Certain portions of this Exhibit have been omitted pursuant to a
request for “Confidential Treatment” under Rule 24b-2 of the Securities and
Exchange Commission.  Such portions have
been redacted and bracketed in the request and appear as [*] in the text of
this Exhibit.  The omitted confidential
information has been filed with the Securities and Exchange Commission.


 


Exhibit 4.52


 


	
   

  	
  PRIVATE
  &

  
	
   

  	
  CONFIDENTIAL

  



 


AGREEMENT


 


This Agreement, made and entered into this 27th
day of October, 1999 by and between NISSHIN FLOUR MILLING CO., LTD., a
corporation duly organized and existing under the laws of Japan, having its
principal place of business at 25, Kanda-Nishiki-cho 1-chome, Chiyoda-ku,
Tokyo, Japan (hereinafter referred to as “NISSHIN”) and LAXDALE LIMITED, a corporation
duly organized and existing under the laws of the United Kingdom, having its
principal place of business at Kings Park House, Laurelhill Business Park,
Polmaise Road, Stirling, UK FK7 9JQ, (hereinafter referred to as “LAXDALE”):


 


WITNESSETH THAT:


 


WHEREAS, LAXDALE is desirous of making research and
development of drug, which will be made from ethyl-eicosapentaenoate, for
treating schizophrenia and any other psychiatric and central nervous system
disorders (hereinafter referred to as the “Drug”) and wishes to conduct
clinical trials of the Drug and to apply for the registration of the Drug to
the regulatory authorities for a new drug approval in the United States, the
European Union, Canada, Australia and New Zealand (such countries hereinafter referred
to as the “Territory”):


 


WHEREAS, LAXDALE is desirous of purchasing additional
ethyl-eicosapentaenoate from NISSHIN for the research, development and clinical
trials and for application to the regulatory authorities for a new drug
approval in the Territory and:


 


WHEREAS, NISSHIN is willing to sell LAXDALE such
ethyl-eicosapentaenoate:


 


The parties hereto agree as follows:


 


ARTICLE 1. PRODUCTS


 


1.1     The Products shall mean bulk
ethyl-eicosapentaenoate (hereinafter referred to as the “Products”) as described
in the specifications annexed hereto as Schedule 1 (hereinafter referred to as
the “Specifications”). The Specifications are also permitted for the bulk
pharmaceutical drug in Japan.    NISSHIN
may change


 


1





















 


the Specifications upon
prior notice to LAXDALE with a reasonable cause to do so, provided that the
Products contain more than ninety five percent (95%) of
ethyl-eicosapentaenoate, and provided they continue to meet the Specifications
for the bulk pharmaceutical drug in Japan.


 


ARTICLE 2. SALE OF THE PRODUCTS


 


2.1     Each individual contract
which will separately be made under this Agreement shall be subject to the
provisions of this Agreement.    Such
individual contract shall set forth quantity, specifications and other terms,
conditions and rights and obligations of the parties hereto except those
stipulated in this Agreement.


 


2.2     LAXDALE shall place an order
for the Products with NISSHIN at least ninety (90) days before its specified
date of shipment of the Products.   
NISSHIN will notify LAXDALE of acceptance of the order and a proposed
date of shipment of the Products within ten (10) working days of receipt of
LAXDALE’s order.    The order shall
become binding on NISSHIN when NISSHIN notifies to LAXDALE that such order is
acceptable to NISSHIN.


 


ARTICLE 3. CONSIDERATION


 


3.1     The initial price of the
Products (hereinafter referred to as the “Price”) shall be [*] yen (¥[*]) per kilogram, FOB Japan. NISSHIN will negotiate to
reduce this price with LAXDALE when the quantity of the Products purchased by
LAXDALE increases.


 


ARTICLE 4. PAYMENT


 


4.1     LAXDALE shall pay the Price
to NISSHIN by remitting to the bank account designated by NISSHIN within
fourteen (14) days after receiving a bill from NISSHIN.


 


ARTICLE 5. DELIVERY


 


5.1     As soon as possible after
NISSHIN confirms the receipt of the payment of the Price but not earlier than
the specified date of shipment stipulated in SECTION 2.1 above, NISSHIN shall
ship the Products to LAXDALE or to a destination designated by LAXDALE,
together with a certificate of analysis.


 


5.2     Title to the Products shall
pass from NISSHIN to LAXDALE when the Products effectively pass to LAXDALE at
the agreed point of delivery.


 


5.3     LAXDALE shall inspect the
Products within twenty (20) working days after the


 


2





















 


date of delivery of the
Products.     LAXDALE shall notify
results of the inspection to NISSHIN within five (5) days after the inspection.


