Document:

EX-10.22

 Exhibit 10.22 

AMENDED AND RESTATED EMPLOYMENT AGREEMENT 

THIS AMENDED AND RESTATED EMPLOYMENT AGREEMENT (this “Agreement”) is entered into by and among eFFECTOR Therapeutics, Inc., a
Delaware corporation (“PubCo”), eFFECTOR Therapeutics Operations, Inc., a Delaware corporation (“OpCo” and, together with PubCo, the “Company”), and Premal Patel, M.D., Ph.D.
(“Executive”), and shall be effective as of closing of the transactions contemplated by that certain Agreement and Plan of Merger (the “Merger Agreement”) by and among PubCo, Locust Walk Acquisition Corp. and Locust
Walk Merger Sub, Inc. and dated May 26, 2021 (the “Effective Date”). 
 WHEREAS, the Company and the Executive
previously entered into that certain Employment Agreement, dated July 13, 2020, (the “Prior Agreement”), which sets forth the terms and conditions of the Executive’s employment with the Company; and 

WHEREAS, in connection with the transactions contemplated by the Merger Agreement, the parties desires to amend and restate the Prior
Agreement on the terms and conditions set forth in this Agreement. 
 NOW, THEREFORE, in consideration of the mutual promises herein
contained, the parties agree as follows: 
 1. Definitions. As used in this Agreement, the following terms shall have the following
meanings: 
 (a) Board. “Board” means the Board of Directors of the Company. 

(b) Cause. “Cause” means any of the following: 

(i) the commission of an act of fraud, embezzlement or dishonesty by Executive, or the commission of some other illegal act by Executive
(other than traffic violations or other offenses or violations outside of the course of Executive’s employment), that has a demonstrable material adverse impact on the Company or any successor or affiliate thereof; 

(ii) a conviction of, or plea of “guilty” or “no contest” to, a felony by Executive; 

(iii) any unauthorized use or disclosure by Executive of confidential information or trade secrets of the Company or any successor or
affiliate thereof that has, or may reasonably be expected to have, a material adverse impact on any such entity; 
 (iv) Executive’s
gross negligence, insubordination or material violation of any duty of loyalty to the Company or any successor or affiliate thereof, or any other demonstrable material misconduct on the part of Executive; 

 (v) Executive’s ongoing and repeated failure or refusal to perform or neglect of
Executive’s duties as required by this Agreement or to comply with the instructions given to him or her by the Chief Executive Officer or the Board; or 

(vi) Executive’s willful, material breach of any Company policy or any material provision of this Agreement; 

provided, however, that, for the matters set forth in clauses (v) or (vi) above, “Cause” shall additionally mean Executive’s
failure to cure such conduct to the reasonable satisfaction of the Board within thirty (30) days of written notice to Executive setting forth in reasonable detail the conduct resulting in such determination of “Cause” and the need for
Executive to cure such matter. Prior to the determination “Cause” under this Section 1(b) has occurred, the Company shall provide the Executive an opportunity to be heard prior to the final decision to terminate the Executive’s
employment hereunder for such “Cause” and make any decision that such “Cause” exists in good faith. 
 The foregoing definition shall
not in any way preclude or restrict the right of the Company or any successor or affiliate thereof to discharge or dismiss Executive for any other acts or omissions, but such other acts or omissions shall not be deemed, for purposes of this
Agreement, to constitute grounds for termination for Cause. 
 (c) Change in Control. “Change in Control” shall have
the meaning given to such term in the eFFECTOR Therapeutics, Inc. 2021 Incentive Award Plan. Notwithstanding the foregoing, in no event shall the transactions occurring in connection with the Merger Agreement constitute a Change in Control and, if a
Change in Control constitutes a payment event with respect to any amount hereunder that provides for the deferral of compensation that is subject to Section 409A, to the extent required to avoid the imposition of additional taxes under
Section 409A, the transaction or event shall only constitute a Change in Control for purposes of the payment timing of such amount if such transaction also constitutes a “change in control event,” as defined in Treasury Regulation Section 1.409A-3(i)(5). 
 (d) Code. “Code” means the Internal Revenue Code of
1986, as amended from time to time, and the Treasury Regulations and other interpretive guidance issued thereunder. 
 (e) Good
Reason. “Good Reason” means the occurrence of any of the following events or conditions without Executive’s written consent: 

(i) a material diminution in Executive’s authority, duties or responsibilities; 

(ii) a material diminution in Executive’s base compensation, unless such a reduction is imposed as part of a generalized reduction in the
base salaries of senior management of the Company; 
 (iii) a change to the geographic location at which Executive must perform his or her
duties on a regular basis to a location that is more than fifty (50) miles from the Company’s then-current offices (excepting reasonable travel on the Company’s business); or 

  
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 (iv) a material breach by the Company or any successor or affiliate of its obligations to
Executive under this Agreement. 
 Executive must provide written notice to the Company of the occurrence of any of the foregoing events or
conditions without Executive’s written consent within thirty (30) days of the occurrence of such event. The Company or any successor or affiliate shall have a period of thirty (30) days to cure such event or condition after receipt of
written notice of such event from Executive. The Executive’s Separation from Service by reason of resignation from employment with the Company for Good Reason must occur within ninety (90) days following the initial existence of the act or
failure to act constituting Good Reason. 
 (f) Involuntary Termination. “Involuntary Termination” means (i) the
Executive’s Separation from Service by reason of Executive’s discharge by the Company other than for Cause, or (ii) the Executive’s Separation from Service by reason of Executive’s resignation of employment with the Company
for Good Reason. Executive’s Separation from Service by reason of Executive’s death or discharge by the Company following Executive’s disability shall not constitute an Involuntary Termination. 

(g) Separation from Service. “Separation from Service,” with respect to the Executive, means the Executive’s
“separation from service,” as defined in Treasury Regulation Section 1.409A-1(h). 

(h) Stock Awards. “Stock Awards” means all stock options, restricted stock and such other awards granted pursuant to
the Company’s stock option and equity incentive award plans or agreements and any shares of stock issued upon exercise thereof; provided, however, that Stock Awards shall not include any Earn-Out Shares
(as defined in the Merger Agreement). 
 2. Services to Be Rendered. 

(a) Duties and Responsibilities. Executive shall serve as Chief Medical Officer of the Company. In the performance of such duties,
Executive shall report directly to the Chief Executive Officer. Executive hereby consents to serve as an officer and/or director of the Company or any subsidiary or affiliate thereof without any additional salary or compensation, if so requested by
the Chief Executive Officer or the Board. Executive shall be employed by the Company on a full time basis. Executive’s primary place of work shall be the Company’s facility in San Diego, California, or such other location as may be
designated by the Chief Executive Officer or the Board from time to time. Executive shall also render services at such other places within or outside the United States as the Chief Executive Officer or the Board may direct from time to time.
Executive shall be subject to and comply with the policies and procedures generally applicable to senior executives of the Company to the extent the same are not inconsistent with any term of this Agreement. 

(b) Exclusive Services. Executive shall at all times faithfully, industriously and to the best of his or her ability, experience and
talent perform to the satisfaction of the Chief Executive Officer or the Board all of the duties that may be assigned to Executive hereunder and shall devote substantially all of his or her productive time and efforts to the performance of
such duties. Subject to the terms of the Proprietary Information and Inventions Agreement referred 

  
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to in Section 5(b), this shall not preclude Executive from devoting time to personal and family investments or serving on community and civic boards, or participating in industry
associations, provided such activities do not interfere with his or her duties to the Company, as determined in good faith by the Chief Executive Officer or the Board. Executive agrees that he or she will not join any boards, other than community
and civic boards (which do not interfere with his or her duties to the Company), without the prior approval of the Chief Executive Officer or the Board.  

3. Compensation and Benefits. The Company shall pay or provide, as the case may be, to Executive the compensation and other benefits and
rights set forth in this Section 3. 
 (a) Base Salary. As of the Effective Date, the Company shall pay to Executive a base
salary of $490,000 per year, payable in accordance with the Company’s usual payroll practices (and in any event no less frequently than monthly). Executive’s base salary shall be subject to review annually by and at the sole discretion of
the Board or its designee. 
 (b) Annual Bonus. Executive shall participate in any bonus plan, program or arrangement that the Board
or its designee may approve for the senior executives of the Company. Commencing with the calendar year in which the Effective Date occurs, Executive’s target bonus under the Company’s annual bonus plan shall be forty percent (40%) of
Executive’s base salary (the “Target Bonus”). Notwithstanding anything to the contrary contained in this Agreement or any applicable bonus plan, program or arrangement, but except as provided in Section 4(d)(ii) Executive
shall not be entitled to receive any such bonus, nor any portion thereof, if Executive is not employed on the day such bonus is paid. 
 (c)
Benefits. Executive shall be entitled to participate in benefits under the Company’s benefit plans and arrangements, including, without limitation, any employee benefit plan or arrangement made available in the future by the Company to
its senior executives, subject to and on a basis consistent with the terms, conditions and overall administration of such plans and arrangements. The Company shall have the right to amend or delete any such benefit plan or arrangement made available
by the Company to its senior executives and not otherwise specifically provided for herein; provided, that any reduction of Executive’s benefits such that Executive’s benefits are, in the aggregate, materially less favorable to
Executive than those benefits offered to Executive as of the Effective Date shall be considered a material breach of this Agreement by the Company. 

(d) Expenses. The Company shall reimburse Executive for reasonable
out-of-pocket business expenses incurred in connection with the performance of his or her duties hereunder, subject to such policies as the Company may from time to
time establish, and Executive furnishing the Company with evidence in the form of receipts satisfactory to the Company substantiating the claimed expenditures. 

(e) Paid Time Off. Executive shall be entitled to such periods of paid time off (“PTO”) each year as provided from time
to time under the Company’s PTO policy and as otherwise provided for senior executive officers. 

  
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 (f) Equity Awards. Executive shall be entitled to participate in any equity or other
employee benefit plan that is generally available to senior executive officers, as distinguished from general management, of the Company. Except as otherwise provided in this Agreement, Executive’s participation in and benefits under any such
plan shall be on the terms and subject to the conditions specified in the governing document of the particular plan. 
 4. End of
Employment Payments, Benefits and Severance. Executive shall be entitled to receive benefits upon a termination of employment only as set forth in this Section 4: 

(a) At-Will Employment; Termination. The Company and Executive acknowledge that Executive’s
employment is and shall continue to be at-will, as defined under applicable law, and that Executive’s employment with the Company may be terminated by either party at any time for any or no reason, with
or without notice. If Executive’s employment terminates for any reason, Executive shall not be entitled to any payments, benefits, damages, awards or compensation other than as provided in this Agreement. Executive’s employment under this
Agreement shall be terminated immediately on the death of Executive. 
 (b) End of Employment Payments. Upon Executive’s
termination of employment with the Company for any reason, or no reason, Executive shall not be entitled to receive any payment or other benefit, except as set forth in Sections 4(c) and 4(d) below, except that Executive shall be entitled to receive
(i) Executive’s fully earned but unpaid base salary, through the date such termination is effective (the “Separation Date”) at the rate then in effect plus all accrued but unused PTO, and (ii) all other amounts or
benefits to which Executive is entitled under any compensation, retirement or benefit plan of the Company at the time of the Separation Date in accordance with the terms of such plans, including, without limitation, any continuation of benefits
required by COBRA or applicable law (the amounts in clauses (i) and (ii), the “Accrued Obligations”). 
 (c)
Severance Upon Involuntary Termination Apart from a Change in Control. Subject to Sections 4(e) and 10(o) below and Executive’s continued compliance with Section 5, if Executive’s employment is Involuntarily Terminated prior to
a Change in Control or more than twelve (12) months following a Change in Control, Executive shall be entitled to receive, in addition to those payments and benefits set forth in Section 4(b) above, but in lieu of any other severance
benefits to which Executive may otherwise be entitled under any severance plan or program of the Company, the benefits provided below: 

(i) Executive shall be entitled to receive Executive’s monthly base salary as in effect immediately prior to the Separation Date for an
additional twelve (12) months after the Separation Date in accordance with the Company’s usual payroll practices (and in any event no less frequently than monthly, although subject to the provisions of Sections 4(e) and 10(o) below), with
the first installment commencing on the first payroll date that is sixty (60) days following the Separation Date (and any installment payments which would otherwise have been paid to Executive before the sixtieth (60th) day following the Separation Date will be paid together with the first installment); and 

  
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 (ii) for the period beginning on the Separation Date and ending on the date which is twelve
(12) full months following the Separation Date (or, if earlier, the date on which the applicable continuation period under COBRA expires), the Company shall arrange to provide or pay the applicable premiums for Executive and his or her eligible
dependents who were covered under the Company’s health insurance plans as of the Separation Date with health (including medical and dental) insurance benefits substantially similar to those provided to Executive and his or her dependents
immediately prior to the Separation Date. Notwithstanding the previous sentence, with regard to such COBRA continuation coverage, if the Company determines in its sole discretion that it cannot provide the foregoing benefit without potentially
violating applicable law (including, without limitation, Section 2716 of the Public Health Service Act), the Company shall in lieu thereof provide to the Executive a taxable monthly payment in an amount equal to the monthly COBRA premium that
the Executive would be required to pay to continue the Executive’s and his or her covered dependents’ group insurance coverages in effect on the Separation Date (which amount shall be based on the premiums for the first month of COBRA
coverage). 
 (d) Severance Upon Involuntary Termination Following a Change in Control.    Subject to Sections
4(e) and 10(o) and Executive’s continued compliance with Section 5, if Executive’s employment is Involuntarily Terminated upon or within twelve (12) months following a Change in Control, Executive shall be entitled to receive, in
addition to those payments and benefits set forth in Section 4(b) above, but in lieu of any severance benefits to which Executive may otherwise be entitled under any severance plan or program of the Company, the benefits provided below: 

(i) Executive shall be entitled to receive Executive’s monthly base salary as in effect immediately prior to the Separation Date for an
additional twelve (12) months after the Separation Date in accordance with the Company’s usual payroll practices (and in any event no less frequently than monthly, although subject to the provisions of Sections 4(e) and 10(o) below), with
the first installment commencing on the first payroll date that is sixty (60) days following the Separation Date (and any installment payments which would otherwise have been paid to Executive before the sixtieth (60th) day following the Separation Date will be paid together with the first installment); 

(ii) for the period beginning on the Separation Date and ending on the date which is twelve (12) full months following the Separation
Date (or, if earlier, the date on which the applicable continuation period under COBRA expires), the Company shall arrange to provide or pay the applicable premiums for Executive and his or her eligible dependents who were covered under the
Company’s health insurance plans as of the Separation Date with health (including medical and dental) insurance benefits substantially similar to those provided to Executive and his or her dependents immediately prior to the Separation Date.
Notwithstanding the previous sentence, with regard to such COBRA continuation coverage, if the Company determines in its sole discretion that it cannot provide the foregoing benefit without potentially violating applicable law (including, without
limitation, Section 2716 of the Public Health Service Act), the Company shall in lieu thereof provide to the Executive a taxable monthly payment in an amount equal to the monthly COBRA premium that the Executive would be required to pay to
continue the Executive’s and his or her covered dependents’ group insurance coverages in effect on the Separation Date (which amount shall be based on the premiums for the first month of COBRA coverage); 

  
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 (iii) Executive shall be entitled to receive an amount equal to (A) the annual Target
Bonus amount for the year in which Executive’s Separation from Service occurs multiplied by (B) 1.0, with such payment occurring, subject to the provisions of Sections 4(e) and 10(o) below, on the first payroll date that is sixty (60) days
following the Separation Date (but no later than March 15 of the calendar year following the calendar year in which the Separation Date occurs); and 

(iv) the vesting and/or exercisability of all of Executive’s outstanding unvested Stock Awards shall be automatically accelerated in full
on the Separation Date. The foregoing provisions are hereby deemed to be a part of each Stock Award and to supersede any less favorable provision in any agreement or plan regarding such Stock Award (and, for the avoidance of doubt, if any Stock
Award is subject to more favorable vesting pursuant to any agreement or plan regarding such Stock Award, such more favorable provisions shall continue to apply and shall not be limited by this clause (iv)). 

