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                                                                    EXHIBIT 10.5

CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE COMMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO THE
OMITTED PORTION.

                                                                    CONFIDENTIAL

                          THE JOHNS HOPKINS UNIVERSITY

                        BIONUMERIK PHARMACEUTICALS, INC.

          JOINT COLLABORATION, LICENSING, AND CLINICAL TRIALS AGREEMENT

         THIS AGREEMENT is made as of February 9, 2000 (the "Effective Date") by
and between The Johns Hopkins University, organized and existing under the laws
of the State of Maryland with its principal place of business at 720 Rutland
Avenue, Baltimore, Maryland 21205 (the "University") and BioNumerik
Pharmaceuticals, Inc., a Texas corporation with its principal place of business
at Suite 1250, 8122 Datapoint Drive, San Antonio, Texas 78229 (the "Company").

                                    RECITALS

         WHEREAS the Company wishes to obtain the opportunity to discuss new
technical developments with a view to potential licenses of certain inventions
discovered and/or developed at the Johns Hopkins University Oncology Center (the
"Center");

         WHEREAS the Center believes that the Company is skillful in the
commercialization of pharmaceutical compounds and seeks to benefit economically
from the Company's efforts;

         WHEREAS the Center desires to do clinical trials for the Company on an
agreed basis respecting overhead costs;

         WHEREAS in consideration of such basis, the Company is willing to give
the Center certain first option rights on any clinical trials to be done by the
Company; and

         WHEREAS in consideration for these collaborations, the Company will pay
to the Center $[**] with the execution and delivery of this Agreement and an
additional $[**] on each of the next [**] anniversaries thereof.

         NOW, THEREFORE, the Parties agree as follows:

[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.

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                                     PART I

                             TECHNICAL COLLABORATION

1.1 General. This Agreement anticipates a five-year collaboration between the
University and the Company (the "Collaboration") providing for the further
development by the Company of compounds invented by members of the faculty of
the Center (collectively, the "Center Faculty") for the treatment of solid
tumors and hematologic malignancies and the potential applications of such
compounds ("Oncology Drugs").

         1.2 Term. The Collaboration will take place during the period
commencing on the Effective Date and continuing for five years thereafter. The
term of the Collaboration may be extended by written agreement between the
parties.

         1.3 Company's Option.

         (a) The University hereby grants to the Company a first option to a
worldwide, royalty bearing, exclusive license to inventions of the Center
Faculty which are made in the course of performing research funded by this
Agreement, subject to the rights of any additional sponsors including U.S.
Government rights under 35 U.S.C. Sections 200-212. Inventions discovered
through research funded by the Company are hereinafter referred to as
"University Inventions".

         (b) The University hereby grants to the Company a first option to a
worldwide, royalty bearing, exclusive license to selected Oncology Drugs
invented by Center Faculty without the Company's financial support and which are
unencumbered by the licensing rights of commercial third parties. Inventions
discovered without the Company's financial support are hereinafter referred to
as "Selected Inventions."

         (c) The Company shall have sixty (60) days from the date of receipt of
an Invention Notice (defined in Section 1.6) to request that the parties enter
license negotiations. In the event that the Company and the University determine
to enter into a license negotiation with

respect to a University Invention or Selected Invention, the University and the
Company will begin such negotiations using the general license form attached
hereto as Exhibit A but further negotiation between the parties will be
unrestricted. The Office of Technology Licensing of the University's School of
Medicine will represent the University in such negotiations.

         1.4 Ownership of Collaboration Results. All inventions and discoveries
shall be owned by the party making the invention or discovery. Any inventions
deemed to be jointly made by the Company and the University shall be owned
jointly by the Company and the University and subject to their respective
license. Record title to patents and patent applications for University
Inventions and/or Selected Inventions shall be held by the University. Record
title to patents and patent applications for inventions made jointly by the
University and the Company shall be joint and subject to their respective
license.

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         1.5 Other Collaborations. Each of the University and the Company shall
be free to conduct other research, whether under the sponsorship of or in
collaboration with, the federal government or other third parties, or otherwise,
provided that the terms and conditions of any such research, sponsorships, or
collaborations shall not conflict with the terms of this Agreement.

         1.6 Notice. The Center Faculty will promptly notify the Office of
Technology Licensing of the University's School of Medicine (the "Licensing
Office") in writing of any University Invention or Selected Invention (the
"Invention Notice"). The Invention Notice will include a detailed written
description of such invention. When a University Invention is not encumbered by
the licensing rights of commercial third parties, the Licensing Office shall
notify the director of the Center, who will promptly submit the Invention Notice
to the Company. In the case of a Selected Invention, the Licensing Office and
the director of the Center will review the Selected Invention and jointly
determine whether the Company is a logical licensee, who is as capable of
developing and commercializing the Selected Invention as other potential
licensees. If the Licensing Office and the director of the Center agree that the
Company is the logical licensee, the director of the Center will promptly submit
the Invention Notice to the Company.

