 During the Term, if either Party identifies the need for, or is otherwise offered, a license, covenant not to sue or similar rights to any Third Party Intellectual Property Rights that such Party in good faith believes is necessary or useful for the Commercialization of the Product in the Field in the Territory (“Additional Rights”), then such Party shall promptly notify the other Party and, in any event, prior to commencing negotiation or entering into an agreement with respect to such Additional Rights, and the Parties’ rights to conduct such negotiations shall be subject to the remaining provisions of this Section 7.5. The Parties shall thereafter conduct good faith discussions regarding whether such Additional Rights are necessary or useful for the Commercialization of the Product in the Field in the Territory or whether they otherwise agree that such Additional Rights should be acquired.

 

(b)                                 uniQure shall have the first right (but not the obligation) to license or otherwise acquire rights to any Additional Rights. If uniQure provides written notice to Chiesi that uniQure declines to exercise such first right, then Chiesi shall have the right (but not the obligation) to pursue acquiring rights to any given Additional Rights. The Party pursuing any given Additional Rights (the “Controlling Party”) shall keep the other Party (the “Non-Controlling Party”) reasonably informed regarding the status thereof and shall use Commercially Reasonable Efforts to obtain from the applicable Third Party licensor the right to sublicense such Additional Rights under the licenses granted to the Non-Controlling Party hereunder.

 

(c)                                  If the Controlling Party acquires rights to any Additional Rights and has the right to grant a sublicense under such Additional Rights to the Non-Controlling Party, and the Non-Controlling Party wishes to include such Additional Rights in the licenses granted to the Non-Controlling Party hereunder, the Non-Controlling Party shall notify the Controlling Party of its desire to do so and the Controlling Party shall provide the Non-Controlling Party a summary of all material restrictions on the scope of the licenses granted under, and all material payment obligations that would be owed by the Non-Controlling Party with respect to, any Third Party agreement applicable to such Additional Rights. The Non-Controlling Party may, upon written notice to the Controlling Party and subject to Section 7.5(d), Section 7.5(e)

 

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and Section 7.5(f), obtain a sublicense under such Additional Rights and include such Additional Rights under the licenses granted to the Non-Controlling Party hereunder.

 

(d)                                 Following such notice from the Non-Controlling Party that it desires to include any given Additional Rights under the license granted to the Non-Controlling Party hereunder, (i) any such Additional Rights that do not carry financial or other obligations or restrictions shall be included automatically under the applicable license hereunder, and (ii) subject to Section 7.5(e) below, any such Additional Rights that carry financial or other obligations or restrictions shall be included under the applicable license hereunder only if the Non-Controlling Party agrees to share the costs of such Additional Rights (including any upfront payment or similar acquisition cost to access such Additional Rights) with the Controlling Party and to assume all other obligations to, and be subject to all restrictions imposed by, the Controlling Party’s licensor to the extent arising from the grant to the Non-Controlling Party under such Additional Rights (including, to the extent access to such terms have been made available to the Non-Controlling Party in unredacted form, all other terms of the Additional Rights Agreement that apply to the licenses granted to the Non-Controlling Party hereunder).

 

(e)                                  If the Parties are unable, after [**] Business Days, to agree as to whether any given Additional Rights are in fact necessary or useful for the Commercialization of the Product in the Field in the Territory or if the Parties are unable to agree to the allocation of the costs (as specified above), then the Parties shall jointly engage an expert panel consisting of patent attorney(s) or expert(s) in the development, manufacturing or commercialization of products comparable to the Product in question and other CMC matters, as applicable, not regularly employed by either Party to resolve such dispute. The decision of such expert panel shall be binding on the Parties as to such dispute.

 

(f)                                   Nothing in this Section 7.5 shall restrict either Party, at such Party’s sole cost and expense, from licensing or otherwise acquiring any additional rights that are not necessary or useful for the Commercialization of the Product in the Field in the Territory.

 

ARTICLE VIII

COMMERCIALIZATION

 

8.1                               Commercialization.

 

(a)                                 Chiesi shall have the sole right and responsibility, at its expense, to Commercialize the Product in the Field in the Territory, including for booking all sales of the Product throughout the Territory. At all times during the Term Chiesi shall in no event use less than Commercially Reasonable Efforts to Commercialize the Product, including compliance with marketing plan and budget, allocation of Minimum FTEs and setting of a Target Price (as defined in Schedule 8.1(a)) in Germany, as further described in Schedule 8.1(a). Notwithstanding the foregoing, Chiesi shall at least use Commercially Reasonable Efforts to achieve the First Commercial Sale of the Product in the Territory in the second half of 2013, provided that uniQure shall ensure availability of sufficient quantities of Product for supply to Chiesi’s customers for such purpose, prior to the First Commercial Sale. In the event Chiesi fails to meet (i) the allocation of Minimum FTEs or (ii) the timelines for submission of each relevant dossier for obtaining the Price and Reimbursement Approval for the Product, as further described in Schedule 8.1(a), and

 

33

 

such failure is not caused by a Force Majeure Event or uniQure’s Failure to Supply, and Chiesi fails to cure such failure within [**] months after receiving written notice of such failure, uniQure shall have the right to terminate this Agreement in its entirety in the event of a failure as described in sub-paragraph (i) above or, at the sole discretion of uniQure, with respect to the particular countries to which such failure relates in the event of a failure as described in sub-paragraph (ii) above.

 

(b)                                 In order to prevent a substantial delay in achieving the First Commercial Sale of the Product in the Territory, certain commercial and development activities have been committed to by uniQure prior to the Effective Date (the “Approved Activities”) attached in Schedule 8.1(b). Such Approved Activities shall be reimbursed by Chiesi at uniQure’s actual cost.

 

(c)                                  Chiesi shall have the sole authority to determine the resale price of the Product in the Field in the Territory.

 

8.2                               Exclusivity.

 

(a)                                 During the Term, Chiesi shall not actively market, advertise for, canvas for or seek orders for the Product outside the Field or Territory or establish any branch, subsidiary, or depot for the supply of the Product outside the Field or Territory. The Parties shall inform each other promptly in case of any Commercialization activities of Third Parties in the Field in the Territory, or of any Commercialization activities of Chiesi or any of its Affiliates outside the Field or Territory to agree — within the limits of applicable competition laws — on any appropriate measures to be taken.

 

(b)                                 During the Term, uniQure shall not offer for sale, sell, license or otherwise Commercialize the Product in the Territory other than in compliance with the terms of this Agreement. uniQure shall be free, however, at any time during the Term, to Commercialize, directly or indirectly, the Product outside the Territory.

 

(c)                                  To the fullest extent consistent with any Applicable Laws, each Party shall, and shall procure that any of its Affiliates will, not directly or indirectly, itself or through or with or on behalf of any Third Party, develop, Manufacture or Commercialize in the Territory any Gene Therapy based product characterized to treat lipoprotein lipase deficiency, other than the Product in accordance with this Agreement. From time to time during the Term, the Parties may negotiate exceptions for Persons which will become Affiliates of a Party due to an acquisition of or by a Party or its Affiliates.

 

ARTICLE IX

TERM AND TERMINATION

 

9.1                               Term.

 

(a)                                 General.  This Agreement shall become effective as of the Effective Date and shall remain in force, on a country-by-country basis, for the longer of (i) twelve (12) years from the First Commercial Sale of the Product in the relevant country of the Territory; (ii) expiry of any regulatory exclusivity granted by any Marketing Authorization or any other Regulatory Approval in the relevant country of the Territory; or (iii) expiry of the last Valid Claim Covering the Product in the relevant

 

34

 

country of the Territory. Unless terminated by a Party with three (3) months written notice to the other Party to the end of the above initial or any subsequent term, this Agreement shall automatically be renewed for successive five (5) year terms (the initial and each subsequent term, the “Term”).

 

(b)                                 Condition Precedent.  This Agreement, except for the obligation to submit the first Firm Order in accordance with Section 2.4(b), and any ancillary agreement concluded between the Parties in connection herewith, including the Quality Agreement and the SDEA, and the Co-Development and License Agreement and the agreement regarding the equity investment of Chiesi in uniQure concluded on the date hereof, shall become effective once the Parties have received consent from or, as the case may be, entered into separate agreements with, the respective Third Party licensors to the subcontracting of the rights and licenses licensed by uniQure as licensee under the Existing Third Party Licenses listed in Schedule 9.1 to Chiesi. uniQure and, to the extent applicable, Chiesi, shall use Commercially Reasonable Efforts to obtain such consent or, as the case may be, enter into such agreements, on or prior to [**]. If, despite the Parties’ Commercially Reasonable Efforts, such consent has not been obtained from or, as the case may be, such agreements have not been entered into with, all such Third Party licensors by the end of [**], this Agreement and all other agreements that are subject to the condition precedent pursuant to sentence 1 shall be deemed null and void as of the Effective Date and the first Firm Order submitted by Chiesi in accordance with Section 2.4(b) shall be deemed withdrawn, unless, prior to the end of such period, following a corresponding request of either Party, the Parties mutually agree in writing on an extension of such period. The Parties agree that (i) costs and expenses incurred in connection with the preparation and execution of this Agreement as well as obtaining of the aforementioned consent or, as the case may be, enter into the aforementioned agreements, shall not be reimbursed, provided, however, that uniQure shall pay back to Chiesi any payments received in connection with this Agreement on or prior to [**] (or such extended period mutually agreed between the Parties in accordance with the foregoing), and (ii) Sections 10.1, 10.2 and 10.6 shall apply mutatis mutandis.

 

9.2                               Termination.  Without prejudice to any other termination rights set forth herein, the Parties shall have the following termination rights:

 

(a)                                 Mutual Agreement.  The Parties may terminate this Agreement at any time during the Term upon mutual agreement in writing.

 

(b)                                 Material Breach.  Either Party may immediately terminate this Agreement in writing if the other Party materially breaches this Agreement and fails to cure such breach within [**] days after receiving written notice of the breach.

 

(c)                                  Insolvency.  Either Party may immediately terminate this Agreement in writing if the other Party ceases to carry on business, is unable to pay its debts when they fall due, is declared bankrupt, or an order is made or a resolution passed for the winding up of that other Party or the appointment of an administrator, receiver, liquidator, or manager of that other Party.

 

(d)                                 IP Challenge.  Either Party may immediately terminate this Agreement in writing if the other Party or any of its Affiliates or, as the case may be, Sub-distributors challenges the validity of any trademark as set forth in Section 2.2(a) or if

 

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Chiesi or any of its Affiliates or Sub-distributors challenges the validity, enforceability, patentability or scope of any Valid Claim included in any Patents.

 

9.3                               Effects of Expiration/Termination.

 

(a)                                 Upon termination of this Agreement by uniQure pursuant to Sections 8.1(a), 9.2(b), 9.2(c) or 9.2(d):

 

(i)                                     Chiesi shall purchase from uniQure any quantity of Product which has been included in a Confirmed Firm Order through the effective date of termination, unless otherwise elected by UniQure pursuant to Section 9.3(a)(ii) below;

 

(ii)                                  (A) all rights, privileges and licenses granted hereunder to Chiesi shall remain in full force and effect until all quantities of Product ordered and delivered hereunder, at the election of uniQure, (y) have been sold by Chiesi, or (z) have been redeemed by uniQure from Chiesi at the Purchase Price originally charged to Chiesi except for such portion of Product as is needed to fill orders then held by Chiesi; and (B) Chiesi shall thereafter not make any use whatsoever of any such rights, privileges and licenses and transfer to uniQure any Marketing Authorization then held by Chiesi or its Sub-distributor, unless required by Applicable Laws or expressly set forth otherwise in this Agreement;

 

(iii)                               save as required under the Quality Agreement or the SDEA, at any time upon written request of the disclosing Party, unless expressly set forth otherwise in this Agreement, the receiving Party shall cease use of and return or at the disclosing Party’s request destroy all Confidential Information of the disclosing Party and all copies thereof except for a single copy of such Confidential Information that may be retained confidentially for legal purposes only;

 

(iv)                              all rights, privileges and licenses granted hereunder to uniQure regarding any alternative Trademark identified by Chiesi and any other trademarks, logos or service marks of Chiesi shall become fully paid-up, irrevocable and perpetual.

 

(b)                                 Upon termination of this Agreement by Chiesi pursuant to Sections 9.2(b), 9.2(c) or 9.2(d):

 

(i)                                     all rights, privileges and licenses granted hereunder to Chiesi regarding the uniQure Intellectual Property Rights, including the rights granted under Section 2.2(a), shall become fully paid-up, irrevocable and perpetual;

 

(ii)                                  all rights, privileges and licenses granted hereunder to uniQure shall terminate and uniQure shall not make any use whatsoever of any alternative Trademark identified by Chiesi and any other trademarks, logos or service marks of Chiesi, unless required by Applicable Laws or expressly set forth otherwise in this Agreement;

 

(iii)                               uniQure shall furnish Chiesi with reasonable cooperation, and continue to supply Chiesi’s requirements of Product for the [**] month period following notice of termination in accordance with the terms and conditions of this Agreement, provided however, that the Purchase Price for the individual Product ordered

 

36

 

after the effective date of termination shall be the Fully Loaded Cost of Goods plus [**] percent ([**]%) markup for each patient dose sold of such particular Product. No later than [**] months prior to the expiration of such [**] month period the Parties shall enter into good faith negotiations regarding the supply of Chiesi’s requirements of Product after expiration of such [**] month period, taking into account a fair adjustment of the transfer price pursuant to Section 2.3(b) for the Product to be supplied to Chiesi after such expiration;

 

(iv)                              save as required under the Quality Agreement or the SDEA, at any time upon written request of the disclosing Party, unless expressly set forth otherwise in this Agreement, the receiving Party shall cease use of and return or at the disclosing Party’s request destroy all Confidential Information of the disclosing Party and all copies thereof except for a single copy of such Confidential Information that may be retained confidentially for legal purposes only.

 

(c)                                  Upon expiration of the Term with respect to this Agreement by a Party exercising its termination right pursuant to Section 9.1(a) or mutual termination pursuant to Section 9.2(a) (unless otherwise agreed between the Parties in such mutual termination agreement):

 

(i)                                     all rights, privileges and licenses granted hereunder to Chiesi shall become fully paid-up, irrevocable and perpetual;

 

(ii)                                  all rights, privileges and licenses granted hereunder to uniQure shall become fully paid-up, irrevocable and perpetual;

 

(iii)                               Chiesi shall purchase from uniQure any quantity of Product which has been included in a Confirmed Firm Order through the effective date of expiration;

 

(iv)                              save as required under the Quality Agreement or the SDEA, at any time upon written request of the disclosing Party, unless expressly set forth otherwise in this Agreement, the receiving Party shall cease use of and return or at the disclosing Party’s request destroy all Confidential Information of the disclosing Party and all copies thereof except for a single copy of such Confidential Information that may be retained confidentially for legal purposes only.

 

Upon expiration of the Term with respect to this Agreement by uniQure exercising its termination right pursuant to Section 9.1(a), uniQure shall continue to supply Chiesi’s requirements of Product for the [**] month period following notice of termination in accordance with the terms and conditions of this Agreement, provided however, that the Purchase Price for the individual Product ordered after the effective date of termination shall be the Fully Loaded Cost of Goods plus [**] percent ([**]%) markup for each patient dose sold of such particular Product. No later than [**] months prior to the expiration of such [**] month period the Parties shall enter into good faith negotiations regarding the supply of Chiesi’s requirements of Product after expiration of such [**] month period, taking into account a fair adjustment of the transfer price pursuant to Section 2.3(b) for the Product to be supplied to Chiesi after such expiration.

 

37

 

(d)                                 Accrued Rights; Surviving Provisions.

 

(i)                                     Notwithstanding the giving of any notice of termination pursuant to this Article 9, each Party shall continue to fulfill such Party’s obligations under this Agreement at all times until the effective date of any such termination.

 

(ii)                                  Termination or expiration of this Agreement for any reason shall be without prejudice to any rights which shall have accrued to the benefit of either Party prior to such termination or expiration.

 

(iii)                               Without prejudice to Section 11.7, to the extent legally permitted, any compensation claims by Chiesi resulting from a direct or analogous application of Article 17 of Council Directive 86/653/EEC, as amended, as transposed into the national laws of the EU Member States for undertaking the Commercialization of the Product in the Territory are expressly excluded and hereby expressly waived by Chiesi.

 

(iv)                              All those provisions which by their scope and nature extend beyond the Term, including Article I, Section 2.1(d) to (h), Article VI, Section 7.1, Section 9.3, Sections 10.1, 10.2 and 10.6, and Article XI, shall survive any expiration or termination of this Agreement, and remain in full force and effect.

 

ARTICLE X

CONFIDENTIALITY

 

10.1                        Confidential Information.  All Confidential Information disclosed by a Party or any of its Affiliates to the other Party or any of its Affiliates before or during the Term shall not be used by the receiving Party or any of its Affiliates except in connection with the activities contemplated by this Agreement, shall be maintained in confidence by the receiving Party and its Affiliates, and shall not otherwise be disclosed by the receiving Party or its Affiliates to any Third Party (except as set forth in the remainder of this Article X), without the prior written consent of the disclosing Party, except to the extent that the Confidential Information:

 

(a)                                 was known or used by the receiving Party or any of its Affiliates prior to its date of disclosure by the disclosing Party;

 

(b)                                 either before or after the date of the disclosure to the receiving Party hereunder or under the Confidentiality Agreement is lawfully disclosed to the receiving Party or any of its Affiliates by a Third Party rightfully in possession of and with the right to disclose such Confidential Information other than under an obligation of confidentiality;

 

(c)                                  either before or after the date of the disclosure to the receiving Party hereunder or under the Confidentiality Agreement becomes generally known to the public through no fault or omission on the part of the receiving Party or its Affiliates;

 

(d)                                 is independently developed by or for the receiving Party or any of its Affiliates without reference to or reliance upon any of the other Party’s Confidential Information; or

 

(e)                                  is required to be disclosed by the receiving Party or its Affiliates to comply with Applicable Laws, which may include the rules of Euronext, of the US

 

38

 

Securities and Exchange Commission, or of any other stock exchange, or to defend or prosecute litigation or arbitration or to comply with legal process; provided that, the receiving Party provides prior written notice of such disclosure to the disclosing Party (to the extent feasible) and only discloses Confidential Information of the other Party to the extent necessary for such legal compliance or litigation purpose; and provided, further, that (i) the receiving Party shall use, or shall cause its Affiliates, as the case may be, to use, reasonable efforts to obtain confidential treatment, or the equivalent, from Euronext, the US Securities and Exchange Commission, or other securities trading institution of any financial information or other information of a competitive or confidential nature, and shall include in such confidentiality request such provisions of this Agreement as may be reasonably requested by the disclosing Party, and (ii) such information shall otherwise remain Confidential Information (subject to the exceptions in this Section 10.1).

 

Notwithstanding the foregoing, paragraphs (a), (b) and (d) shall not alter the requirement to keep the terms and conditions of this Agreement confidential, as set forth herein, subject to the remainder of this Article X.

 

10.2                        Employee, Director, Consultant and Advisor Obligations.  Chiesi and uniQure each agrees that it and its Affiliates shall provide Confidential Information received from the other Party only to the receiving Party’s employees, directors, consultants, agents and advisors, and to the employees, directors, consultants, agents and advisors of the receiving Party’s Affiliates, who have a need to know such Confidential Information to assist the receiving Party in fulfilling its obligations under this Agreement and who are bound by obligations of confidentiality and non-use that are at least as restrictive as those set forth in this Agreement. Each Party shall remain responsible for any failure by any of its or its Affiliates’ employees, directors, consultants, agents and advisors to treat such Confidential Information as required under this Article X.

 

10.3                        Publicity.

 

(a)                                 Following execution of this Agreement, the Parties shall jointly or separately issue a press release, in a text to be agreed upon between the Parties in advance, announcing the execution of this Agreement and the Co-Development and License Agreement.

 

(b)                                 Each Party shall only issue press releases (other than the press release pursuant to paragraph (a) above) or make other public disclosures regarding this Agreement or the Parties’ activities under this Agreement (each such press release or public disclosure, a “Subject Disclosure”):

 

(i)                                     that have been approved in writing in advance by the other Party (such approval not to be unreasonably withheld, conditioned or delayed), including Subject Disclosures that describe one or more of the following:

 

(A)                               the filing for or receipt of Marketing Authorization with respect to the Product in the Territory;

 

(B)                               the receipt of Price and Reimbursement Approval for the Product in the Territory;

 

39

 

(C)                               the receipt of any regulatory exclusivity for the Product in the Territory;

 

(D)                               the achievement of any commercial milestone pursuant to Section 2.1(c)(ii); or

 

(E)                                the first Party’s presence or participation at scientific, financial or investor forums;

 

(ii)                                  subject to Section 10.3(c), if advised by counsel to issue such Subject Disclosure in order to comply with Applicable Laws, which may include the disclosure rules of the US Securities and Exchange Commission or a similar regulatory agency in a country in the Territory or of Euronext or any other stock exchange of other securities trading institution; or

 

(iii)                               subject to Section 10.3(c), if the contents of such Subject Disclosure have previously been made public other than through a breach of this Article X by a Party.

 

(c)                                  Unless not feasible under the circumstances because of the need to comply with Applicable Laws or stock exchange rules, the Party making a Subject Disclosure shall provide the other Party with a draft Subject Disclosure at least [**] Business Days prior to its intended publication for the other Party’s review. Such other Party may provide the first Party with suggested modifications to the draft Subject Disclosure. The first Party shall consider in good faith the other Party’s timely provided suggestions in issuing such Subject Disclosure.

 

(d)                                 For clarity, nothing in this Agreement shall restrict (i) each Party from issuing press releases or making other public disclosures regarding such Party’s development, manufacturing or commercialization activities with respect to any product other than the Product, or (ii) uniQure from issuing press releases or making other public disclosures regarding uniQure’s development, manufacturing or commercialization activities with respect to the Product outside the Field or Territory.

 

10.4                        Other Disclosures.  Notwithstanding anything in this Agreement to the contrary, each Party shall have the right to disclose the other Party’s Confidential Information (including the terms of this Agreement) (as applicable):

 

(a)                                 to such Party’s then-current or potential investors, lenders, acquirers, investment bankers, and other Third Parties in connection with financing, partnering (to the extent consistent with this Agreement) and acquisition activities, solely on a need-to-know basis and under obligations of confidentiality and non-use that are at least as restrictive as those set forth in this Article X;

 

(b)                                 as required by the existing license agreements between uniQure and its Third Party licensors;

 

(c)                                  to enforce Patents, Trademarks and other Intellectual Property Rights in accordance with Sections 2.2(a) and 7.2; or

 

(d)                                 to such Party’s then-current or potential collaborators, and Third Party contractors (including contract manufacturers and Sub-distributors) for purposes of

 

40

 

engaging in the Manufacture or Commercialization of the Product as contemplated hereunder, solely on a need-to-know basis and under obligations of confidentiality and non-use that are at least as restrictive as those set forth in this Article X.

 

10.5                        Publications.

 

(a)                                 Notwithstanding Section 10.3 and Section 10.4, a Party (the “Publishing Party”) which is, or whose Affiliates is, seeking to publish or publicly present scientific or technical data, results or other information with respect to the Product shall provide the other Party and the JCC with a copy of any proposed publication or presentation at least [**] days (or at least [**] days in the case of abstracts or oral public presentations) prior to submission for publication or presentation so as to provide such other Party with an opportunity to recommend any changes it reasonably believes are necessary to continue to maintain such other Party’s Confidential Information in accordance with the requirements of this Agreement or to not jeopardize the patentability of any results or data.

