License Agreement - Gilead Sciences Inc., the Institute of Organic Chemistry and Biochemistry of the Academy of Sciences of the Czech Republic, and Rega Institute for Medical Research


Institute of Organic Chemistry and           Rega Institute for Medical Research
Biochemistry of the Academy of Sciences      Katholieke Universiteit Leuven
of the Czech Republic                        Minderbroedersstraat 10
Flemingovo nam.2                             B-3000 Leuven             
166 10 Praha 6                               Belgium              
Czech Republic                               Attention: Professor Dr. De Clercq
Attention: Dr. Antonin Holy                   


December 27, 2000

RE:   License Agreement between Gilead Sciences, Inc. ("Gilead"), the Institute
      of Organic Chemistry and Biochemistry, as an integral part of the
      Ceskoslovenska akademie ved ("IOCB"), and Rega Stichting v.z.w. ("REGA")
      dated November 15, 1991, as amended prior to the date of this letter
      agreement (such Agreement, the "1991 License Agreement"), and License
      Agreement between Gilead Sciences, Inc., IOCB and REGA dated December 1,
      1992, as amended prior to the date of this letter agreement (such
      Agreement, the "1992 License Agreement"). The 1991 License Agreement and
      the 1992 License Agreement are referred to collectively as the "License
      Agreements".

Dear Drs. Holy and De Clercq:

We are writing to set forth the terms upon which we have agreed to amend the
License Agreements, as described below.

"Amendment Date" as used herein shall mean the date the last signatory to this
letter agreement signs this letter agreement.

We agree as of the Amendment Date as follows:

1.  The following definition shall be added to Article I of the 1991 License
    Agreement:

      "Adefovir" shall mean adefovir dipivoxil, or
      9-[2-[[bis[(pivaloyloxy)methyl]phosphinyl]-methoxy]ethyl]adenine.

2.  The following definition shall be added to Article I of the 1992 License
    Agreement:

      "Tenofovir" shall mean (R) PMPA or tenofovir disoproxil fumarate or
      9-[(R)-2-[[bis[[(isopropoxycarbonyl)oxy]-methoxy]phosphinyl]methoxy]
      propyl]adenine fumarate.

3.  All capitalized terms used in this Section 3 but not defined herein shall
    have the meanings given in the 1991 License Agreement.  Section IV A. b) and
    Section IV A. c) of the 1991 License Agreement shall be deleted and replaced
    in its entirety with the following:

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      "b)  five percent (5%) of NET SALES of LICENSED PRODUCT other than
           LICENSED PRODUCT containing Adefovir as a LICENSED COMPOUND, and
           three percent (3%) of NET SALES of LICENSED PRODUCT containing
           Adefovir as a LICENSED COMPOUND, sold by GILEAD and its AFFILIATES
           and sublicensees, the manufacture, use or sale of which would, but
           for the LICENSE, infringe a VALID CLAIM of LICENSED PATENTS in the
           country of sale, except as set forth in the following sentence. With
           respect to NET SALES which would be royalty-bearing as set forth in
           the previous sentence, but as to which the same LICENSED COMPOUND or
           LICENSED PRODUCT is being sold in such country by any THIRD PARTY
           except under this Agreement, and as to which GILEAD or IOCB/REGA is
           not seeking diligently to enforce its LICENSED PATENTS, GILEAD shall
           pay to IOCB/REGA a total of two and one-half percent (2.5%) of NET
           SALES if such LICENSED COMPOUND or LICENSED PRODUCT is not or does
           not contain Adefovir as a LICENSED COMPOUND, and one and one-half
           percent (1.5%) if such LICENSED COMPOUND or LICENSED PRODUCT is, or
           does contain Adefovir as a LICENSED COMPOUND.

      c)   two and one-half percent (2.5%) of NET SALES of LICENSED PRODUCT not
           containing Adefovir as a Licensed Compound and sold by GILEAD and its
           AFFILIATES and sublicensees that is not covered by LICENSED PATENTS
           but exploits the TECHNICAL INFORMATION and the KNOW-HOW and no
           royalties on LICENSED PRODUCT containing Adefovir as a LICENSED
           COMPOUND and sold by GILEAD and its AFFILIATES and sublicensees that
           is not covered by LICENSED PATENTS but exploits the TECHNICAL
           INFORMATION and the KNOW-HOW."

4.  All capitalized terms used in this Section 4 but not defined herein shall
    have the meanings given in the 1992 License Agreement.  Section IV A. b) and
    Section IV A. c) of the 1992 License Agreement shall be deleted and replaced
    in its entirety with the following:

