Document:

exv10w1

 

Exhibit 10.1

ARGONAUT TECHNOLOGIES, INC.

AMENDMENT TO

CHANGE OF CONTROL SEVERANCE AGREEMENT

     
This Amendment to the Amended and Restated Change of Control
Severance Agreement (the “Agreement”) is made
and entered into effective as of March 17, 2005 (the
“Effective Date”), by and between David Foster
(the “Employee”) and Argonaut Technologies,
Inc., a Delaware corporation (the “Company”).

R E C I T A L

     
The Company and the Employee are parties to an Amended and
Restated Change of Control Severance Agreement dated
August 3, 2004 (the “Prior Agreement”),
which agreement the parties desire to amend in its entirety.

AGREEMENT

     
In consideration of the mutual covenants herein contained and
the continued employment of Employee by the Company, the parties
agree that the Prior Agreement is amended as follows:

		
	 	
    “Section 4, Bonus Upon A Change of Control, is amended
    as follows: In the event of a Negotiated Change of Control,
    Employee shall be entitled to receive a cash bonus equal to
    0.375% of the Value of the Company upon the closing of such
    Negotiated Change of Control.”

     
IN WITNESS WHEREOF, each of the parties has executed this
Agreement, in the case of the Company by its duly authorized
officer, as of the day and year first above written.

	 	 	 
	
	
	
	

	
    COMPANY:

    	 	ARGONAUT TECHNOLOGIES, INC.

    

    By: /s/ Lissa
Goldenstein
Name: Lissa
Goldenstein
Title: President & CEO
	 	 	

	 
	 
	
    
    EMPLOYEE:
    

    	 	/s/ David Foster

    Signature

     
David Foster
    

    Printed Nameexv10w2

 

Exhibit 10.2

ARGONAUT TECHNOLOGIES, INC.

AMENDMENT TO

CHANGE OF CONTROL SEVERANCE AGREEMENT

     
This Amendment to the Amended and Restated Change of Control
Severance Agreement (the “Agreement”) is made
and entered into effective as of March 17, 2005 (the
“Effective Date”), by and between Jeff Labadie
(the “Employee”) and Argonaut Technologies,
Inc., a Delaware corporation (the “Company”).

RECITAL

     
The Company and the Employee are parties to an Amended and
Restated Change of Control Severance Agreement dated
August 3, 2004 (the “Prior Agreement”),
which agreement the parties desire to amend in its entirety.

AGREEMENT

     
In consideration of the mutual covenants herein contained and
the continued employment of Employee by the Company, the parties
agree that the Prior Agreement is amended as follows:

		
	 	
    “Section 4. Bonus Upon A Change of Control, is
    amended as follows: In the event of a Negotiated Change of
    Control, Employee shall be entitled to receive a cash bonus
    equal to 0.375% of the Value of the Company upon the closing of
    such Negotiated Change of Control.”

     
IN WITNESS WHEREOF, each of the parties has executed this
Agreement, in the case of the Company by its duly authorized
officer, as of the day and year first above written.

	 	 	 
	
    COMPANY

    	 	
    ARGONAUT TECHNOLOGIES, INC.
    
	 
	 	 	
    By: /s/ Lissa Goldenstein
    
	 	 	

	 
	 	 	
    Name: Lissa Goldenstein
    
	 	 	

	 
	 	 	
    Title: President & CEO
    
	 	 	

	 
	
    
    EMPLOYEE:
    

    	 	
    /s/ Jeffrey Labadie

    

    Signature
    
	 
	 	 	
    Jeffrey Labadie

    

    Printed Nameexv10w3

 

Exhibit 10.3

ARGONAUT TECHNOLOGIES, INC.

AMENDMENT TO

CHANGE OF CONTROL SEVERANCE AGREEMENT

     
This Amendment to the Amended and Restated Change of Control
Severance Agreement (the “Agreement”) is made and
entered into effective as of March 17, 2005 (the
“Effective Date”), by and between Gordon Tredger
(the “Employee”) and Argonaut Technologies,
Inc., a Delaware corporation (the “Company”).

RECITAL

     
The Company and the Employee are parties to an Amended and
Restated Change of Control Severance Agreement dated
August 3, 2004 (the “Prior Agreement”),
which agreement the parties desire to amend in its entirety.

AGREEMENT

     
In consideration of the mutual covenants herein contained and
the continued employment of Employee by the Company, the parties
agree that the Prior Agreement is amended as follows:

  
 “Section 4. Bonus Upon A Change of Control, is
amended as follows: In the event of a Negotiated Change of
Control, Employee shall be entitled to receive a cash bonus
equal to 0.375% of the Value of the Company upon the closing of
such Negotiated Change of Control.”

     
IN WITNESS WHEREOF, each of the parties has executed this
Agreement, in the case of the Company by its duly authorized
officer, as of the day and year first above written.

	 	 	 
	
    
    COMPANY:

    	 	
    AGRONAUT TECHNOLOGIES, INC.
    
	 
	 	 	
    By: /s/ Lissa Goldenstein
    
	 	 	

	 	 	
    Name: Lissa Goldenstein
    
	 	 	

	 	 	
    Title: President & CEO
    
	 	 	

	 
	
    
    EMPLOYEE:
    

    	 	
    /s/ Gordon Tredger

    
Signature
    
	 
	 	 	
    Gordon Tredger

    
Printed Name<PAGE>

                                                                    EXHIBIT 4.15

                          REGISTRATION RIGHTS AGREEMENT

            This Registration Rights Agreement (the "Agreement") is executed as
of the 8th day of November, 2004 by BioNumerik Pharmaceuticals, Inc., a Texas
corporation (the "Company"), and Takeda Pharmaceuticals Company Limited, a
Japanese corporation ("Takeda") to take effect upon the Effective Date (as
defined herein).

                              W I T N E S S E T H:

            WHEREAS, in accordance with the terms of the Alliance Agreement,
Takeda (i) is acquiring shares of Series I Convertible Preferred Stock and
Series J Convertible Preferred Stock, which, subject to certain conditions, may
be converted into shares of the Company's Common Stock, and (ii) expects to
purchase from time to time shares of the Company's Common Stock, in each case
with the understanding that the Company is granting certain registration rights
to Takeda.

            NOW, THEREFORE, the Company grants the registration rights contained
herein to Takeda, subject to the terms and conditions contained herein:

            1. CERTAIN DEFINITIONS. As used in this Agreement, the following
terms shall have the following respective meanings:

            (a) "Alliance Agreement" means that certain License and Development
      Alliance Agreement, dated October 5, 2004, by and between the Company and
      Takeda.

            (b) "Commission" means the Securities and Exchange Commission or any
other federal agency at the time administering the Securities Act.

            (c) "Common Stock" means the Common Stock, par value $.01 per share,
      of the Company.

            (d) "Conversion Shares" means the shares of Common Stock issued and
      issuable upon conversion of the Convertible Preferred Stock issued to
      Takeda.

            (e) "Convertible Preferred Stock" means, collectively or where no
      distinction is intended, the Company's Series I Convertible Preferred
      Stock and Series J Convertible Preferred Stock, issued by the Company to
      Takeda.

