Exhibit
      10.1

     

    CONFIDENTIAL
      TREATMENT REQUESTED. Confidential portions of this document have been redacted
      and have been separately filed with the Commission.

    
 

    LICENSE
      AGREEMENT

    


    


    This
      Agreement made and entered into as of the 29th
      day of
      September 2006 (the “Effective
      Date”)
      by and
      between Kyowa
      Hakko Kogyo Co., Ltd.,
      a
      Japanese corporation having its principal office at 1-6-1 Ohtemachi, Chiyoda-ku,
      Tokyo, 100-8185, Japan (hereinafter referred to as “KYOWA”)
      and
KERYX
      Biopharmaceuticals, Inc.,
      a
      Delaware corporation having its principal office at 750 Lexington Avenue,
      20th
      Floor,
      New York, New York 10022, the United States of America (hereinafter referred
      to
      as “KERYX”).
      KYOWA
      and KERYX may be individually referred to as a “Party”
      or
      collectively referred to as “Parties”.

    


    


    WITNESSETH

    


    


    WHEREAS,
      KYOWA
      has developed the Compound, and acquired certain intellectual property rights
      relating to such Compound;

    


    WHEREAS,
      KYOWA
      has entered into a clinical trials agreement with the National Cancer Institute
      under which development of the Compound has been conducted;

    


    WHEREAS,
      KERYX
      wishes to obtain a right and license from KYOWA to such intellectual property
      rights in the Field and the KERYX Territory; 

    


    WHEREAS,
      KYOWA
      is
      willing to grant such right and license to KERYX, and KERYX is willing to accept
      such right and license;

    


    NOW,
      THEREFORE,
      the
      Parties agree as follows:

    
 

    SECTION
      1. DEFINITIONS

    


    In
      this
      Agreement the following terms shall have the following meanings:

     

    
      
        
          	1.1.	
                  “Affiliates”
                    shall mean, with respect to either Party, any business entity
                    which
                    controls, is controlled by, or is under common control with such
                    Party. A
                    corporation or non-corporate business entity shall be regarded
                    as in
                    control of another corporation if it owns or directly or indirectly
                    controls more than fifty percent (50%) of the voting stock of
                    the other
                    corporation.

                


        

         

      

    

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

       

    

    
      	
              1.2.

            	
              “Annual
                Payment” shall
                have the meaning set forth in Section
                8.6.

            


    

    
      	
              1.3.

            	
              “Approval”
                shall mean the technical, medical and scientific license, registrations,
                authorizations and approvals of any national, supra-national, regional,
                state or local regulatory agency, necessary for the development,
                testing,
                commercial manufacture, distribution, marketing, promotion, offer
                for
                sale, use, import, export and sale of a
                Product.

            


    

    
      	
              1.4.

            	
              “Authority”
                shall mean a governmental authority having jurisdiction over import,
                export, development, manufacture, marketing or sales of pharmaceutical
                products, not limited to the FDA.

            


    

    
      	
              1.5.

            	
              “Business
                Day”
                shall mean a day other than a Saturday, Sunday, national or bank
                holiday
                in Japan or the United States of
                America.

            


    

    
      	
              1.6.

            	
              “Combination
                Product” shall
                mean any pharmaceutical product in finished form which contains the
                Compound and one or more active pharmaceutical ingredients other
                than the
                Compound, which is used in the Field.


            


    

    
      	
              1.7.

            	
              “Combination
                Therapy”
                shall mean the use of Compound as an active pharmaceutical ingredient
                in
                the Product, which is used with other pharmaceutical products in
                the
                Field.

            


    

    
      	
              1.8.

            	
              “Compound”
                shall
                mean KW-2401 (UCN-01), the chemical structure of which is specified
                in
                Exhibit 1 hereof. 

            


    

    
      	
              1.9.

            	
              “Control”,
                or
                “Controlled”
                means, with respect to a particular information or intellectual property
                right, (i) that the Party owns and has the ability to grant to the
                other
                Party the licenses to such item provided for herein, without violating
                the
                terms of any agreement or other arrangement with any Third Party,
                and/or
                (ii) that the Party has a license to such item and has the ability
                to
                grant to the other Party the licensees to such item provided for
                herein,
                without violating the terms of any agreement or other arrangement
                with any
                Third Party.

            


    

    
      	
              1.10.

            	
              “Data”
                shall
                mean and include all data relating to the Compound and the Product,
                and
                all chemistry, manufacturing and control data relating to the development
                and manufacture of the Compound and the Product, results of pre-clinical
                and clinical studies and all other documentation containing or embodying
                any pre-clinical, clinical and chemistry and manufacturing and control
                data relating to any application for any Approval for a Product.
                

            


    

    
      	
              1.11.

            	
              “Development
                Plan”
                shall mean a written plan to be prepared by KERYX for all activities
                that
                are reasonably required to obtain MAA and/or NDA for the Product
                in the
                KERYX Territory. The Development Plan as of the Effective Date is
                attached
                hereto as Exhibit 5.

            


    

    
      	
              1.12.

            	
              “EMEA”
                shall
                mean the European Agency for the Evaluation of Medicinal Products
                in the
                European Union.

            


    

     

    
      
        
        

      

      
        2

        
          

        

      

      
        
        

      

    

     

    
      	
              1.13.

            	
              “Expiration”
                of
                a patent shall mean the expiration, abandonment or cancellation of
                all of
                the claims of the patent which are being practiced, or, the declaration
                of
                invalidity or non-enforceability of all the claims of the patent
                being
                practiced by a court or other governmental authority of competent
                jurisdiction (including final rejection in re-examination or re-issue
                proceedings) for which the period to file an appeal has expired,
                and from
                which no further appeal has been taken during the applicable appeal
                period
                or is not allowed to be taken against such
                declaration.

            


    

    
      	
              1.14.

            	
              “FDA”
                shall mean the Food and Drug Administration of the United States
                Department of Health and Human
                Services.

            


    

    
      	
              1.15.

            	
              “Field”
                shall mean the treatment and prevention of any diseases in human
                beings.
                

            


    

    
      	
              1.16.

            	
              “Gross
                Sales”
                of
                the Product made by KERYX or the Sublicensees shall mean the aggregate
                total amount of the invoice prices charged for such Product in Product
                sales, computed in respect of invoice applicable to the transfer
                between
                parties constituting an arm’s-length sales transaction. Sales, transfer or
                other disposition of the Product among KERYX, the Sublicensees and
                their
                respective Affiliates shall not be considered at-arm’s-length.
                

            


    

    
      	
              1.17.

            	
              “Improvement”
                shall mean any invention and/or Know-How made or developed after
                the
                Effective Date, whether patentable or not, that improves any
                characteristics or use of the Compound and/or the Product, including
                but
                not be limited to, the use of the Compound in Combination Product
                or in
                Combination Therapy, or any new Indications of the
                Product.

            


    

    
      	
              1.18.

            	
              “Indication”
                shall mean a recognized disease or condition, sign or symptom of
                a disease
                or condition, or symptom associated with the disease and symptom
                for which
                use of a Product is indicated. For purposes of this Agreement and
                the
                payment of milestones, all cancer disease, conditions or symptoms
                shall
                collectively qualify as one
                indication.

            


    

    
      	
              1.19.

            	
              “KERYX
                Data”
                shall mean any Data Controlled by KERYX, which has been developed
                or
                acquired by KERYX or the Sublicensees during the Term. KERYX Data
                shall
                include, but not be limited to, the Data regarding KERYX Improvements.
                

            


    

    
      	
              1.20.

            	
              “KERYX
                Improvements”
                shall mean any Improvements Controlled by KERYX, which have been
                developed
                by or otherwise brought under the Control of KERYX or the Sublicensees
                during the Term. 

            


    

    
      	
              1.21.

            	
              “KERYX
                Territory”
                shall mean any and all countries of the world other than the KYOWA
                Territory.

            


    

    
      	
              1.22.

            	
              “Know-How”
                shall mean any technical and other information, whether patentable
                or not,
                including without limitation technology, experience, formulae, concepts,
                discoveries, trade secrets, inventions, modifications, improvements,
                data,
                results, designs, formulae, ideas, analyses, methods, techniques,
                assays,
                research plans, procedures, tests, processes (including manufacturing
                processes, specifications and techniques), laboratory records, chemical,
                pharmacological, toxicological, clinical, analytical and quality
                control
                data, reports, summaries, and information contained in submissions
                to, and
                information from, regulatory authorities which are not generally
                known.

            


    

     

    
      
        
        

      

      
        3

        
          

        

      

      
        
        

      

    

     

    
      	
              1.23.

            	
              “KYOWA
                Data”
                shall mean any Data in the Field which has been developed or acquired
                by
                KYOWA and under KYOWA’s Control as of the Effective Date or which has been
                developed by or brought under the Control of KYOWA during the Term.
                KYOWA
                Data shall include, but not limited to, any documents filed with
                regulatory agencies and the Data regarding KYOWA Improvements. For
                clarity, KYOWA Data shall not include the NCI
                Data.

            


    

    
      	
              1.24.

            	
              “KYOWA
                Improvements”
                shall mean any Improvements in the Field Controlled by KYOWA, which
                have
                been developed by or otherwise brought under the Control of KYOWA
                during
                the Term. For clarity, KYOWA Improvements shall not include the NCI
                Data.
                

            


    

    
      	
              1.25.

            	
              “KYOWA
                Know-How”
                shall mean any Know-How relating to the Compound in the Field Controlled
                by KYOWA and KYOWA Data which has been developed or acquired by KYOWA
                as
                of the Effective Date. 

            


    

    
      	
              1.26.

            	
              “KYOWA
                Patent Rights A”
                shall mean the Patent Rights in the Field owned or Controlled by
                KYOWA as
                of the Effective Date relating to the Compound as listed in Exhibit
                2, and
                any additional Patent Rights in the Field to which KYOWA acquires
                rights
                during the Term , which pertain in any way to the Compound or the
                Product.
                Exhibit 2 shall be updated from time to time by KYOWA.
                

