Exhibit 4.1

    

    

    KADMON HOLDINGS, INC.

    

    

    AND

    

    

    U.S. BANK NATIONAL ASSOCIATION,

    

    

    as Trustee

    

    

    FIRST SUPPLEMENTAL INDENTURE

    

    

    Dated as of November 9, 2021

    

    

    3.625% Convertible Senior Notes due 2027

    

    

    
      

      
        


      

    

    
    

    

    FIRST SUPPLEMENTAL INDENTURE, dated as of November 9, 2021 (this “Supplemental Indenture”), among Kadmon Holdings, Inc., a Delaware corporation (the “Company”), as issuer, and
      U.S. Bank National Association, a national banking association organized under the laws of the United States of America, as trustee (the “Trustee”),
      to the Indenture, dated as of February 16, 2021 (as supplemented or otherwise modified prior to the date hereof, the “Indenture”), between the
      Company and the Trustee.

    

    

    WHEREAS, the Company has heretofore executed and delivered the Indenture, pursuant to which the Company issued its 3.625% Convertible
      Senior Notes due 2027 (the “Notes”) in the original aggregate principal amount of $240,000,000;

    

    

    WHEREAS, the Company has entered into an Agreement and Plan of Merger, dated as of September 7, 2021 (as amended, supplemented, restated or
      otherwise modified, the “Merger Agreement”), by and among the Company, Sanofi, a French société anonyme (the “Parent”), and Latour Merger Sub, Inc., a Delaware corporation and an indirect wholly-owned subsidiary of Parent (“Merger Sub”);

    

    

    WHEREAS, pursuant to the terms of the Merger Agreement, Merger Sub will merge with and into the Company (the “Merger”) on the date hereof with the Company, as the surviving entity in the Merger, becoming a wholly owned subsidiary of Parent as of the date hereof;

    

    

    WHEREAS, the Merger constitutes a Common Stock Change Event under the Indenture;

    

    

    WHEREAS, Section 5.09(A) of the Indenture provides that, at or before the effective time of any Common Stock Change Event, the Company and the resulting, surviving or transferee Person (if not the Company) of such Common Stock Change Event will execute and deliver to the Trustee a
      supplemental indenture pursuant to Section 8.01(F) of the Indenture, which supplemental indenture will (x) provide for subsequent conversions of Notes in the manner set
        forth in Section 5.09 of the Indenture; (y) provide for subsequent adjustments to the Conversion Rate pursuant to Section 5.05(A) of the Indenture in a manner consistent with Section 5.09 of the Indenture; and (z) contain such other provisions, if
        any, that the Company reasonably determines are appropriate to preserve the economic interests of the Holders and to give effect to the provisions of Section 5.09(A) of the Indenture;

    

    

    WHEREAS, in connection with the Merger, each outstanding share of Common Stock prior to the effective time (other than certain shares of
      Common Stock as set forth in the Merger Agreement) shall be converted into the right to receive an amount in cash equal to $9.50, without interest, in accordance with the terms of the Merger Agreement;

    

    

    WHEREAS, Section 8.01 of the Indenture provides that the Company and the Trustee may amend or supplement the Indenture without the consent
      of any Holder to, among other things, (i) enter into supplemental indentures pursuant to, and in accordance with, Section 5.09 of the Indenture in connection with a Common Stock Change Event; or (ii) make any change to the Indenture that does not,
      individually or in the aggregate with all other such changes, adversely affect the rights of the Holders, as such, in any material respect;

    

    

    WHEREAS, in connection with the execution and delivery of this Supplemental Indenture, the Trustee has received an Officer’s Certificate
      and an Opinion of Counsel as contemplated by Sections 8.06, 11.02 and 11.03 of the Indenture; and

    

    

    
      

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    WHEREAS, the Company has requested that the Trustee execute and deliver this Supplemental Indenture and have satisfied all requirements
      necessary to make this Supplemental Indenture a valid instrument in accordance with its terms.

    

    

    WITNESSETH:

    

    

    NOW THEREFORE, in consideration of the foregoing and for other good and valuable consideration, the receipt of which is hereby
      acknowledged, the Company covenants and agrees with the Trustee as follows for the equal and ratable benefit of the Holders:

    

    

    ARTICLE 1

    

    

    DEFINITIONS

    

    

    Section 1.01. Definitions in the
        Supplemental Indenture. Unless otherwise specified herein or the context otherwise requires:

    

    

    (a) a term defined in the Indenture has the same meaning when used in this Supplemental Indenture unless the definition of such term is
      amended or supplemented pursuant to this Supplemental Indenture;

    

    

    (b) the terms defined in this Article and in this Supplemental Indenture include the plural as well as the singular; and

    

    

    (c) unless otherwise stated, a reference to a Section or Article is to a Section or Article of this Supplemental Indenture.

