Document:

EX-10.15

 Exhibit 10.15 

FIRST AMENDMENT TO EMPLOYMENT AGREEMENT 

THIS FIRST AMENDMENT TO EMPLOYMENT AGREEMENT (this “Amendment”) is entered into as of May 5, 2017, by and between G1
Therapeutics, Inc., a Delaware corporation (the “Company”) and Jay C. Strum, Ph.D. (the “Employee”). 
 WITNESSETH:

 WHEREAS, Employee and the Company entered into an Employment Agreement effective as of July 1, 2014, (the “Employment
Agreement”); 
 WHEREAS, Employee and the Company wish to alter certain terms of the Employment Agreement, particularly with respect to
Employee’s employment compensation, subject to and effective upon the completion of the Company’s initial public offering of its common stock (the “IPO”); and 

WHEREAS, in light of the foregoing, Employee and the Company desire to mutually and voluntarily amend the Employment Agreement pursuant to the
terms as set forth herein. 
 NOW, THEREFORE, in consideration of the foregoing, the mutual promises herein contained, and other good and
valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties hereto, intending to be legally bound, agree as follows. 

1. AMENDMENT TO SECTION 3(a) OF THE EMPLOYMENT AGREEMENT. Section 3(a) of the Employment Agreement is modified, subject to and
effective upon the completion of the IPO, by replacing the existing Section 3(a) in its entirety with a new Section 3(a) as follows: 
  

	 	a)	BASE SALARY. The Company will pay Employee a base salary (the “Base Salary”) at an annual rate of Two Hundred Thirty-Five Thousand Dollars ($235,000.00), payable in equal installments in accordance with
the Company’s customary payroll practices as in effect from time to time. The Base Salary may be reviewed from time to time by the Company and may be increased in the sole discretion of the Board. The Base Salary may also be decreased in
connection with any Company-wide decrease in executive compensation. 

 2. AMENDMENT TO SECTION 3(b) OF THE EMPLOYMENT
AGREEMENT. Section 3(b) of the Employment Agreement is modified, subject to and effective upon the completion of the IPO, by replacing the existing Section 3(b) in its entirety with a new Section 3(b) as follows: 

 

	 	b)	 ANNUAL BONUS. As long as Employee remains employed by the Company, will be eligible to receive an annual
calendar year bonus based upon Employee’s and the Company’s achievement of certain individual and Company goals that will be set for Employee by the Board or its designee (the “Annual Bonus”). The amount of the target Annual
Bonus will be equal to thirty percent (30%) of Employee’s then-current Base Salary as of the date of the payment; provided that the actual amount of the Annual Bonus may be greater or less than such target amount. One half of the Annual

	 	
Bonus awarded for any given year will be paid in cash, and the other half of the Annual Bonus awarded for any given year will be paid, in the sole discretion of the Company, either in cash or in
the form of options to acquire shares of the Company’s common stock (or other equity interests as selected by the Company), in any case subject to the terms and conditions of the Company’s 2017 Employee, Director and Consultant Equity
Incentive Plan. For any grant of stock options or equity issued pursuant to this Section 3(b), the number of options or other equity interests allocated to the non-cash portion of the Annual Bonus will be
determined by the Company in its sole discretion. The Board or its designee will have the sole discretion to set the applicable individual and Company goals, to determine whether the goals have been met, and to determine the amount of the Annual
Bonus. The Annual Bonus for any given year will be paid between January 1 and January 31 in the year immediately following the year in which the Annual Bonus, if any, is earned. Employee must be employed by the Company on December 31
of the bonus year in order to receive the Annual Bonus for that year. 

 3. PROPER AMENDMENT. The parties expressly
acknowledge and agree that this Amendment constitutes a proper amendment and modification of the Employment Agreement by written agreement executed by the parties pursuant to Section 8 of the Employment Agreement. 

4. REMAINDER OF EMPLOYMENT AGREEMENT. Except as expressly set forth in this Amendment, the provisions of the Employment Agreement
remain in full force and effect, in their entirety, in accordance with their terms. 
 5. MISCELLANEOUS. This Amendment shall be
governed, construed, and interpreted in accordance with the laws of the State of North Carolina, without giving effect to conflicts of laws principles. The parties agree that this Amendment may only be modified in a signed writing executed by both
parties. This Amendment shall be binding upon and shall inure to the benefit of the parties hereto and their respective heirs, successors and assigns. This Amendment may be executed in separate counterparts, each of which is deemed to be an original
and all of which taken together constitute one agreement. Facsimile or PDF reproductions of original signatures will be deemed binding for the purpose of the execution of this Amendment. 

[SIGNATURE PAGE FOLLOWS] 

  
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 IN WITNESS WHEREOF, the parties have executed this Amendment to Employment Agreement to be
effective as of the day and year first above written. 
  

									
	Company:	 		 		 	
			
	G1 THERAPEUTICS, INC.	 		 	Employee:
					
	By:	 	 /s/ Mark A. Velleca
	 		 	By:	 	 /s/ Jay C. Strum

		 	Mark A. Velleca	 		 		 	Jay C. Strum, Ph.D.
		 	President and Chief Executive Officer	 		 		 	

  
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 EXECUTIVE EMPLOYMENT AGREEMENT 

This EXECUTIVE EMPLOYMENT AGREEMENT (the “Agreement”), is made and entered into effective as of July 1, 2014 (the
“Effective Date”), by and between G1 Therapeutics, Inc., a Delaware corporation (the “Company”), and Jay C. Strum, Ph.D. (“Employee”). 

