Document:

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                                                                   EXHIBIT 10.22

                            COOPERATIVE RESEARCH AND
                              DEVELOPMENT AGREEMENT

                                   (CACR-352)

                          CLINICAL DEVELOPMENT OF Adp53

                                      [*]
                                      [*]
                                      CTEP
                                      DCTD

                                      [*]
                    RHONE-POULENC RORER PHARMACEUTICALS, INC.

                                      [*]
                           INTROGEN THERAPEUTICS, INC.

                                  PREPARED BY
              TECHNOLOGY DEVELOPMENT AND COMMERCIALIZATION BRANCH
                           NATIONAL CANCER INSTITUTE

         [*] Certain information on this page has been omitted and filed
             separately with the Commission. Confidential treatment has been
             requested with respect to the omitted portions.
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                              PUBLIC HEALTH SERVICE

                 COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT

This Cooperative Research and Development Agreement, hereinafter referred to as
"CRADA," consists of this Cover Page, an attached Agreement, and various
Appendices referenced in the Agreement. This Cover Page serves to identify the
Parties to this CRADA:

                  (1) the following Bureau(s), Institute(s), Center(s) or
Division(s) of the National Institutes of Health ("NIH"), the Food and Drug
Administration ("FDA"), and the Centers for Disease Control and Prevention
("CDC"):

                              THE CANCER THERAPY EVALUATION PROGRAM
                              DIVISION OF CANCER TREATMENT AND DIAGNOSIS
                              THE NATIONAL CANCER INSTITUTE

, hereinafter singly or collectively referred to as the Public Health Service
("PHS"); and

                  (2)         RHONE-POULENC RORER PHARMACEUTICALS, INC.,

which has offices at          500 ARCOLA ROAD
                              COLLEGEVILLE, PENNSYLVANIA 19426

, hereinafter referred to as "RPRP"
and

                  (3)         INTROGEN THERAPEUTICS, INC.,

which has offices at          301 CONGRESS AVENUE, SUITE 1850
                              AUSTIN, TEXAS 78701

, hereinafter referred to as "Introgen"

PHS CRADA CACR-0352
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                 COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT

ARTICLE 1. INTRODUCTION

This Cooperative Research and Development Agreement (CRADA) between PHS and the
Collaborator will be effective when signed by all Parties. The research and
development activities which will be undertaken by each of the Parties in the
course of this CRADA are detailed in the Research Plan (RP) which is attached as
Appendix A. The funding and staffing commitments of the Parties are set forth in
Appendix B. Any exceptions or changes to the CRADA are set forth in Appendix C.

ARTICLE 2. DEFINITIONS

As used in this CRADA, the following terms shall have the indicated meanings:

2.1      "AFFILIATE" means any corporation or other business entity controlled
         by, controlling, or under common control with Collaborator. For this
         purpose, "control" means direct or indirect beneficial ownership of at
         least fifty (50) percent of the voting stock or at least fifty (50)
         percent interest in the income of such corporation or other business.

2.2      "Cooperative Research and Development Agreement" or "CRADA" means this
         Agreement, entered into by PHS pursuant to the Federal Technology
         Transfer Act of 1986, as amended, 15 U.S.C. 3710a et seq. and
         Executive Order 12591 of October 10, 1987.

2.3      "GOVERNMENT" means the Government of the United States as represented
         through the PHS agency that is a Party to this agreement.

2.4      "IP" means intellectual property.

2.5      "INVENTION" means any invention or discovery which is or may be
         patentable or otherwise protected under title 35, United States Code,
         or any novel variety or plant which is or may be protectable under the
         Plant Variety Protection Act (7 U.S.C. 2321 et seq.).

2.6      "PRINCIPAL INVESTIGATOR(S)" or "PIS" means the persons designated
         respectively by the Parties to this CRADA who will be responsible for
         the scientific and technical conduct of the RP.

2.7      "PROPRIETARY/CONFIDENTIAL INFORMATION" means confidential scientific,
         business, or financial information provided that such information does
         not include:

         2.7.1    information that is publicly known or available from other
                  sources who are not under a confidentiality obligation to the
                  source of the information;

         2.7.2    information which has been made available by its owners to
                  others without a confidentiality obligation;

         2.7.3    information which is already known by or available to the
                  receiving Party without a confidentiality obligation; or

         2.7.4    information which relates to potential hazards or cautionary
                  warnings associated with the production, handling or use of
                  the subject matter of the Research Plan of this CRADA.

2.8      "RESEARCH MATERIALS" means all tangible materials other than Subject
         Data first produced in the

Model PHS CRADA
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         performance of this CRADA.

2.9      "RESEARCH PLAN" or "RP" means the statement in Appendix A of the
         respective research and development commitments of the Parties to this
         CRADA.

2.10     "SUBJECT INVENTION" means any Invention of the Parties, conceived or
         first actually reduced to practice in the performance of the Research
         Plan of this CRADA.

2.11     "SUBJECT DATA" means all recorded information first produced in the
         performance of this CRADA by the Parties.

ARTICLE 3. COOPERATIVE RESEARCH

3.1      PRINCIPAL INVESTIGATORS. PHS research work under this CRADA will be
         performed by the PHS laboratory identified in the RP, and the PHS
         Principal Investigator (PI) designated in the RP will be responsible
         for the scientific and technical conduct of this project on behalf of
         PHS. Also designated in the RP is the Collaborator PI who will be
         responsible for the scientific and technical conduct of this project on
         behalf of the Collaborator.

3.2      RESEARCH PLAN CHANGE. The RP may be modified by mutual written consent
         of the Principal Investigators. Substantial changes in the scope of the
         RP will be treated as amendments under Article 13.6.

ARTICLE 4. REPORTS

4.1      INTERIM REPORTS. The Parties shall exchange formal written interim
         progress reports on a schedule agreed to by the PIs, but at least
         within [*] after this CRADA becomes effective and at least within [*]
         thereafter. Such reports shall set forth the technical progress made,
         identifying such problems as may have been encountered and establishing
         goals and objectives requiring further effort, any modifications to the
         Research Plan pursuant to Article 3.2, and all CRADA-related patent
         applications filed.

4.2      FINAL REPORTS. The Parties shall exchange final reports of their
         results within [*] after completing the projects described
         in the RP or after the expiration or termination of this CRADA.

ARTICLE 5. FINANCIAL AND STAFFING OBLIGATIONS

5.1      PHS AND COLLABORATOR CONTRIBUTIONS. The contributions of the Parties,
         including payment schedules, if applicable, are set forth in Appendix
         B. PHS shall not be obligated to perform any of the research specified
         herein or to take any other action required by this CRADA if the
         funding is not provided as set forth in Appendix B. PHS shall return
         excess funds to the Collaborator when it sends its final fiscal report
         pursuant to Article 5.2, except for staffing support pursuant to
         Article 10.3. Collaborator acknowledges that the U.S. Government will
         have the authority to retain and expend any excess funds for up to
         [*] subsequent to the expiration or termination of the CRADA to
         cover any costs incurred during the term of the CRADA in undertaking
         the work set forth in the RP.

5.2      ACCOUNTING RECORDS. PHS shall maintain separate and distinct current
         accounts, records, and other evidence supporting all its obligations
         under this CRADA, and shall provide the Collaborator a final fiscal
         report pursuant to Article 4.2.

5.3      CAPITAL EQUIPMENT. Equipment purchased by PHS with funds provided by
         the Collaborator shall be the property of PHS. All capital equipment
         provided under this CRADA by one party for the use of another Party
         remains the property of the providing Party unless other disposition is
         mutually agreed upon by in

Model PHS CRADA
Form 053096 Page 3 of 11

         [*] Certain information on this page has been omitted and filed
             separately with the Commission. Confidential treatment has been
             requested with respect to the omitted portions.
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         writing by the Parties. If title to this equipment remains with the
         providing Party, that Party is responsible for maintenance of the
         equipment and the costs of its transportation to and from the site
         where it will be used.

ARTICLE 6. INTELLECTUAL PROPERTY RIGHTS AND PATENT APPLICATIONS

6.1      REPORTING. The Parties shall promptly report to each other in writing
         each Subject Invention resulting from the research conducted under this
         CRADA that is reported to them by their respective employees. Each
         Party shall report all Subject Inventions to the other Party in
         sufficient detail to determine inventorship. Such reports shall be
         treated as Proprietary/Confidential Information in accordance with
         Article 8.4.

6.2      COLLABORATOR EMPLOYEE INVENTIONS. If the Collaborator does not elect to
         retain its IP rights, the Collaborator shall offer to assign these IP
         rights to the Subject Invention to PHS pursuant to Article 6.5. If PHS
         declines such assignment, the Collaborator may release its IP rights as
         it may determine.

6.3      PHS EMPLOYEE INVENTIONS. PHS on behalf of the U.S. Government may elect
         to retain IP rights to each Subject Invention made solely by PHS
         employees. If PHS does not elect to retain IP rights, PHS shall offer
         to assign these IP rights to such Subject Invention to the Collaborator
         pursuant to Article 6.5. If the Collaborator declines such assignment,
         PHS may release IP rights in such Subject Invention to its employee
         inventors pursuant to Article 6.6.

6.4      JOINT INVENTIONS. Each Subject Invention made jointly by PHS and
         Collaborator employees shall be jointly owned by PHS and the
         Collaborator. The Collaborator may elect to file the joint patent or
         other IP application(s) thereon and shall notify PHS promptly upon
         making this election. If the Collaborator decides to file such
         applications, it shall do so in a timely manner and at its own expense.
         If the Collaborator does not elect to file such application(s), PHS on
         behalf of the U.S. Government shall have the right to file the joint
         application(s) in a timely manner and at its own expense. If either
         Party decides not to retain its IP rights to a jointly owned Subject
         Invention, it shall offer to assign such rights to the other Party
         pursuant to Article 6.5. If the other Party declines such assignment,
         the offering Party may release its IP rights as provided in Articles
         6.2, 6.3, and 6.6.

6.5      FILING OF PATENT APPLICATIONS. With respect to Subject Inventions made
         by the Collaborator as described in Article 6.2, or by PHS as described
         in Article 6.3, a Party exercising its right to elect to retain IP
         rights to a Subject Invention agrees to file patent or other IP
         applications in a timely manner and at its own expense and after
         consultation with the other Party. The Party shall notify the other
         Party of its decision regarding filing in countries other than the
         United States in a timely manner. The Party may elect not to file a
         patent or other IP application thereon in any particular country or
         countries provided it so advises the other Party ninety (90) days prior
         to the expiration of any applicable filing deadline, priority period or
         statutory bar date, and hereby agrees to assign its IP right, title and
         interest in such country or countries to the Subject Invention to the
         other Party and to cooperate in the preparation and filing of a patent
         or other IP applications. In any countries in which title to patent or
         other IP rights is transferred to the Collaborator, the Collaborator
         agrees that PHS inventors will share in any royalty distribution that
         the Collaborator pays to its own inventors.

6.6      RELEASE TO INVENTORS. In the event neither of the Parties to this CRADA
         elects to file a patent or other IP application on a Subject Invention,
         either or both (if a joint invention) may retain or release their IP
         rights in accordance with their respective policies and procedures.
         However, the Government shall retain a nonexclusive, non-transferable,
         irrevocable, royalty-free license to practice any such Subject
         Invention or have it practiced throughout the world.

6.7      PATENT EXPENSES. The expenses attendant to the filing of patent or
         other IP applications generally shall be paid by the Party filing such
         application. If an exclusive license to any Subject Invention is
         granted to the

Model PHS CRADA
Form 053096 Page 4 of 11

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         Collaborator, the Collaborator shall be responsible for [*] past and
         future out-of-pocket expenses in connection with the preparation,
         filing, prosecution and maintenance of any applications claiming such
         exclusively-licensed inventions and any patents or other IP grants that
         may issue on such applications. The Collaborator may waive its
         exclusive license rights on any application, patent or other IP grant
         at any time, and incur no subsequent compensation obligation for that
         application, patent or IP grant.

6.8      PROSECUTION OF INTELLECTUAL PROPERTY APPLICATIONS. Within one month of
         receipt or filing, each Party shall provide the other Party with copies
         of the applications and all documents received from or filed with the
         relevant patent or other IP office in connection with the prosecution
         of such applications. Each Party shall also provide the other Party
         with the power to inspect and make copies of all documents retained in
         the patent or other IP application files by the applicable patent or
         other IP office. Where licensing is contemplated by Collaborator, the
         Parties agree to consult with each other with respect to the
         prosecution of applications for PHS Subject Inventions described in
         Article 6.3 and joint Subject Inventions described in Article 6.4. If
         the Collaborator elects to file and prosecute IP applications on joint
         Subject Inventions pursuant to Article 6.4, PHS will be granted an
         associate power of attorney (or its equivalent) on such IP
         applications.

ARTICLE 7. LICENSING

7.1      OPTION FOR COMMERCIALIZATION LICENSE. With respect to Government IP
         rights to any Subject Invention not made solely by the Collaborator's
         employees for which a patent or other IP application is filed, PHS
         hereby grants to the Collaborator an option to elect an exclusive or
         nonexclusive commercialization license, which is substantially in the
         form of the appropriate model PHS license agreement. This option does
         not apply to Subject Inventions conceived prior to the effective date
         of this CRADA that are reduced to practice under this CRADA, if prior
         to that reduction to practice, PHS has filed a patent application on
         the invention and has licensed it or offered to license it to a third
         party. The terms of the license will fairly reflect the nature of the
         invention, the relative contributions of the Parties to the invention
         and the CRADA, the risks incurred by the Collaborator and the costs of
         subsequent research and development needed to bring the invention to
         the marketplace. The field of use of the license will be commensurate
         with the scope of the RP.

7.2      EXERCISE OF LICENSE OPTION. The option of Article 7.1 must be exercised
         by written notice mailed within [*] after either (i) Collaborator
         receives written notice from PHS that the patent or other IP
         application has been filed; or (ii) the date Collaborator files such IP
         application; whichever comes first. Exercise of this option by the
         Collaborator initiates a negotiation period that expires [*] after the
         exercise of the option. If the last proposal by the Collaborator has
         not been responded to in writing by PHS within this [*] period, the
         negotiation period shall be extended to expire [*] after PHS so
         responds, during which month the Collaborator may accept in writing the
         final license proposal of PHS. In the absence of such acceptance, PHS
         will be free to license such IP rights to others. In the event that the
         Collaborator elects the option for an exclusive license, but no such
         license is executed during the negotiation period, PHS agrees not to
         make an offer for an exclusive license on more favorable terms to a
         third party for a period of [*] without first offering Collaborator
         those more favorable terms.

7.3      LICENSE FOR PHS EMPLOYEE INVENTIONS AND JOINT INVENTIONS. Pursuant to
         15 U.S.C. 3710a(b)(1)(A), for inventions made by PHS employees or
         jointly with a Collaborator under this CRADA, pursuant to Articles 6.3
         and 6.4, the Collaborator grants to PHS a nonexclusive,
         nontransferable, irrevocable, paid-up license to practice the invention
         or have the invention practiced throughout the world by or on behalf of
         the Government. In the exercise of such license, the Government shall
         not publicly disclose trade secrets or commercial or financial
         information that is privileged or confidential within the meaning of 5
         U.S.C. 552(b)(4) or which would be considered as such if it had been
         obtained from a non-Federal party.

7.4      LICENSE IN COLLABORATOR INVENTIONS. Pursuant to 15 U.S.C. 3710a(b)(2),
         for inventions made solely by

Model PHS CRADA
Form 053096 Page 5 of 11

         [*] Certain information on this page has been omitted and filed
             separately with the Commission. Confidential treatment has been
             requested with respect to the omitted portions.
<PAGE>   7
         Collaborator employees under this CRADA, pursuant to Article 6.2, the
         Collaborator grants to PHS a nonexclusive, nontransferable,
         irrevocable, paid-up license to practice the invention or have the
         invention practiced throughout the world by or on behalf of the
         Government for research or other Government purposes.

7.5      THIRD PARTY LICENSE. Pursuant to 15 U.S.C. 3710a(1)(B), if PHS grants
         an exclusive license to a Subject Invention made wholly by PHS
         employees or jointly with a Collaborator under this CRADA, pursuant to
         Articles 6.3 and 6.4, the Government shall retain the right to require
         the Collaborator to grant a responsible applicant a nonexclusive,
         partially exclusive, or exclusive sublicense to use the invention in
         Collaborator's licensed field of use on terms that are reasonable under
         the circumstances; or if the Collaborator fails to grant such a
         license, to grant the license itself. The exercise of such rights by
         the Government shall only be in exceptional circumstances and only if
         the Government determines (i) the action is necessary to meet health or
         safety needs that are not reasonably satisfied by Collaborator, (ii)
         the action is necessary to meet requirements for public use specified
         by Federal regulations, and such requirements are not reasonably
         satisfied by the Collaborator; or (iii) the Collaborator has failed to
         comply with an agreement containing provisions described in 15 U.S.C.
         3710a(c)(4)(B). The determination made by the Government under this
         Article is subject to administrative appeal and judicial review under
         35 U.S.C. 203(2).

7.6      JOINT INVENTIONS NOT EXCLUSIVELY LICENSED. In the event that the
         Collaborator does not acquire an exclusive commercialization license to
         IP rights in all fields in joint Subject Inventions described in
         Article 6.4, then each Party shall have the right to use the joint
         Subject Invention and to license its use to others in all fields not
         exclusively licensed to Collaborator. The Parties may agree to a joint
         licensing approach for such IP rights.

ARTICLE 8. PROPRIETARY RIGHTS AND PUBLICATION

8.1      RIGHT OF ACCESS. PHS and the Collaborator agree to exchange all Subject
         Data produced in the course of research under this CRADA, whether
         developed solely by PHS or jointly with the Collaborator. Research
         Materials will be shared equally by the Parties to the CRADA unless
         other disposition is agreed to by the Parties. All Parties to this
         CRADA will be free to utilize Subject Data and Research Materials for
         their own purposes, consistent with their obligations under this CRADA.

8.2      OWNERSHIP OF SUBJECT DATA AND RESEARCH MATERIALS. Subject to the
         sharing requirements of Paragraph 8.1 and the regulatory filing
         requirements of Paragraph 8.3, the producing Party will retain
         ownership of and title to all Subject Inventions, all Subject Data and
         all Research Materials produced solely by their investigators. Jointly
         developed Subject Inventions, Subject Data and Research Materials will
         be jointly owned.

8.3      DISSEMINATION OF SUBJECT DATA AND RESEARCH MATERIALS. To the extent
         allowed under law, the Collaborator and PHS agree to use reasonable
         efforts to keep Subject Data and Research Materials confidential until
         published or until corresponding patent applications are filed. Any
         information that would identify human subjects of research or patients
         will always be maintained confidentially. Collaborator shall have the
         exclusive right to use any and all CRADA Subject Data in and for any
         regulatory filing by or on behalf of Collaborator, except that PHS
         shall have the exclusive right to use Subject Data for that purpose,
         and authorize others to do so, if the CRADA is terminated or if
         Collaborator abandons its commercialization efforts.

8.4      PROPRIETARY/CONFIDENTIAL INFORMATION. Each Party agrees to limit its
         disclosure of Proprietary/Confidential Information to the amount
         necessary to carry out the Research Plan of this CRADA, and shall place
         a confidentiality notice on all such information. Confidential oral
         communications shall be reduced to writing within 30 days by the
         disclosing Party. Each Party receiving Proprietary/Confidential
         Information agrees that any information so designated shall be used by
         it only for the purposes described in the attached Research Plan. Any
         Party may object to the designation of

Model PHS CRADA
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         information as Proprietary/Confidential Information by another Party.
         Subject Data and Research Materials developed solely by the
         Collaborator may be designated as Proprietary/Confidential Information
         when they are wholly separable from the Subject Data and Research
         Materials developed jointly with PHS investigators, and advance
         designation of such data and material categories is set forth in the
         RP. The exchange of other confidential information, e.g., patient-
         identifying data, should be similarly limited and treated. Jointly
         developed Subject Data and Research Material derived from the
         Research Plan may be disclosed by Collaborator to a third party under a
         confidentiality agreement for the purpose of possible sublicensing
         pursuant to the Licensing Agreement and subject to Article 8.7.

8.5      PROTECTION OF PROPRIETARY/CONFIDENTIAL INFORMATION. Proprietary/
         Confidential Information shall not be disclosed, copied, reproduced or
         otherwise made available to any other person or entity without the
         consent of the owning Party except as required under court order or the
         Freedom of Information Act (5 U.S.C. Section 552). Each Party agrees to
         use its best efforts to maintain the confidentiality of
         Proprietary/Confidential Information. Each Party agrees that the other
         Party is not liable for the disclosure of Proprietary/Confidential
         Information which, after notice to and consultation with the concerned
         Party, the other Party in possession of the Proprietary/Confidential
         Information determines may not be lawfully withheld, provided the
         concerned Party has been given an opportunity to obtain a court order
         to enjoin disclosure.

8.6      DURATION OF CONFIDENTIALITY OBLIGATION. The obligation to maintain the
         confidentiality of Proprietary/Confidential Information shall expire at
         the earlier of the date when the information is no longer Proprietary
         Information as defined in Article 2.5 or three (3) years after the
         expiration or termination date of this CRADA. The Collaborator may
         request an extension to this term when necessary to protect
         Proprietary/Confidential Information relating to products not yet
         commercialized.

8.7      PUBLICATION. The Parties are encouraged to make publicly available the
         results of their research. Before either Party submits a paper or
         abstract for publication or otherwise intends to publicly disclose
         information about a Subject Invention, Subject Data or Research
         Materials, the other Party shall be provided thirty (30) days to review
         the proposed publication or disclosure to assure that
         Proprietary/Confidential Information is protected. The publication or
         other disclosure shall be delayed for up to thirty (30) additional days
         upon written request by any Party as necessary to preserve U.S. or
         foreign patent or other IP rights.

ARTICLE 9. REPRESENTATIONS AND WARRANTIES

9.1      REPRESENTATIONS AND WARRANTIES OF PHS. PHS hereby represents and
         warrants to the Collaborator that the official signing this CRADA has
         authority to do so.

9.2      REPRESENTATIONS AND WARRANTIES OF THE COLLABORATOR.

         (a) The Collaborator hereby represents and warrants to PHS that the
         Collaborator has the requisite power and authority to enter into this
         CRADA and to perform according to its terms, and that the
         Collaborator's official signing this CRADA has authority to do so. The
         Collaborator further represents that it is financially able to satisfy
         any funding commitments made in Appendix B.

         (b) The Collaborator certifies that the statements herein are true,
         complete, and accurate to the best of its knowledge. The Collaborator
         is aware that any false, fictitious, or fraudulent statements or claims
         may subject it to criminal, civil, or administrative penalties.

ARTICLE 10. TERMINATION

10.1     TERMINATION BY MUTUAL CONSENT. PHS and the Collaborator may terminate
         this CRADA, or portions thereof, at any time by mutual written consent.
         In such event the Parties shall specify the disposition of all

Model PHS CRADA
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         property, inventions, patent or other IP applications and other results
         of work accomplished or in progress, arising from or performed under
         this CRADA, all in accordance with the rights granted to the Parties
         under the terms of this Agreement.

10.2     UNILATERAL TERMINATION. Either PHS or the Collaborator may unilaterally
         terminate this entire CRADA at any time by giving written notice at
         least thirty (30) days prior to the desired termination date, and any
         rights accrued in property, patents or other IP rights shall be
         disposed of as provided in paragraph 10.1.

10.3     STAFFING. If this CRADA is mutually or unilaterally terminated prior to
         its expiration, funds will nevertheless remain available to PHS for
         continuing any staffing commitment made by the Collaborator pursuant to
         Article 5.1 above and Appendix B, if applicable, for a period of
         [*] after such termination. If there are insufficient funds to
         cover this expense, the Collaborator agrees to pay the difference.

10.4     NEW COMMITMENTS. No Party shall make new commitments related to this
         CRADA after a mutual termination or notice of a unilateral termination
         and shall, to the extent feasible, cancel all outstanding commitments
         and contracts by the termination date.

10.5     TERMINATION COSTS. Concurrently with the exchange of final reports
         pursuant to Articles 4.2 and 5.2, PHS shall submit to the Collaborator
         for payment a statement of all costs incurred prior to the date of
         termination and for all reasonable termination costs including the cost
         of returning Collaborator property or removal of abandoned property,
         for which Collaborator shall be responsible.

ARTICLE 11. DISPUTES

11.1     SETTLEMENT. Any dispute arising under this CRADA which is not disposed
         of by agreement of the Principal Investigators shall be submitted
         jointly to the signatories of this CRADA. If the signatories are unable
         to jointly resolve the dispute within thirty (30) days after
         notification thereof, the Assistant Secretary for Health (or his/her
         designee or successor) shall propose a resolution. Nothing in this
         Article shall prevent any Party from pursuing any additional
         administrative remedies that may be available and, after exhaustion of
         such administrative remedies, pursuing all available judicial remedies.

11.2     CONTINUATION OF WORK. Pending the resolution of any dispute or claim
         pursuant to this Article, the Parties agree that performance of all
         obligations shall be pursued diligently in accordance with the
         direction of the PHS signatory.

ARTICLE 12. LIABILITY

12.1     PROPERTY. The U.S. Government shall not be responsible for damages to
         any Collaborator property provided to PHS, where Collaborator retains
         title to the property, or any property acquired by Collaborator for its
         own use pursuant to this CRADA.

12.2     NO WARRANTIES. EXCEPT AS SPECIFICALLY STATED IN ARTICLE 9, THE PARTIES
         MAKE NO EXPRESS OR IMPLIED WARRANTY AS TO ANY MATTER WHATSOEVER,
         INCLUDING THE CONDITIONS OF THE RESEARCH OR ANY INVENTION OR PRODUCT,
         WHETHER TANGIBLE OR INTANGIBLE, MADE, OR DEVELOPED UNDER THIS CRADA, OR
         THE OWNERSHIP, MERCHANTABILITY, OR FITNESS FOR A PARTICULAR PURPOSE OF
         THE RESEARCH OR ANY INVENTION OR PRODUCT.

12.3     INDEMNIFICATION. The Collaborator agrees to hold the U.S. Government
         harmless and to indemnify the Government for all liabilities, demands,
         damages, expenses and losses arising out of the use by the Collaborator
         for any purpose of the Subject Data, Research Materials and/or Subject
         Inventions produced in whole or part by PHS employees under this CRADA,
         unless due to the negligence or willful misconduct

Model PHS CRADA
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         [*] Certain information on this page has been omitted and filed
             separately with the Commission. Confidential treatment has been
             requested with respect to the omitted portions.
<PAGE>   10

         of PHS, its employees, or agents. The Collaborator shall be liable for
         any claims or damages it incurs in connection with this CRADA. PHS has
         no authority to indemnify the Collaborator.

12.4     FORCE MAJEURE. Neither Party shall be liable for any unforeseeable
         event beyond its reasonable control not caused by the fault or
         negligence of such Party, which causes such Party to be unable to
         perform its obligations under this CRADA, and which it has been unable
         to overcome by the exercise of due diligence. In the event of the
         occurrence of such a force majeure event, the Party unable to perform
         shall promptly notify the other Party. It shall further use its best
         efforts to resume performance as quickly as possible and shall suspend
         performance only for such period of time as is necessary as a result of
         the force majeure event.

ARTICLE 13. MISCELLANEOUS

13.1     GOVERNING LAW. The construction, validity, performance and effect of
         this CRADA shall be governed by Federal law, as applied by the Federal
         Courts in the District of Columbia. Federal law and regulations will
         preempt any conflicting or inconsistent provisions in this CRADA.

13.2     ENTIRE AGREEMENT. This CRADA constitutes the entire agreement between
         the Parties concerning the subject matter of this CRADA and supersedes
         any prior understanding or written or oral agreement.

13.3     HEADINGS. Titles and headings of the articles and subarticles of this
         CRADA are for convenient reference only, do not form a part of this
         CRADA, and shall in no way affect its interpretation.

Model PHS CRADA
Form 053096 Page 9 of 11
<PAGE>   11

13.4     WAIVERS. None of the provisions of this CRADA shall be considered
         waived by any Party unless such waiver is given in writing to the other
         Party. The failure of a Party to insist upon strict performance of any
         of the terms and conditions hereof, or failure or delay to exercise any
         rights provided herein or by law, shall not be deemed a waiver of any
         rights of any Party.

13.5     SEVERABILITY. The illegality or invalidity of any provisions of this
         CRADA shall not impair, affect, or invalidate the other provisions of
         this CRADA.

13.6     AMENDMENTS. If either Party desires a modification to this CRADA, the
         Parties shall, upon reasonable notice of the proposed modification or
         extension by the Party desiring the change, confer in good faith to
         determine the desirability of such modification or extension. Such
         modification shall not be effective until a written amendment is signed
         by the signatories to this CRADA or by their representatives duly
         authorized to execute such amendment.

13.7     ASSIGNMENT. Neither this CRADA nor any rights or obligations of any
         Party hereunder shall be assigned or otherwise transferred by either
         Party without the prior written consent of the other Party.

13.8     NOTICES. All notices pertaining to or required by this CRADA shall be
         in writing and shall be signed by an authorized representative and
         shall be delivered by hand or sent by certified mail, return receipt
         requested, with postage prepaid, to the addresses indicated on the
         signature page for each Party. Notices regarding the exercise of
         license options shall be made pursuant to Article 7.2. Any Party may
         change such address by notice given to the other Party in the manner
         set forth above.

13.9     INDEPENDENT CONTRACTORS. The relationship of the Parties to this CRADA
         is that of independent contractors and not agents of each other or
         joint venturers or partners. Each Party shall maintain sole and
         exclusive control over its personnel and operations. Collaborator
         employees who will be working at PHS facilities may be asked to sign a
         Guest Researcher or Special Volunteer Agreement appropriately modified
         in view of the terms of this CRADA.

13.10    USE OF NAME OR ENDORSEMENTS. By entering into this CRADA, PHS does not
         directly or indirectly endorse any product or service provided, or to
         be provided, whether directly or indirectly related to either this
         CRADA or to any patent or other IP license or agreement which
         implements this CRADA by its successors, assignees, or licensees. The
         Collaborator shall not in any way state or imply that this CRADA is an
         endorsement of any such product or service by the U.S. Government or
         any of its organizational units or employees. Collaborator issued press
         releases that reference or rely upon the work of PHS under this CRADA
         shall be made available to PHS at least 7 days prior to publication for
         review and comment.

13.11    EXCEPTIONS TO THIS CRADA. Any exceptions or modifications to this CRADA
         that are agreed to by the Parties prior to their execution of this
         CRADA are set forth in Appendix C.

13.12    REASONABLE CONSENT. Whenever a Party's consent or permission is
         required under this CRADA, such consent or permission shall not be
         unreasonably withheld.

Model PHS CRADA
Form 053096 Page 10 of 11
<PAGE>   12

ARTICLE 14. DURATION OF AGREEMENT

14.1     DURATION. It is mutually recognized that the duration of this
         project cannot be rigidly defined in advance, and that the contemplated
         time periods for various phases of the RP are only good faith
         guidelines subject to adjustment by mutual agreement to fit
         circumstances as the RP proceeds. In no case will the term of this
         CRADA extend beyond the term indicated in the RP unless it is revised
         in accordance with Article 13.6.

14.2     SURVIVABILITY. The provisions of Articles 4.2, 5-8, 10.3-10.5, 11.1,
         12.2-12.4, 13.1, 13.10 and 14.2 shall survive the termination of this
         CRADA.

Model PHS CRADA
Form 053096 Page 11 of 11
<PAGE>   13

                              CRADA SIGNATURE PAGE

By executing this Agreement, each of the undersigned represents and confirms
that he or she is fully authorized to bind the identified entity to its terms.
Each of the undersigned expressly certifies or affirms that the contents of any
statement made or reflected in this document are truthful and accurate.

AGREED TO AND ACCEPTED BY:

FOR THE NATIONAL CANCER INSTITUTE:

/s/ ALAN S. RABSON                                                  9/11/98
------------------------------------------                      ----------------
ALAN S. RABSON, M.D.                                            DATE
DEPUTY DIRECTOR, NCI

Mailing Address for Notices:

National Cancer Institute
Technology Development and Commercialization Branch
Executive Plaza South, Room 450
6120 Executive Boulevard
Rockville, MD, 20852

FOR RHONE-POULENC RORER PHARMACEUTICALS, INC.    FOR INTROGEN THERAPEUTICS, INC.

/s/ ROSS J. OEHLER                               /s/ DAVID G. NANCE
---------------------------                      -----------------------------
ROSS J. OEHLER                                   DAVID G. NANCE
ASSISTANT SECRETARY                              PRESIDENT AND CEO

10/13/98                                         October 30, 1998
---------------------------                      -----------------------------
Date                                             Date

                                    Page S-1
<PAGE>   14

                                                                        CACR-352
                                   APPENDIX A

                                  RESEARCH PLAN

TITLE OF CRADA: [*]

NIH/ADAMHA PRINCIPAL INVESTIGATORS:         [*]
and his/her laboratory:                     [*]

                                            CTEP DCTD

COLLABORATOR PRINCIPAL INVESTIGATOR:        [*]
                                            [*]
                                            RHONE-POULENC RORER
                                              PHARMACEUTICALS, INC.

                                            [*]
                                            [*]
                                            INTROGEN THERAPEUTICS, INC.

TERM OF CRADA: (4) years

CONFLICTS OF INTEREST INFORMATION: Describe any relevant past, present or
contemplated relationships between the NIH/ADAMHA Principal Investigator and
his/her Laboratory and the Collaborator in sufficient detail to permit reviewers
of this CRADA to determine whether or not any conflicts of interest exist:

SEE CONFLICT OF INTEREST FORM ATTACHED HERETO.

The Research Plan which follows this page should be concise but of sufficient
detail to permit reviewers of this CRADA to evaluate the scientific merit of the
proposed collaboration. The RP should explain the scientific importance of the
collaboration and the research goals of NIH/ADAMHA and the Collaborator. The
respective contributions in terms of expertise and/or research materials of
NIH/ADAMHA and Collaborator should be summarized. Initial and subsequent
projects contemplated under the RP, and the time periods estimated for their
completion, should be described, and pertinent methodological considerations
summarized. Pertinent literature references may be cited and additional relevant
information included. Include additional pages to identify the Principal
Investigators of all other Parties to this CRADA.

         [*] Certain information on this page has been omitted and filed
             separately with the Commission. Confidential treatment has been
             requested with respect to the omitted portions.

                                    Page A-i

<PAGE>   15
                                   APPENDIX A

                                 RESEARCH PLAN

            [*]

            [*] Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                             Al
<PAGE>   16
      [*]

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

                                A2
<PAGE>   17

                                      [*]

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                       A3
<PAGE>   18

                                      [*]

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                       A4
<PAGE>   19

                                      [*]

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                       A5
<PAGE>   20

                                      [*]

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                       A6
<PAGE>   21
                                   APPENDIX B

               FINANCIAL AND STAFFING CONTRIBUTIONS OF THE PARTIES

                             ALLOCATION OF RESOURCES

                               NIH CONTRIBUTIONS

PERSONNEL NCI will conduct clinical research of Adp53, hereinafter, Agent, under
its intramural and extramural research programs. NCI estimates that one to three
person-years per year of effort will be dedicated to its participation in the
clinical studies, Steering Committee meetings, updates to its IND, compiling
data, Agent management, monitoring, and furthering the Clinical Trial Program.
The Principal Investigators, [*] and [*] will manage the NCI responsibilities of
the CRADA.

FINANCIAL

NCI will provide no funding to RPRP or INTROGEN for collaborative research and
development pursuant to this CRADA, inasmuch as financial contributions by the
U.S. government to non-Federal parties under a CRADA are prohibited under the
Federal Technology Transfer Act of 1986 (15 U.S.C. Section 3710 a(d)(1)).

                           COLLABORATOR CONTRIBUTIONS

PERSONNEL

RPRP and INTROGEN, primarily through their jointly designated Collaborator
Principal Investigators, [*] (currently an employee of RPRP, see Appendix C,
Article 3.1), or her successor, and [*] (currently an employee of INTROGEN), or
his successor, intend to commit two person-years per year of effort to
coordinate their respective obligations of RPRP and INTROGEN under the Research
Plan.

CLINICAL DATA SUPPORT

The requesting Party or Parties, RPRP and/or INTROGEN, as applicable, will pay
Clinical Trial Monitoring Services (CTMS) for the cost of reformatting and
reproducing the Raw Data if either or both, RPRP and INTROGEN, request copies of
Raw Data from CTMS in a format different from the format as set forth in CTMS'
contract with Cancer Therapy Evaluation Program (CTEP), DCTD, NCI.

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                       B1
<PAGE>   22

Any arrangement which involves the collection of more than the summarized data
(Summary Data) provided annually to the DCTD will be at the expense of the
requesting Party or parties, RPRP and/or INTROGEN, as applicable. Should RPRP
and/or INTROGEN choose to review Patient Research Records at the research
site(s), such a review shall be at the expense of the requesting Party or
Parties, RPRP and/or INTROGEN, as applicable, and shall only occur after
agreement and notification of the investigators by NCI.

ANCILLARY STUDY SUPPORT

RPRP will also provide funding separate from this CRADA in the amount of [*]
directly to the approved study sites on an "as needed" basis to be divided among
the investigators conducting the trials to support the additional studies
approved in connection with the clinical trial program. Furthermore, RPRP will
provide funding, if needed, to support the clinical studies in other disease
sites.

INTROGEN is currently supporting all correlative laboratory studies in their
laboratory such as immunohistochemistry for p53, TUNEL essays, viral
dissemination, p53 sequencing and in situ PCR. In the event that INTROGEN is
unable to continue this arrangement, RPRP will assume responsibility for
ensuring the completion of all correlative laboratory studies approved.

