Document:

<PAGE>   1

                                                                  EXHIBIT 10.49

                      FLUMISTTM SUPPLY AGREEMENT AMENDMENT

     This FLUMISTTM SUPPLY AGREEMENT AMENDMENT (the "Amendment"), dated as of
January 1, 2001, is by and between AVIRON, a Delaware corporation with its
principal place of business at 297 North Bernado Avenue, Mountain View,
California 94043 ("AVIRON") and American Home Products Corporation ("AHPC"),
acting through its Wyeth-Ayerst Laboratories Division, a Delaware corporation
with is principal place of business at 555 Lancaster Avenue, St. Davids,
Pennsylvania 19087 ("WYETH"). AVIRON and WYETH are sometimes referred to as the
"Parties."

     WHEREAS, AVIRON and WYETH entered into a FluMist Supply Agreement, dated
January 11, 1999 ("Supply Agreement"), establishing the Parties' respective
rights and obligations concerning the manufacture and supply of bulk and
Finished Product;

     WHEREAS, the Parties hereby desire to revise and amend the Supply
Agreement;

     NOW THEREFORE, the Parties hereby agree as follows:

1. All capitalized terms, unless defined herein, shall have the definition
   assigned such term(s) by the Supply Agreement.

2. Notwithstanding anything in the Supply Agreement to the contrary, including
   but not limited to Articles 3 and 7, WYETH agrees to pay and AVIRON agrees to
   accept an advance payment of $10 million in full satisfaction of all duties,
   obligations and responsibilities of WYETH under Section 7.2(a) of the Supply
   Agreement (the "January Advance Payment").

<PAGE>   2

3. AVIRON shall, as provided in Section 7.2(a) of the Supply Agreement, apply
   the January Advance Payment to the payment of its costs and expenses incurred
   in connection with its manufacture for commercial sale of Frozen Product for
   the 2001 Flu Season ("2001 Product"). In the event the Parties elect not to
   sell 2001 Product for the 2001 Flu Season, such 2001 Product and any
   unexpended portions of the January Advance Payment shall be applied by AVIRON
   to any clinical trials supporting field use conducted by the parties.

4. The January Advance Payment shall be wired transferred to AVIRON's account
   at, State Street Bank & Trust Company for credit to AVIRON's account #
   17039843 (payment per Supply Agreement) no later than January 15, 2001.

5. Notwithstanding anything in the Supply Agreement to the contrary, WYETH
   agrees to pay and AVIRON agrees to accept an advance payment of $10 million
   (the "April Advance Payment"), provided no later March 31, 2001, both Parties
   agree (in writing) to plan a commercial launch of Frozen Product for the 2001
   Flu Season (the "2001 Launch"). In the event of such agreement, the April
   Advance Payment shall be wired transferred, (per wire instructions set forth
   in Paragraph 4 hereof) to AVIRON no later than April 7, 2001.

6. The April Advance Payment shall be applied by AVIRON to the payment of costs
   and expenses to be incurred in connection with its manufacture for commercial
   sale of Frozen Product for the 2001 Flu Season. In the event the 2001 Launch
   does not occur, the full April Advance Payment shall be credited against any
   payment obligations (as contemplated by Article 3 and 7 of the Supply
   Agreement) of WYETH for the 2002 Flu Season.

<PAGE>   3

     IN WITNESS WHEREOF, the Parties have caused this Amendment to be executed
as of the date first written above by their respective officers thereunto duly
authorized.
<TABLE>
<S>                                       <C>
AMERICAN HOME PRODUCTS CORP.              AVIRON
THROUGH ITS WYETH-AYERST
LABORATORIES DIVISION

By:  /s/ Kevin L. Reilly                  By: /s/ Carol A. Olson
     ---------------------------------        ---------------------------------

Name: Kevin L. Reilly                     Name: Carol A. Olson
     ---------------------------------        ---------------------------------
Title: President                          Title: Sr. VP, Commercial Development
     ---------------------------------        ---------------------------------
     Wyeth-Lederle Vaccines &
     Nutritionals
</TABLE><PAGE>   1
                   CONFIDENTIAL TREATMENT REQUESTED BY AVIRON
[***] - CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
[***], IS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24B-2 OF THE SECURITIES ACT OF 1934, AS AMENDED.

