Document:

Exhibit 4.1
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RHYTHM PHARMACEUTICALS, INC.
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AMENDMENT NO. 1 TO
AMENDED AND RESTATED INVESTORS’ RIGHTS AGREEMENT
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This Amendment No. 1 to Amended and Restated Investors’ Rights Agreement (this “Amendment”) is entered into as of January 25, 2021, by and among Rhythm Pharmaceuticals, Inc., a Delaware corporation (the “Company”), and the undersigned Investors (the “Amending Investors”) party to that certain Amended and Restated Investors’ Rights Agreement, dated as of August 21, 2017 (the “Investors’ Rights Agreement”), by and among the Company and the Investors named therein.  Capitalized terms used and not defined herein shall have the respective meanings assigned to such terms in the Investors’ Rights Agreement.
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WHEREAS, the Company previously entered into the Investors’ Rights Agreement;
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WHEREAS, Section 6.6 of the Investors’ Rights Agreement provides that the Investors’ Rights Agreement generally may be amended with the written consent of (i) the Company and (ii) the holders of a majority of the Registrable Securities then outstanding and held by the Holders (collectively, the “Required Parties”); and
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WHEREAS, the Amending Investors constitute the Required Parties, and the Company and the Required Parties desire to amend the Investors’ Rights Agreement as set forth below.
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NOW, THEREFORE, in consideration of the foregoing, the Company and the undersigned Amending Investors agree as follows:
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		1.
	AMENDMENTS

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(a)The definition of “Registrable Securities” in Section 1 of the Investors’ Rights Agreement is hereby amended and restated in its entirety to read as follows:
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““Registrable Securities” means (i) the Common Stock issuable or issued upon conversion of any series of Preferred Stock; (ii) any Common Stock held by the Investors as of immediately prior to the closing of the IPO; (iii) any Common Stock issued or issuable (directly or indirectly) upon conversion and/or exercise of any other securities of the Company held by the Investors as of immediately prior to the closing of the IPO; and (iv) any Common Stock issued as (or issuable upon the conversion or exercise of any warrant, right, or other security that is issued as) a dividend or other distribution with respect to, or in exchange for or in replacement of, the securities referenced in clauses (i), (ii) and (iii) above; provided, however, Registrable Securities shall exclude, in all cases, (x) any shares sold or otherwise disposed of by a Person in a transaction in which the applicable rights under this Agreement are not assigned pursuant to Subsection 6.1 or (y) any shares for which registration rights have terminated pursuant to Section 2.13 of this Agreement.”
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(b)Section 2.13 of the Investors’ Rights Agreement is hereby amended and restated in its entirety to read as follows:
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“2.13 Termination of Registration Rights. The right of any Holder to request registration or inclusion of Registrable Securities in any registration pursuant to Subsections 2.1 or 2.2
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of this Agreement or to receive any notices hereunder or to vote, consent to, waive or otherwise exercise any rights with respect to any amendment, consent, waiver or other right hereunder shall terminate, and any shares held by a Holder shall cease to be Registrable Securities, upon the earliest to occur of:
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(a) the closing of a Deemed Liquidation Event, as such term is defined in the Restated Certificate, as amended and in effect from time to time;
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(b) such time as either (i) Rule 144 or another similar exemption under the Securities Act is available for the sale of all of such Holder’s shares without limitation during a three-month period without registration and without the requirement for the Company to be in compliance with the current public information required under Rule 144(c)(1) or (ii) such Holder no longer holds any Registrable Securities;
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(c) the fifth (5th) anniversary of the closing of the IPO; and
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(d) such time as the Holder is not an Affiliate of the Company.”
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		2.
	MISCELLANEOUS.

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Each of the undersigned Amending Investors represents and warrants to the Company, severally and not jointly, that the number of shares of Common Stock that it holds on the date hereof is set forth on the applicable signature page hereto.
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Except as specifically amended herein, the Investors’ Rights Agreement is hereby ratified and confirmed and shall remain in full force and effect. Each reference in the Investors’ Rights Agreement to “this Agreement,” “hereunder,” “hereof,” “herein” or words of like import shall mean and be a reference to the Investors’ Rights Agreement, as amended by this Amendment.
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This Amendment and any controversy arising out of or relating to this Amendment shall be governed by and construed in accordance with the internal laws of the State of Delaware, without regard to conflict of law principles that would result in the application of any law other than the law of the State of Delaware.
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This Amendment may be executed in several counterparts (including by facsimile or other electronic means), each of which shall be deemed an original, but all of which together shall constitute one and the same instrument.
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[Signature Page Follows]
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IN WITNESS WHEREOF, each undersigned Investor has executed this Amendment as of the date first written above.
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NEW ENTERPRISE ASSOCIATES 13, L.P.
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By: NEA Partners 13, L.P., its General Partner
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By: NEA 13 GP, LTD, its General Partner
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By:/s/ Louis Citron​ ​​ ​​ ​​ ​
Name: Louis S. Citron
Title: Chief Legal Officer
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Registrable Securities Held at IPO: 4,362,306
Registrable Securities Sold: 0
Total Registrable Securities Held on Date Hereof: 4,909,956
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NEA VENTURES 2009, LIMITED PARTNERSHIP
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By:/s/ Louis Citron​ ​​ ​​ ​​ ​
Name: Louis S. Citron
Title: Vice President
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Registrable Securities Held at IPO: 0
Registrable Securities Sold: 0
Total Registrable Securities Held on Date Hereof: 2,350
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[Rhythm Pharmaceuticals. – Signature Page to Amendment No. 1 to Investors’ Rights Agreement]

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IN WITNESS WHEREOF, each undersigned Investor has executed this Amendment as of the date first written above.
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MPM BIOVENTURES V, L.P.
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By: MPM BIOVENTURES V GP LLC, its General Partner
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By: MPM BIOVENTURES V LLC, its Managing Member
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By:/s/ Nicholas McGrath​ ​​ ​​ ​​ ​
Name: Nicholas McGrath
Title: Authorized Signatory
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Registrable Securities Held at IPO: 2,959,906
Registrable Securities Sold: 1,122,046
Total Registrable Securities Held on Date Hereof: 1,837,860
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MPM ASSET MANAGEMENT INVESTORS BV5 LLC
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By: MPM BIOVENTURES V LLC, its Manager
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By:/s/ Nicholas McGrath​ ​​ ​​ ​​ ​
Name: Nicholas McGrath
Title: Authorized Signatory
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Registrable Securities Held at IPO: 114,987
Registrable Securities Sold: 43,589
Total Registrable Securities Held on Date Hereof: 71,398
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[Rhythm Pharmaceuticals. – Signature Page to Amendment No. 1 to Investors’ Rights Agreement]

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IN WITNESS WHEREOF, each undersigned Investor has executed this Amendment as of the date first written above.
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/s/ David Meeker​ ​​ ​​ ​​ ​
David Meeker
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Registrable Securities Held at IPO: 76,335
Registrable Securities Sold: 0
Total Registrable Securities Held on Date Hereof: 76,335
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[Rhythm Pharmaceuticals. – Signature Page to Amendment No. 1 to Investors’ Rights Agreement]

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IN WITNESS WHEREOF, each undersigned Investor has executed this Amendment as of the date first written above.
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/s/ Keith Gottesdiener​ ​​ ​​ ​​ ​
Keith Gottesdiener
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Registrable Securities Held at IPO: 585,539
Registrable Securities Sold: 79,500
Total Registrable Securities Held on Date Hereof: 506,039
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[Rhythm Pharmaceuticals. – Signature Page to Amendment No. 1 to Investors’ Rights Agreement]

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Acknowledged and Agreed:
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RHYTHM PHARMACEUTICALS, INC.
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By: /s/ David Meeker​ ​
Name: David Meeker
Title: President and CEO

[Rhythm Pharmaceuticals. – Signature Page to Amendment No. 1 to Investors’ Rights Agreement]Exhibit 10.2