         1.7 Educational Advancement. The University does not guarantee that any
patentable or non-patentable Oncology Drugs will result from the Collaboration.
The Company understands that the University's primary mission is educational and
that the Collaboration is intended to forward that mission.

         1.8 Consultation. The Company will make available its chief-executive
officer, Frederick H. Hausheer, M.D. ("Dr. Hausheer"), to confer on-site with
the Center one day per year, the Center Faculty, and the Center's investigators
and researchers concerning Oncology Drugs developed by the Center Faculty. Dr.
Hausheer's consultations will be without charge to the University.

         1.9 Confidentiality. During the period this agreement is in effect and
for a period of three (3) years thereafter, the University and the Company agree
to keep in confidence and to use solely as contemplated in this agreement all
information received from the other party under this agreement or obtained
pursuant to or in connection with the Collaboration. All reasonable efforts will
be used to avoid disclosure to any third party of any information supplied or
developed under this agreement, unless the prior written consent of the other
party is obtained. The preceding confidentiality requirements will not extend to
any information which (a) is or becomes public knowledge, after the time it
becomes public; (b) the receiving party can show by written or other tangible
evidence was in its possession at the time of disclosure hereunder and which the
receiving party without breach of any obligation is free to disclose to others;
(c) was received by the receiving party from a third party who did not acquire
it, directly or indirectly, from the disclosing party under any obligation of
confidentiality and which the third party is free to disclose to others; (d) is
required to be disclosed by a court of law or by the regulations of a federal
agency, subject to the earliest practical notification by the party obligated to
make such disclosure so as to enable the other party to obtain such protective
orders as may be available; or (e) is independently developed by the receiving
party and which the receiving party can show by written or other tangible
evidence was so independently developed.

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         1.10 Publication. Notwithstanding the foregoing, and except for
information supplied by the Company and not otherwise known to the University,
the University may publish in scientific journals research results arising from
activities funded by the Company, from University Inventions, and from Selected
Inventions for which the Company is given notice pursuant to Section 1.6, in
accordance with the following procedures:

                  (a) the University will submit the proposed manuscript to the
Company at least thirty (30) days prior to submission for publication; and

                  (b) within thirty (30) days of the receipt of such manuscript,
the Company will advise the University whether the Company has determined that
the manuscript contains patentable subject matter relating to a University
Invention and whether the Company wishes that a patent application be filed.

         If the Company notifies the University that the manuscript includes no
confidential information and/or that the Company does not wish patent action to
be taken, or if the Company does not so notify the University within the thirty
(30) day period, the University will be free to publish. If the Company wishes
patent action to be taken, it will notify the University of its decision and
patent protection will be sought pursuant to Section 1. 111. Neither the
University nor any of its employees will submit the manuscript for publication
or disclose its contents to third parties until patent applications have been
filed. The patent application(s) will be filed within ninety (90) days of the
University's receipt of the Company's notice requesting that the University seek
patent protection. After the earlier of ninety (90) days or the filing of a
patent application, the University will be free to submit and publish the
manuscript. However, no publication of any compounds, structures or other
information which is confidential information of BioNumerik will be made by the
University without the prior written consent of the Company, which consent will
not be unreasonably withheld.

         1.11 Patents. Except as provided in Section 1.10, the Company may for a
period of sixty (60) days after the Company's receipt of the Invention Notice
elect to seek patent protection for any University Invention or Selected
Invention with respect to which it negotiates a license. In the event the
Company determines to seek patent protection, the Company will inform the
University in writing of its election. The University will then cause to be
prepared, filed, prosecuted, and maintained at the Company's expense patent
applications and/or patents resulting therefrom, provided, however, that in the
event that the Company and the University are unable to negotiate a license for
such invention, the Company's liability for any additional patent expenses shall
cease upon the University's receipt of the Company's written notification that
it no longer wishes to continue negotiations, and the University will, upon
licensing the invention to a commercial third party, reimburse the Company for
all patent expenses which the Company incurred. Such patent preparation, filing,
prosecution, and maintenance will be performed through outside patent counsel
selected by the University and approved by the Company, which approval will not
be unreasonably withheld. In the event the Company determines not to seek patent
protection as provided herein, the University will be free to seek such
protection at the University's expense.

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                                     PART II

                            CLINICAL TRIAL AGREEMENT

         2.1 Clinical Trials. The Company hereby grants to the Center [**]. In
the event the University and the Company are unable to agree upon the material
terms of a clinical trials agreement within such thirty (30) day period, the
University's rights herein shall terminate with respect to that Oncology Drug.
In addition, nothing herein shall prevent the Company from conducting
negotiations with other potential clinical trial sites concurrently with its
negotiations with the University. In connection with any agreement entered with
respect to the Trials, the Company agrees to reimburse the University's direct
and indirect costs, provided, however, that the University agrees that total
indirect costs for such Trials will not exceed [**] ([**] %) of total direct
costs, and the costs and terms of such Trials will otherwise be in accordance
with and no less favorable to the Company than the Company's existing clinical
trials agreements with the University.

                                    PART III

                                PERIODIC PAYMENTS

         3.1 Upon the execution and delivery of this Agreement by the
University, the Company will pay to the Center $[**]. Upon each of the next [**]
succeeding anniversaries of the date of this Agreement, the Company will pay to
the Center an additional $[**]. In addition, the Center and the Company will
discuss in good faith and determine a reasonable portion of the above-referenced
annual amount paid to the Center that will be allocated to fund a fellowship or
other research agreed upon by the Company and the Center.

[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.

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                                     PART IV

                                  MISCELLANEOUS

         4.1 University Name. The Company will not use the name, likeness, or
logo of the Johns Hopkins University; its Schools, Divisions, Departments, or
Centers; The Johns Hopkins Hospital and Health System; or Johns Hopkins'
faculty, employees, students, or trustees in any of the Company's fund-raising
documents, publications, advertisements, or marketing and promotional materials
without the prior written consent of the University. The University shall have
three business days from the date of receipt of the Company's request for
written consent to review such request.

         4.2 Breach/Default. Upon breach or default of any of the terms and
conditions of this Agreement, the non-defaulting party will deliver a written
notice of such default to the defaulting party (the "Default Notice"). If the
default is not cured within sixty (60) days after the defaulting party's receipt
of the Default Notice, the non-defaulting party may terminate this Agreement.

         4.3 Assignment. This Agreement may not be assigned or transferred by
any party without the prior written consent of the parties, provided, however,
that the Company may assign or transfer its rights and obligations under this
Agreement to a successor to all or substantially all of its assets or business,
whether by sale, merger, operation of law, or otherwise, and the Company shall
provide written notice to the University of any such assignment.

         4.4 Independent Contractor. For the purposes of this agreement and all
services to be provided hereunder, the parties will be and will be deemed to be
independent contractors and not agents or employees of the other party. Neither
party will have authority to make any statement, representation, or commitment
of any kind, or to take any action which will be binding on the other party,
except as may be expressly provided for herein or authorized in writing.

         4.5 Waiver and Amendment. The terms of this agreement may be waived or
amended only with the written consent of the parties.

         4.6 Entire Agreement. This agreement constitutes the full and entire
understanding and agreement between the parties with regard to the subjects
hereof, and no party shall be liable or bound to any other party in any manner
by warranties, representations, or covenants except as specifically set forth
herein. In addition to this agreement, the existing Collaboration Agreement,
dated as of November 19, 1996, between the Company and the University regarding
the area of DNA methylation, the Master Clinical Trial Research Agreement, first
dated as of March 9, 1995, between the University and the Company, and the
related protocol, confidentiality and other agreements between the University
and the Company, shall each remain and continue in full force and effect after
the date hereof in accordance with their terms.

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         4.7 Notices. Any notice required by this agreement shall be effective
upon deposit when given by prepaid, first class, certified mail, return receipt
requested, addressed to:

If to the University:        Michael B. Amey
                             Assistant Dean for Research Administration
                             The Johns Hopkins University School of Medicine
                             720 Rutland Ave., Administration Building, Room 129
                             Baltimore, Maryland 21205

with a copy to:              Martin D. Abeloff, M.D.
                             Professor and Director
                             The Johns Hopkins Oncology Center (157)
                             600 North Wolfe Street
                             Baltimore, Maryland 21287

If to the Company:           Frederick H. Hausheer, M.D.
                             Chairman
                             BioNumerik Pharmaceuticals, Inc.
                             8122 Datapoint Drive, Suite 1250
                             San Antonio, Texas 78229

         4.8 Governing Law. This Agreement shall be governed in all respects by
and construed in accordance with the laws of the State of Maryland as applied to
agreements among Maryland residents to be performed entirely in Maryland.

         4.9 Headings. The headings of the several sections of this agreement
are intended for convenience of reference only and are not intended to be a part
of or to affect the meaning or interpretation of this Agreement.

         4.10 Severability. If any provision of this agreement shall be found by
a court to be void, invalid, or unenforceable, the validity, legality, and
enforceability of the remaining provisions shall not be in any way affected or
impaired thereby.

         4.11 Counterparts. This agreement may be executed in counterparts, each
of which shall be deemed an original, but each of which together shall
constitute one and the same instrument.

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         IN WITNESS WHEREOF, the parties have executed this Agreement as of the
date first above written.

THE JOHNS HOPKINS UNIVERSITY                BIONUMERIK PHARMACEUTICALS, INC.

By:                                         By:
       ---------------------------                 -----------------------------
Name:  Michael B. Amey                      Name:  Frederick H. Hausheer, M.D.
Title: Assistant Dean                       Title: Chairman & Chief Executive
       for Research Administration                 Officer

Date:  2/16/00                              Date:  2/8/00

The undersigned have read this Agreement and agree to its terms:

----------------------------
Frederick H. Hausheer, M.D.

----------------------------
Martin D. Abeloff, M.D.<PAGE>   1
                                                                  EXHIBIT 10.6

CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE COMMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO THE
OMITTED PORTION.

                             COLLABORATION AGREEMENT

                                     Between

                          The Johns Hopkins University
                               Baltimore, MD 21287

                                       and

                        BioNumerik Pharmaceuticals, Inc.
                              San Antonio, TX 78229

<PAGE>   2

                             COLLABORATION AGREEMENT

THIS COLLABORATION AGREEMENT (this "Agreement") is entered into effective as of
November 19, 1996 by and between BioNumerik Pharmaceuticals, Inc., a Texas
corporation ("BioNumerik" or the "Company") and The Johns Hopkins University, a
Maryland corporation (the "Institution"). BioNumerik and the Institution,
intending to be legally bound, agree as follows:

WHEREAS, the Institution and BioNumerik wish to establish a joint research
program in which BioNumerik and the Institution will collaborate on the
discovery and development of novel therapeutic agents which modulate DNA
methylation in cancer.

NOW, THEREFORE, the parties hereto agree as follows:

1. TERM OF RESEARCH PROGRAM. Subject to the provisions for termination
hereinafter provided, the term of the research program to be conducted pursuant
to this Agreement (the "Program") shall be for a period (the "Program Term")
commencing November 19, 1996 and terminating at the close of business on
November 19, 2001, provided that [**].

2. PRINCIPAL INVESTIGATORS. For as long as he remains at the Institution, Dr.
Stephen Baylin shall direct and act as principal investigator for the
Institution's portion of the Program. During the Program Term, Dr. Frederick H.
Hausheer shall direct and act as principal investigator for the BioNumerik
portion of the Program.

3. SCOPE OF THE PROGRAM.

         (a)      Year One Program Objectives.

The overall Program will be aimed at the discovery and development of novel
therapeutic agents which modulate DNA methylation in cancer. The focus of the
Program during year one will include the following:

         (i) [**]

         (ii) [**]

         (iii) [**]

         (iv) [**]

[**]

[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.

<PAGE>   3

         (b) Later Years Program Objectives.

The focus of the Program during the second through fifth years of the Program
will be to [**].

4. ADDITIONAL BIONUMERIK RESPONSIBILITIES.

         (a) Upon the execution of this Agreement, BioNumerik will make an
initial payment of [**] to the Institution. During the first year of the
Program, BioNumerik will provide such additional funding with respect to work in
Dr. Baylin's laboratory at the Institution in such amounts as may be agreed upon
from time to time by BioNumerik and the Institution. The payment of such agreed
upon amounts shall be made quarterly by BioNumerik. In the following years of
the Program, additional research funding will be provided by BioNumerik for
additional research at the Institution as may be agreed upon by BioNumerik and
the Institution based on the achievement of mutually agreeable research
milestones.

         (b) BioNumerik will also undertake sole responsibility for endeavoring
to obtain patent protection (including payment of future patent filing fees) on
new chemical entities which are developed under the Program and which are
identified as either joint inventions or sole inventions of BioNumerik, in the
United States and such other countries in the remainder of the world as it may
determine. The Institution will cooperate with BioNumerik in providing such
information and assistance, and executing such documents and instruments, as may
be requested by BioNumerik from time to time in connection with prosecution of
patents relating to the New Inventions and Discoveries (as hereinafter defined).
The Institution will take responsibility for obtaining patent protection for all
sole Institution inventions.

         (c) BioNumerik will be responsible for supporting the clinical
development of a new drug which is intended for possible human treatment in the
focus area of the Program. As described in Section 9, the Institution will have
a right of first offer to take the selected novel therapeutic entity into
clinical trials.

[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.

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5. PUBLICATION RIGHTS.

Dr. Baylin and the Institution shall have rights to publish the results of the
collaborative research work conducted pursuant to the Program that are
consistent with the rights normally associated with collaborative academic and
industry research, subject, in all cases, to prepublication notice sent to
BioNumerik at least 30 days in advance of publication submission and
prepublication review by BioNumerik. No publication of any compounds, structures
or other information which is confidential information of BioNumerik will be
made by the Institution or Dr. Baylin without the prior written consent of
BioNumerik (which consent will not be unreasonably withheld and in any event
will not be withheld longer than 90 days after receipt of a manuscript of the
proposed publication). Dr. Baylin, the Institution and BioNumerik further agree
to delay publication for up to 90 days when requested by BioNumerik to permit
patent applications to be filed or where otherwise requested by BioNumerik to
protect business strategy or intellectual property rights. Authorship on any
specific publication resulting from the Program will be determined jointly by
Dr. Baylin and Dr. Hausheer.

