Document:

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                                                                    EXHIBIT 4.12

                            STOCK PURCHASE AGREEMENT

         This Stock Purchase Agreement (this "Agreement") is entered into as of
the 22nd day of September, 2000, 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 joint venture agreement
dated as of August 30, 2000 (the "Joint Venture Agreement").

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

1. SUBSCRIPTION FOR SHARES

         1.1 Subject to the terms and conditions hereof, GRELAN hereby
subscribes for and purchases 46,512 shares of Series G Preferred Stock for a
total purchase price of U.S. $4,000,000.00, 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 9, 2000, provided that all of the conditions set forth in
Section 4 hereof have been complied with. (The shares of Series G 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. $4,000,000.00, 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 3,635,299 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,
1,113,279 shares of Series E Convertible Preferred Stock, and 288,791 shares of
Series F Convertible Preferred Stock issued and outstanding. BIONUMERIK has

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reserved up to 5,335,571 shares of common stock of BIONUMERIK (the "Common
Stock") for issuance upon conversion of the Series A, Series B, Series C, Series
D, Series E, Series F, and Series G Preferred Stock (including conversion of the
Shares), and up to 2,260,378 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

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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
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, 2000
and interim financial statements for the period ending July 31, 2000
(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 July 31, 2000 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. Except as described in the
Schedules hereto, 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.

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         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. Except as described on Schedule 2.1(b) hereto,
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.

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     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.

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                (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 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.

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         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:

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

               (ii) the By-laws of BIONUMERIK.

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            (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 G
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 or
Controller 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 or in the Schedules hereto, 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 Joint Venture 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 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

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Shares or on GRELAN's assets, liabilities, condition (financial or otherwise),
operating results, business, or prospects.

            (b) The Joint Venture 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, 2002, 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.

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            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
Joint Venture 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 Joint Venture 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.

                                       10
<PAGE>

                        (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.

9. MISCELLANEOUS

            9.1 Entire Agreement; Amendment. This Agreement, the Registration
Rights Agreement and the Joint Venture 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

                                       11
<PAGE>

issuable upon conversion of the Shares). In addition, those obligations under
the Joint Venture Operating Agreement and under the existing confidentiality
agreements, materials transfer agreements, stock purchase agreements and related
agreements between and among GRELAN and BIONUMERIK, and in certain cases certain
third parties, 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 Joint Venture
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 Joint Venture 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.

            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

                                       12
<PAGE>

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<PAGE>
                                                                    EXHIBIT 4.13

                          REGISTRATION RIGHTS AGREEMENT

         This Registration Rights Agreement (the "Agreement") is executed as of
the 28th day of October, 1999 by BioNumerik Pharmaceuticals, Inc., a Texas
corporation (the "Company") and Grelan Pharmaceutical Co., Ltd., a Japanese
corporation ("Grelan" or the "Purchaser").

                                   WITNESSETH:

         WHEREAS, the Purchaser is purchasing shares of the Company's Preferred
Stock (as defined herein) with the understanding that the Company is granting
certain registration rights to the Purchaser.

         NOW, THEREFORE, the Company grants the registration rights contained
herein to the Purchaser, 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:

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

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

         "Conversion Shares" means the shares of Common Stock issued and
issuable upon conversion of the Preferred Stock issued to the Purchaser.

         "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.

         "Holders" means the Purchaser 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.

         "Initiating Holders" means any Holder or Holders who in the aggregate
hold more than fifty percent (50%) of the then-outstanding Registrable
Securities, but no less than the number of Registrable Securities issued or
issuable upon conversion of twenty five percent (25%) of the total number of
shares of Preferred Stock issued by the Company to the Purchaser.

         "Preferred Stock" means the Series F Convertible Preferred Stock, par
value $.01 per share, of the Company.

         "Registrable Securities" means (i) the Conversion Shares and (ii) any
Common Stock issued as a dividend or other distribution with respect to or in
exchange for or in replacement of the

<PAGE>

Conversion Shares or Preferred Stock issued to the Purchaser, 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.

         "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.

         "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.

         "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.

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

         "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.

         "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.

         "Series F Persons" means those persons other than the Purchaser who are
entitled to registration rights pursuant to a Registration Rights Agreement (the
"Series F Registration Rights Agreement") relating to registration rights which
are concurrent with the registration rights granted to the Series F Persons.

