EXHIBIT 10.6
Certain information in this document, marked by [***], has been omitted pursuant to Item 601(b)(10)(iv) of Regulation S-K under the Securities Act of 1933, as amended, because it is both (i) not material and (ii) would likely cause competitive harm to the registrant if publicly disclosed.
RESEARCH COLLABORATION, OPTION AND LICENSE AGREEMENT*
by and between
Silence Therapeutics PLC
and
ASTRAZENECA AB
Dated as of March 24, 2020
|
|
Cooley (UK) LLP, Dashwood, 69 Old Broad Street, London EC2M 1QS, UK
T: +44 (0) 20 7583 4055 F: +44 (0) 20 7785 9355 www.cooley.com
* Schedules have been omitted pursuant to item 601(a)(5) of regulation s-k and will be furnished on a supplemental basis to the securities and exchange commission upon request.
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| Page | |
ARTICLE 1 DEFINITIONS | 2 | |
ARTICLE 2 COLLABORATION MANAGEMENT | 32 | |
2.1 | Joint Steering Committee. | 32 |
2.2 | Specific Responsibilities of the JSC | 32 |
2.3 | Disbandment. | 34 |
2.4 | Location of Meetings. | 34 |
2.5 | Conduct of Meetings. | 34 |
2.6 | Procedural Rules. | 35 |
2.7 | Decision Making. | 36 |
2.8 | Limitations on Authority. | 37 |
2.9 | Alliance Manager. | 37 |
2.10 | Expenses | 38 |
ARTICLE 3 TARGET SELECTION | 38 | |
3.1 | Collaborative Process to Identify Potentially Eligible Targets. | 38 |
3.2 | Review of Nominated Target. | 38 |
3.3 | Eligible Target Pool. | 39 |
3.4 | Validation Research. | 41 |
3.5 | Designation of Selected Targets | 41 |
3.6 | Total Number of Selected Targets | 41 |
3.7 | Research of Selected Targets. | 42 |
3.8 | Staggering of Selected Target Selection. | 42 |
3.9 | Substitute Targets. | 42 |
ARTICLE 4 RESEARCH | 44 | |
4.1 | Overview. | 44 |
4.2 | Research Plans. | 44 |
4.3 | Conduct of the Research Plan. | 45 |
4.4 | Conclusion of the Research Plan; Development Candidate Data Package. | 50 |
4.5 | Material Increases in Silence Obligations under a Research Plan. | 51 |
ARTICLE 5 EXCLUSIVITY | 52 | |
5.1 | Mutual Exclusivity During the Exclusivity Period. | 52 |
5.2 | AZ Exclusivity after the Option Exercise. | 53 |
ARTICLE 6 OPTION GRANTS | 53 | |
6.1 | Option Grant to AZ. | 53 |
6.2 | Antitrust Clearance. | 53 |
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Option Exercise Payment. | 55 | |
6.4 | Non-Exercise of the Option | 55 |
ARTICLE 7 LICENSE GRANTS | 56 | |
7.1 | License Grants to AZ. | 56 |
7.2 | License Grants to Silence | 56 |
7.3 | Sublicenses. | 57 |
7.4 | Distributorships and Promotion. | 57 |
7.5 | Retention of Rights. | 57 |
7.6 | No Implied Licenses. | 58 |
7.7 | No [***]. | 58 |
7.8 | Confirmatory Patent License. | 58 |
ARTICLE 8 DEVELOPMENT AND COMMERCIALIZATION | 58 | |
8.1 | Overview. | 58 |
8.2 | Transfer of Know-How | 59 |
8.3 | Diligence | 59 |
8.4 | Reporting. | 59 |
8.5 | Regulatory Support | 59 |
8.6 | Co-Development Option. | 60 |
ARTICLE 9 MANUFACTURING & SUPPLY | 62 | |
9.1 | Silence Manufacturing. | 62 |
9.2 | AZ Obligations. | 63 |
9.3 | Cooperation and Technology Transfer. | 63 |
ARTICLE 10 PAYMENTS AND RECORDS | 64 | |
10.1 | Upfront Payment. | 64 |
10.2 | Research Collaboration Milestones. | 64 |
10.3 | Sales-Based Milestones | 67 |
10.4 | Royalties. | 68 |
10.5 | Compulsory License. | 71 |
10.6 | Estimated Sales Levels | 71 |
ARTICLE 11 PAYMENT; RECORDS; AUDITS | 72 | |
11.1 | Royalty Payments and Reports | 72 |
11.2 | Mode of Payment. | 72 |
11.3 | Taxes. | 72 |
11.4 | Financial Records | 75 |
11.5 | Audit. | 76 |
11.6 | Audit Dispute | 76 |
11.7 | Confidentiality. | 77 |
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77 | ||
12.1 | Patent Working Group. | 77 |
12.2 | Ownership of Intellectual Property. | 77 |
12.3 | Maintenance and Prosecution of Patents. | 79 |
12.4 | Enforcement of Patents. | 84 |
12.5 | Infringement Claims by Third Parties. | 89 |
12.6 | Invalidity or Unenforceability Defenses or Actions. | 89 |
12.7 | UPC. | 94 |
ARTICLE 13 CONFIDENTIALITY AND NON-DISCLOSURE | 95 | |
13.1 | Confidentiality Obligations. | 95 |
13.2 | Permitted Disclosures. | 96 |
13.3 | Use of Name. | 97 |
13.4 | Public Announcements | 98 |
13.5 | Publications. | 98 |
13.6 | Return of Confidential Information | 100 |
ARTICLE 14 REPRESENTATIONS AND WARRANTIES | 101 | |
14.1 | Mutual Warranties | 101 |
14.2 | Additional Warranties by Silence | 102 |
14.3 | Mutual Covenants. | 104 |
14.4 | Additional Covenants of Silence. | 105 |
14.5 | Certification of Representations and Warranties of Silence. | 106 |
14.6 | Disclaimer of Warranties. | 106 |
ARTICLE 15 INDEMNITY | 106 | |
15.1 | Indemnification of Silence | 106 |
15.2 | Indemnification of AZ. | 107 |
15.3 | Indemnification Procedure. | 108 |
15.4 | Special, Indirect, and Other Losses. | 108 |
15.5 | Insurance. | 109 |
ARTICLE 16 TERM AND TERMINATION | 109 | |
16.1 | Term. | 109 |
16.2 | Termination by AZ for Convenience. | 109 |
16.3 | Termination for Material Breach. | 110 |
16.4 | Termination by Silence for Patent Challenge. | 110 |
16.5 | Termination for Insolvency | 111 |
16.6 | Effects of Termination. | 112 |
ARTICLE 17 MISCELLANEOUS | 120 | |
17.1 | Force Majeure. | 120 |
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Export Control. | 120 | |
17.3 | Silence Change of Control | 121 |
17.4 | Assignment | 123 |
17.5 | Severability | 123 |
17.6 | Governing Law | 124 |
17.7 | Dispute Resolution. | 124 |
17.8 | Interim Relief | 125 |
17.9 | Notices. | 125 |
17.10 | Entire Agreement; Amendments | 126 |
17.11 | English Language. | 126 |
17.12 | Waiver and Non-Exclusion of Remedies | 126 |
17.13 | No Benefit to Third Parties | 127 |
17.14 | Further Assurance. | 127 |
17.15 | Rights in Bankruptcy | 127 |
17.16 | Relationship of the Parties | 128 |
17.17 | Counterparts; Facsimile Execution. | 128 |
17.18 | AZ Affiliates | 129 |
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THIS LICENSE AND COLLABORATION AGREEMENT (“Agreement”) is made and entered into effective as of March 24, 2020 (the “Effective Date”) by and between
(1) | Silence Therapeutics PLC, a public limited company organized under the laws of England and Wales under no. 2992058 and with its registered office at 27 Eastcastle Street, London, UK W1W 8DH (“Silence”), and |
(2) | ASTRAZENECA AB, a corporation organized under the laws of Sweden under no. 556011-7482 with its registered office at SE-151 85 Södertälje, Sweden and with offices at Pepparedsleden 1, SE-431 83 Mölndal, Sweden (“AZ”); and |
Silence and AZ are sometimes referred to herein individually as a “Party” and collectively as the “Parties”.
