***Text Omitted and Filed Separately
                                                Confidential Treatment Requested
                                            Under 17 C.F.R. ss.ss. 200.80(b)(4),
                                                            200.83 and 240.24b-2

                                 AMENDMENT FIRST

This first  amendment (the  "Amendment"),  dated December 31, 1998,  ("Effective
Date  of this  Amendment")  entered  by and  between  SUGEN,  Inc.,  a  Delaware
corporation,  located at 230 East Grand Avenue, South San Francisco,  California
94080-4811 ("SUGEN") and ASTA Medica  Aktiengesellschaft,  a German corporation,
with headquarters at Weissmuellerstrasse  45, D-60314 Frankfurt am Main, Germany
("ASTA  Medica")  amends and with  respect  to the terms  below  supersedes  the
respective terms in the Collaboration Agreement by and between the same Parties,
dated December 5, 1995 (the "Agreement").  All other terms and conditions of the
Agreement shall abide this Amendment.  SUGEN and ASTA Medica are each considered
a "Party" and together considered the "Parties" hereto.

Whereas,  ASTA  Medica  seeks to extend  the  period of time for  screening  and
selection of Active Compounds under the Raf and Her2 Projects,  as referenced in
Section 2.5 of the Agreement; and

Whereas, under Article 5 of the Agreement, in which SUGEN contracts for services
to be  performed  by ASTA Medica and charged  against a monetary  credit held by
ASTA Medica, SUGEN seeks to fully utilize the remaining credit for the provision
of the contract services;

Now Therefore,  in  consideration  of the foregoing and the covenants and mutual
promises, the Parties hereby agree to amending the Agreement as follows:

1.  Extension  of the Raf  Project.  ASTA Medica  [...***...]  extend  screening
activities  under the Raf Project beyond the current final date of  [...***...].
During such [...***...].  In the event that [...***...] in consideration of such
extension. Such compensation shall be payable as follows:

         A. [...***...] payable by ASTA Medica in cash [...***...]; and

         B.  [...***...]  payable by ASTA  Medica in exchange  for SUGEN  Common
Stock,  to be issued and sold to ASTA Medica on March 31, 1999  pursuant to that
certain Common Stock Purchase  Agreement,  by and between ASTA Medica and SUGEN,
dated  contemporaneously  herewith, at a price per share equal to twice the fair
market value thereof.  Such fair market value shall be determined to be equal to
the  average  last  reported  sales  price of a share of SUGEN  Common  Stock as
reported  for the NASDAQ  (National  Market) for the twenty (20)  business  days
preceding the day on which the payment is made.

2. Her2 Project.
<PAGE>
         2.1  Extension  of  the  Her2  Project.  In  consideration  of  SUGEN's
agreement to extend the  Screening  Period (as defined in Section  2.4(c) of the
Agreement) and screening  activities  under the Her2 Project until  [...***...],
ASTA Medica shall pay SUGEN [...***...] payable as follows:

          A.  [...***...]  (US$375,000)  payable by ASTA Medica in exchange  for
          SUGEN Common  Stock,  to be issued and sold to ASTA Medica on December
          31, 1998 pursuant to that certain Common Stock Purchase Agreement,  by
          and between ASTA Medica and SUGEN, dated  contemporaneously  herewith,
          at a price per share  equal to twice the fair  market  value  thereof.
          Such fair market value shall be  determined to be equal to the average
          last reported sales price of a share of SUGEN Common Stock as reported
          for the NASDAQ  (National  Market) for the twenty (20)  business  days
          preceding the day on which the payment becomes due;

          B. [...***...] payable by ASTA Medica in cash [...***...]; and

          C.  [...***...]  payable by ASTA Medica in exchange  for SUGEN  Common
          Stock, to be issued and sold to ASTA Medica on March 31, 1999 pursuant
          to that certain Common Stock Purchase  Agreement,  by and between ASTA
          Medica and SUGEN,  dated  contemporaneously  herewith,  at a price per
          share equal to twice the fair market value  thereof.  Such fair market
          value shall be  determined  to be equal to the average  last  reported
          sales  price of a share  of SUGEN  Common  Stock as  reported  for the
          NASDAQ  (National  Market) for the twenty (20) business days preceding
          the day on which the payment becomes due.

ASTA Medica shall also be responsible for [...***...] in accordance with Section
6.1 of the Agreement  [...***...] in accordance with terms and conditions of the
Agreement and this Amendment.

         2.2 Her2 Project  Research  Payment.  ASTA Medica agrees to pay SUGEN a
research  payment of [...***...]  for research  conducted on the Her2 Project by
SUGEN in  [...***...].  Such payment  shall be payable by ASTA Medica in cash no
later than [...***...].

3.  Termination  of  Projects.  ASTA Medica and SUGEN agree on new  criteria for
continuation  of  Projects  to replace the  corresponding  provision  of Section
4.2(c) of the Agreement. The Parties hereby agree that in the event [...***...],
then such Project  shall  terminate.  Upon such  termination  of a Project,  the
Parties  shall enter into a License  Agreement  as provided  for in the relevant
remaining part of Section 4(c) of the Agreement.

4.  Failure to Comply.  Failure to comply  with the payment  requirements  under
Sections 1 and/or 2 of this Amendment  shall result in ASTA Medica's  forfeiture
of its rights in accordance  with Section 10.2 of the  Agreement  with regard to
the  respective  Project(s)  to which the default in payment and failure to cure
applies.

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<PAGE>
5.  Further  Screening  Activities.  SUGEN  agrees to extend  further  screening
activities  on Active  Compounds as provided for in Section 2.7 of the Agreement
for an additional [...***...], with the new ending date of [...***...].

6.  Non-competition.  ASTA Medica and SUGEN agree that [...***...] under Section
4.3 of the Agreement [...***...] as provided for in Section 1 of this Amendment.

7. Contract  Services  Credit  Extension.  ASTA Medica agrees to extend the time
under which SUGEN is obligated to use a partial  existing  credit (under Section
5.2 of the Agreement) in the remaining  amount equal to the  difference  between
[...***...]  of the original  credit and the total amount of all  statements  of
contract  services  performed by ASTA Medica under  Section 5.1 of the Agreement
through the Effective Date of this  Amendment.  SUGEN's  remaining  credit shall
[...***...]. Such services must be used by SUGEN by [...***...].

8. Independence of Projects. Any decisions with respect to Raf and Her2 Projects
shall be made  independently  of each other,  and  termination of any one of the
Projects shall not result in the  termination of the other or in the termination
of the Agreement.

This Amendment has been executed by the Parties as of the Effective Date of this
Amendment.

SUGEN, Inc.                               ASTA Medica Aktiengesellschaft



By: /s/ Stephen Evans-Freke               By: /s/ Bernard Kastler
   ---------------------------------          ----------------------------------

Stephen Evans-Freke                       Bernard Kastler
------------------------------------      --------------------------------------
Name                                      Name

Chairman and Chief Executive Officer      Member of the Executive Board
Title                                     Title

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