Contract Research and Development Agreement - ImClone Systems Inc. and Boehringer Ingelheim Pharma KG



                                TABLE OF CONTENTS


      
1.       DEFINITIONS
1.1      BI PHARMA KG
1.2      BI PHARMA KG Confidential Information
1.3      Cell Line
1.4      Certificate of Analysis
1.5      cGMP
1.6      C225
1.7      Effective Date
1.8      IMCLONE
1.9      IMCLONE Confidential Information
1.10     Master Cell Bank (MCB)
1.11     Manufacturer's Working Cell Bank (MWCB)
1.12     Phase I
1.13     Phase II
1.14     Phase III
1.15     Process
1.16     Product
1.17     Project
1.18     Project Fee
1.19     Project Manager
1.20     Project Team
1.21     Specifications
1.22     Start Date


2.       COOPERATION BETWEEN THE PARTIES IN THE COURSE OF THE PROJECT
2.1      Designation of Project Manager
2.2      Project Team
2.3      Cooperation
2.4      Access to facilities


3.       IMCLONE'S TASKS AND RESPONSIBILITIES
3.1      License to Use of IMCLONE Cell Line and Intellectual Property
3.2      Materials and Information to be Provided
3.3      Activities to be Performed


December 28, 1998
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4.       BI PHARMA KG'S TASKS AND RESPONSIBILITIES
4.1      BI PHARMA KG's Tasks
4.2      Control of Cell Line
4.3      Quarantine and Testing
4.4      Phase I/II Development Program
4.5      Responsibility for Failed Fermentations and Downstream Operations
4.6      Materials and Information to be Delivered
4.7      Product to be Delivered
4.8      Prior Approval
4.9      Retention Samples
4.10     Additional Work


5.       PHASE I/II TO BE CONDUCTED ON FIXED-FEE BASIS


6.       PHASE I/II PROJECT FEE


7.       ADDITIONAL WORK / FUTURE ACTIVITIES
7.1      Additional Work
7.2      Future Activities
7.3      Others


8.       OWNERSHIP OF PROJECT DATA
8.1      General
8.2      Intellectual Property Rights solely covering the Product
8.3      All other Intellectual Property Rights


9.       REPRESENTATIONS. WARRANTIES AND INDEMNIFICATION
9.1      IMCLONE
9.2      BI PHARMA KG


10.      LIMITATION OF LIABILITY
10.1     No Warranty of Merchantability of Fitness
10.2     Limitation of Liability
10.3     Maximum Amount


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11.      CONFIDENTIALITY
11.1     BI PHARMA KG
11.2     IMCLONE
11.3     Exceptions
11.4     Others


12.      TERM AND TERMINATION
12.1     Term
12.2     Right to Terminate
12.3     Effect of Termination


13.      MISCELLANEOUS
13.1     Force Majeure
13.2     Publicity
13.3     Notices
13.4     Applicable Law
13.5     Compliance with Laws
13.6     Independent Contractors
13.7     Waiver
13.8     Severability
13.9     Entirety
13.10    Assignment


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                   CONTRACT RESEARCH AND DEVELOPMENT AGREEMENT
                                     (C225)


THIS CONTRACT RESEARCH AND DEVELOPMENT AGREEMENT ('Agreement') is made as of
April 30, 1999 by and among ImClone Systems Incorporated, ('IMCLONE'), having
its principal business offices at 180 Varick Street, New York, New York 10014,
U.S.A. and Boehringer Ingelheim Pharma KG ('BI PHARMA KG') a German corporation
having its principal place of business at Birkendorfer Stra(beta)e 65, 88397
Biberach an der Riss, Federal Republic of Germany.


BACKGROUND
----------

IMCLONE is the proprietor of a hybridoma cell line [ *** ] which produces a
monoclonal antibody C225 directed against Epidermal Growth Factor Receptor
(EGFR) as a result of stable transfection with a C225 expression construct, as
well as methods for the purification and analysis of C225.

BI PHARMA KG owns specialized cell culture, processing, protein purification and
Iyophilization facilities that may be suitable for production of C225, and
employs personnel who have experience in production of proteins by cell culture
and purification processes as well as in registration of biopharmaceuticals.

IMCLONE desires to have BI PHARMA KG personnel evaluate, further develop, supply
and scale-up the production process for C225 in BI PHARMA KG's facilities.

IMCLONE and Dr. Karl Thomae GmbH (as of 01.01.1998 and in this Agreement
substituted by BI Pharma KG as the contractual assignee of all rights and
obligations thereunder) have previously entered into a Material Transfer
Agreement for Evaluation dated November 10/24, 1997 to evaluate potential
production and supply of C225.


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AGREEMENT
---------

IN CONSIDERATION OF the mutual covenants set forth in this Agreement, BI PHARMA
KG and IMCLONE hereby agree as follows:

1.       DEFINITIONS

1.1      'BI PHARMA KG'
         shall mean Boehringer Ingelheim Pharma KG.

1.2      'BI PHARMA KG Confidential Information'
         shall mean all technical and other information relating to BI PHARMA
         KG's facilities and associated technologies that is disclosed or
         supplied to, IMCLONE by BI PHARMA KG (except IMCLONE Confidential
         Information) pursuant to this Agreement, whether patented or
         unpatented, including, without limitation, trade secrets, know-how,
         processes, concepts, experimental methods and results and business and
         scientific plans.

1.3      'Cell Line'
         shall mean the IMCLONE cell line [ *** ] that expresses the Product.

1.4      'Certificate of Analysis'
         shall mean a document to be established by mutual agreement describing
         testing methods and results.

1.5      'cGMP'
         shall mean the regulatory requirements for current good manufacturing
         practices promulgated by the FDA under the Federal Food, Drug and
         Cosmetic Act, as amended, 21 C.F.R. Section 210 et seq and 21 C.F.R.
         Section 600-610, as applicable.

