false 0001636282 0001636282 2024-10-11 2024-10-11

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): October 11, 2024

 

 

SPYRE THERAPEUTICS, INC.

(Exact name of Registrant as Specified in Its Charter)

 

 

 

Delaware   001-37722   46-4312787

(State or Other Jurisdiction

of Incorporation)

 

(Commission

File Number)

 

(IRS Employer

Identification No.)

221 Crescent Street

Building 23

Suite 105

   
Waltham, MA     02453
(Address of Principal Executive Offices)     (Zip Code)

Registrant’s Telephone Number, Including Area Code: 617 651-5940

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class

 

Trading

Symbol(s)

 

Name of each exchange

on which registered

Common Stock, $0.0001 Par Value Per Share   SYRE  

The Nasdaq Stock Market LLC

(Nasdaq Global Select Market)

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

 

 

 


Item 1.01

Entry into a Material Definitive Agreement.

IL-23 (SPY003) License Agreement – Paragon Therapeutics, Inc.

On October 11, 2024, Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), and Paragon Therapeutics, Inc., a Delaware corporation (“Paragon”), entered into a license agreement (the “SPY003 License Agreement”), pursuant to which Paragon granted the Company a royalty-bearing, world-wide, exclusive license to develop, manufacture, commercialize or otherwise exploit certain antibodies and products targeting IL-23 in the field of irritable bowel disease (“IBD”).

Under the terms of the SPY003 License Agreement, the Company is obligated to pay Paragon up to $22.0 million based on specific development, regulatory and clinical milestones for the first Company product to reach such milestones, including a $1.5 million fee for nomination of a development candidate, as applicable, and a further milestone payment of $2.5 million upon the first dosing of a human patient in a Phase 1 trial. In addition, the following summarizes other key terms of the SPY003 License Agreement:

 

   

Paragon will provide the Company with an exclusive license in the field of IBD to its patents covering the related antibody, the method of use and its method of manufacture.

 

   

Paragon will not conduct any new campaigns that generate anti-IL-23 monospecific antibodies in the field of IBD for at least 5 years.

 

   

The Company will pay Paragon a low single-digit percentage royalty for single antibody products and a mid single-digit percentage royalty for products containing more than one antibody from Paragon.

 

   

There is a royalty step-down of 1/3rd if there is no Paragon patent in effect during the royalty term.

 

   

The royalty term ends on the later of (i) the last-to-expire licensed patent or Company patent directed to the manufacture, use or sale of a licensed antibody in the country at issue or (ii) 12 years from the date of first sale of a Company product.

 

   

Agreement may be terminated on 60 days’ notice by the Company; on material breach without cure; and to the extent permitted by law, on a party’s insolvency or bankruptcy.


Amended and Restated Biologics Master Services Agreement – WuXi Biologics (Hong Kong) Limited

In April 2023, Paragon and WuXi Biologics (Hong Kong) Limited (“WuXi Biologics”) entered into a biologics master services agreement (the “Original MSA”), which was subsequently novated to the Company by Paragon on September 19, 2023 pursuant to a novation agreement (the “Novation Agreement”) among the Company, Paragon and WuXi Biologics.

On October 14, 2024, the Original MSA was amended and restated by WuXi Biologics and the Company (the “A&R MSA”). Among other things, the A&R MSA added a termination provision that allows the A&R MSA to be terminated, in whole or in part, by the Company in the event that any law is enacted that has, or could be reasonably expected to have, a material adverse effect on the Company or any product of the Company that is the subject of the A&R MSA, in each case, as a result of WuXi Biologics providing services under the A&R MSA or the Company being a party to the A&R MSA. The A&R MSA also incorporated certain technology transfer, discount and priority in access obligations for WuXi Biologics.

Amended and Restated Cell Line License Agreement – WuXi Biologics (Hong Kong) Limited

In April 2023, Paragon and WuXi Biologics entered into a cell line license agreement (the “Original CLLA”), which was subsequently novated to the Company by Paragon pursuant to the Novation Agreement.

On October 14, 2024, the Original CLLA was amended and restated by WuXi Biologics and the Company (the “A&R CLLA”). Among other things, the A&R CLLA added terms that permit the royalties owed under the A&R CLLA to be bought out on a product-by-product basis for a lump-sum payment and certain financial terms to address risks related to potential changes in or new applicable laws.

The foregoing are brief descriptions of the terms and conditions of the SPY003 License Agreement and amendments to the Original MSA and Original CLLA that are detailed in the A&R MSA and the A&R CLLA, respectively, that are material to Company and do not purport to be complete. Each description is each qualified in its entirety by reference to the complete text of the SPY003 License Agreement, the A&R MSA and the A&R CLLA, respectively, copies of which are attached hereto, with confidential terms redacted, as Exhibits 10.1, 10.2 and 10.3, respectively.

 

Item 7.01

Regulation FD Disclosure

On October 14, 2024, the Company issued a press release announcing the expected acceleration of its SPY003 product candidate clinical timelines and presentations of preclinical data for each of its product candidates and combinations of SPY003 with either SPY001 or SPY002.

The information in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.

 

Item 8.01

Other Events.

On October 14, 2024, the Company posted an updated corporate presentation (the “Corporate Presentation”) on its website. The Corporate Presentation includes, without limitation, updates for its anti-α4b7 antibody research program, SPY001, its anti-TL1A antibody research program, SPY002, its anti-IL-23 antibody research program, SPY003, and therapeutic combinations of the foregoing. A copy of the Corporate Presentation is attached hereto as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.



SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

      SPYRE THERAPEUTICS, INC.
Date: October 15, 2024     By:  

/s/ Cameron Turtle

     

Cameron Turtle

Chief Executive Officer

Exhibit 10.1

[***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE THE INFORMATION (I) IS NOT MATERIAL AND (II) IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL.

EXECUTION VERSION

LICENSE AGREEMENT

THIS LICENSE AGREEMENT (“Agreement”) is entered into and effective as of October 11, 2024 (the “Effective Date”), by and between Paragon Therapeutics, Inc., a corporation organized under the laws of the State of Delaware (“Paragon”), having its principal place of business at 221 Crescent Street, Building 23, Suite 105, Waltham, MA 02453, and Spyre Therapeutics, Inc. (“Spyre”), a corporation organized under the laws of the State of Delaware, having its principal place of business at 221 Crescent Street, Building 23, Suite 105, Waltham, MA 02453. Paragon and Spyre are also referred to herein individually as a “Party”, or collectively as the “Parties.”

RECITALS

WHEREAS, Paragon has developed a proprietary platform technology for the discovery and development of antibodies against therapeutically relevant targets;

WHEREAS, pursuant to that certain Second Amended and Restated Antibody Discovery and Option Agreement by and among Paragon, Spyre Therapeutics, LLC (a wholly-owned subsidiary of Spyre) and Parapyre Holding LLC, a Delaware limited liability company, dated as of May 14, 2024 (as such agreement may be further amended from time to time, the “Option Agreement”), Spyre has engaged Paragon to identify, evaluate and develop one or more antibody candidates directed to certain therapeutic targets and has been granted an exclusive option to enter into one or more separate license agreements to develop, manufacture and commercialize the resulting antibodies with respect to a given target;

WHEREAS, Spyre has exercised such option with respect to the Licensed Target (as defined below), and the Parties desire to memorialize the exclusive license from Paragon to Spyre with respect to such Licensed Target, all on the terms and subject to the conditions set forth in this Agreement.

NOW THEREFORE, in consideration of the foregoing premises and the mutual covenants contained herein and other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties, intending to be legally bound, agree as follows:

ARTICLE I

DEFINITIONS.

The following initially capitalized terms have the following meanings (and derivative forms of them shall be interpreted accordingly):

1.1 “Achievement of Development Candidate” means the first to occur of: (a) nomination by Spyre’s Board of Directors of a Spyre Product as a “Development Candidate”; and (b) the initiation by or on behalf of Spyre or its Affiliate or Sublicensee of a toxicology study with respect to a Spyre Product that employs applicable then-current good laboratory practice standards, the results of which are intended to be submitted as part of an IND.

1.2 “Acquired Program” has the meaning set forth in Section 2.2(c).


1.3 “Acquiring Entity” means, collectively, the Third Party referenced in the definition of Change of Control and such Third Party’s Affiliates, other than (a) the applicable Party in the definition of Change of Control, and (b) such Party’s Affiliates, determined immediately prior to the closing of such Change of Control ((a) and (b) collectively, the “Pre-Existing Entities”).

1.4 “Affiliate” means any entity controlled by, controlling, or under common control with a Party hereto. For the purpose of this definition, “control” (including, with correlative meaning, the terms “controlled by” or “under common control”) means the direct or indirect ownership of more than fifty percent (50%) of the voting interest in, or more than fifty percent (50%) in the equity of, or the right to appoint more than fifty percent (50%) of the directors or management of, such corporation or other business entity. Notwithstanding the foregoing, (a) with respect to either Party, Affiliates of such Party do not include [***] or its Affiliates other than such Party and its subsidiaries, (b) Paragon and its Affiliates, on the one hand, and Spyre and its subsidiaries, on the other hand, shall not be deemed to be Affiliates of each other, and (c) subject to Paragon’s obligations under Section 7.3(a), Affiliates of Paragon do not include new entities formed by or on behalf of Paragon for the sole bona fide purpose of further developing, manufacturing, commercializing or otherwise exploiting Antibodies and Antibody products (excluding any Licensed Antibody Technology or Other Licensed Technology) using, among other sources, funds from Third Party investors.

1.5 “Agreement” has the meaning set forth in the preamble.

1.6 “Antibody” means any molecule, including [***].

1.7 “Anti-Corruption Laws” has the meaning set forth in Section 7.2(q)(i).

1.8 “Applicable Law” means any national, supra-national, federal, state or local laws, rules, guidances, and regulations, in each case, as applicable to the subject matter and the Party at issue.

1.9 “Bankruptcy Code” has the meaning set forth in Section 8.4.

1.10 “Bankruptcy Event” has the meaning set forth in Section 8.4.

1.11 “Business Day” means any day other than Saturday, Sunday or a national holiday in the United States.

1.12 “Calendar Quarter” means the respective periods of three (3) consecutive calendar months ending on March 31, June 30, September 30 and December 31.

1.13 “Calendar Year” means each successive period of twelve (12) months commencing on January 1 and ending on December 31.

1.14 “Change of Control” means, with respect to any entity, any of the following: (a) the sale or disposition of all or substantially all of the assets of such entity or its direct or indirect controlling Affiliate to a Third Party; or (b) (i) the acquisition by a Third Party, alone or together with any of its Affiliates, other than an employee benefit plan (or related trust) sponsored or

 

2


maintained by such entity or any of its Affiliates, of more than fifty percent (50%) of the then-outstanding shares of voting capital stock of such entity or its direct or indirect parent entity that holds, directly or indirectly, beneficial ownership of more than fifty percent (50%) of the then-outstanding shares of voting capital stock of such entity (a “Parent Entity”), or (ii) the acquisition, merger or consolidation of such entity or its Parent Entity with or into another entity, other than, in the case of clause (i) or (ii), an acquisition or a merger or consolidation of such entity or its Parent Entity in which the holders of shares of voting capital stock of such entity or its Parent Entity, as the case may be, immediately prior to such acquisition, merger or consolidation will beneficially own, directly or indirectly, at least fifty percent (50%) of the shares of voting capital stock of the acquiring Third Party or the surviving corporation in such acquisition, merger or consolidation, as the case may be, immediately after such acquisition, merger or consolidation, and in each case of (a) or (b), whether through a single transaction or a series of related transactions, but excluding any and all bona fide financing transactions or internal reorganizations for tax purposes (including the change of place of incorporation or domicile of such entity).

1.15 “Claim” has the meaning set forth in Section 9.3.

1.16 “COC Program” has the meaning set forth in Section 2.2(b).

1.17 “Combination Product” has the meaning set forth in Section 1.58.

1.18 “Commercialize” or “Commercializing” means any and all activity to market, promote, distribute, offer for sale, sell, have sold, seek reimbursement, import, have imported, export, have exported, or otherwise commercialize an Antibody or product, including any Licensed Antibody, Derived Antibody, Product, Multispecific Antibody, Multispecific Product, as applicable, and including interacting with Regulatory Authorities following receipt of Regulatory Approval and seeking and maintaining any required Reimbursement Approval. When used as a noun, “Commercialization” means any and all activities involved in Commercializing.

1.19 “Commercially Reasonable Efforts” means those efforts and resources, including reasonably necessary and qualified personnel, equivalent to the efforts and resources that a reasonable international biopharmaceutical company or a pharmaceutical company, in each case, that is of comparable size and resources to the applicable Party would typically devote as part of an active and continuing program of development and commercialization of a pharmaceutical or biologic product of similar market potential, at a similar stage of its product life, taking into account the competitiveness of the marketplace and the proprietary position, regulatory status, and relative safety and efficacy of such product. Commercially Reasonable Efforts requires, with respect to an obligation, that the applicable Party (a) assign responsibility for such obligation to specific employees who are held accountable for progress and monitor such progress on an on-going basis, (b) set and seek to achieve reasonable objectives for carrying out such obligation, and (c) make and implement reasonable decisions and allocate resources designed to advance progress with respect to such objectives.

1.20 “Confidential Information” of a Party means Know-How and any and all non-public scientific, business, regulatory or technical information that is disclosed or made available by or on behalf of one Party (the “Disclosing Party”) to the other Party (the “Receiving Party”) in connection with this Agreement, regardless of whether such information is specifically marked or designated confidential, whether in writing, orally, visually, or otherwise. Notwithstanding any provision of this Agreement to the contrary, the Licensed Antibody Technology shall be the Confidential Information of Spyre.

 

3


1.21 “Control” (including any variations such as “Controlled” and “Controlling”) means, with respect to any technology (including Know-How) or other Intellectual Property Rights, possession by a Party or one of its Affiliates of the ability (whether by ownership, license or otherwise (other than by a license, sublicense or other right granted pursuant to this Agreement)) to grant a license or a sublicense of or under such technology or Intellectual Property Rights without violating the terms of any agreement or other arrangement with any Third Party; provided, that if following the Effective Date (a) Paragon would Control any Patent that would be included in the Licensed Antibody Technology or Other Licensed Patents but for an obligation to pay royalties or other consideration for the Development, Manufacture or Commercialization of a Spyre Product in the Territory in connection with a grant to Spyre of a license under such Patent, and (b) Spyre, pursuant to Section 2.8, consents to being a sublicensee of such Patent and complies with the Reimbursement Obligation, then such Patent shall be deemed Controlled by Paragon. Notwithstanding the foregoing, a Party and its Affiliates shall not be deemed to “Control” any technology or Intellectual Property Rights that (i) prior to the consummation of a Change of Control of such Party is owned or in-licensed, or (ii) after the consummation of a Change of Control of such Party, becomes owned or in-licensed (to the extent such technology or Intellectual Property Rights are developed outside of the scope of the activities conducted hereunder and without use of or reference to any technology or Intellectual Property Rights Controlled by such Party or any Affiliate of such Party immediately before such Change of Control, or any Confidential Information of the other Party), in each case ((i) or (ii)), by a Third Party that becomes an Affiliate of such Party after the Effective Date as a result of such Change of Control or an assignee of such Party after the Effective Date as the result of an assignment of this Agreement in connection with a Change of Control unless prior to the consummation of such Change of Control or assignment, such Party or any of its Affiliates also Controlled such technology or Intellectual Property Rights.

1.22 “Cover” or “Covering” means, with respect to a particular product, any Patent, that, in the absence of a license granted under, or ownership of, such Patent, the making, using, selling, importation, or exportation of such product would infringe a valid and unexpired claim of such Patent.

1.23 “Derived Antibody” means any Antibody that is created by or on behalf of Spyre (other than an Antibody created by Paragon under the Option Agreement), its Affiliates or its or their licensees and: (a) is derived from or constitutes a modification of a Licensed Antibody, including [***], (b) [***] and (c) [***]. For avoidance of doubt, any Antibody that [***] will be deemed a Derived Antibody, irrespective of origin, so long as such Antibody satisfies the requirements of (a), (b) and (c). Notwithstanding the foregoing, a Derived Antibody shall not include (i) [***] or (ii) [***].

1.24 “Designated Multispecific Antibody” has the meaning set forth in Section 2.6(b).

 

4


1.25 “Develop” or “Developing” means any and all activity to discover, evaluate, test (including clinical and non-clinical testing), research, or otherwise develop an Antibody or product, including any Licensed Antibody, Derived Antibody, Product, Multispecific Antibody, or Multispecific Product, as applicable. When used as a noun, “Development” means any and all activities involved in Developing.

1.26 “Directed To” means, with regard to an Antibody or product, that such Antibody or product is developed or designed to (a) [***], and (b) [***].

1.27 “Disclosing Party” has the meaning set forth in Section 1.20.

1.28 “Dispute” has the meaning set forth in Section 10.7(a).

1.29 “Dollar” means a U.S. dollar, and “$” shall be interpreted accordingly.

1.30 “Effective Date” has the meaning set forth in the preamble.

1.31 “Exclusivity Period” means the period commencing on the Effective Date and continuing until the [***] anniversary of the Effective Date.

1.32 “FDA” means the United States Food and Drug Administration, or a successor federal agency thereto.

1.33 “Field” means the prophylaxis, palliation, treatment and diagnosis of human disease and disorders in the therapeutic area of inflammatory bowel disease.

1.34 “First Commercial Sale” means the first sale of a Spyre Product by Spyre, or one of its Affiliates or its or their Sublicensees, to a Third Party after receipt of all Regulatory Approvals required to market and sell the Spyre Product have been obtained in the country in the Territory in which such Spyre Product is sold. Sales for purposes of testing the Spyre Product and sample purposes shall not be deemed a First Commercial Sale. Furthermore, for purposes of clarity, the term “First Commercial Sale” as used in this Agreement shall not include: (a) [***]; (b) [***]; nor (c) [***].

1.35 “Force Majeure” has the meaning set forth in Section 10.2.

1.36 “Governmental Authority” means any national, international, federal, state, provincial, or local government, or political subdivision thereof, or any multinational organization or any authority, agency, or commission entitled to exercise any administrative, executive, judicial, legislative, police, regulatory, or taxing authority or power, or any court or tribunal (or any department, bureau or division thereof, or any governmental arbitrator or arbitral body).

1.37 “IND” means an investigational new drug application or equivalent application that is required to commence clinical trials for a product in the Territory and filed with the applicable Regulatory Authority.

1.38 “Indemnified Party” has the meaning set forth in Section 9.3.

1.39 “Indemnifying Party” has the meaning set forth in Section 9.3.

 

5


1.40 “Intellectual Property Rights” means any and all proprietary rights provided under (a) patent law, including any Patents; (b) copyright law; (c) trademark law; or (d) any other applicable statutory provision or common law principle, including trade secret law, that may provide a right in Know-How, or the expression or use thereof.

1.41 “Inventions” means all Know-How, and all intellectual property rights therein, that are conceived, reduced to practice, discovered, developed, or made by or on behalf of either Party or any Third Parties acting on their behalf (or any of their Representatives, Affiliates, licensees, or sublicensees) in the course of performing activities under this Agreement.

1.42 “JAMS Rules” has the meaning set forth in Section 10.7(a)(ii).

1.43 “Know-How” means all technical information and know-how in any tangible or intangible form, including (a) inventions, discoveries, trade secrets, data, specifications, instructions, processes, formulae, materials (including cell lines, vectors, plasmids, nucleic acids and the like), methods, protocols, expertise and any other technology, including the applicability of any of the foregoing to formulations, compositions or products or to their manufacture, development, registration, use or marketing or to methods of assaying or testing them or processes for their manufacture, formulations containing them or compositions incorporating or comprising them, and (b) all data, instructions, processes, formulae, strategies, and expertise, whether biological, chemical, pharmacological, biochemical, toxicological, pharmaceutical, physical, analytical, or otherwise and whether related to safety, quality control, manufacturing or other disciplines. Notwithstanding the foregoing, Know-How excludes any Patents.

1.44 “Licensed Antibody” means the Antibodies listed in Exhibit B as “Licensed Antibodies” that are Directed To the Licensed Target and that were discovered, generated, identified or characterized by Paragon in the course of performing the Research Program. Notwithstanding the foregoing, the Licensed Antibodies shall not include (a) [***], or (b) [***].

1.45 “Licensed Antibody Invention” means (a) any invention or discovery, whether or not patentable, that was discovered or reduced to practice by or on behalf of Paragon under the Research Program that constitutes the composition of matter of, or any method of specifically making or using, any Licensed Antibody; and (b) all Intellectual Property Rights therein, that in each case is Controlled by Paragon or its Affiliates as of the Effective Date or during the Term. Notwithstanding the foregoing, the Licensed Antibody Inventions shall not include (i) [***], (x) [***], or (y) [***], or (ii) any Intellectual Property Rights therein.

1.46 “Licensed Antibody Patents” means all Patents that Cover the composition of matter of, or any method of specifically making or using, any Licensed Antibody, that in each case are Controlled by Paragon or its Affiliates as of the Effective Date or during the Term, excluding in each case any claims in such Patents that Cover the composition of matter of, or any method of specifically making or using (a) [***], or (b) [***].

1.47 “Licensed Antibody Technology” means (a) the Licensed Antibody Inventions; (b) the Licensed Antibody Patents; (c) the Sequence Information; (d) the Results; (e) the Research Program Materials; and (f) all Intellectual Property Rights therein Controlled by Paragon or its Affiliates as of the Effective Date and during the Term.

 

6


1.48 “Licensed Component” has the meaning set forth in Section 1.58.

1.49 “Licensed Target” means IL-23.

1.50 “Losses” has the meaning set forth in Section 9.1.

1.51 “MAA” means (a) a New Drug Application in the United States, as defined in the United States Federal Food, Drug and Cosmetics Act, and applicable regulations promulgated thereunder by the FDA; (b) a Biologics License Application in the United States, as defined in the United States Public Health Service Act; or (c) any application filed with any Regulatory Authority in a country other than the United States that is equivalent to either of the foregoing.

1.52 “Major Market Country” means any of the following: [***], [***], [***], [***], [***] and [***].

1.53 “Manufacture” or “Manufacturing” means any and all activity to make, have made, produce, manufacture, process, fill, finish, package, label, perform quality assurance testing, release, ship or an Antibody or product, including any Licensed Antibody, Derived Antibody, Product, Multispecific Antibody, or Multispecific Product, as applicable, or any component thereof. When used as a noun, “Manufacture” or “Manufacturing” means any and all activities involved in Manufacturing an Antibody or product, including any Licensed Antibody, Derived Antibody, Product, Multispecific Antibody, or Multispecific Product, as applicable, or any component thereof.

1.54 “Milestone” has the meaning set forth in Section 4.1.

1.55 “Milestone Payment” has the meaning set forth in Section 4.1.

1.56 “Multispecific Antibody” means any Antibody that is comprised of (a) [***], and (b) [***].

1.57 “Multispecific Product” means any product that comprises or contains any Multispecific Antibody.

1.58 “Net Sales” means the gross amounts received for Spyre Product by Spyre, its Affiliates and Sublicensees for sales or other commercial disposition of such Spyre Product in the Territory to unrelated Third Parties, less the following, in each case related specifically to the Spyre Product and actually incurred, paid or accrued by Spyre, its Affiliates or Sublicensees and not otherwise recovered by or reimbursed to Spyre, its Affiliates or Sublicensees;

(a) [***];

(b) [***];

(c) [***];

(d) [***];

 

7


(e) [***]; and

(f) [***].

Net Sales will include [***]. Net Sales will be calculated only once for the first bona fide arm’s length sale of the Spyre Product by Spyre, its Affiliates or its Sublicensees to a Third Party, and will not include sales between or among [***]. Net Sales shall not include any amounts invoiced for [***] (i) [***], (ii) [***], or (iii) [***].

Net Sales shall be determined from the books and records of Spyre, Affiliates of Spyre or any Sublicensee maintained in accordance with U.S. generally accepted accounting principles (GAAP) consistently applied. Spyre further agrees in determining Net Sales, it (or its applicable Affiliate or Sublicensee) will use Spyre’s (or such Affiliate’s or Sublicensee’s) then current standard procedures and methodology.

If a Spyre Product is sold as a Combination Product (as defined below), the Net Sales of such Combination Product for the purpose of calculating royalties and sales-based milestones owed under this Agreement for sales of such Combination Product, shall be determined as follows: [***]. If any Other Component in the Combination Product is not sold separately, Net Sales shall be calculated by [***]. If both the Licensed Component and any of the Other Components are not sold separately, the adjustment to Net Sales shall be determined by the Parties [***] to reasonably reflect [***] of such Combination Product.

For purposes of this definition, “Combination Product” means any pharmaceutical product that contains two (2) or more active ingredients, including (A) one (1) or more Licensed Antibodies, Derived Antibodies or Multispecific Antibodies (the “Licensed Component”), and (B) one (1) or more active pharmaceutical or biological ingredients that are not (x) a Licensed Antibody, Derived Antibody or Multispecific Antibody, or (y) an Antibody owned or controlled by Paragon or its Affiliate, the rights to which have been licensed to Spyre or its Affiliate under a separate agreement (“Other Component(s)”), either as a [***], [***] or [***], and [***].

1.59 “Notice of Dispute” has the meaning set forth in 10.7(a)(i).

1.60 “Other Component(s)” has the meaning set forth in Section 1.58.

1.61 “Other Licensed Know-How” means all Know-How Controlled by Paragon or its Affiliates on the Effective Date or during the Term that (a) was used by or on behalf of Paragon in the performance of the Research Program, and (b) is necessary to Develop, Manufacture, Commercialize or otherwise exploit (i) Licensed Antibodies, or (ii) Products, Multispecific Antibodies or Multispecific Products, in each case solely to the extent comprising or containing a Licensed Antibody. For clarity, the Other Licensed Know-How shall exclude (x) the Licensed Antibody Technology, and (y) any Know-How Controlled by Paragon or its Affiliates relating to (1) that [***], or (2) [***].

1.62 “Other Licensed Patents” means any Patents other than Licensed Antibody Patents Controlled by Paragon or its Affiliates as of the Effective Date or during the Term that (a) include a claim that expressly recites the sequence of a Licensed Antibody or Derived Antibody, and (b) are necessary to Develop, Manufacture or Commercialize Licensed Antibodies or Derived Antibodies in the Field in the Territory. Notwithstanding the foregoing, the Other Licensed Patents shall not include (i) Paragon Multispecific Patents, (ii) the Paragon Platform Patents (as defined in the Option Agreement), or (iii) any Patents that Cover (x) that [***], or (y) [***].

 

8


1.63 “Other Licensed Technology” means all (a) Other Licensed Know-How, and (b) Other Licensed Patents.

1.64 “Paragon Cross License Patents” means any Patents (other than Licensed Antibody Patents or Other Licensed Patents) Controlled by Paragon or its Affiliates as of the Effective Date or during the Term that Cover the composition of matter or method of treatment of the Licensed Antibodies. Notwithstanding the foregoing, the Other Licensed Patents shall not include (a) the Paragon Multispecific Patents, (b) the Paragon Platform Patents (as defined in the Option Agreement), or (c) any Patents that Cover (i) that [***], or (ii) [***].

1.65 “Paragon Indemnitee” has the meaning set forth in Section 9.1.

1.66 “Paragon Multispecific Antibody” means any Multispecific Antibody that is Developed, Manufactured, Commercialized or otherwise exploited by Paragon or its Affiliate or licensees (other than Spyre and its Affiliates and Sublicensees), excluding in each case any Spyre Multispecific Antibodies.

1.67 “Paragon Multispecific Patents” means those Patents that Cover the composition of matter of, or any method of specifically making or using, a Paragon Multispecific Antibody, in each case excluding the Licensed Antibody Patents.

1.68 “Paragon Patents” has the meaning set forth in Section 5.2(c).

1.69 “Paragon Third Party Agreement” has the meaning set forth in Section 2.8.

1.70 “Parent Entity” has the meaning set forth in Section 1.14.

1.71 “Party” has the meaning set forth in the Preamble.

1.72 “Patent Challenge” has the meaning set forth in Section 5.3(a).

1.73 “Patent Infringement” has the meaning set forth in Section 5.3(a).

1.74 “Patents” means (a) unexpired patents and patent applications, (b) any and all patent applications filed either from such patent or patent applications or from a patent application claiming priority from any of those, including divisionals, provisionals, continuations, continuations-in-part, and reissues, (c) substitutions, renewals, registrations, re-examinations, revalidations, extensions, supplementary protection certificates and the like of any such patents and patent applications, and (d) any and all foreign equivalents of the foregoing.

1.75 “Phase I Trial” means a human clinical trial in any country of the type described in 21 C.F.R. §312.21(a), or the foreign equivalent thereof, regardless of where such clinical trial is conducted.

 

9


1.76 “Phase II Trial” means a human clinical trial in any country of the type described in 21 C.F.R. §312.21(b), or the foreign equivalent thereof, regardless of where such clinical trial is conducted.

1.77 “Phase III Trial” means a human clinical trial in any country of the type described in 21 C.F.R. §312.21(c), or the foreign equivalent thereof, regardless of where such clinical trial is conducted.

1.78 “Pre-Existing Entities” has the meaning set forth in Section 1.3.

1.79 “Product” means any product that comprises or contains any Licensed Antibody or Derived Antibody other than as part of a Multispecific Antibody or a Multispecific Product.

1.80 “Prosecute” or “Prosecution” has the meaning set forth in Section 5.2(a).

1.81 “Publication” has the meaning set forth in Section 6.6(b).

1.82 “Receiving Party” has the meaning set forth in Section 1.20

1.83 “Regulatory Approval” means all clearances, approvals (including approval of an MAA as well as any applicable pricing and/or reimbursement approvals), licenses, registrations or authorizations of any Regulatory Authority necessary to commercially distribute, sell and market a pharmaceutical product in a country or territory under this Agreement.

1.84 “Regulatory Authority” means any supranational, multinational, federal, national, state, provincial or local regulatory agency, department, bureau or other Governmental Authority with authority over the clinical development, manufacture marketing or sale of a Product or Spyre Product in a country or region, including the FDA in the United States and the EMA in Europe.

1.85 “Reimbursement Obligation” has the meaning set forth in Section 2.8.

1.86 “Remaining Recovery” has the meaning set forth in Section 5.3(f).

1.87 “Representatives” of a Party means such Party’s officers, directors, employees, contractors, subcontractors, agents and consultants.

1.88 “Research Program” means the Research Program (as defined in the Option Agreement) conducted by the Parties pursuant to the Option Agreement with respect to the Licensed Target.

1.89 “Research Program Materials” means the tangible materials resulting from the Research Program that are Controlled by Paragon or its Affiliates as of the Effective Date or during the Term that are listed in Exhibit C attached hereto, as may amended in writing from time to time upon mutual agreement of the Parties. For clarity, Research Program Materials shall not include materials that are consumed or destroyed in the performance of the Research Program or that are not available to be transferred by Paragon to Spyre without violating the terms of any agreement or other arrangement with a Third Party.

 

10


1.90 “Results” means all data, results, analysis, conclusions, outcomes, information, documentation and reports that are generated by or on behalf of Paragon in performance of the Research Program, excluding in each case any other Licensed Antibody Technology.

1.91 “Retained IL-23 Antibody Patents” means all Patents that Cover the composition of matter of, or any method of specifically making or using, and Retained Il-23 Project Antibodies that in each case are owned by Paragon as of the Effective Date and are set forth on Exhibit E.

1.92 “Retained IL-23 Project Antibodies” has the meaning set forth in the Option Agreement. A list of the Retained IL-23 Project Antibodies, identified by individual sequence identifier numbers, is set forth on Exhibit D.

1.93 “Retained IL-23 Project Antibody Licensee” means any assignee or licensee of Paragon with respect to Paragon’s rights in the Retained IL-23 Project Antibodies and the Retained IL-23 Antibody Patents.

1.94 “Reversion Products” has the meaning set forth in Section 8.5(c).

1.95 “Review Period” has the meaning set forth in Section 6.6(b).

1.96 “ROFN Information” has the meaning set forth in Section 2.7(a).

1.97 “ROFN Negotiation Period” has the meaning set forth in Section 2.7(c).

1.98 “ROFN Period” has the meaning set forth in Section 2.7(a).

1.99 “Royalty Payments” has the meaning set forth in Section 4.2.