            


    

    
      	
              1.27.

            	
              “KYOWA
                Patent Rights B”
                shall mean the Patent Rights in the Field owned or Controlled by
                KYOWA as
                of the Effective Date as listed in Exhibit 3, and any additional
                Patent
                Rights in the Field to which KYOWA acquires rights during the Term,
                which
                pertain in any way to the subject matter claimed or disclosed in
                the
                Patent Rights listed in Exhibit 3. Exhibit 3 shall be updated from
                time to
                time by KYOWA.

            


    

    
      	
              1.28.

            	
              “KYOWA
                Patent Rights”
                shall mean any Patent Rights of KYOWA Patent Rights A and KYOWA Patent
                Rights B. 

            


    

    
      	
              1.29.

            	
              “KYOWA
                Territory” shall
                mean Japan.

            


    

    
      	
              1.30.

            	
              “Launch
                Date” shall
                mean the date set forth in Section
                8.4.

            


    

    
      	
              1.31.

            	
              “Lonza”
                shall
                mean Lonza Ltd. headquartered at Basel,
                Switzerland.

            


    

    
      	
              1.32.

            	
              “MAA”
                shall mean the Market Authorization Application to be filed with
                the
                EMEA.

            


    

    
      	
              1.33.

            	
              “Major
                Countries” shall
                mean the United Kingdom, Germany, France, Italy, Spain and
                Switzerland.

            


    

    
      	
              1.34.

            	
              “NCI”
                shall mean National Cancer
                Institute.

            


    

    
      	
              1.35.

            	
              “NCI
                Agreement”
                shall mean the Clinical Trials Agreement executed between KYOWA and
                NCI on
                September 24, 1999 including its amendments
                thereafter.

            


    

     

    
      
        
        

      

      
        4

        
          

        

      

      
        
        

      

    

     

    
      	
              1.36.

            	
              “NCI
                Data”
                shall mean the Data which has been developed or acquired by NCI under
                NCI
                Agreement.

            


    

    
      	
              1.37.

            	
              “NDA”
                shall mean the new drug application to be filed with the
                FDA.

            


    

    
      	
              1.38.

            	
              “Net
                Sales” shall
                mean the Gross Sales of the Product made by KERYX or the Sublicensees,
                less the following deductible items to the extent that they are documented
                on the applicable invoice or other related document and have in fact
                been
                paid or credited in relation to sales of such
                Product:

            


    

    
      	 	
              1.

            	
              the
                cost of transportation and
                insurance;

            


    

    
      	 	
              2.

            	
              the
                cost of rebates, and allowances 

            


    

    
      	 	
              3.

            	
              the
                sum of trade, quantity and cash
                discounts;

            


    

    
      	 	
              4.

            	
              the
                cost of refunds as cash, credit or free goods supplied due to price
                reduction, including retroactive price reduction, or billing
                errors;

            


    

    
      	 	
              5.

            	
              the
                cost of refunds as cash, credit or free goods supplied in compensation
                for
                the Product damaged, rejected, returned or recalled;
                

            


    

    
      	 	
              6.

            	
              the
                sum of taxes, tariffs, customs duties and other governmental charges
                including mandated credits, refunds and rebates paid with respect
                to such
                sales, however, excluding income or franchise taxes of any kind;
                and

            


    

    
      	 	
              7.

            	
              all
                other reasonable and customary allowances and adjustments actually
                credited to customers.

            


    

    The
      Net
      Sales shall be calculated according to the generally accepted accounting
      principles consistently applied in the United States of America. In the case
      the
      Product is a Combination Product, the Net Sales of the Combination Product
      shall
      be the Gross Sales thereof (after the above deductible items) multiplied by
      the
      fraction which the Parties determine by mutual written agreement, estimating
      each relative contribution in value that the Compound and other active
      pharmaceutical ingredients contained in such Combination Product would make
      to
      the total value of such Combination Product, as well as, the cost of
      development, the cost of goods and other relevant information with respect
      to
      such Combination Product, provided that such fraction should not go below one
      half (0.5).

    The
      sale
      of a Product between KERYX and any of its Sublicensees solely for the research
      and testing of such Product shall be excluded from the computation of Net
      Sales.

    
      	
              1.39.

            	
              “Patent
                Rights”
                shall mean all issued patents and patent applications, certificates
                of
                invention, or applications for certificates of invention, together
                with
                any extensions, registrations, provisionals, divisionals, continuations,
                continuations-in-part (to the extent the claims in such
                continuation-in-part application are directed to subject matter
                specifically described in such prior patent application), and patents
                issuing therefrom, reissues, divisions, continuations, or
                continuations-in-part, reexaminations, substitutions, renewals,
                restorations, additions, registrations, as well as extensions and
                supplementary protection certificates based thereon, and any government
                Approvals or authorizations relating
                thereto.

            


    

     

    
      
        
        

      

      
        5

        
          

        

      

      
        
        

      

    

     

    
      	
              1.40.

            	
              “Product”
                shall
                mean any pharmaceutical product in finished form which contains the
                Compound as an active pharmaceutical ingredient. For avoidance of
                doubt,
                the Combination Product is a
                Product.

            


    

    
      	1.41.	
              “Royalty”
                or“Royalties”
                shall mean the royalties set forth in Sections 8.3, 8.4 and
                8.5.

            


    

    
      	1.42.	
              “SPC”
                shall mean the supplementary protection certificates in Europe and
                any
                similar rights elsewhere in the
                world.

            


    

    
      	1.43.	
              “Strain”
                shall mean the strain which produces the starting material (staurosporine)
                for the Compound. The identification of the strain and the quantity
                to be
                transferred is set forth in Exhibit
                4.

            


    

    
      	1.44.	
              “Sublicensee”
                shall mean any Third Party to which KERYX grants a sublicense under
                the
                KYOWA Patent Rights and the KYOWA Know-How according to Section
                4.

            


    

    
      	1.45.	
              “Term”
                shall
                mean the term set forth in Section
                27.1.

            


    

    
      	1.46.	
              “Third
                Party” shall
                mean any entity other than KYOWA, KERYX and their respective Affiliates.
                .

            


    

    


    SECTION
      2.
      INTERPRETATION

    


    In
      this
      Agreement:

    
      	2.1.	
              Headings
                and titles are inserted for convenience only and shall not affect
                the
                interpretation hereof; 

            


    

    
      	2.2.	
              Unless
                the context requires otherwise, neither singular nor plural of a
                word
                shall not affect the interpretation
                hereof;

            


    

    


    SECTION
      3.
      LICENSE

    


    
      	3.1.	
              KYOWA
                hereby grants to KERYX an exclusive right and license, with the right
                to
                sublicense, under the KYOWA Patent Rights
                A
                and KYOWA Patent Rights B (subject to Sections 8.6 and 27.3) and
                the KYOWA
                Know-How to make, have made, use, have used, sell, offer for sale,
                have
                sold and distribute the Product in the KERYX Territory within the
                Field.
                

            


    

    
      	3.2.	
              KYOWA
                hereby grants to KERYX an exclusive right and license, with the right
                to
                sublicense, under the KYOWA Patent Rights A and KYOWA Patent Rights
                B
                (subject to Sections 8.6 and 27.3) and the KYOWA Know-How to make
                and have
                made, use and have used the Compound in the KERYX Territory within
                the
                Field. 

            


    

    
      	3.3.	
              KYOWA
                hereby grants to KERYX an exclusive right and license, with the right
                to
                sublicense, under the KYOWA Improvements to make, have made, use,
                have
                used, sell, have sold, offer for sale and distribute the Product
                in the
                KERYX Territory within the Field.

            


    

     

    
      
        
        

      

      
        6

        
          

        

      

      
        
        

      

    

     

    
      	3.4.	
              KYOWA
                hereby grants to KERYX an exclusive right and license, with the right
                to
                sublicense, under the KYOWA Improvements to make and have made, use
                and
                have used the Compound in the KERYX Territory within the Field.
                

            


    

    
      	3.5.	
              KYOWA
                hereby grants to KERYX a non-exclusive right and license, with the
                right
                to sublicense in the KERYX Territory to use, have used the Strain
                in order
                to make, or have made the Compound within the
                Field.

            


    

    
      	3.6.	
              Notwithstanding
                the above Sections 3.1 to 3.5, KYOWA reserves the right to make and
                have
                made the Compound and/or the Product in the KERYX Territory for the
                sole
                purpose of developing and marketing the Product in the KYOWA
                Territory.

            


    

    
      	3.7	
              Except
                as otherwise expressly provided in this Agreement, KYOWA hereby grants
                to
                KERYX the right to file with the appropriate Authorities all applications
                and other materials needed to obtain the Approvals necessary to implement
                this Agreement and protect the respective rights of the Parties,
                and KYOWA
                shall provide KERYX with reasonable assistance in such
                filings.

            


    

    


    SECTION
      4.
      DILIGENCE

    


    
      	4.1	
              KERYX
                shall make and shall have Sublicensees make commercially reasonable
                efforts to develop, to manufacture, to market, and to sell the Product
                within the KERYX Territory. When KERYX makes any changes to the
                Development Plan, KERYX shall notify KYOWA and update Exhibit 5
                accordingly. By the end of the month immediately following the month
                of
                the yearly anniversary of the Effective Date, KERYX shall provide
                KYOWA
                with a written report outlining such efforts made by KERYX and the
                Sublicensees during the previous one (1) year period between anniversaries
                of the Effective Date.

            


    

    
      	4.2	
              KERYX
                shall immediately notify KYOWA in writing upon commencement of each
                phase
                in clinical studies conducted by KERYX or, if applicable, by Sublicensees.
                KERYX shall provide any relevant documents, upon request from
                KYOWA.

