Document:

[*] = 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. 
Exhibit 10.1

 LICENSE AND COLLABORATION AGREEMENT
This License and Collaboration Agreement (this “Agreement”) is entered into as of May 15, 2021 (the “Effective Date”) by and between: 
Milestone Pharmaceuticals, Inc., a Quebec corporation with a place of business at 1111 Dr.-Frederik-Philips Blvd., Ste. 420, Montreal, (Quebec), H4M 2X6 Canada (“MIST”), and 
Ji Xing Pharmaceuticals Limited, a limited liability company organized and existing under the laws of Hong Kong, with a business address located at Room 1902, 19/F, Lee Garden One, 33 Hysan Avenue, causeway Bay, Hong Kong Special Administrative Region (“Ji Xing”).  
MIST and Ji Xing are referred to in this Agreement individually as a “Party” and collectively as the “Parties.”  
Recitals
Whereas, MIST, a biopharmaceutical company, is developing etripamil, a novel calcium channel blocker in the form of a nasal spray, for the acute treatment of patients with Paroxysmal Supraventricular Tachycardia and other episodic cardiovascular conditions; 
Whereas, Ji Xing is a pharmaceutical company organized to develop and commercialize pharmaceutical products in the greater China region; and 
Whereas, Ji Xing wishes to obtain an exclusive license from MIST to develop, import and commercialize such product in the Territory, and MIST is willing to grant such a license and to supply such product to Ji Xing for development and commercial use in the Territory, all in accordance with the terms and conditions set forth herein.  
Agreement
Now, Therefore, in consideration of the foregoing premises and the mutual covenants contained herein, the receipt and sufficiency of which are hereby acknowledged, the Parties hereby agree as follows:  
Article 1​
DEFINITIONS
Unless specifically set forth to the contrary herein, the following terms, whether used in the singular or plural, shall have the respective meanings set forth below:  
1.1“Active Ingredient” means any clinically active material that provides pharmacological activity in a pharmaceutical product (excluding formulation components such as coatings, stabilizers, excipients or solvents, adjuvants or controlled release technologies).  
1.2“Affiliate” means, with respect to a Party, any person or entity that directly or indirectly controls, is controlled by or is under common control with such Party.  As used in this 

definition, “control” (and, with correlative meanings, the terms “controlled by” and “under common control with”) means, in the case of a corporation, the ownership of fifty percent (50%) or more of the outstanding voting securities thereof or, an interest that results in the ability to direct or cause the direction of the management and policies of such party or the power to appoint fifty percent (50%) or more of the members of the governing body of the party.  Notwithstanding the foregoing or any provision to the contrary set forth in this Agreement, Affiliates of Ji Xing will exclude [*].
1.3“Applicable Laws” means all statutes, ordinances, regulations, rules or orders of any kind whatsoever of any Governmental Authority that may be in effect from time to time and applicable to the activities contemplated by this Agreement.  
1.4“Arising Product IP” means [*].  
1.5“Business Day” means a day other than Saturday, Sunday or any day on which banks located in San Francisco, U.S. or Beijing, China are authorized or obligated to close.  Whenever this Agreement refers to a number of days, such number shall refer to calendar days unless Business Days are specified.  
1.6“Calendar Quarter” means the period commencing on January 1 of each Calendar Year and ending on March 31 of the same Calendar Year, the period commencing on April 1 of each Calendar Year and ending on June 30 of the same Calendar Year, the period commencing on July 1 of each Calendar Year and ending on September 30 of the same Calendar Year and the period commencing on October 1 of each Calendar year and ending on December 31 of the same Calendar Year, as the context shall require.  
1.7“Calendar Year” means each twelve (12) month period commencing on January 1 and ending on December 31.  
1.8“cGMP” means, in respect of MIST’s obligations under this Agreement, all applicable current Good Manufacturing Practices as set forth in 21 C.F.R. Parts 4, 210, 211, 601, 610 and 820, and in respect of Ji Xing’s obligations under this Agreement, the equivalent Applicable Laws in any relevant country or region in the Territory, each as may be amended and applicable from time to time.  
1.9“Change of Control” means, with respect to a Party, (a) a merger, reorganization, consolidation or other transaction involving such Party and any entity that is not an Affiliate of such Party as of the Effective Date, which results in the voting securities of such Party outstanding immediately prior thereto ceasing to represent at least fifty percent (50%) of the combined voting power of the surviving entity immediately after such merger, reorganization, consolidation or other transaction, or (b) any entity that is not an Affiliate of such Party as of the Effective Date becoming the beneficial owner of fifty percent (50%) or more of the combined voting power of the outstanding securities of such Party, or (c) any entity that is not an Affiliate of such Party as of the Effective Date acquiring the power (whether through ownership interest, contractual right, or otherwise, including the result of any government action) to direct or cause the direction of the management and policies of such Party.  

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[*] = 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.

1.10“Clinical Trial” means any clinical testing of the Product in human subjects.  
1.11“CMO” means any Third Party contract manufacturing organization.
1.12“Commercialization” or “Commercialize” means all activities directed to commercializing, promoting, selling, offering for sale and related importing and exporting activities, but excluding Manufacturing.  
1.13“Committee” means the JSC, JDC, JCC or any subcommittee established by the JSC, as applicable. 
1.14“Compound” means MIST’s proprietary calcium channel blocker known as etripamil, having chemical structure set forth in Exhibit A attached hereto, and including any [*]. 
1.15“Confidential Information” of a Party means all Know-How, unpublished patent applications and other proprietary and confidential information and data of a financial, commercial, business, scientific or technical nature of such Party that is (a) disclosed by or on behalf of such Party or any of its Affiliates or agents, or is otherwise made available to the other Party or any of its Affiliates, whether made available orally, in writing or in electronic form; or (b) learned by the other Party or come to the attention of the other Party in connection with the performance of this Agreement by either Party.  
1.16“Control” or “Controlled” means, with respect to any Know-How, Patents or other intellectual property rights, that a Party has the legal authority or right (whether by ownership, license or otherwise) to grant to the other Party a license, sublicense, access or other right (as applicable) under such Know-How, Patents, or other intellectual property rights, on the terms and conditions set forth herein, in each case without breaching the terms of any agreement with a Third Party.
1.17“Development” or “Develop” means all development activities to obtain and maintain Regulatory Approval for the Product, including all pre-clinical studies and Clinical Trials of the Product, distribution of Product for use in Clinical Trials (including placebos and comparators), statistical analyses, the preparation of regulatory filings and all regulatory affairs related to any of the foregoing, but excluding Manufacturing.  
1.18“Diligent Efforts” means [*]. 
1.19“Device” means any device for the delivery of the Compound by nasal spray, including the device as set forth in Exhibit A.  
1.20“Dollars” or “$” means U.S. dollars, the lawful currency of the U.S.  
1.21“FDA” means the U.S. Food and Drug Administration or its successor.  
1.22“Field” means all prophylactic and therapeutic uses in humans.  

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[*] = 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.

1.23“First Commercial Sale” means, with respect to a Product in any country or jurisdiction, the first sale of such Product to a Third Party for distribution, use or consumption in such country or jurisdiction after the Regulatory Approvals have been obtained for such Product in such country or jurisdiction.  For clarity, First Commercial Sale shall not include any sale or transfer of the Product prior to receipt of Regulatory Approval, such as so-called “treatment IND sales,” “named patient sales” and “compassionate use sales.” 
1.24“GAAP” means, with respect to a person or entity’s accounting standard in a country or jurisdiction, (a) if in regards to the U.S., U.S. generally accepted accounting principles, (b) if in regards to mainland China, the PRC generally accepted accounting principles, (c) if in regard to any country or jurisdiction other than the U.S. and mainland China, either (i) the International Financial Reporting Standards issued by the International Financial Reporting Standards Foundation and the International Accounting Standards Board, or (ii) the applicable accounting standards as published by the preeminent accounting society for that country or jurisdiction and followed by such person or entity, in each case of (a), (b) and (c), consistently applied and that provide for, among other things, assurance that the accounting and reported results are credible and accurate.  
1.25“GCP” means all applicable Good Clinical Practice standards for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of Clinical Trials, including, as applicable, (a) as set forth in the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use Harmonized Tripartite Guideline for Good Clinical Practice (CPMP/ICH/135/95) and any other guidelines for good clinical practice for trials on medicinal products in the Territory, (b) the Declaration of Helsinki (2004) as last amended at the 52nd World Medical Association in October 2000 and any further amendments or clarifications thereto, (c) 21 C.F.R. Parts 50 (Protection of Human Subjects), 56 (Institutional Review Boards) and 312 (Investigational New Drug Application), as may be amended from time to time, and (d) the equivalent Applicable Laws in the Territory, each as may be amended and applicable from time to time and in each case, that provide for, among other things, assurance that the clinical data and reported results are credible and accurate and protect the rights, integrity, and confidentiality of trial subjects.  
1.26“Generic Product” means, with respect to a Product in a particular Region in the Territory, any pharmaceutical product that (a) contains the same [*] Active Ingredients as such Product [*]; (b) [*] in such Region ([*] in such Region) [*] in such Region; (c) is [*] the Product, as determined by [*]; and (d) is sold in such Region by a Third Party that is not a sublicensee of Ji Xing or its Affiliates and did not purchase such product in a chain of distribution that included any of Ji Xing or its Affiliates or sublicensees. 
1.27“GLP” means all applicable Good Laboratory Practice standards, including, as applicable, as set forth in the then current good laboratory practice standards promulgated or endorsed by the U.S. Food and Drug Administration as defined in 21 C.F.R. Part 58, or the equivalent Applicable Laws in the region in the Territory, each as may be amended and applicable from time to time.  

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[*] = 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.

1.28“Governmental Authority” means any court, commission, authority, department, ministry, official or other instrumentality of, or being vested with public authority under any law of, any country, region, state or local authority or any political subdivision thereof, or any association of countries.  
1.29“IND” means any investigational new drug application, clinical trial application, clinical trial exemption or similar or equivalent application or submission for approval to conduct human clinical investigations filed with or submitted to a Regulatory Authority in conformance with the requirements of such Regulatory Authority.
1.30“Know-How” means any proprietary scientific or technical information, results and data of any type whatsoever, in any tangible or intangible form whatsoever, including databases, safety information, practices, methods, techniques, specifications, formulations, formulae, knowledge, know-how, skill, experience, test data including pharmacological, medicinal chemistry, biological, chemical, biochemical, toxicological and clinical test data, analytical and quality control data, stability data, studies and procedures, and manufacturing process and development information, results and data.  
1.31“Licensed IP” means Licensed Know-How and Licensed Patents.  
1.32“Licensed Know-How” means all Know-How Controlled by MIST or its Affiliates as of the Effective Date or at any time during the Term that is necessary or reasonably useful for the Development, Manufacture or Commercialization of the Product in the Field in the Territory; provided, however, that Licensed Know-How shall exclude [*].  
1.33“Licensed Patents” means all Patents in the Territory Controlled by MIST or its Affiliates as of the Effective Date or at any time during the Term that are necessary or reasonably useful for the Development, Manufacture or Commercialization of the Product in the Field in the Territory; provided, however, that Licensed Patents shall exclude [*].  Licensed Patents existing as of the Effective Date are set forth in Exhibit B.  
1.34“Manufacture” and “Manufacturing” mean activities directed to manufacturing, processing, filling, finishing, packaging, labeling, quality control, quality assurance testing and release, post-marketing validation testing, inventory control and management, storing and transporting the Product.  
1.35“Manufacturing Cost” means, with respect to the Compound, Device or Product supplied by MIST to Ji Xing hereunder:  
(a)if the Compound, Device or Product [*]; and 
(b)if the Compound, Device or Product [*].  
1.36“MIST Licensees” means any and all licensees and sublicensees of MIST or a MIST’s Affiliate for the Product (other than Ji Xing, Ji Xing’s Affiliates and sublicensees).  

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[*] = 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.

1.37“NDA” means a New Drug Application, as defined by the FDA, or equivalent application for approval (but not including pricing and reimbursement approvals) to market a pharmaceutical product in a country or jurisdiction outside the U.S.  
1.38“Net Sales” means the [*] on sales of the Product by Ji Xing, its Affiliates, or sublicensees for sale of the Product to a Third Party in the Territory, less following deductions, to the extent reasonable, customary and allocable to such Product:  
(a)[*]; 
(b)[*]; 
(c)[*]; 
(d)[*]; 
(e)[*]; and
(f)[*]
Each of the amounts set forth above shall be determined from the books and records of Ji Xing, its Affiliate or sublicensee, maintained in accordance with GAAP consistently applied.  For the avoidance of doubt, if a single item falls into more than one of the categories set forth in clauses (a)-(f) above, such item may not be deducted more than once.  
With respect to any sale of the Product [*].
Sales between Ji Xing and its Affiliates and sublicensees shall be disregarded for purposes of calculating Net Sales except if such purchaser is an end user.  Net Sales also exclude any sale or transfer of the Product for free or below cost in early access, compassionate use or named patient programs. 
Notwithstanding the foregoing, Net Sales shall not include amounts (whether actually existing or deemed to exist for purposes of calculation) for Product distributed for use in Clinical Trials. 
1.39“NMPA” means National Medicine Products Administration of China (formerly known as the China Food and Drug Administration), or its successor.  
1.40“Patents” means all national, regional and international patents and patent applications, including divisions, continuations, continuations-in-part, additions, re-issues, renewals, extensions, substitutions, re-examinations or restorations, registrations and revalidations, and supplementary protection certificates and equivalents to any of the foregoing.  
1.41“Person” means any natural person, corporation, general partnership, limited partnership, joint venture, proprietorship or other business organization or a Governmental Authority.

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[*] = 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.

1.42“Phase 1 Clinical Trial” means any human clinical trial of the Product that would satisfy the requirements of 21 § CFR 312.21(a) or corresponding foreign regulations.  
1.43“Phase 2 Clinical Trial” means any human clinical trial of the Product that would satisfy the requirements of 21 § CFR 312.21(b) or corresponding foreign regulations.  
1.44“Phase 3 Clinical Trial” means any human clinical trial of the Product that would satisfy the requirements of 21 § CFR 312.21(c) or corresponding foreign regulations.  
1.45“Pivotal Clinical Trial” means any human clinical trial of the Product that is intended (as of the time of Initiation of such clinical trial) to obtain the results and data to support the filing of an NDA (including label expansion but excluding the data that may be necessary to support the pricing and/or reimbursement approval), including so called Phase 2/3 trials and any human clinical trial that would satisfy the requirements of 21 § CFR 312.21(c) or corresponding foreign regulations.  [*]
1.46“Product” means any pharmaceutical product that uses a Device to deliver the Compound (as the sole Active Ingredient) by nasal spray.  
1.47“PSVT” means Paroxysmal Supraventricular Tachycardia. 
1.48“Regulatory Approval” means, with respect to the Product in a country or jurisdiction, all approvals from the Regulatory Authorities necessary to market and sell the Product in such country or jurisdiction, including pricing and reimbursement approval.  
1.49“Regulatory Authority” means any applicable Governmental Authority responsible for granting Regulatory Approvals for Product, including the FDA, NMPA, and any corresponding national or regional regulatory authorities.  
1.50“Regulatory Exclusivity” means any exclusive marketing rights or data exclusivity rights (other than Patents) conferred by any Regulatory Authority with respect to a pharmaceutical or medical product, including without limitation [*].  
1.51“Regulatory Materials” means any regulatory application, submission, notification, communication, correspondence, registration, approval and other filings made to, received from or otherwise conducted with a Regulatory Authority regarding the Product, including any NDA and Regulatory Approval.  
1.52“Territory” means the People’s Republic of China, including mainland China, Hong Kong Special Administrative Region, Macau Special Administrative Region, and Taiwan, each of which shall be referred to as a “Region”.  
1.53“Third Party” means an entity other than MIST, Ji Xing and Affiliates of either of them.  
1.54“U.S.” means United States of America, including all possession and territories thereof.  

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[*] = 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.

1.55“Upstream Licenses” means any and all agreements between MIST or any of its Affiliates, on the one hand, and any Third Party (the “Upstream Licensor”), on the other hand, pursuant to which MIST has (a) in-licensed any Patent or Know-How owned or Controlled by such Third Party that are included as part of the Licensed Patents or Licensed Know-How or (b) agreed to provisions that would require Ji Xing to make any payments (including royalties) to any Third Party or to undertake or observe any restrictions or obligations with respect to the Development, Manufacture or Commercialization of Compound, Device, or Product in the Field.  
1.56“Valid Claim” means a claim of a pending patent application or an issued and unexpired Patent (as may be extended through supplementary protection certificate or patent term extension or the like) that has not been revoked, held invalid or unenforceable by a patent office, court or other Governmental Authority of competent jurisdiction in a final and non-appealable judgment (or judgment from which no appeal was taken within the allowable time period) and which claim has not been disclaimed, denied or admitted to be invalid or unenforceable through reissue, re-examination or disclaimer or otherwise; provided that [*].
1.57Additional Definitions.  The following table identifies the location of definitions set forth in various Sections of the Agreement: 
	Defined Terms 
	Section

	Agreed Percentage
	Section 8.9(b)

	Agreement
	Preamble

	Alliance Manager
	Section 3.1

	Assigning Party 
	Section 8.9(c)

	Commercialization Plan
	Section 7.3

	Competing Product
	Section 2.7(b)

	Development Plan
	Section 4.3

	Effective Date
	Preamble

	Executive Officers
	Section 3.2

	FCPA
	Section 15.7(a)

	FCPA Covered Person
	Section 15.7(a)

	ICC
	Section 14.3(a)

	Incremental Taxes
	Section 8.9(c)

	Indemnified Party
	Section 12.3

	Indemnifying Party
	Section 12.3

	Initiation
	Section 8.3(b)(iii)

	JCC
	Section 3.4

	JDC
	Section 3.3

	Ji Xing
	Preamble

	Ji Xing Indemnitee(s)
	Section 12.2

	Joint Commercialization Committee
	Section 3.4

	Joint Development Committee
	Section 3.3

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[*] = 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.

	Defined Terms 
	Section

	Joint Steering Committee
	Section 3.2

	JSC
	Section 3.2

	Losses
	Section 12.1

	MIST
	Preamble

	MIST Indemnitee(s)
	Section 12.1

	MIST Trademarks
	Section 9.6(b)

	Non-Compete Period
	Section 2.6

	Other Product
	Section 2.7(a)

	Parties
	Preamble

	Party
	Preamble

	Pharmacovigilance Agreement
	Section 5.6

	Phase 1 Waiver
	Section 8.3(a)

	Phase 3 Waiver
	Section 8.3(a)

	Prior CDA
	Section 10.6

	Product Infringement
	Section 9.3(b)

	Product Marks
	Section 9.6(a)

	Region
	Section 1.52

	Remedial Action
	Section 5.9

	ROFN
	Section 2.7(b)

	Royalty Term
	Section 8.5(b)

	[*]
	[*]

	SEC
	Section 10.5(b)

	Successful completion
	Section 8.3(b)(iii)

	Supply Agreement
	Section 6.1

	Technology Transfer Plan
	Section 4.4(a)

	Term
	Section 13.1(a)

	Upstream Licensor
	Section 1.55

​
​
Article 2​
LICENSES
2.1License Grant to Ji Xing.  Subject to the terms and conditions of this Agreement, MIST hereby grants to Ji Xing:
(a)an exclusive (even as to MIST but subject to MIST’s retained rights as set forth in Section 2.3) royalty-bearing license, with the right to grant sublicenses solely in accordance with Section 2.2, under the Licensed IP to Develop, use, import, sell, offer for sale and otherwise Commercialize the Product in the Field in the Territory, 

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[*] = 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.

(b)a non-exclusive license, with the right to grant sublicenses solely in accordance with Section 2.2, under the Licensed IP to Manufacture the Product in the Territory using the Compound and Device supplied by MIST solely for the purposes set forth in Section 2.1(a), and
(c)upon MIST’s written consent that Ji Xing may Manufacture the Compound in the Territory, a non-exclusive license, with the right to grant sublicenses solely in accordance with Section 2.2, under the Licensed IP to Manufacture the Compound and the Product in the Territory using the Device supplied by MIST solely for the purposes set forth in Section 2.1(a).  
For clarity, the foregoing license does not include any right for Ji Xing to Manufacture the Compound (except with MIST’s written consent and in accordance with Section 2.1(c)) or Device, or Develop, use, import, sell, offer for sale and otherwise Commercialize a generic version of the Product.  
2.2Right to Sublicense.  
(a)Subject to the terms and conditions of this Agreement, Ji Xing shall have the right to grant sublicenses of the license granted to it under Section 2.1: (i) to any Affiliate [*], which shall require [*], provided [*]; and (ii) from [*] to Third Parties, which shall require [*].  
(b)Each sublicense under the Licensed IP shall be subject to a written agreement that is consistent with the terms and conditions of this Agreement.  [*].  
(c)Ji Xing shall provide a copy of each sublicense agreement to MIST within [*] after the grant of a sublicense, provided that Ji Xing shall be permitted to redact sensitive or proprietary information from any such agreement which terms are not necessary for MIST to confirm Ji Xing’s compliance with its obligations hereunder, and such sublicense agreement shall be treated as Ji Xing’s Confidential Information.  Ji Xing shall remain directly responsible for all of its obligations under this Agreement that have been delegated or sublicensed to any sublicensee.  [*].  Ji Xing shall not grant a sublicense to any sublicensee that has been debarred or disqualified by a Regulatory Authority.  
2.3MIST Retained Rights.  Notwithstanding the exclusive license granted to Ji Xing under Section 2.1(a), MIST hereby expressly retains the rights to use the Licensed IP in the Field in the Territory to (a) perform its obligations under this Agreement, and (b)[*].  For clarity, MIST retains the exclusive right to practice, license and otherwise exploit the Licensed IP outside the scope of the license granted to Ji Xing under Section 2.1, including the exclusive right to Develop, Manufacture and Commercialize the Product outside the Territory and to Manufacture and have Manufactured the Compound and Device anywhere in the world.  MIST also retains the non-exclusive right to Manufacture and have Manufactured the Product in the Territory.  
2.4No Implied Licenses; Negative Covenant.  Except as set forth herein, neither Party shall acquire any license or other right or interest, by implication or otherwise, under any Know-How, Patent or other intellectual property of the other Party.  Ji Xing shall not, and shall not permit any of its Affiliates or sublicensees to, practice any Licensed IP outside the scope of the license granted by MIST to Ji Xing under Section 2.1 of this Agreement.  

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[*] = 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.

2.5No Diversion.  Each Party hereby covenants and agrees that it shall not, and shall ensure that its Affiliates and sublicensees shall not, either directly or indirectly, promote, market, distribute, import, sell or have sold any Product, including via the Internet or mail order, to any Third Party or to any address or Internet Protocol address or the like in the other Party’s territory or to any Third Party that such Party knows (or reasonably should know after due inquiry) has previously exported or is likely to export the Product to the other Party’s territory.  Neither Party shall engage, nor permit its Affiliates and sublicensees to engage, in any advertising or promotional activities relating to any Product for use directed primarily to customers or other buyers or users of the Product located in any country or jurisdiction in the other Party’s territory, or solicit orders from any prospective purchaser located in any country or jurisdiction in the other Party’s territory.  If a Party or its Affiliates or sublicensees receive any order for the Product from a prospective purchaser located in a country or jurisdiction in the other Party’s territory, such Party shall immediately refer that order to such other Party and shall not accept any such orders.  Neither Party shall, nor permit its Affiliates and sublicensees to, deliver or tender (or cause to be delivered or tendered) any Product to any Third Party for use in or distribution into the other Party’s territory[*].  
2.6Non-Compete.  During the time period after the Effective Date and until [*] (the “Non-Compete Period”), neither Ji Xing nor any of its Affiliates shall[*].  
2.7MIST Obligations.
(a)Right of First Refusal.  MIST hereby grants to Ji Xing a right of first refusal to obtain a license to develop and commercialize in the Field in the Territory any [*] (an “Other Product”) as follows.  If, during the Term, MIST intends to develop or commercialize any Other Product in the Territory either by itself or through its Affiliate(s) or through a partner [*], MIST shall notify Ji Xing before [*] or entering into such agreement with any Third Party with respect to such a license, as the case may be, and in good faith provide Ji Xing the opportunity to negotiate a license (if MIST is conducting such development without a Third Party) or match any bona fide terms offered by a Third Party.  If Ji Xing chooses not to negotiate such license or match such terms, then MIST shall have the right to develop and commercialize such Other Product in the Territory by itself or through its Affiliate(s), or enter into an agreement with such Third Party to grant such a license to any Third Party, without any further obligations to Ji Xing. 
(b)Right of First Negotiation.  MIST hereby grants to Ji Xing a right of negotiation (the “ROFN”) to obtain a license to develop and commercialize in the Field in the Territory any [*] (a “Competing Product”) as follows.  If during the Non-Compete Period, MIST intends to, either by itself or any of its Affiliates or in collaboration with a Third Party, develop or commercialize any Competing Product in the Territory [*], MIST shall notify Ji Xing of such intention in writing about the Competing Product prior to develop or commercialize such Competing Product in the Territory or commencing discussions or negotiations with any Third Party regarding the Competing Product in the Territory.  Ji Xing may exercise the ROFN by notifying MIST’s its intention within [*] after receiving MIST’s notice, and upon Ji Xing’s exercise of ROFN, MIST will exclusively negotiate in good faith with Ji Xing for [*] the terms of a binding written agreement that grants Ji Xing the right to develop and commercialize such Other Product in the Field in the Territory.  If Ji Xing does not exercise the ROFN, or the Parties fail to 

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[*] = 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.

reach a binding agreement during such [*] period, the ROFN with respect to such Competing Product will expire.  For clarity, if MIST and Ji Xing enter into a binding written agreement that grants Ji Xing the right to develop and commercialize a Competing Product in the Field in the Territory, then such Competing Product shall be [*].
2.8Performance by Subcontractors.  Subject to the terms and conditions of this Agreement, Ji Xing may, without MIST’s consent or approval, engage subcontractors for purposes of conducting Development, Manufacturing, Commercialization and other activities for Ji Xing under this Agreement, provided that [*], and further provided that [*]; (c) any subcontractor shall be bound by a written agreement that is consistent with the terms and conditions of this Agreement.  Ji Xing will remain directly responsible for any obligations under this Agreement that have been delegated or subcontracted to any subcontractor, and will be directly responsible for the performance of its subcontractors.
Article 3​
GOVERNANCE
3.1Alliance Managers.  Within [*] after the Effective Date, each Party shall appoint (and notify the other Party of the identity of) a representative having the appropriate qualifications (including a general understanding of pharmaceutical development, manufacture and commercialization issues) to act as its alliance manager under this Agreement (the “Alliance Manager”).  The Alliance Managers shall facilitate the flow of information and otherwise promote communication, coordination and collaboration between the Parties and raise cross-Party and/or cross-functional issues in a timely manner.  Each Party may replace its Alliance Manager by written notice to the other Party.  
3.2Joint Steering Committee.  The Parties hereby establish a joint steering committee (the “Joint Steering Committee” or the “JSC”) to manage the overall collaboration of the Parties under this Agreement, which committee shall include the Chief Executive Officer of MIST and the Chairman of Ji Xing (the “Executive Officers”).  The JSC shall in particular (a) review and discuss the overall strategy for the Development and Commercialization of the Product in the Field in the Territory; (b) provide a forum for the discussion and coordination of the Parties’ activities under this Agreement; (c) direct and oversee the operation of the JDC, JCC and any other joint subcommittee established by JSC, including resolving any disputed matter of the JDC, JCC and other joint subcommittees; (d) establish other joint subcommittees as necessary or advisable to further the purpose of this Agreement; and (e) perform such other functions as expressly set forth in this Agreement or allocated to it by the Parties’ written agreement.  
3.3Joint Development Committee.  The Parties hereby establish a joint development committee (the “Joint Development Committee” or the “JDC”) to oversee the Development of the Product in the Field in the Territory under this Agreement, which committee shall be comprised of [*] representatives from each Party.  Each Party shall appoint its JDC representatives within [*] after the Effective Date.  The JDC shall in particular: (a) review, discuss and approve the Development Plan and amendment thereto; (b) review and discuss the progress and results of the Development of the Product in the Field in the Territory; (c) provide a forum for and facilitate communications between the Parties with respect to the Development of the Product; (d) provide 

12
[*] = 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.

updates on the Manufacture and supply of the Compound, Drug and Product by MIST to Ji Xing; (e) [*], and (f) perform such other functions as may be appropriate to further the purposes of this Agreement with respect to the Development of the Product, as directed by the JSC.  
3.4Joint Commercialization Committee.  At a time to be determined by the JSC (but no later than [*]), the Parties shall establish a joint Commercialization committee (the “Joint Commercialization Committee” or the “JCC”) to oversee the Commercialization of the Product in the Field in the Territory under this Agreement, which committee shall be comprised of [*] representatives from each Party.  The JCC shall in particular:  (a) review and discuss the Commercialization Plan and amendment thereto; (b) review and discuss the progress and results of the Commercialization of the Product in the Field in the Territory; (c) provide a forum for and facilitate communications between the Parties with respect to the Commercialization of the Product; and (d) perform such other functions as may be appropriate to further the purposes of this Agreement with respect to the Commercialization of the Product, as directed by the JSC.  
3.5Limitation of Authority.  Each Committee shall only have the powers expressly assigned to it in this Article 3 and elsewhere in this Agreement and shall not have the authority to (a) modify or amend the terms and conditions of this Agreement; (b) waive either Party’s compliance with the terms and conditions of this Agreement; or (c) determine any such issue in a manner that would conflict with the express terms and conditions of this Agreement.  
3.6Committee Members.  Each Party’s representatives on the Committees shall be an officer or employee of the applicable Party having sufficient seniority within such Party to make decisions arising within the scope of the applicable Committee’s responsibilities.  Each Party may replace its representatives on any Committee upon written notice to the other Party.  Each Party shall appoint one of its representatives on each Committee to act as a co-chairperson of such Committee.  
3.7Meetings.  Each Committee shall hold meetings at such times as it elects to do so, but in no event shall such meetings be held less frequently than [*].  Each Party may call additional ad hoc Committee meetings as the needs arise with reasonable advance notice to the other Party.  Meetings of any Committee may be held in person, by audio or video teleconference.  In-person Committee meetings shall be held at locations selected alternatively by the Parties.  The co-chairpersons of the applicable Committee shall jointly prepare the agenda and minutes for each Committee meeting.  Each Party shall be responsible for all of its own expenses of participating in the Committee meetings.  No action taken at any Committee meeting shall be effective unless at least [*] of each Party is participating in such Committee meeting.  
3.8Non-Member Attendance.  Each Party may from time to time invite a reasonable number of participants, in addition to its representatives, to attend any Committee meeting in a non-voting capacity; provided that if either Party intends to have any Third Party (including any consultant) attend such a meeting, such Party shall provide prior written notice to the other Party.  Such Party shall also ensure that such Third Party is bound by confidentiality and non-use obligations consistent with the terms of this Agreement.  

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[*] = 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.

3.9Decision-Making.  All decisions of each Committee shall be made by unanimous vote, with each Party’s representatives collectively having one vote.  If after reasonable discussion and good faith consideration of each Party’s view on a particular matter before the JDC, JCC or any subcommittee established by the JSC, the representatives of the Parties on such Committee cannot reach an unanimous decision as to such matter within [*] after a Party has requested resolution of such matter by such Committee, such matter shall be referred to the JSC for resolution.  If after reasonable discussion and good faith consideration of each Party’s view on a particular matter before the JSC (including matter referred to the JSC by JDC, JCC or any subcommittee established by the JSC), the representatives of the Parties on the JSC cannot reach an unanimous decision as to such matter within [*] after a Party has requested resolution of such matter by the JSC, then:  
(a)[*]; and  
(b)[*].  
3.10Discontinuation of Committees.  The activities to be performed by each Committee shall solely relate to governance under this Agreement, and are not intended to be or involve the delivery of services.  Each Committee shall continue to exist until the first to occur of (a) the Parties mutually agreeing to disband such Committee; or (b) MIST providing written notice to Ji Xing of its intention to disband and no longer participate in such Committee.  Once the Parties mutually agree or MIST has provided written notice to disband any Committee, such Committee shall have no further obligations under this Agreement and, thereafter, the Alliance Managers shall be the contact persons for the exchange of information under this Agreement, and decisions of such Committee shall be decisions as between the Parties, subject to the same respective decision-making rights and limitations set forth in Section 3.9 and other terms and conditions of this Agreement.  
Article 4​
DEVELOPMENT
4.1General.  Subject to the terms and conditions of this Agreement, Ji Xing shall be responsible for the Development of the Product in the Field in the Territory, including the performance of Clinical Trials of the Product in the Field in the Territory necessary for Regulatory Approval.  
4.2Development Diligence.  Ji Xing shall use Diligent Efforts to Develop the Product and obtain and maintain Regulatory Approval of the Product in the Field in the Territory. 
4.3Development Plan.  All Development of the Product by or on behalf of Ji Xing under this Agreement shall be conducted pursuant to a written Development plan that sets forth the timeline, budget and other aspects of all clinical and regulatory activities to be conducted by or on behalf of Ji Xing to obtain Regulatory Approval of the Product in the Field in each Region in the Territory (the “Development Plan”).  As of the Effective Date, the Parties have agreed to the initial Development Plan, which is attached hereto as Exhibit C.  From time to time, but at least once every [*], Ji Xing shall propose updates or amendments to the Development Plan in consultation with MIST and submit such proposed updated or amended plan to the JSC for review, 

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[*] = 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.

discussion, and approval.  Once approved by the JSC, the updated or amended Development Plan shall become effective.  
4.4Technology Transfer.  
(a)As of the Effective Date, the Parties have agreed to a technology transfer plan (the “Technology Transfer Plan”, which is attached hereto as Exhibit D) for MIST to provide Ji Xing with access to the Licensed Know-How (including clinical data but for clarity excluding Manufacturing related Licensed Know-How) that is [*].  Within [*] after the Effective Date, MIST shall provide Ji Xing with access to such Licensed Know-How in accordance with the Technology Transfer Plan and, if specified, in a form set forth in the Technology Transfer Plan.  MIST shall provide the Licensed Know-How only in the English language, and Ji Xing shall be responsible for the translation of the Licensed Know-How into the Chinese language at Ji Xing’s own cost and expense.  Ji Xing may request MIST to provide additional information to Ji Xing regarding such Licensed Know-How that is encompassed in the Technology Transfer Plan that Ji Xing reasonably believes is missing or is otherwise necessary or reasonably useful for Ji Xing’s exploitation of the disclosed Licensed Know-How, and MIST shall provide such additional information as promptly as practicable but in any event within [*] after the receipt of such request.  The initial technology transfer shall be deemed completed [*].
(b)In addition to the technology transfer obligation under Section 4.4(a), at any time, if either Party becomes aware that MIST is in possession of Licensed Know-How existing as of the Effective Date that is not set forth in the Technology Transfer Plan and is not provided in response to Ji Xing’s request for additional information under Section 4.4(a), such Party shall notify the other Party in writing, and MIST shall promptly provide Ji Xing with such Licensed Know-How.  MIST shall periodically notify Ji Xing if any additional Licensed Know-How comes into MIST’s Control during the Term of this Agreement (including any data resulting from the Development of the Product conducted by MIST outside the Territory) and promptly provide Ji Xing with access to such additional Licensed Know-How.  The transfer of any addition Licensed Know-How under this Section 4.4(b) shall not be deemed part of the “initial technology transfer” for the purpose of Section 8.1(b) no matter when such transfer occurs.
(c)In connection with the transfer of Licensed Know-How to Ji Xing, MIST shall also provide Ji Xing with reasonable technical assistance to help Ji Xing to understand and use such Licensed Know-How in connection with the Development of the Product, including reasonable access to MIST’s technical personnel involved in the research and Development of the Product.  Ji Xing shall reimburse MIST for both out-of-pocket cost and internal cost incurred by MIST to provide such technical assistance, except for the internal cost of the first [*] FTE hours of assistance, which shall be provided at MIST’s cost.  MIST’s internal costs shall be reimbursed at a rate of [*].
4.5Development Collaboration.  [*].  MIST shall [*], shall coordinate with Ji Xing with respect to such Development work, and shall keep Ji Xing reasonably informed on the progress and result of such Development work.  [*].