Background
(A) | Silence owns certain intellectual property rights with respect to the research and development of RNAi Molecules (as defined below). |
(B) | AZ is a leading global, science-led biopharmaceutical company researching, developing and commercializing innovative medicines for patients worldwide. |
(C) | The Parties have agreed to collaborate to perform drug discovery and research on certain Eligible Targets and Selected Targets, which will be chosen by the Parties, for the treatment of human disease, including cardiovascular, renal, metabolic and respiratory diseases. AZ wishes to obtain, and Silence wishes to grant to AZ, an option to obtain a license under Silence’s rights in such technology and related intellectual property rights to develop and commercialize Licensed Products directed to those Selected Targets. |
NOW, THEREFORE, in consideration of the mutual promises and conditions hereinafter set forth, and other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties, intending to be legally bound, do hereby agree as follows:
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As used in this Agreement, the following capitalized terms, whether used in the singular or plural, shall have the meanings set out below:
1.1 | “Accounting Standards” means, with respect to each Party, International Financial Reporting Standards (IFRS). |
1.3 | “Agreement” means this agreement and all schedules, appendices and other addenda attached hereto as any of the foregoing may be amended in accordance with the provisions of this Agreement. |
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1.14 | “AZ Background Patents” means any and all Patents Controlled by AZ or any of its Affiliates on the Effective Date or during the Term that Cover any AZ Background Know-How. |
1.19 | “AZ Research Patents” means any and all Patents Controlled by AZ after the Effective Date that Cover any AZ Research Know-How. |
1.21 | “Business Day” means a day other than a Saturday or Sunday on which banking institutions in Stockholm, Sweden and London, England are open for business. |
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1.24 | “Centralized Approval Procedure” means the procedure through which an MAA filed with the EMA results in a single marketing authorization valid throughout the European Union. |
1.28 | “Collaboration” means the collaboration between the Parties which is the subject matter of this Agreement. |
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and “Commercializing” means to engage in Commercialization, and “Commercialized” has a corresponding meaning. |
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1.46 | “Effective Date” means the effective date of this Agreement as set forth in the preamble hereto. |
1.50 | “EMA” means the European Medicines Agency and any successor agency or authority having substantially the same function. |
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| 1.52.5 | [***] (whether [***], or [***]relates to such Eligible Target or Selected Target, as the case may be) [***]. |
1.55 | “FDA” means the United States Food and Drug Administration and any successor agency or authority having substantially the same function. |
1.56 | “Field” means all therapeutic, prophylactic, palliative and diagnostic uses in humans and animals. |
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1.59 | “FTE Cost” means the FTE Rate multiplied by the number of FTEs applied by Silence to the performance of the relevant activity in accordance with the applicable Research Plan. |
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principles and the other products in that facility); and, notwithstanding anything to the contrary, such actual cost will exclude all costs which cannot be linked to a specific Manufacturing activity such as charges for corporate overhead which are not controllable by the Manufacturing plant, together with any idle or excess capacity costs that are not reasonably necessary to meet the supply demand as set forth in the applicable Research Plan or Supply Agreement, any indirect taxes, and any amounts payable by Silence to a Third Party due to the negligence or misconduct of Silence or its Affiliates; and (b) in respect of any activities subcontracted to a Third Party, the amount invoiced by the relevant Third Party for such activity, which amount shall be passed-through to AZ without any mark-up by Silence or its Affiliates. |
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1.67 | “HSR Act” means the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended, and all rules and regulations promulgated thereunder. |
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1.74 | “Initiation” means, with respect to a Clinical Study, the first dosing of the first (1st) human subject in such Clinical Study. “Initiate” has a correlative meaning. |
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| (a) | trade, cash and quantity discounts; |
| (b) | taxes on sales (such as sales, value added, or use taxes) to the extent added to the sale price and set forth separately as such in the total amount invoiced; |
| (c) | amounts repaid or credited by reason of rejections, defects, return goods allowance, recalls or returns, or because of retroactive price reductions; |
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| entities and institutions)) which effectively reduce the selling price or gross sales of such Licensed Product; |
| (e) | the portion of administrative fees paid during the relevant time period to group purchasing organizations, pharmaceutical benefit managers or Medicare Prescription Drug Plans relating to such Licensed Product; |
| (f) | freight, insurance, import/export, and other transportation charges to the extent added to the sale price and set forth separately as such in the total amount invoiced; |
| (g) | [***]; and |
| (h) | [***] provided always that [***]. |
Net Sales shall not include transfers or dispositions for charitable, promotional, pre-clinical, clinical, regulatory, or governmental purposes, provided such transfers or dispositions take place for no consideration. Net Sales shall include the amount or fair market value of all other consideration received by AZ, its Affiliates, or Sublicensees in respect of a Licensed Product, whether such consideration is in cash, payment in kind, exchange, or other form. Net Sales shall not include sales between or among AZ, its Affiliates, or Sublicensees.
Subject to the above, Net Sales shall be calculated in accordance with the standard internal policies and procedures of AZ, its Affiliates, or Sublicensees, which must be in accordance with Accounting Standards and consistent with the audited net sales reported externally by AZ.
For the purposes of calculating Net Sales, all Net Sales shall be converted into Dollars in accordance with Section 11.2.
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In the event a Licensed Product is a Combination Product, the Net Sales for such Combination Product shall be calculated as follows:
| i. | If AZ, its Affiliate, or Sublicensee separately sells in such country or other jurisdiction, (A) a product containing as its sole active ingredient a Licensed Compound contained in such Combination Product (the “Mono Product”) and (B) products containing as their sole active ingredients the Other Active Ingredients in such Combination Product, the Net Sales attributable to such Combination Product shall be calculated by multiplying actual Net Sales of such Combination Product by the fraction A/(A+B) where: “A” is AZ’s (or its Affiliate’s or Sublicensee’s, as applicable) average Net Sales price during the period to which the Net Sales calculation applies for the Mono Product in such country or other jurisdiction and “B” is AZ’s (or its Affiliate’s or Sublicensee’s, as applicable) average Net Sales price during the period to which the Net Sales calculation applies in such country or other jurisdiction, for products that contain as their sole active ingredients the Other Active Ingredients in such Combination Product. |
| ii. | If AZ, its Affiliate, or Sublicensee separately sells in such country or other jurisdiction the Mono Product but does not separately sell in such country or other jurisdiction products containing as their sole active ingredients the Other Active Ingredients in such Combination Product, the Net Sales attributable to such Combination Product shall be calculated by multiplying the Net Sales of such Combination Product by the fraction A/C where: “A” is AZ’s (or its Affiliate’s or Sublicensee’s, as applicable) average Net Sales price during the period to which the Net Sales calculation applies for the Mono Product in such country or other jurisdiction, and “C” is AZ’s (or its Affiliate’s or Sublicensee’s, as applicable) average Net Sales price in such country or other jurisdiction during the period to which the Net Sales calculation applies for such Combination Product. |
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| iv. | If AZ, its Affiliates, and Sublicensees do not separately sell in such country or other jurisdiction both the Mono Product and the Other Active Ingredients in such Combination Product, the Net Sales attributable to such Combination Product shall be determined by the Parties in good faith based on the relative fair market value of such Mono Product and such Other Active Ingredient(s). If the Parties cannot agree on such relative value, the Dispute shall be resolved pursuant to Section 17.7. |
1.90 | “Option Exercise Date” means, on an Option-by-Option basis, the date that Silence receives written notification that AZ wishes to exercise such Option, pursuant to Section 6.1. |
1.91 | “Option Exercise Effective Date” means on an Option-by-Option basis, the later of (i) the Option Exercise Date and (ii) the date on which the last applicable Antitrust Clearance is obtained. |
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(c)), and (e) any similar patent rights, including so-called pipeline protection or any importation, revalidation, confirmation, or introduction patent or registration patent or patent of additions to any of such foregoing patent applications and patents. |
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1.104 | “PMDA” means Japan’s Pharmaceuticals and Medical Devices Agency and any successor agency or authority having substantially the same function. |
1.105 | “Product Specific Patent” means [***] that (a) specifically and solely claims [***] (including [***]) and/or [***], and (b) does not claim [***] that [***] other than [***]. |
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1.119 | “Restricted Targets” means those human gene targets which, at the time that AZ proposes them as Nominated Targets, are: |
1.120 | “Returned Target” has the meaning set out in Section 16.6.1. |
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1.124 | “Selected Target” means any one of the human gene targets designated by AZ as a Selected Target in accordance with Section 3.5, provided that [***]. |
1.128 | “Silence Acquiror” means any AZ Competitor acquiring a Controlling Interest in Silence (or in a Holding Company of Silence) or its property or business pursuant to a Silence Change of Control. |
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(a) a transaction in which Silence (or a Holding Company of Silence) sells, conveys or otherwise disposes of all or substantially all of its property or business; or
(b) (i) a transaction in which Silence (or a Holding Company of Silence) merges or consolidates with any other Person (other than a wholly-owned subsidiary of Silence (or of a Holding Company of Silence)), or (ii) any other transaction or series of transactions; in each case of clause (i) or (ii), in consequence of which any Person and/or any group of Persons acting in concert (as such expression is defined in the Code) acquires a Controlling Interest in Silence (or in a Holding Company of Silence).