         "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 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 Preferred Stock had been fully converted.

                                       2
<PAGE>

         2. REGISTRATION OF REGISTRABLE SECURITIES.

         2.1 Registration on Request.

         (a) Request. Subject to the limitations provided herein, commencing on
December 31, 2001, 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 the fifth anniversary of the effective date of the Company's
first registration statement under the Securities Act, 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, but no less than the number of Registrable Securities
issued or issuable upon conversion of twenty five percent (25%) of the total
number of shares of Preferred Stock issued by the Company to the Purchaser, 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; provided, however, that the rights of Holders hereunder shall be

                                       3
<PAGE>

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 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 "Warrant Purchasers") requesting registration
pursuant to the Series B Registration Rights Agreement, the Series C
Registration Rights Agreement, the Series D Registration Rights Agreement, the
Series E Registration Rights Agreement, the Series F Registration Rights
Agreement, and/or the agreement granting registration rights to the Warrant
Purchasers (the "Warrant Purchaser Registration Agreement") (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, 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, Warrant Purchasers and Holders
that are requested to be included in such registration pursuant to the Series B
Registration Rights Agreement, the Series C Registration Rights Agreement, the
Series D Registration Rights Agreement, the Series E Registration Rights
Agreement, the Series F Registration Rights Agreement, the Warrant Purchaser
Registration Agreement or this Agreement, as the case may be.

         (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, 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.

                                       4
<PAGE>

         (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.

         (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, and 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.

         (i) Form S-3. Notwithstanding the other provisions of this Section 2.1,
until the fifth anniversary of the effective date of the Company's first
registration statement under the Securities Act, 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

                                       5
<PAGE>

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 $500,000.

         (j) Notwithstanding anything to the contrary contained herein, 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
prior to the fifth anniversary of the effective date of the Company's first
registration statement under the Securities Act 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.

         (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

                                       6
<PAGE>

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, and 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.

         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:

                  (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

                                       7
<PAGE>

         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;

               (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;

                                       8
<PAGE>

                  (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;

                  (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

                                       9
<PAGE>

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
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

                                       10
<PAGE>

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.

         (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

                                       11
<PAGE>

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 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

                                       12
<PAGE>

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 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

                                       13
<PAGE>

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 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 Purchaser) of the Purchaser
or (ii) to an immediate or remote transferee of the Purchaser who after such
transfer is the Holder of at least 50% of the number of Registrable Securities

                                       14
<PAGE>

purchased by such original Purchaser (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).

         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 two-thirds (2/3)
of the then outstanding Registrable Securities. The parties hereto recognize
that the Company may, without the consent of Purchaser or any Holder, grant
registration rights to other purchasers of Preferred Stock and enter into the
Series F Registration Rights Agreement with such purchasers, which agreement
shall contain registration rights substantially similar to the registration
rights contained herein.

         3.4 Notices, etc. All notices and other communications required or
permitted hereunder shall be in writing and shall be mailed by first class mail,
postage prepaid, or otherwise delivered by hand or by messenger including
Federal Express or similar courier service, addressed (a) if to the Purchaser at
6-6 Nihonbashi Kobunacho, Chuo-ku, Tokyo 103-0024, Japan or at such other
address as such party shall have furnished to the Company in writing, or (b) if
to the Company at 8122 Datapoint Drive, Suite 1250, San Antonio, Texas 78229,
Attn: Chief Executive Officer, or at such other address as the Company shall
have furnished to the other parties hereto.

         Each such notice or other communication shall for all purposes of this
Agreement be treated as effective upon receipt.

         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.

                                       15
<PAGE>

         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.

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

                                    "COMPANY"

                                    BIONUMERIK PHARMACEUTICALS, INC.

                                    By:    /s/ FREDERICK H. HAUSHEER
                                           ------------------------------------
                                           Frederick H. Hausheer, M.D.
                                    Title: Chairman and Chief Executive Officer

                                    "PURCHASER"

                                    GRELAN PHARMACEUTICAL CO., LTD.

                                    By:    /s/ HISAYUKI NOGUCHI
                                           ------------------------------------
                                           Hisayuki Noguchi
                                    Title: President and Chief Executive Officer

                                       16

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