1. EMPLOYMENT; DUTIES. The Company agrees to employ Employee as its Chief Scientific Officer, and Employee agrees to accept such
employment upon the terms and conditions hereinafter set forth. Employee will perform such services for the Company as are customarily associated with such position and as may otherwise be assigned to the Employee from time to time by the
Company’s Chief Executive Officer or his designee. Employee will devote his full business time and attention to the business and affairs of the Company, and will perform his duties diligently and to the best of his ability, in compliance with
the Company’s policies and procedures and the laws and regulations that apply to the Company’s business. 
 2. TERM;
TERMINATION. Employee’s employment under this Agreement will commence as of the Effective Date and will continue until terminated by either party. Employee’s employment with the Company is
at-will, and either party can terminate the employment relationship and/or this Agreement at any time, for any or no cause or reason, and with or without prior notice. Upon termination of Employee’s
employment by either party for any reason, Employee will resign his position(s), if any, as an officer or director of the Company, as a member of the Company’s Board of Directors (the “Board”) and any Board committees, as well
as any other positions he may hold with or for the benefit of the Company and/or its affiliates. 
 3. COMPENSATION. As compensation
for the services to be rendered by Employee under this Agreement, the Company will provide the following compensation and benefits during Employee’s employment hereunder. 

(a) BASE SALARY. The Company will pay Employee a base salary at an annual rate of One Hundred Eighty Thousand Dollars ($180,000.00)
(the “Base Salary”), payable in equal installments in accordance with the Company’s customary payroll practices as in effect from time to time. Effective as of July 1, 2015, the Base Salary will be increased to $200,000
per year, provided that the Company has (i) completed an equity financing (which will include for such purpose the issuance of debt convertible into Company equity) in a transaction or a series of transactions leading to the Company’s
receipt of aggregate proceeds totaling at least $10,000,000, or (ii) completed a strategic partnership transaction with a biopharmaceutical company resulting in the receipt by the Company of at least $10,000,000 in non-contingent proceeds. If neither of the conditions described in clause (i) or (ii) above has occurred as of July 1, 2015, then the Base Salary will not be increased on such date, but instead will
be increased to $200,000 only when the first of either such conditions is thereafter met. In addition, the Base Salary may be reviewed from time to time by the Company and may be increased in the sole discretion of the Company. The Base Salary may
also be decreased in connection with any Company-wide decrease in executive compensation. 

 (b) ANNUAL BONUS. Employee will be eligible to receive an annual calendar year bonus
based upon Employee’s and the Company’s achievement of certain individual and Company goals that will be set for Employee by the Board or its designee (the “Annual Bonus”). The amount of the target Annual Bonus will be
equal to twenty percent (20%) of Employee’s then-current Base Salary as of the date of the payment. One half of the Annual Bonus awarded for any given year will be paid in cash, and the other half of the Annual Bonus awarded for any given year
will be paid, in the sole discretion of the Company, either in cash or in the form of options to acquire shares of the Company’s common stock (or other equity interests as selected by the Company), in any case subject to the terms and
conditions of the Company’s 2011 Equity Incentive Plan. For any grant of stock options or equity issued pursuant to this Section 3(b), the number of options or other equity interests allocated to the
non-cash portion of the Annual Bonus will be determined by the Company in its sole discretion. The Board will have the sole discretion to set the applicable individual and Company goals, to determine whether
the goals have been met, and to determine the amount of the Annual Bonus. The Annual Bonus for any given year will be paid between January 1 and January 31 in the year immediately following the year in which the Annual Bonus, if any, is
earned. Employee must be employed by the Company on December 31 of the bonus year in order to receive the Annual Bonus for that year. 

(c) STOCK OPTIONS. Subject to approval by the Board, Employee will be granted, effective as of the date of Board approval, incentive
stock options to purchase 81,000 shares of the Company’s common stock (the “Options”). The Options will be granted pursuant to and subject to the terms and conditions of the Company’s 2011 Equity Incentive Plan and will be
further subject to the terms of a stock option agreement as approved by the Board setting forth the exercise price, vesting conditions and other restrictions. One fourth of the total number of such Options will vest on the first anniversary of the
date hereof, and one forty eighth (1/48th) of the total number of Options will vest each month over the following thirty six (36) months thereafter, so long as Employee remains employed by the Company through each such vesting date. Fifty
Percent (50%) of any unvested options held by Employee (including, for this purpose only, any unvested Options granted pursuant to this Section 3(c) and any options previously granted to Employee) will immediately vest upon the consummation of a
Change in Control (as defined below) and any remaining unvested options (including, for this purpose only, any unvested Options granted pursuant to this Section 3(c) and any options previously granted to Employee) will immediately vest if
Employee’s employment is terminated by the Company without Cause (as defined below) or Employee resigns with Good Reason (as defined below) within ninety (90) days following a Change in Control. A “Change in Control” means
(i) the Company’s merger or consolidation with or into another entity such that the stockholders of the Company prior to such transaction do not or are not expected to own a majority of the voting stock of the surviving entity,
(ii) the sale or other disposition of all or substantially all of the assets of the Company, (iii) the sale or other disposition of greater than 50% of the then-outstanding voting stock of the Company by the holders thereof to one or more
persons or entities who are not then stockholders of the Company. 
 (d) VACATION. Employee will be eligible to accrue up to four
(4) weeks of paid time off per calendar year (prorated for any partial years), which paid time off must be used in accordance with, and is otherwise subject to, the Company’s policies and procedures. 