                                                                   EXHIBIT 10.50

                            AMENDMENT NUMBER ONE (1)
                     TO COOPERATIVE RESEARCH AND DEVELOPMENT
                               AGREEMENT AI-000062

This Amendment Number One (1) to Cooperative Research and Development Agreement
("CRADA") AI-00062 between Aviron ("Collaborator") and the National Institute of
Allergy and Infectious Diseases ("NIAID"), will be effective as of the date of
the last duly authorized signature below. The CRADA, which is entitled
"Development of a Live, Attenuated Cold-Adapted Influenza Vaccine," was executed
on June 12, 1995 for a term of five (5) years.

The purpose of this Amendment is to allow for a change in Principal Investigator
(PI) for the NIAID and for the funding of additional NIAID travel and NIAID
personnel by Collaborator.

This Amendment is being executed in duplicate. Collaborator shall retain one
original, and one original shall be retained by NIAID.

Except as herein amended, all of the other terms and conditions of the CRADA
shall remain in full force and effect.

Pursuant to Article 14.6 of the CRADA, both parties do hereby amend the CRADA as
follows:

APPENDIX B (RESEARCH PLAN)

On the title page of Appendix B "Carole A. Heilman, Ph.D." is deleted and
replaced by "Pamela McInnes, Ph.D.", as the NIH Principal Investigator.

APPENDIX C (FINANCIAL AND STAFFING CONTRIBUTIONS OF THE PARTIES)

Section II of Appendix C is deleted in its entirety and replaced by the
following:

"II.     To be provided to NIAID by Aviron annually:
         ------------------------------------------

         A.      Supply funds:               [***]
         B.      Equipment funds:            [***]
         C.      Travel funds:               [***]
                                             travel to contract and cooperative
                                               agreement sites
                                             travel to scientific meetings
                                             travel to DSMB

CRADA AI-000062
AMENDMENT NUMBER ONE (1)
PAGE 1 OF 3
<PAGE>   2

         D.      Personnel funds:            [***]
                                             [***]

         E.      Contract support:           [***]
         F.      Overhead:                   [***]

                          SIGNATURES BEGIN ON NEXT PAGE

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[***], IS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24B-2 OF THE SECURITIES ACT OF 1934, AS AMENDED.

CRADA AI-000062
AMENDMENT NUMBER ONE (1)
PAGE 2 OF 3
<PAGE>   3

                   AMENDMENT NUMBER ONE (1) TO CRADA A1-000062

                                 SIGNATURE PAGE

FOR NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES:

/s/ John R. LaMontague, Ph.D.                                August 3, 1999
-------------------------------------------------------      --------------
John R. LaMontague, Ph.D.                                    Date
Deputy Director

FOR AVIRON:

/s/ J. Leighton Read, M.D.                                   July 29, 1999
-------------------------------------------------------      -------------
J. Leighton Read, M.D.                                       Date
Chairman and CEO

                   CONFIDENTIAL TREATMENT REQUESTED BY AVIRON
[***] - CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
[***], IS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24B-2 OF THE SECURITIES ACT OF 1934, AS AMENDED.

CRADA AI-000062
AMENDMENT NUMBER ONE (1)
PAGE 3 OF 3<PAGE>   1

                   CONFIDENTIAL TREATMENT REQUESTED BY AVIRON

[***] - CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
[***], IS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24B-2 OF THE SECURITIES ACT OF 1934, AS AMENDED.

                                                                   EXHIBIT 10.51

                            AMENDMENT NUMBER TWO (2)
                     TO COOPERATIVE RESEARCH AND DEVELOPMENT
                                AGREEMENT AI-0062

This Amendment Number Two (2) to Cooperative Research and Development Agreement
("CRADA") AI-0062 between Aviron ("Collaborator") and the National Institute of
Allergy and Infectious Diseases ("NIAID"), will be effective as of the date of
the last duly authorized signature below. The CRADA, which is entitled
"Development of a Live, Attenuated Cold-Adapted Influenza Vaccine," was executed
on June 12, 1995 for a term of five (5) Years and was first amended on August 3,
1999.

The purposes of this second Amendment are to add clinical trial-related
provisions to the CRADA, to modify the Research Plan and budget to allow for
[***], and to extend the term of the CRADA for an additional three (3) Years to
allow [***] described in the modified Research Plan.

This Amendment is being executed in duplicate. The Collaborator shall retain one
original, and one original shall be retained by NIAID.

Except as herein amended, all of the other terms and conditions of the CRADA
shall remain in full force and effect.

Pursuant to Article 14.6 of the CRADA, both Parties do hereby amend the CRADA as
follows:

I.      Extension of CRADA Term

        In order to continue the clinical research program described in Appendix
        B (Research Plan) of the CRADA as modified below, the term of the CRADA
        is extended by three (3) years. The new expiration date for the CRADA
        will be June 12, 2003.