 

(b)                                 If the non-Publishing Party notifies the Publishing Party that such publication or presentation, in the non-Publishing Party’s reasonable judgment, (i) discloses an invention for which the non-Publishing Party desires to seek patent protection, or (ii) contains any Confidential Information of the non-Publishing Party, or could be expected to have an adverse effect on the commercial value of any Confidential Information disclosed by the non-Publishing Party to the Publishing Party, the Publishing Party shall delete such Confidential Information from the proposed publication or presentation and shall further delay such publication or presentation for a period reasonably sufficient to permit the timely preparation and filing of a patent application(s) on any invention disclosed in such publication or presentation (but no more than [**] days from the date of the non-Publishing Party’s notice thereof).

 

10.6                        Term.  All obligations of confidentiality imposed under this Article X shall expire [**] years following termination or expiration of this Agreement, except to the extent any Existing Third Party License between uniQure and its Third Party licensors extends such obligations; provided, however, that the receiving Party shall maintain the confidentiality of any of the other Party’s trade secrets indefinitely until such trade secret is no longer a trade secret.

 

ARTICLE XI

MISCELLANEOUS

 

11.1                        Entire Agreement, Amendments. This Agreement and the attachments hereto contain the entire understanding and agreement of the Parties with respect to the subject matter hereof and cancel and supersede any and all prior negotiations, correspondence, understandings and agreements between the Parties, whether oral or written, regarding such subject matter, including the Memorandum of Understanding dated 21 December 2012 and the Confidentiality Agreement, but expressly excluding the Co-Development and License Agreement. Except for the rights expressly conferred on the JSC or JCC, this Agreement cannot be modified except by a written document bearing the signatures of both Parties. The same applies to any waiver of this written form requirement.

 

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11.2                        Assignments. Except as expressly provided herein, neither this Agreement nor any rights and obligations hereunder shall be assignable by a Party without the prior written consent of the other Party; provided, however, that a Party may assign this Agreement to any Affiliate or to any successor in interest by way of merger, acquisition or sale of all or substantially all of its assets to which this Agreement relates, provided that such successor agrees in writing to be bound by the terms of this Agreement as if it were the assigning Party. This Agreement shall be binding upon the successors and permitted assigns of the Parties. Any assignment not in accordance with this Section 11.2 shall be void.

 

11.3                        Severability. Should any provision of this Agreement be or become invalid, ineffective or unenforceable as a whole or in part, the validity, effectiveness and enforceability of the remaining provisions shall not be affected thereby. Any such invalid, ineffective or unenforceable provision shall be deemed replaced by such valid, effective and enforceable provision as comes closest to the economic intent and the purpose of such invalid, ineffective or unenforceable provision. The aforesaid shall apply mutatis mutandis to any gap in this Agreement.

 

11.4                        Notices. Other than as expressly specified in this Agreement, all notices and consents required to be provided hereunder shall be in writing and provided by hand, by recorded delivery mail (return receipt requested), by facsimile, or by recognized overnight courier service to the other Party at its address or facsimile number shown below or such other address or facsimile number notified by such other Party from time to time.

 

If to uniQure, addressed to:

 

uniQure Biopharma B.V.

P.O. Box 22506

1100 DA Amsterdam

The Netherlands

Attention: CEO

Fax: +31 20 566 9272

 

If to Chiesi, addressed to:

 

Chiesi Farmaceutici S.p.A.

Via Palermo, 26/A

43122 Parma

Italy

Attention: CEO

Copy to: Corporate Development, Head and General Counsel

Fax: +39 0521 774468

 

11.5                        Waiver. Any failure of either Party to enforce any provision hereof shall not constitute a waiver by that Party of its right subsequently to enforce the same or any other provision hereof. The waiver of any provision of this Agreement shall only be effective if in writing signed by the Party claimed to have waived such provision.

 

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11.6                        Force Majeure. Neither Party shall lose any rights hereunder or be liable to the other Party for damages or losses on account of failure of performance by the defaulting Party if the failure is occasioned by war, civil insurrection, strike, fire, Act of God, earthquake, tempest, flood, epidemic, blackout, lockout, embargo, governmental acts or orders or restrictions, delays in delivery and non-supply by exclusive suppliers, where such delay or non-supply occurs as a result of such Force Majeure, or any other reason where failure to perform is beyond the reasonable control of such Party (each a “Force Majeure Event”) and such failure to perform is not caused by the negligence, intentional conduct or misconduct of the non-performing Party and such Party has exerted all reasonable efforts to avoid or remedy such Force Majeure Event; provided, however, that in no event shall a Party be required to settle any labor dispute or disturbance.

 

11.7                        Independence. The relationship between the Parties is that of independent contractors and neither Party shall have the power to bind or obligate the other Party in any manner. It is further understood and agreed that neither Party nor its Affiliates, nor its and their respective directors, officers and employees, shall be deemed an agent or employee of the other Party or its Affiliates.

 

11.8                        Third Party Beneficiaries.  All rights, benefits and remedies under this Agreement are solely intended for the benefit of uniQure and Chiesi. No Third Party shall have any rights whatsoever to (i) enforce any obligation contained in this Agreement; (ii) seek a benefit or remedy for any breach of this Agreement; or (iii) take any other action relating to this Agreement under any legal theory, including but not limited to, actions in contract, tort (including negligence, gross negligence and strict liability), or as a defense, setoff or counterclaim to any action or claim brought or made by the Parties.

 

11.9                        Governing Law, Dispute Resolution. The validity and interpretation of this Agreement shall be governed by the laws of England without regard to its conflicts of laws principles and to the express exclusion of the United Nations Conventions on Contracts for the International Sale of Goods (CISG). Any dispute arising under, out of or relating to this Agreement shall be referred to and finally determined under the Rules of Arbitration of the International Chamber of Commerce by three (3) arbitrators appointed in accordance with the said Rules. The place of arbitration shall be London, United Kingdom. The language to be used in said proceedings shall be English.

 

11.10                 Costs.  Except as expressly provided in this Agreement or as separately agreed upon in writing between the Parties, each Party shall bear its own costs incurred in connection with the implementation of the obligations under this Agreement.

 

11.11                 Construction.  Each Party agrees that this Agreement shall be interpreted without regard to any presumption or rule requiring construction against the Party causing this Agreement to be drafted.

 

11.12                 Language.  This Agreement shall be written and executed in, and all other communications under or in connection with this Agreement shall be in, the English language. Any translation into any other language shall not be an official version thereof, and in the event of any conflict in interpretation between the English version and such translation, the English version shall control.

 

11.13                 Counterparts.  This Agreement may be executed simultaneously in any number of counterparts, any one of which need not contain the signature of more than one

 

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Party but all such counterparts taken together shall constitute one and the same agreement. A pdf file of this Agreement contained in an email, including the signed signature pages hereto, will be deemed to be an original.

 

[Signature Page Follows]

 

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IN WITNESS WHEREOF, the Parties have executed this Commercialization Agreement as of the Effective Date.

 

	
UNIQURE BIOPHARMA B.V.
    	
UNIQURE BIOPHARMA B.V.
    
	
 
    	
 
    
	
 
    	
 
    
	
By:
    	
/s/ Piers Morgan
    	
 
    	
By:
    	
/s/ Hans Preusting
    
	
 
    	
Name:
    	
Mr. Piers Morgan 
    	
 
    	
Name:
    	
Mr. Hans Preusting 
    
	
 
    	
Title:
    	
Chief Financial Officer
    	
 
    	
Title:
    	
Business Development, Vice President
    
	
 
    	
 
    
	
 
    	
 
    
	
CHIESI FARMACEUTICA S.p.A.
    	
CHIESI FARMACEUTICI S.p.A.
    
	
 
    	
 
    
	
 
    	
 
    
	
By:
    	
/s/ Alberto Chiesi
    	
 
    	
By:
    	
/s/ Ugo Di Francesco
    
	
 
    	
Name:
    	
Mr. Alberto Chiesi 
    	
 
    	
Name:
    	
Mr. Ugo Di Francesco 
    
	
 
    	
Title:
    	
President
    	
 
    	
Title:
    	
CEO
    
							

 

45

 

SCHEDULE 1.9
 Certificate of Analysis

 

	
CONTROLLED DOCUMENT — CONFIDENTIAL
    	
 
    	

    

 

Certificate of Analysis

 

	
SMS number
    	
 
    	
 
    
	
Product
    	
 
    	
Glybera® Drug Product (Final Product)
    
	
Part number
    	
 
    	
C0114 rev.
    
	
Batch number
    	
 
    	
 
    
	
Production stage
    	
 
    	
Drug product
    
	
Expiry date
    	
 
    	
Page 1 of 1
    

 

	
Test, Method
    	
 
    	
Specification
    	
 
    	
Result
    
	
[**]
    	
 
    	
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[**]
    	
 
    	
[**]
    	
 
    	
 
    

 

Remarks:

 

Conclusion

 

	
Authorized signature:
    	
 
    	
 
    
	
Name:
    	
 
    	
 
    
	
Date:
    	
 
    	
 
    
	
 
    	
 
    	
 
    

 

	
Visiting address
    	
 
    	
Postal address
    	
 
    	
 
    
	
Meibergdreef 61
    	
 
    	
P.O. Box 22506
    	
 
    	
tel +31 (0)20 566 7394
    
	
1105 BA Amsterdam
    	
 
    	
1100 DA Amsterdam
    	
 
    	
fax +31 (0)20 566 9272
    
	
The Netherlands
    	
 
    	
The Netherlands
    	
 
    	
info@uniqure.com
    

 

 

SCHEDULE 1.10
 Certificate of Compliance

 

	
Document No.: QA-SOP-XXX-0036-EX
    	
 
    	
 
    	
 
    	
 
    
	
Revision No.:

Page No.: 1 of 1

Effective date:
    	
 
    	
Preparation of   Certificates — 
   Exhibit X: Certificate of Release
    	
 
    	

    

 

	
Product name:
    	
 
    	
Date manufactured:
    
	
Quantity:
    	
 
    	
Expiry/retest date:
    
	
Batch number:
    	
 
    	
Storage conditions:
    

 

	
Manufacturer:
    	
 
    	
UniQure
    
	
Production Site:
    	
 
    	
Meibergdreef 61, 1105 BA Amsterdam, The   Netherlands
    

 

Release tests:

 

o:  All test results are within approved specifications.

 

Certification statement:

 

uniQure is certified by the Dutch Health Authorities (Ministerie van VWS), per manufacturing license number 108990F, to manufacture biological products (gene therapies).

 

I hereby certify that this batch has been manufactured at the above-stated site in full compliance with the EU GMP requirements, and meets the authorized quality specifications registered in uniQures’ quality systems.  The batch manufacturing and analytical records were reviewed and are found to be in compliance with GMP.

 

	
Name:
    	
 
    
	
Position:
    	
Qualified Person
    
	
Signature:
    	
 
    
	
 
    	
 
    
	
Date:
    	
 
    

 

47

 

SCHEDULE 1.63
  Patents

 

UniQure Patent Portfolio:  GLYBERA

 

	
UniQure Ref.
    	
 
    	
Country
    	
 
    	
Owners
    	
 
    	
Official No.
    	
 
    	
Case
   Status
    	
 
    	
Filing
   Date
    	
 
    	
Date
   Registration
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    

 

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of four pages were omitted. [**]

 

48

 

In-licensed patent portfolio:  GLYBERA

 

	
Licensor
    	
 
    	
Owners
    	
 
    	
Official No.
    	
 
    	
Case Status
    	
 
    	
Filing Date
    	
 
    	
Date
   Registration
    
	
[**]
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    
	
[**]
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
[**]
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    
	
[**]
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    
	
[**]
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
[**]
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
[**]
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
[**]
    	
 
    	
 
    	
 
    	
 
    

 

Note:

 

[**]

 

49

 

SCHEDULE 1.66
 Product

 

Glybera: AAV1_LPLS447X

 

Marketing Authorization Numbers: EU/1/12/791/001

 

50

SCHEDULE 1.78

 

Initial Specifications

 

	
Module 3
   3.2.P.5
    	
 
    	
Glybera
   [alipogene tiparvovec]
    	
 
    	
uniQure
    

 

1.             SPECIFICATIONS

 

Before QC testing the samples taken from the drug product batch are stored at the same conditions and subjected to one freeze thaw cycle.

 

The proposed release and shelf life specifications for Glybera drug product are shown in Table 1 below:

 

Table 1:  Release and shelf life specifications for Glybera

 

	
Test parameter
    	
 
    	
Acceptance Criteria
    
	
General tests and test for contamination
    
	
[**]
    	
 
    	
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51

 

	
 
    	
 
    	
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[**]
    	
 
    	
[**]
    
	
[**]
    	
 
    	
[**]
    

 

[**]

 

52

 

SCHEDULE 2.2(a)
 Trademarks

 

uniQure’s Trademark Portfolio:  GLYBERA - uniQure

 

	
Catchword
    	
 
    	
Type
    	
 
    	
Country
    	
 
    	
Classes
    	
 
    	
Appl.No.
    	
 
    	
Appl.date
    	
 
    	
Reg.No.
    	
 
    	
Rcg.datc
    	
 
    	
Rcn.date
    	
 
    	
Applicant
    	
 
    	
Status
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	

   G device
    	
 
    	
Logotype
    	
 
    	
EU
    	
 
    	
05, 44
    	
 
    	
8640609
    	
 
    	
10/26/2009.
    	
 
    	
8640609
    	
 
    	
5/10/2010.
    	
 
    	
10/26/2019.
    	
 
    	
uniQure IP B.V.
    	
 
    	
Registered
    
	
GLYBERA
    	
 
    	
Wordmark
    	
 
    	
EU
    	
 
    	
05. 44
    	
 
    	
5901269
    	
 
    	
5/1/2007.
    	
 
    	
5901269
    	
 
    	
5/14/2009.
    	
 
    	
5/1/2017.
    	
 
    	
uniQure IP B.V.
    	
 
    	
Registered
    
	
GLYBERA
    	
 
    	
Wordmark
    	
 
    	
TR
    	
 
    	
05
    	
 
    	
2007026778
    	
 
    	
17.05.2007
    	
 
    	
2007026778
    	
 
    	
17.05.2007
    	
 
    	
17.05.2017
    	
 
    	
uniQure IP B.V.
    	
 
    	
Registered
    
	
GLYBERA
    	
 
    	
Wordmark
    	
 
    	
RU
    	
 
    	
05
    	
 
    	
2008707340
    	
 
    	
13.03.2008
    	
 
    	
377215
    	
 
    	
20.04.2009
    	
 
    	
13.03.2018
    	
 
    	
Amsterdam Molecular Therapeutics (AMT)   Holding N.V.
    	
 
    	
Registered
    
	
GLYBERA
    	
 
    	
Wordmark
    	
 
    	
CH
    	
 
    	
05
    	
 
    	
551392007
    	
 
    	
14.05.2007
    	
 
    	
562178
    	
 
    	
11.09.2007
    	
 
    	
14.05.2017
    	
 
    	
Amsterdam Molecular Therapeutics (AMT)   Holding N.V.
    	
 
    	
Registered
    
	
GLYBERA
    	
 
    	
Wordmark
    	
 
    	
IS
    	
 
    	
05
    	
 
    	
14642007
    	
 
    	
14.05.2007
    	
 
    	
8122007
    	
 
    	
04.07.2007
    	
 
    	
04.07.2017
    	
 
    	
Amsterdam Molecular Therapeutics (AMT)   Holding N.V.
    	
 
    	
Registered
    
	
GLYBERA
    	
 
    	
Wordmark
    	
 
    	
NO
    	
 
    	
05
    	
 
    	
200705606
    	
 
    	
15.05.2007
    	
 
    	
241553
    	
 
    	
19.10.2007
    	
 
    	
19.10.2017
    	
 
    	
Amsterdam Molecular Therapeutics (AMT)   Holding N.V.
    	
 
    	
Registered
    
	
GLYBERA
    	
 
    	
Wordmark
    	
 
    	
DZ
    	
 
    	
05
    	
 
    	
72791
    	
 
    	
24.10.2007
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
Amsterdam Molecular Therapeutics (AMT)   Holding N.V.
    	
 
    	
Pending
    
	
GLYBERA
    	
 
    	
Wordmark
    	
 
    	
EG
    	
 
    	
05
    	
 
    	
208229
    	
 
    	
22.10.2007
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
Amsterdam Molecular Therapeutics (AMT)   Holding N.V.
    	
 
    	
Pending
    
	
GLYBERA
    	
 
    	
Wordmark
    	
 
    	
MA
    	
 
    	
05
    	
 
    	
113550
    	
 
    	
23.10.2007
    	
 
    	
113550
    	
 
    	
23.10.2007
    	
 
    	
23.10.2017
    	
 
    	
Amsterdam Molecular Therapeutics (AMT)   Holding N.V.
    	
 
    	
Registered
    
	
GLYBERA
    	
 
    	
Wordmark
    	
 
    	
TN
    	
 
    	
05
    	
 
    	
EE072667
    	
 
    	
24.10.2007
    	
 
    	
EE72667
    	
 
    	
19.05.2009
    	
 
    	
24.10.2017
    	
 
    	
Amsterdam Molecular Therapeutics (AMT)   Holding N.V.
    	
 
    	
Registered
    

 

53

 

	
 

GLYBERA device
    	
 
    	
Logotype
    	
 
    	
EU
    	
 
    	
05, 44
    	
 
    	
8640641
    	
 
    	
10/26/2009.
    	
 
    	
8640641
    	
 
    	
5/10/2010.
    	
 
    	
10/26/2019.
    	
 
    	
uniQure IP B.V.
    	
 
    	
Registered
    
	
UNIQURE
    	
 
    	
Wordmark
    	
 
    	
EU
    	
 
    	
01, 05, 42, 44
    	
 
    	
10431005
    	
 
    	
11/21/2011.
    	
 
    	
 
    	
 
    	
4/25/2012
    	
 
    	
11/21/2021.
    	
 
    	
uniQure IP B.V.
    	
 
    	
Registered
    

 

54

 

SCHEDULE 2.2(b)
 uniQure Trademark Guidelines

 

uniQure

 

TRADEMARK GUIDELINES

 

The trademarks of uniQureBiopharmaB.V. and its subsidiary uniQure IP B.V. -hereinafter “uniQure” or “Company” - are valuable and important intellectual property assets of the Company. It is crucial that you protect the value of our trademarks by using them properly. These guidelines, which are updated from time to time, set out our policies for your use of such assets.

 

If you are a licensee of uniQure trademarks, your license agreement will specify the trademarks that you are authorized to use and may provide additional special trademark usage guidelines. You may NOT use our trademarks in a manner that incorrectly suggests that uniQure sponsors or endorses or is otherwise associated with your activities, products, and services, except as set forth in your license agreement with us.

 

Registered trademarks:

 

UniQure is owner of the following trademark registrations in the European Union:

 

	
Trademark
    	
 
    	
Type
    	
 
    	
Country
    	
 
    	
goods/services
    	
 
    	
Reg. No.
    	
 
    	
Reg. Date
    
	
GLYBERA
    	
 
    	
Word
    	
 
    	
EU
    	
 
    	
Class 5: Pharmaceutical products; biological preparations for use in   medical and clinical gene therapy and cell therapy; clinical medical reagents   for use in gene therapy; gene diagnosis, and gene testing; pharmaceutical   preparations, vaccines for use in gene therapy: gene therapy and prophylaxis   products; all the aforementioned goods exclusively in the treatment of   metabolic disorders including such disorders which are single gene disorders   and disorders which are a result of one more mutations within the lipoprotein   lipase gene 

 

Class 44: Gene delivery, gene transfer, gene regulation and gene modulation   for the treatment of metabolic disorders, including such disorders which are   single gene disorders, and disorders which are a result of one more mutations   within in the lipoprotein lipase gene, ocular disorders
    	
 
    	
5901269
    	
 
    	
5/14/2009
    
	

    	
 
    	
word and device
    	
 
    	
EU
    	
 
    	
Class 5: Pharmaceutical products; biological preparations for use in   medical and clinical gene therapy and cell therapy; clinical medical
    	
 
    	
8640641
    	
 
    	
5/10/2010
    

 

 

	
Trademark
    	
 
    	
Type
    	
 
    	
Country
    	
 
    	
goods/services
    	
 
    	
Reg. No.
    	
 
    	
Reg. Date
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
reagents for use in gene therapy, gene   diagnosis, and gene testing; pharmaceutical preparations, vaccines for use in   gene therapy; gene therapy and prophylaxis products, all the aforementioned   goods exclusively in the treatment of metabolic disorders including such   disorders which are single gene disorders and disorders which are a result of   one more mutations within the lipoprotein lipase gene 

 

Class 44: Gene delivery, gene transfer, gene regulation and gene modulation   for the treatment of metabolic disorders, including such disorders which are   single gene disorders, and disorders which are a result of one more mutations   within the lipoprotein lipase gene and ocular disorders
    	
 
    	
 
    	
 
    	
 
    
	

    	
 
    	
device
    	
 
    	
EU
    	
 
    	
Class 5: Viral systems, gene therapy systems, nucleic acid delivery   systems, viral vectors, non-viral vectors, gene therapy vectors, nucleic acid   delivery vectors, and cells transformed by viral vectors, non-viral vectors,   gene therapy vectors or nucleic acid delivery vectors for medical purposes;   pharmaceutical products; biological preparations for use in medical and   clinical gene therapy, nucleic acid-based therapy and cell therapy; clinical   medical reagents for use in nucleic acid-based therapy, gene therapy, cell   therapy, gene diagnosis and gene testing; pharmaceutical preparations,   vaccines, prophylaxis products and other products for use in nucleic   acid-based therapy, gene therapy and cell therapy 

 

Class 44: Gene and nucleic acid delivery, gene and nucleic acid transfer,   gene and nucleic acid regulation and gene and nucleic acid modulation for the   treatment of metabolic disorders, ocular disorders, diseases of the nervous   system, blood disorders, liver disorders, muscular disorders, muscular   skeletal disorders, cancers, infectious diseases, inflammatory and   auto-immune diseases, vascular disorders, inherited disorders, genetic   disorders and single gene disorders.
    	
 
    	
8640609
    	
 
    	
5/10/2010
    

 

 

	
Trademark
    	
 
    	
Type
    	
 
    	
Country
    	
 
    	
goods/services
    	
 
    	
Reg. No.
    	
 
    	
Reg. Date
    
	
UNIQURE
    	
 
    	
Word
    	
 
    	
EU
    	
 
    	
Class 1: Viral systems, gene therapy systems, nucleic acid delivery   systems, viral vectors, non-viral vectors, gene therapy vectors, nucleic acid   delivery vectors, and cells transformed by viral vectors, non-viral vectors,   gene therapy vectors and nucleic acid delivery vectors for non-medical   research purposes

 

Class 5: Viral systems, gene therapy systems, nucleic acid delivery   systems, viral vectors, non-viral vectors, gene therapy vectors, nucleic acid   delivery vectors, and cells transformed by viral vectors, non-viral vectors,   gene therapy vectors or nucleic acid delivery vectors for medical purposes;   pharmaceutical products; biological preparations for use in medical and   clinical gene therapy, nucleic acid-based therapy and cell therapy; clinical   medical reagents for use in nucleic acid-based therapy, gene therapy, cell   therapy, gene diagnosis and gene testing; pharmaceutical preparations,   vaccines, prophylaxis products and other products for use in nucleic   acid-based therapy, gene therapy and cell therapy

 

Class 42: Research, product development and consultancy in the field of   biotechnology, biologics, pharmaceutics, medical science, chemistry and   biochemistry

 

Class 44: Gene and nucleic acid delivery, gene and nucleic acid transfer,   gene and nucleic acid regulation and gene and nucleic acid modulation for the   treatment of metabolic disorders, ocular disorders, diseases of the nervous   system, blood disorders, liver disorders, muscular disorders, muscular   skeletal disorders, cancers, infectious diseases, inflammatory and   auto-immune diseases, vascular disorders, inherited disorders, genetic   disorders and single gene disorders.
    	
 
    	
10431005
    	
 
    	
4/25/2012
    

 

UniQure is also the owner of the other trademark registrations and applications in the Territory identified in Schedule 2.2(a).

 

57

 

Basic Trademark Rules:

 

·                  The most prominent use (which is usually the first use of our registered trademarks in a title, heading, and text of a document) should have the superscripted registered trademark symbol ®.  If that symbol is not available, then use (R).

 

·                  Distinguish our trademarks. Visually set off our trademarks from the surrounding text.

 

·                  Our trademarks are never plural or possessive.

 

·                  Never modify the form of our trademarks, whether the trademarks are an acronym, word, words or graphic design.  Unless otherwise specifically permitted in writing, word trademarks should not be modified by abbreviations, translations or connections (e.g., by a hyphen or otherwise) to other words or trademarks.  Our trademarks should not be split over any lines.  All logos should be reproduced in strict compliance with the established graphical form.

 

·                  Colors of our trademarks. The preferred treatment for the company logo is as follows:

 

 

The logo has to be displayed in printed letters. Only the “Q” is in upper case.

 

·                  Attribute our trademarks by properly acknowledging our ownership interest in them (e.g., “Glybera is a trademark or registered trademark of uniQure IP B.V.”).  Such attribution statement may appear in any conventional location within a document or packaging (e.g., header, footer, footnote, etc.).

 

·                  Logo, size and proportion treatments. The “Glybera” word and device mark and the “G” device mark (logos) set forth in the table above must always be reproduced exactly as pictured in the table above, in the specific typefaces shown.  No other typefaces are permitted. The logos can be reproduced in color or black& white and may be proportionately enlarged or reduced so long as legibility is ensured. uniQure reserves the right to introduce specific requirements as to the color and font size of its trademarks and logos. The logos are independent trademarks and should not be incorporated into other trademarks, logos, and artwork. The logos may appear in proximity to a licensee’s trademarks and logos and other artwork, but with a clear visual separation.

 

·                  Inquiries regarding the Trademark Guidelines. In case of inquiries regarding these Trademark Guidelines uniQure may be contacted at the following address: Meibergdreef 61, 1105 BA Amsterdam, The Netherlands.

 

 

·                  Updates of the Trademark Guidelines. uniQure may at any time make changes to these Trademark Guidelines with a future effect. uniQure will give licensee no less than three (3) months prior written notice if changes are made to the Trademark Guidelines.

 

***

 

59

 

SCHEDULE 2.3
 Definition
 Fully Loaded Cost of Goods

 

	
Item per [**] batch
    	
 
    	
Costs* [EUR]
    
	
 
    	
 
    	
 
    
	
Clean room occupancy
    	
 
    	
[**]
    
	
Cell bank vial
    	
 
    	
[**]
    
	
Virus banks vials
    	
 
    	
[**]
    
	
Raw materials
    	
 
    	
[**]
    
	
External release assays (QC)
    	
 
    	
[**]
    
	
External QP
    	
 
    	
[**]
    
	
Personnel (MF, QC, QA)
    	
 
    	
[**]
    
	
Packaging (incl. release)
    	
 
    	
[**]
    
	
Stability study batch allocation
    	
 
    	
[**]
    
	
 
    	
 
    	
 
    
	
Total
    	
 
    	
[**]
    

 

Norms:

 

Number of patients per batch                           [**]

 

Batch success rate                                               [**]%

 

Result Fully loaded costs:

 

COG per patient                                                 EUR                 [**]*
 COG per batch                                                    EUR                 [**]*

 

COG relevant for Glybera Manufacturing Cost Reimbursement:

 

COG per patient                                                 EUR                 [**]*
 COG per batch                                                    EUR                 [**]*

 

* = as of the Effective Date

 

60

 

SCHEDULE 2.4(d)
 Minimum Order Quantity

 

The minimum Order Quantity is [**] patient doses.

 

61

 

SCHEDULE 2.6
 Technology Transfer

 

The following is a non-exhaustive list describing key steps which the Parties would typically envisage for a transfer of the Manufacturing of the Product to another manufacturing site:

 

	
Steps
    	
 
    	
Estimated Timelines
    
	
· if transferred to a Third Party manufacturer: select and contract   manufacturer party
    	
 
    	
[**]
    
	
· tech transfer (on paper)
    	
 
    	
[**]
    
	
· obtain time slot
    	
 
    	
[**]
    
	
· process validation at CMO
    	
 
    	
[**]
    
	
· file type II variation
    	
 
    	
[**]
    
	
· review and approval type II variation
    	
 
    	
[**]
    
	
Total
    	
 
    	
[**]
    

 

62

 

SCHEDULE 3.1
 MA/MAA Filing and Maintenance Activities and Fees Template

 

	
State
    	
 
    	
Activity
    	
 
    	
Fee
   Allocation
    	
 
    	
Responsible
   Party
    	
 
    	
Timeline
    
	
Albania
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Andorra
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Bosnia and Herzegovina
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Croatia
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Macedonia
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Monaco
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Montenegro
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Republic of San Marino
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Serbia
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Switzerland
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    

 

63

 

	
State
    	
 
    	
Activity
    	
 
    	
Fee
   Allocation
    	
 
    	
Responsible
   Party
    	
 
    	
Timeline
    
	
Vatican City
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Algeria
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Armenia
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Azerbaijan
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Belarus
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Brazil
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
China
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Egypt
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Georgia
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Kazakhstan
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Kirghizstan
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    

 

64

 

	
State
    	
 
    	
Activity
    	
 
    	
Fee
   Allocation
    	
 
    	
Responsible
   Party
    	
 
    	
Timeline
    
	
Mexico
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Moldova
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Morocco
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Pakistan
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Russia
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Tajikistan
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Tunisia
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Turkey
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Turkmenistan
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Ukraine
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Uzbekistan
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    

 

65

 

	
State
    	
 
    	
Activity
    	
 
    	
Fee
   Allocation
    	
 
    	
Responsible
   Party
    	
 
    	
Timeline
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    

 

66

 

SCHEDULE 3.2
 Regulatory Plan

 

A.            For the EU Member States:

 

1.             Quality

 

1.1          Specific Obligations

 

The following obligations were included in the Day 210 Assessment Report with the requirement to submit them as Type II variations prior to implementation.

 

	
Source
    	
 
    	
Name
    	
 
    	
Description
    	
 
    	
Due date
    	
 
    	
Status
    	
 
    	
Progress
    
	
D210   AR
    	
 
    	
Ii/003-SO1
    	
 
    	
Newly   developed release assay for cellular SF+ DNA submitted and approved by a Type   II variation.
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    
	
D210   AR
    	
 
    	
II/004-SO2
    	
 
    	
An   improved or newly developed release assay for SF+ proteinor a combined   SF+/Baculovirus protein approved by a Type II variation
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    
	
D210   AR
    	
 
    	
II/004-SO3
    	
 
    	
Assays   for Rep and Cap genes will be validated and acceptance criteria for accuracy   and precision will be justified in the validation report.
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    
	
D210   AR
    	
 
    	
II/001-SO4
    	
 
    	
To   complete the validation of the residual infectious baculovirus assay ([**]   wells), the LOD should be experimentally confirmed, in addition the presented   risk assessment should be revised taking into account the experimentally   determined LOD.
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    
	
D210   AR
    	
 
    	
II/002-SO5
    	
 
    	
An   improved release assay for replication competent AAV should be submitted and   approved via a Type II variation
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
[**]
    
	
D210   AR
    	
 
    	
II/Oxx—SO6
    	
 
    	
To   improve the virus safety profile of the product, an additional manufacturing   process step should be developed
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
 
    

 

67

 

	
Source
    	
 
    	
Name
    	
 
    	
Description
    	
 
    	
Due date
    	
 
    	
Status
    	
 
    	
Progress
    
	
D210   AR
    	
 
    	
II/Oxx-SO7
    	
 
    	
Additional   manufacturing process step validated to ensure that the process is capable,   of inactivating or removing at least the maximal baculovirus load used in   production.
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
 
    
	
D210   AR
    	
 
    	
II/Oxx—SO8
    	
 
    	
eCTD   update: Clarify the MOI to be used for any new WSV and qualification strategy   at the time of introduction of new WSV
    	
 
    	
[**]
    	
 
    	
[**]
    	
 
    	
 
    

 

The baseline eCTD Module 3 has been submitted on [**].

 

68

 

1.2          Commitments

 

The commitments listed below have been made during the review and authorisation procedure. For those commitments accompanied in the D120 or D180 responses by a planned date for completion, the definite completion and submission dates have to be submitted in a Letter of Undertaking. For some commitments no completion date was mentioned. Those will not be mentioned in the Letter of Undertaking and will be considered at a later stage during the yearly product quality review.

 

	
Source
    	
 
    	
Name
    	
 
    	
Description
    	
 
    	
Due date
    	
 
    	
Status
    
	
D120Q#60 and D180Q#20, 21
    	
 
    	
LU3
    	
 
    	
Stability study on the first batch of drug   substance stored in the new container is recommended to be performed prior to   product being released for patient treatment.
    	
 
    	
[**]
    	
 
    	
[**]
    
	
D120Q#2 and D180Q#1
    	
 
    	
LU5
    	
 
    	
Assess how long the baculovirus sequences   are persisting in vivo in mice
    	
 
    	
[**]
    	
 
    	
[**]
    
	
D120Q#2 and D180Q#1
    	
 
    	
LU6
    	
 
    	
Further characterization by N6S and analysis   of [**] new batches by NGS
    	
 
    	
[**]
    	
 
    	
[**]
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
D120Q#71 and D180Q#24
    	
 
    	
LU1
    	
 
    	
Review and revise the specification for the   ratio of full to infectious virus particles based on data from [**] batches   to allow meaningful specifications to be set.
    	
 
    	
[**]
    	
 
    	
[**]
    
	
D120Q#84 and D180Q#28
    	
 
    	
LU4
    	
 
    	
To provide details on the outcome of the   further development, validation and proposed implementation of the S2 cell   line that is non-permissive to baculovirus.
    	
 
    	
[**]
    	
 
    	
[**]
    
	
D120Q#59
    	
 
    	
LU7
    	
 
    	
Review specifications for protein impurity 2   when data of [**] batches are available
    	
 
    	
[**]
    	
 
    	
[**]
    

 

69

 

1.3          Other variations

 

	
Variation
    	
 
    	
Description
    	
 
    	
Planned submission
   date
    	
 
    	
Status
    
	
II/007
    	
 
    	
New test method for residual VHH
    	
 
    	
[**]
    	
 
    	
[**]
    
	
II/008
    	
 
    	
Improved test method for residual LPL
    	
 
    	
[**]
    	
 
    	
[**]
    
	
II/009
    	
 
    	
New test method for infectious vector titre
    	
 
    	
[**]
    	
 
    	
[**]
    
	
II/Oxx
    	
 
    	
Total to Full particles ratio specification   to be adapted (lower limit removed)
    	
 
    	
[**]
    	
 
    	
[**]
    
	
Tbd*
    	
 
    	
Changes to the stability protocol to remove   sterility testing at the end of shelf life. A new container closure study is   to be initiated
    	
 
    	
[**]
    	
 
    	
[**]
    

 

70

 

Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A total of one page was omitted. [**]

 

B.            For the Territory outside of the EU Member States:

 

The Parties shall agree upon the Regulatory Plan for any remaining countries of the Territory outside of the EU Member States in the first meeting of the JCC after the Effective Date.

 

71

 

SCHEDULE 7.3
 Existing Third Party Licenses

 

Overview:

 

	
Licensor
    	
 
    	
Title of Agreement
    	
 
    	
Date
    	
 
    	
Relevant Intellectual Property Rights

(including quality of license, i.e. exclusive / non-exclusive rights)
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Xenon Pharmaceuticals Inc. (formerly Xenon Genetics   Inc.)
    	
 
    	
Sublicense and research agreement between   Xenon Genetics Inc. and Amsterdam Molecular Therapeutics BV
    	
 
    	
June 18, 2001
    	
 
    	
Exclusive sublicensable, not further   sublicensable without written consent
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
US Public Health   Service (PHS, NIH, HHS)
    	
 
    	
Public Health Service Patent License   Agreement - Nonexclusive
    	
 
    	
May 2, 2007
    	
 
    	
Non-exclusive, sub-licensable upon written   approval prior review
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Ampliphi Biosciences   Corporation (legal successor of Targeted Genetics)
    	
 
    	
License agreement 

 

Amendment No1 to the license agreement
    	
 
    	
December 5, 2006 

 

March 12, 2012
    	
 
    	
Non-exclusive, non-sublicensable
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Aventis Pharma S.A.
    	
 
    	
License agreement
    	
 
    	
December 20, 2006
    	
 
    	
Exclusive, non-transferable and   non-assignable
    

 

72

 

	
Salk Institute for   Biological Studies
    	
 
    	
License agreement between Salk Institute for   Biological Studies and Amsterdam Molecular Therapeutics BV, RNA export   element WPRE
    	
 
    	
February 8, 2008
    	
 
    	
Non-exclusive, non-transferable
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Asklepios Biopharmaceutical   Inc. (AskBio)
    	
 
    	
Non-exclusive license agreement
    	
 
    	
September 3, 2010
    	
 
    	
Non-exclusive, sublicensable
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
Protein Sciences   Corporation
    	
 
    	
License agreement — non-exclusive (expressSF+ cells) 
    	
 
    	
March 22, 2007 
    	
 
    	
Non-exclusive, non-sublicensable 
    
	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    	
 
    
	
 
    	
 
    	
License agreement — non-exclusive (expressSF+ cells) - AMENDMENT
    	
 
    	
June 13, 2012
    	
 
    	
Exclusive (with respect to Product),   sublicensable
    

 

Text of Agreements:

 

[full text of agreements to be provided to Chiesi on CD-ROM within [**] Business Days after signing of this Agreement]

 

73

 

SCHEDULE 8.1(a)
 Commercially Reasonable Efforts

 

At all times during the Term Chiesi shall in no event use less than Commercially Reasonable Efforts to Commercialize the Product as further described in this Schedule 8.1(a). Such efforts shall include:

 

Compliance with Marketing Plan and Budget

 

Chiesi shall perform all activities related to the Commercialization of the Product set forth in the marketing plan and budget to be agreed upon between the Parties annually (the “Marketing Plan”). The Marketing Plan shall require Chiesi to perform promotional activities typically applied in the pharmaceutical industry for orphan drugs, to draw the attention and interest to the Product and to render technical support to explain the efficacy of the Product, including detailing and training physicians, pharmacists or other prescribers. The detailing of the Products shall include: (a) regular visits and calls made to physicians and pharmacists by Chiesi’s marketing/detailing staff to provide Product information; and (b) activities implemented to call the attention of physicians, pharmacists and other prescribers such as organizing conferences, seminars, physicians- and pharmacists training sessions(including responsibility of the risk management plan (RMP) required with training materials in local language), lectures, mailings with announcements and product brochures, publications in professional magazines, and participation in trade exhibitions or symposia, subject to the requirements and limitations of any Applicable Laws.

 

The Marketing Plan shall further include details on the responsibility of Chiesi for (a) the provision and review of marketing materials, (b) training and maintaining a sufficient number of suitably qualified sales force, (c) training and maintaining a sufficient number of suitably qualified medical personnel, (d) collection and conveyance to uniQure of general market data (including customer requirements with respect to the Product; market analysis; and competition.

 

The Marketing Plan for the first year of the Agreement, attached hereto as Appendix A, sets forth the obligations of Chiesi in connection with the First Commercial Sale of the Product in the Territory.

 

Allocation of Minimum FTEs

 

Chiesi shall allocate a minimum number of FTEs in the Territory as follows (“Minimum FTEs”):

 

·                  1st anniversary after the Effective Date: [**] FTEs

 

·                  2nd anniversary after the Effective Date: [**] FTEs

 

·                  3rd anniversary after the Effective Date: [**] FTEs

 

·                  4th anniversary after the Effective Date: [**] FTEs

 

·                  5th  anniversary after the Effective Date: [**] FTEs

 

74

 

Beginning in 2013, prior to [**] of each year, Chiesi shall submit the Marketing Plan for any subsequent years to uniQure for its review and approval, which shall not be unreasonably withheld or delayed.

 

Setting of Target Price

 

First Submission (Germany) by uniQure

 

Notwithstanding the provisions hereunder, but without prejudice to Section 4.1(f)(ii), the Parties hereby agree that uniQure shall submit a dossier to the competent reimbursement body in Germany (GBA) before end 2013, which shall include a target manufacturer selling price (Herstellerabgabepreis) (the “Target Price”) of no less than EUR [**]. In case upon further investigation Chiesi is of the opinion that such Target Price in Germany can only be set at a lower level, Chiesi shall start consultations with uniQure on such lower Target Price at least [**] prior to uniQure submitting the dossier to the competent reimbursement body with the goal of both Parties agreeing to a lower Target Price mutually acceptable to the Parties. If the Parties cannot agree on such mutual lower Target Price before the end of such [**] period, uniQure shall submit the dossier to the competent reimbursement body with a Target Price of at least EUR [**]. The Target Price submitted to the German GBA is to be used as reference price in the other European countries mentioned below and hence such Target Price shall be used for all submissions by Chiesi in such other European countries.

 

In line with the Marketing Plan, Chiesi shall start with the Commercialization of the Product in Germany irrespective of the competent reimbursement body having rendered its final decision, provided all other requirements to start Commercializing the Product in Germany have been fulfilled.

 

Timelines for Price and Reimbursement Submissions in other European countries by Chiesi, unless otherwise agreed upon between the Parties in due course

 

[**]

 

75

 

Confidential Materials omitted and filed separately with the Securities and Exchange Commission.  A total of 42 pages were omitted. [**]

 

76

 

SCHEDULE 8.1(b)
 Approved Activities

 

[**]

 

77

 

SCHEDULE 9.1
 Upstream Licenses Relevant for Condition Precedent

 

	
Licensor
    	
 
    	
Title of Agreement
    	
 
    	
Date
    	
 
    	
Note
    
	
Xenon Pharmaceuticals Inc. (formerly Xenon   Genetics Inc.)
    	
 
    	
Sublicense and research agreement between   Xenon Genetics Inc. and Amsterdam Molecular Therapeutics BV
    	
 
    	
June 18, 2001
    	
 
    	
Exclusive sublicensable, not further   sublicensable without written consent
    
	
US Public Health Service (PHS, NIH, HHS)
    	
 
    	
Public Health Service Patent License   Agreement - Nonexclusive
    	
 
    	
May 2, 2007
    	
 
    	
Non-exclusive, sub-licensable upon written   approval prior review
    
	
Ampliphi Biosciences Corporation (legal   successor of Targeted Genetics)
    	
 
    	
License agreement 

 

Amendment No1 to the license agreement
    	
 
    	
December 5, 2006 

 

March 12, 2012
    	
 
    	
Non-exclusive, non-sublicensable
    
	
Aventis Pharma S.A.
    	
 
    	
License agreement
    	
 
    	
December 20, 2006
    	
 
    	
Exclusive, non-transferable and   non-assignable
    
	
Salk Institute for Biological Studies
    	
 
    	
License agreement between Salk Institute for   Biological Studies and Amsterdam Molecular Therapeutics BV, RNA export   element WPRE
    	
 
    	
February 8, 2008
    	
 
    	
Non-exclusive, non-transferable
    

 

78

 

Note:

 

The Parties agree that the condition precedent may be fulfilled not only by subcontracting of the rights and licenses licensed by uniQure as licensee under the Existing Third Party Licenses but also by equivalent arrangements mutually agreed between the Parties and the respective Third Party licensor (for instance in cases, where the Third Party licensor (such as the Salk Institute for Biological Studies) is of the opinion that a sublicense is not required for the activities performed by Chiesi, its Affiliates and Sub-distributors in connection with this Agreement).

 

79Exhibit 10.13

 

Confidential Materials omitted and filed separately with the

Securities and Exchange Commission. Double asterisks denote omissions.

 

LICENSE AGREEMENT

 

by and among

 

FUNDACIÓN PARA LA INVESTIGACIÓN MÉDICA APPLICADA (1)

 

PONTEGADEA BIOTECHNOLOGICA, S.L. SOCIEDAD DE DESAROLLO DE NAVARA, S.A., CIERVANA, S.L., CINAMAR, S.A, MASAVEU DE INVESTIGACIONES Y DESAROLLO, S.L., INVESTIGACIONES 2001 CORPCAN, S.L., ALAZADY BIOTECNOLÓGICA, S.L., SOCIEDAD ANDALUZA DE INVESTIGACIÓN DE LA SALUD, S.L.U., INSTITUTO DE EDUCACIÓN E INVESTIGACIÓN S.A, LOYALTY SQUARE, S.L., UNICARTERA CAJA 2, S.L., CAJA RURAL DE NAVARRA, SOCIEDAD COOPERATIVA LIMITADA DE CREDITO, UNGRIA PATENTES Y MARCAS, S.A., FUERTES I MÁS D, S.L., GAINMÉDICA, S.L., UNIÓN TEMPORAL DE EMPRESES LEY 18/1982, DE 26 MAYO NÚM 1.334/2003 (2)

 

PROYECTO DE BIOMEDICINA CIMA S.L. (3)

 

DIGNA BIOTECH, S.L. (4)

 

AND

 

AMSTERDAM MOLECULAR THERAPEUTICS (AMT) B.V. (5),

 

dated as of 21st May, 2010

 

 

LICENSE AGREEMENT

 

THIS LICENSE AGREEMENT dated as of 21 May, 2010 (the “Agreement”) is made by and among:

 

(1)                                 Fundación para la Investigación Médica Applicada (“FIMA”) incorporated under the laws of Spain, by means of the public deed executed on December 10th, 1998, before the Notary Public of Madrid, Victor Manual Garrido de Palma, under the number 3001 of its protocol; with Tax Identification Number G82198524 and with registered offices at Calle Pintor Paret, 5, 1 F, Pamplona, Spain; duly represented by Mr Franciso Errasti Goenaga;

 

(2)                                 Pontegadea Biotecnologica, S.L, Sociedad de Desarrollo de Navarra, S.A., Ciervana, S.L., Cinamar, S.A., Masaveu de Investigaciones y Desarrollo, S.L., Investigaciones 2001 CORPCAN, S.L., Alazady Biotecnológica, S.L., Sociedad Andaluza de Investigación de la Salud, S.L.U., Instituto de Educación e Investigación S.A., Loyalty Square, S.L., Unicartera Caja 2, S.L., Caja Fural de Navarra, Sociedad Cooperativa Limitada de Credito, Ungria Patentes y Marcas, S.A., Fuertes I Más D, S.L., Gainmédica, S.L., Unión Temporal de Empresas Ley 18/1982, de 26 de Mayo, Núm. 1.334/2003, (the collaborative reseach consortium known as “UTE CIMA”), incorporated under the laws of Spain, by means of the public deed executed on June 3rd, 2003, before the Notary Public of Pamplona, Jose Javier Castiella Rodriques, under the number 1461 of its protocol, with Tax Identification Number G31790595 and with registered offices at Avda. De Carlos III, 36, 1 Dcha, Pamplona, Spain; duly represented by Mr Antonio Martin Catón;

 

(3)                                 Proyecto de Biomedicina CIMA S.L. (“Proyecto”) with corporate address at Avda. Carlos III. 36, 1 dcha., 31003 Pamplona, Navarra, Spain; duly represented by Mr Antonio Martin Canton;

 

(4)                                 Digna Biotech, S.L. (“Digna”) with corporate address at C/ Etxesakan 28, oficina 5, 31180 Cizur Maryo, Navarra, Spain, bearer of Tax Identification Number B-31778509, duly represented by Mr Pablo Ortiz Bétes;