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[*] = 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.

4.6Development Cost.  Ji Xing shall be solely responsible for all the costs and expenses it incurs to Develop the Product in the Territory.  
4.7Data Exchange and Use.  In addition to its adverse event and safety data reporting obligations pursuant to Section 5.6, each Party shall promptly provide the other Party with copies of all data and results and all supporting documentation (e.g. protocols, CRFs, analysis plans) generated from its Development of the Product.  Ji Xing shall have the right to use the data provided by MIST for the purpose of obtaining and maintaining Regulatory Approval for and Commercializing the Product in the Field in the Territory.  MIST shall have the right to use the data provided by Ji Xing for the purpose of obtaining and maintaining Regulatory Approval for and Commercializing the Product outside the Territory.  
4.8Development Records.  Ji Xing shall maintain complete, current and accurate records of all Development activities conducted by or on behalf of Ji Xing hereunder, and all data and other information resulting from such activities.  Such records shall fully and properly reflect all work done and results achieved in the performance of the Development activities in good scientific manner appropriate for regulatory and patent purposes.  Ji Xing shall document all non-clinical studies and Clinical Trials in formal written study reports according to Applicable Laws and national and international guidelines (e.g., ICH, GCP, GLP, and cGMP).  MIST shall have the right to review and copy such records maintained by Ji Xing at reasonable times and to use such records and obtain access to the original for its research and development activities and regulatory and patent purposes or for other legal proceedings.  
4.9Development Reports.  Ji Xing shall keep MIST reasonably informed as to the progress and results of its and its Affiliates’ and sublicensees’ Development of the Product.  Without limiting the foregoing, the status, progress and results of the Development of the Product in the Territory shall be discussed at meetings of the JDC.  At least [*] before each regularly scheduled JDC meeting, Ji Xing shall provide the JDC with a written report summarizing its Development activities and the results thereof, covering subject matter at a level of detail reasonably required by MIST and sufficient to enable MIST to determine Ji Xing’s compliance with its diligence obligations pursuant to Section 4.2.  In addition, Ji Xing shall make available to MIST such additional information about its Development activities as may be reasonably requested by MIST from time to time.  
Article 5​
REGULATORY 
5.1General.  The Development Plan shall set forth the regulatory strategy for seeking Regulatory Approvals of the Product in the Field in each Region in the Territory.  Ji Xing shall be responsible for all regulatory activities necessary for obtaining and maintaining Regulatory Approvals of the Product in the Field in the Territory, which regulatory activities shall be performed at Ji Xing’s own cost and expense and in accordance with the regulatory strategy set forth in the Development Plan.  Through the JDC, Ji Xing shall keep MIST informed of regulatory developments related to the Product in the Territory, including any decision by any Regulatory Authority in the Territory regarding the Product.  

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[*] = 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.

5.2Regulatory Approval Holder.  Subject to Applicable Laws, Ji Xing shall apply for Regulatory Approvals of the Product in the Field in each Region in the Territory in its own name, and Ji Xing (or an Affiliate or a permitted sublicensee of Ji Xing) shall be named as the holder of such Regulatory Approvals in the Territory.  MIST will reasonably cooperate with Ji Xing, at Ji Xing’s expense, to enable Ji Xing (or an Affiliate or a sublicensee of Ji Xing) to acquire and hold any or all such Regulatory Approvals and Regulatory Materials in the Territory, provided, however, that if Applicable Laws in the Territory do not allow Ji Xing (or an Affiliate or a permitted sublicensee of Ji Xing) to hold Regulatory Approvals or Regulatory Materials for the Product in the Field in the Territory, then [*].
5.3Regulatory Materials.  Ji Xing shall provide MIST with drafts in English of all material Regulatory Materials a reasonable time (to the extent reasonably practicable, no less than [*]) prior to submission for review and comment, and shall consider in good faith reasonable comments received from MIST no later than [*] prior to submission.  [*]  In addition, Ji Xing shall notify MIST of any material Regulatory Materials submitted to or received from any Regulatory Authority in the Territory and shall provide MIST with copies thereof within [*] after submission or receipt, and shall notify MIST of any other material communication with any Regulatory Authority in the Territory within [*] after such communication.  [*]  Upon Ji Xing’s request and at Ji Xing’s cost, MIST shall assist Ji Xing in addressing any additional requirements requested by any Regulatory Authority in the Territory within a reasonable time (depending on the events), including providing existing supplementary data or documentation.
5.4Regulatory Meetings.  Ji Xing shall provide MIST with reasonable (to the extent reasonably practicable, no less than [*]) advance notice of any meeting or discussion with any Regulatory Authority in the Territory related to the Product.  Ji Xing shall lead such meeting or discussion; provided, however, that if permissible under Applicable Laws and permitted by the Regulatory Authority, MIST or its designee shall have the right, but not the obligation, to attend and participate in such meeting or discussion.  If MIST elects not to attend such meeting or discussion, Ji Xing shall promptly provide MIST with a written English summary of such meeting or discussion.  
5.5Right of Reference.  Each Party hereby grants to the other Party the right of reference to all Regulatory Materials pertaining to the Product submitted by or on behalf of such Party.  Ji Xing may use such right of reference to MIST’s Regulatory Materials for the purpose of obtaining and maintaining Regulatory Approval of the Product in the Field in the Territory.  MIST may use such right of reference to Ji Xing’s Regulatory Materials for the purpose of obtaining and maintaining Regulatory Approval of the Product outside the Territory.  
5.6Adverse Events Reporting; Quality.  Promptly following the Effective Date, but in any event no later than [*], the Parties shall enter into a pharmacovigilance and adverse event reporting agreement setting forth the worldwide pharmacovigilance procedures for the Parties with respect to the Product, such as safety data sharing, adverse events reporting and prescription events monitoring (the “Pharmacovigilance Agreement”).  Such procedures shall be in accordance with, and enable the Parties to fulfill, local and national regulatory reporting obligations under Applicable Laws.  MIST shall establish and maintain the global safety database for the Product.  Each Party shall hold the primary responsibility for reporting quality complaints, adverse events 

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[*] = 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.

and safety data related to the Product in its territory to such database and to the applicable Regulatory Authorities in its territory, as well as responding to safety issues and to all requests of Regulatory Authorities in its territory related to the Product, in each case at its own cost and to the extent required by the Applicable Laws.  Each Party agrees to comply with its respective obligations under the Pharmacovigilance Agreement and to cause its Affiliates, licensees and sublicensees to comply with such obligations. 
5.7Regulatory Audits and Inspection.  Upon reasonable advance notice (at least [*] in advance), MIST or its representatives acceptable to Ji Xing (such acceptance not to be unreasonably withheld, delayed or conditioned) shall have the right to audit [*].  Such audit may not be conducted [*] and will take place during regular business hours of the audited party and shall be conducted under obligations of confidentiality.  [*]  Ji Xing shall also permit the Regulatory Authorities outside the Territory to conduct audits and inspections of Ji Xing, its Affiliates, sublicensees or subcontractors relating to the Product, and shall [*].
5.8No Harmful Actions.  If MIST believes that Ji Xing is taking or intends to take any action with respect to the Product that could have a material adverse impact upon the regulatory status of the Product outside the Territory, MIST shall have the right to bring the matter to the attention of the JDC, and the Parties shall promptly meet to discuss in good faith to resolve such concern.  Without limiting the foregoing, unless the Parties otherwise agree, (a) Ji Xing shall not communicate with any Regulatory Authority outside the Territory regarding the Product, unless so ordered by such Regulatory Authority, in which case Ji Xing shall immediately notify MIST of such order; and (b) Ji Xing shall not submit any Regulatory Materials or seek Regulatory Approvals for the Product outside the Territory.  
5.9Remedial Actions.  Each Party shall notify the other immediately, and promptly confirm such notice in writing, if it obtains information indicating that any Product may be subject to any recall, corrective action or other regulatory action by any Governmental Authority or Regulatory Authority (a “Remedial Action”).  The Parties shall assist each other in gathering and evaluating such information as is necessary to determine the necessity of conducting a Remedial Action.  Ji Xing shall have sole discretion with respect to any matters relating to any Remedial Action in the Territory, including the decision to commence such Remedial Action and the control over such Remedial Action.  The cost and expenses of any Remedial Action in the Territory shall be borne solely by Ji Xing.  Ji Xing shall, and shall ensure that its Affiliates and sublicensees will, maintain adequate records to permit Ji Xing to trace the distribution, sale and use of the Product in the Territory.  
Article 6​
MANUFACTURE AND SUPPLY 
6.1Promptly after the execution of this Agreement, the Parties shall enter into a supply agreement (the “Supply Agreement”), pursuant to which MIST shall, either by itself or through its Affiliates or Third Party contract manufacturers, Manufacture and supply, and Ji Xing shall purchase from MIST, all of Ji Xing’s and its Affiliates’, sublicensees’ and sub-distributors’ requirements of the Compound and Device for Development and Commercialization use in the Field in the Territory.  If the Parties mutually agree, MIST may also Manufacture and supply the 

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[*] = 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.

Product to Ji Xing for Development and Commercialization use in the Field in the Territory.  For clarity, Ji Xing shall not have the right to Manufacture the Compound, unless with MIST consent as described in 2.1(c), or the Device.  
6.2Ji Xing shall pay for the Compound, Device and Product supplied by MIST at a price equal to (i) the Manufacturing Cost plus [*] mark up, for Compound, Device and Product supplied to Ji Xing [*]; and (ii) the Manufacturing Cost plus [*] mark up, for Compound, Device and Product supplied [*].  This price does not include any sales, use, excise, value added, transfer or other taxes or duties levied or assessed by any Governmental Authority on the transfer and sale of the Compound, Device and Product to Ji Xing, all of which shall be borne and paid by Ji Xing.    
6.3Audit by Ji Xing.  MIST shall (and shall ensure its MIST’s Third Party contract manufacturer to) keep complete and accurate records in accordance with GAAP and in sufficient detail relating to the Manufacture of the Compound, Device and Products supplied to Ji Xing [*].  Upon no less than [*] prior notice, Ji Xing will have the right to have an independent certified public accountant, selected by Ji Xing and reasonably acceptable to MIST to inspect such records for the purpose of determining the accuracy of the Manufacturing Cost due within the prior [*] period.  Such audit may not be conducted more than [*] unless [*] and will take place at the location(s) where such records, materials, documents are maintained by MIST upon reasonable prior written notice, during regular business hours and under obligations of confidentiality.  If it is determined that any amounts were overpaid or underpaid during such period, MIST will pay Ji Xing such overpaid amounts or Ji Xing will pay MIST the underpaid amounts within [*] of the date the independent certified public accountant’s written report.  The fees charged by such independent certified public accountant will be paid by Ji Xing, unless it is determined that any overpaid amounts exceed [*] of the total amount payable by Ji Xing to MIST for the period then being audited, in which case MIST will be responsible for the fees charged by such independent certified public accountant.
6.4Manufacture Technology Transfer Option.  Upon MIST’s consent that Ji Xing may, Manufacture (by itself, or through Affiliates or a CMO) the Compound and the Product (but not the Device) in the PRC, the Parties will discuss in good faith a manufacturing technology transfer plan, pursuant to which MIST will, at Ji Xing’s cost, provide access to and transfer to Ji Xing, or an Affiliate or a CMO [*], all Licensed Know-How that is necessary or reasonably useful for Ji Xing, or an Affiliate or the CMO [*] to Manufacture the Compound and the Products (but not the Device) in the Territory.  Upon reasonable request from Ji Xing and at Ji Xing’s cost, MIST will also provide to Ji Xing all necessary assistance and services to enable Ji Xing, or an Affiliate or the CMO [*], to Manufacture the Compound and the Product (but not the Device) in substantially the same manner as MIST, its Affiliate or MIST’s Third Party contracting manufacturer Manufactures the Compound and the Product (but not the Device) for Ji Xing.
Article 7​
COMMERCIALIZATION
7.1General.  Subject to the terms and conditions of this Agreement, Ji Xing shall, either by itself or through its Affiliates, sublicensees or Third Party contractor(s), be solely responsible for the Commercialization of the Product in the Field in the Territory, at Ji Xing’s own 

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[*] = 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.

cost and expense, including developing and executing a commercial launch plan, product marketing and promotion, marketing access and pricing strategy, negotiating with applicable Governmental Authorities regarding the price and reimbursement mechanisms, booking sales, product distribution, providing customer support (including handling medical queries), and performing other related functions, subject to the terms of this Agreement, including Section 7.6.  
7.2Commercialization Diligence.  Ji Xing shall use Diligent Efforts to Commercialize the Product in the Field in each Region in the Territory in which it receives Regulatory Approval.  Without limiting the foregoing, Ji Xing shall achieve [*].  
7.3Commercialization Plan.  No later than [*], Ji Xing shall submit to the JCC for review and discussion a written Commercialization plan that sets the timeline and details of all major Commercialization activities planned for the Product in the Territory (the “Commercialization Plan”).  Thereafter, from time to time, but at least [*], Ji Xing shall prepare updates or amendments to the Commercialization Plan to reflect changes in such plans, including [*], and submit such updated or amended plan to JCC for review and discussion before adopting such update or amendment.  For clarity, [*].  The Commercialization of the Product in the Territory shall be conducted in accordance with the Commercialization Plan.
7.4Coordination of Commercialization Activities.  The Parties recognize that they may benefit from the coordination of certain activities in support of the Commercialization of the Product across their territories.  As such, the Parties may coordinate such activities where appropriate, including scientific and medical communication and product positioning.  If the Parties agree to jointly conduct any specific Commercialization activities for the benefit of the Product in both Parties’ territories, the Parties shall negotiate and agree on the details of such activities, including allocation of responsibilities, budget and cost sharing.  
7.5Marketing Materials.  Upon Ji Xing’s reasonable request, MIST shall provide Ji Xing with copies of marketing, promotion and commercialization materials Controlled by MIST and pertaining to the Commercialization of Product.  Subject to the terms and conditions of this Agreement, Ji Xing shall have the right to use such materials in connection with the Commercialization of the Product in the Field in the Territory, but Ji Xing shall be responsible for the translation of such materials into the Chinese language at Ji Xing’s own cost and expense.  Ji Xing shall Commercialize the Product, including conducting marketing and advertisement activities, in accordance with Applicable Laws and shall not [*] that are (a) [*], and (b) [*].
7.6Pricing.  Ji Xing shall advise the JSC of its proposed pricing for the Product in each Region in advance of commencing price discussions with Regulatory Authorities or other parties involved in reimbursement decisions.  Ji Xing shall consider in good faith any comments received from MIST with respect to pricing of the Product and shall keep MIST informed on the status of any application for pricing or reimbursement approval for the Product in any Region in the Territory, including any discussion with Regulatory Authority with respect thereto.  [*], Ji Xing shall [*]; provided, however, that Ji Xing shall not [*], and further provided that, in the event [*], then the Parties will discuss in good faith [*].  

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7.7Commercialization Reports.  Ji Xing shall keep MIST reasonably informed of its, its Affiliates’ and sublicensees’ Commercialization activities with respect to the Product.  Without limiting the foregoing, Ji Xing shall update the JCC at each regularly scheduled JCC meeting regarding the Commercialization activities with respect to the Product in the Territory.  Each such update shall be in a form to be agreed by the JCC and shall summarize Ji Xing’s, its Affiliates’ and sublicensees’ significant Commercialization activities with respect to the Product in the Territory, covering subject matter at a level of detail reasonably required by MIST and sufficient to enable MIST to determine Ji Xing’s compliance with its diligence obligations pursuant to Section 7.2.  In addition, Ji Xing shall make available to MIST such additional information about its Commercialization activities as may be reasonably requested by MIST from time to time.  
Article 8​
PAYMENTS AND MILESTONES
8.1Upfront Payment.  In partial consideration of the rights granted by MIST to Ji Xing hereunder, Ji Xing shall pay to MIST a one-time, non-refundable and non-creditable upfront payment of fifteen million Dollars ($15,000,000), which shall be paid in two installments as follows: (a) ten million Dollars ($10,000,000) within [*] after the Effective Date; and (b) five million Dollars ($5,000,000) within [*] after the [*]. 
8.2Equity Investment.  [*] following the execution of this Agreement, MIST, RTW Master Fund, Ltd., RTW Innovation Master Fund, Ltd. and RTW Venture Fund Limited, shall enter into the Securities Purchase Agreement set forth on Exhibit E hereto, pursuant to which RTW Master Fund, Ltd., RTW Innovation Master Fund, Ltd. and RTW Venture Fund Limited,  will purchase pre-funded warrants issued by MIST for an aggregate purchase price of Five Million Dollars ($5,000,000).  Such warrants shall be exercisable for such number of MIST common shares as is equal to (a) Five Million Dollars ($5,000,000) divided by (b) [*] each at an exercise price equal to $0.01 per share.
8.3Development Milestones Payments.  
(a)Milestone Events.  Subject to the remainder of this Section 8.3, Ji Xing shall pay to MIST the following one-time, non-refundable and non-creditable Development milestone payments set forth in the table below upon the first achievement of the corresponding milestone event:  
	Development Milestone Event 
	Milestone Payment

	
1)
[*]

	[*]

	
2)
[*]

	[*]

	
3)
[*]

	[*]

	
4)
[*]

	[*]

	
5)
[*]

	[*]

	
6)
[*]

	[*]

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7)
[*]

	[*]

	Total
	$[*]

​
(b)Milestone Conditions.  
(i)Each milestone payment set forth above shall be due and payable only once, regardless of how many times such milestone event is achieved and/or the number of Products that achieves such milestone event.  The aggregate milestone payments under this Section 8.3 shall not exceed [*].  
(ii)Each milestone payment set forth above shall be due and payable irrespective of whether such milestone event is achieved by MIST, Ji Xing, their Affiliates, licensee or sublicensee.  
(iii)As used herein, [*] of a Clinical Trial means [*], and [*] of a Clinical Trial means [*]. 
(iv)If [*], then milestone [*] shall be deemed achieved upon [*]. 
(v)In the event that any milestone events have not been achieved at the time of achievement of a milestone event having a higher number than the skipped milestone event, and such higher number milestone event is for the same indication and same country or region as the skipped milestone, then the skipped milestone event shall be deemed achieved at the time of achievement of the higher number milestone event.  
(c)Notice and Payment.  For milestones set forth above to be achieved [*], [*] shall notify [*] in writing within [*] after the first achievement of such milestone.  For milestones set forth above to be achieved [*], [*] shall notify [*] in writing within [*] after the first achievement of such milestone; provided, however, that in each case, failure to notify a Party shall be without prejudice to any milestone payment obligation once achievement of such milestone is notified.  MIST will invoice Ji Xing for the corresponding milestone payments promptly after it becomes aware of the achievement of such milestone, and Ji Xing shall pay to MIST the corresponding milestone payment within [*] after the achievement of such milestone and the receipt of a corresponding invoice from MIST.  
8.4Sales Milestone Payments.  
(a)Milestone Events.  Subject to the remainder of this Section 8.4, Ji Xing shall pay to MIST the following one-time, non-refundable and non-creditable sales milestone payments set forth in the table below when the aggregated annual Net Sales of all Products sold in the Territory first reach the corresponding threshold value indicated below.  
	Aggregate annual Net Sale of all Products in the Territory 
	Milestone Payment

	
1.
[*]

	[*]

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2.
[*]

	[*]

	
3.
[*]

	[*]

	
4.
[*]

	[*]

	
5.
[*]

	[*]

	
6.
[*]

	[*]

	Total
	[*]

​
(b)Milestone Conditions.  Each sales milestone payment set forth above shall be due and payable only once, regardless of how many times such milestone event is achieved.  The aggregate milestone payments under this Section 8.4 shall not exceed [*].  For clarity, the sales milestone payments in this Section 8.4 are additive, such that if more than one sales milestone set forth above is achieved in the same time period, then the milestone payments for all such sales milestones shall be payable.  
(c)Notice and Payment.  As part of the royalty report in Section 8.5(d), Ji Xing shall provide written notice to MIST if the aggregated annual Net Sales of the Product in the Territory first reaches any threshold value set forth in Section 8.4(a) above during the time period to which such report pertains.  Promptly following the delivery of the applicable quarterly report stating a sales milestone has been achieved, MIST will invoice Ji Xing for the corresponding milestone payments, and Ji Xing shall pay to MIST the corresponding milestone payments within [*] after Ji Xing receives such invoice.
8.5Royalty Payments.  
(a)Royalty Rates.  Subject to the remainder of this Section 8.5, Ji Xing shall make quarterly non-refundable royalty payments to MIST on the Net Sales of all Products sold in the Territory, as calculated by multiplying the applicable royalty rate set forth in the table below by the corresponding amount of incremental, aggregated annual Net Sales of all Products sold in the Territory in the applicable Calendar Year.  
	For that portion of annual Net Sale of the Product in the Territory
	Royalty Rate

	

1)
less than or equal to [*]

	[*]

	

2)
greater than [*] 
but less than or equal to [*]

	[*]

	

3)
greater than [*] 
but less than or equal to [*]

	[*]

	

4)
greater than [*] 
but less than or equal to [*]

	[*]

	

5)
greater than [*]

	[*]

​

23
[*] = 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.

(b)Royalty Term.  Ji Xing’s obligation to pay royalties pursuant to this Section 8.5 shall continue, on a Product-by-Product and Region-by-Region basis, until the latest of (i) [*]; (ii) [*]; and (iii) [*] (the “Royalty Term”).  
(c)Royalty Reductions.  
(i)If a Product is generating Net Sales in a Region in a Calendar Quarter during the applicable Royalty Term at a time when there is no Valid Claim in the Licensed Patent in such Region that claims such Product, including [*], then, subject to Section 8.5(c)(iii), the royalty rate applicable to Net Sales of such Product in such Region in such Calendar Quarter shall be reduced to [*] of the average royalty rate otherwise applicable to all Net Sales of the Product in the Territory in such Calendar Quarter under Section 8.5(a). 
(ii)If a Product is generating Net Sales in a Region in a Calendar Quarter during the applicable Royalty Term at a time when a Generic Product with respect to such Product is being sold in such Region, and the Net Sales of such Product in such Calendar Quarter is less than [*] of the average Net Sales of such Product in the [*] immediately before the launch of the Generic Product in such Region, then, subject to Section 8.5(c)(iii), the royalty rate applicable to Net Sales of such Product in such Region in such Calendar Quarter shall be reduced to [*] of the average royalty rate otherwise applicable to all Net Sales of the Product in the Territory in such Calendar Quarter under Section 8.5(a). 
(iii)Notwithstanding the foregoing, in no event shall the operation of Section 8.5(c)(i) or (ii), individually or in combination, reduce the royalties paid to MIST with respect to the Net Sales of any Product in any Region in the Territory in any Calendar Quarter to less than [*] of the amount that would otherwise have been due pursuant to Section 8.5(a) with respect to such Net Sales.  
(d)Royalty Report and Payment.  Within [*] after the end of each Calendar Quarter, commencing with the first Calendar Quarter in which there is any Net Sale of the Product anywhere in the Territory, Ji Xing shall provide MIST with a report that contains the following information for the applicable Calendar Quarter, on a Product-by-Product and Region-by-Region basis: [*] a calculation of the royalty payment due on such sales in Dollars, including the exchange rate and any reduction under Section 8.5(c)[*].  Promptly following the delivery of the applicable quarterly report, MIST will invoice Ji Xing for the royalties due to MIST with respect to Net Sales for such Calendar Quarter and Ji Xing shall pay such amounts to MIST within [*] following Ji Xing’s receipt of such invoice.  
8.6Currency; Exchange Rate.  All payments to be made by Ji Xing to MIST under this Agreement shall be made in Dollars by bank wire transfer in immediately available funds to a bank account designated by written notice from MIST.  The rate of exchange to be used in computing the amount of currency equivalent in Dollars shall be made at the average of the closing exchange rates reported in The Wall Street Journal (U.S., Eastern Edition) for the first, middle and last business days of the applicable reporting period for the payment due.  

24
[*] = 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.

8.7Late Payments.  Time is of the essence in respect of all payment obligations of Ji Xing under this Agreement.  In addition, if either Party does not receive payment of any sum due to it on or before the due date therefor, simple interest shall thereafter accrue on the sum due to such Party from the due date until the date of payment at a per-annum rate of [*] or the maximum rate allowable by Applicable Laws, whichever is less.  
8.8Financial Records and Audits.  Ji Xing shall (and shall ensure that its Affiliates and sublicensees will) maintain complete and accurate records in accordance with GAAP and in sufficient detail to permit MIST to confirm the accuracy of Net Sales reported by Ji Xing and amounts payable under this Agreement.  Upon no less than [*] prior notice, such records shall be open for examination, during regular business hours, for a period of [*] from the creation of individual records, and not more often than [*], by an independent certified public accountant selected by MIST and reasonably acceptable to Ji Xing, for the sole purpose of verifying for MIST the accuracy of the Net Sales and royalty reports provided by Ji Xing under this Agreement.  MIST shall bear the cost of such audit unless such audit reveals an underpayment by Ji Xing of more than [*] of the amount actually due for the time period being audited, in which case Ji Xing shall reimburse MIST for the costs of such audit.  Ji Xing shall pay to MIST any underpayment discovered by such audit within [*] after the accountant’s report, plus interest (as set forth in Section 8.7) from the original due date.  [*].
8.9Taxes.
(a)[*].  In the event that Ji Xing is required, under Applicable Laws, to withhold any deduction or tax from any payment due to MIST under this Agreement, [*]; provided, however, that [*].  Ji Xing shall promptly furnish MIST, as applicable, [*].  Each Party agrees to cooperate with the other Party in claiming exemptions from such deductions or withholdings under any agreement or treaty from time to time in effect.
(b)Notwithstanding the foregoing, if any withholding taxes or value added taxes are imposed with respect to any payment contemplated under this Agreement as a result of a (sub)license, an assignment or other transfer by a Party of its rights or obligations hereunder to another entity (including its Affiliate), or as a result of a subsequent (sub)license, assignment or transfer following such (sub)license, assignment or transfer (such Party, the “Assigning Party”), in each case, pursuant to Section 15.2 or Section 2.2, and such withholding taxes or value added taxes would not have been imposed with respect to such payment under then-applicable tax laws if such Party had not (sub)licensed, assigned or transferred its rights or obligations hereunder (or had such subsequent transfer not occurred) (such incremental withholding taxes and/or value added taxes, “Incremental Taxes”), then the Assigning Party (or its successor or assignee) shall bear all such Incremental Taxes without increasing the other Party’s tax obligations. 
Article 9​
INTELLECTUAL PROPERTY
9.1Arising Product IP. 
(a)To the extent permissible under the Applicable Laws, MIST shall solely own all Arising Product IP, regardless of inventorship, and Ji Xing shall and hereby does assign 

25
[*] = 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.

to MIST all the right, title and interest in and to all Arising Product IP invented or generated by or on behalf of Ji Xing, its Affiliates or sublicensees, and agrees to execute such instrument and take such further action requested by MIST to evidence and perfect such assignment and to obtain and maintain patent and other intellectual property protection for such Arising Product IP.  
(b)To the extent the assignment of any Arising Product IP by Ji Xing to MIST is not permissible under the Applicable Laws, Ji Xing shall and hereby does grant to MIST an exclusive (even as to Ji Xing but subject to the license granted by MIST back to Ji Xing as part of Licensed IP), worldwide, sublicensable (through multiple tiers), royalty free, fully paid, worldwide, perpetual and irrevocable license under such Arising Product IP for any and all uses.
(c)All Arising Product IP (regardless of whether invented or developed by MIST itself, assigned by Ji Xing to MIST under Section 9.1(a), or exclusively licensed by Ji Xing to MIST under Section 9.1(b) above) shall be deemed Confidential Information of MIST and shall be included in the Licensed IP and licensed to Ji Xing under the terms and conditions of this Agreement.  
(d)Each Party shall promptly disclose to the other Party all Arising Product IP invented or generated by or on behalf of such Party under this Agreement, including any invention disclosures, or other similar documents, submitted to it by its employees, agents or independent contractors describing such Arising Product IP, and shall promptly respond to reasonable request from the other Party for additional information relating to such Arising Product IP.  
(e)Each Party shall promptly disclose to the other Party all Arising Product IP invented or generated by or on behalf of such Party under this Agreement, including any invention disclosures, or other similar documents, submitted to it by its employees, agents or independent contractors describing such Arising Product IP, and shall promptly respond to reasonable request from the other Party for additional information relating to such Arising Product IP.  
(f)Other than the Arising Product IP, the ownership of all intellectual property rights generated from the Parties’ activities under this Agreement will be determined based on the principles of inventorship in accordance with the laws where such intellectual property rights are generated.
9.2Patent Prosecution.  
(a)As between the Parties, MIST shall have the first right (but not the obligation) to file, prosecute and maintain all Licensed Patents (including Patents claiming Arising Product IP) throughout the world.  Ji Xing shall reimburse MIST for the reasonable and documented cost and expense incurred specifically to file, prosecute and maintain the Licensed Patents in the Territory within [*] after the receipt of invoice from MIST.  
(b)MIST shall consult with Ji Xing and keep Ji Xing reasonably informed of the status of the Licensed Patents in the Territory and shall promptly provide Ji Xing with all material correspondence received from any patent authority in the Territory in connection therewith.  In addition, MIST shall promptly (at least [*] prior to the intended submission) provide Ji Xing with drafts of all proposed material filings and correspondence to any patent authority in 

26
[*] = 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.

the Territory with respect to the Licensed Patents for Ji Xing’s review and comment prior to submission.  MIST shall confer with Ji Xing and consider in good faith Ji Xing’s comments prior to submitting such filings and correspondences in the Territory, provided that Ji Xing shall provide such comments within [*] (or a shorter period reasonably designated by MIST if [*] is not practicable given the filing deadline through no delay of MIST) of receiving the draft filings and correspondences from MIST.  
(c)MIST shall notify Ji Xing of any decision to cease prosecution and/or maintenance of any Licensed Patents in any Region in the Territory.  MIST shall provide such notice at least [*] prior to any filing or payment due date, or any other due date that requires action in order to avoid loss of rights, in connection with such Licensed Patent in such Region.  In such event, MIST shall permit Ji Xing, at Ji Xing’s discretion and expense, to continue the prosecution and maintenance of such Licensed Patent in such Region in the Territory. 
(d)Each Party shall provide the other Party all reasonable assistance and cooperation in the patent prosecution efforts under this Section 9.2, including providing any necessary powers of attorney and executing any other required documents or instruments for such prosecution.  
9.3Patent Enforcement.  
(a)Each Party shall promptly notify the other Party if it becomes aware of any alleged or threatened infringement by a Third Party of any of the Licensed Patents in the Territory, and any related declaratory judgment, opposition, or similar action alleging the invalidity, unenforceability or non-infringement of any of the Licensed Patents in the Territory.  
(b)As between the Parties, Ji Xing shall have the first right (but not the obligation) to bring and control any legal action in connection with any infringement of the Licensed Patents in the Territory that [*] in the Field in the Territory (a “Product Infringement”), at Ji Xing’s own expense as it reasonably determines appropriate.  If Ji Xing does not bring such legal action within [*] after the notice provided pursuant to Section 9.3(a), MIST shall have the right (but not the obligation) to bring and control any legal action in connection with such Product Infringement in the Territory, at MIST’s own expense as it reasonably determines appropriate.  
(c)At the request and expense of the Party bringing an action under Section 9.3(b) above, the other Party shall provide reasonable assistance in connection therewith, including by executing reasonably appropriate documents, cooperating in discovery and joining as a party to the action if required by Applicable Laws to pursue such action.  In connection with any such enforcement action, the enforcing Party shall keep the other Party reasonably informed on the status of such action and shall not enter into any settlement admitting the invalidity or non-infringement of, or otherwise impairing the other Party’s rights in the Licensed Patents without the prior written consent of the other Party.  The non-enforcing Party shall be entitled to separate representation in such enforcement action by counsel of its own choice and at its own expense.  
(d)Any recoveries resulting from enforcement action relating to a claim of Product Infringement in the Territory shall be first applied against payment of each Party’s costs 

27
[*] = 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.

and expenses in connection therewith.  Any such recoveries in excess of such costs and expenses shall be retained by the enforcing Party, provided that if Ji Xing is the enforcing Party, then such excess recoveries shall be [*].  
(e)MIST shall have the exclusive right to bring and control any legal action to enforce the Licensed Patents against any infringement that is not a Product Infringement, at MIST’s own expense and as it reasonably determines appropriate, and shall have the right to retain all recoveries.  
9.4Infringement of Third Party Rights.  
(a)Each Party shall notify the other Party of any allegations it receives from a Third Party that the Development, Manufacture or Commercialization of any Product in the Field in the Territory under this Agreement infringes the intellectual property rights of such Third Party.  Such notice shall be provided promptly, but in no event after more than [*] following receipt of such allegations.  Such notice shall include a copy of any summons or complaint (or the equivalent thereof) received regarding the foregoing.  Thereafter, the Parties shall promptly meet to consider the claim or assertion and the appropriate course of action and may, if appropriate, agree on and enter into a “common interest agreement” wherein the Parties agree to their shared, mutual interest in the outcome of such potential dispute.  Each Party shall assert and not waive the joint defense privilege with respect to all communications between the Parties.  
(b)Ji Xing shall be solely responsible for the defense of any such infringement claims brought against Ji Xing, at Ji Xing’s own cost and expense; provided, however, that the provisions of Section 9.3 shall govern the right of Ji Xing to assert a counterclaim of infringement of any Licensed Patents; and provided further that Ji Xing shall [*].  Ji Xing shall keep MIST informed on the status of such defense action, and MIST shall have the right, but not the obligation, to participate and be separately represented in such defense action at its sole option and at its own expense.  MIST shall also have the right to control the defense of any infringement claim brought against MIST, at MIST’s own cost and expense, provided that [*].  
9.5Patent Marking.  Ji Xing shall mark the Product sold in the Territory in accordance with the applicable patent marking laws, and shall require all of its Affiliates and sublicensees to do the same.  To the extent permitted by Applicable Laws, Ji Xing shall indicate on the product packaging, advertisement and promotional materials that the Product is in-licensed from MIST.  
9.6Trademarks.  
(a)Subject to Sections 9.6 (b) and 9.6(c) below, Ji Xing shall have the right to brand the Product sold in the Territory using any trademarks and trade names it determines appropriate for the Product, which may vary by Region or within a Region (the “Product Marks”); provided that Ji Xing shall not select any mark or China-approved drug name that is confusingly similar to any MIST Trademarks as a Product Mark. Ji Xing shall own all rights in the Product Marks in the Territory and shall register and maintain the Product Marks in the Territory that it determines reasonably necessary, at Ji Xing’s own cost and expense.