            (f) "Effective Date" means the "Effective Date" as defined in the
      Alliance Agreement which will be the next business day after which the
      following have occurred: (1) either (a) the expiration or earlier
      termination of any notice and waiting period under the Hart-Scott-Rodino
      Antitrust Improvements Act of 1976, as amended, and the rules and
      regulations promulgated thereunder (the "HSR Act") or (b) the approval of
      the transactions contemplated in the Alliance Agreement under the HSR Act,
      unless an HSR Act filing is deemed unnecessary by Takeda at its sole
      discretion, and (2) Company's obtaining any necessary approvals by
      Company's shareholders of the issuance of the Convertible

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<PAGE>

      Preferred Stock, the Conversion Shares, the R&D Shares and the execution
      of the Registration Rights Agreement with respect to the Convertible
      Preferred Stock, the Common Shares and the R&D Shares.

            (g) "Exchange Act" means the Securities Exchange Act of 1934, as
      amended, or any similar federal statute and the rules and regulations of
      the Commission thereunder, all as the same shall be in effect at the time.

            (h) "Holders" means Takeda and any holder of Registrable Securities
      to whom the registration rights conferred by this Agreement have been
      transferred in compliance with Section 2.10 hereof.

            (i) "Initiating Holders" means any Holder or Holders who in the
      aggregate hold more than fifty percent (50%) of the then-outstanding
      Registrable Securities.

            (j) "R&D Shares" means the shares of Common Stock purchased by
      Takeda in connection with its obligations to fund research and development
      by the Company pursuant to the Alliance Agreement.

            (k) "Registrable Securities" means (i) the Conversion Shares, (ii)
      the R&D Shares, and (iii) any Common Stock issued as a dividend or other
      distribution with respect to or in exchange for or in replacement of the
      Conversion Shares, the R&D Shares or the Convertible Preferred Stock
      issued to Takeda; provided, however, that Registrable Securities shall not
      include any shares of Common Stock which have previously been registered
      or which have been sold pursuant to Rule 144.

                  The terms "register," "registered" and "registration" refer to
      a registration effected by preparing and filing a registration statement
      in compliance with the Securities Act, and the declaration or ordering of
      the effectiveness of such registration statement.

            (l) "Rule 144" means Rule 144 as promulgated by the Commission under
      the Securities Act, as such Rule may be amended from time to time, or any
      similar successor rule that may be promulgated by the Commission.

            (m) "Series A Persons" means those persons entitled to registration
      rights pursuant to Section 10 of the Preferred Stock Purchase Agreement
      dated February 19, 1993 between BioNumerik Pharmaceuticals, Inc., a
      Delaware corporation and predecessor by merger to the Company ("BioNumerik
      Delaware"), and certain purchasers of its securities, as amended.

            (n) "Series B Persons" means those persons entitled to registration
      rights pursuant to that certain Registration Rights Agreement (the "Series
      B Registration Rights Agreement") dated as of August 8, 1994 and relating
      to registration rights granted by BioNumerik Delaware to purchasers of its
      Series B Convertible Preferred Stock.

            (o) "Series C Persons" means those persons entitled to registration
      rights pursuant to that certain Registration Rights Agreement (the "Series
      C Registration Rights

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<PAGE>

      Agreement") dated as of August 24, 1995 and relating to registration
      rights granted by the Company to purchasers of its Series C Convertible
      Preferred Stock.

            (p) "Series D Persons" means those persons entitled to registration
      rights pursuant to that certain Registration Rights Agreement (the "Series
      D Registration Rights Agreement") dated as of July 10, 1996 and relating
      to registration rights granted by the Company to purchasers of its Series
      D Convertible Preferred Stock.

            (q) "Series E Persons" means those persons entitled to registration
      rights pursuant to that certain Registration Rights Agreement (the "Series
      E Registration Rights Agreement") dated as of January 21, 1998 and
      relating to registration rights granted by the Company to purchasers of
      its Series E Convertible Preferred Stock.

            (r) "Series F Persons" means (i) those persons entitled to
      registration rights pursuant to that certain Registration Rights Agreement
      (the "Grelan Series F Registration Rights Agreement") dated as of October
      28, 1999 between the Company and Grelan Pharmaceutical Co., Ltd.
      ("Grelan"), and (ii) those persons other than Grelan who are entitled to
      registration rights pursuant to that certain Registration Rights Agreement
      (the "Series F Registration Rights Agreement") dated as of March 14, 2000
      and relating to registration rights granted by the Company to purchasers
      of its Series F Convertible Preferred Stock.

            (s) "Series G Persons" means those persons entitled to registration
      rights pursuant to that certain Registration Rights Agreement (the "Grelan
      Series G Registration Rights Agreement") dated as of October 3, 2000
      between the Company and Grelan.

            (t) "Series H Persons" means those persons entitled to registration
      rights pursuant to that certain Registration Rights Agreement (the "Series
      H Registration Rights Agreement") dated as of December 2, 2003 and
      relating to registration rights granted by the Company to purchasers of
      its Series H Convertible Preferred Stock.

            (u) "Series I Convertible Preferred Stock" means the Company's
      Series I Convertible Preferred Stock, par value $0.01 per share.

            (v) "Series J Convertible Preferred Stock" means the Company's
      Series J Convertible Preferred Stock, par value $0.01 per share.

            (w) "Securities Act" means the Securities Act of 1933, as amended,
      or any similar federal statute and the rules and regulations of the
      Commission thereunder, all as the same shall be in effect at the time.

                  For purposes of the definitions of "Holder" and "Initiating
      Holders" above, holders of Convertible Preferred Stock shall be deemed to
      be the holders of Registrable Securities issuable upon conversion thereof;
      and for the purpose of calculating any percentage of Registrable
      Securities, the calculation shall be made as if the Convertible Preferred
      Stock had been fully converted.

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<PAGE>

            2. REGISTRATION OF REGISTRABLE SECURITIES.

            2.1 Registration on Request.

            (a) Request. Subject to the limitations provided herein, commencing
      on December 31, 2005, or on the first anniversary of the effective date of
      the Company's first registration statement under the Securities Act,
      whichever shall first occur, until December 31, 2012, upon the written
      request (specifying that it is being made pursuant to this Section 2.1) of
      the Initiating Holders, requesting that the Company effect the
      registration under the Securities Act of at least fifty percent (50%) of
      the then-outstanding Registrable Securities, and specifying (x) the
      intended method of disposition thereof, (y) whether or not such requested
      registration is to be an underwritten offering, and (z) the price range
      (net of underwriting discounts and commissions) acceptable to such Holder
      or Holders to be received for such Registrable Securities, the Company
      will within 10 business days after the Company receives such written
      request give written notice of such requested registration to all other
      Holders of Registrable Securities and thereupon the Company will use
      reasonable efforts to effect the registration under the Securities Act of:

                  (i) the Registrable Securities which the Company has been so
            requested to register by such Initiating Holders, and

                  (ii) all other Registrable Securities which the Company has
            been requested to register by the other Holders thereof by written
            request given to the Company within 15 days after the giving of such
            written notice by the Company (which request shall specify the same
            information called for by the original request to effect
            registration described above), all to the extent requisite to permit
            the disposition (in accordance with Section 2.1(b) hereof) of the
            Registrable Securities so to be registered.

            (b) Method of Distribution. The Holders of 51% of the Registrable
      Securities to be included in such registration statement shall determine
      the method of distribution of the Registrable Securities so included;
      provided, however, that if no agreement of Holders of 51% or more of the
      Registrable Securities to be included in such registration statement is
      obtained, then if Holders of more than 30% of the Registrable Securities
      to be included in such registration statement request an underwritten
      public offering, an underwritten public offering shall be the method of
      distribution with other methods permitted to the extent the managing
      underwriter for such offering, in its sole discretion, agrees to other
      methods of distribution being covered by such registration statement.

            (c) Registration of Other Securities. Whenever the Company shall
      effect a registration pursuant to this Section 2.1 in connection with an
      underwritten offering, no securities other than Registrable Securities
      shall be included among the securities covered by such registration unless
      (i) the managing underwriter of such offering shall have advised each
      Holder of Registrable Securities to be covered by such registration in
      writing that the inclusion of such other securities would not adversely
      affect such offering or (ii) the Holders of more than 51% or more of all
      Registrable Securities to be covered by such registration shall have
      consented in writing to the inclusion of such other securities;

                                       4

<PAGE>

      provided, however, that the rights of Holders hereunder shall be subject
      to (A) the prior right of Series A Persons requesting registration
      (whether pursuant to "demand" or "piggyback" registration rights) to
      include all of the securities requested to be registered by such Series A
      Persons in such registration, and (B) the concurrent right of Series B
      Persons, Series C Persons, Series D Persons, Series E Persons, Series F
      Persons, Series G Persons, Series H Persons, and persons holding
      securities obtained through the exercise of warrants issued to certain
      placement agents and finders in connection with the sale of the Company's
      Series E Convertible Preferred Stock (the "Series E Warrant Purchasers")
      requesting registration pursuant to the registration rights granted by the
      Company to such Series B Persons, Series C Persons, Series D Persons,
      Series E Persons, Series F Persons, Series G Persons, Series H Persons,
      and Series E Warrant Purchasers (whether pursuant to "demand" or
      "piggyback" registration rights) to include securities in such
      registration on a pro rata basis with the Registrable Securities of
      Holders to be included in such registration, so that the relative
      proportion of the amount of securities held by Series B Persons, Series C
      Persons, Series D Persons, Series E Persons, Series F Persons, Series G
      Persons, Series H Persons, Series E Warrant Purchasers and Holders that
      are actually included in such registration is the same as the relative
      proportion of the total amount of securities held by Series B Persons,
      Series C Persons, Series D Persons, Series E Persons, Series F Persons,
      Series G Persons, Series H Persons, Series E Warrant Purchasers and
      Holders that are requested to be included in such registration pursuant to
      the registration rights granted by the Company to such Series B Persons,
      Series C Persons, Series D Persons, Series E Persons, Series F Persons,
      Series G Persons, Series H Persons, Series E Warrant Purchasers or
      Holders, as the case may be; provided, however, that the rights of Takeda
      as a Holder hereunder shall, to the extent determined by Takeda to be
      appropriate for sales by Takeda pursuant to Section 8.4(e) of the Alliance
      Agreement, be a prior right of Takeda to such extent (whether pursuant to
      "demand" or "piggyback" registration rights) and in preference to the
      registration rights of other Holders and Series A Persons, Series B
      Persons, Series C Persons, Series D Persons, Series E Persons, Series F
      Persons, Series G Persons, Series H Persons and Series E Warrant
      Purchasers to include Registrable Securities requested by Takeda to be
      registered in such registration to the extent of 50% of the total number
      of shares to be registered for the account of selling shareholders (and in
      place of the rights Takeda would otherwise have to participate in
      registration rights as to the remaining 50% balance of shares to be
      registered for the account of selling shareholders, except to the extent
      other selling shareholders do not request registration as to such
      remaining balance).

            (d) Registration Statement Form. Registrations under this Section
      2.1 shall be on such appropriate registration form of the Commission (i)
      as shall be selected by the Company, and (ii) as shall permit the
      disposition of such Registrable Securities in accordance with the method
      or methods of disposition selected pursuant to Section 2.1(b) hereof.

            (e) Expenses. Except as otherwise provided in this Section 2.1(e) or
      in Section 2.1(i), the Company shall bear all expenses incurred in
      connection with two effective registrations pursuant to Section 2.1 hereof
      and each registration pursuant to Section 2.2 hereof (excluding in each
      case underwriting discounts and commissions applicable to Registrable
      Securities), including, without limitation, in each case: (i) all
      registration,

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<PAGE>

      filing and National Association of Securities Dealers fees; (ii) all fees
      and expenses of complying with securities or blue sky laws; (iii) all word
      processing, duplicating and printing expenses, messenger, delivery and
      shipping expenses; (iv) the fees and disbursements of the accountants and
      counsel for the Company, including the expenses of any special audits or
      "cold comfort" letters or opinions required by or incident to such
      registrations; (v) the fees and disbursements of the accountants and
      counsel for the Company for services rendered in connection with inclusion
      of Registrable Securities in the registration; provided, however, that if
      the accountants or the counsel for the Company refuse or decline to
      undertake such representation because of an actual or perceived conflict
      of interest or otherwise, then the Company shall bear the reasonable fees
      and disbursements of one firm of counsel and one firm of accountants (as
      appropriate) retained by the Holders of such Registrable Securities; (vi)
      premiums and other costs of policies of insurance maintained for the
      benefit of the Company against liabilities arising out of the public
      offering of the Registrable Securities; (vii) any fees and disbursements
      of underwriters customarily paid by issuers or sellers of securities, but
      excluding underwriting discounts and commissions, if any. In all cases,
      each Holder of Registrable Securities shall pay the underwriting discounts
      and commissions applicable to the securities sold by such Holder.

            (f) Effective Registration Statement. The Company's obligation to
      effect a registration requested pursuant to this Section 2.1 shall not be
      deemed to have been fulfilled (i) unless a registration statement with
      respect thereto has become effective (unless a substantial cause of the
      failure of such registration statement to become effective shall be
      attributable to one or more Holders of Registrable Securities whose
      securities were to have been included in such registration statement),
      (ii) if after it has become effective, such registration is interfered
      with by any stop order, injunction or other order or requirement of the
      Commission or other governmental agency or court for any reason, resulting
      in a failure to consummate the offering of Registrable Securities offered
      thereby, (iii) if after a registration statement with respect thereto has
      become effective, the offering of Registrable Securities offered thereby
      is not consummated due to factors beyond the control of the Holders of
      such Registrable Securities, including without limitation in the context
      of a proposed firm commitment underwriting, the fact that the underwriters
      have advised the Holders of such Registrable Securities that such
      Registrable Securities cannot be sold at a net price equal to or above the
      net price specified in the notice to the Company at the time of the
      request, or (iv) if the conditions to closing specified in the purchase
      agreement or underwriting agreement entered into in connection with such
      registration are not satisfied (unless a substantial cause of such
      conditions to closing not being satisfied shall be attributable to one or
      more Holders of Registrable Securities whose Registrable Securities were
      included in such registration statement).

            (g) Selection of Underwriters. If a requested registration pursuant
      to this Section 2.1 involves an underwritten offering, the underwriter or
      underwriters thereof shall be selected by the Company with the approval of
      the Holders of at least 50% of the Registrable Securities to be so
      registered, which approval will not be unreasonably withheld.

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<PAGE>

            (h) Priority in Requested Registrations. If a requested registration
      pursuant to this Section 2.1 involves an underwritten offering, and the
      managing underwriter shall advise the Company in writing (with a copy to
      each Holder requesting registration) that, in its opinion, the number of
      securities requested to be included in such registration exceeds the
      number which can be sold in such offering within a price range acceptable
      to the Holders of more than 50% of the Registrable Securities requested to
      be included in such registration, then the Registrable Securities
      requested to be registered pursuant to this Section 2.1 shall be reduced
      to the number of Registrable Securities which the Company is so advised
      can be sold in (or during the time of) such offering by decreasing the
      Registrable Securities requested to be registered (pro rata among the
      Holders requesting such registration on the basis of the percentage of the
      Registrable Securities held by such Holder immediately prior to the filing
      of the registration statement with respect to such registration). Nothing
      in this Section 2.1(h) shall affect (i) the rights of Series A Persons
      requesting registration to include all of the securities requested to be
      registered by such Series A Persons in such registration without reduction
      prior to the inclusion of any Registrable Securities requested to be
      registered hereunder, or (ii) the rights of Series B Persons, Series C
      Persons, Series D Persons, Series E Persons, Series F Persons, Series G
      Persons, Series H Persons and Series E Warrant Purchasers requesting
      registration to include securities in such registration on a pro rata
      basis with the Registrable Securities of Holders hereunder in the same
      manner as described in Section 2.1(c) hereof; provided, however, that the
      rights of Takeda as a Holder hereunder shall, to the extent determined by
      Takeda to be appropriate for sales by Takeda pursuant to Section 8.4(e) of
      the Alliance Agreement, be a prior right of Takeda to such extent (whether
      pursuant to "demand" or "piggyback" registration rights) and in preference
      to the registration rights of other Holders and Series A Persons, Series B
      Persons, Series C Persons, Series D Persons, Series E Persons, Series F
      Persons, Series G Persons, Series H Persons and Series E Warrant
      Purchasers to include Registrable Securities requested by Takeda to be
      registered in such registration to the extent of 50% of the total number
      of shares to be registered for the participate in registration rights as
      to the remaining 50% balance of shares to be registered for the account of
      selling shareholders, except to the extent other selling shareholders do
      not request registration as to such remaining balance).

            (i) Form S-3. Notwithstanding the other provisions of this Section
      2.1, commencing on the first anniversary of the Effective Date of the
      Company's first registration statement under the Securities Act until
      December 31, 2012, the Company shall be required upon the written request
      of Holder(s) by this Section 2.1 to effect, and bear all expenses (as
      determined pursuant to Section 2.1(e) hereof) incurred in connection with,
      up to two registrations on Form S-3 (or any successor similar form) of
      Registrable Securities during such period, provided that the Registrable
      Securities to be registered thereon are expected to have an aggregate
      disposition price (before deductions for underwriting discounts and
      commissions) of at least $2,000,000.

            (j) During the time period specified in Section 2.1(a), the Company
      shall be required, upon the written request of Holder(s) in accordance
      with this Section 2.1 and subject to the other provisions contained in
      this Section 2.1 to effect, and bear all expenses (as determined pursuant
      to Section 2.1(e) hereof) incurred in connection with, up to two
      registrations pursuant to this Section 2.1 (other than registrations on
      Form S-3 or any

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<PAGE>

      successor similar form). Notwithstanding anything to the contrary
      contained herein, no Holder shall have the right to request registration
      of Registrable Securities pursuant to this Section 2.1 or to include
      Registrable Securities in an incidental registration pursuant to Section
      2.2 with respect to any Registrable Securities that such Holder is
      eligible to sell under Rule 144 of the Securities Act without any volume
      limitations. In addition, the Company shall not be obligated to prepare
      and file any other registration statement pursuant to this Section 2.1
      within 180 days of the consummation of an underwritten public offering of
      Common Stock pursuant to a registration statement filed under the
      Securities Act.

            2.2 Incidental Registration.

            (a) Right to Include Registrable Securities. If the Company at any
      time after the first anniversary of the Effective Date and prior to
      December 31, 2012 proposes to register any of its securities under the
      Securities Act (other than by a registration on Form S-8, S-4 or any
      successor similar forms or any other form not available for registering
      the Registrable Securities for sale to the public and other than pursuant
      to Section 2.1 hereof), whether or not for sale for its own account, it
      will each such time, at least 15 days prior to filing the registration
      statement, give written notice to all Holders of Registrable Securities of
      its intention to do so. Upon the written request of Holders of an
      aggregate of at least 25,000 shares (appropriately adjusted for
      subdivisions and combinations of shares of Common Stock and dividends on
      Common Stock payable in shares of Common Stock hereafter) of Registrable
      Securities, made within 15 days after the receipt of any such notice
      (which request shall specify the Registrable Securities intended to be
      disposed of by each such Holder and the intended method of disposition
      thereof), the Company will use reasonable efforts to effect the
      registration under the Securities Act of all Registrable Securities which
      the Company has been so requested to register by the Holders of such
      Registrable Securities, to the extent requisite to permit the disposition
      (determined pursuant to the provisions of Section 2.1(b) hereof) of the
      Registrable Securities so to be registered, provided that if, at any time
      after giving written notice of its intention to register any securities
      and prior to the effective date of the registration statement filed in
      connection with such registration, the Company shall determine for any
      reason not to register or to delay registration of such securities, the
      Company may, at its election, give written notice of such determination to
      each Holder of Registrable Securities and, thereupon, (i) in the case of a
      determination not to register, shall be relieved of its obligation to
      register any Registrable Securities in connection with such registration
      (but not from its obligation to pay expenses in accordance with Section
      2.1(e) hereof), without prejudice, however, to the rights of any Holder or
      Holders of Registrable Securities entitled to do so to request that such
      registration be effected as a registration under Section 2.1 hereof, and
      (ii) in the case of a determination to delay registering, shall be
      permitted to delay registering any Registrable Securities being registered
      pursuant to this Section 2.2(a), for the same period as the delay in
      registering such other securities. No registration effected under this
      Section 2.2 shall relieve the Company of its obligation to effect any
      registration upon request under Section 2.1 hereof.