            


    

    
      	4.3	
              Within
                ten (10) Business Days after KERYX or the Sublicensee is officially
                notified by the Authority that the Approval for sales of the Product
                in
                the KERYX Territory is granted by such Authority, KERYX shall notify
                or
                have such Sublicensee notify KYOWA in writing, and shall send or
                have such
                Sublicensee send to KYOWA a copy of (1) the certificates for such
                grant
                and (2) any related documentation.

            


    

    


    
      
        
        

      

      
        7

        
          

        

      

      
        
        

      

       

    

    SECTION
      5.
      SUBLICENSE

    


    KERYX
      shall have the right to grant a sublicense under the license granted hereunder,
      provided:

    
      	5.1.	
              that
                KERYX shall obtain KYOWA’s prior written approval, which shall not be
                unreasonably withheld;

            


    

    
      	5.2.	
              that,
                KERYX shall notify KYOWA in writing of (a) the identity of such intended
                Sublicensee and (b) the key terms and conditions of such intended
                sublicense;

            


    

    
      	5.3.	
              that,
                KERYX shall not substantially change the key terms and conditions
                of the
                sublicense without prior written consent of KYOWA, which shall not
                be
                unreasonably withheld;

            


    

    
      	5.4.	
              that,
                the Sublicensee shall not grant a further sublicense hereunder without
                KYOWA’s prior written consent, provided that KYOWA shall not unreasonably
                withhold such consent.

            


    

    
      	5.5.	
              that
                KERYX shall be responsible for the Sublicensee’s compliance with all the
                obligations under this Agreement which apply to such
                Sublicensee;

            


    

    
      	5.6.	
              that,
                KERYX shall defend and indemnify KYOWA with respect to any claims
                arising
                out of KERYX’s acts or failure to act relating to such sublicense;
                

            


    

    
      	5.7.	
              that
                such sublicense shall be subject to termination upon expiration or
                early
                termination of this Agreement for any cause;
                and

            


    

    
      	5.8.	
              that
                the Royalties shall be payable to KYOWA from KERYX with respect to
                the Net
                Sales by any Sublicensee, regardless of whether or not the Sublicensee
                has
                actually paid any royalties due to KERYX.


            


    

    


    SECTION
      6.
      DATA TRANSFER AND ASSISTANCE

    


    
      	6.1.	
              KYOWA
                shall provide KERYX with KYOWA Data and KYOWA Know-How reasonably
                required
                for production, development and regulatory approval of the Product
                in the
                field of the treatment and prevention of cancer (“Cancer-field”), at
                KYOWA’s reasonable judgment, within one (1) month of the Effective Date.
                KYOWA shall continue providing any KYOWA Data in the Cancer-field
                during
                the Term. KYOWA shall also provide KERYX with KYOWA Data in the field
                other than Cancer-field, if any, when KYOWA completes the preparation
                for
                clinical studies, at the latest, Provided however, KYOWA has no
                obligations to acquire any new KYOWA Data. KERYX agrees that any
                KYOWA
                Data shall be held in confidence pursuant to Section 15
                below.

            


    

    
      	6.2.	
              KYOWA
                Data shall be transferred on “as is” basis. Notwithstanding the foregoing,
                in the event that KERYX requests KYOWA to translate KYOWA Data from
                Japanese to English, and KYOWA accepts such request, such KYOWA Data
                may
                be transferred to KERYX from KYOWA in English after a reasonable
                period
                for such translation. KERYX shall bear the costs and expenses of
                such
                translation. 

            


    

     

    
      
        
        

      

      
        8

        
          

        

      

      
        
        

      

    

     

    
      	6.3.	
              The
                ownership of KYOWA Data transferred to KERYX from KYOWA hereunder
                shall
                remain with KYOWA. KERYX may utilize such KYOWA Data only for exercise
                of
                the rights granted to KERYX by KYOWA hereunder and for no other
                Purpose.

            


    

    
      	6.4	
              Within
                three (3) months from the Effective Date, at a time mutually agreed
                by the
                Parties, KYOWA will host a technical review meeting (up to two days)
                in
                Tokyo to provide KERYX an opportunity to discuss and ask questions
                about
                the KYOWA Data and KYOWA Know-How with knowledgeable KYOWA staff
                to ensure
                no misunderstanding or confusion exists. To facilitate the meeting
                KERYX
                will provide to KYOWA, at least two (2) weeks in advance of the meeting,
                a
                written summary of questions or areas to be discussed. Each Party
                shall
                bear their own expenses for the
                meeting.

            


    

    
      	6.5.	
              During
                the first two (2) years from the Effective Date, KYOWA will answer
                by
                letter, facsimile or email to the questions which KERYX may have
                regarding
                the KYOWA Data. KERYX shall notify KYOWA in writing as to whom KERYX
                designates among its employees, officers and directors as its contact
                person for such assistance. 

            


    

    



    SECTION
      7. STRAIN TRANSFER, TECHNICAL ASSISTANCE AND MANUFACTURE 

    


    
      	7.1.	
              KYOWA
                shall provide KERYX with technical information concerning the cultivation
                of the Strain and instruction for maintenance of Strain purity and
                potency
                (“Strain Information”) within one (1) month of the Effective
                Date.

            


    

    KYOWA
      shall provide KERYX or a contract manufacturer designated by KERYX with the
      Strain within thirty (30) days after specific site is instructed to KYOWA by
      KERYX. Such thirty (30)-day period shall exclude the period of time required
      to
      obtain permission from the Authorities for the transfer of the Strain, if
      necessary. Upon request of KERYX, KYOWA may arrange culture media for the Strain
      as set forth in Exhibit 4 for KERYX at KERYX’s cost.

    The
      Parties acknowledge that the Strain and the Strain Information are a part of
      KYOWA Know-How.

    KERYX
      shall be responsible for maintaining the cell bank of the Strain. In the case
      KERYX requests additional supply of the Strain, KYOWA may charge reasonable
      costs for such supply.

    
      	7.2.	
              During
                the two (2) year period immediately following the Effective Date,
                KYOWA
                shall, at KERYX’s written request and KYOWA’s reasonable consent as to
                timing, duration and the number of employees, KYOWA shall send its
                employees to KERYX’s designated premises during KERYX’s normal business
                hours, to instruct KERYX’s employees, officers or directors for
                cultivation of the Strain and manufacture of the Compound on
                non-commercial scale. 

            


    

     

    
      
        
        

      

      
        9

        
          

        

      

      
        
        

      

    

    

      *****Confidential
        material redacted and filed separately with the Commission.

    

     

    The
      total
      working man-hours shall not exceed two hundred (200) working man-hours. At
      one
      premise, the working man-hours per day per person shall be at least eight (8)
      hours. 

    The
      rate
      of man-hour is ***** per working man-hour. No charge shall be payable for *****
      (other than out-of-pocket disbursements). Travel time shall not be considered
      the time for such technical assistance. 

    KERYX
      shall bear KYOWA’s out-of-pocket costs and disbursements including translation
      costs for relevant documents incurred in connection with the technical
      assistance, including hotel accommodation and business class air transportation.
      

    KERYX
      shall make payment for these items specified in this Section 7.2 in US Dollars
      within two (2) months of KERYX’s receipt of KYOWA’s invoice
      therefor.

    
      	7.3.	
              KYOWA
                shall make reasonable efforts to provide the technical assistance
                to make
                the information understood by KERYX, provided however, KYOWA shall
                not
                guarantee the manufacture of the Compound by KERYX or its designated
                contract manufacturer. KERYX shall be solely responsible for manufacture
                of the Compound, and KYOWA will not supply any Compound to KERYX
                for the
                purposes of conducting clinical trials. KYOWA will supply to KERYX
                reasonable quantity of Compound for the purposes of demonstration
                of
                regulatory equivalency or as analytical standard. KYOWA will charge
                KERYX
                for such Compound at *****.

            


    

     

     

    SECTION
      8. CONSIDERATIONS

    


    
      	8.1.	
              (Initial
                Payment) 

            


    

    KERYX
      shall pay to KYOWA a non-refundable, one-time payment of Six Hundred Thousand
      US
      Dollars (US$600,000) within fifteen (15) days of the Effective
      Date.

    
      	8.2.	
              (Milestone
                Payment) 

            


    

    In
      consideration for the rights and license granted to KERYX by KYOWA with respect
      to KYOWA Patent Rights A and related KYOWA Know-How pursuant to Section 3,
      KERYX
      shall pay to KYOWA the following non-refundable, one-time milestone
      payments:

    1.
      *****
      within twenty-four (24) months of the Effective Date;

    2.
      For
      the first Indication:

    (i)
      *****
      within ninety (90) days of KERYX’s or its Sublicensee’s initiation of the Phase
      III clinical trial for the Product;

    (ii)
      ***** within ninety (90) days of the earlier to occur of the following: (a)
      KERYX’s or its Sublicensee’s filing of NDA for the Product in the USA, or
      (b)KERYX’s or its Sublicensee’s filing of MAA for the Product in the EU.


    (iii)
      ***** within ninety (90) days from the day KERYX or its Sublicensee obtains
      the
      first marketing Approval from FDA for the Product;

     

    
      
        
        

      

      
        10

        
          

        

      

      
        
           

        

      

    

    

      *****Confidential
        material redacted and filed separately with the Commission.

    

     

    (iv)
      ***** within ninety (90) days from the day KERYX or its Sublicensee obtains
      the
      first marketing Approval for the Product in a first country of the Major
      Countries. 

    3.
      For
      the second Indication:

    (i)
      *****
      within ninety (90) days of KERYX’s or its Sublicensee’s initiation of the Phase
      I clinical trial for the Product;

    (ii)
      ***** within ninety (90) days of KERYX’s or its Sublicensee’s initiation of the
      Phase III clinical trial for the Product;

    (iii)
      ***** within ninety (90) days of the earlier to occur of the following: (a)
      KERYX’s or its Sublicensee’s filing of NDA for the Product in the USA, or
      (b)KERYX’s or its Sublicensee’s filing of MAA for the Product in the EU.


