Document:

Exhibit 4.5
                                                                    to Form 20-F

                            DATED 1ST DECEMBER , 2001

                               LION BIOSCIENCE AG

                                       AND

                            BAYER AKTIENGESELLSCHAFT

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

                                  1ST AMENDMENT

                   RELATING TO A DEVELOPMENT AGREEMENT BETWEEN
                               LION BIOSCIENCE AG
                                       AND
                        BAYER AG DATED 13TH OCTOBER, 2000

                                    CONTENTS

CLAUSE                                                                      PAGE

1.       Interpretation........................................................1
2.       First Output for December 2001........................................1
3.       Deliverables for Milestone 2 A........................................2
4.       Other Changes of the Development Agreement in 2002....................2
5.       Amendments of the Development Agreement in 2002.......................2
6.       Miscellaneous.........................................................4

ANNEX

1.       First Output for 12th December, 2001..................................5

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THIS AGREEMENT is made on 1st December, 2001 BETWEEN:

(1)      LION BIOSCIENCE AG ("LION"), Waldhofer Str. 98, 69123 Heidelberg,
         Germany, registered with the commercial register of the local court in
         Heidelberg under HR B 5706; and

(2)      BAYER AKTIENGESELLSCHAFT ("BAYER"), 51368 Leverkusen, Germany.

WHEREAS

(A)      LION and Bayer entered into a novel and innovative type of
         collaboration to implement existing IT tools at Bayer but also to
         develop novel IT tools such as pharmacophore informatics tools to
         significantly enhance lead identification and optimization capabilities
         for pharmaceutical and agrochemical discovery and development on 13th
         October, 2000 ("DEVELOPMENT AGREEMENT").

(B)      In order to obtain a first output from the Development Agreement in
         2001, albeit not of the scope originally envisaged for the 1st and 2nd
         milestones, the parties wish to agree on the specifications of this
         first output to be delivered to Bayer in December 2001.

(C)      LION and Bayer agree to waive the date of the 1st milestone (after
         failure of the 1st acceptance test), to integrate the DELIVERABLES and
         WORK PACKAGES of the 1st milestone into the 2nd milestone and to move
         the 2nd milestone into the year 2002 (intending to split it into two
         milestones: milestone 2 A and milestone 2 B), in no event to a date
         earlier than the new milestone 2 A.

(D)      The parties have agreed on the principal details of changes of the
         Development Agreement to be implemented in the first calendar quarter
         of 2002 relating to particular to the future milestones and payment
         schedule.

NOW IT IS HEREBY AGREED as follows:

1.       INTERPRETATION

(1)      In this Agreement including the recitals all terms shall have the same
         meaning as in the Development Agreement unless otherwise defined in
         this agreement or where the context requires otherwise.

(2)      "FIRST OUTPUT" means the list of issues to be addressed by LION by the
         date further specified herein and described in Annex I;

"MILESTONE" has the meaning given to it in clause 1(8) of the Development
Agreement.

2.       FIRST OUTPUT FOR DECEMBER 2001

(1)      On 12th December, 2001 LION shall deliver to Bayer the First Output as
         described in Annex 1. Bayer shall contribute the task described in
         Annex 1a.

(2)      For the avoidance of doubt, the parties acknowledge that the First
         Output is not regarded as completion of a milestone.

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                                       2

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3.       DELIVERABLES FOR MILESTONE 2 A

(1)      The parties agree on a new milestone 2 A on 1st April, 2002. The
         parties shall agree on the specific DELIVERABLES and WORK PACKAGES due
         for the new milestone 2 A in the week of 8th February 2002 at the
         latest.

(2)      The general scope of the specification for the DELIVERABLES and WORK
         PACKAGES for milestone 2 A will be set out between the parties until
         November 16th.

(3)      Clause 4(4) of the Development Agreement shall apply mutatis mutandis.

4.       OTHER CHANGES OF THE DEVELOPMENT AGREEMTN IN 2002

         Subpayment 4 (excluding the Management fee 4), as defined in Annex D of
         the Development Agreement (payable thereunder on 30th January, 2002),
         will be deferred until the DELIVERABLES of milestone 2 A have been, or
         are deemed to be accepted by Bayer according to the procedure of clause
         5 of the Development Agreement.

5.       AMENDMENTS OF THE DEVELOPMENT AGREEMENT IN 2002

         (1) The parties agree to amend the Development Agreement by 30th March,
         2002 latest. The agreement under this subclause (1) shall create a
         legally binding and enforceable obligation on both parties. If the
         parties cannot achieve an agreement about the amendment of the
         Development Agreement, clause 15.4 of the Development Agreement shall
         apply mutatis mutandis.

