Document:

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                                                                    EXHIBIT 4.10

                            STOCK PURCHASE AGREEMENT

   This Stock Purchase Agreement (this "Agreement") is entered into as of the
10th day of July, 1996, between BIONUMERIK PHARMACEUTICALS, INC., a Texas
corporation, with its office located at 8122 Datapoint Drive, Suite 1250, San
Antonio, Texas 78229, U.S.A. (hereinafter referred to as "BIONUMERIK"); and
GRELAN PHARMACEUTICAL CO., LTD., a Japanese corporation having its place of
business at 4-3 Sakaecho 3-chome, Hamura-City, Tokyo 205, Japan (hereinafter
referred to as "GRELAN").

                                    RECITALS

A. BIONUMERIK and GRELAN are parties to that certain collaboration agreement
dated as of May 28, 1996 (the "Collaboration Agreement").

B. BIONUMERIK and GRELAN have entered into this Agreement to provide for the
purchase by GRELAN of shares of Series D Convertible Preferred Stock, par value
$.01 per share, of BIONUMERIK (the "Series D Preferred Stock") in accordance
with the terms of the Collaboration Agreement.

1.    SUBSCRIPTION FOR SHARES

      1.1 Subject to the terms and conditions hereof, GRELAN hereby subscribes
for and purchases 46,512 shares of Series D Preferred Stock for a total purchase
price of $1,000,000.00 (One Million U.S. Dollars), such consideration to be paid
and such shares to be issued to GRELAN at a closing (the "Closing") to be held
at a time and place agreed upon by GRELAN and BIONUMERIK, which in any event
will be no later than 10 business days after all of the conditions set forth in
Section 4 hereof have been complied with. (The shares of Series D Preferred
Stock sold to GRELAN hereunder are hereinafter referred to as the "Shares").

      1.2 At the Closing, BIONUMERIK shall deliver to GRELAN a stock
certificate, registered in the name of GRELAN, representing the aggregate number
of the Shares referred to in Section 1.1 above. Upon GRELAN's receipt of such
stock certificate, GRELAN shall remit to BIONUMERIK an amount of cash equal to
US $1,000,000.00, by wire transfer to the account of BIONUMERIK.

2.    REPRESENTATIONS AND WARRANTIES OF BIONUMERIK

      BIONUMERIK hereby represents and warrants to GRELAN as follows:

      2.1 Authorized Stock. The authorized capital stock of BIONUMERIK currently
consists of 15,000,000 shares of common stock, par value $.01 per share and
10,000,000 shares of preferred stock, par value $.01 per share. As of the date
of this Agreement, there are 3,379,711 shares of Common Stock, 1,775,646 shares
of Series A Convertible Preferred Stock, 1,136,967 shares of Series B
Convertible Preferred Stock and 672,598 shares of Series C Convertible Preferred
Stock issued and outstanding. BIONUMERIK has reserved up to 3,631,723 shares of
common stock of BIONUMERIK (the "Common Stock") for issuance upon conversion of
the Series A, Series B and Series C Preferred

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Stock and conversion of the Shares, and up to 2,743,856 shares of Common Stock
for issuance to employees, consultants, directors and shareholders pursuant to
outstanding options, warrants and conversion rights, or options to be issued
under BIONUMERIK's 1993 Stock Option Plan or the 1995 Director Stock Option Plan
described in the Financial Statements (defined below).

      Except as described in the Financial Statements, in the Articles of
Incorporation, in the Stockholders Agreement (as defined in Exhibit B hereto) or
on Schedule 2.1 (a) hereto, there are, and immediately following the Closing,
there will be: (1) no outstanding warrants, options, agreements, convertible
securities or other commitments or instruments pursuant to which BIONUMERIK is
or may become obligated to issue, sell, repurchase or redeem any shares of
capital stock or other securities of BIONUMERIK; (2) no preemptive, contractual
or similar rights to purchase or otherwise acquire shares of capital stock of
BIONUMERIK pursuant to any provision of law or Articles of Incorporation or
By-laws of BIONUMERIK or any agreement to which BIONUMERIK is a party; (3) no
cumulative voting rights for any of BIONUMERIK's capital stock; and (4) no
agreements, written or oral, between BIONUMERIK and any holder of its
securities, or, to the best of BIONUMERIK's knowledge and belief, among holders
of its securities, relating to the acquisition, disposition or voting of the
securities of BIONUMERIK.

      To the best of BIONUMERIK's knowledge and belief, except as set forth on
Schedule 2.1(b) hereto, BIONUMERIK owns, has obtained a license to, or otherwise
has sufficient access and rights to, all of the patents, patent rights, patent
applications, registered trademarks and service marks, trademark rights,
trademark applications, trade names, copyrights and licenses that are reasonably
necessary for the conduct of the business of BIONUMERIK as now being conducted
and substantially as proposed to be conducted (hereinafter collectively referred
to as "Intellectual Property"). To the best of BIONUMERIK's knowledge and
belief, the Intellectual Property constitutes valid rights that do not infringe
or conflict with the rights of any third party. There is neither pending nor
threatened, or, to the best of BIONUMERIK's knowledge and belief, any basis for,
any claim or litigation against BIONUMERIK contesting the validity or right to
use any of the Intellectual Property, and BIONUMERIK has not received any notice
of infringement upon or conflict with any asserted right of others nor is there
a basis for such a notice. To the best of BIONUMERIK's knowledge and belief, no
person, corporation or other entity is infringing BIONUMERIK's rights to the
Intellectual Property. Except as set forth on Schedule 2.1 (b) hereto,
BIONUMERIK has no obligation to compensate others for the use of any
Intellectual Property, nor has BIONUMERIK granted any license or other right to
use, in any manner, any of the Intellectual Property, whether or not requiring
the payment of royalties. The foregoing representations contained in this
paragraph are made subject to the exceptions that (i) no guarantee or
representation is or can be made that patents will issue on any existing patent
applications and (ii) certain of the Company's Intellectual Property may be
subject to certain rights that may be asserted or reserved by the U.S.
Government in accordance with government regulations governing research
conducted pursuant to government funding.

      2.2 Organization and Good Standing; Articles of Incorporation and Bylaws.
BIONUMERIK is a corporation duly organized, validly existing and in good
standing under the laws of the State of Texas. BIONUMERIK has the requisite
corporate power and authority to own and operate its properties and assets and
to carry on its business as currently conducted. BIONUMERIK has furnished to
GRELAN true, correct and complete copies of its Articles of Incorporation and
Bylaws, as presently in effect.

      2.3 Corporate Power and Authorization. BIONUMERIK has the corporate power
and authority (a) to execute and deliver this Agreement and the Registration
Rights Agreement, the form of which is attached hereto as Exhibit A (the
"Registration Rights Agreement"), (b) to issue and sell the Shares hereunder,
(c) to issue and deliver the Common Stock of BIONUMERIK issuable upon

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conversion of the Shares and (d) to perform its obligations under the terms of
this Agreement and the Registration Rights Agreement. All corporate action on
the part of BIONUMERIK, its directors and shareholders necessary for the
authorization, execution, delivery and performance by BIONUMERIK of this
Agreement and the Registration Rights Agreement and the authorization, sale,
issuance and delivery of the Shares (and the Common Stock issuable upon
conversion of the Shares) has been taken or will be taken prior to the Closing.
At the Closing, this Agreement and the Registration Rights Agreement will
constitute valid and binding obligations of BIONUMERIK, enforceable in
accordance with their terms, except as the enforceability thereof may be limited
by bankruptcy, insolvency or other laws relating to or affecting creditors'
rights generally and by general equitable principles. At the Closing, the Shares
will be duly authorized and, when issued in compliance with the provisions of
this Agreement, will be validly issued, fully paid and nonassessable, and will
have the rights, preferences, and privileges described on Exhibit B hereto. At
the Closing, the Common Stock issuable upon the conversion of the Shares (the
"Conversion Stock") will have been duly and validly authorized and reserved for
issuance and, when issued in compliance with the provisions of this Agreement,
will be validly issued, fully paid and nonassessable; and the Shares and such
Conversion Stock, when issued and delivered, will be free of any liens or
encumbrances created by BIONUMERIK or, to the best of BIONUMERIK'S knowledge or
belief, any third parties, and will not be subject to preemptive or any other
similar rights, except for those rights that have previously been waived;
provided, however, that the Shares (and the Conversion Stock) will be subject to
certain restrictions on transfer under applicable securities laws and as set
forth herein.

      2.4 Financial Statements. BIONUMERIK has provided GRELAN with audited
financial statements of BIONUMERIK as of and for the year ended March 31, 1996
(the "Financial Statements"). The Financial Statements are complete and correct
in all material respects and have been prepared in accordance with generally
accepted accounting principles applied on a consistent basis throughout the
periods indicated. The Financial Statements fairly present the financial
condition and operating results of BIONUMERIK as of the date and for the periods
indicated.

      2.5 Absence of Certain Developments. Since March 31, 1996, there have been
no changes in the assets, liabilities, condition (financial or otherwise),
operating results, business or prospects of BIONUMERIK from that reflected in
the Financial Statements, except changes in the ordinary course of business that
have not been, individually or in the aggregate, materially adverse to the
assets, properties, condition (financial or otherwise), operating results,
business or prospects of BIONUMERIK.

      2.6 Absence of Undisclosed Liabilities. BIONUMERIK does not have any
liability or obligation, absolute or contingent, that is not reflected in the
Financial Statements, other than obligations and liabilities which taken
individually or in the aggregate would not have a material adverse effect on
BIONUMERIK's assets, liabilities, condition (financial or otherwise), operating
results, business or prospects.

      2.7 Taxes. BIONUMERIK has filed all tax returns and reports required by
law to be filed, and has paid all taxes, assessments and other governmental
charges that are due and payable, except for those matters reasonably being
contested by BIONUMERIK and those matters which, individually and in the
aggregate, would not have a material adverse effect on BIONUMERIK's assets,
liabilities, condition (financial or otherwise), operating results, business or
prospects. The charges, accruals and reserves on the books of BIONUMERIK in
respect of taxes are considered adequate by BIONUMERIK.

      2.8 Compliance with Other Instruments. BIONUMERIK is not in violation or
default of any provision of its Articles of Incorporation or Bylaws, or in
default of any material mortgage,

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indebtedness, indenture, contract, agreement, instrument, judgment or decree to
which BIONUMERIK is a party or by which it is bound. To the best of BIONUMERIK's
knowledge and belief, all parties to any such mortgage, indebtedness, indenture,
contract, agreement or instrument are in material compliance with the terms and
conditions of the same. The execution, delivery and performance by BIONUMERIK of
this Agreement and the Registration Rights Agreement, and the consummation of
the transactions contemplated hereby and thereby, will not result in any
violation of or conflict with any applicable provision of law, statute or rule,
or with BIONUMERIK's Articles of Incorporation or Bylaws, and will not result in
any violation of or conflict with, or constitute a default under, any material
mortgage, indebtedness, indenture, contract, agreement, instrument, judgment or
decree to which BIONUMERIK is a party or by which it or any of its properties or
assets is bound or in the creation of any material mortgage, pledge, lien,
encumbrance or charge upon any of the properties or assets of BIONUMERIK.

      2.9 Litigation, etc. There are no actions, suits, arbitrations, claims,
legal or administrative proceedings or investigations pending or, to
BIONUMERIK's knowledge and belief, threatened against BIONUMERIK or against any
of its officers, directors or principal shareholders in their capacities as
officers, directors or shareholders or which otherwise involve BIONUMERIK's
business or operations.

      2.10 Governmental Consent. No consent, approval or authorization of or
registration, qualification, designation, declaration or filing with any
governmental authority on the part of BIONUMERIK is required in connection with
the valid execution, delivery and performance of this Agreement, the offer, sale
or issuance of the Shares (and the issuance of the Conversion Stock), or the
consummation of any other transaction contemplated hereby, except for customary
filings that may be required to comply with applicable securities laws.

      2.11 Compliance With Law. BIONUMERIK is conducting its business and
operations in material compliance with all governmental rules and regulations
applicable thereto, and is not in violation or default in any material respect
under any statute, law, ordinance, rule, regulation, judgment, order, decree,
concession, grant, franchise, license or other governmental authorization or
approval applicable to it or any of its properties.

      2.12 Offering. Subject to the accuracy of GRELAN's representations in
Section 3 hereof, the offer, sale and issuance of the Shares as contemplated by
this Agreement, and the issuance of the Conversion Stock, will constitute
transactions exempt from the registration requirements of Section 5 of the
Securities Act.

      2.13 Environmental Matters.

            (a) Except as set forth in Schedule 2.13(a) attached hereto, to the
best of BIONUMERIK's knowledge and belief, any use, generation, manufacture,
refinement, treatment, transportation, storage, handling, disposal, transfer,
production, process or release by BIONUMERIK (together defined as "Release") of
any Hazardous Materials (as hereinafter defined) in any manner or by any means
has been in material compliance with any applicable Environmental Laws (as
hereinafter defined). To the best of BIONUMERIK's knowledge and belief,
BIONUMERIK and any prior owner or tenant of the Property (as hereinafter
defined) have not Released any Hazardous Material or other pollutant or effluent
into, on or from the Property in a way that would have a material adverse effect
on BIONUMERIK's assets, liabilities, condition (financial or otherwise),
operating results, business or prospects.

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                  As used herein, the term "Property" shall include, without
limitation, land, buildings and laboratory facilities owned or leased by
BIONUMERIK or as to which BIONUMERIK now has any primary duties,
responsibilities (for clean-up, remedy or otherwise) or liabilities under any
Environmental Laws, or as to which BIONUMERIK has such duties, responsibilities
or liabilities because of past acts or omissions of BIONUMERIK or its
predecessors, or because BIONUMERIK or its predecessors in the past was such an
owner or operator of, or bore some other relationship with, such land, buildings
and/or laboratory facilities, all as more fully described in Schedule 2.13(a)
attached hereto.

                  The term "Hazardous Materials" shall include without
limitation, any flammable explosives, petroleum products, petroleum by-products,
radioactive materials, hazardous wastes, hazardous substances, toxic substances
or similar materials classified as hazardous under Environmental Laws.

                  As used herein, "Environmental Laws" shall mean all applicable
federal, state and local laws, ordinances, rules and regulations that regulate,
fix liability for, or otherwise directly relate to, the production, development,
handling, use (including use in industrial processes, in construction, as
building materials, or otherwise), storage and disposal of hazardous and toxic
wastes and substances, and to the discharge, leakage, presence, migration,
threatened Release or Release (whether by disposal, a discharge into any water
source or system or into the air, or otherwise) of any pollutant or effluent.

            (b) No notice of lien under any Environmental Laws has been filed
against any Property of BIONUMERIK.

            (c) The use of the Property by BIONUMERIK for any future
development, construction and operation of property purchased, leased or
otherwise acquired by BIONUMERIK shall, in all material respects, comply with,
and are (or if such property has not yet been purchased, leased or otherwise
acquired by BIONUMERIK, shall be) lawful, permitted and conforming uses in all
material respects under all applicable building, fire, safety, subdivision,
zoning, sewer, environmental, securities, health, insurance and other laws,
ordinances, rules, regulations and plan approval conditions of any governmental
or public body or authority.

            (d) To the best of BIONUMERIK's knowledge and belief, the Property
does not contain: (i) asbestos in any form; (ii) urea formaldehyde foam
insulation; (iii) transformers or other equipment which contain dielectric fluid
containing levels of polychlorinated biphenyls; (iv) radon, or (v) any other
chemical, material or substance that is not being handled in material compliance
with applicable Environmental Laws.

                  BIONUMERIK has not received any notice that BIONUMERIK is a
party potentially responsible for costs incurred at a cleanup site or corrective
action under any Environmental Laws. BIONUMERIK has not received any requests
for information in connection with any inquiry by any federal, state or local
governmental authority concerning disposal sites or other environmental matters.

            (f) BIONUMERIK has maintained all environmental and operating
documents and records substantially in the manner and for the time periods
required by the Environmental Laws and any other similar and applicable laws,
regulations or orders.

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            (g) To the best of BIONUMERIK's knowledge and belief, no part of the
Property of BIONUMERIK is (i) located within any wetlands area, (ii) subject to
any wetlands regulations, or (iii) included in or is proposed for inclusion in,
or abuts any property included in or proposed for inclusion in, the National
Priority List or any similar state lists.

            (h) GRELAN has had no control over, or authority with respect to,
the waste disposal operations of BIONUMERIK.

            (i) BIONUMERIK understands that the foregoing representations and
warranties shall be deemed material and to have been relied upon by GRELAN.

3.    REPRESENTATIONS AND WARRANTIES OF GRELAN

      GRELAN represents and warrants to BIONUMERIK as follows:

      3.1 Power and Authorization. GRELAN has the full right, power and
authority to enter into this Agreement and the Registration Rights Agreement.
This Agreement and the Registration Rights Agreement constitute valid and
binding obligations of GRELAN, enforceable in accordance with their terms,
except as the enforceability thereof may be limited by bankruptcy, insolvency or
other laws relating to or affecting creditors' rights generally or by general
equitable principles. Any consents, permits, approvals and/or registrations to
be obtained or effected under the laws of Japan in connection with the issuance
of the Shares and the related transactions described herein will have been
obtained or effected prior to the Closing.

      3.2 Experience. GRELAN is a sophisticated investor and is capable of
evaluating the merits and risks of its investment in BIONUMERIK and has the
capacity to protect its own interests.

      3.3 Access to Data. GRELAN has had an opportunity to discuss BIONUMERIK's
business, management, financial affairs and prospects with BIONUMERIK's
management and the opportunity to review BIONUMERIK's facilities. GRELAN has
also had an opportunity to ask questions of officers and management of
BIONUMERIK, which questions were answered to its satisfaction and GRELAN has
obtained all information it deems necessary for its purchase of the Shares.
GRELAN recognizes that its purchase of the Shares is a speculative investment
and involves a high degree of risk and that it may sustain a total loss of its
investment.

      3.4 Purchase for Investment. GRELAN is acquiring the Shares and the
Conversion Stock for investment for its own account, and not with the view to,
or for resale in connection with, any distribution of any part thereof. GRELAN
acknowledges that there has never been any representation, guarantee or warranty
made by BIONUMERIK or any agent or representative of BIONUMERIK, expressly or by
implication (i) as to the percentage or amount of profit, if any, to be realized
as a result of its investment in the Shares or (ii) that the limited or past
performance or experience on the part of BIONUMERIK will in any way indicate the
predictable results of the ownership of the Shares or of the overall financial
performance of BIONUMERIK.

      3.5 Restricted Securities. GRELAN has no need of liquidity in this
investment and acknowledges and understands that it must bear the economic risk
of this investment for an indefinite period of time because the Shares and the
Conversion Stock must be held indefinitely unless subsequently registered under
the Securities Act and other applicable securities laws or unless an exemption
from such registration is available. GRELAN understands that any transfer agent
of BIONUMERIK will be issued stop-transfer instructions with respect to such
shares unless such transfer

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is subsequently registered under the Securities Act and other applicable
securities laws or unless an exemption from such registration is available, and
that each certificate representing the Shares or the Conversion Stock will bear
a restrictive legend to such effect as well as legends reflecting the existence
of this Agreement. GRELAN understands that no public market now exists for any
of the securities issued by BIONUMERIK and that there is no assurance that a
public market will ever exist for BIONUMERIK's securities.

4.    CLOSING CONDITIONS

      Conditions to Obligations of GRELAN. It shall be a condition precedent to
the obligations of GRELAN hereunder to be performed at the Closing that :

            (a) The representations and warranties of BIONUMERIK contained
herein shall be true and correct on and as of the date of the Closing with the
same force and effect as though such representations and warranties had been
made on and as of such date.

            (b) All proceedings to have been taken and all waivers and consents
to be obtained in connection with the transactions contemplated by this
Agreement shall have been taken or obtained, and all documents incidental
thereto shall be reasonably satisfactory to GRELAN and its counsel, and GRELAN
and its counsel shall have received copies (executed or certified, as may be
appropriate) of all documents which GRELAN or its counsel may reasonably have
requested in connection with such transaction, including without limitation
copies (executed or certified, as the case may be) of the following documents:

                  (i) the Articles of Incorporation of BIONUMERIK after being
amended to include substantially the terms and provisions of the Shares
described in Exhibit B to this Agreement; and

                  (ii) the By-laws of BIONUMERIK.

            (c) All legal matters incident to the purchase of the Shares shall
be reasonably satisfactory to GRELAN's counsel.

            (d) A duly executed amendment to BIONUMERIK's Articles of
Incorporation containing substantially the terms and provisions of the Shares
described in Exhibit B shall have been filed with and accepted by the Secretary
of State of Texas, and evidence of the foregoing in form reasonably satisfactory
to GRELAN shall have been delivered to GRELAN.

            (e) BIONUMERIK shall have delivered to GRELAN a certificate or
certificates, dated the Closing Date, of the Secretary or Assistant Secretary of
BIONUMERIK certifying as to (i) the resolutions of BIONUMERIK's Board of
Directors and shareholders authorizing the execution and delivery of this
Agreement, the issuance to GRELAN of the Shares, the execution and delivery of
such other documents and instruments as may be required by this Agreement, and
the consummation of transactions contemplated hereby, and certifying that such
resolutions were duly adopted and have not been rescinded or amended as of such
date, and (ii) the name and the signature of the officers of BIONUMERIK
authorized to sign, as appropriate, this Agreement and the other documents and
certificates to be delivered pursuant to this Agreement by either BIONUMERIK or
any of its officers.

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            (f) BIONUMERIK shall have delivered to GRELAN a certificate or
certificates, dated the Closing Date, of the Chief Executive Officer and the
President of BIONUMERIK certifying as to the representations and warranties made
by BIONUMERIK pursuant to this Agreement.

            (g) BIONUMERIK shall have delivered to GRELAN a certificate or
certificates, dated the Closing Date, of the Chief Financial Officer of
BIONUMERIK certifying that since March 31, 1996, there has been no material
adverse change in the financial condition of BIONUMERIK, and that except to the
extent reflected in the Financial Statements referred to in Section 2.4 and
except for liabilities arising in the ordinary course of business, BIONUMERIK
has no material accrued or contingent liabilities arising out of any transaction
or state of facts existing prior to the date of this Agreement.

            (h) Any consents, permits, approvals, qualifications and/or
registrations required to be obtained or effected under any applicable state
securities or "blue sky" laws of any U.S. jurisdiction shall have been obtained
or effected.

            (i) The Collaboration Agreement shall be in full force and effect.

      4.2 Conditions to Obligations of BIONUMERIK.It shall be a condition
precedent to the obligations of BIONUMERIK hereunder to be performed at the
Closing that:

            (a) The representations and warranties of GRELAN contained herein
shall be true and correct as of the date of such Closing with the same force and
effect as though such representations and warranties had been made on and as of
such date.

            (b) The Collaboration Agreement shall be in full force and effect.

5.    VOTING OF SHARES

During the term of this Agreement and for so long as GRELAN (or any of its
assignees or transferees) is an owner of Shares (or the Conversion Stock),
GRELAN agrees to vote all Shares (including all shares of Conversion Stock)
owned by it (whether such Shares are voted at a meeting of shareholders or by
written consent) in favor of each and every matter proposed by the Board of
Directors of BIONUMERIK, so long as such matter does not negatively and
materially affect the Shares as a class on a per share basis with respect to
liquidation preference, conversion rate, voting rights, dividend rights, or
other material rights in a manner that is disproportionate from a monetary,
voting, or equity ownership standpoint to the relative proportionate effect of
such proposed matter on other classes of BIONUMERIK preferred stock.

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6.    TRANSFER OF SHARES

      6.1 Restrictions on Transfer. GRELAN agrees that it will not sell, assign,
dispose of, or transfer (collectively "Transfer") or pledge or encumber any
Shares (or shares of Conversion Stock) (i) during the term of this Agreement to
a purchaser which markets products which compete, directly or indirectly, with
products of BIONUMERIK or (ii) prior to June 30, 1998, except upon 60 days
notice to BIONUMERIK in the event GRELAN reasonably determines that there has
been a material adverse change in the business or operations of BIONUMERIK,
which adverse change has not been cured or remedied within such 60 day notice
period. Any pledge or encumbrance by GRELAN will provide that any required
transfer or disposal of any shares of stock pursuant to such pledge or
encumbrance will be subject to complying with BIONUMERIK's right of first
refusal contained in Section 6.2 hereof.

      6.2 Right of First Refusal. Subject to the restrictions on Transfers
contained in Section 6.1 above, if GRELAN wishes to Transfer during the term of
this Agreement any or all of the Shares (or shares of Conversion Stock) then
owned by GRELAN, GRELAN shall first give a written notice (the "Transfer
Notice") to BIONUMERIK specifying the number and type of shares GRELAN wishes to
transfer (the "Transfer Shares"), the price per share of the Transfer Share at
which it wishes to transfer, the name and address of the proposed transferee,
and containing an irrevocable offer (open to acceptance for a period of 60 days
after the date such Transfer Notice is received) to sell the Transfer Shares to
BIONUMERIK at the price per share stated in such Transfer Notice, which price
shall be equal to the price per share at which GRELAN proposes to transfer such
shares (the "Transfer Price"). BIONUMERIK (or its designee(s)) shall have the
right to purchase all, but not less than all, of the Transfer Shares, by giving
GRELAN notice of the determination to purchase such shares within 60 days of
BIONUMERIK's receipt of such Transfer Notice. The closing of the purchase by
BIONUMERIK of the Transfer Shares and payment for such shares to GRELAN pursuant
to this Section 6.2 shall take place at such location as GRELAN shall designate
within 30 days after GRELAN's receipt of the determination to purchase such
shares. Payment for such shares shall be made by check or by wire transfer
against duly endorsed certificates representing the Transfer Shares to be
purchased. The Transfer Shares shall be delivered free and clear of all
encumbrances other than those imposed by this Agreement.

      If, at the end of the 60th day after the Transfer Notice is received, a
notice of acceptance of the offer contained in such Transfer Notice has not been
received by GRELAN, or if notice of acceptance covering less than all of the
Transfer Shares has been received by GRELAN, then GRELAN shall have 90 days in
which to transfer any or all of the Transfer Shares at a price not lower than
the Transfer Price and on terms no more favorable to the transferee than those
contained in the Transfer Notice, provided, however, that no Transfer may be
made to any third party unless and until such party delivers to BIONUMERIK a
written agreement, in form and substance reasonably satisfactory to BIONUMERIK,
to be bound by the terms and provisions hereof. If at the end of such 90 day
period, GRELAN has not completed the transfer of all of the Transfer Shares,
GRELAN shall no longer be permitted to Transfer such shares pursuant to this
Section 6.2 without again complying with this Section in its entirety.

      6.3 Permitted Transfers. Notwithstanding the foregoing provisions hereof,
GRELAN may Transfer Shares to an Affiliate of GRELAN (as defined in the
Collaboration Agreement), provided such Affiliate delivers to BIONUMERIK a
written agreement, in form and substance reasonably satisfactory to BIONUMERIK,
to be bound by the terms and provisions hereof.

7.    BIONUMERIK PURCHASE RIGHTS

      7.1 Purchase Rights. BIONUMERIK (or its designee(s)) shall have the right
to purchase all, but not less than all, of the Shares owned by GRELAN (including
all shares of Conversion

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Stock) upon the occurrence of any of the events specified in clauses (a), (b),
or (c) below of this Section 7.1:

      (a) The Collaboration Agreement is terminated.

      (b) GRELAN fails to vote any shares owned by it in accordance with Section
5 hereof, and BIONUMERIK and GRELAN have been unable to agree on a mutually
satisfactory resolution of the relevant matter for a period of 60 days after
such matter has first been proposed to GRELAN, provided, that if BIONUMERIK and
GRELAN are unable to agree within such 60 day period specified above whether or
not such matter is a matter requiring the favorable vote of GRELAN in accordance
with Section 5, then BIONUMERIK may submit the question of whether GRELAN has
voted in accordance with Section 5 to an independent law firm or investment
banking firm (the "Independent Party") that is reasonably satisfactory to GRELAN
and is selected in good faith by BIONUMERIK's Board of Directors. If such
Independent Party within 60 days of its selection concludes that GRELAN has not
voted in accordance with Section 5 or that such Independent Party cannot
definitively determine whether GRELAN has voted in accordance with Section 5
with respect to such proposed matter, then BIONUMERIK (or its designee(s)) shall
have the right to purchase all, but not less than all, of the Shares owned by
GRELAN (including all shares of Conversion Stock) at the fair market value of
the shares to be purchased determined in the same manner provided in Section 7.2
and the closing of such purchase and payment for such shares shall take place
not later than 30 days after the end of the 60 day determination period
applicable to the Independent Party, with the location, method of payment and
delivery of shares to be determined in the same manner provided in Section 7.3.
All fees and expenses of the Independent Party shall be paid by BIONUMERIK.
Nothing in this Section 7.1(b) shall prevent either party from submitting to
arbitration in accordance with Section 9.5 the question of whether or not GRELAN
voted in accordance with Section 5, provided, however, that the submission of
any such matter to arbitration shall not delay or prevent BIONUMERIK's ability
to exercise its purchase rights under this Section 7.1(b) within the time
periods specified herein.

      (c) GRELAN shall become bankrupt or insolvent or any proceeding is
commenced to place its business in the hands of a receiver, assignee or trustee
in bankruptcy, or any proceeding is commenced for company reorganization (kaisha
kosei), arrangement (seiri), composition (wagi), dissolution (kaisan) and
liquidation (seisan), whether voluntarily or otherwise, and such proceedings are
not dismissed within ninety (90) days of the commencement of any such
proceeding.

      7.2 Determination of Purchase Price. If the purchase right is exercised
pursuant to Section 7.1 (a), (b) or (c) above, the purchase price to be paid by
BIONUMERIK to GRELAN shall be equal to the fair market value of the shares to be
purchased, as determined by a qualified independent appraiser, that is
reasonably satisfactory to GRELAN and is selected in good faith by the Board of
Directors of BIONUMERIK, which appraiser has a recognized and established
expertise in evaluating and valuing pharmaceutical and biotechnology companies.
All fees and expenses of such appraiser shall be paid by BIONUMERIK.

      7.3 Closing. Upon the occurrence of any of the events set forth in Section
7.1 (a), (b), or (c) above, BIONUMERIK may exercise its purchase right by giving
written notice to GRELAN within 60 days of the occurrence of such event. The
closing of such purchase by BIONUMERIK and payment for such shares to GRELAN
shall take place within 60 days after receipt by GRELAN of BIONUMERIK's notice
to exercise such purchase right with the closing to occur at such location as
GRELAN shall designate. Payment for such shares shall be made by check or by
wire transfer against duly endorsed certificates representing the shares to be
purchased. The purchased shares shall be delivered free and clear of all
encumbrances other than those imposed by this Agreement.

                                       10
<PAGE>

8.    TERMINATION

   This Agreement shall continue until, and shall terminate automatically upon
the first to occur of any of the following:

   (a) Execution of a written agreement of termination by BIONUMERIK and GRELAN
(or if GRELAN is not the owner of all the Shares, by the owner or owners of at
least two-thirds (2/3) of the shares of Common Stock issued or issuable upon
conversion of the Shares); or

   (b) The dissolution, liquidation or winding up of BIONUMERIK.

9.    MISCELLANEOUS

      9.1 Entire Agreement; Amendment. This Agreement, the Registration Rights
Agreement and the Collaboration Agreement constitute the full and entire
understanding and agreement between the parties with regard to the subject
hereof and thereof. Except as expressly provided herein, neither this Agreement
nor any term hereof may be amended, waived, discharged or terminated other than
by a written agreement of BIONUMERIK and GRELAN (or if GRELAN is not the owner
of all the Shares, by the owner or owners of at least two-thirds (2/3) of the
shares of Common Stock issued or issuable upon conversion of the Shares). In
addition, those obligations under that certain Confidentiality Agreement dated
as of January 23, 1996 between GRELAN and BIONUMERIK shall continue in full
force and effect in accordance with their terms.

      9.2 Successors and Assigns. Except as otherwise provided herein, this
Agreement shall inure to the benefit of, and be binding upon, the successors and
assigns of the parties hereto. This Agreement may only be assigned under the
circumstances permitting assignment of the Collaboration Agreement.

      9.3 Notice/Reports. Any reports, notices or other communications required
or permitted to be given by either party hereto will be given in writing by
personal delivery, courier service or facsimile, or by registered or certified
air mail, postage prepaid, return receipt requested, addressed to the same
address provided for in the Collaboration Agreement or to such other address as
either party may indicate by proper notice to the other in the same manner as
provided herein. All notices are deemed effective on the date of receipt or, if
delivery is not accepted, on the fifth (5th) business day after placement with
the addressee, an overnight courier service or a post office, as applicable.

      Notwithstanding the foregoing, the notice referred to in Sections 6.2 and
7.3 shall be given by personal delivery, courier service, or registered or
certified airmail mentioned above.

      9.4 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 of any single breach or default be deemed a waiver of any other
breach or default therefore or thereafter occurring. Any waiver, permit, consent
or approval of any kind or character of any breach or default under this
Agreement, or any waiver 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.

                                       11
<PAGE>

      9.5 Arbitration. All disputes, controversies or differences which may
arise between the parties, out of or in relation to or in connection with this
Agreement, or the breach thereof, shall be finally settled by arbitration by the
American Arbitration Association in Honolulu, Hawaii, U.S.A., by a panel of
three (3) arbitrators in accordance with the then current American Arbitration
Association International Arbitration Rules, provided that the arbitrators will
first render a preliminary decision setting forth their grounds for decision and
providing at least thirty (30) days for each of the parties to respond. The
parties hereto expressly waive any right to appeal such decision or to challenge
the decision in any court. Judgment thereof may be entered in any court of
competent jurisdiction in the United States or Japan. This clause shall not be
used to prohibit the right of either party to seek injunctive relief in
appropriate circumstances.

      9.6 Severability. Should any provision of this Agreement be held to be
invalid, unenforceable, or against public policy, the remaining provisions
hereof shall not be affected thereby. In such event, the parties hereto shall
negotiate in good faith to modify this Agreement so as to effect the original
intent of the parties as closely as possible with respect to those provisions
which were held to be invalid, unenforceable or against public policy.

      9.7 Construction / Official Language. This Agreement shall be construed in
accordance with the laws of the State of Texas, U.S.A. English shall be the
official language of this Agreement and any related agreement provided for
hereunder and all communications between the parties hereto shall be conducted
in that language.

      9.8 Counterparts. This Agreement may be executed in multiple counterparts,
each of which shall be an original, and all of which together shall constitute
one instrument.

      9.9 Effect of Headings. The section headings used in this Agreement are
used for convenience only and are not to be considered in construing or
interpreting this Agreement.

   IN WITNESS WHEREOF, the parties hereto have executed this Agreement as of the
day and year first written above.

GRELAN PHARMACEUTICAL CO., LTD.           BIONUMERIK PHARMACEUTICALS, INC.

By: /s/ EUGENE SATOSHI TAKAGI             By: /s/ FREDERICK H. HAUSHEER
    ___________________________________       __________________________________
    Eugene Satoshi Takagi                     Frederick H. Hausheer, M.D.
    President & Chief Executive Officer       Chairman & Chief Executive Officer

Date: July 10, 1996                       Date: July 10, 1996

                                       12<PAGE>

                                                                    EXHIBIT 4.11

                            STOCK PURCHASE AGREEMENT

   This Stock Purchase Agreement (this "Agreement") is entered into as of the
22nd day of October, 1999, between BIONUMERIK PHARMACEUTICALS, INC., a Texas
corporation, with its office located at 8122 Datapoint Drive, Suite 1250, San
Antonio, Texas 78229, U.S.A. (hereinafter referred to as "BIONUMERIK"); and
GRELAN PHARMACEUTICAL CO., LTD., a Japanese corporation having its place of
business at 6-6 Nihonbashi Kobunacho, Chuo-ku, Tokyo, 103-0024 Japan
(hereinafter referred to as "GRELAN").

                                    RECITALS

A. BIONUMERIK and GRELAN are parties to that certain collaboration agreement
dated as of May 28, 1996, as amended as of June 8, 1999 (collectively, the
"Collaboration Agreement").

B. BIONUMERIK and GRELAN have entered into this Agreement to provide for the
purchase by GRELAN of shares of Series F Convertible Preferred Stock, par value
$.01 per share, of BIONUMERIK (the "Series F Preferred Stock") in accordance
with the terms of the Collaboration Agreement.

1.    SUBSCRIPTION FOR SHARES

      1.1 Subject to the terms and conditions hereof, GRELAN hereby subscribes
for and purchases 47,619 shares of Series F Preferred Stock for a total purchase
price of U.S. $2,000,000.00 (Two Million U.S. Dollars), such consideration to be
paid and such shares to be issued to GRELAN at a closing (the "Closing") to be
held at a time and place agreed upon by GRELAN and BIONUMERIK, which in any
event will be no later than October 29, 1999, provided that all of the
conditions set forth in Section 4 hereof have been complied with. (The shares of
Series F Preferred Stock sold to GRELAN hereunder are hereinafter referred to as
the "Shares").

      1.2 At the Closing, BIONUMERIK shall deliver to GRELAN a stock
certificate, registered in the name of GRELAN, representing the aggregate number
of the Shares referred to in Section 1.1 above. Upon GRELAN's receipt of such
stock certificate, GRELAN shall remit to BIONUMERIK an amount of cash equal to
U.S. $2,000,000.00, by wire transfer to the account of BIONUMERIK.

2.    REPRESENTATIONS AND WARRANTIES OF BIONUMERIK

      BIONUMERIK hereby represents and warrants to GRELAN as follows:

      2.1 Authorized Stock. The authorized capital stock of BIONUMERIK currently
consists of 15,000,000 shares of common stock, par value $.01 per share and
10,000,000 shares of preferred stock, par value $.01 per share. As of the date
of this Agreement, there are 3,546,494 shares of Common Stock, 1,775,646 shares
of Series A Convertible Preferred Stock, 1,203,571 shares of Series B
Convertible Preferred Stock, 672,598 shares of Series C Convertible Preferred
Stock, 46,512 shares of Series D Convertible Preferred Stock, and 1,113,279
shares of Series E Convertible Preferred Stock, issued and outstanding.
BIONUMERIK has reserved up to 5,147,780 shares of common stock of

<PAGE>

BIONUMERIK (the "Common Stock") for issuance upon conversion of the Series A,
Series B, Series C, Series D, Series E, and Series F Preferred Stock (including
conversion of the Shares), and up to 2,351,183 shares of Common Stock for
issuance to employees, consultants, advisors, directors and shareholders
pursuant to outstanding options, warrants and conversion rights, or options to
be issued under BIONUMERIK's 1993 Stock Option Plan, as amended or the 1995
Director Stock Option Plan, as amended, described in the Financial Statements
(defined below).

      Except as described in the Financial Statements, in the Articles of
Incorporation, in the Stockholders Agreement (as defined in Exhibit B hereto),
in that certain Stock Purchase Agreement, dated as of July 10, 1996, between
Grelan and BioNumerik (the "Grelan Series D Stock Purchase Agreement"), in that
certain Stock Purchase Agreement, dated as of October 22, 1999 between Grelan
and BioNumerik (the "Grelan Series F Stock Purchase Agreement"), or on Schedule
2.1 (a) hereto, there are, and immediately following the Closing, there will be:
(1) no outstanding warrants, options, agreements, convertible securities or
other commitments or instruments pursuant to which BIONUMERIK is or may become
obligated to issue, sell, repurchase or redeem any shares of capital stock or
other securities of BIONUMERIK; (2) no preemptive, contractual or similar rights
to purchase or otherwise acquire shares of capital stock of BIONUMERIK pursuant
to any provision of law or Articles of Incorporation or By-laws of BIONUMERIK or
any agreement to which BIONUMERIK is a party; (3) no cumulative voting rights
for any of BIONUMERIK's capital stock; and (4) no agreements, written or oral,
between BIONUMERIK and any holder of its securities, or, to the best of
BIONUMERIK's knowledge and belief, among holders of its securities, relating to
the acquisition, disposition or voting of the securities of BIONUMERIK.

      To the best of BIONUMERIK's knowledge and belief, except as set forth on
Schedule 2.1(b) hereto, BIONUMERIK owns, has obtained a license to, or otherwise
has sufficient access and rights to, all of the patents, patent rights, patent
applications, registered trademarks and service marks, trademark rights,
trademark applications, trade names, copyrights and licenses that are reasonably
necessary for the conduct of the business of BIONUMERIK as now being conducted
and substantially as proposed to be conducted (hereinafter collectively referred
to as "Intellectual Property"). Except as set forth on Schedule 2.1(b), to the
best of BIONUMERIK's knowledge and belief, the Intellectual Property constitutes
valid rights that do not infringe or conflict with the rights of any third
party. Except as set forth on Schedule 2.1(b), there is neither pending nor
threatened, or, to the best of BIONUMERIK's knowledge and belief, any basis for,
any claim or litigation against BIONUMERIK contesting the validity or right to
use any of the Intellectual Property, and BIONUMERIK has not received any notice
of infringement upon or conflict with any asserted right of others nor is there
a basis for such a notice. Except as set forth on Schedule 2.1(b), to the best
of BIONUMERIK's knowledge and belief, no person, corporation or other entity is
infringing BIONUMERIK's rights to the Intellectual Property. Except as set forth
on Schedule 2.1 (b) hereto, BIONUMERIK has no obligation to compensate others
for the use of any Intellectual Property, nor has BIONUMERIK granted any license
or other right to use, in any manner, any of the Intellectual Property, whether
or not requiring the payment of royalties. The foregoing representations
contained in this paragraph are made subject to the exceptions that (i) no
guarantee or representation is or can be made that patents will issue on any
existing patent applications and (ii) certain of the Company's Intellectual
Property may be subject to certain rights that may be asserted or reserved by
the U.S. Government in accordance with government regulations governing research
conducted pursuant to government funding.

      2.2 Organization and Good Standing; Articles of Incorporation and Bylaws.
BIONUMERIK is a corporation duly organized, validly existing and in good
standing under the laws of the State of Texas. BIONUMERIK has the requisite
corporate power and authority to own and operate its properties and assets and
to carry on its business as currently conducted. BIONUMERIK has furnished to

                                       2
<PAGE>

GRELAN true, correct and complete copies of its Articles of Incorporation and
Bylaws, as presently in effect.

      2.3 Corporate Power and Authorization. BIONUMERIK has the corporate power
and authority (a) to execute and deliver this Agreement and the Registration
Rights Agreement, the form of which is attached hereto as Exhibit A (the
"Registration Rights Agreement"), (b) to issue and sell the Shares hereunder,
(c) to issue and deliver the Common Stock of BIONUMERIK issuable upon conversion
of the Shares and (d) to perform its obligations under the terms of this
Agreement and the Registration Rights Agreement. All corporate action on the
part of BIONUMERIK, its directors and shareholders necessary for the
authorization, execution, delivery and performance by BIONUMERIK of this
Agreement and the Registration Rights Agreement and the authorization, sale,
issuance and delivery of the Shares (and the Common Stock issuable upon
conversion of the Shares) has been taken or will be taken prior to the Closing.
At the Closing, this Agreement and the Registration Rights Agreement will
constitute valid and binding obligations of BIONUMERIK, enforceable in
accordance with their terms, except as the enforceability thereof may be limited
by bankruptcy, insolvency or other laws relating to or affecting creditors'
rights generally and by general equitable principles. At the Closing, the Shares
will be duly authorized and, when issued in compliance with the provisions of
this Agreement, will be validly issued, fully paid and nonassessable, and will
have the rights, preferences, and privileges described on Exhibit B hereto. At
the Closing, the Common Stock issuable upon the conversion of the Shares (the
"Conversion Stock") will have been duly and validly authorized and reserved for
issuance and, when issued in compliance with the provisions of this Agreement,
will be validly issued, fully paid and nonassessable; and the Shares and such
Conversion Stock, when issued and delivered, will be free of any liens or
encumbrances created by BIONUMERIK or, to the best of BIONUMERIK'S knowledge or
belief, any third parties, and will not be subject to preemptive or any other
similar rights, except for those rights that have previously been waived;
provided, however, that the Shares (and the Conversion Stock) will be subject to
certain restrictions on transfer under applicable securities laws and as set
forth herein.

      2.4 Financial Statements. BIONUMERIK has provided GRELAN with audited
financial statements of BIONUMERIK as of and for the year ended March 31, 1999
and interim financial statements for the period ending September 30, 1999
(collectively, the "Financial Statements"). The Financial Statements are
complete and correct in all material respects and have been prepared in
accordance with generally accepted accounting principles applied on a consistent
basis throughout the periods indicated. The Financial Statements fairly present
the financial condition and operating results of BIONUMERIK as of the date and
for the periods indicated.

      2.5 Absence of Certain Developments. Since September 30, 1999 and except
as described in the Schedules hereto, there have been no changes in the assets,
liabilities, condition (financial or otherwise), operating results, business or
prospects of BIONUMERIK from that reflected in the Financial Statements, except
changes in the ordinary course of business that have not been, individually or
in the aggregate, materially adverse to the assets, properties, condition
(financial or otherwise), operating results, business or prospects of
BIONUMERIK.

      2.6 Absence of Undisclosed Liabilities. BIONUMERIK does not have any
liability or obligation, absolute or contingent, that is not reflected in the
Financial Statements, other than obligations and liabilities which taken
individually or in the aggregate would not have a material adverse effect on
BIONUMERIK's assets, liabilities, condition (financial or otherwise), operating
results, business or prospects.

                                       3
<PAGE>

      2.7 Taxes. BIONUMERIK has filed all tax returns and reports required by
law to be filed, and has paid all taxes, assessments and other governmental
charges that are due and payable, except for those matters reasonably being
contested by BIONUMERIK and those matters which, individually and in the
aggregate, would not have a material adverse effect on BIONUMERIK's assets,
liabilities, condition (financial or otherwise), operating results, business or
prospects. The charges, accruals and reserves on the books of BIONUMERIK in
respect of taxes are considered adequate by BIONUMERIK.

      2.8 Compliance with Other Instruments. BIONUMERIK is not in violation or
default of any provision of its Articles of Incorporation or Bylaws, or in
default of any material mortgage, indebtedness, indenture, contract, agreement,
instrument, judgment or decree to which BIONUMERIK is a party or by which it is
bound. To the best of BIONUMERIK's knowledge and belief, all parties to any such
mortgage, indebtedness, indenture, contract, agreement or instrument are in
material compliance with the terms and conditions of the same, except for any
non-compliance which, individually and in the aggregate, is not expected to have
a material adverse effect on BioNumerik's assets, liabilities, condition
(financial or otherwise), operating results, business or prospects. The
execution, delivery and performance by BIONUMERIK of this Agreement and the
Registration Rights Agreement, and the consummation of the transactions
contemplated hereby and thereby, will not result in any violation of or conflict
with any applicable provision of law, statute or rule, or with BIONUMERIK's
Articles of Incorporation or Bylaws, and will not result in any violation of or
conflict with, or constitute a default under, any material mortgage,
indebtedness, indenture, contract, agreement, instrument, judgment or decree to
which BIONUMERIK is a party or by which it or any of its properties or assets is
bound or in the creation of any material mortgage, pledge, lien, encumbrance or
charge upon any of the properties or assets of BIONUMERIK.

      2.9 Litigation, etc. There are no actions, suits, arbitrations, claims,
legal or administrative proceedings or investigations pending or, to
BIONUMERIK's knowledge and belief, threatened against BIONUMERIK or against any
of its officers, directors or principal shareholders in their capacities as
officers, directors or shareholders or which otherwise involve BIONUMERIK's
business or operations.

      2.10 Governmental Consent. No consent, approval or authorization of or
registration, qualification, designation, declaration or filing with any
governmental authority on the part of BIONUMERIK is required in connection with
the valid execution, delivery and performance of this Agreement, the offer, sale
or issuance of the Shares (and the issuance of the Conversion Stock), or the
consummation of any other transaction contemplated hereby, except for customary
filings that may be required to comply with applicable securities laws.

      2.11 Compliance With Law. BIONUMERIK is conducting its business and
operations in material compliance with all governmental rules and regulations
applicable thereto, and is not in violation or default in any material respect
under any statute, law, ordinance, rule, regulation, judgment, order, decree,
concession, grant, franchise, license or other governmental authorization or
approval applicable to it or any of its properties.

      2.12 Offering. Subject to the accuracy of GRELAN's representations in
Section 3 hereof, the offer, sale and issuance of the Shares as contemplated by
this Agreement, and the issuance of the Conversion Stock, will constitute
transactions exempt from the registration requirements of Section 5 of the
Securities Act.

                                       4
<PAGE>

      2.13 Environmental Matters.

            (a) Except as set forth in Schedule 2.13(a) attached hereto, to the
best of BIONUMERIK's knowledge and belief, any use, generation, manufacture,
refinement, treatment, transportation, storage, handling, disposal, transfer,
production, process or release by BIONUMERIK (together defined as "Release") of
any Hazardous Materials (as hereinafter defined) in any manner or by any means
has been in material compliance with any applicable Environmental Laws (as
hereinafter defined). To the best of BIONUMERIK's knowledge and belief,
BIONUMERIK and any prior owner or tenant of the Property (as hereinafter
defined) have not Released any Hazardous Material or other pollutant or effluent
into, on or from the Property in a way that would have a material adverse effect
on BIONUMERIK's assets, liabilities, condition (financial or otherwise),
operating results, business or prospects.

                  As used herein, the term "Property" shall include, without
limitation, land, buildings and laboratory facilities owned or leased by
BIONUMERIK or as to which BIONUMERIK now has any primary duties,
responsibilities (for clean-up, remedy or otherwise) or liabilities under any
Environmental Laws, or as to which BIONUMERIK has such duties, responsibilities
or liabilities because of past acts or omissions of BIONUMERIK or its
predecessors, or because BIONUMERIK or its predecessors in the past was such an
owner or operator of, or bore some other relationship with, such land, buildings
and/or laboratory facilities, all as more fully described in Schedule 2.13(a)
attached hereto.

                  The term "Hazardous Materials" shall include without
limitation, any flammable explosives, petroleum products, petroleum by-products,
radioactive materials, hazardous wastes, hazardous substances, toxic substances
or similar materials classified as hazardous under Environmental Laws.

                  As used herein, "Environmental Laws" shall mean all applicable
federal, state and local laws, ordinances, rules and regulations that regulate,
fix liability for, or otherwise directly relate to, the production, development,
handling, use (including use in industrial processes, in construction, as
building materials, or otherwise), storage and disposal of hazardous and toxic
wastes and substances, and to the discharge, leakage, presence, migration,
threatened Release or Release (whether by disposal, a discharge into any water
source or system or into the air, or otherwise) of any pollutant or effluent.

            (b) No notice of lien under any Environmental Laws has been filed
against any Property of BIONUMERIK.

            (c) The use of the Property by BIONUMERIK and any future
development, construction and operation of property purchased, leased or
otherwise acquired by BIONUMERIK shall, in all material respects, comply with,
and are (or if such property has not yet been purchased, leased or otherwise
acquired by BIONUMERIK, shall be) lawful, permitted and conforming uses in all
material respects under all applicable building, fire, safety, subdivision,
zoning, sewer, environmental, securities, health, insurance and other laws,
ordinances, rules, regulations and plan approval conditions of any governmental
or public body or authority.

                                       5
<PAGE>

            (d) To the best of BIONUMERIK's knowledge and belief, the Property
does not contain: (i) asbestos in any form; (ii) urea formaldehyde foam
insulation; (iii) transformers or other equipment which contain dielectric fluid
containing levels of polychlorinated biphenyls; (iv) radon, or (v) any other
chemical, material or substance that is not being handled in material compliance
with applicable Environmental Laws.

            (e) BIONUMERIK has not received any notice that BIONUMERIK is a
party potentially responsible for costs incurred at a cleanup site or corrective
action under any Environmental Laws. BIONUMERIK has not received any requests
for information in connection with any inquiry by any federal, state or local
governmental authority concerning disposal sites or other environmental matters.

            (f) BIONUMERIK has maintained all environmental and operating
documents and records substantially in the manner and for the time periods
required by the Environmental Laws and any other similar and applicable laws,
regulations or orders.

            (g) To the best of BIONUMERIK's knowledge and belief, no part of the
Property of BIONUMERIK is (i) located within any wetlands area, (ii) subject to
any wetlands regulations, or (iii) included in or is proposed for inclusion in,
or abuts any property included in or proposed for inclusion in, the National
Priority List or any similar state lists.

            (h) GRELAN has had no control over, or authority with respect to,
the waste disposal operations of BIONUMERIK.

            (i) BIONUMERIK understands that the foregoing representations and
warranties shall be deemed material and to have been relied upon by GRELAN.

3.    REPRESENTATIONS AND WARRANTIES OF GRELAN

      GRELAN represents and warrants to BIONUMERIK as follows:

      3.1 Power and Authorization. GRELAN has the full right, power and
authority to enter into this Agreement and the Registration Rights Agreement.
This Agreement and the Registration Rights Agreement constitute valid and
binding obligations of GRELAN, enforceable in accordance with their terms,
except as the enforceability thereof may be limited by bankruptcy, insolvency or
other laws relating to or affecting creditors' rights generally or by general
equitable principles. Any consents, permits, approvals and/or registrations to
be obtained or effected under the laws of Japan in connection with the issuance
of the Shares and the related transactions described herein will have been
obtained or effected prior to the Closing, provided that a report on the stock
purchase will be filed with the Bank of Japan within the required time period
following the Closing.

      3.2 Experience. GRELAN is capable of evaluating the merits and risks of
its investment in BIONUMERIK and has the capacity to protect its own interests.

      3.3 Access to Data. GRELAN has had an opportunity to discuss BIONUMERIK's
business, management, financial affairs and prospects with BIONUMERIK's
management and the opportunity to review BIONUMERIK's facilities. GRELAN has
also had an opportunity to ask questions of officers and management of
BIONUMERIK, which questions were answered to its satisfaction and GRELAN has
obtained all information it deems necessary for its purchase of the Shares.
GRELAN

                                       6
<PAGE>

recognizes that its purchase of the Shares is a speculative investment and
involves a high degree of risk and that it may sustain a total loss of its
investment.

      3.4 Purchase for Investment. GRELAN is acquiring the Shares and the
Conversion Stock for investment for its own account, and not with the view to,
or for resale in connection with, any distribution of any part thereof. GRELAN
acknowledges that there has never been any representation, guarantee or warranty
made by BIONUMERIK or any agent or representative of BIONUMERIK, expressly or by
implication (i) as to the percentage or amount of profit, if any, to be realized
as a result of its investment in the Shares or (ii) that the limited or past
performance or experience on the part of BIONUMERIK will in any way indicate the
predictable results of the ownership of the Shares or of the overall financial
performance of BIONUMERIK.

      3.5 Restricted Securities. GRELAN has no need of liquidity in this
investment and acknowledges and understands that it must bear the economic risk
of this investment for an indefinite period of time because the Shares and the
Conversion Stock must be held indefinitely unless subsequently registered under
the Securities Act and other applicable securities laws or unless an exemption
from such registration is available. GRELAN understands that any transfer agent
of BIONUMERIK will be issued stop-transfer instructions with respect to such
shares unless such transfer is subsequently registered under the Securities Act
and other applicable securities laws or unless an exemption from such
registration is available, and that each certificate representing the Shares or
the Conversion Stock will bear a restrictive legend to such effect as well as
legends reflecting the existence of this Agreement. GRELAN understands that no
public market now exists for any of the securities issued by BIONUMERIK and that
there is no assurance that a public market will ever exist for BIONUMERIK's
securities.

4.    CLOSING CONDITIONS

      4.1 Conditions to Obligations of GRELAN. It shall be a condition precedent
to the obligations of GRELAN hereunder to be performed at the Closing that:

            (a) The representations and warranties of BIONUMERIK contained
herein shall be true and correct on and as of the date of the Closing with the
same force and effect as though such representations and warranties had been
made on and as of such date, provided that BIONUMERIK may update the disclosure
contained in such representations and warranties from time to time so long as
the events and information described in such updated disclosure, whether
individually or in the aggregate, would not reasonably be expected to have a
material adverse effect on the purchase and sale of the Shares or on
BIONUMERIK's assets, liabilities, condition (financial or otherwise), operating
results, business, or prospects.

            (b) All proceedings to have been taken and all waivers and consents
to be obtained in connection with the transactions contemplated by this
Agreement shall have been taken or obtained, and all documents incidental
thereto shall be reasonably satisfactory to GRELAN and its counsel, and GRELAN
and its counsel shall have received copies (executed or certified, as may be
appropriate) of all documents which GRELAN or its counsel may reasonably have
requested in connection with such transaction, including without limitation
copies (executed or certified, as the case may be) of the following documents:

                                       7
<PAGE>

                  (i) the Articles of Incorporation of BIONUMERIK after being
amended to include substantially the terms and provisions of the Series F
Preferred Stock (including the Shares) described in Exhibit B to this Agreement;
and

                  (ii) the By-laws of BIONUMERIK.

            (c) All legal matters incident to the purchase of the Shares shall
be reasonably satisfactory to GRELAN's counsel.

            (d) A duly executed amendment to BIONUMERIK's Articles of
Incorporation containing substantially the terms and provisions of the Series F
Preferred Stock (including the Shares) described in Exhibit B shall have been
filed with and accepted by the Secretary of State of Texas, and evidence of the
foregoing in form reasonably satisfactory to GRELAN shall have been delivered to
GRELAN.

            (e) BIONUMERIK shall have delivered to GRELAN a certificate or
certificates, dated the Closing Date, of the Secretary or Assistant Secretary of
BIONUMERIK certifying as to (i) the resolutions or minutes of meetings of
BIONUMERIK's Board of Directors and shareholders authorizing, as applicable, the
execution and delivery of this Agreement, the issuance to GRELAN of the Shares,
the execution and delivery of such other documents and instruments as may be
required by this Agreement, and the consummation of transactions contemplated
hereby, and certifying that such resolutions were duly adopted and have not been
rescinded or amended as of such date, and (ii) the name and the signature of the
officers of BIONUMERIK authorized to sign, as appropriate, this Agreement and
the other documents and certificates to be delivered pursuant to this Agreement
by either BIONUMERIK or any of its officers.

            (f) BIONUMERIK shall have delivered to GRELAN a certificate or
certificates, dated the Closing Date, of the Chief Executive Officer and the
Vice President, Administration of BIONUMERIK certifying as to the
representations and warranties made by BIONUMERIK pursuant to this Agreement.

            (g) BIONUMERIK shall have delivered to GRELAN a certificate or
certificates, dated the Closing Date, of the Chief Financial Officer of
BIONUMERIK certifying that since the date of the most recent Financial
Statements, there has been no material adverse change in the financial condition
of BIONUMERIK, and that except to the extent reflected in the Financial
Statements referred to in Section 2.4 and except for liabilities arising in the
ordinary course of business, BIONUMERIK has no material accrued or contingent
liabilities arising out of any transaction or state of facts existing prior to
the date of this Agreement.

            (h) Any consents, permits, approvals, qualifications and/or
registrations required to be obtained or effected under any applicable state
securities or "blue sky" laws of any U.S. jurisdiction shall have been obtained
or effected.

            (i) The Collaboration Agreement shall be in full force and effect.

      4.2 Conditions to Obligations of BIONUMERIK.It shall be a condition
precedent to the obligations of BIONUMERIK hereunder to be performed at the
Closing that:

            (a) The representations and warranties of GRELAN contained herein
shall be true and correct on and as of the date of the Closing with the same
force and effect as though such

                                       8
<PAGE>

representations and warranties had been made on and as of such date, provided
that GRELAN may update the disclosure contained in such representations and
warranties from time to time so long as the events and information described in
such updated disclosure, whether individually or in the aggregate, would not
reasonably be expected to have a material adverse effect on the purchase and
sale of the Shares or on GRELAN's assets, liabilities, condition (financial or
otherwise), operating results, business, or prospects.

            (b) The Collaboration Agreement shall be in full force and effect.

5.    VOTING OF SHARES

During the term of this Agreement and for so long as GRELAN (or any of its
assignees or transferees) is an owner of Shares (or the Conversion Stock),
GRELAN agrees to vote all Shares (including all shares of Conversion Stock)
owned by it (whether such Shares are voted at a meeting of shareholders or by
written consent) in favor of each and every matter proposed by the Board of
Directors of BIONUMERIK, so long as such matter does not negatively and
materially affect the Shares as a class on a per share basis with respect to
liquidation preference, conversion rate, voting rights, dividend rights, or
other material rights in a manner that is disproportionate from a monetary,
voting, or equity ownership standpoint to the relative proportionate effect of
such proposed matter on other classes of BIONUMERIK preferred stock.

6.    TRANSFER OF SHARES

      6.1 Restrictions on Transfer. GRELAN agrees that it will not sell, assign,
dispose of, or transfer (collectively "Transfer") or pledge or encumber any
Shares (or shares of Conversion Stock) (i) during the term of this Agreement to
a purchaser which markets products which compete, directly or indirectly, with
products of BIONUMERIK or (ii) prior to June 30, 2001, except upon 60 days
notice to BIONUMERIK in the event GRELAN reasonably determines that there has
been a material adverse change in the business or operations of BIONUMERIK,
which adverse change has not been cured or remedied within such 60 day notice
period. Any pledge or encumbrance by GRELAN will provide that any required
transfer or disposal of any shares of stock pursuant to such pledge or
encumbrance will be subject to complying with BIONUMERIK's right of first
refusal contained in Section 6.2 hereof.

      6.2 Right of First Refusal. Subject to the restrictions on Transfers
contained in Section 6.1 above, if GRELAN wishes to Transfer during the term of
this Agreement any or all of the Shares (or shares of Conversion Stock) then
owned by GRELAN, GRELAN shall first give a written notice (the "Transfer
Notice") to BIONUMERIK specifying the number and type of shares GRELAN wishes to
transfer (the "Transfer Shares"), the price per share of the Transfer Share at
which it wishes to transfer, the name and address of the proposed transferee,
and containing an irrevocable offer (open to acceptance for a period of 60 days
after the date such Transfer Notice is received) to sell the Transfer Shares to
BIONUMERIK at the price per share stated in such Transfer Notice, which price
shall be equal to the price per share at which GRELAN proposes to transfer such
shares (the "Transfer Price"). BIONUMERIK (or its designee(s)) shall have the
right to purchase all, but not less than all, of the Transfer Shares, by giving
GRELAN notice of the determination to purchase such shares within 60 days of
BIONUMERIK's receipt of such Transfer Notice. The closing of the purchase by
BIONUMERIK of the Transfer Shares and payment for such shares to GRELAN pursuant
to this Section 6.2 shall take place at such location as GRELAN shall designate
within 30 days after GRELAN's receipt of the determination to purchase such
shares. Payment for such shares shall be made by check or by wire

                                       9
<PAGE>

transfer against duly endorsed certificates representing the Transfer Shares to
be purchased. The Transfer Shares shall be delivered free and clear of all
encumbrances other than those imposed by this Agreement.

      If, at the end of the 60th day after the Transfer Notice is received, a
notice of acceptance of the offer contained in such Transfer Notice has not been
received by GRELAN, or if notice of acceptance covering less than all of the
Transfer Shares has been received by GRELAN, then GRELAN shall have 90 days in
which to transfer any or all of the Transfer Shares at a price not lower than
the Transfer Price and on terms no more favorable to the transferee than those
contained in the Transfer Notice, provided, however, that no Transfer may be
made to any third party unless and until such party delivers to BIONUMERIK a
written agreement, in form and substance reasonably satisfactory to BIONUMERIK,
to be bound by the terms and provisions hereof. If at the end of such 90 day
period, GRELAN has not completed the transfer of all of the Transfer Shares,
GRELAN shall no longer be permitted to Transfer such shares pursuant to this
Section 6.2 without again complying with this Section in its entirety.