(e) Release. As a condition to Executive’s receipt of any post-termination benefits pursuant to Sections 4(c) and 4(d) above
(collectively, the “Severance Benefits”), Executive shall execute and not revoke a general release of all claims in favor of the Company (the “Release”) in the form attached hereto as Exhibit A. In the event
the Release does not become effective within the fifty-five (55) day period following the Separation Date, Executive shall not be entitled to the aforesaid payments and benefits. 

(f) Exclusive Remedy. Except as otherwise expressly required by law (e.g., COBRA) or as specifically provided herein, all of
Executive’s rights to salary, severance, benefits, bonuses and other amounts hereunder (if any) accruing after the Separation Date shall cease upon such date. In the event of Executive’s termination of employment with the Company,
Executive’s sole remedy shall be to receive the payments and benefits described in this Section 4. In addition, Executive acknowledges and agrees that he or she is not entitled to any reimbursement by the Company for any taxes payable by
Executive as a result of the payments and benefits received by Executive pursuant to this Section 4, including, without limitation, any excise tax imposed by Section 4999 of the Code. Any payments made to Executive under this
Section 4 shall be inclusive of any amounts or benefits to which Executive may be entitled pursuant to the Worker Adjustment and Retraining Notification Act, 29 U.S.C. Sections 2101 et seq., and the Department of Labor regulations thereunder,
or any similar state law. 
 (g) No Mitigation. Except as otherwise provided in Sections 4(c)(ii) and 4(d)(ii) above, Executive shall
not be required to mitigate the amount of any payment provided for in this Section 4 by seeking other employment or otherwise, nor shall the amount of any payment or benefit provided for in this Section 4 be reduced by any compensation
earned by Executive as the result of employment by another employer or self-employment or by retirement benefits; provided, however, that loans, advances or other amounts owed by Executive to the Company may be offset by the Company
against amounts payable to Executive under this Section 4. 
 (h) Return of the Company’s Property. In the event of
Executive’s termination of employment for any reason, the Company shall have the right, at its option, to require Executive to vacate his or her offices prior to or on the Separation Date and to cease all activities on the Company’s
behalf. Upon Executive’s termination of employment in any manner, as a condition to the Executive’s receipt of any severance benefits described in this Agreement, Executive shall immediately surrender to the Company all lists, books and
records of, or in connection with, the Company’s business, and all other property belonging to the Company, it being distinctly understood that all such lists, books and records, and other documents, are the property of the Company. Executive
shall deliver to the Company a signed statement certifying compliance with this Section 4(h) prior to the receipt of any severance benefits described in this Agreement. 

  
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 5. Certain Covenants. 

(a) No Conflicts. Except as may otherwise be approved by the Board, during the term of Executive’s employment, Executive shall not
have any ownership interest (of record or beneficial) in, or have any interest as an employee, salesman, consultant, officer or director in, or otherwise aid or assist in any manner, any firm, corporation, partnership, proprietorship or other
business that engages in any county, city or part thereof in the United States and/or any foreign country in a business which competes directly or indirectly (as determined by the Board) with the Company’s business in such county, city or part
thereof, so long as the Company, or any successor in interest of the Company to the business and goodwill of the Company, remains engaged in such business in such county, city or part thereof or continues to solicit customers or potential customers
therein; provided, however, that Executive may own, directly or indirectly, solely as an investment, securities of any entity if Executive (i) is not a controlling person of, or a member of a group which controls, such entity; or
(ii) does not, directly or indirectly, own five percent (5%) or more of any class of securities of any such entity. 
 (b)
Confidential Information. Executive and the Company have entered into the Company’s standard employee proprietary information and inventions agreement (the “Proprietary Information and Inventions Agreement”). Executive
agrees to perform each and every obligation of Executive therein contained. 
 (c) Solicitation of Employees. Executive shall not
during the term of Executive’s employment and for twelve (12) months following any Separation of Service (regardless of whether or not Executive receives any Severance Benefits) (the “Restricted Period”), directly or
indirectly, solicit or encourage to leave the employment of the Company or any of its affiliates, any employee of the Company or any of its affiliates. 

(d) Rights and Remedies Upon Breach. If Executive breaches or threatens to commit a breach of any of the provisions of this
Section 5 (the “Restrictive Covenants”), the Company shall have the following rights and remedies, each of which rights and remedies shall be independent of the other and severally enforceable, and all of which rights and
remedies shall be in addition to, and not in lieu of, any other rights and remedies available to the Company under law or in equity: 
 (i)
Specific Performance. The right and remedy to have the Restrictive Covenants specifically enforced by any court having equity jurisdiction, all without the need to post a bond or any other security or to prove any amount of actual damage or
that money damages would not provide an adequate remedy, it being acknowledged and agreed that any such breach or threatened breach will cause irreparable injury to the Company and that money damages will not provide adequate remedy to the Company;
and 

  
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 (ii) Accounting and Indemnification. The right and remedy to require Executive
(A) to account for and pay over to the Company all compensation, profits, monies, accruals, increments or other benefits derived or received by Executive or any associated party deriving such benefits as a result of any such breach of the
Restrictive Covenants; and (B) to indemnify the Company against any other losses, damages (including special and consequential damages), costs and expenses, including actual attorneys’ fees and court costs, which may be incurred by them
and which result from or arise out of any such breach or threatened breach of the Restrictive Covenants. 
 (e) Severability of
Covenants/Blue Pencilling. If any court determines that any of the Restrictive Covenants, or any part thereof, is invalid or unenforceable, the remainder of the Restrictive Covenants shall not thereby be affected and shall be given full effect,
without regard to the invalid portions. If any court determines that any of the Restrictive Covenants, or any part thereof, are unenforceable because of the duration of such provision or the area covered thereby, such court shall have the power to
reduce the duration or area of such provision and, in its reduced form, such provision shall then be enforceable and shall be enforced. Executive hereby waives any and all right to attack the validity of the Restrictive Covenants on the grounds of
the breadth of their geographic scope or the length of their term. 
 (f) Enforceability in Jurisdictions. The Company and Executive
intend to and do hereby confer jurisdiction to enforce the Restrictive Covenants upon the courts of any jurisdiction within the geographical scope of such covenants. If the courts of any one or more of such jurisdictions hold the Restrictive
Covenants wholly unenforceable by reason of the breadth of such scope or otherwise, it is the intention of the Company and Executive that such determination not bar or in any way affect the right of the Company to the relief provided above in the
courts of any other jurisdiction within the geographical scope of such covenants, as to breaches of such covenants in such other respective jurisdictions, such covenants as they relate to each jurisdiction being, for this purpose, severable into
diverse and independent covenants. 
 (g) Definitions. For purposes of this Section 5, the term “Company” means
not only PubCo and OpCo, but also any company, partnership or entity which, directly or indirectly, controls, is controlled by or is under common control with PubCo or OpCo. 

(h) Defend Trade Secrets Act Notice of Immunity Rights. Executive acknowledges that the Company has provided Executive with the
following notice of immunity rights in compliance with the requirements of the Defend Trade Secrets Act: (i) Executive shall not be held criminally or civilly liable under any Federal or State trade secret law for the disclosure of Proprietary
Information (as defined in the Proprietary Information and Inventions Agreement) that is made in confidence to a Federal, State, or local government official or to an attorney solely for the purpose of reporting or investigating a suspected
violation of law, (ii) Executive shall not be held criminally or civilly liable under any Federal or State trade secret law for the disclosure of Proprietary Information that is made in a complaint or other document filed in a lawsuit or other
proceeding, if such filing is made under seal and (iii) if Executive files a lawsuit for retaliation by the Company for reporting a suspected violation of law, Executive may disclose the Proprietary Information to his or her attorney and use
the Proprietary Information in the court proceeding, if the Executive files any document containing the Proprietary Information under seal, and does not disclose the Proprietary Information, except pursuant to court order. 

  
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 6. Insurance; Indemnification. 

(a) Insurance. The Company shall have the right to take out life, health, accident,
“key-man” or other insurance covering Executive, in the name of the Company and at the Company’s expense in any amount deemed appropriate by the Company. Executive shall assist the Company in
obtaining such insurance, including, without limitation, submitting to any required examinations and providing information and data required by insurance companies. 

(b) Indemnification. Executive will be provided with indemnification against third party claims related to his or her work for the
Company as required by Delaware law. The Company shall provide Executive with directors and officers liability insurance coverage at least as favorable as that which the Company may maintain from time to time for members of the Board and other
executive officers. 
 7. Arbitration. Any dispute, claim or controversy based on, arising out of or relating to Executive’s
employment or this Agreement shall be settled by final and binding arbitration in San Diego, California, before a single neutral arbitrator in accordance with the National Rules for the Resolution of Employment Disputes (the
“Rules”) of the American Arbitration Association (“AAA”), and judgment on the award rendered by the arbitrator may be entered in any court having jurisdiction. The Rules may be found online at www.adr.org.
Arbitration may be compelled pursuant to the California Arbitration Act (Code of Civil Procedure §§ 1280 et seq.). If the parties are unable to agree upon an arbitrator, one shall be appointed by the AAA in accordance with
its Rules. Each party shall pay the fees of its own attorneys, the expenses of its witnesses and all other expenses connected with presenting its case; however, Executive and the Company agree that, to the extent permitted by law, the
arbitrator may, in his or her discretion, award reasonable attorneys’ fees to the prevailing party. Other costs of the arbitration, including the cost of any record or transcripts of the arbitration, AAA’s administrative fees, the fee of
the arbitrator, and all other fees and costs, shall be borne by the Company. This Section 7 is intended to be the exclusive method for resolving any and all claims by the parties against each other for payment of damages under this Agreement or
relating to Executive’s employment; provided, however, that Executive shall retain the right to file administrative charges with or seek relief through any government agency of competent jurisdiction, and to participate in any
government investigation, including but not limited to (i) claims for workers’ compensation, state disability insurance or unemployment insurance; (ii) claims for unpaid wages or waiting time penalties brought before the California
Division of Labor Standards Enforcement; provided, however, that any appeal from an award or from denial of an award of wages and/or waiting time penalties shall be arbitrated pursuant to the terms of this Agreement; and
(iii) claims for administrative relief from the United States Equal Employment Opportunity Commission and/or the California Department of Fair Employment and Housing (or any similar agency in any applicable jurisdiction other than California);
provided, further, that Executive shall not be entitled to obtain any monetary relief through such agencies other than workers’ compensation benefits or unemployment insurance benefits. This Agreement shall not limit either
party’s right to obtain any provisional remedy, including, without limitation, injunctive or similar relief, from any court of competent jurisdiction as may be necessary to protect their rights and interests pending the outcome of arbitration,
including without limitation injunctive relief, in any court of competent jurisdiction pursuant to California Code of Civil Procedure § 1281.8 or any similar statute of an applicable jurisdiction. Seeking any such relief shall not be deemed to
be a waiver of such party’s right to compel arbitration. Each party hereby expressly waives his, her or its right to a jury trial. 

  
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 8. General Relationship. Executive shall be considered an employee of the Company
within the meaning of all federal, state and local laws and regulations including, but not limited to, laws and regulations governing unemployment insurance, workers’ compensation, industrial accident, labor and taxes. 

9. Section 280G of the Code. 

(a) Best Pay Provision. In the event that any payment or benefit received or to be received by Executive pursuant to the terms of any
plan, arrangement or agreement (including any payment or benefit received in connection with a change in ownership or control or the termination of Executive’s employment) (all such payments and benefits being hereinafter referred to as the
“Total Payments”) would be subject (in whole or part) to the excise tax (the “Excise Tax”) imposed under Section 4999 of the Code, then the Total Payments shall be reduced to the extent necessary so that no
portion of the Total Payments is subject to the Excise Tax but only if (i) the net amount of such Total Payments, as so reduced (after subtracting the amount of federal, state and local income taxes on such reduced Total Payments and after
taking into account the phase out of itemized deductions and personal exemptions attributable to such reduced Total Payments) is greater than or equal to (ii) the net amount of such Total Payments without such reduction (after subtracting the
net amount of federal, state and local income taxes on such Total Payments and the amount of Excise Tax to which Executive would be subject in respect of such unreduced Total Payments and after taking into account the phase out of itemized
deductions and personal exemptions attributable to such unreduced Total Payments). Except to the extent that an alternative reduction order would result in a greater economic benefit to the Executive on an
after-tax basis, the parties intend that the Total Payments shall be reduced in the following order: (w) reduction of any cash severance payments otherwise payable to Executive that are exempt from
Section 409A of the Code, (x) reduction of any other cash payments or benefits otherwise payable to Executive that are exempt from Section 409A of the Code, but excluding any payment attributable to the acceleration of vesting or
payment with respect to any Stock Award that is exempt from Section 409A of the Code, (y) reduction of any other payments or benefits otherwise payable to Executive on a pro-rata basis or such other
manner that complies with Section 409A of the Code, but excluding any payment attributable to the acceleration of vesting and payment with respect to any Stock Award that is exempt from Section 409A of the Code, and (z) reduction of
any payments attributable to the acceleration of vesting or payment with respect to any Stock Award that is exempt from Section 409A of the Code; provided, in case of clauses (x), (y) and (z), that reduction of any payments or benefits
attributable to the acceleration of vesting of Company Stock Awards shall be first applied to Stock Awards with later vesting dates; provided, further, that, notwithstanding the foregoing, any such reduction shall be undertaken in a manner that
complies with and does not result in the imposition of additional taxes on the Executive under Section 409A of the Code. The foregoing reductions shall be made in a manner that results in the maximum economic benefit to Executive on an after-tax basis and, to the extent economically equivalent payments or benefits are subject to reduction, in a pro rata manner. 