1.6      'C225'
         shall mean a chimerized monoclonal antibody directed against EGFR
         produced by the Cell Line.

1.7      'Effective Date'
         shall mean the date first above written, which shall be the effective
         date of this Agreement.

1.8      'IMCLONE'
         shall mean ImClone Systems Incorporated or an affiliate of ImClone
         Systems Incorporated.

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1.9      'IMCLONE Confidential Information'
         shall mean the Cell Line, Process, Product and all technical,
         scientific or business and other materials and information that are
         disclosed or supplied to BI PHARMA KG by IMCLONE or developed on behalf
         of IMCLONE by BI PHARMA KG (excluding BI PHARMA KG Confidential
         Information) pursuant to this Agreement whether patented or unpatented,
         including, without limitation, trade secrets, know-how, processes,
         concepts, experimental methods and results and business and scientific
         plans.

1.10     'Master Cell Bank (MCB)'
         shall mean a cell bank established by BI PHARMA KG derived from a
         suspension serum-free adapted cell line to be produced at BI PHARMA KG.

1.11     'Manufacturer's Working Cell Bank (MWCB)'
         shall mean a cell bank established by BI PHARMA KG derived from the
         MCB.

1.12     'Phase I'
         shall refer to process transfer of the Process to a [ *** ] scale at BI
         PHARMA KG, continued scale-up to a [ *** ] and [ *** ] pilot
         fermentation scale and establishment of a downstream purification
         process according to APPENDIX 1, all of which has been completed as of
         the Effective Date.

1.13     'Phase II'
         shall refer to demonstrating the process at small scale [ *** ],
         performing Product equivalency testing and establishing a filling
         process of the corresponding Product as well as the scale-up to [ *** ]
         pilot scale and cGMP production of clinical grade material at that
         scale to be undertaken by BI PHARMA KG pursuant to this Agreement and
         according to the updated Master Projectplan (APPENDIX 1.1) dated
         November 1998. The agreed upon process format for Phase II of the
         project is given in APPENDIX 6. [ *** ].

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1.14     'Phase III'
         shall refer to a second project, which may be implemented by separate
         agreement between IMCLONE and BI PHARMA KG following completion of
         Phase II activities, involving scaling the Process from the [ *** ]
         fermentation scale implemented in Phase II to the [ *** ].

1.15     'Process'
         shall refer to a proprietary IMCLONE process for using the Cell Line,
         including defined procedures, equipment and analytical methodologies
         for in-process control, release testing and Product characterization,
         that has been used by IMCLONE to produce the Product at the laboratory
         scale, which shall be disclosed by IMCLONE to BI PHARMA KG to enable BI
         PHARMA KG to carry out the Project or, if and when applicable, the
         modified process after further development and scale up by BI PHARMA KG
         to the [ *** ] fermentation scale.

1.16     'Product'
         shall mean the biologically active C225 produced by the Cell Line in
         accordance with the Process.

1.17     'Project'
         shall mean the Phase I and Phase II contract research program described
         herein, in which IMCLONE shall transfer the Process to BI PHARMA KG to
         be implemented, scaled-up and evaluated at the [ *** ] fermentation
         scale in and by BI PHARMA KG's facility and equipment. The primary
         objectives of the Project will be to transfer, establish and scale up
         the Process in the BI PHARMA KG facility, successfully demonstrate that
         Product can be reproducibly manufactured in BI PHARMA KG's facilities
         at [ *** ] scale, and generate a report compiling a summary of data
         generated in the Project. The proposed workscopes and timelines for the
         Project are laid down in the Master Projectplans attached hereto as
         APPENDIX 1 and APPENDIX 1.1. Phase I has been completed as of the date
         of this Agreement.

1.18     'Project Fee'
         shall have the meaning specified in Section 6 hereof.

1.19     'Project Manager'
         shall have the meaning specified in Section 2.1 hereof.

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1.20     'Project Team'
         shall have the meaning specified in Section 2.2 hereof.

1.21     'Specifications'
         shall mean the specifications for the Product and the respective test
         methods attached hereto as APPENDIX 5 on the basis of the
         specifications provided by IMCLONE and as such specifications may be
         amended from time to time by mutual agreement of IMCLONE and BI PHARMA
         KG according to further development of the Process and Product.

1.22     'Start Date'
         shall mean February 1, 1998 (according to the Master Projectplan
         APPENDIX 1).


2.       COOPERATION BETWEEN THE PARTIES IN THE COURSE OF THE PROJECT

2.1      Designation of Project Manager.
         BI PHARMA KG and IMCLONE shall each identify a Project Manager, and if
         they choose, the supervisor of the Project Manager. The Project Manager
         or the Project Manager's supervisor will be exclusively responsible for
         communicating all instructions and information concerning the Project
         to the other party and shall be the person or people to whom such
         instructions and information are communicated by the other party. Each
         Project Manager or the Project Manager's supervisor will be available
         on a weekly basis for consultation at prearranged times during the
         course of the Project or as may otherwise be reasonably required or
         advisable. In the absence of the Project Manager or the Project
         Manager's supervisor, a substitute shall be appointed. Additional modes
         or methods of communication and decision making may be implemented with
         the mutual consent of each party.

2.2      Project Team.
         BI PHARMA KG and IMCLONE shall each name representatives to a Project
         Team, which shall consist of knowledgeable specialists in appropriate
         disciplines who shall be responsible for planning and executing the
         Project and any subsequent interactions between the parties. At regular
         intervals, the Project Managers shall schedule meetings between each
         company's representatives for the purpose of communicating Project
         updates and providing a forum for strategic decision making and rapid
         resolution of issues.