1.100 “Royalty Term” means, on a Spyre Product-by-Spyre Product and country-by-country basis, the period commencing on First Commercial Sale of the applicable Spyre Product in the applicable country in the Territory and ending, with respect to the particular Spyre Product and country at issue on the latest of the following dates: (a) the twelfth (12th) anniversary of the date of First Commercial Sale of such Spyre Product in such country; or (b) the expiration of the last-to-expire Valid Claim of a Licensed Antibody Patent or a Spyre Antibody Patent Covering the Manufacture, use or sale of such Spyre Product in the country at issue.

1.101 “Sequence Information” means any files of Paragon containing all Licensed Antibody sequences generated under the Research Program.

1.102 “Spyre Antibody Patents” means all Patents that Cover the composition of matter of, or any method of specifically making or using any Licensed Antibody or Derived Antibody that, in each case, are owned or in-licensed by Spyre or its Affiliates or Sublicensees as of the Effective Date or during the Term, provided that, if a Change of Control of Spyre occurs, the Spyre Antibody Patents shall not include any Patents owned or in-licensed by the Acquiring Entity as of the closing of such Change of Control.

1.103 “Spyre Cross License Patents” means any Patents Controlled by Spyre or its Affiliates as of the Effective Date or during the Term that Cover the composition of matter or method of treatment of the Retained IL-23 Project Antibodies. Notwithstanding the foregoing, the Other Licensed Patents shall not include any Patents that Cover (a) that [***], or (b) [***].

 

11


1.104 “Spyre Indemnitee” has the meaning set forth in Section 9.2.

1.105 “Spyre Intellectual Property” means any Patents, Know-How or other Intellectual Property Rights that are Controlled by Spyre and are necessary for, and actually used (or held for use) by Spyre or its Affiliates as of the effective date of termination of this Agreement in the Development, Manufacturing, or Commercialization of Spyre Products.

1.106 “Spyre Invention” means (a) any Invention that is owned or Controlled by Spyre, and (b) all Intellectual Property Rights therein, provided that, in each case (a) – (b), Spyre Inventions shall not include (i) any Inventions owned or Controlled by Paragon or its Affiliate, the rights to which have been licensed to Spyre or its Affiliate under this Agreement or a separate agreement, or (ii) any Intellectual Property Rights therein.

1.107 “Spyre Multispecific Antibody” means any Multispecific Antibody that is Developed, Manufactured, Commercialized or otherwise exploited by Spyre, its Affiliates or Sublicensees, excluding in each case, and subject to Section 2.7, any Paragon Multispecific Antibody.

1.108 “Spyre Multispecific Patents” means those Patents that Cover the composition of matter of, or any method of specifically making or using, a Spyre Multispecific Antibody.

1.109 “Spyre Multispecific Product” means any product that comprises or contains any Spyre Multispecific Antibody.

1.110 “Spyre Product” means, individually or collectively, as applicable, Licensed Antibodies, Derived Antibodies, Products, Spyre Multispecific Antibodies and Spyre Multispecific Products.

1.111 “Sublicensee” means any Affiliate of Spyre or any Third Party with respect to Spyre, to whom Spyre grants a sublicense of, or other authorization or permission granted under, the rights granted to Spyre in Section 2.1.

1.112 “Target” means a protein molecule that (a) is chemically distinct from other molecules, and (b) wherein a binding entity derives recognized therapeutic value from binding to such molecule.

1.113 “Term” has the meaning set forth in Section 8.1.

1.114 “Territory” means worldwide.

1.115 “Third Party” means any person or entity other than Paragon or Spyre or an Affiliate of either Paragon or Spyre.

1.116 “Third Party Claim” has the meaning set forth in Section 9.1.

 

12


1.117 “Transfer Period” has the meaning set forth in Section 2.5(c).

1.118 “US” or “United States” means the United States of America and its possessions and territories, including Puerto Rico.

1.119 “Valid Claim” means, with respect to a particular country, a claim (including a process, use or composition of matter claim) of an issued and unexpired patent (or a supplementary protection certificate thereof) that has not (a) irretrievably lapsed or been abandoned, permanently revoked, dedicated to the public or disclaimed, or (b) been held invalid, unenforceable or not patentable by a court, governmental agency, national or regional patent office or other appropriate body that has competent jurisdiction, which holding, finding or decision is final and unappealable or unappealed within the time allowed for appeal.

ARTICLE II

LICENSES; TECHNOLOGY TRANSFER; MULTISPECIFIC ANTIBODIES.

2.1 License Grants.

(a) Subject to the terms of this Agreement, Paragon hereby grants to Spyre a royalty-bearing, exclusive (even as to Paragon and its Affiliates, subject to Paragon’s retained rights under Section 2.4) license, including the right to sublicense through multiple tiers, under the Licensed Antibody Technology to Develop, Manufacture, Commercialize, or otherwise exploit Licensed Antibodies, Derived Antibodies and Products in the Field in the Territory.

(b) Subject to the terms of this Agreement, including Section 2.7, Paragon hereby grants to Spyre a royalty-bearing, non-exclusive right and license, including the right to sublicense through multiple tiers, under the Licensed Antibody Technology to Develop, Manufacture, Commercialize or otherwise exploit Multispecific Antibodies and Multispecific Products in the Field in the Territory.

(c) Subject to the terms of this Agreement, Paragon hereby grants to Spyre a royalty-bearing, non-exclusive license, including the right to sublicense through multiple tiers, under the Other Licensed Patents to Develop, Manufacture, Commercialize or otherwise exploit Licensed Antibodies, Derived Antibodies, Multispecific Antibodies, Products and Multispecific Products in the Field in the Territory.

(d) Subject to the terms of this Agreement, Paragon hereby grants to Spyre a royalty-bearing, non-exclusive license, including the right to sublicense through multiple tiers, under the Other Licensed Know-How to Develop, Manufacture, Commercialize or otherwise exploit (i) Licensed Antibodies, or (ii) Products, Multispecific Antibodies or Multispecific Products, in each case solely to the extent comprising or containing a Licensed Antibody, in the Field in the Territory.

(e) Subject to the terms of this Agreement, Paragon hereby grants to Spyre a non-exclusive license, including the right to sublicense through multiple tiers, under the Paragon Cross License Patents to Develop, Manufacture, Commercialize or otherwise exploit the Licensed Antibodies solely in the Field in the Territory.

 

13


(f) Subject to the terms of this Agreement, Spyre hereby grants to Paragon a non-exclusive license, including the right to sublicense through multiple tiers, under the Spyre Cross License Patents to Develop, Manufacture, Commercialize or otherwise exploit the Retained IL-23 Project Antibodies solely in the Field in the Territory.

2.2 Exclusivity.

(a) Subject to the terms of this Section 2.2, to the maximum extent permissible under Applicable Law, during the Exclusivity Period, Paragon shall not, and shall ensure that its Affiliates do not, directly or indirectly, conduct any activity, either on its own or with, for the benefit of, or sponsored by, any Third Party, including granting any license to any Third Party that would permit such Third Party, to develop, manufacture, commercialize or otherwise exploit any monospecific Antibody that is Directed To the Licensed Target in the Field. It will not be a violation of this Section 2.2(a) if Paragon or its Affiliate, directly or through a Third Party, (i) conducts screening activities solely for the purposes of ensuring compliance with this Section 2.2(a), (ii) conducts activities in accordance with the terms of this Agreement, the Option Agreement or any other written agreement between the Parties, or (iii) conducts activities with the prior written consent of Spyre.

(b) Notwithstanding anything herein to the contrary, if a Change of Control occurs with respect to Paragon or its Parent Entity, and the Acquiring Entity (or any of such Acquiring Entity’s successors or assigns, other than the relevant Pre-Existing Entities) as of the Change of Control has a program or product (or rights thereto) that would otherwise violate Section 2.2(a) (each, a “COC Program”), then (i) Section 2.2(a) shall not apply with respect to such COC Program, and (ii) such Acquiring Entity will be permitted to continue such COC Program after such Change of Control and such continuation will not constitute a violation of Section 2.2(a), provided, that the Licensed Antibody Technology and Confidential Information of Paragon and Spyre relating to the Spyre Products is not used in the COC Program.

(c) Notwithstanding anything herein to the contrary, if Paragon or its Parent Entity (i) acquires a Third Party entity that has a program or product (or rights thereto) that would otherwise violate Section 2.2(a), or (ii) acquires asset(s) from a Third Party entity that would otherwise violate Section 2.2(a) (each, an “Acquired Program”), then (1) Section 2.2(a) shall not apply with respect to such Acquired Program, and (2) Paragon or its Parent Entity will be permitted to continue such Acquired Program after such acquisition and such continuation will not constitute a violation of Section 2.2(a), provided, that the Licensed Antibody Technology and Confidential Information of Paragon and Spyre relating to the Spyre Products is not used in the Acquired Program.

2.3 Sublicenses. Spyre shall have the right to grant sublicenses under the rights granted to it in Section 2.1 to its Affiliates and Third Parties; provided, that (a) each such sublicense shall be granted in writing and each such relevant sublicense agreement shall be consistent with all relevant terms, conditions and restrictions of this Agreement, (b) Spyre will provide Paragon with a true and complete copy of each sublicense agreement (other than sublicense agreements with Third Party service providers) and any amendments thereto within [***] days following the execution thereof (which sublicense agreement and amendments may be redacted except to the extent necessary for Paragon to determine Spyre’s compliance with this Agreement), and (c) Spyre shall remain responsible for all of its payments and other performance obligations due under this Agreement, notwithstanding any license or sublicense that it may grant.

 

14


2.4 No Implied Licenses; Reservation of Rights. Except as expressly set forth herein, no right or license under any Patents, Know-How or Intellectual Property Right of either Party is granted or shall be granted by implication hereunder. All such rights or licenses are or shall be granted only as expressly provided in this Agreement, and each Party reserves to itself all rights not expressly granted under this Agreement. Notwithstanding anything to the contrary under this Agreement, Paragon retains rights under the Licensed Antibody Technology solely to perform its obligations and exercise its rights under this Agreement and the Option Agreement. Spyre acknowledges and agrees that it has no rights under this Agreement or the Option Agreement with respect to any Antibodies that were discovered, generated, identified or characterized by Paragon in the course of performing the Research Program (including the Retained IL-23 Project Antibodies) other than the Licensed Antibodies and the Derived Antibodies.

2.5 Information Transfer and Support to Spyre.

(a) As soon as possible and within not more than [***] days after the Effective Date, Paragon shall provide Spyre with the Results and Sequence Information in existence as of the Effective Date not already provided to Spyre under the Option Agreement. Additionally, on a continuing basis during the term of the Research Program, as soon as possible and within not more than [***] days after additional Results or Sequence Information come into existence or are identified by Paragon that in each case have not already been provided to Spyre under the Option Agreement, Paragon shall disclose and transfer such additional Results and Sequence Information to Spyre.

(b) Upon the reasonable request of Spyre made from time to time during the Term, Paragon shall promptly disclose and transfer to Spyre tangible embodiments of the Other Licensed Know-How that is the subject of Spyre’s request.

(c) The Parties acknowledge and agree that Exhibit C has been agreed by the Parties as of the Effective Date, and that materials that are different than or in addition to the materials set forth on Exhibit C may result from the Research Program to the extent that the Research Program continues to be performed following the Effective Date. Upon the reasonable request of Spyre made at any time prior to the end of the [***] day period following the expiration of the Research Term (as defined in the Option Agreement), the Parties shall update Exhibit C to reflect the tangible materials, including samples, reagents, nucleic acids and Antibodies, resulting from the Research Program that constitute Research Program Materials hereunder. During the period beginning on the Effective Date and ending [***] months after the expiration of the Research Term (the “Transfer Period”), at [***] request and expense, Paragon will provide Spyre or a Third Party designated by Spyre with any Research Program Materials, provided that any Third Party recipient of such Research Program Materials shall be bound by the relevant terms of this Agreement and that the Research Program Materials are used solely to further Develop, Manufacture and Commercialize the Spyre Products. For clarity, [***] shall be responsible for any out-of-pocket costs incurred by Paragon or its Affiliates to store and maintain the Research Program Materials during the Transfer Period.

 

15


(d) Each Party shall bear all costs and expenses incurred by such Party in connection with the disclosure and transfer of any Results and Sequence Information as set forth above.

(e) During the [***] day period following completion of the Research Program, in the event Spyre makes any reasonable request for assistance in order to understand the Licensed Antibody Technology and use the Licensed Antibody Technology to continue the uninterrupted Development of the Licensed Antibodies, Paragon shall provide up to [***] month of additional assistance during such period, at [***] cost and expense at the then current [***] Rate (as defined in the Option Agreement) in the Option Agreement. Paragon shall consider and discuss in good faith any additional requests for assistance made by Spyre, which assistance may be provided upon mutual agreement of the Parties.

2.6 Paragon Rights with Respect to Multispecific Antibodies.

(a) Subject to the terms of this Agreement, including Section 2.6(b) below and Section 2.7, Paragon reserves and retains the non-exclusive right under the Licensed Antibody Technology to Develop, Manufacture, Commercialize and otherwise exploit Multispecific Antibodies and Multispecific Products in the Field in the Territory. If Paragon exercises such right, then Paragon shall pay royalties to Spyre in accordance with Article IV, mutatis mutandis, with respect to any Multispecific Antibodies and Multispecific Products that are Commercialized by Paragon or its Affiliates or sublicensees (other than Spyre and its Affiliates and Sublicensees) in the Field in the Territory, provided, that references to Spyre Antibody Patents in clause (b) of the Royalty Term definition and Section 4.3 shall be disregarded.

(b) Spyre has designated [***] Licensed Antibody or Derived Antibody as its lead compound and [***] Licensed Antibody or Derived Antibody as its backup compound, as set forth on Exhibit B (each such designated Licensed Antibody or Derived Antibody, a “Designated Multispecific Antibody”). From and after receipt of Spyre’s notice, Paragon’s rights under Section 2.6(a) shall expressly exclude the right to Develop, Manufacture, Commercialize or otherwise exploit (i) Multispecific Antibodies that have identical sequence identity within their variable regions as a Designated Multispecific Antibody, or (ii) Multispecific Products that comprise or contain any Multispecific Antibody referenced in clause (i). For the avoidance of doubt, if Paragon engages in Development or Manufacture of a Multispecific Antibody that meets the criteria of clause (i) or (ii) above before Spyre designates such Multispecific Antibody as a Designated Multispecific Antibody, then Paragon shall not be in breach of this Agreement, provided that, Paragon ceases all such Development or Manufacture within [***] days following receipt of Spyre’s written notice of designation.

2.7 Right of First Negotiation.

(a) Commencing on the Effective Date and continuing until the [***] anniversary thereof (the “ROFN Period”), Paragon will promptly notify Spyre in writing if (i) Paragon has developed a descriptive research plan with respect to the Development of a Multispecific Antibody or a plan to license or grant rights in a Multispecific Antibody to a Third Party, or (ii) Paragon enters into [***] negotiations pursuant to an offer to or from any Third Party relating to the foregoing. Together with such notice, Paragon will provide to Spyre all material

 

16


information and research plans developed by Paragon with respect to such Multispecific Antibody (the “ROFN Information”). Spyre will have [***] days from receipt of the ROFN Information to deliver a written notice to Paragon of Spyre’s desire to engage in negotiations for an agreement concerning the Development, or exclusive license or grant of rights to, such Multispecific Antibody.

(b) If Spyre does not provide such written notice to Paragon of its interest to engage in such negotiations within such [***] day period, then (i) Paragon shall be free to enter into an agreement with a Third Party with respect to the grant of a license or other rights to such Multispecific Antibody and corresponding Multispecific Products without further obligation to Spyre under this Section 2.7, and (ii) Spyre’s license under Section 2.1(b) shall automatically exclude any right to Develop, Manufacture, Commercialize or otherwise exploit the identical Multispecific Antibodies Developed by or on behalf of Paragon and corresponding Multispecific Products.

(c) If Spyre does provide Paragon such written notice within such [***] day period, the Parties will negotiate [***] on an exclusive basis for a period of up to [***] months from the date of Spyre’s notice (“ROFN Negotiation Period”), an agreement for the Development, or exclusive license or grant of rights to, such Multispecific Antibody and corresponding Multispecific Products. Prior to and during the ROFN Negotiation Period, Paragon shall not enter into an agreement with respect to such Multispecific Antibody with any Third Party that will prevent Paragon from entering into an agreement with Spyre for the Development, or exclusive license or grant of rights to, such Multispecific Antibody and corresponding Multispecific Products. Unless and until the Parties have entered into an agreement with respect to such Multispecific Antibody and corresponding Multispecific Products, Spyre shall have no rights or license with respect to such Multispecific Antibody and corresponding Multispecific Products except as otherwise expressly provided in Section 2.1. In the event that the Parties have not entered into an agreement with respect to such Multispecific Antibody and corresponding Multispecific Products prior to the expiration of the ROFN Negotiation Period, then (i) Paragon shall be free to enter into an agreement with a Third Party with respect to the grant of a license or other rights to such Multispecific Antibody and corresponding Multispecific Products without further obligation to Spyre under this Section 2.7, and (ii) Spyre’s license under Section 2.1(b) shall automatically exclude any right to Develop, Manufacture, Commercialize or otherwise exploit the identical Multispecific Antibodies Developed by or on behalf of Paragon and corresponding Multispecific Products.

2.8 Third Party In-Licenses. If Paragon (or its Affiliate) enters into any in-license agreement with a Third Party after the Effective Date with respect to any Patent that would, if Controlled by Paragon, be included within the Licensed Antibody Patents or the Other Licensed Patents (each such agreement, a “Paragon Third Party Agreement”), Paragon shall notify Spyre in writing that it entered into such Paragon Third Party Agreement and provide a copy of such Paragon Third Party Agreement to Spyre, which may be redacted solely concerning [***] or other confidential terms not applicable to sublicensees. Spyre shall have the right, by delivery of notice to Paragon, to elect to take a sublicense under such Patents in-licensed by Paragon under such Paragon Third Party Agreement. If Spyre elects to become a sublicensee thereunder pursuant to this Section 2.8, then (a) the applicable Patents under such Paragon Third Party Agreement shall be included within the Licensed Antibody Patents or the Other Licensed Patents, as applicable,

 

17


that are licensed to Spyre under Section 2.1, (b) Spyre shall reimburse Paragon for its pro rata share of royalties or other consideration, as mutually agreed by the Parties, for Spyre’s Development, Manufacture, Commercialization or other exploitation of a Spyre Product in the Field in the Territory in connection with a grant to Spyre of such Patents (the “Reimbursement Obligation”), and (c) Spyre shall comply with the terms of such Paragon Third Party Agreement to the extent applicable to Spyre as a sublicensee of such Patents. In the event of any conflict between the terms of this Agreement and any Paragon Third Party Agreement applicable to a sublicense granted by Paragon to Spyre in accordance with this Section 2.8, the terms of the Paragon Third Party Agreement shall control solely to the extent necessary for the Parties to maintain compliance with such Paragon Third Party Agreement. Spyre shall comply with the Reimbursement Obligation by paying to Paragon any amounts subject to the Reimbursement Obligation within the earlier of (i) [***] days after Spyre’s receipt from Paragon of an invoice for such payment, and (ii) the date when such payment is due to the counterparty licensor under the applicable Paragon Third Party Agreement, provided that such payment shall not be due prior to the date when such amounts are payable by Paragon to the counterparty licensor under the applicable Paragon Third Party Agreement.

ARTICLE III

DEVELOPMENT, MANUFACTURING & COMMERCIALIZATION.

3.1 Spyre Responsibilities.

(a) As between the Parties, Spyre shall be solely responsible for and shall have the sole right to control, all aspects of the Development, Manufacturing, and Commercialization of the Spyre Products in the Field in the Territory during the Term, including distribution, product positioning, product strategy, product branding, core messaging, marketing, promotion, detailing activities and all decisions relating to the setting of prices in the Territory, invoicing and booking sales, establishing all terms of sale, and all regulatory activities.

(b) As between the Parties, Spyre shall be solely responsible for, and shall have the sole right to control, the selection, registration and maintenance of all trademarks associated with the Spyre Products in the Field in the Territory. As between the Parties, Spyre shall solely own such trademarks in the Territory and pay all relevant costs thereof.

3.2 Regulatory. As between the Parties, Spyre shall control all regulatory matters, including the regulatory strategy, regulatory filings, regulatory activities (including clinical trials for Spyre Products) and communication with each Regulatory Authority for the Spyre Products in the Field in the Territory. Spyre shall have the right to reference any relevant data included within the Licensed Antibody Technology for the purposes of regulatory filings and safety reporting, including all nonclinical data, pre-approval and post-approval clinical use data, and regulatory data with respect thereto, and Paragon shall cooperate as reasonably requested by Spyre with respect to providing to Spyre when requested, and on a timely basis, any of the foregoing information, data filings or reporting. Spyre or its designee shall be the party to file an application to each applicable Regulatory Authority in the Territory for, and to obtain and maintain, in its own name, Regulatory Approval for the Spyre Products in each country in the Territory.

 

18


3.3 Diligence; Reporting. Spyre shall use Commercially Reasonable Efforts (a) to Develop and seek Regulatory Approval for at least one Spyre Product in the Field in the United States and at least one other Major Market Country, and (b) upon receipt of Regulatory Approval for a given Spyre Product in a given country, to Commercialize such Spyre Product in such country, in each case ((a) or (b)) either by itself or through its Affiliates or Sublicensees or its or their respective contractors. Additionally, on or before [***] of each year during the Term, Spyre shall deliver to Paragon a report summarizing its material development efforts with respect to the Spyre Products, including a summary of current and anticipated preclinical and clinical activities, a summary of the status of any regulatory filings and any anticipated regulatory filings, and achievement of any Milestones, during the preceding [***]; provided, however, that Spyre may satisfy the reporting obligations set forth in this Section 3.3 by providing Paragon with copies of any annual report or other filings with a securities exchange that include the relevant information. For the avoidance of doubt, if Spyre determines, in its sole discretion, that it is inconsistent with the use of Commercially Reasonable Efforts to pursue Commercialization of a Spyre Product in any country (other than the United States), it will not be considered a material breach of this Agreement to cease Development or Commercialization of such Spyre Product with respect to such country.

ARTICLE IV

FINANCIAL TERMS.

4.1 Milestone Payments. Spyre shall make the following one-time payments to Paragon (or to such other designee(s), as requested by Paragon in an invoice) (each payment, a “Milestone Payment”), based on the achievement of the corresponding milestone (each, a “Milestone”) by Spyre, its Affiliates, or its Sublicensees with respect to the first Spyre Product to achieve such Milestone. Spyre shall, within [***] Business Days after it or its Affiliates achieve a Milestone, or within [***] Business Days after it learns that its or its Affiliate’s Sublicensee has achieved a Milestone, notify Paragon of the achievement of such Milestone in writing. Following receipt of such notice, Paragon shall invoice Spyre for such Milestone Payment, which invoice shall specify whether Paragon or its designee should receive such Milestone Payment and the bank account information into which such Milestone Payment should be paid. Spyre shall make such Milestone Payment to Paragon or Paragon’s designee within [***] days after receipt of Paragon’s invoice. Each Milestone Payment shall be paid no more than once, and Spyre’s total Milestone Payments hereunder shall not exceed Twenty-Two Million Dollars ($22,000,000).For avoidance of doubt, upon achievement of any Milestone, all prior unachieved Milestones shall be deemed thereby achieved and, if the Milestone Payment for any such prior Milestone has not previously been paid, it shall thereupon also be paid at the same time that the Milestone Payment for such subsequent achieved Milestone is paid.

 

19


    

Milestone

  

Milestone Payment

#1

   Achievement of Development Candidate    One Million Five Hundred Thousand Dollars ($1,500,000)

#2

   First dosing of a human patient in a Phase I Trial of a Spyre Product    Two Million Five Hundred Thousand Dollars ($2,500,000)

#3

   First dosing of a human patient in a Phase II Trial of a Spyre Product    Three Million Dollars ($3,000,000)

#4

   First dosing of a human patient in a Phase III Trial of a Spyre Product    Five Million Dollars ($5,000,000)

#5

   Receipt of Regulatory Approval from the FDA of a Spyre Product    Ten Million Dollars ($10,000,000)

4.2 Royalties. During the applicable Royalty Term (which shall be measured on a country-by-country and Spyre Product-by-Spyre Product basis), Spyre shall pay royalties to Paragon (or to such other designee(s), as requested by Paragon) equal to [***] percent ([***]%) of Net Sales of all Spyre Products sold by Spyre, its Affiliates or its Sublicensees in the Field in the Territory (“Royalty Payments”). If any Spyre Product contains (a) a combination of more than one Licensed Antibody, Derived Antibody and/or Multispecific Antibody, or (b) a combination of (i) one or more Licensed Antibodies, Derived Antibodies or Multispecific Antibodies, and (ii) one or more other Antibodies owned or Controlled by Paragon or its Affiliates, the rights to which have been licensed to Spyre or its Affiliates under a separate agreement, then, in each case (a) or (b), the royalty rate for the Royalty Payments payable to Paragon with respect to such Spyre Product shall be increased to [***] percent ([***]%) of Net Sales of such Spyre Product. For clarity, (x) any Net Sales of Spyre Product made in a given country after the expiration of the Royalty Term for such Spyre Product in such country will not be royalty-bearing; and (y) in the event that the Royalty Payment is increased to [***] percent ([***]%) of Net Sales of any Spyre Product pursuant to clause (b) above, then the maximum aggregate royalty payable pursuant to this Agreement and such separate agreement referenced in clause (b)(ii) above will exceed not [***] percent ([***]%).

4.3 Royalty Reductions for No Valid Claim. If, during any Calendar Quarter during the Royalty Term for a particular Spyre Product in a particular country, no Valid Claim of a Licensed Antibody Patent Covers the Manufacture or Commercialization of such Spyre Product in such country, then the royalty rate for the Royalty Payments set forth in Section 4.2 for such Calendar Quarter shall be reduced to (a) [***] percent ([***]%) for any Spyre Product in such country that was otherwise subject to a royalty rate of [***] percent ([***]%), and (b) [***] percent ([***]%) for any Spyre Product in such country that was otherwise subject to a royalty rate of [***] percent ([***]%).

4.4 Payment Reports. Within [***] days after the end of the [***], Spyre shall provide to Paragon a written report, on a [***] basis, stating the [***]; the [***], including [***]; and [***]. All Royalty Payments described in such written report shall be made by Spyre at the same time it submits such written report to Paragon. All such Royalty Payments shall be paid to Paragon or Paragon’s designee, provided that in the case of payment to a designee, Paragon has notified Spyre in writing [***] days prior to the due date for any Royalty Payment of the designee to be paid and the bank account information for such designee.

 

20


4.5 Payment Method. All payments due under this Agreement to Paragon shall be made in U.S. Dollars by bank wire transfer in funds to an account designated by Paragon from time to time reasonably in advance of any payment due date.

4.6 Taxes. The Parties agree to cooperate with one another and use reasonable efforts to minimize obligations for any and all income or other taxes required by Applicable Law to be withheld or deducted from any Royalty Payments, Milestone Payments or other payments made by Spyre to Paragon or its designee(s) under this Agreement, including by completing all procedural steps, and taking all reasonable measures, to ensure that any withholding tax is reduced or eliminated to the extent permitted under Applicable Law, including income tax treaty provisions and related procedures for claiming treaty relief. To the extent that Spyre is required to deduct and withhold taxes on any payment to Paragon or its designee(s), Spyre shall: (i) deduct such taxes from such payment to Paragon or its designee(s), (ii) pay the amounts of such taxes to the proper Governmental Authority in a timely manner, and (iii) promptly submit to Paragon an official tax certificate or other available evidence of such withholding sufficient to enable Paragon or its designee(s) to claim such payment of taxes. For the avoidance of doubt, Spyre’s remittance of such withheld amounts to the appropriate Governmental Authority, together with payment to Paragon or its designee(s) of the remaining amount owed, shall constitute full satisfaction of the applicable payment due to Paragon. Spyre shall provide Paragon with any reasonably requested tax forms or certificates available to Spyre in order to allow Paragon or its designee(s) to recover, as permitted by Applicable Law, withholding taxes, value added taxes or similar obligations resulting from payments made hereunder or to obtain the benefit of any present or future treaty against double taxation which may apply to such payments. Paragon shall promptly provide Spyre with any requested tax forms that may be reasonably necessary in order for Spyre to not withhold tax or to withhold tax at a reduced rate under an applicable bilateral tax income treaty.

4.7 Foreign Exchange. If any currency conversion shall be required in connection with the calculation of amounts payable hereunder, such conversion shall be made using the exchange rates reported on the [***] Business Day prior the payment due date for the purchase and sale of Dollars, as reported by the Wall Street Journal (East Coast Edition).

4.8 Late Payments. Any amount owed by Spyre to Paragon under this Agreement that is not paid within the applicable time period set forth herein will accrue interest at the per annum rate of [***] percentage point above the then-applicable United States prime rate as quoted in the Wall Street Journal (East Coast Edition) (or if it no longer exists, a similarly authoritative source), calculated on a [***] basis, or, if lower, the highest rate permitted under Applicable Law.

4.9 Blocked Currency. If by Applicable Law of a country in which Net Sales occurred, conversion of funds into Dollars or transfer of funds from such country to the United States is restricted, forbidden or delayed for more than [***] days, then Spyre can elect, at its sole discretion, that the amounts accrued in such country and owed by Spyre to Paragon under this Agreement shall be paid to Paragon in such country in local currency by deposit in a local bank designated by Paragon, unless the Parties otherwise agree in writing.

 

21


4.10 Records; Inspection.

(a) Spyre shall, and shall cause its applicable Affiliates to, create and keep complete and accurate records of its sales and other dispositions of all Spyre Products, including all records that are reasonably necessary for the purposes of calculating all payments due under this Agreement.

(b) Upon reasonable advance written notice to Spyre, Paragon shall have the right to retain a nationally recognized (in the US) independent certified public accounting firm to perform on behalf of Paragon an audit, conducted in accordance with U.S. generally accepted accounting principles (GAAP), of such books and records of Spyre or its applicable Affiliates as may be reasonably necessary to verify the accuracy of any reports provided pursuant to Section 4.4 hereunder for any Calendar Quarter ending not more than [***] calendar months prior to the date of such request. Such audits shall be conducted during normal business hours, shall not occur more frequently than [***] in each Calendar Year and shall not be conducted more than [***] with respect to any reporting period, in each case other than for cause. All information disclosed or observed during any audit pursuant to this Section 4.10 shall be the Confidential Information of Spyre, and Paragon shall cause the accounting firm to retain all such information as Confidential Information, including, if requested by Spyre, by requiring such accounting firm to enter into a customary confidentiality agreement with Spyre prior to the initiation of any such audit.

(c) Upon completion of any audit hereunder, the accounting firm shall provide both Spyre and Paragon a written report disclosing whether the reports submitted by Spyre are correct or incorrect, whether the amounts paid are correct or incorrect, and in each case, the specific details concerning any discrepancies. No other information regarding Spyre’s records shall be provided to Paragon.

(d) Paragon shall bear its internal expenses and the out-of-pocket costs for engaging such accounting firm in connection with performing such audits; provided, however, that if any such audit uncovers an underpayment by Spyre that exceeds [***] percent ([***]%) of the total owed for such payment or payment period, as applicable, then Spyre shall reimburse Paragon or its designee(s) for the amounts actually paid to such accounting firm for performing such audit.

(e) If such accounting firm concludes that Spyre has in aggregate underpaid amounts owed to Paragon during the audited period, Spyre shall pay Paragon or its designee(s) the amount of the discrepancy within [***] days of the date Paragon delivers to Spyre such accounting firm’s written report and an invoice for such amounts. If such accounting firm concludes that Spyre has in aggregate overpaid amounts owed to Paragon during the audited period, then Spyre may, at its election, either credit such overpaid amount against any future payment obligation to Paragon or require Paragon to refund such amounts within [***] days.

 

22


ARTICLE V

INTELLECTUAL PROPERTY.

5.1 Ownership. As between the Parties (a) Paragon solely owns the Licensed Antibody Technology, the Other Licensed Patents and the Retained IL-23 Antibody Patents, (b) Spyre solely owns the Spyre Inventions, including any Derived Antibodies and Spyre Multispecific Antibodies to the extent they constitute Spyre Inventions, (c) each Party solely owns all Intellectual Property Rights owned or Controlled by such Party as of the Effective Date or that come into the ownership or control of such Party during the Term outside the scope of this Agreement, and (d) ownership of Inventions shall be determined in accordance with U.S. laws of inventorship. Other than rights granted to Spyre under this Agreement with respect to the Licensed Antibody Technology and the Other Licensed Patents, nothing in this Agreement shall affect Paragon’s rights in any Patents, Know-How or other Intellectual Property Rights owned or controlled by Paragon or its Affiliates, now or in the future. Other than rights granted to Paragon under Section 8.5(c) of this Agreement with respect to the Spyre Intellectual Property, nothing in the Agreement shall affect Spyre’s rights in any Patents, Know-How or other Intellectual Property Rights owned or controlled by Spyre or its Affiliates, now or in the future.

5.2 Patent Prosecution.

(a) Prosecution Generally. For the purpose of this Article V, “Prosecute” and “Prosecution” shall include any patent interference, opposition, pre-issuance Third Party submission, ex parte re-examination, post-grant review, inter partes review or other similar proceeding, appeals or petitions to any board of appeals in a patent office, appeals to any court for any patent office decisions, reissue proceedings and applications for patent term extensions and the like.

(b) Prosecution of Licensed Antibody Patents.

(i) As between the Parties, Spyre shall have the first right to prepare, file, Prosecute and maintain the Licensed Antibody Patents, in each case, at Spyre’s sole expense. Spyre shall provide Paragon (and, at the direction of Paragon, shall also provide directly to the Retained IL-23 Project Antibody Licensee) with copies of all material correspondence from and to any patent office relating to such Licensed Antibody Patents, and Spyre shall provide Paragon (and, at the direction of Paragon, shall also provide directly to the Retained IL-23 Project Antibody Licensee) with drafts of all proposed filings to any patent office with respect to such Licensed Antibody Patents before submission of such filings, with reasonably adequate time for Paragon’s (and the Retained IL-23 Project Antibody Licensee’s) review and comment. Spyre will take into consideration Paragon’s and the Retained IL-23 Project Antibody Licensee’s reasonable comments prior to submitting such filings. At Spyre’s request, Paragon will sign all documents and take any other actions required for filing, maintenance and grant of Licensed Antibody Patents.

(ii) Spyre shall notify Paragon of any decision not to prepare or file, or to abandon, cease Prosecution or not maintain any Licensed Antibody Patent anywhere in the Territory. Spyre shall provide such notice at least [***] days prior to any filing or payment due date, or any other due date that requires action, in connection with such Licensed Antibody Patent. In such event, Paragon shall have a backup right, but not the obligation, to prepare, file, or continue Prosecution or maintenance of, such Licensed Antibody Patent, at Paragon’s expense.

(iii) Each Party shall cooperate with the other Party in the preparation, filing, Prosecution and maintenance of Licensed Antibody Patents, including in each case by providing the prosecuting Party with data and other information as appropriate and executing all necessary affidavits, assignments and other paperwork.

 

23


(c) Prosecution by Paragon. Except with respect to Licensed Antibody Patents (which are addressed in Section 5.2(b)), Paragon (directly or indirectly through the Retained IL-23 Project Antibody Licensee) shall be solely responsible for, and have sole discretion over, preparing, filing, Prosecuting and maintaining any Patents (including the Other Licensed Patents, Paragon Multispecific Patents and Retained IL-23 Antibody Patents) that it owns in whole or in part or otherwise Controls (the “Paragon Patents”). Paragon’s Prosecution of any Paragon Patents shall be at Paragon’s sole expense. Notwithstanding the foregoing, in Prosecuting any Paragon Multispecific Patents, Paragon hereby agrees that during the Term, neither Paragon nor any of its Affiliates or licensees will file, or assist any Third Party in filing, any Patent that includes a claim that expressly recites the sequence of a Licensed Antibody or Derived Antibody other than as part of a Paragon Multispecific Antibody. In the Prosecution by Paragon or the Retained IL-23 Project Antibody Licensee of any Retained IL-23 Antibody Patents, (i) Paragon shall provide or cause to be provided (directly or indirectly through the Retained IL-23 Project Antibody Licensee) to Spyre copies of all material correspondence from and to any patent office relating to such Retained IL-23 Antibody Patents, and (ii) Paragon shall provide or cause to be provided (directly or indirectly through the Retained IL-23 Project Antibody Licensee) to Spyre drafts of all proposed filings to any patent office with respect to such Retained IL-23 Antibody Patents before submission of such filings, with reasonably adequate time for Spyre’s review and comment, and Paragon or the Retained IL-23 Project Antibody Licensee, as applicable, will take into consideration Spyre’s reasonable comments prior to submitting such filings.

(d) Patent Prosecution Costs Prior to the Effective Date. No later than [***] days after the Effective Date, Spyre shall reimburse Paragon for any actual costs and expenses incurred by Paragon that are related to the Prosecution of any Licensed Antibody Patents prior to the Effective Date and that have not already been paid by Spyre. Spyre will promptly reimburse Paragon for any future Prosecution costs and expenses incurred by Paragon with respect to the Licensed Antibody Patents.

(e) CREATE Act. Notwithstanding anything to the contrary in this Agreement, each Party will have the right to invoke the Cooperative Research and Technology Enhancement Act of 2004, 35 U.S.C. § 103(c)(2)-(c)(3) (the “CREATE Act”) when exercising its rights under Article V of this Agreement, without the prior written consent of the other Party. Where such Party intends to invoke the CREATE Act, it will notify the other Party and the other Party will cooperate and coordinate its activities with such Party with respect to any submissions, filings or other activities in support thereof. The Parties acknowledge and agree that this Agreement is a joint research agreement (JRA) as defined in the CREATE Act.

(f) Disclosure of Antibody Patents. Upon the request of Paragon, Spyre shall deliver to Paragon a list of the then-existing Spyre Antibody Patents. Upon the request of Spyre, Paragon shall deliver to Spyre a list of the then-existing Retained IL-23 Antibody Patents.

 

24


5.3 Patent Enforcement and Defense.

(a) Notice of Patent Infringement and Patent Challenge. Each Party shall give the other Party notice of any known or suspected infringement by a Third Party (“Patent Infringement”) of any Licensed Antibody Patent and any known or suspected challenge by a Third Party against the validity or enforceability (“Patent Challenge”) of any Licensed Antibody Patent or Retained IL-23 Antibody Patent within [***] days after such Patent Infringement or Patent Challenge comes to such Party’s attention.

(b) Spyre’s First Right to Enforce or Defend. Spyre shall have the first right, but not the obligation, to bring and control any legal action, including by declaratory judgment action, patent litigation or similar proceeding, in connection with any Patent Infringement or Patent Challenge with respect to the Licensed Antibody Patents in the Territory at its own expense and discretion as it reasonably determines appropriate. Spyre shall keep Paragon (and, at the direction of Paragon, the Retained IL-23 Project Antibody Licensee) informed and reasonably consult with Paragon (and, at the direction of Paragon, the Retained IL-23 Project Antibody Licensee) in the course of such legal action. Paragon shall have the right to be represented in any such legal action by counsel of its choice at its own expense.

(c) Paragon’s First Right to Enforce or Defend. Paragon (or, at Paragon’s discretion, the Retained IL-23 Project Antibody Licensee) shall have the sole right, but not the obligation, to bring and control any legal action, including by declaratory judgment action, patent litigation or similar proceeding, in connection with any Patent Infringement or Patent Challenge with respect to the Paragon Patents in the Territory at its own expense and discretion as it reasonably determines appropriate. Paragon (directly or indirectly through the Retained IL-23 Project Antibody Licensee) shall keep Spyre informed and reasonably consult with Spyre in the course of legal action to enforce or defend any Retained IL-23 Antibody Patent.

(d) Settlement. In connection with any such legal action or proceeding, Spyre shall not enter into any settlement admitting the invalidity or unenforceability of Licensed Antibody Patents without the prior written consent of Paragon (such consent not to be unreasonably conditioned, withheld, or delayed), and Paragon shall not enter into any settlement admitting the invalidity or unenforceability of the Retained IL-23 Antibody Patents without the prior written consent of Spyre (such consent not to be unreasonably conditioned, withheld, or delayed).

(e) Paragon’s Backup Right to Enforce or Defend. If Spyre does not initiate a legal action for Patent Infringement or Patent Challenge with respect to any Licensed Antibody Patent within [***] days after a notice from Paragon under Section 5.3(a), then Paragon shall have a backup right, but not the obligation, to initiate such legal action at its own expense.

(f) Allocation of Recoveries. Any recoveries resulting from such legal action initiated by Spyre or Paragon hereunder relating to Patent Infringement or Patent Challenge in each case solely with respect to the Licensed Antibody Patents, including pursuant to a settlement, shall be applied as follows: (i) first to reimburse the [***] of each of the Parties in such action; and (ii) second, any amounts remaining after paying the amounts due each Party under clause (i) (the “Remaining Recovery”) shall be allocated as follows: (1) [***]; or (2) [***].

 

25


(g) Cooperation with Patent Enforcement. At the request of the enforcing Party (and at the requesting Party’s expense), the other Party shall reasonably cooperate and provide any information or assistance in connection with any legal action under this Section 5.3, including executing reasonably appropriate documents, cooperating in discovery and, if required by Applicable Law, joining as a party to the legal action at its own expense.

5.4 Third Party Patent Proceedings.

(a) Spyre’s First Right to Challenge Third Party Patents. Spyre shall have the sole and exclusive right, but not the obligation, to bring and control any legal action to challenge any Patents controlled by a Third Party, including by declaratory judgment action, patent interference, opposition, pre-issuance submission, ex parte re-examination, post-grant review, inter partes review, patent litigation or similar proceeding, in each case that are necessary or useful to Develop, Manufacture, Commercialize or otherwise exploit any Spyre Product.

(b) Cooperation by Paragon. At the request of Spyre, Paragon shall cooperate and provide any information or assistance in connection with any legal action under this Section 5.4, including executing reasonably appropriate documents, cooperating in discovery and, if required by Applicable Law, joining as a party to the action at Spyre’s cost and expense.

5.5 Common Interest Agreement. At the request of either Party to conduct the activities under this Article V, the Parties shall cooperate in good faith to enter into a customary, mutually-agreed common-interest agreement intended to preserve attorney-client privilege with respect to disclosures and communications by or on behalf of either Party or its Affiliates in connection with such activities.

ARTICLE VI

PROTECTION OF CONFIDENTIAL INFORMATION.

6.1 Confidentiality. Except to the extent expressly authorized by this Agreement, the Receiving Party agrees that, during the Term, for [***] years thereafter, and, with respect to any Know-How that constitutes a trade secret, for long as such Know-How constitutes a trade secret, it shall keep confidential and shall not publish or otherwise disclose to any Third Party, and shall not use for any purpose other than as expressly provided for in this Agreement, any Confidential Information of the Disclosing Party. The Receiving Party may disclose Confidential Information of the Disclosing Party to those of the Receiving Party’s Representatives who have a need for such information, provided that the Receiving Party shall advise such Representatives of the confidential nature thereof, shall ensure that each such Representative is bound in writing by obligations of confidentiality and non-use at least as stringent as those contained in this Agreement, and shall be responsible for the compliance of its Representatives with the terms of this Agreement. The Receiving Party shall use at least the same standard of care as it uses to protect proprietary or confidential information of its own (but in no event less than reasonable care) to ensure that its Representatives do not disclose or make any unauthorized use of the Confidential Information of the Disclosing Party. The Receiving Party shall promptly notify the Disclosing Party upon discovery of any unauthorized use or disclosure of the Confidential Information of the Disclosing Party.

 

26


6.2 Exceptions. The Receiving Party’s obligations under Section 6.1 shall not apply to any Confidential Information of the Disclosing Party that the Receiving Party can prove by competent evidence: (a) is now, or hereafter becomes, through no act or failure to act on the part of the Receiving Party in breach of this Agreement, generally known or available; (b) is known by the Receiving Party at the time of receiving such information from the Disclosing Party; (c) is hereafter furnished to the Receiving Party by a Third Party, as a matter of right and without restriction on disclosure; or (d) is independently discovered or developed by the Receiving Party, without the aid, use or application of any Confidential Information of the Disclosing Party.

6.3 Authorized Disclosure. Notwithstanding the provisions of this Article VI, the Receiving Party may disclose Confidential Information of the Disclosing Party, without violating its obligations under this Agreement, to the extent the disclosure is:

(a) required by a valid order of a court or other Governmental Authority of competent jurisdiction or as otherwise required by Applicable Law, rule, regulation (including securities laws), government requirement, or as may be required in connection with any filings made with, or by the disclosure policies of, a stock exchange (including, for clarity, any such disclosures required to be made by Paragon or its Affiliates or licensees in connection with the Development, Manufacture, Commercialization or other exploitation of Multispecific Antibodies), provided that the Receiving Party shall give reasonable prior written notice to the Disclosing Party of such required disclosure and, at the [***] request and expense, shall cooperate with the Disclosing Party’s efforts to contest such requirement, to obtain a protective order requiring that the Confidential Information so disclosed be used only for the purposes for which the order was issued or the law required, or to obtain other confidential treatment of such Confidential Information;

(b) reasonably necessary to file or Prosecute patent applications, Prosecute or defend litigation or otherwise establish rights or enforce obligations under this Agreement, or obtain or maintain approval to conduct clinical trials or Regulatory Approvals, in each case, in accordance with this Agreement (including, for clarity, any such disclosures that are reasonably necessary to made by Paragon or its Affiliates or licensees in connection with the Development, Manufacture, Commercialization or other exploitation of Multispecific Antibodies); or

(c) under appropriate confidentiality provisions substantially equivalent to those in this Agreement (but of shorter duration if customary in the case of subclause (ii)): (i) in connection with the performance of its obligations or as reasonably necessary or useful in the exercise of its rights under this Agreement, including the right to grant licenses or sublicenses as permitted hereunder and the right to Develop, Manufacture, Commercialize and otherwise exploit Antibodies and products (including Multispecific Antibodies and Multispecific Products) to which it has rights hereunder, or (ii) to actual or bona fide potential licensees, acquirers, merger partners, assignees, collaborators, investment bankers, investors or lenders.

6.4 Use of Names. Except as set forth in Section 6.6(b), neither Party shall use the other Party’s name or trademarks in any advertising, sales, or promotional material or in any publication without the prior written consent of the other Party.

 

27


6.5 Confidentiality of this Agreement. This Agreement and its terms are considered Confidential Information of both Parties, and each Party shall keep confidential and shall not publish or otherwise disclose the terms of this Agreement without the prior written consent of the other Party, except as expressly permitted by Section 6.3, and except that both Parties may disclose this Agreement and its terms to its legal, financial and investment banking advisors; bona fide potential and actual investors, acquirers, merger partners, assignees, collaborators, investment bankers, lenders, licensees, sublicensees or strategic partners in connection with license or partnering transactions, due diligence or similar investigations by such Third Parties or in confidential financing documents; and counsel or other advisors for the foregoing; provided, in each case, that any such Third Party agrees to be bound by obligations of confidentiality and non-use at least as restrictive as those set forth in this Article VI (provided that the confidentiality term applicable to such Third Party may be shorter so long as it is commercially reasonable).

6.6 Publicity.

(a) Subject to Section 6.6(b), neither Party will generate or allow any publicity regarding this Agreement or the transactions contemplated hereunder without the other Party first approving such press release or publication in writing, except for any public disclosure by or on behalf of a Party that is, in the opinion of such Party’s counsel, required by Applicable Law or the rules of a stock exchange on which the securities of such Party are listed (or to which an application for listing has been submitted) and except that a Party may, once a press release or other public written statement is approved in writing by both Parties, make subsequent public disclosure of the information contained in such press release or other public written statement without the further approval of the other Party.

(b) The Parties shall collaborate and cooperate [***] to devise a Publication (as defined below) strategy for the Spyre Products that is mutually acceptable to both Parties. Prior to publicly presenting or publishing any data, results or analyses relating to a Spyre Product generated by or on behalf of Spyre pursuant to this Agreement (each such proposed presentation or publication, a “Publication”), Spyre will provide Paragon with a copy of such proposed Publication to review, discuss, and determine whether to approve at least [***] days (or such shorter period of time as is reasonably practicable) prior to the earlier of its presentation or intended submission for publication (such applicable period, the “Review Period”), provided that the Review Period for any poster or other presentation presented at a conference or other industry event shall be at least [***] days. Spyre will not submit or present any Publication until (i) Paragon has approved (not to be unreasonably withheld, conditioned or delayed) such Publication or provided written comments thereon, in each case, during such Review Period, or (ii) the applicable Review Period has elapsed without approval or written comments from Paragon, in which case Spyre may proceed and the Publication will be considered approved in its entirety. If Spyre receives written comments from Paragon on any Publication during the applicable Review Period, then it will incorporate such comments where appropriate, provided, that upon Paragon’s request, (1) Spyre shall remove any Confidential Information of Paragon from such Publication, and (2) Spyre shall delay such Publication for up to [***] days to enable filing of Patents. Paragon will not publicly present or publish any Publication including Confidential Information of Spyre relating specifically to the Licensed Antibodies or Derived Antibodies without Spyre’s prior written consent, which consent may be withheld for any reason or no reason; provided, that the foregoing shall not limit Paragon’s right to publicly present or publish any Publication relating to

 

28


Multispecific Antibodies. Each Publication shall include proper attribution, including the use of such Party’s trademarks and name, to the non-publishing Party, as applicable, and each non-publishing Party expressly authorizes the inclusion of such reference in the applicable Publication and licenses the use of such trademarks and name solely for inclusion in any such Publication.

6.7 Return of Confidential Information. Promptly after the termination or expiration of this Agreement for any reason, each Party will return to the other Party or destroy, as such other Party will direct, all tangible manifestations of such other Party’s Confidential Information at that time in the possession of the receiving Party, subject to the receiving Party’s right to maintain one copy of such tangible manifestations of such other Party’s Confidential Information solely for purposes of monitoring its compliance with this Agreement.

ARTICLE VII

REPRESENTATIONS, WARRANTIES AND COVENANTS.

7.1 Mutual Representations. Each Party represents and warrants to the other Party that:

(a) it is duly organized and validly existing under the laws of its jurisdiction of incorporation or formation, and has full corporate or other power and authority to enter into this Agreement and to carry out the provisions hereof;

(b) it is duly authorized to execute and deliver this Agreement and to perform its obligations hereunder;

(c) no consent, approval, permit, governmental order, declaration or filing with, or notice to, any Governmental Authority or any Third Party is required by or with respect to such in connection with the execution and delivery of this Agreement and the consummation of the transactions contemplated hereby; and

(d) this Agreement is legally binding upon it, enforceable in accordance with its terms, and does not and will not conflict with any agreement, instrument, or understanding, oral or written, to which it is or may become a party or by which it may be or become bound.

7.2 Representations of Paragon. Paragon hereby represents and warrants to Spyre as of the Effective Date that:

(a) Paragon has set forth in Exhibit A a true, correct and complete list of all the Licensed Antibody Patents and Other Licensed Patents existing as of the Effective Date (including title, all inventors, owners, assignees, filing date, grant date, expiration date and status);

(b) Unless otherwise set forth in Exhibit A, Paragon exclusively owns all Licensed Antibody Patents and Other Licensed Patents;

(c) There are no licenses or sublicenses pursuant to which Paragon licenses as of the Effective Date any of the Licensed Antibody Technology or Other Licensed Technology from any Third Party, nor, to Paragon’s actual knowledge, are any such licenses necessary to Develop, Manufacture and Commercialize the Licensed Antibodies;

 

29


(d) Paragon has the right under the Licensed Antibody Technology and the Other Licensed Technology to grant to Spyre the licenses and other rights set forth in this Agreement, and it has not granted any license or other right under the Licensed Antibody Technology that is inconsistent with the licenses and other rights granted to Spyre hereunder;

(e) There is no pending or, to Paragon’s knowledge, threatened litigation, nor has Paragon received any written notice from any Third Party, asserting or alleging that the development, manufacture or commercialization of the Licensed Antibody Technology or Other Licensed Technology prior to the Effective Date infringed or misappropriated the intellectual property rights of such Third Party;

(f) To Paragon’s knowledge, Paragon has not withheld from Spyre any information with respect to the Licensed Antibody Technology or the Other Licensed Know-How that would reasonably be expected to be materially adverse to Spyre’s Development, Manufacture, or Commercialization of any Product in the Territory as contemplated under this Agreement;

(g) To Paragon’s knowledge, Paragon has, and any of Paragon’s Affiliates involved in the Research Program have, (i) conducted all research and development under the Research Program in accordance with Research Plan (as defined in the Option Agreement), and (ii) conducted the Research Program in compliance with all Applicable Laws;

(h) To Paragon’s knowledge, Paragon has provided true, correct and complete copies of all Results developed under the Research Program and all other deliverables required under the Research Program have been provided or delivered to Spyre and are true, correct and complete in all material respects;

(i) Paragon has properly filed, Prosecuted and maintained all Licensed Antibody Patents and Other Licensed Patents;

(j) Paragon has complied with all duties of disclosure and has not engaged in any inequitable conduct with respect to all Licensed Antibody Patents and Other Licensed Patents that were filed prior to the Effective Date;

(k) All Licensed Antibody Patents and Other Licensed Patents listed in Exhibit A that have been issued as of the Effective Date are in full force and effect and are, to Paragon’s knowledge, valid and enforceable;

(l) Other than the Patents listed in Exhibit A, as of the Effective Date, neither Paragon nor any of its Affiliates own or have any rights in, to or under any Patents Covering the composition of matter of, or any method of specifically making or using, any Licensed Antibody;

(m) There are no judgments against or awards or settlements against Paragon or any of its Affiliates, and there are no claims, actions, or proceedings pending or, to Paragon’s knowledge, threatened, nor to Paragon’s knowledge are there any formal inquiries initiated or written notices received that are reasonably likely to lead to the institution of any such legal

 

30


proceedings, in each case (i) relating to any Licensed Antibodies, Derived Antibodies, Other Licensed Technology or Licensed Antibody Technology or alleging that any Third Party has any right to or under any Products, Licensed Antibodies, Derived Antibodies, Licensed Antibody Technology or Other Licensed Know-How that would conflict with the rights granted in this Agreement; or (ii) alleging that any Licensed Antibody Patent is unpatentable, invalid, unenforceable or infringed;

(n) (i) Each Representative employe or engaged by Paragon or its Affiliate to conduct the activities under the Research Program have assigned or licensed, or are under contractual obligations to assign or license, to Paragon all inventions conceived, reduced to practice or otherwise related to Licensed Antibodies, Derived Antibodies and Licensed Antibody Technology; (ii) to Paragon’s knowledge, no Representative employed by Paragon or its Affiliate that conducts activities under a Research Program has any obligations under agreements or Applicable Law to assign any interest in any such inventions to any Third Party; and (iii) each Representative employed or engaged by Paragon or its Affiliate to conduct the activities under a Research Program have existing obligations under agreements or Applicable Law to maintain as confidential Paragon’s Confidential Information as well as confidential information of other parties (including of Spyre and its Affiliates);

(o) None of Paragon, its Representatives, or any other person used by Paragon in the performance of the Research Program or otherwise in connection with this Agreement has been or is (i) debarred, convicted, or is subject to a pending debarment or conviction, pursuant to section 306 of the United States Food Drug and Cosmetic Act, 21 U.S.C. § 335a, (ii) listed by any government or regulatory agencies as ineligible to participate in any government healthcare programs or government procurement or non-procurement programs (as that term is defined in 42 U.S.C. § 1320a-7b(f)), or excluded, debarred, suspended or otherwise made ineligible to participate in any such program, or (iii) convicted of a criminal offense related to the provision of healthcare items or services, or is subject to any such pending action. Paragon agrees to inform Spyre in writing promptly if Paragon or any person who is performing activities on its behalf under the Agreement is subject to the foregoing, or if any action, suit, claim, investigation, or proceeding relating to the foregoing is pending or threatened;

(p) No funding, facilities, or personnel of any Governmental Authority or any public or private educational or research institutions were used to develop or create any Licensed Antibody Technology or Other Licensed Technology (to the extent that such Other Licensed Technology is owned by Paragon or its Affiliates), and neither Paragon nor any of its Affiliates has entered into a government funding relationship that would result in rights to any Products, Licensed Antibodies, Derived Antibodies, Licensed Antibody Technology or Other Licensed Technology (to the extent that such Other Licensed Technology is owned by Paragon or its Affiliates) residing in the U.S. Government, the National Institutes of Health, or other agency, and the licenses granted hereunder are not subject to overriding obligations to the U.S. Government as set forth in Public Law 96-517 (35 U.S.C. §§ 200-204), or any similar obligations under the laws of any other country in the Territory; and

 

31


(q) To the [***] knowledge of [***] of Paragon, with respect to this Agreement and the Option Agreement, neither Paragon nor any of its directors, officers, employees, distributors, consultants, agents, representatives, sales intermediaries, or other Third Parties acting on behalf of Paragon or any of its Affiliates:

(i) has taken any action in violation of any applicable anti-corruption laws, anti-money laundering laws or laws restricting or regulating global trade (collectively, “Anti-Corruption Laws”);

(ii) has conducted or initiated any internal investigation with respect to any alleged act or omission arising under or relating to any potential noncompliance with any Anti-Corruption Law, or been the subject of current, pending, or threatened investigation, formal or informal inquiry, enforcement proceedings, or received any notice, request, or citation for alleged violations of such laws;

(iii) has engaged in any direct or indirect dealings or transactions in or with a person, entity or country found on the Specially Designated Nationals and Blocked Persons List maintained by the U.S. Office of Foreign Assets Control, or engaged in any direct or indirect dealings with Sudan, individuals ordinarily resident in Sudan, or entities incorporated under the laws of Sudan prior to October 12, 2017; or

(iv) has offered, paid, given, promised to pay or give, or authorized the payment or gift of, received, or solicited anything of value, directly or indirectly, to any public official, for the purposes of: influencing any act or decision of any public official in his or her official capacity; inducing any public official to do or omit to do any act in violation of his or her lawful duty; securing any improper or undue advantage; or inducing any public official to use his or her influence with a government, Governmental Authority, or commercial enterprise owned or controlled by any government (including state-owned or controlled veterinary, laboratory or medical facilities) in obtaining or retaining any business whatsoever.

7.3 Covenants of Paragon. Paragon hereby covenants to Spyre during the Term that:

(a) Paragon will not grant a Third Party any license or other right in the Licensed Antibody Technology or the Other Licensed Technology that would conflict with the rights and licenses granted to Spyre hereunder with respect to such Licensed Antibody Technology;

(b) Paragon will, and will direct each Affiliate of Paragon and subcontractor conducting activities under this Agreement to, conduct all such activities in compliance with Applicable Laws, including all applicable Anti-Corruption Laws and U.S. sanctions;

(c) Paragon will comply with the terms of each Paragon Third Party Agreement, will maintain each Paragon Third Party Agreement, will not amend a Paragon Third Party Agreement in a manner that (i) adversely effects Spyre in any material respect, or (ii) increases any financial obligations under a Paragon Third Party Agreement that will result in an increase in Spyre’s Reimbursement Obligation, in each case of (i) and (ii) without Spyre’s prior written consent, and will not take any actions that could reasonably cause any Paragon Third Party Agreement to lapse or terminate; and

 

32


(d) Paragon will, and will direct each applicable Affiliate of Paragon to, execute and deliver such additional documents and instruments and to perform such additional acts as may be necessary or appropriate to enable Spyre to exercise its rights and obligations under Sections 5.2, 5.3 and 5.4.

7.4 Compliance with Laws. Each Party shall, and shall ensure that its Affiliates and its and its Affiliates’ Representatives and sublicensees, comply with Applicable Laws in all material respects in the performance of its obligations and the exercise of its rights under this Agreement.

7.5 DISCLAIMER OF WARRANTIES. EXCEPT AS EXPRESSLY SET FORTH HEREIN, EACH PARTY EXPRESSLY DISCLAIMS ANY AND ALL WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, INCLUDING THE WARRANTIES OF DESIGN, MERCHANTABILITY, DURABILITY, MERCHANTABLE QUALITY, FITNESS FOR A PARTICULAR PURPOSE, NON-INFRINGEMENT OF THE INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES, OR ARISING FROM A COURSE OF DEALING, USAGE OR TRADE PRACTICES.

ARTICLE VIII

TERM; TERMINATION.

8.1 Term. The term of this Agreement shall commence on the Effective Date and shall expire on a country-by-country and Spyre Product-by-Spyre Product basis on the expiration of the Royalty Term for such Spyre Product in such country, in each case, unless earlier terminated by a Party as set forth below in this Article VIII (the “Term”). Upon expiration (but not termination) of the Agreement, the licenses granted in Section 2.1 shall survive and become royalty-free, fully paid-up, perpetual and irrevocable with respect to the applicable Spyre Product in the applicable country.

8.2 Termination by Spyre. Spyre shall have the right to terminate this Agreement in its entirety or on a country-by-country or Spyre Product-by-Spyre Product basis for any or no reason upon sixty (60) days’ prior written notice to Paragon.

8.3 Material Breach. Either Party may terminate this Agreement in its entirety for the material breach of this Agreement by the other Party, if such material breach remains uncured ninety (90) days (or thirty (30) days with respect to any failure to make any payments owing to a Party hereunder) following notice from the non-breaching Party to the breaching Party specifying such breach, provided that, in the event of a dispute regarding the existence or cure of a material breach, no termination shall become effective until such dispute is finally resolved pursuant to Section 10.7 in favor of the non-breaching Party and the breaching Party fails to cure such material breach within ninety (90) days thereafter.

8.4 Insolvency. Each Party will have the right to terminate this Agreement in the event of a Bankruptcy Event with respect to the other Party. “Bankruptcy Event” means the occurrence of any of the following: (a) the institution of any bankruptcy, receivership, insolvency, reorganization or other similar proceedings by or against a Party under any bankruptcy, insolvency,

 

33


or other similar law now or hereinafter in effect, including any section or chapter of the United States Bankruptcy Code, as amended or under any similar laws of the United States or any state thereof (the “Bankruptcy Code”), where in the case of involuntary proceedings such proceedings have not been dismissed or discharged within [***] days after they are instituted, (b) the insolvency or making of an assignment for the benefit of creditors or the admittance by a Party of any involuntary debts as they mature, (c) the institution of any reorganization, arrangement or other readjustment of debt plan of a Party not involving the Bankruptcy Code, (d) appointment of a receiver for all or substantially all of a Party’s assets, or (e) any corporate action taken by the board of directors of a Party in furtherance of any of the foregoing actions.

8.5 Effect of Termination of this Agreement. If this Agreement terminates for any reason (excluding expiration under Section 8.1), whether with respect to a particular Spyre Product, particular country or in its entirety, then the following shall apply:

(a) All licenses and other rights granted by Paragon under this Agreement with respect to the terminated Spyre Product(s) and terminated country(ies) shall terminate, except as required for Spyre, its Affiliates and/or its Sublicensees to perform any of its obligations that survive termination, including to continue to complete or wind down (at [***] expense in the event of a termination by Spyre under Section 8.3) any ongoing clinical trials for any Spyre Product, as may be required by Applicable Law or ethical principles.

(b) No later than [***] days after the effective date of such termination, each Party shall return or cause to be returned to the other Party, or destroy, all Confidential Information received from the other Party and all copies thereof related to the terminated Spyre Product(s) in the terminated country(ies); provided, however, that each Party may retain any Confidential Information reasonably necessary for such Party’s ongoing obligations and rights under this Agreement which do not terminate, and each Party may keep one (1) copy of Confidential Information received from the other Party in its confidential files for record purposes and such copy shall remain subject to Article VI of this Agreement.

(c) Upon Paragon’s written request to Spyre (which must be provided to Spyre within [***] days after the effective date of termination), Paragon and Spyre shall [***] discuss [***], for a period of up to [***] days following such written request, terms and conditions under which Spyre may be willing to grant to Paragon [***], [***] license under the Spyre Intellectual Property to Develop, Manufacture, Commercialize or otherwise exploit the terminated Spyre Products in the Field in the terminated countries that were the subject of any Development, Manufacturing or Commercialization activities performed by Spyre or its Affiliates under this Agreement prior to such termination, (“Reversion Products”), as well as the potential transfer of materials, ongoing clinical trials, and applicable regulatory filings and relevant data generated by Spyre with respect to the Reversion Products and necessary for the continued Development, Manufacture, Commercialization and exploitation of such Reversion Products, such agreement to include commercially reasonable financial and other terms, which terms shall take into consideration Spyre’s contributions made in the Development, Manufacture, Commercialization and other exploitation of the Reversion Products, provided, that Spyre is under no obligation to enter into such license.