Notwithstanding the foregoing subsection (b), a Silence Change of Control will not include any transaction or series of related transactions principally conducted by Silence (or a Holding Company of Silence) for bona fide equity financing purposes in which cash is received, or indebtedness is cancelled or converted, or a combination thereof occurs and pursuant to which the Person and/or any group of Persons acting in concert (as such expression is defined in the Code) acquiring the Controlling Interest in Silence (or in a Holding Company of Silence) is not an AZ Competitor.
For purposes of Section 1.128 and this Section 1.132, the following capitalized terms shall have the meanings set out below:
“AZ Competitor” means a Person that is (a) [***] and/or (b) [***]; and
“Code” means the City Code on Takeovers and Mergers;
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“Controlling Interest” means an interest in shares giving to the holder or holders the power to secure (a) by means of the holding of shares or the possession of voting power in relation to that or any other body corporate and/or (b) as a result of any powers conferred by the articles of association or other document regulating that or any other body corporate (i) the election of a majority of the members of the company’s board of directors or similar governing body and/or (ii) that the affairs of the company are conducted in accordance with such holder or holder’s wishes; and
“Holding Company” has the meaning given to “holding company” in section 1159 of the Companies Act 2006.
1.137 | “Silence Research Patents” means any and all Patents Controlled by Silence after the Effective Date that Cover any Silence Research Know-How. |
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| 1.149.1 | all references to a particular clause or schedule shall be a reference to that clause or schedule in or to this Agreement as it may be amended from time to time pursuant to this Agreement; |
| 1.149.2 | the headings are inserted for convenience only and shall be ignored in construing this Agreement; |
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| 1.149.3 | words importing the masculine gender shall include the feminine and vice versa and words in the singular include the plural and vice versa; |
| 1.149.4 | the words “include”, “included”, and “including” are to be construed without conveying any limitation to the generality of the preceding words; |
| 1.149.5 | reference to any statute or regulation includes any modification or re-enactment of that statute or regulation; |
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ARTICLE 2
COLLABORATION MANAGEMENT
| 2.2.1 | collaboratively discuss and identify human gene targets which the Parties may be interested to pursue as part of the Collaboration; |
| 2.2.2 | receive notification from Silence as to whether a Nominated Target is or is not a Restricted Target; |
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| 2.2.4 | review, discuss and determine whether to suspend the Eligible Target Pool Cap in accordance with Section 3.3.1; |
| 2.2.6 | review and discuss the activities to be conducted in each Research Plan for confirmation by the Parties pursuant to Section 3.7. |
| 2.2.7 | identify a Research Plan Team Leader for each Party, which individuals shall establish a project team for each Research Plan; |
| 2.2.8 | review and discuss the overall status of each Research Plan and the conduct of Research activities under each Research Plan; |
| 2.2.9 | review and discuss the results of each activity under each Research Plan, whether completed or ongoing; |
| 2.2.10 | review and agree to any amendment to a Research Plan; |
| 2.2.11 | establish a Patent Working Group to review and discuss the prosecution strategy for Silence Research Patents and Joint Research Patents, as set forth more fully in Section 12.1; |
| 2.2.13 | on an as-needed basis, establish subcommittees to perform specific duties of the JSC, direct each such subcommittee to perform the functions for which it is established, and oversee each subcommittee, including resolution of disputes raised to the JSC by any subcommittee; |
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a meeting of the JSC on less than fifteen (15) Business Days’ notice in the event that such Party reasonably believes that a significant matter must be addressed by the JSC within such sooner timeframe, and such Party shall provide any materials reasonably adequate to enable an informed decision to be made by the JSC at such meeting. An individual designated by the chairperson of the JSC shall prepare and circulate the minutes of each meeting for review and approval of the Parties within thirty (30) days after the meeting. The Parties shall agree on the minutes of each meeting promptly, but in no event later than the next meeting of the JSC. |
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| within the scope of the JSC, then the dispute shall first be referred to the Senior Officers of the Parties, who shall confer in good faith on the resolution of the issue. Any final decision mutually agreed by the Senior Officers shall be conclusive and binding on the Parties. |
| (ii) | subject to the provisions of [***], the disputed issue relates to [***]or [***], as further set out [***]; |
provided that (and in the case of [***], subject to [***]), in no event shall either Silence or AZ have any obligation to [***] that [***] or [***];
| (b) | [***] shall have final decision-making authority as to [***]: |
| (i) | [***]; |
provided that: (x) [***] shall not use its final decision-making authority to (a) [***] or (b) subject to [***], [***] that [***] or [***].
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2.10 | Expenses. Each Party shall be responsible for all travel and related costs and expenses for its members and other representatives to attend meetings of, and otherwise participate in, the JSC. |
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| is a compelling business reason to do so, including in the event of the publication of meaningful and relevant new data relating to the applicable human gene target, provided further that the decision to approve such suspension of such limitation may only be made by unanimous vote of the JSC and, failing such agreement by the JSC, may not be submitted for further consideration by the Senior Officer pursuant to Section 2.7.1 or be subject to a Party’s final decision making authority established in Section 2.7.2; |
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| (a) | is designated by AZ as a Selected Target pursuant to Section 3.5(i); |
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then, such Eligible Target will no longer be included in the Eligible Target Pool, and, subject to the provisions of Sections 3.2 and 3.3, the Parties shall be entitled to designate a different Nominated Target to take its place as an Eligible Target pursuant to Section 3.2. For the avoidance of doubt, any Eligible Target which fails to become a Selected Target shall not count towards the total number of Selected Targets AZ is entitled to designate pursuant to Section 3.6.
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| 3.9.1 | If, prior to the Option Exercise Date with respect to a particular Selected Target, AZ acting reasonably, forms the view that a compound meeting the Development Candidate Criteria will not be identified, then, upon written notice to Silence, AZ may substitute such Selected Target for a new Selected Target (a “Substitute Target”) provided that: |
| (a) | no more than [***] Selected Targets may be substituted pursuant to this Section 3.9; |
| (b) | no more than [***] years of the relevant Research Plan Term relating to the Replaced Target has elapsed; |
| (c) | any Substitute Target is deemed a Selected Target pursuant to the process set out in Section 3.5; and |
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| (ii) | grant to Silence the license set out in Section 16.6.1 in respect of each Replaced Target, and all associated RNAi Molecules, Licensed Compounds and Licensed Products generated in the relevant Research Plan. |
For clarity, if [***], AZ shall [***] any RNAi Molecules, Licensed Compounds or Licensed Products generated in the relevant Research Plan and which are directed to such Replaced Target, [***] grant to Silence any licenses to intellectual property in respect thereof.
