Research and License Agreement - ImClone Systems Inc. and Merck KGaA


       Amendment of May 1996 to the Research and License Agreement between
                   ImClone Systems Incorporated and Merck KGaA

     WHEREAS ImClone Systems (hereinafter 'ImClone') and Merck KGaA (hereinafter
'Merck') are parties to a Research and License Agreement effective April 1, 1990
which has been previously amended on September 1, 1993 and on November 2, 1993;
and

     WHEREAS the parties intend to further modify the Agreement to represent the
current intent of the parties with respect to the development of BEC-II and
gp75, the parties hereby modify and amend the Agreement in the following
respects:

1. The recitation of the parties on page one of the Agreement shall replace the
name E. Merck with the name Merck KGaA.

2. Section 1.16 shall be modified to read in its entirety as follows:

    '1.16 The term 'Research and  Development  Protocol' shall mean the plan for
    the  conduct of the  Research  and  Development,  as set forth in Schedule E
    attached hereto and specifically  incorporated herein, and as may be amended
    by the parties  from time to time,  including  with  respect to  Alternative
    Product(s).'

3. Section 1.17 shall be modified to read in its entirety as follows:

    '1.17 The term 'Research and  Development  Period' shall mean that four year
    period during which the initial  research on BEC-II and gp75 was  performed,
    in accordance with the terms of Article 3 hereof, which four year period has
    concluded.'


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4. Section 2.1 shall be modified to read in its entirety as follows:

    '2.1 ImClone hereby grants to Merck an exclusive license,  with the right to
    sublicense,  in the Field under Licensed Patents and/or Licensed  Technology
    to make,  have made,  use, sell, or have sold Licensed  Products  worldwide,
    with the  exception  of North  America.  ImClone  retains  all rights to the
    Licensed Patents and the Licensed Technology other than granted hereby.'

5. Section 2.2 shall be modified to read in its entirety as follows:

    '2.2 Merck hereby grants to ImClone an exclusive license,  with the right to
    sublicense,  to all rights which it may have to Licensed Technology to make,
    have made, use, sell or have sold Licensed Products in North America.'

6. Section 2.3 shall be modified to read in its entirety as follows:

    '2.3  If,  during  the term of the  Agreement,  ImClone  intends  to grant a
    license, exclusive or otherwise (or right to distribute) in the Field, under
    Licensed Patent(s) and/or Licensed Technology, to make, use or sell Licensed
    Product(s) in North America,  it shall so notify Merck in writing and afford
    Merck the  opportunity  to  negotiate  terms for such a license.  Should the
    parties not enter into such a license in writing  within ninety (90) days of
    such  written  notification  to Merck,  the offer  shall be deemed  formally
    withdrawn.'

7. Section 2.5(b) shall be modified to read in its entirety as follows:

    '2.5 ImClone  hereby grants to Merck an exclusive  license,  with a right to
    sublicense,   in  the  Field,   to  such  rights  as  ImClone  may  hold  to
    Improvements,  to make, have made, use, sell or have sold Licensed  Products
    worldwide outside North America.'


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8. Section 2.5(c) shall be modified in its entirety to read as follows:

    '2.5(c) If ImClone  grants  Merck a license (or right to  distribute)  under
    Section  2.3 above,  then  ImClone  shall grant Merck a license (or right to
    distribute) in the Field to such rights as ImClone may hold to  Improvements
    to make,  have  made,  use,  sell or have sold  Licensed  Products  in North
    America.'

9. Section 2.5(d) shall be modified so that the first sentence shall read in its
entirety as follows (the remainder of the section shall remain unchanged):

    '2.5(d) Merck hereby grants to ImClone an exclusive license,  with the right
    to sublicense,  to such rights as Merck may hold to  Improvements,  to make,
    have made,  use, sell or have sold Licensed  Products in North  America,  at
    conditions to be negotiated in good faith by the parties hereto.'

10. Section 3.2 shall be modified to add a sentence at the end of the section as
follows:

    'The funds  required  herein for the  support of  research of the BEC-II and
    gp75 had been paid by Merck, and Merck shall have no further  obligations as
    a result of this Section 3.2'

11. Section 3.4 shall be modified so that it shall read in its entirety as
follows:

    '3.4.  The  Research  and  Development  Protocol  includes the plans for the
    conduct and management of clinical  trials,  development and  manufacturing,
    further research,  and for the filing for appropriate  regulatory  approvals
    for the sale of the  Licensed  Products.  All of such  clinical  trials  and
    regulatory   submissions  shall  be  the  responsibility  of  Merck  in  the
    territories wherein it has a license and/or assignment  hereunder.  However,
    it is the intention of the parties, as further set forth in the Research and
    Development  Protocol,  to  conduct  a  multi-site   multi-national  pivotal
    clinical  trial  for the  BEC-II.