 

34


8.6 Survival of Sublicenses. Upon termination of this Agreement, at the written request of any Sublicensee who is not then in breach of its sublicense agreement, such sublicense agreement will survive such termination of this Agreement, and Paragon will negotiate [***] the terms and conditions of a direct license with such Sublicensee that is consistent with the terms of this Agreement (as adjusted for the scope of license, products, field of use and other provisions of the original sublicense). Each sublicense that may be amended to become a direct license between Paragon and a Sublicensee shall ensure that any and all economic rights, payments or benefits due to Spyre will be preserved and payable to Spyre and will designate Spyre a third-party beneficiary to enforce such rights. In each such instance, Spyre will have the right to review and approve the terms of such agreement between Paragon and such Sublicensee as related to Spyre’s economic rights, which approval shall not be unreasonably withheld, conditioned or delayed.

8.7 Accrued Rights; Survival. The expiration or termination of this Agreement for any reason shall not release either Party from any liability or obligation that, at the time of such expiration or termination, has already accrued to the other Party or that is attributable to a period prior to such expiration or termination, nor will expiration or any termination of this Agreement preclude either Party from pursuing all rights and remedies it may have under this Agreement, or at law or in equity, with respect to breach of this Agreement. In the event of expiration or any termination of this Agreement, the following provisions of this Agreement shall survive such expiration or termination in accordance with their respective terms and conditions: Article I (Definitions); Section 2.1 (License Grant from Paragon) (upon expiration (but not termination) of this Agreement as set forth in Section 8.1 (Term)); Section 2.3 (Sublicenses) (with respect to any payments or other performance obligations prior to conversion (if any) to a direct license pursuant to Section 8.6); Section 2.4 (No Implied Licenses; Reservation of Rights); Section 4.1 (Milestone Payments) (with respect to any outstanding payment obligations incurred prior to the date of termination or expiration); Section 4.2 (Royalties) (with respect to any outstanding payments accrued prior to the effective date of termination); Section 4.4 (Payment Reports) (with respect to the last Calendar Quarter of the Term to the extent not already reported and any outstanding payment obligation with respect to any royalty payments accrued prior to the date of termination or expiration); Section 4.5 (Payment Method) to 4.9 (Blocked Currency) (for the duration of any outstanding payment obligations under this Agreement); Section 4.10 (Records; Inspection) (for the duration set forth therein); Section 5.1 (Ownership); Section 7.5 (Disclaimer of Warranties); Article VI (Protection of Confidential Information) (for the duration set forth therein); Section 8.5 (Effect of Termination of this Agreement); Section 8.6 (Survival of Sublicenses); Section 8.7 (Accrued Rights; Survival); Article IX (Indemnification); and Article X (Miscellaneous).

ARTICLE IX

INDEMNIFICATION.

9.1 By Spyre. Spyre hereby agrees to defend, indemnify and hold harmless Paragon, its Affiliates and its or their Representatives (each, an “Paragon Indemnitee”) from and against any and all losses, damages, liabilities, expenses and costs, including reasonable legal expense and attorneys’ fees (collectively, “Losses”), to which any Paragon Indemnitee may become subject (a) as a result of any claim, demand, action, or other proceeding by any Third Party (“Third Party Claim”) to the extent such Losses result from: (i) the gross negligence, recklessness or willful misconduct of any Spyre Indemnitee in the performance of this Agreement; (ii) Spyre’s breach of

 

35


any of its representations, warranties or covenants under this Agreement; or (iii) Spyre’s Development, Manufacture and Commercialization of the Spyre Products; and (b) to the extent such Losses result from the termination, suspension, revocation or other loss of any Licensed Antibody Patents as a result of any negligence or breach of this Agreement by Spyre, its Affiliates or Sublicensees, in each case ((a) to (b)), except in each case to the extent that any Losses are attributable to the breach of this Agreement by, or the negligence, recklessness or willful misconduct of, or otherwise indemnifiable by, any Paragon Indemnitee.

9.2 By Paragon. Paragon hereby agrees to defend, indemnify, and hold harmless Spyre, its Affiliates, and its or their Representatives (each, a “Spyre Indemnitee”) from and against any and all Losses to which any Spyre Indemnitee may become subject (a) as a result of any Third Party Claim to the extent such Losses result from: (i) the gross negligence, recklessness or willful misconduct of any Paragon Indemnitee in the performance of this Agreement; or (ii) Paragon’s breach of any of its representations, warranties or covenants under this Agreement; and (b) to the extent such Losses result from: (i) the termination, suspension, revocation or other loss of any Licensed Antibody Patents as a result of any negligence or breach of this Agreement by Paragon or its Affiliates; or (ii) any claim or demand from any employee or contractor of Paragon or its Affiliates who is an inventor of any Licensed Antibody Patents with respect to ownership thereof, in each case ((a) to (b)), except to the extent that any Losses are attributable to the breach of this Agreement by, or the negligence, recklessness or willful misconduct of, or otherwise indemnifiable by, any Spyre Indemnitee.

9.3 Indemnification Procedures. The Party claiming indemnity under this Article IX (the “Indemnified Party”) will give written notice to the Party from whom indemnity is being sought (the “Indemnifying Party”) promptly after learning of the Third Party Claim for which indemnity is being sought (“Claim”). The Indemnifying Party’s obligation to defend, indemnify and hold harmless pursuant to Section 9.1 or Section 9.2, as applicable, will be reduced to the extent the Indemnified Party’s delay in providing notification pursuant to the previous sentence results in material prejudice to the Indemnifying Party; provided, however, that the failure by an Indemnified Party to give such notice or otherwise meet its obligations under this Section 9.3 will not relieve the Indemnifying Party of its indemnification obligation under this Agreement. At its option, the Indemnifying Party may assume the defense and have exclusive control, at its own expense, of any Claim for which indemnity is being sought by giving written notice to the Indemnified Party within [***] days after receipt of the notice of the Claim. The Indemnified Party will provide the Indemnifying Party with reasonable assistance, at the Indemnifying Party’s expense, in connection with the defense. The Indemnified Party may participate in and monitor such defense with counsel of its own choosing at its sole expense; provided, however, the Indemnifying Party will have the right to assume and conduct the defense of the Claim with counsel of its choice. The Indemnifying Party will not settle any Claim without the prior written consent of the Indemnified Party, not to be unreasonably withheld, unless the settlement involves only the payment of money. The Indemnified Party will not settle any such Claim without the prior written consent of the Indemnifying Party. If the Indemnifying Party does not assume and conduct the defense of the Claim as provided above, (i) the Indemnified Party may defend against, and consent to the entry of any judgment or enter into any settlement with respect to the Claim in any manner the Indemnified Party may deem reasonably appropriate, provided, that the Indemnified Party reasonably consults with the Indemnifying Party prior to entering into any settlement, and (ii) the Indemnified Party reserves any right it may have under this Article IX to obtain indemnification from the Indemnifying Party.

 

36


9.4 Limitation of Liability. EXCEPT FOR LIABILITY FOR BREACH OF ARTICLE VI, FOR BREACH OF SECTIONS 2.1 OR 2.2, FOR BREACH OF ANY INTELLECTUAL PROPERTY RIGHTS HELD BY A PARTY, FOR THE FRAUD OR WILLFUL MISCONDUCT OF A PARTY OR FOR INDEMNIFICATION CLAIMS UNDER THIS ARTICLE IX, IN NO EVENT SHALL EITHER PARTY BE ENTITLED TO RECOVER FROM THE OTHER PARTY ANY SPECIAL, INCIDENTAL, CONSEQUENTIAL OR PUNITIVE DAMAGES IN CONNECTION WITH THIS AGREEMENT, EVEN IF THE OTHER PARTY HAD NOTICE OF THE POSSIBILITY OF SUCH DAMAGES.

9.5 Insurance. During the Term and for a period of [***] years thereafter, each Party shall maintain at its expense insurance coverage consistent with normal business practices and adequate to cover the risks associated with its performance of any activities hereunder. Each Party hereby expressly acknowledges and agrees that the maintenance of such insurance coverage shall not relieve it of its obligations under this Agreement.

ARTICLE X

MISCELLANEOUS.

10.1 Independent Contractor Relationship. Paragon’s relationship with Spyre is that of an independent contractor, and nothing in this Agreement should be construed to create a partnership, joint venture, or employer-employee relationship. Neither Party is an agent of the other Party or authorized to make any representation, contract, or commitment on behalf of the other Party.

10.2 Force Majeure. Neither Party will be charged with any liability for delay or failure in performance of an obligation under this Agreement (other than any obligation to pay monies when due) to the extent such delay or failure is due to a cause beyond the reasonable control of the affected Party, such as war, riots, labor disturbances, epidemic, pandemic, fire, explosion, and compliance in good faith with any Applicable Law (in each case, a “Force Majeure”). In addition, a Force Majeure event may include reasonable measures affirmatively taken by a Party or its Affiliates to respond to the COVID-19 pandemic or any other pandemic (or other Force Majeure event), such as requiring employees to stay home, closures of facilities, delays of clinical trials, or cessation of activities in response to the pandemic.  The Party affected by a Force Majeure will give prompt written notice to the other Party of the nature of the cause of any material delay or failure to perform, its anticipated duration and any action being taken to avoid or minimize the effect. The Party affected will use its diligent efforts to avoid or remove such causes of delay or failure to perform and to mitigate the effect of such occurrence, and will continue performance in accordance with the terms of this Agreement whenever such causes are removed. The Party affected will give prompt written notice to the other Party of such resumed performance. If any such failure or delay in a Party’s performance hereunder continues for more than [***] days, the other Party may terminate this Agreement upon written notice to the affected Party.

 

37


10.3 Entire Agreement; Amendment. This Agreement and the Option Agreement, together with all Exhibits attached hereto, constitutes the final, complete, and exclusive agreement of the Parties with respect to the subject matter hereof and supersedes all prior and contemporaneous understandings and agreements, relating to its subject matter. This Agreement (including its Exhibits) may not be changed, modified, amended, or supplemented except by a written instrument signed by both Parties.

10.4 Non-Waiver. The failure of a Party to insist upon strict performance of any provision of this Agreement or to exercise any right arising out of this Agreement shall neither impair that provision or right nor constitute a waiver of that provision or right, in whole or in part, in that instance or in any other instance. Any waiver by a Party of a particular provision or right shall be in writing, shall be as to a particular matter and, if applicable, for a particular period of time and shall be signed by such Party.

10.5 Severability. Should one or more of the provisions of this Agreement become void or unenforceable as a matter of Applicable Law, then this Agreement shall be construed as if such provision were not contained herein and the remainder of this Agreement shall be in full force and effect, and the Parties will use their best efforts to substitute for the invalid or unenforceable provision a valid and enforceable provision which conforms as nearly as possible with the original intent of the Parties.

10.6 Assignment. Neither this Agreement nor any rights or obligations hereunder may be assigned by either Party without the prior written consent of the other Party (which consent shall not be unreasonably withheld); provided, however, that (a) Paragon may assign to an Affiliate or a Third Party financing source its rights to receive some or all of the payments payable hereunder together with the right to receive Confidential Information of Spyre, provided Paragon shall not be permitted to share Spyre Confidential Information unless and except to the extent necessary to obtain Affiliate or Third-Party financing, provided, further, that any such Affiliate or Third Party agrees to be bound by obligations of confidentiality and non-use at least as restrictive as those set forth in Article VI; and (b) either Party may assign this Agreement and its rights and obligations hereunder without the other Party’s consent to (i) its Affiliates or (ii) its successor to all or substantially all of the business of such Party to which this Agreement relates, whether by merger, sale of stock, sale of assets or otherwise. The assigning Party shall provide the other Party with prompt written notice of any such assignment set forth in clauses (a) and (b) above. Except for an assignment pursuant to clause (a) above, 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. Any assignment not in accordance with this Agreement shall be void.

 

38


10.7 Dispute Resolution.

(a) The Parties recognize that a bona fide dispute as to certain matters may arise from time to time during the Term relating to either Party’s rights or obligations hereunder or otherwise relating to the validity, enforceability or performance of this Agreement, including disputes relating to alleged breach or termination of this Agreement but excluding any disputes relating to Article VI or disputes relating to the determination of the validity, scope, infringement, enforceability, inventorship or ownership of the Parties’ respective Intellectual Property Rights (hereinafter, a “Dispute”). In the event of the occurrence of any Dispute, the Parties will follow the following procedures in an attempt to resolve the dispute or disagreement:

(i) The Party claiming that such a Dispute exists will give notice in writing (a “Notice of Dispute”) to the other Party of the nature of the Dispute. The Dispute will be referred to the then Chief Executive Officer of Paragon and the then Chief Executive Officer of Spyre (or, if no Chief Executive Officer of Spyre has been appointed, the Chief Operating Officer of Spyre) who will meet no later than [***] days following the initial receipt of the Notice of Dispute and use reasonable endeavors to resolve the Dispute.

(ii) If, within [***] days of initial receipt of the Notice of Dispute, the Dispute has not been resolved, or if, for any reason, the meeting described in Section 10.7(a)(ii) hereof has not been held within [***] days of initial receipt of the Notice of Dispute, then the Parties agree that such Dispute will be finally resolved through binding arbitration to be administered by JAMS pursuant to its Comprehensive Arbitration Rules and Procedures and in accordance with the Expedited Procedures in those Rules (the “JAMS Rules”), as specifically modified by the provisions of this Section 10.7(a)(iii) and Section 10.7(a)(iv).

(iii) The arbitration will be conducted by a panel of three arbitrators. Within [***] days after the initiation of the arbitration, each Party will nominate one person to act as arbitrator, and the two arbitrators so named will then jointly appoint the third arbitrator within [***] days of their appointment, who will serve as chairman of the panel. All three arbitrators must be independent Third Parties having at least [***] years of dispute resolution experience (which may include judicial experience) or legal or business experience in the biotech or pharmaceutical industry. If either Party fails to nominate its arbitrator, or if the arbitrators selected by the Parties cannot agree on a person to be named as chairman within such [***]-day period, JAMS will make the necessary appointments for such arbitrator(s) or the chairman. Once appointed by a Party, such Party will have no ex parte communication with its appointed arbitrator.

(iv) Notwithstanding the provisions of Section 10.7(a)(ii), in the event that the Dispute involves an amount in question of less than $[***], then the arbitration will be conducted by one arbitrator, selected in accordance with the JAMS Rules.

(v) The place of arbitration will be in Boston, Massachusetts or such other venue as the Parties may mutually agree. The arbitration proceedings and all communications with respect thereto will be in English. Any written evidence originally in another language will be submitted in English translation accompanied by the original or a true copy thereof. The arbitrator(s) shall have the power to decide all matters in Dispute, including any questions of whether or not such matters are subject to arbitration hereunder. The arbitration will be governed by the Federal Arbitration Act, 9 U.S.C. §§1 et seq., and judgment upon the award rendered by the arbitrators may be entered in any court having competent jurisdiction thereof. The existence, content and results of any arbitration proceedings pursuant to this Section 10.7 will be deemed the Confidential Information of both Parties.

 

39


(b) Notwithstanding any provision of this Agreement to the contrary, either Party may immediately initiate litigation in any court of competent jurisdiction seeking any remedy at law or in equity, including the issuance of a preliminary, temporary or permanent injunction, to preserve or enforce its rights under this Agreement.

(c) The Parties agree that any disputes relating to Article VI or disputes relating to the determination of the validity, scope, infringement, enforceability, inventorship or ownership of the Parties’ respective Intellectual Property Rights shall be subject to the exclusive jurisdiction of the state and federal courts in Boston, Massachusetts and each Party hereby submits to such jurisdiction.

10.8 Governing Law. This Agreement shall be governed by and construed in accordance with the laws of the Commonwealth of Massachusetts without reference to conflicts of laws principles.

10.9 Notices. Any notice to be given under this Agreement must be in writing and delivered either in person, by internationally recognized express courier, by email, or by facsimile, to the Party to be notified at its address(es) given below, or at any address such Party has previously designated by prior written notice to the other. Notice shall be deemed sufficiently given for all purposes upon the earliest of: (a) the date of actual receipt; (b) if delivered by express courier, the next Business Day the express courier regularly makes deliveries; or (c) if delivered by email, upon the date upon which the receipt of such email is confirmed by return email. Together with any notice provided by a Party to the other Party in accordance with this Section 10.9, the Party shall send a copy of such notice by email to the other Party.

If to Paragon:  Paragon Therapeutics, Inc.

221 Crescent Street

Building 23, Suite 105

Waltham, MA 02453

Attn: Chief Operating Officer

Email: [***]

If to Spyre:   Spyre Therapeutics, Inc.

221 Crescent Street

Building 23, Suite 105

Waltham, MA 02453

Attn: Chief Executive Officer

Email: [***]

10.10 Interpretation. Except where the context expressly requires otherwise, (a) the use of any gender herein shall be deemed to encompass references to either or both genders, and the use of the singular shall be deemed to include the plural (and vice versa), (b) the words “include”, “includes” and “including” shall be deemed to be followed by the phrase “without limitation”, (c) the word “will” shall be construed to have the same meaning and effect as the word “shall”, (d) any definition of or reference to any agreement, instrument or other document herein shall be construed as referring to such agreement, instrument or other document as from time to time amended, supplemented or otherwise modified (subject to any restrictions on such amendments, supplements or modifications set forth herein), (e) any reference herein to any person or entity shall be construed to include such person’s or entity’s successors and assigns, (f) the words

 

40


“herein”, “hereof” and “hereunder”, and words of similar import, shall be construed to refer to this Agreement in its entirety and not to any particular provision hereof, (g) all references herein to Sections or Exhibits shall be construed to refer to Sections or Exhibits of this Agreement, and references to this Agreement include all Exhibits hereto, (h) the word “notice” means notice in writing (whether or not specifically stated) and shall include notices, consents, approvals and other written communications contemplated under this Agreement, (i) provisions that require that a Party, the Parties or any committee hereunder “agree,” “consent” or “approve” or the like shall require that such agreement, consent or approval be specific and in writing, whether by written agreement, letter, approved minutes or otherwise (but excluding e-mail and instant messaging), (j) references to any specific law, or article, section or other division thereof, shall be deemed to include the then-current amendments thereto or any replacement or successor law thereof, and (k) the term “or” shall be interpreted in the inclusive sense commonly associated with the term “or.” The headings of clauses contained in this Agreement preceding the text of the sections, subsections and paragraphs hereof are inserted solely for convenience and ease of reference only and shall not constitute any part of this Agreement or have any effect on its interpretation or construction. Ambiguities and uncertainties in this Agreement, if any, shall not be interpreted against either Party, irrespective of which Party may be deemed to have caused the ambiguity or uncertainty to exist. This Agreement has been prepared in the English language, and the English language shall control its interpretation. In addition, all notices required or permitted to be given hereunder, and all written, electronic, oral, or other communications between the Parties regarding this Agreement shall be in the English language. To the extent there is any inconsistency or conflict between the terms and conditions of this Agreement and any Exhibit, the terms and conditions of this Agreement will prevail.

10.11 No Third-Party Rights. The provisions of this Agreement are for the exclusive benefit of the Parties and their successors and permitted assigns, and no other person shall have any right or claim against any Party by reason of these provisions or be entitled to enforce any of these provisions against any Party.

10.12 Counterparts. This Agreement may be executed in counterparts, each of which shall be deemed an original document, and all of which, together with this writing, shall be deemed one instrument. This Agreement may be executed by facsimile or PDF signatures, which signatures shall have the same force and effect as original signatures.

10.13 Expenses. Each Party shall pay its own costs, charges and expenses incurred in connection with the negotiation, preparation and completion of this Agreement.

10.14 Binding Effect. This Agreement shall be binding upon and inure to the benefit of the Parties and their respective legal representatives, successors and permitted assigns.

10.15 Construction. The Parties hereto acknowledge and agree that: (a) each Party and its counsel reviewed and negotiated the terms and provisions of this Agreement and have contributed to its revision; (b) the rule of construction to the effect that any ambiguities are resolved against the drafting Party shall not be employed in the interpretation of this Agreement; and (c) the terms and provisions of this Agreement shall be construed fairly as to all Parties hereto and not in a favor of or against any Party, regardless of which Party was generally responsible for the preparation of this Agreement.

 

41


10.16 Cumulative Remedies. No remedy referred to in this Agreement is intended to be exclusive unless explicitly stated to be so, but each shall be cumulative and in addition to any other remedy referred to in this Agreement or otherwise available under law.

10.17 Performance by Affiliates. A Party may perform some or all of its obligations under this Agreement through Affiliate(s) or may exercise some or all of its rights under this Agreement through Affiliates, subject to the terms of this Agreement. However, each Party shall remain responsible and be guarantor of the performance by its Affiliates and shall cause its Affiliates to comply with the provisions of this Agreement in connection with such performance as if such Party were performing such obligations itself, and references to a Party in this Agreement shall be deemed to also reference such Affiliate. In particular and without limitation, all Affiliates of a Party that receive Confidential Information of the other Party pursuant to this Agreement shall be governed and bound by all obligations set forth in Article VI, and shall be subject to the intellectual property provisions of Article V as if they were the original Party to this Agreement (and be deemed included in the actual Party to this Agreement for purposes of all intellectual property-related definitions). A Party and its Affiliates shall be jointly and severally liable for their performance under this Agreement.

[Remainder of Page Left Intentionally Blank; Signature Page Follows]

 

42


IN WITNESS WHEREOF, the Parties have by duly authorized persons executed this Agreement as of the Effective Date.

 

PARAGON THERAPEUTICS, INC.     SPYRE THERAPEUTICS, INC.
By:   /s/ K. Evan Thompson     By:   /s/ Cameron Turtle
Name:   K. Evan Thompson     Name:   Cameron Turtle
Title:   Chief Operating Officer     Title:   Chief Executive Officer

 

[SIGNATURE PAGE TO LICENSE AGREEMENT]

Exhibit 10.2

[***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE IT IS BOTH (I) NOT MATERIAL AND (II) IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL.

AMENDED AND RESTATED BIOLOGICS MASTER SERVICES AGREEMENT

This Amended and Restated Biologics Master Services Agreement (this “Agreement”) is effective as of the latest date of signature (the “Effective Date”) and is between Spyre Therapeutics, Inc., a Delaware corporation, with an office at 221 Crescent Street, Building 17, Suite 102B, Waltham, MA 02453 (“Client”) and WuXi Biologics (Hong Kong) Limited, with its registered address at Flat/RM826, 8/F Ocean Centre Harbour City, 5 Canton Road TST, Hong Kong (“Provider”), each of Client and Provider being a “Party,” and collectively the “Parties.”

A. Client discovers and develops biologics.

B. Provider coordinates the biologics development and manufacturing services, including those provided by certain affiliated operating companies.

C. The Parties desire that Provider or its Affiliates provide services to Client on a project-by-project basis. The services for each project (the “Services”) will be provided pursuant to a separate and distinct contract (a “Work Order”) that incorporates certain terms of this Agreement.

D. Provider and Paragon Therapeutics, Inc. entered into a Biologics Master Services Agreement dated as of June 20, 2022 (the “Original Agreement”), which was novated by Paragon Therapeutics, Inc. to Client.

E. On November 28, 2023 Client effected a change of its name from Aeglea Biotherapeutics, Inc. to Spyre Therapeutics, Inc.

F. Provider and Client now wish to amend and restate the Original Agreement on the terms and conditions set forth herein.

The Parties therefore agree as follows:

 

1.

CERTAIN DEFINITIONS

 

1.1

Affiliate” of a Person means any other Person that directly or indirectly Controls, is controlled by, or is under common Control with, the Person.

 

1.2

Applicable Law” means all applicable laws, regulations and current Good Manufacturing Practice (cGMP) and other official guidelines and directives of any Authority relevant to the Services performed under this Agreement, and the supply, use, marketing or sale of the Product.

 

1.3

“Authority” means any government regulatory authority responsible for granting approvals for the performance of Services under this Agreement or for issuing regulations pertaining to the Manufacture and/or use of Product in the intended country of use, including the FDA.

 

1


1.4

Cell Line” means the cell line that has been developed to produce a Product.

 

1.5

Certificate of Analysis” means a certificate of analysis for testing of Specifications of a Product in a form agreed to by the Parties.

 

1.6

Certificate of Compliance” means a document issued by WuXi Biologics attesting that a Product Batch has been manufactured in compliance with cGMP (as applicable) and that Manufacturing Batch records have been reviewed and approved by WuXi Biologics’ Quality Assurance.

 

1.7

Certificate of Testing” means a certificate for testing of selected Specifications of a Product in a form agreed by both Parties, for the selected testing performed by WuXi Biologics.

 

1.8

Confidential Information” of a Party (the “Disclosing Party”) means all information and materials disclosed by or on behalf of the Party to the other Party (the “Receiving Party”) or its Related Persons (as defined below) in connection with this Agreement that is reasonably considered to be confidential and is not generally available to the public. The Confidential Information of both Parties includes the existence, terms and objectives of this Agreement, and the nature of any dispute and the outcome of any arbitration proceedings arising out of or in connection with this Agreement. All data and information developed by either party relating specifically to the Products, including manufacturing and batch records and Cell Line validation data generated by Provider under Work Orders, constitutes Client’s Confidential Information (but for clarity, any of Provider’s standard operating procedures and other internal documents related to Provider’s platform shall remain Provider’s Confidential Information). Confidential Information excludes:

 

  (a)

information that at the time of disclosure to Receiving Party is in the public domain (through no act or omission of Receiving Party);

 

  (b)

information that was known by Receiving Party prior to receipt from Disclosing Party (as proven by Receiving Party’s written records);

 

  (c)

information that is disclosed to Receiving Party by a third party without an obligation of confidentiality and having the legal right to do so (as proven by Receiving Party’s written records); and

 

  (d)

information that is independently developed by Receiving Party without any benefit of, and not being derived or arising from, Confidential Information.

 

1.9

Control” over a Person means (a) owning 50% or more of the voting securities or other ownership interests of the Person or (b) having the power to direct the management or policies of the Person.

 

2


1.10

Facility” means the facility(ies) of Provider identified in the applicable Work Order.

 

1.11

FDA” means the United States Food and Drug Administration, and any successor agency having substantially the same functions.

 

1.12

Intellectual Property” means patents and patent applications, trademarks and applications, trade names, service marks, domain names, copyrights and copyright applications and registrations, schematics, industrial models, inventions, know-how, trade secrets, computer software programs and other intangible proprietary information including Confidential Information.

 

1.13

Interfering Law” has the meaning given to it in Section 11.4 (Termination for Legal Reason).

 

1.14

Material Adverse Effect” means, with respect to an applicable Interfering Law, that the Interfering Law, individually or in the aggregate with other Interfering Law(s), is or could reasonably be expected to become materially adverse to, or has or could reasonably be expected to have a materially adverse effect on, the prospects of a Product or the business or prospects of Client or any of its business lines as a result of Provider providing any Services to Client pursuant to this Agreement or any Work Order or as a result of Client being a party to this Agreement. By way of example, and not limitation, an Interfering Law will be deemed to have a Material Adverse Effect if such Interfering Law would or could reasonably be expected to (a) have a material adverse effect on the economic prospects or profitability of any Product, (b) materially adversely affect Client as a result of having Provider as a service provider under this Agreement or a Work Order (including as the manufacturer of any particular Product) as opposed to an alternative service provider performing comparable services, or (c) impact Client’s ability to enter into a contract with a governmental entity, receive grant funds from a governmental entity, or consummate a transaction with a potential collaborator, licensee, or acquiror (including, without limitation, an acquiror of Client or its assets).

 

1.15

Person” means an individual, a corporation, a partnership, an association, a trust or other entity or organization, including a government or political subdivision or an agency thereof.

 

1.16

Product” means the drug substance, drug product, or a part or derivative of the drug substance or drug product, that is manufactured through the Services or to be produced by a Cell Line.

 

1.17

Specifications” means the list of tests, references to any analytical procedures and appropriate acceptance criteria which are numerical limits, ranges or other criteria for tests described in order to establish a set of criteria to which Product at any stage of Manufacture should conform to be considered acceptable for its intended use that are provided by or approved by Client, as such specifications are amended or supplemented from time to time by Client in writing.

 

3


2.

SERVICES

 

2.1

Work Orders. Provider shall provide the Services to Client pursuant to each Work Order that is entered into during the term of this Agreement. The preferred form of Work Order is provided in Exhibit A. Each Work Order will automatically incorporate the terms of this Agreement and be a separate and distinct agreement. If there is a contradiction between a provision of this Agreement and a Work Order, then the provision in this Agreement will take precedence unless the Work Order specifically states that it takes precedence over such named provision, in which case such precedence shall be limited in application to the Services under such Work Order. For clarity, this Agreement is non-exclusive in nature, and Client is not obligated to enter any Work Order in connection with this Agreement or to use any service or equipment provided by Provider. Client may enter into any agreement with any third party for any purpose, including to have such third party perform any activities that are identical or similar to activities contemplated to be or actually performed by Provider in connection with this Agreement or any Work Order. In addition, the Parties stipulate and agree that no human biological samples, human genetic information, or other sensitive personal data or information, including personal health data and human genomic data, or United States government-related data or information will be exchanged or made accessible between the Parties pursuant to this Agreement.

 

2.2

Manufacturing. Both Parties will comply with the manufacturing terms in Exhibit B.

 

2.3

Clinical Supply. As applicable, the Parties will comply with the clinical supply terms in Exhibit D.

 

2.4

MOU. The Parties will comply with the Memorandum of Understanding in Exhibit E (the “MOU”). In the event of any conflict between the terms and conditions of the MSA and the MOU with respect to the pricing or the availability or Services, the provisions of the MOU will control.

 

2.5

Affiliates

 

  (a)

Provider may delegate or subcontract the Services, or any part thereof, to an Affiliate of Provider listed on Exhibit C for the provision of Services described. If the Services are provided by an Affiliate, then references to Provider in this Agreement will be deemed to be references to the Affiliate with the necessary modifications. Provider shall be liable for the performance of the Affiliate to the same extent as if the performance was that of Provider.

 

  (b)

An Affiliate of a Party may enter into a Work Order instead of the Party. If a Work Order is entered into by an Affiliate, then references to the Party in this Agreement will be deemed to be references to the Affiliate with the necessary modifications. The Party shall be liable for the performance of the Affiliate to the same extent as if the performance was that of the Party.

 

4


3.

CONTRACT PRICE; PAYMENT

 

3.1

Contract Price: Subject to any adjustment pursuant to the MOU, Client shall pay Provider the undisputed fees in the amount and manner provided in the applicable Work Order (the “Contract Price”). The Contract Price may be charged in accordance with a lump-sum or other pricing structure as agreed by the Parties. The Contract Price will include [***].

 

3.2

Expenses. Client shall reimburse Provider for reasonable and documented expenses that are (a) authorized by Client, (b) described in the applicable Work Order, or (c) described in this Agreement, including Sections [***].

 

3.3

Milestones. If a Work Order includes a payment for completion of a project stage or other milestone, then Provider shall notify Client [***] after the milestone is achieved. Client will be deemed to have agreed that the milestone was achieved unless it notifies Provider otherwise within [***] of receiving such notice. Each milestone payment is designed to reflect the fair value of the corresponding Services, and is not dependent on any other milestone unless otherwise specified in the Work Order.

 

3.4

Payment. Client shall pay undisputed amounts in each of Provider’s invoices within [***] of receipt by wire transfer to the account designated by Provider. All payments made under this Agreement and any Work Order will be made [***]. The Contract Price is exclusive of, and Client shall pay, any applicable taxes (other than taxes on Provider’s income) and other fees of any nature imposed by or under the authority of any government authority. Client may withhold any payment that the Client disputes [***] provided that Client informs Provider of such dispute within the original time for payment, in which case the Parties will meet to resolve the dispute [***].

 

3.5

No Clawbacks. Other than as agreed by the parties, under this Agreement or an applicable Work Order, the Contract Price and other payments under this Agreement and any applicable Work Order are non-cancelable and non-refundable, provided that Provider shall refund any pre-payments made for Services not performed.

 

3.6

Payment Default. In the event of an overdue undisputed amount (a “Payment Default”), interest of [***]% will accrue [***] on the overdue payment as of the date of the Payment Default. If the Payment Default is not rectified within [***] after Client’s receipt of notice of such Payment Default, then it will be deemed an incurable material breach of the applicable Work Order, and Provider may terminate the Work Order pursuant to Section 11.3(b).

 

3.7

Annual Review. At [***], each Party to a Work Order may propose a prospective adjustment of the Contract Price to reflect documented changes in pricing factors including foreign exchange fluctuation, cost reductions and efficiency increases, inflation or deflation and changes in the price of raw materials. The Parties shall negotiate [***] with the aim of identifying a mutually acceptable amendment of the Work Order; provided that the then-current Contract Price may not be increased by a percentage greater than the lesser of (a) the percentage of inflation occurring within the preceding calendar year (as measured by a Price Index applicable to the country where the Services are provided) and (b) five percent (5%).

 

5


4.

PROVISION OF SERVICES

 

4.1

Specifications. Provider shall provide all the Services at the Facility or other facilities agreed by both parties and in accordance with the Specifications of the applicable Work Order.

 

4.2

Qualifications. Provider shall ensure that the persons that provide the Services (the “Personnel”) (a) have the appropriate skills, training and experience and (b) are bound by confidentiality obligations consistent with the terms of this Agreement.

 

4.3

Compliance. Provider shall provide the Services in compliance with Applicable Law and applicable Good Practice (“GxP”) guidelines in all material respects.

 

4.4

On-Site Monitoring. Representatives of Client may, [***], visit the facilities where the Services are provided and consult informally during such visits with appropriate Personnel in order to monitor the Services. The representatives will be bound by rules applicable to the facilities and may, [***], be prohibited from entering or only given limited access to certain areas within the facilities. Provider may require that Client or the representatives execute an agreement that regulates the representatives’ conduct during its visit. Client shall be responsible for all expenses incurred in connection with such visits [***], and all its personnel must be subject to the same level of confidentiality as in this Agreement.

 

4.5

Regulatory Inspections. Provider will permit visits and/or inspections by regulatory Authorities of any country as required by Applicable Law, and will permit Client or its agents to be present and participate in any visit or inspection by such regulatory Authority of the Facility (to the extent it relates in any way to any Product) or the manufacturing process. Provider will give as much advance notice as possible to Client of any such visit or inspection. Provider will provide Client with a redacted (only to protect confidential information of Provider’s other customers and remove the contents not related to the Client’s project ) copy of any report or other written communication received from such Authority in connection with such visit or inspection, and any written communication received from any regulatory Authority relating to the Product, the Facility (if it relates to or affects the development and/or manufacture of Product) or the manufacturing process, within [***] after receipt, and will consult with, and unless legally prohibited by regulatory Authorities, seek approval from, Client before responding to each such communication if time permits. Provider will provide Client with a copy of its final responses within [***] after submission. [***]

 

6


4.6

Facility. Provider will not change the location of such Facility or use any additional facility for the performance of manufacturing Services under this Agreement without at least [***] prior written notice to, and prior written consent from, Client, which consent will not be unreasonably withheld or delayed (it being understood and agreed that Client may withhold consent pending satisfactory completion of a quality assurance audit and/or regulatory impact assessment of the new location or additional facility, as the case may be). Provider will maintain, [***], the Facility and all Equipment required for the Manufacture of Product in a state of repair and operating efficiency consistent with the requirements of cGMP (if applicable) and all Applicable Law. Provider will be responsible for performing all validation of the Facility, Equipment and cleaning and maintenance processes employed in the Manufacturing Process in accordance with cGMP (if applicable), Provider’s SOPs, the applicable Quality Agreement (if any), and Applicable Law. Provider will be responsible for obtaining, [***], any Facility or other licenses or permits, and any regulatory and government approvals necessary for the performance of Services by Provider under this Agreement. [***], Provider will provide Client with copies of all such approvals, and Client will have the right to use any and all information contained in such approvals in connection with regulatory approval and/or commercial development of Product.

 

5.

SOURCING OF MATERIAL

 

5.1

Materials. Provider shall, [***], purchase all materials necessary for the Services (the “Materials”). If a Material is not commercially available, then Client may elect to (a) supply, [***], the Material to Provider; or (b) amend the applicable Work Order to permit the use of a commercially available substitute. Provider shall perform the market research and propose a list of vendors in compliance with Applicable Law and applicable GxP in all material respects, [***]. Provider shall take the inventory risk of the selected materials, such as the damages to pass through materials caused by improper storage or pollutions, [***].

 

5.2

Client Materials. If a Material is to be supplied by Client (a “Client Material”), then Client shall provide the Client Material [***]and provide such information as may be required by Provider or Applicable Law concerning the stability, storage and safety requirements of the Client Material. Provider shall ensure that the Client Material will be (a) used solely for the purpose of providing the Services, (b) only distributed to Personnel on a need-to-know basis for the provision of the Services and (c) preserved and protected in a manner consistent with the specifications of the applicable Work Order and any relevant standard operating procedures or other instructions provided by Client. Client will at all times retain title to and ownership of the Client Materials, Product, any intermediates and components of Client Materials or Product, and any work in process at each and every stage of the Manufacturing Process. Provider will provide within the Facility an area or areas where the Client Materials, Product, any intermediates and components of Client Materials or Product, and any work in process are segregated and stored in accordance with the Specifications and cGMP (if applicable), and in such a way as to be able at all times during the period of the Agreement or applicable Work Order to clearly distinguish such materials from products and materials belonging to Provider, or held by it for a third party’s account. Provider will ensure that Client Materials (which are under Provider’s

 

7


  control), Product, any intermediates and components of Product, and any work in process are free and clear of any liens or encumbrances arising from disputes with any third party. Provider will at all times during the period of the Agreement or applicable Work Order take such measures as are required to protect the Client Materials, Product, any intermediates and components of any Client Materials or Product, and any work in process from loss, damage and theft at all stages of the Manufacturing Process. Client agrees that it is responsible to insure such items against theft, damage or loss and under no circumstances shall Provider be liable for loss or damage to any such items. The foregoing agreement does not limit the Provider’s liability for Client Materials’ (for clarity, such Client Materials should be specified in the applicable Work Orders) loss or damage solely resulting from Provider’s gross negligence or willful misconduct while the Services are being performed or while such Client Materials are in the Provider’s care. Provider will [***] notify Client if at any time it believes any Product or Client Materials, or any intermediates and components of any Client Materials or Product, or any work in process have been damaged, lost or stolen.

 

5.3

Unused Client Materials and Other Materials. Provider shall, [***], return, destroy or otherwise dispose of unused Client Materials [***] after the earlier of (a) completion of the Services for which the Client Materials were provided, (b) termination of the applicable Work Order, or (c) receipt of written instructions from Client pertaining to its disposition. Provider may dispose of other unused Materials at its sole discretion upon [***] prior written notice to Client, and Client may elect during the [***] period to have the Client Materials transferred to Client.

 

6.

RECORDS

 

6.1

Storage for Records. All materials, data and documentation obtained or generated by Provider in the course of providing the Services, including all computerized records and files (“Records”), will be maintained in a secure area in accordance with industry standards and Applicable Law, [***]. While it is the Parties’ intent that Provider shall retain ownership of any Provider IP or Provider Confidential Information contained in the Records, the Records with exclusion of the Provider IP and Provider Confidential Information are the sole and exclusive property of Client and Client shall be able to use the Records, unencumbered, for purposes related to the Product.

 

6.2

Retention of Records. Upon termination of the applicable Work Order, Provider shall, at Client’s option, (a) destroy the Records, (b) deliver the Records to Client, or (c) retain the Records for [***] and then destroy the Records. If the Records are to be destroyed, then Provider shall give [***] notice to Client, and Client may elect during the [***] period to have the Records transferred to Client. Notwithstanding the foregoing, the Records may be retained solely to the extent as required by Applicable Law or as otherwise necessary for regulatory or insurance purposes.

 

8


6.3

Storage for Product. All the Products shall be stored in Provider’s facilities for [***] free of Charge after Provider’s issuance of a Certificate of Compliance with 1) a Certificate of Analysis (if full lot release testing is performed by Provider) or 2) a Certificate of Testing (if Client requests only selected lot release testing to be performed by Provider), as applicable, and a monthly storage fee for Products shall be charged after the [***] period. Client agrees that the commercial value and/or cost of replacement or remanufacture of any Products provided to Provider for storage is a matter that, as between Client and Provider, is within the sole and exclusive knowledge of Client. Client agrees that it is responsible to insure such items against damage or loss and shall purchase appropriate insurance to cover its Products stored in Provider’s facilities. [***]. Transportation of Product by Provider on behalf of Client shall be made at the sole risk and expense of Client, notwithstanding the use of any INCOTERMS delivery term on any waybill or other documentation relating to the transportation. Provider shall not be liable for the actions or omission of any delivery services or carriers or freight forwarders.

 

7.

INTELLECTUAL PROPERTY

 

7.1

Ownership

 

  (a)

Except as otherwise provided in this Agreement, (i) Provider has no ownership rights in any Intellectual Property that is owned by Client, or licensed by any third party to Client, or any of its Affiliates, including Product, (“Client IP”) and (ii) Client has no ownership rights in any Intellectual Property that is owned by Provider, or licensed by any third party to Provider, or any of its Affiliates (“Provider IP”).

 

  (b)

Provider shall ensure that each of the Personnel vests in Provider, or its applicable Affiliate, any and all rights that such person(s) might otherwise have in the Intellectual Property created or developed in connection with the provision of the Services, and all Intellectual Property relating to such inventions (excluding moral rights) (“Project IP”). Improvements, modifications, and derivatives of Client IP constitute Project IP. Provider hereby assigns and shall assign (and require its Affiliates to assign) all rights, title and interests in Project IP to Client. Client will, [***], have sole control of filing and prosecuting applications for, and maintenance and enforcement of, patents for Project IP. Provider shall, [***], use [***] to assist Client to obtain, maintain, and enforce the Project IP. Client shall use [***] to [***] notify Provider of any patents granted for Project IP. Provider will be responsible for all payments to be made to Personnel of Provider and its Affiliates in accordance with any Applicable Law requiring remuneration for inventions. For the avoidance of doubt, Provider has no right to file, prosecute, maintain, protect, defend, or enforce Intellectual Property that covers any Product.

 

  (c)

Notwithstanding the foregoing, Intellectual Property created or developed in connection with the provision of the Services (i) that relates solely to Provider IP, (ii) that relates to experimental methods independent of Client IP and Project IP, or (iii) that relates to manufacturing processes generally, in each case without reliance or reference to Client IP or Project IP (collectively, “Manufacturing Improvements”), is Provider IP and not Project IP.

 

9


7.2

General Licenses

 

  (a)

Provider acknowledges and agrees that it does not acquire a license or any other right to Client IP except for the limited purpose of carrying out its duties and obligations under this Agreement and that such limited, non-exclusive, license will expire upon the completion of such duties and obligations or the termination or expiration of this Agreement, whichever is the first to occur.

 

  (b)

Provider hereby grants and shall ensure that each applicable Affiliate will grant and hereby does grant, to Client and its applicable Affiliates a non-exclusive, perpetual, irrevocable, royalty-free, non-transferable (except in the case of Section 14.2) and sublicensable (through multiple tiers) license to Client and its Affiliates to use Provider IP solely to develop, Manufacture, have Manufactured, distribute, offer for sale, sell, and otherwise dispose of Product. Provider may, at its discretion, grant to Client the right to use Manufacturing Improvements under mutually satisfactory terms to be negotiated.

 

7.3

Additional Licenses

In the provision of any given Service under this Agreement, Provider may, prior to the provision of such Service, recommend to incorporate into the process or deliverables some specific Provider IP that would be useful to improve the applicable process or deliverable involved in such Service and that needs an additional license, but which is not necessary for the performance of such Service. With respect to any such Provider IP, Provider shall submit to Client a written list of such Provider IP, describing it in reasonable detail and how such Provider IP will improve the applicable process or deliverable. Within [***] of Client’s receipt of the information noted in the preceding sentence, Client will notify Provider of its decision as to whether to incorporate such Provider IP into the process or deliverables. Provider shall not incorporate such Provider IP into the process or deliverables without Client’s express written consent (which Client may withhold at its sole discretion) or if Provider does not have sufficient rights in such specific Provider IP to enable Client to exploit such Provider IP under any such additional license. For any specific Provider IP (a) included in the process or deliverables for which Provider has failed to notify Client, or (b) for which Client has not expressly consented to the inclusion thereof, Client’s rights to such Provider IP shall be the same as Client’s rights in the process or deliverables and such Provider IP will be licensed to Client as provided in Section 7.2(b). If Client agrees that some specific Provider IP may be incorporated in the process or deliverables for the purpose of improving such process or deliverable, as applicable, then both parties shall negotiate such additional license to such Provider IP [***].

 

8.

REPRESENTATIONS AND WARRANTIES

 

8.1

Mutual. Each Party represents and warrants that (a) it validly exists under the laws of the jurisdiction in which it was organized, (b) it has the full power, right and authority to execute and deliver this Agreement and to perform its obligations under this Agreement, (c) this Agreement once executed will constitute a legal, valid and binding agreement enforceable against it and (d) its performance of this Agreement will not conflict with any obligations it may have to any other person.

 

10


8.2

Infringement. Client represents and warrants that, to the best of its knowledge, the use of Client Intellectual Property and Client Materials in the performance of Services in accordance with this Agreement will not infringe the Intellectual Property rights of any third party.

 

8.3

Provider Representations and Warranties. Provider represents and warrants to Client that (i) neither it nor any of the Personnel involved in the Services has been debarred, or, to the best of its knowledge, is under consideration for debarment, by the United States Food and Drug Administration from working in or providing services to any pharmaceutical or biotechnology company pursuant to the Generic Drug Enforcement Act of 1992 or any other governmental authority pursuant to analogous laws; (ii) to the best of its knowledge, the Provider IP will not violate the intellectual property rights of any third party and it will [***] notify Client in writing should it become aware of any claims asserting such violation; and (iii) at the time of delivery to Client, the Product Manufactured under this Agreement will have been Manufactured in accordance with cGMP (if applicable) and all other Applicable Law, the Manufacturing Process, the applicable Quality Agreement, and Specifications.

 

8.4

Compliance with Law. Each Party represents and warrants that it shall, and shall ensure that each of its Affiliate will, comply with all Applicable Law in connection with performance of this Agreement and any Work Orders. Each Party shall [***] notify the other Party upon becoming aware of a breach of this Section. Breach of this Section with respect to the U.S. Foreign Corrupt Practices Act or any other applicable anti-bribery law will be deemed an incurable material breach for purposes of Section 11.3(b).

 

9.

INDEMNIFICATION; LIMITATION ON LIABILITY; INSURANCE

 

9.1

Third Party Claims Against Client. Provider shall defend, indemnify and hold Client and its Affiliates and its directors, officers, employees, agents and consultants and legal, financial, accounting and other advisors (“Related Persons”) harmless from and against any and all liabilities and damages (including reasonable attorneys’ fees) (“Losses”) resulting from any third party claims, demands, suits or proceedings (“Claims”) to the extent arising out of or relating to (a) its performance of the Services, (b) a material breach of this Agreement by Provider, (c) a material violation of Applicable Law by Provider or any of its Related Persons, or (d) the gross negligence, recklessness or willful misconduct of Provider or any of its Related Persons during the course of activities carried out in connection with this Agreement (except to the extent that such Losses are within the scope of the indemnification obligation of Client under Section 9.2). The indemnification obligations set forth in this Section 9.1 do not apply to the extent that the Loss arises in whole or in part from the gross negligence, recklessness or willful misconduct of Client or any of its Related Persons or Client’s material breach of this Agreement.

 

11


9.2

Third Party Claims Against Provider. Client shall defend, indemnify and hold Provider and its Related Persons harmless from and against any and all Losses resulting from any Claims to the extent arising out of or relating to (a) Client’s use of Project IP or deliverables produced in accordance with this Agreement and the written instructions of Client that were provided or produced under a Work Order (including use of any license under Provider IP), or Provider’s appropriate or proper use of Client Materials or Client IP provided by Client for use in the Services or due to compliance to any written instructions provided by Client for use in the Services; (b) a material breach of this Agreement by Client, (c) a material violation of Applicable Law by Client or any of its Related Persons, (d) the gross negligence, recklessness or willful misconduct of Client or any of its Related Persons during the course of activities carried out in connection with this Agreement, or (e) development or manufacture, use, handling, storage, or other disposition of Products by or on behalf of Client or any of its Affiliates, sublicensees, agents or contractors (except by Provider), including Claims and threatened Claims based on product liability, bodily injury, risk of bodily injury, death or property damage or the failure to comply with any Applicable Law; except to the extent that such Losses are within the scope of the indemnification obligation of Provider under Section 9.1. The indemnification obligations set forth in this Section 9.2 do not apply to the extent that the Loss arises in whole or in part from the negligence, recklessness or willful misconduct of Provider or any of its Related Persons, or Provider’s material breach of this Agreement.

 

9.3

Intellectual Property Claims. Client shall defend, indemnify and hold Provider and its Related Persons harmless from and against Losses resulting from Claims to the extent arising out of or related to infringement of any third party Intellectual Property rights in connection with the Services or the Product and where the infringement would not have occurred but for Provider’s reliance upon Client’s written requirements, specifications and Client IP. To the extent Claims that are based on Provider IP independent of the Services or Product under this Agreement or Provider’s breach of this Agreement, Client shall not be required to defend, indemnify, and hold Provider and its Related Persons harmless from those Losses. Provider shall defend, indemnify and hold Client and its Related Persons harmless from and against Losses resulting from Claims to the extent arising out of or related to infringement of any Intellectual Property rights related to the Services and that are based on Provider IP.

 

9.4

Defense. Each Party shall notify the other Party within [***] upon learning of a Claim that is subject to indemnification pursuant to Sections 9.1, 9.2, or 9.3 (but failure to notify shall not relieve the indemnifying Party of its indemnification obligations unless such failure materially prejudices its ability to defend the claim). The indemnifying Party shall control, [***], the defense of the Claim [***] with counsel of its choice. The indemnified Party shall use [***] to cooperate in the defense at the indemnifying Party’s request and expense, and may participate in the Claim [***] using its own counsel. No compromise or settlement of any Claim may be made by the indemnifying Party without the indemnified Party’s written consent; provided that, if a settlement contains an absolute waiver of liability for the indemnified party, and each party has acted in compliance with the requirements of this Section 9.4, then the indemnified party’s consent will be deemed given.

 

12


9.5

Limitations on Liability

 

  (a)

NEITHER PARTY WILL BE LIABLE UNDER ANY LEGAL THEORY (WHETHER TORT, CONTRACT OR OTHERWISE) FOR SPECIAL, INDIRECT, INCIDENTAL, CONSEQUENTIAL OR PUNITIVE DAMAGES ARISING OUT OF OR RELATED TO THIS AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, INCLUDING LOST PROFITS ARISING FROM OR RELATING TO ANY BREACH OF THIS AGREEMENT, HOWEVER CAUSED, EVEN IF THE PARTY HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES, EXCEPT AS A RESULT OF A BREACH OF THE CONFIDENTIALITY AND NON-USE OBLIGATIONS, OR FOR GROSS NEGLIGENCE OR WILLFUL MISCONDUCT. NOTHING IN THIS SECTION IS INTENDED TO LIMIT OR RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY.

 

  (b)

[***].

 

9.6

Insurance. Each Party shall ensure that insurance coverage is carried and maintained with a financially sound and reputable insurer against loss from such risks and in such amounts as is sufficient to support its obligations under this Agreement. Each Party shall provide a copy of the applicable insurance policy if requested by the other Party.

 

10.

CONFIDENTIALITY AND PUBLICITY

 

10.1

Confidentiality. During the term of this Agreement and for [***] thereafter (other than with respect to trade secrets, which shall remain confidential for so long as they are protected under Applicable Law), the Receiving Party shall, and shall ensure that it, its Affiliates, and its Related Persons will, (a) maintain the Confidential Information of the Disclosing Party in confidence, (b) not use the Confidential Information of the Disclosing Party other than solely in connection with this Agreement and (c) not disclose the Confidential Information of the Disclosing Party to any third party other than (i) those of its Related Persons that have a need to know the Confidential Information in connection with the Services and are obligated to maintain the Confidential Information in confidence on terms at least as strict as those contained herein, and (ii) notify the Disclosing Party of any unauthorized disclosure of its Confidential Information [***] upon becoming aware of such disclosure. Notwithstanding the foregoing, Client may disclose the existence of this Agreement and Confidential Information of Provider confidentially in connection with a potential financing or acquisition or collaboration, provided, however, Client shall be liable for the acts and consequences of such disclosure.

 

13


10.2

Return of Confidential Information. Upon termination of this Agreement, and if requested in writing by the Disclosing Party within [***] thereafter, the Receiving Party shall cause all Confidential Information of the Disclosing Party to be [***] destroyed or returned to the Disclosing Party; provided, however, that the Receiving Party may, subject to its obligations of confidentiality hereunder, retain (a) a single secure copy of any Confidential Information for legal archival purposes, and (b) electronic back-up files that have been created by routine archiving and back-up procedures need not be deleted.

 

10.3

Publicity. Each Party shall not, and shall ensure that its Related Persons will not, use the name, symbols or marks of the other Party or any of its Affiliates in any advertising or publicity material or make any form of representation or statement that would constitute an express or implied endorsement by the other Party or any of its Affiliates of any commercial product or service, without the other Party’s or Affiliate’s prior written consent.

 

10.4

Audits. Provider and its Affiliates may have in the past provided, and may currently or in the future provide, services to other customers that are similar to the Services. Provider is absolutely committed to protecting Client’s Confidential Information and Intellectual Property, and shall not use such Confidential Information or Intellectual Property for the benefit of any person other than Client. In order to protect the Confidential Information of Client and the confidential information of other customers, Provider shall use [***] to ensure that other customers do not seek the disclosure of Confidential Information of Client, and Client hereby agrees it shall not seek the disclosure of confidential information of other customers of Provider. Notwithstanding the foregoing, if Client wishes to conduct an audit that relates to services provided to another customer for purposes of confirming that Client’s Intellectual Property is adequately protected, then Provider shall use [***] to seek the other customer’s approval to waive confidentiality obligations to the extent necessary to allow Client to conduct the audit in a manner that does not involve disclosure of the other customer’s confidential information to Client. If another customer wishes to conduct an audit that relates to the Services for purposes of confirming that the other customer’s Intellectual Property is adequately protected, then Client shall discuss whether to waive Provider’s confidentiality obligations to Client to the extent necessary to allow the other customer to conduct the audit in a manner that does not involve disclosure of Client’s Confidential Information to the other customer. Such audits may involve an independent auditor designated by Provider and paid for by the person seeking the audit.

 

11.

TERM AND TERMINATION

 

11.1

Term of Agreement. The term of this Agreement commences on the Effective Date and, unless earlier terminated pursuant to this Section 11, will expire on the later of (a) five (5) years from the Effective Date; or (b) the completion of Services under all Work Orders executed by the parties prior to the fifth anniversary of the Effective Date. The term of this Agreement may be extended by Client continuously for additional [***] periods upon written notice to Provider at least [***] prior to the expiration of the then-current term.

 

14


11.2

Termination by Client. Client will have the right, in its sole discretion, to terminate this Agreement or any Work Order (a) for convenience upon thirty (30) days’ prior written notice to Provider or (b) immediately upon written notice if Provider fails to obtain or maintain any material governmental licenses or approvals required in connection with the Services. Client shall pay off Provider for the Services rendered and the non-cancellable obligations occurred prior to the termination date; provided that Provider will use good faith efforts to mitigate such non-cancellable obligations if applicable.

 

11.3

Work Orders. Work Orders are subject to the terms of this Agreement and are not affected by the termination of this Agreement unless such Work Order is terminated together with the Agreement. The term of each Work Order commences on the date indicated in the Work Order and will, unless terminated earlier in accordance with this Agreement, terminate upon completion of the Services. Notwithstanding the foregoing, either Party may terminate a Work Order:

 

  (a)

at any time with six (6) months’ advance notice to the other Party, provided, however, Provider shall provide sufficient evidence to prove that there is reasonable cause to terminate the Work Order and discuss with Client in good faith prior to the termination; provided further, if Provider terminates a Work Order pursuant to this clause 11.3(a), then no termination or cancellation fees shall be paid by Client and Provider shall continue to provide Services for the irrelative Work Orders; or

 

  (b)

immediately upon notice to the other Party if

 

  (i)

a material breach of the Work Order by the other Party remains uncured thirty (30) days after notice of the material breach was received by such other Party; or

 

  (ii)

the other party files a petition in bankruptcy, or enters into an agreement with its creditors, or applies for or consents to the appointment of a receiver or trustee, or makes an assignment for the benefit of creditors, or becomes subject to involuntary proceedings under any bankruptcy or insolvency law (which proceedings remain undismissed for sixty (60) days); or

 

  (iii)

a Force Majeure Event occurs that will, or continues to, prevent performance (in whole or substantial part) of this Agreement or any pending Work Order by the other party for a period of at least ninety (90) days. In the case of a Force Majeure Event relating solely to a pending Work Order, the right to terminate will be limited to such Work Order.

 

15


11.4

Termination for Legal Reason. If any applicable law (including any Applicable Law), rule, regulation, guideline, or order in effect and as amended from time-to-time or any potential change in or new applicable law, rule, regulation, guideline, or order (including H.R.8333 or S.3558 (known as the BIOSECURE Act)) (any such law, rule, regulation, guideline, or order, new or existing, or any change or potential change to any of the foregoing, an “Interfering Law”) would or could reasonably be expected to have a Material Adverse Effect, then Client will have the right to terminate this Agreement and any and all Work Orders immediately by providing written notice to Provider describing the Interfering Law and the Material Adverse Effect such Interfering Law would or could reasonably be expected to have and explaining why such Interfering Law has caused Client to need to terminate this Agreement or any Work Order in order to avoid or mitigate such Material Adverse Effect. 

 

11.5

Technology Transfer. Without limiting any of Client’s technology transfer rights or Provider’s technology transfer obligations under that certain Amended & Restated Cell Line License Agreement between Client and Provider executed in October 2024 upon Client’s prior written request and with [***] notice to Provider, (whether during the Term of this Agreement or upon termination of this Agreement or any Work Order), Provider shall [***] to, disclose, make available, and conduct a full transfer to Client or any of its Affiliates or any third party (as directed by Client), all materials and information, including Provider IP, (in each case, owned or controlled by Provider or any of its Affiliates) (a) with respect to tangible materials, as reasonably requested by Client and (b) that are necessary or reasonably useful for Client and such Affiliates and third parties to Manufacture and otherwise Exploit the Product (“Technology Transfer”). The Parties shall [***] agree to a schedule and plan for such Technology Transfer and will use [***] to conduct and complete the Technology Transfer in accordance with such plan and schedule. Provider will provide reasonable assistance to enable Client, its Affiliates, or such third party manufacturer to manufacture Product, provided, however, it is the third party manufacturer’s responsibility to manufacture such Product after the transfer, and Provider will not be responsible for the third party manufacturer’s success or failure to manufacture any Products. Initiation of such technology transfer will be determined by Client. Provider will be compensated for such Technology Transfer activities by Client (as well as for any Services rendered), as mutually agreed by the Parties in writing, (i) on an hourly rate basis or (ii) by payment of a non-creditable, non-refundable lump-sum payment. Provider will provide reasonably requested ongoing technical support and assistance if requested by Client with such support and assistance reimbursed on a reasonable time, materials and hourly rate basis. The electronic portion of any Technology Transfer (i.e., the transfer of intangible intellectual property, documents, records, etc. necessary to effectively transfer the Manufacturing Process) requested due to termination of this Agreement due to an Interfering Law pursuant to Section 11.4 (x) will be provided by Provider [***] and (y) will include [***] non-chargeable hours of Provider consultation to Client, valid [***] from the date of signature of the Technology Transfer agreement; provided that, regardless of the reason that the Technology Transfer is requested, Client shall be responsible for all reasonable and documented third-party shipping costs associated with shipment of any tangible materials (e.g., cell banks, reference standards, etc.) which will be passed through to Client at cost. For clarity, Provider will complete any additional consultation or other “non-electronic” work required to effect the subject Technology Transfer at rates agreed [***] by the Parties.

 

16


11.6

Survival. Upon termination of this Agreement or a Work Order, all outstanding rights and obligations between the Parties arising out of or in connection with this Agreement or the Work Order, as the case may be, will [***] terminate, other than any obligations that (a) matured prior to the effective date of the termination or (b) by its nature are intended to survive, including Sections 2.1, 4.2, 4.3, 4.6, 6.1, 6.2, 11.4, 11.5, 11.6, 11.7 and Articles 1, 7-10, 12 and 14. Provider will, upon receipt of a termination notice from Client, [***] cease performance of the applicable Services and will take all reasonable steps to mitigate the out-of-pocket expenses incurred in connection therewith. Within [***] after the close-out of a Work Order, Provider will provide to Client a written itemized statement of all work performed by it in connection with the terminated Work Order, an itemized breakdown of the payments associated with that work, and a final invoice for that Work Order. If Client has pre-paid to Provider more than the amount in a final invoice then Provider agrees to [***] refund that money to Client, or to credit the excess payment toward another existing or future Work Order, at the election of Client.

 

11.7

Termination Fee.

If a Work Order is terminated early by Client under Section 11.2, 11.3 or 11.4, then Client shall pay Provider for the Services rendered in accordance with the terms of this Agreement and all non-cancelable obligations in connection with the Services to the extent specified in the applicable Work Order; provided that Provider will use good faith efforts to mitigate such non-cancellable obligations. At Client’s request, Provider will deliver to Client or Client’s designee any applicable materials that Client has paid for pursuant to this paragraph.

 

  (a)

If non-manufacturing Services, as specified in the applicable Work Order, are terminated by Provider due to Client’s material breach pursuant to Section 11.3(b), then Provider may charge Client a termination fee equal to [***] of the remaining value of such non-manufacturing Services within the Work Order as liquidated damages in connection with the redeployment of reserved Personnel and administrative overhead and costs.

 

  (b)

If manufacturing Services are terminated by Provider due to Client’s material uncured breach or at Client’s request, Client may be charged cancellation fees as specified in Section 12; If manufacturing Services (manufacturing run(s) including non-GMP manufacturing, GMP manufacturing, and engineering run) are terminated by Provider due to a Client request to cancel or due to a termination of the applicable Work Order by Provider because of Client’s uncured material breach pursuant to Section 11.3(b), Client shall be charged cancellation fees as specified in Section 12 below. If Client requests to 1) postpone or reschedule, or

 

17


  2) materially change the production scale or batch size of, a manufacturing run originally scheduled under an executed Work Order and/or this Agreement, the same cancellation terms in Section 12 will apply, provided that no cancellation fees will be charged in where such termination results from Provider’s breach of this Agreement, or its negligence or willful misconduct.

 

12.

CANCELLATION TERMS FOR MANUFACTURING SERVICES

 

12.1

Cancellation of non-GMP Drug Substance Manufacturing. If a notice to cancel a non-GMP drug substance manufacturing batch in an executed Work Order and/or this Agreement is received, Provider will use [***] to find an alternative customer or project to fill the manufacturing slot and reallocate raw materials purchased by Provider under the applicable Work Order for such non-GMP batch. In the case where no alternative customer or project can be identified to fill the slot(s) or use such raw materials, charges for cancelling the related work under this Agreement (“Cancellation Charge(s)”) will be applied based on the following, unless the termination is pursuant to Section 11.4 (Termination for Legal Reason) or as a result of Provider’s material breach of this Agreement, in which case no Cancellation Charge(s) will be applied:

 

  (a)

[***] except the cost of raw materials purchased by Provider under the applicable Work Order for such non-GMP batch, if the cancellation notice is received [***] before the scheduled vial thaw;

 

  (b)

[***] of a non-GMP manufacturing batch fee plus the cost of raw materials purchased by Provider under the applicable Work Order for such non-GMP batch, if the cancellation notice is received [***] before the scheduled vial thaw;

 

  (c)

[***] of a non-GMP manufacturing batch fee plus the cost of raw materials purchased by Provider under the applicable Work Order for such non-GMP batch, if the cancellation notice is received [***] before the scheduled vial thaw;

 

  (d)

[***] of a non-GMP manufacturing batch fee plus the cost of raw materials purchased by Provider under the applicable Work Order for such non-GMP batch, if the cancellation notice is received [***] prior to the scheduled vial thaw.

 

  (e)

[***] of a non-GMP manufacturing batch fee plus the cost of raw materials purchased by Provider under the applicable Work Order for such non-GMP batch, if the cancellation notice is received [***]; and

 

  (f)

[***] of a non-GMP batch fee plus the cost of raw materials purchased by Provider under the applicable Work Order for such non-GMP batch, if the cancellation notice is received [***].