 

(5)                                 Amsterdam Molecular Therapeutics (AMT) B.V. (“AMT”) a company with limited liability incorporated under the laws of The Netherlands with registered office at Meibergdreef 61, NL-1105 BA Amsterdam, The Netherlands, duly represented by Mr. Piers Morgan;

 

WHEREAS

 

(A)                               FIMA and UTE CIMA collaborate in a project called “CIMA Project” for medical investigation and research.  On June 3rd, 2003, FIMA and UTE CIMA entered into a Investigation Contract in the frame of a contractual joint venture (“Joint Venture”) by virtue of which FIMA, in consideration for the remuneration agreed between the parties, carries out those investigations required for the fulfillment of the purpose of CIMA Project, with the results derived from said investigations by FIMA being owned solely and automatically by UTE CIMA;

 

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(B)                               Pursuant to the Joint Venture, UTE CIMA undertook to assign to Proyecto, all of UTE CIMA’s right, title and interest in any results derived from the above investigations, when such results might be subject to protection and/or exploitation according to the intellectual property regulations;

 

(C)                               Proyecto has an agreement with Digna dated June 14th, 2005 under which Digna undertakes to carry out on behalf of Proyecto prosecution, maintenance, enforcement and defense tasks of the above intellectual property.  In addition, Proyecto has entered into an agreement with Digna dated June 25th, 2005, amended on December 20th, 2005, under which Digna is entitled to an exclusive worldwide license to develop and commercialize the above results;

 

(D)                               AMT is a biopharmaceutical company that owns or controls Patents, Know-How and Materials relating to the research, development, registration, manufacture and commercialization of therapies based on constructs including adeno-associated virus (“AAV”) vectors;

 

(E)                                In July 2005, FIMA, UTE CIMA and AMT entered into an agreement (“2005 Agreement”) for the conduct of a collaborative research and development program to construct an AAV vector which could be used in the therapy of porphyria which was since extended to include research and development into reducing the immunogenicity of the AAV therapies.  In anticipation of the successful generation of an AAV vector which could be used in the therapy of porphyria, the parties discussed potential opportunities for the further development and commercialization of Products (as defined in the 2005 Agreement);

 

(F)                                 On May 1, 2007, the Parties entered into a Commercialization Agreement (“2007 Commercialization Agreement”) pursuant to which, inter alia, (i) Digna relinquished its rights to develop and commercialize Products (as defined in the 2007 Commercialization Agreement) under such Intellectual Property to facilitate the 2007 Commercialization Agreement, (ii) AMT was granted exclusive rights to develop and commercialize Products (as defined in the 2007 Commercialization Agreement) and (iii) the 2005 Agreement was terminated;

 

(G)                               On July 25th, 2007, AMT, FIMA, UTE CIMA, PB CIMA and Digna entered into an agreement to give AMT and its Affiliates privileged access to the results of the research being conducted by or upon behalf of UTE CIMA and FIMA (“Privileged Access Agreement”) with an option for AMT to participate in the Development of Candidate Products (as those terms are defined in the Privileged Access Agreement) and, if this yielded positive results for AMT or its Affiliates to have the right to take an exclusive license under relevant intellectual property to further research, develop, make, register and commercialize such Candidate Product;

 

(H)                              In relation to the Candidate Product Virus encoded IGF-1 for the treatment of liver cirrhosis, AMT exercised its option to take an exclusive license pursuant to which Digna, Proyecto and AMT entered into a license agreement dated November 9th, 2007 (the “Virus encoded IGF License”);

 

(I)                                   The Parties now wish to modify their collaboration under aforementioned agreements and to refocus their efforts and resources to the further development and commercialization of a gene therapy treatment for acute intermittent porphyria under the terms and conditions set forth below;

 

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IT IS NOW AGREED AS FOLLOWS

 

ARTICLE 1                           DEFINITIONS

 

For purposes of this Agreement, the terms defined in this Article 1 shall have the meanings specified below.  Certain other capitalized terms are defined elsewhere in this Agreement.

 

1.1                               “Affiliate” any company, partnership or other business entity which Controls, is Controlled by or it under common Control with any of the Parties.  For the purposes of this definition “Control” refers to any of the following (i) the possession, directly or indirectly, of the power to direct the management or policies of an entity, whether through ownership of voting securities, by contract or otherwise; (ii) ownership of fifty percent (50%) or more of the voting securities entitled to vote for the election of directors in the case of a corporation, or of fifty percent (50%) or more of the equity interest in the case of any other type of legal entity; (iii) status as a general partner in any partnership, or any other arrangement whereby a Party controls or has the right to control the board of directors or equivalent governing body of a corporation or other entity.

 

1.2                               “Agreement” or “License Agreement” means this License Agreement.

 

1.3                               “AMT Background IP” means any IP owned or Controlled by AMT prior to the Effective Date or developed or acquired by AMT after the Effective Date, but excluding Joint Patent Rights and excluding any IP that has been developed prior to the Effective Date under the collaborative research programs jointly carried out by the Parties. AMT Background IP does, however include manufacturing knowhow developed by AMT within or outside said collaborative research programs.

 

1.4                               “Calendar Quarter” means each period of three months ending on 31 March, 30 June, 30 September or 31 December and “Quarterly” shall be construed accordingly.

 

1.5                               “Calendar Year” means each successive period of twelve calendar (12) months commencing on 1 January.

 

1.6                               “CIMA Parties” means FIMA, UTE CIMA, Proyecto and Digna jointly and a “CIMA Party” means FIMA, UTE CIMA, Proyecto or Digna.

 

1.7                               “CIMA Background IP” means any IP owned or Controlled by a CIMA Party at the Effective Date or developed or acquired by a CIMA Party after the Effective Date outside the scope of this Agreement and/or the Collaborative Development Agreement and that is useful for the development or Commercialization of the Product, but excluding Joint Patent Rights and excluding any IP that has been developed prior to the Effective Date under the collaborative research programs jointly carried out by the Parties.

 

1.8                               “Collaborative Development Agreement” means the agreement between Digna and ATM attached hereto as Exhibit 2.

 

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1.9                               “Commercialization”, “Commercializing” or “Commercialize” means all activities relating to the import, advertising, promotion and other marketing, pricing and reimbursement, detailing, distribution, storage, handling, offering for sale and selling, customer service and support, post Regulatory Approval regulatory activities including phase IV clinical trials and adverse event reporting in relation to the Product.

 

1.10                        “Commercially Reasonable Efforts” means in respect of AMT efforts and resources commonly used by biotechnology companies of a similar size to AMT based on funds raised.

 

1.11                        “Confidential Information” means, subject to the exceptions set forth in Article 8.3 (i) the terms and conditions of this Agreement and the Collaborative Development Agreement, for which each Party will be considered a Disclosing Party and a Recipient Party; and (ii) any non-public information, whether or not patentable, disclosed or provided by one Party to the other Party in connection with this Agreement, including, without limitation, any information which release is likely to prejudice the commercial interests of the parties, or is considered as a trade secret, including information regarding such Party’s strategy, business plans, objectives, research, technology, products, business affairs or finances including any non-public data relating to development or Commercialization of any Product and other information of the type that is customarily considered to be confidential information by parties engaged in activities that are substantially similar to the activities being engaged in by the Parties under this Agreement, for which the Party making such disclosure will be considered the Disclosing Party and the receiver will be the Recipient Party.

 

1.12                        “Control” (including variations such as “Controlled”) means with respect to any Intellectual Property, possession of the right, whether directly or indirectly, and whether by ownership, license or otherwise, to assign, or grant a license, sub-license or other right to or under, such Intellectual Property without violating the terms of any agreement or other arrangement with any Third Party.

 

1.13                        “Cover”, “Covered” or “Covering” means, with respect to a Patent Right that, but for a license under an issued Valid Claim included in such Patent Right, the manufacture, use, transportation, sale, offer for sale, or importation of the Product would infringe such Valid Claim or, in the case of a Patent Right that is a patent application, would infringe a Valid Claim in such patent application if it were to issue as a patent.

 

1.14                        Disclosing Party” means the Party which discloses Confidential Information to the other Party or Parties.

 

1.15                        “Disorder” means acute intermittent porphyria.

 

1.16                        “Documents” means analyses, books, CD-ROM, USB stick, charts, comments, computations, designs, discs, diskettes, files, graphs, ledgers, notebooks, paper, photographs, plans, records, recordings, reports, research notes, tapes and other graphic or written data or other media and other computer information storage means on which Know How is permanently stored and advertising and promotional materials of any nature whatsoever including preparatory materials for the same.

 

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1.17                        “Effective Date” means the date first set forth above.

 

1.18                        “Gene Therapy Field” means the use of genetic material in any of the following ways for the treatment or prophylaxis of a disease (a) delivery of a functional version of a mutant gene or any other DNA that encodes for a therapeutic molecule into the nucleus or mitochondiea of patient’s cells (b) by the insertion of a normal gene into a non-specific location within the genome to replace a non-functional gene; or (c) by swapping an abnormal gene for a normal gene (through homologous recombination); or (d) by repairing an abnormal gene through selective reverse mutation which returns the gene to its normal function; or (e) by altering the regulation (the degree to which a gene is turned on or off) of a particular gene.

 

1.19                        “Intellectual Property” or “IP” means Patent Rights, Know How and/or Materials.

 

1.20                        “Joint Patent Rights” means the patent application set forth in Exhibit 1 that is filed in the names of Amsterdam Molecular Therapeutics (AMT) IP B.V. and Proyecto de Biomedicina CIMA S.L jointly and any and all Patent Rights deriving from said patent application anywhere in the world.

 

1.21                        “Know-How” means technical and other information which is not in the public domain, including information comprising or relating to concepts, discoveries, data, designs, formulae, ideas, inventions, Materials, methods, models, research plans, procedures, designs for experiments and tests and results of experimentation and testing (including results of research or development) processes (including manufacturing processes, specifications and techniques), laboratory records, chemical, pharmacological, toxicological, clinical, analytical and quality control data, clinical and non-clinical trial data, case report forms, data analyses, reports, manufacturing data or summaries and information contained in submissions to and information from ethical committees and Regulatory Authorities. Know How includes Documents containing Know How, including but not limited to any rights including trade secrets, copyright, database or design rights protecting such Know How. The fact that an item is known to the public shall not be taken to preclude the possibility that a compilation including the item, and/or a development relating to the item, is not known to the public.

 

1.22                        “Launch” means the first arms-length commercial sale to a Third Party of the Product by AMT, its Affiliates or sub-licensees after grant of required Regulatory Approval and after pricing or reimbursement approval has been granted (if required in that country). Sales for test marketing, clinical trial purposes or compassionate or similar use do not constitute a Launch.

 

1.23                        “Losses” means any and all losses, damages, liabilities, costs and expenses (including, without limitation, reasonable attorneys’ fees and expenses). In calculating “Losses”, the duty to reasonably mitigate on the part of the Party suffering the Losses shall be taken into account.

 

1.24                        “Materials” means any chemical or biological substances including but not limited to blood samples, nucleotide or nucleotide sequence including DNA and RNA sequences, genes, vector or construct including plasmids, phages or viruses, host organism including bacteria, fungi, algae, protozoa and hybridoma’s, eukaryotic or prokaryotic cell line or expression system or any development strain or product of that cell line or expression system,

 

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protein including any peptide or amino acid sequence, enzyme, antibody or protein conferring targeting properties and any fragment of a protein or a peptide enzyme or antibody, assay or reagent, any other genetic or biological material or micro-organism.

 

1.25                        “Net Revenues” means:

 

(i)                                     Any signature fee or other up-front fee due to be received by AMT or any of its Affiliates from a licensee being appointed by AMT or any of its Affiliates to further develop and/or Commercialize a Product; and

 

(ii)                                  Any milestone or other payments due to be received by AMT or any of its Affiliates from a licensee being appointed by AMT or any of its Affiliates to further develop and/or Commercialize a Product which payments are payable on an event to occur in relation to the development or Commercialization thereof but always excluding sums received by AMT or any of its Affiliates from such licensee which reimburse AMT for the cost and expense (but only the cost and expenses and no profit element) of research or development work to be undertaken by or upon behalf of AMT of its Affiliate directly related to the development of Product; and

 

(iii)                               Any sums due to be received by AMT or any of its Affiliates from a licensee appointed by AMT or any of its Affiliates to Commercialize a Product which sums are calculated by reference to the sales volumes of the Product by such licensee as a percentage of a net sales or similar definition, but always excluding any sums received by AMT or its Affiliates for sales of Products by AMT or Affiliates to distributors or other Third Parties, provided that those sums are accounted as “Net Sales”.

 

In the event that AMT, or its Affiliate, receives non-monetary consideration from a licensee to further develop and/or Commercialize a Product, Net Revenues shall be calculated based on the fair market value of such consideration.

 

1.26                        “Net Sales” means the gross amount invoiced for sales of Product, in arm’s length sales by AMT or its Affiliates to Third Parties, less the following deductions from such gross amounts which are actually incurred, allowed, accrued or specifically allocated:

 

(i)                                     normal and customary trade cash and quantity discounts actually given, credits, price adjustments or allowances for damaged Products, returns or rejections of Products;

 

(ii)                                  chargeback payments and rebates (or the equivalent thereof) for Product granted on a customary trade basis to group purchasing organizations, managed health care organizations or to federal, state/provincial, local and other governments, including their agencies, or to trade customers;

 

(iii)                               reasonable and customary freight, shipping insurance and other transportation expenses directly related to the sale of Product (if actually borne by AMT or its Affiliates without reimbursement from any Third Party);

 

(iv)                              required distribution commissions/fees payable to any Third Party providing distribution services to AMT;

 

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(v)                                 sales, value-added, excise taxes, tariffs and duties, and other taxes and governmental charges directly related to the sale, to the extent that such items are included in the gross invoice price of Product and are actually borne by AMT, its Affiliates, without reimbursement from any Third Party (but not including taxes assessed against the income derived from such sale); and

 

(vi)                              actual uncollectible amounts for Product where collectability is determined in accordance with IFRS consistently applied to all AMT products.

 

In the event that AMT, or its Affiliate, receives non-monetary consideration from a Third Party for sale of Product, Net Sales shall be calculated based on the fair market value of such consideration.

 

1.27                        “Parties” means the parties to this Agreement and “Party” means a party to this Agreement.

 

1.28                        “Patent Rights” means a (i) all national, regional and international patents and patent applications, including provisional patent applications, (ii) all patent applications filed either from such patents, patent applications or provisional applications or from an application claiming priority from any of these, including divisional, continuations, continuations-in-part, provisions, convened provisionals and continued prosecution applications, (iii) any and all patents that have issued or in the future issue from the foregoing patent applications (i) and (ii), including author certificates, inventor certificates, utility models, petty patents and design patents and certificates of invention, (iv) any and all extensions or restorations by existing or future extension or restoration mechanisms, including revalidations, reissues, re-examinations and extensions (including any supplementary protection certificates and the like) of the foregoing patents or patent applications (i), (ii) and (iii), and (v) any similar rights, including so-called pipeline protection, or any importation, revalidation, confirmation or introduction patent or registration patent or patent of additions to any such foregoing patent applications and patents.

 

1.29                        “Product” means any product that is, or that utilizes technology Covered by the Joint Patent Rights.

 

1.30                        “Previous Agreements” means the 2005 Agreement, the Privileged Access Agreement, the Virus encoded IGF License and the 2007 Commercialization Agreement jointly.

 

1.31                        “Receiving Party” means any Party receiving Confidential Information from another Party;

 

1.32                        “Regulatory Approval” means all approvals from Regulatory Authorities in any country in the Territory required lawfully to develop, clinically test, manufacture and market the Product in any such country, any establishment license application filed with the FDA or other Regulatory Authority to obtain approval of the facilities and equipment to be used to manufacture a Product, any Investigational New Drug or other investigational filing, including but not limited to any authorization for the import, manufacture and clinical testing of the Product (whether or not in filled and finished form), and any product pricing approvals where applicable.

 

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1.33                        “Regulatory Authority” means any relevant national (e.g., the FDA, EU member states authorities), supra-national (e.g., the European Commission, the Council of the European Union, or the EMEA), or other relevant governmental entity in any jurisdiction of the world involved in the granting of Regulatory Approvals for pharmaceutical product.

 

1.34                        “Territory” means the world.

 

1.35                        “Third Party” means a party other than any of the Parties or any of their respective Affiliates.

 

1.36                        “Valid Claim” means either a claim of (a) an issued, unexpired patent which has not been revoked or held unenforceable or invalid by a decision of a court or governmental agency of competent jurisdiction from which no appeal can be taken, or with respect to which an appeal is not taken within the time allowed for appeal, and which has not been disclaimed, denied or admitted to be invalid or unenforceable through reissue, disclaimer or otherwise, or (b) any patent application which has not been cancelled, withdrawn, or abandoned, or been pending for more than [**] years from the earliest priority date claimed for such application, unless and until such claim becomes an issued claim of an issued patent.

 

ARTICLE 2                           TERMINATION OF PREVIOUS AGREEMENTS

 

2.1                               General.  The Parties agree that with effect from the Effective Date all the terms of the Previous Agreements (including but not limited to the financial obligations of AMT thereunder, whether or not already due and outstanding prior to the termination of the Previous Agreements) are terminated and to be replaced in their entirety by the terms of this Agreement, save for the clauses that will survive as set forth in Section 2.2 hereof and that each Party has no claim against each other Party in connection with the termination of the Previous Agreements agreed herein but for the surviving clauses set forth below.

 

2.2                               Surviving clauses. The following clauses in the Previous Agreements will survive:

 

2.2.1                     Privileged Access Agreement

 

(a)                                 Article 5 (Confidentiality, Publicity and Press Releases)

 

(b)                                 Article 9 (Governing Law)

 

(c)                                  Article 10 (Jurisdiction)

 

2.2.2                     2007 Commercialization Agreement

 

(a)                                 Article 2 (termination of, inter alia, 2005 Agreement)

 

(b)                                 Section 3.1 (ownership of Collaborative Research IP, as defined in the 2007 Commercialization Agreement)

 

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(c)                                  Section 3.4 (waiver and release of Digna regarding the development or Commercialization of Products (as defined in the 2007 Commercialization Agreement)

 

(d)                                 Article 6 (Confidentiality)

 

(e)                                  Sections 7 (Representations and Warranties)

 

(f)                                   Article 11 (Dispute Resolution)

 

2.2.3                     Virus Encoded IGF License

 

(a)                                 Article 6 (Confidentiality)

 

(b)                                 Article 10 (Governing Law)

 

(c)                                  Article 11 (Jurisdiction)

 

2.3                               For the avoidance of doubt:  (i) as per the Effective Date of this Agreement, the license granted to AMT under Optioned IP (as defined in the Virus Encoded IGF License) shall terminate, the costs of further maintenance, prosecution, enforcement and defense of the Optioned IP shall be borne by Digna and AMT shall cease the development, manufacture and Commercialization of Virus Encoded IGF, (ii) the license granted to AMT under the 2007 Commercialization Agreement to develop and Commercialize Products (as defined in the 2007 Commercialization Agreement) is replaced by the license granted to AMT under Article 3 of this Agreement subject to the terms and conditions of this Agreement and (iii) any amount due and outstanding by AMT under the Virus Encoded IFG License is waived by the CIMA Parties with effect as from the Effective Date.

 

ARTICLE 3                           OWNERSHIP AND LICENSE

 

3.1                               Ownership of Background. AMT is and remains the sole owner of the AMT Background IP. The CIMA Parties are and remain the sole owner of the CIMA Background IP. The Joint Patent Rights are and remain jointly owned by Amsterdam Molecular Therapeutics (AMT) IP B.V. and Proyecto de Biomedicina CIMA S.L.

 

3.2                               Grant of Rights from the CIMA Parties to AMT. As appropriate, UTE CIMA and Proyecto hereby grant to AMT and its Affiliates:

 

3.2.1                     an exclusive right and license, with the right to grant sublicenses, under Proyecto’s interest, right and title in the Joint Patent Rights to use, develop, make, have made and Commercialize Products within the Territory; and

 

3.2.2                     a non-exclusive, fully paid up, royalty free, right and license, with the right to grant sublicenses, under the CIMA Background IP required for the use, development, manufacture and/or Commercialization of the Product within the Territory and in the Gene Therapy Field and only to the extent required for said purpose. The CIMA Parties shall notify

 

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AMT in writing regularly (at least [**]) on any CIMA Background IP developed after the Effective Date, describing such new developed CIMA Background IP.

 

3.3                               Registration of license. The CIMA Parties shall upon first request of AMT cooperate in the registration of the licenses granted to AMT hereunder in the patent registers of the applicable patent offices, at AMT’s expense.

 

3.4                               Commercially Reasonable Efforts. AMT agrees to use Commercially Reasonable Efforts to further develop, manufacture and Commercialize Products as soon as reasonably practicable. If AMT does not fulfill its financial obligations under the Collaborative Development Agreement and/or in any other way does not use Commercially Reasonable Efforts to further develop, manufacture and Commercialize Products as soon as reasonably practicable,, DIGNA might revoke the license.

 

ARTICLE 4                           COLLABORATIVE DEVELOPMENT AGREEMENT

 

4.1                               Development Plan. The Parties acknowledge that Digna and AMT have entered into that certain Collaborative Development Agreement of even date herewith (attached hereto as Exhibit 2, the “Collaborative Development Agreement”) aimed at the further developed of a Product for treatment or prevention of acute intermittent porphyria.

 

ARTICLE 5                           ROYALTIES ON NET SALES AND NET REVENUES

 

5.1                               Royalties on Net Sales. If the Product is Commercialized by AMT, AMT shall pay a [**] percent royalty on Net Sales on all Products on a Product-by-Product and country-by-country basis for the longer of the two following periods: (i) for so long as there are Valid Claims of Joint Patent Rights in such country of sale; or (ii) for the period of orphan drug marketing exclusivity granted by the applicable regulatory authority on a country by country basis, being ten (10) years in the European Union or seven (7) years in the United States post Launch of the Product, as applicable.

 

5.2                               Royalties on Net Revenues. If the further development and/or Commercialization of a Product is licensed to a Third Party, AMT shall pay a [**] percent of Net Revenues received by AMT from any licensee under any license granted by AMT under the Joint Patent Rights for so long as such Net Revenues are received.

 

5.3                               Payment to Digna. All royalties shall be paid to Digna. Digna shall be responsible for the apportionment of the sums paid to Digna hereunder to the respective CIMA Parties, pursuant to the agreements executed between them, and for payment of the same according to that apportionment. All other CIMA Parties agree with payment of the royalties by AMT to Digna.

 

5.4                               Additional licenses. The Parties acknowledge that any vector license required by AMT from NIH to use, develop, make, have made or Commercialize Products will be borne by AMT. In the event that a license, sublicense or similar right from one or more Third Parties is necessary in order to make, have made, use, offer to sell, sell or import Product other than said licenses from NIH, then, upon notification to the CIMA Parties, AMT, its Affiliates or licensees may acquire such a license, sublicense or similar right and AMT may offset a total of [**]percent

 

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([**]%) of any royalty or other payments paid in connection therewith against any royalty payments due to Digna under this Article 5; provided, however, that in no event shall the total royalty payable to Digna on any Product be less than [**] percent ([**] %) of the Net Sales of such Product sold by AMT, its Affiliates or licensees as a result of such off-set.

 

5.5                               Quarterly Basis. All sums due to Digna under Sections 5.1 and 5.2 shall be calculated and payable on a Quarterly basis, and shall be paid in EURO within [**] days following the end of each Calendar Quarter. Each such payment shall be accompanied by a written report indicating the amount of Net Sales in the Territory and Net Revenues during such Calendar Quarter (including quantity of Product sold by party -i.e AMT, its Affiliates and licensees), the gross amounts that correspond to such Net Sales and Net Revenues, the currency conversion rates used (if any) and a calculation of the sums due.

