Document:

Exhibit
      4.1.2

    GENTIUM
      S.P.A.

     

    AMENDMENT
      NO. 1 TO

     

    AMENDED
      AND RESTATED 2004 EQUITY INCENTIVE PLAN

     

    THIS
      AMENDMENT NO. 1
      to the
      Amended and Restated 2004 Equity Incentive Plan (the “Plan”) of Gentium S.p.A.
      (the “Company”) is made as of March 26, 2007. All capitalized terms not defined
      herein are set forth in the Plan.

     

    WHEREAS,
      the
      Company wishes to amend the Plan to extend the term of the Plan and the
      mandatory subscription date for ordinary shares available under such
      Plan;

     

    NOW
      THEREFORE,
      

     

    1.  Section
      4(c)(v)(A) of the Plan is hereby amended and restated in its entirety to
      read:

     

    (a)  All
      NSOs
      granted to a Non-Employee Director under this Section 4(c) shall terminate
      on
      the earlier of:

     

    (A) Ten
      (10)
      years after the date of grant;

     

    (B) September
      30, 2019; and

     

    (C) The
      date
      ninety (90) days after the termination of such Non-Employee Director’s Service
      for any reason.

     

    2.  Section
      6(d) of the Plan is hereby amended and restated in its entirety to
      read:

     

    Exercisability
      and Term.
      Each
      Stock Option Agreement shall specify the date when all or any installment of
      the
      Option is to become exercisable. The Stock Option Agreement shall also specify
      the term of the Option; provided that the term of an ISO shall in no event
      end
      on the earlier of ten years after the date of grant and September 30, 2019.
      No
      Option can be exercised after the expiration date provided in the applicable
      Stock Option Agreement. A Stock Option Agreement may provide for accelerated
      exercisability in the event of the Optionee’s death, Disability or retirement or
      other events and may provide for expiration prior to the end of its term in
      the
      event of the termination of the Optionee’s Service. A Stock Option Agreement may
      permit an Optionee to exercise an Option before it is vested, subject to the
      Company’s right of repurchase over any Shares acquired under the unvested
      portion of the Option (an “early exercise”), which right of repurchase shall
      lapse at the same rate the Option would have vested had there been no early
      exercise. In no event shall the Company be required to issue fractional Shares
      upon the exercise of an Option.

     

    3. Section
      15(a) of the Plan is
      hereby
      amended and restated in its entirety to read:

     

    
      
         

      

      
         

        
          

        

      

      
         

      

    

     

    (a)  Term
      of the Plan.
      The
      Plan shall become effective on the IPO Date, subject to the approval of the
      Company’s shareholders. No Options shall be exercisable until such shareholder
      approval is obtained. In the event that the shareholders fail to approve the
      Plan within twelve (12) months after its adoption by the Board, any Awards
      made
      shall be null and void and no additional Awards shall be made. The Plan shall
      terminate on September 30, 2019 or on any earlier date pursuant to Section
      15(b)
      of the Plan.

     

    4. The
      Plan
      as modified herein shall remain in full force and effect as so
      modified.

     

    [Remainder
      of page intentionally blank]

     

    
      
         

      

      
         

        
          

        

      

      
         

      

    

    To
      record
      the adoption of this Amendment No. 1 to the Plan by the Board, the Company
      has
      caused its duly authorized officer to execute this Amendment No. 1 to the Plan
      on behalf of the Company.

    
      	 	 	 
	 	GENTIUM
              S.p.A.
	 
 	 
 	 
 
	 	By:  	/s/
              Laura Iris
              Ferro, M.D.   
	 	 	
              
Laura
              Iris Ferro, M.D.
	 	 	 
	 	Title: 	President and Chief Executive
              OfficerExhibit
      4.2.2

    GENTIUM
      S.P.A.

     

    AMENDMENT
      NO. 1 TO

     

    AMENDED
      AND RESTATED NONSTATUTORY STOCK OPTION PLAN AND
      AGREEMENT

     

    THIS
      AMENDMENT NO. 1
      to the
      Amended and Restated Nonstatutory Stock Option Plan and Agreement (the “Plan”)
      of Gentium S.p.A. (the “Company”) is made as of March 26, 2007. All capitalized
      terms not defined herein are set forth in the Plan.

     

    WHEREAS,
      the
      Company wishes to amend the Plan to extend the term of the Plan and the
      mandatory subscription date for ordinary shares available under such
      Plan;

     

    NOW
      THEREFORE,
      

     

    1.  Section
      25 of the Plan is hereby amended and restated in its entirety to
      read:

     

    25. Effective
      Date and Duration of the NSO Plan and Agreement.
      The NSO
      Plan and Agreement shall be effective as of September 30, 2004. The Board may
      suspend or terminate the NSO Plan and Agreement at any time. Unless sooner
      terminated, the NSO Plan and Agreement shall terminate at midnight on September
      30, 2014.

