Manufacture and Supply Agreement, dated February 16, 2018, between the Registrant and Pfizer

This SPK-9001 MANUFACTURE AND SUPPLY AGREEMENT (this “Agreement”) is made as of February 16, 2018 (the “Effective Date”), by and between Pfizer Inc., a corporation organized and existing under the laws of the State of Delaware, with offices at 235 East 42nd Street, New York, New York 10017 (“Customer”), Spark Therapeutics, Inc., a corporation organized and existing under the laws of the State of Delaware, with offices at 3737 Market Street, Suite 1300, Philadelphia, Pennsylvania 19104 (“Supplier”). Customer and Supplier may be referred to herein individually as a “Party” and collectively as the “Parties”.

WHEREAS, Customer and Supplier are Parties to a License Agreement, dated as of December 6, 2014, as amended from time to time (the “License Agreement”), under which Supplier licensed and Customer acquired and received certain rights in the Compounds and Licensed Products as further defined in that License Agreement; and

WHEREAS, Customer desires to obtain the Product Deliverable (as defined below) for use in the Manufacture of certain Licensed Product and Supplier desires to provide Customer with such Product, in accordance with the terms and conditions set forth in this Agreement;

NOW, THEREFORE, in consideration of the promises and mutual covenants expressed herein, and intending to be legally bound thereby, the Parties hereby agree as follows:

Terms defined in the preamble of and elsewhere in this Agreement have the meanings set forth therein, capitalized terms not otherwise defined herein shall have the meaning given to such terms in the License Agreement, and the following terms have the meanings set forth below:

into account the stage of development of the Product.

Pursuant the terms of this Agreement, Supplier shall Manufacture and deliver, and Customer shall purchase, the Product Deliverable.

The Parties will establish a manufacturing committee (the “Manufacturing Committee”) to oversee all activities relating to Manufacturing of the Product Deliverable. The Manufacturing Committee shall be composed of representatives from each Party in the following areas of expertise: (i) alliance management/project management, (ii) quality control/analytical development, (iii) Manufacturing / bioprocess development and (iv) quality assurance. The Manufacturing Committee will meet and manage the project schedule set forth in Schedule A.

Notwithstanding anything to the contrary herein, the Manufacturing Start Date and the outside date for Supplier Release are firm. Supplier agrees to use its Commercially Reasonable Efforts to start the Manufacture of the Batch by the Manufacturing Start Date, complete the Manufacture of the Product Deliverable, enable shipment of the Product

Deliverable to [**], and provide the Customer with the analytical results of the Product Deliverable by the dates set forth in Schedule A. In addition, the Parties acknowledge that the dates set forth in Schedule A for determining Customer's obligation to pay the Second Payment are intended to be firm dates.

Customer shall purchase the Product Deliverable from Supplier at the Price and in accordance with the terms of this Agreement, wherein “Price” shall have the meaning set forth in Schedule A.

The Price includes all taxes except such sales and use taxes which Supplier is required by Relevant Law to collect from Customer. Such taxes, if any, will be separately stated in Supplier's invoice and will be paid by Customer to Supplier unless Customer provides evidence of an exemption to Supplier. Supplier shall be solely responsible for the timely payment of all such taxes to the applicable taxing authority, and Supplier shall pay (without reimbursement by Customer), and shall hold Customer harmless from and against, any penalties, interest or additional taxes that may be levied or assessed as a result of the failure or delay of Supplier to pay any such taxes.

The Parties agree to comply with the requirements and provisions set forth in the Quality Agreement attached hereto as Schedule C and made a part hereof. In the event of a conflict between the terms of the Quality Agreement and the terms of this Agreement, the terms of this Agreement shall prevail except with respect to final disposition of the Product Deliverable as set forth in the Quality Agreement, unless the Parties explicitly specify in the Quality Agreement that a particular provision of the Quality Agreement is to control over a particular provision in this Agreement.

Subject to Section 8.1, Supplier, at no cost to Customer, shall provide Records relating to the Manufacture of the Product Deliverable, as reasonably requested by Customer, to assist Customer in its preparation for subsequent EOP2 Meetings, its preparation of any filings with a Regulatory Authority relating to the Compound or Licensed Product and its preparation for or of any other meeting or communication with any Regulatory Authority relating to the Compound or Licensed Product.

Supplier shall perform all raw material, in-process, and bulk finished product tests substantially consistent with those same tests performed for the Process 2 Product made by Supplier in 2016, and checks required to assure the quality of the Product Deliverable and any tests or checks required by the Quality Agreement and Relevant Laws. Supplier is responsible for obtaining inventory for these tests and is also responsible for providing all necessary technical, quality and operational resources. All tests and test results shall be performed, documented and summarized by Supplier in accordance with the Quality Agreement, Customer’s reasonable instructions and Relevant Laws.

approval of Customer. Supplier shall render all Non-Complying Product unusable prior to disposal.