(2)      The amendments shall be:

          (a)  shift of all remaining milestones according to a new milestone
               schedule starting with milestone 2A due on 1st April 2002 as
               mentioned above and further milestones being due every six months
               from the day of milestone 2 A until milestone 4 on 1st October,
               2003 and a final milestone on 1st December, 2003;

          (b)  extended duration of the Development Agreement at least until 1st
               January, 2004;

          (c)  an acceptance period of 30 days starting with the date of
               delivery of the deliverables of each milestone according to
               clause 5 of the Development Agreement;

          (d)  future subpayments of Bayer according to clause 7.2 of the
               Development Agreement being made dependent on the acceptance of
               Bayer of key DELIVERABLES of a milestone. If the key DELIVERABLES
               have been, or are deemed to be accepted by Bayer, according to
               the procedure of clause 5 of the Development Agreement, the
               payment of Bayer shall be due within 30 days of such (deemed)
               acceptance date, but not earlier than the date of the
               corresponding milestone as defined under (e) below;

          (e)  The implementation of the following new payment schedule,
               including a final payment in January 2004 after finalization of
               the project, for the subpayments:

               -    1st April, 2002 or after the acceptance (as defined under d
                    above) of milestone 2 A, whichever is later:

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                                        3

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                    subpayment 4* of US$2,000,000;

               -    1st October 2002 or after acceptance (as defined under d
                    above) of milestone 2B, whichever is later: subpayment 5* of
                    US$2,000,000;

               -    1st April 2003 or after acceptance (as defined under d
                    above) of milestone 3, whichever is later: subpayment 6* of
                    US$1,803,750;

               -    1st October, 2003 or after acceptance (as defined under d
                    above) of milestone 4, whichever is later subpayment 7* of
                    US$1,803,750;

               -    1st December 2003 or after final acceptance (as defined
                    under d above), whichever is later: final payment of $US
                    1,000,000;

          (f)  the implementation of the following new payment schedule for the
               management fee which shall be split in the following three
               installments (not considering the payment of US$ 541,666.67 on
               30th January, 2002):

             30th July, 2002: Management fee 5 of US$541,666.67;
             30th January, 2003: Management fee 6 first half of US$270,833.34;
             30th July, 2003: Management fee 6 second half of US$270,833.34;

          (g)  Definition of key DELIVERABLES and the corresponding ACCEPTANCE
               TEST in mutual agreement between Bayer and Lion according to
               clause 4.4 of the Development Agreement, but at least 5 months
               before the date of the corresponding milestone;

          (h)  Lion's performing of project planning and risk assessment before
               definition of the key DELIVERABLES.

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                                        4
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6.       MISCELLANEOUS

(1)      The Development Agreement and all of its provisions will continue in
         full force and effect as legal, valid and binding obligations of each
         of the parties subject as provided in this 1st amendment or
         necessitated by results of implementing this 1st amendment.

(2)      Clause 18 of the Development Agreement shall apply to this 1st
         amendment mutatis mutandis.

Executed by and on behalf of LION bioscience AG

Heidelberg, 11.12.2001

/s/ Friedrich von Bohlen und Halbach                    /s/ Reinhard Schneider
------------------------------------                    ------------------------

Dr Friedrich von Bohlen und Halbach                     Dr. Reinhard Schneider
CEO                                                     CIO

Executed by and on behalf of Bayer AG

Leverkusen,

/s/ Wolfgang Hartwig                                    /s/ Armin Buchmeier

Prof. Dr. Wolfgang Hartwig                              Dr. Armin Buchmeier
Head of Pharma Research                                 KB RP Legal DepartmentExhibit 4.6
                                                                    to Form 20-F

                             DATED MARCH 29TH, 2002

                               LION BIOSCIENCE AG

                                       and

                            BAYER AKTIENGESELLSCHAFT

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

                                  2ND AMENDMENT

                   RELATING TO A DEVELOPMENT AGREEMENT BETWEEN
                               LION BIOSCIENCE AG
                                       AND
                        BAYER AG DATED 13TH OCTOBER, 2000
                    ----------------------------------------

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                                    CONTENTS

CLAUSE                                                                      PAGE

1.       Interpretation........................................................1
2.       Milestone 2 A and ACCEPTANCE TEST.....................................1
3.       Milestones, Acceptance, Payment Schedules and Term....................2
4.       Miscellaneous.........................................................3

ANNEX

1.       Annex B/II: DELIVERABLES and WORK PACKCAGES for milestone 2 A.........4
2.       Annex E/II: ACCEPTANCE TEST for milestone 2 A........................21

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                                        1

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THIS AGREEMENT is made on March 29th, 2002 BETWEEN:

(1)      LION BIOSCIENCE AG ("LION"), Waldhofer Str. 98, 69123 Heidelberg,
         Germany, registered with the commercial register of the local court in
         Heidelberg under HR B 5706; and

(2)      BAYER AKTIENGESELLSCHAFT ("BAYER"), 51368 Leverkusen, Germany.

WHEREAS

(A)      LION and Bayer entered into a novel and innovative type of
         collaboration to implement existing IT tools at Bayer but also to
         develop novel IT tools such as pharmacophore informatics tools to
         significantly enhance lead identification and optimization capabilities
         for pharmaceutical and agrochemical discovery and development on 13th
         October, 2000 ("DEVELOPMENT AGREEMENT").

(B)      LION and Bayer agreed on the principal details of changes of the
         Development Agreement to be implemented in the first calendar quarter
         of 2002 relating in particular to the future milestones and payment
         schedule in a 1st amendment to the Development Agreement dated 1st
         December, 2002 and signed by LION on 11th December, 2001.