 

18


12.2

Cancellations for Drug Substance cGMP Manufacturing Run or Engineering Run. If a notice to cancel a drug substance cGMP manufacturing run or an engineering run in an executed Work Order and/or this Agreement (as the case may be) is received, Provider will use [***] to find an alternative customer or project (but excluding any project under existing contract with Provider) for the manufacturing slot and reallocate raw materials purchased by Provider under the applicable Work Order for purposes of such cGMP manufacturing run or engineering run. In the case where no alternative customer or project can be identified to fill the slot(s) or use such raw materials, Cancellation Charge(s) will be applied based on the following, unless the termination is pursuant to Section 11.4 (Termination for Legal Reason) or as a result of Provider’s material breach of this Agreement, in which case no Cancellation Charge(s) will be applied:

 

  (a)

[***] except the cost of raw materials purchased by Provider under the applicable Work Order for purposes of such cGMP manufacturing run or engineering run, if the cancellation notice is received [***] before the scheduled vial thaw;

 

  (b)

[***] of the cGMP manufacturing run or engineering run batch fee plus the cost of raw materials purchased by Provider under the applicable Work Order for purposes of such cGMP manufacturing run or engineering run, if the cancellation notice is received [***] before the scheduled vial thaw;

 

  (c)

[***] of the cGMP manufacturing run or engineering run batch fee plus the cost of raw materials purchased by Provider under the applicable Work Order for purposes of such cGMP manufacturing run or engineering run, if the cancellation notice is received [***] before the scheduled vial thaw or anytime thereafter.

 

12.3

Cancellation for Drug Product cGMP Manufacturing Run or Engineering Run. If a notice to cancel a cGMP drug product manufacturing run or an engineering run in an executed Work Order and/or this Agreement (as the case may be) is received, Provider will use [***] to find an alternative customer or project (but excluding any project under existing contract with Provider) to fill the manufacturing slot(s). In the case where no alternative customer or project can be identified to fill the slot(s), Cancellation Charge(s) will be applied based on the following, unless the termination is pursuant to Section 11.4 (Termination for Legal Reason) or as a result of Provider’s material breach of this Agreement, in which case no Cancellation Charge(s) will be applied:

 

  (a)

[***], except the cost of raw materials purchased by Provider under the applicable Work Order for purposes of such cGMP manufacturing run or engineering run, if the cancellation notice is received [***] before the scheduled manufacturing run;

 

  (b)

[***] of the cGMP manufacturing run or engineering run batch fee plus the cost of raw materials purchased by Provider under the applicable Work Order for purposes of such cGMP manufacturing run or engineering run, if the cancellation notice is received [***] before the scheduled manufacturing run;

 

19


  (c)

[***] of the cGMP manufacturing run or engineering run batch fee plus the cost of raw materials purchased by Provider under the applicable Work Order for purposes of such cGMP manufacturing run or engineering run, if the cancellation notice is received [***] before the scheduled manufacturing run or anytime thereafter.

 

13.

SHIPPING

 

13.1

All materials to be provided by Provider to Client will be delivered FCA (carrier named by Client) (Incoterms 2020), including Product and other deliverables produced under a Work Order, returned Client Materials, returned Records and returned Confidential Information. For the avoidance of doubt, FCA (carrier named by Client) means Provider is responsible for handing over the materials, cleared for export, to a carrier named by Client. Client assumes risk at hand over and pays all costs as specified in Incoterms 2020.

 

13.2

All materials to be provided by Client to Provider will be delivered DDP (site designated by Provider) (Incoterms 2020), including Client Materials. For the avoidance of doubt, DDP (site designated by Provider) means Client is responsible for delivery to and unloading at the site designated by Provider and pays all costs including import duties and taxes.

 

14.

MISCELLANEOUS

 

14.1

Force Majeure. Force Majeure” means and includes such circumstances or occurrences which are beyond the reasonable control of the Party that materially prevent such Party from performing any of such Party’s obligations under this Agreement (other than the payment of money), and that are not caused by the Party’s negligence, which may include, but not limited to, acts of God; pandemic(such as Covid-19), strikes and labour problems affecting an entire industry or region; lightning, fire, flood, washout, storm, or other actions of the elements; government actions, including embargos, sanctions, prohibitions; and war, civil disturbances or other imposition of sanctions by a governmental authority with jurisdiction over a Party. Neither Party shall be liable for non-fulfilment of its obligations or in breach under this Agreement if such non-fulfilment is due to Force Majeure for the duration of such Force Majeure. Each Party shall use [***] to mitigate adverse consequences in the event of such Force Majeure. A Party that is prevented from performing any of its obligations due to Force Majeure will [***] give notice to the other Party of the event and the obligations as to which performance is prevented or delayed. If a Force Majeure situation continues for more than [***], the unaffected Party may terminate any affected Work Order upon notice to the affected Party, without penalty or liability (including without limitation penalties described in Section 12).

 

14.2

Assignment; Novation. This Agreement may not be assigned by a Party without the prior written consent of the other Party; provided, however, that (i) a Party may assign this Agreement to any of its Affiliates with net worth or insurance commensurate with such Party’s obligations and sufficient capacity and personnel, without such consent, but with notice to the other Party; and (ii) Client may, without Provider’s consent, assign this Agreement (a) to a third party in connection with the transfer or sale of all or substantially all of its assets or the line of business or Product to which this Agreement relates; (b) to a

 

20


  successor entity or acquirer in the event of a merger, consolidation or change of control. Any purported assignment in violation of this Section is void. This Agreement binds the Parties’ successors and assigns. Notwithstanding anything to the contrary in this Agreement, upon written notice from Client that Client has executed an exclusive license as to all or substantially all of the Client’s assets or Product to which one or more Work Orders relates, Provider shall, and hereby does (and Client, by providing such notice, also shall, and hereby does): (i) novate this Agreement and the applicable Work Orders to the Client’s exclusive licensee, on a form of novation agreement provided by Client and reasonably accepted by Provider (which acceptance shall not be unreasonably withheld, conditioned, or delayed) at the time of such novation; and (ii) enter into a new agreement that is an exact copy of this Agreement and includes only those Work Orders that are not subject to the novation in clause (i).

 

14.3

Notices. All notices, requests, demands and other formal or legal communications required under this Agreement must be in writing and will be deemed to have been given or made and sufficient in all respects when delivered by reputable international courier to the following addresses:

To Client:

Spyre Therapeutics, Inc.

221 Crescent Street, Building 23, Suite 105, Waltham, MA 02453

Attn: [***]

Tel.: [***]

Email: [***]

To Provider:

WuXi Biologics (Shanghai) Co., Ltd.

Area 301-A, Building No.2, 299 Fute Zhong Road

China (Shanghai) Pilot Free Trade Zone

Shanghai, China 200131

Attn: [***]

Email: [***]

 

14.4

Independent Contractor. The Parties are independent contractors, and nothing contained in this Agreement may be deemed or construed to create a partnership, joint venture, employment, franchise, agency, fiduciary or other relationship between the Parties.

 

14.5

Non-Solicitation. During the term of this Agreement and for [***] thereafter, Client shall not directly or indirectly induce or solicit (or authorize or assist in the taking of any such actions by any third party) any employee or consultant of Provider or any of its Affiliates that have provided Services under this Agreement to leave his or her employment or business association. Hiring advertisements and efforts not directed at a particular individual do not constitute a solicitation in violation of this Section 14.5.

 

21


14.6

Governing Law. The laws of the State of New York, USA, without regard to any choice of law principle that would require the application of the law of another jurisdiction, govern all matters relating to this Agreement and the enforcement thereof. The parties expressly reject any application to this Agreement of (a) the United Nations Convention on Contracts for the International Sale of Goods; and (b) the 1974 Convention on the Limitation Period in the International Sale of Goods, as amended by that certain Protocol, done at Vienna on April 11, 1980.

 

14.7

Arbitration. The Parties shall engage in [***] consultation to resolve any dispute arising out of or in connection with this Agreement. Such consultation will begin [***] after one Party has delivered to the other Party a request for consultation. If the dispute cannot be resolved within [***] following the date on which the request for consultation is delivered, then either Party may submit the dispute to the JAMS International Arbitration Rules (“Arbitration”). The Arbitration tribunal will consist of three arbitrators. Within [***] after the commencement of the Arbitration, each Party shall select one person to act as arbitrator, each of whom must be a practicing or retired attorney or judge having at least [***] of litigation experience within the biopharmaceutical industry. The two arbitrators so selected shall select the chair within [***] of the commencement of the Arbitration, whom must a practicing or retired attorney or judge having at least [***] of litigation experience within the biopharmaceutical industry. If the arbitrators selected by the Parties are unable or fail to agree upon the third arbitrator within the allotted time, the third arbitrator shall be appointed by JAMS in accordance with the JAMS International Arbitration Rules. All arbitrators shall serve as neutral, independent and impartial arbitrators. The Arbitration shall be conducted in accordance with the expedited procedures set forth in the JAMS International Arbitration Rules. The place of arbitration will be New York City. The official language of the arbitration will be English. The arbitration proceedings will be confidential, and the arbitrator may issue appropriate protective orders to safeguard each Party’s Confidential Information. During the course of arbitration, the Parties shall continue to implement the terms of this Agreement including all Work Orders then in effect. The arbitral award will be final and binding upon the Parties, and the Party to the award may apply to a court of competent jurisdiction for enforcement of the award. Notwithstanding the foregoing, each Party has the right to institute an action in a court of proper jurisdiction for injunctive or other equitable relief pending a final decision by the arbitrator.

 

14.8

Entire Agreement; Non-Reliance. This Agreement, together with each Work Order, contains the entire agreement between the Parties with respect to the subject matter of this Agreement. Prior agreements are hereby superseded. For the avoidance of doubt, prior confidentiality obligations are superseded to the extent that they cover Confidential Information. Each Party disclaims that it is relying on any representations or warranties other than those set forth in this Agreement.

 

22


14.9

Amendment and Restatement of Original Agreement. The Parties agree that, as of the Effective Date, the Original Agreement is hereby amended and restated. As of the Effective Date, terms of the Original Agreement are no longer in force or effect and are hereby superseded and replaced by the terms of this Agreement. For clarity, all Work Orders executed prior to the Effective Date will remain in full force and effect, subject to the terms and conditions of this Agreement.

 

14.10

Amendment. No modification or waiver of any term of this Agreement or any other form of amendment to this Agreement will be binding unless made expressly in writing and signed by both Parties.

 

14.11

No Third Party Beneficiaries. The provisions of this Agreement are for the sole benefit of the Parties.

 

14.12

Waiver. The waiver by either Party of any breach of any term of this Agreement will not constitute a waiver of any other breach of the same or any other term. Failure or delay on the part of either Party to fully exercise any right under this Agreement will not constitute a waiver or otherwise affect in any way the same or any other right.

 

14.13

Severability. If any provision in this Agreement is held to be invalid, illegal or unenforceable in any respect, then (a) the provision will be replaced by a valid and enforceable provision that achieves as far as possible the intention of the Parties and (b) all other provisions of this Agreement will remain in full force and effect as if the original agreement had been executed without the invalidated, illegal or unenforceable provision.

 

14.14

Independent Counsel. Each Party has had the opportunity to consult independent counsel, and as such, this Agreement will not be construed to have been drafted by one Party or the other but will be construed as having been jointly drafted when interpreting its provisions.

 

14.15

Counterparts. This Agreement may be executed in one or more counterparts, each of which will be deemed an original, but all of which together constitute one and the same instrument. Executed counterparts may be exchanged by facsimile or e-mail in PDF or similar electronic format.

[Signature page follows]

 

23


Thus, this Agreement is effective as of the latest date set forth below.

 

WuXi Biologics (Hong Kong) Limited     Spyre Therapeutics, Inc.
By:   /s/ Chris Chen     By:   /s/ Cameron Turtle
Name:   Chris Chen     Name:   Cameron Turtle
Title:   CEO     Title:   Chief Executive Officer
Date:   October 13, 2024     Date:   October 14, 2024

 

24


Exhibit A—Form of Work Order

WORK ORDER (NUMBER [•])

This work order is dated [•] and is between Spyre Therapeutics, Inc. (“Client”) and [WuXi Biologics (Hong Kong) Limited] (“Provider”).

The terms of the Biologics Master Services Agreement between Spyre Therapeutics, Inc. and WuXi Biologics (Hong Kong) Limited, dated [•] (the “Master Services Agreement”), are hereby incorporated by reference into this Work Order. Any modifications to the Master Services Agreement will be deemed to be references to this Work Order automatically. Each capitalized term used but not defined in this Work Order has the meaning given in the Master Services Agreement.

In the event that any Services set forth in this Work Order are for Clinical Supply Services, the terms set forth in Exhibit D of the Master Services Agreement shall apply to this Work Order.

 

1.

SERVICES INFORMATION

 

1.1

Title

[Project title]

 

1.2

Description

[Description of the Services including deliverables and specifications]

 

1.3

Tasks and Timeframe. Provider shall complete the Services in accordance with the following schedule:

 

    

Task

  

Completion Date

1      
2      
3      
4      

 

1.4

Client Materials

[Description of the Client Materials to be provided by Client to Provider that are necessary to perform the Services]

 

1.5

Reporting and Transfer of Data and Results

[Description of how data and results should be reported and transferred to Client, including electronic protocols for secure transmission of data and instructions for physical handling and shipping of materials if chemicals are being synthesized or other materials are to be transferred to Client]


1.6

Additional Requirements

[Any additional requirements such as additional obligations of the parties that do not appropriately fit into the task list and special handling of materials]

 

2.

FEES; PAYMENT SCHEDULE

 

2.1

General Terms. Expenses, milestones, payment and default and other general terms are provided in Section 3 of the Master Services Agreement.

 

2.2

Contract Price and Upfront Payment. The Contract Price will be USD [•]. On signing of this Work Order, Client shall pay Provider [•] % of the Contract Price as a non-refundable upfront payment.

 

2.3

Milestones. The table below lists milestones and related information.

 

    

Milestone

   Deliverable   Milestone Payment

1

  

[Description including work

required, criteria for achievement

and timeline]

   [•]   [•]

2

   [•]    [•]   [•]

 

2.4

Payment Instructions. Unless an invoice provides otherwise, Client shall pay the invoice in USD by wire transfer to the account listed below (as may be amended from time to time):

 

[***]

     [ ***]         

[***]

     [ ***]         

[***]

     [ ***]         

[***]

     [ ***]         

[***]

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

[***]

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

If any applicable law, rule, or regulation (including any Applicable Law) prohibits or prevents Client from transferring, or having transferred on its behalf, payments owed to Provider hereunder, then Client will [***] notify Provider of the conditions preventing such transfer and such payments will be deposited in a recognized banking institution designated by Provider.

 

A-2


3.

COMMUNICATIONS

 

3.1

Technical Communications. All technical communications required under this Work Order are to be sent via reputable international courier or email and addressed as follows:

 

If to Client:    If to Provider:
[•]    [•]
[•]    [•]
[•]    [•]
Attn: [•]    Attn: [•]
Tel.: [•]    Tel.: [•]
Email: [•]    Email: [•]

Thus, this Work Order is executed on the date stated in the introductory clause.

 

Spyre Therapeutics, Inc.     WuXi Biologics (Hong Kong) Limited
By:         By:    
Name:       Name:  
Title:       Title:  

 

A-3


Exhibit B—Manufacturing

[***]


Exhibit C: Affiliates of Provider

[***]


Exhibit D – Clinical Supply Terms

[***]


Exhibit E – MEMORANDUM OF UNDERSTANDING

BETWEEN SPYRE THERAPEUTICS, INC.

AND WUXI BIOLOGICS (Hong Kong) Limited

WHEREAS, WuXi Biologics (Hong Kong) Limited (“WuXi Biologics”) provides a comprehensive, integrated range of services for the discovery, development, and manufacturing of biologics;

WHEREAS, Spyre Therapeutics, Inc. a Delaware corporation with principal offices located at 221 Crescent Street, Building 23, Suite 105, Waltham, MA 0245 (“Spyre”) discovers and develops biologics therapeutics;

WHEREAS, Spyre and WuXi Biologics are parties to the Amended and Restated Biologics Master Services Agreement executed in October 2024 (each of Spyre and WuXi Biologics being a “Party,” and collectively the “Parties”) (“MSA”);

WHEREAS, from time-to-time the Parties may contract under the MSA for WuXi Biologics to provide certain services as described in a Work Order (as defined in the MSA) for Products (as defined in the MSA) (“Product”);

WHEREAS, Spyre and WuXi Biologics desire that this Memorandum of Understanding (“MOU”) memorialize certain terms that will be applicable to Work Orders between WuXi Biologics or its affiliates and Spyre with respect to Products; and

WHEREAS, WuXi Biologics desires to provide a discount on its Services (as defined below) to Spyre and provide Spyre with priority in access to [***];

IN CONSIDERATION THEREOF, THE PARTIES do hereby agree as follows:

 

  1.

The Parties agree and understand that the projects that are eligible for the Discount are those projects where services are to be provided by WuXi Biologics or its affiliates under the MSA or any Work Order, including one or more of the following: [***] (“Services”).

 

  2.

As acknowledgment of both the working relationship between the Parties and satisfaction of the level of service provided by WuXi Biologics to date, during the term of the MSA, Spyre will in good faith consider engaging WuXi Biologics to provide Services for future programs. This good faith consideration does not constitute any type of assurance or commitment from Spyre that it shall engage WuXi Biologics with respect to any specific Services or level of Services, but indicates that Spyre will continue to consider WuXi Biologics for Services for additional projects in good faith. Unless earlier terminated by Spyre in its sole discretion, this good faith consideration by Spyre will continue until the earlier of five (5) years from the date of the last Party to sign below or the termination or expiration of the MSA. The foregoing is subject to: (i) WuXi Biologics’ ability to provide


  Services for each Product in accordance with agreed-upon specifications, in the quantities, and on the timeframes reasonably requested by Spyre; (ii) Spyre’s right to engage a backup supplier using either its own future development and manufacturing resources or a third party’s development and manufacturing resources, (iii) WuXi Biologics’ ability to provide Services at a competitive overall cost; and (iv) WuXi Biologics’ and its affiliates continued performance under the MSA and executed Work Orders.

 

  3.

WuXi Biologics agrees to and shall provide the following discount (“Discount”) [***]to Spyre: [***]% off the prices on [***] charges under the MSA.

 

  4.

Notwithstanding the foregoing Section 3, the Discount (a) shall not be applicable to (i) [***] and (ii) [***] and (b) [***]. Further, the Parties agree that [***] are excluded from the Discount.

 

  5.

WuXi Biologics agrees to and shall provide Spyre priority in lead time (“Priority Lead Time”) [***]. Priority Lead Time shall mean that, as soon as it is able, but in any event, within [***] of executing any Work Order under the MSA, WuXi Biologics or its applicable affiliate will start working on the Spyre’s Work Order. WuXi Biologics agrees to provide (a) preferential access [***], and, following batch failure, when a re-supply run is required and (b) information regarding the availability of manufacturing slots as reasonably requested by Spyre in connection with any executed Work Order or potential Work Order that is subject to active negotiations between the Parties.

 

  6.

THE PARTIES AGREE THAT THEY WILL COMPLY WITH THE TERMS AND CONDITIONS OF THIS MOU.

 

  7.

THE TERMS OF THIS MOU CAN BE TERMINATED EITHER BY SPYRE IN ITS SOLE DISCRETION OR BY MUTUAL AGREEMENT IN WRITING BY THE PARTIES AND, IN ANY EVENT, WILL EXPIRE UPON THE TERMINATION OR EXPIRATION OF THE MSA.

 

  8.

NOTHING IN THIS MOU SHALL BE CONSTRUED AS A BAR TO OR PROHIBITION OF ANY FUTURE COLLABORATION OR OTHER AGREEMENTS THAT MAY BE NEGOTIATED BETWEEN WUXI BIOLOGICS AND SPYRE.

 

  9.

THIS MOU DOES NOT CONSTITUTE A LEGALLY BINDING COMMITMENT OR OBLIGATION BY SPYRE TO ENGAGE WUXI BIOLOGICS OR ITS AFFILIATES FOR ANY PARTICULAR SERVICES. A BINDING COMMITMENT WITH RESPECT TO ANY SERVICE WILL ONLY ARISE UPON EXECUTION AND DELIVERY OF THE APPLICABLE WORK ORDER, WHICH WILL BE SUBJECT TO THIS MOU AND THE MSA IN ALL RESPECTS.


  10.

THIS MOU IS HEREBY DEEMED INCORPORATED INTO, MADE A PART OF, AND GOVERNED BY THE TERMS OF THE MSA IN ALL RESPECTS.

EXCEPT AS SET FORTH HEREIN, THE MSA AND EACH WORK ORDER EXECUTED THEREUNDER REMAINS IN FULL FORCE AND EFFECT.

Exhibit 10.3

[***] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT,

MARKED BY BRACKETS, HAS BEEN OMITTED BECAUSE THE INFORMATION (I) IS NOT

MATERIAL AND (II) IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL.

AMENDED AND RESTATED CELL LINE LICENSE AGREEMENT

This Amended and Restated Cell Line License Agreement (“Agreement”), effective as of the latest date of signature (the “Effective Date”), is entered and made by and between WuXi Biologics (Hong Kong) Limited, having an address at Flat/RM826, 8/F Ocean Centre Harbour City, 5 Canton Road TST, Hong Kong (“WuXi Biologics”) and Spyre Therapeutics, Inc., a Delaware corporation, with an office at 221 Crescent Street, Building 17, Suite 102B, Waltham, MA 02453 (“Licensee”). WuXi Biologics and Licensee may be referred to herein individually as a “Party” and collectively as the “Parties.”

 

  A.

WuXi Biologics and Paragon Therapeutics, Inc. entered into a Cell Line License Agreement, dated June 20, 2022 (the “Original Cell Line License Agreement”), which was novated by Paragon Therapeutics, Inc. to Licensee.

 

  B.

On November 28, 2023 Licensee effected a change of its name from Aeglea Biotherapeutics, Inc. to Spyre Therapeutics, Inc.

 

  C.

The Parties now wish to amend and restate the Original Cell Line License Agreement on the terms and conditions set forth herein.

Now, therefore, the Parties agree as follows:

 

1.

Definitions

 

  1.1

“Affiliate” of a person means any other person that directly or indirectly Controls, is Controlled by, or is under common Control with, the person.

 

  1.2

Client Product means any [***] of interest to Licensee that is designated by the Licensee to be produced by the Licensed Cell Line. The current list of Client Products is set forth in Appendix I. The Parties shall cause each additional Client Product covered under this Agreement to be specified in an amendment to this Agreement executed by both Parties from time to time.

 

  1.3

Combination Product” means a Drug Product that contains one or more Client Product(s) (a) together with one or more other therapeutically active pharmaceutical agents (whether co-formulated or co-packaged or otherwise sold for a single price); or (b) together (whether co-packaged or otherwise sold for a single price) with any product, technology, device, software, application, process, or service (each (a) and (b), an “Other Component”). For clarity, Client Products are not Other Components.

 

  1.4

Confidential Information” of a Party (the “Disclosing Party”) means all non-public scientific, technical, financial regulatory or business information and materials disclosed by or on behalf of the Disclosing Party to the other Party (the “Receiving Party”) or its Related Persons (defined below) in connection with this Agreement. Confidential information shall be identified


  as confidential in writing or, if disclosed verbally or by observation, summarized in writing and submitted to the Receiving Party within [***] of the oral or visual disclosure thereof; provided, however, information need not be labeled or marked “confidential” to be deemed Confidential Information hereunder, if under the circumstances it is, or should be, understood to be confidential. The Confidential Information of both Parties includes the existence, terms and objectives of this Agreement, and the nature of any dispute and the outcome of any arbitration proceedings arising out of or in connection with this Agreement.

 

  1.5

Construct” means a [***] developed by WuXi Biologics that is used for delivering genetic code and for transfecting and/or transforming the Host Cell Line for purposes of creating the Licensed Cell Line.

 

  1.6

“Control” over an entity means (a) owning 50% or more of the voting securities or other ownership interests of such entity or (b) having the power to direct the management or policies of such entity.

 

  1.7

Drug Product means the final dosage form which contains Client Product(s), in association with other active or inactive ingredients.

 

  1.8

“Drug Substance” means bulk Client Product, which has not yet been packaged into its final dosage form.

 

  1.9

“Host Cell Line” means the proprietary host cell line developed by WuXi Biologics, and designated by WuXi Biologics as the [***], that is used to make the Licensed Cell Line.

 

  1.10

“Licensed Cell Line” means a transformed or transfected (using WuXi Biologics’ Construct(s)) version of the Host Cell Line that produces the Client Product.

 

  1.11

“Licensed Know-How” means any know-how and non-public information owned or controlled by WuXi Biologics that is used or incorporated in the Process or that is necessary or useful to operate the Process as further described in the Technology Transfer Package. The word “control” when used in connection with Licensed Know-How includes both exclusively and non-exclusively licensed know-how and non-public information, as well a right of WuXi Biologics to transfer such know-how and non-public information to Licensee. As used in this definition “know-how” means all confidential and proprietary commercial, technical, scientific and other know-how and information, trade secrets, knowledge, technology, methods, processes, practices, formulae, instructions, skills, techniques, procedures, experiences, ideas, technical assistance, designs, drawings, assembly procedures, records, computer programs, specifications, data and results (including biological, chemical, pharmacological, toxicological, pharmaceutical, physical and analytical, preclinical, clinical, safety, manufacturing and quality control data and know-how, and including study designs and protocols).


  1.12

Licensed Patent Rights” means any and all patent rights that are owned or controlled by WuXi Biologics or its Affiliates as of the Effective Date or thereafter that cover (a) any (i) Construct or (ii) Licensed Cell Line or (b) the manufacture, use, sale, or importation of either of the foregoing ((i) or (ii)).

 

  1.13

Marketing Authorization Approval” means, with respect to a country or extra-national territory, any and all approvals (including a New Drug Application or Biologics License Application approved by the FDA), licenses, registrations or authorizations of any Regulatory Authority necessary in order to commercially distribute, sell or market a product in such country or some or all of such extranational territory, including any pricing or reimbursement approvals.

 

  1.14

Materials means the biological materials, including the Licensed Cell Line, provided to Licensee pursuant to the license granted under this Agreement.

 

  1.15

Material Adverse Effect” means, with respect to an applicable Interfering Law, that the Interfering Law, individually or in the aggregate with other Interfering Law(s), is or could reasonably be expected to become materially adverse to, or has or could reasonably be expected to have a materially adverse effect on, the prospects of a Client Product or the business or prospects of Licensee or any of its business lines as a result of WuXi Biologics performing any activities pursuant to or contemplated by this Agreement, including the manufacturing activities contemplated by Section 5.1, or as a result of Licensee being a party to this Agreement. By way of example, and not limitation, an Interfering Law will be deemed to have a Material Adverse Effect if such Interfering Law would or could reasonably be expected to (a) have a material adverse effect on the economic prospects or profitability of any Client Product, (b) materially adversely affect Licensee as a result of having WuXi Biologics as a service provider with respect to activities performed in connection with or contemplated by this Agreement (including as the manufacturer of any particular Client Product) as opposed to an alternative service provider performing comparable services, or (c) impact Licensee’s ability to enter into a contract with a governmental entity, receive grant funds from a governmental entity, or consummate a transaction with a potential collaborator, licensee, or acquiror (including, without limitation, an acquiror of Licensee or its assets).

 

  1.16

“Media and Feeds” means any proprietary media and feeds used in the Process.


  1.17

Net Sales” means the amount earned and recognized as revenue by Licensee and its Affiliates or sublicensees for bona fide sales of Drug Product to a third-party ([***]), less:

 

   

[***];

 

   

[***];

 

   

[***];

 

   

[***];

 

   

[***];

 

   

[***]; and

 

   

[***].

Net Sales will not include [***]. Such amounts will be determined from the books and records of [***], maintained in accordance with GAAP consistently applied.

After giving effect to the deduction from Net Sales described in the previous paragraph (the “Deduction”), in the case of any Combination Product containing an Other Component sold in a given country and reporting period for a single price, Net Sales for the purpose of determining royalties of such Combination Product in such country will be calculated by [***].

After giving effect to the Deduction, if, on a country-by-country basis in a particular reporting period, the Client Product(s) is sold separately in the same dosage and form in a country, but the Other Component(s) in the Combination Product is not sold separately in the same dosage and form in such country, then Net Sales for the purpose of determining royalties of the Combination Product sold for a single price for such country will be calculated by [***].

After giving effect to the Deduction, if, on a country-by-country basis in a particular reporting period, the Client Product(s) in the Combination Product is not sold separately in the same dosage and form in such country, but the Other Component(s) included in the Combination Product are sold separately in the same dosage and form in such country, then Net Sales for the purpose of determining royalties of the Combination Product sold for a single price for such country will be calculated by [***].

If neither the Client Product(s) nor the Other Component(s) are sold separately in the same dosage and form in a given country during a particular reporting period, then Net Sales for the purpose of determining royalties of the Combination Product sold for a single price will, after giving effect to the Deduction, be negotiated by the Parties in good faith based on [***]of the [***] of the Client Product(s) and each of the Other Component(s) included in such Combination Product when sold in the same dosage and form in such country, and consistent with the dispute resolution procedure under Section 13.4 (Arbitration).


  1.18

Process means a process for manufacture of Client Product utilizing Licensed Know-How, Materials and Media and Feeds, which process is further described in the Technology Transfer Package.

 

  1.19

Regulatory Authority” means any applicable supranational, national, regional, state or local regulatory agency, department, bureau, commission, council, or other government entity involved in regulating development of and granting regulatory approval for a pharmaceutical product, including the FDA and EMA.

 

  1.20

“Related Persons” means a Party’s Affiliates and their respective directors, officers, employees and agents.

 

  1.21

Research Cell Bank” is a [***].

 

  1.22

Technology Transfer Package means all information and data describing the Process, together with all Licensed Know-How, Materials and Media and Feeds necessary or useful for the development and manufacture of Client Product using the Licensed Cell Line and/or the Process.

 

  1.23

“Third Party” means any person other than the Parties to this Agreement.

 

  1.24

“Third Party Manufacturer” means (i) a Third Party whose primary business is contract manufacturing, or (ii) a Third Party who has a contractual arrangement with Licensee or with a sublicensee of Licensee that includes manufacturing of Client Product and/or Drug Product by such Third Party for Licensee or such sublicensee.

 

2.

License

 

  2.1

WuXi Biologics hereby grants to Licensee and its Affiliates a non-exclusive, worldwide license, with the right to grant sublicenses as provided in Section 2.3, under the Licensed Patent Rights, Licensed Know-How, Licensed Cell Line, Materials, and Media and Feeds to:

 

  i.

develop, manufacture, have manufactured, make, have made, import, sell, have sold, offer for sale, keep, commercialize and otherwise deal in, use and exploit (“Exploit”) Client Product for any and all purposes; and

 

  ii.

Exploit Drug Substance and Drug Product for any and all purposes.

 

  2.2

The Licensee or its Affiliates may contract with a Third Party Manufacturer for the limited purpose of developing and manufacturing Client Product on behalf of the Licensee or its Affiliates, provided that, such Third Party Manufacturers are bound by the contract to comply with the confidentiality and use terms of this Agreement, and that the Licensee or its Affiliates will remain liable for any Third Party Manufacturers’ breach of this Agreement.


  (1)

For the benefit of doubt, a Third Party Manufacturer cannot manufacture Client Product, Drug Substance or Drug Product utilizing the Licensed Cell Line and Licensed Know-How without first being contracted with a Licensee, its Affiliates or sublicensee.

 

  (2)

A Third Party Manufacturer that has been granted a sublicense cannot grant, issue or transfer a sublicense to another Third Party.

 

  2.3

Subject to the terms and conditions of this Agreement, Licensee shall have the right to grant sublicenses through multiple tiers to one or more Third Parties for the rights granted to Licensee under this Agreement. Each sublicense agreement, through each tier of sublicensing, shall be in writing and provided that the applicable sublicensee is bound by all applicable terms and conditions of this Agreement, and Licensee or its Affiliates shall remain liable for any sublicensee’s breach of this Agreement. Licensee shall inform WuXi Biologics in writing any and all such sublicenses. Licensee will notify WuXi Biologics in writing of any sublicense agreement with a sublicensee within [***] of the execution of such agreement. Any sublicense granted by Licensee to any rights licensed to it hereunder will terminate [***] upon the termination of the license by WuXi Biologics under the terms of this Agreement; provided, that such sublicensed rights will not terminate if, as of the effective date of such termination, a sublicensee is not in material default of its obligations under its sublicense agreement, and within [***] of such termination, the sublicensee agrees in writing to be bound directly to WuXi Biologics under a license agreement substantially similar to this Agreement with respect to the rights sublicensed hereunder.