6. CONFIDENTIALITY.

Each party to this Agreement (a "receiving party") who receives Confidential
Information (as defined below) disclosed by the other party to this Agreement (a
"disclosing party") shall not, during the term of this Agreement and for five
(5) years after termination of this Agreement, make use of or disclose, without
the prior written consent of the disclosing party, Confidential Information
disclosed by the disclosing party or any of its Affiliates. Each receiving party
further agrees that it will return to each disclosing party all written
materials in its possession embodying Confidential Information of such
disclosing party. For purposes of this Agreement, "Confidential Information"
includes intellectual property or other information obtained by a receiving
party from a disclosing party and which is marked as confidential or which the
disclosing party could reasonably be expected to desire be held in confidence,
or the disclosure of which would likely be embarrassing, detrimental or
disadvantageous to the disclosing party or its Affiliates. Confidential
Information, however, shall not include information (a) which is, at the time in
question, in the public domain through no wrongful act of the receiving party,
(b) which is later disclosed to a receiving party by one not under obligations
of confidentiality to the disclosing party, or (c) which is required by court or
governmental order, to be disclosed. Each of the Institution and Dr. Baylin
recognizes and agrees that BioNumerik shall at all times during this Agreement
and after termination of this Agreement retain ownership of its patents,
copyrights, trade secrets and other proprietary information and neither Dr.
Baylin nor the Institution shall have any right to use or disclose any such
patents, copyrights, trade secrets or other proprietary information unless
consented or agreed to in writing by BioNumerik. BioNumerik recognizes and
agrees that the Institution shall at all times during this Agreement and after
termination of this Agreement retain ownership of its patents, copyrights, trade
secrets and other proprietary information and BioNumerik shall not have any
right to use or disclose any such patents, copyrights, trade secrets or other
proprietary information except as provided herein or in other written agreements
with the Institution.

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7. REPORTING AND RECORD KEEPING.

Written progress reports will be exchanged by the parties at least twice a year.
Interim data will be provided, reviewed and jointly discussed by the parties in
the interim. It is agreed that each party hereto and its authorized
representative(s), and regulatory authorities, to the extent required by law,
may, during regular business hours, arrange in advance with the other party to:
(1) examine and inspect such other party's facilities required for performance
of the Program; and (2) inspect and copy on a confidential basis all data and
work products of such party relating to the Program. Each party shall prepare
and maintain complete and accurate written records, accounts, reports and data
of the research conducted by it under the Program.

8. INTELLECTUAL PROPERTY.

         (a) New Inventions and Discoveries. For purposes of this Agreement,
"New Inventions and Discoveries" shall mean any invention or discovery conceived
or reduced to practice during and as a part of the research performed pursuant
to or in accordance with the Program (i) solely by Dr. Baylin and/or the
Institution's staff or employees supervised by him, or (ii) jointly by such an
individual or individuals with one or more employees of BioNumerik. All such New
Inventions and Discoveries developed solely by Dr. Baylin and/or the
Institution's staff or employees supervised by him shall be owned by the
Institution, subject to the licensing provisions set forth in this Section 8.
All jointly developed New Inventions and Discoveries shall be owned jointly by
the Institution and BioNumerik, subject to the licensing provisions set forth in
this Section 8. All inventions and discoveries arising out of the Program that
are developed solely by BioNumerik shall be owned solely by BioNumerik. For
purposes of this Agreement, inventions and discoveries shall include all
inventions, methods, ideas, discoveries and improvements, whether patentable or
not.

         (b) Definitions. The following terms shall have the following meanings
for purposes of this Agreement.

         (i) "Affiliate(s)" means with respect to each party, any organization,
company, firm, or other entity which controls, is controlled by, or is under
common control with said party. An entity shall be deemed to have control of
another entity if itowns directly or indirectly a majority of the voting shares
or is entitled directly or indirectly to appoint a majority of the directors of
the other entity.

         (ii) [**].

[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.

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         (iii) "Know-How" shall mean all data, information and technology
directly relating to the New Inventions and Discoveries including, without
limitation, formulae, specifications, designs, chemical and physical data
concerning synthesis, processes, formulations, applications, and marketing,
which is developed by Dr. Baylin or the Institution's staff or employees
supervised by him prior to and/or during this Agreement.

         (iv) "Product(s)" shall mean a pharmaceutical preparation or
formulation which contains a compound or other novel chemical entity developed
as a direct result of and during the term of the Program, or which utilizes or
incorporates a New Invention and Discovery or Know-How which led directly to the
development of such compound or other novel chemical entity.