28
[*] = 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.

(b)Ji Xing acknowledges that MIST may develop a global branding strategy for the Product and adopt the key distinctive colors, logos, images, symbols, and trademarks to be used in connection with the Commercialization of the Product throughout the world (collectively and including any Chinese language versions thereof, the “MIST Trademarks”).  MIST shall own all rights in the MIST Trademarks and shall have the sole right (but not the obligation) to register, maintain and enforce the MIST Trademarks in any country in the world as it determines appropriate, at MIST’s own cost and expense.  
(c)Subject to the terms and conditions of this Agreement and for no additional considerations, MIST hereby grants to Ji Xing an exclusive license to use the MIST Trademarks solely in connection with the Commercialization of the Product in the Field in the Territory during the Term of this Agreement, and if Ji Xing elects to Commercialize the Product in the Territory using the MIST Trademarks, Ji Xing shall do so in a manner consistent with MIST’s global branding strategy for the Product.  
Article 10​
CONFIDENTIALITY
10.1Confidentiality.  Except to the extent expressly authorized by this Agreement or otherwise agreed in writing by the Parties, each Party agrees that, for the Term and for a period of [*] thereafter, it shall keep confidential and shall not publish or otherwise disclose and shall not use for any purpose other than as provided for in this Agreement (which includes the exercise of any rights or the performance of any obligations hereunder) any Confidential Information of the other Party pursuant to this Agreement.  
10.2Exceptions.  The foregoing confidentiality and non-use obligations shall not apply to any portion of the Confidential Information that the receiving Party can demonstrate by competent written proof:  
(a)was already known to the receiving Party, other than under an obligation of confidentiality, at the time of disclosure by the other Party; 
(b)was generally available to the public or otherwise part of the public domain at the time of its disclosure to the receiving Party; 
(c)became generally available to the public or otherwise part of the public domain after its disclosure and other than through any act or omission of the receiving Party in breach of this Agreement; 
(d)is subsequently disclosed to the receiving Party by a Third Party who has a legal right to make such disclosure; or 
(e)is subsequently independently discovered or developed by the receiving Party without the aid, application, or use of the disclosing Party’s Confidential Information, as evidenced by a contemporaneous writing.  

29
[*] = 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.

10.3Authorized Disclosure.  Notwithstanding the obligations set forth in Section 10.1, a Party may disclose the other Party’s Confidential Information and the terms of this Agreement to the extent:
(a)such disclosure is reasonably necessary (i) for the filing or prosecution of Patents as contemplated by this Agreement; (ii) in connection with regulatory filings for the Product; or (iii) for the prosecuting or defending litigation as contemplated by this Agreement;  
(b)such disclosure is reasonably necessary: (i) to such Party’s directors, attorneys, independent accountants or financial advisors for the sole purpose of enabling such directors, attorneys, independent accountants or financial advisors to provide advice to the receiving Party, provided that in each such case on the condition that such directors, attorneys, independent accountants and financial advisors are bound by confidentiality and non-use obligations consistent with those contained in this Agreement; or (ii) to actual or potential investors, acquirors, licensors, licensees, collaborators or other business or financial partners (including royalty financing partners) solely for the purpose of evaluating or carrying out an actual or potential investment, acquisition, license, collaboration, financing or other business transaction; provided that in each such case on the condition that such disclosees are bound by confidentiality and non-use obligations consistent with those contained in the Agreement; or  
(c)such disclosure is required by judicial or administrative process, provided that in such event such Party shall promptly inform the other Party of such required disclosure and provide the other Party an opportunity to challenge or limit the disclosure obligations.  Confidential Information that is disclosed by judicial or administrative process shall remain otherwise subject to the confidentiality and non-use provisions of this Article 10, and the Party disclosing Confidential Information pursuant to law or court order shall take all steps reasonably necessary, including seeking of confidential treatment or a protective order, to ensure the continued confidential treatment of such Confidential Information.  
10.4Scientific Publication.  Except to the extent required by Applicable Laws, Ji Xing shall not publish [*], without MIST’s review and approval, which shall not be unreasonably withheld or delayed.  Ji Xing shall deliver to MIST for review and approval a copy of [*] at least [*] before its intended submission for publication.  MIST shall have the right to require modifications of the proposed publication or presentation to protect MIST’s Confidential Information and for trade secret reasons [*].  MIST may also delay the submission of the proposed publication or presentation for an additional [*] as may be reasonably necessary to seek patent protection for the information disclosed in such proposed publication or presentation.  Ji Xing agrees to acknowledge the contribution of MIST and MIST’s employees in all publications relating to the Product as scientifically appropriate.  
10.5Publicity.  
(a)The Parties have agreed on language of a joint press release announcing this Agreement, which is attached hereto as Exhibit F, to be issued by the Parties promptly after the Effective Date.  Subject to the rest of this Section 10.5, no disclosure of the terms of this Agreement may be made by either Party, and no Party shall use the name, trademark, trade name or logo of 

30
[*] = 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.

the other Party, its Affiliates or their respective employee(s) in any publicity, promotion, news release or disclosure relating to this Agreement or its subject matter, without the prior express written permission of the other Party, except as may be required by Applicable Laws.  Following the initial joint press release announcing this Agreement, either Party shall be free to disclose or publicize, without the other Party’s prior written consent, the existence of this Agreement, the identity of the other Party, and those terms of this Agreement that have already been publicly disclosed in accordance herewith.  
(b)A Party may disclose this Agreement and its terms in securities filings with the U.S. Securities Exchange Commission (or equivalent foreign agency) (“SEC”) to the extent required by Applicable Laws after complying with the procedure set forth in this Section 10.5.  In such event, 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 agrees to promptly (and in any event, no less than [*] after receipt of such confidential treatment request and proposed redactions) give its input in a reasonable manner in order to allow the Party seeking disclosure to file its request within the time lines prescribed by applicable SEC regulations.  The Party seeking such disclosure shall exercise commercially reasonable efforts to obtain confidential treatment of this Agreement from the SEC as represented by the redacted version reviewed by the other Party.  
(c)Each Party acknowledges that the other Party may be legally required to make public disclosures (including in filings with the SEC or other agency) of certain material developments or material information generated under this Agreement and agrees that each Party may make such disclosures as required by Applicable Laws, provided that the Party seeking such disclosure first provides the other Party a copy of the proposed disclosure, and provided further that (except to the extent that the Party seeking disclosure is required to disclose such information to comply with Applicable Laws) if the other Party demonstrates to the reasonable satisfaction of the Party seeking disclosure, within [*] of such Party’s providing the copy, that the public disclosure of previously undisclosed information will materially adversely affect the development and/or commercialization of a Product being developed and/or commercialized, the Party seeking disclosure will remove from the disclosure such specific previously undisclosed information as the other Party shall reasonably request to be removed.  
10.6Prior CDA.  This Agreement supersedes the Confidentiality Agreement between the Parties dated [*] (the “Prior CDA”) with respect to information disclosed thereunder.  All information exchanged between the Parties under the Prior CDA shall be deemed Confidential Information of the disclosing Party and shall be subject to the terms of this Article 10.  
10.7Equitable Relief.  Each Party acknowledges that a breach of this Article 10 may not reasonably or adequately be compensated by damages in an action at law and that such a breach may cause the other Party irreparable injury and damage.  By reason thereof, each Party agrees that the other Party shall be entitled, in addition to any other remedies it may have under this Agreement or otherwise, to preliminary and permanent injunctive and other equitable relief to prevent or curtail any breach of the obligations relating to Confidential Information set forth herein.  

31
[*] = 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.

10.8Attorney-Client Privilege.  Neither Party is waiving, nor shall be deemed to have waived or diminished, any of its attorney work product protections, attorney-client privileges or similar protections and privileges or the like, as a result of disclosing information pursuant to this Agreement, or any of its Confidential Information (including Confidential Information related to pending or threatened litigation) to the other Party, regardless of whether the disclosing Party has asserted, or is or may be entitled to assert, such privileges and protections.  The Parties: (a) share a common legal and commercial interest in such disclosure that is subject to such privileges and protections; (b) are or may become joint defendants in proceedings to which the information covered by such protections and privileges relates; (c) intend that such privileges and protections remain intact should either Party become subject to any actual or threatened proceeding to which the disclosing Party’s Confidential Information covered by such protections and privileges relates; and (d) intend that after the Effective Date, both the receiving Party and the disclosing Party shall have the right to assert such protections and privileges.  
Article 11​
REPRESENTATIONS AND WARRANTIES
11.1Representations and Warranties of Each Party.  Each Party represents, warrants, and covenants (as applicable) to the other Party that: 
(a)it is a company or corporation duly organized, validly existing, and in good standing under the laws of the jurisdiction in which it is incorporated, and has full corporate power and authority and the legal right to own and operate its property and assets and to carry on its business as it is now being conducted and as contemplated in this Agreement;  
(b)it has the corporate power and authority and the legal right to enter into this Agreement and perform its obligations hereunder, it has taken all necessary corporate action on its part required to authorize the execution and delivery of the Agreement and the performance of its obligations hereunder, and this Agreement has been duly executed and delivered on behalf of such Party, and constitutes a legal, valid, and binding obligation of such Party that is enforceable against it in accordance with its terms, subject to applicable bankruptcy, insolvency, reorganization, moratorium and similar laws affecting creditors’ rights and remedies generally; 
(c)it is not a party to, and will not enter into during the Term, any agreement that would prevent it from granting the rights granted to the other Party under this Agreement or performing its obligations under the Agreement; and 
(d)in the course of performing its obligations or exercising its rights under this Agreement, it shall comply with all Applicable Laws, including as applicable, cGMP, GCP, and GLP standards, and shall not employ or engage any person or entity who has been debarred by any Regulatory Authority, or, to such Party’s knowledge, is the subject of debarment proceedings by a Regulatory Authority.  
11.2Representations and Warranties of MIST.  MIST represents, warrants, and covenants (as applicable) to Ji Xing that:

32
[*] = 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.

(a)it has the right under the Licensed IP to grant the licenses to Ji Xing as purported to be granted under Section 2.1 of this Agreement; 
(b)it has not granted, and will not grant during the Term, any license or other right under the Licensed IP that is inconsistent with the license granted to Ji Xing under Section 2.1;  
(c)Exhibit B includes all Licensed Patents as of the Effective Date.  MIST is the sole and exclusive owner of the Licensed Patents, all of which are free and clear of any claims, liens, charges or encumbrances.  All Licensed Patents are (i) subsisting and in good standing and (ii) being diligently prosecuted in the respective patent offices in accordance with Applicable Laws, and all applicable fees have been paid on or before the due date for payment.  To its knowledge, all Licensed Patents and have been filed and maintained properly and correctly and all issued Licensed Patents are valid;
(d)it has not received any written notice from any Third Party asserting or alleging that the Development of the Product prior to the Effective Date infringed or misappropriated the intellectual property rights of such Third Party; 
(e)there are no pending or, to MIST’s knowledge, threatened (in writing), adverse actions, claims, suits or proceedings against MIST or any of its Affiliate involving the Licensed IP or the Compound, Device, or Product.  No claim or litigation has been brought or, to MIST’s knowledge, threatened by any Person (i) alleging that the Licensed Patents are invalid or unenforceable, (ii) asserting the misuse, or non-infringement of any of the Licensed Patents, (iii) challenging MIST’s Control of the Licensed Patents or (iv) alleging misappropriation of the Know-How used in the Development or Manufacture of the Compound, Device, or Product by or on behalf of MIST prior to the Effective Date;
(f)to its knowledge, it (and any Third Party acting under its authority) (i) has complied in all material respects with all Applicable Laws and applicable governmental regulations and industrial standards (including GLP, GCP, and GMP) in connection with the Development, Manufacture, storage and disposition of the Compound, Device and Product (including information and data provided to Regulatory Authorities), and (ii) has not used any employee, consultant or contractor who has been debarred by any Regulatory Authority, or is the subject of a debarment proceeding by any Regulatory Authority in connection therewith; 
(g)no Upstream License exists as of the Effective Date.
11.3Representations and Warranties of Ji Xing.  Ji Xing represents, warrants, and covenants (as applicable) to MIST that:
(a)there is no pending or, to Ji Xing’s knowledge, threatened (in writing), adverse actions, claims, suits or proceedings against Ji Xing or any of its Affiliate that involve any antitrust, anti-competition, anti-bribery or corruption violations or that may reasonably be expected to adversely affect Ji Xing’s ability to perform its obligations under this Agreement; 

33
[*] = 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.

(b)neither Ji Xing nor any of its Affiliates is, or has been, debarred or disqualified by any Regulatory Authority nor will any of them be debarred or disqualified by any Regulatory Authority at any time throughout the Term; 
(c)it has sufficient financial wherewithal to (i) perform all of its obligations pursuant to this Agreement, and (ii) meet all of its obligations that come due in the ordinary course of business; 
(d)it has, and will at all times throughout the Term have, the requisite approvals, permits, licenses, expertise, resources, experience and skill reasonably required to perform its obligations under this Agreement.  
11.4NO OTHER WARRANTIES.  EXCEPT AS EXPRESSLY STATED IN THIS AGREEMENT, NO REPRESENTATIONS OR WARRANTIES WHATSOEVER, WHETHER EXPRESS OR IMPLIED, INCLUDING WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, NON-INFRINGEMENT, OR NON-MISAPPROPRIATION OF THIRD PARTY INTELLECTUAL PROPERTY RIGHTS, ARE MADE OR GIVEN BY OR ON BEHALF OF A PARTY.  ALL REPRESENTATIONS AND WARRANTIES, WHETHER ARISING BY OPERATION OF LAW OR OTHERWISE, ARE HEREBY EXPRESSLY EXCLUDED.  Ji Xing acknowledges and agrees that the Product is the subject of ongoing clinical research and development and that MIST cannot assure the safety, usefulness or successful Development or Commercialization of the Product.  
Article 12​
INDEMNIFICATION
12.1Indemnification by Ji Xing.  Ji Xing shall indemnify, defend and hold harmless MIST, its Affiliates, and their directors, officers, employees and agents (individually and collectively, the “MIST Indemnitee(s)”) from and against all losses, liabilities, damages and expenses (including reasonable attorneys’ fees and costs) incurred in connection with any claims, demands, actions or other proceedings by any Third Party (individually and collectively, “Losses”) to the extent arising from:  
(a)the Development, Manufacture, and Commercialization of the Product in the Territory by Ji Xing or any of its Affiliates or sublicensees (including product liability claims resulting therefrom); or 
(b)the negligence, willful misconduct or breach of this Agreement (including any representations, warranty or covenant of Ji Xing) by any Ji Xing Indemnitee;
except in each case to the extent such Losses arise out of the negligence, willful misconduct or breach of this Agreement by any MIST Indemnitee or arise from, are based on, or result from any activity or occurrence for which MIST is obligated to indemnify Ji Xing under Section 12.2.
12.2Indemnification by MIST.  MIST shall indemnify, defend and hold harmless Ji Xing, its Affiliates, and their directors, officers, employees and agents (individually and collectively, the “Ji Xing Indemnitee(s)”) from and against all Losses to the extent arising from:

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(a)activities conducted by or on behalf of MIST, its Affiliates or MIST Licensees, or contractors related to the Development or Manufacture of Licensed Products anywhere in the world prior to the Effective Date (including product liability claims resulting therefrom);
(b)the Development, Manufacture, and Commercialization of the Product outside the Territory by MIST or any of its Affiliates or MIST Licensees (including product liability claims resulting therefrom); 
(c)the Development of the Product in the Territory by MIST or any of its Affiliates or MIST Licensees (including product liability claims resulting therefrom); or
(d)the negligence, willful misconduct or breach of this Agreement (including any representations, warranty or covenant of MIST) by any MIST Indemnitee; 
except in each case to the extent such Losses arise out of the negligence, willful misconduct or breach of this Agreement by any Ji Xing Indemnitee or arise from, are based on, or result from any activity or occurrence for which Ji Xing is obligated to indemnify MIST under Section 12.1.
12.3Indemnification Procedure.  If either Party is seeking indemnification under Sections 12.1 or 12.2 (the “Indemnified Party”), it shall inform the other Party (the “Indemnifying Party”) of the claim giving rise to the obligation to indemnify pursuant to such Section within [*] after receiving notice of the claim (it being understood and agreed, however, that the failure or delay by an Indemnified Party to give such notice of a claim shall not affect the indemnification provided hereunder except to the extent the Indemnifying Party shall have been prejudiced as a result of such failure or delay to give notice).  The Indemnifying Party shall have the right to assume the defense of any such claim for which it is obligated to indemnify the Indemnified Party.  The Indemnified Party shall cooperate with the Indemnifying Party and the Indemnifying Party’s insurer as the Indemnifying Party may reasonably request, and at the Indemnifying Party’s cost and expense.  The Indemnified Party shall have the right to participate, at its own expense and with counsel of its choice, in the defense of any claim that has been assumed by the Indemnifying Party.  Neither Party shall have the obligation to indemnify the other Party in connection with any settlement made without the Indemnifying Party’s written consent, which consent shall not be unreasonably withheld or delayed.    
12.4Mitigation of Loss.  Each Indemnified Party shall take and shall procure that its Affiliates take all such reasonable steps and action as are reasonably necessary or as the Indemnifying Party may reasonably require in order to mitigate any claims (or potential losses or damages) under this Article 12.  Nothing in this Agreement shall or shall be deemed to relieve any Party of any common law or other duty to mitigate any losses incurred by it.  
12.5Limitation of Liability.  NEITHER PARTY SHALL BE LIABLE TO THE OTHER FOR ANY SPECIAL, CONSEQUENTIAL (WHICH SHALL BE DEEMED TO INCLUDE, WITHOUT LIMITATION, ALL DAMAGES CONSTITUTING LOSS OF PROFIT, LOSS OF REVENUE AND LOSS OF GOODWILL), INCIDENTAL, PUNITIVE, OR INDIRECT DAMAGES ARISING FROM OR RELATING TO ANY BREACH OF THIS 

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AGREEMENT, REGARDLESS OF ANY NOTICE OF THE POSSIBILITY OF SUCH DAMAGES.  NOTWITHSTANDING THE FOREGOING, NOTHING IN THIS SECTION 12.5 IS INTENDED TO OR SHALL LIMIT OR RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF ANY PARTY UNDER SECTION 12.1 OR 12.2, OR DAMAGES AVAILABLE FOR A PARTY’S BREACH OF SECTION 2.7 OR ARTICLE 10.  
12.6Insurance.  Each Party shall procure and maintain insurance, including product liability insurance, with respect to its activities hereunder and which is consistent with normal business practices of prudent companies similarly situated at all times during which any Product is being clinically tested in human subjects or commercially distributed or sold.  Each Party shall provide the other Party with evidence of such insurance upon request and shall provide the other Party with written notice at least [*] prior to the cancellation, non-renewal or material changes in such insurance.  Such insurance shall not be construed to create a limit of either Party’s liability under this Agreement.  
Article 13​
TERM AND TERMINATION
13.1Term.  
(a)The term of this Agreement shall commence upon the Effective Date and continue in full force and effect, on a Product-by-Product and Region-by-Region basis, until the expiration of the Royalty Term for such Product in such Region, unless earlier terminated as set forth in Section 13.2 below (the “Term”).  
(b)Upon expiration (but not early termination) of the Royalty Term with respect to a particular Product in a particular Region, the licenses granted by MIST to Ji Xing under Section 2.1 with respect to such Product in such Region shall continue and shall become fully paid-up, royalty-free, perpetual and irrevocable, and [*] shall also continue except that [*].    
13.2Termination.  
(a)Termination by Ji Xing for Convenience.  At any time, Ji Xing may terminate this Agreement in its entirety by providing written notice of termination to MIST, which notice includes an effective date of termination at least one hundred eighty (180) days after the date of the notice.  
(b)Termination for Material Breach.  If either Party materially breaches this Agreement, then the non-breaching Party may deliver notice of such breach to the other Party, which notice will (i) expressly reference this Section 13.2(b), (ii) reasonably describe the alleged material breach which is the basis of such termination, and (iii) clearly state the non-breaching Party’s intent to terminate this Agreement if the alleged breach is not cured within the [*].  Notwithstanding the foregoing, (A) if such material breach, by its nature, is curable, but is not reasonably curable within the applicable cure period, then such cure period will be extended if the alleged breaching Party provides a written plan for curing such breach to the non-breaching Party and uses Diligent Efforts to cure such breach in accordance with such written plan; provided, however, that no such extension will exceed [*] without the written consent of the non-breaching 

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Party; and (B) if the breaching Party disputes (1) whether it has materially breached this Agreement, (2) whether such material breach is reasonably curable within the applicable cure period, or (3) whether it has cured such material breach within the applicable cure period, to the extent the breaching Party notifies the non-breaching Party in writing of any such dispute within [*] after the non-breaching Party’s receipt of the termination notice, such dispute will be resolved pursuant to Article 14, and this Agreement may not be terminated during the pendency of such dispute resolution procedure.  During the pendency of such dispute, the applicable cure period shall be tolled, all the terms of this Agreement shall remain in effect, and the Parties shall continue to perform all of their respective obligations hereunder.  
(c)Termination for Insolvency.  Each Party shall have the right to terminate this Agreement in its entirety immediately upon written notice to the other Party in the event that (i) such other Party files in any court or agency pursuant to any statute or regulation of any jurisdiction a petition in bankruptcy or insolvency or for reorganization or similar arrangement for the benefit of creditors or for the appointment of a receiver or trustee of such other Party or its assets, (ii) such other Party is served with an involuntary petition against it in any insolvency proceeding and such involuntary petition has not been stayed or dismissed within [*] of its filing, or (iii) such other Party makes an assignment of substantially all of its assets for the benefit of its creditors.  
(d)Termination for [*].  Except to the extent the following is unenforceable under the laws of a particular jurisdiction, MIST may terminate this Agreement in its entirety with [*] prior written notice to Ji Xing if Ji Xing or its Affiliates or sublicensees, individually or in association with any other person or entity, commences a legal action challenging [*].  Notwithstanding the foregoing, MIST will not have the right to terminate this Agreement under this Section 13.2(d) if (i) such legal action was brought by a Third Party sublicensee and Ji Xing has terminated such sublicense within such [*] period, (ii) such legal action is based solely on the scope of a Licensed Patent or whether a claim therein qualifies as a Valid Claim and was made in defense of a breach claim first brought by MIST against Ji Xing, or (iii) such legal action is dismissed within [*] of MIST’s notice to Ji Xing under this Section 13.2(d) and not thereafter continued.
(e)Termination for [*].  If, at any time during the Term, Ji Xing does not [*], then MIST may treat such lack of activity as Ji Xing’s material breach of this Agreement and exercise the right to terminate this Agreement pursuant to Section 13.2(b), provided, that,[*].
13.3Effect of Termination.  Upon any termination of this Agreement:  
(a)License to Ji Xing.  All licenses and other rights granted by MIST to Ji Xing under the Licensed IP shall terminate, and all sublicenses granted by Ji Xing shall also terminate.  
(b)Regulatory Materials.  Ji Xing shall (and shall cause its Affiliates and sublicensees to), as instructed by MIST, either (i) if permitted by Applicable Laws, promptly transfer and assign to MIST or its designee all Regulatory Materials and Regulatory Approvals for the Product in the Territory, (ii) continue to hold any such Regulatory Materials and Regulatory 

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Approvals for the sole benefit of MIST or its designee (in which case, Ji Xing shall appoint MIST or its designee as the exclusive distributor (with the right to subcontract and appoint sub-distributors) under such Regulatory Materials and Regulatory Approvals for the Product in the Territory, and also as its agent to interact with the applicable Regulatory Authority in the Territory with respect to such Regulatory Materials and Regulatory Approvals), until such time MIST or its designee files its own Regulatory Materials and obtains its own Regulatory Approvals for the Product in the Territory; and/or (iii) terminate or withdraw any such Regulatory Materials and Regulatory Approvals.  Upon MIST’s request, Ji Xing shall also provide MIST with reasonable assistance and cooperation regarding any inquiries and correspondence with Regulatory Authorities relating to the Product. 
(c)Data. Ji Xing shall (and shall cause its Affiliates and sublicensees to) promptly transfer and assign to MIST, at no cost to MIST (except where the Agreement is terminated by Ji Xing for MIST’s uncured material breach pursuant to Section 13.2(b)), all data generated from the Development of the Product, including all Clinical Trials conducted by or on behalf of Ji Xing, its Affiliates and sublicensees, and all pharmacovigilance data (including all adverse event databases) relating to the Product in the Territory.  
(d)Inventory.  Ji Xing will have the right, for a period of [*] following termination of this Agreement, to sell or otherwise dispose of any Product in the Territory, on hand at the time of such termination or in the process of Manufacturing.  Upon expiration of the [*], MIST shall have the right (but not the obligation) to purchase from Ji Xing any or all of the inventory of the Product then held by Ji Xing or its Affiliates or sublicensees at a price equal to [*], provided that [*].
(e)Transition Assistance.  Ji Xing shall (and shall cause its Affiliates and sublicensees to) reasonably cooperate with MIST to facilitate orderly transition of the Development, Manufacture and Commercialization of the Product to MIST, including (i) assigning or amending as appropriate, upon request of MIST, any agreements or arrangements with Third Party vendors (including distributors) to Develop, Manufacture, supply, promote, distribute, sell or otherwise Commercialize the Product or, to the extent any such Third Party agreement or arrangement is not assignable to MIST, reasonably cooperating with MIST to arrange to continue to provide such services for a reasonable time after termination; (ii) to the extent that Ji Xing or its Affiliate or sublicensee is performing any activities described above in (i), reasonably cooperating with MIST to transfer such activities to MIST or its designee, and continuing to perform such activities on MIST’s behalf for a reasonable time after termination until such transfer is completed (not to exceed [*]); and (iii) providing MIST with reasonable quantities of materials used or generated by Ji Xing, its Affiliates and sublicensees in the Development and Commercialization of the Product in the Territory, such as clinical brochures and promotional materials, or any chemical or biological materials, that were not received from MIST.  
(f)Ongoing Clinical Trials.  If at the time of such termination, any Clinical Trials for the Product are being conducted by or on behalf of Ji Xing, its Affiliates or sublicensees, then, at MIST’s election on a trial-by-trial basis and to the extent permissible under Applicable Laws:  (i) Ji Xing shall (and shall cause its Affiliates and sublicensees to) fully cooperate with MIST to transfer the conduct of all such Clinical Trials to MIST, and MIST shall assume any and 

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all liability and costs for such Clinical Trials after the effective date of such termination; or (ii) Ji Xing shall (and shall cause its Affiliates and sublicensees to), orderly wind down, in compliance with Applicable Laws, the conduct of any such Clinical Trial which is not assumed by MIST under clause (i). 
(g)Return of Confidential Information.  Ji Xing shall (and shall cause its Affiliates and sublicensees to) promptly return or destroy (at MIST’s election) all tangible materials comprising, bearing or containing any Confidential Information of MIST that are in Ji Xing’s or its Affiliates’ or sublicensees’ possession or control.  
(h)Termination Press Releases.  Subject to the provisions of Section 10.5, the Parties shall cooperate in good faith to coordinate public disclosure of the termination of this Agreement and the reasons therefor, and neither Party shall, except to the extent required by Applicable Laws, disclose any such information without the prior approval of the other Party.  The principles to be observed in such disclosures shall be accuracy, compliance with Applicable Laws and regulatory guidance documents, and reasonable sensitivity to potential negative investor reaction to such news.  
(i)Trademarks.  Ji Xing shall (and shall cause its Affiliates and sublicensees to) promptly transfer and assign to MIST all Product Marks (excluding any such mark that includes, in whole or in part, any corporate name or logos of Ji Xing or its Affiliates or sublicensees).
(j)Transition Costs.  MIST will reimburse Ji Xing for the internal and external costs incurred in performing such transition activities or providing such assistance under Sections 13.3(b), 13.3(e), 13.3(f) and 13.3(i), unless this Agreement is terminated by MIST in accordance with Section 13.2(b) or Section 13.2(d) or by Ji Xing in accordance with Section 13.2(a).
(k)Termination by Ji Xing for MIST’s Material Breach.  If this Agreement is terminated by Ji Xing for MIST’s uncured material breach pursuant to Section 13.2(b), without limiting the foregoing, in consideration of Ji Xing’s assignment to MIST all Arising Product IP under this Agreement and Ji Xing’s performance of the assignment, transition, and assistance activities post such termination, on a Product-by-Product and Region-by-Region basis, MIST shall pay to Ji Xing royalties for exploiting the Product in the Territory for [*] starting from the First Commercial Sale of such Product in such Region by or on behalf of MIST, at the applicable royalty rate set forth below: 
(i)[*] in a Region in the Territory, if [*];
(ii)[*] in a Region in the Territory, if [*]; and
(iii)[*] in a Region in the Territory, if [*].
The definition of Net Sales and Sections 8.5 through 8.8 (excluding 8.5(a) and 8.5(b)) shall apply mutatis mutandis with respect to the sale of the Product by or on behalf of MIST in the Territory.

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13.4Survival.  Expiration or termination of this Agreement shall not relieve the Parties of any obligation accruing prior to such expiration or termination.  Without limiting the foregoing, the following provisions shall survive the termination or expiration of this Agreement for any reason: Article 1 (DEFINITIONS), Article 10 (CONFIDENTIALITY)(for the duration stipulated therein), Article 12 (INDEMNIFICATION) (excluding Section 12.6(Insurance)), Article 14 (DISPUTE RESOLUTION), Article 15 (MISCELLANEOUS) (as applicable, and excluding Section 15.7 (Foreign Corrupt Practices Act Compliance) and Section 15.16 (Further Actions)), Section 6.4 (Audit by Ji Xing)(for the duration stipulated therein), Sections 8.5 (Royalty Payments) through 8.9 (Taxes) (solely with respect to payment obligations accrued prior to such expiration or termination), Section 9.1 (Arising Product IP), Section 11.4 (No Other Warranties), Section 13.1(b) (Term) (solely in the event of expiration), Section 13.3 (Effects of Termination), Section 13.4(Survival), Section 13.5 (Termination Not Sole Remedy).  
13.5Termination Not Sole Remedy.  Termination is not the sole remedy under this Agreement and, whether or not termination is effected and notwithstanding anything contained in this Agreement to the contrary, all other remedies shall remain available except as agreed to otherwise herein.  
Article 14​
DISPUTE RESOLUTION
14.1Disputes.  The Parties recognize that disputes as to certain matters may from time to time arise during the Term which relate to either Party’s rights and/or obligations hereunder.  It is the objective of the Parties to establish procedures to facilitate the resolution of disputes arising under this Agreement in an expedient manner by mutual cooperation and without resort to litigation.  To accomplish this objective, the Parties agree to follow the procedures set forth in this Article 14 to resolve any controversy or claim arising out of, relating to, or in connection with any provision of this Agreement, if and when a dispute arises under this Agreement.  
14.2Internal Resolution.  With respect to all disputes arising between the Parties under this Agreement, including, without limitation, any alleged breach under this Agreement or any issue relating to the interpretation or application of this Agreement, if the Parties are unable to resolve such dispute within [*] after such dispute is first identified by either Party in writing to the other, the Parties shall refer such dispute to the Executive Officers of the Parties for attempted resolution by good faith negotiations within [*] after such notice is received.  
14.3Binding Arbitration.  
(a)If the Parties fail to resolve the dispute through escalation to the Executive Officers under Section 14.2, and a Party desires to pursue resolution of the dispute, the dispute shall be submitted by either Party for resolution in arbitration administered by the International Chamber of Commerce (“ICC”) pursuant to its arbitration rules and procedures then in effect.  
(b)The arbitration shall be conducted by a panel of three arbitrators experienced in the pharmaceutical business.  Within [*] after initiation of arbitration, each Party shall select one person to act as arbitrator and the two Party-selected arbitrators shall select a third arbitrator (who shall be the chairperson of the arbitration panel) within [*] of their appointment.  