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| 4.2.3 | Order of Precedence. If the terms of a Research Plan contradict, or create inconsistencies or ambiguities with, the terms of this Agreement, then the terms of this Agreement shall govern. |
| 4.3.1 | Diligence. |
| (a) | Silence shall not be required to perform any activities beyond those activities assigned to it in the applicable Research Plan. |
| (b) | The Parties shall use their respective Commercially Reasonable Efforts to carry out the tasks allocated to them in each agreed Research Plan, taking into account the scope of work initially planned under such Research Plan. Each Party shall use its Commercially Reasonable Efforts to adhere to any timeframes set forth in a Research Plan. |
| (a) | Generally. Except as provided in this Section 4.3.2 and Section 4.5, each Party shall be solely responsible for the costs and expenses |
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| incurred by such Party in connection with the performance of the Research activities assigned to such Party under and in accordance with each Research Plan and applicable Research Budget, unless otherwise expressly agreed in writing; and Silence shall not be required to incur any costs, fees or expenses beyond what is set forth in the applicable Research Plan. |
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| of a Substitute Target where Silence has utilized less than [***] of the Research Budget allocated to the Replaced Target which such Substitute Target replaced, then Silence shall be required to expend [***] of the Research Budget allocated to the Replaced Target for the performance of activities conducted on, or in relation to, the Substitute Target, unless otherwise agreed by the Parties in writing. |
| (b) | Substitute Target Research Plan Term. The Research Plan Term in respect of a Substitute Target shall not be reduced by any period of time spent on Research for the corresponding replaced Selected Target (whether or not the corresponding Research Budget is re-set pursuant to Section 4.3.3(a)) and shall be fully re-set in all cases, unless otherwise agreed by the Parties in writing. |
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| Agreement, conceived, discovered, developed, or otherwise made by such Subcontractors or Affiliates will vest in, are assigned to or shall be licensed to one of the Parties in accordance with ARTICLE 12, and (iv) Silence shall be responsible for the management of all of its Subcontractors and shall remain fully liable to AZ for the acts and omissions of such Subcontractors. |
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| (b) | Inspection. Each Party shall have the right to reasonably inspect the other Party’s records, and shall provide copies of all requested records, to the extent reasonably required for the exercise or performance of the requesting Party’s rights under this Agreement; provided, however, that the requesting Party shall maintain such records and the Information of the other Party as Confidential Information of the other Party in accordance with ARTICLE 13 hereof and shall not use such records or Information except to the extent otherwise permitted by this Agreement. |
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| Leaders shall provide the Development Candidate Data Package to the JSC for review. The JSC shall promptly review the Development Candidate Data Package for confirmation as to the extent to which the Development Candidate Criteria have been achieved. |
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| 4.4.4 | Option Evaluation by AZ. Following an Option Trigger Event, AZ will communicate to Silence in writing prior to expiry of the applicable Option Term whether AZ elects to exercise its Option in accordance with Section 6.1. |
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| the JSC, which updated package shall be reviewed in accordance with the process set forth in Section 4.4. |
| 4.5.2 | Increase to Research Budget; Costs. In the event Silence’s obligations pursuant to a Research Plan are increased as provided in Section 4.5.1, AZ shall bear all costs agreed to in such Research Plan extension, including all costs of FTEs involved in performing such work by or on behalf of Silence (which costs shall be charged by Silence to AZ at the FTE Cost). |
| 5.1.1 | Research and Development. During the Exclusivity Period, on an Eligible Target-by-Eligible Target and Selected Target-by-Selected Target basis, each Party shall not, and shall ensure that its respective Affiliates do not, whether on their own or with or through a Third Party, Research or Develop any [***] the relevant Eligible Target or Selected Target, except in the performance of their respective obligations under this Agreement. |
| 5.1.2 | Commercialization. During the Exclusivity Period, on an Eligible Target-by-Eligible Target and Selected Target-by-Selected Target basis, each Party shall not, and shall ensure that its respective Affiliates do not, whether on their own or with or through a Third Party, Commercialize [***] the relevant Eligible or Selected Target, except in the performance of their respective obligations under this Agreement. |
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applicable waiting periods. Where AZ has made its filings within the aforementioned time limit, the Option Exercise Effective Date shall automatically be extended until all applicable Antitrust Clearances (and/or all other such clearances) are granted, unless applicable Antitrust Laws permit a notified deal to close before Antitrust Clearance. Nothing in this Section 6.2 or otherwise in this Agreement shall require either Party to divest any assets, or to take action (beyond cooperation with the other Party) to respond to any “Second Request” from the FTC or similar request from any other Governmental Authority, in connection with any clearance filing. Each Party shall be responsible for all costs and expenses, including filing fees and attorneys’ fees, incurred by such Party in connection with the preparation and filings associated with obtaining Antitrust Clearance, and/or in connection with any other such clearance needed from any other Governmental Authority; provided, that AZ will bear all filing fees required by FTC or another Governmental Authority for submission in connection with obtaining Antitrust Clearance under the HSR Act or any applicable Antitrust Laws outside the Major Markets. In the event that all applicable Antitrust Clearances, in jurisdictions where applicable Antitrust Laws do not permit a notified deal to close before Antitrust Clearance, have not been granted within [***] days after the provision of written notice of the exercise of the relevant Option by AZ to Silence then Silence or AZ may terminate this Agreement insofar as it relates to the relevant Selected Target and the provisions of Section 6.4 shall apply to such Selected Target; provided, however, that such right to terminate shall not be available to a Party to the extent any action or failure to act by such Party has resulted in the failure of any applicable Antitrust Clearance to be obtained within such period of time. |
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| 6.4.2 | grant to Silence the license set out in Section 16.6.1 in respect of each Expired Target, and all associated RNAi Molecules, Licensed Compounds and Licensed Products. |
For clarity, if [***], AZ shall [***] any RNAi Molecules, Licensed Compounds or Licensed Products generated in the relevant Research Plan and which are directed to such Expired Target, [***] grant to Silence any licenses to intellectual property in respect thereof.
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licenses granted to AZ in Section 7.1 and outside the scope of its covenants under Section 5.1. |
7.7 | No [***]. Notwithstanding anything to the contrary in this Agreement, AZ shall not, directly or indirectly, [***]. |
ARTICLE 8
DEVELOPMENT AND COMMERCIALIZATION
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ARTICLE 9
MANUFACTURING & SUPPLY
| 9.1.1 | Silence, either directly or through one or more Third Party contract manufacturers, shall: |
| (a) | be responsible for all Manufacturing activities necessary to perform any of its obligations under a Research Plan, [***]; |
| (b) | upon receipt of a written request by AZ or as agreed between the Parties in the applicable Research Plan, use its Commercially Reasonable Efforts to Manufacture such quantity as expressly |
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| agreed in writing between the Parties, of Licensed Product for each DRF Study for each Selected Target; and |
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Target. AZ shall reimburse Silence for its costs and expenses incurred in complying with this Section 9.3 at the relevant FTE Cost. For clarity, (i) nothing shall require Silence to create any new Know-How, undertake any additional Manufacturing activities, or undertake any activity not specified in the relevant Research Plan (ii) and, on an Selected Target-by-Selected Target basis, Silence’s obligation shall be limited to no more than [***] of effort ([***]) to be taken within [***] months of the date that the first material is delivered to AZ by or on behalf of Silence pursuant to Section 9.1.1(c), in respect of such Selected Target. |
ARTICLE 10
PAYMENTS AND RECORDS
| 10.1.1 | Within [***] days after receipt of an invoice in respect thereof, which invoice may be delivered by Silence on the Effective Date, AZ shall pay to Silence the non-refundable, non-creditable sum of Twenty Million Dollars ($20,000,000). |
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Milestone Payment | |
[***] | [***] |
[***] | [***] |
[***] | [***] |
[***] | [***] |
[***] | [***] |
[***] | [***] |
[***] | [***] |
[***] | [***] |
[***] | [***] |
[***] | [***] |
Total | $140,000,000 |
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(A) (i) Only one of each of the milestones shall be payable for such Bispecific Product upon the achievement of any of the milestone events set forth in this Section 10.2, irrespective of such Bispecific Product being designed to [***] two Selected Targets, and (ii) such milestones shall only be payable to the extent they have not already been paid for each of the Monospecific Products (as defined below) designed to [***] one of the Selected Targets, against which the Bispecific Product is directed;
(B) If a Licensed Product is designed to [***] only one of the Selected Targets, against which the relevant Bispecific Product is directed (a “Monospecific Product”), each of the milestones shall, to the extent it has already been paid for the Bispecific Product, be payable only once upon the achievement of any of the milestone events by the first Monospecific Product, but not by the second and any further Monospecific Products. Schedule 10.2.3 provides some exemplary scenarios for how the milestones are determined pursuant to this Section 10.2 for a Bispecific Product and its corresponding Monospecific Products.