 

5.6                               Currency. Whenever for the purpose of calculating royalties conversion from any foreign currency shall be required, such conversion shall be made as follows. When calculating the Net Sales, the amount of such sales in foreign currencies shall be converted into EURO using the average monthly rate of exchange for such currencies at the time published in Financial Times in accordance with current standard practices in the market. AMT shall make all payments under this Agreement in EURO. If AMT becomes obliged by law to make a deduction or withholding in respect of tax from any amount payable under this Agreement it shall make this deduction.

 

5.7                               Records. AMT and its Affiliates shall keep and AMT shall require its licensees to keep, full, true and accurate records and books of account containing all particulars that may be necessary for the purpose of calculating all royalties payable to Digna for a minimum period of [**] years after each payment. Upon timely notice by Digna, AMT shall permit an independent certified public accountant selected by Digna and acceptable to AMT, which acceptance shall not be unreasonably withheld, to have access during normal business hours to such records of AMT and its Affiliates as may be reasonably necessary to verify the accuracy of the royalty reports described herein. Any such certified public accountant shall first be required to enter into a confidentiality agreement in form reasonably acceptable to AMT. AMT shall use commercially reasonable efforts to schedule all such verifications within [**] days after Digna makes its written request. Such verifications shall be conducted not more than [**]. If Digna’s independent certified public accountant concludes that additional royalties were owed to Digna during such period, the additional fees shall be paid by AMT within [**] days after the date Digna delivers to AMT such independent certified public accountant’s written report so concluding, unless AMT shall have a good faith dispute as to the conclusions set forth in such written report, in which case AMT shall provide written notice to Digna within such [**] day period of the nature of its disagreement with such written report. In the event Digna’s independent certified public accountant concludes that there was an overpayment of royalties to Digna during such period, the overpayment shall be repaid by Digna within [**] days after the date AMT received such independent certified public accountant’s written report so concluding or, at the election of AMT, be credited against future royalties, unless Digna shall have a good faith dispute as to the conclusions set forth in such written report, in which case Digna shall provide written notice to AMT within such [**] day period of the nature of its disagreement with such written report. In the event a Party provides written notice of such a dispute hereunder, the Parties shall thereafter, for a period of [**] days, attempt in good faith to resolve such dispute and if they are unable to

 

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do so then either Party may take appropriate legal actions to enforce its rights hereunder. The fees charged by such independent certified public accountant shall be paid by Digna unless the audit discloses an underpayment of the fees payable by AMT for the audited period of more than [**] percent ([**]%) or more than [**] EURO (€ [**]), in which case AMT shall pay the reasonable fees and expenses charged by such accountant.

 

5.8                               Taxes. All payments to Digna under the terms of the Agreement are expressed to be exclusive of value added tax howsoever arising and AMT shall pay to Digna in addition to those payments all value added tax for which Digna is liable to account in relation to any supply made or deemed to be made for value added tax purposed to this Agreement on receipt of a tax invoice or invoices from Digna.

 

5.9                               Transfer of amounts. Payments made to Digna under this Agreement shall be made by wire transfer to the following account of Digna:

 

Bank: BBVA,
 Bank address: Avda. Carlos III, 33, 31004 Pamplona 
 Swift Code: BBVAESMMXXX 
 IBAN: ES89 0182 5000 8802 0156 0335

 

or any other bank account that may be notified by Digna to AMT from time to time.

 

ARTICLE 6                           FILING, MAINTENANCE AND PROSECUTION OF PATENT RIGHTS

 

6.1                               AMT Background IP. AMT shall have the exclusive responsibility, at its sole expense, to file, maintain, prosecute, defend and enforce Patent Rights including within the AMT Background IP, using patent counsel at its election.

 

6.2                               CIMA Background IP. Digna or a CIMA Party designated by Digna shall have the exclusive responsibility, at its sole expense, to file, maintain, prosecute, defend and enforce Patent Rights including within the CIMA Background IP, using patent counsel at its election.

 

6.3                               Joint Patent Rights.

 

6.3.1                     Filing, Maintenance and Prosecution. AMT shall have the exclusive responsibility to file, maintain and prosecute the Joint Patent Rights, using patent counsel at its election. The costs thereof shall be jointly borne by Proyecto and AMT. AMT will consult with Digna, keep Digna reasonably informed and obtain the prior approval from Digna regarding the status and strategies associated with any Patent Rights included in the Joint Patent Rights. Digna, in turn, will keep the other CIMA Parties reasonable informed. If AMT elects, in its sole discretion, not to initiate or continue to pursue the further prosecution of one or more Patent Rights included in the Joint Patent Rights in any particular country, then it shall, subject to any contractual obligations to Third Parties, notify Digna in writing of such election at least [**] days prior to the last available date to allow Digna to take action to preserve such Patent Rights included in the Joint Patent Rights at Digna’s expense.

 

6.3.2                     Enforcement. In the event that either Party identifies activities of Third Parties that (allegedly) infringe the Joint Patent Rights, it will notify the other Party and AMT shall decide whether it is necessary to commence proceedings as claimant and it shall be entitled

 

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to request each and any of the CIMA Parties to join AMT as co-claimant, and the CIMA Parties shall decide whether to join or not at its sole election. If AMT succeeds in any such infringement proceedings whether at trial or by way of settlement, the first charge on any costs, damages or profits in such proceedings or settlement shall be the costs incurred by AMT and the CIMA Parties that have acted as co-claimants. If such sums are less than the costs incurred they shall be apportioned between AMT and the CIMA Parties in the proportion to the Parties’ expenditure. Where the sums exceed the costs incurred, AMT on the one hand and the CIMA Parties that acted as co-claimant together on the other hand shall allocate the balance between them in the same proportion as the allocation of net revenues described in section 5.2. AMT is not entitled to settle such dispute without Digna’s prior written consent. In case AMT decides not to commence proceedings as claimant, the CIMA Parties shall be entitled to commence them at its sole cost. In such a case, any sum derived from said infringement proceedings shall be for the CIMA Parties. The CIMA Parties shall not be entitled to settle such dispute without AMT’s prior written consent.

 

6.3.3                     Defense. In the event that one or more patents or patent applications included in the Joint Patent Rights are challenged by a Third Party (by way of interference, opposition, invalidity actions or otherwise), the Parties shall decide whether they want to jointly defend such patents or patent applications included in the Joint Patent Rights and jointly bear the costs. If the CIMA Parties do not want to bear half of the costs of such defense, AMT shall have the right (but not the obligation) to take the appropriate actions to defend such patents and patent application included in the Joint Patent Rights. In such event, AMT shall be entitled to deduct up to [**]% of the costs incurred by AMT regarding such defense actions from the royalty payable by AMT to the CIMA Parties hereunder. Any awards will be allocated in accordance with Section 6.3.2. AMT (or the CIMA Parties, as the case may be) shall not be entitled to settle any challenge dispute without the other Party’s prior written consent.

 

6.4                               Cooperation. Each of the Parties shall make available to the other (or to the other’s authorized attorneys, agents or representatives) its employees, agents or consultants to the extent necessary or appropriate to enable the appropriate Party to file, prosecute and maintain patent applications and resulting patents with respect to inventions owned by a Party, at the expense of this Party and for periods of time sufficient for such Party to obtain the assistance it needs from such personnel. Where appropriate, each of the Parties shall sign or cause to have signed all documents relating to said patent applications or patents at no charge to the other Party.

 

6.5                               Third Party Claims of Infringement. If during the period of this Agreement, either Party receives any notice, claim or proceedings from any Third Party alleging infringement of that Third Party’s intellectual property by reason of development or Commercialization of the Product, the Party receiving that notice shall (i) forthwith notify the other Party of the notice, claim or proceeding and (ii) neither Party shall make any admission of liability and notwithstanding that one of CIMA Parties may have received the notice, AMT shall at its own cost and expense be responsible for and shall have conduct of any and sole authority to defend or settle such claims or proceedings. If AMT reasonable believes that Third Party rights are valid and that infringement may be occurring, or believes that it is economically or otherwise advantageous to seek a license, it may, subject to Section 5.4, seek a license from such Third Party on appropriate commercial terms.

 

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ARTICLE 7                           ACCESS RIGHTS

 

7.1                               General. The Parties contemplate to collaborate on the identification and development of future products (other than the Products) within the Gene Therapy Field. Therefore, the Parties have agreed as follows:

 

7.1.1                     Disclosure. During term of this License Agreement, the CIMA Parties shall disclose to AMT inventions such CIMA Party has, whether or not together with other CIMA Parties, conceived, developed or reduced to practice within the Gene Therapy Field (“Inventions”). Such inventions shall be disclosed in writing to AMT within reasonable time (no longer than [**] months) after such invention has been conceived, developed or reduced to practice. The reports describing such inventions shall be deemed to be Confidential Information of the CIMA Parties.

 

7.1.2                     The CIMA Parties herewith grant to AMT the exclusive first right to negotiate a license to Inventions and any IP associated therewith under market prevailing terms and conditions. The relevant CIMA Party shall be owner of any right, title and interest in such Invention.

 

7.1.3                     In the event that AMT is interested in the further development and Commercialization of an Invention, AMT shall notify the CIMA Party that has sent the written report describing the Invention to AMT in writing within [**] months after receipt of such report. In such event, the Parties shall in good faith negotiate the terms and conditions for an exclusive license to such Invention and any IP associated therewith. In case AMT has not notified in writing to the corresponding CIMA Party its interest in the Invention within the above [**] months period, the CIMA Parties shall be entitled to offer such Invention to Third Parties (whether as a license, assignment or any other agreement), without any further right for AMT.

 

7.1.4                     In case AMT has notified its interest within said [**] months, but the Parties are not able to reach an agreement on the terms of such exclusive license for such Invention and IP rights associated therewith within [**] months after the notification of its interest by AMT, the CIMA Parties may freely offer such Invention to Third Parties provided that they shall not accept an offer from a Third Party for such Invention unless they have first offered AMT the right to match such offer and AMT has not notified by writing within [**] days its will to match such offer (and on the understanding that if AMT matches such offer, the CIMA Parties will grant an exclusive license under the Invention and IP rights associated therewith under the thus matched terms and conditions).

 

ARTICLE 8                           CONFIDENTIALITY

 

8.1                               General. Each Party undertakes to keep strictly confidential the Confidential Information and to use it only for the purpose of this Agreement.

 

8.2                                   No disclosure / restriction to use. Each Receiving Party undertakes to not disclose the Confidential Information to any third party except to those of its officers and employees who need to have access to the same. Each Party shall before disclosing any Confidential Information to any of its officers or employees make each such person aware of such restrictions and to use and disclosure and shall procure that such persons comply with such restrictions. If the Receiving Party wishes to disclose Confidential Information to any consultant or advisor who is

 

14

 

not an officer or employee it shall obtain the Disclosing Party’s prior written consent and shall furnish to the Disclosing Party with a confidentiality agreement signed by such consultant or advisor on the same terms and conditions of this Agreement.

 

8.3                                   Exceptions. The obligations to maintain confidentiality and to respect the restriction of the use shall not apply where, as properly evidenced by documentation: (i) is or becomes patented, published or otherwise becomes publicly known other than by acts of the Party obligated not to disclose such Confidential Information in contravention of this Agreement; (ii) can be shown by written documents to have been disclosed to the Receiving Party by a Third Party, provided, that such information was not obtained by such Third Party directly or indirectly from the other Party under this Agreement; (iii) prior to disclosure under this Agreement, was already in the possession of the Receiving Party; or (iv) can be shown by written documents to have been independently developed by the Receiving Party without use of the other Party’s Confidential Information or breach of any of the provisions of this Agreement.

 

8.4                               Permitted disclosure. Notwithstanding the above obligations of confidentiality and non-use a Recipient Party may:

 

8.4.1                     disclose Confidential Information to a Regulatory Authority as reasonably necessary to obtain Regulatory Approval in a particular jurisdiction to the extent consistent with the licenses granted under terms of this Agreement; and

 

8.4.2                     disclose Confidential Information: (a) to the extent such disclosure is reasonably necessary to comply with the order of a court; or (b) to the extent such disclosure is required to comply with a legal requirement, including to the extent such disclosure is required in publicly filed financial statements or other public statements under rules governing a stock exchange (e.g. the rules of the Netherlands, United States Securities and Exchange Commission, NASDAQ, NYSE, UKLA or any other stock exchange on which securities issued by either Party may be listed); provided, to the extent possible bearing in mind such legal requirements and subject to the next subsequent sentence of this Section 8.4, such Party shall provide the other Party with a copy of the proposed text of such statements or disclosure [**] Business Days in advance of the date on which the disclosure is to be made to enable the other Party to review and provide comments, which shall be followed as long as they are reasonable, unless a shorter review time is agreed. If the compliance with a legal requirements requires filing of this Agreement, the filing Party shall to the extent possible seek confidential treatment of portions of this Agreement from the relevant competent authority and shall provide the other Party with a copy of the proposed filings at least [**] Business Days prior to filing for the other Party to review any such proposed filing. Each Party agrees that it will obtain its own legal advice with regard to its compliance with legal requirements and will not rely on any statements made by the other Party relating to such legal requirements

 

8.4.3                     disclose Confidential Information by filing or prosecuting Patent Rights, the filing or prosecution of which is contemplated by this Agreement, without violating the above secrecy provision; it being understood that publication of such filings occurs in some jurisdictions within [**] months of filing, and that such publication shall not violate the above secrecy provision;

 

8.4.4                     disclose Confidential Information to such Recipient Party’s Affiliates, contractors (including clinical researchers) distributors, licensee’s, agents, consultants, as such

 

15

 

Recipient Party reasonably determines is necessary to receive the benefit of this Agreement or to fulfill its obligations pursuant to this Agreement; provided, however, any such persons must be obligated to substantially the same extent as set forth in Section 8.2 to hold in confidence and not make use of such Confidential Information for any purpose other than those permitted by this Agreement;

 

8.4.5                     disclose Confidential Information, only to the extent reasonably required (i) to its actual or potential investment bankers; (ii) to existing and potential investors in connection with an offering or placement of securities for purposes of obtaining financing for its business and to actual and prospective lenders for the purpose of obtaining financing for its business; and (iii) to a bona fide potential acquirer or merger partner for the purposes of evaluating entering into a merger or acquisition, provided, however, any such persons must be obligated to substantially the same extent as set forth in Section 8.2 to hold in confidence and not make use of such Confidential Information for any purpose other than those permitted by this Agreement; and

 

8.4.6                     Disclose Confidential Information to its legal advisers for the purpose of seeking advice.

 

8.5                               Press Release. Neither Party shall make any public announcement or statement to the public containing Confidential Information without the prior written consent of the other Parties. No such public announcement or statements shall be made without the prior review and consent of the appropriate individual designated for the purpose by the other Parties.

 

ARTICLE 9                           REPRESENTATIONS AND WARRANTIES

 

9.1                               Mutual Warranties. Each Party represents and warrants to the other Parties that:

 

(a)                                 It has full power to extend the rights and licenses granted hereunder and perform its obligations hereunder;

 

(b)                                 It has full power and authority to enter into this Agreement and has taken all necessary action on its part required to authorize the execution and delivery of this Agreement;

 

(c)                                  The execution, delivery and performance of this Agreement and its compliance with the terms and provisions hereof does not conflict with, or result in a breach of any of the terms and provisions of, or constitute a default under any agreement to which any Party is a party; and

 

(d)                                 The execution, delivery and performance of this Agreement by each Party does not require the consent, approval or authorization of or notice, filing or registration with Regulatory Authority.

 

9.2                               Warranties of CIMA Parties. The CIMA Parties jointly and severally represent and warrant to AMT that, at the Effective Date, (i) Proyecto is the owner of the undivided interest in the Joint Patent Rights; and that (ii) they have not previously entered into any agreement, whether written or oral, with respect to, or otherwise assigned, licensed, transferred,

 

16

 

conveyed or otherwise encumbered its/their rights, title or interest in or to the Joint Patent Rights (including by granting any covenant not to sue with respect thereto).

 

9.3                               Indemnification. AMT shall defend, indemnify and hold the CIMA Parties harmless from and against any Losses arising out of Third Party claims, suits or demands based on alleged or actual bodily injury or death or any other damage resulting from the development of Product or Commercialization of Product by AMT, its Affiliates or licensees. Losses shall not include any liability, claims, lawsuits, losses, damages, costs or expenses to the extent the same are determined to be the result of any CIMA Parties, their Affiliates, any Third Party engaged by Digna under the Collaborative Development Agreement and/or their directors officers, employees and agents negligence or willful misconduct.

 

AMT shall obtain and maintain insurance coverage in respect of the development and commercialization of the Product (notwithstanding Digna’s obligation to obtain and maintain insurance coverage as set forth in the Collaborative Development Agreement). Evidence of the existence and continuation of such insurance shall be provided to the CIMA Parties and AMT, respectively, upon request.

 

9.4                               The CIMA Parties shall immediately notify AMT (and each of the other CIMA Parties) in writing of any Third Party claim or action that may give rise to Losses (a “Claim Notice”) for which AMT has to indemnify pursuant to Section 9.3. AMT undertakes at its expense, to assume sole control and responsibility for dealing with the Third Party and the Third Party claim, including the right to settle the Third Party claim on any terms AMT chooses, by giving written notice to Digna without [**] days after receipt of a Claim Notice. The CIMA Parties shall be entitled to participate in. but not control, the defense of a Third Party claim by having their view regularly solicited by Digna who shall in turn liaise with AMT regarding the conduct of the Third Party Claim. Where proceedings are commenced, the CIMA Parties shall be entitled to retain counsel of their choice for such purpose, provided, however, that such retention shall be at each of the CIMA Parties’ own cost and expense.

 

ARTICLE 10                    TERM / TERMINATION

 

10.1                        This License Agreement shall commence on the Effective Date and shall continue until the payment obligations set out in Article 5 expire following which the Parties agree that the Agreement will have been fully performed. All licenses granted under this Agreement shall become perpetual, irrevocable, fully paid-up and royalty free on a country-by-country basis when there are not outstanding payment obligations in relation to such country.

 

10.2                        Termination for breach or insolvency. Notwithstanding any other provision hereof, each Party may forthwith terminate this Agreement:

 

(a)                                 as a result of a material breach or default in the performance of any obligation, condition or covenant of this Agreement by the other Party or Parties, if such default or noncompliance shall not have been remedied within [**] days after receipt by the defaulting Party of a notice thereof from the other Party; or

 

(b)                                 if the other Party receives suspension of payment or, whether voluntarily or involuntarily, is declared bankrupt, or if such Party becomes permanently unable

 

17

 

to perform its obligations hereunder for reasons other than suspension of payment or bankruptcy, such as, for example, liquidation, dissolution or winding-up.

 

10.3                        Termination for termination of the Collaborative Development Agreement. Each Party may terminate this Agreement in the event that the Collaborative Development Agreement is terminated.

 

10.4                        Termination by AMT for convenience. AMT may terminate this Agreement for convenience upon 2 months written notice.

 

10.5                        Effect of Termination.

 

10.5.1              In the event of termination, the licenses granted by the CIMA Parties to AMT as set forth in Article 3 of this Agreement shall terminate. In the event of termination by Digna pursuant to Section 10.2, by Digna or AMT pursuant to Section 10.3 (other than termination of the Collaborative Development Agreement by AMT for breach or insolvency of Digna) or Section 10.4, the CIMA Parties shall have the exclusive rights, with the right to grant sublicenses, to use the Joint Patent Rights for the further development and Commercialization of Products as treatment or prevention of the Disorder without financial obligations to AMT, and each of the CIMA Parties collectively on the one hand and AMT on the other hand shall have the non-exclusive rights, without the right to sublicense, to use the Joint Patent Rights for the development and Commercialization of products as treatment or preventions of disorders other than the Disorder without financial obligations to the other Party or Parties. In the event of termination by AMT pursuant to Section 10.2 or by Digna or AMT pursuant to Section 10.3 (other than termination of the Collaborative Development Agreement by Digna for breach or insolvency of AMT), AMT shall have the exclusive rights, with the right to grant sublicenses, to use the Joint Patent Rights for the further development and Commercialization of Products or products as treatment or prevention of the Disorder, or disorders other than the Disorder without financial obligations to CIMA Parties.

 

10.6                        The Articles 2, 3.1, 5.7, 6, 8, 9, 12, 13 and 14 survive expiration or termination of this Agreement for any reason (subject to Section 10.5).

 

ARTICLE 11                    ASSIGNMENT

 

Save as otherwise provided in this Agreement no Party shall without the prior written consent of the other assign the benefit and/or burden of this Agreement provided always that any Party may assign this Agreement to an Affiliate of said Party or any purchaser of the whole or part of said Party’s assets or to a company with which said Party is merging, provided that such Affiliate, purchaser or merger company undertakes to the other Parties to be bound by the terms of this Agreement. The CIMA Parties shall not transfer, assign or encumber (their interest in the) ownership of the CIMA Background IP or the Joint Patent Rights without AMT’s prior written consent, other than to an Affiliate or in connection with an above permitted assignment of its rights. AMT shall not transfer, assign or encumber its interest in the ownership of the Joint Patent Rights without Digna’s prior written consent other than to an Affiliate or in connection with an above permitted assignment of its rights.

 

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ARTICLE 12                    NOTICES

 

Any notices required or provided under this Agreement shall be in writing and shall be given by facsimile or by certified mail addressed to the applicable Party as set out below:

 

	
AMT
    	
Mr. Piers Morgan
    
	
 
    	
PO Box 22506
    
	
 
    	
1100DA Amsterdam
    
	
 
    	
The Netherlands
    
	
 
    	
 
    
	
UTE   CIMA
    	
Mr. Antonio   Martin Cantón
    
	
 
    	
UTE   PROYECTO CIMA AVDA. PÍO XII, 22, OFICINA 1. 31008
    
	
 
    	
PAMPLONA,   NAVARRA
    
	
 
    	
Spain
    
	
 
    	
 
    
	
FIMA
    	
Mr. Franciso   Errasti Goenaga
    
	
 
    	
Calle   Pintor Paret 5,1° F Pamplona,
    
	
 
    	
Spain
    
	
 
    	
 
    
	
DIGNA
    	
Mr. Pablo   Ortiz Betes
    
	
 
    	
DIGNA   BIOTECH S.L.AVDA. PÍO XII, 22, OFICINA 2. 31008 PAMPLONA,
    
	
 
    	
NAVARRA
    
	
 
    	
Spain
    
	
 
    	
 
    
	
PROYECTO
    	
Mr. Antonio   Martin Cantón
    
	
 
    	
PROYECTO DE   BIOMEDIC1NA CIMA AVDA. PÍO XII, 22, OFICINA I.
    
	
 
    	
31008   PAMPLONA, NAVARRA
    
	
 
    	
Spain
    

 

ARTICLE 13                    GOVERNING LAW

 

The validity construction and performance of this Agreement shall be governed by the laws of The Netherlands.

 

ARTICLE 14                    JURISDICTION

 

All disputes arising out of or in connection with this Agreement shall be finally settled under the Rules of Arbitration of the International Chamber of Commerce by one or more arbitrators appointed in accordance with said Rules. The arbitration to take place in Paris and to be conducted in English.

 

ARTICLE 15                    MISCELLANEOUS

 

15.1                        Interpretation.

 

15.1.1              If an ambiguity or a question of intent or interpretation arises with respect to this Agreement, this Agreement shall be construed as if drafted jointly by the Parties and no presumption or burden of proof shall arise favoring or disfavoring any Party by virtue of the authorship of any provisions of this Agreement.