AGENT Adp53

INTROGEN shall provide to NCI [*] Agent in sufficient quantities to complete the
studies approved pursuant to this CRADA. Furthermore, INTROGEN will provide
Certificates of Analysis to NCI for each lot of finished product provided which
verify the suitability of Agent for use in the scheduled preclinical studies or
clinical trial protocols.

If, for sufficient cause, or as otherwise agreed, INTROGEN is unable to supply
Agent [*] to NCI, RPRP, shall ensure supply of sufficient quantities of Agent to
NCI [*] to complete the scheduled preclinical studies or clinical trial
protocols under the Research Plan together with the above-required Certificates
of Analysis.

FUNDING

RPRP agrees to provide up to [*] per year to the NCI for the term of the CRADA
for transportation and lodging costs to support the participation of DCTD staff
at selected scientific or development meetings, where such participation will
substantially foster development of Agent. RPRP and DCTD must mutually agree to
the activities that are appropriate under this Agreement. Travel costs are
limited by the Federal Travel Rules and Regulations for the government staff
whether paid for by government funds or private Collaborators.

Any additional funding will not be added to this CRADA without an appropriate
written executed amendment pursuant to Article 13.6.

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                       B2
<PAGE>   23

No funds provided under this CRADA by RPRP will be used by NCI to pay the
salary of full-time tenured federal employees.

PAYMENT SCHEDULE

Payments shall be made annually, the first payment due within 30 days of the
execution of this CRADA. Checks should be made payable to the National Cancer
Institute and addressed to CRADA Funds Coordinator: Technology Development and
Commercialization Branch, NCI; 6120 Executive Blvd., Suite 450; Rockville, MD
20852 with a clear reference to the NCI CRADA Number and Title:

                  CACR 0352: "CLINICAL DEVELOPMENT OF ADP53".

                                       B3
<PAGE>   24

                                                                      CACR-352

                                   APPENDIX C

                   EXCEPTIONS OR MODIFICATIONS TO THIS CRADA

                                    Page C-i
<PAGE>   25
                                   APPENDIX C

                   EXCEPTIONS OR MODIFICATIONS TO THIS CRADA

AMEND ARTICLE 1 "INTRODUCTION" TO READ AS FOLLOWS:

ARTICLE 1. INTRODUCTION

This Cooperative Research and Development Agreement (CRADA) among PHS,
RHONE-POULENC RORER PHARMACEUTICALS, INC., AND INTROGEN THERAPEUTICS, INC., will
be effective when signed by all Parties, retroactive to April 9, 1996 (Letter of
Intent). The research and development activities which will be undertaken by
each of the Parties in the course of this CRADA are detailed in the Research
Plan (RP) which is attached as Appendix A. The funding and staffing commitments
of the Parties are set forth in Appendix B. Any exceptions or changes to the
CRADA are set forth in Appendix C. The Intellectual Property and Licensing is
set forth in Appendix D. A sample "Annual Scientific, Commercial, and Financial
Report" is included as Appendix E. A model Amendment is included as Appendix F.
A model termination letter is included as Appendix G. A model expiration letter
is included in Appendix H. This CRADA is made under the authority of the Federal
Technology Transfer Act, 15 U.S.C. Section 3710a and is governed by its terms.

AMEND SECTION 2.1 TO READ AS FOLLOWS:

2.1  "AFFILIATE" means any corporation or other business entity controlled by,
     controlling, or under common control with RPRP and/or Introgen. For this
     purpose, "control" means direct or indirect beneficial ownership of at
     least fifty (50) percent of the voting stock or at least fifty (50) percent
     interest in the income of such corporation or other business.

AMEND SECTION 2.6 TO READ AS FOLLOWS:

2.6  "PRINCIPAL INVESTIGATOR(S)" OR "PIS" means the persons designated
     respectively by the Parties to this CRADA who will be responsible for the
     scientific and technical conduct of the Research Plan (as

                                      C 2
<PAGE>   26
     defined in Section 2.9)

AMEND SECTION 2.7.4 TO READ AS FOLLOWS:

2.7.4     information which relates to potential hazards or cautionary warnings
          associated with the production, handling or use of the Agent
          designated in the Research Plan of this CRADA (as defined in Section
          2.13 below).

ADD THE FOLLOWING NEW SECTIONS TO ARTICLE 2. "DEFINITIONS":

2.12 "ADVERSE DRUG EXPERIENCE" means an adverse clinical experience as defined
     under 21 C.F.R. 310.305 and 312.32 where applicable.

2.13 "AGENT" means Adenovirus p53 vector (Adp53).

2.14 "ANNUAL REPORT" means the brief report of the progress of an IND associated
     investigation which the IND sponsor is required to submit to the FDA within
     60 days of the anniversary date that the IND went into effect (pursuant to
     21 C.F.R. 312.33).

2.15 "CLINICAL DATA AND RESULTS" means all information, data and results
     developed or obtained in connection with clinical trials conducted under
     the Research Plan whether by intramural research scientists or extramural
     grantee or contract investigators.

2.16 "CLINICAL DATA AND RESULTS AND RAW DATA IN NIH'S POSSESSION AND CONTROL"
     means all information, data and results collected from NIH intramural
     preclinical or clinical studies performed pursuant to the Research Plan,
     all data obtained by NIH under contracts with extramural contract
     investigator(s) for completion of studies within the scope of the Research
     Plan, and all information and data in the NCI-sponsored IND for Agent.

2.17 "CONTRACT" means a funding agreement that is a research and development
     contract that provides that the contractor perform for the benefit of the
     Government, with an expectation of completion of the stated research goals
     and the delivery of a report, data, materials or other product. Generally,
     Contracts are administered under the Federal

                                      C 3
<PAGE>   27
     Acquisition Regulations (FAR) codified at Title 48 C.F.R., Chapter 1 or the
     Health Services Acquisition Regulations (HSAR) codified at Title 48 C.F.R.,
     Chapter 3.

2.18 "CTA" means Clinical Trial Agreement.

2.19 "CTEP" means the Cancer Therapy Evaluation Program, DCTD, NCI, the program
     within NCI which plans, assesses and coordinates all aspects of clinical
     trials including extramural clinical research programs, internal resources,
     treatment methods and effectiveness, and compilation and exchange of data.

2.20 "DCTD" means Division of Cancer Treatment and Diagnosis, NCI.

2.21 "ENTITY" means a party that is not a Party to this CRADA.

2.22 "FDA" means the US Food and Drug Administration.

2.23 "GRANT" means a funding agreement that is an award of financial assistance
     which may be provided for support of basic research in a specific field of
     interest to the funding Federal agency.

2.24 "IND" means an Investigational New Drug Application submitted to the FDA to
     receive approval to conduct experimental clinical trials.

2.25 "MULTI-PARTY DATA" means clinical data from clinical studies sponsored by
     NCI pursuant to CTAs or CRADAs, where such data are collected under
     protocols involving combinations of investigational agents from more that
     one CTA or CRADA collaborator.

2.26 "NCI" means the National Cancer Institute, NIH, PHS, DHHS.

2.27 "PROTOCOL REVIEW COMMITTEE" (OR "PRC") means the CTEP/DCTD committee that
     reviews and approves studies involving NCI investigational agents and/or
     activities supported by NCI.

2.28 "RAW DATA" means the primary quantitative and empirical data first
     collected by the intramural and extramural investigators from experiments
     and clinical trials conducted within the scope of the

                                      C 4

<PAGE>   28
     Research Plan of this CRADA.

2.29 "STEERING COMMITTEE" means the joint NCI, RPRP, and Introgen research and
     development team whose composition and responsibilities with regard to the
     clinical experiments performed under this CRADA are described in Article
     3.3 of this CRADA.

2.30 "SUMMARY DATA" means a summary of the Raw Data provided to the NCI by the
     extramural investigators that will be included by NCI in an Annual Report
     to an NCI-sponsored IND, and made available by NCI to RPRP and Introgen.

AMEND SECTION 3.1 TO READ AS FOLLOWS:

3.1   PRINCIPAL INVESTIGATORS. The PHS Principal Investigators (PIs) designated
      in the RP will be responsible for the scientific and technical conduct of
      this project on behalf of PHS. RPRP and Introgen have jointly designated
      [*] and [*] respectively, as the Collaborator PIs who will be responsible
      for the scientific and technical conduct of this project on behalf of RPRP
      and Introgen, coordinating RPRP and Introgen's activities under this
      CRADA. [*] will be the primary contact and correspondent under the CRADA
      with respect to Phase II and later clinical trials conducted under the
      CRADA. [*] will be the Primary contact and correspondent under the CRADA
      with respect to Phase I clinical trials conducted under the CRADA.

ADD A NEW SECTION 3.3 AS FOLLOWS:

3.3  STEERING COMMITTEE AND CRADA RESEARCH. The Parties agree to establish a
     Steering Committee comprising at least the Principal Investigators
     designated pursuant to Article 3.1 to conduct and monitor the research of
     the Agent in accordance with the Research Plan. Members of the Steering
     Committee shall continue to remain employed by their respective employers
     under their

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

                                      C 5
<PAGE>   29
     respective terms of employment.

     Agent's clinical development under the Research Plan shall be a
     collaborative undertaking by RPRP, Introgen, and NCI. Details of this
     development beyond those set forth in the Research Plan shall be formulated
     and approved in Steering Committee meeting(s) before implementation of
     large-scale or resource intensive studies. The clinical development plans
     formulated and approved by the Steering Committee shall be implemented
     either intramurally at the NCI or extramurally under NCI-sponsored funding
     agreements.

     Additional CRADA information, including Steering Committee meeting reports,
     Protocol Review Committee records, clinical trial protocols, Institutional
     Review Board approval information, IND and general regulatory information,
     and preclinical and clinical data in NCI's possession and control shall
     remain on file with NCI.

     RPRP and/or Introgen, have the option to sponsor their own clinical trials
     and hold their own IND(s) for studies performed which are independent of
     this CRADA from which all data is proprietary solely to the sponsoring
     Party or Parties.

ADD A NEW SECTION 3.4 AS FOLLOWS:

3.4  CLINICAL PROTOCOLS. Clinical protocol proposals for each study within the
     scope of the Research Plan will be solicited from selected intramural and
     extramural clinical investigators. Each clinical protocol should describe
     in detail the research to be conducted at each center and must be submitted
     to the PRC for approval prior to implementation. Each clinical protocol
     received by NCI will be forwarded to RPRP and Introgen for review and
     comment approximately two weeks before it is reviewed by the PRC. Comments
     from RPRP and/or Introgen received by CTEP before the PRC meeting will be
     discussed by the PRC, will be given due consideration, and will
     incorporated into the protocol, absent good cause. Comments from RPRP,
     Introgen or the CTEP staff that are agreed upon in the PRC meeting

                                      C 6
<PAGE>   30
     will be formatted as a consensus review, which is returned to the
     investigator for necessary and/or suggested changes before the protocol can
     be given final approval and submitted to the FDA. A copy of the final
     approved protocol will be forwarded to RPRP and Introgen at the same time
     as it is submitted to the FDA consistent with Section 3.5 below.

          3.4.1 CLINICAL BROCHURES. Introgen and RPRP shall provide all clinical
          brochures for use in studies conducted hereunder, and only such
          clinical brochures which are inclusive of NCI study information if
          pertinent and appropriate, on Adp53 shall be used.

ADD A NEW SECTION 3.5 AS FOLLOWS TO REFLECT THE IND SPONSORSHIP UNDER THIS
CRADA:

3.5  INVESTIGATIONAL NEW DRUG APPLICATION. The Parties expect that either NCI,
     RPRP and/or Introgen will submit an IND or INDs for the studies conducted
     under the Research Plan, which may cross-reference an IND or Drug Master
     File held by the other(s). All information in INDs will be fully shared
     among NCI, RPRP, and Introgen for the studies conducted under the Research
     Plan, except as follows: If NCI files an IND for AGENT that is the subject
     of this CRADA, RPRP and/or Introgen, may, at its/their option, supply
     information in support of the IND in the form of a Drug Master File
     directly to the FDA so long as RPRP and/or Introgen grant(s) NIH a right to
     cross-reference such information in its IND filing. In the event that RPRP
     and/or Introgen supplies CONFIDENTIAL information directly to NCI in
     support of an NCI IND, such information will be protected in accordance
     with the corresponding Confidentiality provisions of Article 8 of this
     Agreement. All protocols and clinical studies conducted under this CRADA
     will be as mutually agreed by RPRP, Introgen and NCI.

ADD A NEW SECTION 3.6 AS FOLLOWS:

3.6  DRUG INFORMATION AND SUPPLY. Introgen and/or RPRP agree to provide NCI
     [*] clinical-grade Agent in

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

                                      C 7
<PAGE>   31
     sufficient quantity to complete the preclinical studies and clinical trial
     protocol(s) sponsored by NCI that are within the scope of the Research
     Plan. Furthermore, Introgen agrees to provide [*] Agent or
     unformulated analytical grade Agent or metabolites, if available, to NCI to
     supply extramural investigators for the development of mutually agreed upon
     analytical assays or ancillary correlative studies conducted in conjunction
     with NCI-sponsored protocols. Introgen will provide Certificates of
     Analysis to NCI for each lot of finished product provided. PHS agrees to
     use any materials provided by Introgen and/or RPRP, including, but not
     limited to Agent, solely for the purposes of conducting approved studies
     under this CRADA. [*]

     The contact person for NCI will be Mr. Alfred Fallavollita, Chief,
     Pharmaceutical Management Branch (Telephone Number 301-496-5725) and the
     Introgen contact will be Dr. James Merritt, (Telephone Number
     713-797-9960).

ADD A NEW SECTION 3.7 AS FOLLOWS:

3.7  PROTECTION OF HUMAN SUBJECTS AND APPROPRIATE CARE OF LABORATORY ANIMALS.
     All human clinical trials performed under this CRADA shall conform to the
     appropriate Federal law, including, but not limited to all applicable FDA
     regulations and DHHS regulations relating to the protection of human
     subjects (see 45 C.F.R. Part 46). NCI, RPRP and Introgen also agree to
     comply with all applicable Federal statutes and Public Health Service
     policies relating to the use and care of laboratory animals (see 7 U.S.C.
     2131 et seq.) Additional information is available from the Office of
     Protection from Research Risk, Telephone: 301-496-7163.

ADD THE FOLLOWING TO THE END OF ARTICLE 4.1 "INTERIM REPORTS":

     Steering Committee reports or copies of Annual Reports updating the

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

                                       C 8
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     progress of the CRADA research shall satisfy the reporting requirements
     under this Article 4.1. In addition, copies of the Annual Reports and other
     pertinent IND data (including, but not limited to, clinical brochure data,
     and formulation and preclinical data, including toxicology findings)
     created hereunder, shall be exchanged by the Parties as they become
     available.

ADD A NEW SECTION 4.3 AS FOLLOWS:

4.3  ADVERSE DRUG EXPERIENCE REPORTING. DCTD shall report all serious or
     unexpected adverse events to FDA in accordance with the reporting
     obligations of 21 CFR 312.32 and will, concurrently, forward all such
     reports to RPRP and Introgen. All other adverse event reports received by
     DCTD shall be reported to the FDA consistent with 21 CFR 312.32 and 312.33.
     In addition, copies of the Annual Reports and other pertinent IND data
     (including, but not limited to, Clinical Brochure data, formulation and
     preclinical data, including toxicology findings) will be provided to RPRP
     and Introgen as they become available.

     In the event that RPRP and/or Introgen, inform(s) the FDA of any serious or
     unexpected adverse events, RPRP and/or Introgen must notify the NCI at the
     same time. NCI will then notify the investigator(s) conducting studies
     under NCI-sponsored protocols.

ADD A NEW SECTION 4.4 AS FOLLOWS:

4.4  ANNUAL REPORTS. NCI shall provide RPRP and Introgen with a copy of the
     Annual Report simultaneously with the submission of the Annual Report to
     the FDA.

AMEND ARTICLE 5 "FINANCIAL AND STAFFING OBLIGATIONS" TO READ AS FOLLOWS:

5.1  PHS, RPRP AND INTROGEN CONTRIBUTIONS. The contributions of the Parties,
     including payment schedules, if applicable, are set forth in Appendix B.
     PHS shall not be obligated to perform any of the research specified herein
     or to take any other

                                       C 9
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     action required by this CRADA if the funding is not provided as set forth
     in Appendix B. PHS shall return excess funds to RPRP when it sends its
     final fiscal report pursuant to Article 5.2, except for staffing support
     pursuant to Article 10.3. RPRP and Introgen acknowledge that the U.S.
     Government will have the authority to retain and expend any excess funds
     for up to [*] subsequent to the expiration or termination of the
     CRADA to cover any costs incurred during the term of the CRADA in
     undertaking the work set forth in the RP.

5.2  ACCOUNTING RECORDS. PHS shall maintain separate and distinct current
     accounts, records, and other evidence supporting all its obligations under
     this CRADA, and shall provide RPRP and Introgen a final fiscal report
     pursuant to Article 4.2.

5.3  CAPITAL EQUIPMENT. Equipment purchased by PHS with funds provided by RPRP
     and/or Introgen shall be the property of PHS. All capital equipment
     provided under this CRADA by a Party or Parties for the use of another
     Party or Parties remains the property of the providing Party or Parties
     unless other disposition is mutually agreed upon by in writing by the
     respective Parties. If title to this equipment remains with the providing
     Party or Parties, that/those Party/Parties shall be responsible for
     maintenance of the equipment and the costs of its transportation to and
     from the site where it will be used.

AMEND ARTICLE 6 "INTELLECTUAL PROPERTY RIGHTS AND PATENT APPLICATIONS" TO READ
AS FOLLOWS:

6.1  REPORTING. The Parties shall promptly report to each other in writing each
     Subject Invention resulting from the research conducted under this CRADA
     that is reported to them by their respective employees. Each Party shall
     report all Subject Inventions to the other Parties in sufficient detail to
     determine inventorship. Such reports shall be treated as Proprietary/
     Confidential Information in accordance with Article 8.4.

6.2  RPRP AND/OR INTROGEN EMPLOYEE INVENTIONS. RPRP and Introgen may elect to
     retain intellectual property rights to each

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

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         Subject Invention made solely or jointly by their respective employees.
         If RPRP and/or Introgen does not elect to retain its respective sole or
         joint IP rights, RPRP and/or Introgen shall offer to assign said IP
         rights to the Subject Invention to PHS pursuant to Article 6.5. If PHS
         declines such assignment, RPRP and/or Introgen may release their IP
         rights as they may individually or jointly determine.

6.3      PHS EMPLOYEE INVENTIONS. PHS on behalf of the U.S. Government may
         elect to retain IP rights to each Subject Invention made solely by
         PHS employees. If PHS does not elect to retain IP rights, PHS shall
         offer to assign these IP rights to such Subject Invention to RPRP and
         Introgen collectively pursuant to Article 6.5. If RPRP or Introgen
         decline such an offer, the other company may obtain these IP rights.
         If both RPRP and Introgen decline such assignment, PHS may release IP
         rights in such Subject Invention to its employee inventors pursuant
         to Article 6.6.