II.     Modifications to Appendix B (Research Plan)

        Appendix B is amended by changing or adding the following for CRADA
        Years 4 through 8:

        A.     Background

               As stated in the original Research Plan, dated May 19, 1995, the
               CRADA has been, and continues to be, undertaken to advance the
               live attenuated, cold-adapted (ca) influenza vaccine system
               ("CAIV-T") to an FDA-approved vaccine for use [***]. To
               accomplish this goal, it was felt, in 1995, that the NIH and the
               Collaborator would need to show that the vaccine could be
               consistently

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PAGE 1 OF 16                                                        CONFIDENTIAL

<PAGE>   2

               manufactured and remain safe after transfer to a new producer,
               and that [***] envisioned was efficacious in the target
               populations.

               Clinical trials conducted under the CRADA since 1995, include
               [***]. The original goals of the CRADA, i.e. to show consistent
               manufacture and safety after transfer to a new producer, and
               efficacy in a target population, [***]

        B.     Description of the Revised Clinical Research Program

               This Research Plan describes a clinical research program that
               includes, or will include the following studies:

                      [***]

                      [***]

                      [***]

                      [***]

                      [***]

               [***]

        C.     Respective Contributions of the Parties

               Changes in each Party's contributions to the clinical studies for
               CRADA Years 6, 7 and 8 are as follows:

                      Enrollment of Subjects by DMID Contractors        [***]
                      and Grantees
                      Operations Manual, Case Report Forms              [***]
                      IND preparation and filing                        [***]
                      Data reports for regulatory filings               [***]
                                                                        (related
                                                                        to IND
                                                                        sponsor)
                      Supply of all vaccine for                         [***]
                      investigator-proposed trials
                      Special requirements of                           [***]
                      investigator-proposed trials
                      Monitoring of Study sites:

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PAGE 2 OF 16                                                        CONFIDENTIAL

<PAGE>   3

                          Study #1 [(***)]                              [***]
                          Study #2 [(***)]                              [***]
                          Study #3 [(***)]                              [***]
                          Study #4 [(***)]                              [***]
                          Study #5 [(***)]                              [***]
        Note:  NIH is not required to produce the live virus challenge lots as
               described in the original Research Plan.

III.    Modifications to Appendix C (Financial and Staffing Contributions of the
        Parties)

        Appendix C is amended by changing the following for CRADA Years 1
        through 5:

        Item E. ("Contract support"), including accompanying footnote 2, of
        Section III. entitled "Annual Collaborator Contributions (internal)" is
        hereby deleted in its entirety.

        Appendix C is amended by changing or adding the following for CRADA
        Years 6, 7 and 8:

        I.     Annual NIH Institute (DMID, NIAID) Contributions (internal):

               A.     Supply funds:         [$***]

               B.     Equipment funds:      [$***] (photocopier and/or computer
                                                   equipment)

               C.     Time requirements of NIAID personnel: [***] FTE
                                                                  Professional
                                                            [***] FTE
                                                                  Administrative

               D.     Contract and Grant/Cooperative Agreement support provided
                      to Study site institutions by NIAID:

<TABLE>
                      CONTRACTS                                     ANNUAL BUDGET
                      ---------                                     -------------
<S>                                                                 <C>
                      [***]                                             $ [***]
                      [***]                                             $ [***]
                      [***]                                             $ [***]
                      [***]                                             $ [***]
                      [***]                                             $ [***]
                      [***]                                             $ [***]
                      Sub-Total                                         $* [***]*
</TABLE>

                   CONFIDENTIAL TREATMENT REQUESTED BY AVIRON
[***] - CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
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PAGE 3 OF 16                                                        CONFIDENTIAL

<PAGE>   4

        *Exact amounts spent at any one Contract site may vary from Year to Year
        but the annual total Contract expenditure is expected to remain constant
        at approximately 2.0 million U.S.
        dollars per year.

<TABLE>
                      COOPERATIVE AGREEMENT                     ANNUAL BUDGET
<S>                                                             <C>
                      [***]                                           $ [***]
                      Sub-Total                                       $ [***]
                      Total NIAID Support                             $ [***]
</TABLE>

II. Funds to be Provided to NIH (DMID, NIAID) by the Collaborator Annually:

        A.     Supply funds:                [$***]

        B.     Equipment funds:             [$***]

        C.     Travel funds:                [$***]

                                            travel to contract and cooperative
                                            agreement sites travel to scientific
                                            meetings travel to DSMB

        D.     Personnel funds:             [$***]

                                            [***]

        E.     Contract support:            [$***]

        F.     Overhead:                    [$***]

               Total:                       [$***]

        No full-time permanent NIH employees will be supported by funds provided
        by the Collaborator to NIH under this CRADA.

        CRADA payment schedule and instructions:

               1.     Funds for CRADA Year 6 are due at NIAID on [***], which is
                      the [***]

               2.     Funds for subsequent CRADA Years are due at NIAID [***]

                      3. The Collaborator shall make CRADA checks payable to
                      "National Institute of Allergy and Infectious Diseases,"
                      shall reference the CRADA

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PAGE 4 OF 16                                                        CONFIDENTIAL

<PAGE>   5

                      number (AI-0062) and the NTH CAN number (if known) on the
                      checks, and send them to NIAID as follows:

                             Office of Technology Development
                             National Institute of Allergy and Infectious
                               Diseases
                             National Institutes of Health
                             31 Center Drive, MSC 2137
                             Building 31, Room 3B62
                             Bethesda, MD 20892-2137
                             Attn: Director

               4.     The Collaborator authorizes NIAID to redistribute these
                      funds between categories to support the objectives of this
                      CRADA.

III.    Annual Collaborator Contributions (internal): (All U.S. Dollars in
        Thousands ($000))

<TABLE>
<CAPTION>
                                                      Year 6    Year 7    Year 8
                                                      ------    ------    ------
<S>                                                  <C>        <C>       <C>
        A.        Supply funds:                      [$ ***       ***      ***
        B.        Equipment funds(1):                 $ ***       ***      ***
        C.        Travel funds:                        $***       ***      ***
        D.        Time requirements of Company          ***       ***      ***
                  personnel (approximate FTE
                  Requirements)
        E.        Monitoring Costs:                   $ ***       ***     ***]
</TABLE>

               Notes:

               Internal contributions shown are estimated costs, dependent upon
               trial scheduling, and not including costs relating to study drugs
               provided by Collaborator.

IV.     Modifications to the CRADA (Appendix D)

        The Agreement is modified as follows:

        A.     The following twelve new provisions are added to Article 2:

--------

(1)     Collaborator will provide sufficient support to fulfill its obligations
        under the Research Plan.

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PAGE 5 OF 16                                                        CONFIDENTIAL

<PAGE>   6

               2.9    "ADVERSE DRUG EXPERIENCE" means an adverse clinical
                      experience as defined under 21 C.F.R. Section 310.305 or
                      Section 312.32 as applicable.

               2.10   "ANNUAL REPORT" means the brief report of the progress of
                      an IND associated investigation that the IND sponsor is
                      required to submit to the FDA within sixty (60) days of
                      the anniversary date on which the IND went into effect
                      (pursuant to 21 C.F.R. Section 312.33).

               2.11   "CLINICAL DATA AND RESEARCH RESULTS IN NIH'S POSSESSION
                      AND CONTROL" means all data obtained by NIH under
                      Contract(s) with Extramural Investigator(s) for completion
                      of Studies within the scope of the Protocol(s), and all
                      information and data in the NIH-sponsored INDs for the
                      Study Drug.

               2.12   "CONTRACT" means a written funding agreement between the
                      Government and an eligible party ("the Contractor"), which
                      is subject to the Federal Acquisition Regulations, Title
                      48 CFR. For purposes of this CRADA, the term "Contract"
                      includes research and development Contracts, under which
                      the Contractor performs research and development work for
                      the Government with an expectation of the delivery to the
                      Government of a report, data, material(s) and/or other
                      product(s) resulting from the research and development
                      work.

               2.13   "EXTRAMURAL INVESTIGATOR(s)" means the principal
                      investigator(s) who conduct(s) research under an
                      NIH-funded Contract, Grant or Cooperative Agreement.

               2.14   "GRANT" means a financial assistance mechanism through
                      which the Government provides money, property, or both to
                      an eligible party to carry out a Government-approved
                      project or activity. A "Cooperative Agreement" is a type
                      of Grant in which there is substantial programmatic
                      involvement of the Government funding agency in the
                      project or activity.

               2.15   "IND" means an Investigational New Drug Application
                      submitted to the FDA to receive approval to conduct
                      experimental clinical trials.

               2.16   "INFLUENZA PROGRAM OFFICER" means the individual within
                      DMID who has primary responsibility for the research
                      activities of the DMID Influenza Program and all
                      administrative responsibility for that program's Grants
                      and Cooperative Agreements, and who serves as the liaison
                      between the Collaborator and the Project Officer and/or
                      the Extramural Investigator(s).