  
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 (e) BENEFITS. Employee will (subject to applicable eligibility requirements) receive such
other benefits as are provided from time to time to other similarly-situated employees of the Company pursuant to the Company’s policies and procedures as they may be instituted from time to time. All such benefits are subject to the provisions
of their respective plan documents in accordance with their terms. Employee acknowledges and agrees that the Company has the unilateral right to amend, modify or terminate its employee benefit plans or policies to the maximum extent allowed by law.

 (f) EXPENSE REIMBURSEMENT. The Company will reimburse Employee for all reasonable business expenses incurred by Employee in
connection with the performance of his duties hereunder, subject to Employee’s compliance with the Company’s reimbursement policies in effect from time to time. 

(g) WITHHOLDINGS. The Company will withhold from any amounts payable under this Agreement, such federal, state and local taxes, as the
Company reasonably determines are required to be withheld pursuant to applicable law. 
 4. EFFECT OF TERMINATION. 

(a) GENERALLY. When Employee’s employment with the Company is terminated for any reason, Employee, or his estate, as the case may
be, will be entitled to receive the compensation and benefits earned through the effective date of termination, along with reimbursement for any approved business expenses that Employee has timely submitted for reimbursement in accordance with the
Company’s expense reimbursement policy or practice. 
 (b) SEPARATION BENEFITS UPON CERTAIN TERMINATIONS. If the Company
terminates Employee’s employment without Cause (as defined below), or if Employee resigns his employment for Good Reason (as defined below), then conditioned upon Employee executing a Release (as defined below) following such termination,
Employee will be entitled to receive the continued payment of Employee’s then-current Base Salary for a period of three (3) months after termination (the “Separation Benefits”). Effective as of July 1, 2015, the
Separation Benefits will be increased to a period of six (6) months of salary continuation, provided that the Company has (i) completed an equity financing (which will include for such purpose the issuance of debt convertible into Company
equity) in a transaction or a series of transactions leading to the Company’s receipt of aggregate proceeds totaling at least $10,000,000, or (ii) completed a strategic partnership transaction with a biopharmaceutical company resulting in
the receipt by the Company of at least $10,000,000 in non-contingent proceeds. If neither of the conditions described in clause (i) or (ii) above has occurred as of July 1, 2015, then the
Separation Benefits will not be so increased as of such date, but instead will be increased to six (6) months of salary continuation only when the first of either such conditions is thereafter met, provided that Employee is employed by the
Company on such date. The Separation Benefits are conditioned upon Employee executing a release of claims in a form satisfactory to the Company (the “Release”) within the time specified therein, which Release is not revoked within any time
period allowed for revocation under applicable law. The Separation Benefits will be payable to Employee over time in accordance with the Company’s payroll practices and procedures beginning on the sixtieth (60th) day following the termination
of Employee’s employment with the Company, provided that the Company, in its sole discretion, 

  
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may begin the payments earlier. For avoidance of doubt, the termination of Employee’s employment as a result of his death or disability (meaning the inability of Employee, due to the
condition of his physical, mental or emotional health, effectively to perform the essential functions of his job with or without reasonable accommodation for a continuous period of more than 90 days or for 90 days in any period of 180
consecutive days, as determined by the Board in its sole discretion in consultation with a physician retained by the Company) will not constitute a termination without Cause triggering the rights described in this Section 4(b). 

(c) CAUSE. For purposes of this Agreement, “Cause” means: (i) Employee’s fraud, embezzlement or
misappropriation with respect to the Company; (ii) Employee’s material breach of fiduciary duties to the Company; (iii) Employee’s willful or negligent misconduct that has or may reasonably be expected to have a material adverse
effect on the property, business, or reputation of the Company; (iv) Employee’s material breach of this Agreement; (v) Employee’s willful failure or refusal to perform his material duties under this Agreement or failure to follow
any specific lawful instructions of the Board; (vi) Employee’s conviction or plea of nolo contendere in respect of a felony or of a misdemeanor involving moral turpitude; (vii) Employee’s alcohol or substance abuse which has a
material adverse effect on Employee’s ability to perform his duties under this Agreement; or (viii) Employee’s engagement in a form of discrimination or harassment prohibited by law (including, without limitation, discrimination or
harassment based on race, color, religion, sex, national origin, age or disability). In the event that the Company concludes that Employee has engaged in acts constituting in Cause as defined in clause (iii), (iv), (v), or (vii) above, prior to
terminating this Agreement for Cause the Company will provide Employee with at least fifteen (15) days’ advance written notice of the specific circumstances constituting such Cause, and an opportunity to correct such circumstances. 

(d) GOOD REASON. In order for Employee to resign for Good Reason, Employee must provide written notice to the Company of the existence
of the Good Reason condition within thirty (30) days of the initial existence of such Good Reason condition. Upon receipt of such notice, the Company will have fifteen (15) days during which it may attempt to remedy the Good Reason
condition and not be required to provide for the benefits described in Section 4(b) above as a result of such proposed resignation if successfully remedied. If the Good Reason condition is not remedied within such fifteen (15) day period,
Employee may resign based on the Good Reason condition specified in the notice effective no later than thirty (30) days following the expiration of the fifteen (15) day cure period. For purposes of this Agreement, “Good
Reason” means the occurrence of any of the following events without Employee’s consent: (i) a material reduction of Employee’s Base Salary not generally applicable to other executive-level employees of the Company,
(ii) a material diminution of the Employee’s authority, duties, or responsibilities, (iii) a relocation of Employee’s primary workplace to a location that is more than fifty (50) miles from the location of Employee’s
primary workplace as of the date hereof, or (iv) the Company’s material breach of this Agreement. 
 (e) APPLICATION OF
INTERNAL REVENUE CODE SECTION 409A. Notwithstanding anything to the contrary set forth herein, any payments and benefits provided under this Section 4 that constitute “deferred compensation” within the meaning of Section 409A
of the Internal Revenue Code and the regulations and other guidance thereunder and any state law of similar effect (collectively “Section 409A”) will not commence in connection with 