September 1, 2021
RE: Chief Medical Officer Appointment
Dear Linda,
Congratulations on your promotion to Chief Medical Officer with Rhythm Pharmaceuticals, Inc. (referred to in this letter as “Rhythm” or the “Company”) effective September 10, 2021, reporting to David Meeker, President & Chief Executive Officer. Below you will find important information about your position, rewards and benefits. All other terms and conditions, other than those expressly outlined in this letter, remain the same from your original offer letter dated June 16, 2021.
Employment.  You will be responsible for performing the duties associated with the position above or as the Company may otherwise assign to you. Your primary place of employment will initially be in the Company’s offices located in Boston, Massachusetts; however, you will be expected to travel as may be necessary to fulfill your responsibilities.  In the course of your employment with the Company, you will be subject to, and required to comply with, all Company policies and all applicable laws and regulations.
Base Salary.  In this role, your salary will be $450,000 annualized, subject to all required and elected taxes and other withholdings.  Your salary may be adjusted from time to time in accordance with normal business practice and in the sole discretion of the Company.
Annual Incentive Bonus.  Following the end of each fiscal year and subject to the approval by the Company’s Board of Directors in its sole discretion, you will be eligible to earn an incentive bonus, based on your performance and the Company’s performance, during each applicable fiscal year, and subject to your continued employment in good standing on the date of payment of such incentive bonus.  Your target annual incentive bonus opportunity will be increased to 40% of your annualized base salary.  Any annual bonus for fiscal 2021 may be prorated based on the length of your service as Senior Vice President, Clinical and Chief Medical Officer, respectively, during 2021.
Signing Bonus.  You acknowledge that the Company paid to you a one-time cash signing bonus of $90,000, less applicable withholdings, in connection with your commencement of employment (the “Signing Bonus”).  In the event you resign or are terminated for Cause (as defined below) within twenty-four (24) months following your employment commencement date, you will be required to repay the gross amount of the Signing Bonus within ninety (90) days of your termination date.  In addition, as set forth in your original offer letter, the Company will pay you a one-time cash signing bonus of $15,000, less applicable withholdings, should you relocate to Boston, Massachusetts within the first year of your employment.  Such payment will be made within [thirty (30)] days of your relocation, subject to your continued employment through such payment date.
Equity Grant.  In addition to your new hire grant in your original offer letter, the Company will grant to you 15,000 stock options and 2,500 restricted stock units, subject to the approval of the Board of Directors of the Company. The stock options and restricted stock units will be subject to the terms of the Company’s 2017 Equity Incentive Plan and an award agreement to be entered into between you and the Company.
Benefits.  You may participate in any and all benefit programs that the Company establishes and makes available to its employees from time to time, subject to the terms and conditions of those programs. The Company’s benefits programs are subject to change at any time in the Company’s sole discretion.
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Linda Shapiro, page 2
September 1, 2021

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Vacation.  Per your original offer letter, you will be eligible for annual paid vacation of four (4) weeks. Your accrual and use of vacation time will be pursuant and subject to any vacation or time off policy the Company may establish or modify from time to time.  The Company’s vacation policy and your vacation entitlement are subject to change at any time in the Company’s sole discretion.
Severance.  If the Company terminates your employment without Cause or you resign your employment with the Company for Good Reason (in either event, a “Qualifying Termination”), then, subject to your execution of a general release of claims acceptable to the Company (the “Release”), the expiration of any revocation period provided in the Release and your continued compliance with the terms of the NDA (as defined below), the Company will provide severance pay to you in an amount equal to your then-current base salary rate for a period of nine (9) months (the “Severance Amount”).
If there is a Qualifying Termination within the three (3) months immediately preceding or the twelve (12) months immediately following a Change of Control (as such term is defined in the Plan), then, subject to your timely execution of a Release following your Separation from Service (as defined below), the expiration of any revocation period provided in the Release and your continued compliance with the terms of the NDA, the Company will, in lieu of the Severance Amount, provide you with severance pay in an amount equal to your then-current base salary rate for a period of nine (9) months plus an amount equal to 100% of your then-applicable target annual incentive bonus for the fiscal year in which such Qualifying Termination occurs (the “Change of Control Severance Amount”).
In addition, in the event of your Qualifying Termination, if following your Separation from Service, you are eligible for and timely elect continued medical insurance coverage pursuant to COBRA, then, subject to your timely execution of a Release following your Separation from Service (as defined below), the expiration of any revocation period provided in the Release and your continued compliance with the terms of the NDA,  the Company will reimburse you for or pay on your behalf the applicable premiums for you and your eligible dependents during the period commencing on the date of your Separation from Service and ending on the earlier to occur of (a) the final day of the applicable severance period and (b) the date you otherwise become ineligible for continued coverage under COBRA. Notwithstanding the foregoing, if the Company determines that it cannot provide such reimbursement of premiums to you without potentially violating applicable law, the Company shall not be obligated to make any such payments or reimbursements to you.
Any Severance Amount or Change of Control Severance Amount to which you may be entitled under this letter will be paid in substantially equal installments in accordance with the Company’s ordinary payroll practices, beginning on the first payroll date following the date that is sixty (60) days after the date of your Separation from Service and with the first installment to include any amounts that would otherwise have been payable prior to such first payroll date.  To be eligible for any Severance Amount, Change in Control Severance Amount or COBRA reimbursement hereunder, you must execute and deliver the Release to the Company and allow it to become effective within thirty (30) days following your Separation from Service.
If a Qualifying Termination occurs at any time within the three (3) months immediately preceding or the twelve (12) months immediately following a Change of Control, then each outstanding equity award in the Company held by you shall immediately vest and, if applicable, become exercisable with respect to one hundred percent (100%) of the shares of the Company subject thereto. The foregoing provisions of this paragraph shall apply notwithstanding anything express or implied to the contrary in any agreement or award between you and the  Company, or in any plan of the Company, that is applicable to such outstanding equity award.
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Linda Shapiro, page 3
September 1, 2021