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If the arbitrators selected by the Parties are unable or fail to agree upon the third arbitrator, the third arbitrator shall be appointed by ICC.  If, however, the aggregate award sought by the Parties is less than [*] and equitable relief is not sought, the arbitration shall be conducted by a single arbitrator agreed by the Parties (or appointed by ICC if the Parties cannot agree).  
(c)The seat and location of the arbitration shall be [*], and the language of the proceedings shall be English.  The arbitral tribunal shall determine the dispute by applying the provisions of this Agreement and the governing law set forth in Section 15.6.  The Parties agree that any award or decision made by the arbitral tribunal shall be final and binding upon them and may be enforced in the same manner as a judgment or order of a court of competent jurisdiction.  
(d)By agreeing to arbitration, the Parties do not intend to deprive any court of its jurisdiction to issue, at the request of a Party, a pre-arbitral injunction, pre-arbitral attachment or other order to avoid irreparable harm, maintain the status quo, preserve the subject matter of the dispute, or aid the arbitration proceedings and the enforcement of any award.  Without prejudice to such provisional or interim remedies in aid of arbitration as may be available under the jurisdiction of a competent court, the arbitral tribunal shall have full authority to grant provisional or interim remedies and to award damages for the failure of any Party to the dispute to respect the arbitral tribunal’s order to that effect.  
(e)Each Party shall bear its own attorney’s fees, costs, and disbursements arising out of the arbitration, and shall pay an equal share of the fees and costs of the administrator and the arbitrator; provided, however, the arbitrator shall be authorized to determine whether a Party is the prevailing party, and if so, to award to that prevailing party reimbursement for any or all of its reasonable attorneys’ fees, costs and disbursements (including, for example, expert witness fees and expenses, travel expenses, etc.), and/or the fees and costs of the administrator and the arbitrator.  
(f)Notwithstanding anything in this Section 14.3, in the event of a dispute with respect to the validity, scope, enforceability or ownership of any Patent or other intellectual property rights, and such dispute is not resolved in accordance with Section 14.2, such dispute shall not be submitted to an arbitration proceeding in accordance with this Section 14.3, unless otherwise agreed by the Parties in writing, and instead either Party may initiate litigation in a court of competent jurisdiction in any country in which such rights apply.  
Article 15​
MISCELLANEOUS
15.1Force Majeure.  Neither Party shall be held liable to the other Party nor be deemed to have defaulted under or breached this Agreement for failure or delay in performing any obligation under this Agreement to the extent such failure or delay is caused by or results from causes beyond the reasonable control of the affected Party, including embargoes, war, acts of war (whether war be declared or not), insurrections, riots, civil commotions, strikes, lockouts or other labor disturbances, epidemic or pandemic, fire, floods, or other acts of God or any other deity, or acts, omissions or delays in acting by any Governmental Authority.  The affected Party shall notify the other Party of such force majeure circumstances as soon as reasonably practical, and shall promptly undertake all reasonable efforts necessary to mitigate such force majeure circumstances.  

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15.2Assignment.  
(a)Except as provided in Section 15.2(b) below, this Agreement may not be assigned or otherwise transferred, nor may any right or obligation hereunder be assigned or transferred, by either Party without the prior written consent of the other Party.  Any attempted assignment not in accordance with the foregoing shall be null and void and of no legal effect.  Any permitted assignee shall assume all assigned obligations of its assignor under this Agreement.  The terms and conditions of this Agreement shall be binding upon, and shall inure to the benefit of, the Parties and their respected successors and permitted assigns.  
(b)Notwithstanding the foregoing, either Party may, without consent of the other Party, assign this Agreement and its rights and obligations hereunder in whole or in part to an Affiliate of such Party, or in whole to its successor-in-interest in connection with the sale of all or substantially all of its stock or its assets to which this Agreement relates, or in connection with a merger, acquisition or similar transaction.
(c)[*]. 
15.3Performance by Affiliates.  Each Party may discharge any obligations (other than the payment obligations set forth under Article 8) and exercise any right hereunder through any of its Affiliates, without notice to and without consent from, the other Party, and each Party hereby guarantees the performance by its Affiliates of such Party’s obligations under this Agreement, and shall cause its Affiliates to comply with the provisions of this Agreement in connection with such performance.
15.4Severability.  If any one or more of the provisions contained in this Agreement is held invalid, illegal or unenforceable in any respect, the validity, legality and enforceability of the remaining provisions contained herein shall not in any way be affected or impaired thereby, unless the absence of the invalidated provision(s) adversely affects the substantive rights of the Parties.  The Parties shall in such an instance use their best efforts to replace the invalid, illegal or unenforceable provision(s) with valid, legal and enforceable provision(s) which, insofar as practical, implement the purposes of this Agreement.  
15.5Notices.  All notices which are required or permitted hereunder shall be in writing and sufficient if delivered personally, sent by facsimile (and promptly confirmed by personal delivery, registered or certified mail or overnight courier), sent by nationally-recognized overnight courier or sent by registered or certified mail, postage prepaid, return receipt requested, addressed as follows:
If to MIST:
Milestone Pharmaceuticals, Inc. 
7422 Carmel Executive Drive, Suite 300 
Charlotte, NC  28226
Attn: [*]

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with a copy to:
Cooley LLP 
3175 Hanover Street 
Palo Alto, CA 94304, USA 
Attn:[*] 
Fax:[*]
If to Ji Xing:
Ji Xing Pharmaceuticals Limited
​
c/o RTW Investments, LP
40 10th Avenue, 7th Floor
New York, NY 10014
Attn: [*]
Email:[*]
​
with a copy to:
Ropes & Gray LLP
36/F, Park Place
1601 Nanjing Road West
Shanghai, The People’s Republic of China
Attn: [*]
Email:  [Geoffrey.Lin@ropesgray.com]
Fax:  [*]
or to such other address as the Party to whom notice is to be given may have furnished to the other Party in writing in accordance herewith.  Any such notice shall be deemed to have been given (a) when delivered if personally delivered or sent by facsimile on a Business Day; (b) on the second Business Day after dispatch if sent by internationally-recognized overnight courier; or (c) on the fifth Business Day following the date of mailing if sent by mail.  
15.6Governing Law.  This Agreement shall be governed by and construed in accordance with the laws of the State of New York, U.S., without giving effect to any choice of law principles that would require the application of the laws of a different jurisdiction.  The application of the U.N. Convention on Contracts for the International Sale of Goods is excluded.  
15.7Foreign Corrupt Practices Act Compliance.  
(a)Compliance with FCPA.  The U.S. government imposes and enforces prohibitions on the payment or transfer of anything of value to governments, government officials, political parties or political party officials (or relatives or associates of such officials) (“FCPA Covered Person”) for the purpose of illegally influencing them, whether directly or indirectly, to obtain or retain business.  This U.S. law is referred to as the Foreign Corrupt Practices Act 

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(“FCPA”), and it can have application to conduct of a U.S. corporation’s foreign subsidiaries, employees, agents and distributors.  A summary of the law and related information can be found at http://www.justice.gov/criminal/fraud/fcpa.  By signing this Agreement, Ji Xing represents, warrants and covenants (as applicable) to MIST that:  
(i)it is familiar with the provisions and restrictions contained in the OECD Convention and FCPA; 
(ii)it shall comply with the FCPA in the Development and Commercialization of the Product under this Agreement; 
(iii)it shall not, in the course of its duties under the Agreement, offer, promise, give, demand, seek or accept, directly or indirectly, any gift or payment, consideration or benefit in kind to any FCPA Covered Person that would or could be construed as an illegal or corrupt practice; 
(iv)it is not an FCPA Covered Person or affiliated with any FCPA Covered Person; and 
(v)it shall immediately notify MIST of any attempt by any FCPA Covered Person to directly or indirectly solicit, ask for, or attempt to extort anything of value from Ji Xing, its Affiliates or sublicensees, and shall refuse any such solicitation, request or extortionate demand except a facilitating payment as expressly permitted under the FCPA.  
(b)Compliance Certificate.  From time to time upon request from MIST, Ji Xing shall submit a compliance certificate in the form reasonably requested by MIST that (i) it fully understands its obligations under this Section 15.7 and any other Applicable Laws mentioned herein or as may come into existence from time to time after the Effective Date; (ii) it has been complying with this Section 15.7 and any other Applicable Laws mentioned herein or as may come into existence from time to time after the Effective Date; and (iii) it shall continue to comply with this Section 15.7 and any other Applicable Laws mentioned herein or as may come into existence from time to time after the Effective Date.  
(c)No Action.  In no event shall any Party be obligated under the Agreement to take any action or omit to take any action that such Party believes, in good faith, would cause it to be in violation of any Applicable Laws, including the anti-bribery laws referenced in this Section 15.7.  
(d)Due Diligence.  MIST shall have the right to visit the offices of Ji Xing from time to time during the term of the Agreement on an “as needed” basis and conduct due diligence in relation to Ji Xing’s business related to performance of its obligations under this Section 15.7 and may do so in the way it deems necessary, appropriate or desirable so as to ensure that Ji Xing complies with this Section 15.7 and any other Applicable Laws in its business operations.  Ji Xing shall make every effort to cooperate fully with MIST in any such due diligence.  
(e)Audit.  In the event that MIST has reason to believe that a breach of any obligation of Ji Xing under this Section 15.7 has occurred or may occur, MIST shall have the right 

44
[*] = 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.

to select an independent third party to conduct an audit of Ji Xing and review relevant books and records of Ji Xing, to satisfy itself that no breach has occurred.  Unless otherwise required under Applicable Laws or by order of a competent court or regulatory authority, MIST shall ensure that the selected independent third party shall keep confidential all audited matters and the results of the audit.  MIST shall not disclose to the U.S. or foreign government, its agencies and/or any other government or non-government party, information relating to a possible violation by Ji Xing of any Applicable Law, including a violation of the FCPA or any other applicable anti-bribery law, unless MIST is required to do so under Applicable Laws.   
15.8Entire Agreement; Amendments.  The Agreement, together with the Exhibits attached hereto, contains the entire understanding of the Parties with respect to the subject matter hereof.  All express or implied agreements and understandings, either oral or written, with regard to the subject matter hereof (including the licenses granted hereunder) are superseded by the terms of this Agreement.  Neither Party is relying on any representation, promise, nor warranty not expressly set forth in this Agreement.  This Agreement may be amended, or any term hereof modified, only by a written instrument duly executed by authorized representatives of both Parties hereto.  
15.9Headings.  The captions to the several Sections hereof are not a part of this Agreement, but are merely for convenience to assist in locating and reading the Sections of this Agreement.  
15.10Independent Contractors.  It is expressly agreed that MIST and Ji Xing shall be independent contractors and that the relationship between the two Parties shall not constitute a partnership, joint venture or agency.  Neither MIST nor Ji Xing shall have the authority to make any statements, representations or commitments of any kind, or to take any action, which shall be binding on the other Party, without the prior written consent of the other Party.  
15.11Waiver.  The waiver by either Party of any right hereunder, or the failure of the other Party to perform, or a breach by the other Party, shall not be deemed a waiver of any other right hereunder or of any other breach or failure by such other Party whether of a similar nature or otherwise.  
15.12Cumulative Remedies.  No remedy referred to in this Agreement is intended to be exclusive, but each shall be cumulative and in addition to any other remedy referred to in this Agreement or otherwise available under law.  
15.13Waiver of Rule of Construction.  Each Party has had the opportunity to consult with counsel in connection with the review, drafting and negotiation of this Agreement.  Accordingly, the rule of construction that any ambiguity in this Agreement shall be construed against the drafting Party shall not apply.  
15.14Business Day Requirements.  In the event that any notice or other action or omission is required to be taken by a Party under this Agreement on a day that is not a Business Day then such notice or other action or omission shall be deemed to be required to be taken on the next occurring Business Day.  

45
[*] = 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.

15.15Translations.  This Agreement is in the English language only, which language shall be controlling in all respects, and all versions hereof in any other language shall be for accommodation only and shall not be binding upon the Parties.  All communications and notices to be made or given pursuant to this Agreement, and any dispute proceeding related to or arising hereunder, shall be in the English language.  If there is a discrepancy between any translation of this Agreement and this Agreement, this Agreement shall prevail.  
15.16Further Actions.  Each Party agrees to execute, acknowledge and deliver such further instruments, and to do all such other acts, as necessary or appropriate in order to carry out the purposes and intent of this Agreement.  
15.17Construction.  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 shall be construed to include the person’s successors and assigns, (f) the words “herein”, “hereof” and “hereunder”, and words of similar import, shall be construed to refer to this Agreement in its entirety and not to any particular provision hereof, (g) all references herein to Sections, Schedules, or Exhibits shall be construed to refer to Sections, Schedules or Exhibits of this Agreement, and references to this Agreement include all Schedules and 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, rule or regulation, or Section, section or other division thereof, shall be deemed to include the then-current amendments thereto or any replacement or successor law, rule or regulation thereof, and (k) the term “or” shall be interpreted in the inclusive sense commonly associated with the term “and/or.” 
15.18Counterparts.  This Agreement may be executed in two or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument.  Each Party shall be entitled to rely on the delivery of executed facsimile copies of counterpart execution pages of this Agreement and such facsimile copies shall be legally effective to create a valid and binding agreement among the Parties.  
{Signature Page Follows}
​

46
[*] = 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.

​

In Witness Whereof, the Parties intending to be bound have caused this License and Collaboration Agreement to be executed by their duly authorized representatives as of the Effective Date.  
	Milestone Pharmaceuticals, Inc.
	Ji Xing Pharmaceuticals Limited

By:​ ​​ ​By:​ ​
Name:​ ​​ ​Name:​ ​
Title:​ ​​ ​Title:​ ​
Date:​ ​​ ​Date:​ ​
​
​

[*] = 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.

​

List of Exhibits
​
Exhibit A:Compound and Device
Exhibit B:Existing Licensed Patents
Exhibit C:Initial Development Plan 
Exhibit D:Technology Transfer Plan 
Exhibit E:Securities Purchase Agreement
Exhibit F:Joint Press Release 
Schedule 2.8:Approved Subcontractors
​

[*] = 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.

​

Exhibit A
Compound and Device
Compound Description
[*]

[*] = 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

​

Exhibit B
​
Existing Licensed Patents
​
[*]
​
​

[*] = 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

​

​
Exhibit C
Initial Development Plan
[*]
​
​

[*] = 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

​

Exhibit D
Technology Transfer Plan
​
[*] 
​
​
​

[*] = 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

​

Exhibit E
​
Securities Purchase Agreement
[*]

[*] = 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

​

Exhibit F
​
Press Release
​
​
Milestone Pharmaceuticals Announces Exclusive License Agreement with Ji Xing Pharmaceuticals to Develop and Commercialize Etripamil for PSVT in Greater China
- Ji Xing Pharmaceuticals to develop and commercialize etripamil for patients with PSVT in Greater China -
- Milestone to receive a $15 million upfront cash payment and a $5 million equity investment by RTW Investments, LP -
Montreal and Charlotte, N.C., May 17, 2021 -- Milestone Pharmaceuticals Inc. (Nasdaq: MIST), a biopharmaceutical company focused on the development and commercialization of innovative cardiovascular medicines, today announced an exclusive license and collaboration agreement with Ji Xing Pharmaceuticals (Ji Xing) to develop and, if approved, commercialize the investigational drug etripamil in patients with paroxysmal supraventricular tachycardia (PSVT) and additional cardiovascular conditions in Greater China.  Ji Xing is a biotechnology company headquartered in Shanghai and backed by RTW Investments, LP (RTW) focused on advancing innovative medicines in China.
“This agreement marks an important step toward realizing our vision for etripamil to benefit patients living with PSVT globally while strengthening our balance sheet and executional capabilities through partnership,” said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals. “We look forward to partnering with the talented team at Ji Xing to develop and commercialize this promising therapy in the licensed regions.”
“Etripamil has the potential to change the treatment paradigm for PSVT and could serve as a meaningful new therapeutic option for patients,” said Peter Fong, Chief Executive Officer of Ji Xing and Head of Company Creation at RTW. “We are delighted to expand Ji Xing’s cardiovascular focus by partnering with Milestone and look forward to unlocking the full therapeutic potential of etripamil for patients with PSVT in China.” 
Under the terms of the agreement, Milestone will grant Ji Xing an exclusive license to develop and, if regulatory approval is obtained, commercialize etripamil in patients with PSVT in Greater China. Milestone will receive an upfront cash payment consisting of $15 million and a $5 million equity investment by RTW. In addition, Milestone is eligible to receive up to $107.5 million in milestone payments and royalties on future sales of etripamil in Greater China. Milestone will supply etripamil and delivery devices to Ji Xing. Ji Xing will be responsible for development and commercialization costs in Greater China.
About Paroxysmal Supraventricular Tachycardia
Paroxysmal supraventricular tachycardia (PSVT) is a rapid heart rate condition characterized by intermittent episodes of supraventricular tachycardia (SVT) that start and stop suddenly and without warning that affects approximately two million Americans. Episodes of SVT are often associated with symptoms including palpitations, sweating, chest pressure or pain, shortness of breath, sudden onset of fatigue, lightheadedness or dizziness, fainting, and anxiety. Certain calcium channel blockers have long been approved for the treatment of PSVT as well as other cardiac conditions. However, calcium channel blockers approved for the 

[*] = 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

​

termination of SVT episodes must be administered intravenously under medical supervision, usually in an emergency department or other acute care setting.
About Etripamil
Etripamil, Milestone's lead investigational product, is a novel calcium channel blocker designed to be a rapid-response therapy for episodic cardiovascular conditions. As a nasal spray that is self-administered by the patient, etripamil has the potential to shift the current treatment experience for many patients from the emergency department to the at-home setting. Milestone is conducting a comprehensive development program for etripamil, with Phase 3 trials ongoing in paroxysmal supraventricular tachycardia (PSVT) and a Phase 2 proof-of-concept trial is now underway in patients with atrial fibrillation and rapid ventricular rate (AFib-RVR).
About Ji Xing Pharmaceuticals
Backed by RTW Investments, LP, Ji Xing is a privately held, leading biotechnology company headquartered in Shanghai committed to bringing innovative science and medicines to underserved Chinese patients with serious and life-threatening diseases.
About RTW Investments
RTW Investments, LP (“RTW”) is a New York-based, global, full life-cycle investment firm that focuses on identifying transformational and disruptive innovations across the biopharmaceutical and medical technologies sectors.  As a leading partner of industry and academia, RTW combines deep scientific expertise with a solution-oriented investment approach to support emerging medical therapies and the companies and/or academics developing them. 
For further information about RTW, please visit www.RTWfunds.com.
About Milestone Pharmaceuticals
Milestone Pharmaceuticals Inc. (Nasdaq: MIST), is a biopharmaceutical company focused on the development and commercialization of innovative cardiovascular medicines. Milestone’s lead product candidate etripamil is currently in a Phase 3 clinical-stage program for the treatment of paroxysmal supraventricular tachycardia (PSVT) and in a Phase 2 proof-of-concept trial for the treatment of patients with atrial fibrillation and rapid ventricular rate (AFib-RVR). Milestone Pharmaceuticals operates in Canada and the United States. For more information, visit www.milestonepharma.com and follow the Company on Twitter at @MilestonePharma. 
​
Forward-Looking Statements
​
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate," "estimate," “potential,” "intend" and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Milestone's expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include statements regarding the potential of etripamil as a promising therapy for PSVT 

[*] = 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

​

patients, and Milestone’s and Ji Xing’s intention and ability to develop and commercialize etripamil in China.  Important factors that could cause actual results to differ materially from those in the forward-looking statements include, but are not limited to, the risks inherent in biopharmaceutical product development and clinical trials, including the lengthy and uncertain regulatory approval process, uncertainties related to the timing of initiation, enrollment, completion and evaluation of clinical trials, and whether the clinical trials will validate the safety and efficacy of etripamil for PSVT or other indications, among others, as well as risks related to pandemics and public health emergencies, including those related to COVID-19, and risks related the sufficiency of Milestone’s capital resources and its ability to raise additional capital. These and other risks are set forth in Milestone's filings with the U.S. Securities and Exchange Commission, including in its quarterly report on Form 10-K for the year ended December 31, 2020, under the caption "Risk Factors." Except as required by law, Milestone assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.
​
Contact:
David Pitts
Argot Partners
212-600-1902
david@argotpartners.com
​

[*] = 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

​

​
Schedule 2.8
Approved Subcontractors
[*]

[*] = 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 confidentialEX-4.4

 Exhibit 4.4 
  

 
  

BARCLAYS PLC, 
 as Issuer, 

THE BANK OF NEW YORK MELLON, LONDON BRANCH, 

as Trustee and Paying Agent 
 and

 THE BANK OF NEW YORK MELLON SA/NV, LUXEMBOURG BRANCH, 

as Contingent Capital Security Registrar 
  

 
 SIXTH SUPPLEMENTAL INDENTURE 

Dated as of August 11, 2021 
  

 
 To the Contingent Capital Securities
Indenture, dated as of August 14, 2018, 
 among the Issuer, the Trustee and Paying Agent and the Contingent Capital Security Registrar

 $1,500,000,000 4.375% Fixed Rate Resetting Perpetual Subordinated Contingent Convertible Securities 

 
  

 

 TABLE OF CONTENTS 

 

							
	ARTICLE I	  

	
	DEFINITIONS AND OTHER PROVISIONS OF GENERAL APPLICATION	  

			
	SECTION 1.01.	 	 Definitions.
	  	 	2	 
			
	SECTION 1.02.	 	 Effect of Headings.
	  	 	14	 
			
	SECTION 1.03.	 	 Separability Clause.
	  	 	14	 
			
	SECTION 1.04.	 	 Benefits of Instrument.
	  	 	14	 
			
	SECTION 1.05.	 	 Relation to Base Indenture.
	  	 	14	 
			
	SECTION 1.06.	 	 Construction and Interpretation
	  	 	14	 
	
	ARTICLE II	  

	
	$1,500,000,000 4.375% FIXED RATE RESETTING PERPETUAL SUBORDINATED CONTINGENT CONVERTIBLE SECURITIES	  

			
	SECTION 2.01.	 	 Creation of Series; Establishment of Form.
	  	 	16	 
			
	SECTION 2.02.	 	 Interest.
	  	 	17	 
			
	SECTION 2.03.	 	 Payment of Principal, Interest and Other Amounts
	  	 	17	 
			
	SECTION 2.04.	 	 Optional Redemption
	  	 	18	 
			
	SECTION 2.05.	 	 Regulatory Event Redemption
	  	 	18	 
			
	SECTION 2.06.	 	 Notice of Redemption
	  	 	18	 
			
	SECTION 2.07.	 	 Automatic Conversion upon Capital Adequacy Trigger Event.
	  	 	18	 
			
	SECTION 2.08.	 	 Conversion Shares.
	  	 	22	 
			
	SECTION 2.09.	 	 Conversion Shares Offer.
	  	 	23	 
			
	SECTION 2.10.	 	 Settlement Procedure.
	  	 	24	 
			
	SECTION 2.11.	 	 Failure to Deliver a Conversion Shares Settlement Notice
	  	 	26	 
			
	SECTION 2.12.	 	 Additional Amounts and FATCA Withholding Tax
	  	 	27	 
	
	ARTICLE III	  

	
	ANTI-DILUTION	  

			
	SECTION 3.01.	 	 Adjustment of Conversion Price and Conversion Shares Offer Price
	  	 	27	 
			
	SECTION 3.02.	 	 No Retroactive Adjustments
	  	 	30	 
			
	SECTION 3.03.	 	 Decision of an Independent Financial Advisor
	  	 	30	 

  
 ii 

							
			
	SECTION 3.04.	 	 Rounding Down and Notice of Adjustment to the Conversion Price and the Conversion Shares Offer
Price.
	  	 	31	 
			
	SECTION 3.05.	 	 Qualifying Takeover Event.
	  	 	31	 
	
	ARTICLE IV	  

	
	MISCELLANEOUS PROVISIONS	  

			
	SECTION 4.01.	 	 Effectiveness
	  	 	32	 
			
	SECTION 4.02.	 	 Original Issue
	  	 	32	 
			
	SECTION 4.03.	 	 Ratification and Integral Part
	  	 	33	 
			
	SECTION 4.04.	 	 Priority
	  	 	33	 
			
	SECTION 4.05.	 	 Successors and Assigns
	  	 	33	 
			
	SECTION 4.06.	 	 Counterparts
	  	 	33	 
			
	SECTION 4.07.	 	 Governing Law
	  	 	33	 

  

					
	 EXHIBIT A – Form of Global Security
	  	 	A-1	 
	 EXHIBIT B – Form of Automatic Conversion Notice
	  	 	B-1	 
	 EXHIBIT C – Form of Capital Adequacy Trigger Event Officers’ Certificate
	  	 	C-1	 
	 EXHIBIT D – Form of Conversion Shares Offer Notice
	  	 	D-1	 
	 EXHIBIT E – Form of Conversion Shares Settlement Request Notice
	  	 	E-1	 

  
 iii 

 SIXTH SUPPLEMENTAL INDENTURE, dated as of August 11, 2021 (the “Sixth
Supplemental Indenture”), among BARCLAYS PLC, a public limited company registered in England and Wales, as Issuer (hereinafter called the “Company”), having its registered office at 1 Churchill Place, London E14 5HP, United
Kingdom, THE BANK OF NEW YORK MELLON, LONDON BRANCH, a New York banking corporation, as Trustee (herein called the “Trustee”) and Paying Agent, having its Corporate Trust Office at One Canada Square, London E14 5AL, United Kingdom
and THE BANK OF NEW YORK MELLON SA/NV, LUXEMBOURG BRANCH, as Contingent Capital Security Registrar, having an office at 2-4 Rue Eugene Ruppert, Vertigo Building – Polaris, Luxembourg, L-2453, Luxembourg (herein called the “Contingent Capital Security Registrar”), to the CONTINGENT CAPITAL SECURITIES INDENTURE, dated as of August 14, 2018 among the Company, the Trustee and
the Contingent Capital Security Registrar, as heretofore amended and supplemented (the “Base Indenture” and, together with this Sixth Supplemental Indenture, the “Indenture”). 

RECITALS OF THE COMPANY 

WHEREAS, the Company, the Trustee and the Contingent Capital Security Registrar are parties to the Base Indenture, which provides for the
issuance by the Company from time to time of Contingent Capital Securities in one or more series; 
 WHEREAS, Section 9.01 of the Base
Indenture permits supplements thereto without the consent of Holders of Contingent Capital Securities to establish the form or terms of Contingent Capital Securities of any series as permitted by Sections 2.01 and 3.01 of the Base Indenture; 

WHEREAS, as contemplated by Section 3.01 of the Base Indenture, the Company intends to issue a new series of Contingent Capital
Securities to be known as the Company’s “$1,500,000,000 4.375% Fixed Rate Resetting Perpetual Subordinated Contingent Convertible Securities” (the “Securities”) under the Indenture; 

WHEREAS, the Company has taken all necessary corporate action to authorize the execution and delivery of this Sixth Supplemental Indenture;

 NOW, THEREFORE, THIS SIXTH SUPPLEMENTAL INDENTURE WITNESSETH: 

For and in consideration of the premises and the other good and valuable consideration, the receipt and sufficiency of which is hereby
acknowledged, the Company, the Trustee and Paying Agent and the Contingent Capital Security Registrar mutually agree as follows with regard to the Securities: 

  
 - 1 - 

 ARTICLE I 

DEFINITIONS AND OTHER PROVISIONS OF GENERAL APPLICATION 

SECTION 1.01. Definitions. 
 Except
as otherwise expressly provided or unless the context otherwise requires, all terms used in this Sixth Supplemental Indenture that are defined in the Base Indenture shall have the meanings ascribed to them in the Base Indenture. The following terms
used in this Sixth Supplemental Indenture have the following respective meanings with respect to the Securities only: 

“Acquirer” means the Takeover Person that controls the Company following a Takeover Event. For the purposes of
this definition, “control” means the acquisition or holding of legal or beneficial ownership of more than 50% of the votes which may ordinarily be cast on a poll at a general meeting of the Company or the right to appoint or remove a
majority of the board of directors of the Company. On and after the date of a Qualifying Takeover Event, references herein to “Ordinary Shares” shall be read as references to “Approved Entity Shares.” 

“Approved Entity” means a body corporate which, on the occurrence of the Takeover Event and thereafter, has in
issue Approved Entity Shares. 
 “Approved Entity Shares” means ordinary shares in the capital of a body
corporate that constitutes equity share capital or the equivalent (or depository or other receipts representing the same) which are listed and admitted to trading on a Recognized Stock Exchange and is not share capital which, if the Securities could
convert into such share capital in accordance with Section 2.08 of this Sixth Supplemental Indenture, would cause a Relevant Tax Effect in circumstances where, if the Securities could instead only convert into ordinary shares of the Company,
would not cause a Relevant Tax Effect. Such shares shall cease to be “Approved Entity Shares” if they do not satisfy the definition above on the Conversion Date. In relation to an Automatic Conversion in respect of which the Conversion
Date falls on or after the QTE Effective Date, references herein to “Conversion Shares” shall be deemed to be references to “Approved Entity Shares”. 

“Automatic Conversion” means the irrevocable and automatic release of all of the Company’s obligations
under the Securities (other than the CSO Obligations, if any) in consideration of the Company’s issuance of the Conversion Shares at the Conversion Price to the Conversion Shares Depository (on behalf of the Holders and Beneficial Owners of the
Securities) or to the relevant recipient of such Conversion Shares, all in accordance with the terms of the Securities. 

“Automatic Conversion Notice” means the written notice (substantially in the form attached hereto as
Exhibit B) to be delivered by the Company to the Trustee directly and to the Holders of the Global Securities via DTC (or, if the Securities are definitive Securities, by the Company to the Trustee directly and to the Holders at their
addresses 

  
 - 2 - 

 
shown on the Contingent Capital Security Register) specifying (i) that a Capital Adequacy Trigger Event has occurred, (ii) the Conversion Date or expected Conversion Date,
(iii) the Conversion Price, (iv) that the Company has the option, at its sole and absolute discretion, to elect that a Conversion Shares Offer be conducted and that the Company will issue a Conversion Shares Offer Notice via DTC within ten
(10) Business Days following the Conversion Date notifying Holders of the Company’s election and (v) that the Securities shall remain in existence for the sole purpose of evidencing (a) the right of the Holders to receive
Conversion Shares or Conversion Shares Offer Consideration, as applicable, from the Conversion Shares Depository and (b) the Company’s CSO Obligations, if any, and that the Securities may continue to be transferable until the Suspension
Date, which shall be specified in the Conversion Shares Offer Notice. 
 “Base Indenture” has the meaning
set forth in the first paragraph of this Sixth Supplemental Indenture. 
 “Business Day” means any weekday,
other than one on which banking institutions are authorized or obligated by law, regulation or executive order to close in London, United Kingdom, or in New York City, New York. 

“Calculation Agent” means The Bank of New York Mellon, London Branch, or its successor appointed by the
Company pursuant to the calculation agent agreement between the Company and The Bank of New York Mellon, dated as of the date hereof. 

“Cancellation Date” means (i) with respect to any Security for which a Conversion Shares Settlement
Notice is received by the Conversion Shares Depository on or before the Notice Cut-off Date, the applicable Settlement Date and (ii) with respect to any Security for which a Conversion Shares Settlement
Notice is not received by the Conversion Shares Depository on or before the Notice Cut-off Date, the Final Cancellation Date. 

“Capital Adequacy Trigger Event” shall occur if at any time the Fully Loaded CET1 Ratio (as defined herein) is
less than 7.00%. Whether a Capital Adequacy Trigger Event has occurred at any time shall be determined by the Company and such determination shall be binding on the Trustee and Holders of the Securities. 

“Capital Adequacy Trigger Event Officers’ Certificate” has the meaning set forth in Section 2.07(o)
hereof. 
 “Cash Component” means that portion, if any, of the Conversion Shares Offer Consideration
consisting of cash. 
 “Cash Dividend” means any dividend or distribution in respect of the Ordinary Shares
to Shareholders of the Company which is to be paid or made in cash (in whatever currency), however described and whether payable out of share premium account, profits, retained earnings or any other capital or revenue reserve or account and
including a distribution or payment to Shareholders upon or in connection with a reduction of capital. 