         (c) Grant of License. The Institution hereby grants to BioNumerik an
exclusive, world-wide, royalty bearing license for both sole and joint rights of
the Institution (including the right to grant sublicenses) to formulate, market,
manufacture and use the New Inventions and Discoveries and Know-How and to
practice, market and exploit the New Inventions and Discoveries and Know-How and
any products utilizing or obtained from use of the New Inventions and
Discoveries and Know-How, and to otherwise exercise, practice and use all rights
under the New Inventions and Discoveries and Know-How during the License Period.
Such grant is subject to the retained right of the Institution to make, have
made, provide and use for its and The Johns Hopkins Health System's non-profit
internal research purposes New Inventions and Discoveries and Know-How. Should
any federal grant money be used to develop New Inventions and Discoveries or
Know-How, this grant shall also be subject to the rights retained by the United
States Government under P.L. 96-517, as amended by P.L. 98-620.

The Institution agrees to give BioNumerik notice prior to using any federal
grant money in connection with the Program. The Institution further agrees to
use reasonable measures to protect trade secrets and other intellectual property
rights that are covered by the Institution's retained right contained in this
Section 8(c).

         (d) License Period. The License Period means the period commencing on
the effective date hereof and ending on the later of (i) the latest expiration
date of any patents that may issue on the New Inventions and Discoveries, and
(ii) 20 years from the effective date hereof.

         (e) Earned Royalties.

                  (i) [**]
         (A) [**]
         (B) [**]
         (C) [**]

[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.

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         Notwithstanding the above provision of this Section 8(e), in the event
that (i) any patents on any New Inventions and Discoveries have expired or been
declared invalid during the License Period and any generic form of Product(s)
enters the marketplace or (ii) all of the patents on any New Inventions and
Discoveries have expired or been declared invalid within the License Period, the
parties shall negotiate in good faith reduced royalty rates for the rest of the
License Period.

               (ii) Payment of royalties in accordance with this Section 8(e)
shall be made quarterly by BioNumerik to the Institution (or its designated
Affiliate). In the case of a Product(s) which contains compounds, entities,
and/or technology licensed from the Institution pursuant to this Agreement and
also pursuant to that certain Fellowship Agreement, dated as of November 19,
1996, between the Institution and BioNumerik, the Institution shall only be
entitled to a single royalty amount, which royalty amount shall not exceed the
royalty amount due under this Agreement.

               (iii) [**]

         (f) Diligence/Minimum Royalties.

         BioNumerik agrees to use reasonable commercial efforts to develop and
market the Product(s). Beginning with the calendar year commencing on January
1st immediately following the first commercial sale of a Product(s), BioNumerik
will [**].

               (g) Sublicenses. BioNumerik is hereby granted the right to grant
sublicenses under the license granted pursuant to this Section 8 to its
Affiliates and to third parties, provided that all payments from any sublicensee
shall be included in Adjusted Gross Product Revenues as described above.

               (h) Institution Representations.

               (i) The Institution hereby represents and warrants to BioNumerik
that it has the right to grant licenses to BioNumerik on an exclusive basis in
accordance with the terms and conditions of this Agreement.

               (ii) The Institution further represents and warrants to
BioNumerik that: (A) it has not licensed any rights to the New Inventions and
Discoveries or Know-How to any party other than BioNumerik; and (B) there are no
liens, mortgages, pledges, claims, charges or other encumbrances that are
applicable to the New Inventions and Discoveries or other rights licensed
hereunder.

[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.

                                       7
<PAGE>   8

               (iii) The Institution hereby agrees to take any and all actions
as may be reasonably requested by BioNumerik to further evidence BioNumerik's
license rights granted hereunder.