 

  2.4

Except as expressly provided in this Agreement, nothing in this Agreement shall be deemed to have granted Licensee (by implication, estoppel or otherwise) any right, title, license, or other interest in or with respect to any intellectual property, Know-How or information owned or controlled by WuXi Biologics.

 

  2.5

Invoicing of License fees will commence from [***].

 

3.

Transfer of Materials and Licensed Know-How

 

  3.1

WuXi Biologics shall notify Licensee in writing within [***] following the date on which WuXi Biologics completes transfection of the Host Cell Line to generate the Licensed Cell Line. Thereafter, [***] upon written request and the completion of due payment by Licensee (and in any event within [***] following designation of a Third Party Manufacturer), WuXi Biologics shall disclose, make available, and conduct a full transfer, and shall cause its


  Affiliates to disclose, make available, and conduct a full transfer to Licensee, its Affiliates, or any one or more of its Third Party Manufacturers designated by Licensee, all Materials and Licensed Know-How, that is necessary or reasonably useful for Licensee and Third Party Manufacturers to solely develop and manufacture the Client Product. The Parties shall [***] agree to a schedule and plan for such transfer of the Materials and Licensed Know-How and will conduct the transfer in accordance with such plan and schedule. WuXi Biologics will provide [***] assistance to enable such Licensee, Affiliate(s) of Licensee or Third Party Manufacturer, as applicable, to manufacture Client Product, provided, however, it is the Third Party Manufacturer’s full responsibility to manufacture such Client Product after the transfer, WuXi Biologics will not be responsible for the Third Party Manufacturer’s success or failure to manufacture any Client Products. Initiation of such technology transfer will be determined by Licensee. WuXi Biologics will be compensated for such transfer activities by Licensee, as mutually agreed by the Parties in writing, (a) on an [***] rate basis or (b) by payment of a non-creditable, non-refundable lump-sum payment from Licensee for such creation and delivery, in each case, to the extent not previously or otherwise compensated for such activities. WuXi Biologics will provide [***] requested ongoing technical support and assistance if requested by Licensee with such support and assistance reimbursed on a [***] rate basis.

 

4.

License Fee

As consideration for the license granted in Section 2 of this Agreement, and the representations and warranties set forth in Section 10 of this Agreement, Licensee agrees to pay WuXi Biologics a fixed non-creditable, non-refundable license fee of USD [***] for the Licensed Cell Line used for any and all Client Product(s).

 

5.

Cell Line Royalties and Related Payments.

 

  5.1

If Licensee manufactures all of its commercial supplies of the applicable Drug Substance using manufacturing facilities other than WuXi Biologics’ or its Affiliates’ manufacturing facilities, Licensee shall pay to WuXi Biologics a Royalty of [***] on the applicable Drug Product’s global Net Sales sold by Licensee, its Affiliates, or sublicensees, paid to WuXi Biologics [***]. If Licensee manufactures part of its commercial supplies of the applicable Drug Substance using WuXi Biologics’ or its Affiliates’ manufacturing facilities, the Royalty shall be reduced accordingly on [***] basis, depending on [***]. If Licensee manufactures all of its commercial supplies of the applicable Drug Substance by WuXi Biologics or its Affiliates, no Royalty is applicable and no Royalty payment shall be due hereunder.


  5.2

Notwithstanding the foregoing, in lieu of Licensee paying WuXi Biologics the Royalty provided for in Section 5.1, on a Drug Product-by-Drug Product basis, Licensee may, at its sole discretion, at any time pay WuXi Biologics a fixed non-creditable, non-refundable fee (a “Royalty Buyout Payment”), after which payment Licensee will no longer owe any Royalty with respect to such Drug Product, as follows:

 

  (1)

The Royalty Buyout Payment for a Drug Product that contains [***] shall be in the amount of $[***] USD.

 

  (2)

The Royalty Buyout Payment for a Drug Product that contains [***] shall be in the amount of $[***] USD [***].

 

  (3)

Notwithstanding the foregoing, the Royalty Buyout Payments attributable to [***] shall be capped at $[***] USD.

 

  (4)

By way of examples and without limiting the foregoing, (a) [***] and (b) [***].

 

  (5)

Upon the applicable Royalty Buyout Payments being fully paid with respect a Drug Product, the rights and licenses granted with respect to such Drug Product under this Agreement (including for clarity in Section 2.1) shall become fully paid-up, royalty free, perpetual, and irrevocable.

 

  5.3

Notwithstanding Section 5.1 or 5.2, if any applicable law, rule, regulation, guideline, or order in effect and as amended from time-to-time or any potential change in or new applicable law, rule, regulation, guideline, or order (including H.R.8333 or S.3558 (known as the BIOSECURE Act)) (any such law, rule, regulation, guideline, or order, new or existing, or any change or potential change to any of the foregoing, an “Interfering Law”) would or could reasonably be expected to have a Material Adverse Effect, then [***].

 

  (1)

Notwithstanding the foregoing, [***].

 

  (2)

For clarity, [***].

 

6.

Payment Terms

Licensee shall pay WuXi Biologics’ undisputed invoice(s) within [***] of receipt by Licensee. Such payments will be made by wire transfer to the account designated by WuXi Biologics. Invoices must be submitted, and payment must be made, [***].

 

7.

Bank Account Details

Unless the Parties otherwise mutually agree in writing, and such mutual agreement is set forth in a particular invoice, Licensee shall pay each invoice by wire transfer to the account designated by WuXi Biologics. With respect to Net Sales invoiced in U.S. dollars, the Net Sales and the amounts due hereunder will be expressed in U.S. dollars. With respect to Net Sales invoiced in a currency other than U.S. dollars, payments will be calculated based on standard methodologies employed by Licensee or its Affiliates or sublicensees for consolidation purposes for the [***] for which remittance is made for Royalties.


8.

Restriction

Licensee agrees that no attempt will be made by or on behalf of Licensee to modify or reverse engineer the Licensed Cell Line or attempt to reverse engineer, recreate or assemble the Construct(s). Licensee shall only use the Licensed Cell Line in the way as permitted by this Agreement and shall not use or have used the Licensed Cell Line for any purpose other than as provided hereunder, including operating the Process, the manufacture of Client Product, Drug Substance and Drug Product, and for other purposes reasonably related to securing Marketing Authorization Approval for the Client Product and/or Drug Product. Licensee shall not transfer the Licensed Cell Line to any Third Party except to a permitted sublicensee, as described in Section 2.2 above, permitted Third Party Manufacturer, or an assignee.

 

9.

Indemnity

 

  9.1

Licensee agrees to indemnify, hold harmless and defend WuXi Biologics, its Affiliates, and their respective directors, officers, employees and agents harmless (collectively, “WuXi Indemnitees”) from and against any and all liabilities and damages (including reasonable attorneys’ fees) resulting from any and all claims from any Third Party (“Claims”) to the extent arising from the use of the Licensed Cell Line, Client Product, Drug Substance or Drug Product by Licensee; except to the extent WuXi Biologics is obligated to indemnify Licensee in accordance with Section 9.2 of this Agreement, and provided further that Licensee shall have no obligation to indemnify any such Claims that arise from WuXi Biologics’ (i) negligence or intentional misconduct in connection with the Licensed Cell Line (ii) material breach of this Agreement (including the representations and warranties set forth in Section 10); or (iii) Host Cell Line components of the Licensed Cell Line or any Media and Feeds.

 

  9.2

WuXi Biologics will indemnify Licensee, its Affiliates, its sublicensees and their respective directors, officers, employees and agents, and their respective successors, heirs and assigns (collectively, “Licensee Indemnitees”), and defend and hold each of them harmless, from and against any and all Losses in connection with any and all Third-Party Claims against Licensee Indemnitees to the extent arising from or occurring as a result of: (i) the breach by WuXi Biologics of any provision of this Agreement; or (ii) any negligence or willful misconduct on the part of any WuXi Indemnitee in connection with the Host Cell Line components of the Licensed Cell Line, except in each case to the extent Licensee is obligated to indemnify WuXi Biologics in accordance with Section 9.1 of this Agreement.


  9.3

Each party must notify the other party within [***] of receipt of any claims made for which the other party might be liable hereunder. The indemnifying party will have the sole right to defend, negotiate, and settle such claims. The indemnified party will be entitled to participate in the defense of such matter and to employ counsel at its expense to assist in such defense. No compromise or settlement of any Claim may be made by the indemnifying Party without the indemnified Party’s written consent; provided, however, that the indemnifying party will have final decision-making authority regarding all aspects of the defense of any claim. The party seeking indemnification will provide the indemnifying party with such information and assistance as the indemnifying party may reasonably request, at the expense of the indemnifying party.

 

  9.4

Limitation of Liability. NEITHER PARTY WILL BE LIABLE UNDER ANY LEGAL THEORY (WHETHER TORT, CONTRACT OR OTHERWISE) FOR SPECIAL, INDIRECT, INCIDENTAL, CONSEQUENTIAL OR PUNITIVE DAMAGES ARISING OUT OF OR RELATED TO THIS AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, INCLUDING LOST PROFITS ARISING FROM OR RELATING TO ANY BREACH OF THIS AGREEMENT, HOWEVER CAUSED, EVEN IF THE PARTY HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES, EXCEPT AS A RESULT OF A BREACH OF THE CONFIDENTIALITY AND NON-USE OBLIGATIONS IN SECTION 11. NOTHING IN THIS SECTION 9.4 IS INTENDED TO LIMIT OR RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF EITHER PARTY.

 

10.

Representations and Warranties

 

  10.1

WuXi Biologics represents and warrants that: (i) it is a corporation duly organized validly existing and in good standing under the laws of Hong Kong; (ii) the execution, delivery and performance of this Agreement have been duly authorized by all necessary corporate action on the part of WuXi Biologics; (iii) the performance of WuXi Biologics’ obligations under this Agreement will not conflict with its charter documents or result in a material breach of any agreements, contracts or other arrangements to which it is a party; (iv) WuXi Biologics will not before the termination of this Agreement enter into any agreements, contracts or other arrangements that would be materially inconsistent with its obligations under this Agreement; (v) WuXi Biologics has sufficient facilities, experienced personnel and other capabilities reasonably suited to enable it to perform its obligations under this Agreement; (vi) WuXi Biologics has the right to grant the licenses or sublicenses, as the case may be, therefor granted under this Agreement; (vii) WuXi Biologics is the sole and exclusive owner of the Licensed Patent Rights Licensed, Know-how and Licensed Cell Line, or otherwise has the right to license the Licensed Patent Rights, Licensed Know-how and Licensed Cell Line and grant rights to Licensee as set forth in this Agreement and during the Term of the Agreement, (viii) to the best of its knowledge WuXi Biologics is and will remain entitled to grant to Licensee the licenses and rights specified or contemplated by this Agreement, and to the Licensed Know-How and Licensed Patent Rights, (ix) as of the


  Effective Date, neither WuXi Biologics nor any of its Affiliates has received any notice challenging WuXi Biologics’ ownership or right to use the Licensed Know-How in relation to the Licensed Cell Line and, Host Cell Line component of the Licensed Cell Line, (x) to the best of WuXi Biologics’ knowledge, there are no valid grounds for any claim against WuXi Biologics or any of its Affiliates except for any claims caused by Licensee’s DNA sequence related to the Client Product incorporated into the Licensed Cell Line.

 

  10.2

Licensee represents and warrants that: (i) it is a corporation duly organized validly existing and in good standing under the laws of the Commonwealth of Massachusetts; (ii) the execution, delivery and performance of this Agreement have been duly authorized by all necessary corporate action on the part of Licensee; (iii) the performance of Licensee’s obligations under this Agreement will not conflict with its charter documents or result in a material breach of any agreements, contracts or other arrangements to which it is a party; (iv) Licensee has sufficient facilities, experienced personnel and other capabilities reasonably suited to enable it to perform its obligations under this Agreement; and (v) Licensee will not before the termination of this Agreement enter into any agreements, contracts or other arrangements that would be materially inconsistent with its obligations under this Agreement.

 

  10.3

Disclaimer of Warranties. OTHER THAN AS PROVIDED IN THIS AGREEMENT, THE LICENSED KNOW-HOW, AND LICENSED CELL LINES ARE PROVIDED AND LICENSED TO LICENSEE “AS IS”, THE PARTIES MAKE NO REPRESENTATIONS AND EXTEND NO WARRANTIES OR CONDITIONS OF ANY KIND, EITHER EXPRESS OR IMPLIED, WITH RESPECT THERETO OR TO THE PRODUCTS, INCLUDING, BUT NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSEVALIDITY OF THE RIGHTS LICENSED HEREUNDER, OR NONINFRINGEMENT OF THE INTELLECTUAL PROPERTY RIGHTS OF THIRD PARTIES.

 

11.

Confidentiality

 

  11.1

Subject to the exceptions listed below, during the term of this Agreement and for [***] thereafter, the Receiving Party shall, and shall ensure that its Related Persons will, (a) maintain the Disclosing Party’s Confidential Information in confidence, (b) not use such Confidential Information other than in connection with this Agreement, and (c) not disclose such Confidential Information to any Third Party other than (i) those of its Related Persons that have a need to know such Confidential Information in connection with the Activities conducted pursuant to the Agreement and are obligated to maintain such Confidential Information in confidence and (ii) to the extent required by applicable law or judicial order, or to the extent reasonably necessary to prosecute or defend litigation or arbitration in relation to this Agreement, and, in either case, only after the Receiving Party gives the Disclosing Party [***] advance written notice of such requirement and [***] with the Disclosing Party’s efforts to limit


  or avoid such disclosure, to seek a protective order or secure confidential treatment of the Confidential Information, and/or to seek any other remedies available to the Disclosing Party at law or in equity. Notwithstanding the foregoing, the existence of this Agreement and its non-technical terms may be disclosed confidentially in connection with a potential financing, collaboration or acquisition or in discussion with a potential acquirer of Client Product.

 

  11.2

The Receiving Party’s obligations set forth in Section 11.1 do not apply to Confidential Information if (a) the information is public knowledge or becomes public knowledge after disclosure through no act or omission of the Receiving Party or any of its Related Persons, (b) the information can be shown by the Receiving Party to have been lawfully in its possession prior to disclosure, (c) the information was rightfully received on a non-confidential basis from a Third Party that was not obligated to maintain the information in confidence, or (d) the Receiving Party can show that equivalent information was developed independently by the Receiving Party without reference to the Disclosing Party’s Confidential Information.

 

  11.3

Licensee may disclose the Confidential Information of WuXi Biologics to a Third Party for the purpose of exercising Licensee’s license rights hereunder (including disclosure to potential Third Party sublicensees), provided that Licensee shall, prior to such disclosure, ensure that each Third Party to which disclosure is to be made is made aware of the obligations contained in this Agreement and agrees to be subject to obligations of confidentiality and non-use no less onerous than those contained in this Agreement. Any breaches of the obligations of confidentiality and non-use contained in this Agreement by such Third Party shall be treated as a breach of such obligations by Licensee.

 

  11.4

Notwithstanding anything to the contrary in this Agreement, a Party may disclose this Agreement and its terms, and material developments or material information generated under this Agreement, in securities filings with the U.S. Securities and Exchange Commission (or equivalent foreign agency) and any rules of stock exchanges where the Parties may be listed to the extent required by applicable law after complying with the procedure set forth in this Section 11.4. In such event, unless otherwise required to comply with applicable law, the Party seeking such disclosure will prepare a draft confidential treatment request and proposed redacted version of this Agreement to request confidential treatment for this Agreement, and the other Party will [***] give its input in a [***] in order to allow the Party seeking disclosure to file its request within the timelines proscribed by applicable laws and regulations. The Party seeking such disclosure shall exercise [***] to obtain confidential treatment of this Agreement from the U.S. Securities and Exchange Commission (or equivalent foreign agency) as represented by the redacted version reviewed by the other Party.


  11.5

The provisions of this Section 11 shall survive termination or expiry of this Agreement.

 

12.

Termination

 

  12.1

Voluntary Termination by Licensee.

Licensee shall have the right to terminate this Agreement upon six (6) months’ prior written notice to WuXi Biologics, and upon payment of all undisputed amounts due to WuXi Biologics through such termination effective date.

 

  12.2

Termination for Default

 

  (a)

Nonpayment. In the event Licensee fails to pay any undisputed amounts due and payable to WuXi Biologics hereunder and fails to make such payments within thirty (30) days after receiving written notice of such failure, WuXi Biologics may terminate this Agreement [***] upon written notice to Licensee.

 

  (b)

Material Breach. In the event that either Party commits a material breach of its obligation under this Agreement and fails to cure that breach within sixty (60) days after receiving written notice thereof, the other Party may terminate this Agreement [***] upon written notice to such breaching Party.

 

  12.3

Termination Upon Bankruptcy. If either Party makes an assignment for the benefit of creditors, appoints or suffers appointment of a receiver or trustee over all or substantially all of its property, files a petition or commences a proceeding under any bankruptcy or insolvency act in any state or country or has any such petition or application filed against it which is not discharged within [***] of the filing thereof, then the other Party may thereafter terminate this Agreement effective [***] upon written notice to such Party. All rights and licenses granted under or pursuant to this Agreement by WuXi Biologics are, and will otherwise be deemed to be, for purposes of the relevant provisions of the Bankruptcy and Insolvency Act, R.S.C. 1985, c. B-3 (“BIA”), including Sections 65.11(7), 65.13(9), 72.1 and 246.1 of the BIA, and the relevant provisions of the Companies’ Creditors Arrangement Act, R.S.C. 1985, c. C-36 (“CCAA”), including Sections 32(6) and 36(8) of the CCAA (the BIA and CCAA being referred to collectively as the “Insolvency Legislation”), a grant of a “right to use” “intellectual property” as used in the Insolvency Legislation. The Parties agree that Licensee and its Affiliates and sublicensees, as licensees of such rights under this Agreement, will retain and may fully exercise all of their rights and elections under the Insolvency Legislation subject to the payment of amounts provided for herein. Without limiting Licensee’s rights under the Insolvency Legislation, if WuXi Biologics becomes insolvent or makes an assignment for the benefit of its creditors or there is filed by or against it any bankruptcy, receivership, reorganization or similar proceeding pursuant to or under the Insolvency Legislation or otherwise, Licensee will be entitled to a copy of any and all information specified in the Technology Transfer Package unless WuXi Biologics, or its trustee or receiver, elects within [***] to continue to perform all of its obligations under this Agreement.


  12.4

Expiration or termination of this Agreement for any reason will not relieve either party of any obligation accruing prior to or intended to survive such expiration or termination. Notwithstanding the foregoing, unless this Agreement is terminated by Licensee pursuant to Section 12.2(b), Section 5 (Cell Line Royalties and Related Payments) shall survive termination or expiry of this Agreement.

 

13.

Miscellaneous.

 

  13.1

Assignment. This Agreement may not be assigned or otherwise transferred by either Party (subject to Licensee’s right to sublicense its rights hereunder) without the prior written consent of the other Party, which consent shall not be unreasonably withheld, conditioned or delayed; provided, however, that a Party may, without such consent, assign this Agreement in its entirety (a) to an Affiliate, or (b) to a Third Party in connection with a merger, acquisition, consolidation or a sale involving all or substantially all of the assets or business of such Party. Any attempted assignment or transfer in violation of this Section 13.1 shall be void.

 

  13.2

Regulatory Assistance. WuXi Biologics will provide assistance to Licensee, and any sublicensee, in respect of Licensee’s or such sublicensee’s regulatory filing activities for the Client Product and/or Drug Product, at Licensee’s or such sublicensee’s reasonable cost and expense on [***] rate.

 

  13.3

Governing Law. The laws of the State of New York, USA, without regard to any choice of law principle that would require the application of the law of another jurisdiction, govern all matters relating to this Agreement and the enforcement thereof.

The parties expressly reject any application to this Agreement of (a) the United Nations Convention on Contracts for the International Sale of Goods; and (b) the 1974 Convention on the Limitation Period in the International Sale of Goods, as amended by that certain Protocol, done at Vienna on April 11, 1980.

 

  13.4

Arbitration. The parties shall engage in good faith consultation to resolve any dispute arising out of or in connection with this agreement. Such consultation will begin [***] after one party has delivered to the other party a request for consultation. If the dispute cannot be resolved [***] following the date on which the request for consultation is delivered, then either party may submit the dispute to JAMS International Arbitration Rules (“Arbitration”). The Arbitration tribunal will consist of three arbitrators. Within [***] after the commencement of the Arbitration, each Party shall select one person to act as


  arbitrator, each of whom must be a practicing or retired attorney or judge have at least [***] of litigation experience within the biopharmaceutical industry. The two arbitrators so selected shall select the chair within [***] of the commencement of the Arbitration, whom must a practicing or retired attorney or judge have at least [***] of litigation experience within the biopharmaceutical industry. If the arbitrators selected by the Parties are unable or fail to agree upon the third arbitrator within the allotted time, the third arbitrator shall be appointed by JAMS in accordance with the JAMS International Arbitration Rules. All arbitrators shall serve as neutral, independent and impartial arbitrators. (ii) The Arbitration shall be conducted in accordance with the expedited procedures set forth in the JAMS International Arbitration Rules. The place of arbitration will be Manhattan, New York. The official language of the arbitration will be English. The arbitration proceedings will be confidential, and the arbitrator may issue appropriate protective orders to safeguard each party’s Confidential Information. During the course of arbitration, the parties shall continue to implement the terms of this agreement. The arbitral award will be final and binding upon the parties, and the party to the award may apply to a court of competent jurisdiction for enforcement of the award. Notwithstanding the foregoing, each party has the right to institute an action in a court of proper jurisdiction for injunctive or other equitable relief pending a final decision by the arbitrator.

 

  13.5

Counterparts. This Agreement may be executed in two (2) or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. This Agreement may be executed by facsimile, .pdf or other electronically transmitted signatures and such signatures shall be deemed to bind each Party hereto as if they were the original signatures.

 

  13.6

Amendment and Restatement of Original Cell Line License Agreement. The Parties agree that, as of the Effective Date, the Original Cell Line License Agreement is hereby amended and restated. As of the Effective Date, terms of the Original Cell Line License Agreement are no longer in force or effect and are hereby superseded and replaced by the terms of this Agreement.


IN WITNESS WHEREOF, the Parties hereto have caused this AGREEMENT to be duly executed as of the latest date set forth below.

 

WuXi Biologics (Hong Kong) Limited     Spyre Therapeutics, Inc.
By:   /s/ Chris Chen     By:   /s/ Cameron Turtle
Print Name: Chris Chen     Name: Cameron Turtle
Title: Director     Title: Chief Executive Officer
Date: October 13, 2024     Date: October 14, 2024

Exhibit 99.1

 

LOGO

Spyre Therapeutics Announces Expected Acceleration of SPY003 (IL-23p19)

Clinical Timelines and Presentations at UEGW supporting Spyre’s Portfolio of

Potentially Best-in-Class Antibodies and Combinations

SPY003, a novel half-life extended IL-23p19 monoclonal antibody (mAb), with first-in-human dosing now

expected first quarter 2025

New data on SPY003 presented at UEGW demonstrating robust preclinical activity including comparable

potency and a greater than three-fold extension in half-life in NHPs relative to risankizumab1. Spyre

portfolio now uniquely includes extended half-life molecules targeting α4b7, TL1A, and IL-23 with

potential Q8W-Q12W maintenance dosing.

Additional preclinical data on SPY003 in combination with SPY001 or SPY002 presented at UEGW

showing enhanced preclinical efficacy and pharmacodynamics

WALTHAM, Mass., October 14, 2024 (PR NEWSWIRE) – Spyre Therapeutics, Inc. (NASDAQ: SYRE) (the “Company” or “Spyre”), a clinical-stage biotechnology company utilizing best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches to target improved efficacy and convenience in the treatment of inflammatory bowel disease (“IBD”), today announced updated pipeline progress and timelines, as well as scientific presentations at the United European Gastroenterology Week (“UEGW”) Congress.

 

   

First-in-human dosing of SPY003 (anti-IL-23) in healthy volunteers is now expected to start during the first quarter of 2025. SPY003 is a novel, half-life extended mAb targeting IL-23p19 (“IL-23”). Approved inhibitors of IL-23 are effective and well tolerated treatments of moderate-to-severe IBD, with commercially available therapies dosed six times per year. SPY003 has the potential to be dosed quarterly or twice a year as a monotherapy in maintenance. The company expects to share interim data from the accelerated first-in-human trial in the second half of 2025.

 

   

Spyre presented preclinical data on SPY003 for the first time at UEGW, expanding its portfolio of half-life extended antibodies to three validated targets in IBD. The presentation illustrated in vitro potency comparable to risankizumab1 and pharmacokinetics indicating that SPY003 has a half-life of ~30 days in non-human primates (“NHPs”), a greater than three-fold increase relative to risankizumab1. These data demonstrate that SPY003 exhibits high selectivity and affinity for IL-23 and potently inhibits downstream cellular signaling. With an extended half-life in NHPs, SPY003 demonstrates therapeutic potential for effective and well-tolerated treatment of Crohn’s disease (“CD”) and Ulcerative Colitis (“UC”) with less frequent dosing than approved therapies. In conjunction with its previously disclosed SPY001 (anti-α4b7) and SPY002 (anti-TL1A) programs, the company has a unique portfolio of antibodies that have the potential to be delivered in combination on a unified, Q8W-Q12W dosing frequency in maintenance.

 

1


LOGO

 

   

Spyre presented preclinical data combining anti-IL-23 with either anti-α4b7 or anti-TL1A for the first time at UEGW. The presentation included in vitro studies and in vivo murine colitis model on anti-IL-23 combined with anti-TL1A and anti-α4b7, respectively. The models showed that IL-23 and TL1A have a synergistic effect on promoting IL-17 secretion from human and mouse immune cells, and that the combination of anti-IL-23 and anti-TL1A suppresses IL-17 secretion more effectively than either agent alone. In a T-cell transfer model of IBD, combination therapy with anti-IL-23 and anti-b7 improved body weight and reduced colonic CD4+ infiltration and IL-17 levels relative to monotherapy.

 

   

Additional preclinical data for SPY001 (anti-α4b7) and SPY002 (anti-TL1A) presented at UEGW. These presentations included in vitro potency compared to benchmark antibodies, nonclinical safety data, and pharmacokinetics demonstrating extended half-life in NHPs. For SPY002, characterization of the two development candidates planned for first-in-human studies in Q4 2024 is further described. Human pharmacokinetic simulations for SPY001 and both SPY002 candidates support potential Q8-12W dosing regimens in IBD.

“The Spyre team has made significant progress in advancing its potentially best-in-class molecules into first-in-human studies within an expected nine-month window,” said Cameron Turtle, DPhil, chief executive officer of Spyre. “With these promising molecules against the top three validated targets in IBD, we believe that Spyre is uniquely positioned to develop monotherapy and combination products with the potential to meaningfully improve both efficacy and convenience compared to today’s standard of care.”

The posters were presented at the UEGW Congress on Saturday, October 12, 2024, and details are as follows:

Title: A Novel Monoclonal Antibody Drug Candidate SPY001 Targeting Integrin α4b7 for the Treatment of IBD: In Vitro Properties and Non-Human Primate Pharmacokinetics and Safety

Poster #PP1103

Title: Characterization of Two Novel Extended Half-life Monoclonal Antibody Drug Candidates Targeting TL1A for the Treatment of IBD

Poster #MP450

 

2


LOGO

 

Title: Development and Characterization of SPY003, a Novel Extended Half-life Monoclonal Antibody Drug Candidate Targeting IL-23 for the Treatment of IBD

Poster #MP118

Title: Combining IL-23 Blockade with Anti-α4b7 or Anti-TL1A for the Treatment of IBD is Supported by In Vitro and Mouse IBD Model Experiments

Poster #PP1111

Full session details can be accessed via the UEGW program. New data disclosures are also available in Spyre’s updated corporate presentation.

 

1 

Synthesized comparator antibody

About Spyre Therapeutics

Spyre Therapeutics is a clinical-stage biotechnology company that aims to create next-generation of inflammatory bowel disease (IBD) products by combining best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches. Spyre’s pipeline includes investigational extended half-life antibodies targeting α4b7, TL1A, and IL-23.

For more information, please visit http://spyre.com.

Forward-Looking Statements

This press release contains “forward-looking” statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical fact are forward-looking statements. These forward-looking statements include statements regarding the Company’s business strategy, including the Company’s potential success of developing best-in-class therapeutics for IBD with the potential to meaningfully improve both efficacy and convenience compared to today’s standard of care, the potential efficacy, safety and dosing profile of its product candidates, the potential therapeutic benefits of its product candidates as monotherapies or in combinations and their potential extended half-life, and the timing of clinical trials and interim data release, including first-in-human studies for SPY002 and SPY003. The words “believe,” “may,” “will,” “potentially,” “estimate,” “continue,” “anticipate,” “predict,” “target,” “intend,” “could,” “would,” “should,” “project,” “plan,” “expect,” the negatives of these terms, and similar expressions that convey uncertainty of future events or outcomes are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond Spyre’s control) or other assumptions that may cause actual results or performance to be materially different from those expressed or

 

3


LOGO

 

implied by these forward-looking statements. These risks and uncertainties include, but are not limited those uncertainties and factors described under the heading “Risk Factors” and “Note about Forward-Looking Statements” in Spyre’s most recent Quarterly Report on Form 10-Q filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors included in other filings by Spyre from time to time. Should one or more of these risks or uncertainties materialize, or should any of Spyre’s assumptions prove incorrect, actual results may vary in material respects from those projected in these forward-looking statements. Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth therein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements in this press release, which speak only as of the date they are made and are qualified in their entirety by reference to the cautionary statements herein. Spyre does not undertake or accept any duty to make any updates or revisions to any forward-looking statements. This press release does not purport to summarize all of the conditions, risks and other attributes of an investment in Spyre.