  
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Employee’s termination of employment unless and until Employee has also incurred a “separation from service” (as such term is defined in Treasury Regulation Section 1.409A-1(h) (a “Separation From Service”), unless the Company reasonably determines that such amounts may be provided to Employee without causing Employee to incur the additional 20% tax under
Section 409A. The parties intend that each installment of the Separation Benefits payments provided for in this Agreement is a separate “payment” for purposes of Treasury Regulation Section
1.409A-2(b)(2)(i). For the avoidance of doubt, the parties intend that payments of the Separation Benefits set forth in this Agreement satisfy, to the greatest extent possible, the exemptions from the
application of Section 409A provided under Treasury Regulation Sections 1.409A-1(b)(4), 1.409A-1(b)(5) and 1.409A-1(b)(9).
However, if the Company determines that the Separation Benefits constitute “deferred compensation” under Section 409A and Employee is, on the termination of service, a “specified employee” of the Company or any successor entity
thereto, as such term is defined in Section 409A, then, solely to the extent necessary to avoid the incurrence of the adverse personal tax consequences under Section 409A, the timing of the Separation Benefits payments will be delayed
until the earlier to occur of: (i) the date that is six months and one day after Employee’s Separation From Service, or (ii) the date of Employee’s death (such applicable date, the “Specified Employee Initial Payment
Date”), the Company (or the successor entity thereto, as applicable) will (A) pay to Employee a lump sum amount equal to the sum of the Separation Benefits payments that Employee would otherwise have received through the Specified
Employee Initial Payment Date if the commencement of the payment of the Separation Benefits had not been so delayed pursuant to this Section and (B) commence paying the balance of the Separation Benefits in accordance with the applicable
payment schedules set forth in this Agreement. 
 (f) NO FURTHER OBLIGATIONS. Except as expressly provided above or as otherwise
required by law, the Company will have no obligations to Employee in the event of the termination of this Agreement for any reason. 
 5.
EMPLOYEE REPRESENTATIONS. Employee represents and warrants that he is not obligated or restricted under any agreement (including any non-competition or confidentiality agreement), judgment, decree,
order or other restraint of any kind that could impair Employee’s ability to perform the duties and obligations required of Employee hereunder. Employee further agrees that he will not divulge to the Company any confidential information and/or
trade secrets belonging to others, including Employee’s former employers, nor will the Company seek to elicit from Employee such information. Consistent with the foregoing, Employee will not provide to the Company, and the Company will not
request, any documents or copies of documents containing such information. 
 6. PRIOR AGREEMENTS. Employee and the Company have
previously entered into a Non-Competition and Non-Solicitation Agreement dated as of October 8, 2013 (the
“Non-Competition Agreement”) and an Employee Confidentiality and Inventions Agreement dated as of March 31, 2013 (the “Confidentiality Agreement”). The Non-Competition Agreement and the Confidentiality Agreement remain in force and effect pursuant to their terms, and neither is altered or amended by this Agreement. 

7. NOTICES. Any notice required to be given hereunder will be sufficient if in writing and hand delivered or sent by mail, return
receipt requested, postage prepaid, in the case 

  
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of Employee, to his address shown on the Company’s records, and in the case of the Company, to 79 T.W. Alexander Drive, 4401 Research Commons, Suite 105, Research Triangle Park, NC 27709, or
to such other addresses as either party shall specify to the other. 
 8. AMENDMENT; WAIVER. No amendment of any provision of this
Agreement will be valid unless the amendment is in writing and signed by the Company and Employee. No waiver of any provision of this Agreement will be valid unless the waiver is in writing and signed by the waiving party. The failure of a party at
any time to require performance of any provision of this Agreement will not affect such party’s rights at a later time to enforce such provision. No waiver by a party of any breach of this Agreement will be deemed to extend to any other breach
hereunder or affect in any way any rights arising by virtue of any other breach. 
 9. GOVERNING LAW; VENUE. This Agreement will be
governed by and construed in accordance with the laws of the State of North Carolina, without regard to that body of law known as choice of law. The parties agree that any litigation arising out of or related to this Agreement or Employee’s
employment by the Company will be brought exclusively in any state or federal court in Durham County, North Carolina. Each party (i) consents to the personal jurisdiction of said courts, (ii) waives any venue or inconvenient forum defense
to any proceeding maintained in such courts, and (iii) agrees not to bring any proceeding arising out of or relating to this Agreement or Employee’s employment by the Company in any other court. 

10. BENEFIT. This Agreement will be binding upon and will inure to the benefit of each of the parties hereto, and to their respective
heirs, representatives, successors and permitted assigns. Employee may not assign any of his rights or delegate any of his duties under this Agreement. 

11. ENTIRE AGREEMENT. This Agreement contains the entire agreement and understanding by and between the Company and Employee with
respect to the subject matter hereof, and any representations, promises, agreements or understandings, written or oral, not herein contained will be of no force or effect. Notwithstanding the foregoing, the
Non-Competition Agreement and the Confidentiality Agreement remain in force and effect pursuant to their terms, and neither is altered or amended by this Agreement. 