6.4      PHS JOINT INVENTIONS WITH RPRP AND/OR INTROGEN. Each Subject Invention
         made jointly by PHS and RPRP and/or Introgen employees shall be jointly
         owned by PHS and the Party or Parties making the invention. In
         accordance with Section 6.7, Introgen may elect to file the joint
         patent or other IP application(s) on behalf of both Introgen and RPRP
         thereon and shall notify PHS promptly upon making this election whether
         the joint Subject Invention is owned by PHS and Introgen and/or RPRP.
         If Introgen decides to file such applications, it shall do so in a
         timely manner and at its own expense. If Introgen does not elect to
         file such application(s), PHS on behalf of the U.S. Government shall
         have the right to file the joint application(s) in a timely manner and
         at its own expense. If any Party decides not to retain its IP rights to
         a jointly owned Subject Invention, it shall offer to assign such rights
         to the other inventing Party/Parties pursuant to Article 6.5. If the
         other Party declines such assignment, the offering Party may release
         its IP rights as provided in Articles 6.2, 6.3, and 6.6.

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6.5  FILING OF PATENT APPLICATIONS. With respect to Subject Inventions made by
     RPRP and/or Introgen as described in Article 6.2, or by PHS as described in
     Article 6.3, a Party exercising its right to elect to retain IP rights to a
     Subject Invention agrees to file patent or other IP applications in a
     timely manner and at its own expense and after consultation with the other
     Parties. The Parties shall notify the other Parties of their decision
     regarding filing in countries other than the United States in a timely
     manner. The Parties may elect not to file a patent or other IP application
     thereon in any particular country or countries provided it so advises the
     other Parties ninety (90) days prior to the expiration of any applicable
     filing deadline, priority period or statutory bar date, and hereby agrees
     to assign its/their IP right, title and interest in such country or
     countries to the Subject Invention to the other Parties and to cooperate in
     the preparation and filing of a patent or other IP applications. In any
     countries in which title to patent or other IP rights made under this CRADA
     is transferred to RPRP and/or Introgen, RPRP and/or Introgen agrees that
     PHS inventors will share in any royalty distribution that RPRP and/or
     Introgen pays to its own inventors.

6.6  RELEASE TO INVENTORS. In the event none of the Parties to this CRADA elects
     to file a patent or other IP application on a Subject Invention, the
     Parties (if a joint invention) may retain or release their IP rights in
     accordance with their respective policies and procedures. However, the
     Government shall retain a non exclusive, non-transferable, irrevocable,
     royalty-free license to practice any such Subject Invention or have it
     practiced throughout the world by or on behalf of the Government.

6.7  PATENT EXPENSES. The expenses attendant to the filing of patent or other IP
     applications generally shall be paid by the Party filing such application.
     Introgen expressly agrees to assume full responsibility, at its expense,
     for taking all action with respect to filing, prosecuting, and obtaining
     patents and other suitable forms of protection for Collaborator Subject
     Inventions made by Introgen and/or RPRP, and if Introgen so elects under
     Article 6.4 for PHS joint inventions made with RPRP and/or Introgen under
     the RP provided that Introgen's

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choice of patent counsel is mutually acceptable to RPRP. If an exclusive or a
co-exclusive license to any Subject Invention is granted to either or both RPRP
and Introgen, the respective Party or Parties shall be responsible for [*] past
and future out-of-pocket expenses in connection with the preparation, filing,
prosecution and maintenance of any applications claiming such licensed
inventions and any patents or other IP grants that may issue on such
applications. RPRP and/or Introgen may waive its license rights on any
application, patent or other IP grant at any time, and incur no subsequent
compensation obligation for that application, patent or IP grant.

6.8     PROSECUTION OF INTELLECTUAL PROPERTY APPLICATIONS.  Within one month of
receipt or filing, each Party shall provide the other Parties with copies of the
applications and all documents received from or filed with the relevant patent
or other IP office in connection with the prosecution of such applications. Each
Party shall also provide the other Parties with the power to inspect and make
copies of all documents retained in the patent or other IP application files by
the applicable patent or other IP office. Where co-exclusive licensing is
contemplated by RPRP and Introgen, the Parties agree to consult with each other
with respect to the prosecution of applications for PHS Subject Inventions
described in Article 6.3 and joint Subject Inventions described in Article 6.4.
Introgen expressly agrees to assume full responsibility at its expense for
taking all action with respect to filing, prosecuting, and obtaining patents and
other suitable forms of protection for Subject Inventions made by Introgen
and/or RPRP, and if Introgen so elects under Article 6.4 for PHS joint
inventions made with RPRP and/or Introgen under the RP provided that Introgen's
choice of patent counsel is mutually acceptable to RPRP. If either RPRP and/or
Introgen elect to file and prosecute IP applications on joint Subject Inventions
pursuant to Article 6.4, PHS will be granted an associate power of attorney (or
its equivalent) on such IP applications.

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

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AMEND ARTICLE 7 "LICENSING" TO READ AS FOLLOWS:

7.1  OPTION FOR COMMERCIALIZATION LICENSE. With respect to Government IP rights
     to any Subject Invention not made solely by the employees of RPRP or
     Introgen, for which a patent or other IP application is filed, PHS grants
     to RPRP and Introgen, individually, an option to elect a co-exclusive
     commercialization license which is substantially in the form of the
     appropriate model PHS license agreement/s. In the event that either party
     declines the option for a co-exclusive license, the other Party may
     exercise the option to an exclusive license. Unless agreed otherwise,
     Introgen shall negotiate on behalf of Introgen and/or RPRP. This option
     does not apply to Subject Inventions conceived prior to the effective date
     of this CRADA that are reduced to practice under this CRADA, if prior to
     that reduction to practice, PHS has filed a patent application on the
     invention and has licensed it or offered to license it to an Entity. The
     terms of the license will fairly reflect the nature of the invention, the
     relative contributions of the Parties to the invention and the CRADA, the
     risks incurred by RPRP and Introgen individually, and the costs of
     subsequent research and development needed to bring the invention to the
     marketplace. The field of use of the license will be commensurate with the
     scope of the RP. PHS acknowledges that Agent has been actually reduced to
     practice with respect to the treatment of cancer, independent of the CRADA
     and prior to the performance of the Research Plan.

7.2  EXERCISE OF LICENSE OPTION. The option of Article 7.1 must be exercised by
     written notice mailed within [*] after either (i) RPRP and
     Introgen, respectively, receives written notice from PHS that the patent or
     other IP application has been filed; or (ii) the date Introgen files such
     IP application (Party responsible for patent prosecution); whichever comes
     first. Exercise of this option by either or both RPRP and Introgen
     initiates a negotiation period that expires [*] after the
     exercise of the option. If the last proposal by RPRP and/or Introgen has
     not been responded to in writing by PHS within this [*] period,
     the negotiation period shall be extended

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

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<PAGE>   38
         to expire [*] after PHS so responds, during which month RPRP and/or
         Introgen may accept in writing the final license proposal of PHS. [*]
         In the event that RPRP and/or Introgen elects the option for a
         co-exclusive license but no such license is executed during the
         negotiation period, PHS agrees not to make an offer for an exclusive
         license on more favorable terms to an Entity for a period of [*]
         without first offering RPRP and Introgen those more favorable terms.
         These times may be extended at the sole discretion of PHS upon good
         cause shown in writing by Collaborator.

7.3      LICENSE FOR PHS EMPLOYEE INVENTIONS AND JOINT INVENTIONS. Pursuant to
         15 U.S.C. Section 3710a(b)(1)(A), for Subject Inventions made under
         this CRADA by PHS employee(s) or jointly by such employee(s) and
         employees of RPRP and/or Introgen pursuant to Articles 6.3 and 6.4 and
         licensed pursuant to the option of Article 7.1, RPRP and/or Introgen,
         as applicable, grant(s) to PHS a nonexclusive, nontransferable,
         irrevocable, paid-up license to practice the invention or have the
         invention practiced throughout the world by or on behalf of the
         Government. In the exercise of such license, the Government shall not
         publicly disclose trade secrets or commercial or financial information
         that is privileged or confidential within the meaning of 5 U.S.C.
         552(b)(4) or which would be considered as such if it had been obtained
         from a non-Federal party.

7.4      LICENSE IN RPRP AND INTROGEN INVENTIONS. Pursuant to 15 U.S.C. Section
         3710a(b)(2), for inventions made solely by RPRP and/or Introgen
         employees under this CRADA, pursuant to Article 6.2, RPRP and Introgen
         grants to the Government a nonexclusive, nontransferable, irrevocable,
         paid-up license to practice the invention or have the invention
         practiced throughout the world by or on behalf of the Government for
         research or other Government purposes.

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

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7.5  LICENSE TO AN ENTITY. Pursuant to 15 U.S.C. Section 3710a(1)(B), if PHS
     grants an exclusive or co-exclusive license to a Subject Invention made
     wholly by PHS employees or jointly with RPRP and/or Introgen under this
     CRADA, pursuant to Articles 6.3 and 6.4, the Government shall retain the
     right to require RPRP and/or Introgen to grant to a responsible applicant a
     non-exclusive, partially exclusive or exclusive sublicense to use the
     invention in RPRP and/or Introgen's licensed field of use on terms that are
     reasonable under the circumstances; or if RPRP and/or Introgen fail to
     grant such a license, to grant the license itself. The exercise of such
     rights by the Government shall only be in exceptional circumstances and
     only if the Government determines (i) the action is necessary to meet
     health or safety needs that are not reasonably satisfied by RPRP and/or
     Introgen, (ii) the action is necessary to meet requirements for public use
     specified by Federal regulations, and such requirements are not reasonably
     satisfied by RPRP and/or Introgen or (iii) RPRP and/or Introgen has failed
     to comply with an agreement containing provisions described in 15 U.S.C.
     3710a(c)(4)(B). The determination made by the Government under this Article
     is subject to administrative appeal and judicial review under 35 U.S.C.
     203(2).

7.6  JOINT INVENTIONS NOT EXCLUSIVELY LICENSED. In the event that RPRP and/or
     Introgen do(es) not acquire a co-exclusive or exclusive commercialization
     license to IP rights in all fields in joint Subject Inventions described
     in Article 6.4, then each Party shall have the right to use the joint
     Subject Invention and to license its use to others in all fields not
     exclusively or co-exclusively licensed to RPRP and Introgen. The Parties
     may agree to a joint licensing approach for such IP rights.

AMEND SECTION 8.1 TO READ AS FOLLOWS:

8.1  RIGHT OF ACCESS. PHS, RPRP and Introgen agree to exchange all Subject Data
     produced in the course of research under this CRADA, whether developed
     solely or jointly by and Party/Parties. Research Materials will be shared
     equally by the Parties to the CRADA unless other disposition is agreed to
     by the

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

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         Parties. All Parties to this CRADA will be free to utilize Subject Data
         and Research Materials for their own purposes, consistent with their
         obligations under this CRADA.

AMEND SECTION 8.3 TO READ AS FOLLOWS:

8.3      DISSEMINATION OF SUBJECT DATA AND RESEARCH MATERIALS. To the extent
         allowed under law, RPRP, Introgen and PHS agree to use reasonable
         efforts to keep Subject Data and Research Materials confidential until
         published or until corresponding patent applications are filed. Any
         information that would identify human subjects of research or patients
         will always be maintained confidentially. To the extent permitted by
         law, RPRP and Introgen, respectively, shall have the co-exclusive right
         to use any and all CRADA Subject Data in and for any regulatory filing,
         or for any commercialization purpose, consistent with Articles 8.7 and
         13.10, except that PHS shall have the exclusive right to use Subject
         Data for said purpose/s, and authorize others to do so, if the CRADA is
         terminated or if RPRP and Introgen abandon their commercialization
         efforts consistent with the terms of Section 10.6.

AMEND SECTION 8.4 AS FOLLOWS:

8.4      PROPRIETARY/CONFIDENTIAL INFORMATION. Each Party agrees to limit its
         disclosure of Proprietary/Confidential Information received from
         another Party to this CRADA to other Entities to the amount necessary
         to carry out the Research Plan of this CRADA, and shall place a
         confidentiality notice on all such information. Confidential oral
         communications shall be reduced to writing within 30 days by the
         disclosing Party. Each Party receiving Proprietary/Confidential
         Information of another Party pursuant to this CRADA, agrees that any
         information so designated shall be used by it only for the purposes
         described in the attached Research Plan. Any Party may object to the
         designation of information as Proprietary/Confidential Information by
         another Party. Subject Data and Research Materials developed solely by
         RPRP or Introgen may be designated as Proprietary/Confidential
         Information when they are wholly separable from the Subject Data and
         Research Materials developed jointly with

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         PHS investigators, and advance designation of such data and material
         categories is set forth in the RP. The exchange of other confidential
         information, e.g., patient-identifying data, should be similarly
         limited and treated. Jointly developed Subject Data and Research
         Material derived from the Research Plan may be disclosed by RPRP and/or
         Introgen to a third party under a confidentiality agreement for the
         purpose of possible sublicensing pursuant to the Licensing Agreement
         and subject to Article 8.7.

                  In addition, a Party may disclose Proprietary/Confidential
                  Information of another Party with the written consent of such
                  other Party, which consent will not be unreasonably withheld.

AMEND SECTION 8.6 AS FOLLOWS:

8.6      DURATION OF CONFIDENTIALITY OBLIGATION. The obligation to maintain the
         confidentiality of Proprietary/Confidential Information shall expire
         at the earlier of the date when the information is no longer
         Proprietary/Confidential Information as defined in Article 2.7 or
         three (3) years after the expiration or termination date of this CRADA
         unless, after the said three (3) years, any Party informs the other
         Parties that the Proprietary/Confidential Information is still secret
         and confidential, in which case the obligation shall extend for a
         further period of two (2) additional years. RPRP and/or Introgen may
         request additional extensions to this term when necessary to protect
         Proprietary/Confidential Information relating to products not yet
         commercialized.

AMEND SECTION 8.7 AS FOLLOWS:

8.7      PUBLICATION. The Parties are encouraged to make publicly available the
         results of their research. Except as provided at the end of this
         paragraph with respect to abstracts, before NCI, RPRP, Introgen or any
         combination thereof, submits a paper for publication or otherwise
         intends to publicly disclose information about a Subject Invention,
         Subject Data, additional Clinical Data and Results and Raw Data in
         NIH's Possession and Control, or Research Materials, the other Parties
         shall be provided thirty (30) days to review the proposed publication
         or disclosure to assure that

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     Proprietary/Confidential Information is protected. The publication or other
     disclosure shall be delayed for up to thirty (30) additional days upon
     written request by any Party as necessary to preserve U.S. or foreign
     patent or other IP rights. Abstracts presented by NCI investigators will be
     sent to NCI's Regulatory Affairs Branch for forwarding to RPRP and Introgen
     after submission but prior to presentation or publication to permit
     preservation of U.S. and foreign patent rights.

ADD A NEW SECTION 8.8 AS FOLLOWS:

8.8  EXTRAMURAL RESEARCH AND DATA. In pursuing the development of Agent pursuant
     to this CRADA, NIH may utilize extramural investigators for part or all of
     the completion of this Research Plan through either Federal Grants or
     Federal Contracts. Participation by extramural contract or grantee
     investigators shall be determined after competitive solicitation and review
     of study protocols by NIH. However, said extramural contract or grantee
     investigators are not Parties to this CRADA, and this CRADA does not
     address rights to intellectual property created by such investigators.
     Nonetheless:

     a.  Subject to the other provisions of Article 8 of this CRADA, NIH shall
         maintain, to the extent permitted by law, all IND, Clinical Data and
         Results and Raw Data in NIH's Possession and Control as Proprietary and
         CONFIDENTIAL, and make them available co-exclusively to RPRP and
         Introgen for each Party's (including sublicensees and affiliates) own
         use and for use in obtaining FDA approval for the commercial marketing
         of Subject Inventions and Agent products. Accordingly, said data shall
         not be transferable to an Entity without the written permission of the
         NCI.

     b.  NIH shall not execute a Contract for preclinical studies or clinical
         trials for the development of Agent unless the extramural contract
         investigator agrees to confidentiality provisions at least as
         restrictive as provided in this CRADA and to the co-exclusive use of
         data, by RPRP and Introgen, in accordance with Article 8.8 (a), for
         each Party's own use and for use in obtaining FDA approval for

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          the commercial marketing of Agent. The NCI investigators agree to use
          Agent only for the conduct of the approved protocols.

     c.   NCI shall urge all extramural grantee investigators participating in
          the studies sponsored by NCI and using Agent to cooperate
          co-exclusively with RPRP and Introgen in providing Clinical Data and
          Results and Raw Data for use in obtaining pharmaceutic regulatory
          approval for the commercial marketing of Agent. However, NCI's urging
          will not constitute a term or condition for making a grant award to
          said extramural investigators.

     d.   In seeking direct access to Clinical Data and Results and Raw Data or
          any other information that is in the possession of extramural contract
          or grantee investigators working with Agent under the sponsorship of
          NCI, RPRP and/or Introgen shall first contact the Regulatory Affairs
          Branch, (RAB) NCI [telephone: 301-496-7912]. Subsequent to
          authorization by RAB, RPRP and/or Introgen may directly contact the
          extramural investigators. Costs associated with providing Clinical
          Data and Results or Raw Data to RPRP and/or Introgen in customized
          formats shall be borne by the requesting party or parties.

     e.   RPRP's and Introgen's co-exclusive access under subsection (a) above
          to Clinical Data and Results and Raw Data in NIH's Possession and
          Control is dependent, however, upon RPRP and/or Introgen's continued
          development and commercialization of the technology. In the event that
          RPRP and Introgen discontinue development or commercialization of the
          technology without the transfer of its development efforts to another
          party, NCI retains the right to make the Clinical Data and Results and
          Raw Data in NIH's Possession and Control available to another
          collaborator, consistent with the terms of Section 10.6.

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ADD A NEW ARTICLE 8.9 "MULTI-PARTY DATA RIGHTS" AS FOLLOWS:

8.9  MULTI-PARTY DATA RIGHTS. For clinical protocol(s) where Agent is used in
     combination with another proprietary investigational agent supplied to NCI
     pursuant to a CTA or CRADA between NCI and an Entity, the access and use of
     Multi-Party Data by RPRP and Introgen, and Entity, shall be co-exclusive as
     follows:

     a.  NCI will provide RPRP, Introgen and Entity with notice regarding the
         existence and nature of the agreements governing their collaborations
         with NIH, the design of the proposed combination protocol(s), and the
         existence of any obligations that might restrict NCI's participation in
         the proposed combination protocols.

     b.  RPRP and Introgen shall agree to permit use of the Multi-Party Data
         from these trials by Entity to the extent necessary to allow Entity to
         develop, obtain regulatory approval for, or commercialize its own
         investigational agent(s). However, this provision will not apply unless
         Entity also agrees to RPRP's and Introgen's reciprocal use of
         Multi-Party Data.

     c.  RPRP, Introgen and Entity must agree in writing prior to the
         commencement of the combination trials that each will use the
         Multi-Party Data solely for the development, regulatory approval, and
         commercialization of its own investigational agent(s).