  
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 (b) Determinations. All determinations regarding the application of this
Section 9 shall be made by an independent accounting firm or consulting group with nationally recognized standing and substantial expertise and experience in performing calculations regarding the applicability of Section 280G of the Code
and the Excise Tax retained by the Company prior to the date of the applicable change in ownership or control (the “280G Firm”). For purposes of determining whether and the extent to which the Total Payments will be subject to the
Excise Tax, (i) no portion of the Total Payments shall be taken into account which (x) does not constitute a “parachute payment” within the meaning of Section 280G(b)(2) of the Code (including by reason of
Section 280G(b)(4)(A) of the Code) and, in calculating the Excise Tax, or (y) constitutes reasonable compensation for services actually rendered, within the meaning of Section 280G(b)(4)(B) of the Code, in excess of the “base
amount” (as defined in Section 280G(b)(3) of the Code) allocable to such reasonable compensation, (ii) no portion of the Total Payments the receipt or enjoyment of which Executive shall have waived at such time and in such manner as
not to constitute a “payment” within the meaning of Section 280G(b) of the Code shall be taken into account, and (iii) the value of any non-cash benefit or any deferred payment or benefit
included in the Total Payments shall be determined by the 280G Firm in accordance with the principles of Sections 280G(d)(3) and (4) of the Code. All determinations related to the calculations to be performed pursuant to this this
“Section 280G Treatment” section shall be done by the 280G Firm. The 280G Firm will be directed to submit its determination and detailed supporting calculations to both Executive and the Company within fifteen (15) days after
notification from either the Company or Executive that Executive may receive payments which may be “parachute payments.” Executive and the Company will each provide the 280G Firm access to and copies of any books, records, and documents as
may be reasonably requested by the 280G Firm, and otherwise cooperate with the 280G Firm in connection with the preparation and issuance of the determinations and calculations contemplated by this Agreement. The fees and expenses of the 280G Firm
for its services in connection with the determinations and calculations contemplated by this Agreement will be borne solely by the Company. 

10. Miscellaneous. 
 (a)
Modification; Prior Claims. This Agreement and the Proprietary Information and Inventions Agreement set forth the entire understanding of the parties with respect to the subject matter hereof, supersedes all existing agreements between them
concerning such subject matter, including, without limitation, the Prior Agreement. This Agreement may be amended or modified only with the written consent of Executive and an authorized representative of the Company. No oral waiver, amendment or
modification will be effective under any circumstances whatsoever. 
 (b) Assignment; Assumption by Successor. The rights of the
Company under this Agreement may, without the consent of Executive, be assigned by the Company, in its sole and unfettered discretion, to any person, firm, corporation or other business entity which at any time, whether by purchase, merger or
otherwise, directly or indirectly, acquires all or substantially all of the assets or business of the Company. The Company will require any successor (whether direct or indirect, by purchase, merger or otherwise) to all or substantially all of the
business or assets of the Company expressly to assume and to agree to perform this Agreement in the same manner and to the same extent that the Company would be required to perform it if no such succession had taken place; provided,
however, that no such assumption shall relieve the Company of its obligations hereunder. As used in this Agreement, the “Company” shall mean the Company as hereinbefore defined and any successor to its business and/or assets
as aforesaid which assumes and agrees to perform this Agreement by operation of law or otherwise. 

  
 12 

 (c) Survival. The covenants, agreements, representations and warranties contained in
or made in Sections 4, 5, 6, 7, 9 and 10 of this Agreement shall survive any Executive’s termination of employment. 
 (d)
Third-Party Beneficiaries. This Agreement does not create, and shall not be construed as creating, any rights enforceable by any person not a party to this Agreement. 

(e) Waiver. The failure of either party hereto at any time to enforce performance by the other party of any provision of this Agreement
shall in no way affect such party’s rights thereafter to enforce the same, nor shall the waiver by either party of any breach of any provision hereof be deemed to be a waiver by such party of any other breach of the same or any other provision
hereof. 
 (f) Section Headings. The headings of the several sections in this Agreement are inserted solely for the convenience of the
parties and are not a part of and are not intended to govern, limit or aid in the construction of any term or provision hereof. 
 (g)
Notices. Any notice required or permitted by this Agreement shall be in writing and shall be delivered as follows with notice deemed given as indicated: (i) by personal delivery when delivered personally; (ii) by overnight courier
upon written verification of receipt; (iii) by email, telecopy or facsimile transmission upon acknowledgment of receipt of electronic transmission; or (iv) by certified or registered mail, return receipt requested, upon verification of
receipt. Notice shall be sent to Executive at the address listed on the Company’s personnel records and to the Company at its principal place of business, or such other address as either party may specify in writing. 

(h) Severability. All Sections, clauses and covenants contained in this Agreement are severable, and in the event any of them shall be
held to be invalid by any court, this Agreement shall be interpreted as if such invalid Sections, clauses or covenants were not contained herein. 

(i) Governing Law and Venue. This Agreement is to be governed by and construed in accordance with the laws of the State of California
applicable to contracts made and to be performed wholly within such State, and without regard to the conflicts of laws principles thereof. Except as provided in Sections 5 and 7, any suit brought hereon shall be brought in the state or federal
courts sitting in San Diego, California, the parties hereto hereby waiving any claim or defense that such forum is not convenient or proper. Each party hereby agrees that any such court shall have in personam jurisdiction over it and consents to
service of process in any manner authorized by California law. 
 (j) Non-transferability of
Interest. None of the rights of Executive to receive any form of compensation payable pursuant to this Agreement shall be assignable or transferable except through a testamentary disposition or by the laws of descent and distribution upon the
death of Executive. Any attempted assignment, transfer, conveyance, or other disposition (other than as aforesaid) of any interest in the rights of Executive to receive any form of compensation to be made by the Company pursuant to this Agreement
shall be void. 

  
 13 

 (k) Gender. Where the context so requires, the use of the masculine gender shall
include the feminine and/or neuter genders and the singular shall include the plural, and vice versa, and the word “person” shall include any corporation, firm, partnership or other form of association. 

(l) Counterparts. This Agreement may be executed in one or more counterparts, each of which shall be deemed an original, but all of
which together shall constitute one and the same Agreement. 
 (m) Construction. The language in all parts of this Agreement shall in
all cases be construed simply, according to its fair meaning, and not strictly for or against any of the parties hereto. Without limitation, there shall be no presumption against any party on the ground that such party was responsible for drafting
this Agreement or any part thereof. 
 (n) Withholding and other Deductions. All compensation payable to Executive hereunder shall be
subject to such deductions as the Company is from time to time required to make pursuant to law, governmental regulation or order. 
 (o)
Code Section 409A. 
 (i) This Agreement is not intended to provide for any deferral of compensation
subject to Section 409A of the Code, and, to the maximum extent permitted by applicable law, amounts payable to Executive pursuant to Sections 4(c)(i), 4(c)(ii), 4(d)(i), 4(d)(ii) and 4(d)(iii) shall be made in reliance upon Treasury Regulation
Section 1.409A-1(b)(9) (with respect to separation pay plans) or Treasury Regulation Section 1.409A-1(b)(4) (with respect to short-term deferrals). To the extent applicable, this Agreement shall be interpreted in accordance with Code
Section 409A and Department of Treasury regulations and other interpretive guidance issued thereunder. For purposes of Section 409A of the Code, the right to a series of installment payments under this Agreement shall be treated as a right to a
series of separate payments. For purposes of this Agreement, all references to Executive’s “termination of employment” shall mean Executive’s Separation from Service. 

(ii) If the Executive is a “specified employee” (as defined in Section 409A of the Code), as determined by the Company in
accordance with Section 409A of the Code, on the Separation Date, to the extent that the payments or benefits under this Agreement are subject to Section 409A of the Code and the delayed payment or distribution of all or any portion of
such amounts to which Executive is entitled under this Agreement is required in order to avoid a prohibited distribution under Section 409A(a)(2)(B)(i) of the Code, then such portion deferred pursuant to this Section 9(o)(ii) shall be paid
or distributed to Executive in a lump sum on the earlier of (A) the date that is six (6)-months following Executive’s Separation from Service, (B) the date of Executive’s death or (C) the earliest date as is permitted under
Section 409A of the Code. Any remaining payments due under the Agreement shall be paid as otherwise provided herein. 

  
 14 

 (iii) If Executive and the Company determine that any payments or benefits payable under
this Agreement intended to comply with Sections 409A(a)(2), (3) and (4) of the Code do not comply with Section 409A of the Code, Executive and the Company agree to amend this Agreement, or take such other actions as Executive and the
Company deem reasonably necessary or appropriate, to comply with the requirements of Section 409A of the Code and the Treasury Regulations thereunder (and any applicable transition relief) while preserving the economic agreement of the parties.
To the extent that any provision in this Agreement is ambiguous as to its compliance with Section 409A of the Code, the provision shall be read in such a manner that no payments payable under this Agreement shall be subject to an
“additional tax” as defined in Section 409A(a)(1)(B) of the Code. 
 (iv) Any reimbursement of expenses or in-kind benefits payable under this Agreement shall be made in accordance with Treasury Regulation Section 1.409A-3(i)(1)(iv) and shall be paid on or before the last day
of Executive’s taxable year following the taxable year in which Executive incurred the expenses. The amount of expenses reimbursed or in-kind benefits payable in one year shall not affect the amount
eligible for reimbursement or in-kind benefits payable in any other taxable year of Executive’s, and Executive’s right to reimbursement for such amounts shall not be subject to liquidation or
exchange for any other benefit. 
 (Signature Page Follows) 

  
 15 

 IN WITNESS WHEREOF, the parties have executed this Agreement as of the date first set forth
above. 
  

			
	EFFECTOR THERAPEUTICS, INC.
		
	By:	 	
                     
                        

 
			
	Name:	 	  

 
			
	Title:	 	
                     
                    

	
	EFFECTOR THERAPEUTICS OPERATIONS, INC.

 
			
		
	By:	 	
                     
                    

 
			
	Name:	 	  

 
			
	Title:	 	
                     
                            

	
	EXECUTIVE
	
	  

	Premal Patel, M.D., Ph.D.

 EFFECTOR THERAPUETICS 

SIGNATURE PAGE TO AMENDED AND RESTATED EMPLOYMENT AGREEMENT 

 EXHIBIT A 

GENERAL RELEASE OF CLAIMS 

[The language in this Release may change based on legal developments and evolving best practices; this form is provided as an example of
what will be included in the final Release document.] 
 This General Release of Claims (“Release”) is entered into as
of this _____ day of ________, ____, between Premal Patel, M.D., Ph.D. (“Executive”), eFFECTOR Therapeutics, Inc., a Delaware corporation (“PubCo”) and eFFECTOR Therapeutics Operations, Inc., a Delaware corporation
(“OpCo” and, together with PubCo, the “Company”) (collectively referred to herein as the “Parties”). 

WHEREAS, Executive and the Company are parties to that certain Amended and Restated Employment Agreement effective as of [ 🌑 ] (the “Agreement”); 
 WHEREAS, the Parties agree that were it not for
execution and enforceability of this Release, Executive would not be entitled to receive the Severance Benefits (as defined below) set forth in the Agreement; and 

WHEREAS, the Parties now wish to fully and finally to resolve all matters between them. 

NOW, THEREFORE, in consideration of, and subject to, the severance benefits payable to Executive pursuant to the Agreement, the adequacy of
which is hereby acknowledged by Executive, and which Executive acknowledges that he or she would not otherwise be entitled to receive, Executive and the Company hereby agree as follows: 

1. General Release of Claims by Executive. 

(a) Executive, on behalf of himself or herself and his or her executors, heirs, administrators, representatives and assigns, hereby agrees to
release and forever discharge the Company and all predecessors, successors and their respective parent corporations, affiliates, related, and/or subsidiary entities, and all of their past and present investors, directors, stockholders, officers,
general or limited partners, employees, attorneys, agents and representatives, and the employee benefit plans in which Executive is or has been a participant by virtue of his or her employment with or service to the Company (collectively, the
“Company Releasees”), from any and all claims, debts, demands, accounts, judgments, rights, causes of action, equitable relief, damages, costs, charges, complaints, obligations, promises, agreements, controversies, suits, expenses,
compensation, responsibility and liability of every kind and character whatsoever (including attorneys’ fees and costs), whether in law or equity, known or unknown, asserted or unasserted, suspected or unsuspected (collectively,
“Claims”), which Executive has or may have had against such entities based on any events or circumstances arising or occurring on or prior to the date hereof or on or prior to the date hereof, arising directly or indirectly out of,
relating to, or in any other way involving in any manner whatsoever Executive’s employment by or service to the Company or the termination thereof, including any and all claims 

 
arising under federal, state, or local laws relating to employment, including without limitation claims of wrongful discharge, breach of express or implied contract, fraud, misrepresentation,
defamation, or liability in tort, and claims of any kind that may be brought in any court or administrative agency including, without limitation, claims under Title VII of the Civil Rights Act of 1964, as amended, 42 U.S.C. Section 2000,
et seq.; the Americans with Disabilities Act, as amended, 42 U.S.C. § 12101 et seq.; the Rehabilitation Act of 1973, as amended, 29 U.S.C. § 701 et seq.; the Civil Rights Act of
1866, and the Civil Rights Act of 1991; 42 U.S.C. Section 1981, et seq.; the Age Discrimination in Employment Act, as amended, 29 U.S.C. Section 621, et seq. (the “ADEA”); the Equal Pay Act, as
amended, 29 U.S.C. Section 206(d); regulations of the Office of Federal Contract Compliance, 41 C.F.R. Section 60, et seq.; the Family and Medical Leave Act, as amended, 29 U.S.C. § 2601
et seq.; the Fair Labor Standards Act of 1938, as amended, 29 U.S.C. § 201 et seq.; the Employee Retirement Income Security Act, as amended, 29 U.S.C. § 1001 et seq.; and the
California Fair Employment and Housing Act, California Government Code Section 12940, et seq. 
 Notwithstanding the
generality of the foregoing, Executive does not release the following claims: 
 (i) Claims for unemployment compensation or
any state disability insurance benefits pursuant to the terms of applicable state law; 
 (ii) Claims for workers’
compensation insurance benefits under the terms of any worker’s compensation insurance policy or fund of the Company; 

(iii) Claims pursuant to the terms and conditions of the federal law known as COBRA; 

(iv) Claims for indemnity under the bylaws of the Company, as provided for by California law or under any applicable insurance
policy with respect to Executive’s liability as an employee, director or officer of the Company; 
 (v) Claims for
Executive’s right to bring to the attention of the Equal Employment Opportunity Commission or the California Department of Fair Employment and Housing or any other federal, state or local government agency claims of discrimination, or from
participating in an investigation or proceeding conducted by the Equal Employment Opportunity Commission or any other federal, state or local government agency; provided, however, that Executive does release his or her right to secure any damages
for alleged discriminatory treatment; 
 (vi) Claims based on any right Executive may have to enforce the Company’s
executory obligations under the Agreement; 
 (vii) Claims Executive may have to vested or earned compensation and benefits;
and 

 (viii) Executive’s right to communicate or cooperate with any
governmental agency. 
 (b) EXECUTIVE ACKNOWLEDGES THAT HE OR SHE HAS BEEN ADVISED OF AND IS FAMILIAR WITH THE PROVISIONS OF CALIFORNIA CIVIL
CODE SECTION 1542, WHICH PROVIDES AS FOLLOWS: 
 “A GENERAL RELEASE DOES NOT EXTEND TO CLAIMS THAT THE CREDITOR OR RELEASING PARTY
DOES NOT KNOW OR SUSPECT TO EXIST IN HIS OR HER FAVOR AT THE TIME OF EXECUTING THE RELEASE AND THAT, IF KNOWN BY HIM OR HER, MUST HAVE MATERIALLY AFFECTED HIS OR HER SETTLEMENT WITH THE DEBTOR OR RELEASED PARTY.” 