12. CAPTIONS; RULE OF CONSTRUCTION. The captions in this Agreement are for convenience only and in no way define, bind or describe the
scope or intent of this Agreement. The terms and provisions of this Agreement will not be construed against the drafter or drafters hereof. All parties hereto agree that the language of this Agreement will be construed as a whole according to its
fair meaning and not strictly for or against any of the parties hereto. 
 13. COUNTERPARTS. This Agreement may be executed in one or
more counterparts, each of which will be deemed an original but all of which together will constitute one and the same agreement. Facsimile or PDF reproductions of original signatures will be deemed binding for the purpose of the execution of this
Agreement. 
 14. SEVERABILITY. Each provision of this Agreement is severable from every other provision of this Agreement. Any
provision of this Agreement that is determined by any court of competent jurisdiction to be invalid or unenforceable will not affect the validity or 

  
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enforceability of any other provision. Any provision of this Agreement held invalid or unenforceable only in part or degree will remain in full force and effect to the extent not held invalid or
unenforceable. 
 15. SURVIVAL. The terms of Sections 4 through 15 will survive the termination or expiration of this Agreement for
any reason. 
 IN WITNESS WHEREOF, the parties have executed this Agreement effective as of the Effective Date. 

 

					
	G1 THERAPEUTICS, INC.:

 
					
		
	By:	 	 /s/ Mark Velleca

		
	Name:	 	Mark Velleca
		
	Title:	 	CEO

 
					
	
	EMPLOYEE:
		
	 /s/ Jay C. Strum
	 	[SEAL]
	Jay C. Strum, Ph.D.

  
 10EX-4.1

 Exhibit 4.1 

Execution Version 
  

 
 FIRST SUPPLEMENTAL INDENTURE DATED AS
OF MAY 8, 2017 
 TO 

SENIOR DEBT INDENTURE DATED OCTOBER 31, 2014 

BETWEEN 
 STATE STREET CORPORATION

 AND 
 U.S. BANK NATIONAL
ASSOCIATION 
 Trustee 
  

 

 THIS FIRST SUPPLEMENTAL INDENTURE (“Supplemental Indenture”) is dated as of May 8,
2017 between STATE STREET CORPORATION, a corporation duly organized and existing under the laws of the Commonwealth of Massachusetts, as the Company, and U.S. Bank National Association, a national banking association duly organized and existing
under the laws of the United States of America, as Trustee. All terms used in this Supplemental Indenture which are defined in the Senior Debt Indenture dated as of October 31, 2014 between said parties (as supplemented or amended prior to the
date hereof, the “Original Indenture”), and are not otherwise defined in this Supplemental Indenture, shall have the meanings assigned to them in the Original Indenture. 

W I T N E S S E T H : 

WHEREAS, the Company and the Trustee are parties to the Original Indenture; 

WHEREAS, Section 901(5) of the Original Indenture provides that without the consent of the Holders of any Securities, the Company, when
authorized by a Board Resolution, and the Trustee may enter into indentures supplemental to the Original Indenture to add to, change or eliminate any of the provisions of the Original Indenture in respect of one or more series of Securities,
provided that any such addition, change or elimination (A) shall neither (i) apply to any Security of any series issued prior to the execution of such supplemental indenture and entitled to the benefit of such provision nor
(ii) modify the rights of the Holder of any such Security with respect to such provision or (B) shall become effective only when there is no such Security Outstanding; 

WHEREAS, the Company wishes to make certain changes relating to covenants, covenant breaches, events of default, remedies and permitted
transfers, with the amendments applying only to Securities issued after the time this Supplemental Indenture is executed and not applying to, or modifying the rights of Holders of, any other Securities; 

WHEREAS, the entry into this Supplemental Indenture by the parties hereto is in all respects authorized by the provisions of the Original
Indenture; and 
 WHEREAS, all things necessary to make this Supplemental Indenture a valid indenture and agreement according to its terms
have been done; 
 NOW, THEREFORE: 

In consideration of the covenants and other provisions set forth in this Supplemental Indenture and the Original Indenture, the Company and
the Trustee mutually covenant and agree with each other, and for the equal and proportionate benefit of the respective Holders of the applicable Securities from time to time, as follows: 

ARTICLE 1 
 Amendment of Original
Indenture 
 Section 1.01.    Applicability. Section 1.02 of this Supplemental Indenture
(a) shall, except as otherwise may be provided pursuant to Section 301 of the Original Indenture with respect to 

  
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any particular Security issued after the date hereof, apply to Securities issued after the execution of this Supplemental Indenture and (b) shall not apply to, or modify the rights of
Holders of, any Securities issued before such execution. For purposes of this Section 1.01, a Security shall be deemed to be issued at the time of the original issuance of the Security pursuant to Section 301. The Trustee shall have no
obligation to determine whether any Security has been issued after or before the execution of this Supplemental Indenture. The Trustee may conclusively rely and shall be fully protected in acting or refraining from acting upon any such determination
made by the Company. 
 Section 1.02.    Amendments 

(a)    Section 101 of the Original Indenture is hereby amended by adding the following definition immediately following
the definition of “corporation”: 
 ““Covenant Breach” means, with respect to the Securities of any series: 

(1)    default in the deposit of any sinking fund payment, when and as due by the terms of a Security of that series; or

 (2)    default in the performance, or breach, of any covenant or warranty of the Company in this Indenture (other
than a covenant or warranty a default in whose performance or whose breach is specifically dealt with in Section 501 of this Indenture or which has expressly been included in this Indenture solely for the benefit of Securities of one or more
other series), and continuance of such default or breach for a period of 90 days after there has been given, by registered or certified mail, to the Company by the Trustee or to the Company and the Trustee by the Holders of at least 25% in principal
amount of the Outstanding Securities of such series a written notice specifying such default or breach and requiring it to be remedied and stating that such notice is a “Notice of Covenant Breach” hereunder. 