 

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15.1.2     Whenever the context may require, any pronoun shall include the corresponding masculine, feminine and neuter forms. The words “include”, “includes” and “including” shall be deemed to be followed by the phrase “without limitation.” The word “will” shall be construed to have the same meaning and effect as the word “shall.” Unless the context requires otherwise, (A) any definition of or reference to any agreement, instrument or other document herein shall be construed as referring to such agreement, instrument or other document as from time to time amended, supplemented or otherwise modified (subject to any restrictions on such amendments, supplements or modifications set forth herein or therein), (B) any reference to any laws herein shall be construed as referring to such laws as from time to time enacted, repealed or amended, (C) any reference herein to any Person shall be construed to include the Person’s successors and assigns, (D) the words “herein”, “hereof and “hereunder”, and words of similar import, shall be construed to refer to this Agreement in its entirety and not to any particular provision hereof, (E) any reference herein to the words “mutually agree” or “mutual written agreement” shall not impose any obligation on either Party to agree to any terms relating thereto or to engage in discussions relating to such terms except as such Party may determine in such Party’s sole discretion and; (F) all references herein to Articles, Sections or Schedules shall be construed to refer to Articles, Sections and Schedules of this Agreement.

 

15.2        Force Majeure. Neither Party shall be held liable or responsible to the other Party nor be deemed to have defaulted under or breached this Agreement for failure or delay in fulfilling or performing any term of this Agreement when such failure or delay is caused by or results from causes beyond the reasonable control of the affected Party, including fire, floods, embargoes, war, acts of war (whether war is declared or not), insurrections, riots, civil commotions, strikes, lockouts or other labor disturbances, acts of God or acts, omissions or delays in acting by any governmental authority or the other Party; provided, however, that the Party so affected shall use Commercially Reasonable Efforts to avoid or remove such causes of non-performance, and shall continue performance hereunder with reasonable dispatch wherever such causes are removed. Each Party shall provide the other Parties with prompt written notice of any delay or failure to perform that occurs by reason of force majeure. The Parties shall mutually seek a resolution of the delay or the failure to perform in good faith.

 

15.3        Severability. Each Party hereby agrees that it does not intend to violate any public policy, statutory or common laws, rules, regulations, treaty or decision of any government agency or executive body thereof of any country or community or association of countries. Should one or more provisions of this Agreement be or become invalid, the Parties hereto shall substitute, by mutual consent, valid provisions for such invalid provisions which valid provisions in their economic effect are sufficiently similar to the invalid provisions that it can be reasonably assumed that the Parties would have entered into this Agreement with such valid provisions. In case such valid provisions cannot be agreed upon, the invalidity of one or several provisions of this Agreement shall not affect the validity of this Agreement as a whole, unless the invalid provisions are of such essential importance to this Agreement that it is to be reasonably assumed that the Parties would not have entered into this Agreement without the invalid provisions.

 

15.4        Exhibits. The Exhibits to this Agreement form an integral part of this Agreement.

 

15.5        Entire Agreement. This Agreement (including the Exhibits thereto) contains the entire understanding of the Parties with respect to the subject matter hereof and supersedes all

 

20

 

prior or contemporaneous oral or written agreements of the Parties with respect to the subject matter hereof, including the Previous Agreements. This Agreement may be amended, or any term hereof modified, only by a written instrument duly executed by both Parties hereto.

 

15.6        Headings. The captions to the several Articles and Sections hereof are not a part of this Agreement, but are merely guides or labels to assist in locating and reading the several Articles and Sections hereof.

 

15.7        Independent Contractors. It is expressly agreed that the Parties to this Agreement shall be independent contractors and that the relationship between the Parties shall not constitute a partnership, joint venture or agency. Neither Party shall have the authority to make any statements, representations or commitments of any kind, or to take any action, which shall be binding on the other(s), without the prior consent of the other Parties to do so.

 

15.8        Waiver. Except as expressly provided herein, the waiver by either Party hereto of any right hereunder or of any failure to perform or any breach by the other Party shall not be deemed a waiver of any other right hereunder or of any other failure to perform or breach by said other Party, whether of a similar nature or otherwise, nor shall any singular or partial exercise of such right preclude any further exercise thereof or the exercise of any other such right.

 

15.9        Counterparts. This Agreement may be executed in one more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument.

 

15.10      Benefit. Nothing in this Agreement or the agreements referred to herein, expressed or implied, shall confer on any person other than the Parties hereto or thereto, or their respective permitted successors or assigns, any rights remedies, obligations or liabilities under or by reason of this Agreement, the agreements referred to herein, or the transactions contemplated herein or therein.

 

15.11      Further Assurances. Each Party shall, as and when requested by another Party, do all acts and execute all documents as may be reasonably necessary to give effect to the provisions of this Agreement.

 

[Remainder of page intentionally left blank]

 

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IN WITNESS WHEREOF, the Parties have executed this Collaboration Agreement as of the date first written above.

 

 

	
 
    	
 
    
	
FIMA
    	
 
    
	
By: Mr. Franciso Errasti Goenaga
    	
 
    
	
Title: Presidente
    	
 
    
	
 
    	
 
    
	
 
    	
 
    
	
/s/ Antonio   Martin Cantón
    	
 
    
	
UTE CIMA
    	
 
    
	
By: Antonio   Martin Cantón
    	
 
    
	
Title:   Gerente – Manager
    	
 
    
	
 
    	
 
    
	
 
    	
 
    
	
/s/   Mr. Antonio Martin Cantón
    	
 
    
	
Proyecto de   Biomedicina CIMA S.L.
    	
 
    
	
By:   Mr. Antonio Martin Cantón
    	
 
    
	
Title:   Director General – General Manager
    	
 
    
	
 
    	
 
    
	
 
    	
 
    
	
/s/ Pablo Ortiz Betés
    	
 
    
	
Digna Biotech S.L.
    	
 
    
	
By: Mr. Pablo Ortiz Betés
    	
 
    
	
Title: Director General
    	
 
    
	
 
    	
 
    
	
 
    	
 
    
	
/s/ Piers Morgan
    	
 
    
	
Amsterdam Molecular Therapeutics (AMT) B,V.
    	
 
    
	
By: Mr. Piers Morgan
    	
 
    
	
Title: Chief Financial Officer
    	
 
    

 

22

 

Exhibit 1

 

JOINT PATENT RIGHTS

 

[**]

 

23

 

Exhibit 2

 

COLLABORATIVE DEVELOPMENT AGREEMENT BETWEEN DIGNA AND AMT

 

24

 

COLLABORATIVE DEVELOPMENT AGREEMENT

 

by and among

 

DIGNA BIOTECH, S.L.

 

AND

 

AMSTERDAM MOLECULAR THERAPEUTICS (AMT) B.V.

 

dated as of 21st of May, 2010

 

 

COLLABORATIVE DEVELOPMENT AGREEMENT

 

THIS COLLABORATIVE DEVELOPMENT AGREEMENT dated as of 21 May, 2010 (the “Agreement”) is made by and among:

 

(1)                                 Digna Biotech, S.L.  (“Digna”) with corporate address at C/ Etxesakan 28, oficina 5, 31180 Cizur Maryo, Navarra, Spain, beare of Tax Identification Number B-31778509, duly represented by Mr.  Pablo Ortiz Betés.

 

and

 

(2)                                 Amsterdam Molecular Therapeutics (AMT) B.V.  (“AMT”) a company with limited liability incorporated under the laws of The Netherlands with registered office at Meibergdreef 61, NL-1105 BA Amsterdam, The Netherlands, duly represented by Mr. Piers Morgan

 

WHEREAS

 

(A)          Digna and AMT, together with FIMA, UTE CIMA and Proyecto (as defined in the License Agreement), have entered into a License Agreement of even date herewith;

 

(B)          Digna has broad expertise and Know How in the field of acute intermittent porphyria and has, through hospitals with which it collaborates, access to relevant patient populations;

 

(C)          AMT has broad expertise and Know How in the field of development and manufacturing of products as gene therapy treatment;

 

(D)          the Parties now want to combine their expertise and knowledge aimed at the preclinical and clinical development of a gene therapy product as treatment for and/or prevention of acute intermittent porphyria under the terms and conditions set forth below;

 

IT IS NOW AGREED AS FOLLOWS

 

ARTICLE 1                                                   DEFINITIONS

 

For purposes of this Agreement, the terms defined in this Article 1 shall have the meanings specified below.  Certain other capitalized terms are defined elsewhere in this Agreement.

 

1.1          “Affiliate” any company, partnership or other business entity which Controls, is Controlled by or it under common Control with any of the Parties.  For the purposes of this definition “Control” refers to any of the following (i) the possession, directly or indirectly, of the power to direct the management or policies of an entity, whether through ownership of voting securities, by contract or otherwise; (ii) ownership of more than fifty percent (50%) of the voting securities entitled to vote for the election of directors in the case of a corporation, or of more than fifty percent (50%) of the equity interest in the case of any other type of legal entity; (iii) status as a general partner in any partnership, or any other arrangement whereby a Party controls or has

 

1

 

the right to control the board of directors or equivalent governing body of a corporation or other entity.

 

1.2          “Agreement” means this Collaborative Development Agreement.

 

1.3          “AMT Background IP” has the same meaning as assigned to it in the License Agreement.

 

1.4          “CIMA Background IP” has the same meaning as assigned to it in the License Agreement.

 

1.5          “CIMA Parties” has the meaning assigned to it in the License Agreement.

 

1.6          “Clinical Trial” means each and any clinical trial and/or other study where the Product is administered to humans or that involves human subjects carried out in the context of the current Agreement, as set out in the Development Plan and Protocol.  Specifically, Clinical Trial refers to Phase I/II clinical trial.  Any other clinical trial not set out in the Development Plan but added to the Development Plan by decision of the Joint Steering Committee will be covered by a separate Agreement.  .

 

1.7          “Confidential Information” means, subject to the exceptions set forth in Article 10.3 (i) the terms and conditions of this Agreement, for which each Party will be considered a Disclosing Party and a Recipient Party; and (ii) any non-public information, whether or not patentable, disclosed or provided by one Party to the other Party in connection with this Agreement, including, without limitation, any information which release is likely to prejudice the commercial interests of the parties, or is considered as a trade secret, including information regarding such Party’s strategy, business plans, objectives, research, technology, products, business affairs or finances including any non-public data relating to development or Commercialization of any Product and other information of the type that is customarily considered to be confidential information by parties engaged in activities that are substantially similar to the activities being engaged in by the Parties under this Agreement, for which the Party making such disclosure will be considered the Disclosing Party and the receiver will be the Recipient Party.

 

1.8          “Development Plan” means the comprehensive plan (including activities assigned to each of Digna and AMT, timelines and budget) for the preclinical and clinical development of the Product aimed at obtaining Regulatory Approval for the Product, attached hereto as Exhibit 1.

 

1.9          Disclosing Party” means the Party which discloses Confidential Information to the other Party or Parties.

 

1.10        “Disorder” means acute intermittent porphyria

 

1.11        “Documents” means analyses, books, CD-ROM, USB stick, charts, comments, computations, designs, discs, diskettes, files, graphs, ledgers, notebooks, paper, photographs, plans, records, recordings, reports, research notes, tapes and other graphic or written data or other media and other computer information storage means on which Know How is permanently

 

2

 

stored and advertising and promotional materials of any nature whatsoever including preparatory materials for the same.

 

1.12        “Effective Date” means the date first set forth above.

 

1.13        “EU Clinical Trial Directive” means Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use” and all legislation of the EU member states implementing this directive.

 

1.14        “GCP” means the ICH Harmonized Tripartite Guideline for Good Clinical Practice together with such other good clinical practice requirements as are specified in Directive 2001/20/EC of the European Parliament and the Council of 4 April 2001 relating to medicinal products for human use and in guidance published by the European Commission pursuant to such Directive and including the EU detailed guidelines on good clinical practice specific to advanced therapy medicinal products of December 3, 2009.

 

1.15        “Hospital” means Clínica Universidad de Navarra and any other premises as designated by the Joint Steering Committee to conduct the Clinical Trial.

 

1.16        “IMPD” means Investigational Medicinal Product Dossier as defined in Clinical Trials Directive (2001/20/EC).

 

1.17        “Intellectual Property” or “IP” means Patent Rights, Know How and Materials together.

 

1.18        “Joint Steering Committee” means the committee to be established by the Parties to manage the Development Program pursuant to Section 7.1.

 

1.19        “Know-How” means technical and other information which is not in the public domain, including information comprising or relating to concepts, discoveries, data, designs, formulae, ideas, inventions, Materials, methods, models, research plans, procedures, designs for experiments and tests and results of experimentation and testing (including results of research or development) processes (including manufacturing processes, specifications and techniques), laboratory records, chemical, pharmacological, toxicological, clinical, analytical and quality control data, clinical and non-clinical trial data, case report forms, data analyses, reports, manufacturing data or summaries and information contained in submissions to and information from ethical committees and Regulatory Authorities.  Know How includes Documents containing Know How, including but not limited to any rights including trade secrets, copyright, database or design rights protecting such Know How.  The fact that an item is known to the public shall not be taken to preclude the possibility that a compilation including the item, and/or a development relating to the item, is not known to the public.

 

1.20        “License Agreement” means the license agreement of even date herewith between Digna, AMT, UTE CIMA, FIMA and Proyecto.

 

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1.21        “Losses” means any and all losses, damages, liabilities, costs and expenses (including, without limitation, reasonable attorneys’ fees and expenses).  In calculating “Losses”, the duty to reasonably mitigate on the part of the Party suffering the Losses shall be taken into account.

 

1.22        Marketing Authorisation Application” or “MAA” means a new drug license application filed with the competent European Regulatory Authorities to obtain Regulatory Approval for a pharmaceutical product in Europe, or any equivalent application filed with the Regulatory Authority in or for a country or group of countries to obtain Regulatory Approval for a pharmaceutical product in or for that country or with that group of countries.

 

1.23        “Materials” means any chemical or biological substances including but not limited to blood samples, nucleotide or nucleotide sequence including DNA and RNA sequences, genes, vector or construct including plasmids, phages or viruses, host organism including bacteria, fungi, algae, protozoa and hybridoma’s, eukaryotic or prokaryotic cell line or expression system or any development strain or product of that cell line or expression system, protein including any peptide or amino acid sequence, enzyme, antibody or protein conferring targeting properties and any fragment of a protein or a peptide enzyme or antibody, assay or reagent, any other genetic or biological material or micro-organism.

 

1.24        “Monitor” means one or more persons appointed by Digna to monitor compliance of the Clinical Trials with GCP and to conduct source data verification.

 

1.25        “Observational Study” means a Clinical Trial aimed at assessing baseline parameters of patients with the Disorder as further described in the Development Plan.

 

1.26        “Parties” means the parties to this Agreement and “Party” means a party to this Agreement.

 

1.27        “Patent Rights” means a (i) all national, regional and international patents and patent applications, including provisional patent applications, (ii) all patent applications filed either from such patents, patent applications or provisional applications or from an application claiming priority from any of these, including divisional, continuations, continuations-in-part, provisions, converted provisionals and continued prosecution applications, (iii) any and all patents that have issued or in the future issue from the foregoing patent applications (i) and (ii), including author certificates, inventor certificates, utility models, petty patents and design patents and certificates of invention, (iv) any and all extensions or restorations by existing or future extension or restoration mechanisms, including revalidations, reissues, re-examinations and extensions (including any supplementary protection certificates and the like) of the foregoing patents or patent applications (i), (ii) and (iii), and (v) any similar rights, including so-called pipeline protection, or any importation, revalidation, confirmation or introduction patent or registration patent or patent of additions to any such foregoing patent applications and patents.

 

1.28        “Phase I/II” means, for the purpose of this Agreement, a Clinical Trial conducted by a Qualified Service Provider aimed at preliminary determination of safety in patients affected by the Disorder and (ii) determination of dose ranges and a preliminary determination of efficacy in patients affected by the Disorder as further described in the Development Plan.

 

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1.29                        “Phase II/ III” means pivotal human clinical trials conducted at multiple sites, which are sufficiently powered and designed to establish safety and efficacy of one or more particular doses in patients being studied and to provide the statistical basis for marketing approval for the respective drug (for example, as described in 21 C.F.R. § 312.21, or similar clinical study legislation or guidelines in a country other than the United States).

 

1.30                        “Principal Investigator” means Prof. Jesus Prieto or any other person agreed by the Parties to replace him.

 

1.31                        “Product” means a AAV vector containing porphobilinogen deaminase (PBGD) manufactured by AMT or its Affiliates for use within the scope of the Development Plan.

 

1.32                        “Protocol” means the description of a Clinical Trial to be conducted under the Development Plan and all amendments thereto as the Joint Steering Committee may from time to time agree.  The Protocol, once determined by the Joint Steering Committee, will be attached to this Agreement as Exhibit 2.  Any amendments will be signed by the Parties and form a part of this Agreement.

 

1.33                        “Qualified Service Providers” means Third Parties engaged by Digna in the execution of its preclinical or clinical activities under the Development Plan, including CIMA, the Hospital and the Principal Investigator, and that (i) are discussed in the meeting of the Joint Steering Committee prior to its engagement and to which AMT has not imposed reasonable and substantiated objections (ii) meet the quality and other criteria imposed by Spanish legislation regarding Clinical Trial and/or the Spanish Regulatory Authorities for the execution of such activities and (iii) are, if other than CIMA, the Hospital and/or the Principal Investigator, under a written obligation between Digna and the Qualified Service Provider to comply with the obligations of Digna set forth in this Agreement regarding confidentiality, publication and ownership of Results as if they were a Party thereto or, if relating to the conduct of a Clinical Trial, have entered into a written agreement with Digna.

 

1.34                        “Receiving Party” means any Party receiving Confidential Information from another Party;

 

1.35                        “Regulatory Approval” means all approvals from Regulatory Authorities in any country in the Territory required lawfully to develop, clinically test, manufacture and market the Product in any such country, any establishment license application filed with the FDA or other Regulatory Authority to obtain approval of the facilities and equipment to be used to manufacture a Product, any Investigational New Drug or other investigational filing, including but not limited to any authorization for the import, manufacture and clinical testing of the Product (whether or not in filled and finished form), and any product pricing approvals where applicable.

 

1.36                        “Regulatory Authority” means any relevant national (e.g., the FDA, EU member states authorities), supra-national (e.g., the European Commission, the Council of the European Union, or the EMEA), or other relevant governmental entity in any jurisdiction of the world involved in the granting of Regulatory Approvals for pharmaceutical product.

 

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1.37                        “Results” means data, Know How, Materials, inventions, Patent Rights and all other information resulting from the activities by Digna or its Qualified Service Providers under this Agreement, excluding the Joint Patent Rights (as defined in the License Agreement), excluding any IP that has been developed prior to the Effective Date under the collaborative research programs jointly carried out by the Parties, excluding the AMT Background IP and excluding the CIMA Background IP.

 

1.38                        “Territory” means the world.

 

1.39                        “Third Party” means a party other than any of the Parties or any of their respective Affiliates.

 

ARTICLE 2                                                   DEVELOPMENT PLAN GENERAL

 

2.1                               Development Plan.  The activities assigned to each of Digna and AMT with regard to the preclinical and (once successful) clinical development of the Product are set forth in the Development Plan attached hereto as Exhibit 1.  The Development Plan sets forth in detail (i) the proposed overall program of development for the Product, including pre-clinical studies, toxicology, formulation, manufacturing, Clinical Trials and regulatory plans up to and including Phase I/II Clinical Trials, (ii) a summary of estimated costs expected to be incurred by each Party hereunder in performing its activities under the Development Plan and (iii) the timelines.  In general terms (i) AMT shall be responsible for the production of the Product for preclinical studies and Clinical Trials in accordance with all local and European legislation and the Good manufacturing practice (GMP) Guidelines., (ii) Digna shall be responsible for the execution of the preclinical studies and the drafting of the Protocol(s) and (iii) Digna shall act as Sponsor of the Clinical Trial.

 

2.2                               Updated Development Plan.  The Joint Steering Committee may decide to update the Development Program at a later date to revise or expand the Development Program, provided, however, that the Joint Steering Committee shall not assign additional activities to Digna unless (i) AMT agrees to increase its funding for the Development Plan accordingly or (ii) such additional activities are covered under a government grant or subsidy.

 

2.3                               Qualified Service Providers.  Digna may not subcontract its activities under the Development Plan to Third Parties unless such Third Party qualifies as a Qualified Service Provider as defined herein.

 

2.4                               Execution of Development Plan.  Digna and AMT shall use reasonable efforts to execute and substantially perform (or have performed by Qualified Service Providers) the activities assigned to each Party under the Development Program in accordance with the budget and timelines set forth in the Development Plan.

 

ARTICLE 3                                                   CLINICAL TRIAL

 

3.1                               General.  Digna shall act as the Sponsor of the Clinical Trial to be conducted by the Hospital and the Principal Investigator.

 

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3.2                               Separate Clinical Trial Agreement.  Digna shall enter into a separate Clinical Trial agreement with the Hospital, the Principal Investigator and each Qualified Service Provider under terms and conditions that are customary for the kind of services to be provided with regard to human clinical trials, wherein Digna shall impose on the Hospital, the Principal Investigator and other Qualified Service Providers the obligations as set forth in this Article 3, 4.3, 5.1, 9, 10 and 11 and wherein AMT shall be named as third party beneficiary..  AMT shall have the right to review such draft agreements before they are entered into to verify that the obligations of Hospital, Principal Investigator and other Qualified Service Providers as reflected in this Article 3, 4.3, 5.1, 9, 10 and 11 are properly included.

 

3.3                               Trial Site.  The Phase I/II Clinical Trial shall be conducted at the site of the Hospital under supervision of the Principal Investigator.  AMT may, however, require Digna to add additional Hospitals for the conduct of the Clinical Trials pursuant to Section 3.9 hereof.

 

3.4                               Obligations Digna.  Digna shall use reasonable efforts to procure compliance of the Hospital and the Principal Investigator conducting the Clinical Trial with all obligations imposed on Digna under this Agreement to the extent they relate to the conduct of the Clinical Trial as well as the obligations regarding confidentiality, publications and ownership of Results.

 

3.5                               Obligations AMT:  AMT shall share with Digna its expertise and experience in the field of conducting clinical trials with gene therapy products and shall assist Digna in the preparation of the investigator’s brochure, whereby Digna, however, acknowledges that Digna is, as sponsor of the Clinical Trials, responsible for the proper conduct thereof.  AMT shall be responsible for including in the IMPD all required information regarding the manufacture of the Product.  .

 

3.6                               Protocol.  Digna shall be in the lead as to the design of the Protocol for the Clinical Trial, provided that (i) the Protocol is in accordance with the Development Plan and (ii) furthermore provided that any Protocol and any deviation to the Protocol (whether or not instigated by the Regulatory Authorities in Spain) will be agreed with AMT before (re)submitting.  Digna will make its best efforts to ensure that the Hospital and the Principal Investigator shall conduct the Clinical Trial in accordance with: (i) the Protocol (once established by the Joint Steering Committee) for such Clinical Trial; (ii) the terms and conditions of the approval of the relevant ethics committee and (iii) instruction by AMT as to the handling and use of the Product.  The Principal Investigator and the Hospital shall not consent to any change in the Protocol requested by a relevant ethics committee without the prior written consent of Digna and AMT.

 

3.7                               Medical Ethical Approval.  Digna will make its best efforts to ensure that the Hospital and Principal Investigator shall not administer Product to any Clinical Trial subject and that no other clinical intervention mandated by the Protocol takes place in relation to any such Clinical Trial subject until it is satisfied that all relevant regulatory and ethics committee approvals have been obtained.