BEING AWARE OF SAID CODE SECTION, EXECUTIVE HEREBY EXPRESSLY WAIVES ANY RIGHTS HE OR SHE MAY HAVE THEREUNDER, AS WELL AS UNDER ANY OTHER
STATUTES OR COMMON LAW PRINCIPLES OF SIMILAR EFFECT. 
 (c) Executive acknowledges that this Release was presented to him or her on the date
indicated above and that Executive is entitled to have [twenty-one (21)][forty-five (45)]1 days’ time in which to consider it. Executive further
acknowledges that the Company has advised him or her that he or she is waiving his or her rights under the ADEA, and that Executive should consult with an attorney of his or her choice before signing this Release, and Executive has had sufficient
time to consider the terms of this Release. Executive represents and acknowledges that if Executive executes this Release before [twenty-one (21)][forty-five
(45)]2 days have elapsed, Executive does so knowingly, voluntarily, and upon the advice and with the approval of Executive’s legal counsel (if any), and that Executive voluntarily waives any
remaining consideration period. 
 (d) Executive understands that after executing this Release, Executive has the right to revoke it within
seven (7) days after his or her execution of it. Executive understands that this Release will not become effective and enforceable unless the seven (7) day revocation period passes and Executive does not revoke the Release in writing.
Executive understands that this Release may not be revoked after the seven (7) day revocation period has passed. Executive also understands that any revocation of this Release must be made in writing and delivered to the Company at its
principal place of business within the seven (7) day period. 
 (e) Executive understands that this Release shall become effective,
irrevocable, and binding upon Executive on the eighth (8th) day after his or her execution of it, so long as Executive has not revoked it within the time period and in the manner specified in
clause (d) above. 
  

	1 	 NTD: 45 days only if part of a group termination. 

	2 	 NTD: 45 days only if part of a group termination. 

 (f) Executive further understands that Executive will not be given any severance benefits
under the Agreement unless this Release is effective on or before the date that is fifty-five (55) days following the date of Executive’s termination of employment. 

2. Defend Trade Secrets Act Notice of Immunity Rights. Executive acknowledges that the Company has provided Executive with the following
notice of immunity rights in compliance with the requirements of the Defend Trade Secrets Act: (i) Executive shall not be held criminally or civilly liable under any Federal or State trade secret law for the disclosure of Proprietary
Information (as defined in the Proprietary Information and Inventions Agreement (as defined in the Agreement)) that is made in confidence to a Federal, State, or local government official or to an attorney solely for the purpose of reporting or
investigating a suspected violation of law, (ii) Executive shall not be held criminally or civilly liable under any Federal or State trade secret law for the disclosure of Proprietary Information that is made in a complaint or other document
filed in a lawsuit or other proceeding, if such filing is made under seal and (iii) if Executive files a lawsuit for retaliation by the Company for reporting a suspected violation of law, Executive may disclose the Proprietary Information to
his or her attorney and use the Proprietary Information in the court proceeding, if the Executive files any document containing the Proprietary Information under seal, and does not disclose the Proprietary Information, except pursuant to court
order. 
 3. No Assignment. Executive represents and warrants to the Company Releasees that there has been no assignment or other
transfer of any interest in any Claim that Executive may have against the Company Releasees. Executive agrees to indemnify and hold harmless the Company Releasees from any liability, claims, demands, damages, costs, expenses and attorneys’ fees
incurred as a result of any such assignment or transfer from Executive. 
 4. Severability. In the event any provision of this Release
is found to be unenforceable by an arbitrator or court of competent jurisdiction, such provision shall be deemed modified to the extent necessary to allow enforceability of the provision as so limited, it being intended that the Parties shall
receive the benefit contemplated herein to the fullest extent permitted by law. If a deemed modification is not satisfactory in the judgment of such arbitrator or court, the unenforceable provision shall be deemed deleted, and the validity and
enforceability of the remaining provisions shall not be affected thereby. 
 5. Interpretation; Construction. The headings set forth
in this Release are for convenience only and shall not be used in interpreting this Agreement. This Release has been drafted by legal counsel representing the Company, but Executive has participated in the negotiation of its terms. Furthermore,
Executive acknowledges that Executive has had an opportunity to review and revise the Release and have it reviewed by legal counsel, if desired, and, therefore, the normal rule of construction to the effect that any ambiguities are to be resolved
against the drafting party shall not be employed in the interpretation of this Release. Either party’s failure to enforce any provision of this Release shall not in any way be construed as a waiver of any such provision, or prevent that party
thereafter from enforcing each and every other provision of this Release. 

 6. Governing Law and Venue. This Release will be governed by and construed in
accordance with the laws of the United States of America and the State of California applicable to contracts made and to be performed wholly within such State, and without regard to the conflicts of laws principles thereof. Any suit brought hereon
shall be brought in the state or federal courts sitting in San Diego County, California, the Parties hereby waiving any claim or defense that such forum is not convenient or proper. Each party hereby agrees that any such court shall have in personam
jurisdiction over it and consents to service of process in any manner authorized by California law. 
 7. Entire Agreement. This
Release and the Agreement constitute the entire agreement of the Parties in respect of the subject matter contained herein and therein and supersede all prior or simultaneous representations, discussions, negotiations and agreements, whether written
or oral. This Release may be amended or modified only with the written consent of Executive and an authorized representative of the Company. No oral waiver, amendment or modification will be effective under any circumstances whatsoever. 

8. Counterparts. This Release may be executed in multiple counterparts, each of which shall be deemed to be an original but all of which
together shall constitute one and the same instrument. 
 (Signature Page Follows) 

 IN WITNESS WHEREOF, and intending to be legally bound, the Parties have executed the foregoing Release as of
the date first written above. 
  

									
	EXECUTIVE	 		 	EFFECTOR THERAPEUTICS, INC.
				
	  
	 	                	 	By:	 	
                     
    

	Print Name: Premal Patel, M.D., Ph.D. 	 		 	Print Name: 	 	
                     
                

		 		 		 	Title:	 	
                     

				
		 		 		 	EFFECTOR THERAPEUTICS OPERATIONS, INC.
					
		 		 		 	By:	 	
                     

		 		 		 	Print Name: 	 	
                     

		 		 		 	Title:Exhibit 4.2

 

 

 

NATWEST GROUP
PLC

 

as Company

 

and

 

THE BANK OF NEW
YORK MELLON, ACTING THROUGH ITS LONDON BRANCH

 

as Trustee

 

 

  

EIGHTH SUPPLEMENTAL
INDENTURE

 

dated as of June
14, 2021

 

to the

 

AMENDED AND RESTATED
INDENTURE

 

dated as of December
13, 2017

 

and the

 

SEVENTH SUPPLEMENTAL
INDENTURE

 

dated as of August
19, 2020

 

in
respect of

 

$1,500,000,000
1.642% Senior Callable Fixed-to-Fixed Reset Rate Notes due 2027

 

 

 

 

 

     

     

    

This EIGHTH SUPPLEMENTAL
INDENTURE, dated as of June 14, 2021, among NATWEST GROUP PLC, a corporation incorporated in Scotland with registered number SC045551,
as issuer (the “Company”) and THE BANK OF NEW YORK MELLON, acting through its London Branch, a banking corporation
duly organized and existing under the laws of the State of New York, as trustee (the “Trustee”) having its Corporate
Trust Office at One Canada Square, London E14 5AL.

 

WITNESSETH:

 

WHEREAS, the Company
and the Trustee have executed and delivered an amended and restated Indenture dated as of December 13, 2017, as amended and supplemented
by the Seventh Supplemental Indenture dated as of August 19, 2020 (the “Base Indenture”) to provide for the issuance
of the Company’s Senior Debt Securities from time to time;

 

WHEREAS, Section
9.01(f) of the Amended and Restated Indenture provides that the Company and the Trustee may enter into a supplemental indenture to establish
the forms or terms of the Senior Debt Securities of any series without the consent of Holders as permitted under Sections 2.01 and 3.01
of the Amended and Restated Indenture;

 

WHEREAS, the Company
desires to issue, as a single series of Senior Debt Securities under the Base Indenture, $1,500,000,000 1.642% Senior Callable Fixed-to-Fixed
Reset Rate Notes due 2027 (the “Senior Notes”) to be issued pursuant to this Eighth Supplemental Indenture dated as
of June 14, 2021 (the “Eighth Supplemental Indenture” and, together with the Base Indenture, the “Indenture”);

 

WHEREAS, this Eighth
Supplemental Indenture shall amend and supplement the Base Indenture except where this Eighth Supplemental Indenture only applies to
the Senior Notes; to the extent that the terms of the Base Indenture are inconsistent with the provisions of this Eighth Supplemental
Indenture, the terms of this Eighth Supplemental Indenture shall govern;

 

WHEREAS, there are
no debt securities outstanding of any series created prior to the execution of this Eighth Supplemental Indenture which are entitled
to the benefit of the provisions set forth herein or would be adversely affected by such provisions;

 

WHEREAS, the entry
into of this Eighth Supplemental Indenture has been authorized pursuant to a Board Resolution as required by Section 9.01 of the Base
Indenture;

 

    2 

     

    

WHEREAS, the Company
has requested that the Trustee execute and deliver this Eighth Supplemental Indenture, and whereas all actions required by it to be taken
in order to make this Eighth Supplemental Indenture a valid, binding and enforceable instrument in accordance with its terms have been
taken and performed, and the execution and delivery of this Eighth Supplemental Indenture has been duly authorized in all respects; and

 

NOW, THEREFORE,
the Company and the Trustee mutually covenant and agree as follows:

 

Article
1

DEFINITIONS

 

Section 1.01.         
Definition of Terms. For all purposes of this Eighth Supplemental Indenture:

 

(a)       
a term defined anywhere in this Eighth Supplemental Indenture has the same meaning throughout;

 

(b)       
capitalized terms used but not otherwise defined herein shall have the meanings assigned to them in the Base Indenture;

 

(c)       
the singular includes the plural and vice versa;

 

(d)       
headings are for convenience of reference only and do not affect interpretation; and

 

(e)       
for purposes of this Eighth Supplemental Indenture and the Base Indenture, the term “series” shall mean the
series of securities designated as the Senior Notes.

 

Article
2

THE SENIOR DEBT SECURITIES

 

Section 2.01.         
Terms of the Senior Notes. The following terms relating to the Senior Notes are hereby established pursuant to Section
3.01 of the Base Indenture:

 

(a)       
The title of the Senior Notes shall be the “1,500,000,000 1.642% Senior Callable Fixed-to-Fixed Reset Rate Notes due 2027”;

 

(b)       
The aggregate principal amount of the Senior Notes that may be authenticated and delivered under the Indenture shall not initially
exceed $1,500,000,000 (except as otherwise provided in the Indenture);

 

    3 

     

    

(c)       
Principal on the Senior Notes shall be payable on June 14, 2027 (the “Maturity Date”), unless earlier redeemed
in accordance with the provisions set forth in Article 11 of the Indenture;

 

(d)       
The Senior Notes shall be issued in global registered form on or about June 14, 2021;

 

(e)       
The Senior Notes shall bear interest from (and including) June 14, 2021 to (but excluding) June 14, 2026 (the “Reset
Date”), at a rate of 1.642% per annum, and from (and including) the Reset Date to (but excluding) the Maturity Date (the “Reset
Period”), at a rate per annum equal to the applicable U.S. Treasury Rate (as defined below) as determined by the Calculation
Agent on the Reset Determination Date (as defined below), plus 0.900%. Interest on the Senior Notes will be paid semi-annually in arrear
on June 14 and December 14 of each year (each, an “Interest Payment Date”), beginning on December 14, 2021, to (and
including) the Maturity Date.

 

The “Reset
Determination Date” will be the second business day immediately preceding the Reset Date.

 

A “business
day” means any day, other than Saturday or Sunday, that is neither a legal holiday nor a day on which banking institutions
are authorised or required by law or regulation to close in the City of New York or in the City of London.

 

Interest on the
Senior Notes will be calculated on the basis of a 360-day year divided into twelve months of 30 days each and, in the case of an incomplete
month, the actual number of days elapsed in such period.

 

The “Regular
Record Dates” for the Senior Notes will be the 15th day of each May and November of each year, whether or not a business day,
immediately preceding the relevant Interest Payment Date.

 

If any scheduled
Interest Payment Date is not a business day, the Company will pay interest on the next day that is a business day, but interest on such
payment will not accrue during the period from and after such scheduled Interest Payment Date.