Supplier shall promptly notify Customer if at any time Supplier believes that any Product Deliverable has been lost or stolen, or any Product Deliverable has been rendered unsalable.

Supplier shall not use any equipment, dedicated change parts, molds or tooling that are used to Manufacture the Product Deliverable to Manufacture other products containing any of the following compounds: (i) androgens, estrogens and progestin or (ii) herbicides, pesticides, rodenticides, agrochemicals, penicillin, cephalosporin, and beta lactams. Supplier shall not Manufacture any penicillins, cephalosporins or beta lactams in the same Facility as the Product Deliverable.

Supplier represents, warrants and covenants to Customer that the Product Deliverable supplied by Supplier to Customer under this Agreement: (i) shall be Manufactured, packaged, labeled, handled, stored and shipped in compliance with all Relevant Laws including, without limitation, cGMPs and in accordance with the Quality Agreement and this Agreement; (ii) shall be Manufactured, packaged, labeled, handled, stored and shipped in accordance with, and shall conform to, the Specifications; (iii) shall not be adulterated or misbranded within the meaning of Sections 501 and 502, respectively, of the U.S. Federal Food, Drug, and Cosmetic Act and any other Relevant Laws; and (iv) shall be free from defects in material and workmanship.

Supplier represents, warrants and covenants to Customer that the Facility and all equipment utilized in the Manufacture and supply of Product Deliverable hereunder by Supplier shall, during the Term of this Agreement, be maintained in good operating condition and shall be

maintained and operated in accordance with all Relevant Laws and that the appropriate controls are in place, including precautions against release of biologically active materials, to assure safe Manufacture and transport of all Product Deliverable and Product Materials throughout the supply chain.

Supplier represents, warrants and covenants to Customer that Supplier has good title to all Product Deliverable supplied to Customer pursuant to this Agreement and shall pass such title to the Product Deliverable at the time of delivery to Customer free and clear of any security interests, liens, or other encumbrances.

(c)    Supplier further represents, warrants and covenants to Customer that:

to influence any Government Official or any other person in order to gain an improper advantage, and has not accepted, and will not accept in the future such payment;

Supplier represents and warrants to Customer that as of the Effective Date, there is no pending or threatened governmental enforcement action or material private claim against Supplier, or any environmental conditions, events or circumstances that are reasonably likely to limit, impede or otherwise jeopardize the Supplier’s ability to meet its obligations under this Agreement.

Supplier shall be responsible for the health and safety of its Personnel while present at the Facility. Supplier shall comply with all Relevant Laws relating to health and safety.

Supplier covenants that it will perform its obligations under this Agreement in a manner consistent with all of the Pharmaceutical Industry Principles for Responsible Supply Chain Management, as codified as of the Effective Date at http://www.pharmaceuticalsupplychain.org. In addition, Supplier has and will continue to have a documented, comprehensive environmental policy which addresses, among other things,

its ongoing commitment to environmental protection, sustainability, pollution prevention, waste reduction, and energy and water efficiency.

Supplier is not designated as a Restricted Party (as defined below). Supplier has not and will not use, in any capacity in the performance of this Agreement, the services of any person who has been designated as a Restricted Party. Supplier will immediately notify Customer in the event that Supplier or any of its Personnel becomes designated as a Restricted Party during the Term of this Agreement. As used herein, “Restricted Party” means any individual or entity on any of the following lists: the Specially Designated Nationals and Blocked Persons List, Foreign Sanctions Evaders List, and the Sectoral Sanctions Identifications List, as administered by the U.S. Department of the Treasury Office of Foreign Assets Control; the U.S. Denied Persons List, the U.S. Entity List, and the U.S. Unverified List, all administered by the U.S. Department of Commerce the List of Excluded Individuals / Entities, as published by the U.S. Health and Human Services – Office of Inspector General; any lists of prohibited or debarred parties established under the U.S. Federal Food Drug and Cosmetic Act; and the list of persons and entities suspended or debarred from contracting with the U.S. government. Subject to the foregoing, Supplier shall be free to use the services of any person or the entity(s) set forth on Schedule C who will perform testing of the Product Deliverable on behalf of Supplier.

Each of Supplier and Customer hereby represents and warrants to the other Party, as of the Effective Date, that:

Supplier acknowledges that Customer, as a regulated multi-national company, is subject to various governmental and regulatory compliance requirements. Accordingly, subject to Section 8.1, Supplier agrees that in order to allow Customer to comply with Applicable Laws it shall provide Customer with information (for clarity, excluding Records which would be provided pursuant to Section 4.2) regarding Supplier and its operations with respect to the Product Deliverable to Customer upon Customer’s written request and at Customer’s cost.