    (iv)
      ***** within ninety (90) days from the day KERYX or its Sublicensee obtains
      the
      first marketing Approval from FDA for the Product;

    (v)
      *****
      within ninety (90) days from the day KERYX or its Sublicensee obtains the first
      marketing Approval for the Product in a first country of the Major
      Countries.

    
      
        
          	8.3	
                  (Royalty
                    Payment)

                


        

      

    

    
      
        In
          consideration for the rights and license granted to KERYX by KYOWA with
          respect
          to KYOWA Patent Rights A and related KYOWA Know-How pursuant to Section
          3, KERYX
          shall pay to KYOWA a royalty fee of ***** the annual Net Sales in each
          country.


        
          	8.4 	
                  The payment set forth in
                    8.3 shall begin
                    from the first commercial sales of the Product in each country
                    (“Launch
                    Date”)
                    and continue with respect to each Product until the later to
                    occur of the
                    following: *****.


                


        

      

    

    
      	
              8.5

            	
              Upon
                occurrence of (a) or (b) set forth in Section 8.4, and for additional
                ***** from such date, KERYX shall pay to KYOWA a royalty fee of *****
                the
                annual Net Sales of the Product in such
                country.

            


    

    
      	8.6	
              (Annual
                Payment)

            


    

    KERYX
      shall pay to KYOWA a non-refundable, annual payment of ***** each year in
      consideration for the rights and license granted to KERYX by KYOWA pursuant
      to
      Section 3 with respect to KYOWA Patent Rights B and related KYOWA Know-How
      (“Annual
      Payment”).
      The
      first payment shall be made within fifteen (15) days of the Effective Date,
      and
      thereafter to be made within fifteen (15) days of each anniversary date of
      the
      Effective Date during the Term of this Agreement, unless earlier terminated
      in
      accordance with Section 27.3. 

    
      	8.7	
              (Mode
                of Payment) 

            


    

    All
      payments to KYOWA hereunder shall be made in US Dollars in the stated amount
      by
      wire transfer or such other mode agreed upon between the Parties. KERYX shall
      bear the transfer costs or other fees arising from such transaction. Each
      Royalty payment shall be accompanied by a report summarizing in reasonable
      detail the total Net Sales for each Product during the relevant calendar year
      and the calculation of Royalties, if any, due thereon. For purposes of computing
      Royalty payments for Net Sales made outside of the US, such Royalty shall be
      converted into US Dollars, by applying the rate of exchange quoted in the New
      York edition of The Wall Street Journal on the last Business Day of the
      applicable payment period, or such other conversion rate approved by KYOWA.
      

     

    
      
        
        

      

      
        11

        
          

        

      

      
        
        

      

    

    

      *****Confidential
        material redacted and filed separately with the Commission.

    

     

    
      	8.8	
              (Records
                and Audit) 

            


    

    With
      respect to any Product for which Royalties are due pursuant to this Agreement,
      KERYX shall keep and shall have the Sublicensees keep, for five (5) years after
      the end of the calendar year when the Net Sales for Royalty occur, records
      of
      quantities, sales and deductions, in sufficient detail to confirm the accuracy
      of the Royalty calculations hereunder. During the Term and for three (3) years
      thereafter, upon written notice from KYOWA, KERYX shall permit either KYOWA
      representatives or an independent certified public accountant of
      nationally-recognized standing, appointed and paid by KYOWA, at reasonable
      times
      during normal business hours to enter KERYX’s offices or other facilities to
      examine these records solely to the extent necessary to verify such
      calculations. Such examination shall occur only once per year. Such KYOWA
      representatives or public accountant shall be permitted to make copies of such
      records only if a discrepancy is discovered and only to the extent necessary
      to
      explain and pursue the discrepancy. Such investigation shall be at the expense
      of KYOWA, unless it reveals a discrepancy in KERYX’s favor of more than *****,
      in which event KERYX shall pay all reasonable expenses related thereto.


    
      	8.9	
              (Tax
                Withholding)  

            


    

    The
      Parties shall use all reasonable and legal efforts to reduce tax withholding
      on
      payments made to KYOWA hereunder. The Parties shall cooperate in good faith
      to
      provide each other with such documents and certificates as are reasonably
      necessary so as to minimize any withholding tax obligations. KERYX shall provide
      to KYOWA documentation of the payment of any withholding taxes that cannot
      be
      avoided and have therefore been paid so that KYOWA can obtain credit.


    
      	8.10	
              (Blocked
                Payments)  

            


    

    In
      the
      event that, by reason of applicable law or regulations in any country, and
      KERYX
      or Sublicensees are unable to pay KYOWA Royalties or other payments shall be
      deposited in local currency in the relevant country to the credit of KYOWA
      in a
      recognized banking institution designated by KYOWA or, if none is designated
      by
      KYOWA within a period of thirty (30) days, the deposit to the credit of KYOWA
      shall be made in a recognized banking institution selected by KERYX or
      Sublicensees, as the case may be, and identified in a notice in writing given
      to
      KYOWA.

     

    
      
        
        

      

      
        12

        
          

        

      

      
        
        

      

    

     

    SECTION
      9. PATENT PROSECUTION

    


    
      	9.1	
              KYOWA
                shall, at its own cost and discretion, use its commercially reasonable
                efforts to prosecute and to maintain the KYOWA Patent Rights, subject
                to
                Section 9.2. 

            


    

    
      	9.2	
              Concerning
                the patent application Publ.No. EP0850646A1 listed in the Exhibit
                2, KYOWA
                shall, at the request and expense of KERYX, take commercially reasonable
                steps required to prosecute and to maintain in certain countries
                in Europe
                selected by KERYX, other than the Major
                Countries.

            


    

    
      	9.3	
              KYOWA
                shall give notice to KERYX of the grant (allowance), registration
                (issuance), revocation, invalidation, opposition or abandonment of
                any
                KYOWA Patent Rights. In the event that KYOWA desires to discontinue
                maintenance or prosecution of the KYOWA Patent Rights A, KYOWA shall
                upon
                request and confirmation of KERYX’s willingness to pay transfer costs,
                assign such KYOWA Patent Rights A to KERYX at no consideration. Attorney’s
                fees and cost of the assignment of such rights, and the prosecution
                and
                maintenance shall thereafter be borne by KERYX. If requested, KYOWA
                shall
                reasonably assist KERYX in such maintenance and prosecution. KYOWA
                shall
                update any relevant exhibits hereto in writing to include any additional
                KYOWA Patent Rights.

            


    

    
      	9.4	
              In
                the event KYOWA is notified in writing by patent offices that any
                interference, revocation, opposition or similar proceedings are instituted
                against the Patent Rights by a Third Party, KYOWA shall immediately
                inform
                KERYX in writing. KYOWA shall retain the right to take any necessary
                actions in its own discretion and expense. Notwithstanding the above,
                in
                the event that KYOWA advises KERYX that KYOWA declines to defend
                or
                contest such challenge to the Patent Rights and KERYX in writing
                requests
                KYOWA, within ten (10) Business Days after being so informed, to
                undertake
                such defense or contest, the cost of such defense or contest ( “Defense
                Cost”) should be borne by KERYX. KERYX shall pay to KYOWA the Defense
                Cost
                within one (1) month after KERYX’s receipt of KYOWA’s invoice therefor. In
                such case, KYOWA shall not enter into any agreement that would impose
                any
                monetary or other responsibilities or liabilities on KERYX or limit
                or
                reduce KERYX’s rights hereunder without KERYX’s prior written consent
                thereto.

            


    

     

     

    SECTION
      10. PATENT INFRINGEMENT

    


    
      	10.1.	
              Either
                Party shall immediately notify the other Party in writing of any
                infringement or possible infringement on the KYOWA Patent Rights,
                by a
                Third Party, of which they become aware of, and shall simultaneously
                provide the other Party with relevant information. KYOWA is under
                no
                obligation to take any action against such infringement or to bear
                the
                cost of such prevention. KERYX may take legal action against such
                infringement in the KERYX Territory at KERYX’s expense, provided that
                KERYX shall notify KYOWA in writing of such intent in advance and
                regarding developments of the proceedings thereafter. KYOWA shall
                provide
                reasonable assistance to KERYX at KERYX’s written request and expense.
                Notwithstanding the foregoing, KYOWA shall retain the right to take
                any
                necessary actions in its own discretion and expense. Any damages
                or other
                compensation which KERYX may obtain from the Third Party as a result
                of
                such proceedings in the KERYX Territory shall be first allocated
                proportionally to reimbursement for the Parties respective costs
                if any,
                and the remainder shall inure to the benefit of KERYX.
                

            


    

     

    
      
        
        

      

      
        13

        
          

        

      

      
        
        

      

    

     

    
      	10.2.	
              Either
                Party shall immediately notify the other Party in writing of any
                allegation that the Product may infringe any Third Party patents
                or patent
                applications in the KERYX Territory, of which they become aware of,
                and
                shall simultaneously provide the other Party with relevant information.
                Neither Party shall be obligated to defend the other Party or such
                Product
                against or to contest such allegation, nor shall either Party bear
                the
                cost of the other Party for such defense or contest. However, each
                Party
                may, at their own cost defend itself or such Product against such
                allegation. Either Party may settle such case, provided that such
                settlement shall not impose any monetary or other responsibilities
                or
                liabilities upon the other Party. 

            


    

    
 

    SECTION
      11. PATENT
      TERM EXTENSION

    


    KERYX
      agrees to apply for and to exercise due diligence in obtaining an extension
      of
      the term of any patent included in the KYOWA Patent Rights under the applicable
      laws of any country where such extensions are available, including but not
      limited to, the Drug Price Competition and Patent Term Restoration Act in the
      United States. KYOWA agrees to execute such documents and take such additional
      actions as KERYX reasonably request in connection therewith. Each Party shall
      bear its own expenses in connection with the application for such patent term
      extensions. 