 

If the scheduled
Maturity Date or date of redemption or repurchase or repayment of the Senior Notes is not a business day, the Company may pay interest
and principal on the next succeeding business day, but interest on that payment will not accrue during the period from and after the
scheduled maturity date or date of redemption, repurchase or repayment;

 

    4 

     

    

(f)       
The Calculation Agent for the Senior Notes is National Westminster Bank plc or its successor appointed by the Company, pursuant
to a calculation agent agreement entered into on June 14, 2021;

 

(g)       
The U.S. Treasury Rate shall be determined by the Calculation Agent in accordance with the following provisions:

 

“U.S. Treasury
Rate” means, with respect to the Reset Date, the rate per annum equal to: (1) the average of the yields on actively traded
U.S. Treasury securities adjusted to constant maturity, for one-year maturities, for the five business days immediately prior to the
Reset Determination Date and appearing under the caption “Treasury constant maturities” at 5:00 p.m. (New York City time)
on the Reset Determination Date in the applicable most recently published statistical release designated “H.15 Daily Update”,
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 one year; or (2) if such release (or any successor release) is not published during the week immediately prior to the 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 the Reset Date.

 

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 one year as set forth in the most recently published statistical release designated “H.15 Daily Update” 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 one year) at 5:00 p.m. (New York City time) on the Reset Determination
Date on which such rate was set forth in such release (or any successor release).

 

“Comparable
Treasury Issue” means, with respect to the Reset Period, the U.S. Treasury security or securities selected by the Company with
a maturity date on or about the last day of the 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
one year.

 

    5 

     

    

“Comparable
Treasury Price” means, with respect to the Reset Date, (i) the arithmetic average of the Reference Treasury Dealer Quotations
for the Reset Date (calculated on the Reset Determination Date preceding the Reset 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 as quoted in writing to the Calculation Agent by a Reference Treasury Dealer.

 

“Reference
Treasury Dealer” means each of up to five banks selected by the Company (following, where practicable, consultation with the
Calculation Agent), 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 the Reset Date, the arithmetic average,
as determined by the Calculation Agent, of the bid and offered prices for the applicable Comparable Treasury Issue, expressed in each
case as a percentage of its principal amount, at 11:00 a.m. (New York City time), on the Reset Determination Date.

 

All percentages resulting
from any calculation of any interest rate on the Senior Notes will be rounded, if necessary, to the nearest one hundred thousandth of
a percentage point, with five one-millionths of a percentage point rounded upward, and all dollar amounts would be rounded to the nearest
cent, with one-half cent being rounded upward;

 

(a)       
No premium, upon redemption or otherwise, shall be payable by the Company on the Senior Notes; and

 

(b)       
The form of the Senior Notes shall be evidenced by one or more global notes in registered form substantially in the form of Exhibit
A attached to this Eighth Supplemental Indenture and made a part thereof.

 

(c)       
Principal of and any interest on the Senior Notes shall be paid to the Holder through The Bank of New York Mellon, as paying agent
of the Company having offices in London, United Kingdom;

 

(d)       
The Senior Notes shall not be redeemable except as provided in Article 11 of the Base Indenture as amended by ‎Section 3.08
and ‎Section 3.09 of this Eighth Supplemental Indenture. The Senior Notes shall not be redeemable at the option of the Holders at
any time. In connection with any redemption of

 

    6 

     

    

Senior
Notes pursuant to Section 11.08 of the Base Indenture, the date referenced therein shall be June 14, 2021.

 

(e)       
The Company shall have no obligation to redeem or purchase the Senior Notes pursuant to any sinking fund or analogous provision;

 

(f)       
The Senior Notes shall be issued only in denominations of $200,000 and integral multiples of $1,000 in excess thereof;

 

(g)       
The principal amount of, and any accrued interest on, the Senior Notes shall be payable upon the declaration of acceleration thereof
pursuant to Section 5.02 of the Base Indenture, as amended by ‎Section 3.05 of this Eighth Supplemental Indenture;

 

(h)       
Additional Amounts shall only be payable on the Senior Notes pursuant to Section 10.04 of the Base Indenture;

 

(i)       
The Senior Notes shall not be converted into or exchanged at the option of the Company for stock or other securities of the Company;

 

(j)       
The Senior Notes shall be denominated in U.S. Dollars;

 

(k)       
The payment of principal of and interest, if any, on the Senior Notes shall be payable in U.S. Dollars;

 

(l)       
The payment of principal of and interest, if any, on the Senior Notes shall be payable only in the coin or currency in which the
Senior Notes are denominated which, pursuant to ‎(q) above, shall be U.S. Dollars;

 

(m)       
The Senior Notes will be issued in the form of one or more global securities in registered form, without coupons attached, and
the initial Holder with respect to each such global security shall be Cede & Co., as nominee of The Depository Trust Company;

 

(n)       
Except in limited circumstances, the Senior Notes will not be issued in definitive form;

 

(o)       
The Calculation Agent for the Senior Notes is National Westminster Bank plc or its successor appointed by the Company, pursuant
to a calculation agent agreement expected to be entered into on June 14, 2021;

 

(p)       
The Events of Default on the Senior Notes are as set forth in Section 5.01 of the Base Indenture as amended by ‎Section 3.04
of this Eighth Supplemental Indenture; and

 

    7 

     

    

(q)       
The Company may issue additional Senior Notes (“Additional Senior Notes”) after the date hereof having the
same ranking and same interest rate, Maturity Date, redemption terms and other terms as the Senior Notes except for the price to the
public and issue date, provided however that if such additional notes have the same CUSIP, ISIN and/or Common Code as the Outstanding
Senior Notes, such additional notes must be fungible with the Senior Notes for U.S. federal income tax purposes. Any such Additional
Senior Notes, together with the Senior Notes will constitute a single series of securities under the Indenture. There is no limitation
on the amount of notes or other debt securities that the Company may issue under the Indenture.

 

Article
3

AMENDMENTS TO THE BASE INDENTURE

 

Section 3.01.         
Addition of Definitions. With respect to the Senior Notes only, Section 1.01 of the Base Indenture is amended to include
the following definitions (which shall be deemed to arise in Section 1.01 in their proper alphabetical order):

 

“Beneficial
Owners” shall mean (a) if the Senior Debt Securities are in global form, the beneficial owners of the Senior Debt Securities
(and any interest therein) and (b) if the Senior Debt Securities are held in definitive form, the Holders in whose names the Senior Debt
Securities are registered in the Senior Debt Security Register and any beneficial owners holding an interest in such Senior Debt Securities
held in definitive form.

 

“business
day” means any day, other than Saturday or Sunday, that is neither a legal holiday nor a day on which banking institutions
are authorised or required by law or regulation to close in the City of New York or in the City of London.

 

“Calculation
Agent” shall mean National Westminster Bank Plc or its successor appointed by the Company, pursuant to a calculation agent
agreement expected to be entered into on June 14, 2021.

 

“Comparable
Treasury Issue” has the meaning set forth in Section 2.01 of the Eighth Supplemental Indenture.

 

“Comparable
Treasury Price” has the meaning set forth in Section 2.01 of the Eighth Supplemental Indenture.

 

“Default”
has the meaning set forth in Section 5.03.

 

    8 

     

    

“Eighth
Supplemental Indenture” means this Eighth Supplemental Indenture under the Amended and Restated Indenture, dated as of June
14, 2021, among the Company and the Trustee.

 

“Event
of Default” has the meaning set forth in Section 5.01.

 

“Independent
Adviser” means an independent financial institution of international repute or other independent financial adviser experienced
in the international capital markets, in each case appointed by the Company at its own expense.

 

“Interest
Determination Date” has the meaning set forth in Section 2.01 of the Eighth Supplemental Indenture.

 

“Interest
Payment Date” has the meaning set forth in Section 2.01 of the Eighth Supplemental Indenture.

 

“Issue
Date” means June 14, 2021.

 

“Loss
Absorption Disqualification Event” shall be deemed to have occurred if:

 

(i)           
at the time that any Loss Absorption Regulation becomes effective, and as a result of such Loss Absorption Regulation becoming
so effective, in each case with respect to the Company and/or the Regulatory Group, on or after the issue date of the Senior Notes, the
Senior Notes are or, in the Company’s opinion or in the opinion of the PRA are likely not to qualify in full towards the Company’s
and/or the Regulatory Group’s (A) own funds and eligible liabilities and/or (B) loss absorbing capacity instruments; or

 

(ii)           
as a result of any amendment to, or change in, or replacement of, any Loss Absorption Regulation, or any change in the application
or official interpretation of any Loss Absorption Regulation, in any such case becoming effective on or after the issue date of the Senior
Notes, the Senior Notes are or, in the Company’s opinion or in the opinion of the PRA are likely to be, fully or partially excluded
from the Company’s and/or the Regulatory Group’s (A) own funds and eligible liabilities and/or (B) loss absorbing capacity
instruments,

 

in
each case as such minimum requirements are applicable to the Company and/or the Regulatory Group and determined in

 

    9 

     

    

accordance
with, and pursuant to, the relevant Loss Absorption Regulations; provided that in the case of (i) and (ii) above, a Loss Absorption Disqualification
Event shall not occur where the exclusion of the Senior Notes from the relevant minimum requirement(s) is due to the remaining maturity
of the Senior Notes being less than any period prescribed by any applicable eligibility criteria for such minimum requirements under
the relevant Loss Absorption Regulations effective with respect to the Company and/or the Regulatory Group on the issue date of the Senior
Notes.

 

“Loss
Absorption Regulations” means, at any time, the laws, regulations, requirements, guidelines, rules, standards and policies
relating to minimum requirements for own funds and eligible liabilities and/or loss absorbing capacity instruments of the United Kingdom,
the PRA, the United Kingdom resolution authority, the Financial Stability Board and/or of the European Parliament or of the Council of
the European Union then in effect in the United Kingdom including, without limitation to the generality of the foregoing, any delegated
or implementing acts (such as regulatory technical standards) adopted by the European Commission and any regulations, requirements, guidelines,
rules, standards and policies relating to minimum requirements for own funds and eligible liabilities and/or loss absorbing capacity
instruments adopted by the PRA and/or the United Kingdom resolution authority from time to time (whether or not such regulations, requirements,
guidelines, rules, standards or policies are applied generally or specifically to the Company or to the Regulatory Group).

 

“Maturity
Date” has the meaning set forth in Section 2.01 of the Eighth Supplemental Indenture.

 

“PRA”
means the UK Prudential Regulation Authority and/or such other governmental authority in the United Kingdom having primary supervisory
authority with respect to the Company’s business.

 

“Reference
Treasury Dealer” has the meaning set forth in Section 2.01 of the Eighth Supplemental Indenture.

 

“Reference
Treasury Dealer Quotations” has the meaning set forth in Section 2.01 of the Eighth Supplemental Indenture.

 

    10 

     

    

“Regulatory
Group” means the Company, the Company’s subsidiary undertakings, participations, participating interests and any subsidiary
undertakings, participations or participating interests held (directly or indirectly) by any of the Company’s subsidiary undertakings
from time to time and any other undertakings from time to time consolidated with the Company for regulatory purposes, in each case in
accordance with the rules and guidance of the PRA then in effect.

 

“Senior
Creditors” means creditors of the Company whose claims are admitted to proof in the winding up, liquidation, administration
or other insolvency procedure of the Company and who are unsubordinated creditors of the Company.

 

“Senior
Notes” has the meaning set forth in the recitals to the Eighth Supplemental Indenture.

 

“U.S.
Treasury Rate” has the meaning set forth in Section 2.01 of the Eighth Supplemental Indenture.

 

Section 3.02.      
Satisfaction and Discharge. With respect to the Senior Notes only, Section 4.01 of the Base Indenture is amended and restated
in its entirety and shall read as follows:

 

Section
4.01.Satisfaction and Discharge of Amended and Restated Indenture. This Amended and Restated Indenture shall upon Company
Request cease to be of further effect with respect to the Senior Debt Securities (except as to any surviving rights of registration of
transfer or exchange of the Senior Debt Securities herein expressly provided for), and the Trustee, at the expense of the Company, shall
execute proper instruments acknowledging satisfaction and discharge of this Amended and Restated Indenture with respect to the Senior
Debt Securities when:

 

		(a)	all Senior Debt Securities theretofore
                                            authenticated and delivered (other than (A) Senior Debt Securities which have been destroyed,
                                            lost or stolen and which have been replaced or paid as provided in
                                            Section 3.06 and (B) Senior Debt Securities for whose payment money has theretofore been
                                            deposited in trust or segregated and held in trust by the Company and thereafter repaid to
                                            the Company or discharged from such trust, as provided in Section
                                            10.03) have been delivered to the Trustee for cancellation;

 

    11 

     

    

		(b)	the Company has paid or caused to be
                                            paid all other sums payable hereunder by the Company with respect to the Senior Debt Securities;
                                            and

 

		(c)	the Company has delivered to the Trustee
                                            an Officer’s Certificate and an Opinion of Counsel, each stating that all conditions
                                            precedent herein provided for relating to the satisfaction and discharge of this Amended
                                            and Restated Indenture with respect to the Senior Debt Securities have been complied with.

 

Notwithstanding
any satisfaction and discharge of this Amended and Restated Indenture, the obligations of the Company to the Trustee under Section 6.07,
the obligations of the Trustee to any Authenticating Agent under Section 6.14 and the last paragraph of Section 10.03, shall survive
such satisfaction and discharge, including any termination under any bankruptcy law.

 

Section 3.03.     
Application of Trust Money. With respect to the Senior Notes only, Section 4.02 of
the Base Indenture is amended and restated in its entirety and shall read as follows:

 

Section
4.02.[Reserved].

 

Section 3.04.         
Events of Default. With respect to the Senior Notes only, Section 5.01 of the Base Indenture is amended and restated in
its entirety and shall read as follows:

 

Section
5.01.Events of Default. “Event of Default”, wherever used herein with respect to the Senior Debt Securities,
means the making of an order by a court of competent jurisdiction which is not successfully appealed within 30 days of the making of
such order, or valid adoption by the shareholders of the Company of an effective resolution, for the winding-up of the Company (other
than under or in connection with a scheme of amalgamation or reconstruction not involving a bankruptcy or insolvency). The exercise of
any U.K. bail-in power by the relevant U.K. authority shall not constitute a default or an Event of Default under this Section 5.01 or
a Default under Section 5.03.

 

Section 3.05.         
Acceleration of Maturity; Rescission and Annulment. With respect to the Senior Notes only, Section 5.02 of the Base Indenture
is amended by adding the following at the end of the section:

 

If the
Senior Debt Securities become due and payable and the Company fails to pay such amounts (or any damages awarded for breach of

 

    12 

     

    

any obligations
in respect of the Senior Debt Securities or this Amended and Restated Indenture) forthwith upon demand, notwithstanding the continuing
right of any Holder to receive payment of the principal of and interest on the Senior Debt Securities, or to institute suit for the enforcement
of any such payment, each as provided for under Section 316(b) (Directions and Waivers by Bondholders; Prohibition of Impairment of
Holders’ Right to Repayment) of the Trust Indenture Act, the Trustee, in its own name and as trustee of an express trust, may
institute proceedings for the winding up of the Company, and/or prove in a winding up of the Company for all such due and payable amounts
(including any damages awarded for breach of any obligations in respect of the Senior Debt Securities or this Amended and Restated Indenture)
but no other remedy shall be available to the Trustee or the Holders.