     

    2. The
      Plan
      as modified herein shall remain in full force and effect as so
      modified.

     

    [Remainder
      of page intentionally blank]

     

    
      
         

      

      
         

        
          

        

      

      
         

      

    

    To
      record
      the adoption of this Amendment No. 1 to the Plan by the Board, the Company
      has
      caused its duly authorized officer to execute this Amendment No. 1 to the Plan
      on behalf of the Company.

    
      	 	 	 
	 	GENTIUM
              S.p.A.
	 
 	 
 	 
 
	 	By:  	/s/
              Laura Iris
              Ferro, M.D.   
	 	 	
              
Laura
              Iris Ferro, M.D.
	 	 	 
	 	Title: 	President and Chief Executive
              OfficerEXHIBIT
      4.31.2

     

    CONSULTING
      AGREEMENT 

     

    This
      Consulting Agreement (“Agreement”) is by and between KKS-TU GmbH, a German
      Corporation (“KKS”),
      located at Otfried-Müller-Str. 45, 72076 Tubingen, Germany, and Gentium, an
      Italy Corporation (“Gentium”),
      located at Piazza XX Settembre 2, Villa Gardia (Como), Italy.

     

    
      	1.	
              Description
                of Services

            

    

     

    As
      of the
      date hereof, KKS will provide Gentium with clinical and regulatory consulting
      services (“the
      Services”).

     

    KKS
      will
      use its best efforts to perform the Services in accordance with the highest
      standards of its field. KKS will work closely with Gentium by meetings,
      teleconferences and project reviews to assure that the Services are performed
      as
      desired.

     

    
      	2.	
              Performance
                of Services 

            

    

     

    The
      manner in which the Services are to be performed shall be based on Estimated
      Project Budgets (Appendix A “offer A-SC-0071/05”), Appendix B “offer
      A-SC-0076/05”). KKS shall work as many hours as may be reasonably necessary to
      fulfill KKS’s obligations under this Agreement. For translation of documents,
      KKS will inform Gentium on the reason why translation is needed for the scope
      of
      this agreement.

     

    
      	3.	
              Payment
                to KKS 

            

    

     

    By
      the
      5th day of every month. KKS shall submit an invoice to Gentium. All invoices
      will clearly define each task performed. Gentium shall pay KKS no later than
      30
      days following receipt of each invoice.

     

    
      	4.	
              Term
                /Termination 

            

    

     

    This
      Agreement shall be effective for two years from the signature date. Either
      party
      may terminate this Agreement by serving the other party with 60 days prior
      written notice to that effect. In the event of breach that the other party
      breaches this Agreement and fails to cure that breach within 30 days of receipt
      of written notice to that effect.

     

    
      	5.	
              Relationship
                of Parties 

            

    

     

    It
      is
      understood by the parties that KKS is an independent contractor with respect
      to
      Gentium, and not an employee of Gentium. Gentium will not provide fringe
      benefits, including health insurance benefits, paid vacation or any other
      employee benefit, for the benefit of KKS or KKS’s employees.

     

    
      	6.	
              Disclosure
                

            

    

     

    KKS
      and
      Gentium recognize that KKS may work on various and similar projects for other
      clients. It is understood and agreed that KKS will not disclose to Gentium
      any

    
      
        
        

      

      
        -1-

        
          

        

      

      
        
        

      

    

    confidential
      information of past and present clients. Gentium will rely on KKS’s ethical
      judgment to avoid conflicts of interest. Notwithstanding the above, KKS is
      required to disclose any outside activities or interests, including ownership
      or
      participation in the development of prior inventions, that conflict with the
      best interests of Gentium. Prompt disclosure is required under this paragraph
      if
      the activity or interest is related, directly or indirectly, to any activity
      that KKS may be involved with on behalf of Gentium.

     

    
      	7.	
              KKS’s
                Employees and
                Subcontractors

            

    

     

    KKS’s
      employees and professionals with whom they have contracts, if any, who perform
      services for Gentium under this Agreement, shall also be bound by the provisions
      of this Agreement.

     

    
      	8.	
              Confidentiality

            

    

     

    
      	 	
              a.

            	
              Gentium
                recognizes that during the discussions leading up to this Agreement
                and
                during the term of this Agreement, KKS has acquired or will acquire
                from
                Gentium information which Gentium considers to be proprietary and
                confidential. For example, Gentium has or will have products, prices,
                business affairs, future plans, trade secrets, process information,
                customer lists, technical information, product design information,
                and
                other proprietary information (collectively, “Information”) which are
                valuable, special and unique assets of Gentium. KKS agrees that KKS
                will
                not at any time or in any manner, either directly or indirectly,
                [i] use
                any Information for KKS’s own benefit, (ii) use any Information other than
                for the purpose of performing its services under this Agreement,
                or (iii)
                divulge, disclose or communicate in any manner to any third party
                any
                Information without the prior written consent of Gentium. KKS will
                protect
                the Information and treat it as strictly confidential for a period
                of 10
                years. A violation of this paragraph shall be a material violation
                of this
                Agreement. 

            

    

     

    
      	 	
              b.