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| 10.3.1 | Licensed Product Sales Milestone Payments. In partial consideration of the rights granted by Silence to AZ hereunder and subject to the terms and conditions set forth in this Agreement, AZ shall pay to Silence, on a Licensed Product-by-Licensed Product basis, the following non-creditable, non-refundable milestone payments upon the achievement of each of the following milestone events for the Licensed Product (whether by or on behalf of AZ, its Affiliates or Sublicensees); provided, however, if the aggregate, worldwide Net Sales of the relevant Licensed Product do not, within [***] Years from the First Commercial Sale of such Licensed Product, equal or exceed [***], any such sales milestone shall only be payable to the extent the respective milestone event occurs during the [***] Years period from the First Commercial Sale. |
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Sales Milestone Payments | |
Equals or exceeds [***] | [***] |
Equals or exceeds [***] | [***] |
Equals or exceeds [***] | [***] |
Equals or exceeds [***] | [***] |
Total | $250,000,000 |
| 10.3.2 | Notice and Payment. AZ shall notify Silence in writing of the first achievement of any milestone event set forth in this Section 10.3 by or on behalf of AZ or its Affiliates or Sublicensees in its report provided pursuant to Section 11.1 and payment of such milestone shall be due on the date the first such statement that reflects achievement of such sales milestone payment is due. For clarity, each milestone payment set forth in the table above shall be paid only once upon first achievement of the corresponding milestone event by a Licensed Product, regardless of the number of times such event is achieved. |
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Royalty Rate | |
For that portion of Net Sales of a particular Licensed Product in any Year which are up to [***] | [***] |
For that portion of Net Sales of a particular Licensed Product in any Year which are greater than [***] but up to [***] | [***] |
For that portion of Net Sales of a particular Licensed Product in any Year which are greater than [***]but up to [***] | [***] |
For that portion of Net Sales of a particular Licensed Product in any Year which are greater than [***] | [***] |
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| such Third Party pursuant to such agreement from the royalties due to Silence pursuant to Section 10.4. |
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| amounts qualifying for a reduction from payments according to Section 10.5.3, which, in any Quarter cannot be deducted according to this Section 10.5.3(c), may be carried into future Quarters, subject to the foregoing sentence. |
ARTICLE 11
PAYMENT; RECORDS; AUDITS
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| reasonably required to obtain a refund of the withheld taxes, obtain a credit with respect to such taxes paid, or otherwise recover such taxes. In the event that a government authority retroactively determines that a payment made by a Party to the other pursuant to this Agreement should have been subject to withholding (or to additional withholding) taxes, and such Party (the “Withholding Party”) remits such withholding taxes to the government authority, the Withholding Party shall have the right (a) to offset such amount, including any interest and penalties that may be imposed thereon (except to the extent any such interest or penalties result from the negligence of the Withholding Party), against future payment obligations of the Withholding Party under this Agreement, (b) to invoice the other Party for such amount (which shall be payable by the other Party within [***] days of its receipt of such invoice), or (c) to pursue reimbursement by any other available remedy. |
| 11.3.3 | Taxes Resulting from a Party’s Action. Notwithstanding the foregoing in this Section 11.3, if a Party takes any action of its own discretion (not required |
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| by the terms of this Agreement or a Regulatory Authority), including any assignment, sublicense, change of place of incorporation, or failure to comply with Applicable Laws or filing or record retention requirements, which results in an additional or increased withholding obligation with respect to payments to be made pursuant to this Agreement (“Withholding Tax Action”), then such Party shall bear the amount of such withholding to the extent associated with such Withholding Tax Action. For clarity, if AZ undertakes a Withholding Tax Action, then the sum payable by AZ (in respect of which such withholding is required to be made) shall be increased to the extent necessary to ensure that Silence receives a sum equal to the sum which it would have received had no such Withholding Tax Action occurred. For the avoidance of doubt, a change in Applicable Laws that results in a new or increased withholding or deduction obligation, absent either Party taking a Withholding Tax Action, shall not affect the withholding and deduction obligations provided in Section11.3.1. |
| (a) | Each Party represents, warrants and undertakes that neither it nor its Affiliates shall commit a tax evasion facilitation offence under Part 3 of the UK Criminal Finances Act 2017 in connection with or attributable to this Agreement or the transactions contemplated hereby. |
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| the matters referred to in Section 11.3.4(a), in all cases, as reasonably required to enable that other Party to comply with its undertaking in Section 11.3.4(a). |
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in such manner as the Auditor shall determine. Not later than [***] days after such decision and in accordance with such decision, the audited Party shall pay the additional amounts, or the auditing Party shall reimburse the excess payments, as applicable. |
ARTICLE 12
INTELLECTUAL PROPERTY
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| 12.2.3 | AZ Ownership. As between the Parties, AZ or an Affiliate designated by AZ shall own and retain all right, title, and interest in and to any and all AZ Background IP and AZ Research IP, and Silence hereby assigns all of its right, title and interest in and to any AZ Research IP to AZ. |
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| (a) | Prior to AZ’s exercise of the Option corresponding to the applicable Selected Target to which the Licensed Compounds and/or Licensed Products Covered by such Product Specific Patents relate, Silence shall have the first right, but not the obligation, to prepare, file, prosecute, and maintain the Product Specific Patents related to the applicable Selected Target(s) worldwide, at Silence’s sole cost and expense. Silence shall keep AZ reasonably informed of all steps with regard to the preparation, filing, prosecution, and maintenance of such Product Specific Patents, and shall provide AZ with a copy of material communications to and from the patent authorities regarding such Product Specific Patents, including drafts of any material filings or responses to be made to such patent authorities sufficiently in advance of submitting such filings or responses so as to allow AZ a reasonable opportunity to review and comment thereon. Silence shall reasonably consider and reasonably incorporate AZ’s reasonable requests and suggestions with respect to such drafts and with respect to strategies for filing and prosecuting the Product Specific Patents. If Silence, during the Term, determines in its sole discretion to abandon or not maintain any of the Product Specific Patents in the Territory, then Silence shall provide AZ with prior written notice sufficiently in advance of any abandonment to enable AZ, at its sole discretion, to maintain such Product Specific Patent and assume the prosecution, at its sole cost and expense, and on receipt of such notice, Silence shall transfer such prosecution to AZ. |
| (b) | Upon AZ’s exercise of the Option corresponding to the applicable Selected Target to which the Licensed Compounds and/or Licensed Products Covered by such Product Specific Patents relate, AZ shall |
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| 12.3.4 | Joint Research Patents. |
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| informed of all steps with regard to the preparation, filing, prosecution, and maintenance of such Joint Research Patents, and shall provide AZ with a copy of material communications to and from the patent authorities regarding such Joint Research Patents, including drafts of any material filings or responses to be made to such patent authorities sufficiently in advance of submitting such filings or responses so as to allow AZ a reasonable opportunity to review and comment thereon. Silence shall reasonably consider and reasonably incorporate AZ’s requests and suggestions with respect to such drafts and with respect to strategies for filing and prosecuting the Joint Research Patents. If Silence, during the Term, determines in its sole discretion to abandon or not maintain any of the Joint Research Patents in the Territory, then Silence shall provide AZ with prior written notice sufficiently in advance of any abandonment to enable AZ, at its sole discretion, to maintain such Joint Research Patent and assume the prosecution, at its sole cost and expense, and on receipt of such notice, Silence shall transfer such prosecution to AZ. |
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| make an application for any extension or supplementary protection certificate with respect to such Patents in the Territory, it shall inform [***] in sufficient time for [***] to make such application and provide a copy of all documents and other information [***] may need to make such application. Each Party shall keep the other fully informed of its efforts to obtain such extension or supplementary protection certificate. Each Party shall provide prompt and reasonable assistance, as requested by the other, including by taking such action as patent holder as is required under any Applicable Law to obtain such patent extension or supplementary protection certificate. |
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| discretion, bring and control any legal action in connection therewith at its sole expense. |
| 12.4.3 | AZ Patents. AZ shall have the sole right, but not the obligation, to enforce and defend worldwide under its control, and at its own expense, the AZ Background Patents and AZ Research Patents. |
(ii) on or after AZ’s exercise of the Option corresponding to the applicable Selected Target(s) to which the Licensed Compounds and/or Licensed Products Covered by such Product Specific Patents relate, where Silence has assumed the maintenance and prosecution of such Product Specific Patent pursuant to Section 12.3.3(b),
Silence shall have the first right, but not the obligation, to enforce and defend worldwide under its control, and at its own expense, the relevant Product Specific Patents. If Silence does not exercise Commercially Reasonable Efforts to enforce or defend any such Infringement with respect to Product Specific Patents (a) within [***] days following the first notice provided to it pursuant to this Section 12.4.4, or (b) if earlier, [***] Business Days before the time limit, if any, set forth in appropriate laws and regulations for filing of such actions, then AZ may enforce such Product Specific Patents at its own expense.
| (b) | Upon AZ’s exercise of the Option corresponding to the applicable Selected Target to which the Licensed Compounds and/or Licensed |
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| (a) | (i) Prior to AZ’s exercise of the Option corresponding to the applicable Selected Target to which the Joint Research Patents relate, or |
(ii)on or after AZ’s exercise of the Option corresponding to the applicable Selected Target to which the Joint Research Patents relate, where Silence has assumed the maintenance and prosecution of such Joint Research Patent pursuant to Section 12.3.4(b),
Silence shall have the first right, but not the obligation, to enforce and defend worldwide under its control, and at its own expense, the relevant Joint Research Patents. If Silence does not take Commercially Reasonable Efforts to enforce or defend any such Infringement with respect to such Joint Research Patents (a) within [***] days following the first notice provided to it pursuant to this Section 12.4.5, or (b) if earlier, [***] Business Days before the time
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limit, if any, set forth in appropriate laws and regulations for filing of such actions, then AZ may enforce such Joint Research Patent(s) at its own expense.