    


    


    SECTION
      12. THIRD
      PARTY CONTRACT 

    


    
      	12.1	
              KERYX
                acknowledges the existence of the NCI Agreement under which NCI has
                been
                conducting certain clinical studies of the Compound in the US. If
                KERYX
                intends to obtain the NCI Data, KERYX shall be solely responsible
                for
                negotiation with NCI provided that, if necessary, KYOWA will grant
                permission to NCI to release NCI Data to KERYX.


            


    

     

    
      
        
        

      

      
        14

        
          

        

      

      
        
        

      

    

     

    
      	12.2	
              The
                NCI Agreement will expire on August 10, 2006. If NCI intends to continue
                the agreement, KERYX may be requested to become a party to the NCI
                Agreement in the place of KYOWA. In such case, KERYX shall be solely
                responsible for negotiation with NCI provided that KYOWA will give
                consent
                to NCI for KERYX to become a party to the NCI
                Agreement.

            


    

    
      	12.3	
              Under
                the NCI Agreement KYOWA had supplied NCI with the Compound for its
                clinical studies. For such supply KYOWA selected Lonza as a contract
                manufacturer of the Compound. The agreement between KYOWA and Lonza
                has
                expired, and if KERYX intends to have Lonza manufacture the Compound,
                KERYX shall be solely responsible for negotiation with Lonza provided
                that
                KYOWA will authorize Lonza to use the technology to manufacture the
                Compound as well as to make use of the Drug Master File relating
                to the
                Compound thereof.

            


    

    
      	12.4	
              KERYX
                acknowledges that Third Parties may have Patent Rights or Know-How
                relevant to the commercialization of a Product containing the Compound.
                KERYX agrees that KERYX shall be solely responsible to negotiate
                with any
                Third Party, (such Third Party including but not be limited to
                Sloan-Kettering Institute for Cancer Research and Washington State
                University) a license under any patents, technology, know-how and/or
                data.
                

            


    

    
 

    SECTION
      13.
      IMPROVEMENTS

    


    
      	13.1	
              KYOWA
                shall notify KERYX in the event KYOWA makes any Improvements, and
                KYOWA
                shall grant to KERYX an exclusive, irrevocable, royalty-free license,
                with
                the right to sublicense, to make, have made, use, have used, sell,
                have
                sold, offer for sale and distribute the Product under KYOWA Improvements
                in the KERYX Territory in the
                Field.

            


    

    
      	13.2	
              Upon
                discovery by KERYX or its Affiliates, or Sublicensees of any Improvements,
                including but not be limited to the use of Compound in Product for
                Combination Therapy or in Combination Product, KERYX shall immediately
                notify KYOWA in writing. All rights to the KERYX Improvements shall
                belong
                to KERYX, including the right to seek Patent Rights throughout the
                world.

            


    

    
      	13.3	
              KERYX
                shall grant to KYOWA and shall cause its Sublicensees to grant to
                KYOWA an
                exclusive, irrevocable, royalty-free license, with the right to
                sublicense, under KERYX Improvements for any purposes in the KYOWA
                Territory.

            


    

    


    
      
        
        

      

      
        15

        
          

        

      

      
        
        

      

      

        *****Confidential
          material redacted and filed separately with the Commission.

      

       

    

    SECTION
      14. KERYX DATA AND SUPPLY

     

    
      	14.1	
              Upon
                KYOWA’s request, KERYX shall transfer to KYOWA all KERYX Data necessary
                for submission to Authorities in the KYOWA Territory. KYOWA agrees
                that
                such data shall be held in confidence pursuant to Section 15. KYOWA
                shall
                have an exclusive, paid-up license, with the right to grant sublicenses,
                to use such KERYX Data for KYOWA’s development and marketing of the
                Product in KYOWA Territory.

            


    

    
      	14.2	
              For
                KYOWA’s development and marketing in KYOWA Territory, KYOWA reserves the
                rights to purchase the Compound or the Product which KERYX manufactures
                or
                has its contract manufacturer make at
                *****.

            


    

    
      	14.3	
              In
                the event KYOWA chooses to purchase the Compound or the Product from
                KERYX
                as set forth in 14.2, KERYX shall supply to KYOWA with such Compound
                or
                the Product as long as KYOWA markets the Product in the KYOWA Territory,
                or until KYOWA requests termination of the supply with twelve (12)
                months
                prior written notice to KERYX, provided that KYOWA shall provide
                KERYX
                with at least nine (9) month prior notification of its requirement
                of
                Compound or Product with ±
                15% accuracy. If KERYX ceases to manufacture or commission the manufacture
                of the Compound, or if, despite KERYX’s good faith efforts to ensure an
                adequate supply of the Compound, such supply is not readily obtainable,
                KERYX shall have no obligation to provide or obtain Compound to meet
                KYOWA’s needs, and KYOWA shall be free to seek alternative sources, but
                at
                no expense to KERYX.

            


    

    


    SECTION
      15. CONFIDENTIALITY

    


    
      	15.1	
              During
                the Term and for a period of five (5) years after the expiration
                or early
                termination of this Agreement, either Party shall not disclose to
                any
                Third Party any information disclosed by the other Party under this
                Agreement, in written or electronic form, that is marked “confidential” or
                designated in writing as confidential within thirty (30) Business
                Days of
                oral or visual disclosure, or is understood by the Parties to be
                confidential (“Confidential
                Information”).
                

            


    

    
      	15.2	
              Either
                Party shall maintain the Confidential Information in strict confidence,
                and shall use the Confidential Information solely for the purpose
                of this
                Agreement. The receiving Party shall prevent unauthorized use or
                reproduction of the Confidential Information by taking all necessary
                measures, including limiting access to the Confidential Information
                to its
                directors, officers and employees to whom disclosure is necessary
                to
                perform or facilitate the purpose of this Agreement, and who shall
                be
                bound by the confidentiality obligations in this
                Section.

            


    

     

    
      
        
        

      

      
        16

        
          

        

      

      
        
        

      

    

     

    
      	15.3	
              The
                foregoing obligations of confidentiality and limited use shall not
                apply
                to information  which,
                the receiving Party can establish by reasonable proof;
                

            


    

    
      	
            	1.	
              is
                in the public domain at the time of disclosure;
                or

            


    

    
      	
            	2.	
              becomes
                part of the public domain by publication or otherwise after disclosure
                not
                due to any breach hereof by the receiving Party;
                or

            


    

    
      	
            	3.	
              is
                in the possession of the receiving Party at the time of disclosure
                without
                obligations of confidentiality; or

            


    

    
      	
            	4.	
              is
                provided to the receiving Party by a Third Party legally and without
                confidentiality; or

            


    

    
      	
            	5.	
              is
                independently developed by the receiving Party without any knowledge
                or
                access to the disclosing Party’s Confidential Information; or
                

            


    

    
      	
            	6.	
              is
                required by judicial or administrative authorities to disclose; provided,
                however, that the receiving Party shall promptly notify the other
                Party of
                such requirement so that the other Party may seek an appropriate
                protective order; or

            


    

    
      	
            	7.	
              is
                required by any Authority for the purposes of obtaining Approval;
                however
                the providing Party shall endeavor to have that Authority treat the
                information as confidential.

            


    

    
      	15.4	
              Notwithstanding
                Section 15.1, 15.2 and 15.3, KERYX may disclose KYOWA’s Confidential
                Information to its Sublicensees for the purpose of Section 4, provided
                that KERYX shall assure that such Sublicensees comply with the
                confidentiality obligations and limited use set forth in this Section
                15.
                In the event such Sublicensee has ceased to be the Sublicensee after
                KYOWA’s Confidential Information has been disclosed, KERYX shall have such
                Sublicensee immediately return to KERYX or destroy such Confidential
                Information.

            


    

    
      	15.5	
              Upon
                request from the disclosing Party, or upon expiration or early termination
                of this Agreement, the receiving Party shall either return or destroy,
                at
                the discretion of the disclosing Party, all written or graphic
                Confidential Information to the disclosing Party and shall not retain
                any
                copies thereof, provided, however, one copy may be retained in the
                receiving Party’s legal files as a means of determining any continuing
                obligations hereunder. Each Party may request a certificate from
                the other
                Party regarding compliance with this
                Section.

            


    

    
      	15.6	
              Neither
                Party shall make any publications, news release or other public
                announcement, visual or oral, relating hereto without the other Party’s
                prior written approval thereof, which shall not be unreasonably withheld
                or delayed, except as required by law or
                regulation.

            


    

     

     

    
      
        
        

      

      
        17

        
          

        

      

      
        
        

      

    

    SECTION
      16. LIMITED WARRANTY AND DISCLAIMER 

    


    
      	16.1.	
              Each
                Party represents and warrants:

            


    

    
      	
            	1.	
              that
                such Party has the power and right to enter into this Agreement as
                of the
                Effective Date and to perform its obligations hereunder;
                and

            


    

    
      	
            	2.	
              that
                such Party is not a party to any agreement with a Third Party, whether
                written or not, which would prevent such Party from fulfilling any
                of its
                obligations hereunder.

            


    

    
      	16.2	
              KYOWA
                represents and warrants:

            


    

    
      	
            	1.	
              that
                subject to Section 16.3, KYOWA is the owner of the KYOWA Patent Rights
                and
                KYOWA Know-How;

            


    

    
      	
            	2.	
              that
                subject to Section 16.3, KYOWA is entitled to grant to KERYX the
                rights
                granted to KERYX by KYOWA hereunder;
                and

            


    

    
      	
            	3.	
              that,
                to the best knowledge of KYOWA, as of the Effective Date KYOWA knows
                of no
                infirmity in the claimed rights and that no claim or challenge is
                presently pending with regard to those rights, nor is KYOWA aware
                of any
                claim that the Compound violates any Third Party rights..
                

            


    

    
      	16.3	
              KYOWA
                NEITHER REPRESENTS NOR WARRANTS AND
                DISCLAIMS:

            


    

    
      	
            	1.	
              the
                scope, validity and enforceability of the KYOWA Patent Rights and
                the
                KYOWA Improvements;

            


    

    
      	 	
              2.