            	
              Unauthorized
                Disclosure of Information 

            

    

     

    If
      it
      appears that KKS has disclosed with fault (or has threatened to disclose)
      Information in violation of this Agreement, Gentium shall be entitled to an
      injunction to restrain KKS from disclosing, in whole or in part, such
      Information, or from providing any services to any party to whom such
      Information has been disclosed or may be disclosed. Gentium shall not be
      prohibited by this provision from pursuing other remedies, including a claim
      for
      losses and damages. 

     

    
      	 	
              c.

            	
              Services
                by KKS to Third Parties 

            

    

     

    The
      parties recognize that KKS may provide consulting services to third parties.
      However, KKS is bound by the confidentiality provisions of this Agreement,
      and
      KKS may not use the Information, directly or indirectly, for the benefit of
      third parties.

    
      
        
        

      

      
        -2-

        
          

        

      

      
        
        

      

    

    
      	9.	
              Indemnification
                /Hold Harmless

            

    

     

    KKS
      will
      not be held liable for any loss, injury or damage incurred by Gentium or by
      a
      third party as a result of the performance of the Services and/or as a result
      of
      Gentium’s activities, provided that such loss, injury or damage does not arise
      from KKS’s gross negligence or willful misconduct or breach of this Agreement.
      This obligation shall survive the expiration or earlier termination of this
      Agreement.

     

    
      	10.	
              Notices

            

    

     

    All
      notices required or permitted under this Agreement shall be in writing and
      shall
      be deemed delivered when delivered in person or sent certified and return
      receipt requested, postage prepaid, addressed as follows:

     

    
      	 	
              Gentium:

               

            	
              Gentium

              P.zza
                XX Settembre, 2

              22079
                Villa Guardia (Como), Italy

            
	 	 	 
	 	
              Attn:

            	
              Massimo
                Iacobelli, Scientific Director

            
	 	 	 
	 	
              KKS:

               

            	
              KKS-TU
                GmbH 

              Otfried-Müller-Str.
                45 

              72076
                Tübingen, Germany

            
	 	 	 
	 	
              Attn:

            	
              Prof.
                Dr. C. H. Gleiter, Managing Director

            
	 	 	 

    

    Such
      addresses may be changed from time to time by either party by providing written
      notice in the manner set forth above. 

     

    
      	11.	
              Entire
                Agreement

            

    

     

    This
      Agreement contains the entire agreement of the parties and there are no other
      promises or conditions in any other agreement whether oral or written. This
      Agreement supersedes any prior written or oral agreements between the
      parties.

     

    
      	12.	
              Amendment
                

            

    

     

    This
      Agreement may be modified or amended, if the amendment is made in writing and
      is
      signed by both parties,

     

    
      	13.	
              Severability
                

            

    

     

    If
      any
      provision of this Agreement shall be held to be invalid or unenforceable for
      any
      reason, the remaining provisions shall continue to be valid and enforceable.
      If
      a court finds that any provision of this Agreement is invalid or unenforceable,
      but that by limiting such provision it would become valid and enforceable,
      then
      such provision shall be deemed to be written, construed and enforced as so
      limited.

    
      
        
        

      

      
        -3-

        
          

        

      

      
        
        

      

    

    
      	14.	
              Waiver
                of Contractual Right

            

    

     

    The
      failure of either party to enforce any provision of this Agreement shall not
      be
      construed as a waiver or limitation of that party’s right to subsequently
      enforce and compel strict compliance with every provision of this
      Agreement.

     

    
      	15.	
              Governing
                law and jurisdiction

            

    

     

    This
      Agreement shall be governed by and construed in accordance with the laws of
      Italy, without reference to any conflicts of law principles therein, and the
      courts of Como shall have sole jurisdiction in the event of a dispute arising
      between the parties in that regard.

     

    
      	16.	
              Inventions

            

    

     

    Any
      and
      all inventions, discoveries, reports or work product which KKS may make during
      the term of this Agreement relating to the subject matter hereafter (the
“Inventions”) and all know-how which KKS may develop in connection therewith
      shall be Gentium’s property and shall be disclosed promptly and fully to Gentium
      in writing.

     

    The
      obligations set forth in this paragraph shall survive the termination of
      expiration of this Agreement.

     

    
      	
              For:

            	
              Gentium.

            	 	 
	 	 	 	 
	
              By:

            	
              /s/
                Laura Iris Ferro 
                

              

              Laura
                Iris Ferro

            	
              Date:
 	
              Jan.
                17, 2006
                

              

            
	
              Title:

            	
              President

            	 	 
	 	 	 	 
	
              For:

            	
              KKS-TU
                GmbH

            	 	 
	 	 	 	 
	
              By:

               

            	
              /s/
                Prof. Dr. C. H. Gleiter 
                

              

              Prof.
                Dr. C. H. Gleiter

            	
              Date:
 	
              Feb.
                12, 2006
                

              

            
	
              Title:

            	
              Managing
                Director

            	 	 

    

    
 

    
      
        
        

      

      -4-

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