 

3.8                               Regulatory and GCP Compliance.  Digna shall comply with all laws and regulations applicable to the performance of the Clinical Trial including, but not limited to the GCP, the World Medical Association Declaration of Helsinki and any and all local applicable

 

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laws and regulations, as amended from time to time including but not limited to, where applicable, Spanish regulations regarding gene therapy, informed consent and privacy regulations and shall use reasonable efforts to ensure that the Hospital, the Principal Investigator and any other Qualifed Service Provider will comply with such laws and regulations as well..

 

3.9                               Use of Product.  Digna shall use reasonable efforts to ensure that Hospital and Principal Investigator will not use the Product for any purpose other than the conduct of the Clinical Trial and upon termination or expiration of this Agreement all unused Product shall, at AMT’s option, either be returned to AMT or disposed of in accordance with the Protocol.

 

3.10                        Recruitment.  Digna shall oblige the Hospital and Principal Investigator to use their best efforts to recruit the number of Clinical Trial subjects as set forth in the Development Plan (or, if deviating, the Protocol for such Clinical Trial) and shall conduct the Clinical Trial in accordance with the timelines set forth in the Development Plan and the Protocol.  If, for reasons other than AMT’s breach of its obligations under this Agreement, recruitment of Clinical Trial subjects for the Phase I/II Clinical Trial is proceeding at a rate below that, at the discretion of the Joint Steering Committee, required to enable the relevant timeline in the Development Plan to be met, AMT may by notice to Digna require recruitment by the Hospital to cease and/or to add additional hospitals as designed by the Joint Steering Committee, for the conduct of such Clinical Trial.  The terms of the Agreement shall thereafter relate to the number of Clinical Trial subjects who have been accepted for treatment in the Clinical Trial by the Hospital at the date of such notice and the funding as set forth in Article 8 hereof, to the extent it relates to such Clinical Trial, shall be allocated by Digna between the Hospital and such other hospitals involved in such Clinical Trial.

 

3.11                        Monitor.  Digna ensures that the Hospital and Principal Investigator shall permit the Monitor access to the records of Clinical Trial subjects for monitoring and source data verification, such access to be arranged at mutually convenient times and on reasonable notice.  Each of Digna and AMT will alert the Hospital and Principal Investigator promptly to significant issues (in the opinion of the Monitor) relating to the conduct of the Clinical Trial.  In the event that AMT reasonably believes there has been any research misconduct in relation to the Clinical Trial, Digna shall use reasonable efforts to procure that the Hospital and Principal Investigator shall provide all reasonable assistance to any investigation into any alleged research misconduct undertaken by or on behalf of AMT.  At its conclusion, AMT, Digna, the Hospital and Principal Investigator shall review the conduct of the Clinical Trial at the trial site set forth in Section 3.3 hereof, such review to take place within [**] months of trial site close-out.  Digna shall send copies of the reports of the Monitor to the members of the Joint Steering Committee.

 

3.12                        Samples.  Digna shall use reasonable efforts to procure that Hospital and Principal Investigator shall test any clinical samples required to be tested during the course of the Clinical Trial in accordance with the Protocol and at a laboratory that qualifies as a Qualified Service Provider.

 

3.13                        Follow-up.  Digna shall use reasonable efforts to provide that Hospital and Principal Investigator shall give follow-up to subjects for at least the time that is required under the relevant laws and regulations pertaining to (preclinical and clinical trials with) gene therapy products.

 

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3.14                        Not debarred.  Digna shall use its best efforts to ensure that neither the Investigator nor any other person involved in the conduct of the Clinical Trials is or has been debarred.

 

3.15                        No adverse activities.  Digna shall use reasonable efforts to procure that neither the Hospital nor the Principal Investigator shall during the term of this Agreement conduct any human clinical trial which might adversely affect the Hospital’s or Principal Investigator’s ability to perform its obligations under this Agreement within the timelines set forth in the Development Plan.  Digna, furthermore, will negotiate in order to procure a commitment by both the Hospital and the Principal Investigator in the sense that they shall not be engaged in human clinical trials involving gene therapy and/or enzyme replacement therapy and/or any product aimed at treatment or prevention of the Disorder, during the term of this Agreement.

 

ARTICLE 4                                                   REGULATORY FILINGS

 

4.1                               Filing of the IMPD.,  Digna shall file an IMPD for the Product with the Regulatory Authority in Spain.  Without prejudice to the fact that Digna will act as sponsor of the Clinical Trials AMT shall be responsible for the IMPD to the extent it relates to the Product and the manufacturing thereof.  Digna acknowledges that AMT’s information regarding the manufacture of the Product is highly sensitive and proprietary and that AMT will, to the extent allowed by the Regulatory Authorities in Spain, provide such information to the Regulatory Authority in Spain without allowing Digna access thereto.  Digna shall be responsible for the IMPD to the extent it relates to the information relating the Disorder and the Clinical Trials.  For the avoidance of doubt: AMT shall be the sole Party entitled to use, develop and commercialize the Product and to file any additional Regulatory filings for the Product, including an MAA.  To the extent required, Digna herewith assigns in advance (and shall, if such assignment in advance is not possible, upon first request of AMT assign), any and all of its rights that may be obtained by Digna by virtue of filing the IMPD, to AMT.

 

4.2                               Other regulatory interactions.  Digna shall, to the extent permitted by the Regulatory Authorities in Spain, act to communicate with the Regulatory Authority in Spain with regard to the Clinical Trials and the IMPD save for the part of the IMPD that relates to the Product and the manufacturing of the Product.  AMT shall act to communicate with the Regulatory Authorities with regard to the Product and the manufacturing of the Product.  No party will approach, consult and/or negotiate with regulatory authorities without an expressed consent from the other party.  Any regulatory authority interaction will be jointly prepared and agreed between Digna and AMT in advance of any such interactions (without prejudice to AMT’s legitimate interest to keep the information regarding the manufacture of the Product confidential and to minimize access by Digna thereto to the extent allowed by the relevant laws and regulations.

 

4.3                               Local ethical committee approvals.  Ethics Committee.  Digna shall use reasonable efforts to ensure that the Hospital and the Principal Investigator shall collaborate for obtaining and maintaining all approvals from the relevant local research ethics committee of the Hospital (so other than the IMPD) for the conduct of the Clinical Trial and that the Hospital and the Principal Investigator shall keep Digna and AMT fully apprised of the progress of ethics

 

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committee submissions and that they shall provide Digna with all correspondence relating to such submissions.

 

4.4                               Digna shall provide the members of the Joint Steering Committee with all information obtained by Digna from the Qualified Service Providers.

 

ARTICLE 5                                                   AUDIT

 

5.1                               Audit Rights.  AMT shall be entitled to have reasonable access to the facilities of Digna and its Qualified Service Providers (including the Hospital) during regular business hours with reasonable frequency (which shall not be in any case more than [**] per facility per organization) and upon reasonable advance notice and, with regard to each Qualified Service Provider, prior to the execution of the agreement between Digna and such Qualified Service Provider (pre-audit), at AMT’s own expense and during the term of this Agreement, to records and facilities of Digna and its Qualified Service Providers (including the Hospital) relating to the Development Program, but only to the extent reasonably necessary for AMT to ensure compliance by Digna and its Qualified Service Providers with the Development Plan, the Protocol, GCP and other applicable laws and regulations.  In no event shall personal data (as defined in the Spanish Data Protection Act), be disclosed to AMT.

 

ARTICLE 6                                                   MANUFACTURING

 

6.1                               Manufacturing and Supply Product.  AMT shall be solely responsible for the manufacture and supply of the Product for use in the activities under the Development Plan.  To the extent Product is to be used for Clinical Trial, AMT shall supply Product that meets the requirements of the Regulatory Authorities that are competent to obtain Regulatory Approval for the IMPD referred to in Section 4.1.  AMT may, in its sole discretion, subcontract with Third Parties for the manufacture, supply or packaging of the Product.  AMT shall not supply the Product directly to the Hospital without the prior written instruction of Digna to do so.

 

6.2                               AMT will be solely responsible for obtaining and maintaining all the necessary authorizations or clearances set forth in the national and supra-national legislation regarding the manufacturing of the Investigational Medicinal Product and shall provide Digna (or the Hospital directly) with sufficient quantities of Product to execute the preclinical work and/or the Clinical Trials, free of charge.

 

6.3                               AMT shall, upon request of Digna, provide reasonable assistance to Digna in order to comply with all the relevant obligations that are required in its condition of Sponsor as stated in the enforceable legislation, the regulation of clinical good practices or the obligations which may be required at any time by the Regulatory Authority and, if were the case, by the Hospital or the Principal Investigator provided, however, that Digna (and not AMT) shall be responsible that the Clinical Trials and other activities in the course of the development of the Product (other than the manufacture of the Product) is in compliance with applicable laws and regulations.

 

6.4                               DIGNA will have the right to reject the Product if it does not meet the quality, safety and stability specifications previously agreed by the Joint Steering Committee.

 

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6.5                               The Product will be transported by AMT (at AMT’s expense and under AMT’s responsibility) to the clinical site of the Hospital referred to in Section 3.3 hereof or at such other place as Digna and AMT may jointly decide.

 

ARTICLE 7                                                   JOINT STEERING COMMITTEE

 

7.1                               Joint Steering Committee.

 

7.1.1                     Formation and Composition.  Forthwith upon signing this Agreement, Digna and AMT will establish a committee to oversee and manage the activities pursuant to this Agreement (the “Joint Steering Committee”).  The Steering Committee shall be composed of [**] representatives appointed by Digna and [**] representatives appointed by AMT, provided that the size of the Joint Steering Committee may be increased by unanimous agreement of the Joint Steering Committee members so long as the membership has equal representation by Digna and AMT.  The initial representatives on the Joint Steering Committee of Digna shall be [**], and AMT’s initial representatives on the Joint Steering Committee shall be [**] shall designate one (1) of its representatives on the Joint Steering Committee to act as Chair, and the Joint Steering Committee shall appoint one (1) of its members to act as Secretary.  Members of the Joint Steering Committee may be represented at any meeting by another member of the Joint Steering Committee or by a deputy.  Each Party may change one or more of its representatives to the Joint Steering Committee at any time, provided that any such representatives will be senior officers and/or managers of the respective Party, its Affiliates, divisions or business units.  Additionally, each of the Parties may appoint a non-voting special advisor to the Joint Steering Committee.  Each of Parties shall bear all expenses of its respective representatives and other participants in connection with Joint Steering Committee participation, including in connection with the attendance of any meetings thereof.

 

7.1.2                     Functions The Joint Steering Committee shall perform the following functions: (a) coordinate the activities of the Parties and the Qualified Service Providers under the Development Plan; (b) recommend changes to the Development Plan, if applicable; (c) establish scientific and development teams for the execution of the Development Program as it sees fit, and settle any disputes or disagreements that are unresolved by any such teams; (d) serve as the governing body of all activities under this Agreement; and (e) perform such other functions as appropriate to further the purposes of the collaboration under this Agreement as determined by the Parties.

 

7.1.3                     Meetings; Action by Written Consent.  The Joint Steering Committee will meet as needed, but not less than [**], and the members shall determine the form (e.g., in-person, telephone or video conference), timing, frequency and location of meetings.  In principle, the meetings shall alternately take place in Amsterdam and Madrid.  Representatives of either AMT or Digna or their Affiliates who are not members of the Joint Steering Committee may attend meetings of the Joint Steering Committee as agreed to by a representative member of the other Party.  Any action required or permitted to be taken at any meeting of the Joint Steering Committee may be taken without a meeting if all members of the Joint Steering Committee consent thereto in writing, and such writing is filed with the minutes of proceedings of the Joint Steering Committee.

 

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7.1.4                     Decision Making.  Any approval, determination or other action agreed to by unanimous consent of the members of the Joint Steering Committee or their deputies present at the relevant Joint Steering Committee meeting shall be the approval, determination or other action of the Joint Steering Committee, provided at least one representative of each of Digna and of AMT are present at such meeting.  The Joint Steering Committee will work in good faith to resolve any disputes that may arise among its members, provided that in the event any deadlock cannot be resolved in good faith by the Joint Steering Committee during a [**] business day period following initial submission of any approval, determination or other action to the Joint Steering Committee, then the issue shall be submitted to the Chief Executive Officers of AMT and Digna jointly who shall work in good faith to resolve any such dispute within [**] business days.  The joint decision of the Chief Executive Officers of AMT and Digna shall be deemed the approval, determination or action of the Joint Steering Committee.  Any issue that cannot be resolved in good faith by the Chief Executive Officers of AMT and Digna within [**] business days after the Joint Steering Committee has submitted the issue to them, shall be submitted to arbitration in accordance with Article 17 of this Agreement.

 

7.1.5                     Minutes.  The Joint Steering Committee shall keep accurate minutes of its deliberations which shall record all proposed decisions and all actions recommended or taken.  The Secretary shall be responsible for the preparation of draft minutes.  Draft minutes shall be sent to all members of the Joint Steering committee within [**] business days after each meeting.  All records of the Joint Steering Committee shall at all times be available to both Digna and AMT.

 

ARTICLE 8                                                   FUNDING OF DEVELOPMENT PROGRAM

 

8.1                               Development Program.  In consideration for the execution of the Development Program by Digna and its Qualified Service Providers (including the Hospital), AMT shall pay to Digna an aggregate amount of € 1,000,000 (one million euro) to be paid in installments as follows:

 

	
Upon signature of this Agreement
    	
 
    	
[**]
    	
 
    
	
[**]
    	
 
    	
[**]
    	
 
    
	
[**]
    	
 
    	
[**]
    	
 
    
	
[**]
    	
 
    	
[**]
    	
 
    
	
Total
    	
 
    	
€1,000,000
    	
 
    

 

8.2                               The funding set forth in Section 8.1 does not take into account the costs of Phase II/III Clinical Trials which are not within the scope of this Agreement and are subject to further agreement between the Parties (acknowledging that AMT may decide to have the Phase II/III Clinical Trials conduct by Third Parties).  The funding set forth in Section 8.1, furthermore, does not take into account any preclinical work or Clinical Trials not described in the Development Plan that the Joint Steering Committee may decide to execute in order to facilitate the filing for Regulatory Approvals for the Product.  In the event that the Joint Steering Committee decides to

 

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have such additional preclinical work or Clinical Trials conducted by Digna or its Qualified Service Providers, the Parties shall in good faith agree on the amount of the additional funding to be paid by AMT to Digna.

 

8.3                               Payment to Digna.  All amounts under this Article 8 shall be paid by AMT to Digna within [**] days after receipt of the respective invoice.  Digna shall be responsible for the apportionment of the sums paid to Digna hereunder to the Qualified Service Providers engaged by Digna in the execution of the Development Plan pursuant to the agreements executed between Digna and such Qualified Service Providers and for payment of the same according to that apportionment.

 

8.4                               Taxes.  All payments to Digna under the terms of the Agreement are expressed to be exclusive of value added tax howsoever arising and AMT shall, if required, pay to Digna in addition to those payments all value added tax for which Digna is liable to account in relation to any supply made or deemed to be made for value added tax purposed to this Agreement on receipt of a tax invoice or invoices from Digna.  The Parties shall in such event closely cooperate to have such tax amounts refunded to AMT under applicable tax treaties.

 

Transfer of amounts.  Payments made to Digna under this Agreement shall be made by wire transfer to the following account of Digna:

 

Bank: BBVA,
 Bank address: Avda.  Carlos III, 33, 31004 Pamplona 
 Swift Code: BBVAESMMXXX 
 IBAN: ES89 0182 5000 8802 0156 0335

 

or any other bank account that may be notified by Digna to AMT from time to time.

 

8.5                               EU Funding.  The Parties acknowledge that they have applied for a so called European FP7 grant to cover (part of) the costs of the Clinical Trials.  Digna acknowledges that the terms and conditions of the consortium agreement to be entered into between the partners to that FP7 project should not negatively affect the rights of AMT under this Agreement.  Therefore, Digna and AMT shall negotiate and agree with all partners under said FP7 project clauses in the consortium agreement to the effect that Foreground (as defined in the FP7 grant agreement) generated by such partners shall be transferred to AMT.  Any Foreground generated by Digna and [Hospital] under the FP7 project shall be considered Results as defined in this Agreement and AMT shall be the exclusive owner thereof.

 

ARTICLE 9                                                   SOPS / REPORTING / RESULTS

 

9.1                               SOPs.  Digna shall provide AMT with its own Standard Operation Procedures (SOPs) regarding the (organization) of preclinical studies and Clinical Trials within [**] days after the Effective Date.  Digna, furthermore, shall give AMT the right to review the SOPs of each Qualified Service Provider that Digna wishes to engage for the execution of its activities.  AMT acknowledges that such SOPs are proprietary and confidential information of the respective Qualified Service Provider.

 

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9.2                               Report / Data.  Digna shall within [**] months after completion of each activity under the Development Plan, provide the members of the Joint Steering Committee (or ensure that the Qualified Service Provider provides the members of the Joint Steering Committee) with a written report describing in sufficient detail the methodology used, the Results generated, an analysis of the Results and conclusions drawn from the Results.

 

9.3                               Keeping data and records.  Digna shall ensure that the Qualified Service Provider that execute the activities assigned to Digna under the Development Plan prepares and provides AMT with a database of accumulated data from all preclinical studies and/or Clinical Trials of the Product and of adverse information for the Product.  AMT shall keep the trial master file with the essential documents relating to the Clinical Trial as well as any relevant records for at least [**] years after the completion of such activity / Clinical Trial in accordance with the most recent guidelines and regulations on clinical trials in the field of gene therapy (including the detailed EU guidelines on good clinical practice specific to advanced therapy medicinal products of December 3, 2009).  The documents to be included in the trial master file shall, for each preclinical study and/or Clinical Trial, be provided by Digna to AMT within [**] months after completion of the final report relating to such preclinical study and/or Clinical Trial.

 

9.4                               Access.  To the extent permitted by the Spanish Data Protection Act, Digna shall ensure that all Qualified Service Providers and Affiliates provide AMT access to all such data, to the extent necessary to meet or comply with any regulations or other requirements of the FDA, EMEA or other Regulatory Authorities, in each case with respect to Regulatory Approvals or other regulatory purposes

 

9.5                               Ownership of Results.  AMT shall exclusively own and have title, right and interest in and to the Results.  AMT may, at its discretion, file patent applications for the Results in its name and at its expense.

 

ARTICLE 10                                            CONFIDENTIALITY / PUBLICATION

 

10.1                        General.  Each Party undertakes to keep strictly confidential the Confidential Information and to use it only for the purpose of this Agreement.

 

10.2                        No disclosure / restriction to use.  Each Receiving Party undertakes to not disclose the Confidential Information to any third party except to those of its officers and employees who need to have access to the same.  Each Party shall, before disclosing any Confidential Information to any of its officers or employees, make each such person aware of such restrictions and shall procure that such persons comply with such restrictions.  If the Receiving Party wishes to disclose Confidential Information to any consultant or advisor who is not an officer or employee it shall obtain the Disclosing Party’s prior written consent and shall furnish to the Disclosing Party with a confidentiality agreement signed by such consultant or advisor on the same terms and conditions of this Agreement.

 

10.3                        Exceptions.  The obligations to maintain confidentiality and to respect the restriction of the use shall not apply where, as properly evidenced by documentation: (a) is or becomes patented, published or otherwise becomes publicly known other than by acts of the Party obligated not to disclose such Confidential Information in contravention of this Agreement;

 

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(ii) can be shown by written documents to have been disclosed to the Receiving Party by a Third Party, provided, that such information was not obtained by such Third Party directly or indirectly from the other Party under this Agreement; (iii) prior to disclosure under this Agreement, was already in the possession of the Receiving Party; or (iv) can be shown by written documents to have been independently developed by the Receiving Party without use of the other Party’s Confidential Information or breach of any of the provisions of this Agreement.

 

10.4                        Permitted disclosure.  Notwithstanding the above obligations of confidentiality and non-use a Recipient Party may:

 

10.4.1              disclose Confidential Information to a Regulatory Authority as reasonably necessary to obtain Regulatory Approval in a particular jurisdiction to the extent consistent with the licenses granted under terms of this Agreement; and

 

10.4.2              disclose Confidential Information: (a) to the extent such disclosure is reasonably necessary to comply with the order of a court; or (b) to the extent such disclosure is required to comply with a legal requirement, including to the extent such disclosure is required in publicly filed financial statements or other public statements under rules governing a stock exchange (e.g.  the rules of the Netherlands, United States Securities and Exchange Commission, NASDAQ, NYSE, UKLA or any other stock exchange on which securities issued by either Party may be listed); provided, to the extent possible bearing in mind such legal requirements and subject to the next subsequent sentence of this Section 10.4, such Party shall provide the other Party with a copy of the proposed text of such statements or disclosure [**] Business Days in advance of the date on which the disclosure is to be made to enable the other Party to review and provide comments, which shall be followed as long as they are reasonable, unless a shorter review time is agreed.  If the compliance with a legal requirements requires filing of this Agreement, the filing Party shall to the extent possible seek confidential treatment of portions of this Agreement from the relevant competent authority and shall provide the other Party with a copy of the proposed filings at least [**] Business Days prior to filing for the other Party to review any such proposed filing.  Each Party agrees that it will obtain its own legal advice with regard to its compliance with legal requirements and will not rely on any statements made by the other Party relating to such legal requirements

 

10.4.3              disclose Confidential Information by filing or prosecuting Patent Rights, the filing or prosecution of which is contemplated by this Agreement, without violating the above secrecy provision; it being understood that publication of such filings occurs in some jurisdictions within [**] months of filing, and that such publication shall not violate the above secrecy provision;

 

10.4.4              disclose Confidential Information to such Recipient Party’s Affiliates, contractors (including clinical researchers) distributors, licensee’s, agents, consultants, as such Recipient Party reasonably determines is necessary to receive the benefit of this Agreement or to fulfill its obligations pursuant to this Agreement; provided, however, any such persons must be obligated to substantially the same extent as set forth in Section 10.2 to hold in confidence and not make use of such Confidential Information for any purpose other than those permitted by this Agreement;

 

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10.4.5              disclose Confidential Information , only to the extent reasonably required, (i) to its actual or potential investment bankers; (ii) to existing and potential investors in connection with an offering or placement of securities for purposes of obtaining financing for its business and to actual and prospective lenders for the purpose of obtaining financing for its business; and (iii) to a bona fide potential acquirer or merger partner for the purposes of evaluating entering into a merger or acquisition, provided, however, any such persons must be obligated to substantially the same extent as set forth in Section 10.2 to hold in confidence and not make use of such Confidential Information for any purpose other than those permitted by this Agreement; and

 

10.4.6              Disclose Confidential Information to its legal advisers for the purpose of seeking advice.

 

ARTICLE 11                                            PUBLICATION

 

11.1                        Publication of Background IP and Confidential Information.  Neither Digna nor AMT shall submit for written or oral scientific publication any manuscript, abstract or the like which includes Confidential Information or Background IP of the other Party (including joint IP) without first obtaining the prior written consent of the other Party, which consent shall not be unreasonably withheld and Digna shall ensure best reasonable efforts to procure that CIMA Parties comply with the provisions of this Article 11.  The contribution of each Party, if any, shall be mentioned in all publications or presentations by acknowledgement or co-authorship, whichever is appropriate.

 

11.2                        Publication of Results.  The Party wishing to submit any manuscript, abstract or the like regarding the Results for publication shall provide the other Party (the “Reviewing Party”) with a copy of any proposed publication which contains Results to the Reviewing Party at least [**] days before the date of submission of the proposed publication to any publisher.