            	
              future
                grant (allowance) and registration (issuance) of the KYOWA Patent
                Rights
                and the KYOWA Improvements;

            


    

    
      	 	
              3.

            	
              future
                filing, prosecution and maintenance of the KYOWA
                Improvements;

            


    

    
      	 	
              4.

            	
              future
                development of the KYOWA
                Improvements;

            


    

    
      	 	
              5.

            	
              accuracy
                or completeness of the KYOWA Data or any warranty that the use of
                the
                KYOWA Data will not infringe or violate any patent or proprietary
                rights
                of any Third Party;

            


    

    
      	 	
              6.

            	
              non-infringement
                by any product, material or information on the intellectual property
                or
                other rights vested in or enforceable by a Third
                Party;

            


    

    
      	 	
              7.

            	
              successful
                development of the Product;

            


    

    
      	 	
              8.

            	
              Approval
                of the Product by the Authority;
                and

            


    

    
      	 	
              9.

            	
              merchantability
                and fitness for a particular
                purpose.

            


    

    
      	16.4	
              KERYX
                NEITHER REPRESENTS NOR WARRANTS AND
                DISCLAIMS:

            


    

    
      	 	
              1.

            	
              the
                scope, validity and enforceability of the KERYX
                Improvements;

            


    

    
      	 	
              2.

            	
              future
                grant (allowance) and registration (issuance) of the KERYX
                Improvements;

            


    

    
      	 	
              3.

            	
              future
                filing, prosecution and maintenance of the KERYX
                Improvements;

            


    

    
      	 	
              4.

            	
              future
                development of the KERYX Improvements and KERYX
                Data;

            


    

    
      	 	
              5.

            	
              accuracy
                or completeness of the KERYX Data or any warranty that the use of
                the
                KERYX Data will not infringe or violate any patent or proprietary
                rights
                of any Third Party;

            


    

     

    
      
        
        

      

      
        18

        
          

        

      

      
        
        

      

    

     

    
      	 	
              6.

            	
              non-infringement
                by any product, material or information on the intellectual property
                or
                other rights vested in or enforceable by a Third
                Party;

            


    

    
      	 	
              7.

            	
              successful
                development of the Product;

            


    

    
      	 	
              8.

            	
              Approval
                of the Product by the Authority;
                and

            


    

    
      	 	
              9.

            	
              merchantability
                and fitness for a particular
                purpose.

            


    

    
      	16.5	
              EXCEPT
                AS EXPRESSLY PROVIDED FOR HEREIN, NEITHER PARTY MAKES ANY  REPRESENTATION
                OR WARRANTY, WHETHER IMPLIED, STATUTORY OR OTHERWISE,  WITH
                RESPECT TO THE SUBJECT MATTER
                HEREOF.

            


    

    


    SECTION
      17. LIMITED LIABILITY

    


    Neither
      Party shall be liable to the other Party or any Third Party for (1) any
      consequential, indirect, incidental, special or exemplary damages and (2) any
      losses of goodwill, business, contracts, revenues, profits or savings, which
      would be caused in relation hereto, through contract, tort (including
      negligence, but not gross negligence), misrepresentation (but not fraudulent
      misrepresentation), breach of statutory duties or otherwise, even if such Party
      is advised of the possibility of such damages or losses.

    


    SECTION
      18. INDEMNIFICATION

    


    
      	18.1.	
              KERYX
                shall defend, indemnify and hold harmless KYOWA, KYOWA’s Affiliates, their
                respective directors, officers and employees from and against any
                and all
                claims, actions, judgments, expenses (including legal expenses and
                reasonable attorneys’ fees), losses and damages incurred by them, arising
                from any Third Party claim in relation to (1) KERYX exercising the
                license
                under Section 3, (2) the Sublicensee exercising the sublicense under
                Section 5 and (3) KYOWA Data and any related documentation, if any,
                which
                are supplied to KERYX by KYOWA unless such claims, actions, judgments,
                expenses, losses and damages result from gross negligence, wrongful
                intentional actions or omissions or fraud on the part of KYOWA, KYOWA’s
                Affiliate, their respective directors, officers or employees. Such
                claims,
                actions, judgments, expenses, losses and damages include those related
                to
                the products or materials manufactured by or on behalf of KERYX or
                its
                Sublicensees pursuant to this Agreement, in particular (but not limited
                to) those related to the claim that such products or materials have
                caused
                death or bodily injury or have infringed intellectual property rights
                of
                any Third Party.

            


    

     

    
      
        
        

      

      
        19

        
          

        

      

      
        
        

      

    

     

     

    
      	18.2.	
              KYOWA
                shall defend, indemnify and hold harmless KERYX, KERYX’s Affiliates, the
                Sublicensees, their respective directors, officers and employees
                from and
                against any and all claims, actions, judgments, expenses (including
                legal
                expenses and reasonable attorneys’ fees), losses and damages incurred by
                them, arising from any Third Party claim in relation to (1) KYOWA
                exercising the license under Section 13 and (2) a Third Party exercising
                the sublicense under the same unless such claims, actions, judgments,
                expenses, losses and damages result from gross negligence, wrongful
                intentional actions or omissions or fraud on the part of KERYX, KERYX’s
                Affiliates, the Sublicensee, their respective directors, officers
                or
                employees. Such claims, actions, judgments, expenses, losses and
                damages
                include those related to the products or materials manufactured by
                or on
                behalf of KYOWA or KYOWA’s sublicensees, in particular (but not limited
                to) those related to the claim that such products or materials have
                caused
                death or bodily injury or have infringed intellectual property rights
                of
                any Third Party.

            


    

    
      	18.3.	
              In
                the event that a Party is notified of a Third Party claim and seeks
                the
                indemnification for such claim under Section 18.1 or 18.2, from the
                other
                Party, the Party shall (1) inform the indemnifying Party in writing
                of
                such claim as soon as practicable after such notification, (2) permit
                the
                indemnifying Party to assume the direction and control of the defense
                against such claim, (3) cooperate with the indemnifying Party in
                such
                defense at the indemnifying Party’s written request and expense and (4)
                undertake all reasonable steps to mitigate any expenses, losses and
                damages arising in relation to such claim. Further, the indemnifying
                Party
                may settle such claim at its sole discretion, provided that such
                settlement should not impose any obligation on or otherwise adversely
                affect the indemnified Party.

            


    

    


    SECTION
      19. FORCE MAJEURE

    


    The
      failure by either Party to timely perform any obligation under this Agreement
      by
      reason of a cause beyond its reasonable control shall not be deemed to be a
      material breach of this Agreement, but shall be excused to the extent and for
      the duration of such cause, provided the duration is not more than six (6)
      months, and the affected Party shall use commercially reasonable efforts to
      avoid or remove such cause, and shall perform its obligations with the utmost
      dispatch when the cause is removed. 

    


    SECTION
      20. WAIVER

    


    Neither
      Party shall be deemed to have waived any of its rights or remedies conferred
      to
      such Party hereunder unless such waiver is made in writing and signed by a
      duly
      authorized representative of such Party. In particular, no delay or failure
      of
      either Party in exercising or enforcing any of its rights or remedies conferred
      to such Party hereunder shall operate as waiver of such rights or remedies
      or so
      as to preclude or to impair the exercise or enforcement of such rights or
      remedies. Further, partial exercise or enforcement of such rights or remedies
      shall not preclude or impair any other exercise or enforcement of such rights
      or
      remedies.

    


    
      
        
        

      

      
        20

        
          

        

      

      
        
        

      

    

    SECTION
      21. ENTIRE AGREEMENT

    


    This
      Agreement constitutes the entire agreement and understanding between the Parties
      relating to the subject matter hereof and supersedes any and all prior oral
      or
      written agreement, understanding, representation or warranty between them
      relating to the same. The Parties understand and confirm that, as regards the
      subject matter hereof, no director, officer, employee or agent of either Party
      is authorized to make any representation or warranty to the other Party and
      that
      neither Party relies on such representation or warranty, whether made orally
      or
      in writing.

    


    SECTION
      22. AMENDMENT

    


    No
      amendment, modification or supplement of or to this Agreement shall be valid
      unless made in writing and signed by duly authorized representatives of both
      Parties.

     

    SECTION
      23. INDEPENDENT CONTRACTORS

    


    The
      relation between the Parties is that of independent contractors. Nothing herein
      is construed to create any other relation, such as partnership or agency,
      between the Parties. Neither Party shall have any right or authority to create,
      assume or incur any obligations, liabilities or expenses on behalf of the other
      Party.

    


    SECTION
      24. NO SOLICITATION

    


    For
      one
      (1) year after and during the Term hereof, KERYX shall not execute or shall
      not
      have a Third Party execute an employment, consulting or similar Agreement with
      KYOWA’s employees sent to KERYX for technical assistance set forth in Section
      7.

    


    
      
        
        

      

      
        21

        
          

        

      

      
        
        

      

    

    SECTION
      25. ASSIGNMENT

    


    Neither
      Party shall wholly or partially assign or pledge its rights and obligations
      hereunder to any Third Party without the other Party’s prior written consent
      thereto, which consent shall not be unreasonably withheld or delayed.
      Notwithstanding the foregoing, either Party may assign its rights and
      obligations hereunder to a successor of such Party’s whole or substantially
      whole business, provided that such Party should timely notify the other Party
      in
      writing of the fact and its intent to effectuate such assignment.

    


    SECTION
      26. SEVERABILITY

    


    In
      the
      event that any provision of this Agreement has been declared illegal, invalid
      or
      unenforceable in any jurisdiction either by any laws or regulations or by any
      orders or judgments of such competent governmental authorities as
      administrations or courts, this Agreement shall continue in full force and
      effect without said provision, so long as the Agreement, taking into account
      said voided provision(s), continues to provide the Parties with the same
      practical benefits as the Agreement containing said voided provision(s) did
      on
      the Effective Date. If, after taking into account said voided provision(s),
      the
      Parties are unable to realize the practical benefit contemplated on the
      Effective Date, the Parties shall negotiate in good faith to amend this
      Agreement to reestablish the practical benefit provided the Parties on the
      Effective Date.