This Agreement is entered into as of the Effective Date and shall remain in effect until the date that is thirty (30) days after Supplier Release (the “Term”) unless terminated earlier as provided herein.

Either Party may terminate this Agreement immediately upon written notice to the other Party in the event of a material breach by the other Party of any term of this Agreement which material breach remains uncured for [**] following written notice to such breaching Party of such material breach, provided that in the case of a breach related to non-payment of amounts disputed in good faith the running of such cure period shall be tolled until such dispute is resolved, but, for the avoidance of doubt, not with respect to the non-payment of amounts that are not disputed in good faith (e.g., if a portion of a payment amount is not subject to good faith dispute, that portion must be paid within the applicable cure period in order to avoid termination, and the running of such cure period shall not be tolled as to such portion). Notwithstanding the foregoing, if such material breach, by its nature, cannot be cured, the non-breaching Party may terminate this Agreement immediately upon written notice to the breaching Party.

In the event that a Party hereto experiences a Bankruptcy Event (such Party, the “Insolvent Party”); then the Insolvent Party shall immediately notify the other Party of such Bankruptcy Event and such other Party shall be entitled to: (a) terminate this Agreement for cause immediately upon written notice to the Insolvent Party; or (b) request that the Insolvent Party or its successor provide adequate assurances of continued and future performance in form and substance reasonably acceptable to such other Party, which shall be provided by the Insolvent Party within [**] of such request, and the other Party may terminate this Agreement for cause immediately upon written notice to the Insolvent Party in the event

that the Insolvent Party fails to provide such assurances acceptable to the other Party within such [**] period.

Customer may terminate this Agreement effective immediately upon notice to Supplier, if: (i) Supplier breaches any of the representations, warranties and covenants set forth in Section 5.4(c), or (ii) Customer learns (a) that improper payments are being or have been made or offered to Government Officials or any other person by the Supplier or those acting on behalf of the Supplier with respect to this Agreement, or (b) that the Supplier or those acting on behalf of the Supplier with respect to this Agreement has accepted any payment, item, or benefit, regardless of value, as an improper inducement to award, obtain or retain business or otherwise gain or grant an improper business advantage from or to any other person or entity. Further, in the event of such termination, Supplier shall not be entitled to any further payment, regardless of any activities undertaken or agreements with additional third parties entered into by Supplier prior to such termination, and Supplier shall be liable for damages or remedies as provided by this Agreement, at law or in equity.

The termination or expiration of this Agreement shall not affect the survival and continuing validity of Section 4.2, the last sentence of Section 4.4(c), Section 4.4(e), Section 5.10, Article 8, any relevant definitions and any other provision which is expressly or by implication intended to continue in force after such termination or expiration.

Wherever Supplier is required by the terms of this Agreement to provide Records or other information to Customer, the Parties agree that Supplier shall (i) provide to Customer only such Records or other information actually in Supplier’s possession at the time of request by Customer and (ii) provide to Customer such Records or other information in the form that Supplier has such Records or other information.

All matters relating to intellectual property relating to or arising out of this Agreement shall be governed by the terms and conditions set forth in Article 5 of the License Agreement, the terms of which are incorporated by reference herein.

All matters relating to limitation of liability, indemnification and insurance relating to or arising out of this Agreement shall be governed by the terms and conditions set forth in Article 9 of the License Agreement, the terms of which are incorporated by reference herein.

In addition, other than with respect to Supplier’s indemnity obligations under Section 4.4(e) hereof and any liability due to fraud, gross negligence and intentional misconduct, Supplier’s total liability to Customer under this Agreement shall in no event exceed $[**] U.S. Dollars), provided that if Customer Release occurs after [**], Supplier’s total liability to Customer under this Agreement shall not exceed $[**] U.S. Dollars).

All matters relating to Confidential Information (as defined in the License Agreement) disclosed under or relating to or pursuant to this Agreement or arising out of this Agreement shall be governed by the terms and conditions set forth in Article 6 of the License Agreement, the terms of which are incorporated by reference herein.

In addition to the provisions set forth above, the following Sections of the License Agreement are incorporated by reference herein: 1.2 (Interpretation), 4.7 (Adverse Events and Safety Reporting), 10.1 (Assignment), 10.2 (Further Actions), 10.3 (Force Majeure), 10.4 (Notices), 10.5 (Amendment), 10.6 (Waiver), 10.7 (Severability), 10.8 (Export Control), 10.9 (Dispute Resolution), 10.10 (Governing Law), 10.11 (Jurisdiction), 10.12 (No Jury Trial), 10.13 (Entire Agreement), 10.14 (Independent Contractors), 10.17 (Headings) and 10.18 (Counterparts), wherein all references to the License Agreement in said sections are understood to be references to this Agreement.