AMEND ARTICLE 9 "REPRESENTATIONS AND WARRANTIES" TO READ AS FOLLOWS:

9.1  REPRESENTATIONS AND WARRANTIES OF PHS. PHS hereby represents and warrants
     to RPRP and Introgen that the official signing this CRADA has authority to
     do so.

9.2  REPRESENTATIONS AND WARRANTIES OF RPRP AND INTROGEN.

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     (a) RPRP and Introgen, each individually, hereby represents and warrants to
     PHS that it has the requisite power and authority to enter into this CRADA
     and to perform according to its terms, and that RPRP's Official and
     Introgen's Official signing this CRADA, each individually, has authority to
     do so. RPRP and Introgen, each individually, further represents that it is
     financially able to satisfy any funding commitments made in Appendix B.

     (b) RPRP and Introgen, each individually, certifies that the statements
     herein are true, complete, and accurate to the best of its knowledge. RPRP
     and Introgen, respectively, is aware that any false, fictitious, or
     fraudulent statements or claims may subject it to criminal, civil, or
     administrative penalties.

AMEND SECTION 10.1 TO READ AS FOLLOWS:

10.1 TERMINATION BY MUTUAL CONSENT. PHS, RPRP and/or Introgen, may terminate
     this CRADA, or portions thereof, at any time by mutual written consent. In
     such event the Parties shall specify the disposition of all property,
     inventions, patent or other IP applications and other results of work
     accomplished or in progress, arising from or performed under this CRADA,
     all in accordance with the rights granted to the Parties under the terms of
     this Agreement.

AMEND SECTION 10.2 TO READ AS FOLLOWS:

10.2 UNILATERAL TERMINATION. Either PHS or RPRP or Introgen may unilaterally
     terminate this entire CRADA at any time by giving written notice at least
     thirty (30) days prior to the desired termination date, and any rights
     accrued in property, patents or other IP rights shall be disposed of as
     provided in paragraph 10.1. However, in the event of unilateral termination
     or early expiration, RPRP's and Introgen's respective obligations under
     Article 3.6 will survive termination to the extent necessary to complete
     approved clinical studies under mutually agreed upon protocols.

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<PAGE>   46

AMEND SECTION 10.3 TO READ AS FOLLOWS:

10.3 STAFFING. If this CRADA is mutually or unilaterally terminated prior to its
     expiration, funds will nevertheless remain available to PHS for continuing
     any staffing commitment made by RPRP and/or Introgen pursuant to Article
     5.1 above and Appendix B, if applicable, for a period of [*] after such
     termination. If there are insufficient funds to cover this expense, RPRP
     and/or Introgen agree/s to pay the difference.

AMEND SECTION 10.5 TO READ AS FOLLOWS:

10.5 TERMINATION COSTS. Concurrently with the exchange of final reports pursuant
     to Articles 4.2 and 5.2, PHS shall submit to RPRP and/or Introgen, as
     applicable, for payment a statement of all costs incurred prior to the date
     of termination and for all reasonable termination costs including the cost
     of returning RPRP and/or Introgen's property or removal of abandoned
     property, for which RPRP and/or Introgen shall be responsible.

ADD A NEW SECTION 10.6 AS FOLLOWS:

10.6 RESEARCH LICENSE AND ALTERNATIVE SOURCES OF SUPPLY IN THE EVENT RPRP AND
     INTROGEN TERMINATE DEVELOPMENT OF AGENT.

     If both RPRP and Introgen terminate development of AGENT without the
     transfer of development efforts to another Entity, and NCI elects to
     continue its development of the Agents, then:

     a. RPRP and Introgen hereby grant/s to NCI a nonexclusive, nontransferable,
     irrevocable, paid-up license to practice or have practiced solely for use
     in preclinical studies and clinical trials described in the Research Plan
     any patentable invention which RPRP and/or Introgen owns on Agent, its
     manufacture, or on the process of the use of the Agent, throughout the
     world, and solely for [*];

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

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and

b. For use solely in preclinical studies and approved clinical trials, RPRP
and/or Introgen will supply to NCI, [*], Agent from RPRP's and/or Introgen's
inventory, or arrange for an independent contractor to manufacture and supply
NCI with Agent, [*].

RPRP's and/or Introgen's obligation shall last until either a date on which an
alternate source of equivalent materials, acceptable to NCI, can be obtained by
NCI, or [*] after the date of notification from RPRP and/or Introgen to NCI that
RPRP and Introgen terminate their development of Agent whichever comes first.

AMEND SECTION 12.1 TO READ AS FOLLOWS:

12.1 PROPERTY. The U.S. Government shall not be responsible for damages to any
     RPRP and/or Introgen property provided to PHS, where RPRP and/or Introgen
     retains title to the property, or any property acquired by RPRP and/or
     Introgen for its own use pursuant to this CRADA.

AMEND SECTION 12.3 TO READ AS FOLLOWS:

12.3 INDEMNIFICATION. No indemnification for any loss, claim, damage or
     liability is intended or provided by any party under this agreement. Each
     party shall be liable for any loss, claim, damage or liability that said
     party incurs as a result of its activities under this agreement, except
     that the NIH, as an agency of the United States, assumes liability only to
     the extent provided under the Federal Tort claims Act, 28 U.S.C. 2671 et
     seq.

AMEND SECTION 12.4 TO READ AS FOLLOWS:

12.4 FORCE MAJEURE. No Party shall be liable for any unforeseeable event beyond
     its reasonable control not caused by the fault or negligence of such Party,
     which causes such Party to be

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                      C 24
<PAGE>   48
     unable to perform its obligations under this CRADA, and which it has been
     unable to overcome by the exercise of due diligence. In the event of the
     occurrence of such a force majeure event, the Party unable to perform shall
     promptly notify the other Parties. The Party shall further use reasonable
     efforts to resume performance as quickly as possible and shall suspend
     performance only for such period of time as is necessary as a result of the
     force majeure event.

ADD SECTION 12.5 AS FOLLOWS:

12.5 LIABILITIES OF RPRP AND INTROGEN. It is understood and agreed that all
     liabilities and obligations of RPRP and Introgen hereunder are the separate
     obligations of such Parties and not joint several liabilities.

ADD SECTION 12.6 AS FOLLOWS:

12.6 NO EFFECT ON EXISTING AGREEMENTS BETWEEN RPRP AND INTROGEN.

     The provisions of this Agreement are not intended to modify or amend the
     provisions of any existing agreement between RPRP and Introgen.

AMEND SECTION 13.4 TO READ AS FOLLOWS:

13.4 WAIVERS. None of the provisions of this CRADA shall be considered waived by
     any Party unless such waiver is given in writing to the other Parties. The
     failure of a Party to insist upon strict performance of any of the terms
     and conditions hereof, or failure or delay to exercise any rights provided
     herein or by law, shall not be deemed a waiver of any rights of any Party.

AMEND SECTION 13.6 TO READ AS FOLLOWS:

13.6 AMENDMENTS. If any Party desires a modification to this CRADA, the Parties
     shall, upon reasonable notice of the proposed modification or extension by
     the Party desiring the change, confer in good faith to determine the
     desirability of such modification or extension. Such modification shall not
     be effective until a written

                                      C 25
<PAGE>   49

      amendment is signed by the signatories to this CRADA or by their
      representatives duly authorized to execute such amendment.

AMEND SECTION 13.7 TO READ AS FOLLOWS:

13.7  ASSIGNMENT. Neither this CRADA nor any rights or obligations of any Party
      hereunder shall be assigned or otherwise transferred by any Party without
      the prior written consent of the other Parties. Such consent will not
      unreasonably be withheld by any Party. Not withstanding the foregoing,
      Introgen and RPRP each shall have the right to assign this Agreement to
      their subsidiaries, affiliates or successors.

AMEND SECTION 13.9 TO READ AS FOLLOWS:

13.9  INDEPENDENT CONTRACTORS. The relationship of the Parties to this CRADA is
      that of independent contractors and to agents of each other or joint
      venturers or partners. Except as set forth herein, no Party shall have the
      authority to bind or act on behalf of any other Party. Each Party shall
      maintain sole and exclusive control over its personnel and operations.
      RPRP and Introgen employees who will be working at PHS facilities may be
      asked to sign a Guest Researcher or Special Volunteer Agreement
      appropriately modified in view of the terms of this CRADA.

AMEND SECTION 13.10 TO READ AS FOLLOWS:

13.10 USE OF NAME OF ENDORSEMENTS. By entering into this CRADA, PHS does not
      directly or indirectly endorse any product or service provided, or to be
      provided, whether directly or indirectly related to either this CRADA or
      to any patent or other IP license or agreement which implements this CRADA
      by its successors, assignees, or licensees. RPRP and Introgen shall not in
      any way state or imply that this CRADA is an endorsement of any such
      product or service by the U.S. Government or any of its organizational
      units or employees. RPRP and/or Introgen issued press releases that
      reference or rely upon the work of PHS under this CRADA shall be made
      available to PHS at least 7 days prior to publication for review and
      comment.

                                      C 26
<PAGE>   50
ADD A NEW SECTION 13.13 "FDA MEETINGS" AS FOLLOWS:

13.13 FDA MEETINGS. All meetings with FDA concerning clinical studies for the
      development of Agent within the scope of the Research Plan will be
      discussed by RPRP, Introgen and NCI in advance and will be held on
      mutually agreed upon dates. RPRP and Introgen each reserve the right to
      set, jointly  with NCI, the agenda for and attend any such meeting.

AMEND SECTION 14.2 "SURVIVABILITY" BY INCLUDING ARTICLES 4.3 (ADVERSE DRUG
EXPERIENCE REPORTING) AND 10.6 (RESEARCH LICENSE AND ALTERNATIVE SOURCES OF
SUPPLY IN THE EVENT THAT COLLABORATOR TERMINATES DEVELOPMENT OF AGENT) AND THE
LAST SENTENCE OF ARTICLE 10.2 (REGARDING DRUG SUPPLY IN THE EVENT OF EITHER
RPRP'S OR INTROGEN'S UNILATERAL TERMINATION) AS PROVISIONS THAT WILL
SURVIVE TERMINATION OF THIS CRADA.

                                      C 27
<PAGE>   51
                                                                      CACR-352

                                   APPENDIX D

                      INTELLECTUAL PROPERTY AND LICENSING

                                    PAGE D-i
<PAGE>   52
                                                                        CACR-352
                                   APPENDIX D
                      INTELLECTUAL PROPERTY AND LICENSING
--------------------------------------------------------------------------------

                                      [*]

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                      D-1
<PAGE>   53

                                      [*]

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                      D-2
<PAGE>   54

                                                                      CACR-352

                                   APPENDIX E

              ANNUAL SCIENTIFIC, COMMERCIAL, AND FINANCIAL REPORTS

                                    Page E-i
<PAGE>   55
NCI Office of Technology Development and Commercialization Branch, 1992 CACR-352

                         ANNUAL SCIENTIFIC, COMMERCIAL
                              AND FINANCIAL REPORT

As required under Article 4, "Reports," the NIH/ADAMHA Principal Investigator
and Collaborator Principal Investigator will complete this report by "setting
forth technical progress made, identifying such problems as may have been
encountered and establishing goals and objectives requiring further effort." If
necessary, please use additional space and send this report to the NCI Office
of Technology Development and Commercialization Branch, Executive Plaza South,
Room 450, 6120 Executive Boulevard, Rockville, Maryland, 20852.

Please describe any scientific or technical progress:

Please describe any commercial development including staffing and financial
resources involved:

Please provide an accounting and balance of staffing and financial resources
provided to the NIH/ADAMHA principal investigator (i.e.: personnel, equipment
and supplies):

--------------------------------------------------------------------------------
I certify that, to the best of my knowledge, all of the above information is
true and accurate.

   NIH/ADAMHA Principal Investigator's Signature

 ------------------------------------------------      -------------------------
                         [*]                            Date

 ------------------------------------------------      -------------------------
                         [*]                            Date

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.
<PAGE>   56

                                                                      CACR-352

                                   APPENDIX F
                                   AMENDMENTS

                   A model Amendment follows this cover page.

                                    Page F-i
<PAGE>   57
                                   AMENDMENT

CURRENT CRADA TERMS
--------------------------------------------------------------------------------

                              CURRENT CRADA TERMS

<TABLE>
<S>                                   <C>                  <C>
     CRADA #: 00352            TERM EXTENSION(s)(mo):       NIH PI: [*]
     EFFECTIVE DATE: 4/9/96           [ ]                   INSTITUTE: NCI
     EXECUTED DATE:                   [ ]                   DIVISION: DCTD
     ORIG.TERM (MO):                  [ ]                   LABORATORY: CTEP
     TOTAL TERM (MO):                 [ ]                   COLLABORATING PI: [*]
     EXPIRATION:                      [ ]                   COLLABORATOR: RPRP & INTROGEN
</TABLE>

Title: CLINICAL DEVELOPMENT OF Adp53

--------------------------------------------------------------------------------

NEW CRADA TERMS

The purpose of this amendment is to change certain terms of the above
referenced Cooperative Research and Development Agreement. These changes are
reflected below and except for these changes and those of any previous
amendments, all other provisions including the research plan of the original
CRADA remain in full force and effect. Two originals of this amendment are
provided for execution--one is to remain with NCI and the other with the
collaborator.

================================================================================
ACCEPTED AND AGREED TO:
NCI                                                      RPRP & INTROGEN

-----------------------                                  -----------------------
ALAN S. RABSON, M.D.
Deputy Director, NCI

-----------------------                                  -----------------------
Date                                                     Date

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.
<PAGE>   58
                                   APPENDIX G

                                  TERMINATION

              A model termination letter follows this cover page.

                                    Page G-i
<PAGE>   59
              [DEPARTMENT OF HEALTH AND HUMAN SERVICES LETTERHEAD]

Dear Collaborator:

As stipulated in Article 10, "Termination," the NIH/ADAMHA and/or the
Collaborator may terminate the CRADA referenced below by the either mutual
consent (Article 10.1) or unilaterally (Article 10.2). If terminated by mutual
consent, both parties will sign below and shall specify the disposition of all
property, inventions, patent or other intellectual property rights. Two
originals of this termination letter are provided for execution -- one is to
remain with the NCI and the other with the collaborator. If unilateral
termination occurs, this CRADA will cease to exist in thirty (30) days to the
date of this letter and, again, any rights accrued in property, patents or any
other intellectual rights will be specified and disposited.

If this CRADA is either mutually or unilaterally terminated prior to its
expiration, any remaining funds will nevertheless remain available to
NIH/ADAMHA for any continuing staffing commitments made by the Collaborator
pursuant to Articles 5.2 & 10.3 and Appendix B, if applicable, for a period of
six (6) months after such termination. If there are insufficient funds to cover
this expense, the Collaborator agrees to pay the difference (Article 10.3). In
addition, all reasonable termination costs will also be incurred by the
Collaborator. Finally, pursuant to Articles 4.2 and 5.2, a final report is
enclosed and provisions of article 4.2, 5.1, 5.2, 5.3, Articles 6-8, 10.3,
10.5, 11.1, 12.3 and 13.10 shall survive the termination of this CRADA.

                            CRADA MANAGEMENT MODULE
<TABLE>
<S>                                  <C>
          CACR    00352                 NIH/ADAMHA Principal Investigator   [*]
                                                                Institute   NCI
Effective Date                                                   Division   DCTD
                                                               Laboratory   CTEP
  Term (years)    [*]                Collaborating Principal Investigator   [*]
                                                             Collaborator   RPRP & INTROGEN
    Expiration

Title     CLINICAL DEVELOPMENT OF Adp53
</TABLE>

Accepted and Agreed To:

NATIONAL CANCER INSTITUTE                   RPRP & INTROGEN

----------------------------------          ------------------------------------
 Alan S. Rabson, M.D.
 Deputy Director, NCI

-----------------------                     -----------------------
Date                                        Date

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.
<PAGE>   60
                                   APPENDIX H

                                   EXPIRATION

               A model expiration letter follows this cover page.

                                    Page H-i
<PAGE>   61
                                   APPENDIX A

               [DEPARTMENT OF HEALTH & HUMAN SERVICES LETTERHEAD]

                                                            Coordinator
                                                            Document Type:
                                                                          -----
                                                            File Numbers: 00352
                                                                          -----

March 26, 1996

Mr. Martin Savitsky
General Counsel
RPR Gencell
500 Arcola Road
P.O. Box 1200
Collegeville, PA 19426

Re:            Proposed Cooperative Research and Development Agreement (CRADA)
               NCI Principal Investigator:       [*]
               Collaborator Investigator:        [*]
               Title:      Clinical Development of Adenovirus - P53
               RPR FILE NO. A2172, NCI CRADA # 352

Dear Mr. Savitsky,

It is my understanding that a cooperative research and development project
between the parties referenced below is being considered. Accordingly, until a
formal Collaborative Research and Development Agreement (CRADA) is reviewed by
the CRADA Subcommittee and approved by the Director, National Cancer Institute
(NCI), this Letter is offered to permit joint research to commence.

o         The Parties agree that all such trials which may begin prior to the
          execution of the formal CRADA Agreement shall be preceded by the
          appropriate US Food and Drug Association IND approval (or
          international equivalents thereof).

o         The Parties acknowledge that cooperative research pursuant to the
          Research Plan, attached as Appendix A, will be conducted informally by
          the NCI Principal Investigator and Collaborator pending formal
          approval of this CRADA. It is further acknowledged that patentable
          inventions may be made by NCI employees and employees of the
          Collaborator. Pursuant to its authority under Federal Technology
          Transfer Act of 1986, NCI agrees that should this CRADA be approved,
          it will have retroactive effect to the date that the last party has
          executed the Letter for any inventions that may be made under this
          Research Plan.

o         NCI further agrees that this CRADA will have retroactive effect to the
          date that the last party has executed this Letter for confidentiality
          obligations specified in the NIH Model CRADA.

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                       1
<PAGE>   62
o           The NIH Model CRADA provisions for the protection of proprietary
            information are incorporated by reference and in the event that any
            conflict arises between the provisions set forth in the NIH Model
            CRADA and the negotiated CRADA, the terms of the negotiated CRADA
            will control. These provisions include, but are not limited to,
            Article 2.5 and Articles 8.1 to 8.7. The NIH Model CRADA is attached
            as Appendix B.

This letter is not a commitment on the part of either party to enter into a
CRADA. Further, this Letter is effective for a term of (1) year. The one year
term may be extended, provided the CRADA is under active negotiation and the
collaborative research is continuing.

Assuming the necessary approvals are forthcoming, we look forward to a
successful collaboration.