 

Section 3.06.      
Defaults; Collection of Indebtedness and Suits for Enforcement by Trustee. With respect to the Senior Notes only, Section
5.03 of the Base Indenture is amended and restated in its entirety and shall read as follows:

 

Section
5.03.Defaults; Collection of Indebtedness and Suits for Enforcement by Trustee. “Default” wherever used
herein with respect to the Senior Debt Securities of a particular series, means any one of the following events (subject as provided
below, whatever the reason for such Default and whether it shall be voluntary or involuntary or be effected by operation of law pursuant
to any judgment, decree or order of any court or any order, rule or regulation of any administrative or governmental body):

 

		(a)	the Company fails to pay any installment
                                            of interest in respect of the Senior Debt Securities of such series on or before the relevant
                                            Interest Payment Date and such failure continues for 14 days; or

 

		(b)	the Company fails to pay all or any
                                            part of the principal amount of the Senior Debt Securities of such series when it otherwise
                                            becomes due and payable, whether upon redemption or otherwise, and such failure continues
                                            for 7 days.

 

If a Default
occurs and is continuing, the Trustee may commence a proceeding for the winding up of the Company, provided that the Trustee may not
declare the principal amount of any Outstanding Senior Debt Securities of any series to be due and payable.

 

Subject
to applicable law, the Trustee (acting on behalf of the Holders) and the Holders of the Senior Debt Securities by their acceptance thereof
will be deemed to have waived to the fullest extent permitted by law any right of set-off, counterclaim or combination of accounts with
respect to the Senior

 

    13 

     

    

Debt Securities,
the Eighth Supplemental Indenture or this Amended and Restated Indenture (or between the Company’s obligations under or in respect
of any Senior Debt Security and any liability owed by a Holder to the Company) that they (or the Trustee acting on their behalf) might
otherwise have against the Company, whether before or during any winding-up, liquidation or administration of the Company. Notwithstanding
the above, if any of such rights and claims of any such Holder (or the Trustee acting on behalf of such Holders) against the Company
are discharged by set-off, such Holder (or the Trustee acting on behalf of such Holders) will immediately pay an amount equal to the
amount of such discharge to the Company or, in the event of any winding-up, liquidation or administration of the Company, the liquidator
or administrator (or other relevant insolvency official), as the case may be, to be held on trust for the Senior Creditors and until
such time as payment is made will hold a sum equal to such amount on trust for the Senior Creditors and accordingly such discharge shall
be deemed not to have taken place.

 

Notwithstanding
the foregoing and any other provisions, a failure to make any payment on the Senior Debt Securities of any series shall not be a Default
if it is withheld or refused, upon independent counsel’s advice delivered to the Trustee, in order to comply with any applicable
fiscal or other law or regulation or order of any court of competent jurisdiction, provided, however, that the Trustee may require the
Company to take any action which, upon independent counsel’s advice delivered to the Trustee, is appropriate and reasonable in
the circumstances (including proceedings for a court declaration), in which case the Company shall immediately take and expeditiously
proceed with the action and shall be bound by any final resolution resulting therefrom. If any such action results in a determination
that the relevant payment can be made without violating any applicable law, regulation or order then the payment shall become due and
payable on the expiration of the applicable 14-day or seven-day period after the Trustee gives written notice to the Company informing
it of such determination.

 

Upon the
occurrence of any Event of Default or Default, the Company shall give prompt written notice to the Trustee. Except as otherwise provided
in this Article 5, the Trustee may proceed to protect and enforce its rights and the rights of the Holders of the Senior Debt Securities
whether in connection with any breach by the Company of its obligations under the Senior Debt Securities, this Amended and Restated Indenture
or otherwise, including by judicial proceedings, provided that the Company shall not, as a result of any such action by the Trustee,
be required to pay any amount representing or measured by reference to principal or interest on the Senior Debt Securities of any series
prior to any date on which the principal of, or

 

    14 

     

    

any interest
on, the Senior Debt Securities of any such series would have otherwise been payable.

 

No recourse
for the payment of the principal of (or premium, if any) or interest, if any, on any Senior Debt Security, or for any claim based thereon
and no recourse under or upon any obligation, covenant or agreement of the Company in this Amended and Restated Indenture, or in any
Senior Debt Security, or because of the creation of any indebtedness represented thereby, shall be had against any incorporator, stockholder,
officer or director, past, present or future, of the Company or of any successor corporation of the Company, either directly or through
the Company or any successor corporation whether by virtue of any constitution, statute or rule of law, or by the enforcement of any
assessment or penalty or otherwise; it being expressly understood that to the extent lawful all such liability is hereby expressly waived
and released as a condition of, and as a consideration for, the execution of this Amended and Restated Indenture and the issue of the
Senior Debt Securities.

 

No remedy
against the Company, other than as referred to in Article 5 of this Amended and Restated Indenture, shall be available to the Trustee
or the Holders of the Senior Debt Securities whether for the recovery of amounts owing in respect of such Senior Debt Securities or under
this Amended and Restated Indenture or in respect of any breach by the Company of its obligations under this Amended and Restated Indenture
or in respect of the Senior Debt Securities, except that the Trustee and the Holders shall have such rights and powers as they are entitled
to have under the Trust Indenture Act, including the Trustee’s prior lien on any amounts collected following a Default or Event
of Default for payment of the Trustee’s fees and expenses, and provided that any payments on the Senior Debt Securities are subject
to the ranking provisions set forth in this Amended and Restated Indenture.

 

Notwithstanding
any contrary provisions, nothing shall impair the right of a Holder, absent the Holder’s consent, to sue for any payments due but
unpaid with respect to the Senior Debt Securities.

 

Section 3.07.         
With respect to the Senior Notes only, Sections 5.07(a), 5.07(b), 5.11, 5.13, 6.02, 6.03(i), 8.03(c) of the Base Indenture shall
be amended to add the words “or Default” after each appearance of the words “Event of Default”.

 

Section 3.08.         
Additional Amounts. With respect to the Senior Notes only, Section 10.04 of the Base Indenture is amended to delete Sections
10.04(v) and 10.04(vii) and the rest of the Section 10.04 is deemed to have changed to the extent affected by the changes described in
this Section 3.08.

 

    15 

     

    

Section 3.09.         
Optional Redemption Due to Changes in Tax Treatment. With respect to the Senior Notes only, Section 11.08 of the Base Indenture
is amended to replace in the first paragraph the word “Unless” with the words “Subject to Sections 11.04 and 11.11
and unless”.

 

Section 3.10.         
Redemption of Senior Debt Securities. With respect to the Senior Notes only, Article 11 of the Base Indenture is amended
to amend and restate Section 11.04 and to add a Section 11.09, Section 11.10 and Section 11.11, each of which shall read as follows:

 

Section
11.04. Notice of Redemption. Unless otherwise provided as contemplated by Section 3.01 with respect to any series of Senior Debt
Securities, notice of redemption shall be given (i) not less than 5 business days nor more than 60 calendar days prior to the Redemption
Date to each Holder of Senior Debt Securities to be redeemed and (ii) to Trustee at least 5 business days prior to such date, unless
a shorter notice period shall be satisfactory to the Trustee in the manner and to the extent provided in Section 1.06.

 

Any redemption
notice will state:

 

		a)	the Redemption Date;

 

		b)	the Redemption Price;

 

		c)	that, and subject to what conditions,
                                            the Redemption Price will become due and payable on the Redemption Date and that payments
                                            will cease to accrue on such date;

 

		d)	the place or places at which each Holder
                                            may obtain payment of the Redemption Price; and

 

		e)	the CUSIP, Common Code and/or ISIN number
                                            or numbers, if any, with respect to such series of Senior Debt Securities.

 

Notice
of redemption of Senior Debt Securities to be redeemed at the selection of the Company shall be given by the Company or, at the Company’s
Request, by the Trustee in the name and at the expense of the Company.

 

Section
11.09.Optional Redemption. Subject to Section 11.11, the Company may, at the Company’s option and in its sole discretion,
redeem the Senior Debt Securities, in whole but not in part, on June 14, 2026, at a Redemption Price equal to 100% of the principal amount
of the Senior

 

    16 

     

    

Debt
Securities of any series together with any accrued but unpaid interest to, but excluding, the Redemption Date.

 

Section
11.10. Loss Absorption Disqualification Event Redemption. Subject to Sections 11.04 and 11.11, the Company may, at the Company’s
option and in its sole discretion, redeem the Senior Debt Securities, in whole but not in part, at a Redemption Price equal to 100% of
the principal amount of the Senior Debt Securities of any series together with any accrued but unpaid interest to, but excluding, the
Redemption Date, if the Company determines that a Loss Absorption Disqualification Event has occurred and is continuing.

 

Before the
publication of any notice of redemption pursuant to a Loss Absorption Disqualification Event, the Company shall deliver to the Trustee
a certificate signed by two authorised signatories of the Company stating that, in such signatories’ belief, the condition for
redemption has occurred and is continuing as at the date of the certificate, and the Trustee is entitled to conclusively rely on and
shall accept such certificate as sufficient evidence of such occurrence, in which event it shall be conclusive and binding on the Holders.

 

Section
11.11. Conditions to Redemption and Repurchase. Notwithstanding any other provision, the Company may only redeem Senior Debt Securities
of any series prior to their Maturity Date (as provided for in Section 11.08, Section 11.09 and Section 11.10) or repurchase Senior Debt
Securities of any series (and give notice thereof to the Holders of such series of Senior Debt Securities in the case of redemption)
if the Company has obtained the prior consent of the PRA, to the extent such consent is at the relevant time and in the relevant circumstances
required (if at all) by the Loss Absorption Regulations or applicable laws or regulations in effect in the United Kingdom.

 

Article
4

MISCELLANEOUS

 

Section 4.01.      
Effect of Supplemental Indenture. Upon the execution and delivery of this Eighth Supplemental Indenture by the Company
and the Trustee, and the delivery of the documents referred to in ‎Section 4.02 herein, the Base Indenture shall be amended and supplemented
in accordance herewith, and this Eighth Supplemental Indenture shall form a part of the Base Indenture for all purposes in respect of
the Senior Notes.

 

    17 

     

    

Section 4.02.         
Other Documents to Be Given to the Trustee. As specified in Section 9.03 of the Base Indenture and subject to the provisions
of Section 6.03 of the Base Indenture, the Trustee shall be entitled to receive an Officer’s Certificate and an Opinion of Counsel
stating the recitals contained in Section 1.02 of the Base Indenture, and in the case of such Opinion of Counsel, that this Eighth Supplemental
Indenture is authorized or permitted by the Base Indenture, conforms to the requirements of the Trust Indenture Act, and (subject to
Section 1.03 of the Base Indenture) constitutes valid and binding obligations of the Company enforceable in accordance with their terms,
subject to applicable bankruptcy, insolvency and similar laws affecting creditors’ rights generally, concepts of reasonableness
and equitable principles of general applicability and may be subject to possible judicial or regulatory actions giving effect to governmental
actions or foreign laws affecting creditors’ rights, as conclusive evidence that this Eighth Supplemental Indenture complies with
the applicable provisions of the Base Indenture.

 

Section 4.03.         
Confirmation of Indenture. The Base Indenture and this Eighth Supplemental Indenture with respect to the Senior Notes,
is in all respects ratified and confirmed, including without limitation Section 6.07 and Article 12 of the Base Indenture, and the Base
Indenture, this Eighth Supplemental Indenture and all indentures supplemental thereto shall, in respect of the Senior Notes, be read,
taken and construed as one and the same instrument. This Eighth Supplemental Indenture constitutes an integral part of the Base Indenture
with respect to the Senior Notes. In the event of a conflict between the terms and conditions of the Base Indenture and the terms and
conditions of this Eight Supplemental Indenture, the terms and conditions of this Eighth Supplemental Indenture shall prevail with respect
to the Senior Notes.

 

Section 4.04.         
Concerning the Trustee. The Trustee does not make any representations as to the validity or sufficiency of this Eighth
Supplemental Indenture. The recitals and statements herein are deemed to be those of the Company and not the Trustee. In entering into
this Eighth Supplemental Indenture, the Trustee shall be entitled to the benefit of every provision of the Base Indenture relating to
the conduct of or affecting the liability of or affording protection to the Trustee.

 

Section 4.05.         
Governing Law. This Eighth Supplemental Indenture and the Senior Notes shall be governed by and construed in accordance
with the laws of the State of New York, irrespective of conflicts of laws principles, except as stated in Section 1.12 of the Base Indenture,
and except that the authorization and execution by the Company of this Eighth Supplemental Indenture and the Senior Notes shall be governed
by (in addition to the laws of the State of New York

 

    18 

     

    

relevant
to execution) the respective jurisdictions of the Company and the Trustee, as the case may be.

 

Section 4.06.         
Reparability. In case any provision contained in this Eighth 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 4.07.         
Counterparts. This Eighth 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.

 

[Signature Page
Follows]

 

 

 

 

 

 

 

 

 

 

 

    19 

     

    

IN WITNESS WHEREOF,
the parties hereto have caused this Eighth Supplemental Indenture to be duly executed as of the date first written above.

 

	 	NATWEST GROUP PLC, as the Company
	 	 
	 	 
	 	By:     	/s/ Donal Quaid
	 	 	Name: Donal Quaid
	 	 	Title: NWG Treasurer

 

 

	 	THE BANK OF NEW YORK MELLON, LONDON BRANCH, as Trustee
	 	 
	 	 
	 	By:    	/s/ Tom Vanson
	 	 	Name: Tom Vanson
	 	 	Title: Authorized Signatory

  

 

 

[Signature Page
to Eighth Supplemental Indenture]

    (Face of Security continued on next page)

     

    

EXHIBIT A

 

FORM OF SENIOR
NOTES

 

THIS SECURITY IS
A GLOBAL 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.

 

CUSIP
No. [●]

ISIN
No. [●]

 

NATWEST GROUP PLC

 

[●] [●]%
SENIOR CALLABLE FIXED-TO-FIXED RESET RATE NOTES DUE 20[●]

(“SENIOR NOTES”)

 

 

	No. [●]	$[●]

  

NATWEST GROUP plc
(herein called the “Company,” which term includes any successor person under the Indenture (as defined on the reverse
hereof)), for value received, hereby promises to pay to CEDE & CO., or registered assignees, the principal sum of $[●] ([●]
million dollars) on [●], 20[●] (the “Maturity Date”), or on such earlier date as the principal hereof
may become due in accordance with the terms hereof and to pay interest thereon in accordance with the terms set out below.