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         Joint Project meetings shall be conducted by telephone-conference,
         video-conference and face to face meetings. Meeting minutes shall be
         prepared jointly by the Project Managers to record all issues discussed
         and decisions made, subject to final approval of such minutes by both
         parties. Such minutes are considered to be accepted by a party when
         there is no objection made by such a party within a period of 7 (seven)
         days after such minutes have been received by the respective party.

         The present list of the members of the Project Team is attached hereto
         as APPENDIX 2.

2.3      Cooperation.
         BI PHARMA KG and IMCLONE each agree to work together collaboratively on
         the Project as reasonably expeditiously as possible, with the objective
         of completing the Project according to the mutual agreed timelines (see
         APPENDIX 1 and APPENDIX 1.1).

         In the course of the Project, BI PHARMA KG will at all times take into
         consideration and implement the recommendations of IMCLONE as long as
         they do not negatively influence other BI PHARMA KG biotech operations
         and are agreed upon by the Project Team. In the absence of explicit
         instructions from IMCLONE, BI PHARMA KG shall be entitled to employ its
         reasonable judgment in carrying out the Project. BI PHARMA KG shall be
         entitled to rely upon any instructions or directives provided by the
         IMCLONE Project Manager or the IMCLONE Project Manager's supervisor
         and, subject to Sections 4.5 and 4.7 below shall not be responsible for
         failure to achieve any objective or the inability to adhere to any
         guideline due to technical failures, incomplete direction or
         documentation of Process variables, or other causes beyond the control
         of BI PHARMA KG.

2.4      Access to facilities.
         IMCLONE shall permit personnel of BI PHARMA KG, upon reasonable prior
         written notice to IMCLONE, to visit its facilities during appropriate
         times to observe the Process and certain analytical procedures for C225
         as conducted by IMCLONE. BI PHARMA KG shall permit IMCLONE, upon
         reasonable prior notice to BI PHARMA KG, to review the originals of all
         batch records and other primary documents at its facilities and shall
         allow IMCLONE personnel to be present in its facilities at appropriate
         times (e.g. to observe the implementation of the Process). While
         visiting the facility of the other party, personnel of BI PHARMA KG and
         IMCLONE shall comply with all security and safety policies and
         procedures of the other party.

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3.       IMCLONE'S TASKS AND RESPONSIBILITIES

3.1      License to Use of IMCLONE Cell Line and Intellectual Property.
         IMCLONE hereby grants to BI PHARMA KG a limited, non-exclusive right
         and license, without the right to sublicense, to use IMCLONE
         Confidential Information, including but not limited to the Cell Line
         and Process, solely for the purpose of enabling BI PHARMA KG to carry
         out its tasks and responsibilities under this Agreement with respect to
         the Project.

3.2      Materials and Information to be Provided.
         To enable BI PHARMA KG to begin the Project, IMCLONE shall provide:

         (a)  10 vials of the MCB and/or MWCB for Project start, additional
              quantities may be requested.

         (b)  a description of IMCLONE's methods for testing of the Cell Line
              and its progenitor cell line.

         (c)  documentation describing the exact composition of the [ *** ] and
              a sufficient quantity of actual medium to enable BI PHARMA KG to
              begin to culture the Cell Line upon receipt from IMCLONE;

         (d)  a description of the Cell Line and of genetic construct used for
              expression of the Product (for registration according to German
              gene technology law ('Gentechnikgesetz')), and

         (e)  at BI PHARMA KG's reasonable request any additional information
              concerning the Process, analytical test methods, reference
              materials, and any critical reagents to facilitate the Project.

3.3      Activities to be Performed. As the Project is carried out, IMCLONE
         shall:

         (a)  use reasonable efforts to perform the work and tasks as set forth
              and detailed in APPENDIX 3.

         (b)  at BI PHARMA KG's request and subject to Section 2.4 above,
              arrange for BI PHARMA KG personnel to visit IMCLONE's production
              facility to observe and record the Process as carried out by
              IMCLONE in its facility. Any such records shall be considered
              IMCLONE Confidential Information.

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4.       BI PHARMA KG'S TASKS AND RESPONSIBILITIES

4.1      BI PHARMA KG's Tasks.
         In the course of this Agreement BI PHARMA KG shall perform the work and
         tasks as laid down and detailed in APPENDIX 4 hereto.

4.2      Control of Cell Line.
         BI PHARMA KG shall maintain (for safety reasons in two different
         buildings) the Cell Line in safe and secure storage under its control
         in its facilities and shall not permit the transfer of the Cell Line to
         any third party that is not specifically authorized in writing by
         IMCLONE (except to a contract laboratory used for the characterization
         of the MCB or MWCB under substantially the same requirement of
         confidentiality). BI PHARMA KG shall comply with all applicable
         regulatory requirements relating to general safety and biosafety in
         handling the Cell Line and any raw materials used in the Project.

4.3      Quarantine and Testing.
         BI PHARMA KG will quarantine and test samples of the Cell Line already
         provided to it in order to verify that the Cell Line is suitable for
         introduction into BI PHARMA KG's facilities. The quarantine and testing
         time is estimated to be about 2 (two) months.

4.4      Phase I/II Development Program.
         Following quarantine testing of the MWCB (see APPENDIX 4) BI PHARMA KG
         will transfer and establish the production process at laboratory scale
         ( [ *** ] fermentation scale) on the basis of Process information
         supplied by IMCLONE. The agreed upon process format for Phase II of the
         Project is given in APPENDIX 6. Material derived from such a process
         will be tested for analytical equivalence with reference material from
         IMCLONE. Remaining quantities may be used by IMCLONE at its discretion.
         A scale-up will then be performed to the [ *** ] fermentation scale and
         cGMP material [ *** ] for clinical trials will be produced at this
         scale. The workscopes and timelines for such a program are given in the
         Master Projectplans (see APPENDIX 1 and APPENDIX 1.1). The production
         of further clinical material at [ *** ] fermentation scale, if required
         by IMCLONE, has to be agreed upon separately in writing, and shall be
         reflected in an amendment to this Agreement in accordance within the
         terms set forth herein.