 

11.3                        Within [**] days of receipt of the proposed publication under Section 11.2, the Reviewing Party shall either:

 

(a)                                 provide written consent to the proposed publication; or

 

(b)                                 reasonably require to remove the Reviewing Party’s Confidential Information or Background IP whereby AMT shall always have the right to remove Confidential Information regarding its production and manufacturing processes;

 

(c)                                  reasonably require that the proposed publication be delayed or amended (without altering the scientific meaning of the publication) to enable a patent application to be filed regarding any Results contained in the proposed publication.  The delay or amendment required by the Reviewing Party shall be reasonable and in any event, any delay required shall be no longer than three months from the date the other Party provided a copy of the proposed publication to the Reviewing Party.; and/or

 

(d)                                 provide comments and/or amendments in relation to the proposed publication which will be reasonably considered and incorporated by the other party into the publication.

 

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11.4                        In the event of any dispute regarding the proposed publication, the Parties shall resolve such differences in good faith through the Joint Steering Committee as provided for in Article 7.

 

11.5                        If within [**] days of receipt of the proposed publication the Reviewing Party does not:

 

11.5.1              provide consent under Section 11.3(a); or

 

11.5.2              request a delay or amendment under Section 11.3(c),

 

the Reviewing Party shall be deemed to have given consent for the proposed publication for the purposes of Section 11.5(a), always provided that no Party is entitled to publish Confidential Information or Background IP of the other Party, even in absence of a reasonable request as referred to in Section 11.3(b).

 

11.6                        Digna ensures that the CIMA Parties shall comply with this Article 11 as if they were a Party thereto.

 

11.7                        Digna shall use its best efforts to include in the agreements with the Qualified Service Providers clauses regarding publications rights that substantially resemble the ones set forth in this Article 11, including a reasonable review time by Digna (and consequently, AMT) of any proposed scientific publication on the Clinical Trial by such Qualified Service Provider.

 

ARTICLE 12                                            REPRESENTATIONS AND WARRANTIES / INDEMNIFICATION / INSURANCE

 

12.1                        Mutual Warranties.  Each Party represents and warrants to the other Parties that:

 

(a)                                 It has full power to extend the granted hereunder and perform its obligations hereunder;

 

(b)                                 It has full power and authority to enter into this Agreement and has taken all necessary action on its part required to authorize the execution and delivery of this Agreement;

 

(c)                                  The execution, delivery and performance of this Agreement and its compliance with the terms and provisions hereof does not conflict with, or result in a breach of any of the terms and provisions of, or constitute a default under any agreement to which any Party is a party; and

 

(d)                                 The execution, delivery and performance of this Agreement by each Party does not require the consent, approval or authorization of or notice, filing or registration with Regulatory Authority.

 

12.2                        Indemnification by AMT.  AMT indemnifies and holds harmless Digna, its Qualified Service Providers (including the Hospital and the Principal Investigator) and their employees against all claims and proceedings (to include any settlements or ex gratia payments

 

17

 

made with the consent of the Parties hereto and reasonable legal and expert costs and expenses) made or brought (whether successfully or otherwise) by or on behalf of Clinical Trial subjects and (or their dependants) against Digna or a Qualified Service Provider or their employees for personal injury (including death) to Clinical Trial subjects arising out of or relating to the administration of the Product under investigation or any clinical intervention or procedure provided for or required by the Protocol to which the Clinical Trial subjects would not have been exposed but for their participation in the Clinical Trial.  The above indemnity by AMT shall not apply to any such claim or proceeding (i) to the extent that such personal injury (including death) is caused by the negligent or willful misconduct of Digna or a Qualified Service Provider, their employees or agents and/or (ii) to the extent that such personal injury (including death) is caused by the failure of a Qualified Service Provider or its employees to conduct the Clinical Trial in accordance with the Protocol and/or GCP,.

 

12.3                        Indemnification by Digna.  Digna, as Sponsor, indemnifies and holds harmless AMT and its employees against all claims and proceedings (to include any settlements or ex gratia payments made with the consent of the Parties hereto and reasonable legal and expert costs and expenses) made or brought (whether successfully or otherwise) (i) to the extent that such personal injury (including death) is caused by the gross negligent or willful misconduct of Digna, a Qualified Service Provider or their employees and/or (ii) to the extent that such personal injury (including death) is caused by the failure of Digna or a Qualified Service Provider to conduct the Clinical Trial in accordance with the Protocol and/or GCP.

 

Digna’s liability arising out or in connection with any breach of this contract or any act or omission of Digna or its Qualified Service Providers in connection with the Clinical Trial shall, save for willful misconduct or gross negligence of Digna or its Qualified Service Providers, in no event exceed the amount of fees paid by AMT according to clause 8.

 

12.4                        The indemnified Party hereunder shall as soon as reasonably practicable following receipt of notice of such claim or proceeding, notify the indemnifying Party hereunder in writing of a claim and shall, upon the indemnifying Party’s request permit the indemnifying Party to have full care and control of the claim or proceeding using legal representation of its own choosing.

 

12.5                        Insurance.  Each of AMT and Digna will take out appropriate insurance cover their potential liability under this Article 12 (including, Digna in its capacity of Sponsor of the Clinical Trials, an clinical trial insurance as required by the Spanish Regulatory Authorities).  Each Party shall produce to the Qualified Service Provider and to each other on request, copies of insurance policies or other evidence thereof together with evidence that such policies remain in full force and effect.  The terms of any insurance or the amount of cover shall not relieve AMT or Digna of any liabilities under this Agreement.

 

ARTICLE 13                                            TERM / TERMINATION

 

13.1                        Term.  This Agreement shall commence on the Effective Date and shall continue until completion of the Development Plan, save for premature termination in accordance with this Article 13.

 

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13.2                        Termination.  Notwithstanding any other provision hereof, each Party may forthwith terminate this Agreement:

 

(a)                                 as a result of a material breach or default in the performance of any obligation, condition or covenant of this Agreement by the other Party or Parties, if such default or noncompliance shall not have been remedied within [**] days after receipt by the defaulting Party of a notice thereof from the other Party (whereby it is agreed that failure to comply with the Protocol or GCP by Hospital and/or the Principal Investigator is deemed to be a material breach by Digna); or

 

(b)                                 if the other Party is declared insolvent or, whether voluntarily or involuntarily, is declared bankrupt, or if such Party becomes permanently unable to perform its obligations hereunder for reasons other than suspension of payment or bankruptcy, such as, for example, liquidation, dissolution or winding-up.

 

13.3                        Termination by AMT for other reasons.  AMT may, furthermore, terminate this Agreement upon two (2) months written notice in the event that the Joint Steering Committee (subject to Section 7.1.4.) decides to cease further development of the Product for safety, efficacy or technical feasibility or commercial reasons.

 

13.4                        Effect of Termination.

 

13.4.1              Effects of termination by AMT pursuant to Section 13.2.  In the event of termination by AMT pursuant to Section 13.2 the following applies (notwithstanding AMT’s rights by law or equity):

 

(a)                                 AMT remains sole owner of the Results.

 

(b)                                 The Development Plan will be terminated as per the earliest possible date and the funding obligations of AMT as set forth in Article 8 will terminate.  AMT will be free to further develop and Commercialize by itself or with Third Parties at its discretion and is released from any further payments to Digna under this Agreement.

 

13.4.2              Effects of termination by Digna pursuant to Section 13.2 or by AMT pursuant to Section 13.3.  In the event of termination by Digna pursuant to Section 13.2 of by AMT pursuant to Section 13.3, the following applies (notwithstanding Digna’s rights by law or equity):

 

(a)                                 AMT shall assign to Digna co-ownership of the Results.  Digna shall be exclusively entitled to use and Commercialize the Results on a royalty-free basis for the further development and Commercialization of a product for the treatment or prevention of the Disorder.  This right is with the right to sublicense.  Each of AMT and Digna may, on a royalty-free and non-exclusive basis, without the right to sublicense, use the Results for the treatment or prevention of disorders other than the Disorder.  User rights of the Joint Patent Rights in the event of termination of this Agreement are set forth in the License Agreement.

 

(b)                                 AMT shall cease development, manufacture and Commercialization of Products as treatment or prevention of the Disorder;

 

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(c)                                  The Development Plan will be terminated as per the earliest possible date.  The funding obligations of AMT as set forth in Article 8 will terminate as per the effective date of termination of this Agreement.

 

(d)                                 AMT will, if so requested by Digna, enter into good faith discussions with Digna regarding the terms and conditions under which AMT, or a third party engaged by AMT, would be willing to manufacture the Product for Digna or its sublicensee.

 

13.5                        Surviving Articles.  Articles 10, 11, 12, 16 and 17 shall survive expiration or termination of this Agreement for any reason.

 

ARTICLE 14                                            ASSIGNMENT

 

Save as otherwise provided in this Agreement no Party shall without the prior written consent of the other assign the benefit and/or burden of this Agreement provided always that AMT may assign this Agreement to an Affiliate of AMT or any purchaser of the whole or part of AMT’s assets or to a company with which AMT is merging, provided that such Affiliate, purchaser or merger company undertakes to Digna to be bound by the terms of this Agreement.

 

ARTICLE 15                                            NOTICES

 

Any notices required or provided under this Agreement shall be in writing and shall be given by facsimile or by certified mail addressed to the applicable Party as set out below:

 

AMT

 

Mr. Piers Morgan 
 PO Box 22506 
 1100DA Amsterdam 
 The Netherlands

 

Digna

 

Mr. Pablo Ortiz Betés
 DIGNA BIOTECH S.L.AVDA.  PÍO XII, 22, OFICINA 2.31008 PAMPLONA,
 NAVARRA
 Spain

 

ARTICLE 16                                            GOVERNING LAW

 

The validity construction and performance of this Agreement shall be governed by the laws of The Netherlands.

 

ARTICLE 17                                            JURISDICTION

 

All disputes arising out of or in connection with this Agreement shall be finally settled under the Rules of Arbitration of the International Chamber of Commerce by one or more arbitrators

 

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appointed in accordance with said Rules.  The arbitration to take place in Paris and to be conducted in English.

 

ARTICLE 18                                            MISCELLANEOUS

 

18.1                        Interpretation.

 

18.1.1              If an ambiguity or a question of intent or interpretation arises with respect to this Agreement, this Agreement shall be construed as if drafted jointly by the Parties and no presumption or burden of proof shall arise favoring or disfavoring any Party by virtue of the authorship of any provisions of this Agreement.

 

18.1.2              Whenever the context may require, any pronoun shall include the corresponding masculine, feminine and neuter forms.  The words “include”, “includes” and “including” shall be deemed to be followed by the phrase “without limitation.” The word “will” shall be construed to have the same meaning and effect as the word “shall.” Unless the context requires otherwise, (A) any definition of or reference to any agreement, instrument or other document herein shall be construed as referring to such agreement, instrument or other document as from time to time amended, supplemented or otherwise modified (subject to any restrictions on such amendments, supplements or modifications set forth herein or therein), (B) any reference to any laws herein shall be construed as referring to such laws as from time to time enacted, repealed or amended, (C) any reference herein to any Person shall be construed to include the Person’s successors and assigns, (D) the words “herein”, “hereof and “hereunder”, and words of similar import, shall be construed to refer to this Agreement in its entirety and not to any particular provision hereof, (E) any reference herein to the words “mutually agree” or “mutual written agreement” shall not impose any obligation on either Party to agree to any terms relating thereto or to engage in discussions relating to such terms except as such Party may determine in such Party’s sole discretion and; (F) all references herein to Articles, Sections or Schedules shall be construed to refer to Articles, Sections and Schedules of this Agreement.

 

18.2                        Force Majeure.  Neither Party shall be held liable or responsible to the other Party nor be deemed to have defaulted under or breached this Agreement for failure or delay in fulfilling or performing any term of this Agreement when such failure or delay is caused by or results from causes beyond the reasonable control of the affected Party, including fire, floods, embargoes, war, acts of war (whether war is declared or not), insurrections, riots, civil commotions, strikes, lockouts or other labor disturbances, acts of God or acts, omissions or delays in acting by any governmental authority or the other Party; provided, however, that the Party so affected shall use Commercially Reasonable Efforts to avoid or remove such causes of non-performance, and shall continue performance hereunder with reasonable dispatch wherever such causes are removed.  Each Party shall provide the other Parties with prompt written notice of any delay or failure to perform that occurs by reason of force majeure.  The Parties shall mutually seek a resolution of the delay or the failure to perform in good faith.

 

18.3                        Severability.  Each Party hereby agrees that it does not intend to violate any public policy, statutory or common laws, rules, regulations, treaty or decision of any government agency or executive body thereof of any country or community or association of countries.  Should one or more provisions of this Agreement be or become invalid, the Parties hereto shall

 

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substitute, by mutual consent, valid provisions for such invalid provisions which valid provisions in their economic effect are sufficiently similar to the invalid provisions that it can be reasonably assumed that the Parties would have entered into this Agreement with such valid provisions.  In case such valid provisions cannot be agreed upon, the invalidity of one or several provisions of this Agreement shall not affect the validity of this Agreement as a whole, unless the invalid provisions are of such essential importance to this Agreement that it is to be reasonably assumed that the Parties would not have entered into this Agreement without the invalid provisions.

 

18.4                        Exhibits.  The Exhibits to this Agreement form an integral part of this Agreement.

 

18.5                        Entire Agreement.  This Agreement (including the Exhibits thereto) contains the entire understanding of the Parties with respect to the subject matter hereof and supersedes all prior or contemporaneous oral or written agreements of the Parties with respect to the subject matter hereof, including the Previous Agreements.  This Agreement may be amended, or any term hereof modified, only by a written instrument duly executed by both Parties hereto.

 

18.6                        Headings.  The captions to the several Articles and Sections hereof are not a part of this Agreement, but are merely guides or labels to assist in locating and reading the several Articles and Sections hereof.

 

18.7                        Independent Contractors.  It is expressly agreed that the Parties to this Agreement shall be independent contractors and that the relationship between the Parties shall not constitute a partnership, joint venture or agency.  Neither Party shall have the authority to make any statements, representations or commitments of any kind, or to take any action, which shall be binding on the other(s), without the prior consent of the other Parties to do so.

 

18.8                        Waiver.  Except as expressly provided herein, the waiver by either Party hereto of any right hereunder or of any failure to perform or any breach by the other Party shall not be deemed a waiver of any other right hereunder or of any other failure to perform or breach by said other Party, whether of a similar nature or otherwise, nor shall any singular or partial exercise of such right preclude any further exercise thereof or the exercise of any other such right.

 

18.9                        Counterparts.  This Agreement may be executed in one more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument.

 

18.10                 Benefit.  Nothing in this Agreement or the agreements referred to herein, expressed or implied, shall confer on any person other than the Parties hereto or thereto, or their respective permitted successors or assigns, any rights remedies, obligations or liabilities under or by reason of this Agreement, the agreements referred to herein, or the transactions contemplated herein or therein.

 

18.11                 Further Assurances.  Each Party shall, as and when requested by another Party, do all acts and execute all documents as may be reasonably necessary to give effect to the provisions of this Agreement.

 

[Remainder of page intentionally left blank]

 

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IN WITNESS WHEREOF, the Parties have executed this Collaborative Development Agreement as of the date first written above.

 

 

	
/s/ Pablo Ortiz Betés
    	
 
    	
 
    
	
Digna Biotech S.L.
    	
 
    	
 
    
	
By: Pablo Ortiz Betés
    	
 
    	
 
    
	
Title: Director General
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
/s/ Piers Morgan
    	
 
    	
 
    
	
Amsterdam Molecular Therapeutics (AMT) B.V.
    	
 
    	
 
    
	
By: Piers Morgan
    	
 
    	
 
    
	
Title: Chief Financial Officer
    	
 
    	
 
    

 

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EXHIBIT 1

DEVELOPMENT PLAN

 

Project Plan:

 

The aim of this collaboration is to develop an AIP product and to deliver a data package for the product that is suitable for the submission and approval by the European and North American regulatory authorities.  The product should be approved for the general treatment of AIP (both males and females.) The quality of the project has to comply with the national and internationally accepted quality standards.  A quality plan, defining the CRO selection, quality inspections, auditing etc will be agreed between the parties.  It is acknowledged by the Parties that the timelines set out below were drafted at the beginning of the negotiation process on this Agreement and the License Agreement and that, in view of the fact that several months passed since then, the Joint Steering Committee will update the timelines as soon as possible after the signature of this Agreement.

 

	
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Conditions and Specifications

 

PoC in pre-clinical models

 

·                  PoC in rodent disease model

·                  PoC in non-human primates, based on agreed protocol

·                  Go-no-go

·                  efficacy in rodent disease model

·                  10% hepatic transduction and/or PBDG levels [**] fold above normal in rodents

·                  10% hepatic transduction in non-human primates

 

GLP Toxicology

 

·                  Scientific advice from a regulatory body (AEMPS and/or EMA) for safety and toxicology package (duration, number of species, biodistribution, inclusion of immunosuppressants, risk of integration, germ line transmission)

·                  GLP toxicology study in rodents rats or mice (transduction will be compared between mice and rats, only if transduction levels are equal in rats to the transduction levels in mice, rats will be used), 180 days according to relevant EU guideline (EMEA/CHMP/GTWP/125459/2006) with interim sacrifices for acute toxicity [**], and delayed toxicity at early time point [**].  The need for an additional late time point [**] will be discussed.  Biodistribution studies (including gonadal tissues) should provide data on all organs, whether target or not, needs Scientific advice.

·                  Toxicology data in a non-rodent species, using the route of administration intended in the clinic duration similar to rodent study, including bio-distribution (including gonadal tissues) and efficacy endpoints.  This work is not included in the amount payable by AMT to DIGNA under section 8.1.  Costs hereof will be agreed by the Joint Steering Committee and will be funded by AMT.  Needs Scientific advice.  Details to be agreed by the Joint Steering Committee.

·                  GLP germline transmission in female and maternal transmission study in mice, according to the relevant European guidelines, will be conducted in case DNA is found in gonadal tissue.  Details to be agreed by the Joint Steering Committee.  (AMT may decide to conduct additional germline transmission in female and maternal transmission study in mice even if these are not strictly required for the Phase I/II trial, in such case, AMT, at its own choice, would have the option to fund such a study and DIGNA will ensure that such a study is done as agreed).

·                  GLP germ line transmission study in male rabbits (duration exceeding [**] cycles of spermatogenesis, [**]) will be conducted at additional cost.  (The quotation is required prior the final contract signature).

 

Toxicology study design will take into account:

·                  Identification of potential target organs of biological activity (for efficacy studies- i.e.  liver) and of potential target organs of toxicity,

·                  Eventual concomitant medication (e.g.  immunosuppressants, standard co-medication),

·                  Environmental risk/shedding, has to be included in the tox studies.  The Joint Steering Committee will evaluate and agree whether this would be required for the for Phase I/II trial

 

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·                  Analysis of appropriateness of surrogate markers of efficacy/safety,

·                  Any other relevant issues as agreed by the Joint Steering Committee.

 

Deliverable: Toxicology study report suitable for the submission the regulatory authority.

 

Observational, pre-intervention study/studies

 

·                  DIGNA and AMT agree on the need of good quality patient’s data (clinical and biochemical) before entering the interventional study in order to adequately assess the efficacy of the product.  For this reason, patient’s to be included in the Phase I/II clinical trial will be followed for a period between [**] months before entering into the trial.  The type of data to be collected, clinical and analytical, will be agreed by the Joint Steering Committee.

 

·                  Little is known of the natural history of this disease.  The medical history, phenotypic presentation, natural evolution of AIP patients has to be explored and documented (for the ‘group of AIP patients’) over an adequate time period.  In addition, a baseline against which to measure intra-individual post-administration efficacy and safety has to be established per individual study subject.  Main investigator of University Clinic will conduct a observational preparatory study to provide baseline information on the course of the disease by recording episodes AIP, abdominal pain, hospitalizations, extent of any possible known or unknown to be related to AIP symptomatology, incidence of (adverse) clinical events per year, etc., sufficient to provide a clinical picture to obtain a baseline data and to determine how efficacy will be show during the trial.  Also, to allow for inclusion of [**] eligible and willing subjects into the subsequent interventional trial, a sufficient number of subjects needs to included in the observational preparatory study (not everybody would be suitable or willing to progress).  The Joint Steering Committee will evaluate and agree how it can best ensure that sufficient number of subjects is included.

 

·                  The period of observation of the first observational trial should be at an estimated minimum of [**] months on an individual basis, and at least [**] months for the group/cohort (of to-be treated subjects) average.  In parallel to the intervention study, subjects entered into the observational study but not enrolled in the intervention study should continue in the observational study up to [**] months.

 

·                  Observational study needs to comply with the nationally and internationally accepted standard, to make sure that the data are suitable for the regulatory submission for marketing authorisation.  This will be done if so requested by AMT at an additional cost of [**] euros.  The following conditions should be met:

·                  The study should conform to all industry standards, to guidance of Institutional Review Board/Independent Ethics Committee (“IRB/IEC”) approval(s), to all relevant guidance relating to medicines and clinical trials from time to time in force including, but not limited to, the ICH Harmonized Tripartite Guidelines for Good Clinical Practices (E6).

·                  AMT to be provided with a full list of clinical SOPs and copies of the applicable SOPs as requested by AMT prior to the conduct of the study.

·                  Both parties to agree on the content of the study audit plan prior to the start of the study, including any relevant quality plan.

·                  The Principle Investigator (PI) will attempt to secure timely consent from all patients, to be rolled over into an AMT owned by AIP Registry, in which among others natural evolution and long term safety and efficacy after gene therapy will be captured, at a point to be determined.

·                  Go/no go for subsequent intervention study/studies: sufficient disease presentation, manifestation & complication data and sufficient information on natural disease evolution is collected and sufficient individual patient baseline data is acquired, to allow the conclusion that any data to be collected in the interventional study can be used to judge interventional product safety and gauge clinical efficacy using suitable, determinable endpoints.  The go/no go criteria will also include:

 

·                  Site and protocol feasibility that supports the conduct and execution of the proposed study according the agreed timeline

 

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·                  Regulatory and ethical approval and

·                  Actual progress that is consistent with achieving agreed accrual targets and timelines

 

Phase I/II

 

·                  GCP & guidelines compliant as per above

 

·                  The clinical phase I/II should include an estimated minimum [**] patients that are administered the gene therapy drug, and are followed up and clinically assessed for at least [**] months following drug administration.

 

·                  The formal study follow up will be at least [**] years post administration per individual subject; interim analysis and reporting will be planned for, at a minimum once immediately after all subjects have had their [**] months study visit.

 

·                  The PI has to commit to a [**] year follow up of those [**] treated patients, at minimum for safety and efficacy assessments each year during the first [**] years and [**] thereafter, and needs to commit upfront to maintaining adequate study and patient data documentation, and to keep any source documents secure, for [**] years after study drug administration.

 

·                  The clinical trial must include all biochemical, imaging, clinical and functional assays, as well as any other relevant additional assays, to assess the disease state and change therein over time, as well as the phenotypic disease variation, as well as the overall clinical and psychosocial or other health status or change therein over time of the individual trial subjects, both before, during and following drug administration.

 

·                  Study monitoring and source data verification will be carried out and documented to industry accepted standards.

 

·                  AMT will have, at the latest [**] months after the obtaining of each individual data point, access to and exclusive use of the data for the purposes of ultimately obtaining marketing authorizations, in Europe and/or any other country or region in the world.  This data access is needed early on to engage in discussion with relevant regulatory bodies representatives.

 

·                  Within [**] months after the completion of each individual study or study phase, AMT will receive a copy of the essential documents on request and copies of the study database.  Upon completion, AMT will receive a copy of the final, audited, clinical trial database, with data, and those aspects of the Trial Master File that are necessary to file for MAA.

 

·                  Study data only published with approval and agreement of the Liaison Committee

 

27

 

EXHIBIT 2
  PROTOCOL (to be attached once final)

 

Confidential Materials omitted and filed separately with the Securities and Exchange Commission.  A total of 137 pages were omitted. [**]

 

28

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