A Covenant Breach shall not be an Event of Default with respect to any Security, except to the extent otherwise specifically provided pursuant to
Section 301 with respect to such Security.” 
 (b)    The definition of “Intermediate Subsidiary”
contained in Section 101 of the Original Indenture is hereby deleted in its entirety. 
 (c)    Section 101 of the
Original Indenture is hereby amended by adding the following definition immediately following the definition of “Maturity”: 

““Notice of Covenant Breach” has the meaning specified in the definition of “Covenant Breach” in this
Section 101.” 
 (d)    The definition of “Notice of Default” contained in Section 101 of the
Original Indenture is hereby deleted in its entirety. 
 (e)    The first sentence of the sixth paragraph of
Section 104 of the Original Indenture is hereby amended to read in its entirety as follows: 

  
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 “The Trustee may set any day as a record date for the purpose of determining the Holders of
Outstanding Securities of any series entitled to join in the giving or making of (i) any Notice of Covenant Breach, (ii) any declaration of acceleration referred to in Section 502, (iii) any request to institute proceedings referred
to in Section 507(2) or (iv) any direction referred to in Section 512, in each case with respect to Securities of such series.” 

(f)    The eighth paragraph of Section 203 of the Original Indenture is hereby amended to read in its entirety as
follows: 
 “[If applicable, insert — The Indenture contains provisions for defeasance at any time of [the entire
indebtedness of this Security] [or] [certain restrictive covenants, Events of Default and Covenant Breaches with respect to this Security] [, in each case] upon compliance with certain conditions set forth in the Indenture.]” 

(g)    The eleventh paragraph of Section 203 of the Original Indenture is hereby amended by adding the following
sentence at the end of the paragraph: 
 “For the purpose of this paragraph, the term “default” means any event that is, or
after notice or lapse of time or both would become, an Event of Default or Covenant Breach in respect of such Securities.” 

(h)    The twelfth paragraph of Section 203 of the Original Indenture is hereby amended to read in its entirety as
follows: 
 “As provided in and subject to the provisions of the Indenture, the Holder of this Security shall not have the right to
institute any proceeding 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 Event of Default or
Covenant Breach with respect to the Securities of this series, the Holders of not less than 25% in principal amount of the Securities of this series at the time Outstanding shall have made written request to the Trustee to institute proceedings in
respect of such Event of Default or Covenant Breach, as applicable, as Trustee and offered the Trustee reasonable indemnity, and the Trustee shall not have received from the Holders of a majority in principal amount of Securities of this series at
the time Outstanding a direction inconsistent with such request, and shall have failed to institute any such proceeding, for 60 days after receipt of such notice, request and offer of indemnity. The foregoing shall not apply to any suit instituted
by the Holder of this Security for the enforcement of any payment of principal hereof or any premium or interest hereon on or after the respective due dates expressed herein.” 

(i)    Section 301 of the Original Indenture is hereby amended by deleting the existing Clause (18) and replacing
such Clause with the following: 
 “(18) any addition to or change in the covenants set forth in Article Ten or the definition of “Covenant
Breach” set forth in Section 101, which applies to Securities of the series; and”. 
 (j)    Clause
(2)(B) of Section 305 of the Original Indenture is hereby amended to read in its entirety as follows: 

  
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 “(B) there shall have occurred and be continuing an Event of Default or Covenant Breach with respect to such
Global Security or”. 
 (k)    The definition of “Events of Default” contained in Section 501 of the
Original Indenture is hereby amended by deleting the existing Sections 501(2), 501(3), 501(4), 501(5) and 501(6) and replacing them with the following, and references in the Original Indenture to “Events of Default” shall mean Events of
Default as such term is so amended: 
 “(2)    default in the payment of the principal of or any premium on any
Security of that series at its Maturity, and continuance of such default for a period of 30 days; or 
 (3)    [OMITTED]

 (4)    [OMITTED] 

(5)    the entry by a court having jurisdiction in the premises of (A) a decree or order for relief in respect of the
Company in an involuntary case or proceeding under any applicable Federal or State bankruptcy, insolvency, reorganization or other similar law or (B) a decree or order appointing a custodian, receiver, liquidator, assignee, trustee,
sequestrator or other similar official of the Company or all or substantially all of its property, or ordering the winding up or liquidation of its affairs, and, in the case of either clause (A) or (B), the continuance of any such decree or
order for relief or any such other decree or order unstayed and in effect for a period of 90 consecutive days; or 

(6)    the commencement by the Company of a voluntary case or proceeding under any applicable Federal or State bankruptcy,
insolvency, reorganization or other similar law, or the consent by it to the entry of a decree or order for relief in respect of the Company in an involuntary case or proceeding under any applicable Federal or State bankruptcy, insolvency,
reorganization or other similar law, or the consent by it to the appointment of or taking possession by a custodian, receiver, liquidator, assignee, trustee, sequestrator or other similar official of the Company or of all or substantially all of its
property, or the taking of corporate action by the Company in furtherance of any such action; or” 
 (l)    Section
501 of the Original Indenture is hereby amended by adding the following paragraph at the end of such Section: 
 “For the avoidance of
doubt, the events described in clauses (5) and (6) of this Section 501, insofar as they relate to the Bank, shall not constitute an Event of Default.” 

(m)    The first paragraph of Section 502 of the Original Indenture is hereby amended by adding the following
sentence at the end of the paragraph. 
 “For the further avoidance of doubt, except to the extent otherwise specifically provided
pursuant to Section 301 with respect to a particular Security or Securities, neither the Trustee nor any Holder shall be entitled to accelerate the Maturity of any Security, nor shall the Maturity of any Security be otherwise accelerated, as a
result of a Covenant Breach.” 

  
 4 

 (n)    Section 503 of the Original Indenture is hereby amended by deleting
the existing Clause (2) of the first paragraph and replacing such Clause with the following: 
 “(2) default is
made in the payment of the principal of (or premium, if any, on) any Security at the Maturity thereof and such default continues for a period of 30 days,” 

(o)    The second paragraph of Section 503 of the Original Indenture is hereby amended to read in its entirety as
follows: 
 “If an Event of Default or Covenant Breach with respect to Securities of any series occurs and is continuing, the Trustee
may in its discretion proceed to protect and enforce its rights and the rights of the Holders of Securities of such series by such appropriate judicial proceedings as the Trustee shall deem most effectual to protect and enforce any such rights,
whether for the specific enforcement of any covenant or agreement in this Indenture or in aid of the exercise of any power granted herein, or to enforce any other proper remedy.” 

(p)    Section 507 of the Original Indenture is hereby amended by deleting the existing Clauses (1) and (2) and
replacing such Clauses with the following: 
 “(1)    such Holder has previously given written notice to the
Trustee of a continuing Event of Default or Covenant Breach with respect to the Securities of that series; 
 (2)    the
Holders of not less than 25% in principal amount of the Outstanding Securities of that series shall have made written request to the Trustee to institute proceedings in respect of such Event of Default or Covenant Breach, as applicable, in its own
name as Trustee hereunder;”. 
 (q)    The first sentence of Section 511 of the Original Indenture is hereby
amended to read in its entirety as follows: 
 “No delay or omission of the Trustee or of any Holder of any Securities to exercise any
right or remedy accruing upon any Event of Default or Covenant Breach shall impair any such right or remedy or constitute a waiver of any such Event of Default or Covenant Breach or an acquiescence therein.” 

(r)    The second paragraph of Section 513 of the Original Indenture is hereby amended to read in its entirety as
follows: 
 “Upon any such waiver, such default shall cease to exist, and any Event of Default or Covenant Breach arising therefrom
shall be deemed to have been cured, for every purpose of this Indenture; but no such waiver shall extend to any subsequent or other default or impair any right consequent thereon.” 

(s)    The first paragraph of Section 602 of the Original Indenture is hereby amended to read in its entirety as
follows: 

  
 5 

 “If a default occurs hereunder with respect to Securities of any series, the Trustee shall
give the Holders of Securities of such series notice of such default as and to the extent provided by the Trust Indenture Act; provided, however, that in the case of any default of the character specified in Clause (2) of the definition of
“Covenant Breach” in Section 101 with respect to Securities of such series, no such notice to Holders shall be given until at least 60 days after the occurrence thereof. For the purpose of this Section, the term “default”
means any event that is, or after notice or lapse of time or both would become, an Event of Default or Covenant Breach with respect to Securities of such series.” 

(t)    Section 603 of the Original Indenture is hereby amended by deleting the existing Clause (9) and replacing such
Clause with the following: 
 “(9)    the Trustee shall not be deemed to have notice of any default, Event of
Default or Covenant Breach unless a Responsible Officer of the Trustee has actual knowledge thereof or unless written notice of any event which is in fact such a default is received by the Trustee at the Corporate Trust Office of the Trustee, and
such notice references the Securities and this Indenture;”. 
 (u)    Section 608 of the Original Indenture is
hereby amended by adding the following sentence at the end of the paragraph: 
 “For the purpose of determining whether a conflicting
interest exists within the meaning of the Trust Indenture Act, “default” means any event which is, or after notice or lapse of time or both would become, an Event of Default or Covenant Breach.” 

(v)    The first paragraph of Section 801 of the Original Indenture is hereby amended to read in its entirety as
follows: 
 “The Company shall not consolidate with or merge into any other Person or convey, transfer or lease its properties and
assets substantially as an entirety to any Person (other than the conveyance, transfer or lease of its properties and assets substantially as an entirety to one or more of the Company’s Subsidiaries) unless:” 

(w)    Section 801 of the Original Indenture is hereby amended by deleting the existing Clause (2) and replacing such
Clause with the following: 
 “(2)    immediately after giving effect to such transaction and treating any
indebtedness which becomes an obligation of the Company or any Subsidiary as a result of such transaction as having been incurred by the Company or such Subsidiary at the time of such transaction, no Event of Default or Covenant Breach, and no event
which, after notice or lapse of time or both, would become an Event of Default or Covenant Breach, shall have happened and be continuing; and”. 

(x)    Section 1004 of the Original Indenture is hereby amended to read in its entirety as follows: 

  
 6 

 “The Company will deliver to the Trustee, within 120 days after the end of each fiscal
year of the Company ending after the date hereof, an Officers’ Certificate, stating whether or not to the best knowledge of the signers thereof the Company is in default in the performance and observance of any of the terms, provisions and
conditions of this Indenture (without regard to any period of grace or requirement of notice provided hereunder) and, if the Company shall be in default, specifying all such defaults and the nature and status thereof of which they may have
knowledge. For the purpose of this Section, the term “default” means any event that is, or after notice or lapse of time or both would become, an Event of Default or Covenant Breach.” 

(y)    Section 1008 of the Original Indenture is hereby amended to read in its entirety as follows:  
 “So long as any of the Securities shall be outstanding, neither the Company nor any
Subsidiary that owns Voting Stock of the Bank will sell, assign, transfer, grant a security interest in or otherwise dispose of any shares of, securities convertible into or options, warrants or rights to subscribe for or purchase shares of, Voting
Stock of the Bank or of any Subsidiary that owns Voting Stock of the Bank, nor will the Company or any Subsidiary that owns Voting Stock of the Bank permit the Bank to issue any shares of, or securities convertible into, or options, warrants or
rights to subscribe for or purchase, shares of, Voting Stock of the Bank, except that the Company, any such Subsidiary that owns Voting Stock of the Bank, or the Bank, as the case may be, may make any such sale, assignment, transfer, grant of a
security interest, issuance or other disposition if, after giving effect thereto (and assuming for such purpose that all such convertible securities have been fully converted and all such options, warrants or rights have been fully exercised), the
Company (whether directly or indirectly through one or more Subsidiaries (and after adjustment for any stock of a Subsidiary not held directly or indirectly by the Company)) will own in the aggregate at least 80% of the Voting Stock of the Bank then
issued and outstanding free and clear of any security interest. Notwithstanding the foregoing, and for the avoidance of doubt, (i) subject to provisions of Article Eight, the Company may merge, consolidate or combine with the Bank or merge,
consolidate or combine with another corporation and (ii) the Bank may be merged into or consolidated with another corporation organized under the laws of the United States, any State thereof or the District of Columbia if, in the case of a
transaction described in this clause (ii), after giving effect to such merger, consolidation or combination of the Bank, the Company (whether directly or indirectly through any one or more Subsidiaries (and after adjustment for any stock of a
Subsidiary not held directly or indirectly by the Company)) will own in the aggregate at least 80% of the Voting Stock of the resulting entity (whether the Bank or such other corporation) and immediately after giving effect thereto and treating any
such resulting entity as the Bank for purposes of this Indenture, no Event of Default or Covenant Breach, and no event which, after notice or lapse of time or both, would become an Event of Default or Covenant Breach, shall have happened and be
continuing.” 
 (z)    The last sentence of Section 1302 of the Original Indenture is hereby amended to read
in its entirety as follows: 

  
 7 

 “For the avoidance of doubt, following a defeasance of any series of Securities, payment of
the Securities of such series may not be accelerated because of an Event of Default (or for the further avoidance of doubt, because of a Covenant Breach).” 

(aa)    Section 1303 of the Original Indenture is hereby amended to read in its entirety as follows, and references
in the Original Indenture to “Covenant Defeasance” shall mean Covenant Defeasance as such term is defined in Section 1303 as so amended: 

“Upon the Company’s exercise of its option (if any) to have this Section applied to any Securities or any series of Securities, as
the case may be, (1) the Company shall be released from its obligations under Section 1008 and any covenants provided pursuant to Section 301(18), 901(2) or 901(7) for the benefit of the Holders of such Securities and (2) the
occurrence of any breach under Section 1008 or any covenants provided pursuant to Section 301(18), 901(2) or 901(7) for the benefit of the Holders of such Securities shall be deemed not to be or result in an Event of Default or a Covenant
Breach, in each case, with respect to such Securities as provided in this Section on and after the date the conditions set forth in Section 1304 are satisfied (hereinafter called “Covenant Defeasance”). For this purpose, such Covenant
Defeasance means that, with respect to such Securities, the Company may omit to comply with and shall have no liability in respect of any term, condition or limitation set forth in any such specified Section, whether directly or indirectly by reason
of any reference elsewhere herein to any such Section or by reason of any reference in any such Section to any other provision herein or in any other document, but the remainder of this Indenture and such Securities shall be unaffected thereby.
Following a Covenant Defeasance with respect to any Securities or series of Securities, payment of such Securities or series of Securities may not be accelerated because of an Event of Default resulting from a failure to comply with the obligations
or covenants in any such specified section in this Section 1303 (or, for the avoidance of doubt, because of a Covenant Breach).” 

(bb)    Section 1304 of the Original Indenture is hereby amended by deleting the existing Clause (5) and replacing
such Clause with the following: 
 “(5)    No event which is, or after notice or lapse of time or both would
become, an Event of Default or Covenant Breach with respect to such Securities or any other Securities shall have occurred and be continuing at the time of such deposit or, with regard to any such event specified in Sections 501(5) and (6), at any
time on or prior to the 90th day after the date of such deposit (it being understood that this condition shall not be deemed satisfied until after such 90th day).” 

ARTICLE 2 
 Miscellaneous
Provisions 
 Section 2.01.    Other Terms of Indenture. Except insofar as otherwise expressly provided in
this Supplemental Indenture, all provisions, terms and conditions of the Original Indenture are in all respects ratified and confirmed and shall remain in full force and effect. To the extent set forth in Section 1.01 above, this Supplemental
Indenture shall be a part of the Indenture. 

  
 8 

 Section 2.02.    Governing Law. This Supplemental Indenture shall
be governed by and construed in accordance with the laws of the State of New York. 

Section 2.03.    Counterparts. This Supplemental Indenture may be executed in any number of counterparts, each
of which shall be an original; but such counterparts shall together constitute but one and the same instrument. 

Section 2.04.    The Trustee. The recitals contained herein shall be taken as the statements of the Company,
and the Trustee does not assume any responsibility for their correctness. The Trustee makes no representations as to the validity or sufficiency of this Supplemental Indenture. 

  
 9 

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

			
	STATE STREET CORPORATION
		
	By:	 	 /s/ John Slyconish

		 	Name: John Slyconish
		 	Title: Executive Vice President and Treasurer
	
	U.S. BANK NATIONAL ASSOCIATION, as Trustee
		
	By:	 	 /s/ Laura Cawley

		 	Name: Laura Cawley
		 	Title: Vice President

  
 10

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