    


    SECTION
      27. TERM AND TERMINATION

    


    
      	27.1.	
              This
                Agreement shall come into effect as of the Effective Date and, unless
                earlier terminated according hereto, continue to be effective until
                KERYX
                is no longer obligated to pay the Royalties and other considerations
                to
                KYOWA under this Agreement (“Term”).

            


    

    
      	27.2.	
              KERYX
                may at any time terminate this Agreement upon one hundred eighty
                (180)
                days prior written notice.

            


    

    
      	27.3.	
              KERYX
                may at any time unilaterally terminate this Agreement only with respect
                to
                the rights and license granted to KERYX for KYOWA Patent Rights B
                and
                related KYOWA Know-How upon written notice to KYOWA three (3) months
                prior
                to an anniversary date of the Effective Date.


            


    

    
      	27.4.	
              Either
                Party may terminate this Agreement by giving written notice to the
                other
                Party in the following events;

            


    

    
      	
            	1.	
              the
                other Party materially breaches any term or condition of this Agreement
                and fails to remedy such breach within ninety (90) days of receipt
                of the
                written notice requesting to remedy such
                breach.

            


    

     

    
      
        
        

      

      
        22

        
          

        

      

      
        
        

      

    

     

     

    
      	
            	2.	
              the
                other Party files for itself a petition for bankruptcy, reorganization,
                composition, readjustment, receivership or similar procedures under
                any
                applicable bankruptcy, insolvency, reorganization, moratorium or
                similar
                law affecting creditors’ rights and interests (hereinafter referred to as
                “Petition”) ;

            


    

    
      	
            	3.	
              the
                Petition has been filed against the other Party by a Third Party
                and the
                court procedures for such Petition have been pending for more than
                forty
                five (45) days; or

            


    

    
      	
            	4.	
              the
                other Party has been wound up, dissolved or liquidated not for merger
                and
                acquisition or the procedures therefor have been
                started.

            


    

    
      	27.5	
              In
                the event this Agreement has expired in accordance with Section 27.1:
                

            


    

    
      	
            	1.	
              KERYX
                shall thereafter be granted a non-exclusive, paid-up right and license,
                with the right to sublicense, under the KYOWA Patent Rights , KYOWA
                Know-How and KYOWA Improvements to make, have made, use, have used,
                sell,
                offer for sale, have sold and distribute the Product in the KERYX
                Territory within the Field.

            


    

    
      	
            	2.	
              KERYX
                shall immediately return to KYOWA or destroy, under KYOWA’s instruction
                and KERYX’s expense, all Confidential Information disclosed to KERYX by
                KYOWA, except to the extent such Confidential Information is necessary
                for
                KERYX to practice and exploit the rights and the license retained
                by KERYX
                after the expiration.

            


    

    
      	
            	3.	
              The
                license granted by KERYX to KYOWA under Section 13.3 shall survive
                the
                expiration of this Agreement as an exclusive, irrevocable, perpetual
                and
                royalty-free license for any purposes in the KYOWA
                Territory.

            


    

    
      	
            	4.	
              KYOWA
                shall retain the exclusive, paid-up license, with the right to grant
                sublicenses, to use the KERYX Data for KYOWA’s development and marketing
                of the Product in KYOWA Territory, pursuant to Section
                14.1.

            


    

    
      	27.6	
              In
                the event this Agreement is terminated by KERYX in accordance with
                Section
                27.4;

            


    

    
      	
            	1.	
              Subsections
                1 and 2 of Section 27.5 shall
                apply.

            


    

    
      	
            	2.	
              KYOWA
                shall immediately return to KERYX or destroy, under KERYX’s instruction
                and at KYOWA’s expense, all Confidential Information disclosed to KYOWA,
                to KERYX including without limitation any KERYX Data and KERYX
                Know-How.

            


    

    
      	27.7	
              In
                the event this Agreement is terminated by KERYX in accordance with
                Sections 27.2 or by
                KYOWA in accordance with Section
                27.4;

            


    

    
      	
            	1.	
              The
                license granted to KERYX under Section 3 of this Agreement shall
                terminate
                as of the effective date of termination, and KERYX shall cease any
                use of
                the KYOWA Patent Rights, KYOWA Know-How and KYOWA
                Improvements.

            


    

    
      	
            	2.	
              KERYX
                shall transfer to KYOWA, at KERYX’s expense, within a reasonable time
                after the effective date of termination, any and all of KERYX’s Data, any
                physical material of the Compound, the Product or the Strain, and
                any
                patents of KYOWA Patent Rights A assigned to KERYX during the Term
                of this
                Agreement pursuant to Section 9.3, including without limitation,
                any
                rights in NDAs, MAAs and other relevant Approvals acquired by KERYX
                for
                its Product in the KERYX Territory.


            


    

     

    
      
        
        

      

      
        23

        
          

        

      

      
        
        

      

    

     

    
      	
            	3.	
              KERYX
                shall immediately return to KYOWA or destroy, under KYOWA’s instruction
                and at KERYX’s expense, all Strain and all Confidential Information
                disclosed to KERYX by KYOWA, including without limitation any KYOWA
                Data
                and KYOWA Know-How.

            


    

    
      	
            	4.	
              The
                license granted by KERYX to KYOWA under Section 13.3 shall survive
                the
                termination of this Agreement as an exclusive, irrevocable, perpetual
                and
                royalty-free license for any purposes in the KYOWA Territory.
                

            


    

    
      	
            	5.	
              KYOWA
                shall retain the exclusive, paid-up license, with the right to grant
                sublicenses, to use the KERYX Data for KYOWA’s development and marketing
                of the Product, or Product in KYOWA Territory, pursuant to Section
                14.1.
                

            


    

    
      	
            	6.	
              KYOWA
                shall immediately return to KERYX or destroy, under KERYX’s instruction
                and at KERYX’s expense, all Confidential Information, except to the extent
                such Confidential Information is necessary for KYOWA to practice
                and
                exploit the rights and the license retained by KYOWA after the
                termination.

            


    

    
      	27.8	
              In
                the event this Agreement is terminated by KERYX with respect to KYOWA
                Patent Rights B and related KYOWA Know-How pursuant to Section
                27.3;

            


    

    
      	
            	1.	
              Subsections
                1 to 6 of Section 27.7 shall apply mutatis
                mutandis only
                with respect to KYOWA Patent Rights B and related KYOWA
                Know-How.

            


    

    
      	
            	2.	
              KERYX
                shall no longer be obligated thereafter to pay the Annual Payment,
                provided that KERYX shall pay all Annual Payments due before the
                effective
                date of termination.

            


    

    
      	
            	3.	
              KYOWA
                shall no longer be obligated to perform any intellectual property
                obligations set forth in Section 9 and Section 10 with respect to
                Patent
                Rights B. 

            


    

    
      	27.9	
              Expiration
                or termination of this Agreement shall not relieve the Parties of
                any
                obligation accruing prior to such expiration or
                termination.

            


    

    
      	27.10	
              Unless
                otherwise expressly stated in this Agreement, Sections 13, 16, 17,
                18, 28,
                and 29 shall survive the expiration or termination hereof. Section
                15
                shall survive according to Section
                15.1.

            


    

    


    SECTION
      28. ARBITRATION

    


    If
      there
      is any dispute, controversy, difference or question between the Parties with
      respect to any matter arising out of or relating to this Agreement, the Parties
      shall first make efforts to solve such issue amicably. If such issue is not
      solved through such amicable efforts, the Parties shall finally settle such
      issue according to the Rules of Conciliation and Arbitration of the
      International Chamber of Commerce. Such arbitration shall be conducted in the
      English language in New York, New York if initiated by KYOWA, and in Tokyo,
      Japan if initiated by KERYX. The award rendered by the arbitrator(s) shall
      be
      final and binding upon both Parties concerned. 

    


    
      
        
        

      

      
        24

        
          

        

      

      
        
        

      

    

    SECTION
      29. GOVERNING LAW

    


    
      	29.1.	
              This
                Agreement shall be governed by and construed according to the laws
                of
                Japan, exclusive of choice of law rules. To the extent that patent
                law or
                law governing trade secrets, know-how or data must be applied, the
                laws of
                the country governing such rights shall be utilized.
                

            


    

    
      	29.2.	
              The
                Parties agree that the arbitration decisions according to Section
                28 shall
                be enforceable by the courts of competent jurisdiction in Japan,
                the
                United States of America and any other country covered by this Agreement,
                and shall submit to the jurisdictions of such courts solely for such
                enforcement.

            


    

    


    SECTION
      30.  AFFILIATES

    


    Each
      Party may perform its obligations hereunder personally or through one or more
      Affiliate and shall be responsible for the performance of such obligations,
      and
      any liabilities resulting from such performance. Neither Party shall permit
      any
      of its Affiliates to commit any act (including any act of omission) which such
      Party is prohibited hereunder from committing directly.

    


    


    
      
        
        

      

      
        25

        
          

        

      

      
        
        

      

    


    IN
      WITNESS WHEREOF,
      the
      Parties have caused this Agreement to be executed by their duly authorized
      representatives as of the Effective Date.

    


    
 

    
      	KYOWA HAKKO KOGYO
              CO.,
              LTD.	KERYX BIOPHARMACEUTICALS,
              INC. 
	 	 	 	 
	 	 	 	 
	 	 	 	 
	 	 	 	 
	
              By: 
                 /s/  Yoshito
                Imai                                
                

            	 By:  /s/ Michael S.
              Weiss                               
              
	
              
Name:    
Yoshito
              Imai	
              
Name:     Michael
              S.
              Weiss
	Title:       President	Title:       CEO
	           
              Pharmaceuticals Business Unit	 	 
	 	 	 	 


    

    


    


    
      
        
        

      

      
        26

        
          

        

      

      
        
        

      

    


    


    EXHIBIT
      1

    COMPOUND
      CHEMICAL STRUCTURE

    


    


    


    


     


    
      
        26

        


        
        

      

      
        
        

        
          

        

      

      
        
        

      

    


    EXHIBIT
      2

    KYOWA
      PATENT RIGHTS A

    


    


    
      	
              No.