  
 - 3 - 

 “CET1 Capital” means, at any time, the sum, expressed in
pounds sterling, of all amounts that constitute common equity Tier 1 Capital of the Group at such time, less any deductions from common equity Tier 1 Capital required to be made at such time, in each case as determined by the Company on a
consolidated basis in accordance with the Capital Regulations applicable at such time (which determination shall be binding on the Trustee and the Holders and Beneficial Owners). For the purposes of this definition, the term “common equity Tier
1 Capital” shall have the meaning assigned to such term in the Capital Regulations then applicable. 

“Companies Act” means the Companies Act 2006 (UK). 

“Company” has the meaning set forth in the first paragraph of this Sixth Supplemental Indenture, and includes
any successor entity. 
 “Comparable Treasury Issue” means, with respect to any Reset Period, the U.S.
Treasury security or securities selected by the Company with a maturity date on or about the last day of such Reset Period and that would be utilized, at the time of selection and in accordance with customary financial practice, in pricing new
issues of corporate debt securities denominated in U.S. dollars and having a maturity of five years. 
 “Comparable
Treasury Price” means, with respect to any Reset Determination Date, (i) the arithmetic average of the Reference Treasury Dealer Quotations for such Reset Determination Date, after excluding the highest and lowest such Reference
Treasury Dealer Quotations, or (ii) if fewer than five such Reference Treasury Dealer Quotations are received, the arithmetic average of all such quotations, or (iii) if fewer than two such Reference Treasury Dealer Quotations are
received, then such Reference Treasury Dealer Quotation. 
 “Conversion Date” means the date on which the
Automatic Conversion shall take place, or has taken place, as applicable. 
 “Conversion Price” means $2.29
per Conversion Share (subject to certain anti-dilution adjustments pursuant to Section 3.01 hereof). 

“Conversion Shares” means the Ordinary Shares of the Company to be issued to the Conversion Shares Depository
(or to the relevant recipient in accordance with the terms of the Securities) following an Automatic Conversion, which Ordinary Shares shall be in such number as is determined by dividing the aggregate principal amount of the Securities Outstanding
immediately prior to the Automatic Conversion on the Conversion Date by the Conversion Price, rounded down, if necessary, to the nearest whole number of Ordinary Shares. 

“Conversion Shares Component” means that portion, if any, of the Conversion Shares Offer Consideration
consisting of Conversion Shares. 
 “Conversion Shares Depository” means a financial institution, trust
company, depository entity, nominee entity or similar entity to be appointed by the Company on or prior to any date when a function ascribed to the Conversion Shares Depository in the 

  
 - 4 - 

 
Indenture is required to be performed, to perform such functions and which, as a condition of such appointment, such entity will be required to undertake, for the benefit of the Holders and
Beneficial Owners of the Securities, to hold the Conversion Shares (and any Conversion Shares Offer Consideration) on behalf of such Holders and Beneficial Owners of the Securities in one or more segregated accounts, unless otherwise required for
the purposes of the Conversion Shares Offer and, in any event, on terms consistent with the Indenture. 
 “Conversion
Shares Offer” has the meaning set forth in Section 2.09(a) hereof. 
 “Conversion Shares Offer
Agent” means the agent(s), if any, to be appointed on behalf of the Conversion Shares Depository by the Company, in its sole and absolute discretion, to act as placement or other agent of the Conversion Shares Depository to facilitate a
Conversion Shares Offer. 
 “Conversion Shares Offer Consideration” means in respect of each Security
(i) if all of the Conversion Shares are sold in the Conversion Shares Offer, the pro rata share of the cash proceeds from the sale of the Conversion Shares attributable to such Security translated from sterling into U.S. dollars at a
then-prevailing exchange rate (less any foreign exchange transaction costs), (ii) if some but not all of the Conversion Shares are sold in the Conversion Shares Offer, (x) the pro rata share of the cash proceeds from the sale of the
Conversion Shares attributable to such Security translated from sterling into U.S. dollars at a then-prevailing exchange rate (less any foreign exchange transaction costs) and (y) the pro rata share of the Conversion Shares not sold
pursuant to the Conversion Shares Offer attributable to such Security rounded down to the nearest whole number of Conversion Shares, and (iii) if no Conversion Shares are sold in a Conversion Shares Offer, the relevant Conversion Shares
attributable to such Security rounded down to the nearest whole number of Conversion Shares, subject in the case of (i) and (ii)(x) above to deduction from any such cash proceeds of an amount equal to the pro rata share of any stamp
duty, stamp duty reserve tax, or any other capital, issue, transfer, registration, financial transaction or documentary tax that may arise or be paid as a consequence of the transfer of any interest in the Conversion Shares to the Conversion Shares
Depository as a consequence of the Conversion Shares Offer. 
 “Conversion Shares Offer Notice” means the
written notice (substantially in the form attached hereto as Exhibit D) to be delivered by the Company to the Trustee directly and to the Holders of the Global Securities via DTC (or, if the Securities are definitive Securities, by the
Company to the Trustee directly and to the Holders at their addresses shown on the Contingent Capital Security Register) specifying (i) whether or not the Company has elected that a Conversion Shares Offer be made and, if so, the Conversion
Shares Offer Period, (ii) the Suspension Date, (iii) details of the Conversion Shares Depository or (iv) if the Company has been unable to appoint a Conversion Shares Depository, such other arrangements for the issuance and/or
delivery of the Conversion Shares or the Conversion Shares Offer Consideration, as applicable, to the Holders of the Securities as it shall consider reasonable in the circumstances. 

“Conversion Shares Offer Period” means the period during which the Conversion Shares Offer may occur, which
period shall end no later than forty (40) Business Days after the delivery of the Conversion Shares Offer Notice. 

  
 - 5 - 

 “Conversion Shares Offer Price” means £1.65 per
Conversion Share (subject to certain anti-dilution adjustments pursuant to Section 3.01 hereof). 
 “Conversion
Shares Settlement Notice” means a written notice (substantially in the form attached hereto as Exhibit E) to be delivered by a Holder or Beneficial Owner (or custodian, broker, nominee or other representative thereof) to the
Conversion Shares Depository (or to the relevant recipient of the Conversion Shares in accordance with the terms of the Securities), with a copy to the Trustee, no earlier than the Suspension Date containing the following information: (i) the
name of the Holder or Beneficial Owner (or custodian, broker, nominee or other representative thereof), (ii) the aggregate amount of the Tradable Amount of the book-entry interests in the Securities held by
such Holder or Beneficial Owner (or custodian, broker, nominee or other representative thereof) on the date of such notice, (iii) the name to be entered in the Company’s share register, (iv) the details of the CREST or other clearing
system account or, if the Conversion Shares are not a participating security in CREST or another clearing system, the address to which the Conversion Shares (or the Conversion Shares Component, if any, of any Conversion Shares Offer Consideration)
and/or cash (if not expected to be delivered through DTC) should be delivered and (v) such other details as may be required by the Conversion Shares Depository. 

“Conversion Shares Settlement Request Notice” means the written notice to be delivered by the Company to the
Trustee directly and to the Holders and Beneficial Owner of the Securities via DTC (or, if the Securities are definitive Securities, by the Company to the Trustee directly and to the Holders at their registered addresses as shown on the Contingent
Capital Security Register) on the Suspension Date requesting that Holders and Beneficial Owners complete a Conversion Shares Settlement Notice and specifying (i) the Notice Cut-off Date and (ii) the
Final Cancellation Date. 
 “CREST” means the relevant system, as defined in the CREST Regulations, or any
successor clearing system. 
 “CREST Regulations” means the Uncertificated Securities Regulations 2001 (SI
2001 No. 01/378), as amended. 
 “CSO Obligations” means the obligations of the Company under the
Securities that may arise in connection with a Conversion Shares Offer to: (i) facilitate the preparation of a prospectus or other offering document, if applicable, and (ii) take responsibility for such prospectus or other offering
document, which obligations (and any claims relating to a failure to facilitate the preparation of, or take responsibility for, such prospectus or other offering document) shall terminate in the event of the
winding-up or administration of the Company. 
 “Current Market
Price” means, in respect of an Ordinary Share at a particular date, the average of the daily Volume Weighted Average Price of an Ordinary Share on 

  
 - 6 - 

 
each of the five (5) consecutive Dealing Days ending on the Dealing Day immediately preceding such date; provided that, if at any time during the said
five-dealing-day period the Volume Weighted Average Price shall have been based on a price ex-Cash Dividend (or ex- any other entitlement) and during some other part of that period the Volume Weighted Average Price shall have been based on a price cum-Cash Dividend (or cum- any other entitlement), then: 
  

	 	(i)	 if the Ordinary Shares to be issued do not rank for the Cash Dividend (or entitlement) in question, the Volume
Weighted Average Price on the dates on which the Ordinary Shares shall have been based on a price cum-Cash Dividend (or cum- any other entitlement) shall, for the
purposes of this definition, be deemed to be the amount thereof reduced by an amount equal to such Cash Dividend or entitlement per ordinary share as at the date of first public announcement relating to such Cash Dividend or entitlement, in any such
case, determined on a gross basis and disregarding any withholding or deduction required to be made on account of tax, and disregarding any associated tax credit; or 

 

	 	(ii)	 if the Ordinary Shares to be issued do rank for the Cash Dividend (or entitlement) in question, the Volume
Weighted Average Price on the dates on which the Ordinary Shares shall have been based on a price ex-Cash Dividend (or ex- any other entitlement) shall, for the purposes
of this definition, be deemed to be the amount thereof increased by an amount equal to such Cash Dividend or entitlement per ordinary share as at the date of first public announcement relating to such Cash Dividend or entitlement, in any such case,
determined on a gross basis and disregarding any withholding or deduction required to be made on account of tax, and disregarding any associated tax credit, 

and provided further that, if on each of the said five Dealing Days the Volume Weighted Average Price shall have been based on a
price cum-Cash Dividend (or cum- any other entitlement) in respect of a Cash Dividend (or other entitlement) which has been declared or announced but the Ordinary Shares
to be issued do not rank for that Cash Dividend (or other entitlement), the Volume Weighted Average Price on each of such dates shall, for the purposes of this definition, be deemed to be the amount thereof reduced by an amount equal to such Cash
Dividend or entitlement per ordinary share as at the date of first public announcement relating to such Cash Dividend or entitlement, in any such case, determined on a gross basis and disregarding any withholding or deduction required to be made on
account of tax, and disregarding any associated tax credit, 
 and provided further that, if the Volume Weighted Average Price

  
 - 7 - 

 
of an Ordinary Share is not available on one or more of the said five Dealing Days (disregarding for this purpose the proviso to the definition of Volume Weighted Average Price), then the average
of such Volume Weighted Average Prices which are available in that five-dealing-day period shall be used (subject to a minimum of two such prices) and if only one, or
no, such Volume Weighted Average Price is available in the relevant period, the Current Market Price shall be determined in good faith by an Independent Financial Adviser. 

“Dealing Day” means a day on which the Relevant Stock Exchange or relevant stock exchange or securities market
is open for business and on which Ordinary Shares may be dealt in (other than a day on which the Relevant Stock Exchange or relevant stock exchange or securities market is scheduled to or does close prior to its regular weekday closing time). 

“DTC” means The Depository Trust Company, or any successor clearing system. 

“Effective Date” means, for the purposes of Section 3.01(c) hereof, the first date on which the Ordinary
Shares are traded ex-rights on the Relevant Stock Exchange and, for the purposes of Section 3.01(d) hereof, the first date on which the Ordinary Shares are traded
ex-the relevant Cash Dividend on the Relevant Stock Exchange. 
 “Equity
Share Capital” has the meaning provided in Section 548 of the Companies Act. 
 “Extraordinary
Dividend” means any Cash Dividend that is expressly declared by the Company to be a capital distribution, extraordinary dividend, extraordinary distribution, special dividend, special distribution or return of value to shareholders or any
analogous or similar term, in which case the Extraordinary Dividend shall be such Cash Dividend. 
 “Final
Cancellation Date” means the date, as specified in the Conversion Shares Settlement Request Notice, on which the Securities in relation to which no Conversion Shares Settlement Notice has been received by the Conversion Shares Depository on
or before the Notice Cut-off Date shall be cancelled, which date may be up to twelve (12) Business Days following the Notice Cut-off Date. 

“Fully Loaded” means, in relation to a measure that is presented or described as being on a “Fully Loaded
basis,” that such measure is determined without applying the transitional provisions set out in Part Ten of the U.K. CRD Regulation in accordance with the Capital Regulations applicable as at the time such measure is determined. 

“Fully Loaded CET1 Ratio” means, at any time, the ratio of CET1 Capital at such time to the Risk Weighted
Assets at such time, expressed as a percentage and on the basis that all measures used in such calculation shall be determined on a Fully Loaded basis. 

“Group” means the Company (or any successor entity) and its consolidated subsidiaries. 

  
 - 8 - 

 “Governmental Entity” means (i) the United Kingdom
Government, (ii) an agency of the United Kingdom Government or (iii) a Takeover Person or entity (other than a body corporate) controlled by the United Kingdom Government or any such agency referred to in clause (ii) of this
definition. If the Company is then organized in another jurisdiction, the references to “United Kingdom Government” shall be read as references to the government of such other jurisdiction. 

“Indenture” has the meaning set forth in the first paragraph of this Sixth Supplemental Indenture. 

“Independent Financial Adviser” means an independent financial institution of international repute appointed
by the Company at its own expense. 
 “Initial Interest Rate” has the meaning set forth in
Section 2.02(a) hereof. 
 “Interest Payment Date” has the meaning set forth in Section 2.02(a)
hereof. 
 “Issue Date” has the meaning set forth in Section 2.01(f) hereof. 

“Junior Securities” means any Ordinary Shares, securities or other obligations (including any guarantee,
credit support or similar undertaking) of the Company ranking, or expressed to rank, junior to the Securities in a winding-up or administration of the Company. 

“LSE” means the London Stock Exchange plc (or its successor). 

“Margin” has the meaning set forth in Section 2.02(a) hereof. 

“New Conversion Condition” means the condition that shall be satisfied if (a) by not later than seven
(7) Business Days following the completion of a Takeover Event where the Acquirer is an Approved Entity, there shall be arrangements in place for the Approved Entity to provide for issuance of Approved Entity Shares following an Automatic
Conversion of the Securities on terms mutatis mutandis identical to the provisions under Section 2.07 below, and (b) the Company, in its sole and absolute discretion has determined that such arrangements are in the best interest of
the Company and its shareholders taken as a whole having regard to the interests of its stakeholders (including, but not limited to, the Holders of the Securities) and are consistent with applicable law and regulation (including, but not limited to,
the guidance of any applicable regulatory body). 

  
 - 9 - 

 “New Conversion Price” means the amount determined in
accordance with the following formula, which shall apply from the QTE Effective Date: 
 NCP = ECP * (VWAPAES / VWAPOS) 

where: 

“NCP” is the New Conversion Price; 

“ECP” is the Conversion Price in effect on the Dealing Day immediately prior to the QTE Effective Date; 

“VWAPAES” means the average of the Volume Weighted Average Price of the Approved Entity Shares (translated, if
necessary, into the same currency as the price of the Ordinary Shares at the Prevailing Rate on the relevant dealing day) on each of the five Dealing Days ending on the Dealing Day prior to the closing date of the Takeover Event (and where
references in the definition of “Volume Weighted Average Price” to “ordinary share” shall be construed as a reference to the Approved Entity Shares and in the definition of “Dealing Day,” references to the
“Relevant Stock Exchange” shall be to the relevant Recognized Stock Exchange); and 
 “VWAPOS” is
the average of the Volume Weighted Average Price of the Ordinary Shares on each of the five Dealing Days ending on the Dealing Day immediately prior to the closing date of the Takeover Event. 

“Notice Cut-off Date” means the date specified as such in the
Conversion Shares Settlement Request Notice, which date shall be at least forty (40) Business Days following the Suspension Date. 

“Ordinary Shares” means (a) prior to the QTE Effective Date, fully paid ordinary shares in the capital of
the Company and (b) on and after the QTE Effective Date, the relevant Approved Entity Shares. 
 “Parity
Securities” means any preference shares, securities or other obligations (including any guarantee, credit support or similar undertaking) of the Company ranking, or expressed to rank, pari passu with the Securities in a winding-up or administration of the Company. 
 “Prevailing Rate” means,
in respect of any currencies on any day, the spot rate of exchange between the relevant currencies prevailing as at or about 12:00 pm, London time, on that date as appearing on or derived from the relevant page on Bloomberg (or such other
information service provider that displays the relevant information) or, if such a rate cannot be determined at such time, the rate prevailing as at or about 12:00 pm, London time, on the immediately preceding day on which such rate can be so
determined or, if such rate cannot be so determined by reference to the relevant page on Bloomberg (or such other information service provider that displays the relevant information), the rate determined in such other manner as an Independent
Financial Adviser shall in good faith prescribe. 
 “Price” means the Conversion Price or the Conversion
Shares Offer Price, as applicable. 
 “Prospectus Supplement” means the prospectus supplement with respect
to the Securities, dated August 4, 2021, supplementing the prospectus dated March 1, 2021. 

  
 - 10 - 

 “QTE Effective Date” means the date with effect from which
the New Conversion Condition shall have been satisfied. 
 “Qualifying Takeover Event” means a Takeover
Event with respect to which: (i) the Acquirer is an Approved Entity; and (ii) the New Conversion Condition is satisfied. 

“Recognized Stock Exchange” means a Regulated Market or another regulated, regularly operating, recognized
stock exchange or securities market in an OECD member state. 
 “Reference Treasury Dealer” means, with
respect to any Reset Determination Date, each of up to five banks selected by the Company, or the affiliates of such banks, which are (i) primary U.S. Treasury securities dealers, and their respective successors, or (ii) market makers in
pricing corporate bond issues denominated in U.S. dollars. 
 “Reference Treasury Dealer Quotations” means,
with respect to each Reference Treasury Dealer and any Reset Determination Date, the arithmetic average, as determined by the Calculation Agent, of the bid and offered prices (such prices being obtained by the Company and furnished to the
Calculation Agent) for the applicable Comparable Treasury Issue, expressed in each case as a percentage of its principal amount, as at 11:00 a.m. (New York City time), on such Reset Determination Date. 

“Regular Record Date” means the close of business on the Business Day immediately preceding each Interest
Payment Date (or, if the Securities are held in definitive form, the close of business on the 15th Business Day preceding each Interest Payment Date). 

“Regulated Market” means a regulated market as defined by Article 4.1(21) of Directive 2014/65/EU of the
European Parliament and of the Council on markets in financial instruments or as defined in Regulation (EU) No 600/2014 as it forms part of U.K. domestic law by virtue of the Withdrawal Act, as each may be amended or replaced from time to time. 

“Regulatory Event” has the meaning set forth in Section 2.05 hereof. 

“Relevant Currency” means sterling or, if at the relevant time or for the purposes of the relevant calculation
or determination the LSE is not the Relevant Stock Exchange, the currency in which the Ordinary Shares are quoted or dealt in on the Relevant Stock Exchange at such time. 

“Relevant Stock Exchange” means the LSE or, if at the relevant time the Ordinary Shares are not at that time
listed and admitted to trading on the LSE, the principal stock exchange or securities market on which the Ordinary Shares are then listed, admitted to trading or quoted or accepted for dealing. 

“Relevant Tax Effect” means a circumstance, as on the date hereof or at any time thereafter, that interest
payments (or funding costs of the Company as recognized in its accounts) under or with respect to the Securities are not or would not be deductible for UK corporation tax purposes (whether for the Company, or for companies with which the Company is
grouped for United Kingdom tax purposes). 

  
 - 11 - 

 “Reset Date” means September 15, 2028 and each fifth
anniversary thereafter. 
 “Reset Determination Date” means the second (2nd) Business Day immediately
preceding each Reset Date. 
 “Reset Period” has the meaning set forth in Section 2.02(a) hereof. 

“Risk Weighted Assets” means, at any time, the aggregate amount, expressed in pounds sterling, of the risk
weighted assets of the Group at such time, as determined by the Company on a consolidated basis in accordance with the Capital Regulations applicable at such time (which determination shall be binding on the Trustee, the Holders and the Beneficial
Owners). For the purposes of this definition, the term “risk weighted assets” means the risk weighted assets or total risk exposure amount, as determined by the Company in accordance with the Capital Regulations. 

“Securities” has the meaning set forth in the Recitals. 

“Settlement Date” means (i) with respect to any Security in relation to which a Conversion Shares
Settlement Notice is received by the Conversion Shares Depository on or before the Notice Cut-off Date, the later of (a) the date that is two (2) Business Days after the end of the relevant
Conversion Shares Offer Period and (b) the date that is two (2) Business Days after the date on which such Conversion Shares Settlement Notice has been received by the Conversion Shares Depository and (ii) with respect to any Security
in relation to which a Conversion Shares Settlement Notice is not received by the Conversion Shares Depository on or before the Notice Cut-off Date, the date on which the Conversion Shares Depository delivers
the relevant Conversion Shares or Conversion Shares Component, if any, of any Conversion Shares Offer Consideration, as applicable. 

“Shareholders” means the holders of Ordinary Shares. 

“Subsequent Interest Rate” has the meaning set forth in Section 2.02(a) hereof. 

“Suspension Date” means the date specified in the Conversion Shares Offer Notice as the date on which DTC
shall suspend all clearance and settlement of transactions in the Securities in accordance with its rules and procedures, which date shall be no later than thirty-eight (38) Business Days after the
delivery of the Conversion Shares Offer Notice to DTC (and, if the Company elects that a Conversion Shares Offer be made, such date shall be at least two (2) Business Days prior to the end of the relevant Conversion Shares Offer Period). 

“Takeover Event” shall mean an offer made to all (or as nearly as may be practicable all) shareholders (or all
(or as nearly as may be practicable all) such shareholders other than the offeror and/or any associate (as defined in Section 988(1) of the Companies Act) of the offeror), to acquire all or a majority of the issued Ordinary Share Capital (as
defined in Section 1119 of the Corporation Tax Act 2010, or any 

  
 - 12 - 

 
successor provision or legislation) of the Company or if any Takeover Person proposes a scheme with regard to such acquisition and (such offer or scheme having become or been declared
unconditional in all respects or having become effective) the right to cast more than 50% of the votes which may ordinarily be cast on a poll at a general meeting of the Company has or will become unconditionally vested in any Takeover Person and/or
any associate of that Takeover Person (as defined in Section 988(1) of the Companies Act). 
 “Takeover Event
Notice” means a notice to the Holders of the Securities notifying them that a Takeover Event has occurred and specifying: (1) the identity of the Acquirer; (2) whether the Takeover Event is a Qualifying Takeover Event or not;
(3) in the case of a Qualifying Takeover Event, if determined at such time, the New Conversion Price; and (4) if applicable, the QTE Effective Date. 

“Takeover Person” includes any individual, company, corporation, firm, partnership, joint venture,
undertaking, association, organization, trust, state or agency of a state (in each case whether or not being a separate legal entity) or other legal entity. 

“Tradable Amount” has the meaning set forth in 2.01(j) hereof. 

“Trustee” has the meaning set forth in the first paragraph of this Sixth Supplemental Indenture. 

“U.S. Treasury Rate” means, with respect to any Reset Period for which such rate applies, the rate per annum
equal to: (1) the yield, under the heading which represents the average for the week immediately prior to the applicable Reset Determination Date, appearing in the most recently published statistical release designated “H.15,” or any
successor publication that is published by the Board of Governors of the Federal Reserve System that establishes yields on actively traded U.S. Treasury securities adjusted to constant maturity, under the caption “Treasury constant
maturities,” for the maturity of five years; or (2) if such release (or any successor release) is not published during the week immediately prior to such Reset Determination Date or does not contain such yields, the rate per annum equal to
the semi-annual equivalent yield to maturity of the Comparable Treasury Issue, calculated using a price for the Comparable Treasury Issue (expressed as a percentage of its principal amount) equal to the Comparable Treasury Price for such Reset
Determination Date; provided that, if the U.S. Treasury Rate cannot be determined, for whatever reason, as described under (1) or (2) above, “U.S. Treasury Rate” means the rate in percentage per annum as notified by the
Calculation Agent to the Company equal to the yield on U.S. Treasury securities having a maturity of five years as set forth in the most recently published statistical release designated “H.15” under the caption “Treasury constant
maturities” (or any successor publication that is published weekly by the Board of Governors of the Federal Reserve System and that establishes yields on actively traded U.S. Treasury securities adjusted to constant maturity under the caption
“Treasury constant maturities” for the maturity of five years) at 5:00 p.m. (New York City time) on the last available date preceding the Reset Determination Date on which such rate was set forth in such release (or any successor release).

  
 - 13 - 

 “Volume Weighted Average Price” means, in respect of an
Ordinary Share (or an Approved Entity Share, as applicable) on any Dealing Day, the order book volume-weighted average price of an Ordinary Share (or Approved Entity Shares, as applicable) published by or
derived from the relevant page on Bloomberg or such other source as shall be determined in good faith to be appropriate by an Independent Financial Adviser on such Dealing Day, provided that if on any such Dealing Day such price is not available or
cannot otherwise be determined as provided above, the “Volume Weighted Average Price” of an ordinary share (or an Approved Entity Shares, as applicable) in respect of such Dealing Day shall be the volume weighted average price, determined
as provided above, on the immediately preceding Dealing Day on which the same can be so determined or determined as an Independent Financial Adviser might otherwise determine in good faith to be appropriate. 

SECTION 1.02. Effect of Headings. 

The Article and Section headings herein are for convenience only and shall not affect the construction hereof. 

SECTION 1.03. Separability Clause. 

In case any provision in this Sixth Supplemental Indenture shall be invalid, illegal or unenforceable, the validity, legality and
enforceability of the remaining provisions shall not in any way be affected or impaired thereby. 
 SECTION 1.04. Benefits of
Instrument. 
 Nothing in this Sixth Supplemental Indenture, express or implied, shall give to any person, other than the parties hereto
and their successors hereunder and the Holders, any benefit or any legal or equitable right, remedy or claim under the Indenture. 

SECTION 1.05. Relation to Base Indenture. 

This Sixth Supplemental Indenture constitutes an integral part of the Base Indenture. All provisions of this Sixth Supplemental Indenture are
expressly and solely for the benefit of the Holders and Beneficial Owners of the Securities and any such provisions shall not be deemed to apply to any other Contingent Capital Securities issued under the Base Indenture and shall not be deemed to
amend, modify or supplement the Base Indenture for any purpose other than with respect to the Securities. 
 SECTION 1.06.
Construction and Interpretation 
 Unless the express otherwise requires: 

(a) the words “hereof”, “herein” and “hereunder” and words of similar import, when used in this Sixth
Supplemental Indenture, refer to this Sixth Supplemental Indenture as a whole and not to any particular provision of this Sixth Supplemental Indenture; 

(b) the terms defined in the singular have a comparable meaning when used in the plural, and vice versa; 

  
 - 14 - 

 (c) the terms “U.S. dollars” and “$” refer to the lawful currency for
the time being of the United States; 
 (d) the terms “pounds sterling,” “sterling” and “£” mean British
pounds sterling; 
 (e) references herein to a specific Section, Article or Exhibit refer to Sections or Articles of, or an Exhibit to, this
Sixth Supplemental Indenture; 
 (f) wherever the words “include”, “includes” or “including” are used in this
Sixth Supplemental Indenture, they shall be deemed to be followed by the words “without limitation;” 
 (g) references to a Person
are also to its successors and permitted assigns; 
 (h) the use of “or” is not intended to be exclusive unless expressly
indicated otherwise; 
 (i) for purposes of Article III of this Sixth Supplemental Indenture, references therein to any act or statute or
any provision of any act or statute shall be deemed also to refer to any statutory modification or re-enactment thereof or any statutory instrument, order or regulation made thereunder or under such
modification or re-enactment; and 
 (j) references to any issue or offer or grant to Shareholders
“as a class” or “by way of rights” shall be taken to be references to an issue or offer or grant to all or substantially all Shareholders, as the case may be, other than Shareholders, as the case may be, to whom, by reason of the
laws of any territory or requirements of any recognized regulatory body or any other stock exchange or securities market in any territory or in connection with fractional entitlements, it is determined not to make such issue or offer or grant. 

  
 - 15 - 

 ARTICLE II 

$1,500,000,000 4.375% FIXED RATE RESETTING PERPETUAL SUBORDINATED CONTINGENT CONVERTIBLE SECURITIES 

SECTION 2.01. Creation of Series; Establishment of Form. 

(a) There is hereby established a new series of Contingent Capital Securities under the Base Indenture entitled the “$1,500,000,000
4.375% Fixed Rate Resetting Perpetual Subordinated Contingent Convertible Securities.” 
 (b) The Securities shall be issued initially
in the form of one or more registered Global Securities that shall be deposited with DTC on the Issue Date. The Global Securities shall be registered in the name of Cede & Co. and executed and delivered in substantially the form attached
hereto as Exhibit A. 
 (c) The Company shall issue the Securities in an aggregate principal amount of $1,500,000,000. The Company
may from time to time, without the consent of the Holders of the Securities, issue additional securities having the same ranking and same interest rate, interest cancellation terms, redemption terms, Conversion Price and other terms as the
Securities described in this Sixth Supplemental Indenture, except for the price to public and date of issue. Any such additional securities subsequently issued shall rank equally and ratably with the Securities in all respects, so that such further
securities shall be consolidated and form a single series with the Securities. 
 (d) Any proposed transfer of an interest in Securities
held in the form of a Global Security and shall be effected through the book-entry system maintained by DTC. 
 (e) The Securities shall not
have a sinking fund. 
 (f) The Securities shall be issued on August 11, 2021 (the “Issue Date”). 

(g) The Securities shall have no fixed maturity or fixed redemption date, and shall not be redeemable except as provided in Sections 2.04 and
2.05 hereof and Section 11.12 of the Base Indenture. 
 (h) The interest rate on the Securities shall be determined as set forth in
Section 2.02(a) hereof. 
 (i) The Securities shall be issued in denominations of $200,000 in principal amount and integral multiples
of $1,000 in excess thereof. The denominations cannot be changed without the consent of the Trustee. 
 (j) The denomination of each
interest in a Global Security shall be the “Tradable Amount” of such book-entry interest. Prior to an Automatic Conversion, the aggregate Tradable Amount of the interests in each Global
Security shall be equal to such Global Security’s outstanding principal amount. Following an Automatic Conversion, the principal amount of each Security shall be zero, but the Tradable Amount of the
book-entry interests in each Security shall remain unchanged. 

  
 - 16 - 

 SECTION 2.02. Interest. 

(a) From (and including) the Issue Date to (but excluding) September 15, 2028 the interest rate on the Securities shall be 4.375% per
annum (the “Initial Interest Rate”). From and including each Reset Date to (but excluding) the next following Reset Date (each such period, a “Reset Period”), the applicable per annum interest rate (the
“Subsequent Interest Rate”) will, subject to Section 2.02(b) herein, be equal to the sum, as determined by the Calculation Agent, of the then prevailing U.S. Treasury Rate on the relevant Reset Determination Date and 3.410%
(the “Margin”). Each Subsequent Interest Rate shall be determined in compliance with the relevant Capital Regulations. Subject to Sections 3.12 and 3.13 of the Base Indenture and the penultimate sentence of this paragraph, interest,
if any, shall be payable quarterly in arrear on March 15, June 15, September 15 and December 15 of each year (each, an “Interest Payment Date”), commencing on December 15, 2021; provided that
if such Interest Payment Date is not a Business Day, the Interest Payment Date shall be postponed to the next Business Day, but interest on that payment will not accrue during the period from and after the Interest Payment Date. Subject to Sections
3.12 and 3.13 of the Base Indenture, the interest rate on the Securities, if any, will be computed on the basis of a year of 360 days consisting of 12 months of 30 days each and, in the case of an incomplete month, the actual number of days elapsed.
The first date on which interest may be paid will be December 15, 2021 for the period commencing on (and including) August 11, 2021 and ending on (but excluding) December 15, 2021 (and thus a long first interest period). If a date of
redemption is not a Business Day, the Company may pay interest (if any) and principal on the next Business Day, but interest on that payment will not accrue during the period from and after the date of redemption. 

(b) In addition to any other restrictions on payments of principal and interest contained in the Indenture, no repayment of the principal
amount of the Securities or payment of interest on the Securities shall become due and payable after the exercise of any U.K. Bail-in Power by the Relevant U.K. Resolution Authority unless such repayment or
payment would be permitted to be made by the Company under the laws and regulations of the United Kingdom and the European Union applicable to the Company. 

SECTION 2.03. Payment of Principal, Interest and Other Amounts. Payments of principal of and interest, if any, on the Securities
shall be made in such coin or currency of the United States of America as at the time of payment is legal tender for payment of public and private debts and such payments on Securities represented by a Global Security shall be made through one or
more Paying Agents appointed under the Base Indenture to DTC or its nominee, as the Holder or Holders of the Global Security. Initially, the Paying Agent for the Securities shall be The Bank of New York Mellon, London Branch, One Canada Square,
London E14 5AL, United Kingdom and the Contingent Capital Security Registrar shall be The Bank of New York Mellon SA/NV, Luxembourg Branch, 2-4 Rue Eugene Ruppert, Vertigo Building – Polaris, Luxembourg, L-2453, Luxembourg. The Company may change the Paying Agent without prior notice to the Holders of the Securities, and in such an event the Company may act as Paying Agent or Contingent Capital Security Registrar.
Payments of principal of and interest on the Securities represented by a Global Security shall be made by wire transfer of immediately available funds; provided, however, that in the case of payments of principal, such Global Security
is first surrendered to the Paying Agent. 

  
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 SECTION 2.04. Optional Redemption. Subject to the limitations specified in
Section 2.06 of this Sixth Supplemental Indenture and Section 11.08 of the Base Indenture, the Company may, at the Company’s option, redeem the Securities, in whole but not in part, on any day falling in the period commencing on (and
including) March 15, 2028 and ending on (and including) the first Reset Date or on any subsequent Reset Date at a redemption price equal to 100% of the principal amount of the Securities then Outstanding, together with any accrued but unpaid
interest (which excludes any interest cancelled or deemed cancelled as described in Sections 3.12 and 3.13 of the Base Indenture to (but excluding) the date fixed for redemption. 