(C)      LION and Bayer hereby wish implement the agreed changes of the
         Development Agreement as follows.

NOW IT IS HEREBY AGREED as follows:

1.       INTERPRETATION

(1)      In this Agreement including the recitals all terms shall have the same
         meaning as in the Development Agreement unless otherwise defined in
         this agreement or where the context requires otherwise.

(2)      "MILESTONE" has the meaning given to it in clause 1(8) of the
         Development Agreement.

2.       MILESONE 2 A AND ACCEPTANCE TEST

(1)      The parties have agreed on a new milestone 2 A on 1st April, 2002. The
         specific DELIVERABLES and WORK PACKAGES due for this new milestone 2 A
         shall be set out in Annex B/II. The criteria of the ACCEPTANCE TEST
         shall be set out in Annex E/II.

(2)      For the avoidance of doubt, the parties confirm that subpayment 4
         (excluding management fee 4) as defined in Annex D of the Development
         Agreement (payable thereunder on 30th January, 2002) will be reduced to
         US$2,000,000 and deferred until the DELIVERABLES of milestone 2 A have
         been, or are deemed to have been accepted by Bayer according the
         procedure of clause 5 of the Development Agreement.

3.       MILESTONES, ACCEPTANCE, PAYMENT SCHEDULES AND TERM

(1)      All remaining milestones shall be shifted and/or renamed as follows:

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          - milestone 2 B           1ST October, 2002;

          - milestone 3             1st April, 2003;

          - milestone 4             1st October, 2003; and

          - final milestone         1st December 2003.

(2)      From subpayment 5 (inclusive) onwards, subpayments of Bayer according
         to clause 7.2 of the Development Agreement shall be dependent on the
         (deemed) acceptance by Bayer of key DELIVERABLES of a milestone. If the
         key DELIVERABLES have been, or should have been accepted ("deemed
         acceptance"), by Bayer, whichever of the two is the earlier, the
         payment of Bayer shall be due within 30 days of such (deemed)
         acceptance date. Therefore, the payment schedule set out in Annex D of
         the Development Agreement shall be replaced for subpayments 5 and 6 by
         the following payment schedule:

                           - 1st October, 2002 or after (deemed) acceptance (as
                             defined above) of milestone 2B, whichever is later:
                             subpayment 5* of US$2,000,000;

                           - 1st April, 2003 or after (deemed) acceptance (as
                             defined above) of milestone 3, whichever is later:
                             subpayment 6* of US$1,803,750;

                           - 1st October, 2003 or after (deemed) acceptance (as
                             defined above of milestone 4, whichever is later:
                             subpayment &* of US$1,803,750;

                           - 1st December, 2003 or after the final (deemed)
                             acceptance (as defined above), whichever is later:
                             final payment of US$1,000,000;

(3)      Definition of key DELIVERABLES and the corresponding ACCEPTANCE TEST
         shall be in mutual agreement between Bayer and Lion according to clause
         4.4 of the Development Agreement, but at least 5 months before the date
         of the corresponding milestone (2 months in the case of the final
         milestone);

(4)      For the DELIVERABLES of each milestone of an acceptance period of 30
         days shall apply starting with the date of delivery of the DELIVERABLES
         of each milestone according to the clause 5 of the Development
         Agreement.

(5)      The following new payment schedule for the management fee shall be
         implemented and replace the schedule of management fees in Annex D to
         the extent that such management fees have not yet become due (i.e. in
         particular notwithstanding the payment of US$541,666.67 on 30th January
         2003):

         - 30th July, 2002:     management fee 5 of US$541,666.67;

         - 30th January, 2003:  management fee 6 (first half) of US$ 270,833.34;

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         - 30th July, 2003:     management fee 6 (second half) of US$270,833.34.

(6)      LION shall perform the project planning and risk assessment before the
         definition of the key DELIVERABLES.

(7)      The duration of the Development Agreement shall be extended until at
         least until 1st January, 2004.

4.       MISCELLANEOUS

(1)      The Development Agreement and all of its provisions (as changed by the
         1st amendment) will continue in full force and effect as legal, valid,
         and binding obligations of each of the parties subject as provided in
         this 2nd amendment or necessitated by the implementation of this 2nd
         agreement.

(2)      Clause 18 of the Development Agreement shall apply to this 2nd
         amendment mutatis mutandis.

         Executed by and on behalf of LION bioscience AG

         Heidelberg, March 29th, 2002

         /s/ Friedrich von Bohlen und Halbach       /s/ Reinhard Schneider
         ------------------------------------       ----------------------------

         Dr Friedrich von Bohlen und Halbach        Dr. Reinhard Schneider
         CEO                                        CIO

         Executed by and on behalf of Bayer AG

         Leverkusen, ____________________

         /s/ Wolfgang Hartwig                       /s/ Armin Buchmeier

         Prof. Dr. Wolfgang Hartwig                 Dr. Armin Buchmeier
         Head of Pharma Research                    KB RP Legal Department

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