Sincerely,

/s/ THOMAS D. MAYS

Thomas D. Mays, Ph.D., J.D.
Director, NCI Office of Technology Development

================================================================================

ACCEPTED AND AGREED TO:

NATIONAL CANCER INSTITUTE               RHONE POULENC RORER PHARMACEUTICALS INC.

/s/ ALAN RABSON, M.D.                   /s/ KENNETH R. PINA, ESQ.
-----------------------------           -----------------------------------
ALAN RABSON, M.D.                       KENNETH R. PINA, ESQ.
Deputy Director, NCI                    Vice President, General Counsel &
                                        Secretary

March 29, 1996                          April 8, 1996
-----------------                       -----------------
Date                                    Date

INTROGEN THERAPEUTICS, INC.

/s/ DAVID NANCE
-----------------------------
DAVID NANCE
President

April 9, 1996
-----------------
Date

Attachments:
     Appendix A: Proposed Research Plan
     Appendix B: NCI Model CRADA

                                       2
<PAGE>   63
                                   Appendix B

               [DEPARTMENT OF HEALTH & HUMAN SERVICES LETTERHEAD]

March 28, 1997

Mr. Robert Werner
General Counsel
RPR Gencell
500 Arcola Road
P.O. Box 1200
Collegeville, PA 19426

Re:    Proposed Cooperative Research and Development Agreement (CRADA)
       CRADA #: 352
       NCI Principal Investigator: [*]
       Collaborator Investigator:  [*]
       Title: Clinical Development of Adenovirus - p53

Dear Mr. Werner:

It is my understanding that a cooperative research and development project
between the parties referenced below is being considered. Accordingly, until a
formal Cooperative Research and Development Agreement (CRADA) is reviewed by
the CRADA Subcommittee and approved by the Director, National Cancer Institute
(NCI), this Letter is offered to extend the original Letter of Intent, executed
April 8, 1996, in order to permit the joint research to continue. A copy of the
Original Letter of Intent is attached as Appendix A.

o      The Parties agree that all such trials which may begin prior to the
       execution of the formal CRADA Agreement shall be preceded by the
       appropriate U.S. Food and Drug Administration IND approval (or
       international equivalents thereof).

o      The Parties acknowledge that cooperative research pursuant to the
       Research Plan, attached as Appendix B, will be conducted informally by
       the NCI Principal Investigator and Collaborator pending formal approval
       of this CRADA. It is further acknowledged that patentable inventions may
       be made by NCI employees and employees of the Collaborator. Pursuant to
       its authority under Federal Technology Transfer Act of 1986, NCI agrees
       that should this CRADA be approved, it will have retroactive effect to
       the date that the last party has executed the original Letter of Intent
       (April 8, 1996) for any inventions that may be made under this Research
       Plan.

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.
<PAGE>   64
o           NCI further agrees that this CRADA will have retroactive effect to
            the date that the last party has executed this Letter for
            confidentiality obligations specified in the NIH Model CRADA,
            revised 5/30/96 (this model supersedes the CRADA model revised
            12/15/95 attached as Appendix B to the original Letter of Intent
            executed April 8, 1996).

o           The NIH Model CRADA (revised 5/30/96) provisions for the protection
            of proprietary information are incorporated by reference and in the
            event that any conflict arises between the provisions set forth in
            this NIH Model CRADA and the negotiated CRADA, the terms of the
            negotiated CRADA will control. These provisions include but are not
            limited to, Article 2.5 and Articles 8.1 to 8.7. The NIH Model CRADA
            is attached as Appendix C.

This letter is not a commitment on the part of either party to enter into a
CRADA. Further, this Letter is effective for a term not to exceed six (6)
months.

Assuming the necessary approvals are forthcoming, we look forward to a
successful collaboration.

Sincerely,

/s/ THOMAS D. MAYS, PH.D., J.D.
-------------------------------
Thomas D. Mays, Ph.D., J.D.
Director, NCI Office of Technology Development

================================================================================

ACCEPTED AND AGREED TO:

NATIONAL CANCER INSTITUTE               RHONE POULENC RORER PHARMACEUTICALS INC.

/s/ ALAN S. RABSON, M.D.                /s/ KENNETH R. PINA, ESQ.
-----------------------------           -----------------------------------
Alan S. Rabson, M.D.                    Kenneth R. Pina, Esq.
Deputy Director NCI                     Vice President, General Counsel &
                                        Secretary

April 4, 1997                           April 4, 1997
-----------------                       -----------------
Date                                    Date

INTROGEN THERAPEUTICS, INC.

/s/ DAVID NANCE
-----------------------------
David Nance
President

April 16, 1997
-----------------
Date

Attachments:
     Appendix A: Original Letter of Intent
     Appendix B: Proposed Research Plan
     Appendix C: NCI Model CRADA

                                       2
<PAGE>   65
[DEPARTMENT OF HEALTH AND HUMAN SERVICES LOGO]   PUBLIC HEALTH SERVICE
-------------------------------------------------------------------------------
                                                 National Institutes of Health
                                                 National Cancer Institute
                                                 Technology Development and
                                                   Commercialization Branch
                                                 Executive Plaza South, Room 450
                                                 6120 Executive Blvd.
                                                 Rockville, MD 20852
                                                 (301) 496-0477
                                                 (301) 402-2117 Fax

Dear Collaborator:

The Cooperative Research and Development Agreement (CRADA) referenced below is
to or has recently expired. It is agreed that both parties do not want the term
of this CRADA to extend beyond the term indicated. Pursuant to Articles 4.2 and
5.2, a final report is enclosed and provisions of article 4.2, 5.1, 5.2, 5.3,
Articles 6-8, 10.3, 10.5, 11.1, 12.3, and 13.10 shall survive the termination of
this CRADA.

Please sign this letter acknowledging that the CRADA has expired and return a
copy so that this file can be closed out. We hope that this collaboration has
been a positive experience and look forward to future cooperative projects.

Please contact me should you have any questions.

Sincerely,

Suzanne M. Frisbie, Ph.D.

                            CRADA MANAGEMENT MODULE
<TABLE>
<S>                                  <C>
          CACR    00352                 NIH/ADAMHA Principal Investigator   [*]
                                                                Institute   NCI
Effective Date                                                   Division   DCTD
                                                               Laboratory   CTEP
  Term (years)    [*]                Collaborating Principal Investigator   [*]
                                                             Collaborator   RPRP & INTROGEN
    Expiration

Title     CLINICAL DEVELOPMENT OF Adp53
</TABLE>

I hereby acknowledge that this CRADA has expired.

NATIONAL CANCER INSTITUTE                   RPRP & INTROGEN

----------------------------------          ------------------------------------
 Sherry S. Ansher & James Zwiebel            Martine George   &   James Merritt

-----------------------                     -----------------------
Date                                        Date

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.<PAGE>   1
                                                                   EXHIBIT 10.24

    DATED                                                     1998

    (1)  IMPERIAL CANCER RESEARCH TECHNOLOGY LIMITED

    (2)  INTROGEN THERAPEUTICS, INC

OPTION AGREEMENT

 21/05/1998

 REFERENCE

DM/97 - 58598

<PAGE>   2
                                    CONTENTS

<TABLE>
<CAPTION>

CLAUSE

<S>                                                             <C>
1 INTRODUCTION ................................................ 1

2 INTERPRETATION .............................................. 1

3 GRANT OF THE FIRST OPTION ................................... 5

4 EXERCISE OF THE FIRST OPTION ................................ 7

5 THE PROJECT ................................................. 8

6 OWNERSHIP OF TECHNOLOGY AND INTELLECTUAL PROPERTY ...........11

7 CONFIDENTIALITY AND PUBLICATION .............................16

8 TERMINATION .................................................20

9 GENERAL .....................................................22

10 NOTICES AND SERVICE ........................................26

11 MISCELLANEOUS ..............................................27

SCHEDULES

SCHEDULE 1 ....................................................28

   THE EXISTING PATENTS .......................................28

SCHEDULE 2 ....................................................29

   THE TERMS OF THE FIRST LICENCE .............................29

SCHEDULE 3 ....................................................35

   OBJECTIVES OF THE PROJECT ..................................35

SCHEDULE 4 ....................................................36

   THE TERMS OF THE SECOND LICENCE ............................36
</TABLE>

<PAGE>   3
                   CONTENTS AGREEMENT dated             1998

BETWEEN:

(1)  IMPERIAL CANCER RESEARCH TECHNOLOGY LIMITED, incorporated in England and
     Wales with registered number 1662284, whose registered office is at
     Sardinia House, Sardinia Street, London WC2A 3NL, England ('ICRT')

(2)  INTROGEN THERAPEUTICS, INC, incorporated in the State of Delaware, whose
     principal office is at 301 Congress Avenue, Suite 1850, Austin, Texas
     78701, USA ('INTROGEN')

1    INTRODUCTION

1.1  Imperial Cancer Research Fund ('ICRF') and ICRT have identified and carried
     out a programme of research work relating to a tumour suppressor gene known
     as 'PTEN' which has potential diagnostic and therapeutic uses, and in
     respect of which certain patent applications have been made by ICRT,
     details of which are given in Schedule 1.

1.2  Introgen wishes to acquire rights in relation to the Gene in order to
     develop DNA based therapeutic products, in particular for the treatment of
     cancer.

1.3  ICRT is a company wholly owned by ICRF and, by arrangement with ICRF, owns
     and is responsible for the management and exploitation of ICRF technology.

2    INTERPRETATION

2.1  In this Agreement -

     'AFFILIATE' means, in relation to either party, a company which controls
     that party, or is controlled by that party or by a company which controls
     that party; and for these

                                     PAGE 1

<PAGE>   4

     purposes a company controls another company if, either directly or
     indirectly through one or more other companies, it can -

     o    exercise a majority of the votes attached to the shares in the other
          company; or

     appoint or remove a majority of the board of directors of the other
     company;

    'THE EFFECTIVE DATE' means 1st June 1998;

     'THE EXISTING PATENTS' means the patent applications referred to in clause
     1.1, any patents issued in pursuance of any such application, any
     extension, reissue, division, continuation or continuation-in-part of any
     such application or patent and any patent of addition, supplementary
     protection certificate or similar rights based on any such patent;

     'EXISTING TECHNOLOGY' means any Technology relating to the Gene which has
     been obtained, developed, found, produced or made by or for ICRF or ICRT at
     any time prior to the Effective Date;

     'THE FIELD' means the field of [*];

     'THE FIRST LICENCE' means the licence to be granted pursuant to clause 4.1;

     'THE FIRST OPTION' means the option granted by ICRT under clause 3.1;

     'THE FIRST OPTION PERIOD' means the period of [*] from the Effective
     Date;

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

                                     PAGE 2

<PAGE>   5
    'THE GENE' means the PTEN gene referred to in clause 1.1 including, for the
    avoidance of doubt, any splice variants or other derivatives of that gene
    and for the purposes of the foregoing, a "derivative" means a nucleotide
    sequence derived from that gene (including fragments thereof) the product of
    which has tumour suppressor activity;

    'ICRF' means Imperial Cancer Research Fund;

    'INTELLECTUAL PROPERTY' means any patent application or patent (including
    any extension, reissue, division, continuation or continuation-in-part of
    any such application or patent and any patent of addition, supplementary
    protection certificate or similar rights based on any patent), copyright or
    other form of protection, the right to make any application for any such
    protection in any part of the world, and any right in respect of any trade
    secret or other confidential information;

    'THE INVENTION' means the invention(s) claimed or disclosed in the Existing
    Patents;

    'MATERIALS' means any model, prototype, material or substance (including,
    without limitation, any living organism or genetic material), and includes
    any progeny or derivative of any of the foregoing;

    'THE NEGOTIATION PERIOD' means the period of [*] from the date of exercise
    of the First Option or the Second Option, as the case may be, or such longer
    period as the parties may agree in either case;

    'THE PROJECT' means the programme of collaborative research referred to in
    clause 5.1;

    'PROJECT TECHNOLOGY' means any Technology obtained, developed, found,
    produced or made at any time on or after the Effective Date in the course of
    the Project;

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

                                     PAGE 3

<PAGE>   6
     'PROJECT PATENTS' means any patent applications claiming any Project
     Technology, any patents issued in pursuance of any such application, any
     extension, reissue, division, continuation or continuation-in-part of any
     such application or patent and any patent of addition, supplementary
     protection certificate or similar rights based on any such patent;

     'THE SECOND LICENCE' means the agreement to be entered into pursuant to
     clause 6.7;

     'THE SECOND OPTION' and 'THE SECOND OPTION PERIOD' have the meanings given
     in clause 6.6;

     'TECHNOLOGY' means any methods, techniques, processes, discoveries,
     inventions (whether patentable or not), formulae, results of
     experimentation, statistics, data, computer software or plans, any
     Materials and any records in any form relating to any of the foregoing; and

     'YEAR' means a period of 365 (or, in the case of a leap year, 366) days.

2.2  Unless the context otherwise requires, each reference in this Agreement
     to -

     (a)  'WRITING', and any cognate expression, includes a reference to any
          communication effected by facsimile transmission or similar means (but
          not electronic mail);

     (b)  a licence includes a sub-licence; and 'LICENSE' (as a verb) and
          cognate expressions shall be construed accordingly;

     (c)  a statute or a provision of a statute is a reference to that statute
          or provision as amended, re-enacted or extended at the relevant time,
          and includes any statute or a corresponding provision in a statute
          replacing that statute or provision;

                                     PAGE 4

<PAGE>   7

     (d)  'THIS AGREEMENT' is a reference to this Agreement and each of the
          Schedules, as amended or supplemented at the relevant time;

     (e)  a Schedule is a reference to a schedule to this Agreement;

     (f)  a clause or a paragraph is a reference to a clause of this Agreement
          (other than the Schedules) or a paragraph of the relevant Schedule;

     (g)  any reference to the parties includes a reference to their respective
          successors in title and permitted assignees;

     (h)  any reference to a person includes any body corporate, unincorporated
          association, partnership or other legal entity;

     (i)  the singular includes the plural and vice versa; and

     (j)  words importing any gender include any other gender.

2.3  The headings in this Agreement are for convenience only and shall not
     affect its interpretation.

3    GRANT OF THE FIRST OPTION

3.1  ICRT hereby grants to Introgen, on and subject to the terms of this
     Agreement, the exclusive option to obtain an exclusive, world-wide licence
     (to the extent that ICRT is able to grant such a licence under any
     applicable law) in respect of the Existing Patents and any Materials or
     other Existing Technology referred to in clause 5.4, on the terms referred
     to in clause 4.1.

3.2  The First Option shall be exercisable by Introgen, subject to payment of
     the sum referred to in clause 3.3, by giving written notice to ICRT at any
     time during the First Option Period.

                                     PAGE 5

<PAGE>   8

3.3  In consideration of the grant of the First Option, Introgen shall pay to
     ICRT the sum of [*] on the Effective Date.

3.4  The sum referred to in clause 3.3 shall not be refunded in any
     circumstances.

3.5  If Introgen does not duly exercise the First Option during the First
     Option Period, it shall forthwith lapse.

3.6  During the First Option Period ICRT shall diligently prosecute and maintain
     the Existing Patents and keep Introgen fully informed as to the prosecution
     status of the Existing Patents (including, without limitation, furnishing
     to Introgen information relevant to such prosecution and maintenance) and
     shall give fair consideration to suggestions made by Introgen in respect of
     the prosecution strategy in so far as they relate to the Field, but if ICRT
     notifies Introgen in writing that -

     (a)  it wishes to abandon any patent application or patent within the
          Existing Patents which relates to the Field, it shall give a prompt
          written notice Introgen offering to assign it to Introgen at the
          expense of Introgen but otherwise free of charge, and if Introgen does
          not accept the offer in writing within 30 days, ICRT shall have no
          further obligation with respect to the patent or patent application;
          or

     (b)  it does not wish to elect to proceed from PCT stage to national stage
          with respect to any such application in any country, it shall give a
          prompt written notice to Introgen, and ICRT shall have no further
          obligation with respect to the application unless Introgen notifies
          ICRT in writing within thirty (30) days that it wishes ICRT so to
          proceed, in which event ICRT shall do so but at the sole expense of
          Introgen, and accordingly for the purposes of -

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

                                     PAGE 6

<PAGE>   9
          (i)  clause 3.7(b), that application and any Existing Patent granted
               pursuant to it in the relevant country shall be treated as if
               they had been assigned to Introgen; and

          (ii) the provisions of the First Licence as to royalties summarised in
               paragraph 9 of Schedule 2, that application and any Existing
               Patent granted pursuant to it shall be deemed not to exist in the
               relevant country.

3.7  During the First Option Period the out-of-pocket costs and expenses of
     prosecuting and maintaining the Existing Patents shall be borne -

     (a)  in respect of any of the Existing Patents the claims of which relate
          exclusively to any matter outside the Field, by [*];

     (b)  in respect of any of the Existing Patents the claims of which relate
          exclusively to the Field, or which have been assigned to Introgen
          pursuant to clause 3.6(a) (or are treated as if they had been so
          assigned pursuant to clause 3.6(b)(i), [*];

     (c)  in respect of any other of the Existing Patents, by [*];

     and Introgen shall accordingly pay to ICRT the [*] of those
     costs and expenses incurred from time to time within 30 days after receipt
     from ICRT of an account setting out the relevant information to enable its
     share to be ascertained.

4    EXERCISE OF THE FIRST OPTION

4.1  If Introgen exercises the First Option in accordance with clause 3.2, ICRT
     and Introgen shall forthwith use their best endeavours during the
     Negotiation Period to negotiate in good faith the terms and conditions for
     the grant to Introgen of the

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

                                     PAGE 7

<PAGE>   10

     licence referred to in clause 3.1 ('THE FIRST LICENCE'), which shall
     include the terms and conditions set out in Schedule 2 and such other terms
     and conditions (consistent with those set out in Schedule 2) as are
     reasonable and customary in the biopharmaceutical industry for arrangements
     of the type contemplated by the First Licence.

4.2  Upon agreement being reached between ICRT and Introgen as to the terms of
     the First Licence, the parties shall forthwith execute an agreement
     containing the terms so agreed between ICRT and Introgen.

4.3  If, notwithstanding their best endeavours, ICRT and Introgen do not agree
     upon the terms for the grant of the First Licence to Introgen during the
     Negotiation Period, Introgen shall have the right, exercisable by notifying
     ICRT in writing at any time within fifteen (15) days after the expiration
     of the Negotiation Period, to initiate a binding arbitration proceeding,
     pursuant to which the terms and conditions of the First Licence shall be
     established. Any arbitration under this provision shall be held in
     accordance with clause 9.12 by a single arbitrator and the sole issue
     before such arbitrator shall be to establish the terms and conditions of
     the First Licence in accordance with clause 4.1, to the extent that they
     have not been agreed. If Introgen does not exercise the foregoing right to
     initiate arbitration within the applicable fifteen (15) day period, the
     First Option shall lapse.