4.5      Responsibility for Failed Fermentations and Downstream Operations.

Responsibility for Failed Fermentations and Downstream Operations.

         (a)  IMCLONE acknowledges that the Project is experimental in nature
              and that no favorable or useful result can be assured by BI PHARMA
              KG.

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              Accordingly, subject to the provisions of this Section 4.5, BI
              PHARMA KG shall not be responsible to IMCLONE for any failure of
              fermentations or downstream operations including, but not limited
              to, purification, or inability to obtain useful yields of Product
              or the success of the shift to the protein A process for reasons
              not under BI PHARMA KG's control, and the Project Fee shall be
              payable in full regardless of result unless the Project is
              terminated prior to its scheduled completion pursuant to Section
              12 hereof.

         (b)  BI PHARMA KG shall be responsible for all bioreactor fermentations
              and downstream operations including, but not limited to,
              purification that fail for reasons under BI PHARMA KG's control
              including, but not limited to, operator error, mechanical failure,
              or contamination and BI PHARMA KG shall repeat any such failed
              fermentations and downstream operations at its expense to complete
              the workscopes to be performed during the Project according to
              Section 4.4 above.

4.6      Materials and Information to be Delivered.
         BI PHARMA KG will provide IMCLONE with the following materials and
         information at the times indicated:

         (a)  a summary of the test results generated during the 2 (two) months
              quarantine period within 30 (thirty) days following the end of
              such period;

         (b)  within 2 (two) months following completion of each Phase of the
              Project (Phase I and Phase II), a report to IMCLONE, as laid down
              detailed in APPENDIX 7 including, a summary of the data BI PHARMA
              KG collects in the course of the Project and Certificates of
              Analysis for release of Product for clinical use, if any;

         (c)  other interim results as reasonable in appropriate time periods or
              requested by IMCLONE, as mutually agreed by the Project Team.

4.7      Product to be Delivered.
         BI PHARMA KG shall supply Product to IMCLONE from the [ *** ] pilot
         scale and all purified Product (cGMP grade) from the [ *** ] scale runs
         performed by BI PHARMA KG. BI PHARMA KG shall also provide IMCLONE with
         samples of vialed Product that is produced by it. All Product
         delivered, if any, shall conform with the Specifications which have to
         be mutually agreed upon as laid down in APPENDIX 5 and BI PHARMA KG
         shall issue a Certificate of Analysis covering such Specifications.

         If the Product is asserted by IMCLONE not to meet the Specifications,
         both parties shall re-test the Product. If IMCLONE and BI PHARMA KG are
         not able to agree, whether the Product meets the Specifications or

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         not and the parties are unable to resolve their differences, then
         either party may refer the matter to an independent specialized
         institution of international reputation agreeable to both parties for
         final analysis, which shall be binding on both parties hereto.

         All Product produced in the course of the Project shall be retained by
         BI PHARMA KG and stored under conditions specified by IMCLONE (and
         reasonably acceptable to BI PHARMA KG) not longer than 1 (one) year,
         and delivered to IMCLONE as instructed by IMCLONE and at the cost and
         risk of IMCLONE.

4.8      Prior Approval.
         Prior to implementing any deviation from the Project, BI PHARMA KG
         shall notify IMCLONE and obtain the written approval of the Project
         Manager of IMCLONE or other person designated in writing by IMCLONE.


4.9      Retention Samples.
         According to a sampling plan to be agreed upon by the Project Team, BI
         PHARMA KG shall isolate, identify and retain samples of raw materials
         used in fermentations carried out in the course of the Project, of
         Process media at appropriate time points in each fermentation, and of
         Product at each stage of purification. Retention samples shall be
         provided promptly to IMCLONE at its request. Shipment shall be at the
         cost and risk of IMCLONE.

4.10     Additional Work.
         On request of IMCLONE, BI PHARMA KG shall perform additional
         development work to sustain the progress of the Project on conditions
         in terms of money, time and scope to be subject to mutual agreement of
         the parties hereto and defined in an amendment to the Master
         Projectplans attached hereto as APPENDIX 1 and APPENDIX 1.1.


5.       PHASE I/II TO BE CONDUCTED ON FIXED-FEE BASIS

         The Project shall be conducted by BI PHARMA KG for IMCLONE on a fixed
         fee basis, in consideration of payment by IMCLONE of the Project Fee.

   
         The estimated duration of the Project shall be 21 (twenty-one) months 
         from the Start Date as outlined in APPENDIX 1 and APPENDIX 1.1. Phase I
         of the Project has been completed as of the Effective Date.
    

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6.       PHASE I/II PROJECT FEE

         IMCLONE shall pay BI PHARMA KG a Project Fee of DM 8, 950,000
         (eightmillionninehundredandfiftythousand Deutsche Mark) for the
         services provided in carrying out the Project as defined in APPENDIX 1
         and APPENDIX 1.1, regardless of the favorability or usefulness of the
         results (see Section 4.5 above). Of this amount to date DM 3,130,000
         has been paid for the completion of Phase I.

         This fee includes all fees for BI PHARMA KG's services under the
         Master Projectplans for Phase I and Phase II, including but not limited
         to, fees for Cell Line validation, facility use, raw material testing,
         in-process testing services including bulk and finished product
         testing, environmental monitoring as appropriate, and other calibration
         and validation activities required to facilitate the successful
         completion of the technology transfer and production of the clinical
         grade material at the [ *** ] fermentation scale.

         Disposal of organic and hazardous waste is included in the Project Fee.
         The Project Fee shall be payable in installments, each non-refundable
         when paid, as described in APPENDIX 1 and APPENDIX 1.1. To the extent
         BI PHARMA KG is required to repeat any fermentations or downstream
         operations pursuant to Section 4.5 (b) above, any installment related
         to the completion of the fermentation or downstream operation or
         delivery of the Product, as the case may be, shall not be payable until
         such fermentation or downstream operation or delivery of Product, as
         the case may be, has been completed.