 


ARICLE 6. INFORMATION


 


6.1     Provided that it is available
to NISSHIN, NISSHIN will furnish LAXDALE with such information related to the
Products as required by the Food and Drug Administration (FDA) of the United
States or equivalent authorities in other countries.    NISSHIN will also furnish LAXDALE with such
information which LAXDALE may need for making research and development of the
Drug and conducting clinical trials of the Drug in the Territory.


 


6.2     LAXDALE shall not use the
information furnished from NISSHIN for any purpose other than the aforesaid
research, development, clinical trials and for application to the regulatory
authorities for a new drug approval.


 


6.3     In case this Agreement
terminates or is terminated for any reason whatsoever, LAXDALE shall return all
information to NISSHIN furnished from NISSHIN under section 6.1 above.


 


6.4     NISSHIN will prepare a Drug
Master File appropriate for submission to the United States FDA The parties
shall discuss the submission of this Drug Master File to the FDA and to the
equivalent authorities in other countries.


 


ARTICLE 7. WARRANTY


 


7.1     NISSHIN shall only warrant
that the Products which will be supplied by NISSHIN to LAXDALE meet the
Specifications and the certificate of analysis dispatched to LAXDALE with the
Products and shall undertake no further warranty.    NISSHIN does not warrant that the Products
are appropriate materials for manufacturing the Drug.


 


7.2     NISSHIN is not liable for any
claims regarding the Products, if LAXDALE does not comply with the following
terms:


 


7.3     LAXDALE shall use the
Products only for research and development of the Drug or clinical trials of
the Drug in the Territory.


 


1)      LAXDALE shall be aware of
manuals furnished or written warnings given by NISSHIN, for the use of the
Products, all of which are attached hereto as Schedule 2.


 


2)      When defects of the Products
are found and any complaints or claims are made by any third party against
LAXDALE, LAXDALE shall promptly notify NISSHIN such complaints or claims.


 


3





















 


3)      Only if the Products meet
the Specifications, LAXDALE shall use the Products for the clinical trials. In
preparing the Products for clinical trials, LAXDALE shall use encapsulators and
packers who are licensed by the relevant pharmaceutical authorities in the
countries concerned.


 


ARTICLE 8. DEFECTIVE PRODUCTS


 


8.1     In case it is found that the
Products have failed to meet the Specifications or otherwise to conform the
terms of such individual contract or this Agreement due to a cause which has
existed prior to the delivery of the Products to LAXDALE, LAXDALE may terminate
this individual contract, and NISSHIN shall deliver a new lot of the Products
as their replacement to LAXDALE, and LAXDALE shall return such Products at the
expense of NISSHIN.


 


8.2     Notwithstanding the foregoing
provision, right stipulated in SECTION 8.1 shall lapse, when LAXDALE has
delivered a report to NISSHIN under SECTION 5.3 or when such notice was not
delivered to NISSHIN within twenty five (25) working days after the delivery of
the Products to LAXDALE.


 


ARTICLE 9. INDEMNITY


 


9.1     LAXDALE shall indemnify and
hold NISSHIN harmless against all claims, suits, actions or losses of whatever
nature, all costs, attorney’s fees, expenses and damages, arising from a defect
of the Drug made by LAXDALE or any use in the clinical trials of the Drug,
including costs and expenses disbursed by LAXDALE for the defense of such suit
or action, except to the extent that any of the foregoing solely result from
the negligence of NISSHIN or from a breach by NISSHIN of this Agreement. If
such claim is made by a third party against LAXDALE or NISSHIN, the other party
hereto shall cooperate with the opposite party in their investigation of the
cause of the alleged defects and shall discuss how to cope with such claim.


 


9.2     LAXDALE shall indemnify and
hold NISSHIN harmless from and against any and all claims, demands, suits,
actions, losses, damages and liabilities (including attorney’s fees and
expenses and costs of investigation) and other costs and expenses incurred by
NISSHIN as the result of breach of this Agreement by LAXDALE, or any act or
omission of act on the part of LAXDALE, or any of its agents, representatives
or employees.


 


9.3     NISSHIN shall indemnify and
hold LAXDALE harmless from and against any and all claims, demands, suits,
actions, losses, damages and liabilities


 


4





















 


(including attorney’s
fees and expenses and costs of investigation) and other costs and expenses
incurred by LAXDALE as the result of breach of this Agreement by NISSHIN, or
any act or omission of act on the part of NISSHIN, or any of its agents,
representatives or employees.


 


9.4     LAXDALE shall secure and
maintain insurance policies in accordance with normal commercial practice for reasonably
protecting LAXDALE and therefore NISSHIN against any loss, liability or expense
whatever, including personal injury or death, arising or occurring upon or in
connection with LAXDALE’s use in the clinical trials of the Drug.