4.4  If the First Option lapses pursuant to clause 3.5 or 4.3 then, except to
     the extent that clauses 5, 6 and 7 continue to operate, this Agreement
     shall terminate automatically, in which case all rights and obligations of
     the parties shall terminate except as provided in clause 8.4.

5    THE PROJECT

5.1  As further consideration for the grant of the First Option, Introgen shall
     co-operate with ICRT on a programme of collaborative research on the
     following terms.

                                     PAGE 8

<PAGE>   11

5.2  Subject to the following provisions, the Project shall be carried on for a
     period of [*] from the Effective Date.

5.3  The overall objectives of the Project shall be as set out in Schedule 3.
     Within those overall objectives, the detailed objectives and implementation
     of the Project, and the work to be carried out by ICRT and Introgen
     respectively as part of the Project, shall be as agreed between Dr David
     Snary of ICRT and Dr Sunil Chadaof Introgen from time to time, but
     initially as set out in the document attached to this Agreement as Appendix
     A and initialled on behalf of the parties.

5.4  ICRT shall, as soon as practicable after the Effective Date -

     (a)  Supply to Introgen samples of such of the Materials relating to the
          Gene and in the possession or control of ICRT as are reasonably
          necessary to enable Introgen to carry its tasks in relation to the
          Project or as are otherwise requested by Introgen from time to time in
          connection with its evaluation of the Gene with a view to deciding
          whether or not to exercise the First Option or the Second Option; and

     (b)  disclose to Introgen such other of the Existing Technology as is
          relevant to the Project or it exercise of the First Option or the
          Second Option;

    and Introgen shall be entitled to use and practice the Invention, and to use
    any Materials so supplied and any Existing Technology so disclosed during
    the continuance of the Project, for the purposes only of carrying out its
    part of the Project and planning the development and exploitation in the
    Field of the Existing Technology and Project Technology or as otherwise
    reasonably necessary to evaluate the Gene with a view to deciding whether or
    not to exercise the First Option or the Second Option.

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

                                     PAGE 9

<PAGE>   12

5.5  Subject as provided in clause 5.4, the resources to be applied to the
     Project by each of ICRT and Introgen shall be solely at its discretion.

5.6  Introgen shall pay to ICRT, as a contribution to the work to be carried out
     by ICRT as part of the Project, the sum of [*].

5.7  For the avoidance of doubt, each sum payable pursuant to clause 5.6 shall
     not be refunded in any circumstances, and if Introgen exercises the First
     Option before the end of that period, any such sum which is outstanding
     shall continue to be payable.

5.8  If at any time Introgen in its reasonable opinion decides that all, or a
     major part of, the objectives set out in Schedule 3 have been achieved, and
     proposes to proceed to full pre-clinical and clinical development of the
     Gene in the Field, it shall be entitled to terminate the Project by giving
     to ICRT not less than one month's written notice setting out details of its
     description and its proposals.

5.9  If within one year from the Effective Date Introgen has not commenced good
     faith active steps with a view to carrying out its part of the Project for
     any reason, ICRT shall be entitled to terminate the Project by giving to
     Introgen not less than one month's written notice provided that Introgen
     does not commence such steps within such one (1) month period, in which
     case the parties shall forthwith take such steps as may be necessary to
     terminate the Project, and subject to those steps being taken this
     Agreement shall terminate automatically.

5.10 For the purposes of the Project the principal points of contact between the
     parties will be as follows -

          for ICRT:                  Dr David Snary

          for Introgen:              Dr Sunil Chada

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

                                     PAGE 10

<PAGE>   13

5.11 ICRT and Introgen shall ensure that Dr Snary and Dr Chada respectively
     shall communicate and meet with one another as necessary to progress the
     work on the Project, and that each of them shall report their research data
     at semi-annual intervals in a short written report to Introgen and ICRT
     respectively.

5.12 If any employees or other representatives of ICRT are requested to visit
     the premises of Introgen for the purposes of the Project, Introgen shall -

     (a)  at its own cost give all reasonable assistance required by any of them
          for that purpose; and

     (b)  reimburse ICRT for their reasonable travel, accommodation and other
          expenses incurred, within 30 days after receipt of an invoice for the
          sum in question.

5.13 If by agreement with ICRT any employees or other representatives of
     Introgen visit the premises of ICRT for the purposes of the Project -

     (a)  ICRT shall at the cost of Introgen give all reasonable assistance
          required by any of them for that purpose, and Introgen shall reimburse
          to ICRT any out-of-pocket sum incurred by ICRT for that purpose
          within 30 days after receipt of an invoice for the sum in question;
          and

     (b)  Introgen shall be responsible for their travel, accommodation and
          other expenses.

6    OWNERSHIP OF TECHNOLOGY AND INTELLECTUAL PROPERTY

6.1  Subject to provisions of this Agreement, the Invention, the Existing
     Patents, the Existing Technology and all Intellectual Property in respect
     of any of the Existing Technology shall remain the exclusive property of
     ICRT.

                                     PAGE 11

<PAGE>   14

6.2  Any Project Technology, and any Project Patents or other Intellectual
     Property in respect of any Project Technology, shall -

     (a)  if made solely by ICRT staff working on the Project, belong
          exclusively to ICRT;

     (b)  if made solely by Introgen staff working on the Project, belong
          exclusively to Introgen;

     (c)  if made jointly by ICRT staff and Introgen staff working on the
          Project, belong to ICRT and Introgen jointly in equal undivided
          shares.

6.3  Except as otherwise provided in this Agreement and subject to the rights
     and licences granted herein, neither party shall have any obligation to
     account to the other for profits, or to obtain any approval or consent of
     the other party to license or exploit any Intellectual Property, by reason
     of their joint ownership of such Intellectual Property.

6.4  ICRT and Introgen shall discuss and seek to agree upon the extent to which,
     and the countries in which, patent protection for any Project Technology
     owned by ICRT or jointly owned by ICRT and Introgen should be obtained and,
     except to the extent that they otherwise agree in writing -

     (a)  the protection shall be applied for by ICRT in the name of ICRT, or
          jointly in the names of ICRT and Introgen, as the case may be;

     (b)  ICRT shall diligently prosecute and maintain the Project Patents in
          question and keep Introgen fully informed as to the prosecution status
          of the Project Patents (including, without limitation, furnishing to
          Introgen information relevant to such prosecution and maintenance) and
          shall give fair consideration to suggestions made by Introgen in
          respect of the prosecution

                                     PAGE 12

<PAGE>   15

          strategy in as far as they relate to the Field, but if ICRT notifies
          Introgen in writing that -

          (i)  it wishes to abandon any such patent application or patent, it
               shall give a prompt written notice to Introgen offering to assign
               it to Introgen at the expense of Introgen but otherwise free of
               charge, and if Introgen does not accept the offer in writing
               within 30 days, ICRT shall have no further obligation with
               respect to the patent or patent application in question; or

          (ii) it does not wish to elect to proceed from PCT stage to national
               stage with respect to any such application in any country, it
               shall give a prompt written notice to Introgen;

     (c)  where ICRT gives such a notice pursuant to clause 6.4(b)(ii) above,
          ICRT shall have no further obligation with respect to the application
          unless Introgen notifies ICRT in writing within 30 days that it
          wishes ICRT so to proceed, in which event ICRT shall do so but at the
          sole expense of Introgen, and accordingly for the purposes of -

          (i)  clause 6.4(d), that application and any Project Patent granted
               pursuant to it in the relevant country shall be treated as if
               they had been assigned to Introgen; and

          (ii) the provisions of the First Licence as to royalties summarised in
               paragraph 9 of Schedule 2 (as they apply to Project Patents
               pursuant to paragraph 3 of Schedule 4), that application and any
               Existing Patent granted pursuant to it shall be deemed
               not to exist in the relevant country;

                                     PAGE 13

<PAGE>   16

     (d)  the out of pocket costs and expenses of prosecuting and maintaining
          the Project Patents in question shall be borne, as if they were
          Existing Patents, in the manner provided in clause 3.7 which shall
          apply with the necessary changes (and so that the reference therein to
          clause 3.6(b)(i) shall be deemed to be a reference to clause
          6.4(c)(i));

     (e)  Introgen shall keep ICRT informed as to the prosecution status of all
          patent applications within the Project Patents owned by Introgen; and

     (f)  each of ICRT and Introgen shall give the other such assistance as the
          other may reasonably require and at the other party's expense in order
          to obtain and maintain such protection.

6.5  ICRT hereby grants to Introgen the exclusive option to take an exclusive
     licence under any or all of the Project Patents and Project Technology
     owned exclusively by ICRT and the exclusive right to exploit any and all
     Project Patents owned jointly by ICRT and Introgen.

6.6  The option granted under clause 6.5 ('THE SECOND OPTION') shall be
     exercisable by Introgen by giving written notice to ICRT at any time during
     the period ('THE SECOND OPTION PERIOD') of [*] after the termination of the
     Project (except where this Agreement is terminated by ICRT pursuant to
     clause 8.2 or 8.3).

6.7  If Introgen exercises the Second Option in accordance with clause 6.6, the
     First Licence shall be modified to include such Project Patents and Project
     Technology within the scope of the First Licence, in accordance with the
     provisions of Schedule 4, and ICRT and Introgen shall forthwith execute an
     agreement ('THE SECOND LICENCE') to effect such a modification. In the
     event of any disagreement as to the terms of the Second Licence, the
     provisions of clause 4.3 shall apply with the necessary changes.

      [*] Certain information on this page has been omitted and filed
          separately with the Commission. Confidential treatment has been
          requested with respect to the omitted portions.

                                     PAGE 14

<PAGE>   17

6.8  Notwithstanding any licence or right granted by ICRT pursuant to this
     Agreement, ICRT (for itself and ICRF) shall retain -

     (a)  the exclusive right to use any Existing Technology (and any Existing
          Patents or other Intellectual Property in respect thereof) for any
          purpose outside the Field;

     (b)  the exclusive right to use any Project Technology which belongs
          exclusively to ICRT (and any Project Patents or other Intellectual
          Property in respect thereof), for any purpose outside the Field;

     (c)  the exclusive right to use any Project Technology which belongs to
          ICRT and Introgen jointly (and any Project Patents or other
          Intellectual Property in respect thereof) for [*]; and

     (d)  the non-exclusive right to use any Project Technology which belongs to
          ICRT and Introgen jointly (and any Project Patents or other
          Intellectual Property in respect thereof) for research and all other
          applications (except [*]) outside the Field.

6.9  Introgen hereby grants to ICRT (for itself and ICRF) an irrevocable,
     perpetual non-exclusive, worldwide, royalty-free licence, with the right to
     grant sublicenses, in respect of any Introgen Improvement, and any Project
     Patents or other Intellectual Property in respect of any such Introgen
     Improvement, for the purposes of research and the manufacture, sale and use
     of products for [*] outside the Field.

     For the purposes of this Agreement, 'Introgen Improvement' means any
     Project Technology which belongs exclusively to Introgen and which is a
     derivative (as defined in clause 2.1) of the Gene or a method of using the
     Gene (including derivatives thereof); provided, however, Introgen
     Improvements shall not include

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                     PAGE 15

<PAGE>   18

     any vector, delivery system, method, compositions or other subject matter
     which is proprietary to Introgen, or any such Project Technology which
     necessarily involves or includes the use of or combination of any vector,
     delivery system, method, composition or other subject matter.

6.10 If Introgen does not duly exercise the Second Option during the Second
     Option Period, the Second Option shall lapse, and ICRT shall have the
     option, exercisable within a further [*] by giving written notice to
     Introgen, to negotiate for the grant to ICRT of an exclusive licence in
     respect of any Introgen Improvement, a non-exclusive licence in respect of
     any other Project Technology which belongs to ICRT and Introgen jointly,
     and all Project Patents or other Intellectual Property in respect thereof
     (but excluding any rights in respect of any vector, delivery system,
     method, compositions or other technology which is proprietary to Introgen,
     or any such Project Technology which necessarily involves or includes the
     use of or combination of any vector, delivery system, method), to use the
     same for any purpose, on a world-wide, royalty-bearing basis, to the extent
     that Introgen is able to grant such a licence or right.

6.11 If ICRT exercises the option referred to in clause 6.10, ICRT and Introgen
     shall forthwith use their best endeavours to negotiate in good faith the
     terms of an agreement for the grant of the licence or right within the
     period of [*] from the date of exercise of the option (provided that any
     such agreement shall contain the right for ICRT to grant licences (or
     sub-licences) under the Project Patents and Project Technology in question
     to any other person). In the event of any disagreement as to the terms of
     such agreement, the provisions of clause 4.3 shall apply with the necessary
     changes.

7    CONFIDENTIALITY AND PUBLICATION

7.1  Except as provided herein, each party shall maintain in confidence during
     the term of this Agreement and for seven (7) years thereafter, and shall
     not use for any

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                     PAGE 16

<PAGE>   19

     purpose or disclose to any third party, any Technology or other information
     disclosed by the other party in writing and marked "Confidential" or that
     is disclosed orally and confirmed in writing as confidential within
     forty-five (45) days following such disclosure (collectively, 'CONFIDENTIAL
     INFORMATION'), except to the extent that any such Confidential
     Information -

     (a)  is at the time of being so provided or after that time through no
          fault of the party to whom it was so provided becomes public
          knowledge; or

     (b)  was lawfully available on a non-confidential basis to the party to
          whom it was so provided before that time; or

     (c)  can be shown by the party to whom it was so provided to have been
          independently produced by that party without any use of such
          confidential information provided to it by the other party; or

     (d)  is made available to the party to whom it was so provided otherwise
          than in breach of an obligation of confidentiality owed to the other
          party.

7.2  The results of the Project may be made public by either party (or, in the
     case of ICRT, by ICRF) except to the extent that -

     (a)  publication would include any Confidential Information of the other
          party; or

     (b)  publication would prejudice the obtaining of patent protection for an
          invention constituting Project Technology, or the commercial
          exploitation of any unpatented or unpatentable Project Technology
          which remains unpublished.

7.3  To allow time for review of any proposed disclosure of any subject matter
     which may be precluded from being made public under clause 7.2, each of
     ICRT and Introgen shall provide to the other -

                                     PAGE 17

<PAGE>   20

     (a)  a copy of any manuscript disclosing any results of the Project not
          less than 45 days notice before submitting the manuscript for
          publication; and

     (b)  a copy of any slides to be used in an oral presentation disclosing any
          results of the Project together with an outline of the presentation
          not less than 20 working days before making any such oral
          presentation.

7.4  The party receiving any such material pursuant to clause 7.3 shall promptly
     and in any event prior to the proposed date of submission for publication
     review the proposed disclosure and notify the other party in writing of its
     conclusions, failing which the other party shall be free to make the
     proposed disclosure.

7.5  If in the reasonable opinion of the party receiving the material the
     proposed disclosure does not include subject matter which is precluded from
     being made public under clause 7.2, it shall promptly notify the other
     party which shall thereupon be free to make the proposed disclosure.

7.6  If in the reasonable opinion of either party -

     (a)  the proposed disclosure includes subject matter which is precluded
          from being made public under clause 7.2 and which is patentable,
          neither party shall publish or otherwise disclose the material in
          question for a period of three months from the date on which the
          relevant material was received by the party in question and, if a
          patent application is made within that period of three months, for a
          further period as agreed but in any event not exceeding a total of 18
          months from that date (including such period of three months),
          following which the other party shall be free to make the proposed
          disclosure; or

     (b)  the proposed disclosure includes unpatented (or unpatentable) Project
          Technology which that party wishes to maintain as unpublished and
          which

                                     PAGE 18

<PAGE>   21
          has been identified in Project reports pursuant to clause 5.11 as
          being of potential commercial significance, neither party shall
          publish or otherwise disclose the material in question for a period of
          18 months from that date, following which either party shall be free
          to make the proposed disclosure; or

     (c)  the proposed disclosure includes Confidential Information of the
          reviewing party, the disclosing party shall remove such Confidential
          Information prior to such disclosure.

7.7  Notwithstanding the foregoing provisions of this clause 7 above, the
     receiving party may use or disclose Confidential Information of the
     disclosing party

     (a)  to the extent necessary to exercise its rights hereunder (including
          providing such information to bona fide licensees or prospective
          licensees as contemplated by this Agreement or otherwise and to
          potential investors or partners on reasonable terms of
          confidentiality) or to fulfil its obligations and/or duties hereunder;

     (b)  in filing for, prosecuting or maintaining any proprietary rights,
          prosecuting or defending litigation; and

     (c)  in complying with applicable governmental regulations and/or
          submitting information to tax or other governmental authorities; or as
          otherwise required by law;

     provided that if the receiving party is required by law to make any public
     disclosures of Confidential Information of the disclosing party then, to
     the extent it may legally do so, it shall give reasonable advance notice to
     the disclosing party of such disclosure and shall use its reasonable
     efforts to secure confidential treatment of

                                     PAGE 19

<PAGE>   22
          Confidential Information prior to its disclosure (whether through
          protective orders or otherwise).

     8    TERMINATION

     8.1  This Agreement shall be deemed to have come into force on the
          Effective Date and, subject to the following provisions, shall
          continue in force for the respective periods of time provided for in
          this Agreement and otherwise without any time limit.

     8.2  ICRT shall be entitled to terminate this Agreement forthwith by giving
          fifteen (15) days' prior written notice to Introgen if any sum payable
          under this Agreement is not paid in full within seven (7) days after
          the due date for payment and Introgen falls to make such payment
          within such fifteen (15) day period.

     8.3  Either party shall be entitled to terminate this Agreement forthwith
          by giving written notice to the other party if -

          (a)  the other party commits a breach of any of its obligations under
               this Agreement (other than, in the case of Introgen, a breach to
               which clause 8.2 applies) and, falls to remedy to breach within
               thirty (30) days after receiving a written notice from the first
               mentioned party specifying the breach and requiring it to be
               remedied; or

          (b)  the other party goes into liquidation, has a receiver appointed
               over any of its assets, has an administrator appointed, makes any
               voluntary arrangement with any of its creditors, or ceases to
               carry on business, or any similar event under the law of any
               foreign jurisdiction occurs in relation to the other party.

     8.4  On the termination of this Agreement for any reason (including, for
          the avoidance of doubt, any termination or partial termination
          pursuant to clause 4.4 or clause 5.9)

                                PAGE 20

<PAGE>   23
          (a)  the rights and obligations of Introgen under the First Licence
               (if it has been executed) and the Second Licence (if it has been
               executed) or of ICRT under any agreement entered into pursuant to
               clause 6.11 (if it has been executed) shall continue in force;

          (b)  subject to paragraph (a), Introgen shall forthwith cease all use
               of the Gene, the Invention, the Existing Technology and any
               Project Technology which belongs exclusively to ICRT, and destroy
               all Materials in the possession or control of Introgen which have
               been supplied by ICRT or produced or derived from any Materials
               so supplied;

          (c)  except to the extent that paragraph (a) above applies (and that
               accordingly this paragraph (c) does riot apply), ICRT shall be
               entitled to license the Existing Patents and the Existing
               Technology, any Project Patents (other than any of them which
               belong exclusively to Introgen) and any unpatented (or
               unpatentable) Project Technology (other than data which Introgen
               reasonably considers proprietary to itself) to any other person;

          (d)  the provisions of clause 6.1, 6.2, 6.3, 6.8, 6.9, 6.10, 6.11, 7,
               9.10, 9.11 and 9.12 shall continue in force in accordance with
               their terms,

          but subject to the foregoing, and except for any accrued right or
          obligation of either ICRT or Introgen, neither of them shall be under
          any further obligation to the other.

