Exhibit 10.5.1
   




Confidential portions of this
document have been omitted and filed separately with the Commission. The omitted portions
have been marked as follows: “***”. 



EXECUTION
  VERSION  




Addendum
  Agreement 



This Addendum Agreement is
  made this 28 day of December 2000, between Bioglan Pharma PLC of 5, Hunting
  Gate, Hitchin, Hertfordshire SG4 OTJ (“Bioglan”) and Jagotec AG of
  Eptingerstrasse 51, CH-4132 Muttenz, Switzerland (“Jago”). 



Bioglan and Jago entered
  into a Licence and Manufacturing Agreement dated March 13th 2000 (“the
  Licence Agreement”) for the Product Solaraze, for certain European countries
  including the United Kingdom, France, Germany, Italy and Sweden. 



Under such Licence Agreement,
  Jago granted Bioglan a right of first refusal to make, distribute, and sell the
  Product in all other countries of the world. 



Jago and its affiliate SkyePharma
  Inc have the right to grant licences and marketing authorisations for the United
  States of America, Canada and Mexico. Bioglan now wishes to exercise its right
  of first refusal with respect to these countries. 



This Addendum Agreement is intended
to be read in conjunction with the Licence Agreement and, save where expressly stated in
this Addendum Agreement, the terms of the Licence Agreement shall apply to the Additional
Territory and shall remain in full force and effect in relation to the Territory. 



OPERATIVE PARTS  



	Al. 	Definitions
      






In this Agreement all words
  and expressions shall have the meanings as set out in the Licence Agreement
  unless otherwise set out below: 



“Additional Territory”
  shall mean The United States of America, Canada and Mexico.



“Competent Authority”
  shall mean collectively the entities in all countries of the Additional Territory
  responsible for the regulation of the Product.



“FDA” means the United
  States Food and Drug Administration or any successor agency thereto. 



“Marketing Authorisations”
  shall mean all necessary and appropriate regulatory approvals, excluding pricing
  and reimbursement approvals, to put the Product on the market in any country
  of the Additional Territory. 



“NDA” means a New
  Drug Application and all amendments and supplements thereto, filed with the
  United States FDA. 



“NDS” means
  a New Drug Submission and all amendments and supplements thereto, filed with
  the Canadian TPP.



 
	 	
	 



 












EXECUTION VERSION 



“Patent Rights” means
  all rights as set out in the Agreement and shall include all patent rights to
  the Product in the Additional Territory. 



“TPP” means the Canadian
  Therapeutic Products Program. 



	A2 	Marketing
      Authorisations 



SkyePharma Inc (SkyePharma) hereby
transfers NDA No.21-005 and NDS No. 06773 and all Marketing Authorisations related to the
Product to Bioglan.  



	A3 	Fees and
      Royalties 






	A3.1 	 In partial
      consideration for the license granted under this Agreement and in consideration
      for the transfer of the NDA and NDS and all other Marketing Authorisations
      related to the Product, Bioglan has paid or shall pay to Jago the following
      amounts 






	a)  	*** paid on 28th December 2000 






	b)  	*** payable within 5 (five) business days of First Commercial
Sale of Product by Bioglan in any country in the Additional Territory 






	c)  	*** within 5 (five) business days of December 31 2001. 






	d)  	Milestone
      payments in respect of the calendar year in which commercial sales of the
      Product in the Additional Territory shall first reach:




 

	 	*** 

      *** 

      *** 

      *** 

      ***






	  	 The parties
      agree that in no event shall the total milestones payable under this clause
      A3.1(d) exceed *** dollars  (***) 






	  	 The milestone
      payments set out in d) above are based on revenue forecasts for commercial
      sales of the Product of: 






	  	 ***
                 Year 1
      

      ***            Year
      2 

      ***            Year
      3 

      ***            Year
      4 

      ***            Year
      5 






	  	 Where Year
      1 is the first consecutive twelve month period immediately following the
      first commercial sales of the Product in any country of the Additional Territory
      and Years 2, 3, 4 and 5 follow consecutively thereafter 






	A3.2  	In
further consideration for the grant of this exclusive licence in the Additional 






 
	 	
	 



 












EXECUTION VERSION 



	  	
Territories
Bioglan shall pay Jago royalties based on the commercial sales of the Product in the
Additional Territories as follows:  




 

	   	 i) 	In any twelve
      month period of commercial sales of the Product, where sales of the Product
      meet or exceed 50% of the forecast for that year a royalty of *** of Net
      Sales shall apply. 





	   	 ii) 	In any twelve
      month period of commercial sales of the Product, where sales of the Product
      are between 25% and 50% of the forecast for that year, a royalty of ***
      of Net Sales shall apply. 





	   	 iii) 	In any twelve
      month period of commercial sales of the Product, where sales of the Product
      are less than 25% of the forecast for that year, a royalty of *** of Net
      Sales shall apply. 





In the event that commercial
  sales of the Product reach a threshold resulting in a higher royalty payment
  for the first time during any such twelve month period that higher rate will
  apply to all commercial sales of the Product in that 12 month period. A calculation
  will thereafter be made at the end of each twelve month period to determine
  the royalty rate for that preceding twelve month period. 