 


ARTICLE 10. TERM


 


10.1   This Agreement shall remain in
force for a period of three (3) years from the date first above written, and
thereafter shall automatically be renewed on a year to year basis unless either parties hereto gives the other parties
a 6-month written notice in advance to terminate this Agreement.


 


ARTICLE 11. TERMINATION


 


11.1   A party hereto may forthwith
terminate this Agreement for any of the following reasons by giving written
notice to the other parties:


 


a)      Bankruptcy
or insolvency of the other party;


 


b)      Voluntary
or involuntary liquidation of the other party.


 


11.2   If any of the parties hereto is
in default of any of the provisions of this Agreement and does not cure such
default within thirty (30) days after receipt of the notice from the other
party to cure the default, the other party may terminate this Agreement at any
time after the said period.  In such
case, the defaulting party shall compensate the other party or parties who may
suffer from damage caused by the defaulting party. In such case, however, the
individual contract which has already been made shall be honored by the parties
hereto.


 


ARTICLE 12. DEFINITIVE AGREEMENT


 


12.1   If
the parties hereto conclude that the business of the Drug is feasible, the parties
shall negotiate and execute a definitive agreement stipulating the rights and
obligations of the parties, including but not limited to, the prices of the Products,
the following matters;


 


1)      Provided
that NISSHIN can supply the Products, then LAXDALE shall


 


5





















 


purchase from NISSHIN all
of its demands for the Products for its manufacturing of the Drug outside Japan
for ten (10) years from the date when the Drug is firstly marketed as a
pharmaceutical drug for the treatment of psychiatric and neurological
indications in any country outside Japan. Regarding the geographic area inside
Japan, NISSHIN and its associated companies will have the first refusal right
to develop and market the Drug.


 


2)      NISSHIN
shall not knowingly export, sell or distribute the Products to any person or
company who sell or distribute the Drug in the Territory.


 


3)      The
price of the Products shall be paid by LAXDALE in UK pounds and shall not be
more than ten percent (10%) higher than the average market price of the
Products of equal quality available in Japan, the European Union and the United
States.


 


4)      NISSHIN
will use its best efforts to reduce the price of the Products depending upon
the increase in the amount of orders placed by LAXDALE.


 


5)      If,
for any reason whatsoever, NISSHIN cannot supply the volumes of the Products
required by LAXDALE, LAXDALE will then be free to purchase the Products
elsewhere.


 


6)      Should
LAXDALE wish to sell all or a part of entity or transfer all or a part of the
business of the Drug to a third party, LAXDALE shall so notify to NISSHIN and
shall secure for NISSHIN that LAXDALE will endeavor to mediate between NISSHIN
and the third party to enter agreement that the said third party shall purchase
the Products from NISSHIN to manufacture the Drug.    If LAXDALE fails to secure such agreement
from the third party, then LAXDALE will purchase a minimum sales volume up to
fifteen (15) tons per year from NISSHIN for the first year after the third
party launches the Drug in the Territory


 


ARTICLE 13. FORCE MAJEURE


 


13.1   Neither
party hereto shall be liable in any matter for failure or delay in the
fulfillment of all or part of this Agreement, directly or indirectly owing to
the Acts of God, government order or restriction, war, threat of war, war-like
conditions, hostility, sanction, mobilization, blockage, embargo, detention,
revolution, riot, strike, lock-out, plague or other epidemics, fire, flood or
any other causes or circumstances beyond the control of such party.


 


6





















 


ARTICLE 14. ASSIGNMENT


 


14.1   This
Agreement or any right hereunder, in whole or in part, shall not be subject to
assignment by LAXDALE or by NISSHIN without the prior written consent of the
other, such consent not to be unreasonably withheld.


 


14.2   In
the event of a proposed assignment by LAXDALE to an assignee, LAXDALE will
endeavor to ensure that the assignee will enter into an agreement with NISSHIN
under the similar terms and conditions as the agreement between LAXDALE and
NISSHIN.   In particular, LAXDALE will
endeavor to ensure that the assignee buys from NISSHIN at least half its
requirements or, alternatively, assignee buys a minimum of sales volume up to
fifteen (15) tons per year for the first three (3) years after the regulating authority’s
approval is obtained and a minimum of sales volume up to fifty (50) tons per
year for the seven (7) years after that.


 


14.3   If
LAXDALE fails to ensure the minimum purchase requirements described in 14.2,
then LAXDALE will purchase a minimum sales volume up to fifteen (15) tons per
year for the first year after the regulating authority’s approval is obtained.


 


14.4   If
for any reason NISSHIN decides not to supply the assignee on terms similar to
those in this agreement then NISSHIN shall supply a minimum sales volume up to
fifteen (15) tons per year for the first year after the regulating authority’s approval
is obtained.