         The cost of commercially available materials purchased by IMCLONE for
         use at BI PHARMA KG to support development in GLP and cGMP shall be
         creditable to the applicable invoice.

         Each invoice shall be payable within 30 (thirty) days following receipt
         thereof.

7.       ADDITIONAL WORK / FUTURE ACTIVITIES

7.1      Additional Work.
         BI PHARMA KG and IMCLONE may confer to determine if additional work
         relating to Phase I or Phase II should be undertaken pursuant to
         subsequent agreement between BI PHARMA KG and IMCLONE. Neither party
         shall be obligated to conduct any further undertakings on behalf of the
         other except as may be mutually agreed and set forth in a subsequent
         written agreement.

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7.2      Future Activities.
         In the event IMCLONE requires additional Product for the conduct of
         clinical Phase III and/or for commercial supply and IMCLONE determines
         in its sole discretion not to be the producer of that additional
         quantities of Product, then IMCLONE and BI PHARMA KG shall engage in
         good faith negotiations with respect to an agreement(s) for such
         additional supply to contain usual and customary terms for similar
         agreements under comparable circumstances. If the parties are unable to
         agree to terms (including, but not limited to terms regarding quantity
         of Product) within 120 (onehundredtwenty) days after BI PHARMA KG is
         informed of IMCLONE's detailed request in writing, then IMCLONE may
         engage in negotiations for such supply with other third parties;
         provided, however, that IMCLONE shall not consummate any such agreement
         with any third parties on terms that are in the aggregate more
         favorable than those terms offered by BI PHARMA KG to IMCLONE without
         first giving BI PHARMA KG an opportunity to accept the agreement(s) on
         the terms offered to such third parties.

         In case BI PHARMA KG will not exercise its right to enter into
         negotiations with IMCLONE regarding an agreement to govern clinical
         Phase III and/or commercial supply within 30 (thirty) days after the
         written request of IMCLONE or if the parties are not able to conclude
         such final agreement within 120 (onehundredtwenty) days after BI PHARMA
         KG has received the written request of IMCLONE or if BI PHARMA KG has
         not accepted the agreement(s) on the third party terms, then BI PHARMA
         KG shall be deemed to have waived its rights granted under this Section
         7.2.


7.3      Others.
         IMCLONE shall not assert any right to use BI PHARMA KG facilities at
         any future date as a result of its use of BI PHARMA KG facilities
         pursuant to this Agreement, nor shall BI PHARMA KG assert any right to
         use or have access to the Cell Line, Process, Product, MCB or MWCB as a
         result of its activities pursuant to this Agreement.

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8.       OWNERSHIP OF PROJECT DATA

8.1      General.

         All information and intellectual property rights relating to the
         transfer of information under Section 4.6 above, with the exception of
         BI PHARMA KG Confidential Information, shall be the sole and exclusive
         property of IMCLONE and IMCLONE shall have the right to use such
         information for any purpose without further obligation to BI PHARMA KG.

         For the purpose of this Agreement all information regarding BI PHARMA
         KG's facility and technical equipment shall be considered BI PHARMA
         KG'S Confidential Information.

8.2      Intellectual Property Rights solely covering the Product.

         Any and all intellectual property rights solely covering the Product,
         including, but not limited to, patents and patent applications arising
         out of the activities performed under this Agreement shall be the sole
         and exclusive property of IMCLONE, which shall have the sole right to
         file such applications and will meet all costs in relation thereto.
         Upon request of IMCLONE, BI PHARMA KG will assign any and all rights as
         necessary to vest such ownership in IMCLONE.

8.3      All other Intellectual Property Rights.

         All other intellectual property rights that arise out of the activities
         performed under this Agreement, and that do not cover solely the
         Product shall be the sole and exclusive property of BI PHARMA KG and
         IMCLONE shall be granted a non-exclusive, royalty-free and worldwide
         license solely for use to the Product.


9.       REPRESENTATIONS. WARRANTIES AND INDEMNIFICATION

9.1      IMCLONE.

         IMCLONE hereby represents, warrants and agrees that:

         (a)  IMCLONE is free to supply the Cell Line and IMCLONE Confidential
              Information to BI PHARMA KG;

         (b)  IMCLONE is not aware of any special or unusual hazards involved in
              handling the Cell Line or Product;


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         (c)  IMCLONE has full corporate authority to enter into this Agreement
              and this Agreement is binding upon IMCLONE in accordance with its
              terms; and

         (d)  IMCLONE shall indemnify, defend and hold BI PHARMA KG, its
              affiliates, and their respective officers, employees and agents
              harmless from and against all third party losses, damages, costs
              and expenses (including, without limitation, reasonable attorneys'
              fees), including injury to persons or damage to property resulting
              from (i) any breach of the representations and warranties made by
              IMCLONE under this Section, or (ii) any claim of infringement of
              the intellectual property rights of a third party based upon BI
              PHARMA KG's activities using the Cell Line or in implementing or
              using the Process or producing the Product in accordance with the
              instructions and documentation provided by IMCLONE or developed in
              the course of the Project, except those which result from the
              gross negligence or willful misconduct of an indemnified person or
              entity and those for which BI PHARMA KG would have been liable if
              BI PHARMA KG had used cell lines or processes other than Cell
              Lines or Processes, or produced products other than Products.

9.2      BI PHARMA KG.

         BI PHARMA KG hereby represents, warrants and agrees that:

         (a)  BI PHARMA KG has the lawful right to use the facilities and BI
              PHARMA KG Confidential Information to be used for purposes set
              forth in this Agreement;

         (b)  BI PHARMA KG is not aware of any special or unusual hazards that
              would arise as a result of its carrying out of the Project as
              planned;

         (c)  BI PHARMA KG has full corporate authority to enter into this
              Agreement and this Agreement is binding upon BI PHARMA KG in
              accordance with its terms; and

         (d)  BI PHARMA KG shall indemnify, defend and hold IMCLONE its
              affiliates and their respective officers, employees and agents
              harmless from and against all third party losses, damages, costs
              and expenses (including, without limitation, reasonable attorneys'
              fees), including injury to persons or damage to property,
              resulting from (i) any breach of the representations and
              warranties made by BI PHARMA KG under this Section, or (ii) any
              claim that BI PHARMA KG has violated any applicable local law or
              ordinance in carrying out


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              its manufacturing responsibilities under this Agreement or (iii)
              any claim of infringement of the intellectual property rights of a
              third party, except those which result from gross negligence or
              willful misconduct of an indemnified person or entity and those
              based on BI PHARMA KG activities using the Cell Line or in
              implementing or using the Process or producing the Product in
              accordance with the instructions and documentation provided by
              IMCLONE or developed in the course of the Project.

         (e)  BI PHARMA KG warrants that the Project shall be conducted as laid
              down in APPENDIX 1 and APPENDIX 1.1 and in accordance with this
              Agreement and, when appropriate, in compliance with cGMP, and that
              any documentation of Project results or procedures provided to
              IMCLONE by BI PHARMA KG shall be accurate in all material
              respects. With regard to the results see Section 4.5 above.


10.      LIMITATION OF LIABILITY

10.1     No Warranty of Merchantability or Fitness.

         Subject to Section 9.2 above, BI PHARMA KG shall provide the results of
         the Project to IMCLONE without any warranty of any kind, express or
         implied, including, without limitation, any warranties of
         merchantability or fitness for a particular purpose.

10.2     Limitation of Liability.

         IMCLONE acknowledges that BI PHARMA KG has no control over the manner
         in which IMCLONE intends to use any Product or results obtained in the
         Project.

         BI PHARMA KG shall not be liable to IMCLONE for any losses, damages,
         costs or expenses of any nature incurred or suffered by IMCLONE or by a
         third party, arising out of any dispute or other claims or proceedings
         made by or brought against IMCLONE with respect to use of the results
         of the Project, or the use of any Product by IMCLONE or by a third
         party (including, without limitation, product liability claims and
         claims by a third party alleging infringement of its intellectual
         property rights), except as to those under Section 9.2 (d) above, nor
         shall BI PHARMA KG be responsible in any way for dealing with any such
         disputes, claims or proceedings; provided that it shall cooperate with
         IMCLONE with respect to any such disputes or claims to the extent of
         providing necessary or advisable information in connection with
         IMCLONE's defense.


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10.3     Maximum Amount.

         BI PHARMA KG undertakes to use its best efforts to perform the Project
         under the Master Projectplans and to meet the target dates set forth in
         APPENDIX 1 and APPENDIX 1.1 hereto. However, due to the biological
         nature of the work to be performed hereunder BI PHARMA KG's liability
         under this Agreement and its indemnification and hold harmless
         obligations shall in no event amount to more than 10% (ten percent) of
         the Project Fee. This limitation does not apply to willful breach or
         misconduct of BI PHARMA KG or its officers, employees or agents.


11.      CONFIDENTIALITY

11.1     BI PHARMA KG.

         BI PHARMA KG shall not disclose IMCLONE Confidential Information to any
         person other than its employees or employees of affiliated companies of
         the Boehringer Ingelheim group who are bound by similar obligations of
         confidentiality and who have a need to know such information in order
         to perform their duties in carrying out the Project hereunder.

11.2     IMCLONE.

         IMCLONE shall not disclose any BI PHARMA KG Confidential Information to
         any person other than:

         (a)  its employees or consultants who are bound by substantially
              similar obligations of confidentiality and who have a need to know
              such information in order to provide direction to BI PHARMA KG or
              evaluate the results of the Project; or

         (b)  regulatory authorities, for example, the FDA, that require such
              information in order to review an IND or other regulatory filing.

11.3     Exceptions.

         The obligations of confidentiality applicable to IMCLONE Confidential
         Information and BI PHARMA KG Confidential Information shall not apply
         to any information that is:

         (a)  known publicly or becomes known publicly through no fault of the
              recipient;

         (b) learned by the recipient from a third party entitled to disclose
             it;


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         (c)  developed by the recipient independently of information obtained
              from the disclosing party as evidenced by prior written records of
              the recipient;

         (d)  already known to the recipient before receipt from the disclosing
              party, as shown by its prior written records;

         (e)  required to be disclosed by law, regulation or the order of a
              judicial or administrative authority; provided that the recipient
              notifies the disclosing party immediately upon receipt at any such
              order or becoming aware of any such law or regulation, or released
              with the prior written consent of the disclosing party.

11.4     Others.

         No right or license under any patent or proprietary right is granted
         hereunder by virtue of the disclosure of IMCLONE Confidential
         Information or BI PHARMA KG Confidential Information except as
         expressly provided herein. The obligations of both parties under this
         Section 11 shall survive the expiration or termination of this
         Agreement.

         Both IMCLONE and BI PHARMA KG shall use reasonable and customary
         precautions to safeguard IMCLONE Confidential Information and BI
         PHARMA KG Confidential Information, including ensuring that all
         employees or consultants who are provided access to such information
         are informed of the confidential and proprietary nature of such
         information and understand that all such information is required to be
         maintained confidential.


12.      TERM AND TERMINATION

12.1     Term.

         This Agreement shall come into force as of the date first above written
         and commence retroactively as of the Start Date and, unless terminated
         earlier as provided herein, shall terminate upon the date of payment of
         the last sum due hereunder, or upon the date when the last services
         required to be performed hereunder are performed, whichever date shall
         last occur unless specifically extended by further written agreement.

12.2     Right to Terminate.

         If it becomes apparent to either party at any stage of the Project that
         it will not be possible to carry out the Project for scientific or
         technical reasons or as a result of Force Majeure (as described in
         Section 13 below), the parties shall permit 30 (thirty) business days
         for discussion to


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         resolve, if possible, the scientific or technical issue giving rise to
         the problem. If the parties fail to resolve the problem within this 30
         (thirty) day period, either party shall have the right to terminate
         this Agreement, effective upon written notice to the other.

         In the event of such a termination initiated by IMCLONE, the amount due
         to BI PHARMA KG hereunder shall equal all expenses reasonably incurred
         by BI PHARMA KG prior to such termination in respect of the purchase of
         supplies or raw materials plus an allocation of the balance of the
         Project for the period prior to such termination and for a period of 8
         (eight) weeks thereafter. BI PHARMA KG shall cease all work following
         notice by IMCLONE of termination, and shall attempt in good faith to
         minimize expenses hereunder by, for example, canceling any orders that
         can be canceled.

         Either party may terminate this Agreement effective upon written notice
         if either of the following events occurs:

         (a)  The other party commits a breach of this Agreement and the breach
              is not remedied within 30 (thirty) days after the receipt of
              notice identifying the breach, requiring its remedy and stating
              the intent of the party to terminate in the absence of remedy; or

         (b)  The other party (i) becomes unable to pay its debts as they become
              due, (ii) suspends payment of its debts, (iii) enters into or
              becomes subject to corporate rehabilitation or bankruptcy
              proceedings or liquidation or dissolution, (iv) makes an
              assignment for the benefit of its creditors or (v) seeks relief
              under any similar laws for debtor's relief.

12.3     Effect of Termination.

         Upon the expiration or termination of this Agreement:

         (a)  At the request of IMCLONE, BI PHARMA KG shall deliver at the cost
              and risk of IMCLONE all vials of the Cell Line, the MCB and the
              MWCB, as well as description of all methods relating thereto to
              IMCLONE or its designee and shall promptly return all IMCLONE
              Confidential Information to IMCLONE; except for a single copy
              and/or sample for documentation purposes only and

         (b)  IMCLONE shall promptly return all BI PHARMA KG Confidential
              Information to BI PHARMA KG, except for a single copy and/or
              sample for documentation purposes only.

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              The respective rights of BI PHARMA KG and IMCLONE to
              indemnification as set forth in Sections 9 and 10 above shall
              survive termination of this Agreement with respect to any claims
              that relate to or derive from the Project, or any acts or failures
              to act, of either BI PHARMA KG or IMCLONE in connection with the
              Project that occur prior to termination.


13.      MISCELLANEOUS

13.1     Force Majeure.

         Neither party shall be in breach of this Agreement if there is any
         failure of performance under this Agreement (except for payment of any
         amounts incurred hereunder prior to Force Majeure) occasioned by any
         act of God, fire, act of government or state, war, civil commotion,
         insurrection, embargo, prevention from or hindrance in obtaining energy
         or other utilities, labor disputes of whatever nature or any other
         reason beyond the control of either party.

13.2     Publicity.

         Except as required by law (e.g. SEC-requirements), no press release or
         other form of publicity regarding the Project or this Agreement shall
         be permitted to be published unless both parties have indicated their
         consent to the form of the release. Notwithstanding the foregoing,
         IMCLONE may elect to issue a press release or other form of publicity
         regarding the Project at any time, but shall first notify BI PHARMA KG
         of such issuance and provide BI PHARMA KG with an opportunity to
         comment thereon. Nothing in this Section 13.2 shall prevent the parties
         from disclosing this Agreement as required by applicable laws, rules or
         regulations.

13.3.    Notices.

         Any notice required or permitted to be given hereunder by either party
         shall be in writing and shall be (i) delivered personally, (ii) sent
         by registered mail, return receipt requested, postage prepaid or (iii)
         delivered by facsimile with immediate telephonic confirmation of
         receipt, to the addresses or facsimile numbers set forth below: If to
         BI PHARMA KG:            Boehringer Ingelheim Pharma KG
                                  Birkendorfer Strasse 65
                                  D-88397 Biberach an der Riss
                                  Federal Republic of Germany
                                  Attention: Dr. Wolfram Carius
                                  Fax: + 0049 73 51/54-98049
                                  Phone + 0049 73 51/54-9421

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         If to IMCLONE:           ImClone Systems Incorporated
                                  180 Varick Street, 7th Floor
                                  New York, New York 10014
                                  Attention: Mr. John B. Landes,
                                             Vice President,
                                  Business Development and General Counsel
                                  Fax:      001 212 645 1405
                                  Phone: 001 212 645 2054

         Each notice shall be deemed given (i) on the date it is received if it
         is delivered personally, (ii) 1 (one) day after the date it is
         postmarked if it is sent by certified United States mail, return
         receipt requested, postage prepaid or (iii) on the date it is received
         if it is sent by facsimile with immediate telephonic confirmation of
         receipt.

13.4.    Applicable Law.

         This Agreement shall be governed by and construed in accordance with
         the laws of Germany without regard to its choice of law principles. The
         courts of the place of domicile of BI PHARMA KG shall have exclusive
         jurisdiction over all legal matters and proceedings hereunder.

13.5     Compliance with Laws.

         BI PHARMA KG shall perform the work hereunder in conformance with
         GLP/cGMP, as applicable, and all German and/or EU laws, ordinances and
         governmental rules or regulations pertaining thereto.

13.6.    Independent Contractors.

         Each of the parties hereto is an independent contractor and nothing
         herein contained shall be deemed to constitute the relationship of
         partners, joint venturers, nor of principal and agent between the
         parties hereto. Neither party shall hold itself out to third persons as
         purporting to act on behalf of, or serving as the agent of, the other
         party.