SECTION 2.05. Regulatory Event Redemption. Subject to Section 2.06 of this Sixth Supplemental Indenture and
Section 11.08 of the Base Indenture, the Company may, at the Company’s option, at any time, redeem the Securities, in whole but not in part, at a redemption price equal to 100% of the principal amount of the Securities then Outstanding,
together with any accrued but unpaid interest (which excludes any interest cancelled or deemed cancelled as described in Sections 3.12 and 3.13 of the Base Indenture) to (but excluding) the date fixed for redemption, if, on or after the Issue Date,
there is a change in the regulatory classification of the Securities that does, or would be likely to, result in the whole or any part of the outstanding aggregate principal amount of the Securities at any time being excluded from, or ceasing to
count towards, the Group’s Tier 1 Capital (a “Regulatory Event”). 
 SECTION 2.06. Notice of Redemption.
Before the Company may redeem the Securities pursuant to Section 2.04 or Section 2.05 of this Sixth Supplemental Indenture or Section 11.12 of the Base Indenture, the Company shall deliver via DTC (or, if the Securities are definitive
Securities, to the Holders at their addresses shown on the Contingent Capital Security Register) prior notice of not less than thirty (30) days, nor more than sixty (60) days to the Holders of the Securities. The Company shall deliver
written notice of such redemption of the Securities to the Trustee at least five (5) Business Days prior to the date on which the relevant notice of redemption is sent to Holders (unless a shorter notice period shall be satisfactory to the
Trustee). Such notice shall specify the Company’s election to redeem the Securities and the date fixed for such redemption and shall be irrevocable except in the limited circumstances described in Sections 11.04(d), (e) and (f) of the Base
Indenture. The Company shall not be entitled to deliver a notice of redemption after an Automatic Conversion Notice has been delivered. 

SECTION 2.07. Automatic Conversion upon Capital Adequacy Trigger Event. 

(a) If a Capital Adequacy Trigger Event has occurred, then the Automatic Conversion shall occur on the Conversion Date, at which point all of
the Company’s obligations under the Securities (other than the CSO Obligations, if any) shall be irrevocably and automatically released in consideration of the Company’s issuance of the Conversion Shares to the Conversion Shares Depository
(or to the relevant recipient in accordance with the terms of the Securities) on the Conversion Date at the Conversion Price. Under no circumstances shall such released obligations be reinstated. If the Company has been unable to appoint a
Conversion Shares Depository, it shall make such other arrangements for the issuance and/or delivery of the 

  
 - 18 - 

 
Conversion Shares or Conversion Shares Offer Consideration, as applicable, to the Holders of the Securities as it shall consider reasonable in the circumstances (including, without limitation,
issuance of the Conversion Shares to another nominee or to the Holders of the Securities directly), and such issuance shall irrevocably and automatically release all of the Company’s obligations under the Securities (other than the CSO
Obligations, if any) as if the Conversion Shares had been issued to the Conversion Shares Depository. 
 (b) The Automatic Conversion shall
occur without delay upon the occurrence of a Capital Adequacy Trigger Event. 
 (c) The Company shall (a) immediately inform the PRA of
the occurrence of a Capital Adequacy Trigger Event and (b) deliver an Automatic Conversion Notice to the Trustee directly and to the Holders via DTC as soon as practicable after such time. 

(d) The date on which the Automatic Conversion Notice shall be deemed to have been given shall be the date on which it is dispatched by the
Company to DTC (or, if the Securities are definitive Securities, to the Trustee). 
 (e) The Company shall request that DTC post the
Automatic Conversion Notice on its Reorganization Inquiry for Participants System pursuant to DTC’s procedures then in effect (or such other system as DTC uses for providing notices to holders of securities). Within two (2) Business Days
of its receipt of the Automatic Conversion Notice, the Trustee shall transmit the Automatic Conversion Notice to the direct participants of DTC holding the Securities at such time. 

(f) The Automatic Conversion shall occur on the Conversion Date and all of the Company’s obligations under the Securities (other than the
CSO Obligations, if any) shall be irrevocably and automatically released in consideration of the Company’s issuance of the Conversion Shares to the Conversion Shares Depository (or to the relevant recipient in accordance with the terms of the
Securities), and the principal amount of the Securities shall equal zero at all times thereafter (for the avoidance of doubt, the Tradable Amount shall remain unchanged) as a result of the Automatic Conversion. 

(g) Within ten (10) Business Days following the Conversion Date, the Company shall deliver a Conversion Shares Offer Notice to the
Trustee directly and to the Holders of the Global Securities via DTC (or, if the Securities are definitive Securities, by the Company to the Trustee directly and to the Holders at their addresses shown on the Contingent Capital Security Register).

 (h) The Conversion Shares shall initially be registered in the name of the Conversion Shares Depository (or the relevant recipient in
accordance with the terms of the Securities, as applicable) and each Holder and Beneficial Owner of the Securities shall be deemed to have irrevocably directed the Company to issue the Conversion Shares corresponding to the conversion of its holding
of Securities to the Conversion Shares Depository (or to such other relevant recipient). 
 (i) The Conversion Shares Depository (or the
relevant recipient in accordance with the terms of the Securities, as applicable) shall hold the Conversion Shares on behalf of the 

  
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Holders and Beneficial Owners of the Securities, who shall be entitled to direct (each in respect of their pro rata share of the Conversion Shares) the Conversion Shares Depository or such
other relevant recipient, as applicable, to exercise on their behalf all rights of an ordinary shareholder (including voting rights and rights to receive dividends); provided, however, that Holders and Beneficial Owners shall not be
able to sell or otherwise transfer the Conversion Shares until such time as the Conversion Shares have been delivered to the Holders or Beneficial Owners in accordance with the procedures set forth under Section 2.10 hereof. A Holder or
Beneficial Owner’s pro rata share of the Conversion Shares at any particular time shall be determined based on the aggregate amount of the Tradable Amount of the Securities held by such Holder or Beneficial Owner as a proportion of the
aggregate amount of the Tradable Amount of all Securities outstanding at the relevant time rounded down, if necessary, to the nearest whole number of Conversion Shares. 

(j) Provided that the Company issues the Conversion Shares to the Conversion Shares Depository (or the relevant recipient in accordance with
the terms of the Securities) in accordance with the terms of the Securities, with effect from the Conversion Date, Holders and Beneficial Owners of the Securities shall have recourse only to the Conversion Shares Depository (or to such other
relevant recipient, as applicable) for the delivery to them of Conversion Shares or, if the Company elects that a Conversion Shares Offer be made, of any Conversion Shares Offer Consideration to which such Holders and Beneficial Owners are entitled.

 (k) Effective upon, and following, the occurrence of the Automatic Conversion, Holders and Beneficial Owners shall not have any rights
against the Company with respect to repayment of the principal amount of the Securities or payment of interest or any other amount on or in respect of such Securities, which liabilities of the Company shall be irrevocably and automatically released,
and accordingly the principal amount of the Securities shall equal zero at all times thereafter. Any interest in respect of an interest period ending on any Interest Payment Date falling between the date of a Capital Adequacy Trigger Event and the
Conversion Date shall be deemed to have been cancelled pursuant to Section 3.12 of the Base Indenture upon the occurrence of such Capital Adequacy Trigger Event and shall not be due and payable. 

(l) By subscribing for, purchasing or otherwise acquiring the Securities, each Holder and each Beneficial Owner shall be deemed to have
(i) acknowledged and agreed that an interest payment shall not be due and payable on the relevant Interest Payment Date if it has been cancelled or deemed cancelled (in each case, in whole or in part) for any reason in accordance with the terms
of the Securities, (ii) consented to (x) the Automatic Conversion, including the appointment of a Conversion Shares Depository and the issuance of the Conversion Shares thereto (or any related Conversion Shares Offer Consideration,
including the appointment of any Conversion Shares Offer Agent and the sale of the Conversion Shares by the Conversion Shares Depository), and acknowledged that such Automatic Conversion of its Securities (and any related Conversion Shares Offer)
may occur without any further action on the part of such Holder or Beneficial Owner or the Trustee and (y) the exercise of any U.K. Bail-in Power as it may be imposed without any prior notice by the
Relevant U.K. Resolution Authority of its decision to exercise such power with respect to the Securities and (iii) authorized, directed and requested DTC and any direct participant in DTC or other intermediary through which it holds such
Securities to take any and all necessary action, if required, to implement (x) the Automatic 

  
 - 20 - 

 
Conversion (including any related Conversion Shares Offer) and (y) the exercise of any U.K. Bail-in Power with respect to the Securities as it may be
imposed, without any further action or direction on the part of such Holder or Beneficial Owner or the Trustee. 
 (m) The procedures set
forth in this Section 2.07 are subject to change to reflect changes in DTC practices, and the Company may make changes to the procedures set forth in this Section 2.07 to the extent reasonably necessary, in the opinion of the Company, to
reflect such changes in DTC practices. 
 (n) Notwithstanding anything to the contrary contained in the Indenture or the Securities, once
the Company has delivered an Automatic Conversion Notice to DTC following the occurrence of a Capital Adequacy Trigger Event (or following an Automatic Conversion (if sooner)), (i) the Holders and Beneficial Owners shall have no rights whatsoever
under the Indenture or the Securities to instruct the Trustee to take any action whatsoever and (ii) as of the date of the Automatic Conversion Notice, except for any indemnity and/or security provided by any Holder or by any Beneficial Owner
in such direction or related to such direction, any direction previously given to the Trustee by any Holders or by any Beneficial Owners shall cease automatically and shall be null and void and of no further effect; except in each case of
(i) and (ii) of this Section 2.07(n), with respect to any rights of Holders or Beneficial Owners with respect to any payments under the Securities that were unconditionally due and payable prior to the date of the Automatic Conversion
Notice (if any) or unless the Trustee is instructed in writing by the Company to act otherwise. 
 (o) On or (if reasonably practicable)
prior to delivering the Automatic Conversion Notice, the Company shall deliver to the Trustee a certificate signed by two Authorized Officers, in the form attached hereto as Exhibit C, specifying that a Capital Adequacy Trigger Event has
occurred (the “Capital Adequacy Trigger Event Officers’ Certificate”). The Trustee is entitled to conclusively rely on and accept such Capital Adequacy Trigger Event Officers’ Certificate without any duty whatsoever of
further inquiry as sufficient and conclusive evidence of the occurrence of a Capital Adequacy Trigger Event, and such Capital Adequacy Trigger Event Officers’ Certificate shall be conclusive and binding on the Trustee, the Holders and the
Beneficial Owners. 
 (p) All authority conferred or agreed to be conferred by each Holder and Beneficial Owner pursuant to this
Section 2.07, including the consents given by such Holder and Beneficial Owner, shall be binding upon the successors, assigns, heirs, executors, administrators, trustees in bankruptcy and legal representatives of such Holder and Beneficial
Owner. 
 (q) The Trustee shall not be liable with respect to (i) the calculation or accuracy of the Fully Loaded CET1 Ratio in
connection with the occurrence of a Capital Adequacy Trigger Event and the timing of such Capital Adequacy Trigger Event, (ii) the failure of the Company to post or deliver the underlying Fully Loaded CET1 Ratio calculations of a Capital
Adequacy Trigger Event to DTC, the Holders or the Beneficial Owners, (iii) any aspect of the Company’s decision to deliver an Automatic Conversion Notice or the related Automatic Conversion or (iv) the adequacy of the disclosure of
these provisions in the Prospectus Supplement or for the direct or indirect consequences thereof. 

  
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 (r) Following the issuance of the Conversion Shares to the Conversion Shares Depository (or
to the relevant recipient in accordance with the terms of the Securities) on the Conversion Date, the Securities shall remain in existence until the applicable Cancellation Date for the sole purpose of evidencing (a) the Holders’ and
Beneficial Owners’ right to receive Conversion Shares or Conversion Shares Offer Consideration, as applicable, from the Conversion Shares Depository (or such other relevant recipient, as applicable) and (b) the Company’s CSO
Obligations, if any. 
 (s) The Holders and Beneficial Owners shall not at any time have the option to convert to the Securities into
Conversion Shares. 
 (t) The occurrence of an Automatic Conversion shall not constitute a Default. 

(u) Notwithstanding any other provision herein, by subscribing for, purchasing or otherwise acquiring the Securities, each Holder and each
Beneficial Owner (i) agrees to all of the terms of the Securities, including, without limitation, those related to (x) the occurrence of a Capital Adequacy Trigger Event and any related Automatic Conversion and (y) the appointment of
the Conversion Shares Depository, the issuance of the Conversion Shares to the Conversion Shares Depository (or to the relevant recipient in accordance with the terms of the Securities) and the potential sale of the Conversion Shares pursuant to a
Conversion Shares Offer, (ii) agrees that effective upon, and following, the occurrence of the Automatic Conversion, no amount shall be due and payable to the Holders or the Beneficial Owners under the Securities and the liability of the
Company to pay any such amounts (including the principal amount of, or any interest in respect of, the Securities) shall be automatically released, and the Holders and the Beneficial Owners shall not have the right to give any direction to the
Trustee with respect to the Capital Adequacy Trigger Event and any related Automatic Conversion and (iii) waives, to the extent permitted by the Trust Indenture Act, any claim against the Trustee arising out of its acceptance of its trusteeship
for the Securities, including, without limitation, claims related to or arising out of or in connection with a Capital Adequacy Trigger Event and/or any Automatic Conversion. 

SECTION 2.08. Conversion Shares. 

(a) The number of Conversion Shares to be issued to the Conversion Shares Depository on the Conversion Date shall be determined by dividing
the (i) aggregate principal amount of the Outstanding Securities immediately prior to the Automatic Conversion on the Conversion Date by (ii) the Conversion Price rounded down, if necessary, to the nearest whole number of Conversion
Shares. Fractions of Conversion Shares shall not be issued following an Automatic Conversion and no cash payment shall be made in lieu thereof. Upon Automatic Conversion on the Conversion Date, the number of Conversion Shares to be held by the
Conversion Shares Depository for the benefit of each Holder shall be the number of Conversion Shares thus calculated multiplied by a fraction equal to the aggregate amount of the Tradable Amount of the
book-entry interests in the Securities held by such Holder on the Conversion Date divided by the aggregate amount of the Tradable Amount of the book-entry interests of
all the Outstanding Securities immediately prior to the Automatic Conversion on the Conversion Date rounded down, if necessary, to the nearest whole number of Conversion Shares. 

  
 - 22 - 

 (b) The Conversion Shares issued following an Automatic Conversion shall be fully paid and non-assessable and shall in all respects rank pari passu with the fully paid Ordinary Shares of the Company in issue on the Conversion Date, except in any such case for any right excluded by mandatory
provisions of applicable law, and except that the Conversion Shares so issued shall not rank for (or, as the case may be, the relevant Holder or Beneficial Owner shall not be entitled to receive) any rights, the entitlement to which falls prior to
the Conversion Date. 
 (c) Subject to Section 3.05, if a Qualifying Takeover Event occurs, and the Conversion Date falls on or after
the QTE Effective Date, then in such case Approved Entity Shares of the Approved Entity shall be issued to the Conversion Shares Depository on the Conversion Date instead of Conversion Shares with the same effect as if Conversion Shares had been
issued pursuant to Section 2.08(a) above. 
 (d) The Conversion Shares or the Conversion Shares Offer Consideration, as the case may
be, will be delivered to Holders pursuant to the procedures set forth in Section 2.10 below. 
 SECTION 2.09. Conversion Shares
Offer. 
 (a) No later than 10 (ten) Business Days following the Conversion Date, the Company may, in its sole and absolute discretion,
elect that the Conversion Shares Depository make an offer of all or some of the Conversion Shares to all or some of the Company’s ordinary shareholders at a cash price per Conversion Share equal to the Conversion Shares Offer Price, subject as
provided in this Section 2.09 (the “Conversion Shares Offer”). The Company may, on behalf of the Conversion Shares Depository, appoint a Conversion Shares Offer Agent to act as placement or other agent to facilitate the
Conversion Shares Offer. The Company will deliver a Conversion Shares Offer Notice to the Trustee directly and to the Holders of the Securities via DTC within ten (10) Business Days following the Conversion Date specifying whether or not it has
elected that a Conversion Shares Offer be conducted. If the Company elects a Conversion Shares Offer to be conducted, the Conversion Shares Offer Period, during which time the Conversion Shares Offer may be made, shall end no later than forty
(40) Business Days following the delivery of the Conversion Shares Offer Notice. 
 (b) Any Conversion Shares Offer shall be made
subject to applicable laws and regulations in effect at the relevant time and shall be conducted, if at all, only to the extent that the Company, in its sole and absolute discretion, determines that the Conversion Shares Offer is practicable. The
Company or the purchasers of the Conversion Shares sold in any Conversion Shares Offer shall bear the costs and expenses of any Conversion Shares Offer (with the exception of any stamp duty, stamp duty reserve tax, or any other capital, issue,
transfer, registration, financial transaction or documentary tax that may arise or be paid as a consequence of the transfer of Conversion Shares to the Conversion Shares Depository as a consequence of the Conversion Shares Offer), including the fees
of the Conversion Shares Offer Agent, if any. If a prospectus or other offering document is required to be prepared in connection with a Conversion Shares Offer, the Company shall facilitate the preparation of such prospectus or other offering
document, and the Company and/or its directors shall take responsibility for such prospectus or other offering document, in each case, if and to the extent then required by 

  
 - 23 - 

 
applicable laws and regulations then in effect. If so requested by the Conversion Shares Depository as offeror, the Company shall indemnify the Conversion Shares Depository for any losses
incurred in connection with any Conversion Shares Offer. 
 (c) Upon completion of the Conversion Shares Offer, the Company or the
Conversion Shares Depository shall provide notice to the Holders of the Securities of the composition of the Conversion Shares Offer Consideration (and of the deductions to the Cash Component, if any, of the Conversion Shares Offer Consideration (as
set out in the definition of “Conversion Shares Offer Consideration” in Section 1.01)) per $1,000 Tradable Amount of the Securities. The Company reserves the right, in its sole and absolute discretion, to terminate the
Conversion Shares Offer at any time during the Conversion Shares Offer Period by providing at least three (3) Business Days’ notice to the Trustee directly and to the Holders of the Global Securities via DTC (or, if the Securities are
definitive Securities, by the Company to the Trustee directly and to the Holders at their addresses shown on the Contingent Capital Security Register), and, if it does so, the Company may, in its sole and absolute discretion, take steps (including,
without limitation, changing the Suspension Date) to deliver to Holders and Beneficial Owners (or the custodian, nominee, broker or other representative thereof) of the Securities the Conversion Shares at a time that is earlier than the time at
which such Holders and Beneficial Owners (or the custodian, nominee, broker or other representative thereof) would have otherwise received the Conversion Shares Offer Consideration, had the Conversion Shares Offer been completed. 

(d) If the Company elects, in its sole and absolute discretion, that a Conversion Shares Offer be conducted by the Conversion Shares
Depository, each Holder or Beneficial Owner, by subscribing for, purchasing or otherwise acquiring the Securities, shall be deemed to have: (i) irrevocably consented to (x) any Conversion Shares Offer and to the Conversion Shares
Depository’s using the Conversion Shares to settle any Conversion Shares Offer in accordance with the terms of the Securities and (y) the transfer of the beneficial interest it holds in the Conversion Shares to the Conversion Shares
Depository in connection with the Conversion Shares Offer in accordance with the terms of the Securities, and (ii) irrevocably agreed that (x) the Company, the Conversion Shares Depository and the Conversion Shares Offer Agent, if any, may
take any and all actions necessary to conduct the Conversion Shares Offer in accordance with the terms of the Securities, (y) none of the Company, the Trustee, the Conversion Shares Depository or the Conversion Shares Offer Agent, if any,
shall, to the extent permitted by applicable law, incur any liability to the Holders or Beneficial Owners in respect of the Conversion Shares Offer (except for the obligations of the Conversion Shares Depository in respect of the Holders’ and
Beneficial Owners’ entitlement to any Conversion Shares Offer Consideration) and (z) DTC and any direct participant in DTC or other intermediary through which it holds such Securities is authorized, directed and requested to take any and
all necessary action, if required, to implement the Automatic Conversion (including any related Conversion Shares Offer). 

SECTION 2.10. Settlement Procedure. 

(a) Delivery of the Conversion Shares or Conversion Shares Offer Consideration, as applicable, to the Holders and Beneficial Owners of the
Securities shall be made in accordance with the procedures set forth in this Section 2.10, which remain subject to change to reflect changes in clearing system practices. 

  
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 (b) The Conversion Shares Offer Notice shall specify the Suspension Date. 

(c) On the Suspension Date, the Company shall deliver, to the Trustee directly and to the Holders and of the Global Securities via DTC (or, if
the Securities are definitive Securities, by cheque mailed to the Holders at their addresses shown on the Contingent Capital Security Register) a Conversion Shares Settlement Request Notice, pursuant to which the Company shall request that Holders
and Beneficial Owners complete a Conversion Shares Settlement Notice and shall specify the Notice Cut-off Date and the Final Cancellation Date. 

(d) Holders and Beneficial Owners (or the custodian, nominee, broker or other representative thereof) shall not receive delivery of the
relevant Conversion Shares or Conversion Shares Component, as applicable, unless such Holders or Beneficial Owners (or the custodian, nominee, broker or other representative thereof) deliver the applicable Conversion Shares Settlement Notice to the
Conversion Shares Depository on or before the Notice Cut-off Date; provided that, if such delivery is made after the end of normal business hours at the specified office of the Conversion Shares
Depository, such delivery shall be deemed for all purposes to have been made or given on the next following Business Day. 
 (e) With
respect to any Global Securities, the Conversion Shares Settlement Notice must be given in accordance with the standard procedures of DTC (which may include, without limitation, delivery of the notice to the Conversion Shares Depository by
electronic means) and in a form acceptable to DTC and the Conversion Shares Depository. With respect to any definitive Securities, the Conversion Shares Settlement Notice must be delivered to the specified office of the Conversion Shares Depository
together with the relevant Securities. 
 (f) Subject to satisfaction of the requirements and limitations set forth in this
Section 2.10 and provided that the Conversion Shares Settlement Notice and the relevant Securities, if applicable, are delivered on or before the Notice Cut-Off Date, the Conversion Shares Depository
shall deliver the relevant Conversion Shares (rounded down to the nearest whole number of Conversion Shares) or Conversion Shares Component (rounded down to the nearest whole number of Conversion Shares), as applicable, to the Holder or Beneficial
Owner (or custodian, nominee, broker or other representative thereof) of the relevant Securities completing the relevant Conversion Shares Settlement Notice or its nominee in accordance with the instructions given in such Conversion Shares
Settlement Notice on the applicable Settlement Date. 
 (g) Each Conversion Shares Settlement Notice shall be irrevocable. The Conversion
Shares Depository shall determine, in its sole and absolute discretion, whether any Conversion Shares Settlement Notice has been properly completed and delivered, and such determination shall be conclusive and binding on the relevant Holder or
Beneficial Owner. If any Holder or Beneficial Owner fails to properly complete and deliver a Conversion Shares Settlement Notice and the relevant Securities, if applicable, the Conversion Shares Depository shall be entitled to treat such Conversion
Shares Settlement Notice as null and void. 

  
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 (h) Neither the Company, nor any member of the Group shall be liable for any stamp duty,
stamp duty reserve tax, or any other capital, issue, transfer, registration, financial transaction or documentary tax that may arise or be paid as a consequence of the delivery of Conversion Shares or Conversion Shares Component, as applicable,
which tax shall be borne solely by the Holder, Beneficial Owner or, if different, the person to whom the Conversion Shares or that portion, if any, of any Conversion Shares Offer Consideration consisting of Conversion Shares, as applicable, is
delivered. 
 (i) The Conversion Shares and any Conversion Shares Component shall not be available for delivery (i) to, or to a nominee
for, Euroclear or Clearstream, Luxembourg or any other person providing a clearance service within the meaning of Section 96 of the Finance Act 1986 of the United Kingdom or (ii) to a person, or nominee or agent for a person, whose
business is or includes issuing depository receipts within the meaning of Section 93 of the Finance Act 1986 of the United Kingdom, in each case at any time prior to the “abolition day” as defined in Section 111(1) of the Finance
Act 1990 of the United Kingdom, or, if earlier, such other time at which the Company, in its absolute discretion, determines that no charge under Section 67, 70, 93 or 96 of the Finance Act 1986 or any similar charge (under any successor
legislation) would arise as a result of such delivery or (iii) to the CREST account of such a person described in (i) or (ii). 

(j) The Company may make changes to the procedures set forth in this Section 2.10 to the extent such changes are reasonably necessary, in
the opinion of the Company, to effect the delivery of the Conversion Shares or Conversion Shares Offer Consideration, as applicable, to the Holders and Beneficial Owners of the Securities. 

SECTION 2.11. Failure to Deliver a Conversion Shares Settlement Notice. If any Holder or Beneficial Owner (or custodian, nominee,
broker or other representative thereof) fails to deliver a Conversion Shares Settlement Notice and the relevant Securities, if applicable, to the Conversion Shares Depository on or before the Notice Cut-off
Date, the Conversion Shares Depository shall continue to hold the Conversion Shares or any Conversion Shares Component, as applicable to such Holder or Beneficial Owner, until a Conversion Shares Settlement Notice (and the relevant Securities, if
applicable) is so delivered; provided, however, that the relevant Securities shall be cancelled on the Final Cancellation Date, and any Holder or Beneficial Owner (or custodian, nominee, broker or other representative thereof) of
Securities delivering a Conversion Shares Settlement Notice after the Notice Cut-off Date shall be required provide evidence of its entitlement to the relevant Conversion Shares or the Conversion Shares
Component of any Conversion Shares Offer Consideration, as applicable, satisfactory to the Conversion Shares Depository in its sole and absolute discretion in order to receive delivery of such Conversion Shares or of the Conversion Shares Component
of any Conversion Shares Offer Consideration, as applicable. The Company shall have no liability to any Holder or Beneficial Owner of the Securities for any loss resulting from such Holder’s or Beneficial Owner’s failure to receive any
Conversion Shares or Conversion Shares Component of any Conversion Shares Offer Consideration, as applicable, or from any delay in the receipt thereof, in each case as a result of such Holder or Beneficial Owner (or custodian, nominee, broker or
other representative thereof) failing to duly submit a Conversion Shares Settlement Notice and the relevant Securities, if applicable, on a timely basis or at all. 

  
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 SECTION 2.12. Additional Amounts and FATCA Withholding Tax. The Company agrees,
to the extent the Company has actual knowledge of such information, to provide the Paying Agent with sufficient information about any modification to the terms of the Securities for the purposes of determining whether FATCA Withholding Tax applies
to any payment of principal or interest on the Securities. 
 ARTICLE III 

ANTI-DILUTION 

SECTION 3.01. Adjustment of Conversion Price and Conversion Shares Offer Price. Upon the occurrence of any of the events described
below, the Conversion Price and the Conversion Shares Offer Price shall be adjusted as follows: 
 (a) If and whenever there shall be a
consolidation, reclassification or subdivision in relation to the Ordinary Shares of the Company, each of the Conversion Price and the Conversion Shares Offer Price shall be adjusted by multiplying the relevant Price in effect immediately prior to
such consolidation, reclassification or subdivision by the following fraction: 
  

					
		 	A	 	
		 	B	 	

 where: 
  

	 	A	 is the aggregate number of Ordinary Shares of the Company in issue immediately before such consolidation,
reclassification or subdivision, as the case may be; and 

  

	 	B	 is the aggregate number of Ordinary Shares of the Company in issue immediately after, and as a result of, such
consolidation, reclassification or subdivision, as the case may be. 

 Such adjustment shall become effective on the date
the consolidation, reclassification or subdivision, as the case may be, takes effect. 
 (b) If and whenever the Company shall issue any
Ordinary Shares credited as fully paid to the Company’s shareholders as a class by way of capitalization of profits or reserves (including any share premium account or capital redemption reserve) other than (1) where any such Ordinary
Shares are or are to be issued instead of the whole or part of a Cash Dividend which the Company’s shareholders would or could otherwise have elected to receive, (2) where the Company’s shareholders may elect to receive a Cash
Dividend in lieu of such Ordinary Shares or (3) where any such Ordinary Shares are or are expressed to be issued in lieu of a dividend (whether or not a Cash Dividend equivalent or amount is announced or would otherwise be payable to the
Company’s Shareholders, whether at their election or otherwise), each of the Conversion Price and the Conversion Shares Offer Price shall be adjusted by multiplying the relevant Price in effect immediately prior to such issue by the following
fraction: 
  

					
		 	A	 	
		 	B	 	

  
 - 27 - 

 where: 
  

	 	A	 is the aggregate number of Ordinary Shares of the Company in issue immediately before such issue; and

  

	 	B	 is the aggregate number of Ordinary Shares of the Company in issue immediately after such issue.

 Such adjustment shall become effective on the date of issue of such Ordinary Shares. 

(c) If and whenever the Company shall issue any Ordinary Shares to all or substantially all of the Company’s shareholders as a class by
way of rights at a price per ordinary share which is less than 95% of the Current Market Price per ordinary share on the Effective Date, each of the Conversion Price and the Conversion Shares Offer Price shall be adjusted by multiplying the relevant
Price in effect immediately prior to the Effective Date by the following fraction: 
  

					
		 	A + B	 	
		 	A + C	 	

 where: 
  

	 	A	 is the aggregate number of Ordinary Shares of the Company in issue on the Effective Date;

  

	 	B	 is the aggregate number of Ordinary Shares of the Company that the aggregate consideration (if any) receivable
for the Ordinary Shares issued by way of rights would purchase at such Current Market Price per Ordinary Share on the Effective Date; and 

  

	 	C	 is the number of Ordinary Shares to be issued. 

Such adjustment shall become effective on the Effective Date. 

For the purpose of any calculation of the consideration receivable or price pursuant to this Section 3.01(c), the following provisions
shall apply: 
  

	 	(1)	 the aggregate consideration receivable or price for Ordinary Shares issued for cash shall be the amount of such
cash; 

  

	 	(2)	 if the consideration or price determined pursuant to (1) above (or any component thereof) shall be
expressed in a currency other than the Relevant Currency, it shall be converted into the Relevant Currency at the Prevailing Rate on the relevant Effective Date; 

 

	 	(3)	 in determining the consideration or price pursuant to the above, no deduction shall be made for any commissions
or 

  
 - 28 - 

	 	
fees (howsoever described) or any expenses paid or incurred for any underwriting, placing or management of the issue of the relevant Ordinary Shares or otherwise in connection therewith

  

	 	(4)	 the consideration or price shall be determined as provided in clauses (1) – (3) above on the basis of the
consideration or price received, receivable, paid or payable, regardless of whether all or part thereof is received, receivable, paid or payable by or to the Company or another entity; and 

 

	 	(5)	 references herein to “cash” shall be construed as cash consideration within the meaning of
Section 583(3) of the Companies Act. 

 (d) If and whenever the Company shall pay any Extraordinary Dividend to
shareholders of the Company as a class, each of the Conversion Price and the Conversion Shares Offer Price shall be adjusted by multiplying the relevant Price in effect immediately prior to the Effective Date by the following fraction: 

 

					
		 	A – B	 	
		 	A	 	

 where: 
  

	 	A	 is the Current Market Price of one Ordinary Share on the Effective Date; and 

 

	 	B	 is the portion of the aggregate Extraordinary Dividend attributable to one ordinary share, with such portion
being determined by dividing the aggregate Extraordinary Dividend by the number of Ordinary Shares entitled to receive the relevant Extraordinary Dividend. If the Extraordinary Dividend shall be expressed in a currency other than the Relevant
Currency, it shall be converted into the Relevant Currency at the Prevailing Rate on the relevant Effective Date. 

 Such
adjustment shall become effective on the Effective Date. 
 (e) Notwithstanding provisions of Sections 3.01(a)–(d) above: 

(i) where the events or circumstances giving rise to any adjustment pursuant to this section have already resulted or will
result in an adjustment to each of the Prices or where the events or circumstances giving rise to any adjustment arise by virtue of any other events or circumstances that have already given or will give rise to an adjustment to each of the Prices or
where more than one event that gives rise to an adjustment to each of the Prices occurs within such a short period of time that, in the 

  
 - 29 - 

 
opinion of the Company, a modification to the operation of the adjustment provisions is required to give the intended result, such modification shall be made to the operation of the adjustment
provisions as may be determined in good faith by an Independent Financial Adviser to be in its opinion appropriate to give the intended result; 

(ii) such modification shall be made to the operation of the Indenture as may be determined in good faith by an Independent
Financial Adviser to be in its opinion appropriate to ensure that an adjustment to each of the Prices or the economic effect thereof shall not be taken into account more than once; 

(iii) for the avoidance of doubt, the issue of Ordinary Shares following an Automatic Conversion or upon any conversion or
exchange or the exercise of any other options, warrants or other rights shall not result in an adjustment to either of the Prices; 

(iv) in respect of any adjustment pursuant to Sections 3.01(a)-(c) above, such
adjustment shall be made only up to the extent it does not result in a Conversion Price or Conversion Shares Offer Price that, if applied to the number of relevant Securities at the time of such adjustment, would result in a number of Conversion
Shares that constitutes a greater proportion of Conversion Shares as a percentage of the total number of Ordinary Shares issued had the adjustment not been made nor had the corporate event occurred; and 

(v) in respect of any adjustment pursuant to Section 3.01(d) above, such adjustment shall be made only up to the extent it
does not result in a Conversion Price or Conversion Shares Offer Price that, if applied to the number of relevant Securities at the time of such adjustment, would result in the issue of an additional number of Conversion Shares having a value that
is greater than the value of the aggregate Extraordinary Dividend which would be attributable to the Ordinary Shares underlying the Securities had such Ordinary Shares been issued. 

SECTION 3.02. No Retroactive Adjustments. The Company shall not issue any additional Conversion Shares if the Automatic Conversion
occurs after the record date in respect of any consolidation, reclassification or subdivision as described in Section 3.01(a) above, or after the record date or other due date for the establishment of entitlement for any such issue,
distribution, grant or offer (as the case may be) as is described in Sections 3.01(b)–(d) above, but before the relevant adjustment to the relevant Price becomes effective under such Section. 

SECTION 3.03. Decision of an Independent Financial Advisor. If any doubt shall arise as to whether an adjustment is required to be
made to either of the Prices or as to the appropriate adjustment to such Prices, and following consultation between the Company and an Independent Financial Adviser, a written opinion of such Independent Financial Adviser in respect thereof is
delivered, such written opinion shall be conclusive and binding on the Company, the Trustee and the Holders and Beneficial Owners, save in the case of manifest error. 

  
 - 30 - 

 SECTION 3.04. Rounding Down and Notice of Adjustment to the Conversion Price and the
Conversion Shares Offer Price. 
 (a) On any adjustment to the Conversion Price and/or the Conversion Shares Offer Price as provided
under this Article III, if the resultant Conversion Price and Conversion Shares Offer Price is a number with more decimal places than the initial Conversion Price or Conversion Shares Offer Price, as the case may be, that number shall be rounded to
the same number of decimal places as the initial Conversion Price or Conversion Shares Offer Price, as the case may be. No adjustment shall be made to either of the Prices where such adjustment (rounded down if applicable) would be less than 1% of
the relevant Price then in effect. Any adjustment not required to be made, and/or any amount by which the relevant Price has been rounded down, shall be carried forward and taken into account in any subsequent adjustment, and such subsequent
adjustment shall be made on the basis that the adjustment not required to be made had been made at the relevant time and/or, as the case may be, that the relevant rounding down had not been made. 

(b) Notice of any adjustments to the Conversion Price or the Conversion Shares Offer Price shall be given by the Company to Holders via DTC
(or, if the Securities are definitive Securities, via the Trustee) promptly after the determination thereof. 
 (c) The Conversion Price
shall not in any event be reduced to below the U.S. dollar equivalent of the nominal value of the Ordinary Shares (as calculated by the Company on the date any such adjustment becomes effective). The Conversion Shares Offer Price shall not in any
event be reduced to below the nominal value of the Ordinary Shares. 
 SECTION 3.05. Qualifying Takeover Event. 

(a) Within ten (10) Business Days following the occurrence of a Takeover Event, the Company shall give notice thereof to the Holders and
Beneficial Owners of the Securities by means of a Takeover Event Notice. 
 (b) If the Takeover Event is a Qualifying Takeover Event, the
Securities shall, where the Conversion Date falls on or after the QTE Effective Date, be converted into or exchanged for Approved Entity Shares of the Approved Entity, mutatis mutandis as provided under Section 2.07 above, at a
Conversion Price that shall initially be the New Conversion Price, which may be higher or lower than the Conversion Price and references herein to “Conversion Shares” shall be deemed to be references to “Approved Entity Shares.”

 (c) The New Conversion Price shall be subject to adjustment in the circumstances provided for under Section 3.01(a) above (if
necessary with such modifications and amendments as an Independent Financial Adviser acting in good faith shall determine to be appropriate and references herein to “Conversion Shares” shall be deemed to be references to “Approved
Entity Shares”), and the Company shall give notice to the Holders of the Securities of the New Conversion Price and of any such modifications and amendments thereafter. 

  
 - 31 - 

 (d) In the case of a Qualifying Takeover Event: 

(i) the Company shall, to the extent permitted by applicable law and regulation, on or prior to the QTE Effective Date, enter
into such agreements and arrangements (including, without limitation supplemental indentures to the Indenture and amendments and modifications to the terms of the Securities and the Indenture) as may be required to ensure that, effective upon the
QTE Effective Date, the Securities shall be convertible into, or exchangeable for, Approved Entity Shares, mutatis mutandis in accordance with, and subject to, the provisions of Section 2.07 of this Sixth Supplemental Indenture, at the
New Conversion Price and any references to the Conversion Price shall be construed as references to the New Conversion Price; and 

(ii) upon the occurrence of a Capital Adequacy Trigger Event where the Conversion Date falls on or after the QTE Effective
Date, the Company shall procure (to the extent within its control) the issue of the relevant number of Approved Entity Shares mutatis mutandis in the manner provided under Section 2.07 of this Sixth Supplemental Indenture. 

(e) The Trustee shall be obliged (at the expense of the Company) to concur with the Company in making any such amendments and modifications to
the Indenture, and to execute any supplemental indentures to the Indenture in respect thereof, provided that the Trustee shall not be bound to do so if any such amendments or modifications would, in the opinion of the Trustee, have the effect of
(i) exposing the Trustee to any liability against which it is not indemnified and/or secured and/or pre-funded to its satisfaction, (ii) changing, increasing or adding to the obligations or duties of
the Trustee or (iii) removing or amending any protection or indemnity afforded to, or any other provision in favor of, the Trustee under the Indenture and/or the terms of the Securities. 

(f) For the avoidance of doubt, if for any reason (including, without limitation, because the Acquirer is a Governmental Entity), a Takeover
Event is not a Qualifying Takeover Event, there is no provision for any automatic adjustment to the terms of the Securities, whether in the manner provided for in this Article III in respect of Qualifying Takeover Events, or at all, and
Section 2.07 shall apply without any automatic adjustment and “Conversion Shares” will continue to have the meaning set out in Section 1.01. 

ARTICLE IV 

MISCELLANEOUS PROVISIONS 

SECTION 4.01. Effectiveness. This Sixth Supplemental Indenture shall become effective upon its execution and delivery. 

SECTION 4.02. Original Issue. The Securities may, upon execution of this Sixth Supplemental Indenture, be executed by the Company
and delivered by the Company to the Trustee for authentication, and the Trustee shall, upon delivery of a Company Order, authenticate and deliver such Securities as in such Company Order provided. 

  
 - 32 - 

 SECTION 4.03. Ratification and Integral Part. The Base Indenture as supplemented
and amended by this Sixth Supplemental Indenture, is in all respects ratified and confirmed, including without limitation all the rights, immunities and indemnities of the Trustee, and this Sixth Supplemental Indenture shall be deemed an integral
part of the Base Indenture in the manner and to the extent herein and therein provided. 
 SECTION 4.04. Priority. This Sixth
Supplemental Indenture shall be deemed part of the Base Indenture in the manner and to the extent herein and therein provided. The provisions of this Sixth Supplemental Indenture shall, with respect to the Securities and subject to the terms hereof,
supersede the provisions of the Base Indenture to the extent the Base Indenture is inconsistent herewith. 
 SECTION 4.05.
Successors and Assigns. All covenants and agreements in the Base Indenture, as supplemented and amended by this Sixth Supplemental Indenture, by the Company shall bind its successors and assigns, whether so expressed or not. 

SECTION 4.06. Counterparts. This Sixth Supplemental Indenture may be executed manually, by facsimile or by electronic signature in
any number of counterparts, each of which so executed shall be deemed to be an original, but all such counterparts shall together constitute but one and the same instrument. 

SECTION 4.07. Governing Law. This Sixth Supplemental Indenture and the Securities shall be governed by and construed in accordance
with the laws of the State of New York, except for the subordination provisions set forth in Section 12.01 of the Base Indenture and the waiver of set-off provisions set forth in Section 5.04(d) of
the Base Indenture, which are governed by, and construed in accordance with, English law. 

  
 - 33 - 

 IN WITNESS WHEREOF, the parties hereto have caused this Sixth Supplemental Indenture to be
duly executed, all as of the day and year first above written. 
  

					
	BARCLAYS PLC
		
	By:	 	 /s/ Daniel Fairclough

		 	Name:	 	Daniel Fairclough
		 	Title:	 	Managing Director

  

					
	THE BANK OF NEW YORK MELLON, as Trustee and Paying Agent
		
	By:	 	 /s/ Thomas Burgess

		 	Name:	 	Thomas Burgess
		 	Title:	 	Authorized Signatory

  

					
	THE BANK OF NEW YORK MELLON SA/NV, LUXEMBOURG BRANCH, as Contingent Capital Security
Registrar
		
	By:	 	 /s/ Thomas Burgess

		 	Name:	 	Thomas Burgess
		 	Title:	 	Authorized Signatory

 [Signature Page to the Sixth Supplemental Indenture] 

 Exhibit A 

Form of Global Security 
 THIS
SECURITY IS A GLOBAL REGISTERED SECURITY WITHIN THE MEANING OF THE INDENTURE HEREINAFTER REFERRED TO AND IS REGISTERED IN THE NAME OF A DEPOSITARY OR A NOMINEE THEREOF. THIS SECURITY MAY NOT BE EXCHANGED IN WHOLE OR IN PART FOR A SECURITY
REGISTERED, AND NO TRANSFER OF THIS SECURITY IN WHOLE OR IN PART MAY BE REGISTERED, IN THE NAME OF ANY PERSON OTHER THAN SUCH DEPOSITARY OR A NOMINEE THEREOF, EXCEPT IN THE LIMITED CIRCUMSTANCES DESCRIBED IN THE INDENTURE. 

BY PURCHASING THIS SECURITY, IN THE ABSENCE OF A CHANGE IN LAW OR AN ADMINISTRATIVE OR JUDICIAL RULING TO THE CONTRARY, THE HOLDER AGREES TO CHARACTERIZE THIS
SECURITY FOR ALL U.S. FEDERAL INCOME TAX PURPOSES AS PROVIDED ON THE FACE OF THIS SECURITY. 
 This Security is one of a duly authorized issue of securities
of the Company (as defined below) (herein called the “Securities” and each, a “Security”) issued and to be issued in one or more series under and governed by the Contingent Capital Securities Indenture, dated as of
August 14, 2018 (as heretofore amended and supplemented, the “Base Indenture”), as supplemented and amended by the Sixth Supplemental Indenture, dated as of August 11, 2021 (the “Sixth Supplemental
Indenture” and, together with the Base Indenture, the “Indenture”). 
 The rights of the Holder and Beneficial Owners of this
Security are, to the extent and in the manner set forth in Section 12.01 of the Base Indenture and in the subordination provisions of this Security, subordinated to the claims of other creditors of the Company, and this Security is issued
subject to the provisions of that Section 12.01 and in the subordination provisions of this Security, and the Holder of this Security, by accepting the same, agrees to, and shall be bound by, such provisions. The provisions of
Section 12.01 of the Base Indenture and the terms of this paragraph are governed by, and shall be construed in accordance with, English law. 
 The
rights of the Holder of this Security are subject to Section 2.07 of the Sixth Supplemental Indenture. Effective upon, and following, the occurrence of the Automatic Conversion, the Holders and Beneficial Owners of the Securities (and any
interest therein) prior to the occurrence of such Automatic Conversion shall not have any rights against the Company with respect to repayment of the principal amount of this Security or payment of interest or any other amount in respect of this
Security, which liabilities of the Company shall be irrevocably and automatically released, and accordingly the principal amount of this Security shall equal zero at all times thereafter. 

Notwithstanding and to the exclusion of any other term of the Securities or any other agreements, arrangements, or understandings between the Company and any
Holder or Beneficial Owner of the Securities (or the Trustee on behalf of a Holder or Beneficial Owner), by acquiring the Securities, each Holder and Beneficial Owner of the Securities acknowledges, accepts, agrees to be bound by, and consents to,
the exercise of any U.K. Bail-in Power by the Relevant U.K. Resolution Authority (as those terms are defined in the Base Indenture) and the provisions set forth in Section 13.01 of the Base Indenture.

  
 A-1 

 In accordance with Article 14 of the Base Indenture, each Holder and Beneficial Owner that acquires its
Securities in the secondary market shall be deemed to acknowledge and agree to be bound by and consent to the same provisions specified in the Indenture to the same extent as the Holders and Beneficial Owners of the Securities that acquire the
Securities upon their initial issuance, including, without limitation, with respect to the acknowledgement and agreement to be bound by and consent to the terms of the Securities, including in relation to interest cancellation, Automatic Conversion,
the Conversion Shares Offer, the U.K. Bail-in Power and the limitations on remedies specified in this Security and Article V of the Base Indenture. 

  
 A-2 

 BARCLAYS PLC 

4.375% Fixed Rate Resetting Perpetual Subordinated Contingent Convertible Securities 

 

					
	No. 00[●]	 		  	$[●]

 CUSIP NO. 06738E BT1 

ISIN NO. US06738EBT10 
 BARCLAYS
PLC, a company duly incorporated and existing under the laws of England and Wales (herein called the “Company”, which term includes any successor Person under the Indenture hereinafter referred to), for value received, hereby
promises to pay to Cede & Co., or registered assigns, the principal sum of $[●], if and to the extent due, and to pay interest thereon, if any, in accordance with the terms hereof and the Indenture. 

The Securities shall have no fixed maturity or fixed redemption date. From (and including) the Issue Date to (but excluding)
September 15, 2028, the interest rate on the Securities shall be 4.375% per annum (the “Initial Interest Rate”). From and including September 15, 2028 and each fifth anniversary date thereafter, commencing September 15, 2028
(each such date, a “Reset Date”) to (but excluding) the next following Reset Date (each such period, a “Reset Period”), the applicable per annum interest rate (the “Subsequent Interest Rate”) will,
subject to Section 2.02(b) of the Sixth Supplemental Indenture, be equal to the sum of the then prevailing U.S. Treasury Rate on the relevant Reset Determination Date and 3.410% (the “Margin”). Each Subsequent Interest Rate
shall be determined in compliance with the relevant Capital Regulations. Subject to the provisions on the reverse of this Security relating to cancellation and deemed cancellation of interest and to Sections 3.12 and 3.13 of the Base Indenture and
to the following sentence, interest, if any, shall be payable in four equal quarterly installments in arrear on March 15, June 15, September 15 and December 15 of each year (each, an “Interest Payment Date”). The
first date on which interest may be paid will be December 15, 2021 for the period commencing on (and including) August 11, 2021 and ending (but excluding) December 15, 2021 (and thus a long first interest period). If a date of
redemption is not a Business Day, the Company may pay interest (if any) and principal on the next Business Day, but interest on that payment will not accrue during the period from and after the date of redemption. 

The “U.S. Treasury Rate” is, with respect to any Reset Period for which such rate applies, the rate per annum equal to:
(1) the yield, under the heading which represents the average for the week immediately prior to the applicable Reset Determination Date, appearing in the most recently published statistical release designated “H.15,” or any successor
publication that is published by the Board of Governors of the Federal Reserve System that establishes yields on actively traded U.S. Treasury securities adjusted to constant maturity, under the caption “Treasury constant maturities,” for
the maturity of five years; or (2) if such release (or any successor release) is not published during the week immediately prior to such Reset Determination Date or does not contain such yields, the rate per annum equal to the semi-annual
equivalent yield to maturity of the Comparable Treasury Issue, calculated using a price for the Comparable Treasury Issue (expressed as a percentage of its principal amount) equal to the Comparable Treasury Price for such Reset Determination Date;
provided that, if the U.S. Treasury Rate cannot be determined, for whatever reason, as described under (1) or (2) above, 

  
 A-3 

 
“U.S. Treasury Rate” means the rate in percentage per annum as notified by the Calculation Agent to the Company equal to the yield on U.S. Treasury securities having a maturity of five
years as set forth in the most recently published statistical release designated “H.15” under the caption “Treasury constant maturities” (or any successor publication that is published weekly by the Board of Governors of the
Federal Reserve System and that establishes yields on actively traded U.S. Treasury securities adjusted to constant maturity under the caption “Treasury constant maturities” for the maturity of five years) at 5:00 p.m. (New York City time)
on the last available date preceding the Reset Determination Date on which such rate was set forth in such release (or any successor release). 

If any Interest Payment Date is not a Business Day, the Interest Payment Date shall be postponed to the next Business Day, and no further
interest or other payment shall be owed or made in respect of such delay. 
 The interest rate on the Securities, if any, will be computed
on the basis of a year of 360 days consisting of 12 months of 30 days each and, in the case of an incomplete month, the actual number of days elapsed. 

The interest, if any, so payable, and paid or duly provided for, on any Interest Payment Date will, as provided in the Indenture, be paid to
the Person in whose name this Security (or one or more Predecessor Securities) is registered at the close of business on the Regular Record Date for such interest which shall be the close of business on the Business Day immediately preceding each
Interest Payment Date (whether or not a Business Day). 
 In addition to any other restrictions on payments of principal and interest
contained in the Indenture, no repayment of the principal amount of the Securities or payment of interest on the Securities shall become due and payable after the exercise of any U.K. Bail-in Power by the
Relevant U.K. Resolution Authority unless such repayment or payment would be permitted to be made by the Company under the laws and regulations of the United Kingdom and the European Union applicable to the Company. 

Interest on the Securities shall be due and payable only at the sole discretion of the Company, and the Company shall have sole and absolute
discretion at all times and for any reason to cancel (in whole or in part) any interest payment that would otherwise be payable on any Interest Payment Date. If the Company does not make an interest payment in respect of the Securities on the
relevant Interest Payment Date (or if the Company elects to make a payment of a portion, but not all, of such interest payment), such non-payment shall evidence the Company’s exercise of its discretion to
cancel such interest payment (or the portion of such interest payment not paid), and accordingly such interest payment (or the portion thereof not paid) shall not be due and payable. If the Company provides notice to cancel a portion, but not all,
of an interest payment in respect of the Securities, and the Company subsequently does not make a payment of the remaining portion of such interest payment on the relevant Interest Payment Date, such
non-payment shall evidence the Company’s exercise of its discretion to cancel such remaining portion of such interest payment, and accordingly such remaining portion of the interest payment shall also not
be due and payable. 

  
 A-4 

 Interest shall only be due and payable on an Interest Payment Date to the extent it is not
cancelled or deemed cancelled (in each case, in whole or in part) in accordance with the terms of this Security, and any interest cancelled or deemed cancelled (in each case, in whole or in part) pursuant to this Security shall not be due and shall
not accumulate or be payable at any time thereafter, and Holders and Beneficial Owners of the Securities shall have no rights thereto or to receive any additional interest or compensation as a result of such cancellation or deemed cancellation. 

Without limitation on the foregoing paragraph and subject to the extent permitted by the following sentence in respect of partial interest
payments in respect of the Securities, the Company shall not make an interest payment in respect of the Securities on any Interest Payment Date (and such interest payment shall therefore be deemed to have been cancelled and thus shall not be due and
payable on such Interest Payment Date) if either (a) the Company has an amount of Distributable Items on such Interest Payment Date that is less than the sum of (i) all distributions or interest payments made or declared by the
Company since the end of the last financial year and prior to such Interest Payment Date on or in respect of any Parity Securities, the Securities and any Junior Securities plus (ii) all distributions or interest payments payable by the
Company (and not cancelled or deemed cancelled) on such Interest Payment Date (x) on the Securities and (y) on or in respect of any Parity Securities, in the case of each of (i) and (ii), excluding any payments already accounted for
in determining the Distributable Items; or (b) the Solvency Condition is not satisfied in respect of such interest payment. The Company may, in its sole discretion, elect to make a partial interest payment in respect of the Securities on any
Interest Payment Date, only to the extent that such partial interest payment may be made without breaching the restrictions of this paragraph. Any interest cancelled pursuant to this paragraph shall be “deemed cancelled” under the terms of
this Security and the Indenture and shall not be due and payable. Neither the Trustee nor any agent of the Trustee shall be required to monitor compliance with the restriction on interest payments contained in this paragraph or to perform any
calculations in connection therewith. 
 By subscribing for, purchasing or other acquiring the Securities, each Holder and each Beneficial
Owner shall be deemed to have contracted and agreed that (i) interest is payable solely at the discretion of the Company, and no amount of interest shall become due and payable in respect of the relevant interest period to the extent that it
has been (x) cancelled (in whole or in part) by the Company at the Company’s sole discretion and/or (y) deemed cancelled (in whole or in part) as a result of the Company’s having insufficient Distributable Items or failing to
satisfy the Solvency Condition; and (ii) a cancellation or deemed cancellation of interest (in each case, in whole or in part) in accordance with the terms of the Indenture shall not constitute a default in payment or otherwise under the terms
of the Securities or the Indenture. Interest on the Securities shall only be due and payable on an interest payment date to the extent it is not cancelled or deemed cancelled under the terms of this Security and Sections 3.12 and 3.13 of the Base
Indenture. Any interest cancelled or deemed cancelled (in each case, in whole or in part) in the circumstances described in this Security shall not be due and shall not accumulate or be payable at any time thereafter, and Holders and Beneficial
Owners of the Securities shall have no rights thereto or to receive any additional interest or compensation as a result of such cancellation or deemed cancellation of interest in respect of the Securities. 

  
 A-5 

 Payments of principal of and interest, if any, on the Securities shall be made in such coin
or currency of the United States of America as at the time of payment is legal tender for payment of public and private debts and such payments shall be made through one or more Paying Agents appointed under the Base Indenture to the Holder or
Holders of this Security. Initially, the Paying Agent for the Securities shall be The Bank of New York Mellon, London Branch, One Canada Square, London E14 5AL, United Kingdom, and the Contingent Capital Security Registrar shall be The Bank of New
York Mellon SA/NV, Luxembourg Branch, 2-4 Rue Eugene Ruppert, Vertigo Building – Polaris, Luxembourg, L-2453, Luxembourg. The Company may change the Paying Agent or
the Contingent Capital Security Registrar without prior notice to the Holders of the Securities, and in such an event the Company may act as Paying Agent or Contingent Capital Security Registrar. Payments of principal of and interest on the
Securities shall be made by wire transfer of immediately available funds; provided, however, that in the case of payments of principal, this Security is first surrendered to the Paying Agent. 

This Security shall be governed by and construed in accordance with the laws of the State of New York, except for the subordination provisions
referred to herein and set forth in Section 12.01 of Base Indenture, and the waiver of set-off provisions referred to herein and set forth in Section 5.04(d) of the Base Indenture, which are governed
by, and construed in accordance with, English law. 
 Reference is hereby made to the further provisions of this Security set forth on the
reverse hereof, which further provisions shall for all purposes have the same effect as if set forth at this place. 
 All terms used in
this Security which are defined in the Indenture shall have the meanings assigned to them in the Indenture, as defined herein. 
 THIS
SECURITY IS NOT A DEPOSIT LIABILITY OF BARCLAYS PLC AND IS NOT COVERED BY THE UNITED KINGDOM FINANCIAL SERVICES COMPENSATION SCHEME OR INSURED BY THE UNITED STATES FEDERAL DEPOSIT INSURANCE CORPORATION, THE CANADA DEPOSIT INSURANCE CORPORATION OR
ANY OTHER GOVERNMENTAL AGENCY OF THE UNITED STATES, THE UNITED KINGDOM, CANADA OR ANY OTHER JURISDICTION. 
 Unless the certificate of
authentication hereon has been executed by the Trustee referred to on the reverse hereof, directly or through an Authenticating Agent, by manual, facsimile or electronic signature of an authorized signatory, this Security shall not be entitled to
any benefit under the Indenture or be valid or obligatory for any purpose. 
 By purchasing this Security, the Holder of this Security
agrees (in the absence of a statutory, regulatory, administrative or judicial ruling to the contrary) to treat this Security as equity of the Company for U.S. federal income tax purposes. 

  
 A-6 

 IN WITNESS WHEREOF, the Company has caused this instrument to be duly executed. 

 

							
	Date:	 		 	BARCLAYS PLC
				
		 		 	By:	 	  

		 		 		 	Name:
		 		 		 	Title:
				
		 		 	By:	 	  

		 		 		 	Name:
		 		 		 	Title:

 Trustee’s Certificate of Authentication 

This is one of the Securities of the series designated herein referred to in the Indenture. 

 

							
	Date:	 		 	THE BANK OF NEW YORK MELLON,
		 		 	                as Trustee
				
		 		 	By:	 	  

		 		 		 	Authorized Signatory

 [Signature Page to Global Security] 

  
 A-7 

 (Reverse of Security) 

This Security is one of a duly authorized issue of securities of the Company (herein called the “Securities” and each, a
“Security”) issued and to be issued in one or more series under and governed by the Contingent Capital Securities Indenture, dated as of August 14, 2018 (as heretofore amended and supplemented, the “Base
Indenture”), between the Company and The Bank of New York Mellon, London Branch, as Trustee (herein called the “Trustee,” which term includes any successor trustee under the Base Indenture), as supplemented and amended by
the Sixth Supplemental Indenture, dated as of August 11, 2021 (the “Sixth Supplemental Indenture” and, together with the Base Indenture, the “Indenture”), and reference is hereby made to the Indenture, the
terms of which are incorporated herein by reference, for a statement of the respective rights, limitations of rights, duties and immunities thereunder of the Company, the Trustee, the Holders of the Securities and of the terms upon which the
Securities are, and are to be, authenticated and delivered. Insofar as the provisions of the Indenture may conflict with the provisions set forth in this Security, the former shall control for purposes of this Security. All terms used in this
Security that are defined in the Indenture and not otherwise defined herein shall have the meanings assigned to them in the Indenture. 

This Security is one of the series designated on the face hereof, limited to an aggregate principal amount of $1,500,000,000, which amount may
be increased at the option of the Company if in the future it determines that it may wish to sell additional Securities of this series. References herein to “this series” mean the series designated on the face hereof. 

Any amounts to be paid by the Company on the Securities shall be made without deduction or withholding for, or on account of, any and all
present or future income, stamp and other taxes, levies, imposts, duties, charges, fees, deductions or withholdings (“Taxes”) now or hereafter imposed, levied, collected, withheld or assessed by, or on behalf of, the United Kingdom
or any political subdivision of the United Kingdom or authority thereof or therein having the power to tax (each a “Taxing Jurisdiction”), unless such deduction or withholding is required by law. If any such Taxes shall at any time
be required by a Taxing Jurisdiction to be deducted or withheld, the Company shall, subject to the exceptions and limitations set forth in Section 10.04 of the Base Indenture and Section 12.01 of the Base Indenture, pay such additional
amounts of, or in respect of, the principal of, and any interest on, the Securities (“Additional Amounts”) as may be necessary in order that the net amounts paid to the Holders of the Securities, after such deduction or withholding,
shall equal the respective amounts of principal and interest that would have been payable in respect of such Securities had no such deduction or withholding been required. 

Any amounts to be paid by the Company or the Paying Agent on the Securities shall be paid net of any deduction or withholding imposed or
required pursuant to Sections 1471 through 1474 of the U.S. Internal Revenue Code of 1986, as amended (the “Code”), any current or future regulations or official interpretations thereof, any agreement entered into pursuant to
Section 1471(b) of the Code, or any fiscal or regulatory legislation, rules or practices adopted pursuant to any intergovernmental agreement entered into in connection with the implementation of such Sections of the Code (or any law
implementing such an intergovernmental agreement) (a “FATCA Withholding Tax”), and neither the Company nor the Paying Agent shall be required to pay Additional Amounts on account of any FATCA Withholding Tax. 

  
 A-8 

 Any Paying Agent shall be entitled to make a deduction or withholding from any payment which
it makes under the Securities and the Indenture for or on account of (i) any present or future taxes, duties or charges if and to the extent so required by any applicable law and (ii) any FATCA Withholding Tax (together,
“Applicable Law”). In either case, the Paying Agent shall make any payment after a deduction or withholding has been made pursuant to Applicable Law and shall report to the relevant authorities the amount so deducted or withheld.
However, such deduction or withholding will not apply to payments made under the Securities and the Indenture through the relevant clearing systems. In all cases, the Paying Agent shall have no obligation to gross up any payment made subject to any
deduction or withholding pursuant to Applicable Law. In addition, amounts deducted or withheld by the Paying Agent as described in this paragraph will be treated as paid to the Holder of the Securities, and the Company will not pay Additional
Amounts in respect of such deduction or withholding, except to the extent the provisions in this paragraph explicitly provide otherwise. The restrictions on interest payments described on the face of this Security apply to any Additional Amounts
mutatis mutandis. 
 The Company agrees, to the extent the Company has actual knowledge of such information, to provide the Paying
Agent with sufficient information about any modification to the terms of the Securities for the purposes of determining whether FATCA Withholding Tax applies to any payment of principal or interest on the Securities. 

Subject to the limitations specified below, the Company may, at the Company’s option, redeem the Securities, in whole but not in part, on
any day falling in the period commencing on (and including) March 15, 2028 and ending on (and including) the first Reset Date or on any subsequent Reset Date at a redemption price equal to 100% of the principal amount of the Securities then
Outstanding, together with any accrued but unpaid interest (which excludes any interest cancelled or deemed cancelled as specified below) to (but excluding) the date fixed for redemption. 

Subject to the limitations specified below, the Company may also, at any time, at the Company’s option, redeem the Securities, in whole
but not in part pursuant to Section 2.05 of the Sixth Supplemental Indenture and/or Section 11.12 of the Base Indenture. 
 Any
interest payments that have been cancelled or deemed cancelled pursuant to the terms of this Security and the Indenture shall not be payable if the Securities are redeemed pursuant to any of the two preceding paragraphs. 

Before the Company may redeem the Securities pursuant to any of the preceding paragraphs relating to the Company’s rights of redemption,
the Company shall deliver prior notice of not less than thirty (30) days, nor more than sixty (60) days to the Holders of the Securities pursuant to Section 2.06 of the Sixth Supplemental Indenture. 

Notwithstanding any other provision of this Security or the Sixth Supplemental Indenture, the Company may redeem the Securities at the
Company’s option only subject to the limitations specified in Section 11.08 of the Base Indenture. 
 Subject to
Section 11.10 of the Base Indenture, the Company or any member of the Group may purchase or otherwise acquire any of the Outstanding Securities at any price in 

  
 A-9 

 
the open market or otherwise in accordance with the Capital Regulations, and subject to the prior consent of the PRA and/or the Relevant U.K. Resolution Authority (in either case if such consent
is then required by the Capital Regulations) and to applicable law and regulation. 
 An Automatic Conversion shall occur without delay upon
the occurrence of a Capital Adequacy Trigger Event as set forth in Section 2.07 of the Sixth Supplemental Indenture. 
 The Conversion
Price and the Conversion Shares Offer Price shall be subject to adjustment as provided in Article III of the Sixth Supplemental Indenture. 

The Company may, in its sole and absolute discretion, following the occurrence of an Automatic Conversion and no later than 10 (ten) Business
Days following the Conversion Date, elect that the Conversion Shares Depository make an offer of all or some of the Conversion Shares to all or some of the Company’s ordinary shareholders at a cash price per Conversion Share equal to the
Conversion Shares Offer Price, as set forth in and subject to the provisions of Section 2.09 of the Sixth Supplemental Indenture. 

This Security is subject to the provisions regarding the U.K. Bail-in Power Acknowledgement set forth
in Section 13.01 of the Base Indenture. 
 If a Winding-Up Event occurs before the occurrence
of a Capital Adequacy Trigger Event, subject to the subordination provisions of Section 12.01 of the Base Indenture, the outstanding principal amount of this Security shall become immediately due and payable, without the need of any further
action on the part of the Trustee, the Holders or any other Person. 
 A “Winding-Up
Event” shall result if (i) a court of competent jurisdiction in England (or such other jurisdiction in which the Company may be organized) makes an order for the winding-up of the Company which
is not successfully appealed within thirty (30) days of the making of such order, (ii) the Shareholders of the Company adopt an effective resolution for the winding-up of the Company (other than, in
the case of either (i) or (ii) above, under or in connection with a scheme of reconstruction, merger or amalgamation not involving a bankruptcy or insolvency) or (iii) following the appointment of an administrator of the Company, the
administrator gives notice that it intends to declare and distribute a dividend. 
 If the Company fails to pay any amount that has become
due and payable under this Security and such failure continues for fourteen (14) days, the Trustee may provide a written notice of such failure to the Company. If within a period of fourteen (14) days following the provision of such
notice, the failure continues and has not been cured nor waived (a “Non-Payment Event”), the Trustee may, at its discretion, and without further notice to the Company, institute
proceedings in England (or such other jurisdiction in which the Company may be organized) (but not elsewhere) for the winding-up of the Company and/or prove in a
winding-up of the Company and/or claim in a liquidation or administration of the Company. For the avoidance of doubt, if, pursuant to this Security and Sections 3.12 and 3.13 of the Base Indenture, the Company
cancels any interest payment on any Interest Payment Date or if such interest payment is deemed cancelled (in each case, in whole or in part), then such interest payment shall not be due and payable in respect of such Interest Payment Date, and no Non-Payment Event under the Securities will occur or be deemed to have occurred as a result of such cancellation or deemed cancellation (in each case, in whole or in part). 

  
 A-10 

 In addition to the remedies for a Non-Payment Event
provided in the paragraph above, the Trustee, may without further notice, institute such proceedings against the Company as the Trustee may deem fit to enforce any term, obligation or condition binding upon the Company under the Securities or the
Indenture (other than any payment obligation of the Company under or arising from the Securities or the Indenture, including, without limitation, payment of any principal or interest) (such obligation, a “Performance Obligation”),
provided always that the Trustee (acting on behalf of the Holders and Beneficial Owners of the Securities) and the Holders and Beneficial Owners of the Securities may not enforce, and may not be entitled to enforce or otherwise claim, against
the Company any judgment or other award given in such proceedings that requires the payment of money by the Company, whether by way of damages or otherwise (a “Monetary Judgment”), except by proving such Monetary Judgment in a winding-up of the Company and/or by claiming such Monetary Judgment in an administration of the Company. For the avoidance of doubt, the sole and exclusive manner by which the Trustee (acting on behalf of the
Holders and Beneficial Owners of the Securities) and the Holders and Beneficial Owners of the Securities may seek to enforce or otherwise claim a Monetary Judgment against the Company in connection with the Company’s breach of a Performance
Obligation shall be by proving such Monetary Judgment in a winding-up of the Company and/or by claiming such Monetary Judgment in an administration of the Company. By its acquisition of the Securities, each
Holder and Beneficial Owner of the Securities acknowledges and agrees that such Holder and Beneficial Owner shall not seek to enforce or otherwise claim, and will not direct the Trustee (acting on behalf of the Holders and Beneficial Owners of the
Securities) to enforce or otherwise claim, a Monetary Judgment against the Company in connection with the Company’s breach of a Performance Obligation, except by proving such Monetary Judgment in a
winding-up of the Company and/or by claiming such Monetary Judgment in an administration of the Company. 