                                       8

<PAGE>

            (b) Priority in Incidental Registrations. If (i) a registration
      pursuant to this Section 2.2 involves an underwritten offering of the
      securities so being registered, whether or not for sale for the account of
      the Company, to be distributed (on a firm commitment basis) by or through
      one or more underwriters of recognized standing, whether or not the
      Registrable Securities so requested to be registered for sale for the
      account of Holders of Registrable Securities are also to be included in
      such underwritten offering, and (ii) the managing underwriter of such
      underwritten offering shall inform the Company and the Holders of the
      Registrable Securities requesting such registration by letter of its
      belief that the number of securities requested to be included in such
      registration exceeds the number which can be sold in (or during the time
      of) such offering, then the Company may include in such offering all
      securities proposed by the Company to be sold for its own account and may
      decrease the number of Registrable Securities and other securities of the
      Company that persons have requested to be included in such registration by
      (a) first decreasing the securities requested to be included in such
      registration other than Registrable Securities (pro rata among the persons
      requesting such registration on the basis of the number of shares of such
      securities held by such person immediately prior to the filing of the
      registration statement with respect to such registration) and (b) then, to
      the extent necessary, decreasing the Registrable Securities requested to
      be registered (pro rata among the Holders requesting such registration on
      the basis of the percentage of the Registrable Securities held by such
      Holders immediately prior to the filing of the registration statement with
      respect to such registration); provided, however, that the rights of
      Holders hereunder shall be subject to (i) the right of the Series A
      Persons requesting inclusion of securities in such registration to include
      all of the securities requested to be registered by such Series A Persons
      in such registration without reduction prior to the inclusion of any
      Registrable Securities requested to be included in such registration
      pursuant to this Section 2.2., and (ii) the rights of Series B Persons,
      Series C Persons, series D Persons, Series E Persons, Series F Persons,
      Series G Persons, Series H Persons and Series E Warrant Purchasers
      requesting registration to include securities in such registration on a
      pro rata basis with the Registrable Securities of Holders hereunder in the
      same manner as described in Section 2.1(c) hereof; provided, however, that
      the rights of Takeda as a Holder hereunder shall, to the extent determined
      by Takeda to be appropriate for sales by Takeda pursuant to Section 8.4(e)
      of the Alliance Agreement, be a prior right of Takeda to such extent
      (whether pursuant to "demand" or "piggyback" registration rights) and in
      preference to the registration rights of other Holders and Series A
      Persons, Series B Persons, Series D Persons, Series E Persons, Series F
      Persons, Series G Persons, Series H Persons and Series E Warrant
      Purchasers to include all of the Registrable Securities requested by
      Takeda to be registered in such registration in such registration to the
      extent of 50% of the total number of shares to be registered for the
      account of selling shareholders (and in place of the rights Takeda would
      otherwise have to participate in registration rights as to the remaining
      50% balance of shares to be registered for the account of selling
      shareholders, except to the extent other selling shareholders do not
      request registration as to such remaining balance).

            2.3 Registration Procedures. If and whenever the Company is required
to use reasonable efforts to effect the registration of any Registrable
Securities under the Securities Act as provided in Sections 2.1 and 2.2 hereof,
the Company will, subject to the limitations provided herein, as expeditiously
as possible:

                                       9

<PAGE>

            (a) prepare and (as soon thereafter as possible or in any event no
      later than 60 days after the end of the period within which requests for
      registration may be given to the Company or such longer period as the
      Company shall in good faith require to produce the financial statements
      required in connection with such registration) file with the Commission
      the requisite registration statement to effect such registration and
      thereafter use reasonable efforts to cause such registration statement to
      become effective, provided that the Company may discontinue any
      registration of its securities which are not Registrable Securities (and,
      under the circumstances specified in Section 2.2(a) hereof, its securities
      which are Registrable Securities) at any time prior to the effective date
      of the registration statement relating thereto;

            (b) prepare and file with the Commission such amendments and
      supplements to such registration statement and the prospectus used in
      connection therewith as may be necessary to keep such registration
      statement effective and to comply with the provisions of the Securities
      Act with respect to the disposition of all securities covered by such
      registration statement until such time as all of such securities have been
      disposed of in accordance with the intended methods of disposition by the
      seller or sellers thereof set forth in such registration statement;
      provided, however, that the Company shall not in any event be required to
      keep the registration statement effective for a period of more than three
      months after such registration statement becomes effective;

            (c) furnish to each seller of Registrable Securities covered by such
      registration statement such number of conformed copies of such
      registration statement and of each such amendment and supplement thereto
      (in each case including all exhibits), such number of copies of the
      prospectus contained in such registration statement (including each
      preliminary prospectus and any summary prospectus) and any other
      prospectus filed under Rule 424 under the Securities Act, and such other
      documents, as such seller may reasonably request;

            (d) use reasonable efforts to register or qualify all Registrable
      Securities and other securities covered by such registration statement
      under such other securities or blue sky laws of such jurisdictions as each
      seller thereof shall reasonably request, to keep such registration or
      qualification in effect for so long as such registration statement remains
      in effect (provided, however, that the Company shall not in any event be
      required to keep such registration or qualification in effect for a period
      of more than three months after such registration or qualification becomes
      effective), and take any other action which may be reasonably necessary or
      advisable to enable such seller to consummate the disposition in such
      jurisdictions of the securities owned by such seller, except that the
      Company shall not for any such purpose be required to qualify generally to
      do business as a foreign corporation in any jurisdiction wherein it would
      not but for the requirements of this subdivision (d) be obligated to be so
      qualified or to consent to general service of process in any such
      jurisdiction;

            (e) use reasonable efforts to cause all Registrable Securities
      covered by such registration statement to be registered with or approved
      by such other United States federal or state governmental agencies or
      authorities as may be necessary to enable the seller or sellers thereof to
      consummate the disposition of such Registrable Securities;

                                       10

<PAGE>

            (f) furnish to each seller of Registrable Securities a copy, or,
      upon request, a signed counterpart, addressed to such seller (and the
      underwriters, if any) of

                  (i) an opinion of counsel for the Company, dated the effective
            date of such registration statement (or, if such registration
            includes an underwritten public offering, dated the date of the
            closing under the underwriting agreement), and

                  (ii) a "comfort" letter addressed to the underwriters, dated
            the effective date of such registration statement (or, if such
            registration includes an underwritten public offering, dated the
            date of the closing under the underwriting agreement), signed by the
            independent public accountants who have audited the Company's
            financial statements included in such registration statement,
            covering substantially the same matters with respect to such
            registration statement (and the prospectus included therein) and, in
            the case of the accountants' letter, with respect to events
            subsequent to the date of such financial statements, as are
            customarily covered in opinions of issuer's counsel and in
            accountants' letters delivered to the underwriters in underwritten
            public offerings of securities and, in the case of the accountants'
            letter, such other financial matters, and, in the case of the legal
            opinion such other legal matters, as such seller or such Holder (or
            the underwriters, if any) may reasonably request;

            (g) notify each seller of Registrable Securities covered by such
      registration statement, at any time when a prospectus relating thereto is
      required to be delivered under the Securities Act, upon discovery that, or
      upon the happening of any event as a result of which, the prospectus
      included in such registration statement, as then in effect, includes an
      untrue statement of a material fact or omits to state any material fact
      required to be stated therein or necessary to make the statements therein
      not misleading in the light of the circumstances under which they were
      made, and at the request of any such seller, prepare and furnish to such
      seller a reasonable number of copies of a supplement to or an amendment of
      such prospectus as may be necessary so that, as thereafter delivered to
      the purchasers of such securities, such prospectus shall not include an
      untrue statement of a material fact or omit to state a material fact
      required to be stated therein or necessary to make the statements therein
      not misleading in the light of the circumstances under which they were
      made;

            (h) otherwise use reasonable efforts to comply with all applicable
      rules and regulations of the Commission, and make available to its
      security holders, as soon as reasonably practicable, an earnings statement
      covering the period of at least twelve months beginning with the first
      full calendar month after the effective date of such registration
      statement, which earnings statement shall satisfy the provisions of
      Section 11(a) of the Securities Act, and will furnish to each such seller,
      upon request of such seller, prior to the filing thereof a copy of any
      amendment or supplement to such registration statement or prospectus and
      shall not file any such supplement or amendment if such seller shall have
      delivered to the Company an opinion of counsel that such amendment or
      supplement does not comply in all material respects with the requirements
      of the Securities Act or of the rules or regulations thereunder;

                                       11

<PAGE>

            (i) provide and cause to be maintained a transfer agent for all
      Registrable Securities covered by such registration statement from and
      after a date not later than the effective date of such registration
      statement;

            (j) use reasonable efforts to list all Registrable Securities
      covered by such registration statement on any securities exchange on which
      the Common Stock is then listed; and

            (k) refrain from making any sale or distribution of its equity
      securities, except pursuant to any employee stock option plan or other
      employee benefit plan and any preexisting agreement for the sale of such
      securities, for at least 90 days after the closing of the public offering
      pursuant to such registration.