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409A Matters. Each installment payment provided under this letter shall at all times be considered a separate and distinct payment for purposes of Section 409A of the Internal Revenue Code of 1986, as amended (the “Code”). Notwithstanding anything in this letter to the contrary, to the extent required to avoid a prohibited distribution under Section 409A of the Code, the benefits provided under this letter will not be provided to you until the earlier of (a) the expiration of the six-month period measured from the date of your Separation from Service with the Company or (b) the date of your death. Upon the first business day after expiration of the relevant period, all payments delayed pursuant to the preceding sentence will be paid in a lump sum and any remaining payments due will be paid as otherwise provided herein. In no event may you, directly or indirectly, designate the calendar year of any payment to be made to you under this letter, to the extent such payment is subject to Section 409A of the Code. The Company makes no representations or warranty and shall have no liability to you or any other person if any provisions of this letter are determined to constitute deferred compensation subject to Section 409A of the Code but do not satisfy an exemption from, or the conditions of, Section 409A of the Code.  Notwithstanding anything herein to the contrary, in the event that any compensation or benefit that constitutes “nonqualified deferred compensation” within the meaning of Section 409A of the Code, becomes payable upon the occurrence of a change of control, such compensation or benefit shall not be paid unless such change of control constitutes a “change in control event” within the meaning of Section 409A of the Code.
Parachute Payments. Notwithstanding any other provisions of this letter, any Company plan or any other agreement, in the event that any payment or benefit by the Company or otherwise to or for the benefit of you, whether paid or payable or distributed or distributable pursuant to the terms of this letter or otherwise (all such payments and benefits, including the severance payments and benefits hereunder, being hereinafter referred to as the “Total Payments”), would be subject (in whole or in part) to the excise tax imposed by Section 4999 of the Code (the “Excise Tax”), then the Total Payments shall be reduced (in the order provided below) to the minimum extent necessary to avoid the imposition of the Excise Tax on the Total Payments, but only if (i) the net amount of such Total Payments, as so reduced (and after subtracting the net amount of federal, state and local income and employment 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 (but after subtracting the net amount of federal, state and local income and employment taxes on such Total Payments and the amount of the Excise Tax to which you 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).
The Total Payments shall be reduced in the following order: (i) reduction on a pro-rata basis of any cash severance payments that are exempt from Section 409A of the Code, (ii) reduction on a pro-rata basis of any non-cash severance payments or benefits that are exempt from Section 409A of the Code, (iii) reduction on a pro-rata basis of any other payments or benefits that are exempt from Section 409A of the Code and (iv) reduction of any payments or benefits otherwise payable to you on a pro-rata basis or such other manner that complies with Section 409A of the Code; provided, in case of clauses (ii), (iii) and (iv), that reduction of any payments attributable to the acceleration of vesting of Company equity awards shall be first applied to Company equity awards that would otherwise vest last in time.
All determinations regarding the application of this Parachute Payments section shall be made by an accounting firm or consulting group with experience in performing calculations regarding the applicability of Section 280G of the Code and the Excise Tax selected by the Company (the “Independent Advisors”). For purposes of determinations, no portion of the Total Payments shall be taken into account which, in the opinion of the
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Linda Shapiro, page 4
September 1, 2021