Other than the limited remedies specified in this Security and Article V of the Base Indenture, and subject to the second paragraph below, no
remedy against the Company shall be available to the Trustee (acting on behalf of the Holders and Beneficial Owners of the Securities) and to the Holders and Beneficial Owners, whether for the recovery of amounts owing in respect of the Securities
or under the Indenture, or in respect of any breach by the Company of any of the Company’s obligations under or in respect of the terms of such Securities or under the Indenture in relation thereto; provided, however, that the
Company’s obligations to the Trustee under Section 6.07 of the Base Indenture and the Trustee’s rights to have money collected applied first to pay amounts due to it under such Section pursuant to Section 5.07 of the Base
Indenture expressly survive any such Default and are not subject to the subordination provisions of Section 12.01 of the Base Indenture. 

In the case of a Default under this Security, the Trustee shall exercise such of the rights and powers vested in it by the Indenture, and use
the same degree of care and skill in their exercise, as a prudent person would exercise or use under the circumstances in the conduct of his or her own affairs. A “Default” shall occur upon (i) the occurrence of a Winding-Up Event that occurs before the occurrence of a Capital Adequacy Trigger Event or (ii) the occurrence of a Non-Payment Event or (iii) a breach by the Company
of a Performance Obligation. 

  
 A-11 

 Notwithstanding the limitations on remedies specified in this Security and under Article V
of the Base Indenture, (1) the Trustee shall have such powers as are required to be authorized to it under the Trust Indenture Act in respect of the rights of the Holders and Beneficial Owners of the Securities under the provisions of the
Indenture, and (2) nothing shall impair the right of a Holder or Beneficial Owner of the Securities under the Trust Indenture Act, absent such Holder’s or Beneficial Owner’s consent, to sue for any payment due but unpaid with respect
to the Securities; provided that, in the case of (1) and (2) above, any payments in respect of, or arising from, the Securities, including any payments or amounts resulting or arising from the enforcement of any rights under the Trust
Indenture Act in respect of the Securities, shall be subject to the subordination provisions set forth in Section 12.01 of the Base Indenture. Subject to the provisions of the Trust Indenture Act, no Holder shall be entitled to proceed directly
against the Company except as set forth in Section 5.08 of the Base Indenture. 
 The Securities shall constitute the Company’s
direct, unsecured and subordinated obligations, ranking pari passu without any preference among themselves. In the event of a winding up or administration of the Company, the rights and claims of the Holders and Beneficial Owners of the
Securities in respect of or arising from the Securities (including any damages (if payable)) shall be subordinated to the claims of Senior Creditors. If (a) an order is made, or an effective resolution is passed, for the winding-up of the Company (except in any such case for a solvent winding-up solely for the purpose of a merger, reconstruction or amalgamation); or (b) following the
appointment of an administrator of the Company, the administrator gives notice that it intends to declare and distribute a dividend, then (1) if such events specified in (a) or (b) above occur prior to the date on which a Capital Adequacy
Trigger Event occurs, there shall be payable by the Company in respect of each Security (in lieu of any other payment by the Company), such amount, if any, as would have been payable to a Holder of Securities if, on the day prior to the commencement
of the winding-up or such administration and thereafter, such Holder of Securities were the holder of the most senior class of preference shares in the capital of the Company, having an equal right to a return
of assets in the winding-up or such administration to, and so ranking pari passu with, the holders of such class of preference shares (if any) from time to time issued by the Company that has a
preferential right to a return of assets in the winding-up or such administration, and so ranking ahead of the holders of all other classes of issued shares for the time being in the capital of the Company,
but ranking junior to the claims of Senior Creditors, and on the assumption that the amount that such Holder of Securities was entitled to receive in respect of such preference shares, on a return of assets in such
winding-up or such administration, was an amount equal to the principal amount of the relevant Security, together with any damages (if payable), and (2) if such events specified in (a) or (b) above
occur on or after the date on which a Capital Adequacy Trigger Event occurs but prior to the Conversion Date, then for purposes of determining the claim of a Holder of the Securities in such winding-up or such
administration, the Conversion Date in respect of an Automatic Conversion shall be deemed to have occurred immediately prior to the occurrence of such events specified in (a) or (b) above. Other than in the event of a winding-up or administration of the Company as described in this paragraph, payments in respect of or arising from the Securities shall be conditional (i) upon the Company’s being solvent at the time of
payment by the Company, and (ii) in that no sum in respect of or arising from the Securities may fall due and be paid except to the extent that the Company could make such payment and still be solvent immediately thereafter (such condition
referred to herein as the “Solvency Condition”). For purposes of determining whether the Solvency Condition is met, the Company shall be 

  
 A-12 

 
considered to be solvent at a particular point in time if (x) it is able to pay its debts owed to Senior Creditors as they fall due and (y) the Balance Sheet Condition has been met. An
Officer’s Certificate executed in accordance with the Indenture as to the Company’s solvency at any particular point in time shall be treated by the Company, the Trustee, the Holders, the Beneficial Owners and all other interested parties
as correct and sufficient evidence thereof. “Senior Creditors” means creditors of the Company (aa) who are unsubordinated creditors; (bb) whose claims are, or are expressed to be, subordinated (whether only in the event of the winding-up or administration of the Company or otherwise) to the claims of unsubordinated creditors of the Company but not further or otherwise; (cc) who are creditors in respect of any secondary non-preferential debt (“secondary non-preferential debts” shall have the meaning given to it in the 2018 Order (as defined below) and any other law or
regulation applicable to the Company, which is amended by the 2018 Order, as each may be amended or replaced from time to time; or (dd) whose claims are, or are expressed to be, junior to the claims of other creditors of the Company, whether
subordinated or unsubordinated, other than those whose claims rank, or are expressed to rank, pari passu with, or junior to, the claims of the Holders of the Securities. “2018 Order” means the Banks and Building Societies
(Priorities on Insolvency) Order 2018. The “Balance Sheet Condition” shall be satisfied in relation to the Company if the value of its assets is at least equal to the value of its liabilities (taking into account its contingent and
prospective liabilities), according to the criteria that would be applied by the High Court of Justice of England and Wales (or the relevant authority of such other jurisdiction in which the Company may be organized) in determining whether the
Company is “unable to pay its debts” under section 123(2) of the U.K. Insolvency Act 1986 or any amendment or re-enactment thereof (or in accordance with the corresponding provisions of the
applicable laws of such other jurisdiction in which the Company may be organized). Any payment of interest not due by reason of the provisions contained in this paragraph shall be deemed canceled pursuant to the terms of this Security and
Section 3.13 of the Base Indenture. 
 Subject to applicable law, no Holder of Securities may exercise, claim or plead any right of set-off, compensation or retention in respect of any amount owed to it by the Company arising under, or in connection with, the Securities and each Holder of Securities shall, by virtue of its holding of any
Securities, be deemed to have waived all such rights of set-off, compensation or retention. Notwithstanding the foregoing, if any amounts due and payable to any Holder of this Security by the Company in
respect of, or arising under, this Security are discharged by set-off, such Holder shall, subject to applicable law, immediately pay an amount equal to the amount of such discharge to the Company (or, in the
event of its winding-up or administration, the liquidator or administrator of the Company, as the case may be) and, until such time as payment is made, shall hold an amount equal to such amount in trust for
the Company (or the liquidator or administrator of the Company, as the case may be) and, accordingly, any such discharge shall be deemed not to have taken place. By its acquisition of the Securities, each Holder and Beneficial Owner agrees to be
bound by these provisions relating to waiver of set-off. 
 The Indenture permits, with certain
exceptions and subject to certain conditions as therein provided, the amendment thereof and the modification of the rights and obligations of the Company and the rights of the Holders of the Securities of each series to be affected under the
Indenture at any time by the Company and the Trustee with the consent of the Holders of a specified majority in principal amount of the Securities then Outstanding of each series to be 

  
 A-13 

 
affected. The Indenture also contains provisions permitting the Holders of a majority in aggregate principal amount of the Securities of each series then Outstanding, on behalf of the Holders of
all Securities of such series, to waive compliance by the Company with certain provisions of the Indenture and certain past Defaults under the Indenture and their consequences. Any such consent or waiver by the Holder of this Security shall be
conclusive and binding upon such Holder and upon all future Holders of this Security and of any Security issued upon the registration of transfer hereof or in exchange herefor or in lieu hereof, whether or not notation of such consent or waiver is
made upon this Security. 
 As provided in and subject to the provisions of the Indenture, the Holder of this Security shall not have any
right to institute any proceeding, judicial or otherwise, with respect to the Indenture or for the appointment of a receiver or trustee or for any other remedy thereunder, unless such Holder shall have previously given the Trustee written notice of
a continuing Default with respect to the Securities of this series, the Holders of not less than 25% in aggregate principal amount of the Securities of this series then Outstanding shall have made written request to the Trustee to institute
proceedings in respect of such Default as Trustee and offered to the Trustee reasonable security or indemnity against the costs, expenses and liabilities to be incurred in compliance with such request, the Trustee shall not have received from the
Holders of a majority in principal amount of Securities of this series then Outstanding a direction inconsistent with such request, and shall have failed to institute any such proceeding, for sixty (60) days after receipt of such notice,
request and offer of security or indemnity, and, in the case of a proceeding in England (or such other jurisdiction in which the Company may be organized) (but not elsewhere) for the winding-up of the Company,
such proceeding is in the name and on behalf of the Trustee to the same extent (but no further or otherwise) as the Trustee would have been entitled so to do. 

Notwithstanding any contrary provisions in this Security, nothing shall impair the right of a Holder of this Security under the Trust
Indenture Act, absent such Holder’s consent, to sue for any payments due but unpaid with respect to this Security. 
 As provided in
the Indenture and subject to certain limitations therein set forth, the transfer of this Security is registrable in the Contingent Capital Security Register, upon surrender of this Security for registration of transfer at the office or agency of the
Company in any place where the principal of this Security is payable, duly endorsed by, or accompanied by a written instrument of transfer in form satisfactory to the Company and the Contingent Capital Security Registrar duly executed by, the Holder
hereof or his attorney duly authorized in writing. Thereupon one or more new Securities of this series and of like tenor, of authorized denominations and for the same aggregate principal amount, will be issued to the designated transferee or
transferees. 
 This Security, and any other Securities of this series and of like tenor, are issuable only in registered form without
coupons in initial denominations of $200,000 and increments of $1,000 thereafter. The denominations cannot be changed without the consent of the Trustee. The denomination of each interest in this Security shall be the “Tradable
Amount” of such book-entry interest. Prior to an Automatic Conversion, the aggregate Tradable Amount of the interests in this Security shall equal this Security’s outstanding principal amount.
Following an Automatic Conversion, the principal amount of this Security shall equal zero, but the Tradable Amount of the book-entry interests in this Security shall remain unchanged as a result of the
Automatic Conversion. 

  
 A-14 

 No service charge shall be made for any such registration of transfer or exchange, but the
Company may require payment of a sum sufficient to cover any tax or other governmental charge payable in connection therewith. 
 Prior to
due presentment of this Security for registration of transfer, the Company, the Trustee and any agent of the Company or the Trustee may treat the Person in whose name this Security is registered as the owner hereof for all purposes, whether or not
this Security be overdue, and neither the Company, the Trustee nor any such agent shall be affected by notice to the contrary. 
 This
Security shall be governed by and construed in accordance with the laws of the State of New York, except for the subordination provisions referred to herein and set forth in Section 12.01 of the Base Indenture, and the waiver of set-off provisions referred to herein and set forth in Section 5.04(d) of the Base Indenture, which are governed by, and construed in accordance with, English law. 

  
 A-15 

 Exhibit B 

Form of Automatic Conversion Notice1 

NOTICE TO DTC, THE TRUSTEE AND FOR PUBLICATION 

AS A NOTICE TO HOLDERS AND BENEFICIAL OWNERS 

[Barclays Letterhead] 
  

							
		 	To:	  	 [The Depository Trust Company
 55 Water Street,
25th Floor
 New York, NY 10041 0099
 Attn: Mandatory
Reorganization Department
 Fax: +1 (212) 855 5488
 Email:
mandatoryreorgannouncements@dtcc.com]
	  	
				
		 	Cc:	  	 [The Bank of New York Mellon
 Merck House

Seldown
 Poole, Dorset BH15 1PX

United Kingdom
 Attn: International Corporate Trust Services

Email: corpsov2@bnymellon.com
 Fax: 01202 689600

Tel: 01202 689978
	  	 The Bank of New York Mellon
 101 Barclay
Street
 Floor 7-E
 New
York, New York 10286
 United States of America
 Attn:
International Corporate Trust
 Fax: +1 (212) 815-5366]

 Re: Barclays PLC $1,500,000,000 4.375% Fixed Rate Resetting Perpetual Subordinated Contingent Convertible Securities
(CUSIP: 06738E BT1, ISIN: US06738EBT10) – Notice to DTC, Holders and Beneficial Owners of the Occurrence of a Capital Adequacy Trigger Event 
 This
notice is in relation to Barclays PLC’s (the “Company”) $1,500,000,000 4.375% Fixed Rate Resetting Perpetual Subordinated Contingent Convertible Securities (CUSIP: 06738E BT1, ISIN: US06738EBT10) issued on August 11, 2021
(the “Securities”) pursuant to the Contingent Capital Securities Indenture, dated August 14, 2018, as amended and supplemented from time to time, between the Company and The Bank of New York Mellon, London Branch, as Trustee
(the “Trustee”) and Paying Agent, as supplemented and amended by the Sixth Supplemental Indenture, dated August 11, 2021, between the Company and the Trustee (together, the “Indenture”), and pursuant to the
prospectus supplement dated August 4, 2021 supplementing the prospectus dated March 1, 2021. Capitalized terms used herein and not defined herein shall have the respective meanings ascribed to such terms in the Indenture. 

Barclays PLC hereby notifies The Depository Trust Company (“DTC”), the Holders and Beneficial Owners of the Securities that a Capital
Adequacy Trigger Event has occurred with respect to the Securities. Such Capital Adequacy Trigger Event has occurred because the 
  

	1 	 Note: Addresses to be reconfirmed prior to when notice is sent; subject to modification if Securities
are in definitive form and to changes in DTC’s (or successor clearing system) policies and procedures. 

  
 B-1 

 
Group’s Fully Loaded CET1 Ratio as of [Date], as determined by Barclays PLC on a consolidated basis in accordance with the Capital Regulations applicable to the Group on such date,
was less than 7.00%. 
 Upon the occurrence of the Capital Adequacy Trigger Event, the terms of the Securities provide for an Automatic Conversion of the
Securities on the Conversion Date, which [was] [is expected to be] [Date], based on the Conversion Price, which is [Price]. 2 Upon the Automatic Conversion, all of Barclays
PLC’s obligations under the Securities (other than with respect to the CSO Obligations, if any) shall be irrevocably and automatically released in consideration of Barclays PLC’s issuance of ordinary shares of Barclays PLC (the
“Conversion Shares”) to the Conversion Shares Depository (or other relevant recipient). However, the terms of the Securities provide that the Securities shall remain in existence until the applicable Settlement Date for the sole
purpose of evidencing (a) a right to receive Conversion Shares or Conversion Shares Offer Consideration, as applicable, from the Conversion Shares Depository and (b) the Company’s CSO Obligations, if any. 

In addition, the terms of the Securities provide that Barclays PLC may, in its sole and absolute discretion, elect that a Conversion Shares Offer be
conducted, no later than ten (10) Business Days of the Conversion Date. Barclays PLC will deliver to DTC, the Holders and the Beneficial Owners a Conversion Shares Offer Notice specifying, among other things, whether or not Barclays PLC has
elected that a Conversion Shares Offer be conducted and the Suspension Date. The Securities may continue to trade until the Suspension Date. 
 Accordingly,
Barclays PLC hereby instructs DTC to indicate to all participants that payments of principal and interest are no longer payable under the Securities as of the Conversion Date and that the Securities will have no further entitlement to interest or
principal as of such date by making a note to that effect in its systems. 
 Barclays PLC further requests DTC to post this notice on its Reorganization
Inquiry for Participants System (or such other system as DTC uses for providing notices to holders of securities). 
 Should DTC, any Holder or any
Beneficial Owner of the Securities have any inquiries, please contact: 
 [Barclays Contact Person] 

[Telephone] 
 [Fax]

 [Email] 
  

	2 	 Note: To be completed with the Conversion Date and Conversion Price.

  
 B-2 

 Exhibit C 

Form of Capital Adequacy Trigger Event Officers’ Certificate 

BARCLAYS PLC 
 Capital Adequacy
Trigger Event Officers’ Certificate 
 This Capital Adequacy Trigger Event Officers’ Certificate is being delivered in relation to Barclays
PLC’s (the “Company”) $1,500,000,000 4.375% Fixed Rate Resetting Perpetual Subordinated Contingent Convertible Securities (CUSIP: 06738E BT1, ISIN: US06738EBT10) issued on August 11, 2021 (the
“Securities”) pursuant to the Contingent Capital Securities Indenture (the “Base Indenture”), dated August 14, 2018, as amended and supplemented from time to time, between the Company and The Bank of New York
Mellon, as Trustee (the “Trustee”) and Paying Agent, as supplemented and amended by the Sixth Supplemental Indenture, dated August 11, 2021, between the Company and the Trustee (the “Sixth Supplemental
Indenture”), and pursuant to the prospectus supplement dated August 4, 2021, supplementing the prospectus dated March 1, 2021 (the “Prospectus”). 

Pursuant to Section 1.02 of the Base Indenture and Section 2.07 of the Sixth Supplemental Indenture, the undersigned, being authorized signatories
of the Company and authorized by the Company to give this certificate, each hereby certify as follows: 
  

	(a)	 I have read the provisions of the Base Indenture and those of the Sixth Supplemental Indenture, setting forth
certain provisions in respect of the occurrence of a Capital Adequacy Trigger Event (as defined in the Sixth Supplemental Indenture), including Section 2.07 of the Sixth Supplemental Indenture, and the definitions relating thereto;

  

	(b)	 I have reviewed such corporate records and such other documents as I have deemed necessary as a basis for the
opinion hereinafter expressed; 

  

	(c)	 I have also made such other examinations and investigations as I have deemed necessary to enable me to express
an informed opinion as to the matters set forth in (d) below; and 

  

	(d)	 a Capital Adequacy Trigger Event has occurred with respect to the Securities. Such Capital Adequacy Trigger
Event has occurred because the Group’s (as defined in the Sixth Supplemental Indenture) Fully Loaded CET1 Ratio (as defined in the Sixth Supplemental Indenture) as of [Date], as determined by Barclays PLC on a consolidated basis in
accordance with the capital adequacy standards and guidelines of the Prudential Regulation Authority of the United Kingdom (or such other governmental authority having primary responsibility for the prudential supervision of Barclays PLC) on such
date, was less than 7.00%. 

 Concurrently with the delivery of this Capital Adequacy Trigger Event Officers’ Certificate, the
Company is delivering to The Depository Trust Company (“DTC”) an Automatic Conversion Notice (as defined in the Sixth Supplemental Indenture) as a notice to DTC and for publication as a notice to Holders (as defined in the Base
Indenture) and Beneficial Owners (as defined in the Base Indenture) in the form set forth in Exhibit B to the Sixth Supplemental Indenture. 

  
 C-1 

 The Trustee is entitled to conclusively rely on and accept this Capital Adequacy Trigger Event
Officers’ Certificate without any duty whatsoever of further inquiry as sufficient and conclusive evidence of the occurrence of the Capital Adequacy Trigger Event, and this Capital Adequacy Trigger Event Officers’ Certificate shall be
conclusive and binding on the Trustee and the Holders as defined in the Base Indenture) and Beneficial Owners (as defined in the Base Indenture). 
 Dated:

  

			
	BARCLAYS PLC
		
	By:	 	  

		 	Name:
		 	Title:
		
	By:	 	  

		 	Name:
		 	Title:

  
 C-2 

 Exhibit D 

Form of Conversion Shares Offer Notice3 

NOTICE TO DTC, THE TRUSTEE AND FOR PUBLICATION 

AS A NOTICE TO HOLDERS AND BENEFICIAL OWNERS 

[Barclays Letterhead] 
  

							
		 	To:	  	 [The Depository Trust Company
 55 Water Street,
25th Floor
 New York, NY 10041-0099

Attn: Mandatory Reorganization Department
 Fax: +1 (212) 855-5488
 Email: mandatoryreorgannouncements@dtcc.com]
	  	
				
		 	Cc:	  	 [The Bank of New York Mellon
 Merck House

Seldown
 Poole, Dorset BH15 1PX

United Kingdom
 Attn: International Corporate Trust Services

Email: corpsov2@bnymellon.com 
Fax: 01202 689600
 Tel: 01202
689978
	  	 The Bank of New York Mellon
 101 Barclay
Street
 Floor 7-E
 New
York, New York 10286 United States of America
 Attn: International Corporate Trust 
Fax: +1 (212)
815-5366]

 Re: Barclays PLC $1,500,000,000 4.375% Fixed Rate Resetting Perpetual Subordinated Contingent Convertible Securities
(CUSIP: 06738E BT1, ISIN: US06738EBT10) – Notice to DTC, Holders and Beneficial Owners of [Election to Conduct a Conversion Shares Offer][Election Not to Conduct a Conversion Shares Offer] 

This notice is in relation to Barclays PLC’s (the “Company”) $1,500,000,000 4.375% Fixed Rate Resetting Perpetual Subordinated
Contingent Convertible Securities (CUSIP: 06738E BT1, ISIN: US06738EBT10) issued on August 11, 2021 (the “Securities”) pursuant to the Contingent Capital Securities Indenture, dated August 14, 2018, as amended and
supplemented from time to time, between Barclays PLC and The Bank of New York Mellon, London Branch, as Trustee (the “Trustee”) and Paying Agent, as supplemented and amended by the Sixth Supplemental Indenture, dated August 11,
2021, between the Company and the Trustee (together, the “Indenture”), and pursuant to the prospectus supplement dated August 4, 2021, supplementing the prospectus dated March 1, 2021, (the “Prospectus”).
Capitalized terms used herein and not defined herein shall have the respective meanings ascribed to such terms in the Indenture. 
  

	3 	 Note: Addresses to be reconfirmed prior to when notice is sent; subject to modification if
Securities are in definitive form and to changes in DTC (or successor clearing system) policies and procedures. 

  
 D-1 

 Barclays PLC hereby notifies The Depository Trust Company (“DTC”), the Holders and the
Beneficial Owners of the Securities that it has elected that a Conversion Shares Offer [not] be conducted. [The Conversion Shares Offer Period will extend from the date of this notice until
[Date]4. [Conversion Shares Depository] has been appointed as Conversion Shares Depository for the Conversion Shares Offer.]5

 In addition, Barclays PLC hereby notifies DTC, the Holders and the Beneficial Owners of the Securities that the Suspension Date shall be [Date].6 Accordingly, Barclays PLC hereby instructs DTC to implement a “chill” on the clearance and settlement of the Securities on the Suspension Date. As described in the Prospectus, Holders and
Beneficial Owners will not be able to settle the transfer of any Securities following the Suspension Date, and any sale or other transfer of the Securities that a Holder or Beneficial Owner may have initiated prior to the commencement to the
Suspension Date that is scheduled to settle after the Suspension Date will be rejected by DTC and will not be settled within DTC. 
 Barclays PLC further
requests DTC to post this notice on its Reorganization Inquiry for Participants System (or such other system as DTC uses for providing notices to holders of securities). 

Should DTC, any Holder or any Beneficial Owner of the Securities have any inquiries, please contact: 

[Barclays Contact Person] 
 [Telephone] 

[Fax] 
 [Email] 

 

	4 	 Note: Insert the date that the Conversion Shares Offer expires, which shall be no later than
forty (40) business days after the delivery of this Conversion Shares Offer Notice. 

	5 	 Note: If Barclays PLC has been unable to appoint a Conversion Shares Depository (or other nominee),
it shall also include in this notice such other arrangements for the issuance and/or delivery of the Conversion Shares or the Conversion Shares Offer Consideration, as applicable, to the holders of the Securities as it has put in place.

	6 	 Note: Insert the Suspension Date, which is the date on which DTC shall suspend all clearance
and settlement of the Securities, which date shall be no later than thirty-eight (38) business days after the delivery of the Conversion Shares Offer Notice to DTC and at least two (2) business days prior to the end of the Conversion Shares Offer
Period, if any). 

  
 D-2 

 Exhibit E 

Form of Conversion Shares Settlement Request Notice7 

NOTICE TO DTC, THE TRUSTEE AND FOR PUBLICATION 

AS A NOTICE TO HOLDERS AND BENEFICIAL OWNERS 

[Barclays Letterhead] 
  

							
		 	To:	  	 [The Depository Trust Company
 55 Water Street,
25th Floor
 New York, NY 10041 0099
 Attn: Mandatory
Reorganization Department
 Fax: +1 (212) 855 5488
 Email:
mandatoryreorgannouncements@dtcc.com]
	  	
				
		 	Cc:	  	 [The Bank of New York Mellon
 Merck House

Seldown
 Poole, Dorset BH15 1PX

United Kingdom
 Attn: International Corporate Trust Services

Email: corpsov2@bnymellon.com
 Fax: 01202 689600

Tel: 01202 689978
	  	 The Bank of New York Mellon
 101 Barclay
Street
 Floor 7-E
 New
York, New York 10286
 United States of America
 Attn:
International Corporate Trust
 Fax: +1 (212) 815-5366]

 Re: Barclays PLC $1,500,000,000 4.375% Fixed Rate Resetting Perpetual Subordinated Contingent Convertible Securities
(CUSIP: 06738E BT1, ISIN: US06738EBT10) – Notice to DTC, Holders and Beneficial Owners Requesting that Holders and Beneficial Owners Complete a Conversion Shares Settlement Notice 

This notice is in relation to Barclays PLC’s (the “Company”) $1,500,000,000 4.375% Fixed Rate Resetting Perpetual Subordinated Contingent
Convertible Securities (CUSIP: 06738E BT1, ISIN: US06738EBT10) issued on August 11, 2021 (the “Securities”) pursuant to the Contingent Capital Securities Indenture, dated August 14, 2018, as amended and supplemented from
time to time, between Barclays PLC and The Bank of New York Mellon, London Branch, as Trustee (the “Trustee”) and Paying Agent, as supplemented and amended by the Sixth Supplemental Indenture, dated August 11, 2021, between the
Company and the Trustee (together, the “Indenture”), and pursuant to the prospectus supplement dated August 4, 2021, supplementing the prospectus dated March 1, 2021. Capitalized terms used herein and not defined herein
shall have the respective meanings ascribed to such terms in the Indenture. 
 Barclays PLC hereby requests that Holders and Beneficial Owners of the
Securities provide notice to [Name of Conversion Shares Depository (or other nominee)], as [Conversion Shares Depository]8, and the Trustee in the form provided in Appendix A before
[Date]9 (the “Notice Cut-off Date”). 

 

	7 	 Note: Addresses to be reconfirmed prior to when notice is sent; subject to modification
if Securities are in definitive form and to changes in DTC’s (or successor clearing system) policies and procedures. 

	8 	 Note: If Barclays PLC has been unable to appoint a Conversion Shares Depository, this should
refer to the entity undertaking its functions. 

	9 	 Note: The
Notice-Cut-off Date must be at least forty (40) business days following the Suspension Date. 

  
 E-1 

 If a Holder or Beneficial Owner of the Securities properly completes and delivers a Conversion Shares
Settlement Notice on or before the Notice Cut-off Date, the Conversion Shares Depository shall, in accordance with the terms of the Sixth Supplemental Indenture, deliver to such Holder or Beneficial Owner the
relevant Conversion Shares (rounded down to the nearest whole number of Conversion Shares) or Conversion Shares Offer Consideration, as applicable, two (2) Business Days after the date on which the Conversion Shares Settlement Notice is
received by the Conversion Shares Depository. 
 If a Holder or Beneficial Owner of the Securities fails to properly complete and deliver a Conversion
Shares Settlement Notice before the Notice Cut-off Date, the Conversion Shares Depository shall continue to hold the relevant Conversion Shares (or Conversion Shares Component, if applicable). However, the
relevant Securities shall be cancelled on the Final Cancellation Date, which shall be [Date],10 and any Holder or Beneficial Owner delivering a Conversion Shares Settlement Notice after the
Notice Cut-off Date will have to provide evidence of its entitlement to the relevant Conversion Shares (or the relevant Conversion Shares Component, if applicable) satisfactory to the [Conversion Shares
Depository] in its sole and absolute discretion in order to receive delivery of such Conversion Shares (or the relevant Conversion Shares Component, if applicable). 

Barclays PLC further requests DTC to post this notice on its Reorganization Inquiry for Participants System (or such other system as DTC uses for providing
notices to holders of securities). 
 Should DTC, any Holder or any Beneficial Owner of the Securities have any inquiries, please contact: 

[Barclays Contact Person] 
 [Telephone] 

[Fax] 
 [Email] 

 

	10 	 Note: The Final Cancellation Date may be up to twelve (12) business days following the
Notice Cut-Off Date. 

  
 E-2 

 Appendix A 

Form of Conversion Shares Settlement Notice11 

NOTICE TO THE [CONVERSION SHARES DEPOSITORY AND] DTC 
  

							
		 	To:	  	 [The Depository Trust Company
 55 Water Street,
25th Floor
 New York, NY 10041 0099
 Attn: Mandatory
Reorganization Department
 Fax: +1 (212) 855 5488
 Email:
mandatoryreorgannouncements@dtcc.com]
	  	[Contact details of [Conversion Shares Depository] to be included.]
				
		 	Cc:	  	 [The Bank of New York
 Mellon Merck House

Seldown
 Poole, Dorset BH15 1PX United Kingdom

Attn: International Corporate Trust Services
 Email:
corpsov2@bnymellon.com
 Fax: 01202 689600
 Tel: 01202
689978
	  	 The Bank of New York Mellon
 101 Barclay
Street
 Floor 7-E
 New
York, New York 10286
 United States of America
 Attn:
International Corporate Trust
 Fax: +1 (212) 815-5366]

 Re: Barclays PLC $1,500,000,000 4.375% Fixed Rate Resetting Perpetual Subordinated Contingent Convertible Securities
(CUSIP: 06738E BT1, ISIN: US06738EBT10) – Conversion Shares Settlement Notice to the [Conversion Shares Depository and] DTC 
 This notice is in
relation to Barclays PLC’s (the “Company”) $1,500,000,000 4.375% Fixed Rate Resetting Perpetual Subordinated Contingent Convertible Securities (CUSIP: 06738E BT1, ISIN: US06738EBT10) issued on August 11, 2021 (the
“Securities”) pursuant to the Contingent Capital Securities Indenture, dated August 14, 2018, as amended and supplemented from time to time, between Barclays PLC and The Bank of New York Mellon, London Branch, as Trustee
(“Trustee”) and Paying Agent, as supplemented and amended by the Sixth Supplemental Indenture, dated August 11, 2021, between the Company and the Trustee (together, the “Indenture”), and pursuant to the
prospectus supplement dated August 4, 2021, supplementing the prospectus dated March 1, 2021. Capitalized terms used herein and not defined herein shall have the respective meanings ascribed to such terms in the Indenture. 

 

	11 	 Note: Addresses to be reconfirmed prior to when notice is sent; subject to modification if Securities
are in definitive form and to changes in DTC and CREST (or successor clearing system) policies and procedures. 

  
 E-3 

			
	INFORMATION OF THE HOLDER OR BENEFICIAL OWNER FOR DELIVERY OF CONVERSION SHARES OR CONVERSION SHARES OFFER CONSIDERATION
		
	Surname/Company Name	  	First name
	
	Name to be entered in Barclays PLC’s share register
	
	Tradable Amount of the Securities held on the date hereof
		
	CREST participant ID	  	CREST member account (if applicable)
	
	Cash account details (if applicable)
	
	[Account details of clearing system account]12
	
	[Address to which any Conversion Shares should be delivered]13

 YOU MUST DELIVER THE CONVERSION SHARES SETTLEMENT NOTICE TO THE CONVERSION SHARES DEPOSITORY AND THE TRUSTEE VIA DTC BEFORE
[DATE].14 
 If you fail to properly complete and deliver the Conversion Shares
Settlement Notice on or before the Notice Cut-off Date, the Conversion Shares Depository shall continue to hold your Conversion Shares (or Conversion Shares Component, if applicable). However, your Securities
shall be cancelled on the Final Cancellation Date, which shall be [Date],15 and you will have to provide evidence of your entitlement to the relevant Conversion Shares (or the relevant
Conversion Shares Component, if applicable) satisfactory to the Conversion Shares Depository in its sole and absolute discretion in order to receive delivery of such Conversion Shares (or Conversion Shares Component, if any, of any Conversion Shares
Offer Consideration). 
  

	12 	 Note: To be included if the Conversion Shares will be delivered through a clearing system account
other than CREST. 

	13 	 Note: To be included if the Conversion Shares are not a participating security in CREST or any
another clearing system. 

	14 	 Note: The Notice Cut-off Date must be at least forty
(40) business days following the Suspension Date. 

	15 	 Note: The Final Cancellation Date may be up to twelve (12) business days following the Notice
Cut-off Date. 

  
 E-4

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