            It shall be a condition precedent to the obligations of the Company
to take any action with respect to registering a Holder's Registrable Securities
pursuant to this Section 2.3 that such seller of Registrable Securities as to
which any registration is being effected furnish the Company in writing such
information regarding such seller, the Registrable Securities and other
securities of the Company held by such seller, and the distribution of such
securities as the Company may from time to time reasonably request in writing.
If a Holder refuses to provide the Company with any of such information on the
grounds that it is not necessary to include such information in the registration
statement, the Company may exclude such Holder's Registrable Securities from the
registration statement if the Company provides such Holder with an opinion of
counsel to the effect that such information must be included in the registration
statement and such Holder thereafter continues to withhold such information. The
deletion of such Holder's Registrable Securities from a registration statement
shall not affect the registration of the other Registrable Securities to be
included in such registration statement.

            Each Holder of Registrable Securities agrees by acquisition of such
Registrable Securities that upon receipt of any notice from the Company of the
happening of any event of the kind described in Section 2.3(g), such Holder will
forthwith discontinue such Holder's disposition of Registrable Securities
pursuant to the registration statement relating to such Registrable Securities
until such Holder's receipt of the copies of the supplemented or amended
prospectus contemplated by Section 2.3(g) and, if so directed by the Company,
will deliver to the Company (at the Company's expense) all copies, other than
permanent file copies then in such Holder's possession, of the prospectus
relating to such Registrable Securities current at the time of receipt of such
notice.

            2.4 Underwritten Offerings.

            (a) Requested Underwritten Offerings. If requested by the
      underwriters for any underwritten offering of Registrable Securities
      pursuant to a registration requested under Section 2.1 hereof, the Company
      will enter into an underwriting agreement with such underwriters for such
      offering, the portions of such agreement that relate to Holders of
      Registrable Securities being registered to be reasonably satisfactory in
      substance and form to each Holder of Registrable Securities being
      registered and to contain such representations and warranties by the
      Company and such other terms as are generally prevailing in agreements of
      this type, including, without limitation, indemnities

                                       12

<PAGE>

      substantially to the effect and to the extent provided in Section 2.6
      hereof. Each such Holder of Registrable Securities will cooperate with the
      Company in the negotiation of the underwriting agreement and will give
      consideration to the reasonable requests of the Company regarding the form
      thereof, provided that nothing herein contained shall diminish the
      foregoing obligations of the Company. If requested by the underwriters of
      any underwritten offering pursuant to a registration under Section 2.1
      hereof, each Holder of Registrable Securities agrees to enter into an
      agreement with such underwriters not to sell his or its shares of stock in
      the Company for a period of time (not to exceed 180 days) after the
      effectiveness of a registration statement equal to the period of time
      which the sellers of securities in such registration, by separate
      agreement with the underwriters, have agreed not to sell their shares
      after the effectiveness of such registration statement. The Holders of
      Registrable Securities to be distributed by such underwriters shall be
      parties to such underwriting agreement. Any such Holder shall not be
      required to make any representations or warranties to or agreements with
      the Company or the underwriters other than representations, warranties or
      agreements regarding such Holder, such Holder's Registrable Securities and
      other securities of the Company, such Holder's intended method of
      distribution, and any representations, warranties or agreements required
      by law.

            (b) Incidental Underwritten Offerings. If the Company at any time
      proposes to register any of its securities under the Securities Act as
      contemplated by Section 2.2 hereof and such securities are to be
      distributed by or through one or more underwriters, the Company will, if
      requested by any Holder of Registrable Securities as provided in Section
      2.2 hereof and subject to the provisions of Section 2.2(b) hereof, arrange
      for such underwriters to include all the Registrable Securities to be
      offered and sold by such Holder owning the securities to be distributed by
      such underwriters. In such event, the Holders of Registrable Securities to
      be distributed by such underwriters shall be parties to the underwriting
      agreement between the Company and such underwriters. Any such Holder shall
      not be required to make any representations or warranties to or agreements
      with the Company or the underwriters other than representations,
      warranties or agreements regarding such Holder, such Holder's Registrable
      Securities or other securities of the Company, such Holder's intended
      method of distribution and any representations, warranties or agreements
      required by law.

            2.5 Preparation; Reasonable Investigation. In connection with the
preparation and filing of each registration statement under the Securities Act
pursuant to this Agreement, the Company will give the Holders of Registrable
Securities registered under such registration statement, their underwriters, if
any, and one counsel or firm of counsel and one accountant or firm of
accountants representing all the Holders of Registrable Securities to be
registered under such registration statement, the opportunity to participate in
the preparation of such registration statement, each prospectus included therein
or filed with the Commission, and each amendment thereof or supplement thereto,
and will give each of them such access to its books and records and such
opportunities to discuss the business of the Company with its officers and the
independent public accountants who have certified its financial statements as
shall be necessary, in the opinion of such Holders' and such underwriters'
respective counsel, to conduct a reasonable investigation within the meaning of
the Securities Act.

            2.6 Indemnification.

                                       13

<PAGE>

            (a) Indemnification by the Company. In the event any Registrable
      Securities are included in a registration statement under this Section 2,
      to the extent permitted by law, the Company will, and hereby does,
      indemnify and hold harmless the seller of any Registrable Securities
      covered by such registration statement, its directors and officers, each
      other person who participates as an underwriter in the offering or sale of
      such securities and each other person, if any, who controls such seller or
      any such underwriter within the meaning of the Securities Act, against any
      losses, claims, damages or liabilities, joint or several, to which such
      seller or any such director or officer or underwriter or controlling
      person may become subject under the Securities Act or otherwise, insofar
      as such losses, claims, damages or liabilities (or actions or proceedings,
      whether commenced or threatened, in respect thereof) arise out of or are
      based upon any untrue statement or alleged untrue statement of any
      material fact contained in any registration statement under which such
      securities were registered under the Securities Act, any preliminary
      prospectus, final prospectus or summary prospectus contained therein, or
      any amendment or supplement thereto, or any omission or alleged omission
      to state therein a material fact required to be stated therein or
      necessary to make the statements therein not misleading, and the Company
      will reimburse such seller and each such director, officer, underwriter
      and controlling person for any legal or any other expenses reasonably
      incurred by them in connection with investigating or defending any such
      loss, claim, liability, action or proceeding; provided that the Company
      shall not be liable in any such case to the extent that any such loss,
      claim, damage, liability (or action or proceeding in respect thereof) or
      expense arises out of or is based upon an untrue statement or alleged
      untrue statement or omission or alleged omission made in such registration
      statement, any such preliminary prospectus, final prospectus, summary
      prospectus, amendment or supplement in reliance upon and in conformity
      with written information furnished to the Company by such seller expressly
      for use in the preparation thereof, and provided further that the Company
      shall not be liable to any person who participates as an underwriter in
      the offering or sale of Registrable Securities or any other Person, if
      any, who controls such underwriter within the meaning of the Securities
      Act, in any such case to the extent that any such loss, claim, damage,
      liability (or action or proceeding in respect thereof) or expense arises
      out of such person's failure to send or give a copy of the final
      prospectus, as the same may be then supplemented or amended, to the person
      asserting an untrue statement or alleged untrue statement or omission or
      alleged omission at or prior to the written confirmation of the sale of
      the Registrable Securities to such person if such statement or omission
      was corrected in such final prospectus. Such indemnity shall remain in
      full force and effect regardless of any investigation made by or on behalf
      of such seller or any such director, officer, underwriter or controlling
      person and shall survive the transfer of such securities by such seller.