      6.3 Permitted Transfers. Notwithstanding the foregoing provisions hereof,
GRELAN may Transfer Shares to an Affiliate of GRELAN (as defined in the
Collaboration Agreement), provided such Affiliate delivers to BIONUMERIK a
written agreement, in form and substance reasonably satisfactory to BIONUMERIK,
to be bound by the terms and provisions hereof.

7.    BIONUMERIK PURCHASE RIGHTS

      7.1 Purchase Rights. BIONUMERIK (or its designee(s)) shall have the right
to purchase all, but not less than all, of the Shares owned by GRELAN (including
all shares of Conversion Stock) upon the occurrence of any of the events
specified in clauses (a), (b), or (c) below of this Section 7.1:

      (a) The Collaboration Agreement is terminated.

      (b) GRELAN fails to vote any shares owned by it in accordance with Section
   5 hereof, and BIONUMERIK and GRELAN have been unable to agree on a mutually
   satisfactory resolution of the relevant matter for a period of 60 days after
   such matter has first been proposed to GRELAN, provided, that if BIONUMERIK
   and GRELAN are unable to agree within such 60 day period specified above
   whether or not such matter is a matter requiring the favorable vote of GRELAN
   in accordance with Section 5, then BIONUMERIK may submit the question of
   whether GRELAN has voted in accordance with Section 5 to an independent law
   firm or investment banking firm (the "Independent Party") that is reasonably
   satisfactory to GRELAN and is selected in good faith by BIONUMERIK's Board of
   Directors. If such Independent Party within 60 days of its selection
   concludes that GRELAN has not voted in accordance with Section 5 or that such
   Independent Party cannot definitively determine whether GRELAN has voted in
   accordance with Section 5 with respect to such proposed matter, then
   BIONUMERIK (or its designee(s)) shall have the right to purchase all, but not
   less than all, of the Shares owned by GRELAN (including all shares of
   Conversion Stock) at the fair market value of the shares to be purchased
   determined in the same manner provided in Section 7.2 and the closing of such
   purchase and payment for such shares shall take place not later than 30 days
   after the end of the 60 day determination period applicable to the
   Independent Party, with the location, method of payment and delivery of
   shares to be determined in the same manner provided in Section 7.3. All fees
   and expenses of the Independent Party shall be paid by BIONUMERIK. Nothing in
   this Section 7.1(b) shall prevent either party from submitting to arbitration
   in accordance with

                                       10
<PAGE>

   Section 9.5 the question of whether or not GRELAN voted in accordance with
   Section 5, provided, however, that the submission of any such matter to
   arbitration shall not delay or prevent BIONUMERIK's ability to exercise its
   purchase rights under this Section 7.1(b) within the time periods specified
   herein.

      (c) GRELAN shall become bankrupt or insolvent or any proceeding is
   commenced to place its business in the hands of a receiver, assignee or
   trustee in bankruptcy, or any proceeding is commenced for company
   reorganization (kaisha kosei), arrangement (seiri), composition (wagi),
   dissolution (kaisan) and liquidation (seisan), whether voluntarily or
   otherwise, and such proceedings are not dismissed within ninety (90) days of
   the commencement of any such proceeding.

      The exercise by BIONUMERIK of its purchase rights under Section 7.1 shall
not limit any other remedies to which BIONUMERIK may be entitled in connection
with the occurrence of any of the events specified in clauses (a), (b), or (c)
above of this Section 7.1.

      7.2 Determination of Purchase Price. If the purchase right is exercised
pursuant to Section 7.1 (a), (b) or (c) above, the purchase price to be paid by
BIONUMERIK to GRELAN shall be equal to the fair market value of the shares to be
purchased, as determined by a qualified independent appraiser, that is
reasonably satisfactory to GRELAN and is selected in good faith by the Board of
Directors of BIONUMERIK, which appraiser has a recognized and established
expertise in evaluating and valuing pharmaceutical and biotechnology companies.
All fees and expenses of such appraiser shall be paid by BIONUMERIK.

      7.3 Closing. Upon the occurrence of any of the events set forth in Section
7.1 (a), (b), or (c) above, BIONUMERIK may exercise its purchase right by giving
written notice to GRELAN within 60 days of the occurrence of such event. The
closing of such purchase by BIONUMERIK and payment for such shares to GRELAN
shall take place within 60 days after receipt by GRELAN of BIONUMERIK's notice
to exercise such purchase right with the closing to occur at such location as
GRELAN shall designate. Payment for such shares shall be made by check or by
wire transfer against duly endorsed certificates representing the shares to be
purchased. The purchased shares shall be delivered free and clear of all
encumbrances other than those imposed by this Agreement.

8.    TERMINATION

   This Agreement shall continue until, and shall terminate automatically upon
the first to occur of any of the following:

   (a) Execution of a written agreement of termination by BIONUMERIK and GRELAN
(or if GRELAN is not the owner of all the Shares, by the owner or owners of at
least two-thirds (2/3) of the shares of Common Stock issued or issuable upon
conversion of the Shares); or

   (b) The dissolution, liquidation or winding up of BIONUMERIK.

                                       11
<PAGE>

9.    MISCELLANEOUS

      9.1 Entire Agreement; Amendment. This Agreement, the Registration Rights
Agreement and the Collaboration Agreement constitute the full and entire
understanding and agreement between the parties with regard to the subject
hereof and thereof. Except as expressly provided herein, neither this Agreement
nor any term hereof may be amended, waived, discharged or terminated other than
by a written agreement of BIONUMERIK and GRELAN (or if GRELAN is not the owner
of all the Shares, by the owner or owners of at least two-thirds (2/3) of the
shares of Common Stock issued or issuable upon conversion of the Shares). In
addition, those obligations under that certain Confidentiality Agreement dated
as of January 23, 1996 between GRELAN and BIONUMERIK shall continue in full
force and effect in accordance with their terms.

      9.2 Successors and Assigns. Except as otherwise provided herein, this
Agreement shall inure to the benefit of, and be binding upon, the successors and
assigns of the parties hereto. This Agreement may only be assigned under the
circumstances permitting assignment of the Collaboration Agreement.

      9.3 Notice/Reports. Any reports, notices or other communications required
or permitted to be given by either party hereto will be given in writing by
personal delivery, courier service or facsimile, or by registered or certified
air mail, postage prepaid, return receipt requested, addressed to the same
address provided for in the Collaboration Agreement or to such other address as
either party may indicate by proper notice to the other in the same manner as
provided herein. All notices are deemed effective on the date of receipt or, if
delivery is not accepted, on the fifth (5th) business day after placement with
the addressee, an overnight courier service or a post office, as applicable.

      Notwithstanding the foregoing, the notice referred to in Sections 6.2 and
7.3 shall be given by personal delivery, courier service, or registered or
certified airmail mentioned above.

      9.4 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 of any single breach or default be deemed a waiver of any other
breach or default therefore or thereafter occurring. Any waiver, permit, consent
or approval of any kind or character of any breach or default under this
Agreement, or any waiver 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.

      9.5 Arbitration. All disputes, controversies or differences which may
arise between the parties, out of or in relation to or in connection with this
Agreement, or the breach thereof, shall be finally settled by arbitration by the
American Arbitration Association in Honolulu, Hawaii, U.S.A., by a panel of
three (3) arbitrators in accordance with the then current American Arbitration
Association International Arbitration Rules, provided that the arbitrators will
first render a preliminary decision setting forth their grounds for decision and
providing at least thirty (30) days for each of the parties to respond. The
parties hereto expressly waive any right to appeal such decision or to challenge
the decision in any court. Judgment thereof may be entered in any court of
competent jurisdiction in the United States or Japan. This clause shall not be
used to prohibit the right of either party to seek injunctive relief in
appropriate circumstances.

                                       12
<PAGE>

      9.6 Severability. Should any provision of this Agreement be held to be
invalid, unenforceable, or against public policy, the remaining provisions
hereof shall not be affected thereby. In such event, the parties hereto shall
negotiate in good faith to modify this Agreement so as to effect the original
intent of the parties as closely as possible with respect to those provisions
which were held to be invalid, unenforceable or against public policy.

      9.7 Construction / Official Language. This Agreement shall be construed in
accordance with the laws of the State of Texas, U.S.A. English shall be the
official language of this Agreement and any related agreement provided for
hereunder and all communications between the parties hereto shall be conducted
in that language.

      9.8 Counterparts. This Agreement may be executed in multiple counterparts,
each of which shall be an original, and all of which together shall constitute
one instrument.

      9.9 Effect of Headings. The section headings used in this Agreement are
used for convenience only and are not to be considered in construing or
interpreting this Agreement.

   IN WITNESS WHEREOF, the parties hereto have executed this Agreement as of the
day and year first written above.

GRELAN PHARMACEUTICAL CO., LTD.             BIONUMERIK PHARMACEUTICALS, INC.

By: /s/ HASHIME KANAZAWA                    By: /s/ FREDERICK H. HAUSHEER
    ____________________________________        _____________________________
      Hashime Kanazawa, Ph.D.                   Frederick H. Hausheer, M.D.
      C.O.O. & Vice President - Director        Chairman & Chief Executive
                                                Officer

Date: September 22, 2000                    Date: September 22, 2000

                                       13

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