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| 12.6.1 | Notice. Each Party shall promptly notify the other Party in writing of any alleged or threatened assertion of invalidity or unenforceability of any of the Silence Background Patents, Silence Research Patents, or Joint Research Patents by a Third Party, in each case in the Territory and of which such Party becomes aware. |
| 12.6.3 | AZ Patents. AZ shall have the sole right, but not the obligation, to defend and control the defense of the validity and enforceability of the AZ Background Patents and AZ Research Patents. |
| (a) | (i) Prior to AZ’s exercise of the Option corresponding to the applicable Selected Target to which the Licensed Compounds |
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(ii)on or after AZ’s exercise of the Option corresponding to the applicable Selected Target to which the Licensed Compounds and/or Licensed Products Covered by such Product Specific Patents relate, where Silence has assumed the maintenance and prosecution of such Product Specific Patent pursuant to Section 12.3.3(b),
Silence shall have the first right, but not the obligation, to defend and control the defense of the validity and enforceability of the relevant Product Specific Patents. AZ may participate in any such claim, suit, or proceeding in the Territory related to such Product Specific Patents with counsel of its choice at its own expense; provided that Silence shall retain control of the defense in such claim, suit, or proceeding. If Silence elects not to defend or control the defense of any such Product Specific Patents, or otherwise fails to initiate and maintain the defense of any such claim, suit, or proceeding, then AZ may conduct and control the defense of any such claim, suit, or proceeding, at its own expense; provided that AZ shall obtain the written consent of Silence [***], such consent not to be unreasonably withheld, conditioned, or delayed.
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| Territory related to such Product Specific Patents with counsel of its choice at its own expense; provided that AZ shall retain control of the defense in such claim, suit, or proceeding. If AZ elects not to defend or control the defense of any such Product Specific Patents, or otherwise fails to initiate and maintain the defense of any such claim, suit, or proceeding, then Silence may conduct and control the defense of any such claim, suit, or proceeding, at its own expense; provided that Silence shall obtain the written consent of AZ [***], such consent not to be unreasonably withheld, conditioned, or delayed. |
| (a) | (i)Prior to AZ’s exercise of the Option corresponding to the applicable Selected Target to which the Joint Research Patents relate, or |
(ii) on or after AZ’s exercise of the Option corresponding to the applicable Selected Target to which the Joint Research Patents relate, where Silence has assumed the maintenance and prosecution of such Joint Research Patent pursuant to Section 12.3.4(b),
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Silence shall have the first right, but not the obligation, to defend and control the defense of the validity and enforceability of the relevant Joint Research Patents. AZ may participate in any such claim, suit, or proceeding in the Territory related to such Joint Research Patents, in each case that [***] with counsel of its choice at its own expense; provided that Silence shall retain control of the defense in such claim, suit, or proceeding. If Silence elects not to defend or control the defense of any such Joint Research Patents, in each case that [***] in a suit brought in the Territory, or otherwise fails to initiate and maintain the defense of any such claim, suit, or proceeding, then AZ may conduct and control the defense of any such claim, suit, or proceeding, at its own expense; provided, that AZ shall obtain the written consent of Silence [***], such consent not to be unreasonably withheld, conditioned, or delayed. To the extent that there is any claim, suit, or proceeding of any of the Joint Research Patents in the Territory that [***], then [***] defend and control the defense of the validity and enforceability of the Joint Research Patents subject to Applicable Law.
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| Product in a suit brought in the Territory, or otherwise fails to initiate and maintain the defense of any such claim, suit, or proceeding, then Silence may conduct and control the defense of any such claim, suit, or proceeding, at its own expense; provided, that Silence shall obtain the written consent of AZ [***] such consent not to be unreasonably withheld, conditioned, or delayed. To the extent that there is any claim, suit, or proceeding of any of the Joint Research Patents in the Territory that [***], then [***] defend and control the defense of the validity and enforceability of the Joint Research Patents subject to Applicable Law. |
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| Patent, Silence will have the right to determine whether to opt in or opt out (and to opt in again) of the Unified Patent Court system and if requested by Silence, AZ will promptly do all things reasonably necessary and execute all documents required to give effect to such decision(s), provided that Silence will reimburse AZ its reasonable out-of-pocket expenses incurred in performing such acts. |
| 12.7.2 | Upon AZ’s exercise of the Option corresponding to the applicable Selected Target to which the Licensed Compounds and/or Licensed Products Covered by such Product Specific Patents or Joint Research Patent relate, unless and until Silence assumes the maintenance and prosecution of such Patents pursuant to Section 12.3.3(b) or 12.3.4(b), AZ will have the right to determine whether to opt in or opt out (and to opt in again) of the Unified Patent Court system and if requested by AZ, Silence will promptly do all things reasonably necessary and execute all documents required to give effect to such decision(s), provided that AZ will reimburse Silence its reasonable out-of-pocket expenses incurred in performing such acts. |
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ARTICLE 13
CONFIDENTIALITY AND NON-DISCLOSURE
| 13.1.1 | has been published by a Third Party or otherwise is or hereafter becomes part of the public domain through no fault on the part of the receiving Party; |
| 13.1.2 | have been in the receiving Party’s possession prior to disclosure by the disclosing Party without any obligation of confidentiality with respect to such information; |
| 13.1.3 | is subsequently received by the receiving Party from a Third Party without restriction and without breach of any agreement between such Third Party and the disclosing Party; |
| 13.1.4 | that is generally made available to Third Parties by the disclosing Party without restriction on disclosure; or |
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| 13.1.5 | have been independently developed by or for the receiving Party without reference to or use of the disclosing Party’s Confidential Information. |
Specific aspects or details of Confidential Information shall not be deemed to be within the public domain or in the possession of the receiving Party merely because the Confidential Information is embraced by more general information in the public domain or in the possession of the receiving Party. Further, any combination of Confidential Information shall not be considered in the public domain or in the possession of the receiving Party merely because individual elements of such Confidential Information are in the public domain or in the possession of the receiving Party unless the combination and its principles are in the public domain or in the possession of the receiving Party.
13.2 | Permitted Disclosures. Each Party may disclose Confidential Information of the other Party to the extent such disclosure is reasonably necessary in the following instances: |
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Notwithstanding the foregoing, in the event a Party is required to make a disclosure of the other Party’s Confidential Information pursuant to Section 13.2.1 or 13.2.2, it will, except where impermissible, give reasonable advance notice to the other Party of such disclosure and comply with all reasonable requests of the disclosing Party with respect to maintaining confidence in such Confidential Information and in any event shall use the same diligent efforts to secure confidential treatment of such Confidential Information as such Party would use to protect its own Confidential Information, but in no event less than reasonable efforts. In any event, the Parties agree to take all reasonable action to avoid disclosure of Confidential Information. Any information disclosed pursuant to this Section 13.2 shall remain Confidential Information and subject to the restrictions set forth in this Agreement, including the foregoing provisions of this ARTICLE 13.