            	
              Country

            	
              Designated
                Country in EP

            	
              Kind

            	
              Appl.
                No.

            	
              Appl.
                Date

            	
              Publ.
                No.

            	
              Publ.
                Date

            	
              Reg.
                No.

            	
              Reg.
                Date

            	
              Exp.
                Date

            
	
              1

            	
              U.S.A.

            	
               

            	
              Product

            	
              28201

            	
              03.20.87

            	
               

            	
               

            	
              4935415

            	
              06.19.90

            	
              06.19.2007

            
	
               

            	
              Europe

            	
              GB,
                DE, FR, IT

            	
              Product

            	
              87103764

            	
              03.16.87

            	
              0238011

            	
              09.23.87

            	
              0238011

            	
              09.25.91

            	
              03.16.2007

            
	
              2

            	
              U.S.A.

            	
               

            	
              Process(oxidization)

            	
              79560

            	
              06.22.93

            	
               

            	
               

            	
              5344926

            	
              09.06.94

            	
              06.22.2013

            
	
               

            	
              Europe

            	
              GB,
                FR, DE, IT, ES

            	
              Process(oxidization)

            	
              93109935

            	
              06.22.93

            	
              0575955

            	
              12.29.93

            	
              0575955

            	
              09.15.99

            	
              06.22.2013

            
	
              3

            	
              U.S.A.

            	
               

            	
              Formulation(liposome)

            	
              09/025752

            	
              06.12.97

            	
               

            	
               

            	
              6045822

            	
              04.04.00

            	
              06.12.2017

            
	
               

            	
              Europe

            	
              GB,
                FR, DE, IT, ES, CH

            	
              Formulation(liposome)

            	
              97926234

            	
              06.12.97

            	
              0850646

            	
              07.01.98

            	
               

            	
               

            	
               

            
	
               

            	
              Canada

            	
               

            	
              Formulation(liposome)

            	
              2229892

            	
              06.12.97

            	
              2229892

            	
              12.24.97

            	
              2229892

            	
              01.07.03

            	
              06.12.2017

            
	
               

            	
              Australia

            	
               

            	
              Formulation(liposome)

            	
              31066-97

            	
              06.12.97

            	
              3106697

            	
              01.07.98

            	
              718856

            	
              08.03.00

            	
              06.12.2017

            
	
              4

            	
              U.S.A.

            	
               

            	
              Process(isomerization)

            	
              09/466903

            	
              12.20.99

            	
               

            	
               

            	
              6197955

            	
              03.06.01

            	
              12.20.2019

            
	
               

            	
              Europe

            	
              GB,
                FR, DE, IT, CH, LI

            	
              Process(isomerization)

            	
              99125341.0

            	
              12.21.99

            	
              1020471

            	
              07.19.00

            	
              1020471

            	
              05.28.03

            	
              12.21.2019

            
	
               

            	
              Canada

            	
               

            	
              Process(isomerization)

            	
              2293023

            	
              12.17.99

            	
              2293023

            	
              06.22.00

            	
               

            	
               

            	
               

            


    

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

    


    EXHIBIT
      3

    KYOWA
      PATENT RIGHTS B

    


    
      	
              No.

            	
              Country

            	
              Designated
                Country in EP

            	
              Kind

            	
              Appl.
                No.

            	
              Appl.
                Date

            	
              Publ.
                No.

            	
              Publ.
                Date

            	
              Reg.
                No.

            	
              Reg.
                Date

            	
              Exp.
                Date

            
	
              1

            	
              U.S.A.

            	 	
              Leakage
                inhibition from liposome

            	
              10/018349

            	
              06.23.00

            	
               

            	
               

            	
               

            	
               

            	
               

            
	
               

            	
              Europe

            	
              GB,
                FR, DE, IT, ES, CH

            	
              Leakage
                inhibition from liposome

            	
              00939146.7

            	
              06.23.00

            	
              1190705

            	
              03.27.02

            	
               

            	
               

            	
               

            
	
               

            	
              Canada

            	 	
              Leakage
                inhibition from liposome

            	
              2376849

            	
              06.23.00

            	
              2376849

            	
              01.04.01

            	
               

            	
               

            	
               

            
	
               

            	
              Australia

            	 	
              Leakage
                inhibition from liposome

            	
              54298-00

            	
              06.23.00

            	
              5429800

            	
              01.31.01

            	
              780194

            	
              06.23.05

            	
              06.23.2020

            


    

    


     

    


    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

    *****Confidential material redacted and filed separately
      with
      the Commission.

    
 

    EXHIBIT
      4

    STRAIN
      AND MEDIA


    


    
      	1.	
              Strain:
                Streptomyces sp. *****

            


    

     

    
      	2.	
              Media:
                *****,

            


    

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

      *****Confidential material redacted and filed separately
        with
        the Commission.

       

    

    EXHIBIT
      5

    DEVELOPMENT
      PLAN

    


    The
      initial development plan for development of UCN-01 would be pursued through
      the
      following areas which would be designed to run simultaneously:

    


    
      	 	
              (a)

            	
              Pre-clinical

            


    

    


    KERYX
      recognizes that considerable in-vitro
      and
in-vivo
      experiments have been performed with UCN-01. However, KERYX would make UCN-01
      available to collaborators for evaluations that would include but not be limited
      to some or all of the following:

    


    
      	 	
              i.

            	
              Establishment
                of molecular profiles of tumors that are or are not responsive to
                UCN-01.
                Such profiles might be developed through *****. Results may be derived
                from *****. In particular, KERYX would target information related
                to
                *****.

            


    

    


    
      	 	
              ii.

            	
              Additional
                in-vivo
                toxicology might be considered to develop additional single agent
                or
                combination regimens. KERYX recognizes that preclinical opportunities
                may
                be limited *****

            


    

    


    
      	 	
              iii.

            	
              Evaluation
                of novel combinations of UCN-01 with either traditional anti-cancer
                agents
                or newer targeted agents both in-vitro
                and in-vivo.
                In particular, studies of UCN-01 ***** are interesting in light of
                the new
                data *****. UCN-01 *****. Pre-clinical studies ***** suggest that
                UCN-01
                *****. *****.

            


    

    


    
      	 	
              iv.

            	
              Evaluation
                of ***** would be undertaken. 

            


    

    


    KERYX
      will accomplish this pre-clinical strategy by soliciting investigator proposals,
      placing studies through an NCI research CRADA and by contracting with commercial
      laboratories.

    


    
      	 	
              (b)

            	
              Clinical

            


    

    


    KERYX
      would immediately undertake additional clinical studies. Results derived from
      the pre-clinical studies would be rapidly translated into clinical trials,
      and
      clinical studies would provide samples for additional pre-clinical studies.
      

    


    Based
      on
      the results from the initial phase 1 studies, it appears that *****. KERYX
      will
      also consider additional treatment schedules.

    


    KERYX
      believes that oncology drugs should be developed using multiple simultaneous
      strategies that might lead to either FDA subpart H or full
      approvals.

    


    
      	 	
              i.

            	
              Subpart
                H Single Agent Approvals

            


    

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

      *****Confidential material redacted and filed separately
        with
        the Commission.

       

    

    To
      determine possible subpart H approval strategies KERYX would consider the
      following approaches

    


    
      	 	
              a.

            	
              *****.

            


    

    
      	 	
              b.

            	
              *****

            


    

    
      	 	
              c.

            	
              *****.

            


    

    


    For
      each
      subpart H strategy KERYX would also initiate a phase II study. If the FDA
      accepts a subpart H strategy and an appropriate comparator exists, *****.
      *****.

    


    
      	 	
              ii.

            	
              Subpart
                H Combination Approvals

            


    

    


    KERYX
      will also consider the development of strategies in which *****. For these
      strategies, KERYX will consider randomized phase II studies *****. Given that
      UCN-01 is an IV infusion KERYX believes that it will be difficult to conduct
      such studies using a placebo. The combination of *****.

    


    
      	 	
              iii.

            	
              Full
                Approvals

            


    

    


    KERYX
      believes that randomized studies and potentially full approval strategies may
      be
      required for any strategy involving time to progression as an endpoint. These
      strategies would be pursued in areas for which there was no opportunity for
      pursuit of an unmet medical need. One example is *****. 

    


    Potential
      Timelines
      (starting from the date that formulated drug is available for clinical
      studies)

    


    The
      following represent timelines similar to those used for other drugs that KERYX
      has in-licensed at a similar stage. Two scenarios are envisaged

    


    (1)
      Potential indication for phase II subpart-H strategy can be determined from
      data
      available prior to in-licensing

    


    Months
      1
      - 6

    


    *****

    *****

    *****

    *****

    


    *
      to
      begin as soon as drug in-licensed

    


    Months
      7
      -18

    


    *****
      


    *****

    


    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

    *****Confidential
      material redacted and filed separately with the Commission.

     

    Months
      18
      -24

    


    *****

    


    Months
      24
      -36

    


    *****

    *****

    *****

    


    Months
      37
      - 48

    


    *****

    *****

    


    Months
      49
      - 60

    


    *****

    


    (2)
      Potential indication for phase II subpart-H strategy cannot be determined from
      data available prior to in-licensing

    


    Months
      1
      - 6

    


    *****

    *****

    *****

    *****

    


    *
      to
      begin as soon as drug in-licensed

    


    Months
      7
      -18

    


    *****

    


    Months
      18
      -24

    


    *****

    


    Months
      24-36

    


    *****

    


    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

    *****Confidential
      material redacted and filed separately with the Commission.

     

    Months
      36
      -48

    


    *****

    *****

    *****

    


    Months
      49
      - 60

    


    *****

    *****

    


    Months
      60
      - 72

    


    *****

    *****

    


    Months
      72-84

    


    *****