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PAGE 6 OF 16                                                        CONFIDENTIAL

<PAGE>   7

               2.17   "PROJECT OFFICER" means the individual within DMID whose
                      responsibilities include oversight of the Contract(s)
                      relevant to the research to be conducted under this CRADA.

               2.18   "PROTOCOL(s)" means the Study protocols that are described
                      briefly in the Research Plan (Appendix B) and that are
                      incorporated herein by reference.

               2.19   "STUDY(ies)" means the work performed by the Principal
                      Investigators and the Extramural Investigator(s) in
                      connection with the Protocol(s).

               2.20   "STUDY DRUG" means [***]. The term also includes a
                      finished dosage form that does not contain an agent but is
                      intended to be used as a placebo, as stated in the
                      definition of "Drug product" at 21 C.F.R. Section
                      210.3(a)(4).

        B.     Article 3.5 is deleted in its entirety and replaced by the
               following:

               3.5    INVESTIGATIONAL NEW DRUG APPLICATIONS (INDS). The Parties
                      expect that either NIH or the Collaborator will submit an
                      IND that may cross-reference an IND sponsored by the
                      other. The Collaborator will supply all manufacturing
                      information required by the FDA in support of the INDs.

                      a.     The Collaborator owns IND numbers [***] ("Aviron
                             INDs"). [***] The Collaborator shall allow NIH to
                             review, cross-reference or, as appropriate,
                             otherwise use those INDs for the conduct of
                             clinical trials involving the technology that is
                             the subject of this CRADA.

                      b.     [***] NIH shall allow the Collaborator and those
                             corporate entities that Collaborator may from time
                             to time designate in writing to review, cross
                             reference or, as appropriate, otherwise use those
                             INDs for the conduct of clinical trials involving
                             the technology that is the subject of this CRADA,
                             and to fulfill all the requirements necessary to
                             obtain regulatory approval to market products that
                             incorporate the technology that is the subject of
                             this CRADA and to use in patent applications
                             covering the technology. Subject to Article 9.8 and
                             to the extent permitted by law, NIH shall make
                             available [***]

                             c. Both Parties shall keep the information in these
                             INDs confidential in accordance with Article 9.
                             However, nothing in this Agreement shall prohibit
                             NIH or the Extramural Investigator(s) from

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PAGE 7 OF 16                                                        CONFIDENTIAL

<PAGE>   8

                      publishing in accordance with NIH policy or submitting to
                      the U.S. or international patent offices [***]

        C.     The following five new provisions are added to Article 3:

               3.6    PROTOCOL MODIFICATION. The Studies will be conducted in
                      strict accordance with the Protocol(s) and no changes in
                      the finalized Protocol(s) will be made unless mutually
                      agreed upon in advance by both Parties. If the appropriate
                      Institutional Review Board (IRB) [***] the Protocol(s) or
                      the informed consent form(s), both Parties agree to [***]
                      the Protocol(s) and/or informed consent form(s) as
                      appropriate.

               3.7    DRUG INFORMATION AND SUPPLY. The Collaborator agrees to
                      provide to the Extramural Investigators, at time and in
                      quantities that are commercially reasonable, [***] in
                      sufficient quantity to complete the clinical trial
                      Protocol(s) funded by NIH. The Collaborator will provide
                      lot release documents to NIH for each lot of finished
                      Study Drug provided for clinical trials.

               3.8    DRUG DELIVERY AND USAGE. The Collaborator shall ship the
                      Study Drug to the Study sites in appropriately marked
                      containers in accordance with the Code of Federal
                      Regulations.

               3.9    PROTECTION OF HUMAN SUBJECTS. All human clinical trials
                      performed under this CRADA shall conform to the
                      appropriate federal laws including, but not limited to,
                      all applicable FDA regulations and DHHS regulations
                      relating to the protection of human subjects (see 45
                      C.F.R. Part 46). Additional information is available from
                      the NIH Office for Protection from Research Risks,
                      Telephone, 301-496 7163.

               3.10   MONITORING. For each Study, responsibility for clinical
                      site monitoring and the quality assurance of all data will
                      be established prior to the start of the Study. Monitoring
                      shall be done in compliance with FDA Good Clinical
                      Practices Guidelines.

        D.     The following two sentences are added to the end of Article 4.1:

               Copies of the Annual Reports and other pertinent IND data
               (including, but not limited to, clinical brochure data, and
               formulation and preclinical data, including toxicology findings)
               will be exchanged by the Parties as they become available.
               Exchange of copies of the Annual Reports will fulfill the
               Parties' reporting requirements under this Article 4.1.

               Article 4.1 now reads as follows:

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PAGE 8 OF 16                                                        CONFIDENTIAL

<PAGE>   9

               4.1    INTERIM REPORTS. The Parties shall exchange formal written
                      interim progress reports on a schedule agreed to by the
                      PIs, but at least within six (6) months after this CRADA
                      becomes effective and at least within every six (6) months
                      thereafter. Such reports shall set forth the technical
                      progress made, identifying such problems as may have been
                      encountered and establishing goals and objectives
                      requiring further effort. Copies of the Annual Reports and
                      other pertinent IND data (including, but not limited to,
                      clinical brochure data, and formulation and preclinical
                      data, including toxicology findings) will be exchanged by
                      the Parties as they become available. Exchange of copies
                      of the Annual Reports will fulfill the Parties' reporting
                      requirements under this Article 4.1.

        E.     The following new provision is added to Article 4:

               4.3    ADVERSE DRUG EXPERIENCE REPORTING. In accordance with FDA
                      requirements, the Party that sponsors the IND (hereinafter
                      referred to as the "IND Sponsor"), shall establish and
                      maintain records and make reports to the FDA as required
                      by 21 C.F.R. Section 310.305 and 21 C.F.R. Section 312.32
                      as applicable. In the conduct of research under this
                      CRADA, the Parties also agree to adhere to specific NIH
                      and NIAID guidelines and policies for reporting Adverse
                      Drug Reporting, as specified in each Protocol. The IND
                      Sponsor agrees to provide to the other Party copies of all
                      Adverse Drug Experience reports concurrently with their
                      submission to the FDA, including copies of any warning
                      letters or other information affecting the safety and/or
                      well-being of human subjects in research conducted under
                      this CRADA.

        F.     Article 9.1 is deleted in its entirety and replaced by the
               following:

               9.1    RIGHT OF ACCESS. NIH and the Collaborator agree to
                      exchange all Clinical Data and Research Results, and Raw
                      Data produced in the course of research under this CRADA,
                      whether developed solely by NIH, jointly with the
                      Collaborator, or solely by the Collaborator. Tangible
                      research products developed under the CRADA will be shared
                      equally by the Parties to the CRADA unless other
                      disposition is agreed to by the Principal Investigators.
                      The Parties to the CRADA will be free to utilize Clinical
                      Data and Research Results and Raw Data for their own
                      purposes, consistent with their obligations under this
                      CRADA.

                      [***]

        G.     Article 9.2 is deleted in its entirety and replaced by the
               following:

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PAGE 9 OF 16                                                        CONFIDENTIAL

<PAGE>   10

               9.2    OWNERSHIP OF AND ACCESS TO CLINICAL DATA AND RESEARCH
                      RESULTS. Subject to the requirements of Article 3.5 and
                      Article 9.1, the [***] The Collaborator's right of access
                      to data produced by Extramural Investigator(s) is set
                      forth in Article 9.8.

        H.     The seventh sentence of Article 9.3 is amended as follows:

               Unless disclosure is otherwise mutually agreed upon, the Parties
               to this CRADA agree to keep Clinical Data and Research Results in
               NIH's Possession and Control, and Raw Data received by NIH
               confidential, to the extent permitted by law, until published or
               reasonable opportunity has been provided for publication, or
               filing or publication of corresponding IP applications. (The
               Parties mutually agree that Collaborator may share, Clinical Data
               and Research Results, and Raw Data with regulatory agencies and,
               under appropriate confidentiality agreements, its commercial
               partners, advisory bodies and otherwise as necessary to exercise
               its rights under Article 9.2, but shall not publish such
               information in academic journals.)

               Article 9.3 now reads as follows:

               9.3    CONFIDENTIAL INFORMATION. Each Party agrees to limit its
                      disclosure of Confidential Information to [***], and shall
                      place a confidentiality notice on all such information.
                      Materials required for the RP may also be designated as
                      Confidential Information from the party receiving
                      Confidential Information. Each party receiving
                      Confidential Information from the other Party agrees that
                      any information so designated shall be used by it [***].
                      Any party may object to the designation of information as
                      Confidential Information by another Party and may decline
                      to accept such information. In addition to all other
                      information identified as Confidential Information as set
                      forth in Section 2.2 above, [***] may be designated as
                      Confidential Information when they are [***], and advance
                      designation of such data and product categories is set
                      forth in the Research Plan. The exchange of confidential
                      information, e.g., [***] should be similarly limited and
                      treated. Unless disclosure is otherwise mutually agreed
                      upon, the Parties to this CRADA agree to keep [***], to
                      the extent permitted by law, [***]. (The Parties

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<PAGE>   11

                      mutually agree that Collaborator may [***] The use of
                      Confidential Information shall be governed by Sections 9.4
                      and 9.6 below. However, nothing contained herein shall be
                      deemed to [***] consistent with NIH policy. Information
                      provided to one or more third parties pursuant to
                      Confidential Disclosure Agreements in connection with
                      their determination of the desirability of entering into a
                      CRADA for [***] shall be maintained as Confidential
                      Information.

        I.     The following new provisions are added to Article 9:

               9.8    EXTRAMURAL RESEARCH AND DATA. In pursuing the development
                      of the Study Drug under this CRADA, NIH may utilize
                      Extramural Investigator(s) for part or all of the
                      completion of the Protocol(s) through either Grants,
                      including Cooperative Agreements, or Contracts. However,
                      those Extramural Investigator(s) are not parties to this
                      CRADA, and this CRADA does [***],

                      a.     To the extent permitted by law and subject to the
                             other provisions of Article 9 of this CRADA, NIH
                             shall [***] all Clinical Data and Research Results
                             [***] as Confidential Information, and make them
                             available [***] to the Collaborator for [***] and
                             for [***].

                      b.     In the case of an Extramural Investigator(s) being
                             funded under a Contract, NIH shall [***] a Contract
                             for preclinical studies or clinical trials for the
                             development of the Study Drug unless the Extramural
                             Investigator(s) agree(s) to [***] and agrees to
                             [***] in accordance with Article 9.8(a) for [***]
                             and for [***].

                      c.     In the case of an Extramural Investigator(s) being
                             funded under a Grant or Cooperative Agreement, NIH
                             shall [***] all Extramural

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<PAGE>   12

                             Investigator(s) participating in the Studies
                             sponsored by NIH and using the Study Drug to [***]
                             with the Collaborator in providing [***]. However,
                             NIH's [***] will not constitute a [***] a Grant
                             award to the Extramural Investigator(s).

                      d.     Collaborator acknowledges that NIH is [***] for
                             management of clinical trials at the Study site of
                             each Extramural Investigator, and NIH acknowledges
                             the [***] by Collaborator to [***] and agrees to
                             [***] Extramural Investigators to [***] to the
                             Collaborator as described in Article 9.8(c).

                      e.     In seeking direct access to Raw Data, Clinical Data
                             and Research Results or any other information that
                             is in the possession of Extramural Investigator(s)
                             working with the Study Drug under the sponsorship
                             of NIH, the Collaborator shall first contact the
                             Influenza Program Officer, who currently is [***].
                             For efficiency, direct contact between Collaborator
                             and Extramural Investigators for certain types of
                             discussions may be arranged by the NIAID Influenza
                             Program Officer and Collaborator on a study by
                             study basis. Subsequent to authorization by DMID,
                             the Collaborator may directly contact the
                             Extramural Investigator(s). Costs associated with
                             providing Raw Data, Clinical Data and Research
                             Results or any other information to the
                             Collaborator in customized formats shall be borne
                             by the Collaborator.

                      f.     The Collaborator's exclusive access under
                             subsection (a) above to Clinical Data and Research
                             Results in NIH's Possession and Control is
                             dependent, however, upon [***]. If the Collaborator
                             [***] without the transfer of its [***] to another
                             party within [***], NIH retains the right to make
                             the Clinical Data and Research Results in NIH's
                             Possession and Control available to another party.

               9.9    MATERIAL TRANSFER AGREEMENTS BETWEEN COLLABORATOR AND
                      STUDY SITE INSTITUTIONS. The Parties acknowledge that
                      Collaborator requires that an appropriate Materials
                      Transfer Agreement (MTA) be in place and maintained with
                      each Study site institution for each shipment of Study
                      Drug provided as a condition of receipt and use by the
                      Extramural Investigator (to manage and protect, among
                      other matters, the intellectual

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PAGE 12 OF 16                                                       CONFIDENTIAL

<PAGE>   13

                      and physical property rights of Collaborator in the Study
                      Drug). With respect to MTAs, the Parties agree as follows:

                      a.     Collaborator acknowledges that NIH funds the Study
                             site institutions under Contracts or Cooperative
                             Agreements and is the IND Sponsor for certain of
                             the Protocols, and therefore the Study site
                             institutions have certain preexisting contractual
                             or other legal obligations to the NIH. NIH
                             acknowledges that Collaborator entered into certain
                             MTAs with Study site institutions. The Parties
                             collectively acknowledge that these agreements
                             [***]. Accordingly, in order to ensure that [***]
                             do not impede the progress of the Studies, [***].
                             As an example of the foregoing, [***]

                      b.     For further shipments of Study Drug for which
                             Collaborator requires new MTAs, Collaborator shall
                             [***]

        J.     Article 11.2 is deleted in its entirety and replaced by the
               following:

               11.2   UNILATERAL TERMINATION. Either NIH or the Collaborator may
                      unilaterally terminate this entire CRADA at any time by
                      giving written notice at least six (6) months prior to the
                      desired termination date, and any rights accrued in
                      property, patents or other IP rights shall be disposed of
                      as provided in Article 11.1.

        K.     The following new provision is added to Article 11:

               11.6   ALTERNATIVE SOURCES OF SUPPLY AND RESEARCH LICENSE IN THE
                      EVENT THE COLLABORATOR TERMINATES DEVELOPMENT OF THE STUDY
                      DRUG

                      a.     If the Collaborator elects to terminate its
                             development of the Study Drug without the transfer
                             of its development efforts and obligations under
                             this CRADA to another party acceptable to NIH
                             within [***] of discontinuation, and NIH wishes to
                             continue its development of the Study Drug, then
                             the Collaborator shall:

                             (i)    [***]; or

                             (ii)   [***]

                      b.     In the event that Collaborator provides written
                             notification that Collaborator is terminating
                             development of Study Drug, and only to the extent
                             permitted by the Materials Transfer and
                             Intellectual Property Agreement between Aviron and
                             the University of

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PAGE 13 OF 16                                                       CONFIDENTIAL

<PAGE>   14

                      Michigan effective February 24, 1995 (redacted version
                      attached hereto as Exhibit I), the Collaborator [***]

        L.     The following three new provisions are added to Article 14:

               14.13  FDA MEETINGS. All meetings with the FDA concerning
                      clinical studies for the development of the Study Drug
                      within the scope of the CRADA Research Plan will be
                      discussed by the Collaborator and NIH in advance and will
                      be held on mutually agreed upon dates. The Collaborator
                      reserves the right to set jointly with NIH the agenda for
                      any such meeting.

               14.14  CONFLICTS. In the event of a conflict between the
                      Protocol(s) incorporated herein by reference and the other
                      provisions of this Agreement, the other provisions of this
                      Agreement shall prevail.

               14.15  STATUTORY COMPLIANCE. NIH and the Collaborator agree to
                      conduct the Studies in accordance with the applicable
                      portions of the Federal Food, Drug, and Cosmetic Act, 21
                      U.S.C. Section 301 et. seq., and its implementing
                      regulations including FDA good clinical practices
                      guidelines and other applicable federal statutes and
                      regulations.

        M.     Article 15.2 is deleted in its entirety and replaced by the
               following:

               15.2   SURVIVABILITY. The provisions of Articles 3.5, 3.7, 4.2,
                      4.3, Articles 5-9, 11.3, 11.4, 11.5, 11.6, 12.1, 13.2,
                      13.3, 13.4, 14.1, 14.10 and 15.2 shall survive expiration
                      or earlier termination of this CRADA.

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PAGE 14 OF 16                                                       CONFIDENTIAL

<PAGE>   15

                          SIGNATURES BEGIN ON NEXT PAGE

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PAGE 15 OF 16                                                       CONFIDENTIAL

<PAGE>   16

                    AMENDMENT NUMBER TWO (2) TO CRADA AI-0062

                                 SIGNATURE PAGE

FOR NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES:

/s/ John R. LaMontague, Ph.D.               6/12/00
-----------------------------------
John R. LaMontague, Ph.D.                   Date
Deputy Director

Mailing Address for Notices:

Office of Technology Development
National Institute of Allergy and Infections Diseases
National Institutes of Health
Building 31, Room 3B62
31 Center Drive, MSC 2137
Bethesda, MD  20892-2137
(301) 496-2644/tel.
(301) 402-7123/fax
Attn: Director

FOR AVIRON:

/s/ C. Boyd Clarke                          June 6, 2000
-----------------------------------
C. Boyd Clarke                              Date
President and CEO

Mailing Address for Notices:
Aviron
297 North Bernard Avenue
Mountain View, CA  94043
(650) 919-6500/tel.
(650) 919-6610/fax

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PAGE 16 OF 16                                                       CONFIDENTIAL

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