    

    

    ARTICLE 2

    

    

    EFFECT OF MERGER ON CONVERSION

    

    

    Section 2.01. Conversion Right. In
      accordance with and subject to Section 5.09 of the Indenture, from and after the effective time of the Merger, (a) a Reference Property Unit under the Indenture will be comprised of the right to receive an amount in cash equal to $9.50 per share of
      the Company’s common stock; (b) the Conversion Consideration due upon conversion of any Note, and the conditions to any such conversion, will be determined in the same manner as if each reference to any number of shares of Common Stock in Article 5
      of the Indenture (or in any related definitions) were instead a reference to the same number of Reference Property Units; (c) for purposes of Section 4.03 of the Indenture, each reference to any number of shares of Common Stock in such Section (or in
      any related definitions) will instead be deemed to be a reference to the same number of Reference Property Units; (d) the Company will be deemed to elect Physical Settlement in respect of all conversions whose Conversion Date occurs on or after the
      effective date of the Merger and will pay the cash due upon such conversions no later than the fifth (5th) Business Day after the relevant Conversion Date; (e) the Conversion Rate will be adjusted in the same manner as, and at the same time and for
      the same events for which, the Conversion Rate is adjusted pursuant to Section 5.05(A) of the Indenture in a manner consistent with Section 5.09 of the Indenture; and (f)
        the Daily VWAP and Last Reported Sale Price of a Reference Property Unit shall be $9.50.

    

    

    
      

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    ARTICLE 3

    

    

    MISCELLANEOUS

    

    

    Section 3.01. Ratification of Indenture.
      The Indenture, as supplemented by this Supplemental Indenture, is in all respects ratified and confirmed, and this Supplemental Indenture shall be deemed part of the Indenture in the manner and to the extent herein and therein provided.

    

    

    Section 3.02. Trustee Not Responsible for
        Recitals. The recitals herein contained are made by the Company and not by the Trustee, and the Trustee assumes no responsibility for the correctness thereof. The Trustee makes no representation as to the validity or sufficiency of this
      Supplemental Indenture. All of the provisions contained in the Indenture in respect of the rights, privileges, immunities, powers, and duties of the Trustee shall be applicable in respect of the Supplemental Indenture as fully and with like force and
      effect as though set forth in full herein.

    

    

    Section 3.03 Successors. All agreements of the Company and the Trustee in this Supplemental Indenture will bind their respective successors.

    

    

    Section 3.04. Governing Law. THIS
      SUPPLEMENTAL INDENTURE AND ANY CLAIM, CONTROVERSY OR DISPUTE ARISING UNDER OR RELATED TO THIS SUPPLEMENTAL INDENTURE SHALL BE GOVERNED BY, AND CONSTRUED IN ACCORDANCE WITH, THE LAWS OF THE STATE OF NEW YORK.

    

    

    Section 3.05. Headings, Etc. The
      titles and headings of the articles and sections of this Supplemental Indenture have been inserted for convenience of reference only, are not to be considered a part hereof, and shall in no way modify or restrict any of the terms or provisions
      hereof.

    

    

    Section 3.06. Execution in Counterparts.
      This Supplemental Indenture may be executed in any number of counterparts, each of which shall be an original, but such counterparts shall together constitute but one and the same instrument. The exchange of copies of this Supplemental Indenture and
      of signature pages by facsimile or PDF transmission shall constitute effective execution and delivery of this Supplemental Indenture as to the parties hereto and may be used in lieu of the original Supplemental Indenture for all purposes. Signatures
      of the parties hereto transmitted by facsimile or PDF shall be deemed to be their original signatures for all purposes.

    

    

    Section 3.07. Severability. In the
      event any provision of this Supplemental Indenture shall be invalid, illegal or unenforceable, then (to the extent permitted by law) the validity, legality or enforceability of the remaining provisions shall not in any way be affected or impaired.

    

    

    Section 3.08. Waiver of Jury Trial.
      EACH OF THE COMPANY AND THE TRUSTEE HEREBY IRREVOCABLY WAIVES, TO THE FULLEST EXTENT PERMITTED BY APPLICABLE LAW, ANY AND ALL RIGHT TO TRIAL BY JURY IN ANY LEGAL PROCEEDING ARISING OUT OF OR RELATING TO THIS SUPPLEMENTAL INDENTURE OR THE TRANSACTIONS
      CONTEMPLATED HEREBY.

    

    

    Section 3.09. Effectiveness. This
      Supplemental Indenture shall become effective upon, without further action by the parties hereto, the effective time of the Merger.

    

    

    [Signature Page Follows]

    

    

    
      

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

    

    

    	 	
            KADMON HOLDINGS, INC.

          
	 	 	 
	 	
            By:

          	
            
              /s/ Gregory Moss

            

          
	 	 	
            Name: Gregory Moss

          
	 	 	
            Title:   Executive Vice President, General Counsel

          
	 	 	 
	 	
            
              U.S. BANK NATIONAL ASSOCIATION, as Trustee

            

          
	 	 	 
	 	
            By:

          	
            
              /s/ Benjamin J. Krueger

            

          
	 	 	
            Name: Benjamin J. Krueger

          
	 	 	
            Title:   Vice President

          


    

    

    SIGNATURE PAGE TO SUPPLEMENTAL INDENTURE