In all cases Year 1 is the
  first consecutive twelve month period immediately following the first commercial
  sale of the product in any county of the Additional Territory and Years 2, 3,
  4 and 5 follow consecutively thereafter. 



	A4 	Regulatory
      Matters 






	A4.1  	Unless otherwise
      required by applicable laws, Bioglan shall be the owner and holder of all
      Marketing Authorisations during the term of the License granted herein.
      Bioglan agrees at its sole cost and expense to maintain the Marketing Authorizations
      including obtaining any variations or renewals thereof necessary to manufacture,
      market and sell the Product in each country in the Additional Territory.
      






	A4.2  	Each party
      or its relevant Associated Companies shall provide reasonable assistance
      to the other at the other’s request in connection with the transfer
      of the Marketing Authorizations. Bioglan and Jago or their relevant Associated
      Companies shall comply with all Applicable laws within the Additional Territory
      including the provision of information by Bioglan and Jago or their relevant
      Associated Companies to each other necessary for Jago and Bioglan or their
      relevant Associated Companies to comply with any applicable reporting requirements.
      Bioglan shall promptly notify Jago of any comments, responses or notices
      received from, or inspections by, the FDA or other applicable Competent
      Authorities in the Additional Territory which relate to or may impact the
      Product or the manufacture of the Product and shall promptly inform Jago
      of any responses to such comments responses notices or inspections and the
      resolution of any issue raised by the FDA or other Competent Authority in
      the Additional Territory. 






	A4.3  	Each
Party shall advise the other Party by telephone or facsimile within such time as is
required to comply with applicable laws after it becomes aware of any potentially serious
or unexpected adverse event (including adverse drug  






 
	 	
	 



 












EXECUTION VERSION  



	 	experiences as
      defined in 21 C.F.R. S.314.80 or other applicable regulations) (an “ADE”)
      involving the Product. Such advising Party shall provide the other party
      with a written report delivered by confirmed facsimile of any adverse reaction
      stating the full facts known to such Party including but not limited to
      customer name, address, telephone number, batch lot and serial numbers and
      other information as required by Applicable Laws. Bioglan shall have full
      responsibility for (i) monitoring such adverse reactions (ii) data collection
      activities that occur between Bioglan and the patient or medical professional
      as appropriate including any follow-up inquiries which Bioglan deems necessary
      or appropriate and (iii) making any reports to the competent Authorities in
      the Additional Territory. 






	A4.4  	In
the event that Jago requires access to the NDA and/or NDS for commercial reasons outside
the Additional Territory and/or the Territory, Bioglan shall permit such access as the
parties may agree at Jago’s expense and grant a right of reference for use outside the
Additional Territory by Jago, its Associated Companies and their respective sub-licensees. 






	A4.5  	In
the event that Jago desires access to the NDA and/or NDS for commercial reasons for use
only by Jago, its Associated Companies or their respective sub-licensees Bioglan shall
permit such access as the parties may agree at Jago’s expense and grant a right of
reference for use inside the Additional Territory in respect of any product (for use
outside the Field) other than the Product. 






	A5. 	Manufacturing
      






	A5.1  	Bioglan
shall use its commercially reasonable efforts to enter in to a manufacturing and supply
agreement with Patheon Y.M. Inc. (formally Global Pharm Inc) on terms reasonably
acceptable to it as soon after execution of this Agreement as is possible. 






	A6. 	Amendments
      



The following changes to the Licence
Agreement shall apply in respect of both the Territory and the Additional Territory 



	A6.1  	The
definition of  “Good Manufacturing Practice” in relation to the Additional Territory
shall be amended to read, “Good Manufacturing  Practice”  or “GMP” shall mean all applicable
laws of any governmental or regulatory authority having jurisdiction over the
manufacturer of the Products, which laws and regulations relate to current good
manufacturing practices.” 





	A6.2 	The condition
      precedent set out in the Agreement shall be deleted. 




 
	A6.3 	Clause 5.7
      of the Agreement shall be amended to read as follows: 



“Bioglan shall market the
  Product under any trademarks chosen by Bioglan. Bioglan shall meet all responsibilities
  of monitoring such trademarks in the Territory, It is hereby agreed that all
  rights in such trade will vest absolutely in Bioglan”.

  

   

 
	 	
	 



 












EXECUTION VERSION 



	A6.4  	The parties
      agree that the provisions of Clauses 6.1 and 8.7 shall be expanded to include
      the company, *** in addition to ***. 






	A6.5  	Clause
10.6 shall apply in respect of the Additional Territory as if reference to Clause 3.1
were to Clause A3.1 of this Addendum Agreement. 



This Addendum Agreement has been
entered into on the date first written above 



BIOGLAN PHARMA
  PLC 


	 	 /s/ Don
      Gill
      

    
	BY 	Don Gill
      

    
	TITLE 	Director
      

    


JAGOTEC AG 



	 	/s/ Suzanne
      V. McLean
      

    
	BY 	Suzanne
      V. McLean
      

    
	TITLE 	General
      Counsel & Company Secretary
      

    




	 	 /s/ Francesco
      Patalano 
      

    
	BY 	Francesco
      Patalano 
      

    
	TITLE 	Director