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


    Amendment of December 1997 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
(hereinafter the 'Agreement') effective April 1, 1990 which has been previously
amended on September 1, 1993, November 2, 1993, and on May 14, 1996; and

      WHEREAS the parties intend to further modify the Agreement to represent
the current intent of the parties with respect to the marketing of BEC2 in North
America, it being the intent of the parties that ImClone and Merck shall
co-market BEC2 in North America in accordance with the 'Terms of Co-Marketing of
BEC2 by Merck and ImClone in North America' to be negotiated in good faith by
the parties hereafter and appended as Exhibit B to this Amendment; and

      WHEREAS the parties have also on this day entered into a Preferred Stock
Purchase Agreement for the purchase by Merck of ImClone convertible preferred
stock; and

      THE PARTIES HEREBY MODIFY and amend the Agreement in the following
respects (hereinafter the 'Amendment'):

1. 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
      which incorporate BEC2 and gp75 worldwide outside North America; and
      ImClone grants to Merck a Sole License restricted in accordance with
      Exhibit B and the other terms of this Amendment, without the right to
      sublicense, to use, sell or have sold, but not to make, Licensed Products
      which incorporate BEC2 in North America in conjunction with ImClone.'


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

      '2.2 Merck hereby grants to ImClone a Sole License, without 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 which
      incorporate BEC2 in North America in conjunction with Merck in accordance
      with Exhibit B and the other terms of this Amendment; and Merck 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 which incorporate gp75 in North America.'

3. 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) which incorporate gp75 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.'

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

      '2.5(b) ImClone hereby grants to Merck an exclusive license, with the
      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
      which incorporate Improvements to BEC2 and gp75 worldwide outside North
      America; and ImClone grants to Merck a Sole License restricted in
      accordance with Exhibit B and the other terms of this Amendment, without
      the right to sublicense, to such rights as ImClone may hold to
      Improvements to use, sell or have sold, but not to make, Licensed 


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      Products which incorporate Improvements to BEC2 in North America in
      conjunction with ImClone.'

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

      '2.5(c) If ImClone grants Merck a license to Licensed Products which
      incorporate gp75 (or right to distribute) under Section 2.3 above, then
      ImClone shall grant Merck the same kind of license, (or right to
      distribute) in the Field to such rights as ImClone may hold to
      Improvements to make, use or sell Licensed Products which incorporate
      Improvements to gp75 in North America.'

6. 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 a Sole License, without the right
      to sublicense, to such rights as Merck may hold to Improvements, to make,
      use, sell or have sold Licensed Products which incorporate Improvements to
      BEC2 in North America in conjunction with Merck in accordance with Exhibit
      B and the other terms of this Amendment; and Merck 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 which incorporate Improvements to gp75 in North
      America.'

7. Section 3.4 shall be modified to 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 worldwide
      outside North America. 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 to obtain approval for the
      indication of the treatment of limited disease small cell lung carcinoma
      for the 


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      BEC2. Costs, including out-of-pocket costs of ImClone (but not including
      cost of establishment of a manufacturing facility), 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 which incorporate BEC2 worldwide
      shall be paid by Merck. Notwithstanding the previous sentence, Merck's
      sole responsibility to bear the expense of the conduct of such clinical
      trials shall be capped at 17 million DM. To the extent that the expenses
      of the conduct of such clinical trials exceed 17 million DM, such expenses
      shall be shared, 60% for Merck and 40% for ImClone. The expense of the
      conduct of additional clinical trials for other indications shall be
      subject to separate budgets to be negotiated by the parties. It is the
      intent of the parties that ImClone be the party responsible for
      establishment of the manufacturing site for the active agent, at ImClone's
      expense. It is also intended that ImClone be responsible for providing
      supply of the active agent worldwide, at the expense of Merck. However,
      costs of goods in North America, which shall include ImClone's costs plus
      a negotiated provision for overhead, shall be paid out of gross sales of
      the Licensed Product in North America, in accordance with the terms of the
      Co-Marketing Agreement, Exhibit B.'

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

      '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 2
      yielding at least 7.5 grams of material meeting the specifications of the
      Research and Development Protocol (paid);

      b. $1,000,000 upon successful manufacture of bulk cGMP BEC 2 material
      meeting the specifications of the Research and Development Protocol
      (paid);


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      c.     ***               ***;

      d.     $500,000 upon signing of this Amendment;

      e.     ***               ***;

      f.     ***               ***;

      g.     ***               ***;

      h.     ***               ***';

      i.     ***               ***;

      j.     ***               ***;

      k.     ***               ***;

      l.     ***               ***;

      m.     ***               ***;

      n.     ***               ***;

      o.     ***               ***;

      p. In the case that Merck enters into a distribution or sublicensing
      arrangement for the marketing of BEC2 in Japan and receives consideration
      in such transaction 


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

9. 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 *** .'

      '4.4(c) Gross Sales of Licensed Products which incorporate BEC2 in North
      America shall be distributed in accordance with the terms of Exhibit B
      appended hereto entitled 'Terms of Co-Marketing of BEC2 by Merck and
      ImClone in North America' to be negotiated in good faith by the parties
      hereafter and to be appended hereto as Exhibit B. Exhibit B shall
      establish the terms of a co-marketing of BEC2 in North America by Merck
      and is intended to include among other things the following:

      o  Establishment of a committee of the parties to plan and monitor the
         marketing of BEC2 in North America, which is anticipated to involve
         sales by separate but coordinated sales forces of ImClone and Merck and
         coordinated distribution of final product, with ImClone responsible for
         manufacture of the active agent, and costs for manufacture to be paid
         from gross sales in North America.


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Confidential Treatment and filed separately with the Commission.



      o  Defining the components of Gross Margin against which costs
         reimbursable to the parties and shares payable to the parties shall be
         determined (Gross Margin generally to be Net Sales less cost of goods,
         cost of distribution and other third party payments, including
         royalties); and

      o  A division of Gross Margin such that each party will receive a
         guaranteed share of *** of Gross Margin, and the remaining *** of Gross
         Margin shall be divided between the parties in accordance with the
         respective level of sales and marketing expense contributed by the
         parties.'

     IN WITNESS WHEREOF, Amendment to the Agreement has been executed this 
_______ day of December, 1997.

ImClone Systems Incorporated                Merck KGaA

By:      /s/ Samuel D. Waksal               By:      /s/ E. R. Roberts
         ---------------------------                 --------------------------
Name:    Samuel D. Waksal                   Name:    E. R. Roberts

Title:   President & CEO                    Title:   Managing Partner

Date:    December 3, 1997                   Date:    December 3, 1998



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