      "b)  five percent (5%) of NET SALES of LICENSED PRODUCT other than
           LICENSED PRODUCT containing Tenofovir as a LICENSED COMPOUND, and
           three percent (3%) of NET SALES of LICENSED PRODUCT containing
           Tenofovir as a LICENSED COMPOUND, sold by GILEAD and its AFFILIATES
           and sublicensees, the manufacture, use or sale of which would, but
           for the LICENSE, infringe a VALID CLAIM of LICENSED PATENTS in the
           country of sale, except as set forth in the following sentence. With
           respect to NET SALES which would be royalty-bearing as set forth in
           the previous sentence, but as to which the same LICENSED COMPOUND or
           LICENSED PRODUCT is being sold in such country by any THIRD PARTY
           except under this Agreement, and as to which GILEAD or IOCB/REGA is
           not seeking diligently to enforce its LICENSED PATENTS, GILEAD shall
           pay to IOCB/REGA a total of two and one-half percent (2.5%) of NET
           SALES if such LICENSED COMPOUND or LICENSED PRODUCT is not or does
           not contain Tenofovir as a LICENSED COMPOUND, and one and one-half
           percent (1.5%) if such LICENSED COMPOUND or LICENSED PRODUCT is, or
           does contain Tenofovir as a LICENSED COMPOUND.

      c)   two and one-half percent (2.5%) of NET SALES of LICENSED PRODUCT not
           containing Tenofovir as a LICENSED COMPOUND and sold by GILEAD and
           its AFFILIATES and sublicensees that is not covered by LICENSED
           PATENTS but exploits the TECHNICAL INFORMATION and the KNOW-HOW and
           no royalties on LICENSED PRODUCT containing Tenofovir as a LICENSED
           COMPOUND and sold by GILEAD and its AFFILIATES and sublicensees that
           is not covered by LICENSED PATENTS but exploits the TECHNICAL
           INFORMATION and the KNOW-HOW."

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5.  In consideration of your agreement to amend the 1991 License Agreement,
    GILEAD will pay for LICENSED PRODUCT containing Adefovir as provided in
    Section 3 above, to IOCB and REGA together a single payment of One Million
    Seven Hundred Seventy Thousand United States dollars ($1,770,000) as
    follows:

/ / Gilead will pay $885,000 to REGA; and

/ / Gilead will pay $885,000 to IOCB.

6.  In consideration of your agreement to amend the 1992 License Agreement,
    GILEAD will pay for LICENSED PRODUCT containing Tenofovir as provided in
    Section 4 above, to IOCB and REGA together a single payment of Nine Million
    Two Hundred Thirty Thousand United States dollars ($9,230,000) as follows:

/ / Gilead will pay $4,615,000 to REGA; and

/ / Gilead will pay $4,615,000 to IOCB.

7.  REGA, IOCB and Gilead each agree that Section 1 of ANNEX 1 to the Agreement
    made by and between REGA, IOCB and Gilead, effective April 1, 1997
    ("Section 1"), shall be amended such that IOCB and REGA shall each receive
    50% of the amounts payable by Gilead instead of 52% and 48%, respectively.
    Section 1 shall otherwise remain unchanged.

8.  The payments under Section 5 and 6 above shall be net, and no deduction
    shall be made by Gilead in respect of any withholding or other tax payable
    in respect thereof imposed in the United States of America, which shall be
    the responsibility of Gilead for its own account. Gilead hereby agrees to
    indemnify and hold harmless REGA and IOCB against and to reimburse REGA and
    IOCB for all withholding or other taxes paid or payable in the United
    States of America in respect of the payments under Section 5 and 6 above.
    Gilead shall make the payments required under Section 5 and 6 above by wire
    transfer of immediately available funds within five (5) business days of
    Gilead's receipt of a fully countersigned copy of this letter agreement to
    the following accounts:

To REGA:  Generale Bank
          Account No. 230-0190070-67
          Stichting REGA v.z.w., Minderbroedersstraat 10, 3000 Leuven, Belgium

To IOCB:  Ceska narodni banka Praha 1
          Account No. 11338031/0710
          Bank code 0710
          Account holder: Ustav organicke chemie a biochemie, Praha 6, 
          Flemingovo nam.2.
          Czech Republic

9.  IOCB and REGA each agree that no commission, royalty or other obligation
    shall be owed by Gilead to any third party as a result of any payments made
    under this letter agreement.

10. Except as expressly provided in this letter agreement, the License
    Agreements shall remain unchanged.

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The offer contained in this letter agreement shall be valid until, and this
letter agreement shall become binding upon each of us only if Gilead receives a
executed counterpart of this letter agreement by facsimile from all of the
signatories listed below on or before, 11:59 p.m., Pacific Standard Time on
December 27, 2000. To indicate your agreement to amend the License Agreements
and other provisions of this letter agreement as specified above, please sign
below and return to me one copy of this letter by facsimile (650-522-5444). This
letter agreement may be executed in multiple counterparts, each of which shall
be an original and all of which shall together constitute the same document.


Yours sincerely,


Gilead Sciences, Inc.


By:    /s/ John C. Martin, Ph.D.
    John C. Martin, Ph.D.
    President and Chief Executive Officer




Accepted and Agreed,                         Accepted and Agreed,

Institute of Organic Chemistry and           Rega Stichting  v.z.w.
Biochemistry of the Academy of Sciences 
of the Czech Republic

By:    /s/  Dr. Antonin Holy                 By:    /s/  Professor Dr. De Clercq

Name:  Dr. Antonin Holy                      Name:  Professor Dr. De Clercq

Date:  December 27, 2000                     Date:  December 27, 2000


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