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submit the proposed disclosure identifying the other Party in writing to such other Party as far in advance as reasonably practicable (and in no event less than [***] Business Days prior to the anticipated date of disclosure) so as to provide a reasonable opportunity to comment on such disclosure. |
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| Party’s Confidential Information in any such paper and will withhold publication of any such paper or any presentation of same for an additional [***] days in order to permit the Parties to obtain Patent protection if such other Party deems it necessary. |
ARTICLE 14
REPRESENTATIONS AND Warranties
14.1 | Mutual Warranties. Each Party hereby represents and warrants, as of the Effective Date, as follows: |
| 14.1.1 | Organization. It is a company duly organized, validly existing, and in good standing under the laws of the jurisdiction of its organization, and has all requisite power and authority, corporate or otherwise, to execute, deliver, and perform this Agreement. |
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| 14.1.3 | Binding Agreement. This Agreement is a legal, valid, and binding obligation of such Party enforceable against it in accordance with its terms, subject to the effects of bankruptcy, insolvency, or other laws of general application affecting the enforcement of creditor rights, judicial principles affecting the availability of specific performance, and general principles of equity (whether enforceability is considered a proceeding at law or equity). |
| 14.1.4 | No Inconsistent Obligation. It is not under any obligation, contractual or otherwise, to any Person that conflicts with or is inconsistent with the terms of this Agreement, or that would impede the diligent and complete fulfilment of its obligations hereunder. |
14.2 | Additional Warranties by Silence. Except as set forth in Schedule 14.2, Silence hereby represents and warrants to AZ, as of the Effective Date, as follows: |
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| anticipated to be granted to AZ under this Agreement, and (c) Silence Background IP does not include any intellectual property that is in-licensed from a Third Party; |
| 14.2.2 | to Silence’s Knowledge (a) the issued patents within the Silence Background Patents existing as of the Effective Date are valid and enforceable patents and (b) Silence has not received any written notice of any, nor is there any ongoing, claim or threatened claim by any Third Party (i) challenging the scope, validity or enforceability of any issued Silence Background Patents, (ii) asserting the misuse or non-infringement of any of the Silence Background IP, or (iii) challenging Silence’s Control of any of the Silence Background IP; |
| 14.2.3 | (a) it and its Affiliates have, to Silence’s Knowledge, materially complied with all applicable disclosure requirements of the applicable Governmental Authority, in connection with the prosecution and maintenance of the Silence Background Patents existing as of the Effective Date, (b) the pending applications included in Silence Background Patents are being diligently prosecuted in the respective patent offices in the Territory in which Silence has chosen to file in accordance with Applicable Law, (c) to Silence’s Knowledge, Silence has presented all relevant references, documents and information of which it and the inventors are aware to the relevant patent examiner at the relevant patent office, and (d) it has timely paid all filing and renewal fees payable with respect to any such Silence Background Patents; |
| 14.2.4 | Silence and its Affiliates have taken commercially reasonable measures consistent with industry practices to protect the secrecy, confidentiality and value of all information within the Silence Background Know-How existing as of the Effective Date that Silence purports to be confidential or trade secret information; |
| 14.2.5 | the information provided by Silence to AZ regarding the Silence Background IP is true and correct in all material respects and Silence does not have |
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| Knowledge of any material adverse information with respect to the Silence Background IP intended to be used in any Research Plan that has not been disclosed to AZ; |
| 14.2.6 | to Silence’s Knowledge, there is no (a) claim, demand, suit, proceeding, arbitration, inquiry, investigation or other legal action of any nature, civil, criminal, regulatory or otherwise, pending or, to the Knowledge of Silence, threatened against Silence or any of its Affiliates, or (b) judgment or settlement against or owed by Silence or any of its Affiliates; in each case of (a) and (b) in connection with the Silence Background IP or relating to the transactions contemplated by this Agreement; |
| 14.2.7 | to Silence’s Knowledge, all individuals who are current or former officers, employees, agents, advisors, consultants, contractors or other representatives of Silence or any of its Affiliates who are inventors of or have otherwise contributed in a material manner to the creation or development of any Silence Background IP have executed and delivered to Silence or the applicable Affiliate a valid and enforceable assignment; |
| 14.2.8 | to Silence’s Knowledge, no current officer, employee, agent, advisor, consultant or other representative of Silence or any of its Affiliates is in violation of any term of any assignment, license, consulting, employment or other agreement with Silence or such Affiliate regarding the protection of any of the Silence Background IP; |
| 14.2.9 | to Silence’s Knowledge, the development of Silence Background IP as contemplated under this Agreement has been conducted in compliance in all material respects with all Applicable Law; and |
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| of an FDA debarment investigation or proceeding (or similar proceeding of foreign equivalent), in any capacity in connection with this Agreement. |
14.3 | Mutual Covenants. Each Party hereby covenants and agrees, in connection with the performance of its activities under this Agreement: |
| 14.3.1 | it shall not employ, contract with, or retain any person directly or indirectly to perform any of the activities under this Agreement if such person is under investigation by the FDA for debarment or is presently debarred by the FDA pursuant to the Generic Drug Enforcement Act of 1992, as amended (21 U.S.C. § 301, et seq.); |
| 14.3.2 | all Research conducted by or on behalf of it shall be performed in accordance with Applicable Laws, and applicable established internal policies and procedures (if any), including policies and procedures pertaining to research involving laboratory animals or hazardous agents and materials, as applicable. Each Party agrees that any animals used in the performance of studies under each Research Plan will be handled in accordance with established guidelines for the care and use of laboratory animals. Further, each Party covenants that all Research conducted pursuant to this Agreement involving the use of animals was, or will be, reviewed and approved by its or its animal care and use committee prior to commencement of the applicable Research; and |
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| any other Third Party, in each case, related to the transaction in a manner that would violate Anti-Corruption Laws. |
15.1 | Indemnification of Silence. AZ shall indemnify, defend, and hold harmless Silence, its Affiliates, and their respective directors, officers, employees, consultants, contractors |
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and agents (collectively, the “Silence Indemnitees”) from and against any and all losses, damages, liabilities, penalties, costs, and expenses (including reasonable attorneys’ fees and expenses) (collectively, “Losses”) in connection with any and all suits, investigations, claims, or demands of Third Parties (collectively, “Claims”) incurred by or rendered against the Silence Indemnitees arising from or occurring as a result of: |
| 15.1.1 | the Exploitation of any Licensed Product by or on behalf of AZ or any of its Affiliates, Sublicensees, subcontractors, agents, or consultants; or |
| 15.1.2 | the breach by AZ of any warranty, representation, covenant, or agreement made by AZ in this Agreement; or |
| 15.1.3 | the negligence, recklessness or willful misconduct of any AZ Indemnitee; |
provided that such indemnity shall not apply to the extent Silence has an indemnification obligation pursuant to Section 15.2 for such Losses, as to which Losses each Party shall indemnify the other to the extent of their respective liability for such Losses.
| 15.2.1 | the breach by Silence of any warranty, representation, covenant, or agreement made by Silence in this Agreement; or |
| 15.2.2 | the negligence, recklessness or willful misconduct of any Silence Indemnitee; or |
| 15.2.3 | following the grant of the license set out in Section 16.6.1, the Exploitation of any Licensed Product Covered by such license, by or on behalf of Silence or any of its Affiliates, Sublicensees, subcontractors, agents, or consultants; |
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provided that such indemnity shall not apply to the extent AZ has an indemnification obligation pursuant to Section 15.1 for such Losses, as to which Losses each Party shall indemnify the other to the extent of their respective liability for such Losses.