            (b) Indemnification by the Sellers. The Company may require, as a
      condition to including any Registrable Securities in any registration
      statement filed pursuant to Section 2.3 hereof, that the Company shall
      have received an undertaking satisfactory to it from the prospective
      seller of such securities, to indemnify and hold harmless (in the same
      manner and to the same extent as set forth in subdivision (a) of this
      Section 2.6) each underwriter, each person who controls such underwriter
      within the meaning of the Securities Act, the Company, each director of
      the Company, each officer of the Company and each other person, if any,
      who controls the Company within the meaning of the Securities Act, with
      respect to any statement or alleged statement in or omission or alleged
      omission from such

                                       14

<PAGE>

      registration statement, any preliminary prospectus, final prospectus or
      summary prospectus contained therein, or any amendment or supplement
      thereto, if such statement or alleged statement or omission or alleged
      omission was made in reliance upon and in strict conformity with written
      information furnished to the Company by such seller expressly for use in
      the preparation of such registration statement, preliminary prospectus,
      final prospectus, summary prospectus, amendment or supplement; provided
      that such prospective seller shall not be liable to any person who
      participates as an underwriter in the offering or sale of Registrable
      Securities or any other person, if any, who controls such underwriter
      within the meaning of the Securities Act, in any such case to the extent
      that any such loss, claim, damage, liability (or action or proceeding in
      respect thereof) or expense arises out of such person's failure to send or
      give a copy of the final prospectus, as the same may be then supplemented
      or amended, to the person asserting an untrue statement or alleged untrue
      statement or omission or alleged omission at or prior to the written
      confirmation of the sale of Registrable Securities to such person if such
      statement or omission was corrected in such final prospectus. Such
      indemnity shall remain in full force and effect, regardless of any
      investigation made by or on behalf of any underwriter, the Company or any
      such director, officer or controlling person and shall survive the
      transfer of such securities by such seller. In no event shall the
      liability of any selling holder of Registrable Securities under this
      Section 2.6(b) be greater in amount than the dollar amount of the proceeds
      received by such holder upon the sale of the Registrable Securities giving
      rise to such indemnification obligation.

            (c) Notices of Claims, etc. Promptly after receipt by an indemnified
      party of notice of the commencement of any action or proceeding involving
      a claim referred to in the preceding subdivisions of this Section 2.6, as
      a condition to the obligations of the indemnifying party with respect
      thereto, such indemnified party will, if a claim in respect thereof is to
      be made against an indemnifying party, give written notice to the latter
      of the commencement of such action; provided that the failure of any
      indemnified party to give notice as provided herein shall not relieve the
      indemnifying party of its obligations under the preceding subdivisions of
      this Section 2.6, except to the extent that the indemnifying party is
      actually prejudiced by such failure to give notice. In case any such
      action is brought against an indemnified party, the indemnifying party
      shall be entitled to participate in and to assume the defense thereof,
      jointly with any other indemnifying party similarly notified to the extent
      that it may wish, with counsel reasonably satisfactory to such indemnified
      party, and after notice from the indemnifying party to such indemnified
      party of its election so to assume the defense thereof, the indemnifying
      party shall not be liable to such indemnified party for any legal or other
      expenses subsequently incurred by the latter in connection with the
      defense thereof other than reasonable costs of investigation. No
      indemnifying party shall, without the consent of the indemnified party,
      consent to entry of any judgment or enter into any settlement which does
      not include as an unconditional term thereof the giving by the claimant or
      plaintiff to such indemnified party of a release from all liability in
      respect to such claim or litigation.

            (d) Other Indemnification. Indemnification similar to that specified
      in the preceding subdivisions of this Section 2.6 (with appropriate
      modifications) shall be given by the Company and each seller of
      Registrable Securities with respect to any required

                                       15

<PAGE>

      registration or other qualification of securities under any federal or
      state law or regulation of any governmental authority other than the
      Securities Act.

            (e) Indemnification Payments. The indemnification required by this
      Section 2.6 shall be made by periodic payments of the amount thereof
      during the course of the investigation or defense, as and when bills are
      received or expense, loss, damage or liability is incurred.

            (f) Contribution. If the indemnification provided for in this
      Section 2.6 from the indemnifying party is unavailable to an indemnified
      party hereunder in respect of any losses, claims, damages, liabilities or
      expenses referred to therein, then the indemnifying party, in lieu of
      indemnifying such indemnified party, shall contribute to the amount paid
      or payable by such indemnified party as a result of such loss, claims,
      damages, liabilities or expenses in such proportion as is appropriate to
      reflect the relative fault of the indemnifying party and indemnified
      parties in connection with the actions which resulted in such losses,
      claims, damages, liabilities or expenses, as well as any other relevant
      equitable considerations. The relative fault of such indemnifying party
      and indemnified parties shall be determined by reference to, among other
      things, whether any action in question, including any untrue statement of
      material fact or omission or alleged omission to state a material fact,
      has been made by, or relates to information supplied by, such indemnifying
      party or indemnified parties, and the parties' relative intent, knowledge,
      access to information and opportunity to correct or prevent such action.
      The amount paid or payable by a party as a result of the losses, claims,
      damages, liabilities and expenses referred to above shall be deemed to
      include, subject to the limitations set forth in Section 2.6(c) hereof,
      any legal or other fees or expenses reasonably incurred by such party in
      connection with any investigation or proceeding.

            The Company and, as a condition to the registration of any of their
Registrable Securities, the Holders agree that it would not be just and
equitable if contribution pursuant to this Section 2.6(f) were determined by pro
rata allocation or by any other method of allocation which does not take account
of the equitable considerations referred to in the immediately preceding
paragraph. Notwithstanding the provisions of this Section 2.6(f), no underwriter
shall be required to contribute any amount in excess of the amount by which the
aggregate total price at which the Registrable Securities underwritten by it and
distributed to the public were offered to the public exceeds the amount of any
damages which such underwriter has otherwise been required to pay by reason of
such untrue or alleged untrue statement or omission or alleged omission, and no
selling Holder shall be required to contribute any amount in excess of the
amount by which the aggregate total price at which the Registrable Securities of
such selling Holder were offered to the public exceeds the amount of any damages
which such selling Holder has otherwise been required to pay by reason of such
untrue or alleged untrue statement or omission. No person guilty of fraudulent
misrepresentation (within the meaning of Section 11(f) of the Securities Act)
shall be entitled to contribution from any person who was not guilty of such
fraudulent misrepresentation.

            2.7 Reporting Requirements Under Exchange Act. When it is first
legally required to do so, the Company shall register its Common Stock under
Section 12 of the Exchange Act (as hereinafter defined) and shall keep effective
such registration and shall timely file such information, documents and reports
as the Commission may require or prescribe under Section 13

                                       16

<PAGE>

of the Exchange Act. From and after the effective date of the first registration
statement filed by the Company under the Securities Act, the Company shall
(whether or not it shall then be required to do so) timely file such
information, documents and reports which a corporation, partnership or other
entity subject to Section 13 or 15(d) (whichever is applicable) of the Exchange
Act is required to file.