     8.5  Notwithstanding anything herein to the contrary, if either party
          disputes in good faith the other party's right to terminate this
          Agreement pursuant to the foregoing provisions of this clause 8 by
          reason of a breach by the other party, the other party's right to
          terminate shall be stayed unless or until it has been determined in
          accordance with clause 9.12 that such party has such a right and, if
          it is so determined, the party in breach has failed to remedy the
          breach in question within thirty (30) days after such determination.

                                PAGE 21

<PAGE>   24

     9    GENERAL

     9.1  This Agreement and the rights granted under it are personal to each
          party, which may not assign, transfer or charge to any other person
          any of its rights under this Agreement, or subcontract or otherwise
          transfer to any other person any of its obligations under this
          Agreement.

     9.2  Notwithstanding clause 9.1, either party may assign this Agreement
          and its obligations hereunder to a party that is an Affiliate of the
          assigning party at the time of the assignment or a party that succeeds
          to all or substantially all of its business or assets relating to this
          Agreement whether by sale, merger, operation of law or otherwise;
          provided that in either case such assignee promptly enters into an
          agreement in writing with the other party to be bound by the terms and
          conditions of this Agreement.

     9.3  ICRT warrants to Introgen that -

          (a)  except as disclosed in writing to Introgen, ICRT owns all right,
               title and interest in and to the Existing Technology, the
               Existing Patents and all other Intellectual Property of ICRT in
               respect of the Existing Technology and, subject to clause 9.4, it
               has the authority to enter into this Agreement and to grant the
               rights granted by it under this Agreement;

          (b)  the execution by ICRT of, and the performance of its obligations
               under, this Agreement require no governmental or other approvals
               or, if required, all such approvals have been obtained;

          (c)  it has not granted and, except as otherwise provided in this
               Agreement, will not during the continuance of this Agreement
               grant to any third party any rights which are inconsistent with
               the rights granted by it under or pursuant to this Agreement;

                                PAGE 22

<PAGE>   25

          (d)  except as disclosed in writing to Introgen, it is not aware of
               any third party claims or governmental restrictions (other than
               legal provisions of general application) which would restrict its
               ability to grant the rights agreed to be granted by it under this
               Agreement; and

          (e)  except for the Existing Patents, as at the Effective Date ICRT
               does not own or control any patents or patent applications the
               claims of which would dominate the practice of the rights to be
               granted to Introgen pursuant to this Agreement.

     9.4  Without limiting clause 9.3, ICRT does not warrant -

          (a)  the efficacy or usefulness of the Existing Technology or any
               Project Technology; or

          (b)  that the exercise of the rights granted under this Agreement will
               not infringe the patent or other Intellectual Property rights of
               any third party; or

          (c)  that any of the Existing Patents or Project Patents is or will be
               valid or enforceable, or (in the case of an application) will
               proceed to grant.

     9.5  Introgen warrants to ICRT that -

          (a)  it has the authority to enter into this Agreement and to grant
               the rights granted by it under this Agreement;

          (b)  the execution by Introgen of, and the performance of its
               obligations under, this Agreement require no governmental or
               other approvals or, if required, all such approvals have been
               obtained;

          (c)  it has not granted and, except as otherwise provided in this
               Agreement, will not during the continuance of this Agreement
               grant to any third party any

                                    PAGE 23

<PAGE>   26

               rights which are inconsistent with the rights granted by it under
               or pursuant to this Agreement; and

          (d)  it is not aware of any third party claims or governmental
               restrictions (other than legal provisions of general application)
               which would restrict its ability to grant the rights agreed to be
               granted by it under this Agreement.

     9.6  Subject to the terms of the First Licence (if executed), the Second
          Licence (if executed) or any agreement entered into pursuant to clause
          6.11, if either party becomes aware of any infringement of any of the
          Existing Patents or the Project Patents, or any claim is made or
          threatened against either party that the exercise of any rights
          granted under this Agreement infringes the patent or other
          Intellectual Property rights of any third party, it shall forthwith
          notify the other party, whereupon the parties shall consult and seek
          to decide what steps if any to take, and each of them shall give the
          other party (at the other party's expense) such assistance as the
          other party may reasonably request in connection therewith.

     9.7  Neither party nor its representatives or employees (or, in the case of
          ICRT, those of ICRF) shall be deemed in any circumstances to be the
          employees or representatives of the other party (or, in the case of
          ICRT, to be those of ICRF), or shall have any authority or power to
          bind the other party or to contract in its name.

     9.8  This Agreement contains the entire agreement between the parties with
          respect to its subject matter and may not be modified except by an
          instrument in writing signed by the duly authorised representatives of
          the parties, and each party acknowledges that, in entering into this
          Agreement, it does not do so in reliance on any representation,
          warranty or other provision, except as expressly provided herein, and
          any implied warranties are hereby excluded to the fullest extent
          permitted by law, but nothing in this provision shall affect the
          liability of either party for any fraudulent misrepresentation.

                                     PAGE 24

<PAGE>   27
     9.9  Except with regard to the exercise of the First Option and the Second
          Option, no failure or delay by either party in exercising any of its
          rights under this Agreement shall be deemed to be a waiver of that
          right, and no waiver by either party of a breach of any provision of
          this Agreement shall be deemed to be a waiver of any subsequent
          breach of the same or any other provision.

     9.10 If any provision of this Agreement is held by any court or other
          competent authority to be invalid or unenforceable in whole or in
          part, the other provisions of this Agreement and the remainder of the
          affected provision shall continue to be valid.

     9.11 This Agreement (and any licence to be entered into pursuant to this
          Agreement) shall be governed and construed in all respects in
          accordance with the laws of England, and the parties agree to submit
          to the non-exclusive jurisdiction of the English Courts.

     9.12 Any dispute or arising out of, in relation to, or in connection with
          this Agreement, or the validity, enforceability, construction,
          performance or breach hereof, shall be settled by binding arbitration
          in London, England, under the then-current Rules of Arbitration of
          the International Chamber of Commerce Court of Arbitration by a single
          arbitrator appointed in accordance with such rules, provided that if
          either party so requests (and unless otherwise provided hereunder) the
          arbitration shall be conducted by a panel of three (3) arbitrators
          appointed in accordance with the Rules. The decision and/or award
          rendered by the arbitrator(s) shall be written, final and
          non-appealable and may be entered in any court of competent
          jurisdiction. Accordingly, the parties hereby waive any and all rights
          of appeal to the Court under the Arbitration Act 1996. The parties
          agree that, any provision of applicable law notwithstanding, they will
          not request, and the arbitrator shall have no authority to award,
          punitive or exemplary damages against any party. The costs of any
          arbitration, including administrative fees and fees of the
          arbitrator(s), shall be shared equally by the parties, unless
          otherwise determined by the arbitrator(s). Each

                                    PAGE 25

<PAGE>   28
          party shall bear the cost of its own legal and expert fees; provided
          that the arbitrator(s) may in his or their discretion award to the
          prevailing party the costs and expenses incurred by the prevailing
          party in connection with the arbitration proceeding.

     10   NOTICES AND SERVICE

     10.1 Any notice or other information required or authorized by this
          Agreement to be given by either party to the other shall be given by -

          (a)  delivering it by hand;

          (b)  sending it by pre-paid registered post; or

          (c)  sending it by facsimile transmission or similar means of
               communication (but not electronic mail);

          to the other party at the address given in clause 10.4.

     10.2 Any notice or information sent by post in the manner provided by
          clause 10.1(b) which is not returned to the sender as undelivered
          shall be deemed to have been given on the seventh day after the
          envelope containing it was so posted; and proof that the envelope
          containing any such notice or information was properly addressed,
          pre-paid, registered and posted, and that it has not been so returned
          to the sender, shall be sufficient evidence that the notice or
          information has been duly given.

     10.3 Any notice or information sent by facsimile transmission or similar
          means of communication (but not electronic mail) shall be deemed to
          have been duly given on the date of transmission, provided that a
          confirming copy is sent as provided in clause 10.1(b) to the other
          party at the address given in clause 10.4 within 24 hours after
          transmission.

                                PAGE 26

<PAGE>   29

     10.4 The address of either party for service of any legal proceedings
          concerning or arising out of this Agreement, or for the purposes of
          clause 10.1, shall be that of its registered or principal office, or
          such other address as it may last have notified to the other party in
          writing from time to time.

     11   MISCELLANEOUS

     11.1 Each sum payable pursuant to this Agreement is exclusive of any
          applicable Value Added Tax or other taxes or duties (other than taxes
          on profits or income), which shall be additionally payable by Introgen
          together with the relevant sum.

     11.2 Each party shall from time to time do all such acts and execute all
          such documents as may be reasonably necessary in order to give effect
          to the provisions of this Agreement.

     11.3 The parties shall bear their own costs of and incidental to the
          preparation, execution and implementation of this Agreement.

     11.4 Except as required by law, neither party shall make any press or other
          public announcement concerning any aspect of this Agreement or use
          the name of the other (including, in the case of ICRT, that of ICRF)
          without first obtaining the agreement in writing of an authorised
          representative of the other party.

     11.5 This Agreement may be executed in more than one counterpart and shall
          come into force once each party has executed such a counterpart in
          identical form and exchanged it with the other party.

                                    PAGE 27

<PAGE>   30

                                    SCHEDULE 1

                              THE EXISTING PATENTS
<TABLE>
<CAPTION>
    TITLE                               COUNTRY              APPLICATION
                                                               NUMBER           DATE

<S>                                        <C>               <C>               <C>

[*]

</TABLE>

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                PAGE 28

<PAGE>   31
                                   SCHEDULE 2

                         THE TERMS OF THE FIRST LICENCE

1    Parties:       ICRT (the Licensor) and Introgen (the Licensee).

2    Definitions:   'LICENSED PRODUCT' will mean any product (i) which
                    incorporates the Gene, or (ii) the manufacture, use or sale
                    of which would in the absence of the licence granted to
                    Introgen infringe a valid claim within any of the Existing
                    Patents in the country for which the product is sold.

                    A "valid claim" will include the claims of issued patents
                    (including patents of addition, supplementary protection
                    certificates or similar rights based on any such patent) and
                    patent applications; provided that in the case of a patent
                    application which has not been issued, not more than [*]
                    have elapsed from the earliest priority filing date to which
                    the claim is entitled.

                    'LICENSED SUBJECT MATTER' will mean the Existing Technology,
                    the Existing Patents and any other Intellectual Property of
                    ICRT in respect of the Existing Technology.

                    Subject as provided above, the provisions of clause 2 shall
                    apply.

3    Licence:       ICRT will grant to Introgen an exclusive, worldwide licence,
                    with the right to grant and authorise sublicences, under the
                    Licensed Subject Matter to make, have made, use and sell
                    Licensed Products, practice any method, process or procedure
                    and otherwise exploit the Licensed Subject Matter, in each
                    case within the Field. For the avoidance of

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                PAGE 29
<PAGE>   32
                    doubt, Introgen will not have any rights in respect of any
                    [*] or in respect of any [*] outside the Field.

4    Retained       Notwithstanding the foregoing, ICRT (for itself and ICRF)
     Rights:        will retain the rights under the Licensed Subject Matter
                    referred to in clause 6.8.

5    Clinical       Introgen will be responsible for conducting, directly or
     Development:   through third parties, clinical development with respect to
                    Licensed Products. Such clinical development shall include
                    carrying out clinical trials sufficient to market a Licensed
                    Product in all Major Markets. Without limiting the
                    foregoing, Introgen will use the same diligent efforts to
                    initiate and complete such clinical trials as it expends for
                    its other products being developed with similar market
                    potential. The detailed plans and budgets for clinical
                    development will be determined by Introgen in consultation
                    with ICRT (and in default of agreement settled by
                    arbitration pursuant to clause 4.3) and set forth in the
                    Agreement. Introgen will consult with and keep ICRT
                    reasonably informed relating to the scope and progress of
                    such clinical development and will provide semi-annual
                    reports to ICRT on each stage of product development.

                    'MAJOR MARKET' will mean the [*], [*] and the [*].

6    Data Access:   During the term of the Agreement, Introgen will have access
                    to copies of data, reports, analyses and other information
                    in ICRT's possession or control, which are reasonably
                    necessary for Introgen's exercise of its rights under the
                    Licensed Subject Matter. In addition, ICRT will provide
                    Introgen with reasonable quantities of the Gene from time to

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                     PAGE 30

<PAGE>   33
                    time.

7    Licence Fee:   Introgen shall pay to ICRT on the execution of the First
                    Licence [*], which shall be non-refundable and
                    non-creditable against royalties.

8    Milestone      Upon the occurrence of the events set forth below for the
     Payments:      first Licensed Product, Introgen will make the corresponding
                    payment below to ICRT -

<TABLE>
<CAPTION>

         MILESTONE                            AMOUNT
         ---------                            ------
<S>                                           <C>
Completion of [*] trials                       [*]

Completion of [*] trials                       [*]

First approval for [*]                         [*]

First approval for [*]                         [*]

First year where Net Sales of a                [*]
Licensed Product exceeds [*]
    TOTAL                                      [*]
</TABLE>

9    Royalties:     Introgen will pay to ICRT as royalties the following
                    percentages of Net Sales by Introgen and its sublicensees,
                    based upon the aggregate Net Sales of all Licensed
                    Products -

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                     PAGE 31
<PAGE>   34
<TABLE>
<CAPTION>

                   Annual Net Sales   Royalties on Incremental
                   ----------------   ------------------------
                                               Amount
                                               ------

<S>                <C>                          <C>
                   [*]                           [*]

                   [*]                           [*]
</TABLE>

                    The foregoing royalties will be reduced by [*] in countries
                    where no valid claim of any of the Existing Patents covers a
                    Licensed Product.

                    In the event that Licensed Products are sold in combination
                    with one or more other registered products for which a
                    royalty would not otherwise be due, it is understood that
                    Net Sales from the combination product will be reasonably
                    allocated as to be set forth in the First Licence.

                    In the event Introgen, its affiliate or sublicensee becomes
                    obligated to pay a royalty to a third party in respect of
                    patent rights covering the Gene or use thereof such that the
                    total royalty burden on the Gene or use thereof (prior to
                    reductions) is in excess of [*] Introgen may deduct [*] of
                    such excess royalty from the royalty owing to ICRT on the
                    applicable net sales; provided, however, the royalty rate
                    payable on applicable net sales to such third party after
                    adjustments will not exceed the royalty rate payable (after
                    adjustments) to ICRT on such net sales (except with the
                    consent of ICRT, which consent will not be unreasonably
                    withheld) and in no case will the amount paid to ICRT be so
                    reduced to less than [*] of the amount that would otherwise
                    be due to ICRT on such net sales.

                    Each royalty payment will be accompanied by a proper
                    statement and will be made without deduction. Introgen will
                    keep proper accounts

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                    PAGE 32

<PAGE>   35
                    to enable the accuracy of royalty payments to be confirmed,
                    and will allow ICRT access to inspect and take copies.

10   Marketing:     Introgen will be responsible for the establishment, control
                    and implementation of the promotion and marketing strategy,
                    plans and budgets for Licensed Products. Introgen will use
                    the same diligent efforts with respect to the marketing,
                    sale and promotion of Licensed Products for each Major
                    Market as Introgen expends for its own products being
                    developed with similar market potential.

11   Patent         The provisions of clauses 3.6 and 3.7 above will apply
     Prosecution:   throughout the term of the First Licence as they apply
                    during the First Option Period.

12   Miscellaneous: Each party will keep Confidential Information of the other
                    confidential on the same terms as under clause 7 above.

                    The First Licence will be subject to termination on the
                    same terms as under clause 8 above. On termination all
                    rights will revert to ICRT.

                    Introgen will assume responsibility for the exploitation of
                    the Licensed Subject Matter and will indemnify ICRT (and
                    ICRF) accordingly. ICRT (or ICRF) will have no liability
                    howsoever arising under or in connection with the First
                    Licence for loss of profit or indirect or consequential loss
                    or for sums exceeding the amount of royalties paid by
                    Introgen.

                    Clauses 9, 10 and 11 above will apply to the First Licence.

                    The First Licence will include other reasonable and
                    customary terms and conditions contained in similar
                    agreements of this type, in so far

                                     PAGE 33

<PAGE>   36

                    as they are consistent with the above.

                                     PAGE 34

<PAGE>   37

                                   SCHEDULE 3

                            OBJECTIVES OF THE PROJECT

                                      [*]

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                     PAGE 35

<PAGE>   38
                                   SCHEDULE 4

                         THE TERMS OF THE SECOND LICENCE

     1    'LICENSED SUBJECT MATTER' will include, in addition to the Existing
          Patents and Existing Technology, any Project Technology and Project
          Patent owned exclusively by ICRT or owned jointly by ICRT and
          Introgen.

     2    'LICENSED PRODUCT' will mean any product (i) which incorporates the
          Gene, or (ii) the manufacture, use or sale of which would in the
          absence of the licence granted to Introgen infringe a valid claim
          within any of the Existing Patents or the Project Patents owned
          exclusively by ICRT or owned jointly by ICRT and Introgen (or, in the
          latter case, would do so if the Project Patent in question was owned
          exclusively by ICRT) in the country for which the product is sold.

     3    Royalties will be payable, at the rates specified in Schedule 2, on
          Net Sales of Licensed Products (as defined above), where the product
          (i) incorporates the Gene or (ii) is covered by a valid claim of an
          Existing Patent or a Project Patent owned exclusively by ICRT. The
          foregoing royalties will be reduced by [*] in countries where no valid
          claim of an Existing Patent or a Project Patent owned exclusively by
          ICRT covers a Licensed Product.

     4    Clauses 6.3, 6.4, 6.8 and 6.9 shall apply throughout the term of the
          Second Licence.

     5    Subject to paragraphs 1 to 4 above, the provisions of Schedule 2 shall
          apply with the necessary changes (and so that references to Existing
          Technology and Existing Patents shall be construed as references to
          Existing Technology and Existing Patents and/or Project Technology and
          Project Patents owned exclusively by ICRT or owned jointly by ICRT and
          Introgen).

         [*]    Certain information on this page has been omitted and filed
                separately with the Commission. Confidential treatment has been
                requested with respect to the omitted portions.

                                     PAGE 36

<PAGE>   39

     For  IMPERIAL CANCER RESEARCH TECHNOLOGY LIMITED

     /s/ JOHN C. WALL
     --------------------------------
     Director

     For  INTROGEN THERAPEUTICS, INC.

     /s/ MAHENDRA G. SHAH
     --------------------------------
     Director

                                    PAGE 37

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