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Independent Advisors, (i) 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) or (ii) 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. The costs of obtaining such determination and all related fees and expenses (including related fees and expenses incurred in any later audit) shall be borne by the Company.
In the event it is later determined that a greater reduction in the Total Payments should have been made to implement the objective and intent of this Parachute Payments section, you agree to promptly return the excess amount to the Company.
Withholding Taxes. All payments and benefits described in this letter agreement or that you may otherwise be entitled or eligible to receive as a result of your employment with the Company will be subject to applicable federal, state and local tax withholdings.
Definitions
Separation from Service.  For purposes of this letter, “Separation from Service” means a “separation from service” within the meaning of Section 409A of the Code.
Cause.  “Cause” shall mean the occurrence of any of the following events: (i) your commission of any crime involving the Company, or any crime involving fraud, breach of trust, physical or emotional harm to any person, moral turpitude or dishonesty; (ii) any unauthorized use or disclosure by you of the Company’s proprietary information (other than any such use or disclosure that is not intentional and is not material); (iii) any intentional misconduct or gross negligence by you that has a material adverse effect on the Company’s business or reputation; (iv) any material breach by you of any agreement between you and the Company that is not cured within thirty (30) days after receipt of written notice from the Company describing any such breach; or (v) your repeated and willful failure to perform the duties, functions and responsibilities of your position after a written warning from the Company.
Good Reason.  “Good Reason” shall mean your resignation from all positions you then hold with the Company if: (A) without your written consent (i) there is a material diminution in the nature or scope of your responsibilities, duties, authority, or title; (ii) there is a material reduction of your base salary; provided, however, that a material reduction in your base salary pursuant to a salary reduction program affecting all or substantially all of the employees of the Company and that does not adversely affect you to a proportionally greater extent than other similarly situated employees shall not constitute Good Reason; or (iii) you are required to relocate your primary work location to a facility or location that would increase your one way commute distance by more than thirty-five (35) miles from your primary work location as of immediately prior to such change, (B) you provide written notice outlining such conditions, acts or omissions to the Company’s Chief Financial Officer or General Counsel within thirty (30) days immediately following such material change or reduction, (C) such material change or reduction is not remedied by the Company within thirty (30) days following the Company’s receipt of such written notice and (D) your resignation is effective not later than thirty (30) days after the expiration of such thirty (30) day cure period.
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Linda Shapiro, page 5
September 1, 2021

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Invention, Non-Disclosure, Non-Competition and Non-Solicitation Obligations.  The Employee Confidentiality, Assignment of Inventions, Non-Competition and Non-Solicitation Agreement in the form attached hereto as Exhibit A (the “NDA”) that you executed and delivered for the benefit of the Company in connection with your original offer letter, dated June 17, 2021, remains in full effect.
Representation.  You hereby represent and warrant to the Company that the execution, delivery and performance of this letter by you do not and shall not conflict with, breach, violate or cause a default under any contract, agreement, instrument, order, judgment or decree to which you are a party or by which you are bound.
Amendment.  The provisions of this letter may be amended or waived only with the prior written consent of the Company and you, and no course of conduct or course of dealing or failure or delay by you or the Company in enforcing or exercising any of the provisions of this letter shall affect the validity, binding effect or enforceability of the letter or be deemed to be an implied waiver of any similar or dissimilar requirement, provision or condition of this letter at the same or any prior or subsequent time.
At-Will Employment.  This letter shall not be construed as an agreement, either express or implied, to employ you for any stated term, and shall in no way alter the Company’s policy of employment at-will.  Similarly, nothing in this letter shall be construed as an agreement, either express or implied, to pay you any compensation or grant you any benefit beyond the end of your employment with the Company, except as otherwise explicitly set forth in this letter.  This letter supersedes all prior understandings, whether written or oral, with respect to the subject matter of this letter, with the exception that all other terms and conditions, other than those expressly outlined in this letter, remain the same from your original offer letter.
Sincerely,
David Meeker
President & Chief Executive Officer
The foregoing correctly sets forth the terms of my at-will employment with Rhythm.  I am not relying on any representations other than those set forth above.
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	Linda Shapiro
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	Date

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