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ARTICLE 16
Term and Termination
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including under a duty of candor to a patent office), filing a request for or pursuing a re-examination of any of the Silence Background Patents, Silence Research Patents or Joint Research Patents (other than with Silence’s written agreement), or becoming a party to or pursuing an interference; or (z) filing or pursuing any opposition, cancellation, nullity, or other like proceedings against any of the Silence Background Patents, Silence Research Patents or Joint Research Patents; but excluding (i) any challenge raised by AZ or its Affiliates as a defense against a claim, action, or proceeding asserted by Silence or its Affiliates against AZ or its Affiliates or Sublicensees; (ii) any existing challenges, whether in a court or administrative proceeding, against a Silence Background Patent, raised by a Third Party that is acquired by AZ or its Affiliates after the Effective Date, provided that AZ, and AZ procures that its Affiliates, promptly withdraws from any such existing challenge; and (iii) any legal or administrative proceeding derived from a bona fide inventorship dispute between AZ or its Affiliates and Silence or its Affiliates for any AZ Research Patent, Joint Research Patent or Silence Research Patent. |
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within [***] days of the filing thereof or, in the case of an application or petition filed in any other jurisdiction, within [***] days of the filing thereof; or (g) admits in writing its inability generally to meet its obligations as they fall due in the general course (providing always that a request for fulfilment of a specific obligation to be postponed for a specified time shall not amount to an admission that the Party is generally unable to meet its obligations as they fall due), then the other Party may terminate this Agreement in its entirety effective immediately upon written notice to such Party. |
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| (c) | For clarity, the license set out in this Section 16.6.1 shall survive any expiration or termination of this Agreement. Notwithstanding anything to the contrary set forth herein, (i) AZ shall not be obligated to grant any licenses pursuant to this Section 16.6.1 for any Returned Targets [***], and (ii) any licenses granted under this Section 16.6.1 shall be [***]. |
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| reasonable terms and conditions. In any event, Silence shall not be required to negotiate a substitute license agreement if the sub-licensee is in material breach under the respective sublicense Agreement or if the sub-licensee caused a material breach of AZ under this Agreement. |
| (i) | AZ shall, in its discretion and on written notice to Silence, either (i) wind down all Clinical Studies that were Initiated by or on behalf of it prior to the termination of this Agreement (whether terminated in its entirety or with respect to a Selected Target) (“Ongoing Clinical Studies”), or (ii) be responsible for completing (in accordance with the established protocols) all Ongoing Clinical Studies; provided, that if AZ has elected to continue Ongoing Clinical Studies, the Parties may agree in writing to transition such Ongoing Clinical Studies to Silence. |
| (ii) | AZ shall not commence any Clinical Studies with respect to any Licensed Product directed to a terminated Selected Target at any time after it has given or received a notice of termination pursuant to this ARTICLE 16 in respect of such Selected Target. |
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| corresponding terminated Licensed Products to Silence and/or its designee(s) following delivery of notice of termination so that Silence is able to assume responsibility for same as of the effective date of termination. Where the same cannot be fully achieved prior to the effective date of termination, AZ shall continue to provide such reasonable cooperation to Silence and its designee(s) until such transition has been completed. Without limiting the generality of the foregoing, AZ shall provide reasonable consultation and assistance for a period of no more than [***] days after termination for the purpose of transferring or transitioning to Silence AZ Background Know-How and AZ Research Know-How not already in Silence’s possession in each case, to the extent reasonably necessary for Silence to continue the Ongoing Clinical Studies of the Licensed Products in the Territory. |
| (ii) | In the event this Agreement is terminated [***], AZ shall bear all costs and expenses of the disposition of Ongoing Clinical Studies as set forth in this Section 16.6.3. |
| (iii) | In the event this Agreement is terminated [***], Silence shall bear all costs and expenses of the disposition of Ongoing Clinical Studies as set forth in this Section 16.6.3. |
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| that Silence is able to assume responsibility for any Ongoing Clinical Studies and any other Development activities relating to any terminated Selected Target and/or terminated Licensed Product as promptly and efficiently as possible, to ensure that all necessary Regulatory Approvals are maintained and filed for in good time and that Silence has access to all documents, records, information, and correspondence reasonably required in connection therewith. |
| (a) | AZ, its Affiliates and Sublicensees shall be entitled to continue to sell (but not to actively promote after the effective date of termination) any existing inventory of Licensed Products directed to a Selected Target in respect of which this Agreement has been terminated, and for which Regulatory Approval therefor has been obtained, in accordance with the terms and conditions of this Agreement, for a period of [***] months after the effective date of such termination. |
| (b) | In the event this Agreement is terminated [***], Silence shall have the right, at its discretion, to purchase from AZ any or all of the inventory of Licensed Products and Licensed Compounds held by or on behalf of AZ at the date of termination at a price equal to [***]; provided that [***]. Silence shall notify AZ [***] days of the effective date of termination whether Silence elects to exercise such right. |
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| Selected Targets to the extent reasonably necessary for Silence to continue the Development and/or Commercialization of such Licensed Products in the Territory. |
| 16.6.7 | Exclusivity. Upon any termination of this Agreement with respect to a Selected Target, each Party’s obligations under ARTICLE 5 with respect to such Selected Target shall terminate. |
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| 16.6.12 | Accrued Rights; Surviving Obligations. Termination or expiration of this Agreement for any reason shall be without prejudice to any rights that shall have accrued to the benefit of a Party prior to such termination or expiration. Such termination or expiration shall not relieve a Party from obligations that are expressly indicated to survive the termination or expiration of this Agreement. Without limiting the foregoing, the following Articles and Sections shall survive any such termination or expiration: Articles 1 and 15 and Sections 2.7.1, 4.3.7, 11.4, 11.5., 11.6, 11.7, 12.2.5, 13.1, 13.2, 13.3, 13.4, 13.6, 14,6, 16.6, 17.5, 17.6, 17.7, 17.8, 17.9, 17.10, 17.11, 17.2, 17.13, 17.14 and 17.18. |
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| 17.3.1 | The intellectual property of the Silence Acquiror held or developed by such Silence Acquiror prior to or after such acquisition shall be excluded from the Silence Background Patents and Silence Background Know-How, and such Silence Acquiror (and Affiliates of such Silence Acquiror which are not controlled by (as defined under the Affiliate definition in Section 1.2) Silence itself) shall be excluded from the Affiliate definition solely for purposes of the applicable components of the Silence Background Patents and Silence Background Know-How and for the purposes of ARTICLE 5. |
| (a) | Silence (or its successor) will, immediately following the Silence Change of Control or initiation of the Competitive Program, as applicable, establish and implement appropriate firewall procedures to segregate all activities (and the personnel conducting such activities) in such Competitive Program from the activities performed by or on behalf of Silence pursuant to this Agreement, including ensuring that personnel directly involved in working in such Competitive Program shall not have access to any Confidential Information of either Party with respect to activities under this Agreement; |
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| (a) | [***] shall be amended such that [***] shall be [***]. By way of example only, if [***] then the [***]. If [***] then [***]. |
| (b) | For clarity, (i) AZ shall [***] pursuant to [***] and [***] in accordance with the provisions of [***]; and (ii) Silence shall [***] pursuant to (and subject to the limits in) [***]. |
| (c) | [***] shall [***]; |
| (d) | The provisions of [***] shall [***] for [***] days after the Silence COC Notification Date; and |
| (e) | In respect of any [***] within [***] days of the Silence COC Notification Date, whether such [***] or not shall be [***] of such Silence Change of Control. |
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The rights and obligations of the Parties under this Agreement shall be binding upon and inure to the benefit of the successors and permitted assigns of the Parties, and the name of a Party appearing herein will be deemed to include the name of such Party’s successors and permitted assigns to the extent necessary to carry out the intent of this Section 17.4. Any assignment not in accordance with this Section 17.4 shall be null and void.
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promptly to replace such invalid, unenforceable, or illegal part with a valid, enforceable, and legal provision which most closely effectuates the Parties’ original intent. |
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If to AZ, to:
AstraZeneca AB
Pepparedsleden 1,
SE-431 83 Mölndal, Sweden
Attention: Legal Department
[***]
With a copy (which shall not constitute notice) to:
AstraZeneca Pharmaceuticals LP
1800 Concord Pike
Wilmington, Delaware
19803
USA
Attention: Head of Business Development
for BioPharmaceuticals R&D
[***]
If to Silence, to:
Silence Therapeutics Plc
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London W14 8TH
United Kingdom
Attention: John Strafford, VP, Head of Business Development
[***]
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exclude any other right or remedy provided by Applicable Law or otherwise available except as expressly set forth herein. |
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(b) if not delivered under subsection (a) above, following the rejection of this Agreement by or on behalf of the Party subject to such proceeding upon written request therefor by the non-subject Party. The Parties acknowledge and agree that payments made under Sections 10.2 or 10.3 or pursuant to any supply agreement entered into in connection with this Agreement shall not (a) constitute royalties within the meaning of Section 365(n) of the U.S. Bankruptcy Code or any analogous provisions in any other country or jurisdiction or (b) relate to licenses of intellectual property hereunder. |
Silence acknowledges that AZ is an Affiliate of all Persons whose ultimate parent is AstraZeneca plc. In recognition of the foregoing and without prejudice to the provisions of any Section in this Agreement that explicitly refers to AZ’s Affiliates, the Parties agree that any Affiliates of AZ may exercise any of the rights granted to AZ in this Agreement
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or perform any of AZ’s obligations in this Agreement provided that AZ shall be responsible for the performance of any of its obligations that are performed by its Affiliates.
{SIGNATURE PAGE FOLLOWS}
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THIS RESEARCH COLLABORATION, OPTION AND LICENSE AGREEMENT IS EXECUTED by the authorized representatives of the Parties as of the Effective Date.
SILENCE THERAPEUTICS PLC | ||
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By: |
| /s/ Iain Ross |
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Name: |
| Iain Ross |
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Title: |
| Executive Chairman |
ASTRAZENECA AB (publ) | ||
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By: |
| /s/Regina Fritsche Danielson |
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Name: |
| Regina Fritsche Danielson |
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Title: |
| SVP, Early CVRM |
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