                  (iv) The Institution warrants that it has the authority to
acquire and convey title to its interest in the New Inventions and Discoveries
with the exception of certain rights that may possibly be retained by the United
States government. The Institution does not warrant the validity of any patents
or that practice under such patents shall be free of infringement. EXCEPT AS
EXPRESSLY SET FORTH IN THIS SECTION 8, BIONUMERIK AGREES (AND ANY AFFILIATES OR
SUBLICENSEES WHO OBTAIN RIGHTS HEREUNDER SHALL AGREE) THAT THE NEW INVENTIONS
AND DISCOVERIES AND KNOW-HOW ARE PROVIDED "AS IS", AND THAT THE INSTITUTION
MAKES NO REPRESENTATION OR WARRANTY WITH RESPECT TO THE PERFORMANCE OF PRODUCTS)
INCLUDING THEIR SAFETY, EFFECTIVENESS, OR COMMERCIAL VIABILITY. EXCEPT AS
EXPRESSLY SET FORTH IN THIS SECTION 8, THE INSTITUTION DISCLAIMS ALL WARRANTIES
WITH REGARD TO PRODUCTS) LICENSED UNDER THIS AGREEMENT, INCLUDING BUT NOT
LIMITED TO, ALL WARRANTIES, EXPRESS OR IMPLIED, OF MERCHANTABILITY AND FITNESS
FOR ANY PARTICULAR PURPOSE. NOTWITHSTANDING ANY OTHER PROVISION OF THIS
AGREEMENT AND EXCEPT AS EXPRESSLY SET FORTH IN THIS SECTION 8, THE INSTITUTION
ADDITIONALLY DISCLAIMS ALL OBLIGATIONS AND LIABILITIES ON THE PART OF THE
INSTITUTION AND THE FACULTY, EMPLOYEES OR STUDENTS OF THE INSTITUTION THAT ARE
INVENTORS OF ANY OF THE NEW INVENTIONS AND DISCOVERIES OR KNOW-HOW
(COLLECTIVELY, THE "INVENTORS") FOR DAMAGES, INCLUDING, BUT NOT LIMITED TO,
DIRECT, INDIRECT, SPECIAL, AND CONSEQUENTIAL DAMAGES, ATTORNEYS' AND EXPERTS'
FEES, AND COURT COSTS (EVEN IF THE INSTITUTION HAS BEEN ADVISED OF THE
POSSIBILITY OF SUCH DAMAGES, FEES OR COSTS), ARISING OUT OF OR IN CONNECTION
WITH THE MANUFACTURE, USE, OR SALE OF THE PRODUCTS) LICENSED UNDER THIS
AGREEMENT. EXCEPT AS EXPRESSLY SET FORTH IN THIS SECTION 8, BIONUMERIK ASSUMES
(AND ANY AFFILIATES OR SUBLICENSEES WHO OBTAIN RIGHTS HEREUNDER SHALL ASSUME)
ALL RESPONSIBILITY AND LIABILITY FOR LOSS OR DAMAGE CAUSED BY A PRODUCT
MANUFACTURED, USED, OR SOLD BY BIONUMERIK, ITS SUBLICENSEES AND AFFILIATES WHICH
IS A LICENSED "PRODUCT(S)" AS DEFINED IN THIS AGREEMENT.

               (v) The Institution and the Inventors will not, under the
provisions of this Agreement or otherwise, have control over the manner in which
BioNumerik or its Affiliates or its sublicensees or those operating for its
account or third parties who purchase Product(s) from any of the foregoing
entities, practice the inventions or Product(s). BioNumerik shall defend and
hold the Institution, The Johns Hopkins Health System, their present and former
trustees, officers, Inventors, agents, faculty, employees and students
(collectively, the "Institution Parties") harmless as against any judgments,
fees, expenses, or other costs arising from or incidental to any product
liability or other lawsuit, claim, demand or other action brought as a
consequence of the practice of said inventions by any of the foregoing entities,
whether or not the Institution or said Inventors, either jointly or severally,
is named as a party defendant in any such lawsuit.

                                       8
<PAGE>   9

Practice of the inventions covered by Product(s) by an Affiliate or an agent or
sublicensee or a third party on behalf of or for the account of BioNumerik or by
a third party who purchases Product(s) from BioNumerik, shall be considered
BioNumerik's practice of said inventions for purposes of this Paragraph. The
obligation of BioNumerik to defend and indemnify as set out in this Paragraph
shall survive the termination of this Agreement. The parties agree that
BioNumerik shall not be obligated to indemnify or defend the Institution, The
Johns Hopkins Health System or any of the other Institution Parties from any
lawsuit, claim, demand or action brought as a consequence of the practice of any
invention by the Institution or any other Institution Party pursuant to the
retained right of the Institution described in Section 8(c) hereof. The
Institution shall defend and hold BioNumerik and its officers, directors,
shareholders, agents and Affiliates harmless as against any judgments, fees,
expenses, or other costs arising from or incidental to any product liability or
other lawsuit, claim, demand or other action brought as a consequence of the
negligent use of New Inventions and Discoveries and Know-How by the Institution
or any other Institution Party pursuant to the retained right of the Institution
described in Section 8(c) hereof, whether or not BioNumerik or other said
parties, either jointly or severally, is named as a party defendant in any such
lawsuit. The obligation of the Institution to defend and indemnify as set out in
the preceding sentence shall survive the termination of this Agreement. However,
if such retained research use is a clinical trial that BioNumerik sponsors, the
agreement relating to such clinical study will include appropriate language
addressing the indemnification by BioNumerik of the Institution and The Johns
Hopkins Health System, and such indemnification shall take precedence over this
paragraph.

(vi) Prior to initial human testing or first commercial sale of any Product as
the case may be in any particular country, BioNumerik shall establish and
maintain, in each country in which BioNumerik, a BioNumerik Affiliate or
sublicensee shall test or sell Product(s), product liability or other
appropriate insurance coverage in reasonable amounts that are customary to the
industry and that are appropriate to the risks involved in marketing Product(s)
and will annually present evidence to the Institution that such coverage is
being maintained. Upon the Institution's request, BioNumerik will furnish the
Institution with a Certificate of Insurance of each product liability insurance
policy obtained and agrees to increase or change the kind of insurance
pertaining to the Product(s) at the reasonable request of the Institution. The
Institution shall be listed as an additional insured in said insurance policies
of BioNumerik, to the extent reasonably possible.