            Immediately upon becoming subject to the reporting requirements of
either Section 13 or 15(d) of the Exchange Act, the Company shall forthwith upon
request furnish any Holder of Registrable Securities (i) a written statement by
the Company that it has complied with such reporting requirements, (ii) a copy
of the most recent annual or quarterly report of the Company, and (iii) such
other reports and documents filed by the Company with the Commission as such
Holder may reasonably request in availing itself of an exemption for the sale of
Registrable Securities without registration under the Securities Act. The
Company acknowledges and agrees that the purposes of the requirements contained
in this Section 2.7 are (a) to enable any such Holder to comply with the current
public information requirement contained in Paragraph (c) of Rule 144 should
such Holder ever wish to dispose of any of the securities of the Company
acquired by it without registration under the Securities Act in reliance upon
Rule 144 (or any other similar exemptive provision) and (b) to qualify the
Company for the use of registration statements on Form S-3. In addition, the
Company shall take such other measures and file such other information,
documents and reports, as shall hereafter be required by the Commission as a
condition to the availability of Rule 144 under the Securities Act (or any
similar exemptive provision hereafter in effect) and the use of Form S-3. The
Company also covenants to use reasonable efforts, to the extent that it is
reasonably within its power to do so, to qualify for the use of Form S-3.

            2.8 Stockholder Information. The Company may require each Holder of
Registrable Securities as to which any registration is to be effected pursuant
to this Section 2 to furnish the Company such information in writing with
respect to such Holder and the distribution of such Registrable Securities as
the Company may from time to time reasonably request in writing and as shall be
required by law or by the Commission in connection therewith.

            2.9 Forms. All references in this Agreement to particular forms of
registration statements are intended to include, and shall be deemed to include,
references to all successor forms which are intended to replace, or to apply to
similar transactions as, the forms herein referenced.

            2.10 Transfer of Registration Rights. The registration rights
granted to the Holders of Registrable Securities under this Section 2 may not be
transferred without the prior written consent of the Company; provided that such
registration rights may be transferred, in whole or in part, without such prior
written consent in connection with the transfer of Registrable Securities to (i)
an affiliate (defined as any person which directly or indirectly controls, is
controlled by, or is under common control with such other person) of Takeda or
(ii) to an immediate or remote transferee of Takeda who after such transfer is
the Holder of at least 50% of the number of Registrable Securities purchased by
Takeda (appropriately adjusted for subdivisions and combinations of shares of
Common Stock and dividends on Common Stock payable in shares of Common Stock
subsequent to the date of this Agreement); provided, however, that only the
rights

                                       17

<PAGE>

held by Takeda in its capacity as a "Holder" hereunder, but not the priority
registration rights expressly conferred on "Takeda," may be transferred pursuant
to the preceding clause (ii).

            2.11 Notwithstanding any other provision of this Agreement, the
obligations of the Company to effect Registrations on Request or Incidental
Registrations pursuant to any provision of this Article 2 (whether pursuant to
Section 2.1, Section 2.2 or otherwise) shall be subject to the limitation that,
in any event, the Company shall have no obligation to effect a registration of
Registrable Securities or include Registrable Securities in any registration in
an amount in excess of the maximum number of shares of Common Stock of the
Company that could then be sold by Takeda pursuant to Section 8.4(e) of the
Alliance Agreement. In addition, the provisions of this Agreement shall not
operate to allow Takeda or its Affiliates to sell any shares of Common Stock of
the Company more frequently or in a greater amount than such shares could be
sold pursuant to Section 8.4(e) of the Alliance Agreement.

            3. MISCELLANEOUS.

            3.1 GOVERNING LAW. THIS AGREEMENT SHALL BE GOVERNED IN ALL RESPECTS
BY THE LAWS OF THE STATE OF TEXAS WITHOUT REGARD TO THE CONFLICT OF LAWS
PRINCIPLES THEREOF.

            3.2 Successors and Assigns. Except as otherwise provided herein, the
provisions hereof shall inure to the benefit of, and be binding upon, the
successors and assigns of the parties hereto.

            3.3. Amendment. Except as expressly provided herein, this Agreement,
or any provision hereof, may be amended, waived, discharged or terminated upon
the written consent of the Company and the Holders holding at least fifty
percent (50%) of the then outstanding Registrable Securities.

            3.4 Notices. All notices, reports, and audits with respect to this
Agreement shall be made in writing and shall be deemed sufficiently given,
effective upon receipt, when sent by certified mail, return receipt requested,
or when actually delivered, if delivered by hand or by courier, and properly
addressed to the party for whom it is intended as follows:

      If to Takeda:

            General Manager, Division of Americas
            Takeda Pharmaceutical Company Limited
            1-1, Doshomachi 4-chome, Chuo-ku, Osaka, 540-8645, Japan

with a copy to:

            General Manager, Legal Department
            Takeda Pharmaceutical Company Limited
            1-1, Doshomachi 4-chome, Chuo-Ku, Osaka, 540-8645, Japan

                                       18

<PAGE>

If to the Company:

            Chief Executive Officer
            BioNumerik Pharmaceuticals, Inc.
            8122 Datapoint Drive, Suite 1250
            San Antonio, TX 78229

            Each such notice or other communication shall for all purposes of
this Agreement be treated as effective upon receipt, if delivered personally or
by courier.

            3.5 Delays or Omissions. Except as expressly provided herein, no
delay or omission to exercise any right, power or remedy accruing to any party
to this Agreement shall impair any such right, power or remedy of such party nor
shall it be construed to be a waiver of any such breach or default, or an
acquiescence therein, or of or in any similar breach or default thereafter
occurring; nor shall any waiver or any single breach or default be deemed a
waiver of any other breach or default theretofore or thereafter occurring. Any
waiver, permit, consent or approval of any kind or character on the part of any
party of any breach or default under this Agreement, or any waiver on the part
of any party of any provisions or conditions of this Agreement, must be in
writing and shall be effective only to the extent specifically set forth in such
writing. All remedies, either under this Agreement or by law or otherwise
afforded to any party to this Agreement, shall be cumulative and not
alternative.

            3.6 Severability. In the event that any provision of this Agreement
becomes or is declared by a court of competent jurisdiction to be illegal,
unenforceable or void, this Agreement shall continue in full force and effect
without said provision.

            3.7 Titles and Subtitles. The titles and subtitles used in this
Agreement are used for convenience only and are not considered in construing or
interpreting this Agreement.

                                       19

<PAGE>

            IN WITNESS WHEREOF, this Agreement has been executed by the
undersigned parties effective upon the date first set forth above.

                                    BIONUMERIK PHARMACEUTICALS, INC.

                                    By: /s/ FREDERICK H. HAUSHEER
                                        ________________________________________
                                    Name:  FREDERICK H. HAUSHEER
                                    Title: Chairman and Chief Executive Officer

                                    TAKEDA PHARMACEUTICALS COMPANY LIMITED

                                    By:  /s/ SABURO HAMANAKA
                                        ________________________________________
                                    Name:  Saburo Hamanaka
                                    Title: Corporate Officer
                                           General Manager, Division of Americas

                                       20

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