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    Costs,  including  those of ImClone,  as  contemplated  in the  Research and
    Development  Protocol,  for  manufacturing of materials for clinical trials,
    conduct of clinical  trials,  and  regulatory  submissions  (other than drug
    approval  fees  which are the  responsibility  of Merck or  ImClone in their
    respective  territories)  in connection with the development of the Licensed
    Products for the U.S., Europe,  Australia and New Zealand shall be shared by
    the parties in the proportion of 60% by Merck and 40% by ImClone.  It is the
    intent of the parties that  ImClone be the  commercial  manufacturer  of the
    Licensed  Products  worldwide.  Achievement of such shall be as set forth in
    the Research and Development Protocol.'

12. Section 4.2 was amended by the amendment dated November 2, 1993 (the
'Amendment'). It is hereby acknowledged by the parties that Payments one, two,
three and four under Section 4.2(a) through 4.2(c) of the Agreement and Payment
one of the Amendment have been made. Other consideration in the Agreement
originally contemplated in the remainder of Section 4.2, as amended by the
Amendment, and Section 4.3, shall be increased, and the payment structure shall
be as follows, which shall replace Sections 4.2(d), 4.2(e) and Section 4.3 in
their entirety:

     '4.2(d) Upon the achievement of milestone (a) in Section 4.3, a schedule of
     quarterly payments totaling  $4,700,000 shall commence.  The first payment,
     in the  amount  of  $625,000,  shall  be  made  within  30 days  after  the
     achievement  of the  milestone.  Seven  quarterly  payments  shall  be made
     thereafter,  at quarterly intervals, all in the amount of $625,000, but for
     the last  payment,  which  shall be in the  amount  of  $325,000.  The last
     payment  has been  reduced in part to  reflect  the  acknowledgment  of the
     parties  that the payment for the  demonstration  originally  called for in
     Section 4.2(c) was made under dispute, which has been resolved.'

     Section 4.2(e) shall be deleted in its entirety.

     Section 4.3 shall be modified to read in its entirety as follows:


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     '4.3 In  addition,  Merck shall pay ImClone  the  following  non-refundable
     milestone payments:

     a. $500,000 upon the  achievement  of a pilot-scale  (based on the Research
     and  Development  Protocol)  fermentation  in  the  manufacture  of  BEC-II
     yielding at least 7.5 grams of material meeting the  specifications  of the
     Research and Development Protocol;

     b.  $1,000,000  upon  successful  manufacture of bulk cGMP BEC-II  material
     meeting the specifications of the Research and Development Protocol;

     c.     ***               ***;

     d.     ***               ***;

     e.     ***               ***;

     f.     ***               ***;

     g.     ***               ***;

     h.     ***               ***;

     i.     ***               ***;

     j.     ***               ***;

     k. In the case  that  Merck  enters  into a  distribution  or  sublicensing
     arrangement for the marketing of BEC-II in Japan and receives


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***  Portions  of  this  page  have  been  omitted  pursuant  to a  request  for
Confidential Treatment and filed separately with the Commission.



     consideration in such transaction  other than royalties or payments related
     to sales  (e.g.  license  fees,  payments in lieu of  royalties),  *** such
     payments  shall be paid over to  ImClone  at the time or times  that  Merck
     receives such consideration, not to exceed    *** .'

13. Section 4.4 shall be modified to read in its entirety as follows:

     '4.4(a)  On Net Sales of  Licensed  Products  in Europe,  Australia  or New
     Zealand by Merck, its Affiliates, distributors or sublicensees, Merck shall
     pay ImClone *** .'