13.7.    Waiver.

         No waiver of any term, provision or condition of this Agreement whether
         by conduct or otherwise in any one or more instances shall be deemed to
         be or construed as a further or continuing waiver of any such term,
         provision or condition or of any other term, provision or condition of
         this Agreement.

13.8     Severability.

         If any provision of this Agreement is held to be invalid or
         unenforceable by a court of competent jurisdiction all other
         provisions shall continue in full force and effect. The parties hereby
         agree to attempt to substitute for

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         any invalid or unenforceable provision a valid or enforceable provision
         which achieves to the greatest extent possible the economic legal and
         commercial objectives of the invalid or unenforceable provision.

13.9     Entirety.

         This Agreement, including any exhibits and appendices attached hereto
         and referenced herein, constitutes the full understanding of the
         parties and a complete and exclusive statement of the terms of their
         agreement, and no terms, conditions, understandings or agreements
         purporting to modify or vary the terms thereof shall be binding unless
         it is hereafter made in writing and signed by both parties.

13.10    Assignment.

         Neither party may assign this Agreement to a third party, except an
         affiliate (including a subsidiary or division), and either IMCLONE or
         BI PHARMA KG may assign this Agreement in connection with the sale of
         all or substantially all of such party's assets or similar transaction.
         This Agreement shall be binding upon the successors and assigns of the
         parties and the name of a party appearing herein shall be deemed to
         include the names of its successors and assigns.

IN WITNESS WHEREOF, the parties have caused this Agreement to be executed as of
the Effective Date.

Biberach, ...............1999                  New York, April 30, 1999

BOEHRINGER INGELHEIM PHARMA KG                 IMCLONE SYSTEMS INCORPORATED

                   ppa.



Dr. Jacob                 Prof. R. G. Werner         By: John B. Landes
Member of the Board       Head of Industrial
                          Biopharmaceuticals         Title: VP, General Counsel

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APPENDICES:
-----------

Appendix 1:          Master Projectplan including Project Timeline

Appendix 1.1:        Updated Master Projectplan including Project timeline

Appendix 2:          Project Team

Appendix 3:          IMCLONE's Tasks in Detail

Appendix 4:          BI PHARMA KG's Tasks in Detail

Appendix 5:          Test Methods and Specifications for C225

Appendix 6:          Protein A Process Format

Appendix 7:          Summary Data Reports for Phase I and Phase II


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Appendix 1   Page 1 of  2

-------------------------------------------------------------------------------
Master Projectplan: C225
ImClone Systems, Inc./BI Pharma KG
Forecast of proposed Workscope and Cost Estimate


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

   [ ***]

Appendix 1.1  Page 1 of  4
-------------------------------------------------------------------------------
Update May 1999 Master Projectplan: C225
ImClone Systems, Inc./BI Pharma KG
Forecast of proposed Workscope and Cost Estimate


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

   [ ***]

                                   Appendix 2




-------------------------------------------------------------------------------------------------------------
              Function                       Boehringer Ingelheim                      ImClone
-------------------------------------------------------------------------------------------------------------
                                                                       
        Project Team Leader                  Dr. Helmut Hoffmann                Mr. Ronald Martell (?)
                                                                                   Ms. Martie Bohn
-------------------------------------------------------------------------------------------------------------
    Head of Process Development              Dr. Helmut Hoffmann                         (?)
-------------------------------------------------------------------------------------------------------------
 Cell Banking and Characterization,        Dr. Stefanos Grammatikos              Ms. Betsy Hornberger
           Virus Testing                                                           Dr. Daniel Velez
                                                                               Dr. S. Joseph Tarnowski
-------------------------------------------------------------------------------------------------------------
   Small Scale Cell Culture Labs               Dr. Wolfgang Noe                   Mr. Joel Goldstein
                                                                                   Mr. Rajeew Gupta
                                                                                   Dr. Daniel Velez
                                                                               Dr. S. Joseph Tarnowski
-------------------------------------------------------------------------------------------------------------
      Fermentation Pilot Plant                Dr. Ralph Kempken                   Mr. Joel Goldstein
                                                                                   Mr. Rajeew Gupta
-------------------------------------------------------------------------------------------------------------
       Downstream Processing                  Dr. Joachim Walter                   Dr. Daniel Velez
                                                                                  Mr. Joel Goldstein
                                                                               Dr. S. Joseph Tarnowski
-------------------------------------------------------------------------------------------------------------
    Protein Analytical Chemistry             Dr. Michael Schluter                Ms. Betsy Hornberger
-------------------------------------------------------------------------------------------------------------
         Process Validation                 Mr. Norbert Hentschel                  Mr. Glen Noonan
-------------------------------------------------------------------------------------------------------------
              Filling                          Mr. Hans Hormann                   Mr. Edward Patten
-------------------------------------------------------------------------------------------------------------
             Regulatory                        Dr. Uwe Bucheler                  Ms. Gretchen Toolan
-------------------------------------------------------------------------------------------------------------
           Documentation                       Dr. Uwe Bucheler                   Mr. Edward Patten
-------------------------------------------------------------------------------------------------------------
         Quality Assurance                   Mrs. Bettina Schulz
-------------------------------------------------------------------------------------------------------------
              Contract                           Mrs. Kipping
-------------------------------------------------------------------------------------------------------------


                                   APPENDIX 3


                           IMCLONE'S TASKS IN DETAILS


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                                   APPENDIX 4


                         BI PHARMA KG's Tasks in Detail


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APPENDIX 5: TEST METHODS AND SPECIFICATIONS FOR C225


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                                   APPENDIX 6

                            [ *** ] A Process Format


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                                   APPENDIX 7


                  SUMMARY DATA REPORTS FOR PHASE I AND PHASE II