 

The Senior Notes
shall bear interest from (and including) [●], 2021 to (but excluding) [·] (the
“Reset Date”), at a rate of [●]% per annum, and from (and including) the Reset Date to (but excluding) the Maturity
Date (the “Reset Period”), at a rate per annum equal to the applicable U.S. Treasury Rate (as defined below) as determined
by the Calculation Agent on the Reset Determination Date (as defined below), plus [●]%. Interest on the Senior Notes will be paid
semi-annually in arrear on [·] and [·]
of each year (each, an “Interest Payment Date”), beginning on [●], 2021, to (and including) the Maturity Date.
The Company’s obligation to pay the principal of and any interest on the Senior Notes shall not be deferrable.

 

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The “Reset
Determination Date” will be the second business day immediately preceding the Reset Date.

 

A “business
day” means any day, other than Saturday or Sunday, that is neither a legal holiday nor a day on which banking institutions
are authorised or required by law or regulation to close in the City of New York or in the City of London.

 

The “Calculation
Agent” for the Senior Notes is National Westminster Bank plc or its successor appointed by the Company, pursuant to a calculation
agent agreement entered into on [●], 2021. The Calculation Agent shall determine the U.S. Treasury Rate in accordance with the
following provisions:

 

(i)       “U.S.
Treasury Rate” means, with respect to the Reset Date, the rate per annum equal to: (1) the average of the yields on actively
traded U.S. Treasury securities adjusted to constant maturity, for one-year maturity, for the five business days immediately prior to
the Reset Determination Date and appearing under the caption “Treasury constant maturities” at 5:00 p.m. (New York City time)
on the Reset Determination Date in the applicable most recently published statistical release designated “H.15 Daily Update”,
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 one year; or (2) if such release (or any successor release) is not published during the week immediately prior to the 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 the Reset Date.

 

(ii)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 one year as set forth in the most recently published statistical release designated “H.15 Daily Update” 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 one year) at 5:00 p.m. (New York City time) on the Reset Determination
Date on which such rate was set forth in such release (or any successor release).

 

“Comparable
Treasury Issue” means, with respect to the Reset Period, the U.S. Treasury security or securities selected by the Company with
a maturity date on or about the last day of the Reset Period and that would be utilized, at the time of selection

 

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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 one year.

 

“Comparable
Treasury Price” means, with respect to the Reset Date, (i) the arithmetic average of the Reference Treasury Dealer Quotations
for the Reset Date (calculated on the Reset Determination Date preceding the Reset 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 as quoted in writing to the Calculation Agent by a Reference Treasury Dealer.

 

“Reference
Treasury Dealer” means each of up to five banks selected by the Company (following, where practicable, consultation with the
Calculation Agent), 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 the Reset Date, the arithmetic average,
as determined by the Calculation Agent, of the bid and offered prices for the applicable Comparable Treasury Issue, expressed in each
case as a percentage of its principal amount, at 11:00 a.m. (New York City time), on the Reset Determination Date.

 

All percentages
resulting from any calculation of any interest rate on the Senior Notes will be rounded, if necessary, to the nearest one hundred thousandth
of a percentage point, with five one-millionths of a percentage point rounded upward, and all dollar amounts would be rounded to the
nearest cent, with one-half cent being rounded upward.

 

Interest on the
Senior Notes will be calculated on the basis of a 360-day year divided into twelve months of 30 days each and, in the case of an incomplete
month, the actual number of days elapsed in such period.

 

The “Regular
Record Dates” for the Senior Notes will be the 15th day of each [●] and [●] of each year, whether or not a business
day, immediately preceding the relevant Interest Payment Date.

 

If (i) the Company
fails to pay any installment of interest in respect of this Senior Note on or before the relevant Interest Payment Date and such failure
continues for 14 days, or (ii) the Company fails to pay all or any part of the principal amount of this Senior Note when it otherwise
becomes due and payable, whether upon redemption or otherwise, and such failure continues for 7 days (each of (i) and (ii), a “Default”),
the Trustee may commence a proceeding for the winding up of the Company, provided that

 

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the Trustee may
not declare the principal amount of any Outstanding Senior Notes to be due and payable.

 

Payment of the principal
amount of, and any interest on, this Senior Note will 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. Such payment shall be made to the Holder including through a Paying
Agent of the Company outside the United Kingdom for collection by the Holder.

 

Prior to due presentment
of this Senior Note 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 Senior Note is registered as the owner of such Senior Note for the purpose of receiving payment of principal
and interest, if any, on such Senior Note and for all other purposes whatsoever, whether or not such Senior Note be overdue, and neither
the Company, the Trustee nor any agent of the Company or the Trustee shall be affected by notice to the contrary.

 

Reference is hereby
made to the further provisions of this Senior Note set forth on the reverse hereof, which further provisions shall for all purposes have
the same effect as if set forth at this place.

 

Unless the certificate
of authentication hereon has been executed by the Trustee referred to on the reverse hereof by manual signature, this Senior Note shall
not be entitled to any benefit under the Indenture or be valid or obligatory for any purpose.

 

Notwithstanding
any other term of any Senior Notes, the Indenture, or any other agreements, arrangements, or understandings between the Company and any
Holder or Beneficial Owner, by its acquisition of this Senior Note, each Holder (including each Beneficial Owner) of this Senior Note
acknowledges, accepts, agrees to be bound by and consents to the exercise of any U.K. bail-in power by the relevant U.K. authority that
may result in (i) the reduction or cancellation of all, or a portion, of the principal amount of, or interest on, this Senior Note; (ii)
the conversion of all, or a portion, of the principal amount of, or interest on, this Senior Note into ordinary shares or other securities
or other obligations of the Company or another person; and (iii) the amendment or alteration of the maturity of this Senior Note, or
amendment of the amount of interest due on this Senior Note, or the dates on which interest becomes payable, including by suspending
payment for a temporary period; which U.K. bail-in power may be exercised by means of variation of the terms of this Senior Note solely
to give effect to the exercise by the relevant U.K. authority of such U.K. bail-in power. Each Holder (including each Beneficial Owner)
of this Senior Note further acknowledges and agrees that the rights of the Holders and/or Beneficial Owners under this Senior Note are
subject to, and will be

 

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varied, if necessary,
solely to give effect to, the exercise of any U.K. bail-in power by the relevant U.K. authority.

 

For these purposes,
“U.K. bail-in power” means any write-down, conversion, transfer, modification or suspension power existing from time
to time under any laws, regulations, rules or requirements relating to the resolution of banks, banking group companies, credit institutions
and/or investment firms incorporated in the United Kingdom in effect and applicable in the United Kingdom to the Company or other members
of the Group, including but not limited to any such laws, regulations, rules or requirements which are implemented, adopted or enacted
within the context of a European Union directive or regulation of the European Parliament and of the Council establishing a framework
for the recovery and resolution of credit institutions and investment firms (notwithstanding that the U.K. is no longer a member state
of the European Union) and/or within the context of a U.K. resolution regime under the Banking Act 2009, as the same has been or may
be amended from time to time (whether pursuant to the U.K. Financial Services (Banking Reform) Act 2013 (the “Banking Reform
Act 2013”), secondary legislation or otherwise, the “Banking Act”), pursuant to which any obligations of
a bank, banking group company, credit institution or investment firm or any of its affiliates can be reduced, cancelled, modified, transferred
and/or converted into shares or other securities or obligations of the obligor or any other person (or suspended for a temporary period)
or pursuant to which any right in a contract governing such obligations may be deemed to have been exercised, “relevant U.K.
authority” means any authority with the ability to exercise a U.K. bail-in power.

 

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

 

Dated: [●], 2021

 

	 	
    Executed by

     

NATWEST GROUP PLC

    

	 	 
	 	 
	 	By:	 
	 	Name:
	 	Title: Authorized Signatory

 

 

 

     

     

    

CERTIFICATE OF AUTHENTICATION

 

This is one
of the Senior Notes of the series designated herein referred to in the within-mentioned Indenture.

 

Dated: [●], 2021

 

	 	THE BANK OF NEW YORK MELLON, LONDON BRANCH
	 	as Trustee
	 	 	 
	 	By:	 
	 	Authorized Signatory

 

 

 

 

 

 

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[Reverse of Note]

 

This
note is one of a duly authorized issue of securities of the Company (herein called the “Senior Notes”) issued and
to be issued in one or more series under an amended and restated Indenture dated as of December
13, 2017 (the “Amended and Restated Indenture”), as amended and supplemented in respect of the Senior Notes by the
Eighth Supplemental Indenture dated as of [●], 2021 (the “Eighth Supplemental Indenture” and, together with
the Base Indenture, the “Indenture”), in each case among
the Company, as issuer, and The Bank of New York Mellon, acting through its London Branch as trustee (herein called the “Trustee,”
which term includes any successor trustee under the Indenture). Reference is hereby made to the Indenture and all indentures supplemental
thereto for a statement of the respective rights, limitations of rights, duties and immunities thereunder of the Company, the Trustee
and the Holders of the Senior Notes and of the terms upon which the Senior Notes are, and are to be, authenticated and delivered.

 

This Senior Note
is one of the series designated on the face hereof, initially limited in aggregate principal amount to $[●].

 

The Company may,
from time to time, without the consent of the Holders of the Senior Notes, issue Additional Senior Debt Securities having the same ranking
and interest rate, Maturity Date, redemption terms and other terms as the Senior Notes of this series, except for the price to the public
and issue date. Any such Additional Senior Debt Securities, together with the Senior Notes of this series, will constitute a single series
of Senior Notes under the Indenture and shall be included in the definition of “Senior Debt Securities” in the Indenture
where the context requires; provided, however, that if such Additional Senior Debt Securities are not fungible with the Outstanding Senior
Notes of this series for U.S. federal income tax purposes, the Additional Senior Debt Securities must have a CUSIP, ISIN and/or other
identifying number (as the case may be) different from those used for the Outstanding Senior Notes of this series.

 

The Senior Notes
will initially be issued in the form of one or more global Senior Notes (each, a “Global Senior Note”). Except as
provided in the Indenture, a Global Senior Note shall not be exchangeable for one or more definitive Senior Notes.

 

The Senior Notes
of this series will constitute direct, unconditional, unsecured and unsubordinated obligations of the Company, as described herein, ranking
pari passu without any preference among themselves, and equally with all other outstanding unsecured and unsubordinated obligations,
present and future of the Company, except such obligations as are preferred by operation of law.

 

If an Event of Default
with respect to the Senior Notes of this series shall have occurred and be continuing, the Trustee or the Holder or Holders of not less
than 25% in aggregate principal amount of the Outstanding Senior Notes of this series may declare the principal amount of, and any accrued
interest on, all the Senior Notes to be due and

 

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payable immediately,
in the manner, with the effect and subject to the conditions provided in the Indenture.

 

Except as otherwise
provided in Article 5 of the Indenture, the Trustee may proceed to protect and enforce its rights and the rights of the Holders of the
Senior Notes whether in connection with any breach by the Company of its obligations under the Senior Notes, the Indenture or otherwise,
including by judicial proceedings, provided that the Company shall not, as a result of any such action by the Trustee, be required to
pay any amount representing or measured by reference to principal or interest on the Senior Notes prior to any date on which the principal
of, or any interest on, the Senior Notes would have otherwise been payable.

 

If a Default occurs
and is continuing, the Trustee may commence a proceeding for the winding up of the Company, provided that the Trustee may not declare
the principal amount of any Outstanding Senior Notes to be due and payable.

 

Notwithstanding
any other provisions of the Indenture, failure to make any payment on the Senior Notes shall not be a Default if it is withheld or refused,
upon independent counsel’s advice delivered to the Trustee, in order to comply with any applicable fiscal or other law or regulation
or order of any court of competent jurisdiction, provided, however, that the Trustee may require the Company to take any action which,
upon independent counsel’s advice delivered to the Trustee, is appropriate and reasonable in the circumstances (including proceedings
for a court declaration), in which case the Company shall immediately take and expeditiously proceed with the action and shall be bound
by any final resolution resulting therefrom. If any such action results in a determination that the relevant payment can be made without
violating any applicable law, regulation or order then the payment shall become due and payable on the expiration of the applicable 14-day
or seven-day period after the Trustee gives written notice to the Company informing it of such determination.

 

Subject to applicable
law, the Trustee (acting on behalf of the Holders) and the Holders of the Senior Notes by their acceptance thereof will be deemed to
have waived to the fullest extent permitted by law any right of set-off, counterclaim or combination of accounts with respect to the
Senior Notes, the Eighth Supplemental Indenture or the Amended and Restated Indenture (or between the Company’s obligations under
or in respect of the Senior Notes and any liability owed by a Holder to the Company) that they (or the Trustee acting on their behalf)
might otherwise have against the Company, whether before or during any winding-up, liquidation or administration of the Company. Notwithstanding
the above, if any of such rights and claims of any such Holder (or the Trustee acting on behalf of such Holders) against the Company
are discharged by set-off, such Holder (or the Trustee acting on behalf of such Holders) will immediately pay an amount equal to the
amount of such discharge to the Company or, in the event of any winding-up, liquidation or administration of the Company, the liquidator
or administrator (or other relevant insolvency official), as the case may be, to be held on trust for the Senior Creditors and until
such time as payment is made will hold a sum equal to such

 

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amount on trust
for the Senior Creditors and accordingly such discharge shall be deemed not to have taken place.

 

No remedy against
the Company, other than as referred to in Article 5 of the Indenture, shall be available to the Trustee or the Holders of the Senior
Notes whether for the recovery of amounts owing in respect of such Senior Notes or under the Indenture or in respect of any breach by
the Company of its obligations under the Indenture or in respect of the Senior Notes, except that the Trustee and the Holders shall have
such rights and powers as they are entitled to have under the Trust Indenture Act, including the Trustee’s prior lien on any amounts
collected following a Default or Event of Default for payment of the Trustee’s fees and expenses, and provided that any payments
on the Senior Notes are subject to the ranking provisions set forth in the Indenture.

 

All amounts of principal,
premium, if any, and interest on the Senior Notes will be paid by the Company without deduction or withholding for, or on account of,
any and all present and future income, stamp and other taxes, levies, imposts, duties, charges, fees, deductions or withholdings now
or hereafter imposed, levied, collected, withheld or assessed by or on behalf of the United Kingdom or any political subdivision or any
authority thereof or therein having the power to tax (the “U.K. Taxing Jurisdiction”), unless such deduction or withholding
is required by law.

 

If deduction or
withholding of any such taxes, levies, imposts, duties, charges, fees, deductions or withholdings shall at any time be required by the
U.K. Taxing Jurisdiction, the Company will pay such additional amounts with respect to the principal of and premium, if any, and interest
on the Senior Notes (“Additional Amounts”) as may be necessary in order that the net amounts paid to the Holders of
the Senior Notes, after such deduction or withholding, shall equal the amounts of such payments which would have been payable in respect
of such Senior Notes had no such deduction or withholding been required; provided, however, that the foregoing will not apply to any
such tax, levy, impost, duty, charge, fee, deduction or withholding that would not have been payable or due but for the fact that:

 

(i) the Holder or
the beneficial owner of the Senior Note is a domiciliary, national or resident of, or engaging in business or maintaining a permanent
establishment or physically present in, the U.K. Taxing Jurisdiction or otherwise has some connection with the U.K. Taxing Jurisdiction
other than the mere holding or ownership of a Senior Note, or the collection of the payment on any Senior Note,

 

(ii) except in the
case of a winding-up of the Company in the United Kingdom, the Senior Note is presented (where presentation is required) for payment
in the United Kingdom,

 

(iii) the Senior
Note is presented (where presentation is required) for payment more than 30 days after the date payment became due or was provided for,
whichever is later, except to the extent that the Holder would have been entitled to such Additional

 

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Amount on presenting
(where presentation is required) the Senior Note for payment at the close of such 30 day period,

 

(iv) the Holder
or the beneficial owner of the Senior Note or the payment on such Senior Note failed to comply with a request by the Company or its liquidator
or other authorized person addressed to the Holder (x) to provide information concerning the nationality, residence or identity of the
Holder or such beneficial owner or (y) to make any declaration or other similar claim to satisfy any requirement, which in the case of
(x) or (y), is required or imposed by a statute, treaty, regulation or administrative practice of the U.K. Taxing Jurisdiction as a precondition
to exemption or relief from all or part of such deduction or withholding,

 

(v) the withholding
or deduction is required to be made pursuant to Sections 1471 through 1474 of the U.S. Internal Revenue Code of 1986, as amended, any
agreement with the U.S. Treasury entered into with respect thereto, any U.S. Treasury regulation issued thereunder or any other official
interpretations or guidance issued with respect thereto; any intergovernmental agreement entered into with respect thereto, or any law,
regulation, or other official interpretation or guidance promulgated pursuant to such an intergovernmental agreement, or

 

(vi) any combination
of subclauses (i) through (v) above,

 

nor shall Additional
Amounts be paid with respect to a payment on the Senior Notes to any Holder who is a fiduciary or partnership or person other than the
sole beneficial owner of such payment to the extent such payment would be required by the laws of the U.K. Taxing Jurisdiction to be
included in the income for tax purposes of a beneficiary or settlor with respect to such fiduciary or a member of such partnership or
a beneficial owner who would not have been entitled to such Additional Amounts, had it been the Holder.

 

Whenever in the
Indenture there is mentioned, in the context of Senior Notes, the payment of the principal, premium, if any, or interest on, or in respect
of, any Senior Notes, such mention shall be deemed to include mention of the payment of Additional Amounts provided for herein to the
extent that, in such context, Additional Amounts are, were or would be payable in respect thereof pursuant to the provisions of the foregoing
paragraph and as if express mention of the payment of Additional Amounts (if applicable) were made in any provisions hereof where such
express mention is not made.

 

The Company will
have the option to redeem Senior Notes of this series, in whole but not in part, on not less than 5 business days nor more than 60 calendar
days’ notice, at any time, at a Redemption Price equal to 100% of the principal amount, together with accrued but unpaid interest,
if any, in respect of the Senior Notes to the date fixed for redemption, if, at any time, the Company shall determine that as a result
of a change in or amendment to the laws or regulations of the U.K. Taxing Jurisdiction (including any treaty to which a U.K. Taxing Jurisdiction
is a party), or any change in the official

 

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application or interpretation
of such laws or regulations (including a decision of any court or tribunal) which change or amendment becomes effective on or after [●],
2021:

 

(a)           
in making any payment under the Senior Notes, including any payment in respect of principal or premium, if any, or interest, the
Company has or will or would on the next Interest Payment Date become obligated to pay Additional Amounts;

 

(b)           
payment of interest on the next Interest Payment Date in respect of any of the Senior Notes would be treated as a “distribution”
within the meaning of Section 1000 of the Corporation Tax Act 2010 of the United Kingdom (or any statutory modification or re-enactment
thereof for the time being); or

 

(c)           
on the next Interest Payment Date the Company would not be entitled to claim a deduction in respect of such payment of interest
in computing its United Kingdom taxation liabilities (or the value of such deduction to the Company would be materially reduced).

 

In any case where
the Company shall determine that as a result of any change in the official application or interpretation of any laws or regulations it
is entitled to redeem Senior Notes of this series, the Company shall be required to deliver to the Trustee prior to the giving of any
notice of redemption a written legal opinion of independent United Kingdom counsel of recognized standing (selected by the Company) in
a form satisfactory to the Trustee confirming that the relevant change in the official application or interpretation of such laws or
regulations has occurred and that the Company is entitled to exercise its right of redemption.

 

The Company may,
at the Company’s option and in its sole discretion, redeem Senior Notes of this series, in whole but not in part, on [●],
20[●], at a Redemption Price equal to 100% of the principal amount of the Senior Notes of this series together with any accrued
but unpaid interest to, but excluding, the Redemption Date.

 

The Company may,
at the Company’s option and in its sole discretion, redeem Senior Notes of this series, in whole but not in part, at any time during
the Fixed Rate Period and thereafter only on a Floating Rate Period Interest Payment Date, at a Redemption Price equal to 100% of the
principal amount of the Senior Notes of this series together with any accrued but unpaid interest to, but excluding, the Redemption Date,
if the Company determines that a Loss Absorption Disqualification Event has occurred and is continuing. Before the publication of any
notice of redemption pursuant to a Loss Absorption Disqualification Event, the Company shall deliver to the Trustee a certificate signed
by two authorised signatories of the Company stating that, in such signatories’ belief, the condition for redemption has occurred
and is continuing as at the date of the certificate, and the Trustee is entitled to conclusively rely on and shall accept such certificate
as sufficient evidence of such occurrence, in which event it shall be conclusive and binding on the Holders.

 

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Notwithstanding
any other provision, the Company may only redeem Senior Notes of this series prior to their Maturity Date or repurchase Senior Notes
(and give notice thereof to the Holders of this series of Senior Notes in the case of redemption) if the Company has obtained the prior
consent of the PRA, to the extent such consent is at the relevant time and in the relevant circumstances required (if at all) by the
Loss Absorption Regulations or applicable laws or regulations in effect in the United Kingdom.

 

If the Company elects
to redeem Senior Notes of this series, the Senior Notes will cease to accrue interest from the Redemption Date, provided the Redemption
Price has been paid in accordance with the Indenture.

 

Upon
payment of (i) the amount of principal
so declared due and payable and (ii) accrued and unpaid interest, all of the Company’s obligations in respect of the payment of
the principal of, and accrued and unpaid interest on, the Senior Notes of this series shall terminate.

 

The Indenture permits,
with certain exceptions 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 Senior Notes of each series to be affected thereby by the Company and the Trustee with the consent
of the Holders of not less than a majority in principal amount of the Senior Notes at the time outstanding of each such series. The Indenture
also contains provisions permitting the Holders of a majority in aggregate principal amount of the Outstanding Senior Notes of each series,
on behalf of the Holders of all Senior Notes of such series, to waive compliance by the Company with certain provisions of the Indenture
and certain past Events of Default and Defaults under the Indenture and their consequences. Any such consent or waiver by the Holder
of this Senior Note shall be conclusive and binding upon such Holder and upon all future Holders of this Senior Note and of any Senior
Note issued in exchange herefor or in lieu hereof, whether or not notation of such consent or waiver is made upon this Senior Note.

 

No reference herein
to the Indenture and no provision of this Senior Note or of the Indenture shall alter or impair the obligation of the Company, which
is absolute and unconditional, to pay, if and when due and payable, the principal of, and interest on, this Senior Note at the times,
place and rate, and in the coin or currency, herein prescribed.

 

As set forth in,
and subject to, the provisions of the Indenture, no Holder of any Senior Note of this series will have the right to institute any proceeding
with respect to the Indenture, this Senior Note or any remedy thereunder; provided, however, that such limitations do not apply
to a suit instituted by the Holder hereof for the enforcement of payment of the principal or interest as and when the same shall have
become due and payable in accordance with the terms hereof and the Indenture.

 

Notwithstanding
any other term of any Senior Notes, the Indenture, or any other agreements, arrangements, or understandings between the Company and any
Holder or Beneficial Owner, by its acquisition of Senior Notes, each Holder (including each

 

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Beneficial Owner)
of the Senior Notes acknowledges, accepts, agrees to be bound by and consents to the exercise of any U.K. bail-in power by the relevant
U.K. authority that may result in (i) the reduction or cancellation of all, or a portion, of the principal amount of, or interest on,
the Senior Notes; (ii) the conversion of all, or a portion, of the principal amount of, or interest on, the Senior Notes into ordinary
shares or other securities or other obligations of the Company or another person; and (iii) the amendment or alteration of the maturity
of the Senior Notes, or amendment of the amount of interest due on the Senior Notes, or the dates on which interest becomes payable,
including by suspending payment for a temporary period; which U.K. bail-in power may be exercised by means of variation of the terms
of the Senior Notes solely to give effect to the exercise by the relevant U.K. authority of such U.K. bail-in power. Each Holder (including
each Beneficial Owner) of the Senior Notes further acknowledges and agrees that the rights of the Holders and/or Beneficial Owners under
the Senior Notes are subject to, and will be varied, if necessary, solely to give effect to, the exercise of any U.K. bail-in power by
the relevant U.K. authority.

 

For these purposes,
“U.K. bail-in power” means any write-down, conversion, transfer, modification or suspension power existing from time
to time under any laws, regulations, rules or requirements relating to the resolution of banks, banking group companies, credit institutions
and/or investment firms incorporated in the United Kingdom in effect and applicable in the United Kingdom to the Company or other members
of the Group, including but not limited to any such laws, regulations, rules or requirements which are implemented, adopted or enacted
within the context of a European Union directive or regulation of the European Parliament and of the Council establishing a framework
for the recovery and resolution of credit institutions and investment firms (notwithstanding that the U.K. is no longer a member state
of the European Union) and/or within the context of a U.K. resolution regime under the Banking Act 2009, as the same has been or may
be amended from time to time (whether pursuant to the U.K. Financial Services (Banking Reform) Act 2013 (the “Banking Reform
Act 2013”), secondary legislation or otherwise, the “Banking Act”), pursuant to which any obligations of
a bank, banking group company, credit institution or investment firm or any of its affiliates can be reduced, cancelled, modified, transferred
and/or converted into shares or other securities or obligations of the obligor or any other person (or suspended for a temporary period)
or pursuant to which any right in a contract governing such obligations may be deemed to have been exercised, “relevant U.K.
authority” means any authority with the ability to exercise a U.K. bail-in power.

 

By its acquisition
of Senior Notes each Holder (including each Beneficial Owner) of the Senior Notes:

 

(a)       acknowledges
and agrees that upon the exercise of the U.K. bail-in power by the relevant U.K. authority it shall not give rise to a Default or an
Event of Default for purposes of Section 315(b) (Notice of Default) and Section 315(c) (Duties of the Trustee in Case of Default) of
the Trust Indenture Act;

 

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(b)       to
the extent permitted by the Trust Indenture Act, waives any and all claims against the Trustee for, agrees not to initiate a suit against
the Trustee in respect of, and agrees that the Trustee shall not be liable for, any action that the Trustee takes, or abstains from taking,
in either case in accordance with the exercise of the U.K. bail-in power by the relevant U.K. authority with respect to the Senior Notes;
and

 

(c)       acknowledges
and agrees that, upon the exercise of any U.K. bail-in power by the relevant U.K. authority, (a) the Trustee shall not be required to
take any further directions from Holders of the Senior Notes under Section 5.12 of the Base Indenture, and (b) neither the Base Indenture
nor this Eighth Supplemental Indenture shall impose any duties upon the Trustee whatsoever with respect to the exercise of any U.K. bail-in
power by the relevant U.K. authority.

 

Notwithstanding
the foregoing, if, following the completion of the exercise of the U.K. bail-in power by the relevant U.K. authority, the Senior Notes
remain outstanding (for example, if the exercise of the U.K. bail-in power results in only a partial write-down of the principal of the
Senior Notes), then the Trustee’s duties under the Indenture shall remain applicable with respect to the Senior Notes following
such completion to the extent that the Company and the Trustee shall agree pursuant to a supplemental indenture or an amendment to the
Eighth Supplemental Indenture.

 

The exercise of
any U.K. bail-in power by the relevant U.K. authority shall not constitute a default or an Event of Default under Section 5.01 of the
Indenture.

 

By its acquisition
of Senior Notes, each Holder and Beneficial Owner shall be deemed to have:

 

(i)           
consented to the exercise of any U.K. bail-in power as it may be imposed without any prior notice by the relevant U.K. authority
of its decision to exercise such power with respect to the Senior Notes and

 

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(ii)           
authorized, directed and requested DTC and any direct participant in DTC or other intermediary through which it holds such Senior
Notes to take any and all necessary action, if required, to implement the exercise of any U.K. bail-in power with respect to the Senior
Notes as it may be imposed, without any further action or direction on the part of such Holder or Beneficial Owner.

 

No repayment of
the principal amount of the Senior Notes or payment of interest on the Senior Notes shall become due and payable after the exercise of
any U.K. bail-in power by the relevant U.K. authority unless, at the time that such repayment or payment, respectively, is scheduled
to become due, 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 and the Group.

 

Upon the exercise
of the U.K. bail-in power by the relevant U.K. authority with respect to the Senior Notes, the Company shall provide a written notice
to DTC as soon as practicable regarding such exercise of the U.K. bail-in power for purposes of notifying Holders of such occurrence.
The Company shall also deliver a copy of such notice to the Trustee for information purposes.

 

If the Company has
elected to redeem Senior Notes of this series but prior to the payment of the redemption amount with respect to such redemption the relevant
U.K. authority exercises its U.K. bail-in power with respect to any Senior Notes, the relevant redemption notices shall be automatically
rescinded and shall be of no force and effect, and no payment of the redemption amount will be due and payable.

 

Any Holder (including
each Beneficial Owner) that acquires Senior Notes 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 Senior Notes
that acquire the Senior Notes 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 Senior Notes related to the U.K. bail-in power.

 

This Senior Note
will be governed by the laws of the State of New York.

 

Unless otherwise
defined herein, all terms used in this Senior Note which are defined in the Indenture shall have the meanings assigned to them in the
Indenture.

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