IN WITNESS WHEREOF, the Parties hereto have caused this Agreement to be duly executed and delivered as of the Effective Date.

Supplier shall Manufacture the Product Deliverable for the potential treatment of hemophilia B for clinical trial supply purpose in accordance with the terms and conditions set forth in this Agreement including the Quality Agreement.

Scope; Activities, Tasks:

Supplier shall deliver materials and documentation capable of supporting regulatory submission, example activities including (a) Manufacture of [**], “Minimum Product Deliverable Volume”) and (b) [**].

Supplier will participate in mutually scheduled Manufacturing Committee meetings. At each meeting the Manufacturing Committee will have a [**]. The Manufacturing Committee may, [**]. Frequency of Manufacturing Committee meetings [**]. In addition, [**], Supplier will [**]. For the avoidance of doubt, the Manufacturing Committee shall [**].

Supplier shall work with Customer to meet the following requirements (“Additional Requirements”), it being agreed that [**] shall have final decision making authority except with respect to [**], for which [**] shall have the final decision making authority, provided in all cases final decision making is subject to the reasonable objections of the non-decision making party.

Customer acknowledges that any delay on its part beyond the requested response date provided by Supplier with respect to Customer’s review and approval may cause a corresponding delay with respect to Supplier’s Manufacture or delivery of the Product Deliverable. Notwithstanding anything to the contrary in this Agreement, provided that Customer’s delay is not caused by Supplier, Supplier shall have no liability to Customer for such delay, and the amount of the Second Payment shall not be reduced, in the event that such a delay on Customer’s part causes a corresponding delay in Supplier Release.

* Target completion dates are subject to review and revision by Manufacturing Committee as described above

Within [**] after Customer’s receipt of Supplier Release and associated Records such date being extendable for up to [**] upon Customer notifying Supplier in writing of a delay which is caused by a deviation, changes or other documentation as part of the Supplier Release Records (the “Release Deadline”), Customer shall either approve of the Product Deliverable (“Customer Release”) or shall reject the Product Deliverable. In the event that Customer Release has not occurred by the Release Deadline or Customer has rejected the Product Deliverable, Customer agrees (i) not to use the Product Deliverable for any purpose and (ii) within [**] after the Release Deadline, to destroy the Product Deliverable and deliver documentation of such destruction to Supplier.

The total cost for services described in this Statement of Work shall be up to $14,000,000 (fourteen million U.S. Dollars) (the “Price”) which consists of:

will be due and payable within [**] after Customer Release and Customer’s receipt of an invoice as described below.

All invoices should be emailed directly to [**] with a copy to [**]. Please include the following information clearly listed: reference to this Agreement, PO number, amount owed and name and address payment is to be sent to. Suppliers enrolled in Customer's e-Invoicing programs (ASN or OB10) can ignore this PO Note. All invoice or billing related questions should be referred to Customer's Accounting Department at [**] or go to the Accounts Payable Inquiry Tool (APIQ) which can be found at [**].

Pfizer and Spark Therapeutics, Inc. (Spark) may each be referred to herein individually as a “Party” and collectively as the “Parties.”

The Parties wish to further define their individual and collective responsibilities as to the quality aspects of the Product or Service to ensure compliance with applicable Good Manufacturing Practices (GMPs), or other applicable quality standards, applicable regulatory submissions for the Product, applicable regulatory submissions for the Services, other applicable regulatory requirements, and Pfizer’s requirements as specified by Pfizer (the “Pfizer Requirements”).

In order to achieve this purpose, this Quality Agreement includes a detailed listing of the activities and corresponding responsibilities associated with the Product or Service. Unless otherwise indicated, responsibility for each specified activity is assigned to either Pfizer or Spark, or to both Parties.

[**].

The following documents/records will be supplied to Pfizer:

  

Additional documents that may be included in this Appendix (as appropriate to Services) are:

[**]

.

Contractor may not subcontract any of its obligations under this Quality Agreement except pursuant to the provisions of Section 8 of the Quality Agreement. The Parties acknowledge and agree that the Sub-Contractor(s) listed below have satisfied the requirements set forth in Section 8 of the Quality Agreement, have been approved by Pfizer, and may perform activities on behalf of Contractor under the Quality Agreement, subject to Contractor’s and such Sub-Contractor’s continuing obligations under the Quality Agreement, including, without limitation, their respective obligations under Section 8.