     '4.4(b) On Net Sales of Licensed Products outside Europe, Australia and New
     Zealand, excluding North America, by Merck, its Affiliates, distributors or
     sublicensees, Merck shall pay ImClone *** ;'

14. Section 9.1 shall be modified to read in its entirety as follows:

     '9.1  ImClone  represents  that to the best of its  knowledge  Merck's use,
     making,  having made, selling and/or having sold Licensed Products does not
     violate  the  patent  rights  of  any  third  party.   The  parties  hereby
     acknowledge  families  of patent  applications  filed under the name of the
     inventors Koprowski et. al. and entitled 'Induction of Antibody Response to
     Solid Tumors with  Anti-Idiotype  Antibodies,' and the parties  acknowledge
     that Merck has obtained a non-exclusive  worldwide  license by Wistar under
     the patent  applications  mentioned  above,  and that ImClone  shall not be
     required to contribute payments to such license in Merck's territory.'

15. Section 10.2 shall be modified to read in its entirety as follows:

     '10.2 The parties may agree at any time to  terminate  the  Agreement  at a
     fixed date. Prior to or at termination,  as the case may be, if any portion
     of


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***  Portions  of  this  page  have  been  omitted  pursuant  to a  request  for
Confidential Treatment and filed separately with the Commission.



     any payment  under  Section  4.2(d) is due ImClone  through the agreed upon
     termination  date,  based on a proration  according to calendar time,  such
     portion shall be paid by Merck to ImClone. Alternatively, if at termination
     any portion of any payment  pursuant to Section 4.2(d) already  received by
     ImClone is attributable to the period after the termination  date (based on
     a proration  according to calendar time) ImClone shall promptly refund such
     portion to Merck.'

16. Section 10.3 shall be modified to read in its entirety as follows:

     '10.3 Prior to the completion of all payments under Section  4.2(d),  Merck
     shall  have  the  right  to  terminate  the  Agreement,  based  on a  sound
     scientific  determination.  Merck shall give ImClone  written notice of its
     intent to  terminate,  and a meeting  of the  Research  Committee  shall be
     convened  within  two (2) weeks to discuss  the  grounds  for  termination.
     ImClone shall have ninety (90) days from the date of the meeting to provide
     data to substantiate continuation of the work. Merck may then terminate the
     Agreement with immediate  effect.  Prior to or at termination,  as the case
     may be, if any portion of any payment under  Section  4.2(d) is due ImClone
     through the intended date of termination, based on a proration according to
     calendar   time,   such  portion   shall  be  paid  by  Merck  to  ImClone.
     Alternatively,  if at termination  any portion of any payment under Section
     4.2(d) already  received by ImClone is attributable to the period after the
     termination date (based on a proration according to calendar time), ImClone
     shall promptly refund such portion to Merck.'

17. Section 10.6 shall be modified to read in its entirety as follows:

     '10.6  If Merck  fails in a  country  in  which  Merck  has a right to sell
     Licensed Products or Alternative Products to pursue in a timely fashion and
     with  all due  diligence  regulatory  approval  or  sale of an  Alternative
     Product or Licensed Product,  and such failure is not remedied within sixty
     days (60) after  written  notice  from  ImClone  specifying  such  failure,
     ImClone may  


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     immediately,  without further notice or opportunity to cure,  terminate the
     license with respect to such  Licensed  Product or  Alternative  Product in
     such country.'

18.  Section  10.7 shall be modified to remove the word  'other'  from the first
line of the section.

     IN WITNESS  WHEREOF,  this Amendment to the Agreement has been executed
this _______ day of May, 1996.


ImClone Systems Incorporated            Merck KGaA

By:    /s/ Samuel D. Waksal             By:    /s/ Dr. Orth /s/ Dr. Uhl        
       ---------------------------             -----------------------------
Name:  Samuel D. Waksal                 Name:  Dr. Orth  Dr. Uhl

Title: President & CEO                  Title: Principal Officer/ Authorized 
                                               Representative

Date:  May 14, 1996                     Date:  October 23, 1996


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Attachment E:  Research and Development Protocol

1.    BEC-2

      The initial development plan for the development of the product
      established by the parties is attached hereto as encl. 1 (MS-Project EMD
      60 205) and will be amended from time to time.

1.1   Manufacturing of trial medication for the multinational pivotal phase
      II/III study or studies in the indication SCLC

      The trial medication must meet at least the specifications laid down in
      BB-IND 5076 resp. must fulfill new requirements of the US and EU
      authorities (c.f. encl. 1) and show equal potency with adequate methods
      (c.f. section 1.2).