 


ARTICLE 15. ENTIRE AGREEMENT


 


15.1   This
Agreement comprises the entire agreement and understanding among the parties
hereto at the date first above written as to the subject matter hereof and
merges all prior discussions among them. No party to this Agreement shall be
bound by any conditions, definitions, warranties or representations with
respect to the subject matter of this Agreement other than as expressly
provided in this Agreement. Change of any of the provisions of this Agreement
shall be made in writing and duly signed by authorized representatives of the
parties hereto.


 


ARTICLE 16. CONFIDENTIALITY


 


16.1   The parties hereto agree not to divulge to
others, during the term of this Agreement and thereafter, any and all
information, which becomes available under or in connection with this
Agreement, except to the extent that it


 


7





















 


becomes generally
available to the public through no fault of the receiving party or is received
in good faith from an independent third party or is shown by written records to
be in the recipient’s possession prior to receipt from the other party.


 


16.2   Notwithstanding
section 16.1 above, each of the
parties may disclose such information if forced by the laws, governmental
regulations or orders of the governments. In such event, the disclosure shall
not be deemed to be a breach of this Agreement.


 


ARTICLE 17. NO WAIVER


 


17.1   No
waiver by either party of any breach of any covenant, obligation or provisions
of this Agreement shall operate as a waiver of other default of any other
covenant, obligation arising under this Agreement. No waiver shall be effective
unless it is made in writing.


 


ARTICLE 18. GOVERNING LAWS AND JURISDICTION


 


18.1   This
Agreement shall be governed by and construed with the laws of Japan.


 


18.2   All
disputes arising in connection with or related to this Agreement shall finally
be settled under the Rules of Arbitration of Japan Commercial Arbitration
Association by one or more arbitrators appointed in accordance with the said
Rules.


 


IN WITNESS WHEREOF, the parties hereto have caused
their authorized representatives to execute this Agreement on the date first
above written.


 


	
  LAXDALE LIMITED

  	
   

  
	
   

  	
   

  
	
   

  	
   

  
	
   By:

  	
    /s/ David F. Horrobin

  	
   

  	
  Date:

  	
    5 November, 1999

  	
   

  
	
   

  	
    David F. Horrobin, President & CEO

  	
   

  	
   

  
	
   

  	
   

  
	
   

  	
   

  
	
  NISSHIN FLOUR MILLING CO., LTD.

  	
   

  
	
   

  	
   

  
	
   

  	
   

  
	
   By:

  	
    /s/ Michiharu Igoshi

  	
   

  	
  Date:

  	
    Oct.
  28, 1999

  	
   

  
	
   

  	
    Michiharu Igoshi, General Manager

  	
   

  	
   

  



 


8





















 


Schedule 1


 


Specification of
EPA-E bulk


 


Description:    It
is clear, colorless to pale yellow liquid.

It has faint, characteristic odor and taste.

It is very soluble in methanol, ethanol, acetone, glacial acetic acid, ether,
chloroform, cyclohexane and hexane, and practically insoluble in water and
ethylene glycol.


 


	
  Identification :

  	
  (1)

  	
  Color reaction test for
  double bond

  
	
   

  	
   

  	
   

  
	
   

  	
  (2)

  	
  Color reaction test for
  ester

  
	
   

  	
   

  	
   

  
	
   

  	
  (3)

  	
  UV-absorption

  



 


	
  Refractive index (20°C) :

  	
  1.481 ~ 1.491

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Specific gravity (20°C) :

  	
  0.905 ~ 0.915

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Saponification Value :

  	
  165 ~ 175

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Acid Value :

  	
  Not more than 1

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Iodine value :

  	
  365 ~ 390

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Purity:

  	
  (1) Heavy metals :

  	
  Not more than 10 ppm

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  (2) Arsenic :

  	
  Not more than 2 ppm

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  (3) Peroxide Value

  	
  Not more than 2 (meq/kg)

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  (4) Related substances

  	
   

  	
   

  
	
   

  	
  ODTA(C18:4)

  	
  Not more than 1.0%

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  AA(C20:4 w-6)

  	
  Not more than 1.0%

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  ETA(C20:4 w-3)

  	
  Not more than 1.0%

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Total of others

  	
  Not more than 1.0%

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Residue on ignition :

  	
  Not more than 0.10%

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Assay :

  	
  (1) Ethyl eicosapentaenoate :

  	
  Not less than 96.5%

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  (2) Tocopherol content :

  	
  0.17 ~ 0.23%

  	
   

  
										



 





















 


Schedule 2


 


1.     When
you treat the Products (EPA-E bulk), keep the oxygen away from your process of
encapsulating and others.


 


2.     When
you make soft gel capsule of the Products, review and consider to adopt
succinylated gelatin together with normal gelatin.