9. RIGHT OF FIRST OFFER TO CONDUCT CLINICAL TRIALS.

         [**]

[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.

                                       9
<PAGE>   10

10. [**]

11. PROGRAM DURATION / TERMINATION.

         The Program will have a term of five years commencing and ending as
provided in Section 1 of this Agreement. Notwithstanding any other provision of
this Agreement, either party hereto shall have the right at its option to
terminate the Program at any time after year one of the Program by giving 90
days prior written notice to the other party. In the event of termination of the
Program by BioNumerik or the Institution, all rights and duties arising under
the Program and Sections 1, 2, 3 and 4 of this Agreement shall cease as of the
date of such termination. All other provisions of this Agreement, including
without limitation the rights and obligations under Section 8 hereof, shall
survive and continue after any such termination in accordance with their terms.

12. GOVERNING LAW. THIS AGREEMENT IS ENTERED INTO AND SHALL BE GOVERNED BY AND
CONSTRUED IN ACCORDANCE WITH THE LAWS OF THE STATE OF TEXAS, WITHOUT REGARD TO
THE CONFLICT OF LAW PRINCIPLES THEREOF.

13. CONSTRUCTION. Each party to this Agreement has had the opportunity to review
this Agreement with its legal counsel. This Agreement shall not be construed or
interpreted against any party on the basis that such party drafted or authored a
particular provision, parts of or the entirety of this Agreement.

14. ASSIGNMENT. This Agreement and the rights and obligations hereunder may not
be assigned by either party without the prior consent of the other party;
provided, however, that BioNumerik may assign this Agreement without consent to
any entity which acquires all or substantially all of its assets or business,
whether by merger or otherwise.

[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.

                                       10
<PAGE>   11

15. NOTICES. Any notice, consent or approval required under this Agreement shall
be in writing sent by registered or certified airmail, postage prepaid, or by
fax or telex (confirmed by such registered or certified mail) and addressed as
follows:

If to the Institution:      Michael B. Amey
                            Assistant Dean for Research Administration
                            The Johns Hopkins University School of Medicine
                            2024 E. Monument Street, Suite 2-100, Baltimore,
                            MD 21287

with a copy to:             Stephen Baylin, M.D.
                            The Johns Hopkins Oncology Center
                            410 North Bond Street
                            Baltimore, MD 21231

If to BioNumerik:           Frederick H. Hausheer, M.D.
                            8122 Datapoint Drive, Suite 1250
                            San Antonio, TX 78229

         All notices shall be deemed to be effective three business days after
the date of mailing. In case any party changes its address at which notice is to
be received, written notice of such change shall be given without delay to the
other party.

16. ENTIRE AGREEMENT. This Agreement sets forth the entire agreement and
understanding among the parties hereto as to the subject matter hereof and has
priority over all documents, verbal consents or understandings made between the
parties hereto before the conclusion of this Agreement with respect to the
subject matter hereof. None of the terms of this Agreement shall be amended or
modified except in writing signed by the parties hereto. In addition, that
certain Fellowship Agreement, dated as of November 19, 1996, between the
Institution and BioNumerik; that certain Joint Collaboration, Licensing and
Clinical Trials Agreement, dated as of November 30, 1994, between the
Institution and BioNumerik; and that certain Master Clinical Trial Research
Agreement, dated as of April 3, 1995, between the Institution and BioNumerik
shall continue in full force and effect in accordance with their terms.

17. WAIVERS. A waiver by any party of any term or condition of this Agreement in
any one instance shall not be deemed or construed to be a waiver of such term or
condition for any similar instance in the future or of any subsequent breach
hereof.

18. 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.

19. UNIVERSITY NAME. BioNumerik shall not use the name, likeness, or logo of the
Johns Hopkins University; its Schools, Divisions, Departments, or Centers; The
Johns Hopkins Hospital and Health System; or Johns Hopkins' faculty, employees,
students, or trustees in any

                                       11
<PAGE>   12

advertising, promotional, or sales material, whether oral or written, without
the prior consent of the Institution or unless otherwise required by law.

IN WITNESS WHEREOF, the parties have executed this Agreement effective as of
11/19, 1996.

                                       THE JOHNS HOPKINS UNIVERSITY

                                       By:     /s/ N. Franklin Adkison
                                               --------------------------------
                                       Title:  N. Franklin Adkison, Jr. , M. D.
                                               Interim Vice Dean for Research

                                       BIONUMERIK PHARMACEUTICALS, INC.

                                       By:     /s/ Frederick H. Hausheer
                                               --------------------------------
                                               Frederick H. Hausheer, M.D.
                                               Chief Executive Officer

READ AND UNDERSTOOD:

      /s/ Stephen Baylin
-----------------------------------
Stephen Baylin, M.D.

                                       12

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