For Investors :

Eric McIntyre

VP of Finance and Investor Relations

Spyre Therapeutics

Eric.mcintyre@spyre.com

For Media :

Peg Rusconi

peg.rusconi@deerfieldgroup.com

 

4

Exhibit 99.2 Corporate overview October 2024


Disclosures The information contained in this presentation has been prepared by Spyre Therapeutics, Inc. and its affiliates (“Spyre” or the “Company”) and contains information pertaining to the business and operations of the Company. The information contained in this presentation: (a) is provided as at the date hereof, is subject to change without notice, and is based on publicly available information, internally developed data as well as third party information from other sources; (b) does not purport to contain all the information that may be necessary or desirable to fully and accurately evaluate an investment in the Company; (c) is not to be considered as a recommendation by the Company that any person make an investment in the Company; (d) is for information purposes only and shall not constitute an offer to buy, sell, issue or subscribe for, or the solicitation of an offer to buy, sell or issue, or subscribe for any securities of the Company in any jurisdiction in which such offer, solicitation or sale would be unlawful. Where any opinion or belief is expressed in this presentation, it is based on certain assumptions and limitations and is an expression of present opinion or belief only. This presentation should not be construed as legal, financial or tax advice to any individual, as each individual’s circumstances are different. This document is for informational purposes only and should not be considered a solicitation or recommendation to purchase, sell or hold a security. Forward-Looking Information Certain information set forth in this presentation contains “forward-looking statements” within the meaning of applicable United States securities legislation. Except for statements of historical fact, certain information contained herein constitutes forward-looking statements which include but are not limited to statements regarding: expectations regarding the efficacy, durability of effect, including human pharmacokinetics simulations and dosing profiles, and safety of our product candidates; expectations regarding our potential therapeutic combinations and the potential benefits thereof, including human pharmacokinetics simulations and dosing profiles; expectations regarding or plans for discovery, preclinical studies, clinical trials and research and development programs, including timing of clinical trials, receipt of data readouts and clinical trial study designs; expectations regarding the use of proceeds and the time periods over which the Company’s capital resources will be sufficient to fund its anticipated operations; the Company’s business strategy objectives and goals; and management’s assessment of future plans and operations which are based on current internal expectations, estimates, projections, assumptions and beliefs, which may prove to be incorrect. Forward-looking statements can often be identified by the use of words such as “may”, “will”, “could”, “would”, “anticipate”, ‘believe”, expect”, “intend”, “potential”, “estimate”, “scheduled”, “plans”, “planned”, “forecasts”, “goals” and similar expressions or the negatives thereof. Forward-looking statements are neither historical facts nor assurances of future performance. Forward-looking statements are based on a number of factors and assumptions made by management and considered reasonable at the time such information is provided, and forward- looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements including those uncertainties and factors described under the heading “Risk Factors,” “Risk Factor Summary” and “Note about Forward-Looking Statements” in the Company’s most recent Annual Report on Form 10-K, as supplemented and updated by subsequent Quarterly Reports on Form 10-Q and Current Reports on Form 8-K that the Company has filed or will file with the SEC, as well as discussions of potential risks, uncertainties, and other filings by the Company from time to time, as well as risk factors associated with companies that operate in the biopharma industry, including those associated with the uncertainties of drug development. All of the forward-looking statements made in this presentation are qualified by these cautionary statements and other cautionary statements or other factors contained herein. Although management believes that the expectations conveyed by forward-looking statements herein are reasonable based on information available on the date such forward-looking statements are made, there can be no assurance that forward looking statements will prove to be accurate, as actual results and future events could differ materially from those anticipated in such statements. The Company undertakes no obligation to update forward-looking statements if circumstances or management’s estimates or opinions should change except as required by applicable securities laws. The forward-looking statements contained herein are presented for the purposes of assisting readers in understanding the Company’s plan, objectives and goals and may not be appropriate for other purposes. The reader is cautioned not to place undue reliance on forward-looking statements. Industry Information This presentation also contains or references certain industry data that is based upon information from independent industry publications, market research, and surveys and other publicly available sources. Although the Company believes these sources to be generally reliable, such information is subject to interpretation and cannot be verified with complete certainty due to limits on the availability and reliability of data, the voluntary nature of the data gathering process and other inherent limitations and uncertainties. The Company has not independently verified any of the data from third party sources referred to in this presentation and accordingly, the Company makes no representation or warranty as to the origin, validity, accuracy, completeness, currency or reliability of the information in this presentation. 2


Engineering for new heights in the treatment of IBD Our approach Our pipeline 1 TARGET PROGRAM PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Next-generation α4β7 Phase 1 interim data expected YE24 SPY001 monotherapies Phase 1 interim data expected 1H25 TL1A SPY002 Potential SC Q8W-Q12W* Phase 1 interim data expected 2H25 IL-23 SPY003 α4β7 + TL1A SPY120 Paradigm-changing combinationsα4β7 + IL-23 SPY130 Potential SC Q8W-Q12W* TL1A + IL-23 SPY230 1 Spyre holds exclusive worldwide licensed rights for SPY001, SPY002, and SPY003 from Paragon Therapeutics, Inc. SPY003 license is restricted to IBD, all other program licenses are unrestricted as to indication. *SC=subcutaneous, Q8W-Q12W dosing profiles are expected maintenance profiles based on human PK simulations. 3


Multiple opportunities for value creation with next-gen monotherapies and paradigm-changing combinations Next-generation monotherapies Paradigm-changing combinations Monoclonal antibodies engineered for: Fixed-dose combinations designed for: Potency Specificity Efficacy Safety Pharmacokinetics Unified dosing Manufacturability Formulatability Lower COGS Convenience α4β7 TL1A IL-23α4β7 + TL1A IL-23 + α4β7 TL1A + IL-23 4


Each of our monoclonal antibodies build on validated biology and aim to improve efficacy and convenience Next-generation monotherapies Paradigm-changing combinations Monoclonal antibodies engineered for: Fixed-dose combinations designed for: Potency Specificity Efficacy Safety Pharmacokinetics Unified dosing Manufacturability Formulatability Lower COGS Convenience α4β7 TL1A IL-23α4β7 + TL1A IL-23 + α4β7 TL1A + IL-23 5


Our lead programs were chosen based on attractive risk-benefit profiles versus other MOAs Induction clinical remission rates (pbo-adjusted) by MOA 100 1 1 2 2030 IBD SALES : 2030 IBD SALES : Acquired for : Ulcerative colitis Crohn’s disease ~$8B ~$7B 80 ~$12B Stronger efficacy in Stronger efficacy in Encouraging efficacy UC CD 60 and safety profile in UC and CD 3 Gut-selective MOA Well tolerated MOA 40 ~33% Efficacy ceiling ~25% ~25% ~24% ~23% ~20% ~17% ~16% 20 ~12% Primary ~8% ~7% endpoint not met 0 W14 | W6 W12 | W12 W12 | W12 W8 | W4 W10 | W12 W8 | W12 Week No black box warning Not approved No black box warning Black box warning Cardiac monitoring Black box warning Safety α4β7 TL1A IL-23 TNF S1P JAK MOA Example TULISOKIBART Source: Studies include Entyvio UC (VARSITY, assumes a 10% historical pbo control), CD (GEMINI II); tulisokibart UC (ATREMIS-UC), CD (APOLLO-CD, study was open label and adjusted using a historical pbo rate of 16%); Skyrizi UC (INSPIRE), CD (ADVANCE); Humira UC (ULTRA-II), Humira CD (CLASSIC-1, Bio-naïve patients); Zeposia UC (TRUE NORTH), CD (YELLOWSTONE), Rinvoq UC (U-ACCOMPLISH and U-ACHIEVE), CD (U-EXCEL); 1 2 3 EvaluatePharma 2030 Consensus Sales; Merck press release; Ferrante M, et. al. J Crohns Colitis. 2021 Dec 18;15(12):2001-2010. MOA=mechanism of action. 6


Our next-generation antibodies are engineered to match or exceed the potency of first-generation molecules … SPY001 (α4β7) in vitro potency SPY002 (TL1A) in vitro potency SPY003 (IL-23) in vitro potency SPY001 SPY002 SPY003 Risankizumab Vedolizumab Tulisokibart 60 100 50 100 80 40 60 30 50 40 20 20 10 0 0 0 0.01 0.1 1 10 0.001 0.01 0.1 1 10 100 0.01 0.1 1 10 100 mAb Concentration (nM) mAb Concentration (nM) mAb Concentration (nM) Potential for comparable efficacy at similar or lower doses Potential upside: Improved efficacy with higher exposures Note: Data on file. Details on number of replicates per study are included in later sections. SPY001 assay reports inhibition of cells expressing α4β7 binding to MAdCAM-1. SPY002 assay reports inhibition of TL1A-induced apoptosis in TF-1 cells. SPY003 assay reports inhibition of cellular STAT3 signaling. Vedolizumab, tulisokibart, and risankizumab are synthesized comparator antibodies. 7 %Inhibition %Inhibition % Inhibition


… and share a YTE backbone that extends half-life at least twofold in NHPs … SPY001 (α4β7) NHP PK SPY002 (TL1A) NHP PK SPY003 (IL-23) NHP PK SPY001 t = ~22 days SPY002 t = ~24 days SPY003 t = ~30 days 1/2 1/2 1/2 Risankizumab t = ~9 days Vedolizumab t = ~6 days Tulisokibart t = ~12 days 1/2 1/2 1/2 1000 1000 1000 100 100 100 10 10 10 1 1 1 0 14 28 42 56 70 84 98 0 14 28 42 56 70 84 98 0 7 14 21 28 35 42 49 Days Days Days Greater than 2-3x half-life extension vs. competitor molecules across our portfolio Note: Data on file. Pharmacokinetic data shown is from NHP studies, details on number of animals per study are included in later sections. Vedolizumab, tulisokibart, and risankizumab are synthesized comparator antibodies. 8 Serum Conc. (μg/mL) Serum Conc. (μg/mL) Serum Conc. (μg/mL)


… supporting projected unified and less frequent dosing across our portfolio SPY001 (α4β7) Human PK Simulation SPY002 (TL1A) Human PK Simulation SPY003 (IL-23) Human PK Simulation SPY002 SPY001 SPY003 Vedolizumab Tulisokibart Risankizumab Potential unified Q8W-Q12W maintenance dosing Versus Q2W-Q8W dosing for competitor molecules Note: Date on file, figures show median +/- interquartile range. PK simulation for comparator molecules based on published clinical data. 9 Serum Conc. (µg/mL) Serum Conc. (µg/mL) Serum Conc. (µg/mL)


Each of our next-generation monotherapies are expected to be in clinical studies by 1Q 2025 SPY001 SPY002 SPY003 α4β7 TL1A IL-23 Target Comparable potency to >10-fold more potent than Comparable potency to 1,2 Pharmacology vedolizumab tulisokibart risankizumab >3x NHP half-life vs. >2x NHP half-life vs. >3x NHP half-life vs. 2 PK vedolizumab tulisokibart risankizumab ü IND-enabling GLP toxü IND-enabling GLP tox IND-enabling GLP tox Safety Ongoing Top dose NOAEL Top dose NOAEL >150 mg/mL SC formulation >150 mg/mL SC formulation >150 mg/mL SC formulation CMC 3 Target dosing profile Phase 1 Phase 1 initiation expected Phase 1 initiation expected Status ongoing 4Q 2024 1Q 2025 1 2 3 Note: Evaluated in in vitro models; Vedolizumab, tulisokibart, and risankizumab are synthesized comparators; Potential maintenance dosing profile based on human simulations from NHP PK data 10


Spyre is uniquely positioned to deliver paradigm- changing combinations Next-generation monotherapies Paradigm-changing combinations Monoclonal antibodies engineered for: Fixed-dose combinations designed for: Potency Specificity Efficacy Safety Pharmacokinetics Unified dosing Manufacturability Formulatability Lower COGS Convenience α4β7 TL1A IL-23α4β7 + TL1A IL-23 + α4β7 TL1A + IL-23 11


Spyre portfolio aims to address the diverse pathophysiology of IBD by targeting orthogonal pathways Blockade of α4β7 prevents circulating immune cells Neutralization of TL1A suppresses inflammation and Neutralization of IL-23 inhibits cascade of from entering inflamed gut tissues reduces fibrosis by inhibiting fibroblast activation various proinflammatory cytokines anti-IL-23 anti-α4β7 anti-TL1A Created with BioRender.com; Neurath, Markus F. Nature Reviews Gastroenterology & Hepatology 14.5 (2017): 269-278; Solitano, Virginia, et al. Med (2024). 12


A wide body of evidence supports combinations as the future treatment paradigm in IBD Clinical Nonclinical Genetic VEGA has provided POC that combos can In vitro and in vivo models support Individuals with increased expression of two break the efficacy ceiling in IBD higher efficacy for combos targets are at greater risk to develop IBD Odds ratio (95% CI) Δ+22% 200 Combination 1.0 1.1 1.2 1.3 1.4 ~additive absolute clinical IL-23 47% remission rates TL1A 150 ITGA4 (α4β7) 22% 100 25% 24% TNFSF15 (TL1A) 50 25% Combo 0 0.1 1 10 100 1000 TNF IL-23 Combination Conc. ng/ml rd 1 3 party data In-house data In-house analysis 1 Source: Data on file; Feagan, B. G. et al. Lancet Gastroenterol. Hepatol. 8, 307–320 (2023). 13 IL-17 (pg/ml)


Our portfolio of half-life-extended mAbs potentially enables quarterly, co-formulated combinations SPY001 SPY002 SPY003 Combination human PK simulation (SPY120 potential profile) SPY001 MOA α4β7 TL1A IL-23 TNF S1P JAK SPY002 Median +/- IQR Half-life extension üüü (HLE) Efficacious üüüüüü MOA Well tolerated üüü 2x Unified MOA Loading Doses Q8W-Q12W SC Maintenance Dosing 1 rd Notes: Product labels for 3 party data supports mechanisms of action without black box warnings or safety monitoring requirements. Sands, Bruce E., et al. New England Journal of Medicine 391.12 (2024): 1119-1129. mAbs=monoclonal antibodies. Human PK simulation represents median +/- interquartile range utilizing SPY001 and SPY002 individual PK simulations presented in prior slides. 14 1 Third party clinical trials Spyre molecules Serum Conc. (µg/mL)


Spyre combinations have potential being best-in-class with less frequent dosing Expected Annual Maintenance Dosing Program Targets Format Q8W-Q12W SPY120 α4β7 + TL1A Coformulation Q8W-Q12W SPY130 α4β7 + IL-23 Coformulation Q8W-Q12W SPY230 IL-23 + TL1A Coformulation TNF + IL-23 Q4W JNJ-4804 Coformulation Probable black box Q4W ABBV382/Skyrizi α4β7 + IL-23 TBD ABT-981/Skyrizi IL-1 + IL-23 TBD Q2W Note: Expected dosing regimens for SYRE molecules based on human PK simulations and competitor molecule dosing profiles are based on disclosures of the most frequently administered component molecule. Landscape not exhaustive. 15


We intend to readout Ph 1 data for each of our mAbs over the next ~12 months before initiating a platform Ph 2 study 2024 2025 SPY001 (α4β7) Interim data – YE 2024 Phase 1 üFPI – June 2024 SPY002 (TL1A) Interim data – H1 2025 Phase 1 FPI – Q4 2024 SPY003 (IL-23) Interim data – H2 2025 Phase 1 FPI – Q1 2025 Platform FPI – 2025 Phase 2 study 16


SPY001 Next-generation anti-α4β7 antibody


SPY001 is engineered to have next-generation antibody properties Identical epitope target as vedolizumab with comparable potency and selectivity in vitro Half-life extension through validated Fc modification to potentially enable Q8W-Q12W SC dosing IND-enabling tox studies completed with NOAEL at the highest dose tested High concentration (>150 mg/mL) citrate-free SC formulations developed for clinical studies SPY001 Phase 1 study ongoing with interim data expected YE24 18


SPY001 potency & selectivity match vedolizumab in vitro SPY001 & vedolizumab epitope Potent and selective inhibition of cellular adhesion SPY001 and SPY001 and vedolizumab potently inhibit No inhibition of unwanted VCAM-1- vedolizumab MAdCAM-1-mediated (gut) cellular adhesion mediated (CNS) cellular adhesion bind the same α4 Subunit epitope 70 SPY001 (IC = 86 pM) 50 70 SPY001 Vedolizumab (IC = 83 pM) 50 Vedolizumab 60 60 (α4β1) Natalizumab β7 Subunit 50 50 40 40 30 30 20 20 Potent and selective binding to α4β7 10 10 1 0 Antibodyα4β7α4β1αEβ7 0 -10 2 2 SPY001 K <1 nM NB NB 0.01 0.1 1 10 D 0.001 0.01 0.1 1 10 100 mAb Concentration (nM) mAb Concentration (nM) 2 2 Vedolizumab K <1 nM NB NB D 1 Dissociation constant (K ) measured by surface plasmon resonance (SPR) D 2 NB = no binding by a particular antibody to a test molecule Source: Data on file. Vedolizumab is a synthesized comparator antibody. 19 %Inhibition of Total Adhesion (Integrin-mediated Adhesion by MAdCAM-1) %Inhibition of Total Adhesion (Integrin-mediated Adhesion by VCAM-1)


SPY001 exhibits >3x the half-life of vedolizumab in preclinical models >3x increased half-life in Tg276 mice >3x increased half-life in NHPs SPY001 t : ~12 Days SPY001 t : ~22 Days 1/2 1/2 1000 1000 Vedo t : ~4 Days Vedo t : ~6 Days 1/2 1/2 100 10 100 1 0.1 0.01 10 0 7 14 21 28 0 7 14 21 28 35 42 49 Days Days Source: Data on file. Initial group size was n=5 in mouse study (left) and n=6 in NHP study (right). Animals with suspected ADAs were excluded from half-life analysis; this did not impact the mouse study but resulted in n=5/cohort for SPY001 and n=3/cohort for vedolizumab at Day 49 of the NHP study. Vedolizumab used is a synthesized comparator antibody. 20 Serum Conc. (μg/mL) Serum Conc. (μg/mL)


SPY001 Phase 1 trial on track for interim readout of multiple cohorts by YE 2024 Phase 1 study design Phase 1 milestones ü q First subject dosed: June 2024 q Interim FIH data expected YE 2024 from SAD 5 multiple cohorts SAD 4 MAD 2 q Safety and tolerability SAD 3 MAD 1 q Pharmacokinetics SAD 2 q ADA SAD 1 Single-ascending and multiple-ascending dose cohorts • Healthy volunteers • n=8/cohort (3:1 randomization) 21


We aim to demonstrate the following for SPY001 in the expected YE2024 interim Phase 1 readout ≥35-day half-life enables ≥Q8W-Q12W SC maintenance dosing based on PK model 1 Potential to address vedo’s slow onset of action with higher induction exposures 2 Establish SPY001 has favorable safety profile and is well-tolerated 3 Minimal to no impact on ADA rates vs vedolizumab 4 22


Phase 1 interim PK will confirm whether Q8W-Q12W maintenance dosing is feasible, as predicted by NHP data SPY001 human half-life targets Maintenance human PK simulations Q8W based on Q12W based on Half-life (days) SPY001 Q12W SC PK modeling PK modeling Vedolizumab Q2W SC 1 Humans ~35 ~40 17-22 NHPs Humans 25 Q2W SC 2 NHPs 4-14 1 2 Source: Human YTE mAb half-life is on average 3.1x of NHP half-life; Haraya, Kenta, and Tatsuhiko Tachibana. BioDrugs (2023); Rosario, M, et. al. (2017); Feagan, et. al. (2013); Range of half-life observed in vedolizumab NHP studies (BLA review) and internal Spyre preclinical studies. Vedolizumab is a synthesized comparator antibody. PK simulation for comparator molecules based on published clinical data. 23 VEDO SPY001 Serum Conc. (µg/mL)


Interim PK data expected to enable Phase 2 dose selection to maximize efficacy potential of SPY001 Potential upside: Greater remission w/ higher exposure Induction human PK simulations 1 Vedolizumab Week 14 Deep Remission Rates in UC (%) By Week 6 trough concentration quartile SPY001 SPY001 Vedolizumab Vedo Quartile 4 37% (40-100 µg/mL) Targeting majority of patients with C in Quartile 4 trough Quartile 3 31% (32-40 µg/mL) Quartile 2 Vedo W6 20% (25-32 µg/mL) Quartile 4 Quartile 1 12% (2-25 µg/mL) +25% Higher anti-α4β7 mAb exposure may lead to deeper remission 1 Source: Casteele, N. V. et al. Aliment. Pharmacol. Ther. 56, 463–476 (2022); Vedolizumab FDA Clinical Pharmacology Review; PK simulation for comparator molecules based on published clinical data. 24 Serum Conc. (µg/mL)


SPY002 Next-generation anti-TL1A antibody


SPY002 candidates are engineered to achieve an optimal profile Advancing two candidates into Ph1 with novel epitopes that optimize potency and binding profiles in vitro Half-life extension through validated Fc modification to potentially enable Q8W-Q12W SC dosing IND-enabling tox studies completed with NOAEL at the highest dose tested High concentration (>150mg/mL) citrate-free SC formulations developed for clinical studies SPY002 Phase 1 study initiation expected in Q4 2024 26


Each SPY002 development candidate targets a distinct epitope and exhibits unique binding properties Single TL1A subunit epitope Superior or comparable potency in multiple assays Each SPY002 candidate targets a distinct Superior or comparable inhibition of TF-1 Superior or comparable inhibition of IFNγ epitope on a single TL1A monomer apoptosis secretion Duvakitug (TEV-48574) SPY002 candidates RO7790121 RO7790121 (RVT-3101) Duvakitug Tulisokibart Tulisokibart (MK-7240) 100 100 80 80 60 60 40 40 20 20 0 0 • Epitope locations were resolved by CryoEM 0.01 0.1 1 10 100 0.1 1 10 100 1000 10000 100000 mAb Concentration (nM) mAb Concentration (ng/mL) • Illustrative locations are overlayed with the crystal structure of trimeric TL1A Source: Data on file; Duvakitug not benchmarked in IFN secretion assay; Duvakitug, RO7790121, and tulisokibart are synthesized comparator antibodies. γ 27 Inhibition % Inhibition%


SPY002 candidates exhibit increased half-life in NHP compared to first-generation anti-TL1As SPY002 DC1: >2-3x Increased Half-life in NHPs SPY002 DC2: >2-3x Increased Half-life in NHPs SPY002 t : ~24 days SPY002 t : ~24 days 1/2 1/2 Tulisokibart t : ~12 days Tulisokibart t : ~12 days 1/2 1/2 RO7790121 t : ~7 days RO7790121 t : ~7 days 1000 1000 1/2 1/2 100 100 10 10 1 1 0 14 28 42 56 70 84 98 0 14 28 42 56 70 84 98 Time (day) Time (day) Source: Data on file. Notes: Group size was n=5 for SPY002 mAbs and tulisokibart at final endpoints for half-life determination; No RO7790121 detected after day 28; Duvakitug not compared in these models given low human half-life (7-10 days), ECCO 2024 abstract P633; Duvakitug, RO7790121, and tulisokibart are synthesized comparator antibodies. 28 Serum Conc. (μg/mL) Serum Conc. (μg/mL)


SPY002 Phase 1 initiation expected in 4Q 2024 Expected Ph1 study design Phase 1 milestones q Phase 1 initiation expected 4Q 2024 q Interim FIH data expected 1H 2025 SAD 5 q Safety and tolerability SAD 4 SAD 3 MAD 1q Pharmacokinetics SAD 2 q Pharmacodynamics (sTL1A) SAD 1 q ADA Single-ascending and multiple-ascending dose cohorts • Healthy volunteers Phase 1 results to inform which molecule • n=8/cohort (3:1 randomization) advances to Phase 2 development 29


Phase 1 interim PK will confirm whether Q8W-Q12W maintenance dosing is feasible, as predicted by NHP data SPY002 human half-life targets Human PK simulations Q8W based on Q12W based on Half-life (days) PK modeling PK modeling SPY002 Tulisokibart 1 Humans ~30 ~45 24 NHPs Humans 19 Q2-4W SC NHPs 12 1 Source: Human YTE mAb half-life is on average 3.1x of NHP half-life; Haraya, Kenta, and Tatsuhiko Tachibana. BioDrugs (2023); Spyre preclinical studies; Tulisokibart is a synthesized comparator antibody; Prometheus corporate presentation – Ph1 results. 30 TULISOKIBART SPY002 Serum Conc. (µg/mL)


Tulisokibart and RO7790121 dose responses support opportunity for improved efficacy in maintenance Clinical remission (mMayo) Endoscopic improvement W50 or W56 250 mg 48% 48% Q4W TULISOKIBART 100 mg 32% 36% ARTEMIS-UC Q4W Greater maintenance efficacy with higher doses 250 mg 56% 68% TULISOKIBART Q4W APOLLO-CD 100 mg 42% 59% Q4W 450 mg 36% 50% Q4W Greater maintenance RO7790121 150 mg 39% 39% efficacy with higher Q4W TUSCANY-2 doses 50 mg 31% 38% Q4W Source: UEGW 2024 posters OP079 and OP196; Artemis and Apollo patients were re-randomized for maintenance period while Tuscany-2 was a treat-through design. 31


SPY003 Next-generation anti-IL-23 antibody


SPY003 is engineered to have next-generation antibody properties Similar epitope target as risankizumab with comparable potency and selectivity in vitro Half-life extension through validated Fc modification to potentially enable Q12W-Q24W SC maintenance dosing IND-enabling tox studies ongoing High concentration (>150 mg/mL) citrate-free SC formulation developed for clinical studies SPY003 Phase 1 study initiation expected in Q1 2025 Note: SPY003 license is restricted to IBD indications. 33


SPY003 targets a similar epitope as risankizumab with comparable potency in vitro Similar epitope to risankizumab Comparable potency in multiple assays SPY003 and risankizumab bind the SPY003 and risankizumab potently SPY003 and risankizumab potently same p19 subunit of IL-23 inhibit pSTAT signaling inhibit IL-17 release SPY003 Risankizumab 100 100 50 50 0 0 0.01 0.1 1 10 100 1000 0.001 0.01 0.1 1 10 100 SPY003 epitope mAb Concentration (nM) mAb Concentration (nM) Risankizumab epitope Source: Data on file. Risankizumab is a synthesized comparator antibody. 34 % Inhibition % Inhibition


SPY003 exhibits >3x the half-life of risankizumab in NHPs NHP PK profiles of SPY003 and risankizumab Half-life 1000 ~30 days SPY003 100 3.3-fold vs. risankizumab 10 ~9 days Risankizumab 1 0 14 28 42 56 70 84 98 Days Notes: Group size was n = 4 in the NHP studies with n = 4 and n = 3 at the final timepoint for half-life determination for SPY003 and risankizumab, respectively. Source: Data on file. Risankizumab is a synthesized comparator antibody. 35 Serum Conc. (μg/mL)


SPY003 Phase 1 initiation expected in 1Q 2025 Expected Ph1 study design Phase 1 milestones q Phase 1 initiation expected 1Q 2025 q Interim FIH data expected 2H 2025 SAD 5 q Safety and tolerability SAD 4 SAD 3 MAD 1 q Pharmacokinetics SAD 2 q ADA SAD 1 Single-ascending and multiple-ascending dose cohorts • Healthy volunteers • n=8/cohort (3:1 randomization) 36


Phase 1 interim PK will confirm whether Q12W-Q24W maintenance dosing is feasible, as predicted by NHP data SPY003 human half-life targets Human PK simulations SPY003 Q12W based on Q24W based on Half-life (days) Risankizumab PK modeling PK modeling 1 Humans ~45 ~60 30 NHPs Humans 28 Q8W On-body NHPs 9 1 Source: Human YTE mAb half-life is on average 3.1x of NHP half-life; Haraya, Kenta, and Tatsuhiko Tachibana. BioDrugs (2023); Spyre preclinical studies; Skyrizi BLA. Risankizumab is a synthesized comparator antibody. 37 RISA SPY003 Serum Conc. (µg/mL)


Therapeutic combinations A paradigm-change in the treatment of IBD


Spyre is unique in its portfolio approach to evaluating multiple combination regimens Only known portfolio with half-life extended α4β7, TL1A, and IL-23 inhibitors Unified dosing potential across targets Combination toxicology studies initiated High-concentration (>150 mg/mL) citrate-free SC coformulations in development for each program Platform Phase 2 study that will include monotherapy and combo SPY120 • SPY130 • SPY230 agents expected to initiate in 2025 39


Spyre portfolio aims to address the diverse pathophysiology of IBD Blockade of α4β7 prevents circulating immune cells Neutralization of TL1A suppresses inflammation and Neutralization of IL-23 inhibits cascade of from entering inflamed gut tissues reduces fibrosis by inhibiting fibroblast activation various proinflammatory cytokines anti-IL-23 anti-α4β7 anti-TL1A Created with BioRender.com; Neurath, Markus F. Nature Reviews Gastroenterology & Hepatology 14.5 (2017): 269-278; Solitano, Virginia, et al. Med (2024). 40


JNJ’s VEGA study demonstrated the power of combination therapy in IBD VEGA combination study (N=71/arm) – Ulcerative colitis ~Additive absolute W12 MMS clinical remission rates Δ+22% 47% 22% 25% 24% 25% Anti-TNF Anti-IL23 Combination (Golimumab) (Guselkumab) BLACK BOX WARNING PROBABLE BLACK BOX Sources: Feagan, B. G. et al. Lancet Gastroenterol. Hepatol. 8, 307–320 (2023). 41


Spyre combinations are rational alternatives to combos with clinical precedent Clinical trial Precedent combination Spyre combinations & rationale 1 Spyre component exchange EXPLORER Crohn’s – Endoscopic remission % • Exchange TNF for another TNF 35% superfamily targeting agent 30% 27% • TL1A efficacy and safety appears superior on a cross-trial basis SPY120 α4β7 TNF TL1A Anti-α4β7 Anti-TNF Combination 2 VEGA UC – mMS remission % • Exchange TNF for a safer and 47% more effective class 25% 24% • Entyvio was superior to Humira in H2H clinical studies (VARSITY) SPY130 IL-23 TNF α4β7 Anti-IL23 Anti-TNF Combination 2 VEGA UC – mMS remission % • Exchange TNF for another TNF 47% superfamily targeting agent 25% 24% • TL1A efficacy and safety appears superior on a cross-trial basis SPY230 IL-23 TNF TL1A Anti-IL23 Anti-TNF Combination 1 Note: EXPLORER meta-analysis assumes a 27% remission rate for vedolizumab and 30% remission rate for adalimumab; EXPLORER included methotrexate treatment 1 2 Source: Colombel, Jean-Frederic, et al. Clinical Gastroenterology and Hepatology 22.7 (2024): 1487-1496. Feagan, Brian G., et al. The Lancet Gastroenterology & Hepatology 8.4 (2023): 307-320; 42


Combination PK exhibits expected behavior in NHPs and supports planned combination regimens SPY120 human combination PK simulation and potential dosing profile SPY120 NHP combination PK No observed difference in monotherapy PK when SPY001 dosed in combination SPY002 1000 100 10 SPY001 monotherapy SPY001 dosed in combination with SPY002 1 0 14 28 1000 100 10 SPY002 monotherapy SPY002 dosed in combination with SPY001 1 0 14 28 Days Source: Data on file. Human PK simulation represents median +/- interquartile range utilizing SPY001 and SPY002 individual PK simulations presented in prior slides. 43 SPY002 serum conc. (μg/mL) SPY001 serum conc. (μg/mL) Serum Conc. (µg/mL)


Corporate Team and cash runway


Leadership Scott Burrows Brian Connolly Melissa Cooper Paul Fehlner Joshua Friedman Janet Gunzner-Toste Chief Financial Officer Chief Technical Officer SVP, People SVP, Chief Intellectual SVP, Clinical Development SVP, Operations Property Counsel MiRa Huyghe Heidy King-Jones Justin LaFountaine Deanna Nguyen Sheldon Sloan Andrew Spencer Cameron Turtle SVP, Development Chief Legal Officer and SVP, Corporate SVP, Clinical Chief Medical Officer SVP, Preclinical Research Chief Executive Officer Operations Corporate Secretary Development Development and Development 45


Board of Directors Peter Harwin Michael Henderson Tomas Kiselak Jeffrey Albers Mark McKenna Sandra Milligan Laurie Stelzer Cameron Turtle 46


Cash and anticipated milestones 1 $426M 6/30/2024 cash 65.3M 2 Expected runway well into 2027 Shares outstanding 2024 2025 SPY001 (α4β7) Ph1 Interim data Ph1 Initiation Ph1 Interim data SPY002 (TL1A) Ph1 Initiation (1Q) Ph1 Interim data SPY003 (IL-23) Platform Ph2 Ph2 Initiation Expected external TEV-48574 Ph2b MORF057 Ph2b DUET-UC/CD Ph2b events 1 2 Notes: Anticipated milestones as of October 2024; Cash includes cash, cash equivalents, restricted cash & marketable securities as of 6/30/24; Shares outstanding on a pro forma and as-converted basis as of 6/30/24, which (i) gives effect to the full conversion of the Company’s preferred stock, and (ii) disregards beneficial ownership limitations that may limit the ability of certain holders of preferred stock to convert into common stock; see following slide for detailed reconciliation. 47


Shares outstanding As of June 30, 2024 Number of shares Common stock • Shares outstanding 50.8 • Series A preferred stock 13.8 Common stock equivalents • Series B preferred stock 0.7 Common stock and common • Total outstanding 65.3 1 stock equivalents 1 Shares outstanding on a pro forma basis, which includes (i) common stock outstanding as of 6/30/24, (ii) conversion of the Company’s Series B preferred stock as approved at the May 13, 2024 Annual Meeting of Shareholders, and (iii) the exercise of all outstanding pre-funded warrants in May 2024. 48


Thank you Engineering for new heights in the treatment of IBD

v3.24.3
Document and Entity Information
Oct. 11, 2024
Cover [Abstract]  
Amendment Flag false
Entity Central Index Key 0001636282
Document Type 8-K
Document Period End Date Oct. 11, 2024
Entity Registrant Name SPYRE THERAPEUTICS, INC.
Entity Incorporation State Country Code DE
Entity File Number 001-37722
Entity Tax Identification Number 46-4312787
Entity Address, Address Line One 221 Crescent Street
Entity Address, Address Line Two Building 23
Entity Address, Address Line Three Suite 105
Entity Address, City or Town Waltham
Entity Address, State or Province MA
Entity Address, Postal Zip Code 02453
City Area Code 617
Local Phone Number 651-5940
Written Communications false
Soliciting Material false
Pre Commencement Tender Offer false
Pre Commencement Issuer Tender Offer false
Security 12b Title Common Stock, $0.0001 Par Value Per Share
Trading Symbol SYRE
Security Exchange Name NASDAQ
Entity Emerging Growth Company false

Spyre Therapeutics (NASDAQ:SYRE)
Historical Stock Chart
From Oct 2024 to Nov 2024 Click Here for more Spyre Therapeutics Charts.
Spyre Therapeutics (NASDAQ:SYRE)
Historical Stock Chart
From Nov 2023 to Nov 2024 Click Here for more Spyre Therapeutics Charts.