      ImClone is responsible for the production and the quality control as well
      as for the release of bulk, of the final formulation and of the clinical
      trial medication including the appropriate storage and shipment according
      to the requirements of EU and US guidelines. ImClone will coordinate all
      activities necessary to supply BEC-2 for phase II/III clinical trial(s).
      ImClone will provide support Merck for any legal and regulatory release
      requirements or negotiations specific for EU clinical investigations.
      These activities will be carried out in close contact with the responsible
      persons at Merck.

      ImClone will consult with Merck and come to an agreement with Merck on all
      questions related to the establishment of and/or all changes concerning
      upstream processing, downstream processing, formulation, filling, the
      stability program (bulk and final formulation), the specifications
      (including all assays and test procedures) as well as the committed BCG
      medication.

      ImClone will consult with Merck about their contracts with any third party
      contractors and will obtain an approval from Merck for all agreements with
      third party contractors related to the manufacturing of BEC-2 clinical
      trial medication. Merck use its best efforts to review and approve such
      contract agreements within a short period of time.

      Merck will receive the complete documentation (original data and reports)
      on all aspects of manufacturing, including but not limited to cell banks,
      such documentation having to be identical to the documentation available
      to ImClone. Merck will receive, on request, samples of the MCB and the
      WCB.

      Merck will have the right to make audits at ImClone or at the sites of
      third partners of ImClone. Furthermore, ImClone will ensure that Merck has
      access to all available data in original and final report form. ImClone
      will use best efforts to ensure access to original data in the event a
      contractor ceases its operation.




      Costs to be paid to third parties for manufacturing, quality control,
      storage, etc., of the clinical trial material shall be shared by the
      parties according to section 3.4 of the LICENSE AGREEMENT. Any occurring
      costs must be approved in advance by the RESEARCH COMMITTEE.

      Manufacturing costs as well as costs to manufacturing (e.g., costs for
      quality control and batch release) arising at ImClone will be shared by
      Merck only if the BEC-2 production at Celltech Therapeutics fails to meet
      the specification laid down in BB-IND 5076 and if both parities agree to
      manufacturing at ImClone.

1.2   Preclinical studies to verify the identity of BEC-2

      In order to more fully characterize BEC-2 the following will be done

      1.                   ***      .

      2.                   ***      .

      3.                   ***      .

      4.                   ***      .

      Further preclinical studies performed to verify the identity of BEC-2 may
      be included.

      ImClone will consult with Merck about any contracts with third party
      contractors and will obtain an approval from Merck for all agreements with
      third party contractors related to the preclinical studies with BEC-2.
      Merck use its best efforts to review and approve such contract agreements
      within a short period of time.

      Merck will receive the complete documentation (original data and
      reports)on all aspects of preclinical studies performed to verify the
      identity of BEC-2, such documentation having to be identical to the
      documentation available to ImClone.

1.3   Clinical studies

      The parties will jointly prepare, perform, evaluate and report the pivotal
      study or studies necessary for obtaining the approval for marketing of
      BEC-2 both in the US and in the EU. Both parties have the right to perform
      audits at the other party's site and the sites of all clinical
      investigators.

      If both parties do not come to an agreement on the study protocol(s), the
      evaluation of the data or on the final report(s), third party's expertise
      (3 experts, to be named) shall be obtained for arbitration.

***  Portions  of  this  page  have  been  omitted  pursuant  to a  request  for
Confidential Treatment and filed separately with the Commission.



      Furthermore, both parties shall consult each other about additional
      clinical trials which may be performed by one party alone. ImClone will
      provide Merck with the trial material for any such studies to be performed
      by Merck. The parties agree to inform each other on all planned or ongoing
      activities within the RESEARCH COMMITTEE.

1.4   Regulatory Affairs

      a)  ImClone is responsible for providing all sections of regulatory
          dossiers including but not limited to expert reports of

          -IND, CTX and other applications clinical trial licenses 
          -PLA's and other applications for marketing authorization

          Any such documentation will be prepared according to current or then
          applicable FDA, EU, Japan or other national or international
          regulatory requirements.

      b)  Merck will share with ImClone all national or international
          information on the European regulatory status of the BEC-2 project. On
          the other hand, ImClone will use its best efforts to keep Merck
          informed about the US regulatory status of the BEC-2 project.

      c)  An electronic  mail system between the regulatory  departments of both
          companies will be established as soon as possible.

2.    gp75 and other entities covered under this Agreement

      gp75 as referred to in Attachment E of the Agreement dated April 1, 1990
      will be amended by the RESEARCH COMMITTEE.