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                                                                   Exhibit 10.46

                      [Letterhead of Pharmacopeia, Inc.]

                               December 17, 1998


Lewis Shuster
18 East Kincaid Drive
Cranbury, NJ  08512

Dear Lew:

          As you know, the letter agreement between you and Pharmacopeia, Inc.
(the "Company") dated October 4, 1994, as amended on October 10, 1994 (the "1994
Letter"), provided for, among other things, severance payments by the Company in
the event that you are terminated without cause within twenty-four months of the
execution of the "1994 Letter." Now that such term has expired, the purpose of
this letter is to set forth our agreement with respect to the Company's
obligation to make severance payments to you under certain circumstances.  Upon
execution of this letter by both you and the Company, the terms set forth herein
shall become effective immediately.

Termination Without    In the event your employment is terminated by the Company
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Cause:                 without Cause, the Company will continue to pay your base
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                       salary as of the date of termination for twelve months
                       after the date of such termination, provided that the
                       Company's obligation to continue to pay such salary shall
                       cease as of the date you commence full-time employment
                       with another business entity.

                       For the purposes of this agreement, "Cause" shall mean
                       the occurrence of any of the following: (a) any
                       intentional action or intentional failure to act by you
                       which was performed in bad faith and to the material
                       detriment of the Company; (b) your refusal to follow the
                       reasonable directives of the CEO; or (c) conviction of a
                       felony crime involving moral turpitude; provided that in
                       the event that any of the foregoing events is capable of
                       being cured, the Company shall provide written notice to
                       you describing the nature of such event and you shall
                       thereafter have fifteen (15) days to cure such event. In
                       the event your employment is terminated by the Company
                       with Cause, or is terminated by you voluntarily, you
                       shall not be entitled 

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                       to any severance compensation as set forth above.

Termination Upon a     In the event that the Company is acquired by way of
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Change in Control:     merger, sale of assets, or acquisition of more than fifty
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                       percent (50%) of the outstanding voting securities of the
                       Company by a single entity during your employment by the
                       Company (the "Acquisition") and if (A) prior to or
                       contemporaneously with the consummation of an
                       Acquisition, the corporation acquiring the Company's
                       assets or into which the Company is merged fails to
                       assume the obligations of the Company under this
                       Agreement, or (B) within twelve (12) months after an
                       Acquisition your employment shall be involuntarily
                       terminated without Cause, then in either such case you
                       shall be entitled to an immediate lump sum payment by the
                       Company of all severance benefits as described herein.
 
 
At-Will Employment:    Your employment will continue to will, which means it may
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                       be terminated at any time by you or the Company with or
                       without notice and with or without cause.

Governing Law:         The agreements set forth herein shall be construed under
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                       and governed by the laws of the State of New Jersey.

          If the foregoing accurately reflects our agreement, please so indicate
by signing where indicated below and returning the enclosed duplicate copy of
this letter to me.

                                          Sincerely,
                                         
                                          /s/ Joseph Mollica
                                         
                                          Joseph Mollica
                                          On behalf of the Board of Directors 
                                          of Pharmacopeia, Inc.

The foregoing is agreed and accepted:


/s/ Lewis Shuster
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Lewis Shuster

Date: